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When Cancer and Cardiovascular Disease Intersect


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Susan Faye Dent, MD, FICOS

Susan Faye Dent, MD, FICOS

Christine Brezden-Masley, Md, PhD

Christine Brezden-Masley, Md, PhD

Anne Blaes, MD

Anne Blaes, MD

Bogda Koczwara, BMBS

Bogda Koczwara, BMBS

The annual Global Cardio-Oncology Summit (GCOS) was held September 22 to 24 in Minneapolis, with 430 health-care professionals attending from 20 countries. The Summit brings together health-care professionals from diverse disciplines including members of the International Cardio-Oncology Society (ICOS), the only multidisciplinary professional organization focused on an integrated approach to management of cardiovascular disease (CVD) in the context of cancer. The key take-home messages from the meeting are featured here.

The Emerging Concept of Reverse Cardio-Oncology

The impact of cancer and its treatment on the risk of CVD has historically been the focus of cardio-oncology. More recently, emerging epidemiologic data have shown that people diagnosed with CVD are at higher risk of developing cancer,1 and preclinical studies demonstrate inferior cancer outcomes after a CVD event, suggesting molecular crosstalk between cancer and CVD.2 This bidirectional relationship between cancer and CVD has significant implications on cancer care and research, moving beyond prevention and management of cardiotoxicity of cancer drugs into an integrated management of risk of CVD and cancer in individuals with both conditions. As both diseases share common risk factors and benefit from similar lifestyle interventions, this integrated approach to care warrants further consideration.

Cardiovascular Toxicities With Immune Therapies: Beyond Myocarditis

Long-term data on cardiovascular toxicity of immune checkpoint inhibitors show that although immune checkpoint inhibitor–related myocarditis is rare, and some cases are mild,3 proactive management of severe cases is critical to improving clinical outcomes.4 Real-world evidence suggests that the most common CVD observed in recipients of immune checkpoint inhibitors is accelerated atherosclerosis, leading to acute coronary syndromes, heart failure, and stroke.5 This underscores the importance of aggressive management of CVD risk factors in these patients.

Predicting Risk of Cardiotoxicity

Identifying patients with cancer at risk of cardiovascular toxicity could lead to alternative cancer therapies and/or primary prevention strategies. In 2022, the European Society of Cardiology (ESC) Cardio-Oncology guideline6 endorsed the use of the HFA-ICOS risk score7 to determine the baseline risk of cardiotoxicity (low, medium, high, very high) for nine classes of cancer drugs. The CARDIOTOX registry study evaluated the use of the HFA-ICOS risk score in a population of patients with cancer receiving anthracyclines. The HFA-ICOS risk score was strongly predictive of cardiovascular toxicity and all-cause mortality.8 Further studies with different classes of cancer drugs are needed to validate this approach.

Primary Prevention of Cardiotoxicity

Primary prevention strategies (prior to starting cancer therapy) with neurohormonal agents (beta-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and statins) in patients with cancer receiving anthracyclines and/or HER2-targeted therapy have yielded mixed results.9 Current guidelines recommend the use of these agents in patients at high or very high risk of cardiovascular toxicity.6

A recent retrospective analysis of sodium-glucose cotransporter-2 (SGLT2) inhibitors focused on patients with cancer and diabetes and no history of cardiomyopathy or heart failure receiving potentially cardiotoxic cancer therapy. The investigators demonstrated a reduction in cancer therapy–related cardiac dysfunction, all-cause mortality, and all-cause hospitalizations or emergency department visits.10 Prospective studies are needed to determine the potential role of these agents in patients with cancer at risk of cardiotoxicity.

Echocardiography Monitoring: The Utility of Strain Surveillance

Echocardiograms have been widely adopted to monitor cardiac function for patients receiving cancer therapy (mainly for HER2-targeted agents); however, a drop in left ventricular ejection fraction (LVEF) is considered a late sign of cardiac dysfunction. Global longitudinal strain (GLS) assesses myocardial deformation of the left ventricle and is considered a more sensitive indicator of left ventricular dysfunction.

The SUCCOUR-MRI clinical study was a prospective multicenter randomized controlled trial in which patients treated with anthracyclines and drops in GLS (> 12% relative reduction of GLS without a change in LVEF) were randomly assigned to receive cardioprotection with neurohormonal agents vs usual care. At 12 months, patients treated with cardioprotection had better preservation of LVEF (decrease 1.8% vs 5.5 %; P < .001); however, access to cardiac MRI globally may limit this approach.11

Attendees at the 2024 Global Cardio-Oncology Summit in Minneapolis.

Potential for De-escalation of Echocardiography Monitoring

In the pediatric population, more than 70% of patients will be exposed to an anthracycline. Patients receiving 250 mg/m2 of doxorubicin and/or 15 cGy of chest wall radiation are at high risk of cardiotoxicity requiring frequent cardiac imaging.12 Less exposure to cytotoxic chemotherapy and/or radiation decreases the frequency of cardiac imaging, as the risk of cardiotoxicity is significantly less. A recent recommendation from a pediatric survivorship population emphasizes the potential for less monitoring in patients at lower risk of CVD from less cardiotoxic exposure.12 Studies of similar approaches in adult populations are underway.

Survivorship Interventions to Reduce CVD Risk: The Role of Exercise

As the incidence of cancer continues to increase, survival rates are also increasing with the development of improved therapies, specifically the use of immunotherapy, novel cytotoxics, and targeted therapies. It is estimated there will be 35 million new diagnoses of cancer by 2050 (an increase of 77%), with an estimated 17.5 million survivors worldwide.13 Strategies to improve survival, not only to decrease cancer recurrence, but also to reduce CVD mortality and morbidity are imperative, and they extend beyond pharmacologic interventions. Exercise interventions target both cancer and CVD outcomes, directly addressing the bidirectional relationship between the two conditions.

For example, in the OptiTrain study, women with early-stage breast cancer undergoing chemotherapy who were randomly assigned to receive resistance training–high-intensity interval training had an improvement in overall survival at 5 years compared with the control (usual care) and aerobic training.14 These diverse approaches, working together with cardiology colleagues and allied health-care professionals, are the key to optimizing the cardiac health of cancer survivors to sustain the gains in survivorship seen with modern cancer therapies.

DISCLOSURE: Dr. Dent has received honoraria from Novartis, Pfizer, Race Oncology, Bristol Myers Squibb, Myocardial Solutions, Gilead Sciences, and AstraZeneca. Dr. Brezden-Masley, Dr. Blaes, and Dr. Koczwara reported no conflicts of interest.

REFERENCES

1. Ausoni S, Azzarello G: Development of cancer in patients with heart failure: How systemic inflammation can lay the groundwork. Front Cardiovasc Med 7:598384, 2020.

2. Koelwyn GJ, Newman AAC, Afonso MS, et al: Myocardial infarction accelerates breast cancer via innate immune reprogramming. Nat Med 26:1452-1458, 2020.

3. Moradi A, Kodali A, Okoye C, et al: A systematic review of myocarditis induced by immune checkpoint inhibitors: How concerning is the most common cardiotoxicity of immune checkpoint inhibitors? Cureus 15:e42071, 2023.

4. Tocchetti CG, Farmakis D, Koop Y, et al: Cardiovascular toxicities of immune therapies for cancer: A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology. Eur J Heart Fail. August 1, 2024 (early release online).

5. Laenens D, Yu Y, Santens B, et al: Incidence of cardiovascular events in patients treated with immune checkpoint inhibitors. J Clin Oncol 40:3430-3438, 2022.

6. Lyon AR, López-Fernández T, Couch LS, et al: 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society of Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 23:e333-e465, 2022.

7. Lyon AR, Dent S, Stanway S, et al: Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: A position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail 22:1945-1960, 2020.

8. Rivero-Santana B, Saldaña-García J, Caro-Codón J, et al: Anthracycline-induced cardiovascular toxicity: Validation of the Heart Failure Association and International Cardio-Oncology Society risk score. Eur Heart J Aug 6:ehae496, 2024.

9. Omland T, Heck SL, Gulati G: The role of cardioprotection in cancer therapy cardiotoxicity: JACC: Cardio-Oncology state-of-the-art review. JACC CardioOncol 4:19-37, 2022.

10. Bhatti AW, Patel R, Dani SS, et al: SGLT2i and primary prevention of cancer therapy–related cardiac dysfunction in patients with diabetes. JACC CardioOncol. September 22, 2024 (early release online).

11. Marwick TH, Dewar E, Nolan M, et al: Strain surveillance during chemotherapy to improve cardiovascular outcomes: The SUCCOUR-MRI trial. Eur Heart J Sep 1:ehae574, 2024.

12. Ehrhardt MJ, Leerink JM, Mulder RL, et al: Systematic review and updated recommendations for cardiomyopathy surveillance for survivors of childhood, adolescent, and young adult cancer from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 24:e108-e120, 2023.

13. Cao W, Qin K, Li F, et al: Comparative study of cancer profiles between 2020 and 2022 using global cancer statistics (GLOBOCAN). J Natl Cancer Cent 4:128-134, 2024.

14. Rundqvist H, Rietz M, Mijwel S, et al: Effects of a high-intensity exercise intervention on recurrence and survival: The OptiTrain breast cancer trial. ESMO Congress 2024. Abstract 232O. Presented September 16, 2024.

Dr. Dent is a medical oncologist at the University of Rochester New York. Dr. Brezden-Masley is a medical oncologist at the University of Toronto. Dr. Blaes is a medical oncologist at the University of Minnesota, Minneapolis. Dr. Koczwara is a medical oncologist at Flinders Medical Centre and Flinders University, Adelaide, Australia.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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