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Objectives Many patients with heart failure have preserved ejection fraction but also diastolic dysfunction, with no effective therapy. We are developing a new pump (left atrial assist device, LAAD) for implantation at the mitral position to pump blood from the left atrium to sufficiently fill the left ventricle. The purpose of the initial in vitro study was to demonstrate that the LAAD can reduce left atrial pressure (LAP) and increase cardiac output (CO) while maintaining arterial pulsatility and normal aortic valve function using a proof-of-concept device. Methods The LAAD concept was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated the normal function of the native ventricle as well as 3 levels of diastolic heart failure (DHF 1, 2, and 3) by adjusting the diastolic drive pressure to limit diastolic filling of the ventricle. Results Without the LAAD, CO and aortic pressure (AoP) decreased dramatically from 3.8 L/min and 100 mm Hg at normal heart condition to 1.2 L/min and 35 mm Hg at DHF 3, respectively. With LAAD support, both CO and AoP recovered to normal heart values at 3200 rpm and surpassed normal heart values at 3800 rpm. Furthermore, with LAAD support, LAP recovered to almost that of the normal heart condition at 3800 rpm. Conclusions These initial in vitro results support our hypothesis that use of the LAAD increases CO and AoP and decreases LAP under DHF conditions while maintaining arterial pulsatility and full function of the aortic valve.

Objective Cardioscopy is a novel imaging method that allows closed-chest, real-time fiberoptic imaging of intracardiac structures. This study tested the feasibility and safety of cardioscopy as a platform for mitral and tricuspid valve surgery in the beating heart. Methods Through a median sternotomy, cardiopulmonary bypass was established in 10 calves. Lactated Ringer’s solution was administered through the pulmonary artery to eliminate residual blood volumes in the lung vasculature and was drained through a left ventricular cannula. A fiberoptic cardioscope within its translucent outer sheath was inserted through the left ventricle. Irrigating solution was continuously administered through the cardioscope sheath for clearer visualization. An endoscopic clip was used for edge-to-edge repair of the mitral and tricuspid valves. After mitral valve clipping, the cardioscope was inserted into the right ventricle. The solution was administered from the right atrium and continuously drained from the pulmonary artery. After tricuspid valve repair, the animal was weaned from cardiopulmonary bypass. Results Successful double-valve repair was carried out in all 10 cases. All calves were weaned from cardiopulmonary bypass with dobutamine only. Hematocrit values were maintained during the procedure (pre 29.0% ± 3.1% vs post 28.5% ± 3.6%, P = .70). Conclusions This study showed the technical feasibility of beating heart valve surgery using direct cardioscopic visualization. Cardioscopy represents a promising platform for future interventions and surgery under direct visualization in the beating heart.

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.

ObjectivesWe sought to investigate the short-term and midterm effects of left atrial appendage exclusion on left atrial function. Left atrial appendage exclusion is considered a possible therapeutic option for stroke prevention in patients with atrial fibrillation. Favorable outcomes have encouraged widespread use of left atrial appendage exclusion for cardiac surgical patients—even for patients in sinus rhythm who have stroke risk factors; however, the chronic effects on left atrial function of left atrial appendage exclusion are unclear.MethodsNineteen mongrel dogs (29.7 ± 5.2 kg) in sinus rhythm were studied. The Doppler signals from the pulmonary venous flow, transmitral flow, and tissue Doppler imaging of mitral annular motion were obtained before and after left atrial appendage exclusion. Dogs were evaluated in the same manner at 7 days (n = 2), 30 days (n = 7), or 90 days (n = 10) after left atrial appendage exclusion.ResultsExcept for a significant increase in early diastolic transmitral flow velocity after left atrial appendage exclusion (P = .01), no significant differences were found in any parameters related to the transmitral flow and tissue Doppler imaging measurements throughout follow-up. The systolic components of pulmonary venous flow at follow-up revealed a significant reduction relative to baseline (peak systolic velocity P < .0001, systolic velocity-time integral P < .0001), despite the lack of significant changes in left atrial pressure, left ventricular volume, and stroke volume.ConclusionLeft atrial appendage exclusion may affect left atrial reservoir function in the short-term and midterm periods. Further long-term studies with more clinically relevant models are needed.

Objectives Pump-off testing to assess left ventricular recovery is not an option for continuous-flow left ventricular assist devices unless measures are taken to prevent pump regurgitation. The purpose of this bench study was to characterize the hemodynamics and pump flow of the HeartMate II (Thoratec Corp, Pleasanton, Calif) left ventricular assist device at 6000 rpm, the speed commonly used clinically to determine left ventricular recovery. Methods The HeartMate II device was operated in a mock loop at 3 speeds (6000, 8000, and 10,000 rpm). We acquired pressure-flow curves in each steady state. In pulsatile mode with the pneumatic ventricle (heart simulator) activated, pump flow, total flow, and aortic pressure data were obtained under conditions simulating normal heart function or heart failure. Results A large regurgitant flow during diastole was confirmed in normal heart function at 6000 rpm support; however, the net flow was zero, and there were no differences in the mean aortic pressure between 6000 rpm support and no left ventricular assist device support. In contrast, in the heart failure condition, left ventricular assist device flow at 6000 rpm significantly contributed to the mean aortic pressure and total flow because there was less regurgitant flow. Conclusions The net pump flow generated by the HeartMate II device at 6000 rpm depends on the degree of residual left ventricular function. In the setting of improved left ventricular function, at 6000 rpm, we noted a large regurgitant flow that reloaded the left ventricle. Although this "marker" can serve as a useful indicator for left ventricular recovery, assessing left ventricular recovery at this speed is flawed unless measures are taken to prevent regurgitant flow.

Background The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. The atrial exclusion device, previously developed to perform left atrial appendage exclusion on a beating heart, was modified to accommodate different anatomic patterns of the human left atrial appendage and to ensure uniform pressure and occlusion. The purpose of this study was to evaluate this second-generation atrial exclusion device during a midterm period in a canine model. Methods Ten mongrel dogs (mean weight 28.9 ± 4.6 kg) were used in this study. The atrial exclusion device, constructed from two parallel and rigid titanium tubes and two nitinol springs with a knit-braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart using a specially designed delivery tool. Dogs were evaluated at 30 days (n = 4) and 90 days (n = 6) by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histologic inspection. Results Device implantation was performed without complications in all dogs. Complete left atrial appendage exclusion without device migration or hemodynamic instability was confirmed, and there was no damage to the left circumflex artery or pulmonary artery. Macroscopic and microscopic assessments revealed favorable biocompatibility during midterm follow-up. Conclusion The atrial exclusion device enabled rapid, reliable, and safe exclusion of the left atrial appendage. Clinical application may provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

ObjectivesBecause duration of inotropic support after left ventricular assist device implantation has been recognized as a surrogate for right ventricular dysfunction, we sought to (1) identify its preimplantation risk factors, particularly its association with preimplantation right ventricular dysfunction, and (2) assess its impact on clinical outcomes.MethodsBetween 1991 and 2002, left ventricular assist devices were implanted in 207 patients, exclusive of those receiving preoperative mechanical circulatory support, which precluded measuring right ventricular stroke work. Duration of inotropic support was analyzed as a continuous variable, truncated by death or transplantation, and in turn as a risk factor for these 2 events.ResultsInotropic support decreased from 100% on the day of implantation to 57%, 33%, and 22% by days 7, 14, and 21. Its duration was strongly associated with lower preimplantation right ventricular stroke work index, older age, and nonischemic cardiomyopathy and was associated (P < .04) with higher mortality before transplantation but not with transition to transplantation. We identified no preimplantation risk factors for right ventricular assist device use because of its relatively infrequent use in this population (18 patients, only 4 of whom survived to transplantation).ConclusionDuration of inotropic support after left ventricular assist device insertion is strongly correlated with low preimplantation right ventricular stroke work index. In turn, it was associated with reduced survival to transplantation. Thus, right ventricular stroke work measured before implantation might be useful in decision making for biventricular support, destination therapy, or total artificial heart.

Objective The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion or excision of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. We evaluated the ability of a novel device to exclude the left atrial appendage during early and intermediate follow-up periods in a canine model. Methods Eight mongrel dogs (mean weight 29.1 ± 4.0 kg) were used in this study. The occlusion device, constructed from 2 stainless steel strips covered with a knit braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart. Dogs were evaluated at 7 days (n = 2), 30 days (n = 2), and 90 days (n = 4) by epicardial echocardiography, left atrial angiography, histologic inspection, and gross pathology. Results Device implantation was performed without complications in all animals. Complete exclusion of the left atrial appendage from the circulation was confirmed acutely and chronically by echocardiographic and angiographic evaluations. There was no device migration or damage to adjacent structures. Conclusion This novel device enables rapid, reliable, and safe exclusion of the left atrial appendage. The device provides a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

ObjectivesActivation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy.MethodsNorepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index.ResultsConcurrent with improvements of New York Heart Association functional class (2.9 ± 0.5 preoperatively vs 2.0 ± 0.4 postoperatively, P < .001), ejection fraction (23.9% ± 6.6% vs 36.2% ± 6.2%, P < .01), and left ventricular end-diastolic volume index (140.8 ± 33.8 mL/m2 vs 90.6 ± 18.3 mL/m2, P < .01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P < .05), plasma renin activity (5.75 μg/L/h vs 3.45 μg/L/h, P < .05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P = .051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P < .05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = −.745, P < .05 [plasma renin activity]; R = −.808, P < .05 [angiotensin II]).ConclusionsSurgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.

In vitro function of the Cleveland Clinic-Nimbus electrohydraulic total artificial heart met National Heart, Lung, and Blood Institute hemodynamic guidelines for such devices. In a series of in vivo experiments, we implanted the total artificial heart in eight calves (mean weight 87 kg), one for a short-term experiment and seven for long-term experiments. The mean blood flow during support was 7.7 + 1.6 L/min with left atrial pressure 13 ± 6 mm Hg, right atrial pressure 13 ± 4 mm Hg, and aortic pressure 97 ± 9 mm hg. Maximum pump flow (9.6 L/min) occurred after 4 days of support as a result of the high resting cardiac output of the animals. A 10 % to 15 % right pump stroke-volume limit effectively balanced atrial pressures, and afterload insensitivity was confirmed by the in vivo studies. Calves tolerated treadmill exercise studies well, with an average duration of 22 minutes and an average top speed of 2.1 mph. The experiments were terminated after 1 day to 120 days of support (mean 32 days). Most experiments were terminated as a result of correctable mechanical problems. In a separate study of six adult human patients undergoing orthotopic cardiac transplantation, five showed an excellent fit for the Cleveland Clinic-Nimbus total artificial heart. Further studies using chest roentgenograms, chest measurements, and transesophageal echocardiography should help predict fit of the total artificial heart in potential candidates. Initial candidates for a "vented-electric" version of the Cleveland Clinic-Nimbus total artificial heart are patients for whom univentricular (left ventricular assist device) support is not appropriate, but who require mechanical support as a bridge to cardiac transplantation.

Objective: We evaluated the capability of the Myocor Coapsys device (Myocor, Inc, Maple Grove, Minn) to reduce functional mitral regurgitation in a canine model of dilated cardiomyopathy. Methods Functional mitral regurgitation with heart failure was induced in 7 dogs by rapid ventricular pacing. The Coapsys device, which consists of anterior and posterior epicardial pads connected by a subvalvular chord, was then implanted. Heart failure was maintained by continued pacing for 8 weeks. Hemodynamic and echocardiographic measurements were performed at pre- and postsizing and after 8 weeks. The Coapsys subvalvular chord was cut to verify that maintenance of valve competency was due to the device. Results All implants were performed off-pump without atriotomy. Mitral regurgitation was reduced in all animals; mean mitral regurgitation grade was reduced from 2.9 ± 0.7 to 0.7 ± 0.8 (P = .00005) and was maintained at 0.8 ± 0.8 after 8 weeks, without hemodynamic compromise or structural damage to the mitral valve. Mitral regurgitation returned to 3.6 ± 0.8 (P = .102 versus presizing) after cutting the Coapsys subvalvular chord. Conclusion The Coapsys device consistently and chronically reduced functional mitral regurgitation. This device is in clinical trials in the United States.

Objective: An animal model of chronic severe heart failure is needed to evaluate new mechanical devices, surgical procedures, and medical therapies. The purpose of this study was to evaluate a unique new model of severe heart failure developed by means of a novel protocol of rapid ventricular pacing. Methods: Heart failure was induced in 8 mongrel dogs by means of rapid ventricular pacing (230 beats/min) for 4 weeks. After a sham operation, maintenance pacing at a reduced rate (190 beats/min) was continued for another 4 weeks. Results: Left ventricular systolic function was significantly reduced at week 4 and remained low at week 8, including the slope of the end-systolic pressure-volume relationship (2.4 ± 1.0 vs 0.7 ± 0.2 vs 0.8 ± 0.3 mm Hg/mL [baseline vs week 4 vs week 8, respectively]), ejection fraction (63% ± 5% vs 28% ± 7% vs 33% ± 5%), and cardiac output (3.1 ± 0.7 vs 2.0 ± 0.3 vs 2.2 ± 0.7 L/min). Significant ventricular remodeling changes took place with increased ventricular volumes and circumferential wall stress, which were stable between weeks 4 and 8. Serum catecholamine and atrial natriuretic polypeptide levels also increased from baseline but stabilized between weeks 4 and 8. The end-diastolic pressure-volume relationship also showed stable diastolic function between weeks 4 and 8. Conclusions: Induction pacing at 230 beats/min readily created severe heart failure in all animals, and a new technique of maintenance pacing provided a consistent model of severe heart failure. This model can be used to study a variety of new interventions for heart failure. J Thorac Cardiovasc Surg 2002;123:544-9

Objectives We have developed a stentless pericardial mitral valve prosthesis in 2 configurations; the purposes of this acute study in sheep were to assess (1) valve design and implant technique; (2) valve performance; and (3) acute effects on postimplant left ventricular function. Methods A stentless bovine pericardial bileaflet valve was developed with the intent to preserve annular–papillary muscle continuity. This valve, in 2 configurations—with (n = 5) and without (n = 5) flap chordae—was implanted in 10 sheep (mean weight 73 ± 9 kg). Epicardial echocardiography was performed to assess valve performance. Load-independent left ventricular function was also estimated before implantation (baseline), 1 hour after discontinuing cardiopulmonary bypass (rest), and during dobutamine stimulation using conductance technology. Results Implantation was easily accomplished for both configurations. Both configurations had low transvalvular pressure (mean 2.1 ± 1.2 mm Hg at rest; 2.2 ± 1.0 mm Hg with dobutamine stimulation with flap chordae; 1.7 ± 0.5 mm Hg and 1.6 ± 0.3 mm Hg without flap chordae). No mitral regurgitation was observed in 8 sheep, and mild regurgitation was seen in 2 sheep. Compared with baseline, slope of maximum rate of change of left ventricular pressure–end-diastolic volume relation increased with stimulation both with flap chordae (+52 ± 41 mm Hg · s −1 · mL −1 , P = .0005) and without (+20 ± 12 mm Hg · s −1 · mL −1 , P = .003). Conclusions Both configurations of this newly designed stentless mitral bioprosthesis, which preserves annular–papillary muscle continuity using different novel surgical implantation techniques, demonstrated reliable valve performance, with low transvalvular pressure gradients, minimal regurgitation, and acutely preserved postimplant left ventricular function. Further chronic study is needed to verify these results and evaluate reliability of implantation procedures, biocompatibility, and durability.

Objective: We tested a unique new device, the Myosplint device (Myocor, Inc, Maple Grove, Minn), which is designed to change left ventricular shape, reduce left ventricular wall stress, and improve left ventricular systolic function. Methods: Heart failure was induced in 15 dogs over 27 days by rapid pacing (230 beats/min). Seven animals underwent sham surgery, and 8 animals received 3 transventricular Myosplint devices each. Myosplint devices were tightened to create a symmetric bilobular left ventricular shape and were adjusted to produce a calculated 20% reduction in wall stress. Hemodynamic, 2-dimensional, and 3-dimensional echocardiographic studies were recorded at baseline, immediately after Myosplint placement (acute change), and at 1 month after both groups had a reduced rate (190 beats/min) of pacing designed to maintain heart failure. Results: The Myosplint group had significant sustained improvements in left ventricular ejection fraction from baseline, to the acute change, to 1 month (19% ± 5%; 36% ± 8%; 39% ± 13%) and reductions of left ventricular end-systolic volumes (73 ± 9 mL; 34 ± 5 mL; 42 ± 12 mL) and end-systolic wall stress by 39% (341 ± 68 10 3 dynes · cm – 2 to 206 ± 28 10 3 dynes · cm –2 ) acutely and 31% (372 ± 83 10 3 dynes · cm –2 to 250 ± 40 10 3 dynes · cm –2 ) at 1 month. There were no significant changes in mitral regurgitation. Conclusion: Application of a Myosplint device to a dilated impaired left ventricle resulted in reduced wall stress and improved left ventricular systolic function that was sustained at 1 month. Device-based shape change is a promising new opportunity to treat patients with dilated cardiomyopathy.