Two-dimensional speckle-tracking echocardiography in tafamidis-treated patients with transthyretin amyloid cardiomyopathy: a glimmer of hope for viable therapy monitoring?

Abstract Background Treatment with Tafamidis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been shown to have beneficial effects on the left ventricle (LV), as assessed by cardiac magnetic resonance (CMR) imaging. Although CMR represents the gold standard among imaging modalities, its limited availability in clinical practice makes it unfeasible for routine therapy monitoring. Purpose We aimed to determine Tafamidis-induced changes using two-dimensional (2D) speckle-tracking echocardiography and to identify echocardiographic imaging parameters that could be used for specific therapy monitoring. Methods We subjected a series of ATTR-CM patients to transthoracic echocardiography (TTE) at baseline and follow-up and compared patients treated with Tafamidis 61mg once daily (QD) to a historical control cohort treated with Tafamidis 20mg QD, as well as to a historical treatment-naïve control cohort reflecting the natural course of the disease. Results Patients receiving Tafamidis 61mg (n=62) or 20mg (n=21) QD showed stable measurements at follow-up [61mg: 8.5 months, 20mg: 7.0 months] in LV global longitudinal strain (GLS) (61mg: −11.75% vs. −11.58%, p=0.534; 20mg: −10.61% vs. −10.12%, p=0.309), right ventricular (RV) GLS (61mg: −14.18% vs. −13.72%, p=0.377; 20mg: −14.53% vs. −13.99%, p=0.452) and left atrial (LA) reservoir strain (LASr; 61mg: 8.80% vs. 9.42%, p=0.283; 20mg: 8.23% vs. 8.67%, p=0.589), whereas treatment-naïve ATTR-CM patients (n=54) had clear signs of disease progression at the end of the observation period [10.5 months; LV-GLS: −11.71% vs. −10.59%, p=0.001; RV-GLS: −14.36% vs. −12.99%, p=0.038; LASr: 10.67% vs. 8.41%, p=0.005]. Between-group comparison at follow-up revealed beneficial effects of Tafamidis 61mg on LASr (p=0.003), LV-GLS (p=0.030) and interventricular septum (IVS) thickness (p=0.006), resulting in clinical benefits (six-minute walk distance (6-MWD): p=0.006, NT-proBNP: p≤0.001), while patients treated with Tafamidis 20mg QD showed positive effects on LASr (p=0.039) but no differences in LV-GLS (p=0.274), IVS thickness (p=0.068) and clinical status (6-MWD: p=0.124, NT-proBNP: p=0.053) compared to the natural course. Conclusion Treatment with Tafamidis 61mg in ATTR-CM patients delays the increase in IVS thickness and the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2D speckle-tracking imaging may be appropriate for disease-specific therapy monitoring. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This work was supported by the Pfizer Inc. However, Pfizer Inc. did not have influence on study design, data processing, or statistical analysis.