Cardiac Amyloidosis: Epidemiology and Diagnostic Strategies

Cardiac amyloidosis (CA) results from the deposition of amyloid fibrils in the myocardium and is mainly caused by two parent proteins: transthyretin (ATTR) and light chain immunoglobulin (AL). ATTR is further differentiated into wild-type (ATTRwt) and hereditary (ATTRv) forms, based on the presence or absence, respectively, of mutations in the TTR gene. Historically, CA has been overlooked in clinical practice, with many cases misdiagnosed or diagnosed at advanced stages due to overlapping features with other cardiomyopathies, such as hypertrophic cardiomyopathy. However, recent advancements in both diagnostic techniques and awareness have led to an increasing recognition of CA, particularly in patients with heart failure with preserved ejection fraction and other forms of restrictive cardiomyopathy. Moreover, the advent of multimodality imaging has significantly enhanced the diagnosis of CA. Imaging modalities such as echocardiography, cardiac magnetic resonance (CMR), and nuclear scintigraphy (using bone-seeking tracers such as 99mTc-pyrophosphate) play pivotal roles in identifying myocardial involvement early in the disease course. CMR imaging allows precise tissue characterization, identifying myocardial edema, fibrosis, and amyloid deposition; meanwhile, nuclear scintigraphy with 99mTc-pyrophosphate has emerged as a non-invasive, highly sensitive imaging technique for detecting ATTR infiltration in the heart; the diagnosis of AL requires histological confirmation. Following the advent of disease-modifying therapies, the need for early disease detection has become more critical to enhance survival rates and improve quality of life.