Kazuyoshi Doi

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.

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.

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.

In vitro controllability of the MagScrew total artificial heart system.

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the MagScrew TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.

Cleveland clinic CorAide blood pump circulatory support without anticoagulation.

The Cleveland Clinic CorAide left ventricular assist system consists of a permanently implantable centrifugal pump in which the rotating assembly is completely suspended and noncontacting. A series of chronic animal in vivo studies were conducted to evaluate the biologic effects of CorAide circulatory support without the use of anticoagulation therapy. The CorAide pump was implanted in six calves (five calves for 21 to 32 days and one calf for 95 days). The first five calves received intravenous heparin during the early postoperative periods (2–7 days). Heparin administration was then discontinued and no other anticoagulant drugs were used for the duration of the experiments. The last calf did not receive any anticoagulant except for a bolus dose of heparin (200 U/kg) during surgery. Hemodynamics were stable in all six calves, with a mean pump flow of 5.6 ± 1.2 L/min and mean arterial pressure of 100 ± 4 mm Hg. The blood pump surfaces were clean of thrombus in all six calves. Significant findings at autopsy were limited to one case of renal infarction. There was no incidence of mechanical failure, bleeding, or device infection. The CorAide pump can be safely run with minimal or no anticoagulant therapy.

Reduction of mitral regurgitation using the coapsys device: A novel ex vivo method using excised recipients' hearts

The purpose of this study was to evaluate the ex vivo effects of the Coapsys device upon functional mitral regurgitation (MR) in human hearts. We used seven excised hearts from patients who underwent cardiac transplantation. All patients had functional MR of grade 2 or greater associated with dilated (n = 3) or ischemic (n = 4) cardiomyopathy. After the aortic valve was removed, the left ventricle was pressurized from the aorta with saline at a constant pressure. The degree of MR was then subjectively graded from the opened left atrium (from 0 to 4). The last three studies included volumetric measurements of MR. By tightening the device, the mean MR grade was reduced from 3.3 ± 0.8 to 1.1 ± 0.4 (p = 0.0002). In the quantitative analysis, mean regurgitation volume was reduced from 1,108 ± 1,134 ml/min to 236 ± 89 ml/min (p = not significant). The mitral annular septal-lateral dimension decreased from 2.0 ± 0.3 cm to 1.6 ± 0.5 (p = 0.043). The Coapsys device reduced functional MR in the ex vivo study using excised dilated hearts.

Mitral Valve Repair without Cardiopulmonary Bypass or Atriotomy Using the Coapsys Device: Device Design and Implantation Procedure in Canine Functional Mitral Regurgitation Model

BACKGROUND Myocor developed a unique system, the Coapsys annuloplasty system, to treat functional mitral regurgitation (MR) without cardiopulmonary bypass (CPB). This study was conducted to test the feasibility of the Coapsys implantation procedure in a canine functional MR model. METHODS Functional MR with heart failure was induced in 9 dogs by rapid ventricular pacing (230 beats/min for 30 +/- 4 days). The Coapsys device, which consists of anterior and posterior epicardial pads connected by a subvalvular chord, was then surgically implanted. Under epicardial echocardiographic guidance, we placed the Coapsys device across the left ventricular chamber using the delivery instrument and needle assembly. We sized the Coapsys device by drawing the posterior leaflet and annulus toward the anterior leaflet with the sizing instrument. Final device size was selected when MR was minimized or eliminated as assessed by 2-dimensional color Doppler echocardiography. RESULTS In all cases, we successfully implanted the Coapsys device without CPB or atriotomy. MR was reduced an average of 2 grades. No adverse events, such as hemodynamic compromise or structural valve damage, were noted. CONCLUSION Coapsys device implantation was feasible and safe on a beating canine heart. All accessory tools used for device implantation were found useful.

In vivo studies of the MagScrew total artificial heart in calves.

The purpose of this study was to evaluate the in vivo pump performance of our total artificial heart (TAH), the “MagScrew TAH.” The TAH consists of a blood pump and control logic developed at the Cleveland Clinic and the MagScrew actuator and electronic control system developed by Foster-Miller Technologies, Inc. (Albany, NY). MagScrew TAH implantation was performed in two calves. Study durations were 50 and 5 days. The causes of termination were prosthetic valve endocarditis in one case and cable failure in the other. Mean left pump flow ranged from 8.0 to 9.7 L/min, with left atrial pressure of 3.0 to 16.0 mm Hg. Preload sensitivity of the MagScrew TAH demonstrated a Frank-Starling response to preload in automatic mode. The relationship between right and left atrial pressure was well balanced. Mean arterial pressure and mean pulmonary artery pressure were maintained within physiologic ranges over study duration. There were no signs of bleeding, hemolysis, or organ failure. The MagScrew TAH showed physiologic pump performance, and hemodynamics were well maintained without any organ failure. Further development testing will bring the MagScrew TAH to the point of preclinical readiness testing.

In vivo performance and biocompatibility of the MagScrew ventricular assist device

Currently available ventricular assist devices (VADs) have limitations in long-term durability and blood compatibility. We evaluated a prototype of a pulsatile MagScrew VAD for in vivo hemodynamic performance and biocompatibility. The device is composed of an actuator, blood pump housing, diaphragm, pusher plate, and bioprosthetic valves. Its protein-coated (“biolized”) blood-contacting surface inhibits clot formation. Forces between moving parts of the actuator are transmitted magnetically, eliminating a primary source of friction and wear. The pump fills passively and is highly preload sensitive. The device was implanted into three calves for 90, 10, and 57 days, respectively. No anticoagulants were given postoperatively. The device functioned without technical problems during the entire course of each experiment, with mean device flow ranging between 5.4 and 9.0 L/min. Autopsy of the first two calves revealed no sign of embolization and clean blood-contacting surfaces of the devices. The third experiment was complicated by a prosthetic valve endocarditis with infectious embolization, and a few small depositions were found in the pump. In conclusion, the MagScrew VAD has demonstrated a high level of performance and biocompatibility in three calves studied for 10–90 days. Vigorous development is in progress to bring this device to preclinical readiness and thus provide surgeons with the VAD of choice for permanent implantation.

Device based left ventricular shape change: validation of conductance technology in shape changed hearts.

We have reported that device based left ventricular (LV) shape change, accomplished by Myosplint, improved LV systolic function by three-dimensional echocardiography (3-D echo). However, evaluation of this device using the pressure-volume relationship is still important. This study was conducted to validate the use of conductance technology for this evaluation in shape-changed hearts. An ex vivo study using excised ovine hearts (n = 11) and an in vivo study using a canine pacing-induced heart failure model (n = 11) were performed. Three Myosplints were implanted. Before and after the shape changes, volumes measured by a conductance catheter were compared with volumes measured by the amount of saline in the ex vivo study or by 3-D echo in the in vivo study. The conductance volumes were linearly correlated with the saline volumes (r2 = 0.961 ± 0.046;p < 0.0001) in the ex vivo study and with 3-D echo volumes (r2 = 0.757 ± 0.220;p < 0.0001) in the in vivo study. The conductance volumes were linearly correlated with LV volumes even in the shape-changed hearts. This technology can be used to evaluate pressure-volume loops in the shape-changed hearts as long as the conductance volume is calibrated by a reliable method.