Impact of tafamidis on myocardial strain in transthyretin amyloid cardiomyopathy

Abstract

Aims

The impact of tafamidis on myocardial strain in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) have been barely investigated. We aimed to determine tafamidis-induced changes using serial speckle tracking echocardiography and to identify imaging parameters for specific therapy monitoring.

Methods and results

ATTR-CM patients underwent serial TTE with two-dimensional (2 D) speckle tracking imaging. Patients receiving tafamidis free acid 61 mg (n = 62) or tafamidis meglumine 20 mg (n = 21) once daily (QD) showed stable measurements at follow-up (61 mg: 8.5 months, 20 mg: 7.0 months) in LV global longitudinal strain (GLS) (61 mg: −11.75% vs. −11.58%, p = 0.534; 20 mg: −10.61% vs. −10.12%, p = 0.309), right ventricular (RV) GLS (61 mg: −14.18% vs. −13.72%, p = 0.377; 20 mg: −14.53% vs. −13.99%, p = 0.452) and left atrial (LA) reservoir strain (LASr; 61 mg: 8.80% vs. 9.42%, p = 0.283; 20 mg: 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 free acid 61 mg on LASr (p = 0.003) and the LV (LV-GLS: p = 0.030, interventricular septum (IVS): 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 meglumine 20 mg QD showed positive effects on LASr (p = 0.039), but no differences with respect to the LV (LV-GLS: p = 0.274, IVS: p = 0.068) and clinical status (6-MWD: p = 0.124, NT-proBNP: p = 0.053) compared to the natural course.

Conclusions

Treatment with tafamidis free acid 61 mg in ATTR-CM patients delays the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2 D speckle tracking imaging may be appropriate for disease-specific therapy monitoring.

Keywords:

• Transthyretin cardiac amyloidosis
• tafamidis
• strain echocardiography
• speckle tracking
• therapy monitoring

Disclosure statement

R.R. received speaker fees and congress support from Akcea, Alnylam and Pfizer, as well as well as research grants from Pfizer. F.D. received speaker fees and congress support from Bayer, Novartis, Alnylam, Pfizer and AOP, as well as research grants from the Austrian Society of Cardiology and Pfizer. D.D. received speaker fees and congress support from BMS and Pfizer, as well as research grants from Alnylam and the Austrian Society of Cardiology. D.B. received speaker fees and congress support from Bayer, Novartis, Alnylam, Pfizer and AOP, as well as research grants from the Austrian Society of Cardiology and Pfizer. All other authors have nothing to declare.

Data availability statement

All data underlying this article are contained in the article itself. There is no supplementary online material.

Additional information

Funding

This work was supported by the Pfizer Inc. under Grant [ID #56478425]. However, Pfizer Inc. did not have influence on study design, data processing, or statistical analysis.