R1 Prognostic Significance of T-Wave Amplitude Variability for Adverse Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

Background: T-wave amplitude variability (TAV), a marker of beat-to-beat ventricular repolarization instability, has been proposed as a potential risk marker for adverse cardiovascular outcomes, but its prognostic value remains unclear. Objectives: This meta-analysis aimed to quantitatively synthesize evidence on the association between elevated TAV and adverse cardiovascular outcomes. Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library was conducted. Observational studies reporting adjusted effect estimates for the association between TAV and adverse cardiovascular outcomes were included, and separate meta-analyzes were conducted according to effect measures (hazard ratios [HRs] or odds ratios [ORs]) and exposure definition. Effect estimates were pooled using a random-effects model. Statistical heterogeneity was assessed using the Q statistic and I². Results: Seven studies involving 1366 patients were included. HR-based analyzes (n = 3) showed that elevated TAV was significantly associated with an increased risk of adverse outcomes, including mortality and ventricular tachyarrhythmias (pooled HR 2.51, 95% CI 1.57–4.00; I² = 7%). In contrast, OR-based analyzes showed no statistically significant association between TAV and ventricular tachyarrhythmias, whether evaluated as categorical (high vs. low TAV: pooled OR 3.82, 95% CI 0.87–16.84; I² = 75%) or continuous variable (per 1–μV increase: pooled OR 1.11, 95% CI 0.94–1.30; I² = 70%). Conclusion: Elevated TAV is associated with an increased risk of adverse cardiovascular outcomes in HR-based analyzes, supporting its potential utility as a marker of repolarization instability for longitudinal risk stratification. In contrast, its association with ventricular tachyarrhythmias was not significant in OR-based analyzes, which showed substantial heterogeneity. Trial Registration: PROSPERO: CRD420251171782.