Cardiology · Medical Literature
Non-Invasive Myocardial Work Indices (GWI, GCW, GWW, and GWE) as Predictors of Clinical Outcomes Across Cardiac Diseases: A Systematic Review and Meta-Analysis.
Abstract
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.
Clinical relevance
This systematic review and meta-analysis addresses a critical gap in non-invasive cardiac risk stratification by evaluating the prognostic and diagnostic utility of pressure-strain loop-derived myocardial work (MW) indices — GWI, GCW, GWW, and GWE — across a broad spectrum of cardiac diseases including heart failure, ACS, valvular disease, cardiomyopathy, and cancer therapy-related cardiotoxicity (CTRCD). Encompassing 4,710 participants across 24 studies, it directly challenges the clinical overreliance on LVEF and GLS alone by demonstrating that MW indices may capture distinct physiological information with incremental prognostic value. Clinicians managing high-risk cardiovascular populations — particularly those on cardiotoxic oncologic regimens or with advanced cardiomyopathy — should be aware of these indices as they approach potential guideline incorporation.
Key findings
1. The primary pooled random-effects estimate for adverse MW profile predicting clinical risk was 1.12 (95% CI: 0.99–1.27), which did not achieve statistical significance, with substantial heterogeneity (I² = 82.1%), underscoring that a single summary estimate across all cardiac diseases is of limited clinical utility. 2. The all-estimates sensitivity analysis (18 estimates; n = 3,536) reached statistical significance with a pooled random-effects estimate of 1.19 (95% CI: 1.04–1.35), supporting a consistent directional association between adverse MW indices and worse clinical outcomes. 3. The HR-only sensitivity analysis — the most clinically interpretable prognostic model — yielded a pooled HR of 1.18 (95% CI: 0.99–1.41), directionally consistent but not reaching conventional statistical significance, reflecting residual heterogeneity across disease contexts. 4. Disease-specific subgroup analysis revealed the largest effect sizes in cardiomyopathy: GWI demonstrated an HR up to 5.46 in dilated cardiomyopathy, indicating substantially elevated risk of adverse outcomes with impaired myocardial work in this population. 5. Heart failure and valvular heart disease (including asymptomatic aortic stenosis) showed consistent moderate associations, with GRADE certainty rated as moderate for these two categories — the highest certainty levels in the review. 6. GCW demonstrated the highest diagnostic accuracy for CTRCD detection (AUC: 0.97), markedly outperforming GLS (AUC: 0.73) in the same study population, supporting its potential role as a superior monitoring tool in cardio-oncology.
Practice implications
In patients with dilated cardiomyopathy or advanced heart failure, integration of GWI and GCW into routine echocardiographic assessment should be considered for enhanced prognostic stratification beyond LVEF and GLS, particularly when risk-guided therapeutic escalation decisions (e.g., device therapy, advanced HF referral) are being contemplated. In cardio-oncology, GCW (AUC 0.97) should be prioritized over GLS alone for early detection of CTRCD during and after cardiotoxic chemotherapy regimens, given its substantially superior diagnostic accuracy in this context. Clinicians should apply MW indices in a disease-specific rather than uniform fashion — given the high heterogeneity (I² = 82.1%) across disease categories — and recognize that standardized cut-off values have not yet been established, necessitating cautious interpretation until prospective multicenter validation and guideline-level evidence are available.