What question did this study set out to answer?

To review the evolving epidemiology, pathophysiology, screening pathways, and management strategies for transthyretin cardiac amyloidosis across preserved and reduced ejection fraction phenotypes.

January 10, 2026Reviews in Cardiovascular MedicineOpen Access

Transthyretin Cardiac Amyloidosis and Heart Failure: State-of-the-Art Review and Practice Guidance

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Key result

Amyloid-specific therapies for ATTR-CM reduce mortality and morbidity in heart failure.

Why the study?

ATTR-CA is an underdiagnosed cause of HF with evolving noninvasive detection, complex GDMT tolerance, and emerging amyloid-specific therapies.

Key Points

To review the evolving epidemiology, pathophysiology, screening pathways, and management strategies for transthyretin cardiac amyloidosis across preserved and reduced ejection fraction phenotypes.
Synthesized literature on the epidemiology of transthyretin cardiac amyloidosis in heart failure cohorts, focusing on wild-type and hereditary variants.
Evaluated diagnostic methods including noninvasive bone scintigraphy, biomarker evaluation, and imaging for left ventricular hypertrophy.
Assessed conventional guideline-directed medical therapy tolerability alongside emerging amyloid-specific stabilizing, silencing, and degrading agents.
Reported transthyretin cardiac amyloidosis prevalence estimates ranging from 3% to 20% in heart failure with preserved ejection fraction, including 16.8% in a Spanish cohort of 387 patients with wall thickness >=12 mm and 20% in a Swedish cohort of 134 patients with wall thickness >14 mm.
Identified that conventional neurohormonal guideline-directed medical therapies are frequently poorly tolerated or ineffective due to restrictive hemodynamics and autonomic neuropathy.
Demonstrated that noninvasive technetium-labeled bone scintigraphy and disease-modifying therapies, such as transthyretin stabilizers and silencers, have shifted management toward early screening and targeted intervention.

Structured PICO

Population

Patients with transthyretin cardiac amyloidosis (ATTR-CA) and heart failure (both HFpEF and HFrEF)

Intervention

Guideline-directed medical therapy (GDMT) and amyloid-specific therapies (TTR silencers, stabilizers, and degraders)

Early diagnosis and individualized management integrating conventional and amyloid-targeted approaches are essential to improving outcomes in ATTR-CA.

Implication

Supports amyloid-specific therapy integration in ATTR-CA heart failure; leaves open need for randomized confirmation before broad adoption.

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized and underdiagnosed cause of heart failure (HF), encompassing both preserved (HFpEF) and reduced (HFrEF) ejection fraction phenotypes. Once identifiable only following a biopsy, the advent of bone scintigraphy has dramatically improved noninvasive detection and detected a higher community prevalence, particularly among older patients with unexplained left ventricular hypertrophy. ATTR-CA arises from misfolding of transthyretin (TTR), leading to amyloid fibril deposition within the myocardium, which impairs cardiac compliance, conduction, and output. This review explores the evolving epidemiology of ATTR-CA in HF, mechanisms of disease progression, and key features for screening, emphasizing clinical red flags, biomarkers, and imaging features. This review also addresses the nuanced role of guideline-directed medical therapy in this population, where neurohormonal agents may offer limited benefit or be poorly tolerated due to restrictive physiology and autonomic dysfunction. Crucially, the emergence of amyloid-specific therapies, including TTR silencers, stabilizers, and degraders, has transformed the therapeutic landscape, offering mortality and morbidity benefits that were previously unavailable. Early diagnosis and individualized management, integrating conventional and amyloid-targeted approaches, are essential to improving outcomes in this complex and increasingly treatable cardiomyopathy.

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Published by Reviews in Cardiovascular Medicine · CC BY

Cite This Study

Bukhari et al. (2025) studied this question. Amyloid-specific therapies for transthyretin cardiac amyloidosis offer significant mortality and morbidity benefits, transforming treatment outcomes in heart failure.

synapsesocial.com/papers/6963222a91e05aa366cb8b7c https://doi.org/10.31083/rcm46181