Feasibility and efficacy of percutaneously delivered leadless cardiac pacing in an in vivo ovine model.

INTRODUCTION: In this in vivo ovine study, we describe the course of pacing and sensing parameters during follow-up as well as the gross and histopathological features at the implant site of the recently described leadless cardiac pacemaker (LCP). METHODS AND RESULTS: All sheep underwent LCP implantation in the right ventricular (RV) apex. Serial pacing/sensing thresholds were assessed. In the first cohort, 11 animals were followed up for a period of 3 months, followed by necropsy. In the second cohort, 7 additional sheep were followed for a period of up to 18 months. Mean pacing and sensing thresholds in the 3-month cohort were 1.0 ± 0.5 V and 9.0 ± 3.7 mV at implant, and 0.7 ± 0.2 V and 8.1 ± 3.9 mV at 90 days, respectively. At necropsy at 3 months, all devices were securely implanted at the RV apex without extrusion of helix beyond the RV wall. Besides endocardial reactive changes in the RV apex surrounding the distal portion of the LCP, there were no other grossly visible abnormalities. In the second cohort (7 sheep), mean pacing and sensing thresholds were 1.0 ± 0.5 V and 9.9 ± 3.8 mV at implant, and 0.86 ± 0.4 V and 4.25 ± 1 mV, respectively, at 18 months of follow-up. CONCLUSION: We demonstrate that after implantation of the LCP, pacing/sensing parameters remain adequate up to 18 months in follow-up. In addition, pathological changes at the implant site and within the RV are limited in severity at 90 days, supporting the efficacy and safety of this novel approach to pacing.

First-in-Human Experience of Mechanical Preload Control in Patients With HFpEF During Exercise.

Exercise intolerance remains one of the major factors determining quality of life in heart failure patients. In 6 patients with heart failure with preserved ejection fraction (HFpEF) undergoing invasive cardiopulmonary exercise testing, balloon inflation within the inferior vena cava (IVC) was performed during exercise to reduce and maintain pulmonary arterial (PA) pressures. Partial IVC occlusion significantly reduced PA pressures without reducing cardiac output. Partial IVC occlusion significantly reduced respiratory rate at matched levels of exercise. These findings highlight the importance of pulmonary pressures in the pathophysiology of HFpEF and suggest that therapies targeting hemodynamics may improve symptoms and exercise capacity in these patients.

Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response.

BACKGROUND: Surgical edge-to-edge repair has been used in the treatment of mitral regurgitation. We evaluated the ability of a catheter-delivered clip (Evalve, Inc) to achieve edge-to-edge mitral valve approximation without cardiopulmonary bypass and the healing response of this technique. METHODS AND RESULTS: Twenty-one pigs underwent general anesthesia and left thoracotomy. A 10F flexible delivery catheter with a clip was placed into the left atrium. With echocardiographic and fluoroscopic guidance, the clip grasped and approximated the mid portion of the anterior and posterior leaflets. After a double orifice had been confirmed, the clip was detached and the catheter withdrawn. All animals survived and had successful clip placement. Three animals were euthanized at 4 weeks, 9 at 12 weeks, 1 at 17 weeks, 7 at 24 weeks, and 1 at 52 weeks. The clip was well positioned, with leaflet approximation in all animals except 1, in which the clip separated from the posterior leaflet at 4 weeks without affecting valve function. The clip was modified and implanted in 4 pigs; all were intact at 12 to 24 weeks. Scanning electron microscopy showed clip encapsulation with complete endothelialization. Mitral stenosis and thromboembolism did not develop. Two animals developed endocarditis (1 at 12 weeks and 1 at 17 weeks). Progressive healing occurred in all other animals. CONCLUSIONS: Edge-to-edge mitral valve approximation can be successfully and reliably achieved with a catheter-delivered clip without cardiopulmonary bypass, resulting in durable healing. The success of this device supports the development of a percutaneous catheter-based system for mitral valve repair.

Endovascular edge-to-edge mitral valve repair: short-term results in a porcine model.

BACKGROUND: The edge-to-edge technique is an accepted method for the surgical repair of a regurgitant mitral valve. This study reports the initial use of an endovascular technology that enables a double-orifice edge-to-edge mitral valve repair without cardiopulmonary bypass in an animal model. METHODS AND RESULTS: Adult pigs (n=14) were anesthetized, and left thoracotomy was performed for epicardial echo imaging. Using femoral vein access, a steerable guide catheter was placed transseptally into the left atrium. An implantable clip designed to grasp and approximate the middle scallops of the anterior and posterior mitral leaflets was introduced through the guide catheter. The clip was opened in the left atrium, advanced through the mitral orifice, and retracted to grasp the leaflet edges. When a functional double-orifice valve was confirmed by echo, the clip was closed to coapt the leaflets and detached from the delivery catheter. Before final clip detachment, echo demonstrated a double orifice in all 14 animals. In 2 studies, the clip released from the anterior mitral leaflet. Retrospective analysis of echo images indicated an incomplete grasp of the anterior leaflet. Immediate postmortem examination revealed that the clip successfully approximated the middle scallops of the anterior and posterior leaflets in all 12 double-orifice studies. CONCLUSIONS: This study demonstrates for the first time that an endovascular system can be successfully used to perform the edge-to-edge repair technique in a nondiseased porcine model. This technique is potentially applicable as a percutaneous catheterization laboratory procedure for the treatment of mitral regurgitation in humans.

Percutanenous therapies for mitral regurgitation.

Percutaneous therapies for the treatment of mitral regurgitation have emerged rapidly over the past several years. Most of the percutaneous approaches are modifications of existing surgical approaches to mitral annuloplasty or leaflet repair. Most of the percutaneous devices are based on surgical approaches. Catheter-based leaflet repair with the MitraClip is accomplished using an implantable clip to mimic the surgical edge-to-edge technique. Percutaneous annuloplasty can be achieved indirectly via the coronary sinus, or directly from retrograde left ventricular access. Several of these percutaneous approaches have been successfully used in trials or are in the early stages of use in practice.

Percutaneous edge-to-edge mitral valve repair: 2-year follow-up in the first human case.

We report the first-in-human mitral valve repair using percutaneous technology that creates a "surgical-like" edge-to-edge repair. A catheter-delivered clip was introduced transseptally from the femoral vein, advanced through the mitral orifice, retracted to grasp the leaflets, and detached to create a functional double-orifice valve. The patient had an uncomplicated post-procedural course. Echocardiography at 1- and 2-years post procedure showed mild mitral regurgitation and positive ventricular remodeling. The success of this case suggests that percutaneous mitral valve repair may be a feasible therapy for certain patients suffering from mitral regurgitation.

Percutaneous aortic valve replacement and mitral valve repair.

For mitral regurgitation and aortic valve disease warranting replacement, the surgical approach has been the mainstay therapy since the 1960s. Technological advances have provided potentially less invasive alternatives to surgery. Novel catheter-based techniques include aortic valve replacement with a valved stent, and devices aimed at reconfiguring the annulus or approximating a portion of the leaflets for mitral regurgitation. The main considerations regarding aortic valved stents include device anchoring and orientation, potential restriction of coronary flow, optimal method of delivery, ideal leaflet material, stent characteristics, and valve durability. The catheter-based approaches to mitral regurgitation are undergoing further experimental and clinical evaluations, and its success will be partially dependent on a thorough understanding of the underlying valvular pathology. Patient selection will be a critical component in the long-term efficacy of these new therapies. Close collaboration among the cardiovascular specialists and biomedical engineers will enable the development of safe and effective devices.