Cardiac amyloidosis (CA) represents the accumulation and deposition of misfolded protein fibrils in the myocardium, resulting in progressive restrictive cardiomyopathy. Light chain (AL) and transthyretin (TTR) amyloidosis are the most common types of CA. While endomyocardial biopsy remains the gold standard for diagnosing cardiac amyloidosis, its invasive nature and associated risk of complications have led to increased reliance on clinical suspicion and noninvasive imaging modalities as alternative diagnostic tools. Over the last decade, radionuclide imaging studies have become a widely accepted tool in diagnosing ATTR CA, whereas its diagnostic utility in AL CA detection remains limited. Recent advances in PET-CT radiopharmaceuticals have further expanded the potential of nuclear imaging as a comprehensive tool for diagnosis, prognostication, and therapy monitoring. This literature review appraises the current applications of nuclear imaging in the clinical management of cardiac amyloidosis.
Background: Degenerative aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CM), particularly wild-type ATTR (ATTRwt), are age-associated disorders that frequently converge in elderly patients. Their coexistence may obscure diagnosis, amplify heart-failure burden, and complicate risk stratification before and after aortic valve replacement. Methods: This narrative review was conducted using a structured literature search focused on ATTR-CM, AS, transcatheter aortic valve implantation/replacement (TAVI/TAVR), and nuclear cardiology. Priority was given to cohort studies, systematic reviews, consensus documents, and guideline statements. Main findings: Across observational cohorts and meta-analyses, ATTR-CM is consistently identified in a clinically meaningful minority of older patients with severe AS, especially among those referred for TAVI. Reported prevalence varies with age, referral pathway, diagnostic protocol, and whether equivocal grade 1 uptake is included, but most contemporary TAVI-oriented cohorts place definite ATTR-CM in the high single-digit to mid-teen percentage range. Clinical suspicion should increase in patients with disproportionate left-ventricular wall thickening, low-flow low-gradient AS, restrictive physiology, elevated cardiac biomarkers, conduction disease, atrial fibrillation, or extracardiac ATTR clues such as bilateral carpal tunnel syndrome. Conclusions: Bone-avid tracer scintigraphy with 99mTc-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, or 99mTc-hydroxymethylene diphosphonate, interpreted with SPECT or SPECT/CT and combined with mandatory exclusion of a monoclonal protein, enables robust non-biopsy diagnosis of ATTR-CM. In severe AS, nuclear diagnosis should be embedded in a pragmatic, multidisciplinary pathway that identifies patients likely to benefit from valve intervention, ATTR-specific therapy, genetic testing, and tailored follow-up.
