A Comparative Analysis of Cardiac Amyloidosis and Cardiac Sarcoidosis: A Single-Center Experience

<b>Background/Objectives</b>: Cardiac amyloidosis (CA) and cardiac sarcoidosis (CS) are two distinct infiltrative cardiomyopathies that can present with overlapping clinical features, including heart failure and arrhythmias. However, they arise from fundamentally different pathophysiological mechanisms: amyloid protein deposition in CA versus granulomatous inflammation in CS. These differing pathophysiologies result in divergent imaging patterns, clinical trajectories, and treatment strategies. This study aims to compare the clinical presentations, imaging characteristics, and outcomes of patients with CA and CS to identify key differentiating factors that can improve diagnostic precision and guide therapy. <b>Methods</b>: This single-center, retrospective, cross-sectional study analyzed electronic medical records of patients diagnosed with CA (limited to transthyretin CA) or CS at Mount Sinai Morningside system from January 2017 until October 2023. Patients were identified using diagnostic codes and confirmed by histology or disease-specific imaging criteria. Clinical data, transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR) imaging, pyrophosphate scintigraphy (PYP), and fluorodeoxyglucose positron emission tomography (FDG-PET) findings were collected. Statistical comparisons between groups were performed using chi-square tests and independent <i>t</i>-tests, with <i>p</i> < 0.05 considered statistically significant. <b>Results</b>: A total of 16,834 patients were screened and 216 patients were included in the analysis (125 CA, 92 CS). CA patients were older (78.2 vs. 62.0 years, <i>p</i> = 0.01), had greater interventricular septal thickness (1.57 vs. 1.10 cm, <i>p</i> = 0.01), and exhibited diffuse late gadolinium enhancement (LGE) and elevated extracellular volume (ECV) on CMR. CS patients had higher rates of ventricular tachycardia (53.3% vs. 10.7%, <i>p</i> = 0.01), increased myocardial fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) (90%), and more frequent implantable cardioverter-defibrillator (ICD) placement (66.3% vs. 13.0%, <i>p</i> = 0.01). <b>Conclusions</b>: CA and CS demonstrate distinct imaging profiles, arrhythmic risks, and treatment patterns. Early differentiation using advanced imaging is crucial for implementing disease-modifying therapies in CA and for immunosuppression and ICD implantation in CS, thereby improving patient outcomes.