TY - JOUR
T1 - Sustained Improvement in Diastolic Reserve following Percutaneous Pericardiotomy in a Porcine Model of Heart Failure with Preserved Ejection Fraction
AU - Jain, C. Charles
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 - Funding Information:
This research was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health, award numbers UL1TR000114 and UL1TR000135 (to Dr Borlaug). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Borlaug is also supported by R01 HL128526.
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
SP - 232
EP - 241
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
SN - 1941-3297
ER -