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IHJ
According to the ruling of the Medical Sciences Publications Commission No.
14313-80/10/1 and 36914-85/2/10 signed by the Minister of Health and
Medical Education and the Head of the Medical Sciences Publications
Commission of the Islamic Republic of Iran, this journal has been granted
accreditation as a scientific-research journal.
This Journal is indexed in the Scientific Information Database (WWW.SID.IR) and IMEMR
and Index COPERNICUS, SCOPUS, CINAHL and Google Scholar.
ISSN: 1735-7306
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Executive Board:
Chairman: Editor-in-Chief: Executive Manager: Feridoun Noohi, MD A. Hussein Tabatabaei, MD Majid Maleki, MD
Technical Editors: Associate Editors: Assistant Manager: Farshad Amouzadeh, MA Rasoul Azarfarin, MD Shahin Shrani, MD
Hooman Bakhshandeh, MD Shabnam Madadi, MD Reza Golpira, MD
Local Editorial Board: Abdi S. Firouzabadi H. Javidi D. Mostafavi A. Radpour M.
Ahmadi H. Firouzi A. Jebbeli M Motamedi M. R. Sadeghi M. Alizadeh Ghavidel A. R. Firouzi I. Kalantar Motamedi M. H. Nabavizadeh Rafsanjani F. Sadeghpour Tabaee A.
Alizadeh Sani, Z Ghaffari Nejad M. H. Karimi A. Navabi M. A. Sadr Ameli M. A.
Almassi N. Ghasemi M. Kazemi Saleh D. Nazeri I. Sadeghpour A. Aminian B. Gholampour Dehaki M. Kamal hedayat D. Nematipour E. Sattarzadeh R.
Arefi H. Hagh Azali M. Kiavar M. Nikdoost F. Shahmohammadi A.
Azarfarin R. Haghjoo M. Madadi Sh. Nozari Y. Shakibi J. Azarnik H. Haj Sheikholeslami F. Maleki M. Ojaghi Haghigi S. Z. Shirani SH.
Bagherzadeh A. Haji Zeinali AM. Mandegar M. H. Noohi F. Tabatabaei A. H.
Baharestani B. Hakim H. Mehranpour M. Omrani G. Tabatabaei M. B. Bakhshankdeh H. Hashemi J. Mohagheghi A. Oraii S. Yousefi A.A.
Bassiri H. Hashemian M. Mohebbi A. Peighambari M. M. Youssefnia M. A.
Bolourian A. Heidarpour A. Mojtahedzadeh S. Pezeshkian M. Vahedian J. Eslami M. Hosseini K. Momtahen M. Poorhosseini HR Zavarehee A.
Farasatkish R. Hosseini S. Mortezaeian H. Pourmoghaddas M Zand parsa A.F.
International Editorial Consultants:
Alipour M. USA Khaghani A. UK
Anderson D. UK Koolen J. Netherlands Qureshi S. A. UK Bagir R. USA Kranig W. Germany Razavi M. USA
Bellosillo A. Phillipines Kusmana D. Indonesia Robin J. France Davis W. UK M Samuel. India Sadeghi A. USA
Deutsch M. Austria Malek J. USA Samad A. Pakistan
Djavan S. Austria Marco J. France Sheikh S. Pakistan Dorosti K. USA Mee R. USA Sheikhzadeh A. Germany
Elliott M. UK Mirhoseini M. USA Shenasa M. USA
Estafanous F.G. USA Monga M. S. Pakistan Siddiqui H. India Foale R. UK Moosivand T. Canada Sloman G. Australia
Gandjbakhch I. France Moten M. USA Smith W. M. New Zealand
Jahangiri M. UK Nagamia H. USA Tajik A. J. USA Jazayeri M.R. USA Otto A. Turkey Tynan M. UK
Karim S. Indonesia Pavie A. France Wolner E. Austria
Contributing Editors of This Issue:
Abdi S. Jebbeli M Mandegar M. H. Peighambari M. M.
Azarfarin, R. Kamal hedayat D. Mohebbi A. Sadr Ameli M. A.
Bassiri H.A. Madadi, Sh. Noohi F. Shirani, Sh.
Hosseini S. Maleki M. Omrani G.R. Tabatabaei A. H.
Technical Typist: F. Ghomi
Secretary: A. Beheshti
Address: Iranian Heart Association: P.O. Box: 15745-1341, Tehran, IR. Iran. Tel: (009821) 22048174,
Fax: (009821) 22048174
Email: [email protected]
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EDITORIAL
In the Name of God, the Most Beneficent, the Most Merciful
Dear colleagues and friends,
It is with immense pleasure that we present Volume 21, Number 1 (2020) issue of Iranian
Heart Journal, which features some new scintillating studies and case reports in the domains
of cardiovascular medicine and surgery from our Iranian colleagues.
Iranian Heart Journal is indexed in the Web of Science (ISI), the Scientific Information
Database (WWW.SID.IR), IMEMR, Index Copernicus, Scopus, and CINAHL, thereby
facilitating access to published literature. Indubitably, however, our journal is reliant upon
your opinions, ideas, and constructive criticism so as to accomplish its main objective of
disseminating cutting-edge medical knowledge.
As ever before, we look forward to receiving your latest studies and cases.
Yours truly,
A. Hussein Tabatabaei, MD F. Noohi, MD
Editor-in-Chief, Chairman,
Iranian Heart Journal Iranian Heart Journal
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Volume 21, Number 1
2020
CCOONNTTEENNTTSS:: PPaaggee
ORIGINAL ARTICLES: CLINICAL SCIENCE
Efficacy and Safety of Dual Antiplatelet Therapy on Graft Patency After Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial Seifollah Abdi; Mahmood Momtahen; Hossein-Ali Bassiri; Ali Shafiei ; Parham Sadeghipour; Mohsen Madani; Hooman Bakhshandeh
6-16
Clinical and Echocardiographic Characteristics of Patients With Cardiac Tamponade and its Survival Prognostic Factors Behnam Askari; Kamal Khademvatani; Mir-hosein Seyed mohammadzad; Alireza Rostamzadeh; Nuaman Mohammadzaie; Mitra Golmohammadi
17-26
Role of Left Atrial Structure and Function in the Early Prediction of Cardiac Iron Overload in
Transfusion-Dependent β-Thalassemia Patients Mozhgan Parsaee; Nakisa Khansari; Azita Azarkeivan; Mitra Chitsazan; Behshid Ghadrdoost; Hoda Mombeini
27-33
Hospital Facilities at Home for Heart Failure Patients Shiva Khaleghparast; Alireza Maleki; Sepideh Taghavi; Ahmad Amin; Majid Maleki; Mehrdad Oveisi; Behrooz Ghanbari; Zahra Hanifi; Nasim Naderi
34-44
Predictive Power of N-terminal Prohormone of Brain Natriuretic Peptide on Admission and on Discharge for Short- and Long-term Clinical and Echocardiographic Outcomes in Patients With Pulmonary Thromboembolism Abdolvahhab Baradaran; Davood Kazemi Saleh; Yaser Jenab; Susan Hashemi; Arash Jalali; Elham Feizabad
45-54
Chest Pain is Associated With Decreased Irisin Serum Levels in Type 2 Diabetic Patients With Coronary Artery Disease Taybeh Zyaddini; Gholamreza Asadikaram; Mohammad Masoumi
55-66
Association Between Blunted Heart Rate Response to Dipyridamole and Myocardial Ischemia in Diabetic Patients as Compared With Nondiabetic Patients Hadi Malek; Raheleh Hedayati; Nahid Yaghoobi; Hassan Firoozabadi; Fereydoon Rastgou; Ahmad Bitarafan Rajabi
67-74
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CCOONNTTEENNTTSS:: PPaaggee
ORIGINAL ARTICLES: CLINICAL SCIENCE
Fine Particle Air Pollution (PM 2.5) and Cardiovascular Hospitalization in Isfahan in 2012: CAPACITY Study Ehsan Shirvani; Masoumeh Sadeghi; Sayed Mohsen Hosseini; Alireza Khosravi; Katayoun Rabiei; Mojtaba Rahimi; Tohid Jafari-Koshki; Mansour Shishehforoush; Ahmadreza Lahijanzadeh; Elham Moazam; Mohammad Bagher Mohebi; Nizal Sarrafzadegan
75-81
Correlation Between Type II Diabetes Mellitus and Left Atrial Function as Assessed by 2D Speckle-Tracking Echocardiography in Patients Without Coronary Artery Disease Fariba Bayat; Mohammad Khani; Fatemeh Saffarian; Mohammad Amin Shahrbaf
82-93
Prevalence of Anemia in Patients Undergoing Cardiac Surgery and Need for Transfusion During Surgery Regarding Hemoglobin Levels in Rajaie Heart Center
Ali Sadeghi; Rasool Ferasatkish; Avaz Heydarpour; Rasoul Azarfarin; Mohsen Ziyaeifard; Zahra Faritous; Fatemehshima Hadipourzadeh
94-102
Assessment of Global Longitudinal Strain via Speckle-Tracking Echocardiography in Patients With Rheumatoid Arthritis Farahnaz Nikdoust; Samira Safiarian; Atoosa Mostafavi; Farhad Gharibdoust; Seyed Abdol Hussein Tabatabaei
103-109
CASE REPORT
Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Hamid Farzamnia; Farzad Kamali; Mohsen Neshati Pirborji; Ala Keykhavani; Azadeh Meibodi Ardekani; Shabnam Madadi
110-114
Successful Surgical Management of a Retained Guide-Wire Fragment in the Left Main Coronary Artery Masoud Tarbiat; Amir Shams; Farnaz Fariba
115-118
Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Amir Hosein Khandan; Asghar Mohamadi
119-121
INSTRUCTIONS FOR AUTHORS 122-124
FORTHCOMING MEETINGS 125-128
SUBSCRIPTION FORM 129-130
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Original Article DAPI in CABG Abdi et al
Efficacy and Safety of Dual Antiplatelet Therapy on Graft Patency
After Coronary Artery Bypass Graft Surgery:
A Randomized Controlled Trial
Seifollah Abdi1, MD; Mahmood Momtahen
1, MD; Hossein-Ali Bassiri
1, MD;
Ali Shafiei1, MD; Parham Sadeghipour
*1, MD; Mohsen Madani
1, MD;
Hooman Bakhshandeh2, MD, PhD
ABSTRACT
Background: Early vein graft occlusion after coronary artery bypass grafting (CABG) is one of
the major problems after the surgery which directly impacts its short- and long-term
outcomes. One of the potential explanations is aspirin resistance. The aim of this study
was to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) with
clopidogrel and aspirin compared with aspirin alone on the reduction of early graft occ
usion.
Methods: In a multicenter randomized controlled trial with a parallel design, from 2012 to 2015
among 1165 patients, we compared 140 candidates for CABG: 71 in the DAPT group
(300 mg c of clopidogrel and 80–325 mg of aspirin) and 69 in the aspirin group. The
primary outcome was graft patency assessed by coronary computed tomography
angiography performed at 6 months’ follow-up. Bleeding complications were considered
the secondary outcome.
Results: Saphenous vein grafts were occluded in 10 (14.1%) patients in the DAPT and 11
(15.9%) in the control group (P = 0.758). After adjustments for study centers, the
associations remained unchanged (OR [95% CI]: 1.49 [0.59–3.74]). Bleeding endpoints
were also similar in the 2 groups (P > 0.05).
Conclusions: Our study did not demonstrate the superiority of the DAPT regimen over aspirin
monotherapy in patients undergoing elective CABG. Larger multicenter studies may
provide more evidence. (Iranian Heart Journal 2020; 21(1): 6-16)
KEYWORDS: Coronary artery bypass, Platelet aggregation inhibitors, Aspirin, Clopidogrel
1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,
Tehran, IR Iran. 2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
* Corresponding Author: Parham Sadeghipour, MD; Vali-e-Asr St, Niayesh Blvd, Rajaie Cardiovascular, Medical, and Research Center,
Tehran, IR Iran. Email: [email protected] Tel: 02123922092
Received: February 6, 2019 Accepted: March 25, 2019
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arly vein graft failure is still one of
the important caveats of coronary
artery bypass grafting (CABG),
which might translate to major
cardiovascular events. Thrombosis, intimal
hyperplasia, smooth muscle cell
proliferation, and de novo atherosclerosis
plaques have been suggested as a possible
candidate for graft failure, among which
thrombosis plays a crucial role in the early
phase. By blocking cyclooxygenase-1, ASA
inhibits platelet activity and decreases the
rate of graft thrombosis. 1 Despite this
protective approach, around 30% of venous
grafts will become occluded in the first year
after surgery, which may be considered
aspirin resistant. 2,
3 This may be due to the
inability of aspirin to inhibit all aspects of
the platelet activation process and also the
aspirin resistance phenomena. 4 To
overcome these problems, it was suggested
to add clopidogrel in order to lower the rate
of early graft occlusion. To date, there is no
clear consensus regarding the use of dual
antiplatelet therapy (DAPT) after elective
CABG. Several studies have investigated the
clinical use of clopidogrel in the matter, but
they have reached mixed results.
Considering the abovementioned
controversy, this study aimed primarily to
evaluate the effects of a combination of
clopidogrel and aspirin therapy on the
reduction of early graft occlusion evaluated
by coronary computed tomography (CT)
angiography in patients with recent CABG.
METHODS
The study was an open-label multicenter
randomized controlled trial with a parallel
design. It was aimed to evaluate the
superiority of DAPT of clopidogrel and
aspirin compared with aspirin alone on the
reduction of early graft occlusion in patients
with recent CABG.
Study Participants and Settings
The study was conducted from May 2012 to
December 2015 in 3 professional centers for
cardiovascular diseases (Day General
Hospital, Pars General Hospital, and Rajaie
Cardiovascular, Medical, and Research
Center) in Tehran, Iran. All the selected
centers were referral private or teaching
hospitals.
The study protocol was approved by the
ethics committee of Karaj Islamic Azad
University (Code: 030- 8/9/1390).
Inclusion Criteria:
1. Patients’ age ≥ 18 y
2. Candidates for CABG
Exclusion Criteria:
1. Concomitant valve surgeries
2. Concomitant aortic surgery
3. Redo-CABG
4. Patients who did not take aspirin at
least 48 hours before surgery
5. Clopidogrel use within 5 days before
CABG
6. Any condition with increased
bleeding risk, precluding DAPT
7. Significant bleeding in the first 4
hours after surgery, defined as
continuous chest tube drainage > 100
cm3 per hour on average in this time
interval
Totally, 1165 patients who were candidated
to undergo CABG were assessed for the
eligibility criteria by a cardiologist. Every
eligible patient was given a written informed
consent form by the main investigator; and
after signing the form, he/she was registered
in the study.
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Study Groups and Randomization
The participants in this study underwent
randomization (on a 1: 1 basis) via the
permuted block method to either the DAPT
group (clopidogrel and aspirin) or the aspirin
monotherapy group within 24 hours after
surgery. The process of random assignment
was conducted in our data management
center, located in one of the collaborating
hospitals (Rajaie Cardiovascular, Medical,
and Research Center) by the team members
not involved in the conduction of the trial
performed. Random sequence was generated
using the permuted block randomization
method (blocks of 4). After the registration
of each patient in the trial, the nurse in
charge called the center’s data management
center and asked for the assigned study
group. According to the random sequence,
the staff in the center announced the
assigned group as Group A (DAPT) or
Group B (control) to the nurse. The trial was
open-label, and no masking was applied.
The patients who were randomized in the
DAPT group received a loading dose of 300
mg (4 tablets) of clopidogrel (Plavix ®,
Sanofi-Aventis Co) within 24 hours after
surgery and a maintenance dose of 75 mg/d
was continued for 30 days in combination
with 80–325 mg of aspirin. The patients who
were assigned to the control group received
aspirin (80 mg/d). For both groups, aspirin
was recommended for lifelong treatment.
Study Endpoints
The primary endpoint was graft patency
evaluated by CT angiography 6 months after
surgery. A graft was considered patent if no
significant stenosis (≥ 70%) was detected by
CT angiogram; otherwise, it was regarded as
occluded.
The secondary endpoints were:
1) The amount of chest tube output in the
early postoperative period, defined as the
amount of the bloody fluid drained. The
chest tube drainage was considered
significant when its amount exceeded 100
cm3 per hour on average for a 4-hour
interval in the intensive care unit (ICU) after
surgery.
2) The need for blood transfusions with
either of the following criteria:
a. ≥ 2 units of packed red blood cells
b. ≥ 2 units of fresh frozen plasma
c. ≥ 5 units of platelets
3) In-hospital mortality, defined as cardiac
death in the postoperative period and during
hospitalization as a secondary endpoint of
the study.
After undergoing surgery, the patients were
discharged to the ICU, where they were
visited every day by the principal
investigator or eligible cardiologists and
assessed for the study endpoints.
Data Collection and Follow-up
All the data related to the patients’
characteristics, intervention, and bleeding
complications from the index event until
discharge were recorded in a CRF by a
trained and qualified study coordinator (SC).
During the time of hospitalization, all the
participants were monitored in terms of the
amount of chest tube drainage and blood
product transfusion.
Afterward, the patients were asked by the
study coordinator to refer for a visit at 1
month’s follow-up. Treatment adherence
was evaluated, along with any complication,
by the principal investigator.
Six months after surgery, CT-angiography
was performed to evaluate graft patency.
During the recruitment for imaging follow-
up, the patients who refused to attend this
examination were asked to give the reason
for not attending and cases of death were
reported when available.
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After CT angiography for the participant, all
data about the number and type of involved
graft vessel(s) were saved in the CRF.
All the CT angiographic examinations were
double-checked by the radiologist involved
in the study.
Statistical Analysis
The data were analyzed via the intention-to-
treat approach. The data were described as
the mean (± the standard deviation) for the
interval variables with normal distributions,
the median (interquartile ranges) for the
interval variables without normal
distributions, and count (%) for the
categorical variables. Fitness of the
distribution of the interval variables to
normal distribution was assessed using the
one-sample Kolmogorov–Smirnov test.
Associations between DAPT and other
variables were determined using the Student
t-test for the interval variables with normal
distributions, the Mann–Whitney U test for
the interval variables without normal
distributions and the ordinal variables, and
the Pearson χ2
test (or the Fisher exact test,
as needed) for the nominal variables. A P
value ≤ 0.05 was considered statistically
significant.
Adjusted associations between the primary
endpoint (graft occlusion) and DAPT were
investigated using a multivariate binary
logistic model. The study center was
considered a covariate, and other covariates
in the model were chosen if a significant P
value was detected in the bivariate statistical
analysis.
The statistical analyses were performed via
IBM SPSS Statistics 19 for Windows (IBM
Inc, Armonk, NY) and Stata 11 (Stata Inc,
Texas, USA).
RESULTS
Baseline and Background Data
The study was conducted from May 2012 to
December 2015 in 3 centers for
cardiovascular diseases in Tehran, Iran. In
total, 1165 patients were assessed primarily
for the inclusion criteria. Among them, 740
did not satisfy the inclusion criteria and 209
did not participate and sign the informed
consent form. The remaining 216 patients
were randomly assigned to the 2 study arms
(108 in each group). Nonetheless, due to a
nurse’s error, 3 patients were misclassified
and, therefore, 111 participants received
DAPT and 105 received aspirin only.
Finally, 140 (65%) participants (71 in the
intervention group and 69 in the control
group) remained until the end of the study
and their relevant data were used in the
statistical analysis. Seventy-six (35%)
patients quit the study as they chose not to
undergo CT angiography or could not
complete the follow-up course. The study
participants’ flow diagram is presented in
Figure 1.
Table 1 depicts a comparison of the
background characteristics between the 2
groups: the patients who agreed to undergo
CT angiography (ie, those who were entered
in the final analysis) and the patients who
did not. The results showed that the 2 groups
were similar in several aspects; thus, it can
be concluded that the acceptance of CT
angiography was random in the study
participants. The participants’ characteristics
were compared between the study groups,
and the results are presented in Table 2. The
findings suggested that the patients were
roughly similar in the 2 study groups.
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ALLOCATION
ANALYSIS
FOLLOW -UP
Analyzed (n= 69 ) Excluded from analysis (n= 0 )
Figure 1. CONSORT Flow Diagram
Table 1. Comparison of the patients’characteristics between the group that underwent CTA and the group that did not
CTA Performed (n=140) CTA NOT Performed (n=76) P value
Study Group a 0.714
Intervention 71 (50.7%) 40 (52.6%)
Control 69 (49.3%) 35 (46.1%)
Gender a 0.144
Male 113 (80.7%) 54 (71.1%)
Female 27 (19.3%) 21 (27.6%) 0.198
Age (y) b 62 (±9.4) 61 (±9.7)
Center a 0.428
1 28 (20%) 11 (14.5%)
2 33 (23.6%) 15 (19.7%)
3 79 (56.4%) 49 (64.5%)
History of MI a 72 (51.4%) 40 (52.6%) 0.790
Family history a 58 (46.4%) 29 (38.2%) 0.503
Hypertension a 82 (58.6%) 52 (68.4%) 0.121
Dyslipidemia a 95 (67.9%) 48 (63.2%) 0.568
Diabetes a 57 (40.7%) 28 (36.8%) 0.629
Smoking a 77 (55%) 44 (57.9%) 0.730
Coronary Vessel Stenosis a 0.583
Single vessel 13 (9.3%) 4 (5.3%)
Two vessels 29 (20.7%) 17 (22.4%)
Three vessels 98 (70%) 54 (71.1%)
LVEF (%)b 47 (±10.8) 46 (±10.3) 0.882
Results are presented as: a: count (%), b: mean (±standard deviation). CTA, Computed tomography angiography; MI, Myocardial infarction; LVEF, Left ventricular ejection fraction
Assessed for eligibility (n= 1165)
Excluded (n= 949 )
Not meeting inclusion criteria (n= 740)
Declined to participate (n= 209)
Analyzed (n= 71 ) Excluded from analysis (n= 0 )
Allocated to Plavix + aspirin (according to study protocol) (n=108 )
Received allocated intervention (n= 111)
Lost to follow-up (30 patients chose not to undergo CT angiography, 2 patients had chronic kidney disease, 1 patient had hypersensitivity to contrast media, and 3 cases of irrelevant death; total n=36)
Discontinued intervention (n=0)
Allocated to aspirin (according to study protocol) (n= 108)
Received allocated intervention (n= 105)
Did not receive allocated intervention (The nurse in charge
made a mistake about the prescription of Plavix.) (n=3)
Randomized (n= 216)
ENROLLMENT
Lost to follow-up (33 patients chose not to undergo CT angiography, 2 patients had chronic kidney disease, 1 patient had hypersensitivity to contrast media, 1 case of irrelevant death, and 1 patient continued Plavix > 30 days because of carotid stenting: total n=38)
Discontinued intervention (1 occurrence of thoracic surgery due to mediastinitis, 1 because of patient’s willing, total n=2)
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Table 2. Comparison of characteristics between the patients who were entered in the analysis (ITT) (N=140)
Plavix-Aspirin (n=71)
Aspirin (n=69)
P value
Gender a
Male 57 (80.3%) 56 (81.2%) 0.895
Female 14 (19.7%) 13 (18.8%)
Age (y) b 62 (±8.4) 61 (±10.4) 0.423
History of MI a 31 (43.7%) 41 (59.4%) 0.062
Family history a 33 (52.4%) 25 (40.3%) 0.176
Hypertension a 44 (62%) 38 (55.1%) 0.407
Dyslipidemia a 50 (70.4%) 45 (65.2%) 0.501
Diabetes a 24 (33.8%) 33 (47.8%) 0.121
Smoking a 40 (56.3%) 37 (53.6%) 0.884
Coronary Vessel Stenosis a
Single vessel 5 (7%) 8 (11.6%)
0.317 Two vessels 18 (25.4%) 11 (15.9%)
Three vessels 47 (67.6%) 50 (72.5%)
LVEF (%) c 50 (45-55) 50 (35-55) 0.172
Emergent operation a 3 (4.2%) 1 (1.4%) 0.324
Number of grafts c 2 (2-3) 2 (2-3) 0.399
Hemoglobin (g/dL) b 13.4 (2.8) 13.7 (2.4) 0.171
Results are presented as: a: count (%), b: mean (standard deviation), c: median(Q1-Q3). MI, Myocardial infarction; LVEF, Left ventricular ejection fraction
In-Hospital Events
The patients were assessed in terms of
bleeding, transfusion, and other outcomes
and the comparative results are presented in
Table 3. There was no statistical difference
in the chest tube drainage between the 2
groups (P > 0.05). The incidence of
significant bleeding leading to blood product
transfusion was similar between the 2
groups. However, the amount of RBC
transfused to the intervention group was less
than that transfused to the control group (P <
0.05). No death was reported during this
period.
Table 3. Comparison of the findings during hospitalization between the study treatment groups (ITT)
Plavix-Aspirin
(n=71) Aspirin (n=69)
P value
Chest tube drainage (cm3)
First day after surgery b 400 (250 - 500) 400 (250 - 541.5) 0.541
ICU period b 500 (350 - 700) 500 (325 - 725) 0.828
Ward b 0 (0 - 0) 0 (0 - 0) 0.555
Total b 600 (350 - 750) 500 (350 - 875) 0.602
Need for transfusion a 42 (59.2%) 47 (68.1%) 0.271
Hemoglobin before transfusion c (g/dL) 10.6 (2.4) 10.9 (2.7) 0.169
In Transfused Patients:
Units of packed RBCs b 1 (1 - 2) 2 (1 - 3) 0.004
Volume of packed RBCs (cm3)
b 250 (250 - 500) 500 (250 - 775) 0.005
Units of FFP b 3 (1.5 - 3) 3 (1.75 - 3) 0.894
Volume of FFP (cm3)
b 450 (300 - 450) 450 (275 - 450) 0.789
Units of platelet b 3 (2 - 4) 3 (2 - 4) 0.515
Volume of platelet (cm3)
b 150 (100 - 200) 150 (100 - 200) 0.515
Units of whole blood b 1 (1 - 1) 3 (3 - 3) 0.317
Volume of whole blood (cm3)
b 350 (350 - 350) 900 (900 - 900) 0.317
Re-operation because of bleeding a 0 (0%) 1 (1.4%) 0.493
Hospitalization (days after surgery) 6 (6 - 7) 7 (6 - 8) 0.223
Mortality a 0 0 -
Results are presented as: a: count (%), b: median (Q1-Q3), c: mean (standard deviation). FFP, Fresh frozen plasma; RBC, Red blood cells
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Six Months After Surgery
After discharge, there were no records of
bleeding, ischemic events, or mortality.
Graft Occlusion
As the primary endpoint of the study, the
occlusions of venous (and arterial) grafts
were measured via coronary CT
angiography. Saphenous vein grafts were
occluded in 10 (14.1%) patients in the
DAPT group and 11 (15.9%) patients in the
control group (P = 0.758). Arterial graft
occlusion was observed in 5 (7%) patients in
the DAPT group and 3 (4.3%) patients in the
control group (P = 0.492). To adjust the
association between the study intervention
and graft occlusion for each of our 3 centers,
we performed a multivariable logistic
regression analysis (Table 4). The analysis
showed that the study center did not
influence the study outcomes (P > 0.05).
Table 4. Multivariable analysis for adjusting the findings for the centers
Crude OR (95% CI) Adjusted OR (95% CI) P value
Dual antiplatelet therapy 0.86 (0.34 – 2.19) 1.49 (0.59 – 3.74) 0.397
Center of study
1 (reference)
2 0.51 (0.11 – 2.40) 0.392
3 1.66 (0.54 – 5.10) 0.378
Adverse Events
The frequencies of adverse events according
to the study groups are presented in Table 5
(in the study treatment group, n=140) and in
Table 6 (in the randomized patients, n=216).
Additionally, the frequencies of serious
adverse events, compared between the study
groups, are mentioned in Table 7.
Table 5. Frequency of adverse events in the study population until the end of 6 months after follow-up in the study
treatment groups (N=140)
Plavix-Aspirin
(n=71) Aspirin (n=69)
Transient Mild Thrombocytopnia 3 4
Transient Mild Azotemia 1 1
Transient Microscopic Hematuria 1 0
Subcutaneous Emphysema 0 1
Vasovagal Syndrome 1 1
Ventricular Tachycardia 0 1
Fever 1 0
Pneumonia 0 0
Mediastinitis 0 0
Tamponade 0 1
Pericardial Effusion 1 1
Pleural Effusion 4 3
Hematoma at the Site of Saphenectomy 0 1
Wound Infection 2 1
Pressure Ulcer 0 0
Retroperitoneal abscess 0 0
Exsessive Bleeding 0 1
LV Clot 0 1
Death Due to CVA (Out of Hospital) 0 0
Death Due to Cirrhosis (Out of Hospital) 0 0
Death Due to Mediastinitis ( in Hospital) 0 0
Total AEs 14 17
Total Patients with AEs 11 14
Total Patients with AEs Leading to Discontinuation 1 0
Total Patients with SAEs 5 8
LV, Left ventricle; CVA, Cerebrovascular accident; SAE, Serious adverse event
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Table 6. Frequency of adverse events in the study population until the end of 6 months after follow-up in the
randomized patients (n=216)
Plavix-Aspirin
(n=111) Aspirin (n=105)
Transient Mild Thrombocytopnia 3 4
Transient Mild Azotemia 1 1
Transient Microscopic Hematuria 1 0
Subcutaneous Emphysema 0 1
Vasovagal Syndrome 1 1
Ventricular Tachycardia 0 1
Fever 1 0
Pneumonia 0 1
Mediastinitis 1 0
Tamponade 0 1
Pericardial Effusion 2 2
Pleural Effusion 6 4
Hematoma at the Site of Saphenectomy 0 1
Wound Infection 2 1
Pressure Ulcer 2 1
Retroperitoneal abscess 1 0
Exsessive Bleeding 0 1
LV Clot 0 1
Death Due to CVA (Out of Hospital) 0 1
Death Due to Cirrhosis (Out of Hospital) 0 1
Death Due to Mediastinitis ( in Hospital) 1 1
Total AEs 22 24
Total Patients with AEs 21 19
Total Patients with SAEs 7 15
LV, Left ventricle; CVA, Cerebrovascular accident; SAE, Serious adverse event Table 7. Frequency of serious adverse events (SAEs) according to the study groups
Serious Adverse Events
Randomized (n=216)
Analyzed (n=140)
Total DAPT (n=111)
Aspirin (n=105)
Total DAPT (n=71)
Aspirin (n=69)
Death 4 1 3 0 0 0
Requiring/Prolonging Hospitalization 16 5 11 11 4 7
Congenital Anomaly/ Birth Defect 0 0 0 0 0 0
Life-threatening 3 1 2 2 1 1
Persistent/Significant Disability/ Incapacity 0 0 0 0 0 0
Other Medically Important Events 0 0 0 0 0 0
DAPT, Dual antiplatelet therapy
DISCUSSION
In the present study, we compared the effect
of DAPT (ie, aspirin and clopidogrel) with
that of aspirin alone in patients having
undergone elective CABG. Our study was
an open-label multicenter controlled
randomized trial with a parallel design, and
our analysis showed no significant
differences in terms of the primary outcome
(ie, graft patency 6 months after surgery)
between the 2 groups of study. Additionally,
the 2 groups were similar according to
bleeding complications.
Different investigations have shown the
important rate of graft (especially venous
graft) failure early after CABG. Although
different mechanisms including intimal
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hyperplasia, smooth muscle cell
proliferation, and de novo atherosclerosis
plaques have been suggested for the
complication, thrombosis appears to play an
important role in the early phase.
Considering these mechanisms, it seems
logical that potent platelet inhibition with
DAPT may improve graft patency. This
benefit should be weighed against the
potential bleeding complication of the
combined regimen. 6 The mentioned
hypothesis was firstly tested in an acute
coronary syndrome population. The CREDO 7 and CURE
8 trials analyzed the effect of
DAPT vs aspirin alone in an acute coronary
syndrome setting in which DAPT showed
promising results toward decreasing the all-
cause mortality without a significant
increase in major bleeding.
Various studies have evaluated the value of
DAPT in elective CABG patients. Graft
patency, evaluated within 3 to 12 months
following CABG, was their main outcome.
In all of them, ASA and/or clopidogrel were
re-administrated when chest tube drainage
was no longer active. In our study, we chose
to show the effect of DAPT on 6 months’
graft patency.
Goa et al, 9
in their randomized controlled
trial, investigated the value of the DAPT
regimen vs aspirin monotherapy in elective
CABG. Their primary outcome was graft
failure 3 months after surgery. Graft failure
was significantly lower in the DAPT group,
in which a trend toward a decrease in all
grafts failure was also detected. It should,
however, be mentioned that bleeding
complications were not elaborated
separately in their analysis.
Mannacio et al, 10
in their CRYSSA trial,
also studied the effect of DAPT on post-
CABG graft patency and its relation with
single or dual antiplatelet resistance. The
study showed that the DAPT regimen had a
beneficial effect compared with
monotherapy. Their results also revealed
that the combination of ASA and
clopidogrel might overcome the single
antiplatelet drug resistance and the
synergistic activity of combined aspirin and
clopidogrel was a strong predictor of
saphenous vein graft (SVG) patency (RR:
5.1, 95% CI: 1.4 to 16.3; P < 0.01).
Likewise, Gasparovic et al 11
compared
specifically the 2 regimens on an aspirin-
resistance population. There were no
significant differences between the 2 groups
regarding graft patency or bleeding
complications. However, the subgroup
analysis showed a benefit for the DAPT
regimen in the obese population.
The CASCADE trial was also a randomized
study with a genuine design. Their primary
endpoint was the effect of clopidogrel on
intimal hyperplasia 1 year after surgery.
With the help of intravascular ultrasound,
the SVGs were analyzed regarding intimal
hyperplasia. Interestingly, clopidogrel had
no impact on the primary outcome. 12
Recently, van Diepen et al, 13
in their post
hoc secondary analysis of the FREEDOM
trial, showed that the DAPT regimen was
not superior to ASA monotherapy in the
post-CABG population. Their results were
consistent in regard to primary graft patency,
bleeding complications, and subgroup
analysis in which important subgroups such
as the ACS population and higher syntax
scores were evaluated. Verma et al, 14
in
their meta-analysis of studies investigating
the role of the DAPT regimen compared
with aspirin monotherapy in both ACS and
elective populations, showed no additional
benefit from adding clopidogrel to ASA in
the post-CABG population.
Our study did not evaluate the possible
effect of the DAPT regimen on the native
coronary arteries. Previous research has
shown that native coronary vessels are at
risk of plaque rupture and other
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complications in which added clopidogrel
might be beneficial. In a substudy of the
CASCADE trial, Une et al 15
proved the
efficacy of DAPT in reducing native
coronary events compared with ASA
monotherapy. The matter still needs further
investigation.
A limitation of the current study was the
considerable number of registered patients
who chose not to undergo CT angiography
(76 out of 216). As was shown in Table 3,
this might not affect the internal validity of
the study. However, from a sociological
point of view, it may affect the
generalizability of the results and may, thus,
need to be considered in future studies.
In conclusion, there is still no consensus on
the efficacy of the DAPT regimen in patients
candidated for elective CABG. Our results
showed a neutral effect of the DAPT
regimen. Large multicenter randomized
clinical trials are needed to definitely
investigate the role of DAPT in patients with
acute coronary syndrome after CABG and to
clearly identify which patients will benefit
the more.
Acknowledgments
This project was sponsored by Sanofi-Iran.
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al. Aspirin plus clopidogrel therapy
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arteRY bypaSS occlusion After off-pump
procedures) randomised study. Heart, 2012.
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TH, Siami FS, Goodman SG, et al. Dual
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Characteristics of Patients With Cardiac Tamponade and Their Survival Askari et al
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Original Article Characteristics of Patients With Cardiac Tamponade and Their Survival Askari et al Clinical and Echocardiographic Characteristics of Patients With
Cardiac Tamponade and its Survival Prognostic Factors
Behnam Askari1, MD; Kamal Khademvatani
2, MD;
Mir-hosein Seyed mohammadzad2, MD; Alireza Rostamzadeh
2, MD;
Nuaman Mohammadzaie3, MD; Mitra Golmohammadi, MD*
4
ABSTRACT
Background: Cardiac tamponade nearly always requires urgent intervention, but the optimal
management of pericardial effusion is still controversial. The aim of our study was to
introduce the profile and treatment results of patients with tamponade in our referral heart
center.
Methods: From November 2010 to November 2014, our retrospective study was performed on
220 patients with tamponade. All the clinical and echocardiographic findings of the
patients, as well as their operative and follow-up data, were recorded and analyzed.
Results: The overall prevalence of tamponade relative to the entire study population undergoing
heart surgery was 8.5%. There were 106 men and 114 women at a mean age of 55.5 years
(range = 5–99). The most common causes of tamponade were cardiac diseases (21%),
malignancy (20.4%), unknown (20.4%), chronic renal failure (15%), and post-cardiac
surgery complications (10.5%). The approaches for pericardial effusion drainage were the
subxiphoid approach (97.7%), mini-thoracotomy (1.4%), and percutaneous
pericardiocentesis (0.9%). The intraprocedural mortality rate was zero, the mortality rate
during hospital stay was 4.5%, and the recurrence rate was 9.1%. Patients with primary
sanguineous pericardial effusion, malignant etiologies of tamponade, and malignant
pericardial effusion had significantly poor survival. The survival rates at 1 month, 1 year,
2 years, and 3 years were 87.1%, 67.7%, 64.5%, and57.2%, respectively.
Conclusions: We found an association between left pleural effusion and small amounts of
pericardial effusion, hence the necessity of more attention in the echocardiographic
evaluation of these patients. The subxiphoid approach for pericardial effusion drainage is
a safe and simple procedure associated with relatively lower postoperative complications,
mortality, and recurrence rate. Sanguineous pericardial effusion is concomitant with poor
prognoses. (Iranian Heart Journal 2020; 21(1): 17-26)
KEYWORDS: Cardiac tamponade, Subxiphoid pericardial window, Pericardial effusion, Pericardial drainage 1
Department of Cardiovascular Surgery, Seyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran. 2
Department of Cardiology, Seyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran. 3
General Physician, Urmia University of Medical Sciences, Urmia, IR Iran. 4
Department of Cardiac Anesthesiology, Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, IR Iran.
*Corresponding Author: Mitra Golmohammadi, MD
Email: [email protected] Tel: 09123953220
Received: February 6, 2019 Accepted: March 28, 2019
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ericardial effusion is pathological
fluid accumulation in the pericardial
cavity. It is usually due to an
imbalance in fluid formation and absorption.
If this accumulation occurs quickly or
gradually, it can lead to the collapse of the
heart chambers and tamponade, which is a
life-threatening condition. 1
The clinical presentations of pericardial
effusion at the time of diagnosis vary, 2 with
the most common causes of large pericardial
effusion being malignancies, uremia,
infections, collagen vascular disease, and
chest radiation. 1, 3
Cardiac tamponade nearly always requires
urgent intervention, but the optimal
management of pericardial effusion is still
controversial. There are several pericardial
drainage approaches: the percutaneous
approach or pericardiocentesis and the
surgical approach such as the subxiphoid
pericardial window, left mini-thoracotomy,
and the left paraxiphoidian approach, each
of which has its own advantages and
disadvantages. 4- 6
Pericardiocentesis is a less invasive
procedure than surgical procedures; it,
however, has a higher recurrence rate and is
sometimes associated with such
complications as severe bleeding. 6 The
subxiphoid approach is a more invasive
technique but has lower recurrence rates. 1
Optimal urgent decompression targets are
sufficient fluid drainage and sampling,
resection of the pericardial sample for
pathological evaluation, and prevention of
recurrence with minimal morbidity and
mortality. Given that the existing literature
contains conflicting data about various
intervention options, we sought to introduce
the profile and treatment results of patients
with tamponade in our referral heart center.
METHODS
From November 2010 to November 2014,
our retrospective study was performed on
261 patients who were admitted and treated
at Seyed-al-Shohada Heart Center in
Urmia, Iran, for pericardial effusion with
cardiac tamponade. Our study protocol was
approved by the Ethics Committee of Urmia
University of Medical Sciences. Cardiac
tamponade diagnosis and decision for
surgery consultation in all cases were made
by a cardiology specialist based on clinical
evaluations and echocardiography.
Postoperative patients requiring re-
sternotomy and chest re-exploration during
several days after open-heart surgery were
excluded from the study.
All the clinical findings of the patients at the
time of admission such as age, gender,
dyspnea, hypotension, pulse paradox,
elevation of jugular pressure, heartbeat
mutations, and tachycardia were recorded.
Echocardiographic findings such as right
and left atrial collapse, right ventricular
collapse, the ejection fraction, and findings
compatible with fluid accumulation in the
pericardial space were also recorded.
Local anesthesia and intravenous sedation or
general anesthesia were used. The surgical
procedure for most of the patients was the
subxiphoid pericardial window. A 4 to 6-cm
incision was made in the midline and the
upper abdominal region approximately over
the xiphoid process. In the thoracotomy
approach, anterior mini-thoracotomy was
done with a 4 to 6-cm incision beneath the
left nipple and through the fifth intercostal
interspace. After the identification and
incision of the pericardium, pericardial fluid
suction was performed. A chest tube (28 or
32 F) was placed into the pericardial space
through a separate stab wound. Percutaneous
drainage was performed with an 8-cm
P
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18-gauge angiocatheter, guide wire, dilator,
and a pigtail catheter.
The pericardial fluid was sent for culture and
cytological, bacteriological, and histological
analyses. A biopsy specimen (a piece of
pericardium 1 to 2 cm in diameter) was
resected for pathological evaluation. The
fluid volume and its appearance were also
recorded.
When the amount of the mediastinal
drainage was less than 100 cc in 24 hours
and control echocardiography showed no
significant residual effusion, the tube drain
was withdrawn.
Echocardiography was done after 1 month
and 1 year for asymptomatic patients in the
follow-up period and for all symptomatic
patients.
Operative and follow-up data of the patients
such as the drainage technique, the
anesthesia technique, the amount of fluid
drained, the nature of the pericardial fluid,
cytological and pathological findings,
hospital mortality, mortality in the follow-up
period, and the mean survival rate were
recorded.
The data analyses were conducted with
version 20 of SPSS software. The
quantitative data were shown as the mean ±
the standard deviation (SD), and the
qualitative data were presented as
frequencies and percentages. The overall
survival was calculated from the date of
surgery until death or the last follow-up. For
the univariate analysis, both the independent
t-test and the ANOVA test were used to
report any difference in the survival rates
during the follow-up period. Differences
were considered significant if the P value
was < 0.05.
RESULTS
Within a study period of 48 months, 261
patients were diagnosed with tamponade.
Forty-one patients were excluded due to
incomplete medical records. The evaluations
were performed on 106 men and 114 women
at a mean age of 55.57 ± 18.28 years (range
= 5–99). Two patients did not accept
surgical or percutaneous intervention. Two
patients underwent percutaneous drainage
with echocardiography-guided
pericardiocentesis. In the 4-year period, the
overall prevalence of tamponade relative to
the entire study population undergoing heart
surgery was 8.5% (257/3010). The patients’
demographics and clinical characteristics are
described in Table 1. The most prevalent
clinical problem was dyspnea (91.8%).
Table 1. demographic and clinical characteristics of the patients with tamponade (N=220)
Characteristic No %
Age(y) 55.57±18.28 (5-99)
Gender: male female
114(51.8%) 106(48.2%)
BMI(kg/m2) 25.92±4.82 (14.7-38.6)
Diabetes 39(17.7%)
Hypertension 86(39.1%)
Smoking 42(19.1%)
Familial history of tamponade 3(1.4%)
History of any previous surgery 75(34.1%)
History of tamponade drainage 20(9.1%)
Habitation location: urban rural
155(70.5%) 65(29.5%)
Signs: Dyspnea Elevated jugular venous pressure Pulse paradox Hypotension (SBP < 90 mm Hg) Muffled heart sounds
202(91.8%) 64(29.1%) 22(10%) 29(13.2%) 62(28.2%)
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Common ECG findings were sinus
tachycardia 154 (70%), low voltage 78
(35.5%), and electrical alternans 35 (15.9%).
Radiographic evidence of pleural effusion
was present in 38 (17.3%) patients. The
echocardiographic and laboratory findings
are depicted in Table 2.
Table 2. Echocardiographic characteristics of the patients with tamponade (N=220)
Characteristic No %
EF (%): < 30 30-45 45-55 > 55
34(15.5%) 47(21.4%) 59(26.8%) 80(36.4%)
RV collapse 99(45%)
LA collapse 2(0.9%)
RA collapse 85(38.6%)
Respiratory variation: Mitral valve Tricuspid valve
32(14.5%) 17(7.7%)
IVC dilation 54(24.5%)
Swimming heart 10(4.5%)
Fluid amount: Mild(< 5mm) Moderate( 5-15mm) Sever( > 15mm)
5(2.3%) 40(18.2%) 175(79.5%)
Fluid type: Localized Generalized
23(10.5%) 197(89.5%)
Hb(gr/dL) 11.54±2.08 (5-19)
ESR(mm/h) 29.67±28 (1-125)
CRP(mg/lit) 29.1±27.57 ( 0.1-97)
WBC 9356±4429 (4900-30300 )
PLT 137067±24169(35000-1654000)
Cr(mg/dL) 1.46±1.3 (0.5-8.5)
EF, Ejection fraction; RV, Right ventricle; LA, Left atrium; IVC, Inferior vena cava; Hb, Hemoglobin; ESR, Erythrocyte sedimentation rate; CRP, C-reactive protein; PLT, Platelet; Cr, Creatinine
The most common causes of effusion were
cardiac diseases, malignancy, renal failure,
and post-cardiac surgery complications. The
etiology was malignant in 45 (20.5%)
patients and benign in 175 (79.5%) patients.
Unknown etiology accounted for 45
patients. The causes of tamponade are
presented in Table 3.
Table 3. Causes of tamponade (N=220)
Cause No %
Cardiac 46(21%)
Malignancy: Lung cancer Hematological malignancy Gastrointestinal Breast cancer Ovarian Squamous cell carcinoma (neck) Osteosarcoma
45(20.4%) 13(29%) 12(26.7%) 9(19.9%) 8(17.8%) 1(2.2%) 1(2.2%) 1(2.2%)
Chronic renal failure 33(15%)
Post cardiac surgery 23(10.5%)
Autoimmune disease 7(3.2%)
TB 6(2.7%)
Pericarditis 6(2.7%)
Myxedema 5(2.3%)
Liver disease 4(1.8%)
Unknown 45(20.4%)
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Pericardial effusion drainage was performed
on 218 patients. Two patients underwent
percutaneous drainage with
echocardiography-guided pericardiocentesis.
The most common drainage procedure was
surgery via the subxiphoid approach and
general anesthesia. The appearance of
effusion was serous and yellowish in most
patients. The operative and postoperative
data of the patients are shown in Table 4.
Table 4. Operative and postoperative data of the patients (N=218)
Characteristic No %
Operative procedure n (%): Subxiphoid approach Mini-thoracotomy Percutaneous
213(97.7%) 3(1.4%) 2(0.9%)
Anesthesia: General Local
202(92.7%) 16(7.3%)
Volume of drainage fluid, mL 600±391 (10-3000)
Nature of pericardial fluid: Serous Sanguineous Purulent
128(58.2%) 85(38.6%) 5(2.3%)
Operative complication: Renal Pulmonary Arrhythmia None
3(1.4%) 1(0.5%) 2(0.9%) 212(97.2%)
Hospital mortality 10(4.5%)
Follow-up (mon) 0-78
There was no intraprocedural mortality. The
mortality rate during hospital stay was
10(4.5%). The fluid samples and pericardial
biopsy samples were sent for evaluation for
81(36.8%) patients. The cytological findings
included malignancy in 20 (24.7%), normal
in 21 (25.9%), inflammatory in 28 (34.6%),
and bloody in 12 (14.8%) patients.
Additionally, the pericardial biopsy reports
of 81 patients included malignancy in 16
(19.8%), normal in 28 (34.5%), acute
pericardial inflammation in 22 (27.2%),
chronic fibrotic inflammation in 12 (14.8%),
tuberculosis (TB) presentation in 2 (2.5%),
and non-pericardial tissue in 1 (1.2%).
The median follow-up period for all the
study participants was 35.5 (range = 0–78
mon). The survival rates at 1 month
(108/124), 1 year (84/124), 2 years (80/124),
and 3 years (71/124) were 87.1%, 67.7%,
64.5%, and 57.2%, respectively.
The mean survival rate of the patients was
not different significantly in terms of age (P
= 0.15), sex (P = 0.258), smoking (P = 0.6),
diabetes (P = 0.594), hypertension (P = 0.5),
the body mass index (P = 0.71), dyspnea (P
= 0.3), elevated jugular venous pressure (P =
0.293), hypotension (P = 0.45), the ejection
fraction (P = 0.998), fluid amounts (P =
0.549), right atrial collapse (P = 0.068),
respiratory variation (P = 0.356), and
anesthesia type (P = 0.256). Nonetheless,
the etiology of tamponade and cytological
and pathological findings significantly
affected the mean survival rate. The risk
factors affecting survival are presented in
Table 5.
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Table 5. Risk factors affecting survival (N=124) (follow-up of 0–78 months and mean survival of 35.5 months)
Characteristic Mean survival (months)
P value
Demographic Findings 32.67-42.28 >0.05
Clinical findings: Pulse paradox Others
48.58 versus 34.10 31.26-43.1
0.05
>0.05
Echocardiographic Findings 27.3-50.33 >0.05
Operative procedure n (%): Subxiphoid approach Mini-thoracotomy Percutaneous
36.15 11 6
0.614
Etiology of Tamponade: Cardiac Malignancy Chronic renal failure Post cardiac surgery Autoimmune disease TB Pericarditis Myxedema Liver disease Unknown
41.81±24.73 14.93±17.92 33.54±28.37 37.15±17.89 55.40±11.33 47±4.64 35±30.51 58.50±2.12 63.66±9.29 41.46±20.13
0.001
Cytological Findings: Malignancy Normal Inflammatory Bloody
15.55±19.51 45.93±28.88 45.75±27.35 20.50±21.61
0.002
Pathological Evaluation of Pericardium Biopsy: Malignancy Normal Acute inflammation Chronic inflammation TB Non-pericardial tissue
15.45±19.49 44.85±25.85 44.14±30.02 18.28±25.99 47±4.64 11
0.009
DISCUSSION
Pericardial effusion is rarely symptomatic,
and often it is an incidental finding.
However, with rapid or massive fluid
accumulation, signs and consequences of a
dangerous status of life may be created. 7
The diagnosis of significant pericardial
effusion based on clinical signs alone is
usually difficult. One study revealed that the
prevalence rates of hypotension, pulse
paradox, and elevated jugular venous
pressure in patients with echocardiography-
based tamponade were 70%, 60%, and 50%,
correspondingly. Puls paradox (> 10 mm
Hg drop in systolic blood pressure during
normal breathing) underscores the diagnosis
of cardiac tamponade, but it has a low
specificity. 2 In our study, most of the
patients were symptomatic and dyspnea was
the most common symptom (in 91.8%);
nevertheless, the prevalence of hypotension,
puls paradox, and elevated jugular venous
pressure was lower than that reported by
other studies.
Wang et al 8 showed sinus tachycardia in
72%, low voltage in 35% and electrical
alternans in 15.9% of their patients with
tamponade, which is similar to our common
ECG findings.
Transthoracic echocardiography is a reliable,
simple, and noninvasive method for the
diagnosis of tamponade. It diagnoses as
small as 20–50 mL of pericardial fluid.
Hamid et al 9 showed atrial collapse in all
their patients with large pericardial effusion
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and 50% of their patients with moderate
effusion presenting with tamponade. The
increased respiratory variation in the
tricuspid and mitral inflow velocities in
patients with pericardial effusion reveals
tamponade regardless of the amount of
effusion. 2 In our study, cardiac chambers
collapse, respiratory variation, and other
echocardiographic parameters were close to
similar studies, but the number of patients
with low left ventricular ejection fractions
was high because our hospital is the only
referral heart center in West Azerbaijan
province and most heart failure patients are
admitted to this center.
Ekim et al 10
showed left pleural effusion in
26.7% of their patients with purulent
pericarditis. We found radiographical
evidence of left pleural effusion in 38
(17.3%) patients. Considering the
association between left pleural effusion and
small amounts of pericardial effusion and
the possibility of the misdiagnosis of
pericardial effusion, we recommend more
attention in the echocardiographic
evaluation of these patients and re-
evaluation after left pleural effusion
drainage.
Multiple diseases such as malignancies,
uremia, hypothyroidism, infections, chest
trauma, collagen vascular disease, and
unknown causes may lead to pericardial
effusion and tamponade.
The most common malignant tumors
associated with tamponade are carcinoma of
the breast, melanoma, and lymphoma. 11
Jeon et al 6 reported lung cancer, followed
by breast cancer, in 65.5% and 10.9% of
their cases, respectively. A study reported
that 15%–20% of the autopsy specimens of
patients with malignancy exhibited
pericardial or cardiac metastasis. 12
We
detected malignancy etiologies in 20.5% of
all the cases, with the most common
malignant tumors being lung cancer,
hematological malignancy, gastrointestinal
cancer, and breast cancer, respectively. This
distribution of malignant tumors was also
reported in other studies. 1
The rate of pericardial effusion due to
benign diseases in our study was 79.5%,
which is higher than that reported by
previous studies. 1, 2
The prevalence of
patients with heart failure in our study was
high, so that the prevalence of patients with
left ventricular ejection fractions < 55% was
63.6%. Quraishi et al 2 showed normal left
ventricular function in 86.4% of their
patients.
We showed a history of pericardial effusion
drainage in 20 (9.1%) patients, which is
lower than the figure reported by Petcu et al 5 (32%–40% of the patients). A previous
study reported that the recurrence of
pericardial effusion after surgery in patients
with cancer-related pericardial effusion was
27.3%. 6 The reason for the low incidence of
recurrence in our study may be due to the
low prevalence of malignant causes.
Unlike developed countries, TB is the most
common cause of significant pericardial
effusion in developing countries. 13, 14
In our
study, TB was uncommon in that it was
responsible for 2.7% (6 patients) of all the
cases. In another study from Iran by
Mirhosseini et al, 1 the prevalence of TB in
symptomatic pericardial effusion was 6%–
8.6%. In the study by Quraishi et al 2 from
Pakistan, TB was detected in 27% of the
patients with massive pericardial effusion.
Cardiac tamponade is a rare manifestation of
hypothyroidism, 15
and its prevalence in our
patients was 2.3%. We had no traumatic
cases because our patients were treated in a
trauma referral center.
Treatment approaches for patients with
tamponade are different in many centers,
and there is controversy about the standard
procedure. The subxiphoid pericardial
drainage technique was first done by Larrey
in 1829. 17
The advantages of the subxiphoid
technique include simplicity and safety, 3
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inexpensiveness, 1 less postoperative pain,
and earlier postoperative extubation 7 and its
disadvantage is that it is associated with a
high recurrence rate in comparison with the
thoracotomy approach.7
The thoracotomy approach is more effective
at preventing effusion recurrence. 7
However, it is a more invasive operation that
is associated with greater potential for
morbidity, higher ventilation time, more
postoperative pain, 7 higher risk of sudden
hypotension during the induction of general
anesthesia, and difficulty in obese patients
and women with large breasts. 16
Pericardiocentesis is associated with
advantages inasmuch as it is less invasive
and it obviates the need for general
anesthesia; nonetheless, its disadvantages
include great risk of recurrence (as high as
60%) in comparison with window
operations, 6, 7
no direct visualization for
pericardial biopsy taking, 3 and active
bleeding after pericardiocentesis. 6 In our
center, in order to avoid cardiac penetrating
trauma and subsequent sternotomy and
exploration, we usually avoid
pericardiocentesis.
At our center, the subxiphoid technique is
the preferred option for the majority of
patients with tamponade. The recurrence
rate in our study was 9.1% (in 20 patients).
Celik et al 16
reported a recurrence rate of
2.08% for the left mini-thoracotomy
approach for tamponade. In all the recurrent
cases, we chose the subxiphoid technique for
the second drainage; however, for the third
drainage, we opted for the thoracotomy
approach. All 3 recurrent patients, who
underwent the left mini-thoracotomy
approach drainage, had malignancy.
Becit et al 18
reported a recurrence rate of
10% within 1 month following subxiphoid
surgical pericardiostomy in 368 patients.
Celik et al 16
reported that the nature of the
pericardial fluid was hemorrhagic in 37.5%,
serous in 60.4%, and purulent in 2.1% of
their patients, 16
which is similar to our
study.
Our surgical subxiphoid pericardiotomy was
done under local anesthesia in 16 (7.3%)
patients, which is less than the figure
reported by other studies. Celik et al 16
reported surgery under local anesthesia in
77% of their 57 patients. In order to avoid
severe hypotension and cardiac arrest in our
hypotensive patients, we performed the
surgical operations under local anesthesia.
Our postoperative complications were
reported in 2.8% of the cases. Jeon et al 6
reported operative morbidity in 12.7% of
their study patients, which included atrial
fibrillation, prolonged mechanical
ventilation, refractory hypotension,
constrictive pericarditis, and acute renal
failure.
In a study by Petcu et al, 5 hospital mortality
was reported in 13.04% of the patients in the
subxiphoid technique group and 20.37% in
the pericardiocentesis group. In another
study, the rate of hospital mortality in
patients treated with left mini-thoracotomy
was 8.33%. 16
In our study, there was no
surgery-related mortality and the hospital
mortality rate was 4.5%.
In most studies, the mean volume of the
drainage fluid was 600–800 cc. 1, 8
In
contrast to our results, Wagner et al 19
showed that the volume of the drained fluid
was one of the predictors of poor survival
after pericardial effusion drainage. Chiming
in with our results, Celik et al 16
showed that
there was no correlation between the
survival time and the amount of effusion
drained.
In our study, the mean survival rate of the
patients was not significantly different in
terms of demographic and clinical
characteristics such as age, sex, and
hypotension or echocardiographic
characteristics such as the ejection fraction,
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the fluid amount, and cardiac chamber
collapse. Pulse paradox affected the mean
survival rate of our patients (48.58 vs 34.10
mon) with unknown reasons. We found a
significant difference between the mean
survival rates of sanguineous (no
postoperative cases) and serous pericardial
effusions (20.5 vs 45 mon).
The underlying disease of patients with
tamponade is an established risk factor for
survival. 20
Patients with underlying
malignancy and malignant pericardial
effusion have poor survival in comparison
with patients with benign pericardial
effusion. 1, 16
Wagner et al, 19
in a review of
179 patients with pericardial window
surgery, reported poor overall survival for
the lung cancer group (median survival of 5
months). Nonetheless, in a study by Dosios
et al, 21
in contrast to our study, there was no
significant difference in the mean survival
rate between patients with positive and
negative cytological or histological results
for malignant invasion to the pericardium.
Whereas Wang et al 22
reported no
significant difference in the survival rates
between malignant and benign pericardial
effusion cases, we found a significant
difference between these groups in our
study. The etiology of tamponade and
cytological and pathological findings
significantly affected the mean survival rate
(15.5 vs 45 mon).
In a review of patients with cancer-related
pericardial effusion, the mean survival rate
was 4 months (range = 0–39 mon) and the 1-
year survival rate was 21.8%. 6 In another
study, the overall mean survival rate was
10.41 ± 1.79 months and the 1- and 2-year
survival rates were 45 ± 7% and 18 ± 5%,
respectively. 16
The mean survival time in
hematological malignancies was reported to
be 29.20 ± 7.59 months in a previous study. 21
In our study, the mean survival time in
malignant etiologies was 15.5 months. The
survival rates at 1 month (108/124), 1 year
(84/124), 2 years (80/124), and 3 years
(71/124) were 87.1%, 67.7%, 64.5%,
and57.2%, respectively.
CONCLUSIONS
The most common cause of tamponade in
our study was cardiac diseases (21%).
Malignancy etiologies were responsible for
20.5% of the cases. The most common
approach for pericardial effusion drainage
was the subxiphoid approach (> 97%),
which proved to be a safe and simple
procedure. In the current study, the rate of
intraoperative mortality was zero and the
rates of postoperative complications,
hospital mortality, and recurrence were
relatively low. Our results revealed an
association between left pleural effusion and
small amounts of pericardial effusion, which
underscores the significance of due attention
in the echocardiographic evaluation of these
patients. According to our results, patients
with primary sanguineous pericardial
effusion, malignant etiologies of tamponade,
and malignant pericardial effusion had
significantly poor survival.
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Lorell BH, Simons M. Pericardial effusion
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pericardial effusion. European Heart Journal
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Okay T , Tanrikulu N. Surgical properties
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CU, Koc¸ak H, Gu¨rlertop Y. Subxiphoid
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Left Atrial Function in Transfusion-Dependent Thalassemia Parsaee et al
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Original Article Left Atrial Function in Transfusion-Dependent Thalassemia Parsaee et al
Role of Left Atrial Structure and Function in the Early Prediction
of Cardiac Iron Overload in Transfusion-Dependent
β-Thalassemia Patients
Mozhgan Parsaee1, MD; Nakisa Khansari
*2, MD; Azita Azarkeivan
3, MD;
Mitra Chitsazan3, MD; Behshid Ghadrdoost
4, PhD; Hoda Mombeini
5, MD
ABSTRACT
Background: β-thalassemia is the most common monogenic disease caused by abnormalities in
the synthesis of the β-chain of hemoglobin.
Methods: From January 2018 to September 2018, 90 patients (age >18 y) with β-thalassemia
major or intermedia who referred to Rajaei Cardiovascular, Medical, and Research
Center, Tehran, Iran, for the assessment of myocardial iron overload were enrolled. All
the patients were receiving regular blood transfusions and chelating therapy.
Comprehensive transthoracic echocardiographic studies consisting of 2D
echocardiography, tissue Doppler imaging, and real-time 3D echocardiography were
performed.
Results: A total of 90 patients were enrolled in the study. Cardiac iron toxicity (ie, T2* < 20 ms)
was seen in 28 (31%) patients; whereas in 62 (69%) patients, the cardiac iron level was
undetectable (ie, T2* > 20 ms). Patients with T2* < 20 ms had significantly higher serum
ferritin levels than those with T2* > 20 ms (P = 0.02). No significant correlation was
found between the serum ferritin level and T2* (r = −0.08, P = 0.41). The left ventricular
ejection fraction was statistically similar in the 2D and 3D examinations. Left atrial end-
systolic and end-diastolic volumes were greater in the patients with iron cardiotoxicity
than in those with no detectable cardiac iron deposition (P = 0.01 and P <0.001,
respectively). Left atrial strain was also significantly lower in the patients with critical
iron overload. The patients with T2* < 20 ms also had lower left atrial ejection fractions
than those with T2* >20 ms, both in 2D and 3D examinations (both Ps <0.001).
Conclusions: Our study showed that changes in the left atrial structure and function precede
impairment in the left ventricular systolic function in thalassemia patients with critical
myocardial iron loading. (Iranian Heart Journal 2020; 21(1): 27-33)
KEYWORDS: Left atrium, Iron overload, -thalassemia
1 Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran. 2 Departement of Cardiology, Farshchian Heart Center, Hamadan University of Medical Sciences, Hamadan, IR Iran.
3 Department of Thalassemia Clinic, Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IR Iran. 4 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Department of Thalassemia Clinic, 5 Department of Cardiology, Khomeini Hospital, Jundishapour University of Medical Sciences, Ahvaz, IR Iran.
*Corresponding Author: Nakisa Khansary, MD; Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center,
Iran University of Medical Sciences, Tehran, IR Iran. Email: [email protected] Tel: 09188123413
Received: February 12, 2019 Accepted: April 15, 2019
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Left Atrial Function in Transfusion-Dependent Thalassemia Parsaee et al
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-thalassemia is the most common
monogenic disease caused by
abnormalities in the synthesis of the β-
chain of hemoglobin. 1, 2
Recent advances in
available therapies have improved long-term
prognosis in the affected individuals, with
approximately 80% of patients surviving
beyond 40 years. 3 Chronic hemolysis,
enhanced iron absorption by the intestine,
and frequent blood transfusions lead to iron
overload in these patients, ultimately
infiltrating various body organs including
the heart, liver, glands, and skin. 4, 5
Excessive cardiac iron accumulation results
in heart failure and cardiac arrhythmias,
which constitute the major etiologies of
death in patients with transfusion-dependent
thalassemia. 6-8
The gold standard technique to assess
cardiac iron deposition is cardiac magnetic
resonance imaging, 9 although its use is
limited by high costs involved and less
availability. Recently, echocardiographic
modalities including conventional 2D
echocardiography, Doppler
echocardiography, tissue Doppler
echocardiography, and 3D echocardiography
have provided promising results in the
diagnosis of iron overload in patients with
transfusion-dependent thalassemia.
Although most of these modalities have
assessed left ventricular diastolic and
systolic dysfunction as a surrogate marker of
cardiac involvement in thalassemia patients,
there is increasing evidence that ventricular
dysfunction occurs late in the disease course.
On the other hand, the data regarding the
predictive role of the assessment of the left
atrium in the early recognition of cardiac
iron toxicity are still scarce.
Accordingly, in the present study, we aimed
to investigate the association between the
left atrial structure and function and critical
cardiac iron deposition using conventional
2D echocardiography and real-time 3D
echocardiography in patients with β-
thalassemia receiving regular blood
transfusions.
METHODS
Study Population
From January 2018 to September 2018, 90
consecutive adult patients (age >18 y) with
β-thalassemia major or intermedia who were
referred to Rajaei Cardiovascular, Medical,
and Research Center, Tehran, Iran, for the
assessment of myocardial iron overload
were enrolled. All the patients were
receiving regular blood transfusions and
were on chelating therapy (deferoxamine
mesylate).
All the patients provided written informed
consent, and the Institutional Board Review
at Rajaei Cardiovascular, Medical, and
Research Center approved the study
protocol.
Echocardiographic Examination
Comprehensive transthoracic
echocardiographic studies comprised of 2D
echocardiography, tissue Doppler imaging,
and real-time 3D echocardiography were
performed in all the patients by a single
echocardiography specialist using a Philips
EPIQ 7 ultrasound system for cardiology
(Philips Ultrasound, Bothell, WA, USA)
equipped with xMATRIX ultrasound
transducer technology. All the
echocardiographic examinations were
performed in the left decubitus position and
at least 4 days after a recent blood
transfusion.
Magnetic Resonance Imaging
Cardiac magnetic resonance imaging (CMR)
scan was used to quantify myocardial tissue
iron loading by Heart T2* measurements.
All the scans were performed using a torso
β
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coil on a 1.5 T General Electric CVi scanner
via a single breath-hold multi-echo gradient
technique. As described by Anderson et al, 7
critical iron loading was defined as a T2*
value < 20 ms and values ≥ 20 ms were
considered to be uncritical (no detectable
cardiac iron).
Statistical Analysis
All the analyses were conducted using IBM
SPSS Statistics 22 for Windows (IBM Inc,
Armonk, NY, USA). The data were initially
assessed for normality using the
Kolmogorov–Smirnov test. The categorical
variables were presented as numbers and
percentages and were compared using
the χ2 test. The continuous variables were
presented as the mean ± the standard
deviation or the median and the interquartile
range (IQR) and analyzed using the Student
t-test, the Mann–Whitney test, and the
Kruskal–Wallis test, depending on the data
distribution. The relationships were assessed
using the Pearson correlation coefficient (r)
and the Spearman rank correlation
coefficient (ρ), as appropriate. All the P
values were 2-tailed and a P value < 0.05
was considered statistically significant.
RESULTS
A total of 90 patients, including 42 females
(46.6%), at a mean age of 29 ± 6 years were
enrolled in the study. The median serum
ferritin level was 693.50 μg/L (IQR, 309.00
to 1205.25) and mean cardiac T2* was 24.46
± 7.91 ms. Cardiac iron toxicity (ie, T2* <
20 ms) was seen in 28 (31%) patients;
whereas in 62 (69%) patients, the cardiac
iron level was undetectable (ie, T2* > 20
ms). The baseline characteristics of the
patients are summarized in Table 1.
Table 1. Baseline characteristics of the study population
Characteristic P value
Age 29±6
Gender male female
48 (53.4) 42 (46.6)
Dyspnea No Yes
52 (57.8)
NYHA Function Class I II III IV
31 (34.5) 7 (7. 4) 0 (0) 0 (0)
Electrocardiographic Findings Normal PAC PVC
75 (83.3) 14 (15.6) 1 (1.1)
Laboratory Measurements
Hemoglobin 10.4 (9.5-11.5)
Ferritin 693.5 (309-1205.25)
CMR data
T2* 24 918-30.25)
Data are presented as the mean ± the standard deviation or the median (interquartile ranges) and numbers (percentage). CMR, Cardiac magnetic resonance imaging; NYHA, New York Heart Association; PAC, Premature atrial contraction; PVC, Premature ventricular contraction
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The patients with T2* < 20 ms had
significantly higher serum ferritin levels
than those with T2* > 20 ms (1150 [340–
1750] vs 567 [300.75–886.50]; P = 0.02).
However, no significant correlation was
found between the serum ferritin level and
T2* (r = −0.08, P = 0.41).
The left ventricular ejection fraction was
statistically similar between the 2 study
groups, both in 2D and 3D examinations (P
= 0.29 and P = 0.20, respectively)
Left atrial end-systolic and end-diastolic
volumes were greater in the patients with
iron cardiotoxicity than in those with no
detectable cardiac iron deposition (P = 0.01
and P < 0.001, respectively). Left atrial
strain was also significantly lower in the
patients with critical iron overload than in
those without detectable cardiac iron
deposition (P = 0.001). The patients with
T2* < 20 ms also had lower left atrial
ejection fractions than those with T2*>20
ms, both in 2D and 3D examinations (both
Ps < 0.001). All the echocardiographic
variables are compared between the 2 study
groups in Table 2.
The correlations between serum ferritin,
cardiac T2*, and echocardiographic indices
are shown in Table 3.
Table 2. Echocardiographic indices in the patients with T2*< 20 ms and >20 ms
Variable T2*<20 ms (Critical Iron Overload)
(n=28)
T2*>20 ms (No Detectable Iron Overload)
(n=62)
P value
LVEF (2D) (%) 55 (50-55) 55 (53.75-55) 0.29
LVEF (3D) (%) 50.5 (44.25-60.25) 53 (50-60) 0.20
RVEF (3D) (%) 43.5 (38.5-48.75) 48.5 (43.25-52.75) 0.01
LAESV (mL) 42.5 (33.5-53.75) 33 (28-43.25) 0.01
LAEDV (mL) 30 (22-38) 18 (14-22.12) <0.001
LA Stroke volume (mL) 16 (12-22.5) 17.4 (14-23) 0.53
LA volume Normal Enlarged Mild Moderate Severe
10 (35.7) 11 (39.3) 3 (10.7) 4 (14.3)
48 (77.4) 11 (17.8) 2 (3.2) 1 (1.6)
0.001
LA strain 32 (25-38) 40 (33-44) 0.001
LAEF (2D) (%) 35.22±10.40 46.20±12.72 <0.001
LAEF (3D) (%) 35.89±12.25 45.40±13.48 0.002
SPAP (mm Hg) 35 (30-40) 30 (30-35) 0.11
RAEF (2D) (%) 29.88±10.71 40.57±10.92 <0.001
RAEF (3D) (%) 30±2.88 33.75±14.64 0.51
Data are presented as the mean ± the standard deviation or the median (interquartile ranges) and numbers (percentages). LA, Left atrial; LAEF, Left atrial ejection fraction; LAEDV, Left atrial end-diastolic volume; LAESV, Left atrial end-systolic volume; LVEF, Left ventricular ejection fraction; RAEF, Right atrial ejection fraction; RVEF, Right ventricular ejection fraction; SPAP, Systolic pulmonary artery pressure
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Table 3. Correlations between echocardiography-
derived indices and serum ferritin levels and cardiac T2*
ENB’ Serum Ferritin
T2* ms
LVEF (2D) R 0.04 0.19
P 0.66 0.06
LVEF3D R 0.25 0.22
P 0.01 0.03
RV3DEF R 0.20 0.20
P 0.05 0.05
LAESV R 0.18 -0.34
P 0.07 0.001
LAEDV R 0.12 -0.44
P .23 <0.001
SV R 0.03 -0.03
P 0.74 0.77
LA strain R -0.07 0.40
P 0.51 <0.001
LAEF2D R -0.02 0.36
P 0.79 .001
LAEF3D R -0.01 0.33
P 0.91 0.001
SPAP R 0.08 -0.19
P 0.40 0.06
RA_EF2D R 0.07 0.48
P 0.48 <0.001
RAEF3D R 0.62 0.69
P 0.05 0.02
LA, Left atrial; LAEF, Left atrial ejection fraction; LAEDV, Left atrial end-diastolic volume; LAESV, Left atrial end-systolic volume; LVEF, Left ventricular ejection fraction; RAEF, Right atrial ejection fraction; RVEF, Right ventricular ejection fraction; SPAP, Systolic pulmonary artery pressure
DISCUSSION
Iron toxicity greatly affects the long-term
prognosis in patients with β-thalassemia and
is a major cause of morbidity and mortality
in these patients. 3, 6-8
CMR is considered the
gold standard method in the early
recognition of iron deposition in the
myocardium. However, its use is limited due
to high cost and less availability, particularly
in developing countries. As a result,
echocardiography has been introduced as a
less expensive, widely available, and
reproducible method for this purpose,
although its sensitivity and specificity in
assessing cardiac iron accumulation are
limited.
Assessments of the left ventricular function
(ie, the ejection fraction) have been drawn
upon as a marker of iron toxicity, even
though an iron deposition level sufficient
enough to affect the left ventricular function
occurs late in the disease course. Moreover,
high cardiac output due to chronic anemia
masks proper detection of ventricular
dysfunction. As a result, other
echocardiographic indices have been
investigated for the early recognition of iron
accumulation in susceptible patients. A
study by Rodrigues et al 11
showed that the
left atrial volume index, the mitral septal
E/Em ratio, the duration of reverse
pulmonary vein flow, and the mitral E/A
ratio were higher in patients with
asymptomatic thalassemia major than in
healthy individuals and patients with iron
deficiency anemia. However, they found no
significant differences in the left ventricular
structures and systolic function indices
among their 3 study groups. In contrast to
our study, Rodrigues and colleagues did not
evaluate cardiac iron accumulation CMR.
In the present study, to determine the
predictive role of the left atrial structure and
function in the early recognition of cardiac
iron overload in patients with thalassemia,
we employed conventional 2D
echocardiography and real-time 3D
echocardiography with a view to comparing
relevant indices in patients suffering from
thalassemia with and without critical iron
deposition. All the patients were on chronic
blood transfusion and were receiving iron
chelation therapy (deferoxamine mesylate).
Of note, all the participants had preserved
left ventricular functions (ie, ejection
fraction > 40%) and normal left and right
ventricular sizes.
We found that the patients with and without
critical myocardial iron deposition had
statistically comparable left ventricular
ejection fractions, reinforcing the limited
role of the left ventricular function in the
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early identification of myocardial iron
loading, as previously described.
Cardiac involvement in infiltrating diseases
primarily begins with diastolic dysfunction,
causing gradual dilatation in atrial size and
impairment in atrial contraction. 12-15
The
progression of cardiac infiltration would
eventually lead to the deterioration of the
ventricular systolic function. Thus, changes
in the left atrial structure and function might
precede the development of overt pump
failure. In accordance with this hypothesis,
our results demonstrated that patients with
iron cardiotoxicity had significantly lower
left atrial ejection fractions than those
without critical iron deposition, highlighting
the predictive role of the left atrial function
in the early prediction of iron toxicity in
patients with thalassemia receiving chronic
blood transfusions. In a case-control study,
Aggeli et al 16
compared the left atrial
performance in 28 patients with
asymptomatic β-thalassemia who were on
chelating therapy with 20 age- and sex-
matched healthy controls using transthoracic
real-time 3D echo. The thalassemia group
had normal echocardiographic systolic and
diastolic functions; however, unlike the
patients in our study, there was no
myocardial iron disposition according to
MRI. They found that the left atrial active
emptying fraction was reduced in the
thalassemia group compared with the
healthy controls.
We also found a significant correlation
between T2* and the left atrial ejection
fraction (both in 2D and 3D
echocardiography, r = 0. 36, P < 0.001 and r
= 0.33, P < 0.001; respectively). Moreover,
our results showed that the patients with
critical iron loading had higher left atrial
volumes (end-systolic and end-diastolic
volumes) and lower left atrial strain than
those with non-critical iron loading.
However, in the study by Aggeli et al, 16
no
significant differences were seen in the left
atrial volumes (the left atrial maximum
volume at end-systole, the left atrial volume
just before the mitral valve opening, and the
left atrial volume before atrial active
contraction) between patients with
thalassemia and healthy individuals. It
should be noted, however, that the patients
with thalassemia in the aforementioned
study did have cardiac iron deposition,
which might explain discrepancies seen in
their results with our study.
CONCLUSIONS
In conclusion, our study showed that
changes in the left atrial structure and
function precede impairment in the left
ventricular systolic function in patients
suffering from thalassemia with critical
myocardial iron loading. Larger left atrial
systolic and diastolic volumes and poorer
left atrial performance in these patients
might be used as echocardiographic markers
for the early identification of iron
deposition, which, in turn, could affect
management strategies such as the
employment of more aggressive chelating
therapies.
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1. Engle MA, Erlandson M, Smith CH. Late
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2. Olivieri NF. The beta-thalassemias. N Engl J
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3. Borgna-Pignatti C, Rugolotto S, De Stefano
P, et al. Survival and complications in
patients with thalassemia major treated with
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Haematologica 2004;89: 1187–1193.
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4. Weatherall DJ, Clegg JB. Thalassemia a
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5. Westwood MA, Firmin DN, Gildo M, Renzo
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6. Modell B, Khan M, Darlison M. Survival in
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7. Hahalis G, Alexopoulos D, Kremastinos
DT, Zoumbos NC. Heart failure in β-
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V. Cardiac failure in β-thalassemia:
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management. Thalassemia
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MRI. Hematology Am Soc Hematol Educ
Program Book 2011 ;2011(1):443-450.
10. Anderson LJ, Holden S, Davis B, Prescott E,
Charrier CC, Bunce NH, Firmin DN, Wonke
B, Porter J, Walker JM, Pennell DJ:
Cardiovascular T2 star (T2*) magnetic
resonance for the early diagnosis of
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22:2171-2179.
11. Rodrigues A, Guimarães-Filho FV, Braga
JC, Rodrigues CS, Waib P, Fabron-Junior
A, Tan DM, França AC, Okoshi MP, Okoshi
K. Echocardiography in thalassemic patients
on blood transfusions and chelation without
heart failure. Arq Bras
Cardiol. 2013;100(1):75-81.
12. Arbab-Zadeh A, Dijk E, Prasad A, Fu Q,
Torres P, Zhang R, et al. Effect of aging and
physical activity on left ventricular
compliance. Circulation 2004;110:1799–
805.
13. Sievers B, Kirchberg S, Addo M, Bakan A,
Brandts B, Trappe HJ. Assessment of left
atrial volumes in sinus rhythm and atrial
fibrillation using the biplane area-length
method and cardiovascular magnetic
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Cardiovasc Magn Reson 2004;6:855–63.
14. Kremastinos DT, Tsiapras DP, Tsetsos GA,
Rentoukas EI, Vretou HP, Toutouzas PK.
Left ventricular diastolic Doppler
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15. Westwood MA, Wonke B, Maceira AM,
Prescott E, Walker JM, Porter JB, et al. Left
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16. Aggeli A, Felekos I, Poulidakis E, Aggelis
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Original Article Hospital at Home Khaleghparast et al
Hospital Facilities at Home for Heart Failure Patients
Shiva Khaleghparast, PhD1; Alireza Maleki, MD
2*; Sepideh Taghavi, MD
1;
Ahmad Amin, MD1; Majid Maleki, MD
3; Mehrdad Oveisi, PhD
1;
Behrooz Ghanbari, PhD4; Zahra Hanifi, BS
1; Nasim Naderi, MD
1
ABSTRACT
Background: Heart failure is a complex syndrome and also one of the common reasons for
readmission following discharge. This condition imposes an enormous economic burden
on healthcare sectors. The present research aimed to study the establishment of a home
care system for patients with heart failure in order to evaluate the cost-effectiveness of
this system and patient satisfaction.
Methods: The present health system research selected 40 patients as the sample with eligible
criteria. Care was provided by nurses based on physicians’ instructions. In the first visit at
home, a questionnaire on the quality of life was filled out by the patients or the nurses.
The financial data of the medical records of the patients constituted the reference for the
analysis of cost. After the intervention, the questionnaire on the quality of life was filled
out by the patients once again and their satisfaction was measured. The data were
statistically analyzed using the Python programming language and SPSS-16 at the 0.05
level of significance.
Results: The length of stay in the hospital for each patient decreased from 2.1 days to 0.9 days
per month. The number of annual hospitalizations also decreased from 5 to 3, and the
number of annual outpatient visits showed a reduction from 46 to 38 for each patient. The
results of the patient satisfaction assessment also indicated that most of the patients were
satisfied with the services provided to them.
Conclusions: The results showed that our study was cost-effective. We suggest that
interventions be performed on larger scales so that the results can be used in the future as
services available to patients with heart failure. (Iranian Heart Journal 2020; 21(1): 34-44)
KEYWORDS: Home care, Heart failure, Hospital facilities
1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
2 Department of Anesthesiology, Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran.
3 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,
Tehran, IR Iran. 4 Gastrointestinal and Liver Disease Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
*Corresponding Author: Alireza Maleki, MD; Hazrat Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, IR Iran. Email: [email protected] Tel: 02123922192
Received: February 12, 2019 Accepted: April 26, 2019
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eart failure (HF) is a complex,
chronic, and debilitating clinical
syndrome and also one of the
common reasons for readmission following
discharge.1-5
This condition not only
increases complications and mortality while
reducing the quality of life in the process 6
but also imposes an enormous economic
burden on the healthcare sector. The
insufficient attention of patients to the
recommendations made by the treatment
team is a contributing factor for a 50% rate
of readmission in patients with HF. 7, 8
The
statistics show that approximately 5.1 to 5.8
million individuals in the United States and
26 million worldwide suffer from HF,
accounting for 1%–3% of the general
population. 9
In Iran, 3.3% of adults are
afflicted with HF. 10
The prevalence of HF
increases with age, reaching 8.4% and
17.4% among people aged 75 and 85 years,
respectively. This disease is the most
common reason for hospitalization of
individuals aged over 65 years in the United
States and Europe. In addition, it is the cause
of 18%–27% of readmissions within the first
month and 50% of readmissions during the
first 6 months following discharge. 9
Although the mortality rate of this disease
has decreased overall, its 5-year mortality
rate is still equal to that of most cancers, 11
accounting for its description as a
malignancy and its very difficult prognosis.
The signs and symptoms increase as the
disease progresses, and patients exhibit
symptoms such as pain, dyspnea, and
fatigue. Moreover, this disease negatively
affects the quality of life and the
psychosocial status of patients. 2 The high
complications and mortality of this disease
can lead to an increase in treatment costs.
Approximately 1%–2% of national health
costs in the United States and Britain are
spent on patients with HF, 80% of which is
related to hospitalization costs. 9
These
patients do not adhere to their medical
treatment plan according to the guidelines.
Therefore, they need a complex and
multidisciplinary care program. Without
periodic interventions and follow-ups, they
will need emergency hospitalization or
readmission. This indicates the importance
of continuous care and the expansion of
professional services at home. Home care,
remote monitoring, outpatient clinics,
communications, and follow-ups by
professional team members can increase the
safety, satisfaction, and quality of life of
these patients after discharge. 1-3, 12, 13
Quality of life, as a quality index for health
systems, decreases in chronic patients after
discharge. 14
Hence, these patients need an
emotional system that not only saves
medical costs but also improves their
clinical outcomes and quality of life. 2, 15, 16
Recent studies have shown that home care
interventions reduce mortality up to 34%
and readmission by 30%–56% in patients
with HF. 8
However, there are still doubts
with regard to the cost-effectiveness of this
system 15
and there is a need for the
development of evidence to back this
approach. 2
To the best of our knowledge, no
study has been conducted in Iran about the
establishment of this system for patients
with HF. Hence, the present research aimed
to study the establishment of a home care
system for patients with advanced HF
referred to the Heart Failure Department of
Rajaie Cardiovascular, Medical, and
Research Center (RCMRC), tertiary center
for HF programs in Iran, in order to evaluate
the cost-effectiveness of this system and
patient satisfaction.
METHODS
Design
The present research was aimed at studying
satisfaction with regard to the cost-
effectiveness of a health system. To begin, a
home care center was established for
patients with HF at RCMRC. Manpower,
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equipment, and appropriate physical space
were provided in accordance with the
instructions set out by Iran’s Ministry of
Health and Medical Education (139/d/672-
2016 July 25).
Data Collection
The statistical population comprised all
patients with HF hospitalized at RCMRC
from August 2017 to March 2018. Based on
the convenience sampling method, 40
patients were selected as the sample group
consecutively. The inclusion criteria were
those with advanced HF 17
aged over 18,
residing in Tehran, an ejection fracture <
30%, a history of frequent hospitalization, at
least on rehospitalization within 6 months,
no history of surgery in the last 2 months,
and willingness to obtain home care
services. Patients with severe cognitive
impairment or those who needed dialysis
during the intervention were excluded from
the study.
Ethical Considerations
First, a workshop consisting of a briefing
session was scheduled for the staff where
they were provided with necessary
explanations on communication with
patients/families; professional code of
conducts and dress codes; ethical principles;
and principles of HF management including
guideline-directed medical therapies, self-
care measures, and HF nursing roles and
strategies. The study protocol was approved
by the ethics committee of RCMRC
(IR.RHC.REC.1397.001).
Investigation
When patients with advanced HF were being
discharged, their medical records were
reviewed by an HF specialist for the
eligibility of enrollment. Finally, 40 patients
were enrolled in this study. An informed
consent form was obtained, and the patients’
basic information was recorded. Care was
provided by a nurse holding at minimum a
bachelor’s degree and based on the
instructions made by the physician. In the
first visit at home, a questionnaire on the
quality of life was filled out by the patients
themselves or with help from the nurses.
The care provided at home included control
of vital signs; physical examination; diet and
medication training; weight control;
absorption and excretion control through
training and documentation; the
administration of necessary medications
such as diuretics; and blood sampling for
blood chemistry, electrolytes, and
coagulation status based on the patients’
condition and physician’s preference. Self-
care was taught to the patients and
monitored. In addition, phone follow-ups
involved answering the patients’ questions,
clearing any ambiguities, and emphasizing
compliance with the instructions.
The financial data of the medical records of
the patients constituted the reference for the
analysis of hospitalization and outpatient
service cost. The visitation costs consisted of
staff costs, supplies and equipment, and
personnel transfer and phone follow-up costs
included the cost of phone calls and the
wage of experts calling the patients.
Patients’ quality of life was the criteria for
measuring the effectiveness of the study.
Moreover, the number of readmissions, the
length of stay at the hospital, man-hour (the
amount of work performed by the average
worker in 1 hour), and patient satisfaction
with both the system and the provided care
were also determined.
Analysis
Cost-effectiveness analysis was performed
in 3 stages. In the first stage, all costs
consisting of nursing care, telephone follow-
ups, referrals to the clinic, hospital
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admissions, laboratory and pharmaceutical
services, and personnel costs during the 6
months before and after the implementation
of the study were calculated and compared
with each other. In the second stage, the
number of readmissions, the length of stay at
the hospital, and the patients’ quality of life
were compared before and after the
intervention. The required data were
collected using a 3-part questionnaire,
consisting of the personal information of the
patients (14 items), disease-related factors
(15 items), and quality of life 18
(13 items:
physical dimension, 14 items: psychological
dimension, 9 items: socioeconomic
dimension, and 4 items: general health
dimension). The items were scored based on
a 5-point Likert scale from “very much” 5 to
“not at all”. 1 Higher scores indicate a higher
quality of life. The minimum and maximum
scores on this questionnaire were 40 and
200, respectively. The quality of life scores
of 200 and 40 were determined as the
highest level of effectiveness (with a mean
of 5) and a lack of effectiveness (a mean of
1), respectively. This questionnaire was used
by Rezaei in 2006, and its validity has been
confirmed by experts. In addition, the
reliability of this questionnaire has been
reported to be 91%. 18
In the third stage, a
cost-effectiveness analysis was done in 3
steps consisting of the comparison of cost-
effectiveness before and after the
intervention, the determination of the
incremental cost-effectiveness ratio (ICER),
and a sensitivity analysis. The sensitivity
analysis itself was performed in 3 stages as
follows: the identification of non-
deterministic parameters, including the cost
of treatment and patient recovery; the
determination of the acceptable range for
changing the non-deterministic parameters
by making a change of 5% in treatment
costs; and the calculation for the ratio of
incremental cost-effectiveness using new
values of the parameters.
The quality of life questionnaire was refilled
out by all the study population after
completing the home care course, and their
satisfaction was measured. The satisfaction
form measured the patients’ satisfaction in 4
areas of admission, physician, nurse, and
equipment and facilities based on a 3-point
Likert scale from “Yes” (2) to “No” (0). The
data were statistically analyzed using the
Python programming language and SPSS-16
at the 0.05 level of significance.
RESULTS
Out of 40 patients participating in the study,
21 (52%) patients were male and the
educational attainment of half of these
individuals was at an elementary school
level. The demographic information of the
participants is shown in Table 1. Since the
patients were added to the home care project
on different days, the mean and standard
deviation of the number of study days before
and after the implementation of the plan was
96.25 ± 35.80 and 97.75 ± 35.80,
respectively.
During the implementation of this plan, a
total of 138 home visits and 473 phone
consultation sessions were provided to the
patients. The total number of patients’
referrals for admission before and after the
implementation of the study was 54 and 34,
respectively. Table 2 shows all the treatment
costs by services before and after the
implementation of the home care (for 40
patients for 6 months).
The results of the cost analysis also
indicated that the mean total finished cost
per patient was reduced by 50% after the
study. In addition, the total monthly cost
paid by the patients showed a reduction of
about 61%. The finished cost for the
implementation of home care in our study
was considered by adjusting the number of
service providers from 2 to 1 while
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considering one-tenth of the equipment cost
as wear and tear.
Figure 1 shows the finished costs for each
patient per month in payment systems.
Table 1. Demographic characteristics of the patients participating in the study
Frequency Percentage
Sex Male 21 52.5
Female 19 47.5
Age >=51 36 90
41-50 2 5
31-40 2 5
Marital status
Married 29 72.5
Single 11 27.5
Education Elementary 20 50
Diploma 10 25
High school 7 17.5
Bachelor’s degree 2 5
Postgraduate 1 2.5
Jobs Housewife 14 35
Retired 9 22.5
Unemployed 9 22.5
Worker 5 12.5
Freelance 2 5
Employee 1 2.5
Table 2. Treatment costs by services before and after the implementation of the home care
Type Inpatient Outpatient Visits Calls Total
Stage
Pt_Fee Before 15,411 7,717 0 0 23,127
After 3,055 5,914 0 0 8,969
Ins_Fee Before 203,997 13,675 0 0 217,672
After 78,040 10,006 0 0 88,047
Other_Fee Before 20,506 3,092 0 0 23,598
After 19,930 2,426 0 0 22,356
Home care_Fee Before 0 0 0 0 0
After 0 0 11,532 2,659 14,192
Total
Before 239,913 24,484 0 0 264,398
After 101,026 18,346 11,532 2,659 133,563
All 340,939 42,830 11,532 2,659 397,961
*All fees are in 10,000 Rials.
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Figure 1. Finished costs for each patient per month in payment systems
* All fees are in 10,000 Rials.
By adding the cost spent on the
implementation of the home care to the costs
paid by insurance companies, we observed a
32% reduction in the insurance costs. In
addition, reducing the number of service
providers and equipment led to a 54%
reduction in costs (Fig. 2).
Figure 2. Comparison of the finished cost of insurance companies
before and after the implementation of the study
The mean quality of life score among the
studied patients before and after the
implementation of the home care was 2.4 ±
0.39 and 2.9 ± 0.39, respectively.
Accordingly, there was a significant
difference between the quality of life before
and after the intervention (P < 0.001) (Table
3).
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Table 3. Comparison of the mean quality of life before and after the home care intervention
Index Variable
Mean
Standard deviation
Paired
t-statistic
Degree of freedom
Probability
value
95% confidence interval
Lower limit
Upper limit
Quality of life
Before the intervention
2.4 0.39
-17.44
62
<0.001
-0.52
-0.41 After the intervention
2.9 0.39
Based on the study results, the length of stay
at the hospital for each patient decreased
from 2.1 days to 0.9 days per month. The
number of annual hospitalization also
decreased from 5 to 3, and the number of
annual outpatient visits showed a reduction
from 46 to 38 for each patient. The results of
the patient satisfaction assessment also
indicated that 94% of the patients were
satisfied with the services provided. Figure 3
shows the outcomes of the home care
intervention.
Considering the cost-effectiveness ratio data,
the cost for each unit of increase in the
quality of life score after the intervention
was less than that before the intervention.
Given that medical prices varied during the
6 months before and after the intervention,
the incremental cost-effectiveness ratio
determined a total reduction in medical costs
with 1 unit of increase in the mean quality of
life after the home care intervention.
After the completion of the sensitivity
analysis with a 5% change in medical costs
and the recalculation of incremental cost-
effectiveness, this ratio was not significantly
different from the main findings without any
change in medical costs. Therefore, it can be
stated that the study findings are of
acceptable strength. In addition, the man-
hour for physician and nurse was equal to
half an hour and 4 hours for each patient
during a day, respectively.
Figure 3. Outcomes of the home care intervention
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DISCUSSION
The study results showed that the home care
intervention significantly reduced the mean
monthly cost of home care for each patient.
In addition, the length of stay at the hospital
and the annual number of admissions
showed a reduction after the intervention.
The results also indicated that the quality of
life significantly increased after the home
care intervention and the patients were
greatly satisfied with the services provided
to them.
In a study conducted by Maru et al 1
(2015),
home care intervention led to a higher
quality of life and lower medical costs for
patients with chronic HF in a 3.2-year
follow-up period. They also illustrated that
home care interventions significantly
reduced the length of stay at the hospital.
Finally, their findings suggested that home
care interventions were more cost-effective
than hospital interventions for old patients
with HF.
Alina et al 2 (2018) reported a significant
difference in the mean score of quality of
life between 2 groups of patients with HF
who received home care intervention and
conventional treatment. However, they
observed no significant difference between
the 2 groups in terms of distress symptoms
or performance status during a 12-week
follow-up period. Patient satisfaction was
higher and the working pressure of nurses
was lower in the intervention. In addition,
the home care intervention reduced some of
the disease symptoms.
Cowie et al 3 (2010) reported a study
conducted by Tibaldi in Italy, in which 2
interventions consisting of home care
without a cardiologist and hospital
intervention (physicians and nurses) were
compared with each other. The home care
and hospital interventions lasted 21 and 12
days, respectively. The home care services
included the establishment of the venous
route, blood pressure check, and the
administration of intravenous drugs. In the
present study, the home care services also
consisted of vital signs control, training, and
intravenous injections of necessary drugs.
The readmission rate was reported the same
in both groups by Cowie and colleagues,
while the readmission rate showed a
reduction after the home care intervention in
the present study. This difference may be
due to the shorter duration and lower
number of visits at home in the study by
Cowie and coworkers. By contrast, the cost
of home care was lower than hospitalization,
which is consistent with the findings of the
present study. It is noteworthy that part of
the home care intervention in the present
study was related to training and telephone
follow-ups.
Hugylund et al 8 (2015) emphasized the
significance of training patients with HF and
its impact on the improvement of their
quality of life. Additionally, training reduced
the hospitalization days of the patients, 19-21
which is consistent with the findings of the
present study. Baglimeyhem et al 10
(2013)
showed that training was effective in
promoting the health behavior of their
patients with HF. In this regard, Chen et al 15
(2010) stated that telephone counseling by
trained nurses significantly reduced the
hospitalization rate (all-cause admission). In
addition, it reduced the hospitalization days
by 8 days and the 6-month medical expenses
by 2682 dollars for each patient.
In the present study, the quality of life score
presented a significant increase after the
home care intervention. This is consistent
with the results of many previous studies. 1,
8, 16 The reduced length of stay and
readmission rate after the home care
intervention in the present study are also
consistent with many previous studies. 3, 7-9,
12, 15, 22
Overall, the study findings indicated the
cost-effectiveness of home care intervention
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for patients with HF. Ottawa 23
(2015)
reported that the use of telehealth services
such as telephone support or telemonitoring
reduced the rate of hospitalization and
mortality and improved the quality of life
and lifestyle of patients. Telemonitoring
reduces hospitalization and death due to HF
and all other causes. However, the use of
telemonitoring in the hospitals of the
Netherlands made no significant difference
in the annual medical costs of patients Cost-
effectiveness indicated the high level of
uncertainty in decision-making. Another
study conducted in the Netherlands also
showed that telemonitoring failed to cause a
significant difference in patients’ quality of
life and their annual costs. The results of a
study conducted in Canada in 2013 showed
no significant difference between 3 groups
of conventional care, telephone intervention,
and telemonitoring intervention in terms of
medical costs. 13
Kendall Ho 12
(2016) showed that the
telemonitoring of patients with HF at home
was a cost-effective strategy to reduce the
rate of revisits and readmissions and it was
able to improve their comfort and quality of
life in a 90-day period. This difference can
be due to the non-provision of home care
services by expert personnel and the mere
provision of telemonitoring and telephone
follow-ups for patients in previous studies.
CONCLUSIONS
In summary, the present study suggested the
cost-effectiveness of the home care
intervention for patients with HF. Sahlen et
al 11
(2016) also indicated that home care
was a cost-effective strategy for patients
insofar as it saved resources. Reduced
medical costs through home visitations have
been also reported in many other studies. 2, 3,
7, 9, 11, 12, 15, 24
Undoubtedly, modern home care systems for
patients with HF require multidisciplinary
services so that patients and their families
can have access to various specialties at the
required time. Many patients may need to be
hospitalized for these reasons, but many of
these cases can be potentially prevented
through the proper management of chronic
diseases, effective communication, and the
correct monitoring of conditions by patients
and medical teams. If such an intervention is
performed on larger scales, the results can
be used in the future as services available to
patients suffering from HF.
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N-terminal Prohormone of Brain Natriuretic Peptide in Patients With Pulmonary Thromboembolism Baradaran et al
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Original Article N-terminal Prohormone of Brain Natriuretic Peptide in Patients With Pulmonary Thromboembolism Baradaran et al Predictive Power of N-terminal Prohormone of Brain Natriuretic
Peptide on Admission and on Discharge for Short- and Long-term
Clinical and Echocardiographic Outcomes in Patients With
Pulmonary Thromboembolism
Abdolvahhab Baradaran 1, MD; Davood Kazemi Saleh
*1, MD; Yaser Jenab
2, MD;
Susan Hashemi 2, MD; Arash Jalali
3, PhD; Elham Feizabad
3, MD
ABSTRACT
Background: This prospective case-series study was conducted to determine the predictive
power of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on short-
and long-term outcomes in patients with pulmonary thromboembolism (PTE).
Methods: Ninety-two patients (age = 60 ± 1.97 y, 54.7% male) diagnosed with PTE were
recruited. NT-proBNP levels and echocardiographic indices were measured and recorded.
The primary endpoint was considered to be 3-month PTE-related deaths and long-term
adverse outcomes including 1-year all-cause mortality, rehospitalization due to the
recurrence of PTE, right ventricular dysfunction, and pulmonary hypertension.
Results: The serum NT-proBNP level and the right ventricular diameter were significantly
higher in the patients with adverse outcomes than in the outcome-free patients. Several
significant correlations were found between NT-proBNP levels and echocardiographic
indices. During a mean follow-up time of 12 months, 1 patient suffered PTE relapse, 15
patients had right ventricular dysfunction and pulmonary hypertension, and 2 patients
expired. Age was an independent value in the prediction of the adverse outcome (OR:
1.064, 95% CI: 1.01 to 1.11). Discharge NT-proBNP levels, calculated according to a
multiple cutoff point strategy for heart failure, in the PTE patients with adverse outcomes
was 2.36 fold that in the outcome-free patients. The optimal value for discharge NT-
proBNP according to the receiver operating characteristic analysis was 327 pg/mL, with a
sensitivity of 80% and a specificity of 43%.
Conclusions: NT-proBNP measurement during the course of PTE, especially on discharge, may
have a role as an easy-to-use diagnostic tool for determining patients with poor
prognoses. (Iranian Heart Journal 2020; 21(1): 45-54)
KEYWORDS: N-terminal prohormone, Brain natriuretic peptide, Biomarkers, Pulmonary embolism
1 Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. 2 Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IR Iran..
3 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, IR Iran.
*Corresponding Author: Davud Kazemi Saleh, Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Mollasadra St,
Vanak Sq, Tehran, IR Iran.. Zip code: 1435915371 Email: [email protected] Tel: 09121191169
Received: April 7, 2019 Accepted: July 10, 2019
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ulmonary thromboembolism (PTE) is
a potentially fatal disorder, and its
severity ranges from asymptomatic to
multi-organ manifestations. 1-3
Hence, rapid
and accurate diagnosis of patients,
particularly to distinguish high-risk patients
from low-risk ones, presents a challenge to
emergency physicians. The most notable
prognostic modalities currently available are
imaging tools such as echocardiography and
computed tomography angiography (CTA)
and serum biomarkers such as troponins,
plasma leptin concentrations, and heart-type
fatty acid-binding proteins. 4-8
N-terminal prohormone of brain natriuretic
peptide (NT-proBNP) has been proposed as
an additional tool for risk stratification. 9
NT-proBNP, released from myocytes in the
ventricles of the heart, is frequently used in
the diagnosis of congestive heart failure and
in distinguishing between patients with
dyspnea of cardiac or pulmonary origin. It
has also been evaluated for the assessment
and management of several other diseases
such as sepsis, cirrhosis of the liver, and
renal failure. 10
Elevated NT-proBNP levels can identify
patients with acute PTE at high risk of short-
term death and adverse outcome events.
Although evidence has shown that the NT-
proBNP measurement in the primary phase
has excellent power to predict the 30-day
(short) outcome like pulmonary
hypertension and right ventricular
dysfunction in patients with PTE, 11 12
it has
a low positive predictive value; accordingly,
serial measurements in the hospital
admission phase appear to be helpful. 13
Currently, there is a paucity of data on the
sequential measurement of NT-proBNP
from admission to discharge and there are no
known predictive models capable of
forecasting poor long-term outcomes in
patients suffering from PTE. 14
We,
therefore, sought to determine the predictive
power of the sequential measurement of NT-
proBNP on admission and on discharge for
short- and long-term clinical and echo-
cardiographic outcomes in patients with
PTE.
METHODS
This prospective case-series study was
conducted on 92 consecutive patients with a
diagnosis of acute PTE registered in the
Pulmonary Embolism Database of Tehran
Heart Center, affiliated with Tehran
University of Medical Sciences, Tehran,
Iran, between 2013 and 2016. The
definitions of the diagnosis and management
of PTE in our center have been published
previously. 15
The exclusion criteria were comprised of a
history of previous PTE, PTE occurrence
during patient admission due to another
medical condition, and death during the first
hospitalization due to PTE. Also excluded
were patients with hemodynamic instability
at presentation and delayed pulmonary
computed tomography angiography (CTA)
(48 hours after diagnosis).
In all the patients, PTE was defined as the
illustration of partial or complete filling
defects in the pulmonary circulation by
pulmonary spiral CTA scan. According to
pulmonary spiral CTA scans, PTE was
classified as saddle PTE (if the thrombus
was lodged at the level of the bifurcation of
the pulmonary trunk and extended into both
main pulmonary arteries), central PTE (if the
thrombus involved the main branches
through the segmental branches), and
peripheral PTE (if the thrombus involved the
segmental and sub-segmental branches).
Doppler and 2D echocardiographic
examinations were conducted by
experienced operators within 48 hours of
admission, on discharge, and in each follow-
up visit. All the quantifications were
performed in accordance with the
P
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recommendations of the American Society
of Echocardiography Committee. Right
ventricular dysfunction was defined as a
right ventricular diameter > 34 mm or a
right-to-left ventricular ratio > 0.9, or the
presence of wall motion abnormalities in the
right ventricular free wall. Right ventricular
systolic dysfunction was defined as a
tricuspid annular plane systolic excursion
< 16 mm or a pulsed Doppler peak velocity
at the tricuspid annulus < 10 cm/s.
All the patients were cured in the acute
phase with conventional therapeutic doses of
unfractionated or low molecular-weight
heparin. Thrombolytic therapy was used at
the discretion of the treating cardiologist.
The patients were discharged with warfarin
and control of their international normalized
ratio. Complete data on the study
population’s baseline demographic
characteristics as well as clinical, laboratory,
and imaging findings were acquired through
face-to-face interviews and medical files.
Upon admission, the levels of systolic blood
pressure, heart rate, respiratory rate, O2
saturation, and high-sensitivity cardiac
troponin T (hs-cTnT) were measured.
Hemodynamic instability was defined as the
presence of the following in the patients
upon admission: need for cardiopulmonary
resuscitation, systolic blood pressure < 90
mm Hg or a drop in systolic blood pressure
> 40 mm Hg for 15 minutes with signs of
end-organ hypoperfusion or need for
catecholamine prescription to protect
adequate organ perfusion, and systolic blood
pressure < 90 mm Hg.
Within 48 hours of PTE diagnosis and on
discharge, blood samples (2 cc) were taken
from the patients. The samples were
centrifuged at 5 °C at 3000 rpm for 10
minutes. The separated serum was thereafter
stored at −20 °C until the NT-proBNP
measurement. The levels of NT-proBNP
were determined using an ELISA kit (USA).
After discharge, the patients were contacted
and asked to refer to our center for follow-
up evaluations based on their availability
time. In the case of death, the outcome data
were obtained by contacting the deceased
patient’s relatives.
Follow-up was done by clinical
examinations in outpatient clinics or
telephone contacts with the patients or their
relatives. The primary endpoint was
considered to be 3-month PTE-related
deaths; and because of our small sample
size, in addition to 1-year all-cause
mortality, other related outcomes such as
rehospitalization due to the recurrence of
PTE and echocardiographic indices
including right ventricular dysfunction and
pulmonary hypertension were considered to
be long-term adverse outcomes.
This study was approved by our institutional
review board, and all the patients gave
informed consent for the use of their data for
research purposes.
The continuous variables were expressed as
the mean and the standard deviation and
were compared between the patients with
and without outcomes using the independent
samples t-test. When the continuous data
were nonparametric, they were expressed as
the mean and the standard error and were
compared between the groups via the
nonparametric 2-independent samples
(Mann–Whitney U) test. The categorical
variables were displayed as frequencies and
percentages and were compared between the
patients with and without outcomes using
the χ2 or Fisher exact test, as appropriate.
Variables with a P value < 0.2 in the
univariate analysis were chosen as
candidates to enter the multivariable model.
The multiple predictors of long-term
outcomes were found through the
application of a backward logistic regression
model, with the removal and entry
probabilities of 0.1 and 0.05. The effect of
the covariates on the adverse outcomes was
reported as an odds ratio (OR) with a 95%
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confidence interval (CI). The discrimination
power of the model was determined by
applying the area under the receiver
operating characteristics (ROC) curve. IBM
SPSS Statistics for Windows, version 22.0,
was used to conduct the analyses.
RESULTS
Totally, 92 patients diagnosed with acute
PTE were evaluated. During the first
admission, 6 patients died and were, as a
result, excluded. During a mean follow-up
time of 12 months from the diagnosis of
PTE, 13 patients were lost to follow-up
(failure to return for the follow-up visits), 1
patient suffered PTE relapse, 15 (23%)
patients sustained right ventricular
dysfunction and pulmonary hypertension,
and 2 patients expired due to PTE (1 patient
immediately after discharge and the other
after 14 months). Finally, 73 patients were
analyzed in our study. The mean age of the
study population, including 33 (40%)
women, was 60 ± 1.97 years. All the patients
were diagnosed by means of CTA. Only 1
patient needed fibrinolytic therapy. A
previous history of diabetes was reported in
10 (13.7%) patients, hypertension in 26
(35.6%), and dyslipidemia in 13 (17.8%).
Additionally, a previous history of HF was
reported in only a single patient. All the
baseline medical information of the study
population is depicted in Table 1.
Upon admission, 5 (6.2%) patients had
cancer (breast, gallbladder, ovary, prostate,
and testis cancer 1 each). Immobility for
more than 3 days was reported in 17 (21%)
patients and previous deep vein thrombosis
in 4 (4.9%).
On admission, the mean value of NT-
proBNP was 4064.7 ± 577.3 pg/mL, the
mean value of hs-cTnT was 68.2±8.8
ng/mL, the mean value of hemoglobin was
14.3±0.2 g/dL, and the mean value of
creatinine was 1.01 ± 0.04 mg/dL.
Additionally, the mean values of systolic
blood pressure, heart rate, and O2 saturation
were 130.8 ± 2.1 mm Hg, 103.4 ± 2.1, and
92.6%, respectively. On discharge, NT-
proBNP had a mean value of 1876.5 ± 358.1
pg/mL.
The change in the NT-proBNP level over
time was evaluated: There was a decreasing
trend of serum NT-proBNP during
hospitalization, from admission to discharge,
in the 2 study groups and there was a
significant difference in the admission and
discharge NT-proBNP levels between the 2
groups (P < 0.05) (Fig. 1).
Figure 1. Comparison of the trend of
serum NT-proBNP on admission and on discharge between the 2 study groups NT-proBNP, N-terminal prohormone of brain natriuretic peptide
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Table 1. Demographic and clinical characteristics of the study patients
Variable Total
(N=73) Without
Outcomes, n=48 With Outcomes,
n=25 P
value OR (95% CI)
Male 40(54.7) 26(54.1) 14(56) 0.881 1.077(0.407-2.848)
Age (y) 73 54.38±2.39 71.32±2.67 ‹0.001 -
Comorbid Conditions
Diabetes mellitus 10(13.6) 7(14.5) 3(12) 0.761 0.799 (0.188-3.399)
Hypertension 26(35.6) 16(33.3) 10(40) 0.572 1.333 (0.490-3.625)
Dyslipidemia 13(17.8) 7(14.5) 6(24) 0.318 1.850 (0.547-6.256)
Heart failure 1(1.3) 0(0) 1(4) 0.342 0.333 (0.240-0.462)
Risk Factors
Immobility ≥3d 15(20.5) 7(14.5) 8(32) 0.801 2.756 (0.863-8.804)
Previous DVT 4(5.4) 3(6.2) 1(4) 0.689 0.625 (0.062-6.339)
Obesity 29(39.7) 18(37.5) 11(44) 0.590 1.310 (0.490-3.497)
Recent surgery 6(8.2) 4(8.3) 2(8) 0.961 0.957 (0.163-5.620)
Cancer 5(6.8) 4(8.3) 1(4) 0.487 0.458 (0.048-4.336)
Estrogen use 8(10.9) 8(16.6) 0(0) 0.031 0.615 (0.508-0.746)
Recent air travels 6(8.2) 4(8.3) 2(8) 0.961 0.957 (0.163-5.620)
Physical Examination
Heart rate (b/min) 73 105.06±2.81 97.88±4.07 0.135 -
SBP (mm Hg) 73 132.17±3.32 127.56±2.57 0.613 -
RR (min) 73 21.93±0.93 25.25±1.43 0.020 -
O2 saturation (%) 73 93.38±0.55 91.33±1.29 0.249 -
Sign of DVT 12(16.4) 7(14..5) 5(20) 0.371 1.813 (0.487-6.753)
High risk in simplified PESI score 44(60.2) 30(62.5) 14(56) 0.590 0.764 (0.286-2.040)
ECG Findings
RBBB 14(19.1) 8(16.6) 6(24) 0.450 1.579 (0.480-5.196)
S1Q3T3 40(54.7) 26(54.1) 14(56) 0.881 1.077 (0.407-2.848)
Precordial T inversion in V1 42(57.5) 24(50) 18(72) 0.071 2.571 (0.909-7.278)
Echocardiographic Findings
RV dysfunction 629(84.9) 39(81.2) 23(92) 0.223 2.654 (0.527-13.363)
RV diameter 61(83.5) 37(77) 24(96) 0.039 7.135 (0.865-58.887)
Lab Findings
Hemoglobin (g/dL) 73 14.45±0.33 14.16±0.49 0.577 -
White blood cell (mL) 73 11750.65±622.25 11248.33±517.99 0.897 -
Serum creatinine (mg/dL) 73 0.95±0.04 1.10±0.07 0.058 -
High sensitivity cardiac troponin T (ng/L)
73 78.47±12.12 46.02±6.27 0.374 -
D-Dimer (g/L) 73 7.92±0.96 8.681.47 0.964 -
NT-proBNP (admission) (pg/mL) 73 2952.12±569.26 4906.72±1071.07 0.037 -
NT-proBNP (discharge) (pg/mL) 73 1032.69±247.39 3017.46±922.55 0.004 -
Spiral CTA Findings
Pulmonary infarction 18(24.6) 10(20.8) 8(32) 0.294 1.788 (0.600-5.327)
Saddle embolism 15(20.5) 11(22.9) 4(16) 0.708 0.779 (0.211-2.8883)
Segmental artery embolism 5(6.8) 4(8.3) 1(4) 0.487 0.458 (0.048-4.336)
Pleural effusion 10(13.6) 6(12.5) 4(160 0.680 1.333 (0.339-5.243)
Continuous variables are displayed as the mean ± the standard errors and the categorical variables are presented as numbers (%). DVT, Deep vein thrombosis; SBP, Systolic blood pressure; RR, Respiratory rate; RV, Right ventricle; RBBB, Right bundle branch block; NT-proBNP, N-terminal prohormone of brain natriuretic peptide
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As can be seen in Table 1, of all the
variables in the baseline paraclinical
assessment, the serum NT-proBNP level,
especially on discharge, and the right
ventricular diameter were significantly
higher in the patients with adverse outcomes
than in the outcome-free patients.
Furthermore, there were several significant
correlations between the NT-proBNP level
and echocardiographic indices (Table 2).
Table 2. Correlation between plasma NT-proBN at different time points and echocardiographic indices
Parameter RV Diameter RV Function RV:LV Ratio
r P value r P value r P value
NT-proBNP (admission) 0.293 0.009 -0.363 0.001 0.477 ‹0.001
NT-proBNP (discharge) 0.273 0.015 -0.298 0.008 0.567 ‹0.001
NT-proBNP (admission-discharge) 0.138 0.226 -0.198 0.085 0.140 0.237
RV, Right ventricle; LV, Left ventricle; NT-proBNP, N-terminal prohormone of brain natriuretic peptide
The existing literature lacks a cutoff point
for NT-proBNP in patients with PTE; we
were, therefore, obliged to use the cutoff
point of NT-proBNP in patients with heart
failure in order to calculate the diagnostic
markers. Table 3 shows the univariant
comparisons between several parameters. As
is depicted in Table 3, NT-proBNP on
discharge, NT-proBNP–based heart failure,
and age had significant differences between
the patients with and without outcomes (P <
0.05) (Table 3).
NT-proBNP exhibited no predictive effect in
the logistic regression equation, prompting
us to enter the NT-proBNP calculated based
on the multiple cutoff point strategy for
heart failure in our logistic regression
analysis. The results showed that age was an
independent value in the prediction of the
adverse outcome (OR: 1.064, 95% CI: 1.01
to 1.11) and discharge NT-proBNP
calculated based on the multiple cutoff point
strategy for heart failure in the PTE patients
with adverse outcomes was 2.36 fold that in
the outcome-free patients (Table 3).
Moreover, the area under the ROC curve
analysis was used to identify the optimal
plasma level of the discharge NT-proBNP
cutoff value so as to distinguish patients
with and without poor outcomes throughout
the period of the study: The optimal value
was 327 pg/mL. The value of the area under
the ROC curve for the patients throughout
the study was 0.707 (95% CI: 0.583 to
0.831), with a sensitivity of 80% and a
specificity of 43% (Fig. 2).
Table 3. Prediction of the adverse outcomes in the patients with pulmonary thromboembolism
Variables Entered in the Model
Univariate Analysis Multivariable
Analysis
OR (95% CI) P value
OR (95% CI) P value
NT-proBNP (admission) 1.009 0.095
NT-proBNP (discharge) 1.026 0.027
NT-proBNP difference (admission-discharge) 1.000 0.977
NT-proBNP– based HF (discharge) 3.250 0.024 2.360 0.168
Age 1.078 ‹0.001 1.064 0.007
Serum creatinine 3.379 0.095 1.684 0.566
Immobility ≥ 3 d 2.756 0.087 2.614 0.176
HF, Heart failure; NT-proBNP, N-terminal prohormone of brain natriuretic peptide
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Figure 2. Area under the receiver operating characteristics (ROC) curve for serum NT-proBNP
on discharge NT-proBNP, N-terminal prohormone of brain natriuretic peptide
DISCUSSION
Our study showed that in patients with
adverse outcomes, the serum NT-proBNP
level and the right ventricular diameter were
significantly higher than those in outcome-
free patients. There were several significant
correlations between NT-proBNP levels and
echocardiographic indices. We found that
age was an independent value in the
prediction of adverse outcomes and that
discharge NT-proBNP calculated based on a
multiple cutoff point strategy for heart
failure in PTE patients with adverse
outcomes was 2.36 fold that in outcome-free
patients.
PTE is potentially an acute and fatal disease
and requires emergency interventions if the
patient’s life is to be saved. Nonetheless,
usually due to nonspecific symptoms,
diagnosis is delayed and the golden time for
treatment is lost. 16
Recent years have
witnessed the emergence of several
diagnostic modalities for the determination
of patients with poor prognoses. Of course,
it is not feasible to draw upon all these tools
in practice, but NT-proBNP measurement
during the course of PTE appears to be
simple. 17-21
Aside from patients with PTE, the level of
NT-proBNP rises in other groups of patients
with morbid conditions, including heart
failure. 22-24
Similarly, our study showed that
in patients with PTE, higher levels of NT-
proBNP were significantly correlated with
future adverse outcomes such as heart
failure. 25, 26
Interestingly, in our study, the mortality rate
was low by comparison with previous
studies. This variation may be due to a lack
of significant difference in the baseline risk
factors of PTE and the existing underlying
disease between our 2 study groups. Another
possible explanation is that we reported the
death rate after the discharge time in our
study, while previous studies have merely
explained this rate within their patients’
hospitalization period. 14, 27, 28
In our univariate analysis, age and discharge
NT-proBNP had significant correlations
with the adverse outcomes (OR: 1.064, 95%
CI: 1.01 to 1.11 and OR: 1.026 95% CI:
1.003 to 1.049, respectively). Whereas age is
an unchangeable predictor, patients’
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discharge NT-proBNP is a suitable guide for
appropriate follow-up interventions.
In our study, the discharge NT-proBNP
cutoff point according to the ROC curve
analysis was lower than the figures
previously reported. This discrepancy may
be because those investigations assessed
NT-proBNP on admission, while we
assessed it on discharge. In addition, NT-
proBNP has a decreasing trend during the
course of PTE. However, our study supports
this notion that a low level of NT-proBNP is
associated with having a good prognosis in
the course of PTE. 10, 29
We found a significant correlation between
NT-proBNP levels and echocardiographic
indices such as right ventricular dysfunction
and the right-to-left ventricular ratio. It is
worthy of note, however, that
echocardiographic indices—in comparison
with NT-proBNP levels—have low
sensitivity for detecting poor prognoses in
patients with PTE. Echocardiography
should, therefore, be considered a suitable
supplementary paraclinical tool in patients
with PTE. 30-32
First and foremost among the limitations of
the present study is its small sample size.
Another weakness of note is that we
recruited only patients who were diagnosed
with PTE in the emergency department and
not those in whom PTE diagnosis was
missed or those who expired before PTE
diagnosis. That our study population was
selected from a single-center PTE registry
may limit the generalization of our results.
Indeed, had we assessed a larger sample
volume, some results that were significant in
the univariate analysis might have been
statistically significant in the logistic
regression analysis.
CONCLUSIONS
Our study showed that higher serum NT-
proBNP levels and abnormalities in
echocardiographic indices were associated
with adverse outcomes in patients with PTE.
Although natriuretic peptides rise in several
morbidity conditions such as heart failure,
an increase in NT-proBNP should be
deemed an alarm for all-cause mortality in
patients with PTE. Thus, the NT-proBNP
measurement during the course of PTE,
especially on discharge, may have a role as
an easy-to-use diagnostic tool for
determining patients with poor prognoses.
Acknowledgments
Not applicable.
Conflict of Interest
The authors have no conflicts of interest.
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Irisin and Type 2 Diabetes Complications Zyaddini et al
55
Original Article Irisin and Type 2 Diabetes Complications Zyaddini et al
Chest Pain is Associated With Decreased Irisin Serum Levels in
Type 2 Diabetic Patients With Coronary Artery Disease
Taybeh Zyaddini1, MD; Gholamreza Asadikaram
2, PhD;
Mohammad Masoumi3*
, MD
ABSTRACT
Background: This study aimed to determine irisin serum levels in type 2 diabetic patients with
and without coronary artery disease (CAD).
Methods: This study was performed on 56 type 2 diabetic patients with and without CAD and 28
normal controls. The serum levels of irisin, HbA1c, and fasting blood sugar of all the
participants and the severity of CAD in the diabetic patients were determined.
Results: The irisin serum level was significantly decreased in the CAD diabetic patients who
were symptomatic. HbA1c had a moderate positive correlation with the SYNTAX score
in the diabetic patients with CAD. The serum level of irisin was not significantly
different between the evaluated groups.
Conclusions: Based on the results, decreased irisin may be considered a risk factor for type 2
diabetic patients with CAD. Accordingly, the evaluation of patients with decreased irisin
serum levels regarding the prediction of heart infarcts may be valuable. (Iranian Heart
Journal 2020; 21(1): 55-66)
KEYWORDS: Irisin, Type 2 diabetes, Cardiovascular diseases, Angiography
1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IR Iran. 2 Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Biochemistry,
Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, IR Iran. 3 Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, IR Iran.
*Corresponding Author: Mohammad Masoumi, MD; Cardiovascular Research Center and Department of Cardiology, Afzalipur Faculty of Medicine Kerman University of Medical Science, Kerman, IR Iran.
Email: [email protected] Tel:09131409938
Received: February 23, 2019 Accepted: May 26, 2019
iabetes is the most common chronic
disease and affects human life world
wide. 1 It has been estimated that
diabetes will be raised to more than 328
million cases in the near future. 2 It is the
fourth cause of morbidity and mortality in
developed countries. 3 Diabetes can be
associated with several complications
including retinopathy, nephropathy, and
cardiovascular diseases 4, 5
It has been
reported that diabetic patients suffer from
cardiovascular diseases 2 to 5 times more
than nondiabetic individuals. 6 Diabetes can
be associated with the incidence of heart
D
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ischemia and cardiovascular disease-related
complications. Therefore, the identification
of new markers for the prediction of heart
ischemia in diabetic patients who suffer
from cardiovascular diseases is a new aim of
investigators.
Recent investigations have proposed that
irisin, a novel defined myokine, may be
considered a potential marker for the
induction of cardiovascular diseases and
then heart ischemia in diabetic patients. 7
Irisin is a novel glycoprotein produced by
the proteolysis of membrane fibronectin
type ΙΙΙ domain-containing, which happens
in response to the activation of PPAR-γ co-
activator-1α (PGC-1α). 8 It has been
proposed that irisin is an important molecule
that participates in the conversion of white
to brown adipose tissues and, thus, decreases
the risk of obesity, a critical risk factor for
the induction of type 2 diabetes and
cardiovascular diseases. 9 There is some
controversy regarding the serum levels of
irisin in type 2 diabetic patients with and
without coronary artery disease (CAD). 9, 10
However, some investigations have reported
that the serum level of irisin is associated
with decreased risks of insulin resistance
and glucose tolerance. 11, 12
It has also been
hypothesized that the altered expression of
irisin during cardiovascular diseases may be
a mechanism to manipulate the ATP levels
of myocardial cells, which are under
ischemic conditions, to protect them from
further damage. 10
It appears that the altered
expression of irisin may be associated with
either physiological or pathological
responses to heart ischemia. Due to the
recent defined roles played by irisin, it has
been hypothesized that the molecule may
participate in the pathogenesis of type 2
diabetes and its complications. Thus, the
main aim of the present study was to
identify the irisin serum level in type 2
diabetic patients suffering from CAD in
comparison with type 2 diabetic patients
without CAD and healthy controls. Another
aim of the current study was to determine
the relationship between the irisin serum
level and other risk factors such as the
SYNTAX score, HbA1C, and ethnic factors
in the evaluated groups.
METHODS
Subjects
This cross-sectional study was performed
between 2016 and 2017 on type 2 diabetic
patients who referred to Shafa Hospital,
Kerman University of Medical Sciences,
Kerman, Iran. Fifty-six type 2 diabetic
patients with angiography criteria, based on
clinical presentations and paraclinical
indications, and 28 healthy controls without
diabetes and CAD were introduced to the
study. Blood samples were collected in both
groups pre-treated and without anticoagulant
agents to evaluate HbA1C and irisin serum
levels, respectively. Healthy controls were
comprised of individuals who had
angiography criteria but who did not suffer
from diabetes and CAD. The type 2 diabetic
patients were divided into 2 groups
consisting of patients with and without
CAD. The demographic data including age
and sex, as well as other information
regarding the history of familial CAD,
smoking, blood hypertension, drug
consumption, dyslipidemia, and obesity,
were collected from the participants.
Angiography was performed by an expert
cardiologist via the Judkins method and
interpreted by another cardiologist blinded
to the study aims. The severity of CAD was
determined using the SYNTAX scoring
method. 13
The exclusion criteria were as
follows: type 2 diabetes of less than 1 year’s
duration, age < 30 years and > 60 years, and
regular exercise in the recent 12 months (due
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to the effects of exercise on the irisin serum
level).
Determination of the Irisin Serum Level
The irisin serum level was determined using
commercial kits from BioCompare
Company (New York, USA).
Evaluation of HbA1C
The status of HbA1C was evaluated using a
commercial kit according to the
manufacturer’s guidelines.
Statistical Analysis
SPSS software, version 18, was used to
analyze raw data. Based on the normality in
the data distribution, one-way ANOVA was
employed to analyze the differences in irisin,
HbA1C, fasting blood glucose (FBG), age,
and weight between the groups. The χ2 test
was applied to analyze the differences
between the groups regarding gender;
smoking; opium consumption; regular
exercise; chest pain; chronic diarrhea; a
history of diabetes; elevated triglyceride and
cholesterol; heart diseases; familial heart
diseases; hospitalization; and liver, kidney,
and infectious diseases. The independent t-
test was also used to analyze the differences
in the variables within each group between
the male and female patients, between the
participants residing in urban and rural
areas, between the smokers and nonsmokers,
between the opium users and non-users, and
finally between the patients with and
without chest pain. The Pearson correlation
test was also utilized to calculate the
correlation between irisin, FBG, weight, age,
HbA1C, and the SYNTAX score.
RESULTS
The results showed that the serum level of
irisin was not significantly altered (P =
0.097) in the type 2 diabetic patients with
(3.16 ± 0.44 ng/mL) and without (3.35 ±
0.38 ng/mL) CAD and the normal controls
(2.25 ± 0.27 ng/mL) (Fig. 1).
The data analysis revealed that there were no
significant differences between the groups
regarding age (P = 0.08); sex (P = 0.168);
smoking (P = 0.210); opium addiction (P =
0.199); a history of kidney (P = 0.350), liver
(P = 0.376), and familial heart (P = 0.103)
diseases; weight (P = 0.370); regular
exercise (P = 0.304), and chronic diarrhea
(P = 0.583). However, the levels of FBG
and HbA1C were significantly higher in the
type 2 diabetic patients (with and without
CAD) than in the normal controls, while
there were no significant differences
between the 2 diabetic groups regarding
FBG (P = 0.938) and HbA1C (P = 0.202)
(Fig. 1).
The diabetic patients (with and without
CAD) had significantly higher scores of a
history of increased triglyceride (P = 0.012)
and cholesterol (P = 0.027) levels as well as
chest pain (P < 0.001).
The results also showed that the serum
levels of irisin, FBG, and HbA1c were not
changed between the male and female (Fig.
2), between the smoking and nonsmoking
(Fig. 3), and between opium-addicted and
nonaddicted (Fig. 4) type 2 diabetic patients
with and without CAD.
The statistical analysis also revealed that the
serum level of irisin significantly decreased
in the type 2 diabetic patients with CAD
who suffered from chest pain in comparison
with the patients without chest pain (P =
0.039) (Fig. 5). Nonetheless, there were no
significant associations regarding FBG and
HbA1c between the type 2 diabetic patients
with and without CAD who were suffering
from chest pain in comparison with those
without chest pain. The irisin serum level
also was not changed between the type 2
diabetic patients without CAD with chest
pain in comparison with those without chest
pain (P = 0.342).
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The Pearson test demonstrated that HbA1c
had a moderate positive correlation with the
SYNTAX score and a significant correlation
with FBG in the type 2 diabetic patients with
CAD (Table 1 Section A). The evaluation of
the type 2 diabetic patients with CAD (Table
1 Section A) showed that there was a poor
negative correlation between the SYNTAX
score and weight in the patients. HbA1c also
had a significant correlation with FBG in the
type 2 diabetic patients without CAD (Table
1 Section B). Table 1 Section C reveales no
correlation between the variables in the
normal controls.
Table 1. Correlation analysis regarding irisin, FBG, age, HbA1c, the SYNTAX score, and weight
in the type 2 diabetic patients with CAD (A), without CAD (B), and normal controls (C)
FBG Weight Age SYNTAX score HbAIC Irisin A
-0.081 -0.190 -0.085 -0.113 0.017 1 Pearson Correlation Irisin
0.682 0.332 0.667 0.567 0.933 P value
0.885** -0.239 0.176 0.646* 1 0.017 Pearson Correlation HbAIC
0.000 0.220 0.371 >0.001 0.933 P value
0.521 -0.375*** 0.268 1 0.646* -0.113 Pearson Correlation SYNTAX score 0.004 0.050 0.168 >0.001 0.567 P value
FBG Weight Age HbAIC Irisin B
0.267 0.044 0.082 0.361 1 Pearson Correlation Irisin
0.162 0.820 0.674 0.054 P value
HbAIC 0.816***** -0.116 0.125 1 0.361**** Pearson Correlation
>0.001 0.549 0.518 0.054 P value
FBG Weight Age HbAIC Irisin C
-0.05 .081 -0.328 0.161 1 Pearson Correlation Irisin
.980 .687 .095 0.254 P value
HbAIC 0.416 -0.216 0.225 1 0.161 Pearson Correlation
0.095 0.849 0.438 0.254 P value
Data analysis revealed that HbA1c had a moderate positive correlation with the SYNTAX score (*) and a significant correlation with FBG (**) in the type 2 diabetic patients with CAD (A). Evaluation of the type 2 diabetic patients with CAD (A) revealed that there was a poor negative correlation between the SYNTAX score and weight in the patients (***). HbA1c also had a poor and significant correlation with irisin (****) and FBG (*****) in the type 2 diabetic patients without CAD (B). The variables had no significant correlation with each other in the normal controls. CAD, Coronary artery disease; FBG, Fasting blood glucose
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Figure 1. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage, age, and weight
values in the type 2 diabetic patients with and without coronary artery disease (CAD) as well as the healthy controls. The figure demonstrates that there were no significant differences between the groups regarding irisin, age, and weight. However, the serum level of FBG and the HbA1c percentage were significantly higher in the diabetic patients than in the normal controls.
343 x 412 mm (96 x 96 DPI)
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Figure 2. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the male and
female type 2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences between the male and female patients in both groups regarding irisin, FBG, and the HbA1c percentage.
405 x 293 mm (96 x 96 DPI)
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Figure 3. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the smoking and
nonsmoking type2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences between the smoking and nonsmoking patients in both groups regarding irisin, FBG, and the HbA1c percentage.
264 x 205 mm (96 x 96 DPI)
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Figure 4. Serum levels of irisin and fasting blood glucose (FBG) as well as the HbA1c percentage in the opium-
addicted and nonaddicted type 2 diabetic patients with and without coronary artery disease (CAD). The figure demonstrates that there were no significant differences among the opium-addicted and nonaddicted patients in both groups regarding irisin, FBG, and the HbA1c percentage.
411 x 350 mm (96 x 96 DPI)
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Figure 5. Serum levels of irisin and FBG as well as HbA1c percent in the type 2 diabetic patients with and
without CAD who were suffered from chest pain in comparison to without chest pain. The figure shows that irisin significantly decreased in the type 2 diabetic patients with CAD who were suffered from chest pain in comparison to the patients without chest pain (*P = 0.049). There were no significant differences among the type 2 diabetic patients with and without CAD who were suffered from chest pain in comparison to without chest pain.
405 x 341 mm (96 x 96 DPI)
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DISCUSSION
In the present study, the results revealed no
significant differences between the 2 groups
regarding the serum level of irisin;
nevertheless, the statistical analysis
demonstrated that the irisin serum level in
the type 2 diabetic patients with CAD
suffering from chest pain was significantly
decreased when compared with the type 2
diabetic patients with CAD but without
chest pain. Given that chest pain in patients
with CAD is a major criterion in the
induction of heart ischemia, it may be
hypothesized that decreased serum levels of
irisin in patients with chest pain may be
considered a predicting factor for the onset
of heart ischemia. Chiming in with this
notion, Wang et al 14
reported that irisin
played a key role in protecting the
mitochondria function, the myocardial
infarct size, and finally the heart against
ischemia and reperfusion injuries in their
study population. The role played by irisin
in the protection of the mitochondria
function during ischemia was also
documented by Chen and colleagues. 15
Thus, decreased irisin levels following chest
pain in type 2 diabetic patients with CAD
may be a risk factor for susceptibility to
cardiac infarction. Additionally, Aydin et al 16
demonstrated that using iloprost and
sildenafil, 2 pharmaceutical factors to
mediate the resumption of reperfusion,
played a significant role in increasing the
expression of irisin in the heart, liver, and
kidney blood tissues and that it was
associated with improved cardiovascular
diseases. The significant roles played by
irisin in the protection of the cell system
following ischemia via the downregulation
of the ROS-NLRP3 inflammatory signaling
pathway 17
and the induction of the Akt and
ERK1/2 signaling pathways have also been
demonstrated previously.
We also found that the serum level of irisin
had a poor positive correlation with the
HbA1c percentage in our type 2 diabetic
patients without CAD. It has been
documented that obesity is a risk factor for
the development of type 2 diabetes.
Bonfante et al 18
reported that obesity had a
positive association with increased serum
levels of irisin. Rana and colleagues 19
also
showed that increased irisin serum levels
was a major marker for type 2 diabetes,
associated with the increased expression of
pro-inflammatory molecules such as E-
selectins. It has also been reported that irisin
induces glucose metabolism in the p38
MAPK signaling dependent manner. 20
Another investigation reported that, although
the serum level of irisin increased in type 2
diabetic patients, its serum levels decreased
in type 2 diabetic patients who suffered from
nephropathy. 21
Moreover, Shelbaya et al 21
demonstrated that the serum level of irisin
had a negative correlation with advanced
glycation end-products, a factor for the
worsening of type 2 diabetic patients.
Collectively, it appears that irisin is a normal
body response to increased FBG to
minimize the side effects of diabetes. Our
results also showed that the irisin serum
level significantly increased in parallel with
the increased percentage of HbA1c in our
type 2 diabetic patients without CAD. Thus,
it may be hypothesized that irisin is a
response to increased HbA1c to protect the
human cell system from type 2 diabetes
complications.
Our results also showed that the SYNTAX
score had a moderate correlation with
HbA1c, which is a risk factor for the
induction of cardiovascular diseases in type
2 diabetic patients.
We also found no significant differences
between the male and female, smoking and
nonsmoking, and opium-addicted and
nonaddicted type 2 diabetic patients. Thus, it
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appears that although the factors were the
risk factors for the development of type 2
diabetes, they were unable to alter irisin
expression. Further research can elucidate in
more detail the roles played by these
variables in the expression and function of
irisin.
Acknowledgments
We would like to express our thanks to our
type 2 diabetic patients and healthy
volunteers for their cooperation. The study
was supported by Kerman University of
Medical Sciences.
Conflict of Interest
The authors have no conflict of interest to
declare.
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2. Olafsdottir, E., et al., The prevalence of
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3. Khan, A.R., et al., Knowledge, attitude and
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4. Masoomi, M., S. Samadi, and M.
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6. Franks, P.W. and J. Merino, Gene-lifestyle
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7. Kuloglu, T., et al., Irisin: a potentially
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8. Roca-Rivada, A., et al., FNDC5/irisin is not
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9. Moreno-Navarrete, J.M., et al., Irisin is
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12. Liu, J.J., et al., Lower circulating irisin is
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Diabetes Complications, 2013. 27(4): p.
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13. Farooq, V., et al., Combined anatomical and
clinical factors for the long-term risk
stratification of patients undergoing
percutaneous coronary intervention: the
Logistic Clinical SYNTAX score. Eur Heart
J, 2012. 33(24): p. 3098-104.
14. Wang, H., et al., Irisin plays a pivotal role to
protect the heart against ischemia and
reperfusion injury. J Cell Physiol, 2017.
232(12): p. 3775-3785.
15. Chen, K., et al., Irisin protects mitochondria
function during pulmonary
ischemia/reperfusion injury. Sci Transl Med,
2017. 9(418).
16. Aydin, S., et al., The effect of iloprost and
sildenafil, alone and in combination, on
myocardial ischaemia and nitric oxide and
irisin levels. Cardiovasc J Afr, 2017. 28(6):
p. 389-396.
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17. Peng, J., et al., Irisin protects against
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194.
18. Bonfante, I.L.P., et al., Obese with higher
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2017. 61(6): p. 524-533.
19. Rana, K.S., et al., Plasma irisin is elevated in
type 2 diabetes and is associated with
increased E-selectin levels. Cardiovasc
Diabetol, 2017. 16(1): p. 147.
20. Pang, Y., et al., beta-arrestin-2 is involved in
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Original Article Blunted Heart Rate Response to Dipyridamol Stress Testing Malek et al
Association Between Blunted Heart Rate Response to
Dipyridamole and Myocardial Ischemia in Diabetic Patients as
Compared With Nondiabetic Patients
Hadi Malek1, MD; Raheleh Hedayati
2*, MD; Nahid Yaghoobi
1, MD;
Hassan Firoozabadi1, MD; Fereydoon Rastgou
1, MD;
Ahmad Bitarafan Rajabi1, PhD
ABSTRACT
Background: Blunted heart rate response (BHR) during dipyridamole stress testing has been
reported to be related to higher cardiac death. This study was performed to assess the
association between BHR and perfusion abnormalities in diabetic patients undergoing
dipyridamole stress ECG-gated myocardial perfusion imaging (MPI) as compared with
nondiabetic patients.
Methods: A total of 2172 subjects (1602 women and 570 men) at a mean age of 61 ± 11 years
who were referred for MPI to our department were studied. The subjects were divided
into 2 groups on the basis of the presence or absence of diabetes mellitus (849 diabetic vs
1323 nondiabetic subjects).
Results: Dipyridamole-related BHR was noted in 471 (67.7%) patients, demonstrating a
significantly higher incidence in the diabetic patients than in the nondiabetic subjects
(P < 0.05). Both basal systolic and peak systolic blood pressures were significantly
higher in the patients with diabetes mellitus (P < 0.05). However, no significant
difference was noted in the number of segments with perfusion abnormalities in patients
with BHR as compared with the subjects with a normal hemodynamic response, neither
in the diabetic nor in the nondiabetic subjects.
Conclusions: The results of our study suggest that the presence of myocardial perfusion
abnormalities and left ventricular dysfunction is not related to abnormal heart rate
response during dipyridamole stress testing, neither in diabetic nor in nondiabetic
subjects. The incidence of BHR to dipyridamole is significantly higher in diabetic
patients, however. (Iranian Heart Journal 2020; 21(1): 67-74)
KEYWORDS: Diabetes mellitus, Hemodynamic response, Ischemic heart disease, Myocardial perfusion imaging,
Dipyridamole stress testing
1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
2 Rasule Akram General Hospital, Iran University of Medical Sciences, Tehran, IR Iran.
* Corresponding Author: Raheleh Hedayati, MD; Department of Nuclear Medicine, Rasoule Akram General Hospital, Satarkhan St, Tehran, IR Iran.
Email: [email protected] Tel : 00982166509312
Received: February 23, 2019 Accepted: May 11, 2019
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n individual’s heart rate is a
physiological response to
autonomic, central, and peripheral
reflexes as well as intrinsic cardiac control
mechanisms. Different abnormalities could
be responsible for an abnormal heart rate
response to physiological stress including
renal failure, diabetes, and intrinsic cardiac
conditions such as coronary artery disease
(CAD) and cardiomyopathy. 1 Dipyridamole
is routinely employed for pharmacological
stress testing in myocardial perfusion
imaging (MPI). This vasodilator agent has
also been used for the assessment of heart
rate response variability. 2,3,4
Dipyridamole
may cause a modest decrease in blood
pressure, whereas there is a modest increase
in heart rate, which have been believed to be
a normal hemodynamic response to this
vasodilator agent. 5 Chronotropic
incompetence, which is defined as an
attenuated chronotropic response to exercise,
has been considered to be a predictor of
increased mortality. 6,7
Likewise, it has been
shown recently that blunted heart rate
response (BHR) during dipyridamole stress
testing is related to cardiac death. 1,6,7,8
Myocardial ischemia and left ventricular
dysfunction have been shown to be in
association with chronotropic incompetence
during exercise, 8,3
and the same association
might be present in dipyridamole-related
abnormal heart rate response, despite the
fact that the underlying mechanisms are not
yet understood. 9 Furthermore, BHR to
dipyridamole has been associated with a
higher mortality risk, even in the presence of
normal myocardial perfusion, 7 which could
partly be explained by sudden cardiac death
and ventricular arrhythmias related to an
abnormal cardiac autonomic nervous
system, 10,11
Diabetes mellitus is known as
the most common metabolic disease in the
world. 12
It is estimated that 20%–40% of
diabetic patients suffer from cardiac
autonomic neuropathy, which can be
assessed by heart rate variability during the
vasodilator stress test, 13,14
resulting in an
increased risk of cardiovascular-related
mortality. 2,15
Hence, we performed the present study to
assess the association between BHR and
perfusion abnormalities in diabetic patients
undergoing dipyridamole stress ECG-gated
MPI as compared with nondiabetic patients,
using single-photon emission computed
tomography (SPECT).
METHODS
Study Population
Consecutive patients (N = 2172) who
underwent dipyridamole stress ECG-gated
SPECT MPI in Rajaie Cardiovascular,
Medical, and Research Center were enrolled
in this study. The exclusion criteria were
pregnancy, severe obstructive lung disease,
second- or third-degree atrioventricular
block without a functioning pacemaker,
acute myocardial infarction or unstable
coronary syndrome (< 24 h), systolic blood
pressure < 90 mm Hg, hypersensitivity to
dipyridamole, or atrial fibrillation.
Dipyridamole Stress Protocol All the patients were instructed to interrupt
xanthine-containing compounds and
dipyridamole for 24 hours and to be in a
fasting state for 8 hours before testing.
When possible, they were also instructed to
discontinue β-blocking medications for 48
hours and calcium channel blockers as well
as long-acting nitrates for 24 hours. All the
patients underwent a structured interview for
recording demographic data, clinical history,
prior cardiac events, cardiac risk factors,
therapeutic procedures, and prior diagnostic
tests before the study. A 12-lead ECG was
obtained before and during stress testing at
2-minute intervals. The patients underwent
dipyridamole stress SPECT MPI according
A
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to the standard protocol. 16
Dipyridamole in
a dose of 0.56 mg/kg of body weight was
infused intravenously over a 4-minute
period.
Heart rate and blood pressure were
measured at resting state in the supine
position and then every 1 minute after the
commencement of dipyridamole infusion for
a total period of 10 minutes. Next, 99mTc-
Sestamibi was injected 3 to 5 minutes after
the termination of dipyridamole infusion.
The peak stress heart rate was defined as the
maximum recorded heart rate during a 6-
minute period after the completion of
dipyridamole infusion. The peak stress to
baseline heart rate ratios were calculated and
the results were categorized as normal
(ratios ≥ 1.2) or BHR groups (ratios < 1.2),
according to the previously published data. 6,8
Acquisition Protocol
All the patients underwent a 2-day stress-
rest protocol, using 99mTc-Sestamibi with
an injection dose of 10 to 15 mCi in each
phase of the study. A series of 2
acquisitions, composed of a 60- to 90-
minute post-stress as well as a resting-state
acquisition, was carried out for all the
patients. The SPECT acquisitions were
conducted in the step-and-shoot mode with
32 thirty-second or 64 twenty-second
projections, a zoom factor of 1.46, and in a
non-circular 180° arc (45° RAO-to-LPO),
using a PHILIPS BrightView dual-head
gamma camera (USA), an Infinia Hawkeye
dual-head SPECT/CT hybrid camera (GE
Healthcare, USA), or a Symbia T2 dual-
head SPECT/CT hybrid camera (Symbia T2
System; Siemens Medical Solutions, USA),
equipped with low-energy, high resolution
(LEHR) collimators and an automated body
contour detection system.
Post-stress gated MPI with an acceptance
window of 30% was carried out for all the
subjects. All the data were stored in a
64×64×16 computer matrix and
reconstructed with 3D ordered subset
expectation maximization (3D-OSEM),
using 2 iterations and 8 subsets. 17
The
rotating raw images of all the participants
were seen visually, and the studies with
motion artifacts or low-count density were
excluded.
Image Interpretation
The reconstructed and reoriented images
were quality controlled and interpreted by
experienced nuclear physicians, using
AutoQUANT® software for cardiac
quantification and functional analysis. 18
A
semi-quantitative visual analysis of images
was performed on the basis of standard 17-
segment scoring. Each segment was
considered to be normal (with no perfusion
abnormality), ischemic (with reversible
perfusion abnormality), or infarcted (with
persistent perfusion abnormality and after
the exclusion of attenuation artifacts, using
the planar lateral view in the lateral
decubitus portion or CT-based attenuation
correction if available). 19
Gated short-axis images were processed, and
the left ventricular ejection fraction was
automatically calculated. Patients with a
post-stress ejection fraction < 50% were
considered to have left ventricular
dysfunction.
Statistical Analysis
The χ2
test was used for the categorical and
the Student t-test and the Mann–Whitney U
test for the numerical variables. Multivariate
logistic regression models were also
performed to investigate adjusted
associations between the variables.
The data were described as the mean ± the
standard deviation (SD) and as counts (%)
for the interval and the categorical variables,
respectively. A P value < 0.05 was
considered a statistically significant result.
The data were handled and analyzed with
Statistical Program for Social Sciences
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(SPSS 15.0 for Windows, SPSS Inc,
Chicago, Illinois).
RESULTS
A total of 3021 patients, who were referred
to Rajaie Cardiovascular, Medical, and
Research Center for MPI study, were
included in the study. A total of 849 patients
were also excluded from the analysis due to
recent intakes of beta-blockers, calcium
channel blockers, known chronic renal
failure, or incomplete data. Therefore, 2172
patients (1602 women and 570 men) at a
mean age of 61 ± 11 years were enrolled in
this study. Of this total, 520 (23.9%) patients
had diabetes mellitus. The background and
demographic descriptive data are shown in
Table 1 and the comparisons of the
demographic differences, hemodynamic
response, and MPI parameters according to
the presence or absence of diabetes mellitus
are depicted in Table 2.
Dipyridamole-related BHR was noted in
1476 (68%) patients, demonstrating a
significantly higher incidence in the diabetic
patients than in the nondiabetic subjects (P =
0.008). Both basal systolic and peak systolic
blood pressures were significantly higher in
the patients with diabetes mellitus (P =
0.002), whereas no significant difference
was noted in the peak to basal blood
pressure changes. Furthermore, no
significant difference was noted in the
number of either ischemic or infarcted
myocardial segments in the patients with
BHR as compared with the subjects with a
normal hemodynamic response, neither in
the diabetic nor in the nondiabetic subjects
(Table 3).
The adjusted association analysis by logistic
regression models (Table 4) revealed no
significant association between the
incidence of myocardial ischemia and BHR,
whereas there was a statistically significant
association between ischemia and diabetes
mellitus (OR = 1.574; P < 0.001) as well as
hypertension (OR = 1.283; P = 0.010).
DISCUSSION
Normal hemodynamic response to
dipyridamole is reflected by systemic
vasodilatation, with a modest decrease in
blood pressure and a modest increase in
heart rate. 5,20
Despite the fact that CAD has
been introduced as an intrinsic cardiac
condition, responsible for BHR, 5,2,21,22
we
found no association between the incidence
of abnormal perfusion in patients with
dipyridamole-related BHR as compared with
patients with a normal response, neither in
diabetic nor in nondiabetic subjects.
Furthermore, BHR was not related to left
ventricular dysfunction in our study as well.
However, the incidence of BHR was
significantly higher in diabetic patients than
in nondiabetic subjects. One of the
explanations for this finding could be related
to the higher incidence of cardiac autonomic
neuropathy in diabetes mellitus. 1314
In a large cohort of patients undergoing
adenosine stress MPI, Abidov et al 8
demonstrated that several hemodynamic
variables could provide independent
information in the risk assessment of
patients. They found that patients with high
resting heart rates were at a higher risk of
cardiac death and that the peak to basal HR
ratio provided incremental prognostic
information over MPI results, enhancing the
risk stratification of patients regarding
cardiac death, particularly among those with
normal perfusion. Although the authors
showed that this fact might be related to
heart failure, the ventricular function was
not assessed in that study. Furthermore,
diabetes mellitus was not regarded as a
separate entity.
Bhatheja et al 6 also reached the same
conclusion by showing that BHR to
dipyridamole was a predictor of cardiac
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death even in the setting of normal perfusion
scan and normal ECG.
In a recent study by Mathur et al, 1 BHR was
an independent predictor of cardiac
mortality after adjustments for perfusion and
function-related gated SPECT variables.
Our study is in accordance with the
previously published data that found no
association between myocardial ischemia or
infarction and BHR, using MPI. Previous
research has linked BHR to dipyridamole to
higher mortality as a result of an abnormal
cardiac nervous system, predisposing
patients to ventricular arrhythmias and
sudden death. 7,10,11
The findings of our study are also in
accordance with previous epidemiological
studies, which have demonstrated that
diabetic patients have a higher probability of
BHR. 2,9,18
Limitations
Our results are based on a population of
patients who were referred to our
department for gated SPECT MPI study;
therefore, there might be a question on the
implication of the results to a broader
population. Moreover, the current study is
retrospective, in spite of the prospective
collection of all the data. Chronic renal
failure and diabetic neuropathy have been
concluded to cause BHR in previous studies. 2,9,18,20
However, the data concerning these
conditions were unavailable and were not
included in our study. Finally, this study was
carried out in a single nuclear cardiology
center.
Table 1. Background and demographic descriptive data (N = 2172)
Age (y) 61 ± 11
Gender (F/M) 1602/570 (73.8/26.2)
Symptoms:
Atypical chest pain 1151 (53.0)
Typical chest pain 234 (10.8)
DOE 1068(49.2)
Palpitation 579 (26.7)
Arrhythmia 22 (1.0)
None 225 (10.4)
Risk Factors:
Diabetes mellitus 520 (23.9)
Hypertension 1132 (52.1)
Hypercholesterolemia 885 (40.7)
Family history 286 (13.2)
Hemodynamic Variables:
Basal HR (beat per minute) 69.6 ± 17.9
Peak HR (beat per minute) 60.6 ± 34.5
Peak HR/Basal HR <1.2 >1.2
1471(67.7) 693 (31.9)
Basal systolic BP (mm Hg) 138.0 ± 18.0
Basal diastolic BP (mm Hg) 74.1 ± 23.5
Peak systolic BP (mm Hg) 142.0 ± 31.0
Peak diastolic BP (mm Hg) 73.8 ± 23.8
EF 66.2 ± 7.6
Statistics are numbers (%) or the mean ± the standard deviation. HR, Heart rate; BP, Blood pressure
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Table 2. Comparison of the demographic differences, hemodynamic, and MPI parameters in the patients with
diabetes mellitus as compared with the nondiabetic subjects
Characteristic/ Variable
Diabetes Mellitus
P value Yes n = 520
No n = 1652
Age (y) 62 ± 9.8 61 ± 11.3 0.015
Gender (F/M) 385/135 1217/435 0.867
Hemodynamic Variables:
Peak HR/Basal HR ≤1.2 >1.2
378 (72.7) 142 (27.3)
1098 (66.5) 554 (33.5)
0.008
Peak HR (beat per minute) 61.2 ± 35.1 60.4 ± 34.4 0.199
Basal HR (beat per minute) 70.1 ± 20.4 69.5 ± 17.1 0.001
Basal systolic BP (mm Hg) 14.1 ± 1.9 13.8 ± 1.8 0.002
Basal diastolic BP (mm Hg) 73.1 ± 24.6 74.4 ± 23.1 0.586
Peak systolic BP (mm Hg) 14.6 ± 4.1 14.1 ± 2.8 0.002
Peak diastolic BP (mm Hg) 72.8 ± 24.9 74.1 ± 23.4 0.560
Basal/peak systolic BP (mm Hg) 0.9 ± 0.1 0.9 ± 0.1 0.664
Basal/peak diastolic BP (mm Hg) 1.1 ± 1.1 1.1 ± 1.01 0.795
Number of ischemic infarcted segments 348 (66.9) 856 (51.8) <0.001
Number of ischemic segments 341 (65.6) 827 (50.1) <0.001
Number of infracted segments 55 (10.6) 104 (6.3) 0.001
EF 66.8 ± 6.6 66.1 ± 7.8 0.298
Statistics are numbers (%) or the mean ± the standard deviation. Significant P values in bold MPI, Myocardial perfusion imaging; HR, Heart rate; BP, Blood pressure; EF, Ejection fraction Table 3. Comparison of the number of ischemic, infarcted, or ischemic infarcted segments according to the peak to
baseline heart rates in the diabetic patients
Characteristic/ Variable
Peak-to-Baseline Heart Rate P
value ≤1.2 n = 378
>1.2 n = 142
Number of ischemic infarcted segments 256 (67.7) 92 (64.8) 0.526
Number of ischemic segments 252 (66.7) 89 (62.7) 0.393
Number of infracted segments 43 (11.4) 12 (6.5) 0.296
Statistics are numbers (%). Table 4. Multivariate logistic regression analysis for the association between ischemia and HR variability, adjusted for
the EF, diabetes mellitus, hypertension, and hypercholesterolemia
Characteristic/ Variable
B
OR
95% CI for EXP(B) P value Lower Upper
Diabetes mellitus 0.454 1.574 0.000 1.978 0.001
Hypertension 0.249 1.283 0.010 1.551 0.010
Hypercholesterolemia 0.172 1.188 0.083 1.443 0.083
EF 0.001 1.001 0.892 1.013 0.892
Peak to basal HR 0.032 0.969 0.753 1.182 0.753
Significant P values in bold HR, Heart rate; EF, Ejection fraction
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CONCLUSIONS
The incidence of BHR to dipyridamole was
significantly higher in the diabetic patients
in the present study; nonetheless, the results
presented herein suggest that myocardial
perfusion abnormalities and left ventricular
dysfunction are not related to an abnormal
heart rate response during dipyridamole
stress testing, neither in diabetic nor in
nondiabetic subjects. As previously
published data indicate, given an increased
risk of cardiac-related mortality in patients
with BHR during dipyridamole stress
testing, more attention should be paid to the
risk stratification of patients with normal
gated SPECT MPI but with BHR to
dipyridamole stress testing.
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Original Article Air Pollution and CVD Shirvani et al
Fine Particle Air Pollution (PM 2.5) and Cardiovascular
Hospitalization in Isfahan in 2012: CAPACITY Study
Ehsan Shirvani1, MD;
Masoumeh Sadeghi
2, MD; Sayed Mohsen Hosseini*
3, PhD;
Alireza Khosravi4, MD
; Katayoun Rabiei
1, MD, PhD
; Mojtaba Rahimi
5, MD
;
Tohid Jafari-Koshki6, PhD
; Mansour Shishehforoush
7, MS;
Ahmadreza Lahijanzadeh8, PhD; Elham Moazam
9, MD;
Mohammad Bagher Mohebi10
, PhD; Nizal Sarrafzadegan1, MD
ABSTRACT
Background: This study aimed to evaluate the relationship between exposure to PM2.5 and the
number of hospital admissions due to cardiovascular diseases.
Methods: The present time-series, case-crossover study is a part of the CAPACITY study on
patients admitted to 15 hospitals in the Iranian city of Isfahan because of cardiovascular
diseases in 2012. PM2.5 concentrations were calculated in air pollution monitoring
stations and divided into 3 groups of good or moderate, unhealthy for sensitive people,
and unhealthy or hazardous. The relationship between the number of admissions and fine
particle concentrations was assessed.
Results: This study evaluated 15752 participants at a mean age of 59 ± 19.4 years. Men
accounted for 52.6% (n = 8282) of the study population. The mean concentration of fine
particles was 53.77 ± 29.65 micrometers. In most days of the year, the concentration of
PM2.5 was at an unhealthy level for sensitive people. Poisson regression analysis showed
a significant correlation between the number of hospital admissions due to cardiovascular
diseases and ischemic heart diseases and fine particle concentrations in the unhealthy
level for sensitive people (P = 0.001, P = 0.001, and P = 0.002). There was a significant
correlation between PM2.5 concentrations and the number of admissions due to
conductive heart diseases and heart blocks in unhealthy or hazardous levels (P = 0.02 and
P = 0.04).
Conclusions: The number of hospital admissions due to cardiovascular diseases can increase
during air pollution, especially when the concentrations of PM2.5 are elevated. (Iranian
Heart Journal 2020; 21(1): 75-81)
KEYWORDS: Fine particle, Cardiovascular diseases, Air pollution
1 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 2 Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 3 Department of Biostatistics and Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, IR Iran. 4 Hypertension Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, IR Iran. 5 Department of Anesthesiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IR Iran. 6 Road Traffic Injury Research Center and Department of Statistics and Epidemiology, School of Health, Tabriz University of Medical Sciences, Tabriz, IR Iran. 7 Isfahan Disaster Management Office, Isfahan Governer’s Office, Isfahan, IR Iran. 8 Khouzestan Department of Environment, Ahvaz, IR Iran. 9 Cancer Prevention Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran. 10 Information Technology Offices, Isfahan University of Medical Sciences, Isfahan, IR Iran.
*Corresponding Author: Sayed Mohsen Hosseini, PhD; School of Public Health, Isfahan University of Medical Sciences, Isfahan, IR Iran. Email: [email protected] Tel: 09133056890
Received: March, 2, 2019 Accepted: June 10, 2019
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ir pollution in cities is one of the
main health problems worldwide
and is defined as the presence of
harmful or excessive quantities of
substances in the earth’s atmosphere. 1 Air
pollution substances include coarse particles
(PM10: 2.5–10 micrometers), fine particles
(PM2.5: < 2.5 micrometers), and ultraPM2.5
(PM0.1: < 0.1 micrometers). 2
There is evidence indicating a remarkable
correlation between air pollution and
adverse cardiovascular events. 3-6
Epidemiological investigations have
revealed an increase in the level of the
incidence of arrhythmias, the duration of
hospitalization, and mortality and morbidity
after long-term exposure to polluted air. 7
Previous research has also demonstrated that
the inhalation of air pollutants may increase
platelet counts and activity, systemic
inflammation, and the level of oxidative
stress, which can lead to vascular damage,
atherosclerosis, and autonomic dysfunction. 8 In a case-crossover study, an increased
level of PM2.5 for 2 hours increased the risk
of myocardial infarction in 48% of cases. 9
Inhalation of air polluted substances can
decrease heart rates and increase blood
pressure. 10
Studies on the effects of air pollution on
cardiovascular diseases are divided into 2
groups: short-term investigations evaluating
the effects of acute exposure with polluted
air on health and long-term investigation
(eg, cohort studies) assessing the correlation
between air pollution and its chronic effects
on increasing cardiovascular disease risks.
Both of these studies have revealed the
significant relationship between excessive
exposure to polluted air and increased
mortality rates due to cardiovascular
diseases. 10,11
Cardiovascular diseases are prevalent in
Iran, and there is a well-known relationship
between air pollution and cardiovascular
diseases. 6,12
Isfahan is the third most
populated province of Iran with a population
of 2 240 249 in 2016. Isfahan is a great
industrial city featuring several different
industrial factories. 13
Indeed, the city is
surrounded by thermal power plants, steel
companies, cement plants, and oil refineries. 14
To assess air pollution in Isfahan, we
sought to evaluate patients in the majority of
hospitals in Isfahan. PM2.5 is an aqueous
ionic composition in the air that is used for
estimating organic masses in meteorology. 15
Previous studies that have evaluated the
correlation between air pollution and
cardiovascular diseases had small sample
sizes or evaluated the effects of specific
particles on cardiovascular diseases. In the
present study, we aimed to evaluate the
relationship between exposure to PM2.5 and
the number of hospital admissions due to
cardiovascular diseases.
METHODS
The present retrospective time-series case-
crossover study was conducted on the
correlation between air pollution and
cardiovascular and respiratory diseases (air
pollution and cardiovascular and respiratory
diseases: rationale and methodology of the
CAPACITY study). The CAPASITY study
is a comprehensive study on the correlation
between the presence of air pollutants and
hospitalization rates due to cardiovascular
and pulmonary diseases from 2010 to 2012. 16
The current study evaluated the findings
of the year 2012 because PM2.5 was
evaluated only during this year. The study
population consisted of patients admitted to
15 hospitals of the Iranian city of Isfahan
(Sina, Shariati, Sepahan, Askarieh, Amin,
Chamran, Sadoughi, Gharazi, Khanevadeh,
A
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Air Pollution and CVD Shirvani et al
77
Noor, Alzahra, Kashani, Amiralmomenin,
Isabne Maryam, and Feiz) because of
cardiovascular diseases in 2012. Participants
were selected via nonrandom convenience
sampling methods according to hospital
records. The inclusion criteria were as
follows 1) patients with the diagnosis of
cardiovascular diseases based on the
International Classification of Diseases -10
(ICD-10) criteria (International
Classification of Diseases, I00-I99 for
cardiovascular diseases) and 2) residence in
Isfahan city based on addresses in the
patients’ medical records. Patients with
incomplete clinical and paraclinical data
were excluded from this study. The study
protocol was approved by the Regional
Bioethics Committee of Isfahan University
of Medical Sciences (IUMS).
The medical records of patients with
cardiovascular disease diagnoses were taken
from hospital archives. Cardiovascular
diseases were comprised of hypertension,
ischemic heart diseases, conductive heart
diseases and heart blocks, heart failure, and
cerebrovascular disease with ICD-10 (I10-
I15), (I20-I25), (I44-I46), (I50), and (I60-
I69), respectively. The data extracted from
each medical record included demographic
data, as well as diagnostic and therapeutic
data. These data were extracted from paper
medical records or the Hospital Information
System (HIS). About 8 hospitals had HIS
and 7 hospitals had paper medical records.
About 10% of the medical records were
evaluated by cardiologists to assess the
diagnosis of the patients for the quality
control of the study.
Data regarding air pollution with PM2.5, air
temperature, and air humidity were extracted
from the archives of the weather and
pollution monitoring stations in Isfahan
from 2011 to 2012. Hourly records of air
pollutants were extracted from the air
pollution monitoring station archives and
managed in Microsoft Excel files by the lab
experts of Isfahan’s Department of
Environment. The data on PM2.5 were
recorded only in the year 2010. First, the
average 24-hour level of each station and
then the mean level of the PM2.5
concentration in Isfahan were calculated. All
the files related to 24-hour levels of different
stations and the whole Isfahan city were
finally used to evaluate the PM2.5
concentrations. The PM2.5 concentrations
were divided into 3 groups of good or
moderate, unhealthy for sensitive people,
and unhealthy or hazardous. 17
Time-series and case-crossover methods
were simultaneously applied for the data
analysis of all the objectives of the
CAPACITY study. The data analyses were
conducted using R version 3.2.3. A
confidence interval (CI) of 95% was
considered in both Poisson and conditional
regression methods. The Poisson regression
analysis was used to investigate the effect of
the PM2.5 concentration on per day
admission due to cardiovascular diseases,
and the first level of concentration
classification (good or moderate) was
considered the reference level. A 2-sided α
level of 0.05 was used to assess statistical
significance.
RESULTS
The current study evaluated 15752 hospital
patients at a mean age of 59 ± 19.4 years.
Men represented 52.6% (n = 8282) of the
study population. The mean wind speed,
temperature, and humidity were 5.46 ± 2.63
m/s, 60 ± 19.06 °F, and 25.56 ± 8.87%,
respectively. The distributions of the
cardiovascular diseases were as follows:
ischemic heart diseases (60.5%, n = 7580),
hypertension (15.8%, n = 1982),
cerebrovascular disease (12.3%, n = 1535),
heart failure (7.8%, n = 982), and conductive
heart diseases and heart blocks (3.6%,
n = 447).
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The mean concentration of PM2.5 was 53.77
± 29.65 micrometers. The concentration of
PM2.5 in the 1-year period was in the
classification of good or moderate,
unhealthy for sensitive people, and
unhealthy or hazardous in 102 (28%), 187
(51.4%), and 75 (20.6%) days in the year,
respectively.
The one-way ANOVA analysis did not show
any significant correlation between the
concentrations of PM2.5 and the number of
hospital admissions due to different
cardiovascular diseases (P = 0.68) (Table 1).
Table 1. Number of hospital admissions due to cardiovascular diseases in the different concentrations of PM2.5
P value
PM2.5 concentration
Cardiovascular disease Unhealthy or Hazardous Number (%)
Unhealthy for Sensitive People
Number (%)
Good or Moderate Number (%)
0.683
408(20.6) 1047(53.0) 522(26.4) Hypertension
1491(19.7) 4058(53.7) 2010(26.6) Ischemic heart diseases
97(21.7) 227(50.9) 122(27.4) Conductive heart diseases and heart blocks
188(19.2) 522(53.2) 271(27.6) Heart failure
306(20.0) 788(51.4) 438(28.6) Cerebrovascular diseases
The Poisson regression analysis had 3
models, as follows: a primary model without
considering confounding variables; an
analysis considering age and gender; and an
analysis considering age, gender, and
weather variables (wind speed, humidity,
etc). This analysis showed a significant
correlation between the number of per day
admissions due to all cardiovascular diseases
and PM2.5 concentrations in the level of
unhealthy for sensitive people in the 3
models (P = 0.001, P = 0.001, and P =
0.002). There was a statistically remarkable
correlation between the PM2.5 concentrations
and the number of per day admissions due to
ischemic heart diseases in the level of
unhealthy for sensitive people in the 3
models of analysis (P < 0.001, P < 0.001,
and P < 0.01). There was a nonsignificant
correlation between the PM2.5 concentrations
and the number of admissions due to
conductive heart diseases and heart blocks in
the first model (P > 0.05), but this
correlation was significant in the level of
unhealthy or hazardous in the other 2 models
(P = 0.02 and P = 0.04). There was no
significant correlation between the PM2.5
concentrations and the number of per day
admissions due to hypertension,
cerebrovascular diseases, and heart failure
(P > 0.05) (Table 2).
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Table 2. Poisson regression analysis for evaluating the correlation between the number of admissions and the type of
cardiovascular diseases
Cardiovascular Disease
PM2.5 concentration Primary Model Second Model Third Model
IRR(95%CI) P value IRR(95%CI) P value IRR(95%CI) P value
Hypertension
good or moderate 1 1 1
unhealthy for sensitive people
1.09 (0.98,1.22)
0.09 (0.95,1.22)
1.07 0.24
1.08 (0.94,1.24)
0.26
unhealthy or hazardous 1.06
(0.93,1.21) 0.35
1.00 (0.85,1.17)
0.98 0.98
(0.83,1.16) 0.80
Ischemic heart diseases
good or moderate 1 1 1
unhealthy for sensitive people
1.10 (1.04,1.16)
<0.001 1.11
(1.05,1.17) <0.001
1.08 (1.02,1.14)
0.01
unhealthy or hazardous 1.01
(0.94,1.08) 0.82
1.00 (0.94,1.07)
0.93 0.99
(0.93,1.07) 0.95
Conductive heart diseases
and heart blocks
good or moderate 1 1 1
unhealthy for sensitive people
1.01 (0.81,1.26)
0.89 1.31
(0.76,2.26) 0.33
1.29 (0.73,2.33)
0.38
unhealthy or hazardous 1.08
(0.83,1.41) 0.57
2.03 (1.13,3.66)
0.02 1.94
(1.03,3.63) 0.04
Heart failure
good or moderate 1 1 1
unhealthy for sensitive people
1.05 (0.91,1.22)
0.51 1.15
(0.91,1.44) 0.25
1.23 (0.96,1.57)
0.10
unhealthy or hazardous 0.94
(0.78,1.14) 0.54
1.06 (0.79,1.43)
0.68 1.15
(0.84,1.56) 0.39
Cerebrovascular diseases
good or moderate 1 1 1
unhealthy for sensitive people
0.98 (0.87,1.10)
0.75 1.03
(0.89,1.19) 0.71
1.03 (0.87,1.20)
0.76
unhealthy or hazardous 0.95
(0.82,1.10) 0.49
1.03 (0.86,1.25)
0.72 1.04
(0.85,1.26) 0.73
All types of cardiovascular
diseases
good or moderate 1 1 1
unhealthy for sensitive people
1.07 (1.03,1.12)
<0.001 1.07
(1.03,1.12) 0.001
1.06 (1.02,1.11)
0.005
unhealthy or hazardous 1.01
(0.96,1.06) 0.79
1.00 (0.95,1.05)
0.94 1.00
(0.94,1.06) 0.94
DISCUSSION
The present study evaluated the correlation
between PM2.5 concentrations and the
number of per day admissions due to
different cardiovascular diseases in the year
2012. We found a significant correlation
between PM2.5 concentrations and the
number of hospital admissions due to all
cardiovascular diseases, especially ischemic
heart diseases, in the level of unhealthy for
sensitive people. There was also a
significant correlation between the number
of hospital admissions due to conductive
heart diseases and heart blocks in the level
of unhealthy or hazardous PM2.5
concentrations.
Studies have demonstrated that more
exposure to air pollution can increase acute
cardiovascular events and exacerbate
chronic cardiovascular diseases. 8
Researchers have also evaluated the
relationship between air pollution and
cardiovascular diseases. Dominici et al 18
evaluated the relationship between air PM2.5
concentrations and the number of
hospitalization due to cardiovascular and
pulmonary diseases and revealed that an
increase of 10 μg/m3 in PM2.5 daily
concentrations could cause a 1.3% increase
in the number of hospitalization because of
heart failure. Another study on 7 cities in the
United States of America reported that a rise
of 10 μg/m3 in air pollution in a day could
cause a 0.7% increase in the number of
hospitalization due to congestive heart
diseases. 19
Another investigation showed a
significant increase in coronary artery
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Air Pollution and CVD Shirvani et al
80
disease complications after short-term
exposure to PM2.5 air pollution. 20
A study
on a sample of the Iranian population
revealed an annual mortality rate of 4.64%
owing to air pollutants. 21
Air pollution can increase the release of pro-
oxidative and pro-inflammatory mediators
from the lungs to the circulation and also
cause autonomic nerve systemic imbalances.
It has direct effects on the heart and triggers
the entrance of fine and ultraPM2.5 to the
systemic circulation. Oxidative stress
induction by these particles can lead to
impairment in coagulation and thrombosis. 22
Air pollution also increases heart rate,
decreases heart rate variability, and causes
endothelial dysfunction, arterial
vasoconstriction, apoptosis, and
hypertension. Acute exposure to air
pollution can cause plaque instability,
affecting the risk factors of cardiovascular
events, and chronic exposure to air pollution
causes atherosclerosis and hypertension. 8
In the current study, the relationship
between the number of hospital admissions
due to cardiovascular diseases and PM2.5 in
the level of unhealthy for sensitive people is
likely due to the fact that the number of days
with this level of air pollution was more than
that of other situations in the year 2012. The
CAPACITY study showed that the mean
annual pollutants in the years 2010 and 2011
were higher than the standard levels and the
mean concentrations of ozone, carbon
monoxide, and PM10 were lower in the year
2011 than in the year 2010, while the mean
levels of sulfur dioxide and nitrogen dioxide
were higher. 16
Our study had strengths and limitations. One
of the strengths of this study is its large
sample size, allowing the generalization of
the results to the general population.
Another strong point of this study is that we
evaluated each type of cardiovascular
diseases separately. Nonetheless, one of the
limitations of this study is that we
considered only PM2.5 as air pollution; if we
had taken into account all 3 types of
particles (coarse, fine, and ultrafine) and
evaluated the relationship between all these
particles and the number of hospital
admissions due to cardiovascular diseases,
we might have obtained more reliable results
concerning this relationship. In this study,
we did not distinguish between new cases of
cardiovascular diseases and the exacerbation
of previous cardiovascular diseases. Future
studies should take into consideration this
situation and evaluate the past medical
history of patients admitted during air
pollution because of cardiovascular diseases.
In conclusion, the number of hospital
admissions due to cardiovascular diseases
can increase during air pollution, especially
when the concentrations of PM2.5 have risen.
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Correlation Between Type II Diabetes and Left Heart Function Bayat et al
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Original Article Correlation Between Type II Diabetes and Left Heart Function Bayat et al
Correlation Between Type II Diabetes Mellitus and Left Atrial
Function as Assessed by 2D Speckle-Tracking Echocardiography
in Patients Without Coronary Artery Disease
Fariba Bayat1, MD; Mohammad Khani
1, MD;
Fatemeh Saffarian*1
, MD; Mohammad Amin Shahrbaf2, MD
ABSTRACT
Background: Diabetes mellitus (DM) is associated with several comorbidities and complications
such as hypertension, obesity, hyperlipidemia, nephropathy, and cardiovascular diseases.
This study aimed to investigate the correlation between the left atrial (LA) function and
DM via conventional and speckle-tracking echocardiography (STE).
Methods: In this prospective study, from 198 patients with sinus rhythms, 174 patients were
included based on inclusion and exclusion criteria. Conventional and STE examinations
were done for all the patients. The patients’ demographics, comorbidities, and family
history, as well as the results of their angiography or computed tomography angiography,
electrocardiography, and echocardiography, were recorded. The variables were compared
between the groups with and without DM, and the association between the LA function
and DM was studied in the patients.
Results: Totally, 45.2% of the diabetic patients (n = 28) and 38.4% of the nondiabetic patients
(n = 30) had diastolic dysfunction (P = 0.384). The diabetic patients had a lower mean of
the left ventricular end-diastolic diameter, the LA peak strain during the reservoir phase,
the LA pump, and the LA peak positive strain rate during ventricular systole
(all Ps < 0.001) and a higher mean of the left ventricular mass index, the A-wave, the
E/A, the LA peak negative strain rate during early diastole (all Ps <0.001), the left
ventricular end-systolic volume (P = 0.001), the Ea (P = 0.008), the LA ejection fraction
(P = 0.011), and the passive emptying volume (P = 0.026).
Conclusions: The results of the present study indicated LA and left ventricular dysfunction in
diabetic patients. However, the LA function may be affected by several factors, and our
nonrandomized patient selection could also have affected the results. Thus, it is suggested
that future randomized clinical trials compare the LA echocardiographic parameters in
matched groups. (Iranian Heart Journal 2020; 21(1): 82-93)
KEYWORDS: Diabetes mellitus, Left atrium, Atrial function, Echocardiography, STE 1 Department of Cardiology, Modarres Hospital Research and Development Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran. 2 Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
*Corresponding Author: Fatemeh Saffarian, MD; Fellow of Echocardiography, Echo Lab, Shahid Modarres Hospital and Cardiovascular Research Center, Yadegare-Emam Highway, Tehran, IR Iran.
Email: [email protected] Tel: 09125826180
Received: March 15, 2019 Accepted: June 26, 2019
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iabetes mellitus (DM) is one of the
world’s most common chronic
noncommunicable diseases with a
high prevalence in most developing
countries. 1 The prevalence of DM is
estimated to be on the rise because of the
increasing trend of diabetes risk factors,
obesity, and the aging of the populations. 2
In Iran, although the general prevalence of
DM is close to that of the global prevalence
(8%–9%), its prevalence surges in the
elderly and illiterate urban dwellers,
approaching nearly 20%. 3,4
In addition to
the high prevalence of DM, about one-third
of patients are not aware of their disease and
may be, thus, affected by the silent
complications; this issue is associated with a
great mortality rate. 5 The chronicity of
hyperglycemia in diabetic patients
predisposes them to numerous micro- and
macrovascular complications such as
nephropathy, retinopathy, neuropathy,
cardiomyopathy, and vasculopathy. 6,7
Furthermore, DM is associated with several
comorbidities including hypertension,
obesity, and hyperlipidemia, which increase
the risk of complications and mortality rates. 8
The cardiac complications of DM are the
most important diabetes-related
complications and the first cause of
mortality in diabetic patients, 9,10
with the
evidence suggesting a 5-fold increase in the
risk of myocardial infarction and ischemic
stroke and a 2- to 4-fold increase in the risk
of peripheral artery disease in diabetic
patients compared with nondiabetics. 11,12
Several pathophysiologies are suggested for
the etiology of cardiac complications in DM
like inflammation, reactive oxygen, and
endothelial dysfunction. 13-15
In addition to
the complexity of DM, a wide range of
changes is observed in diabetic hearts
including left ventricular (LV) systolic and
diastolic dysfunction (leading to heart
failure), cardiomyocyte hypertrophy,
myocardial interstitial fibrosis, and the
apoptosis of cardiomyocytes. 16,17
The effect of DM on the LV has been
studied and the role of LV dysfunction has
been confirmed in diabetic cardiomyopathy. 18,19
Nevertheless, there is insufficient
evidence on the importance of changes in
the left atrium (LA) in diabetic
cardiomyopathy. 20
Some studies have
shown no influence on the LA diameter, 21
while a significant increase in the LA index
has been observed in other studies. 22,23
Considering the lack of knowledge related to
the LV function in diabetic patients and the
predictive value of the LA in cardiovascular
events, we aimed to study the association
between LA dysfunction and DM in patients
with stable cardiac function by conventional
and speckle-tracking echocardiography
(STE) methods.
METHODS
Study Design
In this prospective study, patients who
referred to Modarres Hospital from March
2018 to July 2018 were considered the study
population. The study sample size was
calculated at 198. The inclusion criteria for
this study were as follows: patients with
sinus rhythms (determined according to the
electrocardiogram [ECG] taken at baseline),
an ejection fraction (EF) > 50% (determined
based on echocardiography taken at baseline
by the echocardiologist), and normal
coronary arteries over the past month
(determined based on angiographic or
computed tomography [CT] angiographic
assessments by the cardiologist). The
exclusion criteria for this study were as
follows: patients with atrial fibrillation or
flutter (based on the initial ECG), EF < 50%,
regional wall motion abnormalities, a left
ventricular end-diastolic diameter (LVEDD)
> 53 mm in women or > 58 in men,
moderate-to-severe valvular regurgitation
D
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and any degree of valvular stenosis,
myocardial hypertrophy with a septal
diameter > 12 mm or poor echo windows
(based on the initial echocardiography), a
history of ischemic heart disease
(myocardial infarction, stent implantation,
and coronary artery bypass graft surgery), a
history of stroke, peripheral artery disease,
uncontrolled blood pressure (> 160/110 mm
Hg), chronic renal or liver or lung disease,
and pregnancy. Accordingly, 24 patients
were excluded from the study: 14 had a poor
echocardiographic view, 6 had moderate-to-
severe valvular disease, and 4 had moderate-
to-severe hypertrophy. Finally, a total of 174
patients were investigated.
Primary Assessment
An ECG was recorded from all the patients
at the baseline of the study. Furthermore, the
height and weight of all the samples were
recorded for calculating the body surface
area (BSA). In addition, the researcher
recorded the patients’ demographics (age
and sex), comorbidities (hyperlipidemia,
hypertension, smoking, DM, and obesity),
drug history, familial history of
cardiovascular diseases, and the duration of
DM in diabetic patients from the patients’
medical records. Systolic pressure > 140
mm Hg and diastolic pressure > 90 mm Hg
were considered high blood pressure. 24
Moreover, the diagnosis of DM was made in
accordance with the American Diabetes
Association criteria. 25
Echocardiographic Assessment
Echocardiography was performed by
conventional and STE methods (Siemens®,
Health Care Acuson SC2000). STE was
performed using eSie VVI software. All the
patients had sinus rhythms during
echocardiography, and an ECG lead
constantly recorded the patients’ ECG.
Echocardiography was done in the left
lateral position based on the American
Society of Echocardiography protocol. 26
In
addition, the LV and LA volumes were
measured and interpreted based on the BSA.
Conventional Echocardiography
The ventricular details recorded in the
conventional method were comprised of
systolic parameters: the LVEDD, the LV
end-systolic diameter, the LV end-diastolic
volume, the left ventricular end-systolic
volume (LVESV), the interventricular septal
end-diastole, the diastolic posterior wall
thickness diameter (PWTd), the left
ventricular mass index (LVMI), and the left
ventricular ejection fraction (LVEF). The
LVMI was measured as , and the
LVM was calculated based on the following
equation 26-28
:
0.8×1.04 [(LVIDd + LVPWTd + IVSTd)3− (LVIDd)
3]+0.6.
The ventricular diastolic parameters
consisted of diastolic dysfunction (DD), the
deceleration time (DT), the S wave, and E
and A waves and their ratio (E/A, Ea, and
E/Ea).
The atrial details recorded encompassed the
LA diameter, which is the maximum
diameter of the LA in the parasternal long-
axis view, the LA volume index or LAVmax,
the left atrial minimum volume (LAVmin),
the left atrial stroke volume (LASV) or the
total emptying volume (TEV) (which is
calculated based on the following formula:
LAVmax- LAVmin and represents the LA
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reservoir function), the left atrial volume
before atrial contraction (LAVpreA), the left
atrial ejection fraction (LAEF) or the active
ejection fraction (AEF) (which is calculated
based on the following algorithm:
and describes the pump
function of the LA at the end of diastole),
the left atrial emptying fraction or total
ejection fraction (TEF) (which is estimated
as LASV/LAVmax and indicates the reservoir
function of the LA during systole), the
active emptying volume (AEV) (which is
calculated based on the following formula:
LAVpreA- LAVmin and describes the pump
function of the LA), the passive emptying
volume (PEV) (which indicates the conduit
role of the LA in early diastole and is
calculated according to the following
formula: LAVmax-LAVpreA), and the passive
ejection fraction (PEF) (which describes the
conduit role of the LA in early diastole and
is calculated according to the following
formula: ). 26
STE
STE was done by using eSie VVI software.
The STE images were recorded in 3 cardiac
cycles at a frame rate (FR) of 40–60. For the
assessment of the strain (S) and strain rate
(SR) of the LA, the endocardium and
epicardium were traced manually and
automatically, respectively. The assessment
of the S and SR of the LA was performed
after the LA was automatically divided into
6 segments. The parameters that were
evaluated by STE were as follows: the left
atrial peak positive strain rate during
ventricular systole (LASRS), the left atrial
peak negative strain rate during early
diastole (LASRE), the left atrial peak
negative strain rate during late systole
(LASRA), the left atrial peak strain during
the reservoir phase (LARES) (before mitral
opening), and the left atrial peak strain
during the pump phase (LA-pump).
Statistical Analysis
The results were presented as the mean ± the
standard deviation (SD) for the quantitative
variables and were summarized as
frequencies (percentages) for the categorical
variables. The patients were categorized into
2 groups of diabetic and nondiabetic, and the
categorical variables were compared
between these 2 groups using the χ2
or Fisher
exact test. Additionally, according to the
one-sample Kolmogorov–Smirnov test, the
data were not normally distributed (P <
0.05); therefore, for the comparison of the
numeric variables between the 2 groups with
and without DM, the Mann–Whitney U test
was used. The correlation between the
variables was tested using the Spearman
correlation coefficient. For the statistical
analyses, the statistical software IBM SPSS
Statistics for Windows, version 21.0, (IBM
Corp 2012. Armonk, NY: IBM Corp) was
used. A P value ≤ 0.05 was considered
statistically significant.
Ethical Considerations
Before the enrollment of the patients into the
study, the design and objectives of the study
were explained to all the participants and
written informed consent was obtained from
those who were willing to participate in the
study. The patients were reassured that they
were free to leave the study whenever they
wished to and that their participation would
not affect their routine care at the medical
center. All the ethical principles of
Helsinki’s declaration on human studies
were met throughout the study. The protocol
of the study was approved by the Ethics
Committee of Shahid Beheshti University of
Medical Sciences.
RESULTS
Among 174 patients, whose details were
analyzed, 96 (55.2%) patients were male and
78 (44.8%) patients were female. The mean
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age of the patients was 53.71 ± 9.21 years
(range = 29–75 y). DM was reported in 62
(35.6%) patients. The results of the Mann–
Whitney U test indicated that the mean age
of the patients was not significantly different
between the groups with and without DM
(54.40 ± 8.23 vs 53.32 ± 9.72 y,
respectively; P = 0.345). Similarly, the
frequency of male and female patients was
not different between the groups with and
without DM (P = 0.374). Table 1
demonstrates the frequency of
comorbidities. The comparison of the
demographics and the frequency of
comorbidities between the patients with and
without DM showed no statistically
significant difference between the groups
(Table 1).
Table 1. Frequency of the patients’ sex and history of underlying diseases
Variable Total, No.
(%) Diabetic Patients
Nondiabetic Patients
P value
Sex Male 96 (55.2%) 37 (59.7%) 59 (52.7%)
0.374 Female 78 (44.8%) 25 (40.3%) 53 (47.3%)
Comorbidities
Hypertension 63 (36.2%) 23 (37.1%) 40 (35.7%) 0.856
Hyperlipidemia 35 (20.1%) 10 (16.1%) 25 (22.3%) 0.329
Smoking 31 (17.8%) 7 (4.02%) 24 (13.79%) 0.094
Family history 18 (10.3%) 1 (1.6%) 17 (15.2%) 0.005
Obesity 23 (13.2%) 5 (8.1%) 18 (16.1%) 0.135
At the baseline of the study, 45% (n=28) of
the diabetic patients received insulin and
81% (n=50) received oral antidiabetic
agents. The mean BSA was 1.88 ± 1.54 m2
(mean ± SD); the results of the Mann–
Whitney U test indicated that the mean BSA
of the patients was not significantly different
between the groups with and without DM
(2.09 ± 2.57 vs 1.77 ± 0.13 m2, respectively;
P = 0.968).
A total of 70 (40.8%) patients had diastolic
dysfunction, and the results of the χ2
test
showed that the frequency of diastolic
dysfunction in the studied patients was not
significantly different between the groups
with and without DM (45.2% vs 38.4%,
respectively; P = 0.384).
The echocardiographic parameters of the LV
compared between the groups with and
without DM are demonstrated in Table 2. As
is shown in Table 2, the mean values of the
LVEDD (P < 0.001) and the Ea (P = 0.008)
were higher in the nondiabetic patients and
the mean values of the LVMI, the A wave,
the E/A (all Ps < 0.001), and the LVESV (P
= 0.001) were higher in the diabetic patients,
while the other echocardiographic
parameters including the deceleration time
(DT), the E/Ea, and the S wave were not
significantly different between the groups
(P > 0.05).
The echocardiographic parameters of the LA
compared between the groups with and
without DM are demonstrated in Table 3.
The LARES, the LA-pump, the LASRS, and
the LASRE (all Ps < 0.001) were higher in
the nondiabetic patients. In addition, the
LAEF (P = 0.011) and the PEV (P = 0.026)
were higher in the diabetic patients. The
other parameters of the LA were not
significantly different between the groups
(P > 0.05).
The correlations between DM and the LA
echocardiographic parameters are presented
in Table 4. As is depicted, the Spearman
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correlation coefficient showed that DM had
a significant association with the LASRE,
the LA-pump, the LARES, and the LASRS
(all Ps < 0.001) (Table 4).
Table 2. Comparison of the values of the LV echocardiographic measures between the patients with and without
diabetes
Variable Total Diabetic Patients
Nondiabetic Patients
P value**
LVEDD (mm) 48.28±6.08 45.24±7.96 49.96±3.85 <0.001
LVESD (mm) 29.48±3.94 29.69±5.19 29.37±3.04 0.573
IVSD (mm) 10.00±1.78 10.21±1.91 9.88±1.79 0.322
PWI (mm) 8.3678±1.73 8.71±1.82 8.17±1.65 0.074
LVMI 80.27±7.29 83.98±8.83 78.22±5.29 <0.001
LVEDV (cc) 72.05±6.32 73.34±7.80 71.33±5.23 0.237
LVESV(cc) 25.86±3.78 27.45±4.31 24.99±3.15 0.001
LVEF % 59.45±3.05 59.98±2.03 59.15±3.46 0.069
Peak E wave velocity (cm/s) 69.85±15.48 69.50±15.67 70.04±15.45 0.957
Peak A wave velocity (cm/s) 68.76±18.12 75.38±17.85 65.06±17.26 <0.001
Septal e' wave (Ea) (cm/s) 7.91±1.78 7.42±1.74 8.18±1.75 0.008
E/A 1.65±7.70 2.53±12.84 1.16±0.80 <0.001
E/Ea 8.49±2.27 8.89±2.45 8.26±2.13 0.065
D.T (ms) 147.33±26.40 152.14±31.74 144.63±22.60 0.208
Septal S' wave (cm/s) 7.42±1.00 7.24±1.09 7.52±0.93 0.278
LVEDD, Left ventricular end-diastolic diameter; LVESD, Left ventricular end-systolic diameter; IVSD, Interventricular septal end-diastole; LVEDV, Left ventricular end-diastolic volume; LVESV, Left ventricular end-systolic volume; LVIDd, Left ventricular diastolic internal diameter; PWI, Diastolic posterior wall thickness; LVMI, Left ventricular mass index; LVEF, Left ventricular ejection fraction; DT, Deceleration time ** The results of the Mann–Whitney U test
Table 3. Comparison of the values of the LA echocardiographic measures between the patients with and without
diabetes
Variable Total Diabetic Patients
Nondiabetic Patients
P value**
LA diameter 3.87±4.61 4.94±7.62 3.27±0.38 0.912
LAVI 26.77±5.91 27.05±6.18 26.62±5.77 0.751
LAVmin 11.93±3.83 11.50±4.23 12.16±3.59 0.147
LAVpreA 17.96±4.74 17.72±5.13 18.09±4.53 0.556
LAEF (AEF) 36.66±5.66 38.16±7.62 35.83±4.01 0.011
LAS.V 15.12±2.50 15.53±3.15 14.89±2.05 0.106
LATEF (TEF) 58.01±4.99 58.24±6.87 57.89±3.58 0.195
AEV 5.97±1.45 6.24±1.71 5.82±1.26 0.154
PEV 8.57±2.46 9.21±3.83 8.22±1.01 0.026
PEF 33.23±4.37 33.48±5.90 33.09±3.25 0.386
LARES 46.54±4.03 44.35±4.65 47.75±3.04 <0.001
LA-pump 18.70±2.64 17.22±3.16 19.52±1.86 <0.001
LASRS 2.53±9.64 1.29±0.58 3.22±11.98 <0.001
LASRE -1.32±0.71 -0.96±0.58 -1.51±0.72 <0.001
LASRA -1.48±0.69 -1.51±0.75 -1.46±0.66 0.586
LAVI, Left atrial volume index; LAVmin, Left atrial minimum volume; LAVpreA, Left atrial volume pre-atrial contraction; LAEF, Left atrial ejection fraction; AEV, Active emptying volume; PEV, Passive emptying volume; PEF, Passive ejection fraction; LASV, Left atrial stroke volume; LARES, Left atrial peak strain during the reservoir phase; LA-pump, Left atrial peak strain in the late diastolic pump; LASRS, Left atrial peak strain during systole; LASRE, Left atrial peak strain during diastole; LASRA, Left atrial peak strain during atrial systole ** The results of the Mann–Whitney U test
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Table 4. Correlations between diabetes mellitus and
echocardiographic parameters
Variable Spearman Coefficient
P value
LARES 0.348 <0.001
LA-pump 0.416 <0.001
LASRS 0.277 <0.001
LASRE -0.397 <0.001
LASRA -0.41 0.587
LARES, Left atrial peak strain during the reservoir phase; LA-pump, Left atrial peak strain in the late diastolic pump; LASRS, Left atrial peak strain during systole; LASR-D, Left atrial peak strain during diastole; LASR-A, Left atrial peak strain during atrial systole
DISCUSSION
The results of the present study showed that
among patients with a stable cardiac
condition (sinus rhythms, LVEFs > 50%,
and normal coronary arteries), the mean
values of the LVEDD, the LARES, the LA-
pump, and the LASRS were higher in the
nondiabetic patients and the mean values of
the LVMI, the A wave, the E/A, the
LASRE, the LVESV, the Ea, the LAEF, and
the PEV were higher in the diabetic patients.
These results indicated that diabetic patients
have several alterations in their LV
including higher LV hypertrophy and LV
dysfunction and several alterations in their
LA, as discussed further.
Several roles have been established for the
LA. It acts as a reservoir for the pulmonary
venous return during the LV contraction and
isovolumetric relaxation, transfers blood
passively into the LV, and contributes to
15%–30% of the LV stroke volume by its
contraction during the final phase of
diastole; therefore its size and function
imply LV compliance. 29
According to the
evidence, the LA volume (size) is an
appropriate predictor of adverse
cardiovascular outcomes 30,31
and the LA
function (indexed to the BSA) is associated
with LV dysfunction, especially diastolic
heart failure. 23,32
However, only a few
studies have evaluated LA changes in
diabetic patients.
A study by Gulmez et al 33
compared the
echocardiographic parameters of 56 diabetic
patients with 56 controls. The results
showed higher LA diameter, indexed Vmax,
LAVpreA, LAVmin, AEV, and TEV in the
diabetic patients, while the A and E waves
and their ratio were not different between
the groups. Furthermore, Gulmez and
colleagues 34
reported high LA diameter,
indexed Vmax, LAVpreA, LAVmin, AEV, and
TEV in their patients with prediabetes (n =
114) compared with their 70 controls. These
results are regarding several LA changes in
diabetic patients and no difference in the LA
function between patients with and without
(pre)diabetes. However, these are not
associated with the current study, as we
found significant differences between the
groups in the A and E waves and their ratio
(A wave, E/A, and Ea), without significant
differences in the LAVpreA, the LAVmin, and
the AEV. Nevertheless, the differences
between our results and those of Gulmez et
al 33,34
could be associated with several
factors such as the duration of diabetes 35
and differences in the patients’ body mass
index and age, which can affect the LA
function. 36
In addition, the results of a study
by Kadappu et al, 37
in line with the present
study, indicated significant differences in the
E and A waves and their ratio between
diabetic patients and controls.
According to the previous studies, the
duration of DM has a significant role in LA
enlargement 35
and patients who show no
change in the LA diameter after 5 years’
follow-up have significant changes after 20
years. 22
Therefore, no difference in the LA
function between the groups in our study
could be attributed to several factors
affecting the LA diameter and function in
diabetic patients.
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Significant changes in the LA of diabetic
patients in the present study included lower
LARES, LA-pump (indicating the LA pump
function), and LASRS (indicating the LA
reservoir function), but higher LASRE
(indicating the conduit function), LAEF, and
PEV. Particularly, all the significant
differences between the groups were in the
STE parameters. Similar to these results,
Mondillo et al 38
reported reduced LASRS,
LARES, LA-pump, and LASRD in patients
with hypertension and DM with normal LA
volumes (< 28 mL/m2). Kadappu et al
37 also
indicated lower strain parameters in all 6
parameters and a higher LA volume index in
diabetic patients. These results are consistent
with those of ours, indicating several LA
strain reductions in diabetic patients.
Nevertheless, patients with DM had higher
LASRE, LAEF, and PEV than the control
group. A study by Liu et al 39
demonstrated
lower LASRS and LARES in diabetic
patients without significant differences in
the LA-pump. These differences in the LA
STE parameters between the studies on
diabetic patients may be related to the
accuracy of different imaging methods. 20
Studies have suggested that the accuracy of
LA mechanics measurement by 2D and 3D
echocardiography is comparable to that of
CT imaging. 40,41
Furthermore, the
measurement of strain rates by STE is
considered a simple, feasible, sensitive, and
reliable method for the evaluation of LA
deformation 42
and the prediction of
cardiovascular adverse events, 43
atrial
fibrillation, and stroke. 44, 45
Additionally,
LA strain is associated with LV diastolic
dysfunction. 46
Thus, impaired LA
deformation, as indicated by LA strain in the
present study, is considered to be the most
important finding, indicating LV diastolic
dysfunction in diabetic patients.
Considering LV measurements, the results
of our study showed a greater LVEDD in the
nondiabetic patients and greater LVESV and
LVMI in the diabetic patients. The results of
a cohort study by Inoue et al 47
indicated the
LVEDD as an independent predictor of all-
cause mortality, better than other
echocardiographic parameters. The LVESV,
indicating LV dysfunction, is also
recommended as a more accurate parameter,
considering the shortcomings in the
measurement of the LV end-systolic
diameter. 48
The LVMI, indicating LV
hypertrophy, is associated with a greater LA
dimension and lower systolic and diastolic
functions and is, thus, regarded as a
predictor of heart failure. 49
The results
obtained in the present study regarding LV
changes also indicate significant LV
dysfunction in diabetic patients, which is
consistent with the results of previous
studies. 18,19,50
While the present study successfully
compared 2 groups of diabetic and
nondiabetic patients with similar baseline
characteristics, this study, like any other,
may have several limitations. One of the
important limitations of the study is
nonrandomized patient selection and
grouping, which could have affected the
results. Moreover, the LA appendix was not
evaluated in the current study. It is,
therefore, recommended that future studies
take this factor into account. The positive
point of the current study is that we
considered any factors that could influence
the results as the exclusion criteria to reduce
the effect of confounding variables.
CONCLUSIONS
The results of the present study showed that
the diabetic patients had a lower mean
LVEDD and a higher mean LVESV and
LVMI, indicating LV dysfunction in the
diabetic patients. Studying LA parameters
showed that the LA volume and function
were not impaired in the diabetic patients.
Additionally, the LAEF and the PEV were
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higher in the diabetic than in the nondiabetic
patients. Meanwhile, strain LA
measurements showed lower LARES, LA-
pump, and LASRS, but a higher LASRE.
These results indicate several LA and LV
dysfunction in diabetic patients. However,
the LA function may be affected by several
factors and our nonrandomized patient
selection could also have affected the
results. Thus, it is suggested that future
randomized clinical trials compare LA
echocardiographic parameters in matched
groups.
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Original Article Prevalence of Anemia in Cardiac Surgery Sadeghi et al
Prevalence of Anemia in Patients Undergoing Cardiac Surgery
and Need for Transfusion During Surgery Regarding Hemoglobin
Levels in Rajaie Heart Center
Ali Sadeghi1, MD; Rasool Ferasatkish
1, MD; Avaz Heydarpour
1, MD;
Rasoul Azarfarin2, MD; Mohsen Ziyaeifard
1, MD; Zahra Faritous
1, MD;
Fatemehshima Hadipourzadeh*1, MD
ABSTRACT
Background: Bleeding occurs during and after cardiac surgery, resulting in postoperative
anemia. If patients have preoperative anemia, the need for blood transfusion increases.
Transfusion is associated with several complications.
Methods: In this study, severe anemia was defined as hemoglobin (Hb) < 8 g/dL, moderate
anemia was defined as Hb = 8–10 g/dL, and mild anemia was defined as Hb = 10–12
g/dL for women and Hb = 10–13 g/dL for men. In the entire study population, the need
for transfusion according to the Hb level and the amount of blood transfusion were
evaluated. The study aimed to determine the association between anemia and the
patients’ age, sex, type of surgery, and weight.
Results: In this study, 306 patients were evaluated in a 3-month period. The mean Hb level of
the patients was 13.1 g/dL (12.08–14.2), and the mean hematocrit level was 39.5%
(36.17–42.15). Anemia was reported in 32.4% of the patients (Hb < 12 g/dL for women
and Hb < 13 g/dL for men). According to the anemia classification, 90.9% of the anemic
patients had mild anemia, 8.1% moderate anemia, and 1% severe anemia. Of the 306
patients, 68.6% did not need to receive packed red blood cells. Additionally, of the 207
patients who were not included in the anemia group, 44 (21.2%) cases received packed
red blood cells due to surgical bleeding. However, of the 99 patients who were anemic,
52 (52.52%) cases needed packed red blood cells.
Conclusions: In the present investigation, about one-third of the study population had anemia
before surgery and these patients required blood transfusion 2.5 times more than those
without anemia. (Iranian Heart Journal 2020; 21(1): 94-102)
KEYWORDS: Anemia, Transfusion, Cardiac surgery
1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
2 Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR
Iran.
*Corresponding Author: Fatemehshima Hadipourzadeh , MD; Fellows of Cardiac Anesthesia, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Vali-Asr Ave, Tehran, IR Iran.
Email: [email protected] Tel: 09166166541
Received: March 15, 2019 Accepted: June 22, 2019
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Prevalence of Anemia in Cardiac Surgery Sadeghi et al
95
According to the World Health
Organization, anemia is defined as
hemoglobin (Hb) < 12 g/dL in women and
< 13 g/dL in men. Preoperative anemia can
be due to several reasons such as iron
deficiency or gastrointestinal bleeding. The
incidence of preoperative anemia in cardiac
surgery ranges between 25% and 32%. 1
Various observational studies have reported
that preoperative anemia is related to
increased neurological and renal
complications. 2,3
Anemic patients have
higher early and late mortality rates than
non-anemic patients undergoing cardiac
surgery. 4 During cardiac surgery, because
of hemostatic abnormalities, intra- and
postoperative bleeding is usually seen,
which can result in postoperative anemia. In
a previous study, up to 44% of the patients
had anemia in the postoperative period. 5
Another investigation reported that every 1
mg/dL decrease in the Hb concentration was
associated with a 13% increase in
cardiovascular events and a 22% increase in
all-cause mortality. 6
Although blood transfusion is necessary in
cardiac surgery, various studies have found
that it also has side effects. In these studies,
the transfusion of red blood cells (RBCs)
was dose-dependently related to
postoperative infections such as
mediastinitis, respiratory infection, and
sepsis and higher mortality. 7,8
Moreover, the
transfusion of packed RBCs is reported to
increase the length of hospital stay. 9
Some authors have described the importance
of a careful preoperative assessment because
it can reduce the risk of bleeding and the
requirement for blood transfusion during the
postoperative period. The evaluation of
serum iron and iron administration and
preoperative erythropoietin may reduce the requirement for transfusion.
10
The aim of the present study was to
determine the prevalence of anemia in
patients undergoing cardiac surgery in
Rajaie Cardiovascular, Medical, and
Research Center, Tehran, Iran, in 2018 to
prevent anemia in preoperative protocols
and treatments for anemia and to reduce the
need for transfusion.
METHODS
In this study, patients after the admission,
blood sample were sent to the laboratory and
the hemoglobin level In this study, severe
anemia was defined as hemoglobin (Hb) < 8
g/dL, moderate anemia was defined as Hb =
8–10 g/dL, and mild anemia was defined as
Hb = 10–12 g/dL for women and Hb = 10–
13 g/dL for men. In this study, the
demographic and clinical variables and the
type of operation of the patients were also
considered and anemia relationship with the
mentioned cases was considered. During the
surgery, the duration of CPB and patient's
need for blood transfusion were recorded
during surgery, and with this, the need for
transfusion was evaluated.
The criteria for entering the plan were all
patients 18 years of age and older who were
referred for coronary surgery and valve
operation or together at the same time
(coronary artery bypass graft surgery and
valve surgery) for elective surgery.
Exit criteria for this study included patients
with congenital heart disease, emergency
patients, Patients who have received blood
transfusion before surgery, patients treated
for anemia, and patients undergoing dialysis.
RESULTS
This research project evaluated 306 patients,
comprised of 197 (64.4%) male and 109
(35.6%) female patients, over a period of 3
months. The average age of the patients was
60 (52–67) years, the mean height was 167
(160–173) cm, the mean weight was 74
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(65–83) kg, and the mean body mass index
was 26 (24–29).
Diabetes mellitus was reported in 5.9% of
the patients and hypertension in 5.2%. Of
the 306 patients, coronary artery bypass
graft surgery (CABG) was performed on
246 (80.4%) patients, 35.9% of whom had 1
graft, 2.9% had 2 grafts, 28.1% had 3 grafts,
12.4% had 4 grafts, and 1% had 5 grafts.
Mitral valve replacement was performed on
51 (16.7%) patients, aortic valve
replacement on 31 (10.1%), tricuspid valve
replacement on 12 (3.9%), and the Bental
surgery on 8 (2.6%). The mean duration of
surgery was 6 hours, the mean duration of
the pump was 83 (110–160) minutes, and
the mean cross-clamping time was 45 (32–
61) minutes.
The study population had a mean Hb level
of 13.1 (12.08–14.2) g/dL and a mean
hematocrit level of 39.5 (36.17–42.15).
Anemia was reported in 32.4% of the study
population. According to the classification
of anemia based on Hb levels (See
Methods), 90.9% of the patients had mild
anemia, 8.1% had moderate anemia, and 1%
had severe anemia.
No significant relationships existed between
anemia and the variables of age, the body
mass index, the duration of surgery, the
duration of bypass, and the duration of
cross-clamping.
In terms of gender, in the anemia group,
58.6% of the patients were male and 41.1%
female; there was no significant relationship
between sex and anemia (P = 0.143).
Additionally, 9.1% of the patients had
anemia and diabetes, and there was no
significant relationship between diabetes and
anemia in this study (P = 0.099). Anemia
and hypertension were reported in 10.1% of
the patients; the relationship between
hypertension and anemia was significant
(P = 0.08). No significant association was,
however, found between the type of surgery
and anemia, nor was there any significant
association between the number of grafts
and anemia in the post-CABG patients
(P = 0.878).
Table 1. Demographic and clinical characteristics of the patients
P value Non-anemic Group (n=207)
Anemic Group (n=99)
0.105 59(52-66) 61(54-69) Age (y) Median (range)
0.143 67.1 % 58.6 % Sex(male)
32.9% 41.1% Sex(female)
0.283 27(24.4-29.4) 26(24.3-29.4) BMI Median (range)
0.671 6(5-6) 6(5-6) Operation time(h) Median (range)
0.741 85(60-110) 80(60-110) CPB time(min) Median (range)
0.882 45(31-63) 44(32-60) Aortic cross-clamp time (min) Median (range)
0.099 4.3% 9.1% DM
0.008 2.9% 10,1% HTN
0.096 77.8% 85.9% CABG
0.870 16.4% 17.2% MVR
0.990 10.1% 10.1% AVR
0.242 4.8% 2% TVR
0.652 2.9% 2% Bental procedure
BMI, Body mass index; CPB, Cardiopulmonary bypass; DM, Diabetes mellitus; HTN, Hypertension; CABG, Coronary artery bypass; MVR, Mitral valve replacement, AVR, Aortic valve replacement; TVR, Tricuspid valve replacement
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Of the 207 patients who were not in the
anemia group, 44 (21.2%) cases received
packed RBCs. Of the 99 patients in the
anemia group, 47 (47.47%) patients did not
need to receive packed RBCs: 97.9% were
in the mild anemia group, 2.1% in the
moderate anemia group, and 0.0% in the
severe anemia group. Fifty-two (52.52%) of
the 99 patients in the anemia group needed
blood transfusion. The patients who needed
1 blood unit comprised 82.5% of the mild
anemia group, 15% of the moderate anemia
group, and 2.5% of the severe anemia group.
The patients who needed 2 blood units
comprised 90.9% of the mild anemia group,
9.1% of the moderate anemia group, and
0.0% of the severe anemia group. The
patients who needed to receive 4 blood units
comprised 100% of the mild group. In this
study, there was no significant relationship
between the severity of anemia and the need
for more blood units (P = 0.362).
The results revealed that about one-third of
the study population had anemia before
surgery and those with anemia were in need
of blood transfusion 2.5 times more than
those without anemia.
DISCUSSION
In this research project, 306 patients were
studied over a period of 3 months. Anemia
was reported 32.4% of the study population.
According to the anemia classification based
on the Hb level (severe anemia: Hb < 8
g/dL, moderate anemia: Hb = 8–10 g/dL,
and mild anemia: Hb = 10–12 g/dL for
women and Hb = 10–13 g/dL for men), of
the patients with anemia, 90.9% had mild
anemia, 8.1% had moderate anemia, and 1%
had severe anemia. Our results demonstrated
no relationship between anemia and the
variables of gender, the body mass index,
the type of surgery, the duration of surgery,
the duration of bypass, and the duration of
cross-clamping. Our results showed no
relationship between anemia and the
underlying disease of diabetes; nonetheless,
we found a significant correlation between
anemia and hypertension (P = 0.08). Our
patients with anemia were also more likely
to require blood transfusion during the
operation, although there was no significant
relationship between the severity of anemia
and blood intake. The transfusion of blood is
commonly performed in heart surgery, but
many studies have associated it with such
side effects as an increased risk of infectious
occurrences (eg, mediastinitis, respiratory
infection, and sepsis), atrial fibrillation,
acute renal failure, cerebrovascular accident,
and acute respiratory distress syndrome, as
well as with an increased length of hospital
stay. 9
A study on 502 patients who underwent
elective cardiac surgery reported that 60% of
the patients had received blood during the
first 72 hours of surgery. 11
In that study,
those who received blood were more likely
to be old, to be female, to need re-surgery, to
have complicated surgery, to have elevated
EuroSCOREs, to have lower levels of Hb
and hematocrit, and to suffer the incidence
of renal disease. In addition, the patients
who received packed RBCs in the first 72
hours after surgery had a higher incidence of
complications such as renal failure,
cardiogenic shock, acute respiratory distress
syndrome, infections, and neurological and
inflammatory complications. Also in that
study, the length of hospital stay was
increased in the patients who received more
than 3 units of packed RBCs (nearly 6 days)
and in the patients who received fewer or up
to 3 units of packed RBCs (up to 1 day)
compared with the patients not on packed
RBCs.
A recent research on 798 hospitals in the
United States for the evaluation of blood and
blood products reported that in the hospitals
performing at least 100 CABGs on
cardiopulmonary bypass (n = 82 446 cases),
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the rates of packed RBC transfusion ranged
from 7.8% to 92.8% for RBCs, from 0% to
97.5% for fresh frozen plasma, and from
0.4% to 90.4% for platelets. 12
In that study,
after adjustments for the patients’ risk
factors, the amount of transfusion in the
hospital varied because of the patients’
geographic locations (P = 0.007) and
academic status (P = 0.03), as well as the
hospital volume (P < 0.001). Also in that
investigation, a higher number of packed
RBCs was associated with female gender,
older age, need for re-surgery or complex
operations, elevated EuroSCOREs, renal
disease, and previous anemia. This finding
highlights the need for further efforts to
improve perioperative care in these
subgroups of patients to avoid blood
transfusion, which leads to complications
such as increased lengths of stay in the
hospital. 13
Guidelines from the Society of Thoracic
Surgeons and the Society of Cardiovascular
Anesthesiologists emphasize the deficiency
of evidence on transfusion triggers after
cardiac surgery. 14
Most transfusion
indications occur in the first 72 hours
postoperatively, starting in the operating
room, where usually the transfusion
indication is due to hemodilution and based
on triggers. 15
The principle for
implementing a restrictive transfusion
strategy is based on the analysis of studies
reporting a deficiency of benefits and, at the
same time, considerably increased costs and
side effects allied to the transfusion of
packed RBCs. These side effects include
acute hemolytic and non-hemolytic
reactions, the transmission of viral and
bacterial diseases, transfusion-associated
acute lung injury, and transfusion with
circulatory overload. 16
Immunosuppression
has also been related to transfusion and may
explain the higher risk of infection and the
recurrence of neoplastic diseases in
transfused patients. 17
In a study on 11 963
patients who underwent isolated CABG,
Koch et al 18
explained that the perioperative
transfusion of packed RBCs was associated
with a dose-dependent increased risk of
cardiac complications after surgery, critical
infections, renal failure, neurological
complications, overall morbidity, prolonged
mechanical ventilation, and in-hospital
mortality. In a retrospective study, Murphy
et al 19
showed that the transfusion of packed
RBCs was strongly associated with
infections, postoperative ischemic
morbidity, hospital stay, early and late
mortality, and hospital charges. De Cocker
et al 20
performed a retrospective analysis on
1566 patients undergoing cardiac surgery
and demonstrated that age > 75 years,
female gender, New York Heart Association
functional class > II, arrhythmias, mitral
regurgitation, requirement for inotropic
support or intra-aortic balloon pumps, non-
elective procedures, and aortic surgery were
the predictive factors for a prolonged stay in
the intensive care unit. Although blood
transfusion was not a potential predictor of
increased lengths of stay in the hospital in
the current study, a prolonged hospital
length of stay merits evaluation because of
its correlation with increased costs and
clinical complications such as exposure to
infectious agents. 21
Previous research has underscored the
significance of meticulous preoperative
assessments with a view to reducing the risk
of bleeding and the need for blood
transfusion during the postoperative period.
22,23 Indeed, an evaluation of serum iron and
iron administration and preoperative
erythropoietin may lessen the need for
transfusion. 10
Recombinant human erythropoietin
(rHuEPO) is used for the treatment of
anemia related to reduced erythropoiesis
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caused by chronic renal disease and some
hematological diseases. 24,25
Various studies have shown the efficacy of
the preoperative administration of rHuEPO
for cardiac surgery to lower erythrocyte
transfusion in patients having autologous
blood donations. 26,27
Furthermore, rHuEPO
has been shown to be safe and effective in
correcting preoperative anemia, and it can be
used in association with iron therapy in
patients with Hb concentrations < 13 g/dL.
28,29 A typical preoperative regimen of
rHuEPO is, however, costly and requires at
least 4 days of hospitalization before
surgery, limiting a more extensive use of
this strategy. 30
Outpatient-based repeated
subcutaneous injections of rHuEPO may be
practical, 28
although it may be associated
with the increased occurrence of therapy-
related complications such as hypertension
and thromboembolism. 31
Moreover, the
absorption of subcutaneously administered
rHuEPO may not be firm and reliable
compared with the intravenous way because
of decreased microcirculation in patients
with cardiac diseases. 32
In a prospective study, patients with
preoperative anemia were randomly
allocated to either the erythropoietin group
or the control group. The erythropoietin
group was given 500 IU/kg of erythropoietin
and 200 mg of iron sucrose intravenously 1
day before cardiac surgery, while the control
group was given the same volume of normal
saline. The initial result was the need for
transfusion during surgery and 4 days after
surgery. The reticulocyte count and the iron
profile were investigated serially and
compared preoperatively and on
postoperative days 1, 2, 4, and 7.
The results of that study showed that single
doses of erythropoietin and supplemental
iron injections 1 day prior to cardiac surgery
clearly reduced the need for the transfusion
of blood after surgery in anemic patients
undergoing valvular cardiac surgery. The
complications of erythropoietin injections
include hypertension, headaches,
tachycardia, nausea, vomiting,
hypercalcemia, diarrhea, and
thromboembolism; nonetheless, these
complications are usually shown in patients
receiving chronic erythropoietin treatment. 28,30
The chronic use in patients with cancer
is associated with an increased risk of
thrombotic disease, but the short-term use
for acute indications even in critical patients
can be safe. 34,35
Limitations
We conducted a retrospective cohort study
using data from the Cardiovascular Surgery
Department of Rajaie Cardiovascular,
Medical, and Research Center, Tehran, Iran.
CONCLUSIONS
The results of the present study revealed that
about one-third of the patients had anemia
before surgery and the anemic patients
required blood transfusion 2.5 times more
than their non-anemic counterparts. Blood
transfusion is associated with side effects
and increases the length of hospital stay and
hospital costs; therefore, diagnostic
evaluations before elective surgery may
reduce the need for transfusion and
complications and, thus, shorten the length
of hospital stay.
Conflict of Interest
The authors declare no conflict of interest in
this work. This research received no
financial support.
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Ventricular Functional Status in Patients With Rheumatoid Arthritis Nikdoust et al
103
Original Article Ventricular Functional Status in Patients With Rheumatoid Arthritis Nikdoust et al
Assessment of Global Longitudinal Strain via Speckle-Tracking
Echocardiography in Patients With Rheumatoid Arthritis
Farahnaz Nikdoust1, MD; Samira Safiarian
1, MD; Atoosa Mostafavi
1, MD;
Farhad Gharibdoust2, MD; Seyed Abdol Hussein Tabatabaei
1*, MD
ABSTRACT
Background: The inflammatory nature of rheumatoid arthritis presents a hypothesis on the
increase in the likelihood of cardiovascular diseases in patients with rheumatoid arthritis.
Recently, the use of speckle-tracking echocardiography to evaluate ventricular strain,
especially the global longitudinal strain (GLS), has provided more comprehensive
information on ventricular dysfunction in these patients. In the present study, we
evaluated changes in the GLS index along with other left and right ventricular parameters
in patients with rheumatoid arthritis compared with healthy controls.
Methods: The study population was comprised of a case group (patients with rheumatoid
arthritis in the active phase during the first 5 years of diagnosis referred to Shariati
Hospital without a history of any other diseases) and a control group (individuals without
a history of rheumatoid arthritis or cardiac abnormalities referred for clinical check-ups).
In both groups, 2D and 3D echocardiographic examinations were performed by a single
cardiologist to assess cardiac functional parameters.
Results: Comparisons of the echocardiographic indices between the 2 groups showed
significantly lower LA (Left Atrium), AO (Aorta), interventricular septal end-diastole
(IVSD), Posterior wall diastolic diameter (PWD), and RVsm (Right Ventricular systolic
celocity) in the group suffering from rheumatoid arthritis than in the control group. The
GLS parameter was significantly lower in the rheumatoid arthritis group than in the
healthy group (-19.5 ± 2.34 vs -20.42 ± 3.07; P = 0.042); however, there was no
difference in the global circumferential strain parameter between the 2 groups
(-19.69 ± 3.55 vs -20.49 ± 1.79; P = 0.566). In contrast, the mean right ventricular GLS
was -18.77 ± 5.34 in the case group versus -21.87 ± 13.99 in the control group, indicating
a significant difference (P = 0.008).
Conclusions: In the echocardiographic assessment of patients with rheumatoid arthritis, a
decrease in the ventricular function parameters, especially the GLS, is expected, which
may be due to the effect of inflammatory factors on the cardiac ventricular strain. (Iranian
Heart Journal 2020; 21(1): 103-109)
KEYWORDS: Rheumatoid arthritis, Global longitudinal strain, Speckle-tracking echocardiography
1Department of Cardiology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran. 2Department of Rheumatology, Faculty of medicine, Tehran University of Medical Sciences, Tehran, IR Iran.
*Corresponding Author: Seyed Abdol Hussein Tabatabaei, MD; Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.
Email: [email protected] Tel: 02188026910
Received: March 10, 2019 Accepted: June 11, 2019
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atients with rheumatoid arthritis are
about 1.5 to 2 times more likely to be
at risk of coronary heart disease. 1,2
This is almost identical to the risk of heart
disease among patients with diabetes
mellitus. 3 This increase in the risk of heart
disease occurs even before the onset of
rheumatoid arthritis manifestations. 4 In the
Framingham Heart Study, a 1.5-fold
increase in the risk of heart disease among
patients with rheumatoid arthritis was noted. 4 Patients with rheumatoid arthritis also have
a high risk of heart failure. 5 This increase in
risk is mainly seen in patients with positive
rheumatoid factors. 6 Most importantly,
patients with heart failure and simultaneous
rheumatoid arthritis also experience a
progressive reduction in the left ventricular
(LV) systolic function manifested by a drop
in the left ventricular ejection fraction
(LVEF). 7 The set of these statements
reflects the fact that patients with
rheumatoid arthritis encounter heart failure
with systolic and diastolic dysfunction of the
LV, the underlying cause of which is
systemic inflammation associated with the
disease. Patients with rheumatoid arthritis
face an increased risk of LV systolic and
diastolic dysfunction; therefore,
echocardiographic evaluations in these
patients are of utmost importance. Because
rheumatoid arthritis is a type of connective
tissue inflammatory disease, this
involvement in the connective and muscular
components of the heart is also contagious;
thus, myocardial and endocardial
disturbances can also be expected in such
patients. Nonetheless, in some patients, and
with regard to the severity of the disease,
heart disease is sometimes asymptomatic
and because patients are not physically
active, changes in the cardiac function may
not be detected until the end stages of the
disease. Echocardiography is very useful in
evaluating and detecting cardiac
disturbances in patients with rheumatoid
arthritis, especially in the early stages of the
disease. Various studies have been
conducted on echocardiographic impairment
in rheumatoid arthritis. Overall, it appears
that the prevalence of valvular involvement
in patients with rheumatoid arthritis, not
least mitral valve regurgitation, followed by
pericardial effusion, is a common and
prevalent finding. 8,9
In addition to
pericardial and valve involvement, what is
revealed in patients with rheumatoid arthritis
is systolic and diastolic dysfunction and
what is predictable in rheumatoid arthritis is
systolic dysfunction (with a reduction in the
LVEF), diastolic dysfunction (accompanied
by changes in the E (E velocity in mitral
inflow), E/A (E velocity/A velocity), IVRT
(Isuvolomic Relaxation time), and
myocardial performance indices), valve
involvement, mitral insufficiency, and mild
pericardial effusion, especially in nodular
types.
Myocardial strain imaging is one of the
advanced echocardiographic methods aimed
at evaluating myocardial deformities during
ventricular contraction and relaxation. 10
The
evaluation of the strain index is reported as
the percentage change in myocardial
dystonia at a point from another point and
can be analyzed and reported through
speckle-tracking echocardiography (STE). 11-13
Accordingly, strain abnormalities for a
wide range of cardiovascular diseases 14
and
strain imaging are accurate and sensitive in
the diagnosis and prediction of systolic
dysfunction. 15-17
The disruption of
myocardial strain can be a symptom of
coronary heart disease, even in the early and
subclinical stages. Given the importance of
identifying cardiovascular and myocardial
infarction in patients with rheumatoid
arthritis, the imaging of myocardial strain in
the early stages of the disease is very
beneficial. 18
In this regard, some studies
P
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have identified the sensitivity and specificity
of the global longitudinal strain (GLS) index
in assessing the infarct size and the severity
of myocardial involvement in coronary heart
disease. 19-21
The GLS index is valuable for
the evaluation of systolic dysfunction
compared with other indicators such as the
LVEF. Indeed, the GLS index can be drawn
upon to assess the severity of myocardial
dysfunction in patients with rheumatoid
arthritis. The present study aimed to assess
and compare the GLS along with other
parameters for cardiac systolic dysfunction
in patients with rheumatoid arthritis.
METHODS
This is a descriptive-analytical case-control
study conducted in Shariati Hospital in
Tehran in 2018. The study population was
comprised of a case group (patients with
rheumatoid arthritis in the active phase
during the first 5 years of diagnosis referred
to Shariati Hospital without a history of any
other diseases except rheumatoid arthritis)
and a control group (individuals without a
history of rheumatoid arthritis or cardiac
abnormalities referred for clinical check-
ups). The American College of
Rheumatology (ACR) diagnostic criteria for
rheumatoid arthritis include 1) morning
stiffness more than an hour, 2) arthritis in 3
or more joints, 3) arthritis in the hand joints
(≥ 1 swollen joint), 4) symmetric arthritis, 5)
the presence of rheumatoid nodules, 6)
positive serum rheumatic factor, and 7)
radiographic X-ray changes of the hands as
the erosion. In both groups, 2D and 3D
echocardiographic examinations were
performed by a single cardiologist to assess
the cardiac functional parameters including
the Left Atrium (LA), the Aorta (AO), the
interventricular septal end-diastole (IVSD),
the Posterior Wall Diastolic Diameter
(PWD), the Posterior Wall Diastolic
Diameter (RVD), the Right Ventricular
systolic velocity (RVsm), the tricuspid
annular plane systolic excursion (TAPSE),
and the 2 strain-related indices of the GLS
and the global circumferential strain (GCS).
For the description of the data, descriptive
analysis was used, including the mean ± the
standard deviation (SD) for the quantitative
variables and frequencies (percentages) for
the categorical variables. The χ2
test, the t-
test, or the Mann–Whitney U test was used
for the comparison of the variables. The
correlations between the quantitative
variables were assessed using the Pearson or
Spearman correlation test. For the statistical
analyses, the statistical software IBM SPSS
Statistics for Windows, version 23.0 (IBM
Corp, released 2013, Armonk, NY) was
used. A P value < 0.05 was considered
statistically significant.
RESULTS
In this study, 35 patients with active
rheumatoid arthritis (mean age = 43.33 ±
22.9 y) and 35 healthy controls (mean age =
34.27 ± 9.10 y) were evaluated for
echocardiographic parameters.
Comparisons of the echocardiographic
indices between the 2 groups (Table 1)
showed significantly lower LA, AO, IVSD,
PWD, and RVSm in the group suffering
from rheumatoid arthritis than in the control
group. The GLS parameter was significantly
lower in the rheumatoid arthritis group than
in the healthy group (-19.5 ± 2.34 vs -20.42
± 3.07; P = 0.042); however, there was no
difference in the GCS parameter between
the 2 groups (-19.69 ± 3.55 vs -20.49 ± 1.79;
P = 0.566). In contrast, the mean RV-GLS
was -18.77 ± 5.34 in the case group versus -
21.87 ± 13.99 in the control group, indicating
a significant difference (P = 0.008). With
respect to the association between age and
the echocardiographic parameters (Table 2),
the patients’ age was adversely correlated
with the RVSm (r = -0.616, P = 0.001) and
with the TAPSE (r = -0.496, P = 0.005), but
not with the other cardiac parameters.
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Table 1. Values of echocardiographic parameters in both case and control groups
Parameter RA Group Healthy Group P value
LA 30.83 ± 4.02 34.07 ± 3.31 0.001
AO 26.53 ± 4.84 29.64 ± 3.87 0.003
IVSD 8.57 ± 1.25 7.64 ± 1.00 0.001
PWD 8.40 ± 1.00 7.42 ± 0.94 0.001
RVD 26.21 ± 3.56 26.89 ± 3.02 0.380
RVSm 11.61 ± 1.23 13.96 ± 1.45 0.001
TAPSE 22.73 ± 3.32 22.60 ± 1.84 0.824
GLS -19.5 ± 2.34 -20.42 ± 3.07 0.042
GCS -19.69 ± 3.55 -20.49 ± 1.79 0.566
RV-GLS -18.77 ± 5.34 -21.87 ± 13.99 0.008
RA, Rheumatoid arthritis; LA, Left Atrium; AO, Aorta; IVSD, Interventricular septal diastolic diameter; PWD, Posterior wall diastolic diameter; RVD, Right ventricular diastolic diameter; RVsm, Right ventricular systolic velocity ;TAPSE, Tricuspid annular plane systolic excursion; GLS, Global longitudinal strain; GCS, Global circumferential strain; RV-GLS, Right ventricular global longitudinal strain
Table 2. Correlations between the patients’ age and the echocardiographic parameters in the affected group
Parameter R Coefficient P value
LA 0.299 0.108
AO 0.298 0.109
IVSD 0.139 0.465
PWD 0.201 0.286
RVD 0.293 0.123
RVSM -0.616 0.001
TAPSE -0.496 0.005
GLS 0.182 0.336
GCS 0.355 0.098
RV-GLS 0.122 0.884
LA, Left Atrium; AO, Aorta ; IVSD, Interventricular septal diastolic diameter; PWD, Posterior wall diastolic diameter ; RVD, Right ventricular diastolic diameter; RVsm, Right ventricular systolic velocity ;TAPSE, Tricuspid annular plane systolic excursion; GLS, Global longitudinal strain; GCS, Global circumferential strain; RV-GLS, Right ventricular global longitudinal strain
DISCUSSION
The inflammatory nature of rheumatoid
arthritis and the role of inflammatory factors
in the development and progression of
coronary artery atherosclerosis and also the
valve defects present a new hypothesis on
the increase in the likelihood of
cardiovascular diseases in patients with
rheumatoid arthritis. This has been
confirmed in clinical observations as well as
heart imaging studies. Recently, the use of
STE to evaluate the ventricular strain,
especially the GLS, has provided more
comprehensive information on ventricular
dysfunction in these patients. In the current
study, we aimed to assess changes in the
GLS index along with other LV and RV
parameters in patients with rheumatoid
arthritis compared with healthy controls. We
found that whereas the decrease in the GLS
index in patients with rheumatoid arthritis
was significant compared with the healthy
controls, these changes were not significant
concerning the GCS index. Additionally,
among the other parameters of the
ventricular function, reductions in the LA,
the AO, the IVSD, the PWD, and the RVSm
in these patients were evident in comparison
with the healthy controls. In other words, the
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consequence of rheumatoid arthritis in the
first 5 years of the active phase of the
disease is the involvement of the LV and the
RV. In this regard, 2 important issues should
also be considered. Firstly, ventricular
echocardiographic changes in patients with
rheumatoid arthritis may not appear in the
early stages of the disease or they may be
asymptomatic; consequently, after years of
active disease and with the progression of
inflammatory processes, changes in the
ventricular function become evident. In
contrast, these changes may begin to appear
subclinically at the very beginning of the
active period of the disease. An
echocardiographic evaluation with the aim
of examining the course of changes in the
parameters of the heart within 5 years of the
active period of the disease is necessary.
The results of the previous studies chime in
with our findings concerning changes in the
ventricular function parameters in
rheumatoid arthritis. In a study by Naseem
et al, 22
the values of the GLS in both LV
and RV for patients with active rheumatoid
arthritis were significantly lower than those
in healthy controls. In addition, the severity
of rheumatoid arthritis activity was
significantly correlated with a further
reduction in the GLS. Cioffi et al 23
reported
reduced GLS values in 24% of their patients.
In a study by Benacka et al, 24
patients with
rheumatoid arthritis had a greater LV mass,
a lower LVEF, and a more prolonged IVCT
(Isovolumic Contraction time). Moreover,
the prolongation of the IVRT and a higher
E/E' ratio showed a much higher degree of
diastolic ventricular dysfunction in the
patients. In the STE evaluation, a significant
reduction in the GLS was also reported.
Benacka et al 25
reported that the active
status of the disease was significantly
correlated with the decrease in the GLS. In
an investigation by Fine et al, 26
the mean
GLS in both RV and LV showed a
significant decrease compared with healthy
controls. Therefore, with the development
and progression of rheumatoid arthritis, the
risk of developing heart disease, in particular
of ventricular dysfunction, is predictable. In
this regard, the efficiency of the GLS
evaluation can be very important and
diagnostic in predicting adverse cardiac
outcomes in patients with rheumatoid
arthritis, which, of course, needs to be
further evaluated.
CONCLUSIONS
In the echocardiographic assessment of
patients with rheumatoid arthritis, a decrease
in the ventricular function parameters,
especially the GLS, is expected, which may
be due to the inflammatory nature of the
disease and the effect of inflammatory
factors on the cardiac ventricular strain.
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13. Langeland S, D'Hooge J, Wouters PF, et al.
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24. Benacka O, Benacka J, Blazicek P, Belansky
M, Payer J, Killinger Z, Lietava J. Speckle
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, Semb AG3, Matre K
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26. Fine NM1, Crowson CS
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Case Report Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Farzamnia et al
Coronary and Cerebral Artery Air Embolism Complicating
Trans-septal Accessory Pathway Ablation
Hamid Farzamnia1, MD; Farzad Kamali MD
1, MD;
Mohsen Neshati Pirborji1, MD, MD; Ala Keykhavani
1, MD;
Azadeh Meibodi Ardekani1, MD; Shabnam Madadi
2, MD
ABSTRACT
A 30-year-old woman presented with frequent episodes of paroxysmal palpitation and
electrocardiographic evidence of minimal pre-excitation of the left lateral accessory pathway.
The patient underwent septostomy, which revealed air bubbles in the left ventricular cavity.
Aspiration was done with a pigtail catheter via the retrograde aortic approach. Transient ST-
elevation in the inferior leads was demonstrated. Left-sided hemiplegia was present after
consciousness, which was completely resolved after 24 hours. (Iranian Heart Journal 2020; 21(1):
110-114)
KEYWORDS: Accessory pathway, Trans-septal catheterization, Air embolism
1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
2 Cardiac Electrophysiology Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences,
Tehran, IR Iran.
*Corresponding Author: Shabnam Madadi, MD; Rajaie Cardiovascular, Medical, and Research Center, Vali-E-Asr Ave, Ayatolah Rafsanjani
Blvd, Tehran 1995614331, IR Iran.
Email:[email protected] Tel: 02123922019
Received: April 6, 2019 Accepted: July 11, 2019
bout 0.1%–0.3% of the general
population have ECG findings in
favour of accessory atrioventricular
pathways, which ise called Wolff–
Parkinson–White (WPW) syndrome in the
presence of arrhythmias. 1
The most common arrhythmias in these
patients are reentrant tachycardia and atrial
fibrillation (AF). The catheter ablation of the
accessory pathway is the treatment of
choice, and it can be done via the retrograde
or trans-septal approach.
We herein describe a patient with WPW
syndrome who suffered coronary and
cerebral air embolism as a complication of
septostomy for trans-septal radiofrequency
catheter ablation.
Case
A 30-year-old woman with a history of
frequent episodes of supraventricular
tachycardia presented with the ECG
manifestations of a minimal left-sided
accessory pathway and WPW syndrome.
A
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An electrophysiological study was
performed in conscious sedation status, and
diagnostic catheters were introduced via the
left and right femoral veins.
Intracardiac ECGs were recorded using the
Bard (Boston Scientific) electrophysiology
system.
The evaluation of the conduction system
revealed the most fused atrioventricular
(AV) signal in the left lateral side of the
coronary sinus (CS) (Fig. 1).
Figure 1. Most fused atrioventricular signal in the left lateral side of the coronary sinus
The retrograde conduction pattern was also
eccentric, and the earliest retrograde atrial
signal was recorded in the distal part of the
CS during right ventricular pacing. A narrow
QRS tachycardia was reproducibly inducible
with programmed atrial and ventricular
stimulation.
Septostomy was attempted with the use of
an Agilis long sheet (Agilis NxT™
Steerable Introducer, St Jude Medical). A
needle was inserted and advanced into the
left atrium without the need for the puncture
of the interatrial septum. Immediately after
the septostomy, air bubbles were observed in
the left ventricular apex (Fig. 2).
Figure 2. Air bubbles in the left ventricular
apex
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Immediately, 100% oxygen was
administrated. The right femoral artery was
cannulated, and a pigtail catheter (Dawson–
Mueller Drainage Catheter) was introduced
via the femoral artery via the retrograde
approach into the left ventricular cavity.
Next, suction was done, during which ST-
elevation in the inferior leads appeared with
sinus bradycardia and manifest accessory
pathway conduction, in favor of AV block
(Fig. 3).
Figure 3. ST-elevation in the inferior leads with sinus bradycardia and accessory pathway conduction, in favor of
atrioventricular block
Rapid right ventricular pacing was done,
100% oxygen was administrated, and an
inotrope was injected. ST-elevation was
resolved in about 1–2 minutes.
The procedure was terminated without any
attempt for ablation. A decision was made
against propofol injection.
After regaining consciousness, the patient
was alert and awake and obeyed orders.
However, she had left-sided hemiparesis
without left central hemifacial weakness.
Brain computed tomography scan was done,
and the results were normal. The distal force
of the left upper extremity was resolved in
about 1 hour, but the proximal force of the
left arm as well as the total force of the left
leg was still compromised. Neurological
consultation was done, and heparin drips and
dexamethasone were recommended by the
neurologist.
Twenty-four hours after the procedure, all
the forces returned to the normal status and
after 72 hours, the patient was discharged in
a good general condition without any
problems.
The follow-up of the patient showed no
problems. Fourteen days later, she
underwent a redo procedure, during which
the accessory pathway was successfully
ablated via the retrograde approach.
Transesophageal echocardiography in the
second admission revealed a patent foramen
ovale, about 2 × 5 mm in size, and a right-
to-left shunt.
DISCUSSION
Radiofrequency ablation for WPW
syndrome can be done via the retrograde or
trans-septal approach. The retrograde
approach may be associated with the risk of
prolonged catheter manipulation and
potential arrhythmogenic ventricular lesions
created during ablation. 2-4
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Potential risks can be avoided using trans-
septal atrial insertion. The approach was
developed in the 1950s and nowadays is one
of the most useful approaches for the
ablation of left-sided targets in
electrophysiology studies. 5,10
Lesh et al 9 reported a case of coronary air
embolism complicating the trans-septal
radiofrequency ablation of the left lateral
accessory pathway during catheter exchange
and recommended continuous flushing with
heparinized saline during the catheter
exchange.
Khurram et al 4 in 2016 reported a case of
catastrophic coronary air embolism during
AF ablation with massive air embolism into
the right coronary artery, leading to the
hemodynamic collapse, and its subsequent
successful management with catheter-based
coronary aspiration.
Murat Tulmac et al 9 reported a case of
massive systemic air embolism during the
aortic root angiography in 2012, with the
collapse of the patient and pulseless
electrical activity. The patient became
electrically stable shortly after
cardiopulmonary resuscitation, but she had
garbled speech and left hemiplegia with
partial weakness and paresthesia in the right
leg and arm. 6-8
The brain computed
tomography of the patient was normal, as
was the case in our patient, and she was
transferred to a center with facilities for
hyperbaric oxygen chamber treatment
(HBOT), and all of her neurological
functions became normal after 1 day.
Our center lacks HBOT facilities. We
administered 100% O2 and after 24 hours,
everything was normal and our patient was
discharged after 72 hours without any
residual defect.
CONCLUSIONS
Air embolism is almost always iatrogenic
during cardiac procedures, and the
administration of 100% O2 or the catheter-
based aspiration of the air may reduce the
risk of sequels.
REFERENCES
1. Luh Oliva Saraswati Suastika and Yudi Her
Oktaviono Multiple Air Embolism During
Coronary Angiography: How Do We Deal
With It? Clin Med Insights Cardiol. 2016;
10: 67–70.
2. CHANG-BUM PARK, HUI-JEONG
HWANG, JIN-MAN CHO, BYUNG-
HYUN JO, and CHONG-JIN KIM Massive
right coronary air embolism in the right
coronary artery during left coronary
angiography: A case report Exp Ther Med.
2013 Apr; 5(4): 1073–1074
3. Voci, P., Yang, Y., Greco, C., Nigri, A., and
Critelli, G. Coronary air embolism
complicating accessory pathway catheter
ablation: detection by echocardiography. J
Am Soc Echocardiogr. 1994; 7: 312–314
4. 4.Khurram Ahmad,MD,* Samuel
Asirvatham,MD,† Sreenivas Kamath,MD,*
Stephen Peck,MD,* Xiaoke
Liu,MD,PhDSuccessful interventional
management of catastrophic coronary
arterial air embolism during atrial fibrillation
ablation,Heart rhythm case reports,March
2016, Volume 2, Issue 2, Pages 153–156
5. Khan, M., Schmidt, D.H., Bajwa, T., and
Shalev, Y. Coronary air embolism:
incidence, severity, and suggested
approaches to treatment. Cathet Cardiovasc
Diagn. 1995; 36: 313–318
6. Rawlins, R.1, Momin, A., Platts, D., and El-
Gamel, A. Traumatic cardiogenic shock due
to massive air embolism. A possible role for
cardiopulmonary bypass. Eur J Cardiothorac
Surg. 2002; 22: 845–846
7. Sinha, S.K., Madaan, A., Thakur, R.,
Pandey, U., Bhagat, K., and Punia, S.
Massive coronary air embolism treated
successfully by simple aspiration by guiding
catheter. Cardiol Res. 2015; 6: 236–238
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Coronary and Cerebral Artery Air Embolism Complicating Trans-septal Accessory Pathway Ablation Farzamnia et al
114
8. French, K.F., Garcia, C., Wold, J.J., Hoesch,
R.I., and Ledyard, H.K. Cerebral air emboli
with atrial-esophageal fistula following
atrial fibrillation ablation a case report and
review. Neurohospitalist. 2011
9. Lesh, M.D., Coggins, D.L., and Ports, T.A.
Coronary air embolism complicating
transseptal radiofrequency ablation of left
free-wall accessory pathways. Pacing Clin
Electrophysiol. 1992; 15: 1105–1108
10. S Madadi, Z Emkanjoo, M Sharifi, H
AhmadpourAn unusual location of the
accessory pathway on the anteromedial side
of the mitral annulusIranian Heart Journal
19 (2), 75-78.
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Surgical Management of Retained Guide-Wire Fragment Tarbiat et al
115
Case Report Surgical Management of Retained Guide-Wire Fragment Tarbiat et al
Successful Surgical Management of a Retained
Guide-Wire Fragment in the Left Main Coronary Artery
Masoud Tarbiat1, MD; Amir Shams
2, MD; Farnaz Fariba
3*, MD
ABSTRACT
Guide-wire fracture during percutaneous coronary interventions is a rare and potentially serious
complication. Herein, we report a case of guide-wire fracture inside the left main coronary
artery following percutaneous coronary intervention in a 58-year-old man. The patient had
severe chest pain, and the extraction of the retained guide-wire fragment was thwarted via
percutaneous retrieval approaches. Ultimately, he had a successful emergency surgical
extraction of THE retained guide-wire fragment and coronary artery bypass graft surgery. This
report indicates that the surgical extraction of a retained guide-wire fragment is still safe and
the only option for its treatment after the failure of retrieval approaches. (Iranian Heart Journal
2020; 21(1): 115-118)
KEYWORDS: Percutaneous coronary intervention, Coronary artery bypass, Coronary vessels
1 Clinical Research Development Unit of Farshchian Hospital, Department of Anesthesiology, School of Medicine, Hamadan University of
Medical Sciences, Hamadan, IR Iran. 2
Clinical Research Development Unit of Farshchian Hospital, Department of Cardiac Surgery, School of Medicine, Hamadan University of
Medical Sciences, Hamadan, IR Iran. 3
Clinical Research Development Unit of Farshchian Hospital, Department of Cardiology, School of Medicine, Hamadan University of Medical
Sciences, Hamadan, IR Iran.
*Corresponding Author: Farnaz Fariba, MD; Department of Cardiology, School of Medicine, Hamadan University of Medical Sciences,
Hamadan, IR Iran.
Email: [email protected] Tel: 09188118143
Received: March 20, 2019 Accepted: June 5, 2019
uide-wire fracture during
percutaneous coronary intervention
(PCI) is a rare and potentially
serious complication, with a reported
incidence of around 0.08%. The first case of
this complication was reported in the late
1980s. 1
The main causes of fracture
mechanisms are wire cutting by directional
or rotational coronary atherectomy catheter,
wire wedging into the distal or winding
vessels, and structural failure. This rare and
dangerous complication may be life-
threatening and sometimes require
emergency cardiac surgery if percutaneous
retrieval fails. 2,3
Herein, we report a case of
guide-wire fracture during an elective PCI,
requiring emergent surgical removal and
coronary artery bypass graft surgery
(CABG).
Case Report
A 58-year-old male smoker with
hypertension was admitted to the emergency
department for the sudden onset of typical
cardiac chest pain and sweating. The patient
had suffered from occlusive coronary artery
disease for about 12 years. Due to the
history of occlusive coronary artery disease,
as well as strong clinical and
electrocardiographic evidence of unstable
G
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angina, he was referred for cardiac
catheterization. Cardiac catheterization,
performed through the right radial artery,
revealed a significant lesion in the
proximal part of the left anterior
descending artery with good retrograde
filling via the ipsilateral collaterals and a
good run-off. The obtuse marginal artery 2
had a 50%–60% lesion in the mid-part
with a good runoff. No other significant
lesion was observed.
The physician decided to treat the artery
percutaneously. He used a guide wire with
hydrophilic coating (PILOT 200) to cross
the total occlusion of the left anterior
descending artery and a BMW guide wire
as an anchoring wire. Unfortunately,
however, the PILOT 200 guide wire was
detached during the procedure. He used
ANDROSNARE MICRO ASM 4 set 3F and
ENSNARE 6F but failed to remove the
detached fragment of the guide wire from
inside the left main coronary artery (Fig. 1 &
2).
Figure 1. Coronary artery angiography,
showing a retained guide-wire fragment within the left main coronary artery (arrow) in the right anterior oblique caudal view
Figure 2. Coronary artery angiography,
showing the retained guide-wire fragment within the left main coronary artery (arrow) in the left anterior oblique caudal view
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Therefore, the patient was referred for
emergent CABG. On admission in the
operating room, the patient was agitated and
suffered severe chest pain. He was in a
stable hemodynamic state with an
epinephrine infusion. Without delay, he was
prepared for the induction of anesthesia. He
was monitored with a pulse oximeter and
standard electrocardiography. The veins on
both arms were immediately cannulated with
16-G catheters after a subcutaneous
lidocaine (1%) injection. The blood pressure
was monitored via the left radial artery. The
patient was induced with sufentanil (50 μg),
etomidate (16 mg), and cisatracurium (16
mg). Anesthesia was maintained using an
infusion of sufentanil (2 μg/kg/h),
propofol (50–75 μg/ kg/min), and
cisatracurium (2 μg/kg/ min). Subsequently,
a catheter was inserted in the right
subclavian vein for central vein pressure
(CVP) monitoring. Under general
anesthesia, median sternotomy was
performed, followed by aortic and right
atrial cannulations (unicaval approach).
Cardiopulmonary bypass (CPB) was
initiated through systemic cooling to 33 °C.
After aortic cross-clamping, an infusion of
antegrade and retrograde cold blood
cardioplegic solutions was done. Following
transverse aortotomy, the remanent of the
guide wire was removed from the left main
coronary artery ostium. Subsequently, the
left internal mammary artery was
anastomosed to the left anterior descending
artery and the obtuse marginal artery 2 was
grafted with the saphenous vein. The grafts
were positioned and checked successfully.
Following rewarming, normal sinus rhythms
occurred. The patient had uneventful
weaning from CPB. The operation course
was uneventful, and he was finally extubated
in the Open Heart Intensive Care Unit after
6 hours. He was in a complete alertness state
without any hemodynamic complications.
Finally, he was discharged home in a good
overall condition 7 days later.
DISCUSSION
Although PCI has been a progressive
technological improvement of devices and
techniques, its accidental complications
remain technically challenging. A fracture
or retained guide wire during PCI is a well-
known rare but feared complication
(estimated incidence of 0.1%–0.2%). The
complications of guide-wire remnants
following guide-wire fracture are
perforation, thrombosis, embolic events, and
vessel occlusion. 2,3
Several risk factors,
sometimes in combination, have been
suggested for guide-wire entrapment. These
suggested risk factors for guide-wire
entrapment are type of procedure (“jailing”
of the wire between overlapping stents or
between stent and vessel wall), type of
lesion (bifurcation lesions, chronic total
occlusions, and lesions in very tortuous and
calcified vessels), type of material used
(hydrophilic wires), and excessive rotation
of the guide wire. In our case, it appears
that the use of a “hydrophilic” wire
facilitated the occurrence of this event. 1,3
The optimal management of guide-wire
entrapment depends on the site and extent
of the guide-wire remnant and is
controversial. Therefore, it should be
managed on an individual basis. The
therapeutic options of guide-wire fracture
are percutaneous retrieval, surgical
removal, or leaving the guide-wire
remnants in-situ. The first preferable option
is the removal of the retained guide-wire
remnants from the coronary circulation. 3
The percutaneous retrieval methods for the
extraction of a retained guide-wire fragment
are the double- or triple-wire rotation
technique, the deep wedging of the guiding
catheter and the traction of the system,
retrieval using the balloon inflation
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technique, retrieval by snare loops, retrieval
using microcatheters (Tornus catheters),
extraction with Bioptome, and stenting over
the retained wire. 3,4
When percutaneous
retrieval techniques fail, some physicians
believe that if the guide-wire remnant is
jailed in a distal portion of a small vessel
without inducing ischemia, conservative
therapy may be safe. Nevertheless, others
believe that leaving guide-wire remnants in
situ is not advisable due to thrombotic risks,
and surgical removal should be performed.
Eventually, the other preferable approach is
surgical extraction. 1,3
Emergent cardiac
surgery is sometimes associated with
significant morbidity and mortality. The
surgical removal of a retained guide-wire
fragment is direct coronary arteriotomy or
aortotomy. The surgical extraction of
proximal wire entrapment is sometimes the
left main coronary arteriotomy and patch
repair. 3,5
In our case, the percutaneous
retrieval of the retained guide-wire fragment
failed. Since the guide-wire fragment was in
the left main coronary artery and the patient
suffered severe chest pain, emergent cardiac
surgery for the removal of the retained
guide-wire fragment and CABG was
performed.
In conclusion, guide-wire fracture during
PCI is a rare complication with favorable
early and long-term outcomes when
recognized timely and managed properly.
Physicians should be aware of this rare
complication and prepared to manage it.
Furthermore, the surgical extraction of A
retained guide-wire fragment is still safe
and the only option for its treatment after
the failure of retrieval approaches.
Conflict of Interest
The authors have no conflict of interest.
Funding/Support
We wish to thank Hamadan University of
Medical Sciences for its support in the
conduct of the present study.
REFERENCES
1. Koulouris S, Saad M. An unusual case of an
angioplasty wire entrapped and fractured
within the struts of a recently implanted
coronary stent: Treatment with the
implantation of a "jailing" stent. Hellenic J
Cardiol 2017;58:236-8.
2. Balbi M, Bezante GP, Brunelli C, Rollando
D. Guide wire fracture during percutaneous
transluminal coronary angioplasty: possible
causes and management. Interactive
CardioVascular and Thoracic Surgery
2010;10: 992-4.
3. Abdulrahman M. Al-Moghairi, Al-Amri H.
Management of retained intervention guide-
wire: A literature review. Current
Cardiology Reviews 2013;9:260-6.
4. Hong YM, M, Lee SR. A case of guide wire
fracture with remnant filaments in the left
anterior descending coronary artery and
aorta. Korean Circ J 2010; 40:475-7.
5. Assar O. Emergency CABG and surgical
retrieval of entrapped coronary stent
balloon: A case report. The Iranian Journal
of Cardiac Surgery 2012;4:41-2.
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Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Khandan et al
119
Case Report Hiccups Are a Rare Symptom of Supraventricular Tachycardia: Case Report Khandan et al
Hiccups Are a Rare Symptom of Supraventricular Tachycardia:
Case Report
Amir Hosein Khandan1, MD; Asghar Mohamadi*
2, MS
ABSTRACT
Paroxysmal supraventricular tachycardia (PSVT) is one of the most common arrhythmias, and it
occurs in the general population with a good prognosis. PSVT occurs in all age groups, with an
incidence rate of approximately 1–3 cases per 1000 persons. We describe a patient presenting
with PSVT and a complaint of hiccups. (Iranian Heart Journal 2020; 21(1): 119-121)
KEYWORDS: Paroxysmal supraventricular tachycardia, Hiccup
1 Lorestan University of Medical Sciences.Khorramabad, IR Iran.
2 Cardiovascular Research Center, Shahid Rahimi Hospital, Lorestan University of Medical Sciences, Khorramabad, IR Iran.
*Corresponding Author: Asghar Mohamadi, MS; Lorestan University of Medical Sciences, Khorramabad, IR Iran. Email: [email protected] Tel: 09106042707
Received: March 6, 2019 Accepted: June 10, 2019
aroxysmal supraventricular
tachycardia (PSVT) is defined as a
sudden increase in heart rate that ends
suddenly. PSVT has different types of
electrophysiologic patterns such as atrial
tachycardia, atrioventricular (AV) nodal
reentry, and atrioventricular reentrant
tachycardia (AVRT). 1
The most common
symptom of this arrhythmia is palpitation
and other symptoms include shortness of
breath, chest discomfort, weakness and
fatigue, lightheadedness, dizziness, and
syncope. 2 We herein describe a 45-year-old
man with PSVT who presented to the
emergency department with a complaint of
hiccups.
Case Report
A 45-year-old man who had a history of
hypertension and cigarette smoking
presented to the emergency department with
a complaint of hiccups. On physical
examinations, the patient had blood pressure
of 120/80 mm Hg, heart rate of 160 bpm,
respiratory rate of 18, and body temperature
of 37 °C. Cardiac examinations were
normal. The patient did not mention a
history of heart disease and did not take any
medication. The reason for his referral to the
hospital was a hiccup of 2 hours’ duration.
He was immediately monitored, and an ECG
was taken. The ECG revealed a regular
narrow complex tachycardia (Fig. 1). Given
a retrograde P-wave just after the QRS, an
AVNRT rhythm was suggested as the first
differential diagnosis. However, other
diagnoses such as an orthodromic AVRT
rhythm could not be ruled out definitively
and a definitive diagnosis required
electrophysiology study. The patient refused
to undergo an electrophysiology study,
forcing the treating physician to interpret the
rhythm based on the surface ECG.
Adenosine (6 mg intravenously) was rapidly
P
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injected, after which the patient suffered
dyspnea. The dyspnea was resolved after 1
hour, and the arrhythmia was converted into
the sinus rhythm. Moreover, the hiccup
disappeared after the termination of the
tachyarrhythmia.
Figure 1. ECG recorded immediately after the presentation of the patient to the emergency department
Given the retrograde P-wave just after the QRS, an atrioventricular reentrant tachycardia rhythm was proposed as the first differential diagnosis.
DISCUSSION
PSVT has several symptoms that include
palpitations, shortness of breath, chest
discomfort, weakness and fatigue,
lightheadedness, dizziness, and syncope. 2
We herein reported a rare symptom of
arrhythmia that our patient suffered due to a
hiccup. The symptoms lasted for several
hours, thus the patient was forced to seek
treatment. A hiccup is an involuntary
contraction of the diaphragm, followed by
laryngeal closure. 3 Many disorders can
cause hiccups including stroke, tumors,
herpes infection, gastroesophageal reflux
disease, various drugs (eg, anti-
Parkinsonism drugs, anesthetic agents, and
steroids), and chemotherapies. 4 Suh et al
5
reported a case in which hiccups were
associated with bradycardia and suggested
that the Valsalva maneuver had enhanced
the parasympathetic tone and caused the
hiccup. Hiccups can also be a sign of more
serious problems in the heart. For example,
hiccups after cardiac pacemakers or
implantable cardioverter-defibrillator
placement are probably a sign of lead
perforation. 7 Hiccups can also be a sign of
the pathological activation of the arc reflex,
and some disorders in the heart such as
myocardial ischemia and the inflammation
of the pericardium can lead to hiccups. In a
case report, myocardial ischemia generated
hiccups, which were treated with coronary
angioplasty. 6 The existing literature is
devoid of an explanation about the
mechanism of hiccups secondary to PSVT;
nonetheless, a possible mechanism that may
be involved is myocardial ischemia that
occurs during tachyarrhythmias and induces
hiccups. Interestingly, in our patient,
although the hiccup increased the vagal tone,
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121
it could not terminate the PSVT and the
authors did not have a clear explanation for
this phenomenon.
The goal of this case report is to introduce a
sign of arrhythmia to emergency department
physicians and cardiologists in order that
they will be aware of this rare symptom of
arrhythmia and suspect PSVT in patients
who refer to the emergency department with
this complaint.
REFERENCES
1. Kadish A, Passman R. Mechanisms and
management of paroxysmal supraventricular
tachycardia. Cardiology in review.
1999;7(5):254-64.
2. Al-Zaiti SS, Magdic KS. Paroxysmal
Supraventricular Tachycardia. Critical Care
Nursing Clinics. 2016;28(3):309-16.
3. Krysiak W, Szabowski S, Stepien M,
Krzywkowska K, Krzywkowski A,
Marciniak P. Hiccups as a myocardial
ischemia symptom. Polskie Archiwum
Medycyny Wewn trznej. 2008;118(3):148.
4. Chang F-Y, Lu C-L. Hiccup: mystery,
nature and treatment. Journal of
neurogastroenterology and motility.
2012;18(2):123.
5. Suh WM, Krishnan SC. Violent hiccups: an
infrequent cause of bradyarrhythmias.
Western Journal of Emergency Medicine.
2009;10(3):176.
6. Saarel EV, Hinkle K, Etheridge SP. Serious
case of the hiccups. HeartRhythm Case
Reports. 2015;1(4):159.
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an extra charge. Contact the Editorial Office
for details.
Electronic manuscripts
All authors are strongly encouraged to
submit their manuscripts via Email using
Microsoft Office Word (2003 or afterward)
in order to allow more rapid editing and
preparation for publication. The author
should retain copies of all files as backup.
Emails should bear the author’s name, short
title of the article, and operating system
used.
All manuscripts and correspondences
should be submitted to:
Hussein Tabatabaei, M.D.
Editor-in-Chief
Iranian Heart Association Journal
P. O. Box: 15745-1341
Tehran 19974 Iran
Tel: (009821) 22048174
Fax: (009821) 22048174
Email: [email protected]
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Forthcoming Meetings
The 38th Annual International Symposium: Clinical Update in Anesthesiology, Surgery and Perioperative Medicine Sunday, January 19, 2020 to Friday, January 24, 2020 St. Kitts Marriott Resort St. Kitts Saint Kitts and Nevis See map: Google Maps STS 56th Annual Meeting & Tech-Con 2020 Saturday, January 25, 2020 to Tuesday, January 28, 2020 New Orleans Ernest N. Morial Convention Center New Orleans, LA United States See map: Google Maps 30th Annual Meeting in Scandinavian Society for Research in Cardiothoracic Surgery (SSRCTS) Thursday, February 6, 2020 to Saturday, February 8, 2020 Bardøla Høyfjellshotell Geilo Norway See map: Google Maps IACTS2020 - 66th Annual Conference of Indian Association of Cardiovascular-Thoracic Surgery Thursday, February 6, 2020 to Sunday, February 9, 2020 Forum - GrandO7 Convention Center Ahmedabad, GJ India See map: Google Maps Indian Association of Cardiovascular Anaesthesia Conference 2020 Friday, February 7, 2020 to Sunday, February 9, 2020 Hotel Holiday Inn and Resort, GOA Goa, GA India See map: Google Maps
28th Congress of the Asian Society for Cardiovascular & Thoracic Surgeon Friday, February 7, 2020 to Monday, February 10, 2020 Shangri La Hotel, Chiang Mai Chiang Mai Thailand See map: Google Maps AATS Mechanical Support for the Heart and Lung Symposium Friday, February 14, 2020 to Saturday, February 15, 2020 Marriot Marquis Houston Houston, TX United States See map: Google Maps C3 Meeting 2020 - Consensus – Controversy – Compromise Sunday, February 16, 2020 to Tuesday, February 18, 2020 InterContinental Hotel Vienna Austria See map: Google Maps 6th Assiut VATS workshop Thursday, February 20, 2020 to Friday, February 21, 2020 Assiut university Heart Hospital , conference hall Assiut Egypt See map: Google Maps WSCTS RCS International TAVI Congress, The Aortic Valve Meeting Friday, February 28, 2020 to Sunday, March 1, 2020 Royal College of Surgeons of Edinburgh Edinburgh United Kingdom See map: Google Maps The Houston Aortic Symposium: Frontiers in Cardiovascular Diseases, the Thirteenth in the Series
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Thursday, March 5, 2020 to Saturday, March 7, 2020 Westin Oaks Hotel Houston United States See map: Google Maps 4th Vienna-ESTS Laryngotracheal Course Thursday, March 5, 2020 to Saturday, March 7, 2020 Medical University of Vienna Vienna Austria See map: Google Maps 16th International Congress of Update in Cardiology and Cardiovascular Surgery Thursday, March 12, 2020 to Sunday, March 15, 2020 Royal Seginus Convention Center Antalya Turkey See map: Google Maps 2020 General Thoracic Surgical Club 33rd Annual Meeting Thursday, March 12, 2020 to Sunday, March 15, 2020 Hilton Tucson El Conquistador Golf & Tennis Resort Tucson, AZ United States See map: Google Maps ESTS School of Thoracic Surgery: Knowledge Track Course Monday, March 16, 2020 to Saturday, March 21, 2020 Lindner Hotel Prague Castle Prague Czech Republic See map: Google Maps 2020 Techno Practicum College Friday, March 20, 2020 to Sunday, March 22, 2020 InterContinental Sydney Sydney, NSW Australia See map: Google Maps
SCTS Annual Meeting & SCTS Ionescu University 2020 Sunday, March 22, 2020 to Tuesday, March 24, 2020 ICC Wales Newport United Kingdom See map: Google Maps 4th Structural Heart Disease Asia Pacific Symposium Thursday, April 2, 2020 to Saturday, April 4, 2020 Grand Millennium Hotel Auckland New Zealand See map: Google Maps The Fredric G. Levin Lung Cancer Symposium Thursday, April 2, 2020 to Friday, April 3, 2020 Sanders Beach-Corinne Jones Resource Center Pensacola, FL United States See map: Google Maps Toronto Anesthesia Symposium Saturday, April 4, 2020 to Sunday, April 5, 2020 MaRS Discovery District Toronto Canada See map: Google Maps 2nd ESTS-ERS Collaborative Course on Thoracic Oncology: Pleura, Mediastinum, Rare Tumours Monday, April 6, 2020 to Wednesday, April 8, 2020 Johnson & Johnson Institute Hamburg Germany See map: Google Maps MI Esophagectomy and Anastomosis Course Thursday, April 16, 2020 to Friday, April 17, 2020 Istanbul, Turkey Istanbul Turkey
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See map: Google Maps AATS Aortic Symposium Thursday, April 23, 2020 to Friday, April 24, 2020 New York Marriott Marquis New York United States See map: Google Maps AATS 100th Annual Meeting Saturday, April 25, 2020 to Tuesday, April 28, 2020 New York Hilton Midtown and Sheraton New York Times Square New York United States See map: Google Maps 10th Anniversary London Core Review Cardiothoracic Surgery Course Thursday, May 7, 2020 to Sunday, May 10, 2020 Royal College Of Physicians London United Kingdom See map: Google Maps 3rd International Conference Sublobar Resections for Lung Cancer Thursday, May 21, 2020 to Friday, May 22, 2020 Grand Nikko Tokyo Dabai Tokyo Dabai Japan See map: Google Maps 28th European Conference on General Thoracic Surgery Sunday, May 31, 2020 to Wednesday, June 3, 2020 World Forum, The Hague, The Netherlands The Hague Netherlands See map: Google Maps ASAIO 66th Annual Conference Wednesday, June 10, 2020 to Saturday, June 13, 2020 Chicago Hilton Chicago, IL United States
See map: Google Maps 7th ECC International Congress on Complications during Cardiovascular Interventions: prevention and management Wednesday, June 10, 2020 to Friday, June 12, 2020 InterContinental Hotel Düsseldorf Germany See map: Google Maps WTSA 46th Annual Meeting Wednesday, June 24, 2020 to Saturday, June 27, 2020 Vail Marriott Mountain Vail, CO United States See map: Google Maps 40th Annual Cardiothoracic Surgery Symposium (CREF 2020) Wednesday, September 2, 2020 to Sunday, September 6, 2020 Marriott Marquis San Diego Marina San Diego, CA United States See map: Google Maps AATS Surgical Treatment of Arrhythmias and Rhythm Disorders Friday, October 2, 2020 to Saturday, October 3, 2020 Westin Boston Waterfront Boston, MA United States See map: Google Maps AATS Clinical Trials Methods Course Thursday, October 22, 2020 to Saturday, October 24, 2020 JB Duke Hotel Durham, NC United States See map: Google Maps AATS International Thoracic Surgical Oncology Summit Friday, October 30, 2020 to Saturday, October 31, 2020 Sheraton Times Square New York City: New York New York City, NY
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United States See map: Google Maps ATCSA 2020 - Annual Congress of the Association of Thoracic and Cardiovascular Surgeons of Asia Thursday, November 5, 2020 to Sunday, November 8, 2020 Hilton Arcadia Phuket Thailand
See map: Google Maps The Aalst Hands-on Cadaveric Endoscopic Mitral Course Tuesday, November 17, 2020 to Friday, November 20, 2020 OLV Clinic Aalst, Belgium Aalst Belgium See map: Google Maps
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SUBSCRIPTION ORDER FORM
Please enter my subscription to Iranian Heart Journal for 500 000 Rials for one year
(Four quarterly issues) beginning (Year)
ADDRESS: Please type or print clearly:
Name:
Address:
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PAYMENT
Check enclosed Cheek or money order must be made to:
Iranian Heart Association
Account no: 6166/1, Mellat Bank, Rajaie Cardiovascular, Medical and Research Center Branch, Tehran,
Iran.
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SUBSCRIPTION ORDER FORM
Please enter my subscription to Iranian Heart Journal for $ 50 us. for one year
(Four quarterly issues) beginning (Year)
ADDRESS: Please type or print clearly:
Name:
Address:
Zip Code: City:
PAYMENT
Check enclosed Cheek or money order must be made to:
Iranian Heart Association
Account no: 116AC252899, Mellat Bank, Mirdamad Branch
Tehran, Iran, Branch code 6507/8
P.O.Box: 15745-1341
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تهران :گيرنده مجلة قلب ايران
17537-1431صندوق پستي
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To:
Iranian Heart Association
P.O.Box: 15745-1341
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