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Strain-Guided Cardioprotective Therapy for Potential Cardiotoxic Cancer
Quick Takes
- This is a follow-up study of the SUCCOUR trial, in which patients treated with anthracyclines who had risk factors with heart failure were randomized to echocardiography global longitudinal strain (GLS)-guided or ejection fraction (EF)-guided cardioprotective therapy.
- The investigators compare the incidence of cardiotoxicity at 3-year follow-up between patients randomized to GLS-guided vs. EF-guided cardioprotective therapy.
- At 3-year follow-up, despite the increase in the use of cardioprotective therapies in the GLS-guided arm, there were no differences in cardiac dysfunction between arms.
Study Questions:
Does echocardiography global longitudinal strain (GLS)-guided cardioprotective therapy compared to ejection fraction (EF)-guided therapy decrease the incidence of cardiac dysfunction at 3 years?
Methods:
This is a substudy of SUCCOUR, an international multicenter prospective randomized controlled trial in which patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or EF-guided (>10% absolute reduction of EF to <55%) cardioprotective therapy. Patients with pre-existing heart failure or left ventricular systolic dysfunction were excluded. Patients were started on an angiotensin-converting enzyme (ACE) inhibitor followed by a beta-blocker if a ≥12% reduction in GLS was noted or >10% decrease in EF to <55%, defined as cancer therapy–related cardiac dysfunction (CTRCD). The primary endpoint was the change in three-dimensional EF from baseline to 3 years.
Results:
Among 331 patients enrolled, 255 (77%, age 54 ± 12 years, 95% women, 26% with hypertension and 13% with diabetes mellitus) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n = 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Cardioprotection was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (p = 0.03). The 3-year change in EF was -0.03% ± 7.9% in the EF-guided group and -0.02% ± 6.5% in the GLS-guided group (p = 0.99), despite a significantly higher number of patients meeting criteria for cardioprotection in the GLS-guided arm (n = 41 vs. n = 18 in the EF-guided arm). Diagnosis of CTRCD at 3 years was 9% in the EF-guided arm and 5% in the GLS-guided arm. At 3 years, 17 patients (5%) had CTRCD (11 in the EF-guided group and six in the GLS-guided group; p = 0.16); one patient in each group was admitted for heart failure.
Conclusions:
GLS-guided cardioprotection was not associated with an improvement in EF at 3 years compared to EF-guided cardioprotection in patients receiving anthracyclines with an increased risk of heart failure.
Perspective:
There has been much heated debate on the usefulness of GLS as a more sensitive measure than EF to monitor for and predict the risk of CTRCD. The SUCCOUR trial was meant to address this question through a randomized clinical trial. As with much of the published literature in the field of cardio-oncology, the trial was plagued by a relatively small sample size, a low event rate, and a definition of CTRCD of which clinical significance is debatable. As such, deriving a conclusion on the advantage of one measure over the other for systematic screening of a condition for which incidence is low remains elusive. Nevertheless, the major lesson learned from SUCCOUR is that novel strategies for baseline risk assessment are sorely needed in order to identify the right population for monitoring, as even the recently published European Society of Cardiology risk score for CTRCD performed very poorly in this study.
Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Novel Agents, Acute Heart Failure, Echocardiography/Ultrasound
Keywords: Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anthracyclines, Breast Neoplasms, Cardiotonic Agents, Cardiotoxicity, Diagnostic Imaging, Echocardiography, Heart Failure, Risk Assessment, Stroke Volume, Trastuzumab
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