Percutaneous Pericardial Resection: A Novel Potential Treatment for Heart Failure With Preserved Ejection Fraction

Abstract

Background: People with heart failure and preserved ejection fraction develop increases in left ventricular (LV) end-diastolic pressures during exercise that contribute to dyspnea. In normal open-chest animal preparations, the pericardium restrains LV filling when central blood volume increases. We hypothesized that resection of the pericardium using a minimally invasive epicardial approach would mitigate the increase in LV end-diastolic pressure that develops during volume loading in normal and diseased hearts with the chest intact.

Methods and results: Invasive hemodynamic assessment was performed at baseline and after saline load before and after pericardial resection in normal canines with open (n=3) and closed chest (n=5) and in a pig model with features of human heart failure and preserved ejection fraction with sternum intact (n=4). In closed-chest animals, pericardiotomy was performed using a novel subxiphoid procedure. In both experimental preparations of normal dogs, pericardiotomy blunted the increase in LV end-diastolic pressure with saline infusion, while enhancing the saline-mediated increase in LV end-diastolic volume. With chest intact in the pig model, percutaneous pericardial resection again blunted the increase in LV end-diastolic pressure secondary to volume expansion (+4±3 versus +13±5 mm Hg; P=0.014), while enhancing the saline-mediated increase in LV end-diastolic volume (+17±1 versus +10±2 mL; P=0.016).

Conclusions: This proof of concept study demonstrates that pericardial resection through a minimally invasive percutaneous approach mitigates the elevation in LV filling pressures with volume loading in both normal animals and a pig model with diastolic dysfunction. Further study is warranted to determine whether this method is safe and produces similar acute and chronic hemodynamic benefits in people with heart failure and preserved ejection fraction.

Keywords: blood volume; heart failure; hemodynamics; humans; pericardium.

Figure 1

[A–D] Illustration depicting release of pericardial restraint using the percutaneous sub-xiphoid approach. Prototypes built to date that can track over a guidewire and grasp the pericardium [E], deliver electrical energy to stimulate the phrenic nerve and cut the pericardium in a forward scissors-like motion [F], and cut the pericardium with an actuating reverse-cutting blade [G].

Figure 2

Left ventricular end diastolic pressures (LVEDP) at rest and following saline load for all individual animals in chest intact experiments before (left panels, solid lines) and after pericardial resection (right panels, dotted lines).

Figure 3

Hemodynamic effects of volume loading before and after pericardial resection. With chest intact, minimally-invasive percutaneous pericardial resection significantly attenuated the increase in left ventricular end diastolic pressure (LVEDP) during rapid saline loading and enhanced the increase in left ventricular end diastolic volume (LVEDV), both in normal dogs (top panels) and in a pig model with features of human HFpEF (bottom panels). Error bars reflect SEM.

Figure 4

Photograph from a representative animal taken after closed-chest experiments were been completed and the sternum was opened prior to sacrifice, showing that the epicardial surface of the heart is unrestrained and lack of pericardial coverage following minimally-invasive percutaneous pericardial resection in a normal canine.