Background: Relative apical sparing of longitudinal strain is widely used as a diagnostic marker of cardiac amyloidosis. However, similar deformation patterns have been reported in other cardiac diseases, raising concerns regarding disease specificity. A comprehensive multimodality synthesis of the relative apical sparing pattern (RASP) across disease entities is lacking. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed, Scopus, and EMBASE were searched through December 2025 for studies reporting RASP or regional longitudinal strain values allowing standardized RASP calculation. Cardiac amyloidosis and major phenocopies-including aortic stenosis, hypertrophic cardiomyopathy, hypertensive heart disease, Fabry disease, mitral valve prolapse, and other cardiomyopathies-were included. Random-effects models were used to compare cardiac amyloidosis with non-amyloid conditions using standardized mean differences (SMDs), with subgroup analyses according to imaging modality (two-dimensional speckle-tracking echocardiography [2D-STE] versus cardiac magnetic resonance feature tracking [CMR-FT]). Results: Fourteen studies (nine 2D-STE and five CMR-FT) were included in the quantitative synthesis. Overall, cardiac amyloidosis was associated with significantly higher RASP compared with non-amyloid conditions (SMD 0.676, 95% CI 0.493-0.860; p < 0.001), with substantial heterogeneity (I2 = 96.9%). Modality-stratified analyses showed a very large pooled effect for 2D-STE (SMD 2.152, 95% CI 1.354-2.950; I2 = 97.6%) and a moderate, homogeneous effect for CMR-FT (SMD 0.594, 95% CI 0.405-0.782; I2 = 0%). Sensitivity analyses confirmed robustness. No significant publication bias was detected by Egger's test. Conclusions: Relative apical sparing is not specific to cardiac amyloidosis but is most pronounced in this condition. Its diagnostic magnitude varies across modalities and clinical contexts, supporting a multiparametric, modality-specific interpretation.
Keywords: Fabry disease; aortic stenosis; cardiac amyloidosis; hypertensive heart disease; hypertrophic cardiomyopathy; mitral valve prolapse; relative apical sparing pattern.