Suma Konety, M.D., M.S., Cardiovascular Division, University of Minnesota

1. Cardiac Care for the Cancer
Survivor
Suma H. Konety, MD, MS
Cardiovascular Division
University of Minnesota

2. Overview
• Cancer treatment related cardiotoxicity –
what, when, how, who?
• Strategies to prevent cardiac toxicity.
• Role of cardiac imaging in screening.
• Future directions to mitigate risk.

3. Current State
• Long term cancer survivors are increasing.
• Cancer treatment can lead to unintended and lasting
damage to the cardiovascular system.
• Many antineoplastic agents cause cardiotoxicity.
• Broad clinical spectrum of cardiac problems.
• The pathophysiology is not completely understood.
• There is no clear consensus on how to treat cardiac
dysfunction in cancer patients.

4. Cancer Therapies Implicated in
Cardiovascular Complications
• Chemotherapy agents • Radiation therapy
– Anthracyclines – Mantle
• Daunorubicin – Mediastinal
• Doxorubicin – Cervical
• Epirubicin
– Supraclavicular
• Idarubicin
• Mitoxantrone – Left breast radiation
– Tyrosine kinase inhibitors
• Trastuzumab
• Avastin
• Sunitinib
• Dasatinib
– Alkylating Agents
• Cyclophosphamides

5. Cardiovascular Complications From
Cancer Therapy
Chemotherapy Radiation therapy
• Cardiomyopathy • Coronary heart disease
– Asymptomatic • Valvular heart disease
– Symptomatic
• Pericardial disease
• Arrhythmias • Vascular disease
• Hypertension • Congestive heart failure
• Coronary heart disease • Arrhythmias
• Dyslipidemia

6. Signs and Symptoms
Cancer Therapy Induced Cardiomyopathy
Symptoms Signs
• Shortness of breath • Jugular venous distension
• Chest pain • Cardiac murmur
• Palpitations • S3, S4
• Swelling of the feet • Pericardial rub
• Abdominal fullness • Rales, wheezes
• Peripheral edema

7. Chemotherapy Induced Cardiomyopathy
• LVEF <50% or a 10% drop in
LVEF is widely accepted as LV
dysfunction in the oncology
community.
• LV dysfunction could be
symptomatic or asymptomatic.
• LV dysfunction could manifest
acutely or have a late onset and
can also be chronic and
progressive.
Yeh ETH, et al. JACC 2009:53.

8. Pathophysiology of Anthracycline Cardiac
Toxicities
• Anthracyclines has been a mainstay of therapy for
breast
cancer, leukemia, lymphoma, sarcoma, etc..
• Damages nuclear DNA, changes calcium handling
and cellular contractility, suppresses factors that
regulate cell survival and protein synthesis.
• Serial imaging is the current screening strategy
• Early detection and treatment could be lifesaving

9. Anthracycline-induced
cardiomyopathy

10. CHF in Breast Cancer Survivors
Using the Surveillance, Epidemiology and End Results (SEER) Medicare database women aged 66 to
70 treated with anthracycline compared with other chemotherapy had a 26% higher risk of CHF.
Pinder MC, et al. JCO 2007;25(25):3808-3815.

11. Strategies For Prevention of
Anthracycline- induced CHF

12. Statins Protect Breast Cancer Patients From
Heart Failure
Using the Cleveland Clinic database women with breast cancer after treatment with
anthracycline who received statin therapy compared to cancer controls not on
statin had a 70% lower risk of incident CHF.
Seicean S, et al. JACC 2012;60:2384-90.

13. SECONDARY PREVENTION

14. Diagnostic Options
Cancer Therapy Induced Cardiomyopathy
• HOW
– Imaging
• Nuclear ventriculography
• Echocardiography – 2D, 3D, strain, stress
• Cardiac magnetic resonance
• Vascular function
– Biomarkers
• NT pro-BNP
• Troponin
• WHO
• WHEN

15. • Observational study of 42 patients with anthracyclines
compared to 15 healthy controls
• On cardiac MR - no myocardial edema or focal scar
• Diffuse myocardial fibrosis was found in the
anthracycline treated patients compared to controls
• Implication -
• Is DF a transition step from normal to irreversible
damage?
• Role of RAS modulators to reverse the remodeling
process?

16. ACC/AHA Guidelines for Evaluation and
Management of HF

17. Secondary Prevention
Cancer Therapy Induced Cardiomyopathy
• There is paucity of well-conducted RCTs that
would provide the evidence to support
pharmacological intervention.
• Studies have failed to demonstrate clinically
significant improvement in cardiac function in
childhood cancer survivors.*
• However, survivors treated with high dose (≥300
mg/m2) of anthracyclines benefited most from
the intervention.*
• In muscular dystrophy patients, there was
survival benefit with afterload reduction.+
* Silber JH et al. J Clin Oncol: 22; 2004.
+ Connuck DM et al. Am Heart J: 155;2008.

18. Risk Factors For Chemotherapy Related
Cardiac Toxicity
COG LTFU Guidelines: 2008

19. Chemotherapy: Screening
COG LTFU Guidelines: 2008

20. Radiation therapy
• 294 patients w/ Hodgkin's
• >35 Gy radiation
• Exercise stress test
• Conventional risk factors were not
consistently present in patients w/ CHD
• 14% (n=40) had CHD, >50% coronary
stenosis
• More common >10 yr after radiation
• Screening recommended 5-10 years
after radiation

21. Radiation Therapy and Heart Disease
Increasing risk of death and coronary events in women treated with higher doses of RT
and increased cardiac risk factors.
Darby SC et al. NEJM: 368; 2013.

22. Risk Factors For Radiation Therapy
Related Cardiac Toxicity
COG LTFU Guidelines: 2008

23. Radiation Therapy: Screening
COG LTFU Guidelines: 2008

24. Referral to the Cardiology
• Subclinical abnormalities on screening
evaluations
– Left ventricular dysfunction LVEF <55%
– Arrhythmias
– QT interval prolongation
• 5-10 years after chest radiation
– > 40 Gy of chest radiation
– > 30 Gy of chest radiation + anthracyclines
• Isometric exercise program in any high risk
patient
– Patients involved in varsity team sports

25. Health Counseling
• Heart health
– Blood pressure (<140/90 mmHg), weight (BMI
<25), cholesterol, glucose
• Heart Healthy diet
– Fresh fruits, vegetables, whole grains
– Calories from fat <35% of total calories eaten each day
– Limit saturated fat
• Daily exercise
– Aerobic exercise generally safe
– Avoid intensive isometric exercises (heavy weight lifting, wrestling)
– High repetition weight lifting using lighter weights safer
• Dental Health
• Tobacco cessation

26. Conclusions
• It is clear that both the disease (cancer) and
the treatment itself carry life threatening risk.
• Variability on susceptibility to cardiac damage
is not completely explained by clinical and
demographic factors, suggesting genetic
predisposition.
• Pharmacogenomics is a promising strategy to
minimize harm and maximize benefits.