Non-Invasive Myocardial Work Indices (GWI, GCW, GWW, and GWE) as Predictors of Clinical Outcomes Across Cardiac...

Non-invasive myocardial work (MW) indices derived from pressure-strain loop analysis, including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), have emerged as novel predictors of clinical outcomes across a broad spectrum of cardiac diseases. The purpose of this systematic review and meta-analysis was to comprehensively synthesize published evidence examining the prognostic value of MW indices for predicting clinical outcomes and their diagnostic performance for identifying disease-specific abnormalities across cardiac conditions, including heart failure, acute coronary syndrome, valvular heart disease, cardiomyopathy, cardiotoxicity in oncology, and cardiac resynchronization therapy response.

A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science (up to May 2026) identified 24 eligible studies encompassing 4,710 participants. Random-effects inverse-variance models with restricted maximum likelihood (REML) estimation and Hartung-Knapp confidence interval correction were applied. Direction-harmonized hazard ratios (HR), odds ratios (OR), and standardized odds ratios (sOR) were pooled as an exploratory summary of ratio-based effects, such that values exceeding 1.0 consistently indicated higher clinical risk with an adverse MW profile, while the HR-only model was retained as the principal prognostic sensitivity analysis. Quality was assessed using the Newcastle-Ottawa Scale and the GRADE framework.

The primary pooled analysis yielded a random-effects estimate of 1.12 (95% CI: 0.99-1.27); however, substantial heterogeneity was observed (I² = 82.1%), reflecting important differences across cardiac disease populations. The all-estimates sensitivity analysis (18 estimates; n = 3,536) achieved statistical significance (RE: 1.19; 95% CI: 1.04-1.35). The HR-only sensitivity analysis yielded a similar effect estimate (RE: 1.18; 95% CI: 0.99-1.41) and represented the most clinically interpretable prognostic analysis. Disease-specific analyses demonstrated heterogeneous effect sizes: the cardiomyopathy subgroup showed the largest associations (HR up to 5.46 for GWI in dilated cardiomyopathy), while heart failure and valvular disease demonstrated consistent moderate associations. Prognostic analyses primarily evaluated mortality, MACE, hospitalization, and other time-to-event outcomes, whereas diagnostic analyses assessed the ability of MW indices to identify disease-specific abnormalities such as CTRCD and impaired microvascular perfusion. GCW demonstrated the highest diagnostic accuracy for cardiotoxicity detection (AUC: 0.97), substantially superior to global longitudinal strain (AUC: 0.73) in the same study population. GRADE certainty was moderate for advanced heart failure and asymptomatic aortic stenosis, and low to very low for other disease categories.

MW indices may provide prognostic and diagnostic information across multiple cardiac diseases; however, individual indices appear to reflect distinct physiological mechanisms and may demonstrate disease-specific prognostic utility. Given the substantial heterogeneity across disease populations, disease-focused interpretation may be more informative than reliance on an overall pooled estimate. These non-invasive echocardiographic indices may offer incremental value beyond LVEF and GLS for cardiovascular risk stratification and monitoring in selected clinical settings, including chronic cardiovascular disease and cancer therapy-related cardiotoxicity. Prospective multicenter studies are required to standardize optimal cut-off values and support future clinical guideline incorporation.