Raymond Dessoffy

Off-pump mitral valve repair using the Coapsys device: a pilot study in a pacing-induced mitral regurgitation model

PURPOSE The purpose of this study was to evaluate the ability of the Myocor Coapsys device to restore leaflet apposition and valve competency off-pump in a canine model of functional mitral regurgitation (MR). DESCRIPTION The Coapsys device was surgically implanted in 10 dogs after MR induction by rapid ventricular pacing. The Coapsys consists of anterior and posterior epicardial pads connected by a subvalvular chord. The annular head of the posterior pad was positioned at the annular level to draw the posterior leaflet and annulus toward the anterior leaflet. Final device size was selected when MR was minimized or eliminated as assessed by color flow Doppler echocardiography. EVALUATION All implants were placed off-pump without atriotomy, and mean MR grade was reduced from 2.9 +/- 0.7 to 0.6 +/- 0.7 (p < 0.001) acutely. No hemodynamic compromise was noted. CONCLUSIONS The Coapsys device consistently and significantly reduced or eliminated functional MR acutely. Further study will be required to assess the chronic stability of the repair in this animal model.

A novel device for left atrial appendage exclusion: The third-generation atrial exclusion device

OBJECTIVE Occlusion of the left atrial appendage is proposed to reduce the risk of stroke in patients with atrial fibrillation. The third-generation atrial exclusion device, modified to provide uniform distribution of pressure at appendage exclusion, was assessed for safety and effectiveness in a canine model and compared with a surgical stapler. METHODS The atrial exclusion device consists of 2 parallel, straight, rigid titanium tubes and 2 nitinol springs with a knit-braided polyester fabric. Fourteen mongrel dogs were implanted with the device at the base of the left atrial appendage via a median sternotomy. In each dog, the right atrial appendage was stapled with a commercial apparatus for comparison. The animals were evaluated at 7 days (n = 3), 30 days (n = 5), and 90 days (n = 6) after implantation by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histology. RESULTS Left atrial appendage exclusion was complete and achieved without hemodynamic instability, and coronary angiography revealed that the left circumflex artery was patent in all cases. A new endothelial tissue layer developed on the occluded orifice of the left atrium 90 days after implantation. This endothelial layer was not evident on the stapled right atrial appendage. CONCLUSION In dogs, the third-generation atrial exclusion device achieved easy, reliable, and safe exclusion of the left atrial appendage with favorable histologic results. Clinical application could provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

IN VIVO ACUTE PERFORMANCE OF THE CLEVELAND CLINIC SELF-REGULATING CONTINUOUS-FLOW TOTAL ARTIFICIAL HEART

BACKGROUND The purpose of this study was to evaluate the acute in vivo pump performance of a unique valveless, sensorless, pulsatile, continuous-flow total artificial heart (CFTAH) that passively self-balances left and right circulations without electronic intervention. METHODS The CFTAH was implanted in two calves, with pump and hemodynamic data recorded at baseline over the full range of pump operational speeds (2,000 to 3,000 rpm) in 200-rpm increments, with pulsatility variance, and under a series of induced hemodynamic states created by varying circulating blood volume and systemic and pulmonary vascular resistance (SVR and PVR). RESULTS Sixty of the 63 induced hemodynamic states in Case 1 and 73 of 78 states in Case 2 met our design goal of a balanced flow and maximum atrial pressure difference of 10 mm Hg. The correlation of calculated vs measured flow and SVR was high (R(2) = 0.857 and 0.832, respectively), allowing validation of an additional level of automatic active control. By varying the amplitude of sinusoidal modulation of the speed waveform, 9 mm Hg of induced pulmonary and 18 mm Hg of systemic arterial pressure pulsation were achieved. CONCLUSIONS These results validated CFTAH self-balancing of left and right circulation, induced arterial flow and pressure pulsatility, accurate calculated flow and SVR parameters, and the performance of an automatic active control mode in an acute, in vivo setting in response to a wide range of imposed physiologic perturbations.

Novel device to change left ventricular shape for heart failure treatment: device design and implantation procedure.

The Myocor Myosplint is designed to decrease left ventricular (LV) wall stress by changing LV shape, thus improving contractile function in dilated hearts. This shape change is accomplished by surgically placing three Myosplints perpendicular to the LV long axis, drawing the LV walls inward, and creating a symmetric, bilobular LV. Specially designed instruments aid in the precise delivery of these devices. The purpose of this study was to test the safety and feasibility of the procedure in dogs. Dilated cardiomyopathy was induced in 40 healthy dogs (26.3 ± 1.7 kg) by ventricular pacing at 230 beats per minute for an average of 25 ± 4 days. Using epicardial echocardiography, we placed the Myosplints across the LV chamber, avoiding the major coronary arteries, papillary muscles, and mitral valve. Once placed, the Myosplints were used to draw the LV walls inward to a prescribed distance. In all cases, we successfully implanted three Myosplints without using cardiopulmonary bypass. There were no complications related to the device or procedure. Myosplint implantation to change LV shape is safe and repeatable on a beating cardiomyopathic canine heart. Further study of the procedure will be needed in humans.

Development of a small implantable right ventricular assist device.

The purpose of this program is to design, develop, and clinically evaluate a new, implantable right ventricular assist device (RVAD) that can be used as a component of an implantable biventricular assist device for patients with severe biventricular heart failure. The initial phase of this program resulted in a prototype RVAD, named DexAide, a modified version of the CorAide left ventricular assist device. In vitro testing was performed in a stand-alone circuit and in a true RVAD mode to evaluate pump performance. Pump flow and power were measured under various afterload and pump speed conditions. The pump performance requirements of 2 to 6 l/min and a pressure rise of 20 to 60 mm Hg were successfully met with pump speeds between 1,800 and 3,200 rpm. The nominal design point of 4 l/min and 40 mm Hg pressure rise was achieved at 2,450 ± 70 rpm with a power consumption of 3.0 ± 0.2 W. The initial in vitro testing met the design criteria for the new DexAide RVAD. Initial in vivo testing is under way, which will be followed by preclinical readiness testing and a pilot clinical trial in this 5-year program.

Development of DexAide right ventricular assist device: update II.

The DexAide right ventricular assist device (RVAD) is a magnetically and hydrodynamically levitated implantable centrifugal pump. Recent progress includes 1) redesign of the inflow/outflow conduits, which yielded two successful 3-month experiments, 2) development of alternative journal bearing materials, and 3) completion of an 18-month duration of in vitro endurance testing. Verification testing of the RVAD electronics has been completed, and a prototype biventricular assist device (BVAD) system has been tested. Acute DexAide/CorAide BVAD implantations via median sternotomy in two calves documented BVAD control algorithms and anatomical fit. A drug-induced chronic calf heart failure model, currently under development in our laboratory, resulted in a successful BVAD implantation in a calf with heart failure. Our future plans are to complete in vitro and in vivo validation of alternative bearing materials, perform preclinical DexAide in vivo and in vitro reliability studies, and obtain Food and Drug Administration (FDA) approval for an Investigational Device Exemption to conduct a clinical pilot study. In conclusion, two successful 3 month in vivo experiments and an 18-month in vitro endurance test were completed. After final bearing material selection, the DexAide design will be “frozen” so that preclinical systems can be manufactured. BVAD experiments using a chronic heart failure model are in progress.

Acute in vivo evaluation of an implantable continuous flow biventricular assist system.

An implantable biventricular assist device offers a considerable opportunity to save the lives of patients with combined irreversible right and left ventricular failure. The purpose of this study was to evaluate the hemodynamic and physiologic performance of the combined implantation of the CorAide™ left ventricular assist device (LVAD) and the DexAide right ventricular assist device (RVAD). Acute hemodynamic responses were evaluated after simulating seven different physiological conditions in two calves. Evaluation was performed by fixing the speed of one individual pump and increasing the speed of the other. Under all conditions, increased LVAD or RVAD speed resulted in increased pump flow. The predominant pathophysiologic effect of independently varying DexAide and CorAide pump speeds was that the left atrial pressure was very sensitive to increasing RVAD speed above 2,400 rpm, whereas the right atrial pressure demonstrated much less sensitivity to increasing LVAD speed. An increase in aortic pressure and RVAD flow was observed while increasing LVAD speed, especially under low contractility, ventricular fibrillation, high pulmonary artery pressure, and low circulatory blood volume conditions. In conclusion, a proper RVAD-LVAD balance should be maintained by avoiding RVAD overdrive. Additional studies will further investigate the performance of these pumps in chronic animal models.

Optimal mitral annular and subvalvular shape change created by the Coapsys device to treat functional mitral regurgitation.

We have reported that the Myocor Coapsys (Myocor, Inc, Maple Grove, MN) device treated functional mitral regurgitation (MR) by reducing mitral annular dimension and repositioning papillary muscles. This study was conducted to evaluate the optimal Coapsys device sizing level. The Coapsys device was implanted in seven dogs after induction of MR by rapid ventricular pacing. The device consists of anterior and posterior pads connected by a subvalvular cord. The device was tightened in 5% increments of the left ventricular epicardial to epicardial dimension up to 40%. Hemodynamic and echocardiographic measurements were repeated at each tightening level. The Coapsys significantly reduced or eliminated functional MR, and the reduction was maximized at the 30% tightening level or lower in all cases. Although the left ventricular end diastolic volume decreased significantly, forward stroke volume was maintained until the 35% tightening level. The forward ejection fraction significantly increased from 33 ± 24% at baseline to 62 ± 42% at 40% tightening level. Mean aortic pressure decreased slightly but significantly. The Coapsys device can be applied over a broad range of tightening levels with significant reduction in MR without negative physiologic impact. This feature makes the device unusable in a variety of clinical settings.

Development of the DexAide right ventricular assist device inflow cannula.

Cannula design and cannulation site can pose major limitations to chronic pump implantations in animal studies. The aim of this study was to evaluate the biocompatibility of various inflow cannula designs for the DexAide right ventricular assist device (RVAD). The DexAide RVAD was implanted for intended durations of 14, 30, or 90 days in 19 animals (mean 20 ± 11 days). Seven inflow cannula designs were evaluated: angled titanium conduit with caged tip (two cases); flexible polyurethane coated polyvinyl chloride (PVC) tube (one case); open ended titanium (one case); a titanium cannula with a flange (six cases); a cannula with a gelatin coated flange (five cases); a cannula with an angled flange (one case); and open ended titanium with two side holes (three cases). The open ended titanium inflow cannula with two side holes positioned through the diaphragmatic surface of the right ventricle (RV) via a right thoracotomy showed good biocompatibility for the chronic animal study. Other cannulae inserted into the infundibular portion of the RV via a left thoracotomy showed significant depositions. Gelatin coated inflow cannula had the advantage to prevent tissue growth around the inflow cannula. The DexAide RVAD pump itself showed good biocompatibility, although nonadherent depositions originating from the inflow cannulae were captured onto the primary impeller blades.

Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation.

Background: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively. Objective: To determine whether the non-invasive index of contractility “preload-adjusted PWRmax” (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation. Methods: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWRmax, the slope of the end systolic pressure–volume relation (Emax), and the maximum rate of change of left ventricular pressure (dP/dtmax) were calculated in a beat to beat fashion. Results: Preload-adjusted PWRmax correlated linearly with load independent Emax (p < 0.0001) and curvilinearly with load dependent dP/dtmax (p < 0.0001), which suggested the load independence of preload-adjusted PWRmax. After five minutes of diltiazem administration, preload-adjusted PWRmax, dP/dtmax, and Emax fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%). Conclusions: Preload-adjusted PWRmax correlates linearly with Emax and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.