Research

The overall objective of this AHA-funded study (NCT05176756) led by Drs. Alexander Fanaroff, Kevin Volpp, and Saro Armenian is to determine the effectiveness of a behaviorally designated gamification intervention with social support to increase physical activity in patients with or at risk for atherosclerotic cardiovascular disease and evaluate the effects of the intervention on physical function, fatigue and quality of life.

Principal Investigators: Dr. Alexander C. Fanaroff, MD, Dr. Kevin Volpp, MD, PhD, and Dr. Saro H. Armenian, DO, MPH

The overall objective of this NIH-funded longitudinal prospective cohort study (NCT01173341) is to determine the role of individual patient characteristics, mechanistic biomarkers, and novel echocardiographic measures of cardiac function in predicting the short- and long-term cardiovascular disease risk in women with breast cancer receiving potentially cardiotoxic therapy including hormone therapies, anthracyclines, HER2+ targeted therapies and radiation.

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

The objectives of this AHA-funded Strategically Focused Research Network Award longitudinal prospective cohort study (NCT 05078190) in women with breast cancer are to determine the associations between individual and structural social determinants of health (SDOH) and cardiotoxicity risk, and how this may differ according to race. A sub-study of this protocol includes a detailed study of allostatic load, characterized as the “wear and tear” from chronic levels of stress placed on physiological systems. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

Dr. Yehoda Martei, MD, MSCE was recently awarded a Robert A. Winn Diversity in Clinical Trials Career Development Award for work in cardio-oncology clinical studies – her pilot proposal focuses on using community health workers to increase diversity in enrollment of two ongoing longitudinal prospective cohort studies, CCT2 and PCT, in cardio-oncology.

This NIH-funded, Phase I, single center, randomized clinical trial (NCT04023110) seeks to determine if a risk guided treatment strategy, as determined by a clinical risk score, that randomizes elevated cardiovascular risk breast cancer patients prior to doxorubicin and/or trastuzumab to carvedilol or usual care is safe, tolerable, and feasible. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

This is a Phase I, multi-center, randomized trial (NCT04737265) of a biomarker-guided strategy using NT-proBNP to identify and treat patients at elevated risk of anthracycline therapy-related cardiotoxicity. The primary objective of this study is to determine if a biomarker guided strategy is feasible and well-tolerated in breast cancer or lymphoma patients treated with doxorubicin. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

The RadComp Study (NCT02603341), short for Radiotherapy Comparative Effectiveness, is a nationwide clinical study comparing two FDA approved radiation therapies for the treatment of breast cancer, PHoton Therapy vs. PRoton Therapy. With this study, we hope to better understand the best available technologies for breast cancer to help patients live a longer, healthier life.

Principal Investigators: Dr. Bonnie Ky, MD, MSCE and Dr. Alexander Lin, MD.

The overall objectives of this NIH-funded ancillary study (NCT04361240) to the RadComp clinical trial are to determine how early subclinical measures of cardiovascular injury and dysfunction differ according to radiation therapy type (proton vs photon) and which radiation therapy dose-volume parameters influence cardiovascular biomarkers.

Principal Investigator: Dr. Bonnie Ky, MD, MSCE.

The overall objective of this pilot study is to define how baseline CV risk differs according to HIV status in breast cancer patients treated with doxorubicin and/or trastuzumab. Our team also seeks to define the association between HIV infection and risk of left ventricular ejection fraction (LVEF) declines and Cancer Therapeutics Related Cardiac Dysfunction (CTRCD) in breast cancer patients treated with doxorubicin and/or trastuzumab. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE 

The objective of this Pfizer-funded Investigator-initiated science is to discover new cardiotoxicity biomarkers and –omics signatures in cancer patients, and how these markers may differ according to self-identified race.

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

Through an NIH-funded K24 grant, we are leveraging the electronic medical records (EMR) of the University of Pennsylvania Health System to determine the impact of race and the SDOH in cardio-oncology through a detailed analysis of patient-level data. We use the EMR to derive large breast and prostate cancer cohorts of patients receiving cardiotoxic cancer therapies and define the individual and structural SDOH and associations with cardiovascular clinical outcomes. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

We propose a registry study (NCT04118530) in hematopoietic stem cell transplant (HSCT) patients with incident atrial fibrillation/atrial flutter (AF/AFL) during the initial 30 days of transplant who will be implanted with the Medtronic Reveal Linq Implantable Cardiac Monitor (ICM) within 90 days of HSCT. We will evaluate the rate of recurrent AF/AFL as well as incident episodes of major cardiovascular events and the safety of ICM implantation in this population.

Principal Investigator: Dr. Michael G. Fradley, MD

This observational, prospective, single center study (NCT04026737) aims to describe the rate of occurrence, natural history and risk factors of cardiovascular events in adult patients treated with CART cells and to determine if baseline or changes in clinical factors, echocardiographic parameters and left ventricle deformation indices, blood biomarkers and cytokine levels can predict subsequent cardiovascular events in patients treated with CART cells. A sub-study of this protocol includes an assessment of heart rate monitoring (ambulatory electrocardiogram monitor) potentially allowing for the early detection of cytokine release syndrome, which could improve treatment outcomes.  

Principal Investigator: Dr. Marielle Scherrer-Crosbie, MD, PhD

Sub Investigators:

Dr. Joseph Carver, MD, FACC

 Dr. Noelle Frey, MD, MS

Dr. Yu Kang, MD, PhD

Amanda (Laney) Smith, MS

Dr. Bénédicte Lefebvre, MD

Dr. Stephen J. Schuster, MD 

CVFAL is an observational, prospective study (NCT03760237) to describe the rates and predictors of cardiovascular events in patients with acute leukemia. We will study whether myocardial strain or biomarkers are predictive of subsequent LV dysfunction and cardiovascular events in patients with acute leukemia. In addition, we will analyze the association of molecular abnormalities with subsequent decline in cardiovascular function in this population. 

Principal Investigator: Dr. Marielle Scherrer-Crosbie, MD, PhD

This is a Phase I, multi-center, randomized trial (NCT04737265) of a biomarker-guided strategy using NT-proBNP to identify and treat patients at elevated risk of anthracycline therapy-related cardiotoxicity. The primary objective of this study is to determine if a biomarker guided strategy is feasible and well-tolerated in breast cancer or lymphoma patients treated with doxorubicin. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

This prospective, longitudinal cohort study aims to evaluate the cumulative incidence of new onset or worsening hypertension in patients treated with the BTK inhibitors acalabrutinib and zanubrutinib. Given the unmet need to better quantitate hypertension and arrhythmia burden in patients treated with BTK inhibitors, we are proposing a study in which a SmartWatch (Apple Watch Generation 8 device, current or future generations), as well as at-home blood pressure monitoring (QARDIO Arm Smart Blood Pressure Cuff) is used to monitor for the development of arrhythmias in either acalabrutinib- or zanubrutinib -treated CLL patients to better determine incidence and prevalence in a real-world population. 

Principal Investigator: Dr. Michale Fradley, MD

This randomized trial (NCT05335928) led by Drs. Tomas Neilan, MD, MPH and Paul Ridker, MD, MPH is being conducted to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants who develop myocarditis after treatment with an Immune checkpoint inhibitor (ICI). The primary aim of this trial is to test in a randomized double-blind placebo-controlled study whether abatacept, administered concurrently with corticosteroids, is associated with a reduction in MACE among participants with recently diagnosed ICI myocarditis.

University of Pennsylvania Site Principal Investigator: Dr. Michael G. Fradley, MD

The overall objective of this observational study (NCT06332131) is to determine the incidence of cardiovascular risk factors and diseases for patients with melanoma who will be treated with adjuvant immune checkpoint inhibitor (ICI) therapy. The investigators will use echocardiograms, blood draws, and PET stress tests to understand how ICI therapy affects the heart and circulatory system.

Principal Investigator: Dr. Marielle Scherrer-Crosbie, MD, PhD

CLARITY is a NIH-funded, multi-center, longitudinal prospective cohort study (NCT04305613) of lung cancer patients treated with radiation therapy with the objectives being to determine associations between radiation therapy dose-volume metrics and changes in biologic and imaging markers of cardiovascular function. We aim to determine the prognostic value of these markers as indicators of adverse cardiovascular outcomes. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

This Children’s Oncology Group phase III trial led by Dr. Todd M. Cooper, DO compares standard chemotherapy (NCT04293562) compares standard chemotherapy to therapy with CPX-351 and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations.   

Children's Hospital of Philadelphia Site Principal Investigator: Dr. Richard Aplenc, MD, PhD, MSCE

AAML 1831 Cardiac Studies Principal Investigator: Dr. Kasey Joanne Leger, MD, MSc 

Echocardiography Core Lab Principal Investigator: Dr. Bonnie Ky, MD, MSCE

The goal of this proposal is to develop a highly unique dataset including detailed demographic, clinical, genomic, treatment, and toxicity data, combined with longitudinal indices of left ventricular size, diastolic, and systolic function from all clinical surveillance echocardiograms. With this unique dataset, we will use novel, sophisticated analytic methods to develop models that: (1) continually update predictions of early cardiotoxicity risk during frontline therapy, (2) predict LV functional trajectories leading to persistent or worsening left ventricular systolic dysfunction (LVSD) in the early/moderate time window after AML therapy, and (3) quantify differences in echo monitoring, early incident LVSD, and evaluate their role as intermediates in disparities in survival outcomes by race/ethnicity and evaluate the role of social determinants of health as drivers of identified disparities.

Principal Investigators: Dr. Kelly D. Getz, PhD, MPH and Dr. Richard Aplenc, MD, PhD, MSCE

This study will evaluate the development of new machine learning methods that can inform how often to monitor clinical markers of disease and how to alter patients’ treatment based on these markers. The research will also create novel methods to interrogate causal mechanisms in the context of adaptive treatment and monitoring strategies as potential targets for further optimization. In addition, evidence will be generated to inform the ideal chemotherapy roadmaps and echocardiographic monitoring schedules for patients treated for pediatric acute myeloid leukemia (AML). 

Principal Investigators: Dr. Jason Roy, PhD, MS and Dr. Kelly Getz, PhD, MPH

The specific goals of this National Heart Lung and Blood Institute funded proposal include the following: (1) determine the natural history cardiotoxicity and the incremental effects of treatment from initial diagnosis, through relapse and early  post-relapse follow-up, (2) to quantify the influence of prevalent salvage therapies on longitudinal changes in LV size, systolic and diastolic function and the incidence of cardiomyopathy, and (3) to evaluate salvage chemotherapy and transplant as mediators of the documented association between early cardiotoxicity onset during frontline therapy and decreased overall survival. 

Principal Investigators: Dr. Kelly D. Getz, PhD, MPH 

The overall objective of this AHA-funded study (NCT05176756) led by Drs. Alexander Fanaroff, Kevin Volpp, and Saro Armenian is to determine the effectiveness of a behaviorally designated gamification intervention with social support to increase physical activity in patients with or at risk for atherosclerotic cardiovascular disease and evaluate the effects of the intervention on physical function, fatigue and quality of life.

Principal Investigators: Dr. Alexander C. Fanaroff, MD, Dr. Kevin Volpp, MD, PhD, and Dr. Saro H. Armenian, DO, MPH

This National Comprehensive Cancer Network (NCCN)-funded study (NCT06064149) is a quality improvement and research initiative to evaluate the feasibility and acceptability of a pragmatic, patient-oriented, web-based tool to educate patients regarding the cardiovascular risks associated with androgen deprivation therapy and to inform them of their individualized, estimated cardiovascular risk and guideline-based risk mitigation recommendations. We will assess the feasibility, acceptability, and data quality of this instrument, as well as preliminarily assess its impact on patient awareness and cardiovascular care access. Through this study, we will better understand both the burden of cardiovascular risk across the prostate cancer treatment spectrum and the gaps in access to adequate treatment of cardiovascular risk factors.   

Principal Investigator: Dr. Vivek Narayan, MD, MSCE

The primary objectives of this AHA-funded Strategically Focused Research Network Award longitudinal prospective cohort study (NCT05096338) in men with prostate cancer are to determine the associations between individual and structural SDOH and cardiotoxicity risk, and how this may differ according to race. A sub-study of this protocol also includes a detailed study of allostatic load. 

Principal Investigator: Dr. Bonnie Ky, MD, MSCE

Dr. Yehoda Martei, MD, MSCE was recently awarded a Robert A. Winn Diversity in Clinical Trials Career Development Award for work in cardio-oncology clinical studies – her pilot proposal focuses on using community health workers to increase diversity in enrollment of two ongoing longitudinal prospective cohort studies, CCT2 and PCT, in cardio-oncology.

RADICAL PC1 is a prospective cohort study of men with a new diagnosis of prostate cancer. The primary objective of RADICAL PC1 is to determine the prevalence of cardiovascular risk factors and disease, and the incidence of major adverse cardiovascular events in men with prostate cancer and in particular men treated with Androgen Deprivation Therapy.

Site (Penn) Principal Investigator: Dr. Bonnie Ky, MD, MSCE

The overall objective of this NIH-funded Phase II clinical trial (NCT04467021) is to determine the feasibility of an Intensive (SBP< 120mmHg) Intervention versus Standard Care (SBP< 140mmHg) Non-Intervention approach to blood pressure (BP) control in metastatic renal cell and thyroid cancer patients initiating vascular endothelial growth factor receptor tyrosine kinase inhibitors. This study is being executed in collaboration with ECOG-ACRIN.  

Principal Investigator: Dr. Bonnie Ky, MD, MSCE and Dr. Kenneth Margulies, MD