Electrocardiographic correlates of disease burden in cardiac transthyretin amyloidosis

Background Wild-type transthyretin amyloidosis (wtATTR) is a systemic disorder characterized by extracellular deposition of amyloid fibrils within the myocardial interstitium. Cardiac involvement leads to restrictive cardiomyopathy and is associated with poor prognosis. Electrocardiography (ECG), including both standard and ambulatory long-term recordings, represents an essential component of the routine diagnostic evaluation in cardiac amyloidosis. (1,2) While typical ECG abnormalities - such as low QRS voltages, conduction delays, and arrhythmias - are well recognized, the relationship between specific ECG parameters and histological or echocardiographic measures of disease severity remains insufficiently characterized. Objectives and Methods This study aimed to investigate the association between classical electrocardiographic parameters and the extent of cardiac involvement in patients with transthyretin amyloidosis (ATTR-CM). A total of 79 patients with histologically confirmed cardiac ATTR amyloidosis were included. Standardized 12-lead ECGs were analyzed with novel digitalization tools and analysis algorithms, focusing on parameters derived from lead I. ECG variables were correlated with histological, echocardiographic, and biochemical indicators of disease burden using linear correlation analysis. Results A significant inverse correlation was found between the R-wave amplitude in the QRS complex and histologically quantified amyloid load (r² = 0.0509, p = 0.0470). Similarly, lower R-wave amplitude correlated with higher NT-proBNP levels (r² = 0.0819, p = 0.0111) and greater relative apical sparing (RELAPS) (r² = 0.1926, p < 0.0001). P-wave duration showed a significant positive correlation with echocardiographically determined conduit strain (r² = 0.1110, p = 0.0471), indicating impaired atrial function. Moreover, prolonged QTc duration was significantly associated with reduced global longitudinal strain (GLS) (r² = 0.1045, p = 0.0044) and right ventricular (RV) strain (r² = 0.0630, p = 0.0454), as well as with increased left ventricular posterior wall thickness (r² = 0.1456, p = 0.0008) and elevated NT-proBNP concentrations (r² = 0.0555, p = 0.0380). Conclusion Low R-wave amplitude, prolonged P-wave duration, and extended QTc interval are significantly associated with histological, echocardiographic, and biochemical markers of disease severity in cardiac ATTR amyloidosis. These findings suggest that simple ECG-derived parameters may serve as non-invasive surrogate markers for assessing disease burden and progression in patients with ATTR-CM.