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Strain guided management of potentially cardiotoxic cancer therapy

journal contribution
posted on 2023-05-21, 12:44 authored by Thavendiranathan, P, Tomoko Negishi, Somerset, E, Kazuaki Negishi, Penicka, M, Lemieux, J, Aakhus, S, Miyazaki, S, Shirazi, M, Galderisi, M, Thomas MarwickThomas Marwick

Background: In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT.

Objectives:This study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care.

Methods: In this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either>=12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year.

Results: Of 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 +- 12 years; 94% women; baseline LVEF: 59 +- 6%; GLS: -20.6 +- 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 +- 6% versus 55 +- 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 +- 10.9% vs. 2.9 +- 7.4%; p = 0.03).

Conclusions: Although the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).

History

Publication title

Journal of the American College of Cardiology

Volume

77

Issue

4

Pagination

392-401

ISSN

0735-1097

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Biomedical

Place of publication

New York

Rights statement

Copyright 2021 The American College of Cardiology Foundation

Repository Status

  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions; Determinants of health

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