Faculty Bibliography

Tissue-engineered heart valves (TEHVs) are expected to be viable grafts. However, it is unknown whether they transit their histological structure after implantation. We developed a novel autologous TEHV (named stent biovalve) for transcatheter implantation, using in-body tissue engineering based on a tissue encapsulation phenomenon. In this study, a time-course histological transition of implanted biovalves was investigated in goats. Three types of stent biovalves were prepared by 2 month embedding of plastic molds mounted with metallic stents, in the subcutaneous spaces. After extracting the molds with tissue and removing the molds only, stent biovalves were constituted entirely from the connective tissues. Stent biovalves were implanted in the aortic or pulmonary valve position of other goats with transcatheter technique. In each animal, the stent biovalve was explanted at 1 month step (from 1 to 6 months) or as long as possible. Total 12 goats (five for aortic and seven for pulmonary) were successfully implanted. The maximum duration became 19 months as a result. Even then the leaflets of the biovalves kept their shape and elasticity, and neither calcification nor thrombi were observed in any cases and duration. Histology showed the recipients' cells covering the laminar surface of the leaflets like the endothelium even after 1 month. The cells have also migrated in the leaflets gradually and finally constructed characteristic 3 layered tissues like native leaflets. Implanted stent biovalves can adapt their histological structure to the environment. They have a potential as viable grafts keeping better function and biocompatibility.

The management of heart failure patients presenting in a moribund state remains challenging, despite significant advances in the field of ventricular assist systems. Bridge to decision involves using temporary devices to stabilize the hemodynamic state of such patients while further assessment is performed and a decision can be made regarding patient management. We developed a new temporary left ventricular assist system employing a disposable centrifugal pump with a hydrodynamically levitated bearing. We used three adult goats (body weight, 58-68 kg) to investigate the 30-day performance and hemocompatibility of the newly developed left ventricular assist system, which included the pump, inflow and outflow cannulas, the extracorporeal circuit, and connectors. Hemodynamic, hematologic, and blood chemistry measurements were investigated as well as end-organ effect on necropsy. All goats survived for 30 days in good general condition. The blood pump was operated at a rotational speed of 3000-4500 rpm and a mean pump flow of 3.2 ± 0.6 L min. Excess hemolysis, observed in one goat, was due to the inadequate increase in pump rotational speed in response to drainage insufficiency caused by continuous contact of the inflow cannula tip with the left ventricular septal wall in the early days after surgery. At necropsy, no thrombus was noted in the pump, and no damage caused by mechanical contact was found on the bearing. The newly developed temporary left ventricular assist system using a disposable centrifugal pump with hydrodynamic bearing demonstrated consistent and satisfactory hemodynamic performance and hemocompatibility in the goat model.

OBJECTIVES:Continuous-flow left ventricular assist devices (CF-LVADs) are widely used to treat patients with end-stage heart failure. Although continuous flow is different from physiological flow, patients show improved outcomes after CF-LVAD implantation. A novel rotational speed (RS) modulation system used with CF-LVAD (EVAHEART) has been developed, which can change RS in synchronization with the native cardiac cycle. We conducted the present study to investigate the influence of the system on pulsatility in peripheral perfusion. METHODS:We implanted EVAHEART devices at the left ventricular apex drainage and the descending aortic perfusion via a left thoracotomy in 7 adult goats (56.8 ± 8.1 kg). Cardiogenic shock was induced by a beta-adrenergic antagonist. We evaluated the pulsatility index and maximal time derivative of flow rate (max dQ/dt) of the carotid, mesenteric and renal arteries. These data were collected with a bypass rate of 100% under 4 conditions: circuit clamp, continuous mode, co-pulse mode (increased RS during systole) and counter-pulse mode (increased RS during diastole). RESULTS:The pulsatility indexes of the carotid and renal artery in the co-pulse mode were significantly higher than in the other modes. Max dQ/dt of the carotid and mesenteric arteries were significantly higher in the co-pulse mode than in the counter-pulse mode. CONCLUSIONS:The co-pulse mode of this novel RS modulation system may provide better pulsatility not only in the large vessels but also in the peripheral vasculature.

BACKGROUND:Femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to maintain blood flow in patients with cardiogenic shock. However, retrograde blood flow increases left ventricular (LV) afterload during femoral VA-ECMO. Additional support by means of an intraaortic balloon pump (IABP) alleviates LV afterload but is associated with significant adverse events. We previously developed a system for rotational speed modulation in synchrony with the native cardiac cycle, for use with implantable continuous-flow LV assist devices. Here, we aimed to evaluate whether our novel rotation speed modulation system can improve coronary artery flow and reduce LV during femoral VA-ECMO. METHODS:VA-ECMO was installed by means of right atrial drainage and distal abdominal aortic perfusion in six adult goats. Cardiogenic shock was induced with β-adrenergic antagonist infusion. An IABP was placed in the descending aorta. LV stroke work, LV end-systolic pressure, and coronary arterial flow were evaluated. Data were collected under five conditions (modes): baseline, circuit-clamp (cardiogenic shock), continuous mode (constant rotational speed), counterpulse mode (increasing rotational speed during diastole), and continuous mode with IABP support. RESULTS:LV stroke work and LV end-systolic pressure tended to be lower in the counterpulse mode, indicating decreased LV work load and afterload in this mode. Furthermore, coronary arterial flow tended to be higher in the counterpulse mode. CONCLUSIONS:Our system enabled an increase in coronary arterial flow and a decrease in LV work load and afterload during VA-ECMO. The system offers the effects of VA-ECMO and an IABP in a single device.

BACKGROUND:Fulminant myocarditis is a life-threatening disease, and myocardial damage expands the right ventricle as well as the left ventricle in some cases. There is a mortality rate of over 40% in patients with fulminant myocarditis who need mechanical circulatory support by peripheral venoarterial extracorporeal membrane oxygenation. CASE PRESENTATION/METHODS:We report a case of a 27-year-old Japanese woman who was successfully bridged to recovery by using a biventricular assist device. She was diagnosed with fulminant myocarditis, and peripheral venoarterial extracorporeal membrane oxygenation was established on the same day. Her left ventricular ejection fraction rapidly decreased from 40% to 5% in 3 days and weaning from venoarterial extracorporeal membrane oxygenation was deemed difficult. Therefore, we performed a ventricular assist device implantation on day 4. A left ventricular assist device was implanted first. However, adequate blood flow did not circulate to the left side of her heart because of right-sided heart failure. Thus, an additional implant of a right ventricular assist device was performed during the operation. Her left ventricular ejection fraction recovered to 50% on day 10. The biventricular assist device was successfully removed on day 14. She has not experienced worsening of biventricular function during her follow-ups for 4 years. CONCLUSIONS:Ventricular assist device therapy should be considered if there is no improvement in cardiac function in patients with fulminant myocarditis regardless of several days of support by venoarterial extracorporeal membrane oxygenation. A right ventricular assist device should always be implemented when necessary because biventricular involvement is not uncommon in fulminant myocarditis.

Excessive left ventricular (LV) volume unloading can affect right ventricular (RV) function by causing a leftward shift of the interventricular septum in patients with mitral regurgitation (MR) receiving left ventricular assist device (LVAD) support. Optimal settings for the LVAD should be chosen to appropriately control the MR without causing RV dysfunction. In this study, we assessed the utility of our electrocardiogram-synchronized rotational speed (RS) modulation system along with a continuous-flow LVAD in a goat model of MR. We implanted EVAHEART devices after left thoracotomy in six adult goats weighing 66.4 ± 10.7 kg. Severe MR was induced through inflation of a temporary inferior vena cava filter placed within the mitral valve. We evaluated total flow (TF; the sum of aortic flow and pump flow [PF]), RV fractional area change (RVFAC) calculated by echocardiography, left atrial pressure (LAP), LV end-diastolic pressure (LVEDP), LV end-diastolic volume (LVEDV), and LV stroke work (LVSW) with a bypass rate (PF divided by TF) of 100% under four conditions: circuit-clamp, continuous mode, co-pulse mode (increased RS during systole), and counter-pulse mode (increased RS during diastole). TF tended to be higher in the counter-pulse mode. Moreover, RVFAC was significantly higher in the counter-pulse mode than in the co-pulse mode, whereas LAP was significantly lower in all driving modes than in the circuit-clamp condition. Furthermore, LVEDP, LVEDV, and LVSW were significantly lower in the counter-pulse mode than in the circuit-clamp condition. The counter-pulse mode of our RS modulation system used with a continuous-flow LVAD may offer favorable control of MR while minimizing RV dysfunction.

We have developed a rotational speed (RS) modulation system for a continuous-flow left ventricular assist device (EVAHEART) that can change RS in synchronization with a patient's electrocardiogram. Although EVAHEART is considered not to cause significant acquired von Willebrand syndrome, there remains a concern that the repeated acceleration and deceleration of the impeller may degrade von Willebrand factor (vWF) multimers. Accordingly, we evaluated the influence of our RS modulation system on vWF dynamics. A simple mock circulation was used. The circulation was filled with whole bovine blood (650 mL), and the temperature was maintained at 37 ± 1°C. EVAHEART was operated using the electrocardiogram-synchronized RS modulation system with an RS variance of 500 rpm and a pulse frequency of 60 bpm (EVA-RSM; n = 4). The pumps were operated at a mean flow rate of 5.0 ± 0.2 L/min against a mean pressure head of 100 ± 3 mm Hg. The continuous-flow mode of EVAHEART (EVA-C; n = 4) and ROTAFLOW (ROTA; n = 4) was used as controls. Whole blood samples were collected at baseline and every 60 min for 6 h. Complete blood counts (CBCs), normalized indexes of hemolysis (NIH), vWF antigen (vWF:Ag), vWF ristocetin cofactor (vWF:Rco), the ratio of vWF:Rco to vWF:Ag (Rco/Ag), and high molecular weight multimers (HMWM) of vWF were evaluated. There were no significant changes in CBCs throughout the 6-h test period in any group. NIH levels of EVA-RSM, EVA-C, and ROTA were 0.0035 ± 0.0018, 0.0031 ± 0.0007, and 0.0022 ± 0.0011 g/100 L, respectively. Levels of vWF:Ag, vWF:Rco, and Rco/Ag did not change significantly during the test. Immunoblotting analysis of vWF multimers showed slight degradation of HMWM in all groups, but there were no significant differences between groups in the ratios of HMWM to low molecular weight multimers, calculated by densitometry. This study suggests that our RS modulation system used with EVAHEART does not have marked adverse influences on vWF dynamics. The low NIH and the absence of significant decreases in CBCs indicate that EVAHEART is hemocompatible, regardless of whether it is operated with the RS modulation system.

We report a case of a 44-year-old man with restenosis of coarctation of aorta (CoA). He had a history of descending aortic replacement for CoA using a graft 14 mm in diameter at 29 years ago. He had reoperation because of pressure gradient of 61 mmHg across the graft and intermittent claudication. Reoperation was done under unilateral lung ventilation with lung collapsed, through 3th and 5th interspace thoracotomy. Left lung adhesion was carefully released with an ultrasonically vibrating scalpel. After full heparinization, femoro-femoral bypass was started and descending aorta was clamped. The old graft was excised, and descending aortic replacement was done with a new graft of 26 mm in a diameter. His postoperative course was uneventful. The intermittent claudication disappeared.

A 44-year-old man was admitted with the diagnosis of active infective endocarditis( IE) due to Streptococcus mitis, complicated with infectious intracranial aneurysm. Preoperative echocardiography showed mobile vegetation on the mitral leaflet, size of which was 20 mm. The magnetic resonance imaging( MRI) demonstrated that the size of aneurysm was increasing, and infectious intracranial aneurysm was treated surgically. Twenty one days after the operation, the mitral valve plasty was performed. He was discharged on foot without any neurological findings. The duration between the brain surgery and the cardiac surgery was thought to be important to prevent the new neurological complication.