At the 2024 Debates and Didactics in Hematology and Oncology Conference, sponsored by Emory’s Winship Cancer Institute, cardiologist-by-training Anant Mandawat, MD, FACC, briefly reviewed how the emerging field of cardio-oncology is blazing a path toward “bigger and bolder cancer care” and offered some thoughts on this intersection between cancer and cardiovascular disease, where oncologists and cardiologists can meet to improve outcomes for patients.1 Dr. Mandawat is Director of the Cardio-Oncology Center of Excellence, Winship Cancer Institute, Heart & Vascular Center, and Assistant Professor of the Department of Medicine at Emory University School of Medicine, Atlanta.
Anant Mandawat, MD, FACC
In a top 10 list of causes of death in the United States, heart disease and cancer dominate, taking the number one and two spots in both men and women. “It doesn’t matter who you are—oncologist, cardiologist, surgeon, radiation oncologist—invariably, you are going to interact with patients who live at the intersection of heart disease and cancer,” stated Dr. Mandawat.
Across all medical specialties, oncology dominates over the others in terms of the number of new innovative agents in phase I through III clinical trials. In addition, indications for newer immunotherapies have expanded.2 And, given the additional therapies and their effectiveness, improvements have been made in the 5-year survival rates for many common cancers, based on data from the Surveillance, Epidemiology, and End Results (SEER) program, he added. In addition, the number of cancer survivors is expected to top 26 million by the year 2040.3
To continue to improve these survival outcomes, according to Dr. Mandawat, we need to turn to the causes of death in patients with cancer that are not related to cancer, and cardiovascular disease plays a prominent role here. “Interestingly, cardiovascular disease is having a big impact on patients all the way from their diagnosis and through their cancer treatment,” he noted. In fact, data from more than 36,000 cancer survivors from Kaiser Permanente–SEER showed that those who also have cardiovascular disease have the worst survival of any group.4
A Clinical Framework to Approach Cardio-Oncology
To better understand the framework of how to approach cardio-oncology, Dr. Mandawat continued, “we have to talk about this concept of a competing therapeutic dynamic between cancer and cardiovascular disease.” For instance, the goal of cancer treatments (chemotherapy, immunotherapy, targeted therapy, and radiation therapy) is to target or destroy malignant cells. In contrast, the goal of managing heart disease is to nourish and protect cardiac myocytes.
More specifically, Dr. Mandawat shared the example of the function of a VEGF inhibitor, with its positive effects on treating cancer cells and potentially deleterious effects on the blood vessels in the heart. “This is the yin and yang that we’re constantly seeing,” he added, “regardless of the type of drug you have, if it has a side effect that can affect the heart.”
Understanding Risk Stratification: Where Oncologists and Cardiologists Can Meet
The poster child for cardiotoxicity is the use of anthracyclines, noted Dr. Mandawat, which has been linked to heart failure. However, he added, “the spectrum of cardiac pathology can be quite broad, including hypertension, coronary disease, valvular disease, pericardial disease, and arrhythmia.” In addition, these cardiac toxicities can be acute or chronic, with coronary vasospasm being one of the acute problems associated with certain cancer therapies.
Clearly, the implications of cardiac toxicity in patients being treated for cancer can be severe and seriously impact their outcomes. These side effects can result in the interruption and/or discontinuation of life-saving cancer therapy. Furthermore, the psychological impact of additional severe comorbidity can be “a gut punch to patients,” said Dr. Mandawat. Finally, individuals who have cardiovascular disease are often disqualified from participating in oncology clinical trials.
Thus, a team-based, integrated approach, including both oncologists and cardiologists, is essential to manage both the cardiovascular and cancer risks. “Collaboration between cardiologists and oncologists can result in bigger and bolder treatment options,” Dr. Mandawat proposed. The goals of cardio-oncology are to maximize cancer treatment, minimize cardiovascular toxicity, and improve overall outcomes for patients.5
Here are a few suggested steps for oncologists to connect with cardiologists in this setting:
- Identify patients who are at an elevated risk for cardiac complications, including those with cardiac comorbidities and those receiving cardiotoxic therapies;
- Develop a collaboration with a cardio-oncologist to co-manage high-risk patients during cancer therapy;
- If cardiac complications develop, establish a process to rapidly assess and treat these complications to limit interruptions in cancer care.
And this integrated approach begins after a cancer diagnosis, Dr. Mandawat explained, and starts with a baseline level of cardiovascular health. “We can see these patients before they start their therapy, and we can optimize risk factors and comorbidities going into therapies that we know are toxic,” he noted.
Then, as patients move through cancer therapy (or therapies), cardiovascular health needs to be continually assessed, to ensure there is no structural heart disease or heart failure. “Once we know the specific type of therapy they are going to receive, we can develop a tailored monitoring plan for them,” explained Dr. Mandawat. If evidence of subclinical cardiovascular toxicity is detected, perhaps via myocardial strain imaging (ie, change in cardiac muscle fiber length over the cardiac cycle, as measured by echocardiography or magnetic resonance imaging), cardioprotective medicine can be considered early. And should there be a decline in ejection fraction or clear clinical symptoms, a cardio-oncologist or cardiologist should be seeing these patients, he added. “The earlier you can catch these patients, the better chance of recovering their overall function,” he said.
Risk stratification is a key component of this integrated approach, as those patients found to be at highest risk should be followed closely. One clear example of how guidelines evolved to protect cardiac health during cancer therapy is the use of anthracyclines. Since the 1960s, these agents have been used in clinical oncology to effectively treat various cancers; by the 1970s, case series were showing the cardiotoxicity associated with certain doses of anthracyclines, explained Dr. Mandawat. The recommendation for dosing has evolved since then, with a better understanding of the cardiac damage caused by cumulative doses. The findings of a study in more than 14,000 survivors of childhood cancer showed that even at small doses, the cumulative effect of anthracyclines can cause cardiac damage.6 Thus, he noted, the current guideline for using anthracyclines in children is a dose of less than 250 mg/m2.
In addition, ASCO released guidelines for those patients at increased risk for developing cardiac toxicity.7 “We have this concept of a two-hit hypothesis: lower dose of anthracycline with a lower dose of radiotherapy,” said Dr. Mandawat. Also, a lower dose might be considered if the patient has multiple cardiovascular risk factors, such as older age, compromised cardiovascular function, history of myocardial infarction, or moderate valvular disease.
Additional Clinical Risk Tools
When the use of other types of therapies for cancer is being considered, there is another way to assess cardiovascular risk. In 2022, European societies released the HFA-ICOS (Heart Failure Association–International Cardio-Oncology Society) cardio-oncology risk calculator.8 “The good part of this calculator,” explained Dr. Mandawat, “is you can select multiple different types of treatment and then enter clinical characteristics about the patient, and it will spit out a risk [low, moderate, high, or very high]. Based on your practice, you can decide which of the patients you want to monitor.”
Myocardial strain imaging is another clinical risk tool that is available, Dr. Mandawat continued. Myocardial segments are tracked through the cardiac cycle for a change in size or deformation. These deformation values are averaged to generate a global longitudinal strain number, and “the higher the absolute number, the better the left ventricular function,” he said.
Evidence of the use of this imaging method was demonstrated in the international, multicenter, randomized SUCCOUR trial.9 In more than 300 patients, with a median follow-up of 1 year, fewer patients on the strain arm had cardiotoxicity compared with the ejection fraction arm. “You can think of it like an early warning system for detecting cardiotoxicity,” Dr. Mandawat added. Then, if need be, cardioprotective medicines can be added earlier. Herrmann has published a useful checklist of cancer treatments by type and their association with various cardiovascular diseases.10
DISCLOSURE: Dr. Mandawat has received grants or research support from Pfizer, Myovant Sciences, the Prostate Cancer Foundation, the National Comprehensive Cancer Network, and the Morningside Center for Innovation.
REFERENCES
1. Mandawat A: Cardio-oncology: A path toward bigger and bolder cancer care. 2024 Debates and Didactics in Hematology and Oncology Conference. Presented July 26, 2024.
2. Maritaz C, Broutin S, Chaput N, et al: Immune checkpoint–targeted antibodies: A room for dose and schedule optimization? J Hematol Oncol 15:6, 2022.
3. Shapiro CL: Cancer survivorship. N Engl J Med 379:2438-2450, 2018.
4. Armenian SH, Xu L, Ky B, et al: Cardiovascular disease among survivors of adult-onset cancer: A community-based retrospective cohort study. J Clin Oncol 34:1122-1130, 2016.
5. Adusumalli S, Alvarez-Cardona J, Khatana SM, et al: Clinical practice and research in cardio-oncology: Finding the ‘Rosetta Stone’ for establishing program excellence in cardio-oncology. J Cardiovasc Transl Res 13:495-505, 2020.
6. Mulrooney DA, Yeazel MW, Kawashima T, et al: Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: Retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339:b4606, 2009.
7. Armenian SH, Lacchetti C, Barac A, et al: Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. December 5, 2016 (early release online).
8. Lyon AR, Dent S, Stanway S, et al: Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies. Eur J Heart Fail 22:1945-1960, 2020.
9. Thavendiranathan P, Negishi T, Somerset E, et al; SUCCOUR investigators: Strain-guided management of potentially cardiotoxic cancer therapy. J Am Coll Cardiol 77:392-401, 2021.
10. Herrmann J: Adverse cardiac effects of cancer therapies: Cardiotoxicity and arrhythmia. Nat Rev Cardiol 17:474-502, 2020.
