Heart failure with preserved ejection fraction (HFpEF) afflicts over 3 million Americans and has no proven effective treatment, making this one of the largest unmet needs in cardiovascular medicine.¹ The primary symptom in HFpEF is dyspnea that develops because of an increase in left ventricular end-diastolic pressures (LVEDP). This increase in LVEDP is transmitted back into the pulmonary capillaries to cause lung congestion and increases pulmonary artery pressures to cause right heart failure.

Elevation in LVEDP is traditionally thought to be exclusively caused by changes in the mechanical properties of the myocardium itself (stiffening). However, a substantial component of the observed increase in LVEDP is actually caused by the restraining effects of the pericardium.² This restraining effect is enhanced when blood return to the heart is increased, as during exercise or congestive heart failure decompensation. We have recently shown in normal dogs and pigs with hemodynamic features of human HFpEF that if this pericardial restraint is acutely removed, there is less increase in LVEDP with volume loading, leading to less pulmonary congestion and dyspnea.³ Removal of pericardial restraint also allows for greater improvement in LV end diastolic volume (LVEDV) and thus more optimal utilization of the Frank-Starling mechanism to augment cardiac output as preload increases.³

We have developed a new method and toolset to unload pericardial restraint using a minimally-invasive procedure that is suitable for use in the cardiac catheterization laboratory, without the need for open heart surgery. The pericardium is accessed through a sub-xiphoid sheath under fluoroscopic guidance.^3,4 Graspers as well as forward and backward cutting tools are then used to resect and incise the anterior pericardium under standard fluoroscopic guidance, similar to an angiogram or right heart catheterization procedure. While our new procedure has not yet been attempted in humans, we have completed multiple experimental studies in animals showing that percutaneous pericardiectomy is feasible, safe, and results in considerable improvement in cardiac hemodynamics in normal animals and a pig model of HFpEF.^3,4 Specifically, we have observed that the increase in left ventricular filling pressures in response saline loading is substantially reduced after pericardial resection, by about 70%. We also see that volume loading of the heart (as happens with exercise or with dietary indiscretion) leads to a greater improvement in left ventricular preload volume, allowing for greater ability to utilize the Frank-Starling reserve mechanism.

The next steps will be to show that salutary effects from pericardial resection are sustained over time in animal models, and then to perform first in man studies to test the acute and chronic effects of this new approach to treating HFpEF. We are currently conducting ongoing studies to accomplish both of these aims, including testing the acute effects of pericardiotomy in patients at the time of surgery.

References

1. Reddy YN, Borlaug BA, Heart failure with preserved ejection fraction. Curr Probl Cardiol 2016;41:145-88.
2. Watkins MW, LeWinter MM. Physiologic role of the normal pericardium. Annu Rev Med 1993;44:171-80.
3. Borlaug BA, Carter RE, Melenovsky V, et al. Percutaneous pericardial resection: a novel potential treatment for heart failure with preserved ejection fraction. Circ Heart Fail 2017;10:e003612.
4. Killu AM, Naksuk N, Desimone CV, et al. Beating heart validation of safety and efficacy of a percutaneous pericardiotomy tool. J Cardiovasc Electrophysiol 2017;28:357-61.

Keywords: Pericardiectomy, Stroke Volume, Capillaries, Blood Pressure, Pulmonary Artery, Heart Failure, Pericardium, Dyspnea, Cardiac Catheterization, Myocardium

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