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Cancer and Heart Disease: Where the two
intersect !
Susan Dent, MD, FRCPC
Medical Oncologist, Duke Cancer Institute
Associate Director, Clinical Breast Cancer Research
Co-Director Duke Cardio-Oncology Program
Founder and past-president, Canadian Cardiac
Oncology Network (CCON)
March 28th
, 2019
Click to edit Master title styleObjectivesObjectives
•To discuss the impact of cancer treatments on the
heart
•To discuss how we can optimize cardiac health in
cancer patients
•To discuss the benefit of a multidisciplinary approach
in optimizing cardiac health in cancer patients
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Click to edit Master title styleCancer Drug Development
Click to edit Master title styleCancer Survivorship
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CANCER STATISTICS
IN CANADA 2015
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““The cured cancer patient of todayThe cured cancer patient of today
does not want to become the heartdoes not want to become the heart
failure patient of tomorrow.”failure patient of tomorrow.”
Eschenhagen T et al. Eur J of Heart Fail 2011; 3:1-10Eschenhagen T et al. Eur J of Heart Fail 2011; 3:1-10
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© Corbis
Anthracyclines
Click to edit Master title styleCardiovascular Side Effects ofCardiovascular Side Effects of
Modern Cancer TherapyModern Cancer Therapy
Arrhythmia
HypertensionAP / MI
Cardiac Dysfunction
Heart Failure Thromboembolism
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Incidence of cardiac events in pediatric cancer survivors
Cardiovascular events in cancer survivors
Patnaik et al. Breast Ca Res, 2011
Helena J. van der Pal et al. JCO 2012
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Cardiovascular Disease:
Important cause of mortality in early breast cancer
Years from diagnosis
PercentMortality
Other causes
Patnaik et al. Breast Ca Res, 2011
CVD
Breast cancer
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What have we learned?
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Shared risk factors for cancer and cardiac disease
Modified from Farmakis D et al. Int J Cardiol 2016
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Johnson CB et al. Can J Cardiol 2016;32:900-907
Virani SA et al. Can J Cardiol 2016; 32:831-41
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Frequent coexistence of cardiac problems
in cancer patients
Oncologic
disease
Cardiac
disease
Courtesy, Dr. Cardinale
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Cardiac Disease & Risk Factors In Older Cancer
Patients
Cancer Site Patients (n) CAD (%) CHF (%) HTN (%) DM (%)
Prostate1
185106 4.0% 20% 35% 14%
Breast2
48353 5.0% 34% 77% 29%
Lymphoma3
6388 2.1% 28% 73% 32%
Colorectal4
1966 11% 0.2% 41% 13%
CAD = coronary disease; CHF = congestive heart failure;
HTN = hypertension; DM = diabetes mellitus
1. Keating et al. European Urology 2013;64:159-166
2. Doyle et al. Int J Radiation Oncology Biol Phys 2007;68:82-93 3. Hershman et al. J Clin Oncol 2008;26:3159-65
4. Hawkes et al. Eur J of Cancer 2011;47:267-76
Click to edit Master title styleEvolution of Cancer Therapy
Anthracyclines
1970s
Trastuzumab
1990’s
Anti-VEGF
Therapy
2000’s
Proteasome
inhibitors
2005
Checkpoint
inhibitors
2010
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VSP Inhibitors
Hypertension
Heart Failure
Thrombosis
Her2 Targeted
Therapies
Cardiomyopathy
Anthracyclines
Radiation
Heart Failure
CAD
Anti-metabolites (5FU)
Ischemia
Vasospasm
Adapted from Moslehi, Cheng. Science Translational Medicine, 2013. Moslehi, NEJM. 2016.
PI3K Inhibitors
Hyperglycemia
Metabolic
?Myocardial/
Arrhythmia
BTK Inhibitors
Ibrututinib:
Arrhythmia/
Atrial Fibrillation
MEK/RAF TKI
Cardiomyopathy
Drugs Affecting UPS
Immunomodulators
(IMiDs): thrombosis
Proteasome inhibitors
(e.g. bortezomib,
carfilzomib): vascular
HDAC inhibitors
Arrhythmia
Cancer
Immunotherapies
Myocarditis
Cancer Survivorship
CML TKIs
Imatinib
Dasatinib/Nilotinib/
Ponatinib:
PAH/Vascular/
Atherosclerosis
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Oncologist
Cardiologist
The cardiologist!
The patient developed
cardiac disease !
The oncologist!
The patient has
a cancer!
Who is responsible for patient care?
Courtesy, Dr.Cardinale
Click to edit Master title styleThe birth of Cardio-Oncology
A clinically based discipline focused on
the cardiovascular health of cancer
patients and cancer survivors
A clinically based discipline focused on
the cardiovascular health of cancer
patients and cancer survivors
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Cardiotoxicity
360° management
The cardio-oncologist
Courtesy, Dr. Cardinale
Health care providers focused on
the prevention, early detection,
management and recovery of
cardiovascular function potentially
resulting from cancer therapies
Health care providers focused on
the prevention, early detection,
management and recovery of
cardiovascular function potentially
resulting from cancer therapies
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England
Italy
Israel
Poland
Japan
Brazil
Argentina
Mexico
Australia
China
Spain
India
Cardio-Oncology
Clinics
Click to edit Master title styleWhat does a clinic offer ?
Education of patients and
health care providers
Resident/fellowship training
Preceptorship
Multidisciplinary rounds
Development of a collaborative research
environment: basic/translational research and
clinical/health outcomes research.
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0rganization of Cardio-Oncology Program
Okwuosa and Barac, JACC 2015
Click to edit Master title styleOttawa Cardiac Oncology Program
Dr. Susan Dent
Medical
Oncologist
Nadine Graham
Research Assistant
Jason Wentzell
Pharmacist
Dr. Jeffrey Sulpher
Medical Oncologist
Dr. Ellamae Stadnick
Cardiologist
Dr. Michele Turek
Cardiologist
Dr. Christopher Johnson
Cardiologist
Dr. Angeline Law
Cardiologist
Dr. Olexiy Aseyev
Cardiac Oncology
Fellow
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Does access to cardio-oncology clinics
impact patient care?
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Seven (2008-2015) Years Experience Of The Ottawa Hospital Cardio-Oncology Clinic:
Patient Characteristics & Clinical Outcomes (n=779)
Kappel C, Johnson C, Rushton M, Aseyev O, Small G, Law A, and Dent S.
Presented at GCOS, 2017; accepted for publication Current
Oncology
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Presented at GCOS 2017; accepted for publication
Current Oncology
Seven (2008-2015) Years Experience Of The Ottawa Hospital Cardio-Oncology Clinic:
Patient Characteristics & Clinical Outcomes (n=779)
Kappel C, Johnson C, Rushton M, Aseyev O, Small G, Law A, and Dent S.
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Impact of a cardio-oncology clinic on
oncology patient access to cardiology
Patients referred to
cardiology:
•70% β blocker
•87% ACEI
•9% loop diuretic
•2% MRA
Yau et al., CCC 2017 abstract
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The Evolution of Cardio-Oncology
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Canadian Cardiac Oncology
Network (CCON)
www.cardiaconcology.ca
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Global Cardio-Oncology Summit (GCOS)
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Journal of Clinical Oncology, on line
December 2016
NCCN Clinical Practice Guidelines in Oncology: Survivorship-
Anthracycline-induced cardiotoxicity (2015)
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Circulation, October 2014
Click to edit Master title stylePublications in Cardio-0ncology
Barac A et al. JACC 2015: 65(25): 2739
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Cardiooncologyjournal.biomedcentral.com
JACC: CardioOncology coming in 2019JACC: CardioOncology coming in 2019
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The Evolution of Cardio-Oncology
1. Yeh ETH, Chang H. JAMA Cardiol. 2016;1(9):1066-1072; 2. Snipelisky D et al. Heart Fail Clin. 2017;13(2):347-359; 3. Barac
A. et al. J Am Coll Cardiol. 2015; 65(25):2739-46; 4. Armenian SH, et al. J Clin Oncol. 2017;10;35(8):893-911; 5. Curigliano G,
et al. Ann Oncol. 2012;23 Suppl 7:vii155-66. 6. Zamorano JL, et al. Eur Heart J. 2016;37(36):2768-2801.
1966 1977 1998 2007 2012 2014 2016 2017
Reports of
anthracycline-
induced
cardiotoxicity
Understanding that
anthracycline-induced
cardiotoxicity depends on
the cumulative dose
Reports of
trastuzumab-
induced
cardiotoxicity
90 PubMed
citations in “cardio
oncology”
Reports of
hypertension,
heart failure,
and vascular
occlusion with
TKIs
ESMO
Clinical
Practice
Guideline
published
812 PubMed
citations in
“cardio
oncology”
37 cardio-
oncology
clinics in
the US
European Society of
Cardiology Position
Paper published
ASCO Clinical Practice
Guideline published
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Challenges
• Better understanding how modern cancer therapies
impact cardiovascular health
• Early identification of cardiac risk
– e.g cardiac imaging, biomarkers
• Strategies to prevent cardiac damage
– Primary and secondary prevention
• Optimal cardiovascular drugs to manage cardiac
damage
• Surveillance and monitoring
– Imaging, frequency and duration
• Lifestyle modification
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“Active participation in growing cardio-
oncology networks may provide critical clues
on potential solutions for these challenges and
open horizons for growth”
Opportunities
Okwuosa and Barac, JACC 2015
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ICOSICOS
ChinaChina
ArgentinaArgentina
PolandPoland
IndiaIndia
International
Collaboration
ItalyItaly
IsraelIsrael
SwitzerlandSwitzerland l
UNDER CONSTRUCTION
BrazilBrazil
SpainSpain
MexicoMexico
JapanJapan
AustraliaAustralia
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RESEARCHRESEARCH
198 registered
CT on diagnosis
and treatment
of cancer
related cardiac
dysfunction
clinical
trials.gov
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• Improvement in cancer therapies has resulted in long term
survivors who may be at risk of cardiotoxicity.
• Individuals with heart disease may develop cancer and
require potentially cardiotoxic cancer therapy.
• Close collaboration among HCP’s is needed in order to
provide the best cancer care while optimizing
cardiovascular health.
• The establishment of cardio-oncology clinics/programs
provides the framework for optimizing clinical care delivery,
education and research and promotion of survivorship
Key Messages
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Thank-you!

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Cancer and Heart Disease - Where the two intersect

  • 1. Click to edit Master title style Cancer and Heart Disease: Where the two intersect ! Susan Dent, MD, FRCPC Medical Oncologist, Duke Cancer Institute Associate Director, Clinical Breast Cancer Research Co-Director Duke Cardio-Oncology Program Founder and past-president, Canadian Cardiac Oncology Network (CCON) March 28th , 2019
  • 2. Click to edit Master title styleObjectivesObjectives •To discuss the impact of cancer treatments on the heart •To discuss how we can optimize cardiac health in cancer patients •To discuss the benefit of a multidisciplinary approach in optimizing cardiac health in cancer patients
  • 3. Click to edit Master title style
  • 4. Click to edit Master title styleCancer Drug Development
  • 5. Click to edit Master title styleCancer Survivorship
  • 6. Click to edit Master title style CANCER STATISTICS IN CANADA 2015
  • 7. Click to edit Master title style ““The cured cancer patient of todayThe cured cancer patient of today does not want to become the heartdoes not want to become the heart failure patient of tomorrow.”failure patient of tomorrow.” Eschenhagen T et al. Eur J of Heart Fail 2011; 3:1-10Eschenhagen T et al. Eur J of Heart Fail 2011; 3:1-10
  • 8. Click to edit Master title style © Corbis Anthracyclines
  • 9. Click to edit Master title styleCardiovascular Side Effects ofCardiovascular Side Effects of Modern Cancer TherapyModern Cancer Therapy Arrhythmia HypertensionAP / MI Cardiac Dysfunction Heart Failure Thromboembolism
  • 10. Click to edit Master title style Incidence of cardiac events in pediatric cancer survivors Cardiovascular events in cancer survivors Patnaik et al. Breast Ca Res, 2011 Helena J. van der Pal et al. JCO 2012
  • 11. Click to edit Master title style Cardiovascular Disease: Important cause of mortality in early breast cancer Years from diagnosis PercentMortality Other causes Patnaik et al. Breast Ca Res, 2011 CVD Breast cancer
  • 12. Click to edit Master title style What have we learned?
  • 13. Click to edit Master title style Shared risk factors for cancer and cardiac disease Modified from Farmakis D et al. Int J Cardiol 2016
  • 14. Click to edit Master title style Johnson CB et al. Can J Cardiol 2016;32:900-907 Virani SA et al. Can J Cardiol 2016; 32:831-41
  • 15. Click to edit Master title style Frequent coexistence of cardiac problems in cancer patients Oncologic disease Cardiac disease Courtesy, Dr. Cardinale
  • 16. Click to edit Master title style Cardiac Disease & Risk Factors In Older Cancer Patients Cancer Site Patients (n) CAD (%) CHF (%) HTN (%) DM (%) Prostate1 185106 4.0% 20% 35% 14% Breast2 48353 5.0% 34% 77% 29% Lymphoma3 6388 2.1% 28% 73% 32% Colorectal4 1966 11% 0.2% 41% 13% CAD = coronary disease; CHF = congestive heart failure; HTN = hypertension; DM = diabetes mellitus 1. Keating et al. European Urology 2013;64:159-166 2. Doyle et al. Int J Radiation Oncology Biol Phys 2007;68:82-93 3. Hershman et al. J Clin Oncol 2008;26:3159-65 4. Hawkes et al. Eur J of Cancer 2011;47:267-76
  • 17. Click to edit Master title styleEvolution of Cancer Therapy Anthracyclines 1970s Trastuzumab 1990’s Anti-VEGF Therapy 2000’s Proteasome inhibitors 2005 Checkpoint inhibitors 2010
  • 18. Click to edit Master title style VSP Inhibitors Hypertension Heart Failure Thrombosis Her2 Targeted Therapies Cardiomyopathy Anthracyclines Radiation Heart Failure CAD Anti-metabolites (5FU) Ischemia Vasospasm Adapted from Moslehi, Cheng. Science Translational Medicine, 2013. Moslehi, NEJM. 2016. PI3K Inhibitors Hyperglycemia Metabolic ?Myocardial/ Arrhythmia BTK Inhibitors Ibrututinib: Arrhythmia/ Atrial Fibrillation MEK/RAF TKI Cardiomyopathy Drugs Affecting UPS Immunomodulators (IMiDs): thrombosis Proteasome inhibitors (e.g. bortezomib, carfilzomib): vascular HDAC inhibitors Arrhythmia Cancer Immunotherapies Myocarditis Cancer Survivorship CML TKIs Imatinib Dasatinib/Nilotinib/ Ponatinib: PAH/Vascular/ Atherosclerosis
  • 19. Click to edit Master title style Oncologist Cardiologist The cardiologist! The patient developed cardiac disease ! The oncologist! The patient has a cancer! Who is responsible for patient care? Courtesy, Dr.Cardinale
  • 20. Click to edit Master title styleThe birth of Cardio-Oncology A clinically based discipline focused on the cardiovascular health of cancer patients and cancer survivors A clinically based discipline focused on the cardiovascular health of cancer patients and cancer survivors
  • 21. Click to edit Master title style Cardiotoxicity 360° management The cardio-oncologist Courtesy, Dr. Cardinale Health care providers focused on the prevention, early detection, management and recovery of cardiovascular function potentially resulting from cancer therapies Health care providers focused on the prevention, early detection, management and recovery of cardiovascular function potentially resulting from cancer therapies
  • 22. Click to edit Master title style
  • 23. Click to edit Master title style England Italy Israel Poland Japan Brazil Argentina Mexico Australia China Spain India Cardio-Oncology Clinics
  • 24. Click to edit Master title styleWhat does a clinic offer ? Education of patients and health care providers Resident/fellowship training Preceptorship Multidisciplinary rounds Development of a collaborative research environment: basic/translational research and clinical/health outcomes research.
  • 25. Click to edit Master title style 0rganization of Cardio-Oncology Program Okwuosa and Barac, JACC 2015
  • 26. Click to edit Master title styleOttawa Cardiac Oncology Program Dr. Susan Dent Medical Oncologist Nadine Graham Research Assistant Jason Wentzell Pharmacist Dr. Jeffrey Sulpher Medical Oncologist Dr. Ellamae Stadnick Cardiologist Dr. Michele Turek Cardiologist Dr. Christopher Johnson Cardiologist Dr. Angeline Law Cardiologist Dr. Olexiy Aseyev Cardiac Oncology Fellow
  • 27. Click to edit Master title style Does access to cardio-oncology clinics impact patient care?
  • 28. Click to edit Master title style Seven (2008-2015) Years Experience Of The Ottawa Hospital Cardio-Oncology Clinic: Patient Characteristics & Clinical Outcomes (n=779) Kappel C, Johnson C, Rushton M, Aseyev O, Small G, Law A, and Dent S. Presented at GCOS, 2017; accepted for publication Current Oncology
  • 29. Click to edit Master title style Presented at GCOS 2017; accepted for publication Current Oncology Seven (2008-2015) Years Experience Of The Ottawa Hospital Cardio-Oncology Clinic: Patient Characteristics & Clinical Outcomes (n=779) Kappel C, Johnson C, Rushton M, Aseyev O, Small G, Law A, and Dent S.
  • 30. Click to edit Master title style Impact of a cardio-oncology clinic on oncology patient access to cardiology Patients referred to cardiology: •70% β blocker •87% ACEI •9% loop diuretic •2% MRA Yau et al., CCC 2017 abstract
  • 31. Click to edit Master title style The Evolution of Cardio-Oncology
  • 32. Click to edit Master title style Canadian Cardiac Oncology Network (CCON) www.cardiaconcology.ca
  • 33. Click to edit Master title style Global Cardio-Oncology Summit (GCOS)
  • 34. Click to edit Master title style
  • 35. Click to edit Master title style Journal of Clinical Oncology, on line December 2016 NCCN Clinical Practice Guidelines in Oncology: Survivorship- Anthracycline-induced cardiotoxicity (2015)
  • 36. Click to edit Master title style Circulation, October 2014
  • 37. Click to edit Master title stylePublications in Cardio-0ncology Barac A et al. JACC 2015: 65(25): 2739
  • 38. Click to edit Master title style1 Cardiooncologyjournal.biomedcentral.com JACC: CardioOncology coming in 2019JACC: CardioOncology coming in 2019
  • 39. Click to edit Master title style
  • 40. Click to edit Master title style The Evolution of Cardio-Oncology 1. Yeh ETH, Chang H. JAMA Cardiol. 2016;1(9):1066-1072; 2. Snipelisky D et al. Heart Fail Clin. 2017;13(2):347-359; 3. Barac A. et al. J Am Coll Cardiol. 2015; 65(25):2739-46; 4. Armenian SH, et al. J Clin Oncol. 2017;10;35(8):893-911; 5. Curigliano G, et al. Ann Oncol. 2012;23 Suppl 7:vii155-66. 6. Zamorano JL, et al. Eur Heart J. 2016;37(36):2768-2801. 1966 1977 1998 2007 2012 2014 2016 2017 Reports of anthracycline- induced cardiotoxicity Understanding that anthracycline-induced cardiotoxicity depends on the cumulative dose Reports of trastuzumab- induced cardiotoxicity 90 PubMed citations in “cardio oncology” Reports of hypertension, heart failure, and vascular occlusion with TKIs ESMO Clinical Practice Guideline published 812 PubMed citations in “cardio oncology” 37 cardio- oncology clinics in the US European Society of Cardiology Position Paper published ASCO Clinical Practice Guideline published
  • 41. Click to edit Master title style Challenges • Better understanding how modern cancer therapies impact cardiovascular health • Early identification of cardiac risk – e.g cardiac imaging, biomarkers • Strategies to prevent cardiac damage – Primary and secondary prevention • Optimal cardiovascular drugs to manage cardiac damage • Surveillance and monitoring – Imaging, frequency and duration • Lifestyle modification
  • 42. Click to edit Master title style “Active participation in growing cardio- oncology networks may provide critical clues on potential solutions for these challenges and open horizons for growth” Opportunities Okwuosa and Barac, JACC 2015
  • 43. Click to edit Master title style ICOSICOS ChinaChina ArgentinaArgentina PolandPoland IndiaIndia International Collaboration ItalyItaly IsraelIsrael SwitzerlandSwitzerland l UNDER CONSTRUCTION BrazilBrazil SpainSpain MexicoMexico JapanJapan AustraliaAustralia
  • 44. Click to edit Master title style RESEARCHRESEARCH 198 registered CT on diagnosis and treatment of cancer related cardiac dysfunction clinical trials.gov
  • 45. Click to edit Master title style • Improvement in cancer therapies has resulted in long term survivors who may be at risk of cardiotoxicity. • Individuals with heart disease may develop cancer and require potentially cardiotoxic cancer therapy. • Close collaboration among HCP’s is needed in order to provide the best cancer care while optimizing cardiovascular health. • The establishment of cardio-oncology clinics/programs provides the framework for optimizing clinical care delivery, education and research and promotion of survivorship Key Messages
  • 46. Click to edit Master title style Thank-you!

Hinweis der Redaktion

  1. Cardiovascular side effects of modern cancer therapy include arrhythmias, ischemia, myocardial infarction, contractile dysfunction, thromboembolism, and hypertension. Thromboembolism and hypertension are more common with newer biological agents. Arrhythmia and induction ischemia is generally not problematic because it is an acute effect that can be solved by slowing down an infusion or stopping the drug. This is not the case with contractile dysfunction and especially late contractile dysfunction, which can potentially lead to heart failure.
  2. Presented at Canadian Cardiovascular Society Meeting, Montreal Oct 2013