Abstract 13305: Energetic Basis of Recovered Ejection Fraction in Human Heart Failure

Introduction: Left ventricular ejection fraction (LVEF) improvement in HFrEF patients is classified as heart failure with improved ejection fraction (HFimpEF) and is associated with better long-term outcomes than persistent HFrEF. HFimpEF is difficult to predict and underlying mechanisms remain poorly understood.

Hypothesis: Better myocardial high-energy phosphate metabolism at baseline predicts future LVEF recovery and outcomes in a general HFrEF population

Methods: We measured cardiac energetics, the ratio of the two main high-energy phosphates, phosphocreatine and ATP (PCr/ATP), and the rate of ATP synthesis through the primary cardiac energy reserve reaction creatine kinase (“CK flux”), in 37 nonischemic HFrEF patients (LVEF ≤40%) with ³¹ P cardiac magnetic resonance spectroscopy (MRS) at 3T. Baseline transthoracic echocardiogram (TTE) was obtained prior to ³¹ P MRS and follow-up consecutive TTEs with the two highest LVEFs meeting HFimpEF criteria (LVEF >40% and ≥10% increase over baseline LVEF) over a median follow-up of 6.9 years were averaged and used to classify HFimpEF.

Results: There were no significant differences in demographics, HF etiology, baseline TTE metrics, or medications between persistent HFrEF (n=22) and eventual HFimpEF (n=15). Cardiac CK flux was significantly higher at baseline in patients who later recovered to HFimpEF than in those who remained HFrEF (p=0.031). Better baseline cardiac CK flux was associated with increases in LVEF (p=0.025) and decreases in LV end-diastolic diameter (p=0.016) over time. By both dichotomous and continuous metrics, better preserved CK flux was associated with future HFimpEF. Fourteen subjects (38%), all persistent HFrEF, experienced cardiac death, transplant, or LVAD and had significantly lower baseline CK flux than outcome-free patients (p=0.017). Cardiac PCr/ATP was not associated with eventual HFimpEF, outcomes, or changes in TTE indices.

Conclusion: Better preserved cardiac CK flux is associated with future LVEF recovery and LV reverse remodeling while lower CK flux is associated with worse cardiac outcomes in HFrEF patients. Interventions restoring CK flux, and possibly other energy-generating metabolic reactions, may elicit myocardial recovery in HFrEF patients.