Associate Professor Of Medicine
Perelman School of Medicine
Location: Smilow TRC 11-105
Admin: Joanna Acosta
Cardio-oncology is a field in rapid evolution and growth. Both cancer and cardiovascular disease are the largest contributors to morbidity and mortality in the United States, with an estimated 14 and 15 million people suffering from each disease, respectively. Despite this tremendous public health burden, there are fundamental gaps in our understanding of disease mechanisms and in the application of evidence-based strategies for the clinical care of this growing population.
The Ky research lab focuses on understanding the underlying mechanisms and predictors of cancer therapy cardiotoxicity and heart failure, and translating this understanding to the clinical care of patients. Our programmatic objectives are to use innovative strategies in deep cardiovascular phenotyping to define an individual cancer patient’s risk of developing subsequent cardiovascular disease. Our ongoing projects focus on determining the role of mechanistic markers in understanding and predicting incident cardiotoxicity and adverse cardiovascular outcomes; focused on the use of circulating biomarkers and imaging-derived measures of myocardial mechanics and sensitive measures of myocardial function. We have established multiple patient cohorts in order to ask these questions of interest.
Dr. Ky also directs the Penn Center for Quantitative Echocardiography, focused on using state-of-the-art 2D, 3D, and Doppler acquisition and quantitation to understand cardiac function and remodeling across various diseases.
Cardiotoxicity of Breast Cancer Therapies
This is an ongoing longitudinal prospective cohort study with the objective of advancing our understanding of the epidemiology of cardiovascular disease with breast cancer therapy; and defining the clinical relevance of novel and conventional biologic markers and 2D and 3D echocardiographic measures in diagnosing and predicting cardiotoxicity. We ultimately seek to develop multimarker risk prediction algorithms which comprehensively integrate key biologic, imaging, and clinical data to identify patients at increased risk for doxorubicin- and doxorubicin + trastuzumab-induced cardiotoxicity.
Cardiotoxicity of Radiation Therapy
The overall objective of this project is to determine if modern day chest radiotherapy results in early, subclinical cardiovascular dysfunction and injury as detected by imaging and biologic markers; which radiation therapy cardiac dose-volume parameters influence these intermediary markers; and if these markers are associated with adverse cardiovascular clinical outcomes.
The overall objective of this study is to use patient-derived in vitro and in vivo models to answer the fundamental question of whether or not pathogenic mutations in BRCA1/2 result in an increased risk of CV disease. Our hypotheses are that 1) detailed CV phenotyping by echocardiography and cardiopulmonary exercise testing will reveal subclinical cardiac dysfunction and impaired cardiorespiratory fitness in breast cancer patients with BRCA1/2 mutations; 2) patient-derived induced pluripotent stem cells can be used to model the individual patient clinical phenotype in BRCA1/2 carriers with cardiac dysfunction.
This is a double-blind, placebo-controlled, randomized clinical trial of 0 or 40 mg of atorvastatin/day in 250 individuals scheduled to receive anthracycline-based chemotherapy for treatment of breast cancer or lymphoma. Magnetic resonance imaging (MRI) procedures are used to determine cardiac function and remodeling. This clinical trial is part of the NCI National Community Oncology Research Base. In addition to our role as an enrolling site, we have an ongoing ancillary study to determine if biomarkers of oxidative and nitrosative stress are clinically and mechanistically informative in cancer patients treated with anthracyclines. Data from our group support a role for biomarkers such as myeloperoxidase (MPO) and the arginine-NO metabolites asymmetric dimethylarginine (ADMA) and monomethylarginine (MMA) in predicting cardiac dysfunction with anthracyclines. Statin therapy has been shown to alter these markers, suggestive of a potential mechanistic link. We hypothesize that these biomarkers will be associated with changes in left ventricular ejection fraction in this population and be useful in the determination of the cardiovascular response to statin therapy.
Sunitinib is a multi-targeted oral tyrosine kinase inhibitor that has revolutionized the treatment of renal cell carcinoma. However, this agent is associated with a risk of cardiovascular toxicity, including marked elevations in blood pressure and declines in left ventricular ejection fraction. The overall objective of this proposal is to determine if early changes in ventricular-vascular function or markers of cardiomyocyte-endothelial cell homeostasis are predictors of sunitinib cardiac toxicity in humans.
- Abnormalities in Three-Dimensional Left Ventricular Mechanics with Anthracycline Chemotherapy are Associated with Systolic and Diastolic Dysfunction. Zhang KW, Finkelman BS, Gulati G, Narayan HK, Upshaw J, Narayan V, Plappert T, Englefield V, Smith AM, Zhang C, Hundley WG, Ky B: Journal of the American College of Cardiology Imaging 2018 Notes: Manuscript accepted, 2018.
- Arginine-Nitric Oxide Metabolites and Cardiac Dysfunction in Patients With Breast Cancer. Finkelman BS, Putt M, Wang T, Wang L, Narayan H, Domchek S, DeMichele A, Fox K, Matro J, Shah P, Clark A, Bradbury A, Narayan V, Carver JR, Tang WHW, Ky B. J Am Coll Cardiol. 2017 Jul 11;70(2):152-162
- Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma. Narayan V, Keefe S, Haas N, Wang L, Puzanov I, Putt M, Catino A, Fang J, Agarwal N, Hyman D, Smith AM, Finkelman BS, Narayan HK, Ewer S, ElAmm C, Lenihan D, Ky B. Clin Cancer Res. 2017 Jul 15;23(14):3601-3609
- Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations With Ejection Fraction Decline, Recovery, and Heart Failure Symptoms Over 3 Years of Follow-Up. Narayan HK, Finkelman B, French B, Plappert T, Hyman D, Smith AM, Margulies KB, Ky B. Circulation. 2017 Apr 11;135(15):1397-1412
- Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction. Beer LA, Kossenkov AV, Liu Q, Luning Prak E, Domchek S, Speicher DW, Ky B. Circ Res. 2016 Oct 28;119(10):1135-1144.
- Noninvasive Measures of Ventricular-Arterial Coupling and Circumferential Strain Predict Cancer Therapeutics-Related Cardiac Dysfunction. Narayan HK, French B, Khan AM, Plappert T, Hyman D, Bajulaiye A, Domchek S, DeMichele A, Clark A, Matro J, Bradbury A, Fox K, Carver JR, Ky B. JACC Cardiovasc Imaging. 2016 Oct;9(10):1131-1141.