Persistent Impairment in Cardiopulmonary Fitness after Breast Cancer Chemotherapy

Abstract

Purpose Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk. Methods Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise. Results Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, −16%; ET, −7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R 2 = 0.47, P < 0.01). Conclusion Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function. Clinical Trial Registration: ACTRN12616001602415.

Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition

“…Several BC therapies can cause cardiovascular injury, including anthracycline chemotherapy, which is associated with a dose-dependent, progressive, myocardial injury [10]. Accordingly, impairments in peak VO 2 could be attributed to "central" limitations that reduce peak exercise cardiac output and left ventricular ejection fraction-the current clinical standard measure for detecting and monitoring cardiotoxicity [7,11,12]. However, "peripheral" impairments in exercise blood flow, citrate synthase activity, and relative reductions in oxidative muscle fiber and capillarity have been reported in individuals after systemic cancer therapy [11,[13][14][15].…”

“…Accordingly, impairments in peak VO 2 could be attributed to "central" limitations that reduce peak exercise cardiac output and left ventricular ejection fraction-the current clinical standard measure for detecting and monitoring cardiotoxicity [7,11,12]. However, "peripheral" impairments in exercise blood flow, citrate synthase activity, and relative reductions in oxidative muscle fiber and capillarity have been reported in individuals after systemic cancer therapy [11,[13][14][15]. Abnormalities in skeletal muscle composition may also limit exercise tolerance; Reding et al reported peak VO 2 was inversely related to the ratio of intermuscular fat (IMF) to skeletal muscle (SM) within the paraspinal muscles in cancer survivors [16].…”

High‐intensity exercise to improve cardiorespiratory fitness in cancer patients and survivors: A systematic review and meta‐analysis

“…8 Chemotherapy and drug therapies have high toxicity and can damage organs such as liver or heart. 9 Depending on treatment course, this may leave to irreversible tissue damage. While cancer survivorship is growing, 10 so is cardiotoxicity.…”

The Utility of Cardiac Reserve for the Early Detection of Cancer Treatment-Related Cardiac Dysfunction: A Comprehensive Overview

“…Specifically, this included a lower LVEF at peak exercise (153), or a lower cardiac index and SV index at peak exercise (152). Recent work from our laboratory has shed some light on the evolution of cardiac reserve impairment in breast cancer patients undergoing anthracycline chemotherapy using exCMR (154,155). In this series of studies, we found that exercise stroke volume tended to be lower shortly following anthracycline chemotherapy (P = 0.06) (155), however over the following 12-months this evolved into a blunted augmentation of LVEF and SV during exercise, resulting in a reduction in peak exercise CO (154).…”

“…Recent work from our laboratory has shed some light on the evolution of cardiac reserve impairment in breast cancer patients undergoing anthracycline chemotherapy using exCMR (154,155). In this series of studies, we found that exercise stroke volume tended to be lower shortly following anthracycline chemotherapy (P = 0.06) (155), however over the following 12-months this evolved into a blunted augmentation of LVEF and SV during exercise, resulting in a reduction in peak exercise CO (154). One of the more intriguing findings comes from a small (n = 48) prospective analysis of mixed adult and pediatric patients with advanced cancer undergoing high-dose anthracycline chemotherapy (156).…”