Assessment of biventricular cardiac function in patients with a Novacor left ventricular assist device.

Novacor left ventricular assist devices were implanted in 10 patients. We used blood-pool radionuclide angiography and echocardiography to evaluate the response of the left and right ventricle to the left ventricular assist. Radionuclide angiography was done before and after implantation of the Novacor left ventricular assist devices in all cases. All patients had diffuse left ventricular enlargement; the mean left ventricular ejection fraction before Novacor left ventricular assist device implantation was 17% +/- 7%. After implantation of the Novacor left ventricular assist devices the left ventricular ejection fraction improved to 47% +/- 19%, with the pump on a 1:1 assist ratio (p < 0.005). The right ventricular ejection fraction before the Novacor left ventricular assist device implantation was 21%, which improved to 32% with the Novacor left ventricular assist devices (p < 0.01). Doppler echocardiography was carried out in nine patients with the left ventricular assist devices. In five patients the aortic valve remained closed throughout systole. In four patients partial aortic valve opening was noted. At an assist ratio of 1:3, complete opening of the aortic valve was noted in all cases (n = 9); the left ventricular ejection fraction decreased to 31%. We conclude that the Novacor left ventricular assist device substantially improves both right ventricular ejection fraction and left ventricular ejection fraction, although the aortic valve typically remains closed.

A clinical trial comparing University of Wisconsin solution and cold cardioplegic solution with load-independent mechanical parameters.

To evaluate the efficacy of University of Wisconsin solution for clinical heart transplantation, load-independent parameters were used to assess left ventricular function after transplantation. Donor hearts were arrested with and stored in buffered cold cardioplegic solution for control (n = 5) and University of Wisconsin solution for the experimental group (n = 5). Orthotopic transplantations were performed in a routine manner. Mean donor age (cardioplegic solution, 28 +/- 5.2 years; University of Wisconsin solution, 28 +/- 5.1 years) and ischemic times (cardioplegic solution, 181 +/- 27 minutes; University of Wisconsin solution, 224 +/- 23 minutes) were similar. Two hours after reperfusion of the heart, transesophageal echocardiography was used to image the left ventricle at the mid-papillary muscle level, and a high-fidelity catheter-tipped manometer was placed in the left ventricle to record left ventricular pressure simultaneously. These images were digitized during apneic baseline conditions and during an acute reduction in preload from inferior vena caval occlusion. The left ventricular cross-sectional areas were measured and matched with left ventricular pressure from the catheter-tipped manometer to reveal pressure-area relationships. The baseline parameters fractional area change and stroke force were calculated. End-systolic elastance, the slope of end-systolic pressure-area relationship and preload recruitable stroke force, the slope of stroke force versus end-diastolic area were calculated from the inferior vena cava occlusion measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of bioprosthetic valve-associated thrombus in ventricular assist device patients.

BACKGROUND: Thromboembolic events may be related to thrombotic deposition on prosthetic valves. In a left ventricular assist device (LVAD) that contains two porcine pericardial bioprosthetic valves in addition to significant associated biomaterial placement, this may be particularly true. Thrombotic deposits on valves removed from LVADs at autopsy or heart transplantation were scored to determine (1) the nature and location of valvular deposition, (2) whether deposition was related to thromboembolic events, (3) correlations between deposition and patient hemodynamic and coagulation parameters, and (4) implant time dependency. METHODS AND RESULTS: Novacor LVADs were implanted in 23 patients as a bridge to transplantation for 1 to 303 days. Photographs of the concave (downstream) and convex (upstream) side of the inflow and outflow valve were made at explant and later scored for (1) total thrombus area (10 = equivalent of cusp area), (2) percent of cusp area occupied by solid thrombus, (3) thrombus color (10 = dark red, 0 = white), and (4) average percent of valve strut height involved with thrombus (from a side view). The inflow valve was shown to have heavier and redder deposition than the outflow valve. This was also true for the concave versus the convex side. Heaviest deposition was seen on the inflow valve concave side, which rests within the LVAD pumping sac and may be subject to poor convection. Patients with neurological thromboembolic events (8/23) during implantation had heavier deposition on the inflow valve concave side (5.7 +/- 2.7 versus 4.6 +/- 2.2, P < .05). Pump volumetric output was also found to negatively correlate with thrombus area on this valve and side (r = -.61, P = .002). Platelet release (platelet factor 4) was correlated with thrombus involvement on the upstream (convex) side of the inflow valve (r = .82, P = .002). No significant dependence of deposition on the implant time was found. CONCLUSIONS: Valve thrombus deposition was related to thromboembolic events. Pump volumetric output and platelet release were found to be related to deposition. These results may have implications for the role of hemodynamics and platelet activation in thromboembolism associated with prosthetic valve placement in general.

Isolated lung transplantation for patients with Eisenmenger's syndrome.

BACKGROUND: Eisenmenger's syndrome remains one of the greatest challenges in lung transplantation. METHODS AND RESULTS: Since October 1990, seven such patients with Eisenmenger's syndrome received isolated pulmonary grafts (six double lungs and one single lung). Mean patient age was 32 +/- 6 years (two men and five women). The preoperative mean pulmonary arterial pressure was 90.7 +/- 31.2 mm Hg, and the ventriculoscintigram showed markedly enlarged right ventricle and normal left ventricular function with ejection fraction of 0.660 +/- 0.115. Three atrial septal defects and four patent ducti arteriosus were repaired concomitantly. Excised lung histology showed plexogenic pulmonary arteriopathy with Heath-Edwards' grade 4 through 6. One double lung patient who had preexisting systemic vascular collapse died intraoperatively. The other six patients tolerated transplantation, and on the first operative day, mean pulmonary artery pressure decreased to 22.4 +/- 7.3 mm Hg (P < .002) and gas exchange was acceptable with an arterial/alveolar oxygen tension ratio of 0.47 +/- 0.15. Two patients died of mediastinal and pulmonary infection. The follow-up for the four survivors ranged from 13 to 25 months after transplantation. CONCLUSIONS: Our preliminary experience shows that concomitant isolated lung transplantation with cardiac repair could be a viable therapeutic option for patients with Eisenmenger's syndrome and normal left ventricular function. Dynamic right ventricular outflow obstruction is a potential hemodynamic problem in these pulmonary recipients.

Efficacy of antihypertensive medication in orthotopic heart transplant recipients and its effect on renal function.

The authors looked at 77 patients following orthotopic heart transplant who received a triple immunosuppressive regimen including cyclosporine to see the effect of various antihypertensive medications on mean arterial blood pressure and renal function. There were 62 men and 15 women retrospectively classified into three groups according to the antihypertensive medications they received. Group 1 included 26 patients followed up for 10.7 +/- 2.7 months who received hydralazine therapy. Group 2 included 32 patients followed up for 9.0 +/- 3.4 months who received angiotensin-converting enzyme inhibition therapy. Group 3 included 19 patients followed up for 10.1 +/- 3.3 months who received beta-adrenergic blocking agents. Mean arterial pressure (MAP), serum blood urea nitrogen (BUN), and serum creatinine (CR) were determined for each group at the start and end of the follow-up period. The MAP at the start of the study was 107 +/- 14 in group 1, 110 +/- 13 in group 2, and 100 +/- 11 in group 3. It was not statistically significantly different in any of the groups. At the end of the follow-up period, MAP was 112 +/- 10, 111 +/- 10, and 106 +/- 12 for the three groups respectively, and it was not significantly different in any group. The serum BUN in group 3 was 25 +/- 8 mg/dL at the start of the study, and it was not significantly lower than that in group 1, 28 +/- 6, but it was significantly different from that in group 2, 34 +/- 9, P less than 0.05. At the end of the follow-up period, the difference was still maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography.

Cardiac events from graft arteriopathy, including myocardial infarction, heart failure resulting from previous myocardial infarction, and sudden death, may limit long-term survival after heart transplantation. To determine the incidence of cardiac events and the use of coronary arteriography in predicting these events, the long-term results (mean follow-up, 3.5 years; standard deviation +/- 2.0) of heart transplantation in 427 patients were reviewed. Cardiac events included 19 cases of myocardial infarction, 13 cases of sudden death, and 10 cases of congestive heart failure. All these events occurred after the first year except for three cases of sudden death and one case of myocardial infarction. Cumulative incidence of cardiac events per patient year was 0.9% within the first year, increasing to 1.9% by 5 years. Cardiac events accounted for 3.8% of the deaths by the end of the first year, rising to 18% of total mortality by 7 years after heart transplantation. In patients dying after the first year of transplantation, deaths from sequelae of coronary artery disease occurred in 36% (20/55). The relative risk ("odds ratio") of any cardiac event was 3.44 (p less than 0.05) in patients with angiographic evidence of obstructive disease compared with those without evidence of disease, risk of cardiac death 4.6 (p less than 0.05) and risk of sudden death, 2.4 (not significant). Of the 13 patients who died suddenly, five seen at autopsy were found to have had a recent myocardial infarction. Of all patients who died of heart disease, recent myocardial infarction was detected in nine who were seen at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Donor-transmitted pneumonia in experimental lung allografts. Successful prevention with donor antibiotic therapy.

Bacterial pneumonia is the most common cause of early morbidity and mortality (less than 2 weeks) after heart-lung transplantation. The majority (76%) of cultures taken from human donor tracheas at the time of explant grew bacteria. The abnormal immune response of the lung allograft and the common finding of bacterial contamination of lung donors led us to hypothesize that clinically silent bacterial contamination of the donor lung progresses to pneumonia in the recipient and that antibiotic treatment of donors will prevent the development of pneumonia in the recipient. Inocula of Streptococcus pneumoniae were instilled into the left middle lobe of normal and donor dogs to identify the number of bacteria that would result in pneumonia in a normal animal and the amount that, when given to a donor, would result in pneumonia in the recipient. Initial studies established that inocula of 10(4) colony-forming units of S. pneumoniae did not result in pneumonia in normal or immunosuppressed animals. When 10(4) colony-forming units or as few as 10(2) were instilled into the left middle lobe of donors 24 hours before explantation and use of the lung for transplantation, severe acute bronchopneumonia developed in all 18 recipients. Treatment of donors with aerosol and intravenous antibiotics, but not with either alone, prevented pneumonia in the recipients. We conclude that bacterial contamination of the donor lung leads to pneumonia in recipients. Intravenous and aerosol antibiotic treatment of donors with bacterial contamination prevents pneumonia in canine lung recipients. Treatment of human donors with this antibiotic regimen may decrease the prevalence of early bacterial pneumonia.

Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation.

Review of 463 heart transplants was undertaken to examine the relationship between level of panel-reactive antibody (PRA) and a standard donor-specific lymphocytotoxic crossmatch (LXM) on the incidence of death from hyperacute, acute, and chronic rejection. Death from chronic rejection was defined as being caused by graft atherosclerosis. Hyperacute rejection was diagnosed in 18 allografts, and only two recipients had PRA greater than 10% and another two a positive LXM. Five-year actuarial freedom from death caused by all forms of rejection correlated with PRA values as follows: PRA 0% to 10% (415 patients), 85%; PRA 11% to 25% (29 patients), 68%; PRA greater than 25% (19 patients), 57% (p less than 0.005). Additionally, there was a positive linear relationship between PRA and duration of acute rejection episodes in the first 3 months after transplantation. A positive retrospective donor-specific LXM was present in 42 of 401 patients; most of them (32 patients) were low positive (10% to 50% cell death), and none could be correlated with antibody specificity toward donor HLA antigens. Five-year actuarial freedom from death caused by rejection was 83% in those with a negative LXM, 74% in those with low-positive, and 79% in those with high-positive LXM (p = NS). Negative LXM result did not reduce the risk of death caused by rejection in any of the PRA subgroups. While PRA greater than 10% is a risk factor for rejection-related events, a negative LXM in patients with an elevated PRA does not reduce the risk of death resulting from acute or chronic rejection.

Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression.

Lymphoproliferative disease developed in 15 heart and five lung transplant recipients during a decade of heart and lung transplantation from 1980 through 1989. The overall incidence of posttransplant lymphoproliferative disease in patients who survived more than 30 days is 4%. The incidence after heart transplantation is 3.4% and after lung transplantation is 7.9% (p = 0.08). The peak occurrence of posttransplant lymphoproliferative disease is 3 to 4 months after transplantation. However, posttransplant lymphoproliferative disease occurring early versus late (defined as before or after 1 year after transplantation) appears to have different clinical outcomes. The mortality of early onset of posttransplant lymphoproliferative disease as a result of lymphoma is 36%; response to reduction in immunotherapy occurs in 89% and presentation with disseminated disease occurs in 23%. The mortality of late onset of posttransplant lymphoproliferative disease as a result of lymphoma is 70%; no patient responded to reduction in immunotherapy and presentation with disseminated disease occurs in 86% of patients. Epstein-Barr virus primary infection was present in 14 and secondary Epstein-Barr virus infection was present in three of the 20 patients with posttransplant lymphoproliferative disease. The other three patients were positive for Epstein-Barr virus also but had no pretransplant sera for comparison. There is no correlation with immunoprophylaxis or maintenance immunosuppression and the development of posttransplant lymphoproliferative disease in our series.

Evolution of human cardiac myocyte dimension during prolonged mechanical support.

In animal models using left ventricular assist systems over long time periods, myocardial cellular atrophy has been reported, raising concern that prolonged clinical use of such systems might lead to deterioration in left ventricular function. At the University of Pittsburgh, long-term clinical use of the Novacor (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.) left ventricular support system for patients awaiting heart transplants has allowed study of the effects of long-term mechanical support on human subjects. This study determined that cardiac myocyte dimension is initially greater in patients with end-stage cardiac disease who require support rather than in patients with the same disease who do not require such support. Although myocyte dimension does decrease within a few days of the inception of support, this decrease merely brings cell size closer to the values usual in patients with chronic end-stage cardiac disease, and no further shrinkage is observed. Thus the Novacor left ventricular assist system does not appear associated with left ventricular atrophy, and its long-term use may not be detrimental to left ventricular function.

Heart transplantation in patients with malignant disease.

We have traditionally pushed the limits of conservative candidate criteria for heart transplantation. We have been gratified by our results in the aged, the diabetic, and the mortally ill. Our inclusion of patients with malignant disease underscores our philosophy to include patients as candidates for transplantation for whom the procedure has reasonable expectation of success. We report here our early results of heart transplantation in 11 patients with malignant disease. Our survival rate in this group is 100%, and all patients are leading active lives with no evidence of recurrent or metastatic tumor. Immunosuppression protocols were adjusted on an individual basis determined by the chemotherapy dosage, duration, and relation to transplantation. Whenever possible a 1-year disease-free interval after completion of adequate cancer therapy is desired before transplantation.