Tafamidis Reduces The Decline In Longitudinal Strain And Stroke Volume In Patients With Transthyretin Amyloid Cardiomyopathy

Abstract

<h3>Introduction</h3> Left ventricular (LV) longitudinal strain and stroke volume are significant predictors of mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and CV-related hospitalizations. Further analysis of changes in echocardiographic measures in ATTR-ACT may provide additional insight into the efficacy of tafamidis. <h3>Hypothesis</h3> Treatment with tafamidis significantly reduces the worsening of echocardiographic variables including LV longitudinal strain and stroke volume in ATTR-CM patients. <h3>Methods</h3> In ATTR-ACT, ATTR-CM patients (variant or wild-type) were treated with tafamidis 80 mg (n=176) or placebo (n=177) for 30 months. Echocardiography was conducted at enrollment, and at Months 6, 18 and 30, using a standardized protocol and analyzed by an independent central laboratory. We compared changes in LV stroke volume (SV), global longitudinal strain (GLS) and mitral inflow E wave/annular diastolic early (e') wave (E/e') in patients treated with tafamidis 80 mg (the approved dose) vs placebo. <h3>Results</h3> Baseline mean (SD) SV (mL), GLS (%) and septal and lateral E/e' were similar in the tafamidis and placebo groups (<b>Table</b>). Each measure worsened over the duration of the trial, as shown by least-squares (LS) mean (SE) change from baseline at Month 30 for each group (<b>Table</b>). This decline was more pronounced in placebo-treated patients, with a significant reduction in LS mean difference (95% CI) with tafamidis vs placebo for each measure (<i>P</i><0.05 for all). Decline in SV and GLS was apparent from Month 6 in all patients; difference between tafamidis and placebo groups was apparent from Month 18. Decline in E/e' (indicative of elevated LV filling pressures) was apparent from Month 6 with placebo but only minimally changed with tafamidis at each time point; difference between tafamidis and placebo was apparent from Month 6. <h3>Conclusions</h3> LV longitudinal strain and stroke volume are significant predictors of mortality in ATTR-CM patients. Treatment with tafamidis significantly reduced worsening progression of LV systolic (GLS, SV) and diastolic function (E/e') over 30 months in ATTR-CM patients. These echocardiographic data provide additional insight into the efficacy of tafamidis.