Abstract Body (Do not enter title and authors here): Background: Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all cases of heart failure (HF) and carries a similar burden as heart failure with reduced ejection fraction (HFrEF). While outcomes in HFrEF have improved with evidence-based therapies, adverse events in HFpEF remain unchanged. Imaging biomarkers such as extracellular volume fraction (ECV) and native T1 relaxation time, assessed by cardiac magnetic resonance imaging (MRI), may provide valuable prognostic information. We aimed to systematically evaluate the clinical utility of MRI-derived native T1 and ECV in risk stratification of patients with HFpEF using updated data.
Methods: A systematic search of PubMed, Embase, Web of Science, and Scopus was conducted in March 2025 per PRISMA guidelines. Studies reporting associations between MRI-derived ECV or native T1 and clinical outcomes in patients with HFpEF were included. Random-effects meta-analyses were used to pool unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for a 1-unit increase in ECV and for comparisons of high vs. low T1 and ECV values based on cut-offs defined in each of the studies in relation to adverse outcomes (all-cause mortality, HF hospitalization, and cardiac mortality).
Results: Sixteen studies with a total of 1276 patients with HFpEF were included. Mean age was 65.8±11.0 years, and 50% were male. After excluding overlapping cohorts, higher ECV was significantly linked with a higher risk of adverse events in unadjusted models (HR 1.14, 95% CI 1.09–1.19, p < 0.001, I2= 46%). ECV was also linked to higher all-cause mortality and HF hospitalization (HR 1.19, 95% CI 1.06–1.33, p < 0.001). Associations remained significant after adjustment for clinical covariates in the studies (aHR 1.09, 95% CI 1.05–1.13, p < 0.001, I2 = 41%). In the comparison of high vs. low ECV, patients with higher ECV tend to have significantly higher rates of adverse events (aHR, 1.71, 95% CI 1.25-2.34, p < 0.001, I2 = 0%). Furthermore, patients with high native T1 values had an increased risk of adverse events, compared to low T1 group (aHR 1.74, 95% CI 1.21–2.50, p < 0.001, I2 = 0%).
Conclusion: MRI-derived ECV and native T1 are clinically relevant predictors of adverse outcomes in HFpEF. By further large-scale studies conducted in future, these imaging markers may help guide risk stratification and personalize treatment decisions in this challenging patient population.