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

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 (O(2)Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O(2)Pulse 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 O(2)Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O(2)Pulse 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 VO(2) was 1376 [1057–1552] mL·min(− 1), peak HR = 150 [122–164] bpm, resulting in an O(2)Pulse 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 %O(2)Pulse (P < .001). CONCLUSIONS: In patients with prior radiotherapy heart exposure, %-predicted O(2)Pulse is inversely associated markers of diffuse fibrosis (ECVF), ventricular wall stress (NTproBNP), radiotherapy heart dose, and positively related to LV function. Increased LV ECVF may reflect a potential etiology of impaired LV SV reserve in patients receiving thoracic radiotherapy for chest malignancies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40959-021-00127-6.