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 (OPulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and OPulse 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 OPulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with OPulse 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 was 1376 [1057-1552] mL·min, peak HR = 150 [122-164] bpm, resulting in an OPulse 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 %OPulse (P < .001).

Conclusions: In patients with prior radiotherapy heart exposure, %-predicted OPulse 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.