Cardiac Energetics in Health and Disease: A Meta-Analysis

Background The cardiac phosphocreatine-to-ATP ratio (PCr/ATP) is the principal non-invasive biomarker of myocardial energetic status, and is measured by phosphorus magnetic resonance spectroscopy (31P-MRS). However, studies of cardiac energetics are typically from single centres with relatively small numbers of patients, leading to unknown generalisability. Methods Here, we use systematic review and meta-analysis of all available studies reporting cardiac PCr/ATP ratios to show pooled reference values across populations (databases searched: Embase, Medline, CENTRAL). We collected data on differing methodological factors to enable adjustment. Results We included 176 studies comprising 7,843 individual participant magnetic resonance examinations between 1987-2025. The pooled PCr/ATP ratio was 1.96 for healthy volunteers (n=2,988), 1.54 for heart failure with reduced ejection fraction (n=575; a 21% reduction), and 1.60 for heart failure with preserved ejection fraction (n=146; an 18% reduction) with further reductions seen across other disease states including valvular disease and diabetes. Methodological factors including field strength, sequence type, and voxel location significantly influenced measurements, though adjustment had minimal effect on pooled estimates. BMI and natriuretic peptides negatively correlated with PCr/ATP, whilst left ventricular systolic function showed positive correlation. Conclusion This comprehensive meta-analysis provides reference PCr/ATP values across cardiac conditions, implicating energetic impairment as a common pathway spanning myocardial diseases of diverse aetiology, and suggests that methodological heterogeneity does not fully account for the observed between-group differences.