Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention

Abstract

Cardiovascular disease (CVD), which includes cardiomyopathy/heart failure, coronary artery disease, stroke, pericardial disease, arrhythmias, and valvular and vascular dysfunction, is a major concern for long-term survivors of childhood cancer. There is clear evidence of increased risk of CVD largely attributable to treatment exposures at a young age, most notably anthracycline chemotherapy and chest-directed radiation therapy, and compounded by traditional cardiovascular risk factors accrued during decades after treatment exposure. Preclinical studies are limited; thus, it is a high priority to understand the pathophysiology of CVD as a result of anticancer treatments, taking into consideration the growing and developing heart. Recently developed personalized risk prediction models can provide decision support before initiation of anticancer therapy or facilitate implementation of screening strategies in at-risk survivors of cancer. Although consensus-based screening guidelines exist for the application of blood and imaging biomarkers of CVD, the most appropriate timing and frequency of these measures in survivors of childhood cancer are not yet fully elucidated. Longitudinal studies are needed to characterize the prognostic importance of subclinical markers of cardiovascular injury on long-term CVD risk. A number of prevention trials across the survivorship spectrum are under way, which include primary prevention (before or during cancer treatment), secondary prevention (after completion of treatment), and integrated approaches to manage modifiable cardiovascular risk factors. Ongoing multidisciplinary collaborations between the oncology, cardiology, primary care, and other subspecialty communities are essential to reduce therapeutic exposures and improve surveillance, prevention, and treatment of CVD in this high-risk population.

Fig 1.

Preclinical models of cardiotoxicity. Robust and diverse preclinical models that include cell culture systems, animal models, and computer simulations have provided a better understanding of the molecular and cellular mechanisms that mediate cancer treatment–related cardiotoxicity. The strengths and limitations of these preclinical models are highlighted. Studies are under way to combine information obtained from clinical observational studies with preclinical models, facilitating the development of novel cardioprotective strategies.

Fig 2.

Harmonized recommendations for cardiomyopathy surveillance for survivors of childhood cancer. Green represents a strong recommendation with a low degree of uncertainty (high quality evidence). Yellow (moderate-quality evidence) and orange (weak-quality evidence) represent moderate-level recommendations. Red represents a recommendation against a particular intervention, with harms outweighing benefits. ACE, angiotensin-converting enzyme; AHA, American Heart Association; ESC, European Society of Cardiology; LV, left ventricular. Reprinted with permission.