Cardiac energetics in health and disease: a meta-analysis
J A Henry, J J H Bray, A Singhal, T Mureyi, L S Couch, M Ahmad, L Valkovic, S Neubauer, A J M Lewis, O J RiderAbstract
Background
The myocardial phosphocreatine-to-adenosine triphosphate ratio (PCr/ATP), quantified using phosphorus magnetic resonance spectroscopy (31P-MRS), represents the primary non-invasive marker of cardiac energetic status. Most prior investigations have been conducted in single-centre cohorts with limited sample sizes, raising uncertainty regarding the robustness and generalisability of reported values.
Purpose
To establish pooled reference myocardial PCr/ATP values across health and cardiovascular disease and to evaluate the impact of methodological variation on reported measurements.
Methods
We performed a systematic review and meta-analysis of all published studies reporting in vivo cardiac PCr/ATP ratios (Embase, MEDLINE, CENTRAL). Study-level data were extracted to determine pooled estimates in healthy individuals and disease populations. Technical parameters, including magnetic field strength, acquisition sequence, and voxel positioning, were recorded to assess methodological influence and enable adjusted analyses.
Results
A total of 176 studies were included, comprising 7,843 cardiac MR spectroscopy examinations conducted between 1987 and 2025. The pooled PCr/ATP ratio in healthy volunteers (n=2,988) was 1.96. Reduced ratios were observed in heart failure with reduced ejection fraction (HFrEF; n=575), with a pooled value of 1.54 (21% lower than controls), and in heart failure with preserved ejection fraction (HFpEF; n=146), with a pooled value of 1.60 (18% lower). Additional reductions were identified in other pathological conditions, including valvular heart disease and diabetes mellitus. Technical factors such as field strength, pulse sequence, and voxel localisation significantly influenced absolute PCr/ATP values; however, adjustment for these variables produced minimal change in pooled disease-specific estimates. Higher body mass index and natriuretic peptide concentrations were associated with lower PCr/ATP ratios, whereas left ventricular systolic function correlated positively with energetic status.
Conclusion
This large-scale meta-analysis defines reference myocardial PCr/ATP values across a spectrum of cardiac conditions, highlighting impaired energetics as a shared feature of diverse myocardial diseases. Despite technical heterogeneity, cross-study comparability appears preserved, supporting broader clinical and research application of cardiac 31P-MRS.Figure