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Cardiac Care for the Cancer Survivor
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Cardiac Care for the Cancer Survivor
Suma H. Konety, MD, MSCardiovascular Division
University of Minnesota
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.
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.
Cancer Therapies Implicated in Cardiovascular Complications
• Chemotherapy agents– Anthracyclines
• Daunorubicin• Doxorubicin• Epirubicin• Idarubicin• Mitoxantrone
– Tyrosine kinase inhibitors• Trastuzumab• Avastin• Sunitinib• Dasatinib
– Alkylating Agents• Cyclophosphamides
• Radiation therapy– Mantle – Mediastinal– Cervical – Supraclavicular – Left breast radiation
Cardiovascular Complications From Cancer Therapy
Chemotherapy • Cardiomyopathy
– Asymptomatic– Symptomatic
• Arrhythmias• Hypertension• Coronary heart disease• Dyslipidemia
Radiation therapy• Coronary heart disease• Valvular heart disease• Pericardial disease• Vascular disease• Congestive heart failure• Arrhythmias
Signs and Symptoms Cancer Therapy Induced Cardiomyopathy
Symptoms• Shortness of breath• Chest pain• Palpitations• Swelling of the feet• Abdominal fullness
Signs• Jugular venous distension• Cardiac murmur• S3, S4• Pericardial rub• Rales, wheezes• Peripheral edema
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.
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
Anthracycline-induced cardiomyopathy
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.
Strategies For Prevention of Anthracycline- induced CHF
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.
SECONDARY PREVENTION
Diagnostic OptionsCancer Therapy Induced Cardiomyopathy
• HOW– Imaging
• Nuclear ventriculography• Echocardiography – 2D, 3D, strain, stress• Cardiac magnetic resonance• Vascular function
– Biomarkers• NT pro-BNP• Troponin
• WHO• WHEN
• 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?
ACC/AHA Guidelines for Evaluation and Management of HF
Secondary PreventionCancer 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.
Risk Factors For Chemotherapy Related Cardiac Toxicity
COG LTFU Guidelines: 2008
Chemotherapy: Screening
COG LTFU Guidelines: 2008
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
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.
Risk Factors For Radiation Therapy Related Cardiac Toxicity
COG LTFU Guidelines: 2008
Radiation Therapy: Screening
COG LTFU Guidelines: 2008
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
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
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.