Relative apical sparing of left ventricular longitudinal strain for the diagnosis of cardiac amyloidosis: a systematic review and meta-analysis

Background Cardiac amyloidosis (CA) is underdiagnosed due to non-specific clinical and echocardiographic features. This systematic review and meta-analysis evaluated the diagnostic accuracy of the left ventricular relative apical sparing (RELAPS) pattern on speckle-tracking echocardiography. Methods A literature search of PubMed, Scopus and Cochrane was conducted through August 2025. RELAPS was defined as the average apical longitudinal strain divided by the sum of average basal and average middle left ventricular longitudinal strains. Diagnostic accuracy was assessed using a bivariate random-effects model. Subgroup analyses by CA subtype and echocardiogram software, and meta-regression for clinical variables, were performed. Optimal cut-offs were determined by maximising the Youden index. Analyses were conducted in R V.4.4.1. Results Forty-one studies (3473 CA; 4525 comparators) were included. Pooled analysis yielded an area under the receiver operating characteristic curve (AUC-ROC) of 0.818, with sensitivity 65.9% (95% CIs 59.2% to 72.0%) and specificity 83.1% (CI 78.5% to 86.8%). The diagnostic oods ratio (DOR) was 9.54 (CI 7.41 to 12.10). In subtype analyses, immunoglobulin light chains (AL-CA) showed AUC-ROC 0.876, sensitivity 59.8% (CI 41.1% to 76.0%) and specificity 92.7% (CI 83.6% to 96.9%); transthyretin (ATTR-CA) showed AUC-ROC 0.822, sensitivity 63.8% (CI 51.2% to 74.8%) and specificity 84.4% (CI 76.7% to 89.9%), with no significant differences between subtypes (sensitivity p=0.760; specificity p=0.172). Three echocardiography software systems were evaluated. GE EchoPAC (26 studies) achieved an AUC-ROC of 0.822 (sensitivity 70.4% (CI 64.1% to 76.0%), specificity 81.2% (CI 75.7% to 85.7%)). Philips QLAB (four studies) performed comparably (AUC-ROC 0.904; sensitivity 67.6% (CI 31.2% to 90.6%), specificity 92.7% (CI 73.6% to 98.3%)). In contrast, TomTec (four studies) had an AUC-ROC of 0.806, but its sensitivity (31.1% (CI 9.4% to 66.3%)) was significantly lower than GE EchoPAC’s (p<0.001), despite a similar specificity (93.6% (CI 78.8% to 98.3%)). Conclusion RELAPS provides moderate diagnostic accuracy for identifying CA, with good specificity and modest sensitivity. Performance varies by analysis software and threshold, underscoring the need for standardised measurement and prespecified cut-offs.