Ian Paterson, Mazankowski Alberta Heart Institute Division of Cardiology, University of Alberta

Transcription

1 Ian Paterson, Mazankowski Alberta Heart Institute Division of Cardiology, University of Alberta

2 Peer Reviewed Funding: CIHR, ACF, AI-HS Industry: Servier Canada Inc, RocheCanada Inc.

3 What is your approach to the cardio-oncology patient? a) Not on my radar b) Allow GP and/or oncologist to manage c) Recommend referral to cardiologist d) Recommend referral to specialized clinic

4 56 year old woman Left breast invasive ductal carcinoma, HER2/neu + Scheduled to receive TCH (Taxotere, Carboplatin and Herceptin) Baseline Echo EF 40% NYHA class 1 Exam unremarkable

5 What would you recommend? a) Continue with cancer therapy plan b) Recommend alternative cancer therapy plan c) Start HF pharmacotherapy and continue with cancer therapy plan d) Start HF pharmacotherapy and recommend alternative cancer therapy

6 What would you recommend? a) Continue with cancer therapy plan b) Recommend alternative cancer therapy plan c) Start HF pharmacotherapy and continue with cancer therapy plan d) Start HF pharmacotherapy and recommend alternative cancer therapy

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8 1. Learn about cancer therapies and their potential cardiovascular effects 2. Identify patients at risk for cardiotoxicity 3. Review current guidelines for treating cardiotoxicity and discuss strategies for preventing cardiovascular complications 4. Discuss a multidisciplinary approach to the care of cardio-oncology patients

9 Toxicity that affects the heart National Cancer Institute Cancer therapy related disturbance in myocardial and/or vascular function * myocyte injury * impaired myocardial energetics/metabolism * endothelial injury/thrombosis * altered vascular smooth muscle cell function * pericardial/valvular injury

10 Frequency and Cause of Death in Early Stage Breast Cancer Cardiotoxicity The Multiple Hit Hypothesis Cause of Death 10 year probability Cardiac 6% Breast Cancer 4% Breast Cancer, Other 2% Cerebrovascular 2% Lung CA 1% Other 1% Hanrahan EO, J Clin Oncol 2007 Haykowsky M, Mackey J J Am Coll Cardiol 2007 CVD only diagnosed in 25.5% cases at time of breast cancer diagnosis Patnaik JL Breast Cancer Res 2011

11 Heart Failure Cardiovascular Effects of Common Cancer Treatments Anthracyclines Hypertension Trastuzumab High dose cyclophosphamide Bortezomib Chest Irradia4on Suni4nib Bevaci- zumab Sorafenib 5- FU/Capecitabine Anastrazole Taxanes Thrombosis Tamoxifen CisplaJn Ischemia

12 McLean BA J Card Fail 2013

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14 Clinical trials Asymptomatic LV dysfunction 10-25% HF incidence 1-5% Medicare data Yeh ETH Am Coll Cardiol 2009 N= 45,537, Age > 65 Time from Dx All Cancer Anthracyclines Trastuzumab A+T 1 year 7.5 / / / / years 13.3 / / / / years 18.7 / / / / 100 Chen J Am Coll Cardiol 2012

15 * Age > 65 or < 4 years * Cumulative dose > 240mg/m 2 * Hypertension * CAD * Cardiac irradiation *? Dyslipidemia * Age > 60 * EF < 55% * Antihypertensive Rx * Concurrent or prior exposure to anthracyclines (>240mg/m 2 ) More precise results can only be attained through collaborative, patient-level pooled analyses stemming from large contemporary cohort studies. Rastogi Proc Am Soc Clin Oncol 2007 Curigliano G Ann Oncol 2012 Lotrionte M Am J Cardiol 2013 Chotenimitkhun Can J Cardiol 2015

16 I = RadiaJon, Anthracyclines II = Trastuzumab III = Anthracyclines Altena R. Lancet Oncol 2009.

17 Cardinale et al J Am Coll Cardiol 2010

18 Plana. JASE 2014

19 Plana. JASE 2014

20 EF Limited availability of 3-D echo and CMR Troponin? time course: serial measurements 67% sensitive for cardiotoxicity Late marker: only 35% Tn I positive had LVEF recovery Global longitudinal strain 10% decrease in GLS predicts cardiotoxicity but variability also 10% 50% diagnostic accuracy Cardinale D. J Clin Oncol 2010 Sawaya H. Am J Cardiol 2010 Sawaya H. Circ Cardiovasc Img 2012

21 1. Hold Chemotherapy if baseline EF < 50% follow-up EF < 50% AND dropped at least 5% AND heart failure follow-up EF < 50% AND dropped at least 10% AND asymptomatic 2. Start HF Pharmacotherapy (ACEi and BB) symptomatic HF and EF < 50% asymptomatic HF and EF < 40%? duration 3. Resume/Discontinuation Chemotherapy follow-up EF > 45% discontinue if follow-up EF < 40% Adapted from: Mackey J Current Oncology 2008 Curigliano G Ann Oncol 2012

22 RCT of 90 patients with hematological malignancies receiving anthracyclines Intervention Group Enalapril + Carvedilol Control Group Bosch et al JACC 2013

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24 * High dose/continuous infusion * Prior CAD * Prior chest irradiation * Concurrent chemotx Yeh ETH. J Am Coll Cardiol * Diltiazem effective in small case series Ambrosy AP. Am J Cardiol Cardinale D. Can J Cardiol 2006.

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26 * HTN 22% * High Grade in 7% * Renal dysfunction RR 1.36 * Responsive to Medical Rx without need to discontinue adjuvant Rx Zhu X. Acta Oncol 2009.

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28 * Radiation dose * Cardiac exposure * Younger age at exposure * Time since exposure * Cardiotoxic chemotx * Clinical risk factors Jaworski C J Am Coll Cardiol 2013 Darby SC New Engl J Med 2013

29 * Lower dose + Targeted * CT planning * No human studies of pharmacotherapy * One recent abstract showing protective effects of captopril in chest irradiated small animals Van der Veen C ESTRO annual meejng April 2013 * CAD * Small vessel lumens * Restenosis rates higher * LIMA often atretic * Higher post CABG mortality * Heart Failure * ACC/AHA guidelines Jaworski C et al J Am Coll Cardiol 2013

30 * Lack of evidence based guidelines * Poorly co-ordinated effort between cardiologists and oncologists * No risk models assessments * Few RCTs for prevention/ treatment

31 140,000 Albertans with Hx of cancer * 30,000 with prior breast CA * 6,000 with prior lymphoma 2ndary prevention: breast CA/lymphoma survivors with HF 18,500 new cancer diagnoses/year * 2,250 new breast CA/year * 650 new lymphoma/year 1ary prevention: breast CA/ lymphoma patients at risk for HF each year Population: 4 Million

32 Edmonton Cardio-Oncology Program Cardiology Team Oncology Team Since Fall 2011 >350 unique patient clinic visits > 1200 echocardiograms

33 Primary Prevention High risk patient for cancer therapy related cardiomyopathy High risk patient for cancer therapy related ischemia High risk for arrhythmia Known cardiovascular disease requiring optimization prior to cancer therapy Secondary Prevention Suspected heart failure or cardiomyopathy/lv dysfunction on surveillance imaging Myocardial infarction or ischemia during adjuvant therapy Worsening and uncontrolled hypertension related to cancer therapy Arrhythmia management Pericardial disease - restrictive or constrictive cardiomyopathy 2015 CJC Position statement in preparation

34 MANTICORE primary prevention RCT (perindopril vs. bisoprolol vs. placebo) TITAN primary prevention RCT risk factor modulation + exercise vs. routine care CAPRI Provincial prospective registry of cancer patients at risk for cardiotoxicity

35 Current treatments in breast cancer have improved survival but increased risk of HF Both systemic and targeted therapies can cause myocyte cell damage and apoptosis Cardiotoxicity associated with worse outcomes but may respond to early treatment More study needed on mechanisms, screening and prevention

36 CCI Edith Pituskin John Mackey Anil Joy Keith Tankel Peter Venner Michael Sawyer MAHI Justin Ezekowitz Sheri Koshman Gavin Oudit Basic Science Mark Haykowsky Lee Jones Richard Thompson Jason Dyck

37 Thank you