TY - JOUR
T1 - Sustained Improvement in Diastolic Reserve Following Percutaneous Pericardiotomy in a Porcine Model of Heart Failure With Preserved Ejection Fraction
AU - Charles Jain, C.
AU - Pedrotty, Dawn
AU - Araoz, Philip A.
AU - Sugrue, Alan
AU - Vaidya, Vaibhav R.
AU - Padmanabhan, Deepak
AU - Arunachalam, Shivaram P.
AU - Lerman, Lilach O.
AU - Asirvatham, Samuel J.
AU - Borlaug, Barry A.
N1 - Publisher Copyright:
© 2021 American Heart Association, Inc.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
KW - Heart failure
KW - Hemodynamics
KW - Pericardiotomy
KW - Pericardium
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U2 - 10.1161/CIRCHEARTFAILURE.120.007530
DO - 10.1161/CIRCHEARTFAILURE.120.007530
M3 - Article
C2 - 33478242
AN - SCOPUS:85102211929
SN - 1941-3289
VL - 14
SP - E007530
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 2
ER -