A systematic review and meta-analysis of diagnostic performance of various echocardiographic parameters in cardiac amyloidosis

Abstract 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 is double: a) to present an up-to-date overview of echocardiographic markers and scores used for differentiating CA among patients with LVH and b) to conduct a meta-analysis of diagnostic accuracy in the field, in order to find which of the studied echocardiographic markers and/or scores 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 2024. The study population consisted of patients with LVH (ventricular wall thickness 12mm). As index tests we considered traditional and novel echocardiographic indices and scores. 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. To succeed various tests’ sensitivities comparison, a fixed specificity level of 0.95 was selected. Results From 28 studies finally included in quantitative synthesis, a total of 6139 patients with LVH was recognized, out of whom 2527 had a definite diagnosis of CA (41.2%). At a specificity level of 0.95, best traditional echo parameters were mitral inflow deceleration time (DT) and E/e’ presenting a sensitivity of 0.64 (95% CI 0.36 to 0.86) and 0.72 (95% CI 0.50 to 0.90) respectively. Strain parameters including global longitudinal strain (GLS), ejection fraction to strain ratio (EFSR) and right ventricular free wall strain (RVFW) displayed pooled sensitivities of 0.78. The indices that demonstrated the best sensitivity were left atrial reservoir strain (LASr) and left atrial conduit strain (LAScd) (0.89 and 0.85 respectively), significantly overpassing relative apical sparing (RALS) or septal apical to base ratio (SAB) (sensitivities of 0.40 and 0.42) (Figure 1). Finally, pooled analysis resulted in different cut-offs for most of the echo parameters compared with their introductory studies (indicative Figure 2). Conclusions Echocardiography is a first-line tool in the diagnostic assessment of CA. As the sensitivity between the different indices varies at a fixed 95% specificity level, not a single echocardiographic marker should be used to rule out CA, but rather a combination of them. Incorporating novel echocardiographic indices, such as left atrial strain parameters, is a useful add-on allowing timely CA diagnosis.Figure 1 Figure 2