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

Justin M Canada; Elisabeth Weiss; John D Grizzard; Cory R Trankle; Leila Rezai Gharai; Franklin Dana; Leo F Buckley; Salvatore Carbone; Dinesh Kadariya; Anthony Ricco; Jennifer H Jordan; Ronald K Evans; Ryan S Garten; Benjamin W Van Tassell; W Gregory Hundley; Antonio Abbate

doi:10.1186/s40959-021-00127-6

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

Cardiooncology. 2022 Jan 18;8(1):1. doi: 10.1186/s40959-021-00127-6.

Authors

Justin M Canada¹, Elisabeth Weiss², John D Grizzard³, Cory R Trankle⁴, Leila Rezai Gharai³, Franklin Dana³, Leo F Buckley^{4

5}, Salvatore Carbone^{4

6}, Dinesh Kadariya⁴, Anthony Ricco², Jennifer H Jordan^{4

7}, Ronald K Evans⁶, Ryan S Garten⁶, Benjamin W Van Tassell⁸, W Gregory Hundley⁴, Antonio Abbate⁴

Affiliations

¹ VCU Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, P.O. Box 980335, 1200 E. Broad Street, Richmond, Virginia, 23298, USA. Justin.M.Canada@vcuhealth.org.
² Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, USA.
³ Department of Radiology, Virginia Commonwealth University, Richmond, Virginia, USA.
⁴ VCU Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, P.O. Box 980335, 1200 E. Broad Street, Richmond, Virginia, 23298, USA.
⁵ Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, USA.
⁶ Department of Kinesiology & Health Sciences, College of Humanities & Sciences, Virginia Commonwealth University, Richmond, Virginia, USA.
⁷ Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
⁸ Department of Pharmacotherapy and Outcome Sciences, Virginia Commonwealth University, Richmond, Virginia, USA.

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 < .001).

Conclusions: In 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.

Keywords: Cardiorespiratory fitness; Extracellular volume fraction; Peak exercise oxygen pulse; Radiotherapy.

Abstract

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