Mechanoenergetic coupling in heart failure with preserved, mid-range and reduced left ventricular ejection fraction

Abstract Background Heart failure (HF) classification based on left ventricular ejection fraction (LVEF) can vary because of changes in filling pressures, afterload, and contractile function. 11C-acetate positron emission tomography (PET) provides a load-independent measure of myocardial external efficiency (MEE) by simultaneous assessment of myocardial oxygen consumption (MVO2), cardiac work, left ventricular mass (LVM), end-systolic wall stress (ESWS), and myocardial blood flow (MBF). Purpose We aimed to characterize mechanoenergetic derangements in patients with HF and to study its interrelation with age, sex and obesity. Methods MEE was measured in 121 participants with 11C-acetate PET, and LVEF was acquired with echocardiography. We investigated healthy controls (n=20) and patients with HF and reduced LVEF <40% (HFrEF; n=25), mid-range LVEF 40–49% (HFmrEF; n=23), as well as patients with asymptomatic aortic valve stenosis (AS) and LVEF ≥50% (AS-asymp; n=38), and symptomatic AS and LVEF ≥50% (defined as HF with preserved LVEF (HFpEF); n=15). Results MEE declined in tandem with reduced LVEF from HFpEF and HFmrEF to HFrEF (p=0.041, p<0.001, and p<0.001 versus control, respectively; Figure 1). Impaired MEE was aggravated with increasing LVM (p=0.001) due to a disproportionate increase in overall left ventricular MVO2. In a multivariate analysis, female sex (p<0.001), a lower body mass index (p<0.001), and advanced age (p=0.01) were associated with a lower MEE (Figure 2). HFpEF, HFmrEF, and HFrEF patients had distinct energetic profiles involving MEE, MVO2, MBF, ESWS, and LVM (Figure 2). Conclusions Mechanoenergetic uncoupling was evident in every clinical state within the HF syndrome and associated with left ventricular hypertrophy and progressive systolic dysfunction. Sex, age, and obesity impacted myocardial energetics. To date, the present study is the largest investigation of mechanoenergetic coupling across several categories of patients with heart failure. 11C-acetate PET extends our pathophysiological comprehension of the HF syndrome beyond LVEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Lundbeck Foundation Relationship between LVEF and MEEMyocardial energetics in heart failure