late postoperative atrial fibrillation after cardiac surgery: a national survey within the cardiac...

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Original article

Late postoperative atrial fibrillation after cardiac surgery: anational survey within the cardiac rehabilitation settingMarco Ambrosettia, Roberto Tramarinb, Raffaele Griffoc, Stefania De Feod,Francesco Fattirollie, Annarita Vestrif, Carmine Ricciog andPier Luigi Temporellih, on behalf of the ISYDE and ICAROSinvestigators of the Italian Society for Cardiovascular Prevention,Rehabilitation and Epidemiology (IACPR-GICR)

Aims The aims of this study were to determine the

incidence and clinical predictors of new-onset and recurrent

late postoperative atrial fibrillation (POPAF) in a large cohort

of patients who underwent cardiac rehabilitation programs

(CRPs) after discharge from surgery units, and the

association between late POPAF and cardiovascular

morbidity and mortality in the medium term.

Methods The ISYDE and ICAROS registries were two

multicenter, prospective studies carried out by the Italian

Association for Cardiovascular Prevention, Rehabilitation

and Epidemiology (IACPR-GICR), providing clinical

information on consecutive patients completing CRP in 165

facilities. Patients following cardiac surgery were

considered, with the exclusion of those with persistent

POPAF at discharge from the surgery units. A total of 2256

patients following cardiac surgery were enrolled (isolated

coronary surgery 62.9%, valve interventions 16%, combined

surgery 21.1%).

Results The mean age of patients was 67 W 10 years, and

the observation period 13 W 20 days. During CRP, POPAF

occurred in 241 (10.7%) patients, with 4.4% new-onset and

6.3% recurrent cases, respectively. In the logistic regression

model, valve surgery (P < 0.05), a history of early POPAF

(P < 0.001), and the presence of postoperative ventricular

arrhythmias (P < 0.05) independently predicted the

occurrence of late POPAF. Lack of prescription of

cardioprotective drugs was not associated with late POPAF.

pyright © Italian Federation of Cardiology. Unaut

1558-2027 � 2011 Italian Federation of Cardiology

Late POPAF increased the 1-year risk of cardiovascular

events after CRP, mainly episodes of decompensated heart

failure.

Conclusion A high level of suspicion for late POPAF, after

discharge from surgery units, should be maintained due to

the risk of occurrence, the low antiarrhythmic effect of

common cardioprotective drugs and the impact on

cardiovascular prognosis.

J Cardiovasc Med 2011, 12:390–395

Keywords: atrial fibrillation, cardiac rehabilitation, cardiac surgery

aCardiovascular Rehabilitation Unit, ‘Le Terrazze’ Clinic, Cunardo, bDivision ofCardiology, European Foundation for Cardiovascular Research – FERB,Cernusco SN, cDivision of Cardiac Rehabilitation, La Colletta Hospital, Arenzano,dDivision of Cardiology, ‘Dr Pederzoli’ Clinic, Peschiera del Garda, eDepartmentof Medical and Surgical Critical Care, Section of Cardiac Rehabilitation,University of Florence and Careggi Hospital, Firenze, fDepartment of PublicHealth and Infectious Disease, Sapienza University of Rome, gDivision of CardiacRehabilitation, Cardiac Sciences Department, S. Anna and S. SebastianoHospital, Caserta and hDivision of Cardiology, IRCCS S. Maugeri Foundation,Veruno, Italy

Correspondence to Marco Ambrosetti, MD, Cardiovascular RehabilitationUnit, ‘Le Terrazze’ Clinic, Via U. Foscolo 6/b, I-21035 Cunardo (VA),ItalyTel: +39 0332992448;e-mail: [email protected], [email protected]

Received 29 December 2010 Revised 9 February 2011Accepted 14 February 2011

IntroductionPostoperative atrial fibrillation (POPAF) is a common

complication after cardiac surgery and is responsible for

increased use of healthcare resources. The peak of

POPAF appears early, within the first 3 days after oper-

ation, being associated with increased rates of postopera-

tive stroke, heart failure, acute coronary syndromes,

thromboembolism, risk of bleeding from anticoagulation

and prolonged in-hospital length of stay.1–3 Although

most patients receive restoration of sinus rhythm before

hospital discharge from surgery facilities, POPAF still

remains the leading cause of hospital readmission follow-

ing cardiac surgery.4

Despite the large body of evidence focused on arrhyth-

mic episodes occurring during in-hospital acute care,

there have been only a few systematic studies with

extended time observation. Most contemporary series

collected data during the average 6–8 days length of stay

in the surgical setting, owing to an inability to accurately

determine the incidence of POPAF after discharge, when

patients are not closely monitored. As a result, the current

contribution of late cases to the epidemiology of POPAF

may be underestimated, both in terms of de-novo or

recurrent arrhythmias. In spite of this, cardiac rehabilita-

tion facilities provide an ideal setting to evaluate late

POPAF, since a large proportion of cardiac surgery

horized reproduction of this article is prohibited.

DOI:10.2459/JCM.0b013e328346a6d3

mailto:[email protected]

mailto:[email protected]

http://dx.doi.org/10.2459/JCM.0b013e328346a6d3

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Late atrial fibrillation after cardiac surgery Ambrosetti et al. 391

patients are directly tracked to supervised cardiac reha-

bilitation programs (CRPs), usually covering the first

month after operation. Identifying a population of

patients who are at increased risk for developing POPAF

after discharge from the surgical setting, would allow a

more targeted intervention strategy to reduce late unfa-

vorable outcomes of cardiac surgery.

The primary aims of this study were to determine the

incidence and clinical predictors of new-onset and recur-

rent POPAF in a large cohort of patients who underwent

CRP after cardiac surgery, and the association between

late POPAF and cardiovascular morbidity and mortality

in the medium term.

MethodsIn the years 2008 and 2009, the Italian Association for

Cardiovascular Prevention, Rehabilitation, and Epide-

miology (IACPR-GICR) carried out two large prospec-

tive, longitudinal, multicentric registries providing

clinical information on patients completing CRP in Italy,

with the acronyms of ISYDE (Italian SurveY on carDiac

rEhabilitation) and ICAROS (Italian survey on CArdiac

RehabilitatiOn and Secondary prevention after cardiac

revascularization). Globally, the two studies enrolled up

to 3500 patients admitted to 165 cardiac rehabilitation

units, representing more than 85% of all 190 registered

facilities in Italy.5 ISYDE explored the whole scenario of

indications to cardiac rehabilitation, whereas ICAROS

focused on patients undergoing coronary revasculari-

zation, also providing 1-year follow-up for major adverse

cardiovascular events, treatments and lifestyle changes.

Both the ISYDE and ICAROS studies shared the same

methodology for data collection, published elsewhere.5,6

In summary, the studies adopted a web-based clinical

record form (e-CRF) running on the institutional website

(www.iacpr.it), designed with jump menus or select

boxes in order to reduce the risk of confounding answers.

Data quality was also improved by the institution of

online guides and helpdesk. All consecutive patients

discharged from cardiac rehabilitation units in the study

period (from 28 January to 10 February 2008 for ISYDE,

and from 17 November to 15 December 2008 for

ICAROS) were considered, and information regarding

indication to cardiac rehabilitation, complications during

the acute phase, comorbidities, provision of the CRP,

lifestyle and therapies were collected. The studies did

not involve any experimentation of drugs or any diag-

nostic tests, care interventions or pharmacological treat-

ments that were not part of the clinical practice routinely

adopted by each participating cardiac rehabilitation unit.

The Ethical Committee of each cardiac rehabilitation

unit approved the protocol, and informed consent was

obtained.

For the purpose of this study, all patients undergoing

cardiac surgery in the ISYDE and ICAROS studies, and

opyright © Italian Federation of Cardiology. Unau

with documented sinus rhythm at the beginning of CRP,

were considered. Patients who displayed atrial fibrilla-

tion at the beginning of CRP were excluded. ‘Late

POPAF’ was defined as any clinically documented epi-

sode of atrial fibrillation occurring following discharge

from hospital after the index operation. ‘Recurrent’ and

‘new-onset’ late POPAF were defined according to the

presence or absence of early POPAF during index

hospital admission.

Statistical analysisPatients were grouped according to the presence or

absence of POPAF during cardiac rehabilitation, and

clinical variables available were compared between

groups. Categorical variables were tested using either

the x2 or the Fisher exact test, when appropriate, and

continuous variables were tested with the two-tailed

Student’s t-test, with a P value of 0.05 or less considered

significant. Selected variables shown to be clinically

significant at univariate analysis were then tested in a

model of binary logistic regression analysis by use of

SPSS version 13.0 software package (SPSS Inc., Chicago,

Illinois, USA), to determine the independent character-

istics associated with late POPAF. For the purpose of the

follow-up analysis, we defined events as the occurrence of

either cardiovascular death, or nonfatal myocardial infarc-

tion or stroke or coronary revascularization or hospitaliz-

ation for decompensated heart failure, whichever first,

and the Kaplan–Meier cumulative event-free survival

was computed.

ResultsStudy populationDuring the study period, a total of 2644 patients were

considered. Of these, 388 (14.7%) were excluded due to

the presence of chronic or persistent atrial fibrillation

after cardiac surgery. Consequently, 2256 patients were

enrolled, with a time distance from cardiac surgery of

18.1� 22.4 days. Isolated coronary artery bypass graft

(CABG) and valve interventions accounted for 1419

(62.9%) and 361 (16.0%) cases, respectively, whereas

combined surgery accounted for the remaining 476

(21.1%) cases. The mean age of patients was 67� 10

years, with a male/female ratio of 3 : 1. Cardiac rehabilita-

tion was mainly offered as inpatient programs (84.3%),

and the observation period was 13� 20 days (range 1–

120; median 19). Early POPAF, resulting in active restor-

ation of the sinus rhythm before discharge from the

surgery unit, was reported in 623 (27.6%) patients.

Occurrence of late POPAF during cardiac rehabilitationDuring cardiac rehabilitation, late POPAF occurred in

241 (10.7%) patients comprising 100 (4.4%) and 141

(6.3%) new-onset and recurrent cases, respectively.

The occurrence of late POPAF among coronary, valve

and combined surgery was 6.6, 21.9 and 14.3%, respect-

ively. The prevalence of recurrent POPAF, as compared

thorized reproduction of this article is prohibited.

http://www.iacpr.it/

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392 Journal of Cardiovascular Medicine 2011, Vol 12 No 6

Fig. 1

93.4%

89.3%

85.9%77.8%

3.1% 9.7% 4.4%4.4% 6.3%

9.7%12.5%3.5%0

300

600

900

1200

1500

1800

2100

Isolated CABG surgery Isolated heart valvesurgery

Combined surgery Overall

N°

of p

ts.

Stable sinus rhythm New-onset POPAF Recurrent POPAF

P = 0.623 P = 0.339 P < 0.01P < 0.01

Distribution of late postoperative atrial fibrillation cases during cardiac rehabilitation, according to the type of surgery (the P value refers to thedifference in new-onset and recurrent postoperative atrial fibrillation).

to new cases (Fig. 1), was significantly higher in the whole

population (P< 0.01) and among patients with combined

coronary and heart valve surgery (9.4 vs. 4.8%, respec-

tively, P< 0.01).


Table 1 Demographic and clinical characteristics in patients with andcardiac rehabilitation

Variable Evaluated (n) Presen

Male sex 2256 1Age >65 years 2256 1Age >75 years 2256Isolated coronary surgery 2256Isolated valve surgery 2256Combined surgery 2256Hypertension 2256 1Diabetes 2256LVEF <50% 1430LVEF <30% 1430Metabolic syndrome 1430Early POPAF 2256 1Postop ventricular arrhythmias 2256Postop ACS 2256Postop stroke/TIA 2256Postop severe anemia 2256Postop renal failure 2256Postop hepatic failure 2256Postop severe pericardial effusion 2256Postop pneumothorax 2256Postop heart failure 2256Postop respiratory failure 2256Postop pulmonary embolism 2256Postop sepsis 2256PAD 2256COPD 2256Chronic renal failure 2256Chronic hepatic disease 2256Chronic neurological disease 2256Chronic gastrointestinal disease 2256Neoplastic disease 2256

ACS, acute coronary syndrome; COPD, chronic obstructive pulmonary disease; LVEF, leatrial fibrillation; Postop, postoperative; TIA, transient ischemic attack. Early POPAF refeunit; late POPAF referred to arrhythmias that occurred after discharge from surgery unitssyndrome was defined according to the National Cholesterol Education Program Adpostoperative history of blood transfusion. Renal failure referred to a serum creatinine lhistory of pericardial drainage. Neoplastic disease referred both to a history of previo

At univariate analysis, late POPAF occurred more fre-

quently (Table 1) in women (P< 0.001) and in the elderly

(P< 0.001), as far as among patients with hypertension

(P< 0.001), left-ventricular ejection fraction less than


without occurrence of late postoperative atrial fibrillation during

ce of late POPAF Absence of late POPAF P

54 (63.9%) 1584 (78.6%) <0.00181 (75.1%) 1240 (61.5%) <0.00186 (35.7%) 499 (24.8%) <0.00194 (39.0%) 1325 (65.8%) <0.00179 (32.8%) 282 (14.0%) <0.00168 (28.2%) 408 (20.2%) <0.0117 (85.1%) 1039 (49.1) <0.00150 (20.7%) 499 (24.8%) 0.18672 (82.8%) 532 (39.6%) <0.001

4 (4.6%) 57 (4.2%) 0.85939 (45.0%) 239 (18%) <0.00121 (50.2%) 502 (24.9%) <0.001

8 (3.3%) 31 (1.6%) <0.017 (2.9%) 56 (2.8%) 0.9073 (1.2%) 30 (1.5%) 0.934

64 (26.6%) 356 (17.7%) <0.00118 (7.5%) 102 (5.1%) 0.158

2 (0.8%) 26 (1.3%) 0.7231 (0.4%) 9 (0.4%) 0.5893 (1.2%) 19 (0.9%) 0.918

13 (5.4%) 61 (3.0%) 0.07311 (4.6%) 53 (2.6%) 0.117

1 (0.4%) 0 (0%) 0.2344 (1.7%) 54 (2.7%) 0.479

49 (20.3%) 306 (15.2%) 0.05051 (21.2%) 243 (12.1%) <0.00135 (14.5%) 142 (7.0%) <0.00124 (10.0%) 54 (2.7%) <0.00124 (10.0%) 76 (3.8%) <0.00126 (10.8%) 151 (7.5%) 0.09418 (7.5%) 78 (3.9%) <0.05

ft-ventricular eject fraction; PAD, peripheral arterial disease; POPAF, postoperativerred to arrhythmias with successful cardioversion before discharge from the surgery, in patients with stable sinus rhythm at the entry of cardiac rehabilitation. Metabolicult Treatment Panel III (NCEP ATP III) criteria. Severe anemia was defined as aevel at least 2.5 mg/dl. Severe pericardial effusion was defined as a postoperativeus neoplasm or active cancer.

C


Fig. 2

8.6%7%6.1% 6.5%

8.9%9.3%

0

5

10

15

20

25

30

ACE-I/ARBs BB Statins

% o

f pts

.

Presence of drug Absence of drug

P = 0.080 P = 0.275 P = 0.317

Occurrence of late postoperative atrial fibrillation according to thepresence of ongoing cardioprotective drugs during cardiacrehabilitation after cardiac surgery. ACE-I, angiotensin-convertingenzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker.Antithrombotic drugs not considered.

Fig. 3

log-rank P = 0.035

Time days

Cum

ulat

ive

surv

ival

noyes

1.00

0.95

0.90

0.85

0.80

0 100 200 300 400

POPAF:

Event-free survival from major cardiovascular events according to thepresence of late postoperative atrial fibrillation during cardiacrehabilitation.

50% (P< 0.001), metabolic syndrome (P< 0.001), history

of early POPAF (P< 0.001), postoperative severe anemia

(P< 0.001), and postoperative ventricular arrhythmias

(P< 0.01). Several chronic conditions, such as renal

failure (P< 0.001) and obstructive pulmonary disease

(P< 0.001), were also significant univariate predictors

of late POPAF. Lack of prescription of single cardiopro-

tective drugs was not significantly associated to increased

occurrence of late POPAF (Fig. 2).

At multivariate analysis, valve surgery [odds ratio (OR)

3.077, 95% confidence interval (CI) 1.023–9.257,

P< 0.05], a history of early POPAF (OR 3.579, 95% CI

2.460–5.206, P< 0.001), and the presence of postopera-

tive ventricular arrhythmias (OR 3.017, 95% CI 1.037–

8.776, P< 0.05) independently predicted the occurrence

of late POPAF.

Follow-upFollow-up was completed among 710 patients after cor-

onary surgery, in 81 (11.4%) of whom late POPAF

occurred during cardiac rehabilitation. Late POPAF

was associated with an increased 1-year risk of major

cardiovascular events after the end of the CRP (P< 0.05;

Fig. 3). The overall event rate was 9.6%, with a higher

incidence among patients with late POPAF (32.1%), as

compared to those without POPAF (6.7%, P< 0.001).


Table 2 Cardiovascular events during follow-up after the end of the card

Events Presence of late POPAF (n¼8

Cardiovascular death 2 (2.5%)Nonfatal MI 0Nonfatal stroke 0Coronary revascularization 1 (1.2%)Hospitalization for decompensated heart failure 23 (28.4%)Total MACE 26 (32.1%)

MACE, major adverse cardiovascular event; MI, myocardial infarction; POPAF, postop

Late POPAF was associated with a significantly higher

risk of rehospitalization for decompensated heart failure

(28.4 vs. 2.2%, P< 0.001), whereas the risks of cardio-

vascular death, myocardial infarction, stroke and coronary

revascularization were similar between the two groups

(Table 2).

DiscussionThe ISYDE and ICAROS studies gave a unique oppor-

tunity to evaluate, on a national basis, the epidemiology

of late POPAF after discharge from cardiac surgery units,

with the following main findings: late POPAF may affect

up to one-tenth of patients after the acute phase, with a

larger presentation as recurrent episodes; the arrhythmia

is often associated with increased cardiovascular events in

the medium term; and several clinical variables, easily

discovered after discharge from the surgery setting, are

associated with an increased risk for late POPAF, and

may be adopted in a prediction model.

When exploring the epidemiology of POPAF after cardiac

surgery, it is important to keep in mind the very wide range

of reported incidence rates, according to population

characteristics, type of surgery, arrhythmia definition

and, importantly, the observation period. Our study popu-

lation appeared representative of all patients discharged


iac rehabilitation program, according to the presence of late POPAF

1) Absence of late POPAF (n¼629) Total (n¼710) P

13 (2.1%) 15 (2.1%) 0.8620 0 –0 0 –

15 (2.4%) 16 (2.3%) 0.77414 (2.2%) 37 (5.2%) <0.00142 (6.7%) 68 (9.6%) <0.001

erative atrial fibrillation.

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394 Journal of Cardiovascular Medicine 2011, Vol 12 No 6

from cardiac surgery units, since it was obtained by a

national cardiac rehabilitation network. Moreover, cardiac

surgery patients rarely have a direct referral pathway to the

general practitioner in Italy, thus minimizing the risk of

enrolment bias. According to the ISYDE and ICAROS

requirements for data collection, patients were categorized

as undergoing coronary, valve and combined surgery, in

order to evaluate the broad spectrum of cardiac conditions.

The detection of late POPAF depended on the single care

process of each cardiac rehabilitation unit, without a stan-

dardized diagnostic method, but reasonably as a result of a

harder look for the arrhythmia due to the large proportion

of inpatients (84%) enrolled, and given the opportunity of

continuous monitoring. A cumulative observation period

of about 30 days was obtained by coupling the average

length of stay in the surgical setting and the duration of

CRP, thus giving the possibility to differentiate early and

late POPAF, as new and recurrent cases.

Considering arrhythmic episodes reported in the acute

phase and during CRP, we obtained a global incidence

of POPAF around 40%, with the highest occurrence of 50%

after valve surgery. Meta-analysis of available data found a

26% incidence rate of POPAF after CABG surgery,7 and a

range between 33 and 69% for valvular and combined

interventions,1,2 confirming type of surgery as a predispos-

ing factor. However, multiple conditions (i.e. local inflam-

mation, chemical stimulation or sympathetic activation)

play a role in the pathophysiology of POPAF, and no single

mechanism surrounding a specific procedure may explain

per se this difference. Focusing on late episodes, their

contribution to the whole amount of POPAF is not neg-

ligible, as in our study 100 out of 723 new cases (14%)

developed after discharge from surgery units, thus provid-

ing the evidence that POPAF is not strictly confined to the

immediate postoperative period. The rate of POPAF

recurrence after discharge was even higher, with up to

one-quarter of patients suffering from a further arrhythmic

episode during the rehabilitation phase. In this context, it

may not be surprising that both ISYDE and ICAROS

registries reported POPAF as one of the leading causes

of morbidity and incremental costs of treatment during

CRP. As for all cases, the relative proportion of new and

recurrent cases in determining late POPAF varied with

type of surgery, with a two-fold higher incidence of recur-

rent arrhythmias after combined intervention, probably

explained by the increased frailty of patients who require

coronary and valve procedures at the same time.

Patients who experienced late POPAF after cardiac

surgery appeared to have a worse prognosis in the medium

term. This finding is in contrast with the historical con-

sideration of POPAF as a ‘benign’ complication of cardiac

surgery. Even after completion of CRP, when tailored

efforts have been made to improve clinical stabilization

and reduce cardiovascular risk, patients with late POPAF

display higher rates of cardiovascular events, mainly epi-

sodes of decompensated heart failure. Unfortunately, our


study was not designed to evaluate the development of

very late POPAF after the end of CRP, so the hypothetical

role of recurrent POPAF in determining further readmis-

sion for heart failure could only be argued.

According to other series,3 one of the most consistent

variables associated with POPAF is increasing age, as

age-related pathologic changes in the atrium are well

known to contribute to arrhythmia susceptibility. Other

relevant factors in several reports were previous arrhyth-

mias, hypertension, chronic heart failure, chronic obstruc-

tive pulmonary disease, renal failure, metabolic syn-

drome and postoperative anemia,8 and for all of these

we confirmed an association with late POPAF. As a major

evidence, valve surgery and the presence of rhythm

disturbances (both atrial or ventricular) in the immediate

postoperative period were found to predict late POPAF

after discharge from surgery units, whereas no relation-

ship emerged between late POPAF and the postopera-

tive use of cardioprotective drugs. Apart from the use of

beta-blockers, antagonists of the renin–angiotensin–

aldosterone system, and statins in coronary patients,

these treatments are not currently licensed for POPAF

prevention, and probably the identification and correc-

tion of precipitant factors (such as anemia, hypoxia or

electrolyte imbalance) still remains the best intervention

to reduce POPAF incidence.

Our study has limitations. The observation period did not

cover the entire postoperative window at risk for late

POPAF, and consequently we cannot exclude that

arrhythmic episodes may affect patients even after dis-

charge from cardiac rehabilitation facilities, both in the

form of symptomatic and asymptomatic presentation.

However, such episodes could be hardly distinguished

from other types of atrial fibrillation, in which cardiac

surgery could not be advocated as the unique proarrhyth-

mic factor. We were also unable to have information

about the use of prophylactic antiarrhythmic medications

(i.e. preoperative regimens with beta-blocker or amio-

darone), with respect to several echocardiographic, elec-

trocardiographic or intraoperative variables that have

been demonstrated to influence the development of

POPAF.8–12 Anyway, apart from inconsistency between

different studies, the insertion of such variables in the

prediction model would have affected the pragmatic aim

to help clinicians to identify patients at risk of late

POPAF, by using readily obtainable clinical indicators.

Moreover, follow-up was available only for patients

enrolled in the ICAROS registry, with a catchment of

about one-third of the whole patient population.

Notwithstanding these limitations, this study provides

information about an often ‘missed’ complication of car-

diac surgery, the diagnostic and therapeutic management

of which just shifts from the acute to the subacute care

context, still remaining an important source of morbidity

and attributable costs.


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AcknowledgementThe study was partially supported by a grant from I.F.B.

Stroder, Italy.

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late postoperative atrial fibrillation after cardiac surgery: a national survey within the cardiac...

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