Septal thickness to QRS voltage ratio in Lead I/aVR: A simple tool for estimating cardiac amyloid burden

Background: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy associated with adverse outcomes. Quantification of myocardial amyloid burden is essential for risk stratification. Although cardiac magnetic resonance (CMR)-derived extracellular volume (ECV) is the reference standard for non-invasive assessment, its use is limited by cost and availability. Therefore, simple and widely accessible tools to estimate amyloid burden are needed. This study aimed to evaluate whether a novel integrated echocardiographic-electrocardiographic (echo-ECG) index, based on the ratio of maximum septal thickness (MST) to QRS voltage in lead I and/or aVR, correlates with CMR-derived ECV in patients with CA. Methods: We retrospectively analysed 138 consecutive patients with transthyretin or light-chain CA who underwent CMR at four Italian referral centres. MST/QRS ratios (MST/QRS I, MST/QRS aVR, and MST/(QRS I + aVR)) were calculated using echocardiography and standard 12‑lead ECG. Results: On multivariable linear regression with ECV as a continuous variable, the integrated echo-ECG indices were independently associated with ECV (all p < 0.001); lower QRS voltages in leads I and aVR were also independently associated with higher ECV (both p < 0.01), whereas total QRS voltage was not. In a secondary analysis dichotomising ECV at the cohort median (47%), the integrated echo-ECG indices showed moderate discrimination for higher ECV (AUC 0.71-0.73). Conclusions: MST-to-QRS voltage ratios in leads I and/or aVR are simple and widely accessible markers that correlate with myocardial amyloid burden and may support non-invasive assessment of disease severity in CA.