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Cardiac-related sympathetic nerve activity during circulation with only the left ventricular assist device.

Circulatory maintenance with a left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation has been evaluated. To assess the effect on the autonomic nervous system, the sympathetic neurogram was analyzed by power spectrum and coherence function. LVAD were inserted between the left atrium and the descending aorta in seven adult mongrel dogs and ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with only LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed during maintenance of the circulation with only LVAD contributed to the sympathetic neurogram.

Animals

Sympathetic nerve activity during maintaining circulation with only left ventricular assist device.

Maintaining circulation with an left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation, was evaluated by the use of the sympathetic neurogram. To evaluate the influences of this method on autonomic nervous system, sympathetic neurogram was analyzed by power spectrum and coherence function. In acute animal experiments using mongrel dogs, LVAD were implanted. After the LVAD implantation, ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results suggest that the arterial pressure which was observed during maintaining the circulation with only LVAD contributed to sympathetic neurogram.

Animals

Differential regional function of the right ventricle during the use of a left ventricular assist device.

The use of a left ventricular assist device (LVAD) as a bridge to transplant is associated with a 52% incidence of RV failure requiring additional inotropic or mechanical support (RVAD). This study evaluated the differential performance of the RV free wall and septum to identify the need for additional RV support. Cross-sectional views of the RV were obtained immediately before, and 1 hr after, Novacor LVAS implantation in 12 consecutive patients using transesophageal echocardiography. Each image was divided into a free wall portion (FW) and a septal portion (SP) by grids drawn from the center of gravity of the end-diastolic endocardial outline to the junction between the FW and the SP. Percentage change between preimplant and postimplant for RV ejection fraction (RVEF), fractional area change for the FW (FAC-FW) and the SP (FAC-SP), and fractional shortening of the FW to SP distance (F-S) is reported for patients based upon the need for RV support: minimal (Group 1), maximal (Group 2). After LVAS implantation, patients showed a reduction in SP fractional area change. However, this reduction was most pronounced in Group 2. The degree of SP impairment may explain the mechanism of RV failure in patients on an LVAD.

Adolescent

In vitro evaluation of an implantable left ventricular assist device.

The development of implantable left ventricular assist devices (LVADs) has almost reached the stage of providing permanent circulatory support in patients who are unsuitable for, or denied, the transplant option. As part of our ongoing haemodynamic evaluation of the Thermo Cardiosystems Inc. (Boston, USA) Mark 14 pneumatic LVAD, pressure-volume loops have been produced from in vitro studies using a modified National Heart Lung and Blood Institute (NHLBI, USA) mock circulatory loop. These studies have demonstrated that during certain phases of the pump cycle non-physiologically high and low pressures are generated within the LVAD. Such abnormal pressures may damage either the bioprosthetic valves in the LVAD or the native heart, and may have adverse effects on cardiovascular control mechanisms.

Evaluation Studies as Topic

An abdominal left ventricular assist device: preclinical studies.

An abdominally positioned left ventricular assist device (ALVAD) has been evaluated in our most recent series of 25 calves weighing 99 plus or minus 12 kg. The ALVAD is a pneumatically actuated bladder pump, positioned subdiaphragmatically and connected between the left ventricular apex and the infrarenal abdominal aorta. The mean survival time in the calves was 41 days and the longest 65 days. The major effects of the pump are reduction of all indices of left ventricular work and increases in systemic perfusion. In the awake, unanesthetized calf, left ventricular pressure, dP/dt, and stroke work were decreased while peak aortic pressure, stroke volume, and cardiac output increased. These effects were corroborated at cardiac catheterization two to four weeks postoperatively; left ventriculograms also showed increases in ejection fraction. These data demonstrate the ALVAD's effectiveness in assuming left ventricular function and support over extended periods. The device has been developed for short-term postoperative clinical use in patients with reversible left ventricular failure.

Abdomen

Biolized intrathoracic left ventricular assist device (LVAD).

The design of an intrathoracic left ventricular assist device (LVAD) is briefly described. The unique feature of the LVAD is that all blood-contacting surfaces are biolized, having either chemically treated natural tissues or protein coatings. The blood-contacting surface of the housing is glutaraldehyde-treated pericardium and is covered with natural rubber and polyurethane. Tri-leaflet valves fabricated from human dura mater are used at the pump inlet; glutaraldehyde-treated bovine aortic valves are used at the outlet. The pumping diaphragm, made of polyolefin rubber with a textured surface, is coated with gelatin and treated with glutaraldehyde. Anticoagulants are not used with this device. Extensive in vivo and in vitro testing in the development of the pumps led to the current configuration having good performance, long life, and improved blood compatibility.

Animals

Myocardium-sparing cannulation technique for left ventricular assist device support.

The left atrium and the left ventricular apex are the most commonly used sites of inflow cannulation for postcardiotomy left ventricular support. A new cannulation technique that requires only an ascending aortotomy is introduced. This procedure can be undertaken with equipment present in any cardiac operating room and may prove to cause fewer complications than conventional cannulation techniques.

Aorta

Implantation technique for the HeartMate left ventricular assist device.

The technique for implanting the HeartMate, an intraabdominally placed, pulsatile left ventricular assist device, is described. This device, which has been developed for potential use in patients requiring permanent left ventricular assistance, is currently undergoing clinical investigation in patients requiring temporary support as they await cardiac transplantation. This clinical experience has demonstrated device safety and efficacy, even for patients requiring extended periods of support.

Abdomen

Prothrombin complex concentrate (PCC) vs. non-PCC strategies for warfarin reversal in left ventricular assist device recipients: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist devices (LVADs) prolong survival in end-stage heart failure, and warfarin thromboprophylaxis is recommended to prevent device thrombosis and thromboembolic complications. When bleeding occurs or emergency surgery is required, rapid anticoagulation reversal is critical. Prothrombin complex concentrate (PCC) provides rapid reversal; however, its risk-benefit profile in LVAD recipients remains unclear. We conducted a systematic review and meta-analysis comparing PCC with non-PCC strategies for warfarin reversal in LVAD recipients. METHODS: MEDLINE, Embase, and Scopus were searched through June 2025 for studies of PCC versus non-PCC strategies for warfarin reversal in LVAD recipients. Two reviewers independently extracted data. Random-effects models were used to pool arm-level estimates and to pool head-to-head comparisons using mean differences or risk ratios (RRs). RESULTS: Eighteen studies involving 779 patients were included. Arm-level pooled estimates for PCC versus non-PCC comparators were 24.0% versus 15.8% for mortality, 16.5% versus 12.1% for thrombotic events, and 3.1 versus 5.7 for FFP units. Arm-level time to INR correction was longer with PCC overall (16.5 versus 13.6 h), driven by one elective cohort, but faster within the ICH subgroup (6.0 versus 13.7 h). In head-to-head comparisons, PCC achieved faster INR correction than non-PCC comparators (mean difference - 7.6 h; p = 0.001) and required fewer FFP units (-2.6 units; p = 0.019), with no significant difference in all-cause mortality (RR 1.14; p = 0.490) or thrombotic events (RR 1.43; p = 0.176). CONCLUSIONS: In head-to-head studies, PCC was associated with faster INR correction and lower FFP requirements than non-PCC strategies, whereas mortality and thrombotic events did not differ significantly. Given the observational evidence, wide confidence intervals, and heterogeneity, equivalent safety cannot be established, and prospective studies are needed to define the relative safety and effectiveness of the two approaches. IMPLICATIONS FOR CLINICAL PRACTICE: PCC-based strategies may be considered for urgent warfarin reversal in LVAD recipients, particularly when rapid INR reduction or avoidance of large-volume plasma transfusion is clinically important. Treatment decisions should account for the indication, bleeding severity, and underlying thrombotic risk. TRIAL REGISTRATION: CRD42024573925.

Humans

Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization.

To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.

Assisted Circulation

Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device.

The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty-five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thromboembolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No device-related thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients (p greater than 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage cardiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology.

Adolescent

The Thermo Cardiosystems implantable left ventricular assist device as a bridge to cardiac transplantation.

The Thermo Cardiosystems left ventricular assist device is a very effective "bridge" to orthotopic cardiac transplantation in a select patient group. Because of the increasing shortage of available donor hearts nationally, the ability to bridge people to transplantation is very desirable. Also, this device does not require systemic anticoagulation and, to date, has not been associated with any embolic events in any of the 40 patients who have undergone implantation of the device.

Adult

Successful bridge to heart transplantation with a new left ventricular assist device.

During the last 5 years, a new pneumatically driven left ventricular assist device has been implanted in 18 heart transplantation candidates who required advanced mechanical circulatory support. The mean duration of support was 80 +/- 74 days, and the cumulative support time was 1400 days. Fifteen patients were successfully supported until the time of heart transplantation. As a result of early experience, in which three of four patients died after heart transplantation because their end-organ function failed to recover, subsequent efforts were made to institute support early, before irreversible organ damage occurred. Eleven of the 12 patients in the later experience are currently alive and well at a mean follow-up of 12.6 +/- 7.5 months. No thromboembolic episodes occurred, and minimal anticoagulation was required. Furthermore, patients were able to participate in rehabilitative exercise programs, thus optimizing their transplantation status. Finally, the findings in these patients have shown the feasibility of providing long-term, or even permanent, cardiac assistance.

Adult

First significant animal survival with a Wankel-type left ventricular assist device.

The authors' laboratory is developing a device for heterotopic left ventricular assistance. It consists of a titanium Wankel-type rotary pump, driven by an hermetically sealed electric motor. In our animal experiments, the motor-pump unit was implanted in the thoracic wall. The pump was connected to the left heart chambers by left atrial cannulation, and to the descending aorta. The motor was connected to the power and control unit by an electric wire through the skin. In this report, the authors describe the first significant animal survival with this system. Laboratory results were encouraging for hemolysis. The pump failed at 13 days due to a deposit of fibrin and blood cells in the gear housing. This problem was not surprising since similar events have been encountered with centrifugal devices. However, further design improvements should allow longer animal survival and clinical application.

Animals

Quantitation of right ventricular shape changes after left ventricular assist device implantation.

Complex effects of left (LV) and right ventricular (RV) interaction account for changes in RV function during LV assist device (LVAD) support. It has been hypothesized that changes in RV cross-sectional shape (RVS) may be a contributing factor in the development of RV dysfunction during LVAD support. To test the hypothesis that the RVS would become more circular as a result of septal shift during LVAD support, 13 patients were studied before and after LVAD implantation. The shape of the RV was quantified using a shape factor (SF) that was equal to (4 x pi x area)/P2, where P is the perimeter of RVS. The RV area and perimeter were measured from digitized images of the RV obtained by transesophageal echocardiography in patients before and after LVAD implantation. The group SF increased considerably after LVAD (SFpre = 0.78 +/- 0.12 versus SFpost = 0.88 +/- 0.07, p < 0.05). Patients were divided into three groups: 1) patients whose RV exhibited a low SF pre-LVAD that increased significantly, 2) those with a moderate SF pre-LVAD that increased slightly, and 3) those who had high pre-LVAD SF (< 0.90) that did not change. The decompression of the LV caused by LVAD implantation results in a shift of the septum from right to left, increasing SF. This increase is more pronounced in some patients. Quantitation of the degree of RV SF change may help predict the development of RV failure during LVAD support.

Adult

Angiotensin-Neprilysin Inhibition and Left Ventricular Assist Device Therapy: Primary Results of the ENVAD-HF Trial.

BACKGROUND: The role of heart failure-specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers. OBJECTIVES: ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients. METHODS: ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes. RESULTS: In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: -1.09 [95% CI: -1.52 to -0.66]; P < 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011). CONCLUSIONS: ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population. (Sacubitril/Valsartan in Left Ventricular Assist Device Recipients [ENVAD-HF], NCT04103554; A multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients, 2019-003888-22).

Humans

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Improved regional myocardial blood flow, left ventricular unloading, and infarct salvage using an axial-flow, transvalvular left ventricular assist device. A comparison with intra-aortic balloon counterpulsation and reperfusion alone in a canine infarction model.

BACKGROUND: It has been suggested that left ventricular unloading at the time of reperfusion provides superior infarct salvage over reperfusion alone. The purpose of this study was to show that the Hemopump transvalvular axial-flow left ventricular assist device provides superior left ventricular unloading, ischemic zone collateral blood flow, and infarct size reduction compared with intra-aortic balloon counterpulsation and reperfusion alone. METHODS AND RESULTS: Eighteen dogs were instrumented with regional myocardial function sonomicrometers in the ischemic and control zones. The left anterior descending coronary artery just distal to the first diagonal branch was instrumented with a silk snare and Doppler flow probe. Additionally, pressure catheters were placed in the left atrial appendage, left ventricular apex, and ascending aorta for hemodynamic measurements. Regional myocardial blood flow was determined by using 15-microns radioactive microspheres. Measurements were made in the control state, immediately after coronary occlusion, at 1 and 2 hours after coronary occlusion, with reperfusion, and 1 hour after reperfusion. In treated animals, left ventricular assistance was maintained during the entire period of occlusion and reperfusion. The Hemopump was associated with a significant decrease in left ventricular systolic and diastolic pressure, whereas mean arterial pressure was maintained. Intra-aortic balloon counterpulsation resulted in no significant changes in left ventricular systolic pressure and a modest decrease in left ventricular diastolic pressure. Regional unloading as assessed by sonomicrometers was significant in the Hemopump animals and absent in the balloon pump animals. Absolute regional myocardial blood flow in the ischemic zone increased slightly (p = 0.002) in the Hemopump animals and did not change in the balloon pump animals. Infarct size expressed as percentage of the zone at risk was 62.6% in the control animals, 27.22% in the balloon pump animals, and 21.7% in the Hemopump animals. CONCLUSIONS: Mechanical unloading of the ventricle during ischemia and reperfusion appears to result in significant infarct salvage compared with reperfusion alone. The Hemopump appears to provide superior left ventricular systolic and diastolic unloading compared with intra-aortic counterpulsation in a canine model.

Animals