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

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.

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.

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).

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.