Ian Paterson, Mazankowski Alberta Heart Institute Division of Cardiology, University of Alberta
Ian Paterson, Mazankowski Alberta Heart Institute Division of Cardiology, University of Alberta
Peer Reviewed Funding:
CIHR, ACF, AI-HS
Industry:
Servier Canada Inc, RocheCanada Inc.
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
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
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
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
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
Toxicity that affects the heart
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
National Cancer Institute
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
Frequency and Cause of Death in Early Stage Breast Cancer
Haykowsky M, Mackey J J Am Coll Cardiol 2007
“Cardiotoxicity” The Multiple Hit Hypothesis
CVD only diagnosed in 25.5% cases at time of breast cancer diagnosis Patnaik JL Breast Cancer Res 2011
Heart Failure Anthracyclines
Trastuzumab Suni4nib
High dose cyclophosphamide
Thrombosis
Tamoxifen
CisplaJn
Hypertension
Bevaci-‐ zumab
Ischemia
5-‐FU/Capecitabine
Sorafenib
Taxanes Anastrazole
Bortezomib
Cardiovascular Effects of Common Cancer Treatments
Chest Irradia4on
McLean BA J Card Fail 2013
Clinical trials Asymptomatic LV dysfunction 10-25% HF incidence 1-5%
Medicare data N= 45,537, Age > 65
Time from Dx All Cancer Anthracyclines Trastuzumab A+T
1 year 7.5 / 100 9.8 / 100 16.7 / 100 22 / 100
2 years 13.3 / 100 15.3 / 100 23.2 / 100 33.2 / 100
3 years 18.7 / 100 20.2 / 100 32.1 / 100 41.9 / 100
Chen J Am Coll Cardiol 2012
Yeh ETH Am Coll Cardiol 2009
* Age > 65 or < 4 years
* Cumulative dose > 240mg/m2
* Hypertension
* CAD
* Cardiac irradiation
* ? Dyslipidemia
* Age > 60
* EF < 55%
* Antihypertensive Rx
* Concurrent or prior exposure to anthracyclines (>240mg/m2)
Rastogi Proc Am Soc Clin Oncol 2007 Curigliano G Ann Oncol 2012 Lotrionte M Am J Cardiol 2013 Chotenimitkhun Can J Cardiol 2015
“More precise results can only be attained through collaborative, patient-level pooled analyses stemming from large contemporary cohort studies.”
Altena R. Lancet Oncol 2009.
I = RadiaJon, Anthracyclines II = Trastuzumab III = Anthracyclines
Cardinale et al J Am Coll Cardiol 2010
Plana. JASE 2014
Plana. JASE 2014
§ 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
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
RCT of 90 patients with hematological malignancies receiving anthracyclines
Bosch et al JACC 2013
Intervention Group Enalapril + Carvedilol Control Group
* High dose/continuous infusion * Prior CAD * Prior chest irradiation * Concurrent chemotx
* Diltiazem effective in small case series
Cardinale D. Can J Cardiol 2006.
Ambrosy AP. Am J Cardiol 2012.
Yeh ETH. J Am Coll Cardiol 2009.
* 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.
* 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
* Lower dose + Targeted
* CT planning
* No human studies of pharmacotherapy
* One recent abstract showing protective effects of captopril in chest irradiated small animals
* 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 Van der Veen C ESTRO annual meeJng April 2013
* Lack of evidence based guidelines
* Poorly co-ordinated effort between cardiologists and oncologists
* No risk models assessments
* Few RCTs for prevention/treatment
140,000 Albertans with Hx of cancer * 30,000 with prior breast CA
* 6,000 with prior lymphoma
2ndary prevention: 3500-7000 breast CA/lymphoma survivors with HF
18,500 new cancer diagnoses/year * 2,250 new breast CA/year
* 650 new lymphoma/year
1ary prevention: 300-600 breast CA/lymphoma patients at risk for HF each year
Population: 4 Million
Edmonton Cardio-Oncology Program
Cardiology Team Oncology Team
Since Fall 2011 >350 unique patient clinic visits > 1200 echocardiograms
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
• 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
• 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
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
Thank you