Cardiac amyloidosis: An underdiagnosed/underappreciated disease

      Highlights

      • Amyloid cardiomyopathy (ACM) is an underestimated cause of LVH and heart failure.
      • There are three types of ACM, wild-type or familial transthyretin and light-chain ACM.
      • Clues in cardiac and extracardiac manifestations of ACM may raise clinical suspicion.
      • Imaging methods (strain echo, CMR, bone scintigraphy) may obviate cardiac biopsy.
      • Newer amyloid-targeted and other therapies applied early may alter the prognosis.

      Abstract

      Cardiac amyloidosis or amyloid cardiomyopathy (ACM), commonly resulting from extracellular deposition of amyloid fibrils consisted of misfolded immunoglobulin light chain (AL) or transthyretin (TTR) protein, is an underestimated cause of heart failure and cardiac arrhythmias. Among the three types of cardiac amyloidosis (wild-type or familial TTR and light-chain), the wild-type (Wt) TTR-related amyloidosis (ATTR) is an increasingly recognized cause of heart failure with preserved ejection fraction (HFpEF), and amyloidosis should be considered in the differential diagnosis of this heart failure group of patients. Recent advances in the diagnosis and drug treatment of ACM have ushered in a new era in early disease detection and better management of these patients. Certain clues in cardiac and extracardiac manifestations of ACM may heighten clinical suspicion and guide further confirmatory testing. Newer noninvasive imaging methods (strain echocardiography, cardiac magnetic resonance and bone scintigraphy) may obviate the need for endomyocardial biopsy in ATTR patients, while newer targeted therapies may alter the adverse prognosis in these patients. Early recognition of ACM is crucial in halting the disease process before irreversible organ damage occurs. Chemotherapy and stem-cell transplantation combined with immunomodulatory therapy may also favorably affect the course and prognosis of light chain ACM. Finally, in select patients with end-stage disease, heart transplantation may render results comparable to non-ACM patients. All these issues are herein reviewed.

      Graphical abstract

      Keywords

      Abbreviations:

      ACM (amyloid cardiomyopathy), AL CM (light chain amyloid cardiomyopathy), AF (atrial fibrillation), ATTR (transthyretin amyloidosis), BNP (brain natriuretic peptide), CM (cardiomyopathy), CMR (cardiac magnetic resonance (imaging)), ECG (electrocardiogram), FLC (free light chain (assay)), HFpEF (heart failure with preserved ejection fraction), LGE (late gadolinium enhancement), LS (longitudinal strain), LV (left ventric-le(−ular)), LVH (left ventricular hypertrophy), TTR (transthyretin)
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