12/16/16 SECTION HEADING Disclosures I have no relevant financial - PDF document

12/16/16 SECTION HEADING Disclosures I have no relevant financial disclosures. Cardio-oncology: A practical overview for the cardiologist Division of Cardiology Department of Medicine Rajni Rao, MD Cardiology Clinic Practice Chief Rajni Rao, MD UCSF Health System Associate Professor of Medicine School of Medicine 2 SECTION HEADING Learner Objectives Case 1 • Epidemiology of cardio- • Screening for • 61 yo woman w/ 1. CHF oncology cardiotoxicity metastatic renal 2. Bradycardia • Understand risk factors • Prevention and cell carcinoma for cardiotoxicity treatment of 3. Hypertension starting cardiotoxicity • Identify manifestations sunitinib. What of cardiotoxicity by 4. Coronary different cancer is most common thrombosis treatment modalities, complication? focusing on the 3 most common offending agents (Biar SM Moslehi J 2013) School of Medicine School of Medicine 3 4 1

12/16/16 SECTION HEADING Case 2 What is cardio-oncology? • 48 year old woman with 1. Cont. w/ treatment – • Cardiac subspecialty focusing on the HER2+ breast cancer, cancer will progress screening, evaluation, prevention, and s/p lumpectomy, otherwise. Repeat treatment of CV complications during or receiving adjuvant echo in 1 month. after cancer therapy chemotherapy and 2. Start carvedilol, trastuzumab. 12 weeks • Cancer treatments are progressing rapidly – lisinopril, continue into treatment, EF with treatment. more drugs being developed for cancer than drops from 56% at any other condition---cardiologists must 3. Prescribe a Life Vest baseline to 33%. No HF for primary sxs. keep up and provide recommendations prevention of SCD. tailored to each patient and their cancer • BP 130/87, HR 77. RRR 4. Hold chemo; start treatment plan no m/r/g. No JVD or ACEI/BB, repeat echo edema. in 4 weeks. • What do you do? (Biar SM Moslehi J 2013) School of Medicine School of Medicine 5 6 “This is our moonshot…to end cancer as Rapid pace of change we know it.” One of the 10 recommendations for the 2016 Cancer Moonshot initiative Minimize cancer treatment’s debilitating side effects…This recommendation calls for research to support development of guidelines for managing patient- reported symptoms and side effects of cancer treatment in adults and children, with the goal of helping patients stay on their drug regimens and improve their quality of life. School of Medicine School of Medicine 7 8 2

12/16/16 SECTION HEADING SECTION HEADING Types of CV complications and What’s the connection? toxicities from cancer treatment • In childhood cancer survivors, CV mortality is 5-fold • Arrhythmia higher than general population • Myocyte necrosis à dilated cardiomyopathy (DCM) • HF patients with cancer have 56% increased • Vascular: VTE, ATE, vasospasm, accelerated mortality atherosclerosis à angina, MI • Cancer treatment accelerates the development of CV • Hypertension disease • RF’s overlap: obesity, tobacco, age, inflammation, poor nutrition • Like HIV and other diseases, cancer is often a chronic condition and patients may live to suffer from heart disease • CV health is essential for good cancer treatment outcomes School of Medicine School of Medicine 9 10 SECTION HEADING SECTION HEADING Cancer timeline Anthracyclines • Daunorubicin 1963 – initially a childhood leukemia 1999 Gleevec (imatinib) treatment revolutionizes tx of CML and kickstarts the • CHF developed with maintenance treatment development of targeted 1963 1st 1977 dose- therapies and • Dose dependent (>300-400 mg/m2) anthracycline dependency kinase discovered identified inhibitors • 30% of children had cardiac dysfunction at long-term follow-up • Anthracyclines block topoisomerase II to prevent DNA replication. Why should that affect terminally 1966 1998 2007 cardiotoxicity Trastuzumab TK/multikinase differentiated cardiac myocytes? reported from (herceptin) inhibitors found daunorubicin cardiotoxicty to cause HTN, identified HF, ATE, VTE School of Medicine School of Medicine 11 12 3

12/16/16 SECTION HEADING SECTION HEADING Trastuzumab Anthracyclines Revolution in breast cancer chemotherapy • Anthracyclines generate toxic hydroxyl radicals • Treatment of metastatic ERBB2 (HER2)-positive • They bind to promoters that regular gene breast cancer transcription and block them • ERBB2 belongs to the family of human epidermal • Acute toxicity: uncommon growth factor receptors (EGFRs). Trastuzumab inhibits the dimerization of ERBB2/ERBB3 – SVT, VT, heart block, acute LV dysfxn • Subacute • However, ERBB2 is also expressed on cardiomyocytes, and deletion of it causes DCM – Esp. with CHOP treatment of lymphoma in elderly patients – A fib, LV dysfunction, HF, ischemia • Chronic – Asymptomatic LV dysfunction à clinical HF – Can present in first year, in first 5 years, and even late (>10 yrs) – Risk factors: cumulative dose (usu >400 mg/m2), age, concomitant trastuzumab (Herceptin), XRT, pre-existing CV disease (CAD, HTN, DM, PAD) School of Medicine School of Medicine 13 14 SECTION HEADING Trastuzumab, the revolution in Aromatase inhibitors breast cancer chemotherapy Drug NYHA II or IV Heart Failure • Used for ER+ and/or PR+ breast cancer Incidence • Block aromatase which turns androgens into Anthracycline + cyclophosphamide + 27% trastuzumab estrogens Anthracycline or cyclophosphamide 8% • Oral daily medications, taken for years to alone Paclitaxel + trastuzumab 13% suppress cancer recurrence Paclitaxel 1% – Arimidex (anastrozole) – Aromasin (exemestane) • Toxicity is synergistic with anthracyclines • Cardiotoxic on its own – Femara (letrozole) • Not dose dependent • Cardiotoxicity: vasodilation, edema, endothelial • Often reversible with cessation of therapy dysfunction, angina/worsening of ischemic • Rechallenge is often well tolerated • Pertuzumab (Perjeta) targets a different domain often added heart disease for synergy/resistance; well tolerated without cardiotoxicity School of Medicine School of Medicine 15 16 4

12/16/16 SECTION HEADING SECTION HEADING Treatment of anthracycline or UCSF breast cancer echo protocol trastuzumab toxicity • For trastuzumab – obtain baseline echo and echo q 3 mo • Cease the use of anthracyclines until completion of trastuzumab • For doxorubicin alternating w/ HER2 agents, then obtain • Treat with ACEI, carvedilol/BB baseline echo and prior to switching from anthracycline to HER2 targeted agent. • Reassess LVEF in 4 weeks • If 10% drop in EF and asymptomatic à hold agent x 4 wks, • Rechallenge with trastuzumab once EF repeat echo. normalizes (>50%) • If EF improves, consider resuming chemo, consider referral to cardiology. • If EF drop is significant, HF sxs, refer to cardiology. Kalay N et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 2006;48:2258-2262. Cardinale D et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibitors. Circulation 2006;114:2474-2481. School of Medicine School of Medicine 17 18 Can cardiomyopathy be predicted? The role of strain imaging Salvo GD, Pergola V, Fadel B, Bulbul ZA, • Holding chemo for 4 weeks and being told Caso P. Strain echocardiography you have cardiac dysfunction when you are and myocardial mechanics: From already dealing with a cancer diagnosis can basics to clinical applications. J be frightening. Cardiovasc Echography 2015;25:1-8 • Are there ways to identify at-risk patients • Strain = dimensionless parameter. Change in length of earlier, and intervene? myocardial segment compared to its baseline length, expressed as a percentage. Strain rate = Rate at which myocardial deformation takes place. 1/s. Less influenced by loading conditions, less influenced by global function, thus a more sensitive assessment of true regional function. • Helps detect more subtle myocardial problems. School of Medicine School of Medicine 19 20 5