Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy

Abstract

Background: Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O2Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O2Pulse following thoracic radiotherapy has not been explored. Methods: Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart dose (≥5 Gray (Gy), ≥10% heart) without a pre-cancer treatment history of HF underwent cardiopulmonary exercise testing to determine O2Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O2Pulse normalized for age/gender/anthropometrics. Results: Thirty patients (median [IQR] age 63 [57–67] years, 18 [60%] female, 2.0 [0.6–3.8] years post-radiotherapy) were included. The peak VO2 was 1376 [1057–1552] mL·min− 1, peak HR = 150 [122–164] bpm, resulting in an O2Pulse of 9.2 [7.5–10.7] mL/beat or 82 (66–96) % of predicted. The ECVF, LV ejection fraction, heart volume receiving ≥10 Gy, and NTproBNP were independently associated with %O2Pulse (P