Kiyotaka Fukamachi

Preoperative Risk Factors for Right Ventricular Failure After Implantable Left Ventricular Assist Device Insertion

BACKGROUND Implantable left ventricular assist device (LVAD) insertion complicated by early right ventricular (RV) failure has a poor prognosis and is generally unpredictable. METHODS To determine preoperative risk factors for perioperative RV failure after LVAD insertion, patient characteristics and preoperative hemodynamics were analyzed in 100 patients with the HeartMate LVAD (Thermo Cardiosystems, Inc, Woburn, MA) at the Cleveland Clinic. RESULTS RV assist device support was required for 11 patients (RVAD group). RVAD use was significantly higher in younger patients, female patients, smaller patients, and myocarditis patients. There was no significant difference in the cardiac index, RV ejection fraction, or right atrial pressure between the two groups preoperatively. The preoperative mean pulmonary arterial pressure (PAP) and RV stroke work index (RV SWI) were significantly lower in the RVAD group (p = 0.015 and p = 0.011, respectively). Survival to transplant was poor in the RVAD group (27%) and was 83% in the no-RVAD group. CONCLUSIONS The need for perioperative RVAD support was low, only 11%. Preoperative low PAP and low RV SWI were significant risk factors for RVAD use.

Axial and centrifugal continuous-flow rotary pumps: A translation from pump mechanics to clinical practice

The recent success of continuous-flow circulatory support devices has led to the growing acceptance of these devices as a viable therapeutic option for end-stage heart failure patients who are not responsive to current pharmacologic and electrophysiologic therapies. This article defines and clarifies the major classification of these pumps as axial or centrifugal continuous-flow devices by discussing the difference in their inherent mechanics and describing how these features translate clinically to pump selection and patient management issues. Axial vs centrifugal pump and bearing design, theory of operation, hydrodynamic performance, and current vs flow relationships are discussed. A review of axial vs centrifugal physiology, pre-load and after-load sensitivity, flow pulsatility, and issues related to automatic physiologic control and suction prevention algorithms is offered. Reliability and biocompatibility of the two types of pumps are reviewed from the perspectives of mechanical wear, implant life, hemolysis, and pump deposition. Finally, a glimpse into the future of continuous-flow technologies is presented.

Alloreactive T Cell Responses and Acute Rejection of Single Class II MHC-Disparate Heart Allografts Are under Strict Regulation by CD4+CD25+ T Cells

Skin but not vascularized cardiac allografts from B6.H-2bm12 mice are acutely rejected by C57BL/6 recipients in response to the single class II MHC disparity. The underlying mechanisms preventing acute rejection of B6.H-2bm12 heart allografts by C57BL/6 recipients were investigated. B6.H-2bm12 heart allografts induced low levels of alloreactive effector T cell priming in C57BL/6 recipients, and this priming was accompanied by low-level cellular infiltration into the allograft that quickly resolved. Recipients with long-term-surviving heart allografts were unable to reject B6.H-2bm12 skin allografts, suggesting potential down-regulatory mechanisms induced by the cardiac allografts. Depletion of CD25+ cells from C57BL/6 recipients resulted in 15-fold increases in alloreactive T cell priming and in acute rejection of B6.H-2bm12 heart grafts. Similarly, reconstitution of B6.Rag−/− recipients with wild-type C57BL/6 splenocytes resulted in acute rejection of B6.H-2bm12 heart grafts only if CD25+ cells were depleted. These results indicate that acute rejection of single class II MHC-disparate B6.H-2bm12 heart allografts by C57BL/6 recipients is inhibited by the emergence of CD25+ regulatory cells that restrict the clonal expansion of alloreactive T cells.

AN INNOVATIVE, SENSORLESS, PULSATILE, CONTINUOUS-FLOW TOTAL ARTIFICIAL HEART: DEVICE DESIGN AND INITIAL IN VITRO STUDY

BACKGROUND We are developing a very small, innovative, continuous-flow total artificial heart (CFTAH) that passively self-balances left and right pump flows and atrial pressures without sensors. This report details the CFTAH design concept and our initial in vitro data. METHODS System performance of the CFTAH was evaluated using a mock circulatory loop to determine the range of systemic and pulmonary vascular resistance (SVR and PVR) levels over which the design goal of a maximum absolute atrial pressure difference of 10 mm Hg is achieved for a steady-state flow condition. Pump speed was then modulated at 2,600 +/- 900 rpm to induce flow and arterial pressure pulsation to evaluate the effects of speed pulsations on the system performance. An automatic control mode was also evaluated. RESULTS Using only passive self-regulation, pump flows were balanced and absolute atrial pressure differences were maintained at <10 mm Hg over a range of SVR (750 to 2,750 dyne.sec.cm(-5)) and PVR (135 to 600 dyne.sec.cm(-5)) values far exceeding normal levels. The magnitude of induced speed pulsatility affected relative left/right performance, allowing for an additional active control to improve balanced flow and pressure. The automatic control mode adjusted pump speed to achieve targeted pump flows based on sensorless calculations of SVR and CFTAH flow. CONCLUSIONS The initial in vitro testing of the CFTAH with a single, valveless, continuous-flow pump demonstrated its passive self-regulation of flows and atrial pressures and a new automatic control mode.

Reduced Pulsatility Induces Periarteritis in Kidney: Role of the Local Renin-Angiotensin System

OBJECTIVE The need for pulsatility in the circulation during long-term mechanical support has been a subject of debate. We compared histologic changes in calf renal arteries subjected to various degrees of pulsatile circulation in vivo. We addressed the hypothesis that the local renin-angiotensin system may be implicated in these histologic changes. METHODS AND RESULTS Sixteen calves were implanted with devices giving differing degrees of pulsatile circulation: 6 had a continuous flow left ventricular assist device (LVAD); 6 had a continuous flow right ventricular assist device (RVAD); and 4 had a pulsatile total artificial heart (TAH). Six other calves were histologic and immunohistochemical controls. In the LVAD group, the pulsatility index was significantly lower (0.28 +/- 0.07 LVAD vs 0.56 +/- 0.08 RVAD, vs 0.53 +/- 0.10 TAH; P < 0.01), and we observed severe periarteritis in all cases in the LVAD group. The number of angiotensin II type 1 receptor-positive cells and angiotensin converting enzyme-positive cells in periarterial areas was significantly higher in the LVAD group (angiotensin II type 1 receptor: 350 +/- 139 LVAD vs 8 +/- 6 RVAD, vs 3 +/- 2 TAH, vs 3 +/- 2 control; P < .001; angiotensin-converting enzyme: 325 +/- 59 LVAD vs 6 +/- 4 RVAD, vs 6 +/- 5 TAH, vs 3 +/- 1 control; P < .001). CONCLUSIONS The reduced pulsatility produced by a continuous flow LVAD implantation induced severe periarteritis in the kidneys. The local renin-angiotensin system was up-regulated in the inflammatory cells only in the continuous flow LVAD group.

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.

Initial safety and feasibility clinical trial of the myosplint device.

Abstract  Background: The Myocor™ Myosplint® device is a passive implantable device for the treatment of heart failure by changing the geometry of the left ventricle (LV). Aim: The purpose of this evaluation was to describe the first human experience with the Myosplint device to demonstrate safety and feasibility. Methods: Of the first consecutive 21 patients, 9 patients received a Myosplint device alone while 12 patients underwent a mitral valve repair as well. Safety and efficacy data were gathered at enrollment and during follow‐up. Results: No serious device‐related adverse events or device failures were observed. Three patients died during the follow‐up period, and 2 patients underwent heart transplantation. There was a significant improvement in the New York Heart Association (NYHA) functional class from 3.0 ± 0.3 at baseline to 2.1 ± 0.7 at 6 months (p = 0.001). Both LV end‐diastolic and end‐systolic volumes had decreased at follow‐up. The LV ejection fraction significantly increased in the Myosplint alone group (from 17.1 ± 4.0% at baseline to 21.8 ± 4.1% at 3 months and 23.1 ± 7.2% at 6 months) but not in the Myosplint and mitral valve repair group. The mitral regurgitation (MR) grade had a significant (p = 0.002) linear relationship with the NYHA functional class. Conclusions: The initial clinical experience of the Myosplint device demonstrated both safety and feasibility, validating the LV shape change concept in humans. A remodeling solution must, however, include MR resolution, to illustrate the need for a device that can simultaneously reduce or eliminate functional MR off‐pump.

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.

Speed modulation of the continuous-flow total artificial heart to simulate a physiologic arterial pressure waveform.

This study demonstrated the concept of using speed modulation in a continuous-flow total artificial heart (CFTAH) to shape arterial pressure waveforms and to adjust pressure pulsatility. A programmable function generator was used to determine the optimum pulsatile speed profile. Three speed profiles [sinusoidal, rectangular, and optimized (a profile optimized for generation of a physiologic arterial pressure waveform)] were evaluated using the CFTAH mock circulatory loop. Hemodynamic parameters were recorded at average pump speeds of 2,700 rpm and a modulation cycle of 60 beats per minute. The effects of varying physiologically relevant vascular resistance and lumped compliance on the hemodynamics were assessed. The feasibility of using speed modulation to manipulate systemic arterial pressure waveforms, including a physiologic pressure waveform, was demonstrated in vitro. The additional pump power consumption needed to generate a physiologic pulsatile pressure was 16.2% of the power consumption in nonpulsatile continuous-flow mode. The induced pressure waveforms and pulse pressure were shown to be very responsive to changes in both systemic vascular resistance and arterial compliance. This system also allowed pulsatile pulmonary arterial waveform. Speed modulation in the CFTAH could enable physicians to obtain desired pressure waveforms by simple manual adjustment of speed control input waveforms.