Opportunities for Earlier Diagnosis and Treatment of Cardiac Amyloidosis

Abstract

Despite the rapid expansion of noninvasive (nonbiopsy) diagnosis, contemporary patients with cardiac amyloidosis too often present with advanced features of disease, such as diminished quality of life, elevated natriuretic peptides, and advanced heart failure. Therapeutics for transthyretin cardiomyopathy (ATTR-CM) are most effective when administered before significant symptoms of cardiac dysfunction manifest, making early identification of affected individuals of paramount importance. Community engagement and ensuring that a broad range of clinicians have working knowledge of how to screen for ATTR-CM in everyday practice will be an important step in moving disease identification further upstream. However, reliance on the appropriate and timely diagnosis by individual clinicians may continue to underperform. This review highlights how targeted screening of special populations may facilitate earlier diagnosis. Systems of care that operationalize screening of high-risk subpopulations and prospective validation of novel approaches to ATTR-CM identification are needed.

Carpal tunnel syndrome, spinal canal stenosis, cardiomyopathy, renal insufficiency, enteropathy, and diffuse myopathy as an expression of systemic ATTR amyloidosis - diagnostics and therapy

“…Cardiac involvement with left ventricular hypertrophy is a decisive factor in patient mortality. Early initiation of therapy is crucial for improving quality of life and prolonged survival [ 9 ]. Drugs that are now available [ 4 ], such as the tafamidis used in our patient, achieve stabilization of the transthyretin tetramer, which slows the progression of the disease [ 10 , 11 ].…”

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow

“…Almost all forms of clinical cardiac amyloidosis are transthyretin amyloidosis (ATTR-CA; wild type and hereditary) or light chain cardiac amyloidosis [ 2 ]. ATTR-CA occurs when the native tetrameric form of TTR protein, pathologically separates to form amyloid fibrils that deposit in different organs while AL-CA occurs when an abnormal clone of plasma cells produces a light chain that is susceptible to misfolding and forming amyloid fibrils [ 5 ].…”

Changes in Left Ventricular Ejection Fraction and Clinical Trajectories of Transthyretin Cardiac Amyloidosis with Systolic Dysfunction

“…Cardiac amyloidosis (CA) is characterized by the extracellular deposition of amyloid fibrils in the heart, with the distinctive histological property of green birefringence when viewed under cross-polarized light microscopy after staining with Congo red. There are two main types of CA, namely transthyretin (TTR) cardiomyopathy (ATTR-CM) and light chain (AL) cardiomyopathy (AL-CM) [1]. In ATTR-CM, the native tetrameric form of TTR, produced mainly in the liver, pathologically dissociates to form amyloid fibrils that deposit in the myocardium, nerves, and soft tissues, and peripheral and/or autonomic neuropathy.…”