Rita L. Vargo

One hundred patients with the heartmate left ventricular assist device: Evolving concepts and technology

BACKGROUND Implantable left ventricular assist devices are common as a bridge to transplantation but are just reaching their goal as an alternative to transplantation. METHODS From December 1991 until December 1996, 97 left ventricular assist devices were implanted as a bridge to transplantation, one as an alternative to transplantation, and two as a bridge to recovery. Included were 64 pneumatic devices and 36 electric devices. Most patients (69%) had ischemic cardiomyopathy and most (53%) had had previous cardiac surgery. Preoperative circulatory support (extracorporeal membrane oxygenation) was used in 25. RESULTS Perioperative insertion of a right ventricular assist device was unusual (11%). The mean duration of support with a left ventricular assist device (bridge to transplantation) was 70 +/- 41 days (up to 206 days). Survival to transplantation was 76%. Cause of death included multiple organ failure (n = 13), perioperative stroke (n = 5), device failure (n = 5), and controller disconnect (n = 1). Significant risk factors for death included (1) preoperative need for ventilator or extracorporeal membrane oxygenation, (2) elevated blood urea nitrogen, creatinine, or bilirubin, and (3) low pulmonary artery pressures. Risks after insertion of the left ventricular assist device were reoperation for bleeding, support with a right ventricular assist device, dialysis, or device failure. Catastrophic failure of the device occurred 14 times in 12 patients and was treated by emergency pump exchange in six instances. Only two device-related thromboembolic episodes were detected. Positive blood cultures were found in 59% of patients, driveline infection in 28%, and pump infection in 11%. CONCLUSIONS The HeartMate device provided excellent hemodynamic support with low device-related thromboembolic events. Infection and reliability of the device contributed to the high cost of therapy. These areas need to be improved for the left ventricular assist device to attain its goal as a viable alternative to transplantation.

Early results with partial left ventriculectomy

OBJECTIVE We sought to determine the role of partial left ventriculectomy in patients with dilated cardiomyopathy. METHODS Since May 1996 we have performed partial left ventriculectomy in 53 patients, primarily (94%) in heart transplant candidates. The mean age of the patients was 53 years (range 17 to 72 years); 60% were in class IV and 40% in class III. Preoperatively, 51 patients were thought to have idiopathic dilated cardiomyopathy, one familial cardiomyopathy, and one valvular cardiomyopathy. As our experience accrued we increased the extent of left ventriculectomy and more complex mitral valve repairs. For two patients mitral valve replacement was performed. For 51 patients the anterior and posterior mitral valve leaflets were approximated (Alfieri repair); 47 patients also had ring posterior annuloplasty. In 27 patients (51%) one or both papillary muscles were divided, additional left ventricular wall was resected, and the papillary muscle heads were reimplanted. RESULTS Echocardiography showed a significant decrease in left ventricular dimensions after resection (8.3 cm to 5.8 cm), reduction in mitral regurgitation (2.8+ to 0), and increase in forward ejection fraction (15.7% to 32.7%). Cardiac index did not increase significantly (2.2 to 2.4 L/min per square meter). Eight patients (15%) required a perioperative left ventricular assist device; one died and was the only perioperative mortality (1.9%). At 11 months, actuarial survival was 87% and freedom from relisting for transplantation was 72%. CONCLUSIONS Improved selection criteria are necessary to avoid early failures, and much more follow-up and analyses of data are mandatory. However, the operation may become a biologic bridge, or even alternative, to transplantation.

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.

Screening Scale Predicts Patients Successfully Receiving Long-term Implantable Left Ventricular Assist Devices

BACKGROUND Although use of long-term implantable left ventricular assist devices (LVAD) is becoming more popular, further reduction of the mortality rate accompanying device insertion through improved patient selection would make this alternative even more appealing. We sought to develop a scoring system that was based on criteria obtainable at the time of evaluation and predictive of successful early outcome and simple to apply. METHODS AND RESULTS Patients (n = 56) undergoing LVAD insertion between 1990 and 1994 were screened for easily obtainable preoperative risk factors. To test the association between survival and each risk factor, a chi 2 analysis was performed, and relative risks were estimated. Oliguria, ventilator dependence, elevated central venous pressure, elevated prothrombin time, and reoperation stats had low probability values and high estimated relative risks. On the basis of these relations, a risk factor-selection scale (RFSS) (range, 0 to 10) was developed by computing appropriate weights for each risk factor. The distribution of patients for each scale score reveal that with RFSS > or = 5, most device recipients will die (P < .001). The average RFSS (+/- SD) of survivors (n = 42) was 2.45 +/- 1.73 compared with 5.43 +/- 2.85 in nonsurvivors (n = 14) (P < .0001). Univariate logistical regression was also significant (score statistic, 16.2; df = 1; P = .001). CONCLUSIONS The RFSS is simple, easy to apply, and statistically valid. Physicians could use the scale as a starting point in discussing the suitability for LVAD implantation in a specific patient and as a basis for comparing patient outcomes.

Effect of the Implantable Left Ventricular Assist Device on Neuroendocrine Activation in Heart Failure

BACKGROUND The HeartMate left ventricular assist device has been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement in their heart failure after HeartMate implantation, we studied the physiological effect of this device on the neurohormonal axis. METHODS AND RESULTS In 13 patients awaiting transplant (mean cardiac index, 1.7 +/- 0.3 L.min-1.m-2) who underwent HeartMate implantation, venous atrial natriuretic peptide, epinephrine, norepinephrine, plasma renin activity, angiotensin, and arginine vasopressin were measured immediately before insertion and at explant/transplantation. Mean time to explant was 86 +/- 40 days. All patients were taken off inotropic medications within 1 month. Mean cardiac index on support before explant was 3.1 +/- 0.9 L.min-1.m-2. Plasma renin activity decreased from 57 +/- 56 ng.mL-1.h-1 at baseline (before insertion) to 3 +/- 3 ng.mL-1.h-1 at explant (mean percent change, 92%; P < .001). Angiotensin II level decreased from 237 +/- 398 U/L at baseline to 14 +/- 14 U/L at explant (mean percent change, 73%; P < .001). Plasma epinephrine level fell from 6800 +/- 1323 pg/mL at baseline to 46 +/- 46 pg/mL at explant (mean percent change, 86%; P < .001). Norepinephrine level decreased from 2953 +/- 1457 pg/mL at baseline to 518 +/- 290 pg/mL at explant (mean percent change, 79%; P < .001). Atrial natriuretic peptide fell from baseline values of 227 +/- 196 to 168 +/- 40 pg/mL at explant (mean percent change, -49%; P = 519); and arginine vasopressin level decreased from 6 +/- 6 pg/mL at baseline to 0.8 +/- 0.5 pg/mL (mean percent change, 69%; P = .002). CONCLUSIONS We provide data supporting that the neurohormonal axis markedly improves after HeartMate implantation, providing biochemical confirmation of the improvement in hemodynamic status.

Factors Influencing HLA Sensitization in Implantable LVAD Recipients

BACKGROUND Patients bridged to transplantation (TX) with the implantable left ventricular assist device (LVAD) may be at increased risk for the development of panel-reactive antibodies (PRA) during support. METHODS To investigate that, we evaluated 60 patients who received the HeartMate LVAD at our institution, of whom 53 had PRA results available for analysis. T lymphocyte PRA levels were examined before LVAD, at the peak PRA level during LVAD support (PEAK), and just before TX. A PRA level more than 10% was considered indicative of sensitization against HLA antigens. RESULTS The only factor that had a significant effect on PRA levels before LVAD was patients sex (1.3% for men versus 7.4% for women; p = 0.005). During LVAD support, peak PRA levels increased significantly and the sex-associated differences were no longer evident (33.3% men, 34.3% women; not significant). At the time of TX, PRAs decreased to 10.9% (men) and 7.0% (women) (not significant). We examined the influence of blood products received before TX on PRA levels. Patients who received less than the median number of total units (median). When examined by the type of blood product, only the number of platelet transfusions significantly increased the peak PRA (median: 46.9%; p = 0.03). Patients who received blood that was leukocyte-depleted tended to have lower TX PRA levels (2.9%) compared with those who did not (13.9%, p = 0.18). Forty-two patients were successfully bridged to TX, with three early and two late deaths after TX. Whereas 39 patients received transplants without intervention, 3 were treated by plasmapheresis with a 77% reduction in their HLA antibody levels at TX as measured by flow cytometry. CONCLUSIONS Patients with the implantable LVAD are at significant risk for the development of anti-HLA antibodies during support. Although this sensitization is often transient, intervention using plasmapheresis may be useful for some patients.

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.

Does successful bridging with the implantable left ventricular assist device affect cardiac transplantation outcome

OBJECTIVES We sought to determine whether cardiac transplant recipients who required a bridge to transplantation with an implantable left ventricular assist device had a different outcome than patients who underwent transplantation without such a bridge. METHODS A retrospective study of 256 cardiac transplants from 1992 to 1996 included 53 patients who received the HeartMate left ventricular assist device and 203 patients who had no left ventricular assist device support. RESULTS Left ventricular assist device transplants increased from 8% of all transplants in 1992 (n = 63) to 32% in 1995 (n = 65) and 43% in 1996 (n = 14 year to date). Patients with and without left ventricular assist device had similar age and sex distributions. Left ventricular assist device recipients were larger (body surface area 1.96 vs 1.86 m2, p = 0.004). They were more likely to have ischemic cardiomyopathy (70% vs 45%, p = 0.001) and type O blood group (51% vs 34%, p = 0.06). All patients with left ventricular assist device and 42% of those without had undergone previous cardiac operations by the time of transplantation (mean number per patient 1.5 vs 0.3, p < 0.001). More patients in the left ventricular assist device group had anti-HLA antibodies before transplantation (T-cell panel reactive antibody level > 10% in 66% of left ventricular assist device group vs 15% of control group, p < 0.0001). Waiting time was longer for the left ventricular assist device than for patients in status I without a left ventricular assist device (median 88 vs 37 days, p = 0.002). There was no difference in length of posttransplantation hospital stay (median 15 days for each) or operative mortality (3.8% vs 4.4%). Mean follow-up averaged 22 months. No significant difference was found in Kaplan-Meier survival estimates. One-year survival was 94% in the left ventricular assist device group and 88% in the control group (difference not significant). Comparison of posttransplantation events showed no significant difference in actuarial rates of cytomegalovirus infection (20% vs 17%) or vascular rejection (15% vs 12%) at 1 year of follow-up. Similar percentages of patients were free from cellular rejection at 1 year of follow-up (12% vs 22%, p = 0.36). CONCLUSIONS Left ventricular assist device support intensified the donor shortage by including recipients who otherwise would not have survived to transplantation. Bridging affected transplant demographics, favoring patients who are larger, have ischemic cardiomyopathy, have had multiple blood transfusions and complex cardiac operations, and are HLA sensitized. Successfully bridged patients wait longer for a transplant than do UNOS status I patients without such a bridge, but they have similar posttransplantation hospital stay, operative mortality, and survival to those of patients not requiring left ventricular assist device support.

Preperitoneal insertion of the HeartMate 1000 IP implantable left ventricular assist device

During a 16-month period, 12 consecutive patients underwent insertion of a HeartMate 1000 IP left ventricular assist device in a preperitoneal pocket that separated the device from the abdomen. All patients were in cardiogenic shock awaiting heart transplantation. Preoperatively, the mean cardiac index was 1.6 L.min-1.m-2, with 11 patients on intraaortic balloon pump support and 2 on extracorporeal membrane oxygenation. The pocket was formed below the rectus abdominis and internal oblique muscles and above the posterior rectus sheath. The pump fit easily in all patients. One patient died of progressive multiorgan failure. Four patients are still on support. Seven patients underwent successful transplantation after a mean duration of 55 days of support (mean pump index was 3.1 L.min-1.m-2 during support). One patient had driveline revision because of an exit site infection but had successful transplantation. The pump was explanted without difficulty at each transplant operation. All patients having transplantation are alive and well. Preperitoneal insertion of the HeartMate left ventricular assist device can be safely performed and may avoid problems posed by intraabdominal left ventricular assist device insertion.

Pulmonary hypertension is not a risk factor for RVAD use and death after left ventricular assist system support

Unlike transplantation candidates, patients with pulmonary hypertension (PHTN) and a high transpulmonary gradient do not appear to be at increased risk for right ventricular dysfunction after left ventricular assist system implant. To verify this observation, we reviewed 63 patients supported with the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Patients were divided into two groups: patients with PHTN (47 patients) had mean pulmonary artery pressure > 30 mm Hg and/or pulmonary vascular resistance > 4 Wood units, and the remainder of patients did not have PHTN (16 patients). Both groups were similar in age (mean, 51 years), gender distribution (% men, 83% vs 94%, not significant), and number of patients with ischemic cardiomyopathy (72% vs 69%, not significant). More patients in the group without PHTN required extracorporeal membrane oxygenation support (38% vs 12%, p = .06). Right ventricular assist device support was instituted in five (11%) patients with PHTN and four (25%) patients without PHTN. A significantly larger number of patients without PHTN died while on support (14% vs 44%, p = .01). Survival after transplantation in both groups was > 90%. Patients with PHTN have higher transpulmonary gradient, show a significant decrease in pulmonary pressure after left ventricular assist system implantation, and have a higher transplantation rate compared to patients without PHTN. A larger patient cohort is needed to determine if the absence of PHTN is a risk factor for RVAD need and poor outcome after LVAS support.