Left atrial structural and mechanical alterations in cardiac amyloidosis: a systematic review and meta-analysis

Introduction The left atrium occupies a central pathophysiological role in cardiac amyloidosis (CA). Amyloid fibril infiltration not only stiffens the myocardium but also directly impairs atrial compliance, reservoir function, and conduit mechanics, creating a substrate for elevated filling pressures, atrial fibrillation, and progressive haemodynamic deterioration. Echocardiographic LA assessment, therefore, holds particular promise as both a diagnostic and prognostic tool in CA; however, the magnitude and consistency of LA abnormalities across patient cohorts have never been formally synthesised. To our knowledge, no prior systematic review or meta-analysis has quantified LA echocardiographic alterations in CA, leaving a critical gap in the evidence supporting structured echocardiographic evaluation of this condition. Purpose To address this unmet need, we conducted a systematic review and meta-analysis quantifying differences in LA structural and functional echocardiographic parameters between patients with CA and healthy controls, with the aim of informing evidence-based echocardiographic protocols for CA diagnosis and monitoring. Methods A comprehensive systematic review was performed in accordance with PRISMA guidelines. Studies comparing LA echocardiographic parameters in CA patients and healthy controls were synthesised using random-effects meta-analysis with restricted maximum likelihood (REML) estimation. Continuous variables were analysed as standardised mean differences (SMDs). Median values were converted to means and standard deviations. Results Of 7,305 studies screened, 24 met inclusion criteria, encompassing 2,339 patients. CA was associated with large-magnitude LA structural and functional alterations across all parameters. LA strain indices demonstrated the greatest effect sizes: LA conduit strain (SMD 2.34, 95% CI 1.93–2.75) and LA reservoir strain (SMD 2.29, 95% CI 2.01–2.57) showed the strongest association with CA. Structural parameters were similarly elevated, with LA diameter (SMD 1.81, 95% CI 1.27–2.35), LA area (SMD 1.75, 95% CI 1.08–2.43), LA contractile strain (SMD 1.62, 95% CI 1.11–2.13), and LA volume index (SMD 1.56, 95% CI 1.27–1.85) all significantly increased. Full results are presented in Table 1. Conclusion This systematic review and meta-analysis demonstrate that CA is characterised by pronounced, consistent LA structural and mechanical abnormalities across all echocardiographic domains. LA strain parameters, particularly conduit and reservoir strain, showed the largest effect sizes and lowest heterogeneity, underscoring their diagnostic value. These findings provide a quantitative foundation for incorporating LA strain analysis into routine multimodal echocardiographic assessment when CA is suspected, and support its inclusion in future CA diagnostic frameworks.