Cardiac Amyloidosis: A Comprehensive Review of Pathophysiology, Diagnosis, and Emerging Therapeutic Strategies
Main Article Content
Abstract
Cardiac amyloidosis (CA) is a life-threatening, infiltrative cardiomyopathy characterized by the extracellular deposition of amyloid fibrils within myocardial tissue. This pathological process results in progressive diastolic and, ultimately, systolic dysfunction, leading to heart failure and associated morbidities. CA predominantly arises from two amyloid types: immunoglobulin light chain (AL) amyloidosis and transthyretin amyloidosis (ATTR), which can be either hereditary (ATTRv) or wild-type (ATTRwt). Given the heterogeneity of clinical manifestations, early diagnosis remains challenging but critical for optimizing patient outcomes. Advanced imaging modalities, including cardiac magnetic resonance (CMR) and bone scintigraphy, alongside tissue biopsy and genetic testing, have revolutionized diagnostic accuracy. Recent advances in targeted therapies, particularly transthyretin stabilizers and RNA-based therapies, are reshaping the clinical landscape. This review aims to elucidate the complex pathophysiology of cardiac amyloidosis, discuss the latest diagnostic criteria and techniques, and evaluate current and emerging therapeutic approaches. Through a comprehensive analysis, this article underscores the importance of early recognition and multidisciplinary management to improve prognosis and quality of life in affected individuals.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Kyle RA. Amyloidosis: A convoluted story. Br J Haematol. 2001;114:529-38.
II. Kyle RA. Amyloidosis: A brief history. Amyloid. 2011;18:6-7.
III. Stewart TG. On the Waxy or Amyloid Form of Bright’s Disease. Edinb Med J. 1861;6:710-28.
IV. Amarelli C, Limongelli G. Cardiac amyloidosis: Watching the tip of the iceberg emerging from the “heart of the sea”. Int J Cardiol. 2021;338:226-8.
V. Rubin J, Maurer M. Cardiac amyloidosis: Overlooked, underappreciated and treatable. Annu Rev Med. 2020;71:201-19.
VI. Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L. Senile systemic amyloidosis affects 25% of the very aged and associated with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study. Ann Med. 2008;40:232-9.
VII. Ravichandran S, Lachmann HJ, Wechalekar AD. Epidemiologic and survival trends in amyloidosis, 1987-2019. N Engl J Med. 2020;382:1567-8.
VIII. Dharmarajan K, Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. J Am Geriatr Soc. 2012;60:765-74.
IX. Ng B, Connors LH, Davidoff R, Skinner M, Falk RH. Senile systemic amyloidosis presenting with heart failure: A comparison with light chain-associated amyloidosis. Arch Intern Med. 2005;165:1425-9.
X. Santarone M, Corrado G, Tagliagambe LM, Manzillo GF, Tadeo G, Spata M, Longhi M. Atrial thrombosis in cardiac amyloidosis: Diagnostic contribution of transesophageal echocardiography. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 1999;12:533-6.
XI. Liao R, Ward JE. Amyloid cardiomyopathy: Disease on the rice. Circ Res. 2017;120:1865-7.
XII. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state of the art review. J Am Coll Cardiol. 2019;73:2872-91.
XIII. Kharoubi M, Bézard M, Galat A, Le Bras F, Poullot E, Molinier- Frenkel V, Fanen P, Funalot B, Moktefi A, Lefaucheur JP, Abulizi M, Deux JF, Lemonnier F, Guendouz S, Chalard C, Zaroui A, Audard V, Bequignon E, Bodez D, Itti E, Hittinger L, Audureau E, Teiger E, Oghina S, Damy T. History of extracardiac/cardiac events in cardiac amyloidosis: Prevalence and time from initial onset to diagnosis. ESC Heart Fail. 2021;8:5501-12.
XIV. Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol. 2016;68:1323-41.
XV. Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O’Fallon WM, Kurland LT. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992;79:1817-22.
XVI. Dubrey SW, Cha K, Skinner M, LaValley M, Falk RH. Familial and primary (AL) cardiac amyloidosis: Echocardiographically similar diseases with distinctly different clinical outcomes. Heart. 1997;78:74-82.