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Cardiac Amyloidosis in the Real World: Clinical Presentations, Disease Overlap, and Therapeutic Imperatives

Karim Ali1, Ahmed E Ali2, Ahmad Alayyat3

  • 1Department of Internal Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA.

Reviews in Cardiovascular Medicine
|November 10, 2025
PubMed

Insights

Cardiac amyloidosis (CA), a significant cause of heart failure, is increasingly recognized. Early detection and tailored therapies can transform CA into a manageable chronic condition, improving patient outcomes.

Area of Science:

  • Cardiology
  • Cardiovascular Medicine
  • Amyloidosis Research

Background:

  • Cardiac amyloidosis (CA) is now a key focus in heart failure research and clinical practice.
  • Previously considered rare, CA is a major cause of heart failure with preserved ejection fraction (HFpEF), arrhythmias, and valvular disease, particularly in older adults.
  • CA involves the deposition of misfolded protein fibrils in the myocardium, impairing cardiac structure and electrical function.

Purpose of the Study:

  • To review the clinical reality of cardiac amyloidosis, often overlooked amidst common cardiovascular syndromes.
  • To explore CA's varied presentations, overlap with HFpEF, diagnostic clues in valvular disorders, and complex arrhythmias.
  • To discuss thromboembolic risk, microvascular dysfunction, preclinical CA management, screening cost-effectiveness, and risk stratification.

Main Methods:

  • Literature review focusing on clinical presentations, diagnostic challenges, and therapeutic strategies for cardiac amyloidosis.
  • Analysis of the overlap between CA and HFpEF, valvular disorders, and arrhythmias.
  • Examination of current research on preclinical CA, risk stratification, and histopathological characterization.

Main Results:

  • Cardiac amyloidosis presents diverse clinical manifestations, often mimicking more common heart conditions.
  • Transthyretin amyloidosis (ATTR) and light-chain (AL) amyloidosis are the primary subtypes affecting the heart.
  • Early detection and intervention are crucial for managing CA and improving prognosis, shifting it from a terminal to a chronic condition.

Conclusions:

  • Timely recognition and tailored interventions are vital for managing cardiac amyloidosis effectively.
  • Addressing challenges like financial toxicity and optimizing screening strategies are essential for improving patient care.
  • Risk stratification and histopathological characterization aid in guiding prognosis and treatment decisions for CA.

Keywords:
AL amyloidosisamyloid biomarkersaortic stenosisartificial intelligence in cardiologybone scintigraphycardiac amyloidosiscardiac magnetic resonance imagingendomyocardial biopsy002Eheart failure with preserved ejection fractiontransthyretin amyloidosis

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