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Georgetown University | Howard University
MedStar Health Research Institute | Oak Ridge National Laboratory | Washington DC Veteran’s Administration Medical Center
Cardio-Oncology:
What Do I Need to Know ?
Ana Barac, MD, PhD, FACC
Associate Professor of Medicine, Georgetown University
MedStar Heart and Vascular Institute, Washington DC
Georgetown University | Howard University
MedStar Health Research Institute | Oak Ridge National Laboratory | Washington DC Veteran’s Administration Medical Center
Disclosures
• No financial disclosures
• Cardiology PI for SAFE-HEaRt, investigator-initiated study funded by Genentech, Inc.
Objectives
• What is Cardio-Oncology ?
• Why ?
• Cardio-Oncology 101
Barac A, Douglas P et al. JACC 2015: 65(25): 2739
Cardiovascular Health of Patients with Cancer and Cancer Survivors
Cardiovascular Health of Patients with Cancer and Cancer Survivors in 2016
Patient Need
• Prevalent and rapidly growing population of cancer survivors
• High burden of CV risk factors (Armenian SH et al. JCO 2016)
• Synergism between CV risk factors, cancer, cancer treatment adverse outcomes
• Gap in knowledge about CV evaluation and treatment of patients undergoing cancer treatment and cancer survivors (Shelburne N, Remick S et al. JNCI 2014)
Professional Need
Cardio-Oncology Survey Final Report
Table1: Respondent Composition9
Professional Role
Cardiology fellowship training director 44%
Cardiology division chief 25%
Pediatric cardiology fellowship training
director10%
Pediatric cardiology division chief 9%
Other cardiology physician 6%
Other pediatric cardiology physician 3%
Cardio-oncology specialist 2%
*Other professional role 1%
Type of InstitutionAcademic medical center 76%
Private/community hospital with fellowship
programs16%
VA or government medical center 2%
Private/community hospital without fellowship
programs2%
Community practice 1%
Other 3%
Heart Failure ProgramTransplant center 56%
Medical heart failure care only 41%
Destination LVAD center but no heart
transplantations4%
Cardiac Cath ProgramInterventional cardiologist 98%
Invasive cardiologist 1%
Other, please specify 1%
Don’t know 1%
Oncology ProgramNCI designated cancer center 53%
Bone marrow transplant center 30%
Dedicated cancer center 26%
Other 9%
No cancer program 3%
Don’t know 9%
CV Consults for Oncology Patients
Q. Please estimate how many consults (inpatient and
outpatient) to the cardiology service at your institution
relate to oncology patients:
11%
1%
37%
48%
3%
0% 10% 20% 30% 40% 50% 60%
Don't know
> 500 / year
100-500 / year
<100 / year
Almost none
Q. Please estimate how many requests for
cardiovascular imaging studies at your institution relate to
oncology patients:
Oncology CV Imaging Requests
12%
17%
52%
17%
12%
0% 10% 20% 30% 40% 50% 60%
Don't know
> 500 / year
100-500 / year
<100 / year
Almost none
Current Clinical Cardio-Oncology Services
Q. Please indicate which description most accurately
defines your current clinical cardio-oncology services:
1%
3%
12%
15%
16%
27%
35%
0% 10% 20% 30% 40%
Don’t know
Not sure what cardio-oncology is
None at present but plan to add these serviceswithin a year
Not at present and do not plan to add theseservices
Single cardiologist with experience in cardio-oncology
Established consultation and evaluation servicewith multiple clinicians and lab services
Pre-operative consulation service for cancerpatients run by general cardiology
Q. What are the greatest barriers or challenges to a
cardio-oncology service or dedicated clinician at
your institution?
5%
7%
9%
27%
29%
36%
38%
44%
44%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%
Don't know
No barriers, we have a robust clinical service
* Other, please specify
Limited interest/ perceived value by oncologists
Limited educational opportunities
Limited infrastructure
Limited interest/ perceived value by cardiologists
No national guidelines or statements in this area
Limited funds
Challenges to Creation of Dedicated Cardio-
Oncology Services
Current Cardio-Oncology Educational Programs
Q. Which description most accurately describes your
institution's educational programs in clinical cardio-
oncology in cardiology?
Level of Understanding
Q. Do you think cardiologists/oncologists in general
have a good level of understanding of ..
3% 4%
18%
14%
27%
19%
30%
43%
17%
11%
4% 5%
1%
3%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
level of understanding of the impact that holding / stoppinganti-cancer treatments for a cardiovascular reason has on
cancer outcomes
level of understanding of the impact that slow or inadequateinvolvement of a cardiologist when a cardiovascular
problem develops in an oncology patient has on cardiacoutcomes
0- Poor level of understanding 1 2 3 4 5-Excellent level of understanding Not Sure
Mean: 2.52 Mean: 2.61
Cardiologists: Self Rating Oncologists: Rated by Cardiologists
Improving Outcomes of Cancer-treatment Related CV Toxicity
AgeSex
Prior exposure
Adverse outcomes Cancer
treatment
CV Risk factors:
HTN, DM, obesity
Genetic risk factors
Identification of High Risk Patient
Modification of exposure
Primary CV prevention
CV Monitoring and screening
Early intervention (preclinical state)
Cancer
OPTIMIZED OUTCOMES
Comprehensive CV Care in Real Time Oncology Patients
Cancer/Cancer Treatment
Host Interaction
CV Risk factors and CV disease
Cancer treatment-related CV toxicities
HEART FAILUREStage A - D
VALVULARDISEASE
CORONARY ARTERY DISEASE
VASCULAR DISEASE
HYPERTENSIONATRIAL
FIBRILLATION
EVIDENCE FOR TREATMENT, MONITORING, PREVENTION AND LIFE STYLE MEASURES?
Comprehensive CV Care in Real Time Oncology World
Cancer/Cancer Treatment
Host Interaction
CV Risk factors and CV disease
Cancer treatment-related CV toxicities
HEART FAILUREStage A - D
VALVULARDISEASE
CORONARY ARTERY DISEASE
VASCULAR MEDICINE
HYPERTENSION
ATRIAL FIBRILLATION
PREVENTION AND LIFE STYLE MEASURES
PartnershipIn Patient
Care!
Standards for Prevention and Monitoring of Cancer-Treatment Related Cardiac Dysfunction
ACC/AHA 2013 Heart Failure Guidelines
FDA package inserts for cancer therapeutics
Children’s Oncology Group (COG) Guidelines
NCCN 2015 Guidelines on Survivorship ASE/EACVI 2014 Expert Consensus for Multimodality Imaging of Adult Patients During and After Cancer therapy
ASCO Clinical Practice Guideline on Prevention and Monitoring of Cardiac dysfunction
Standards for Prevention and Monitoring of Cancer-Treatment Related Cardiac Dysfunction
AHA Scientific Statement: Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy (2013)
SCAI Expert consensus statement: Evaluation, management and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (2016)
Canadian Cardiovascular Society Guidelines for Evaluation and Management of Cardiovascular Complications of Cancer Therapy (2016)
ESC CPG Position Paper (Cardio-Oncology) – Rome 2016
Cancer Therapeutics Associated with Cardiac Dysfunction
• Anthracyclines
Ewer M et al. Heart Failure Clin 2011:7:363
Cardiac Imaging in Oncology
• Reduce the anthracycline dose
Check baseline LV systolic function
Monitor LV function
ERNA (MUGA)
Singal & Iliskovic. NEJM 1998; 339:900
YES vs NO
Cancer Therapeutics Associated with Cardiac Dysfunction
Slamon et al. NEJM. 2001;344:783
• HER2 targeted agents (trastuzumab)
HER2-targeted therapy and cardiotoxicity
• Metastatic BC (AC= doxorubicin + cyclophosphamide)
Cardiotoxicity trastuzumab + AC
(N=143)
AC
(N=135)
Cardiac dysfunction % 28 10
NYHA III/IV CHF, % 19 3
Subsequent trials in Early Breast Cancer
• Stringent CV eligibility criteria
• Changes in administration
• Cardiac monitoring schema
NEW ERA OF CARDIAC MONITORING IN ONCOLOGY TRIALS
Seidman A et al. 2002. J Clin Oncol : 20:1215
Cardiotoxicity in Early Breast Cancer Trials
1 year of Herceptin n
Asymptomatic decline in LVEF, %
Severe HF, %
NSABPB-31 947 NR 3.8
NCCTG N9831 570 NR 3.3
BCIRG006 * 1068 18 1.9
HERA 1678 3.0 0.6
modified from Telli M et al. JCO 2007(25):3525
7-year follow-up assessment of cardiac function in NSABP B-31
Treatment Arms ACP- H (N=947) vs ACP (N=743)
Cardiac events 37 (4.0%) vs 10 (1.3%)
Romond EH et al. JCO 2012;30:3792
Romond EH et al. J Clin Oncol 2012;30:3792
Predictors of trastuzumab-related cardiotoxicity based on NSABP B-31
Risk Factor N CHF (N=37) (%) HR (95% CI)
Age <5050-59>60
485311148
11 (2.3)17 (5.5)9 (6.1)
2.4 (1.1-5.2)2.7 (1.1-6.6)
Baseline LVEF>65%55-64%50-54%
42345170
9 (2.1)19 (4.2)9 (12.9)
2.0 (0.9-4.4)6.7 (2.7-16.9)
Hypertensionmedications – No
Yes744193
24 (3.2)13 (6.7) 2.1 (1.1-4.1)
Population-based Cohort and Risk Prediction
Bowles et al. J Natl Cancer Inst 2012; 104:109
• 12,500 women with breast cancer dg between 1999-2007
Anthracycline alone
Anthracycline + trastuzumab Trastuzumab
Incidence of HF or Cardiomyopathy after Adjuvant Therapy in SEER-Medicare
Chen J. J Am Coll Cardiol 2012;60:2504-12
• Surveillance, Epidemiology and End Results- Medicate data from 2000-2007• 45, 537 women age 67-94
Adjusted 3-year cummulative incidence of HF/CM41.9%
Risk Prediction Model for HF and CM after Adjuvant Therapy for Breast Cancer
Ezaz et al J Am Heart Assoc 2014;3:e000472
• BCIRG-006 – 7 LVEF measurements
– Symptomatic HF– AC-T 0.7% – AC-TH 2%
– TCH 0.4%
• Too many patients not receiving (full) benefit of HER2 therapy for possibly minimal cardiac risk?– Patients excluded
at baseline? Slamon D et al. N Engl J Med. 2011 365(14):1273
18.6%
11.2%
9.4 %
LVEF decrease >10 %
Successes and Challenges of Cardiac Screening in Adjuvant HER2+ Breast Cancer Trials
Primary Prevention of Cardiac Dysfunction
• Clinical trials examining the role of use of beta-blockers and RAAS-system inhibition in patients receiving HER2 targeted therapies
– PRADA (Gulati G et al. Eur Heart J, Feb 2016)
– MANTICORE (Pituskin et al. SABC 2015)
YES vs NO
PRADA vs MANTICORE
• Study Population– All epirubicin, 22%
trastuzumab
• Study design– 2x2, metoprolol and
candesartan
• Primary Outcome– Changes in LVEF by CMR at
10-64 weeks
• Results– Attenuation of LVEF
decline with candesartan (order of 2-3%)
• Study Population– All trastuzumab, 12-33%
anthracycline
• Study design– 1:1:1 bisoprolol,
perindopril, placebo
• Primary Outcome– Changes in LVEDVi by
CMR at 1 year
• Results– Attenuation of LVEF
decline with bisoprolol(order of 4%)
Cancer-Treatment Related Cardiac Dysfunction
1. Which cancer patients are at increased risk for developing cardiac dysfunction?
2. Which preventative strategies minimize risk prior toinitiation of therapy?
3. Which preventive strategies are effective in minimizing risk during the administration of potentially cardiotoxiccancer therapy?
4. What are the preferred surveillance / monitoring approaches during treatment in patients at risk for cardiac dysfunction?
5. What are the preferred surveillance/ monitoring approaches after treatment in patients at risk for cardiac dysfunction?
Armenian S. et al. ASCO Clinical Practice Guideline on Prevention and Monitoring of Cardiac dysfunction (submitted)
Best Practices in Cardio-Oncology
acc.org/cardio-oncology
Want to Know More?
HOW?
Cardio-Oncology Partnership in Practice
• Create Awareness
• Patient and Staff Education
• Comprehensive program
• Input at oncology forums
• Evidence of Growth
• Outcome data
Approaches to Facilitate Institutional Support for Cardio-Oncology
Barac A, Okwuosa T JACC 2015: 66:1193
