A systematic review and meta-analysis of diagnostic performance of left ventricular strain parameters in cardiac amyloidosis

Background Cardiac amyloidosis (CA) is a progressive infiltrative disorder leading to a variety of clinical manifestations and imaging features. Due to its common presentation as left ventricular hypertrophy (LVH) as well as its ominous prognosis, there is an unmet need for accurate and timely discrimination of the disease from other hypertrophic substrates. Purpose The aim of this systematic review and meta-analysis was to conduct a meta-analysis of diagnostic accuracy, in order to find which of the LV echocardiographic deformation parameters studied performs best in CA diagnosis. Methods A systematic review of the literature was conducted in Pubmed, Scopus and Web of Science from inception till September 2025. The study population consisted of patients with LVH (ventricular wall thickness >12mm). As index tests we considered LV strain parameters. The target condition was defined as CA of any type (AL or ATTR). Statistical analysis was performed with ‘diagmeta’ R-package, applying either the common random intercept and common slope model (CICS) or the hierarchical summary receiver operating characteristic (HSROC) model. Diagnostic indices were compared at a fixed specificity of 95%, reflecting the need for high rule-in accuracy in suspected cardiac amyloidosis. Results From 23 studies finally included in quantitative synthesis, a total of 4628 patients with LVH was recognized, out of whom 2231 had a definite diagnosis of CA (48.2%). At a fixed specificity level of 0.95, global longitudinal strain (GLS) and ejection fraction to strain ratio (EFSR) displayed a comparable pooled sensitivity of approximately 0.78 (95% CI 0.61 to 0.92 and 0.57 to 0.92 respectively), outperformig septal apical to base ratio (SAB) with a sensitivity of 0.42 and relative apical sparing (RALS) with a sensitivity of 0.38. Using the CICS model, pooled optimal cut-off values were estimated at 3.181 for SAB with a pooled sensitivity of 0.58 (95% CI 0.41 to 0.74) and a specificity of 0.85 (95% CI 0.72 to 0.92) and at 0.9 for RALS with an estimated sensitivity of 0.63 (95% CI 0.39 to 0.82) and a specificity of 0.81 (95% CI 0.61 to 0.92) (indicative Figures 1 and 2 respectively). Conclusions LV deformation markers are a new arrow in the quiver of echocardiography for the diagnostic assessment of CA. Among these LV strain parameters (GLS, SAB, RALS, EFSR), GLS and EFSR present a higher sensitivity at a fixed 95% specificity level, indicating that they should be more carefully assessed in patients who present with LVH and are suspected for CA.Figure 1Figure 2