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Advances in care are leading to better outcomes for cancer patients, but some cancer treatments can lead to negative impacts on the heart and cardiovascular system, including high blood pressure, irregular heartbeats, heart disease and heart failure.

For many cancer patients who have completed treatment and are years out from their diagnosis, their risk of death from heart disease can be higher than their risk of death from cancer.

The emerging field of cardio-oncology is paving the way for expert, multidisciplinary heart care before, during and after cancer treatment to mitigate adverse effects on cardiovascular health. VCU Massey Cancer Center has been an international leader in this field for the last 10 years.

VCU was recently named as a 2023 International Cardio-Oncology Society (IC-OS) Center of Excellence, receiving the top award of Gold Status for providing high-quality, comprehensive and interdisciplinary heart-related care for patients. VCU is the only medical institution in Virginia to hold this designation.

The cardio-oncology team at Massey and VCU Health Pauley Heart Center offers seamless care for patients during cancer treatment and throughout survivorship, including management of risk factors that may cause heart disease, treatment of late cardiovascular effects of cancer therapy and opportunities to participate in cutting-edge clinical research.

Through ongoing collaborations between multidisciplinary specialists at Massey and Pauley, doctors and scientists across the university and health system are leading a number of clinical trials and research projects investigating more effective strategies for protecting the heart health of cancer patients, from improved monitoring techniques to novel drug combinations.

Cancer treatment and heart damage

The cardio-oncology team at VCU Massey Cancer Center and VCU Health Pauley Heart Center offers seamless heart care for patients during cancer treatment and throughout survivorship.

Damage to the heart caused by chemotherapy or other cancer treatments is known as cardiotoxicity. Cardiotoxicity can occur through many mechanisms, including direct damage to heart cells, damage to vessels supplying blood to the heart or through inflammation. It increases a person’s risk of heart disease or failure. In addition to studying the direct effects of treatments on the heart, researchers also recognize and seek to address disparities that exist in certain minority populations with an increased burden of heart disease related to cancer treatment.

Fadi N. Salloum, Ph.D., a member of the Cancer Prevention and Control (CPC) research program at Massey, associate chair for research in the Department of Internal Medicine at the VCU School of Medicine and associate director of research mentoring and preclinical science at Pauley, currently holds a seven-year grant from the National Heart, Lung and Blood Institute (NHLBI) to investigate the role of sterile inflammation in cardiac dysfunction and heart failure caused by chemotherapy. The findings will be used to facilitate the design and development of novel preventive and therapeutic strategies for cardio-oncology care.

Salloum also co-authored a review  recently published in Translational Research  detailing how different classes of cancer drugs can damage the heart and how therapies that reduce inflammation may protect the heart and reduce cardiotoxicity during cancer treatment.

Arnethea Sutton, Ph.D., member of the CPC research program at Massey and assistant professor in the Department of Kinesiology & Health Sciences at the VCU College of Humanities and Sciences, investigates the roles of psychosocial, sociocultural and cancer care delivery factors that contribute to treatment-related cardiovascular toxicities and poorer outcomes in Black women with breast cancer.

She currently holds grant funding from the National Cancer Institute to unpack the drivers of racial disparities in cardiovascular toxicities among breast cancer survivors.

“Findings from this study may offer opportunities to develop multilevel interventions seeking to improve cardiovascular outcomes in breast cancer survivors by addressing racial disparities associated with cardiotoxicity,” Sutton said.

Using MRI to monitor heart health

Greg Hundley, M.D., director of Pauley and a member of the CPC research program at Massey, was the first person in the world to demonstrate that magnetic resonance imaging (MRI) stress testing can identify patients at risk of a heart attack. He pioneered the use of MRI technology to visualize blood flow through the arteries, and has helped spearhead a movement expanding the use of cardiovascular MRI in cancer research and care, further bolstered by several VCU colleagues.

Jennifer Jordan, Ph.D., member of the CPC research program at Massey and assistant professor in the VCU Department of Biomedical Engineering and Pauley, uses cardiovascular MRI to identify biomarkers of heart complications associated with cancer treatment. She is the co-principal investigator on a first-of-its-kind prospective study looking at the earliest signs of heart vessel damage in young, pre-menopausal breast cancer survivors.

All study participants will receive sophisticated imaging tests at different intervals to look for small changes in the blood vessels that supply blood to the heart. Those include a cardiac MRI stress test at the beginning of the study, and at one-year and two-year intervals. Participants will also receive computerized tomography (CT) imaging of their cardiac arteries at baseline and after two years, along with blood tests to look for biomarkers that correlate with the risk of cardiovascular disease. The participants will be followed for five years.

“The state-of-the-art cardiovascular imaging will allow us to study cardiovascular health in young breast cancer survivors who have decades of survivorship health to protect,” Jordan said.

Wendy Bottinor, M.D., a cardio-oncologist and member of the CPC research program at Massey, studies cardiovascular disease in survivors of childhood, adolescent and young adult-onset cancer. Her team uses cardiovascular MRI and clinical data to understand the factors that influence the development of cardiovascular disease among cancer survivors.

Bottinor currently leads a clinical trial at Massey testing an oral combination medication in adults diagnosed with cancer before age 40 who have heart failure. Participants will be examined with cardiac MRI throughout the trial.

One of Bottinor’s patients — a breast cancer survivor — recently spoke with WTVR CBS 6 about the potential for reducing her risk of heart complications by participating in this clinical trial.

Novel combination therapies to reduce heart failure risk in breast cancer

Scientists at VCU are evaluating new combinations of drugs in an effort to effectively treat breast cancer while mitigating damage to the heart caused by common chemotherapy medications.

Rakesh Kukreja, Ph.D., a member of the Developmental Therapeutics (DT) research program at Massey and a professor in the Department of Internal Medicine at the VCU School of Medicine, and Anindita Das, Ph.D., associate professor in the Division of Cardiology at the VCU School of Medicine, are co-principal investigators on a four-year, $2.2 million R01 grant from the NHBLI to study a novel combination treatment for breast cancer to reduce the risk of heart failure, a common side effect of doxorubicin (DOX) chemotherapy.

DOX alone or in combination with a kinase inhibitor is highly effective in treating breast cancer, but survivors treated with DOX are at an elevated risk of early cardiovascular health complications, including death. There is no effective therapy currently available to reduce or eliminate this risk.

Kukreja and his collaborators will use this grant funding to study the therapeutic effect of the combination of DOX (or DOX with a kinase inhibitor), sildenafil (commercially known as Viagra) and the anti-rejection drug rapamycin to reduce cardiac side effects and improve the efficacy of breast cancer treatment.

“The results of this research could inform the development of an effective treatment option for thousands of breast cancer patients worldwide experiencing the lethal and debilitating cardiotoxic effects of chemotherapy,” Kukreja said.

Additionally, Salloum and Das are also co-principal investigators on another NHLBI grant-funded projectthat seeks to develop novel drugs that combine with chemotherapeutics (such as DOX) to maintain or improve patient outcomes in triple-negative breast cancer, as well as reduce long-term death associated with cardiotoxicity.

Promoting healthy lifestyle choices and interventions

Regular physical activity helps maintain healthy weight, energy levels and overall health; however, adolescent and young adult cancer survivors are often less active than those who have not undergone cancer treatment. Strategies like the use of activity trackers, patient education and support groups are believed to support the reduction of cardiovascular health risks.

Madhu Gowda, M.B.B.S., pediatric hematologist-oncologist at the Children’s Hospital of Richmond at VCU and member of the DT research program at Massey, leads a clinical trial evaluating the effects of an intervention plan — which incorporates the use of a Fitbit, individualized goal setting and social media support groups — on the cardiometabolic health and health-related quality of life among survivors of childhood cancers.

"By providing guidance and support through a peer network, we hope to incorporate an active lifestyle into cancer survivors' journey of moving forward beyond the cure," Gowda said.

Additionally, Mary Helen Hackney, M.D., medical oncologist and director of community oncology at Massey, oversees a clinical trial examining the effects of a cardiovascular health assessment tool among cancer survivors. The intended goal of this multi-center trial is to help initiate more heart health discussions between cancer survivors and their oncology providers, increase routine visits by cancer survivors to primary care and heart specialists, and to influence an uptick in risk reduction and healthy lifestyle activities among survivors.

"This trial is focused on breast cancer survivors, but it can be a launchpad for similar studies with other cancer survivors," Hackney said. "With more and more survivors each year, it is important that we maximize good cardiovascular health and overall wellbeing. This will help non-oncology providers as these patients return to their standard care, and it will help patients understand what they need to do to remain healthy many years beyond their cancer treatment."

For more information about cardio-oncology care at VCU, visit: https://www.vcuhealth.org/pauley-heart-center/programs-and-expertise/cardio-oncology

Written by: Blake Belden