Current diagnostic criteria for transthyretin amyloid (ATTR) cardiomyopathy (ATTR-CM) emphasize increased left ventricular (LV) wall thickness, potentially delaying recognition of early myocardial involvement. We evaluated whether combining ECG (S-wave amplitude in lead aVR, SaVR) with echocardiographic relative apical sparing (RELAPS) enhances the detection of ATTR-CM in patients with absent or mild LV hypertrophy. In this single-centre, retrospective observational study, 39 ATTR patients (72 [64-78] years; 45% female) with interventricular septal thickness ≤13 mm were included. Diagnosis was confirmed by 99mTc-DPD scintigraphy and/or biopsy. Diagnostic performance of RELAPS-SaVR was tested against two comparator groups: patients with mild LV hypertrophy and no evidence of amyloidosis, in addition to age-matched healthy controls with normal cardiovascular status. Peripheral neuropathy was the dominant clinical presentation (66%, n = 26), while overt cardiomyopathy presented in a minority (28%) of patients, consistent with early-stage disease. LVEF was preserved in 92%, and restrictive filling was absent. RELAPS ≥1 and SaVR <7 mm was observed in 87% and 85%, respectively. Individually, RELAPS (AUC 0.83) and SaVR (AUC 0.85) distinguished ATTR-CM from LVH. The combined RELAPS-SaVR model improved discrimination (AUC 0.90), with sensitivity 86%, specificity 94%, positive predictive value 76%, negative predictive value 97%, and overall accuracy 89%. Likelihood ratio testing confirmed its incremental value over RELAPS alone (LR = 19.54; P < 0.001). In this single-centre retrospective study, integrating SaVR with RELAPS improved the detection of ATTR-CM in patients with absent or mild LV hypertrophy. These findings support a simple, non-invasive strategy for early detection that merits prospective validation.