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

Area of Science:

• Cardiology
• Cardiomyopathy Research
• Amyloidosis Studies

Background:

• Transthyretin cardiac amyloidosis (ATTR-CA) is an underdiagnosed cause of heart failure (HF) with preserved and reduced ejection fraction.
• ATTR-CA prevalence is increasing, especially in older adults with unexplained left ventricular hypertrophy, due to improved noninvasive detection via bone scintigraphy.
• The condition results from misfolded transthyretin (TTR) amyloid deposition in the myocardium, impairing cardiac function.

Purpose of the Study:

• To review the evolving epidemiology of ATTR-CA in HF.
• To discuss disease progression mechanisms, screening features (red flags, biomarkers, imaging), and treatment strategies.
• To highlight the impact of emerging amyloid-specific therapies on patient outcomes.

Main Methods:

• Review of current literature on ATTR-CA epidemiology, pathophysiology, diagnosis, and treatment.
• Emphasis on clinical screening, diagnostic biomarkers, and imaging modalities.
• Analysis of guideline-directed medical therapy and novel amyloid-targeted treatments.

Main Results:

• Noninvasive detection of ATTR-CA has significantly improved, revealing higher community prevalence.
• Conventional HF therapies may have limited efficacy or tolerability in ATTR-CA due to restrictive physiology.
• Emergence of TTR silencers, stabilizers, and degraders offers significant mortality and morbidity benefits.

Conclusions:

• Early diagnosis and individualized management are crucial for improving outcomes in ATTR-CA.
• Integrating conventional and novel amyloid-targeted therapies is essential for complex cardiomyopathy patients.
• ATTR-CA is an increasingly recognized and treatable condition, transforming the HF landscape.