Download Curing Cancer and Caring for the Heart: Advancing

Curing Cancer and Caring for the Heart:
Advancing the Care of Our Patients
Bonnie Ky, MD, MSCE
Assistant Professor of Medicine and Epidemiology
Senior Scholar, Center for Epidemiology and Biostatistics
Director, Penn Cardio-Oncology Research Program
Director, Penn Center for Quantitative Echocardiography
Perelman School of Medicine at the University of
Pennsylvania
Patient Presentation
 The patient is a 58 year old female with Her2+ left
sided breast cancer undergoing therapy with
doxorubicin and cytoxan, followed by taxol and
herceptin.
 She has no past medical history and is not taking any
medications.
 Her family history is significant for cardiac disease in
her father. Her social history is unremarkable.
 Her baseline and post-doxorubicin echocardiograms
demonstrate a normal heart function, as assessed by
left ventricular ejection fraction.
Patient Presentation
 After 4 cycles of taxol and
herceptin, her echo
reveals a significant
decline in heart function.
 She denies any
symptoms, except for
fatigue.
 Her physical exam is also
fairly unremarkable,
except for a BP of 142/85.
She Asks…
 Why did this happen? Is it common?
 Is there any way we could have known earlier –
before treatment – that her heart was going to be
damaged?
 Could this have been prevented?
 What will happen to heart?
 How could this affect her children - is her daughter
also at risk for cancer and heart disease?
CV Disease and Cancer are
Two Leading Causes of Death in the US
Number of deaths
CV Disease
Cancer
 Intersection between
cardiovascular (CV)
disease and cancer
 Common biologic basis
 Common risk factors
Year
 Necessary cancer
therapies can also
adversely affect the CV
system
www.cdc.gov
Koene, et al. Circulation. 2016.
Cancer Treatments Can Affect the Heart in
Many Ways
Heart Failure/
Cardiac Dysfunction
(“Weak or stiff heart
muscle”)
Atherosclerosis
(“Heart blockages”)
Arrhythmia
(“Abnormal rhythm”)
Hypertension
(“Stiff Arteries”
or Blood
Pressure
Increases)
Cancer Patients and Survivors are at Increased
CV Risk
 Growing burden of CV disease in cancer patients
HF or Cardiomyopathy Incidence
N = 12,500
Doxorubicin
Herceptin
Doxorubicin & Herceptin
Other
None
20.1
12.1
4.3
Years
 In survivors with prior CV disease, risk of CV
mortality (16.9%) exceeds cancer (14.6%) at 10 years
Aiello Bowles, et al. JNCI. 2012.
Abdel-Qadir, et al. JAMA Cardiol. 2016.
What are our Priorities in the Cardiovascular
Care of Cancer Patients?
Prior to
Cancer
Therapy
During Cancer
Therapy
After Cancer
Therapy
How can we prevent CV disease?
How can we identify high risk patients?
How can we protect the heart?
Penn Cardiotoxicity of Cancer Therapy Cohort
(CCT) Study
Inclusion criteria: Breast cancer, receiving doxorubicin +/- trastuzumab
Current N = 462
Baseline
3 months
6 months
9 months
1 year
2 years ••• 10 years
* Echocardiogram; Blood samples obtained at baseline, and standardized intervals
between echocardiograms, and annually
Narayan…Ky. JACC Imaging. 2016.
Cardiotoxicity of Cancer Therapy (CCT) Study
Objectives
 To understand what is the epidemiology of CV
disease (how many, who, when?)
 To develop a “risk score” using state-of-the-art
imaging, blood markers, genetics (to identify CV
disease before overt symptoms)
 To develop innovative strategies to protect the heart
(and understand who will derive the most benefit)
 To ensure our patients can successfully be treated for
their cancer while protecting their heart (in the short
and long-term)
Novel CV Imaging Techniques
Baseline
Shortening
Strain = L1-L0
L0
 Most pronounced changes
in CV function (ejection
fraction) with doxorubicin &
trastuzumab
• Modest, sustained changes
with doxorubicin
 Major driver of decline (and
recovery) in cardiac
function is blood pressure
N = 1,255 echocardiograms
Maximum follow-up time for this analyses = 3.5 years
Narayan…Ky. Circulation. 2017.
Ventricular-Arterial Coupling
Circumferential Strain, %
Yes Cardiac Dysfunction
No Cardiac Dysfunction
Additional Discoveries:
Blood Markers Can Predict Risk
IgE
IgE
IgE
Control
Control
Case
ImmunoglobulinE (IgE) levels at baseline and
throughout therapy consistently higher in controls,
5 to 58-fold, as compared to cases
Penn Cardio-Oncology
Collaborative & Multi-Disciplinary Research
Genetics
of CV
Disease
Develop
Mouse
Model
Breast
Cancer
Protection
Strategies
Penn
Cardio-Oncology
Sunitinib
Therapy
Pediatrics
(Sarcoma,
Leukemia)
Lymphoma
Radiation
Therapy
Multiple
Myeloma
Prostate
Cancer
Penn Cardio-Oncology
Translational Center of Excellence
 Launching a Cardio-Oncology Translational Center of
Excellence in 2017 with support of the Abramson Cancer
Center, Department of Medicine, and Cardiology
 Goals:
• Build a premier, multi-disciplinary cardio-oncology
program at the forefront of basic, translational, and
clinical research and care
• Bring together scientists and clinicians across basic,
translational and clinical science to catalyze and
accelerate new discoveries
• Paired with clinical mission of delivering state-of-theart, evidence-based medicine to oncology patients and
survivors regionally and nationally
THANK YOU