Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy
- LV surveillance with GLS is associated with a greater use of cardioprotective therapy (CPT), a higher final LVEF, and a lower incidence of cancer therapy-related cardiac dysfunction (CTRCD).
- These results support the use of GLS surveillance in anthracycline-treated patients at high risk for CTRCD followed by early initiation of ACE inhibitors and beta-blockers.
- Additional studies are indicated to better define the threshold for CPT and assess whether a GLS-guided approach to CPT reduces the long-term risk of heart failure and improves clinical outcomes.
What is the impact of global longitudinal strain (GLS)-guided initiation of cardioprotective therapy (CPT) on reduction in left ventricular ejection fraction (LVEF) in patients undergoing potentially cardiotoxic chemotherapy, compared with usual care?
The investigators conducted an international, multicenter, prospective randomized controlled trial, where 331 anthracycline-treated patients with another heart failure (HF) 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 cancer therapy-related cardiac dysfunction (CTRCD) (symptomatic EF reduction >5% or >10% asymptomatic to <55%) over 1 year. Primary outcome analyses were performed on an intention-to-treat basis. Change in LVEF or GLS from baseline to 1-year follow-up between the two groups was compared by using an unpaired Student’s t-test.
Of 331 randomized patients, 2 died and 22 withdrew consent or were lost to follow-up. Among 307 patients (aged 54 ± 12 years, 94% women, baseline LVEF 59 ± 6%, GLS -20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 (0.98-1.07) years, most (n = 278) had breast cancer. HF risk factors were prevalent: 29% had hypertension and 13% had diabetes mellitus. At 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the two 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 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients diagnosed with CTRCD 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).
The authors concluded that although the change in LVEF was not different between the two arms, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range.
This randomized clinical trial reports that LV surveillance with GLS is associated with a greater use of CPT, a higher final LVEF, and a lower incidence of CTRCD. Overall, these results support the use of GLS surveillance in anthracycline-treated patients at high risk for CTRCD followed by early initiation of angiotensin-converting enzyme inhibitors and beta-blockers. Of note, the adoption of GLS-guided surveillance in routine practice does require the commitment of echocardiography laboratories and training of analyzing/reporting clinicians. Additional studies are indicated to better define the threshold for CPT and assess whether a GLS-guided approach to cardioprotective therapy reduces the long-term risk of HF and improves clinical outcomes.
Keywords: Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anthracyclines, Breast Neoplasms, Cardiotonic Agents, Cardiotoxicity, Diabetes Mellitus, Diagnostic Imaging, Echocardiography, Heart Diseases, Heart Failure, Hypertension, Primary Prevention, Risk Factors, Stroke Volume, Ventricular Function, Left
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