Beyond E/e': A Physiology-Based Framework for Emerging Echocardiographic Biomarkers in the Noninvasive Assessment of...

Accurate noninvasive estimation of left ventricular (LV) filling pressure is essential for diagnosing and managing heart failure and other cardiovascular diseases. Although the E/e' ratio remains the cornerstone of contemporary echocardiographic assessment, its diagnostic performance is influenced by loading conditions, myocardial disease, cardiac rhythm, and technical limitations. This review presents a physiology-based framework for emerging echocardiographic biomarkers, examining how each parameter reflects distinct pathophysiological processes-including myocardial relaxation, myocardial performance, atrial remodeling, and structural remodeling-and how these processes contribute to the estimation of LV filling pressure.

A structured narrative review of the contemporary literature was performed, emphasizing studies evaluating both conventional and emerging echocardiographic parameters against invasive hemodynamic reference standards. Biomarkers were classified according to the physiological processes they primarily represent rather than being reviewed as isolated imaging parameters. Particular attention was given to their mechanistic rationale, diagnostic performance, clinical applicability, technical limitations, and potential integration into multiparametric assessment strategies.

Emerging echocardiographic biomarkers provide complementary physiological information beyond conventional Doppler indices. Left atrial reservoir strain and left atrial stiffness primarily reflect chronic pressure elevation and atrial remodeling, whereas diastolic strain rate and left ventricular untwisting characterize impaired myocardial relaxation. Global longitudinal strain and myocardial work predominantly assess myocardial performance, while three-dimensional echocardiography improves structural characterization. Artificial intelligence functions as an integrative analytical approach capable of combining multidimensional imaging and clinical data rather than representing an independent physiological biomarker. Current evidence indicates that no single parameter adequately captures the complex determinants of LV filling pressure. Instead, each biomarker contributes distinct physiological information with varying diagnostic value depending on the underlying disease phenotype and clinical context.

Assessment of LV filling pressure should move beyond the search for a single superior biomarker toward physiology-guided integration of complementary echocardiographic parameters. Future advances should emphasize standardized acquisition protocols, prospective multicenter validation against invasive hemodynamic reference standards, improved reproducibility, and clinically interpretable artificial intelligence-assisted models. Such an integrated physiology-based approach may enhance diagnostic accuracy, refine phenotypic characterization, and facilitate more individualized cardiovascular care.