Myocardial energy metabolism in heart failure: Systematic review and meta-analysis of Phosphorus-31 magnetic resonance spectroscopy phosphocreatine/adenosine triphosphate ratio
Abstract
Objective Phosphorus-31 magnetic resonance spectroscopy (³¹P MRS) is the only non-invasive imaging modality that directly quantifies myocardial energy metabolism in vivo. While extensively studied, its readiness for clinical application in heart failure remains uncertain. This meta-analysis aimed to evaluate the association between myocardial phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio, measured by ³¹P MRS, and heart failure, as a step toward assessing its translational potential as a clinical biomarker. Methods We systematically reviewed studies published from January 1, 1990, to December 31, 2024, using PubMed, Embase, and Web of Science. Eligible studies included cohort studies and randomized controlled trials reporting PCr/ATP ratios in heart failure patients and healthy controls. A random-effects model was used to estimate pooled odds ratios. Risk of bias was assessed using the ROBINS-E tool. Findings Twenty-six observational studies met the inclusion criteria; no randomized trials were identified. Meta-analysis showed a directionally consistent and substantial association between reduced PCr/ATP ratio and heart failure (odds ratio 7.62, 95% CI 4.90–11.85), with moderate between-study heterogeneity (I² = 60% and the prediction interval is [1.35–42.92]). Studies at field strengths >1.5T showed reduced heterogeneity (I² = 18.8%) with a comparable effect size (odds ratio 7.69, 95% CI 5.17–11.43). Prespecified meta-regression did not identify significant…
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