Exercise Therapy and Cardiovascular Toxicity in Cancer

Abstract

Cardio-oncology is an emerging discipline focused predominantly on the detection and management of cancer treatment-induced cardiac dysfunction (cardiotoxicity), which predisposes to development of overt heart failure or coronary artery disease. The direct adverse consequences, as well as those secondary to anticancer therapeutics, extend beyond the heart, however, to affect the entire cardiovascular-skeletal muscle axis (ie, whole-organism cardiovascular toxicity). The global nature of impairment creates a strong rationale for treatment strategies that augment or preserve global cardiovascular reserve capacity. In noncancer clinical populations, exercise training is an established therapy to improve cardiovascular reserve capacity, leading to concomitant reductions in cardiovascular morbidity and its attendant symptoms. Here, we overview the tolerability and efficacy of exercise on cardiovascular toxicity in adult patients with cancer. We also propose a conceptual research framework to facilitate personalized risk assessment and the development of targeted exercise prescriptions to optimally prevent or manage cardiovascular toxicity after a cancer diagnosis.

Keywords: cardiorespiratory fitness; cardiotoxicity; exercise; heart failure; survivorship.

Figure 1

Current and next generation practice in exercise oncology. Current practice (left column) stratifies patients based on tumor type, provides a generic exercise prescription (typically based on predicted maximum heart rate), resulting in a heterogeneous response. Next generation practice (right column) stratifies patients based on multiple factors, provides a targeted exercise prescription based on phenogroup, resulting in optimized efficacy, safety, and tolerability of exercise therapy. CPET, cardiorespiratory exercise test, CRF, cardiorespiratory fitness, Rx, prescription.

Figure 2

Screening/exercise prescription approaches in oncology. Three example screening/exercise prescription approaches that could be applied to research investigations designed to assess the efficacy of exercise on cardiovascular toxicity in the oncology setting: (1) guideline based approach (bottom row) applies ASCO cardiotoxicity guidelines and standard exercise guidelines; (2) ASCO guidelines and VO_2peak-based approach (middle row) applies the addition CPET for risk stratification and exercise prescription design; (3) multidimensional data approach (top row) applies advanced analytics for both risk stratification and targeted exercise prescription design. ASCO, American Society of Clinical Oncology; CPET, cardiorespiratory exercise test.

Figure 3

Phenogrouping model. Phenogrouping model with four steps: (1) characterize patients using multidimensional data (e.g., demographics, blood tests, physical characteristics, treatments types, physiological assessments); (2) develop and internally validate a parsimonious number of homogenous subgroups using machine learning; (3) validate model in an external cohort; (4) identify predictors of primary end point (e.g., CRF) within each subgroup. CRF, cardiorespiratory fitness, A-VO₂ Diff, arterial-venous oxygen content difference, LVEF, left ventricular ejection fraction; HR, heart rate.