Abstract
BackgroundRadiation-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.MethodsPatients 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.ResultsThirty 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 < .001).ConclusionsIn patients with prior radiotherapy heart exposure, %-predicted O2Pulse 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.
Highlights
Incidental cardiac radiation exposure following anticancer thoracic radiotherapy treatment increases risk of heart failure (HF) in a dose-dependent manner [1] with a predominantly restrictive cardiomyopathy phenotype characterized by diffuse fibrosis within the myocardium [2, 3]
When the peak exercise %Percent-predicted peak oxygen pulse (O2Pulse) was evaluated as a continuous variable according to nominal clinical characteristics there were significant differences with respect to smoking status, diabetes, obesity, cancer type, chronic obstructive pulmonary disease (COPD), angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin receptor blockers (ARB) use, and sex
The left ventricle (LV) extracellular volume fraction (ECVF) (β = −.281, P = 0.049), left-ventricular ejection fractions (LVEF) (β = .455, P = 0.002), cardiac V10Gy (β = −.330, P = 0.006), and NTproBNP (β = −.319, P = 0.013) were retained in the model as independent predictors of %O2Pulse while cancer type was Discussion In this cross-sectional analysis of patients with significant incidental heart exposure following thoracic radiotherapy without an established history of cardiovascular disease (CVD) or HF, we found peak exercise %O2Pulse was inversely associated with a cardiac magnetic resonance (CMR)-derived marker of diffuse myocardial fibrosis (LV ECVF), ventricular wall stress (NTproBNP), cardiac radiation dose, and positively related to cardiac function (LVEF)
Summary
Incidental cardiac radiation exposure following anticancer thoracic radiotherapy treatment increases risk of heart failure (HF) in a dose-dependent manner [1] with a predominantly restrictive cardiomyopathy phenotype characterized by diffuse fibrosis within the myocardium [2, 3]. Canada et al Cardio-Oncology (2022) 8:1 following radiotherapy is typically a non-infiltrative disorder with endothelial cell damage resulting in microvascular dysfunction and stimulation of excessive extracellular matrix formation leading to increased myocardial fibrosis [4]. This can lead to a noncompliant left ventricle (LV) that is marked by elevated filling pressures and has limited ability to augment stroke volume (SV) [5]. Knowledge of the relationship between LV ECVF and the peak exercise oxygen pulse may provide mechanistic insight into the cardiac reserve of the cancer survivor following thoracic radiotherapy. The relationship between LV ECVF and O2Pulse following thoracic radiotherapy has not been explored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
