Manipulation of Left Ventricular Loading Conditions is Necessary to Identify Diastolic Dysfunction in Swine with Repetitive Pressure Overload‐Induced HFpEF

Abstract

ObjectiveDiagnosis of heart failure with preserved ejection fraction (HFpEF) is often complicated by the fact that many patients exhibit normal left ventricular (LV) mechanics at rest with a reduction in diastolic compliance that is only revealed when loading conditions are altered (e.g., during exercise stress). In an effort to identify parameters of diastolic function that could be utilized to detect alterations in compliance without manipulation of LV loading conditions, we utilized invasive hemodynamic analysis and speckle‐tracking echocardiography (STE) to assess diastolic strain and stiffness in swine with repetitive pressure overload (RPO)‐induced HFpEF.MethodsSwine (n=13) were subjected to 2‐weeks of RPO via daily intravenous administration of phenylephrine (PE; 400 ug/min; 1 hour/day) through an indwelling jugular vein catheter. Indices of LV relaxation as well as LV minimum and end‐diastolic pressure were obtained invasively before and after RPO at rest and during transient PE‐induced alterations in loading conditions. STE (Vivid 9; GE) was also performed throughout a single cardiac cycle to collect circumferential diastolic strain data, which were used alongside echocardiography‐derived measurements of chamber radius and wall thickness as well as catheter‐derived measurements of LV pressure to calculate regional and global circumferential subendocardial diastolic stiffness before and after RPO.ResultsCompared with baseline measurements, 2‐weeks of RPO did not significantly increase the time constant of LV relaxation (Tau; Figure A) or decrease the rate of LV pressure change during isovolumic relaxation (dP/dtmin; Figure B). Circumferential subendocardial stiffness derived via STE across a single cardiac cycle at rest was also unaffected by RPO (Figure C), despite a significant reduction in diastolic compliance that was revealed by construction of two‐point end‐diastolic pressure‐volume curves (Figure D) after manipulation of loading conditions (Figure E). Interestingly, single‐cycle STE‐derived stiffness measurements made during acute pressure overload were also similar at baseline and after RPO due to persistent elevations in LV minimum diastolic pressure during PE infusion at both timepoints.ConclusionsAlthough reductions in LV diastolic compliance are evident after chronic RPO when loading conditions are manipulated, abnormalities in LV mechanics are not exhibited at rest even when STE is used to assess diastolic stiffness throughout a single cardiac cycle. These findings highlight the challenges associated with identification of myocardial stiffening at rest in patients with HFpEF and reinforce the importance of studying LV mechanics under variable loading conditions.