Spectral transfer function analysis of respiratory hemodynamic fluctuations predicts end-diastolic stiffness in preserved ejection fraction heart failure

Preserved ejection fraction heart failure (HFpEF) diagnosis remains controversial, and invasive left ventricular (LV) hemodynamic evaluation and/or exercise testing is advocated by many. The stiffer HFpEF myocardium may show impaired stroke volume (SV) variation induced by fluctuating LV filling pressure during ventilation. Our aim was to investigate spectral transfer function (STF) gain from end-diastolic pressure (EDP) to indexed SV (SVi) in experimental HFpEF. Eighteen-week-old Wistar-Kyoto (WKY) and ZSF1 lean (ZSF1 Ln) and obese rats (ZSF1 Ob) randomly underwent LV open-chest (OC, n = 8 each group) or closed-chest hemodynamic evaluation (CC, n = 6 each group) under halogenate anesthesia and positive-pressure ventilation at constant inspiratory pressure. Beat-to-beat fluctuations in hemodynamic parameters during ventilation were assessed by STF. End-diastolic stiffness (beta(i)) and end-systolic elastance (E(es)i) for indexed volumes were obtained by inferior vena cava occlusion in OC (multibeat) or single-beat method estimates in CC. ZSF1 Ob showed higher EDP spectrum (P < 0.001), higher STF gain between end-diastolic volume and EDP, and impaired STF gain between EDP and SVi compared with both hypertensive ZSF1 Ln and normotensive WKY controls (P < 0.001). Likewise beta(i) was only higher in ZSF1 Ob while E(es)i was raised in both ZSF1 groups. On multivariate analysis beta(i) and not E(es)i correlated with impaired STF gain from EDP to SVi (P < 0.001), and receiver-operating characteristics analysis showed an area under curve of 0.89 for higher beta(i) prediction (P < 0.001). Results support further clinical testing of STF analysis from right heart catheterization-derived EDP surrogates to noninvasively determined SV as screening/diagnostic tool to assess myocardial stiffness in HFpEF.