Sustained Improvement in Diastolic Reserve Following Percutaneous Pericardiotomy in a Porcine Model of Heart Failure With Preserved Ejection Fraction

Abstract

Background:Heart failure with preserved ejection fraction is increasing in prevalence, but few effective treatments are available. Elevated left ventricular (LV) diastolic filling pressures represent a key therapeutic target. Pericardial restraint contributes to elevated LV end-diastolic pressure, and acute studies have shown that pericardiotomy attenuates the rise in LV end-diastolic pressure with volume loading. However, whether these acute effects are sustained chronically remains unknown.Methods:Minimally invasive pericardiotomy was performed percutaneously using a novel device in a porcine model of heart failure with preserved ejection fraction. Hemodynamics were assessed at baseline and following volume loading with pericardium intact, acutely following pericardiotomy, and then again chronically after 4 weeks. Cardiac structure was assessed by magnetic resonance imaging.Results:The increase in LV end-diastolic pressure with volume loading was mitigated by 41% (95% CI, 27%–45%,P<0.0001; ΔLV end-diastolic pressure reduced from +9±3 mm Hg to +5±3 mm Hg,P=0.0003, 95% CI, −2.2 to −5.5). The effect was sustained at 4 weeks (+5±2 mm Hg,P=0.28 versus acute). There was no statistically significant effect of pericardiotomy on ventricular remodeling compared with age-matched controls. None of the animals developed hemodynamic or pathological indicators of pericardial constriction or frank systolic dysfunction.Conclusions:The acute hemodynamic benefits of pericardiotomy are sustained for at least 4 weeks in a swine model of heart failure with preserved ejection fraction, without excessive chamber remodeling, pericarditis, or clinically significant systolic dysfunction. These data support trials evaluating minimally invasive pericardiotomy as a novel treatment for heart failure with preserved ejection fraction in humans.