Ludhmila Abrahão Hajjar, MD, PhDInCor, Cancer Institute, Hospital SirioLibanes

University of Sao Paulo

CARDIO-ONCOLOGY:AN INTERNATIONAL PERSPECTIVE

CONFLICTS OF INTEREST

• None

Presenter

Presentation Notes

Brazil is going through

Cardio-Oncology

The intersection between diseases

AgeTobaccoDiabetesObesity

HypertensionHyperlipidemia

Sedentary lifestyleEndothelial dysfunctionChronic inflammation

Oxidative stressChemotherapy

RtImmunotherapy

Hormones

CANCER CVD

THE MULTIPLE MECHANISM PHENOMENACytotoxic chemotherapy

Signaling inhibitorsRadiation

ImmunotherapySurgery

Baseline CVRisk Factors

CancerDiagnosis CV Reserve

CARDIOVASCULARDISEASE

AgingCommon risk factors

Surgery

Cardio-Oncology

CARDIOVASCULAR INJURY

Lenemman CG et al. Circ Res. 2016;118:1008-1020.

Cardio-Oncology

CP Inhibitors

PROBLEM

INTERVENTION

OUTCOME

Scene 1

TO AVOID THE PROBLEM

RISKPREDICTION

INTERVENTIONScene 2

Cardio-Oncology

OUTCOME

Cardio-Oncology

HOSPITAL DAS CLINICAS – UNIVERSIDADE DE SAO PAULO

3,000 bedsSao Paulo, Brazil

Public health system21,000 workers

8 Institutes

InCor, 1977 Cancer Institute, 2008

CARDIO-ONCOLOGY

- 28 floors - 5,000 Chemo/month- 84,000 m2 - 4,000 Rt/month- 499 beds - 800 surgeries/month- 45,000 patients - 4 MRI

CANCER INSTITUTE (ICESP) – UNIVERSIDADE DE SAO PAULO

Research Center

articlespublished abstractstotalcitations

Cardio-Oncology – ICESP, Brazil

InCor ICU, 2006CARDIO-ONCOLOGY DEPARTMENT, 2008

Cancer ICU, 2008

Ludhmila HajjarRoberto Kalil FilhoCarolina SilvaCristina BittarGiovanni PintoIsabela BispoMarilia HiguchiSilvia Moullin

CARDIO-ONCOLOGY DEPARTMENT, 2019

Ludhmila Hajjar, Chief,Associate ProfessorRoberto Kalil FilhoFull Professor

Assistants:Carolina SilvaCristina BittarGiovanni PintoIsabela BispoMarilia HiguchiSilvia Moulin

6 Echocardiographists

- 11 clinics (general, cardiotoxicity, perioperative,

thrombosis)

- 600 patients/month

- Clinical evaluation inpatients (500 patients/month)

- CV imaging (MRI, ECHO, CTA, STRESS ECHO)

- August 2017/August 2018: 6,414 echos

- Biomarkers

- Cardio-oncologists involved in ICU care

and perioperative care

- 2 scientifics session/week

- InCor/ICESP

Cardio-Oncology – ICESP, Brazil

Fellows: Clara/Julio/Marina/Paulo

CARDIOLOGY

ONCOLOGY

SURGERY/ANESTHESIAHEMATOLOGY

INTENSIVE CARE UNIT

GERIATRICSRADIOTHERAPY

PHARMACY

REHABILITATIONNURSING

PHYSIOTHERAPYPSYCHOLOGY

GENETICS

TRANSLATIONALMEDICINE

RESEARCH CENTER

Arq Bras Cardiol 2011; 96(2 supl 1): 1-52.

Roberto Kalil FilhoAriane V.S. MacedoMarilia Higuchi dos SantosSílvia Ayub FerreiraIsabela Bispo dos SantosLudhmila Abrahao Hajjar

2016

J.B. DurandMichael Ewer

Lee JonesJavid MoslehiDaniel LenihanSusan Dent

2017

2016

2017

Co-editors:

Carolina SilvaCristina BittarGiovanni PintoIsabela BispoMarilia HiguchiSilvia Moulin

1,344 books in 18 months

Cardio-Oncology

Lenihan DJ et al. J Cardiac Failure. 2016;22:465-71.

FELLOWSHIP IN CARDIO-ONCOLOGY2017-2018

- Aline Moraes, Ana Carolina Berbel, Ana Cristina Dalarmelina, Rodrigo Rocha

- Clara Figueiredo, Julio Siqueira, Marina Bond, Paulo de Souza Neto

2017

2018

www.comissaodenensino.usp.br

Cardio-Oncology

FELLOWSHIP IN CARDIO-ONCOLOGY

CLIN = clinic INP = inpatients OP = optativeHEM = hematologyONC = oncology

MAR APR MAY JUN JUL AGO SEPT OCT NOV DEC JAN FEV

A CLIN INP HEM CLIN INP CLIN FO ONCO OP INP CLIN INP

B INP CLIN INP FO CLIN HEM INP OP ONCO INP CLIN CLIN

C CLIN INP CLIN INP HEM OP CLIN INP CLIN ONCO INP OP

D INP CLIN INP HEM FO INP ONCO CLIN INP CLIN OP CLIN

2017Rodrigo

Ana CarolinaAline

Ana Cristina

2018Julio

MarinaPauloClara

FELLOWSHIP IN CARDIO-ONCOLOGY

BRAZIL ACTIONS TO PROMOTE AND DISSEMINATE CARDIO-ONCOLOGY

2018 - Residency Program in CardiologyHospital SirioLibanes - 1 month in Cardio-OncologyInCor - 15 days in Cardio-Oncology6 Hospitals (out of SP) - 1 month in Cardio-Oncology

2018 - Book Of Cardio-Oncology For ResidentsFull subscription in meetings (all residents)

Creation of the research line – Cardio-Oncology – PhD (2016)

Website (2018) http://cardiooncologiahsl.org.br(Marilia Higuchi, Daniel Lenihan, Javid Moslehi)

Brazilian Society Certification of Centers ofCardio-Oncology (2019)

CARDIO-ONCOLOGYACTIVITIES

CARDIOLOGY MEETINGS

ONCOLOGY MEETINGS

InCor

HospitalSírio-Libanês

ICESP

CENTER OF CARDIO-ONCOLOGY

RESEARCH IN CARDIOLOGY

Brazilian Cardio-oncology Project2017-2021

• 22 research projects

• Supervisors: – Carlos Eduardo Negrão– Roberto Kalil Filho– Ludhmila Abrahão Hajjar– Paulo Hoff– Roger Chammas

U$ 2,000,000

• Coronary angiotomography in the preoperative period as a method of stratification

of cardiovascular risk in cancer patients undergoing major surgery (Cristina Bittar)

• Characterization of Cardiovascular Changes in Septic Shock in Patients with Cancer

(Ana Claudia dos Santos)

• Acute Effects of Doxorubicin and Cyclophosphamide on Autonomic Control and

Vascular Function in Women with Breast Neoplasia (Allan Kluser Sales)

• Impact of Adjuvant Chemotherapy on Cardiovascular Autonomic Regulation in

Patients With Colon Cancer (Raphaela Vilar)

RESEARCH PROJECTS 2017-2021

- Circulating miRNAs as biomarkers of cardiotoxicity and therapeutic potential

in breast cancer (Edilamar Menezes de Oliveira)

- Cardiac Magnetic Resonance with MapT1 in 3T Device for Detection of

Anthracycline Cardiotoxicity in Patients with Lymphoma (Isabela Bispo)

- Participation of aldehyde metabolism in the establishment of doxorubicin-induced cardiomyopathy: preventive and therapeutic effect of Alda-1 (JulioBatista)

- Ivabradine to Prevent Anthracyclines-induced Cardiotoxicity: a randomizedclinical trial (Stephanie Rizk)

- Cardiovascular evaluation in lymphoma survivors (Thiago Liquori)

RESEARCH PROJECTS 2017-2021

• Role of physical exercise in the prevention of cardiotoxicity caused by thechemotherapeutic agent doxorubicin (Igor Santos)

• Effect of Beta-Blocker Treatment and Physical Training on the Muscular Phenotype Streaked in Breast Cancer (Tassia Costa)

• Effect of Physical Exercise on Tumor Cell Survival and Tumor Formation (CleviaPassos)

• Physical activity as strategy for functional normalization of tumor vasculature: impact for the treatment of tumors (Janio Mororo)

RESEARCH PROJECTS 2017-2021

Evaluation of cardiac magnetic resonance imaging with strain as a method of detecting cardiotoxicity in patients ith lymphoma

submitted to anthracycline chemotherapyIsabela Bispo Costa, MD; Carlos E. Rochite, MD, PhD, Prof Ludhmila Abrahão Hajjar, MD, PhD

Design: A pilot study, with a sample of 50 patients.Prospective, observational study.

Population: Patients with lymphoma candidates forchemotherapy with anthracyclines.

Objectives:

• To evaluate CMR imaging with strain performed

sequentially during the treatment as a method of early

detection of anthracycline-induced cardiotoxicity.

• To compare the accuracy of the methods for the detection

of early cardiac damage: RMC strain x ECHO strain.

Baseline

•Electrocardiogram•Biomarkers (troponin and BNP) •Strain echocardiography•Cardiac Magnetic Resonance

T 1

•Electrocardiogram•Biomarkers (troponin and BNP) •Strain echocardiography•Cardiac Magnetic Resonance

T 2

•Electrocardiogram•Biomarkers (troponin and BNP) •Strain echocardiography•Cardiac Magnetic Resonance

Coronary computed tomographic angiography as a method of stratification of cardiovascular risk in

cancer patients undergoing major surgeryCristina Salvadori Bittar, MD, Prof Ludhmila Abrahão Hajjar, MD, PhD

• Design: Prospective, observational study. single-center (Instituto do Cancer, Universidade de São Paulo).

• Population: Cancer patients submitted a Major surgery: thoracic surgeries and open abdominal surgeries.

Pre operative evaluationLipid profileNT pro BNPCoronary CT

Electrocardiogram (ECG)

-

200 patients

Postoperative evaluation24h : CKMB , Troponin , ECG48h: CKMB , Troponin , ECGAfter 30 days: evaluation of

cardiovascular events

If Coronary CT high-risk coronary artery disease• stenosis ≥ 50% of the left coronary trunk• ≥ 70% in three coronary arteries• ≥ 70% in two arteries, one of them being

the anterior descending artery

Evaluation by thecardiologist

PLOS ONE 2018 | https://doi.org/10.1371/journal.pone.0196763

Crit Care Med 2017; 45:766–773.

Hemoglobin

7.0 vs 9.0 g/dL

Anesthesiology 2015; 122:29-38.

Hemoglobin

7.0 vs 9.0 g/dL

Gerent A, Hajjar L et al. Critical Care (2018) 22:133.

128 patients

Usual careEGDT in ICU

Gerent A, Hajjar L et al. Critical Care (2018) 22:133.

Load study, 2017(Cancer surgery subgroup)

Putzu A, Silva C, Hajjar L. Ann. Intensive Care (2018) 8:95

Cardio-Oncology

THE CARDIO-ONCOLOGIST SHOULD ALSO ACT ON:

SEPSIS

PERIOPERATIVE SETTING

ICU

AFTER THE ACUTE INSULT – WHAT HAPPENS ?

LOOKING FOR BETTER OUTCOMES

Pearse RM, Harrison DA, James P et al. Crit Care. 2006;10:R81.

Who is The High-Risk Surgical Patient

Age higher than 65 yearsCardiovascular disease

Respiratory diseaseBrain disease

CancerProcedures lasting more than 90 min

Emergency surgeries

Cardio-Oncology

•- Jean-Louis Vincent – PhD (Belgium)•- Rupert Pearse – PhD (UK)•- Daniel De Backer – PhD (Belgium)•- Donat R. Spahn – PhD (Switzerland)•- Massimo Girardis – PhD (Italy)•- Jean-Louis Teboul – PhD (French)

CHAIR:Ludhmila HajjarJean-Louis Vincent

1,108PARTICPANTS

I INTERNATIONAL SYMPOSIUM ON THE HIGH RISK SURGICAL PATIENTSAO PAULO, BRAZIL

2018

I INTERNATIONAL SYMPOSIUM ON THE HIGH RISK SURGICAL PATIENTSAO PAULO, BRAZIL

2018

VTE MORTALITYInternational Cooperative Pulmonary Embolism Registry

ICOPER registry:• 2454 patients from Europe and North America• Mortality rate at 3 months – 17.4%

Variable Hazard ratio 95% CI

Age > 70 years 1.6 (1.1–2.3)

Cancer 2.3 (1.5–3.5)

Clinical congestive heart failure 2.4 (1.5–3.7)

Chronic obstructive pulmonary disease 1.8 (1.2–2.7)

Systolic blood pressure < 90 mg Hg 2.9 (1.7–5.0)

Respiratory rate > 20/min 2.0 (1.2–3.2)

Right ventricle dysfunction 2.0 (1.3–2.9)

Goldhaber SZ et al. Lancet. 1999;353(9162):1386–1389.

Risk factors for Mortality

PULMONARY EMBOLISM SEVERITY INDEX

European Heart Journal - Quality of Care and Clinical Outcomes (2018) 0, 1–8.

12,180 patients

1,109 cancer patients

European Heart Journal - Quality of Care and Clinical Outcomes (2018) 0, 1–8.

Cardio-Oncology

Antiplatelet agents in cancer patients

Coronary Artery Disease 2017, 28:5–10

12,785 total patients

1,005 cancer patients

Coronary Artery Disease 2017, 28:5–10

PROGRAM – PHILANTROPY IN HFVentricular Assist Devices in Cancer Patients, Brazil

AML, 2 YEARS OF REMISSION, 2017 BREAST CANCER, 3 YEARS OF REMISSION, 2017

PROGRAM – POST ICU DISCHARGE

Silva N, Hajjar L, Cavalcanti AB. Crit Care Med 2016; 44:1327–1337

Objectives: To assess the long-term survival, health-related quality of life, and quality-adjusted life years of cancer patients admitted to ICUs.

Design: Prospective cohort. Setting: Two cancer specialized ICUs in Brazil. Patients: A total of 792 participants

Silva N, Hajjar L, Cavalcanti AB. Crit Care Med 2016; 44:1327–1337

Silva N, Hajjar L, Cavalcanti AB. Crit Care Med 2016; 44:1327–1337

1 year 1.5 Year42.1% 38.1%

1 year 1.5 Year30.1% 19.1%

Silva N, Hajjar L, Cavalcanti AB. Crit Care Med 2016; 44:1327–1337

Cardio-Oncology

WITH THESE PATIENTS, WE NEED TO BE:

1.EFFICIENT2.FAST3.PRESENT4.OPEN TO COLLABORATION

AND MORE IMPORTANT:

“WE MUST PERSONALIZE CARE ANDUNDERSTAND THAT PATIENT IS THE

CENTER OF CARE”

BUT, THE BEST HAS NOT OCCURRED YET …

OCTOBER 3th and 4th

SÃO PAULO, BRAZIL

SUSAN DENTDANIEL LENIHAN

MICHAEL FRADLEYROBERTO KALIL FILHO

LUDHMILA ABRAHAO HAJJAR

SUPPORTED BY:

CARDIO-ONCOLOGISTS WORLDWIDE

ludhmila@usp.br

@draludhmilahajjar

@ludhmilahajjar

THANK YOU !