Effect of Tafamidis on Clinical and Functional Parameters in Transthyretin Amyloid Cardiomyopathy

Abstract

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) has recently gained recognition as a rare and fatal disease. Tafamidis, a first-in-class transthyretin stabilizer, has emerged as a promising agent for attenuating disease progression. Nevertheless, how tafamidis alters clinical and imaging parameters remains unclear.

Objectives: This systemic review and meta-analysis aimed to investigate how tafamidis remodels the myocardium and influences the disease trajectory of ATTR-CM.

Methods: PubMed, EMBASE, and the Cochrane Library were searched for literature from inception to February 2024 which reported either the effects of tafamidis treatment or natural course of ATTR-CM. Outcomes of interests were all clinical and imaging parameters available from at least 2 independent studies.

Results: We identified 30 studies comprising 2,973 participants with ATTR-CM. Pooling all studies with outcomes of both tafamidis and placebo, tafamidis significantly reduced all-cause mortality (OR: 0.19; 95% CI: 0.07 to 0.56) and cardiovascular death (OR: 0.08; 95% CI: 0.02-0.30). Tafamidis also ameliorated the deterioration of 6-minute walk distance (standardized mean difference [SMD] 0.04 vs. -0.29, P = 0.002) and serum N-terminal pro-B-type natriuretic peptide level (SMD: -0.03 vs 0.41, P < 0.001). Regarding imaging parameters, better global longitudinal strain on echocardiography (SMD: 0.06 vs 0.50, P = 0.003), heart to contralateral ratio (SMD: -0.23 vs. -1.17, P = 0.037) on technetium-99m pyrophosphate scintigraphy, extracellular volume (P = 0.003), left (P < 0.001) and right (P = 0.001) ventricular ejection fraction, and right atrium area (P = 0.033) on cardiac magnetic resonance imaging were observed after tafamidis treatment.

Conclusions: Tafamidis improves clinical outcomes and limits the progression of cardiac remodeling in ATTR-CM.

Keywords: amyloidosis; meta-analysis; tafamidis; tissue characterization; transthyretin cardiomyopathy.

Graphical abstract

Figure 1

Literature Search Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram illustrated the process for study inclusion.

Figure 2

Echocardiographic and Technetium-99m Scintigraphic Parameters of Studies Which Pooled the Data of Tafamidis and Placebo Separately Echocardiographic and technetium-99m scintigraphic parameters of studies which pooled the data of tafamidis and placebo separately, including (A) E/e’; (B) global LS; (C) LVEF; (D) H/CL ratio. LS = longitudinal strain; LVEF = left ventricular ejection fraction; H/CL = heart to contralateral.

Figure 3

Amyloid Content by CMR of Studies Which Pooled the Data of Tafamidis and Placebo Separately Amyloid content by cardiac magnetic resonance imaging of studies which pooled the data of tafamidis and placebo separately, including (A) ECV; (B) native T1 mapping; (C) LVMI. ECV = extracellular volume; LVMI = left ventricular mass index.

Figure 4

Functional Assessment by CMR of Studies Which Pooled the Data of Tafamidis and Placebo Separately Functional assessment by cardiac magnetic resonance imaging of studies which pooled the data of tafamidis and placebo separately, including (A) global LS; (B) LVEF; (C) RVEF; (D) LA area; (E) RA area. CMR = cardiac magnetic resonance imaging; LA = left atrium; RA = right atrium; RVEF = right ventricular ejection fraction; other abbreviations as in Figure 2.

Figure 5

Major Adverse Cardiac Events by Pooling Studies Which Directly Compared Tafamidis to Placebo All-cause mortality; cardiovascular death; composite cardiovascular event hospitalization, heart failure hospitalization, or heart failure exacerbation.

Figure 6

Clinical Outcomes of Studies Which Pooled the Data of Tafamidis and Placebo Separately Clinical outcomes of studies which pooled the data of tafamidis and placebo separately, including (A) 6MWD; (B) serum level of NTproBNP. 6MWD = 6-minute walk distance; NTproBNP = N-Terminal pro-B-type natriuretic peptide.

Figure 7

Echocardiographic of Studies Which Directly Compared Tafamidis to Placebo Arms Echocardiographic of studies which directly compared tafamidis to placebo arms, including NTproBNP; LVEF; H/CL; ECV; native T1 mapping; global LS; RVEF; LVMI; RVEDVI. RVEDVI = right ventricular end-diastolic volume index; other abbreviations as in Figures 2, 3, 4, and 6.

Central Illustration

Tafamidis Effectively Attenuates Clinical Progression and Cardiac Remodeling in Transthyretin Amyloid Cardiomyopathy HFF = heart failure hospitalization; TTE = trans-thoracic echocardiogram; other abbreviations as in Figures 2, 3, 4, and 6.