Pulmonary hypertension in patients with bronchiolitis obliterans syndrome listed for retransplantation.

Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.

Aspergillus and endobronchial abnormalities in lung transplant recipients.

STUDY OBJECTIVE: To determine the relationship between aspergillus recovery from the airways of lung transplant recipients and the development of endobronchial abnormalities. DESIGN: Retrospective case series. SETTING: Tertiary-care hospital. PATIENTS: All patients who underwent lung transplantation between December 1991 and June 1999. MEASUREMENTS AND RESULTS: The study cohort included 38 patients. The primary end point was the bronchoscopic identification of an endobronchial abnormality. Aspergillus was isolated from the lungs of nine patients (23.7%). Most of these isolates occurred early after transplantation (mean, 8 weeks). Endobronchial abnormalities arose in seven of the patients (18.4%) and manifested as either exuberant granulation tissue or stricture formation. Six of the 9 (66.6%) patients with aspergillus developed airway lesions, compared to 1 of the 29 patients (3.4%) without aspergillus (p = 0.0002). Endobronchial abnormalities were 19.3 times more likely to occur in patients in whom aspergillus had previously been isolated. As a screening test for the subsequent diagnosis of an airway complication, the recovery of aspergillus had a sensitivity and specificity of 85.7% and 90.3%, respectively. These aspergillus-related endobronchial abnormalities were clinically relevant as evidenced by a mean increase of 25.9% in the FEV(1) after bronchoscopic intervention. CONCLUSION: The early isolation of aspergillus from the airways of lung transplant recipients identifies patients at increased risk for the development of clinically significant endobronchial abnormalities.

Successful use of cyclosporine in a lung transplant recipient with tacrolimus-associated hemolytic uremic syndrome.

Hemolytic-uremic syndrome (HUS) is a rare, but well-described complication in organ transplant recipients maintained on cyclosporine immunosuppression. Tacrolimus is a newer agent with similar immunosuppressant efficacy. In cases of cyclosporine-related HUS in renal transplant recipients, tacrolimus has been used successfully without recurrence of HUS. Tacrolimus has been reported to cause HUS in renal and more recently in cardiac transplant patients. We report a case of HUS in a lung transplant recipient receiving tacrolimus who was subsequently converted to cyclosporine without recurrence of HUS.

Prediction of the mechanisms of enzyme-catalysed reactions using hybrid quantum mechanical/molecular mechanical methods.

The use of hybrid methods, involving both quantum mechanics and molecular mechanics, to model the mechanism of enzyme-catalysed reactions, is discussed. Two alternative approaches to treating the electrostatic interactions between the quantum mechanical and molecular mechanical regions are studied, involving either the inclusion of this term in the electronic Hamiltonian (QM/MM), or evaluating it purely classically (MO + MM). In the latter scheme, possible problems of using force fields that are standard for macromolecular modelling are identified. The use of QM/MM schemes to investigate the mechanism of the enzymes thymidine phosphorylase (ThdPase) and protein tyrosine phosphatase (PTP) is described. For both systems, transition states have been identified using a PM3 Hamiltonian. For ThdPase, concerted motion of the enzyme during the course of the reaction is suggested and, for PTP, a two-step dephosphorylation reaction is indicated, both with quite low barriers.

Cardiac assist devices.

The two primary goals of mechanical circulatory support are to provide adequate perfusion of the vital organs and to decrease cardiac work. The support of the myocardium is in an effort to cause a reversal of cardiac damage. The recovery process apparently takes place in two stages. Initially, there is a rapid functional recovery of cells in marginally ischemia areas. Then there is a slower process of hypertrophy of normal and recovering myofibers. The process involves the reversal of interstitial and of intercellular myocardial edema in areas of viable myocardium while halting the extension of necrosis into reversibly ischemic areas. It appears that this process is extended from 3 to 5 days, and functional recovery can occur for up to 2 weeks. After a 2-week period, there appears to be little functional recovery of myocardial cells. In autopsy series of nonsurvivors, it appears that most of the patients had suffered from biventricular failure. Biventricular failure appears to be one of the more common complications of the support patient. Right ventricular failure will be attempted to be supported by right ventricular assist devices. The right ventricular assist device, unfortunately, adds a level of complication to the recovery process for the bridge-to-transplant or cardiomyopathy patient. The patients who are involved in support fall into three categories: (1) the bridge-to-transplant patient, (2) the patient recovering from postcardiotomy, and (3) the patient who recovers from an acute myocardial insult. It appears that after 2 weeks the recovery period for all of these groups demonstrates no further functional recovery. The bridge-to-transplant patients usually need to be supported until the transplant occurs. The postcardiotomy patient and the acute myocardial failure patient are the most disappointing support group, since they have a higher morbidity and mortality, and a lower chance of recovery. Salvage rates appear to be in approximately the 25% range in the acute insult category.

Synovial sarcoma of the heart. Correlation with cytogenetic findings.

A primary sarcoma of the heart was submitted to cytogenetic studies, which showed a translocation t(X;18)(p11;q11.2). The translocation between X and 18 is a characteristic one in synovial sarcoma of the lower extremities. As the histological appearance was not helpful for further classification of this primary sarcoma, karyotypic analysis proved useful in confirming diagnosis of synovial sarcoma, which, to our knowledge, is an uncommon neoplasm in the heart.

Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system.

OBJECTIVE: This nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. METHODS: Outcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria: pulmonary capillary wedge pressure > or = 20 mm Hg with a systolic blood pressure < or = 80 mm Hg or a cardiac index < or = 2.0 L/minute/m2. In addition, none of the patients met predetermined exclusion criteria. RESULTS: More LVAS patients than control patients survived to transplantation: 53 (71%) versus 12 (36%) (p = 0.001); and more LVAS patients were alive at 1 year: 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days; range, < 1-344 days) than in the control group (average, 12 days; range, 1-72 days). In the LVAS group, the average pump index (2.77 L/minute/m2) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m2) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). CONCLUSIONS: The LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS group, pretransplant mortality decreased by 55%, and the probability of surviving 1 year after transplant was significantly greater than in the control group (90% vs. 67%, p = 0.03). Thus, the HeartMate IP LVAS proved safe and effective as a bridge to transplant and decreased the risk of death for patients waiting for transplantation.

Artificial circulatory support with textured interior surfaces. A counterintuitive approach to minimizing thromboembolism.

BACKGROUND: Although numerous left ventricular assist devices (LVADs) have been used clinically, frequent thromboembolic complications have been reported despite the smooth interior LVAD surfaces and systemic anticoagulant medication. In contrast, the Thermo Cardiosystems HeartMate 1000 IP LVAD has textured interior surfaces that are promptly covered by a densely adherent neointima. We hypothesize that elimination of a direct interface between prosthetic material and blood elements reduces the risk of peripheral embolization and minimizes the necessity for systemic anticoagulant medication. This report defines the thromboembolic risk of this type of LVAD and characterizes the nature and effectiveness of the various anticoagulation regimens that were tested during the initial clinical trial with this device. METHODS AND RESULTS: All values are reported as mean +/- SD. Fifty-four males and three females with an average age of 47 +/- 11 years were supported with the HeartMate 1000 IP LVAD for an average of 62 +/- 76 days at 11 clinical centers in the United States. Patients were prospectively evaluated for thromboembolic complications. Five different anticoagulation regimens were used during the first 4 postoperative weeks: no anticoagulants, low-molecular-weight dextran, heparin, dipyridamole plus aspirin, or miscellaneous agents. After the first 4 weeks, the patients were treated with aspirin plus dipyridamole or miscellaneous agents. Prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen values for the patients were measured at 0.1, 1, 2, 4, 8, 12, 16, 20, 24, 32, and 46 weeks during support. Two patients (3.5%) suffered thromboembolic cerebrovascular complications, an incidence of 0.2 episodes per patient-year of observation. One episode was due to fungal vegetation developing on the device and the other was due to embolization from a previously placed native mechanical aortic valve prosthesis. In the absence of infection, there were no device-related thromboembolic complications. Mean prothrombin time for all groups was 13.3 +/- 0.5 seconds with no significant intergroup differences. Mean partial thromboplastin time during the first 4 weeks for the heparin-treated group was 53.3 +/- 6.6 seconds, which was significantly longer than for all other groups, but fell to control values after heparin was discontinued at 4 weeks. Mean fibrinogen level for all groups was 370 +/- 48 mg/dL, with no intergroup differences. CONCLUSIONS: The HeartMate 1000 IP LVAD provides adequate circulatory support with a low risk of thromboembolism despite minimal systemic anticoagulation. The use of textured surfaces may be an important factor contributing to the low observed risk of thromboembolic complications.

A reliable bridge to cardiac transplantation: the TCI left ventricular assist device.

The Thermo Cardiosystems (TCI) HeartMate, a pneumatically driven, implantable left ventricular assist device, was designed for long-term support of the failing heart. Between February 1990 and August 1992, the HeartMate was implanted in 11 heart transplant candidates because of profound deterioration of left ventricular function. Patients had a mean cardiac index of 1.6 L.min-1 x m-2 and a mean pulmonary capillary wedge pressure of 33 mm Hg despite maximal pharmacologic support with at least three inotropic medications. In addition, 5 patients were being supported with an intraaortic balloon pump. Nine patients were bridged successfully to cardiac transplantation. The mean cardiac index after implantation of the left ventricular assist device was 3.2 L.min-1 x m-2. Support ranged from 2 to 143 days (mean duration, 60 days). One patient died early of low output secondary to right heart failure, and a second died of air embolism, which occurred intraoperatively. All surviving patients became fully ambulatory. There were no thromboembolic complications during a total of 658 patient-days of support on a regimen of only 80 mg of aspirin daily. The 9 bridged patients are currently alive 4 to 34 months after transplantation. The TCI HeartMate provides safe and effective hemodynamic support with low risk of complications and virtual freedom from thromboembolism on a regimen of minimal anticoagulation.

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.

Surgical complications in bridging to transplantation: the Thermo Cardiosystems LVAD.

Left ventricular assistance with a number of different devices has been used to successfully bridge patients to cardiac transplantation. Surgical complications or complications related to the device itself, however, may preclude transplantation or lead to death. We report our recent experience with the Thermo Cardiosystems model 14 "HeartMate" left ventricular assist device in 3 patients. The device was implanted for 15 to 95 days. Complications included mediastinitis and peritonitis associated with the device in place before transplantation, and colonic perforation, and a late diaphragmatic hernia after transplantation. Despite these and other minor complications, all 3 patients underwent successful cardiac transplantation. Mechanical support for the right ventricle was not necessary. The Thermo Cardiosystems left ventricular assist device provided excellent support in a range of physiological conditions with no mechanical malfunction despite the surgical complications.

Mediastinitis complicating successful mechanical bridge to heart transplantation.

A 22-year-old man with severe end-stage cardiomyopathy required placement of a left ventricular assist device. Purulent mediastinitis and peritonitis developed while the device was in place. The patient survived a prolonged course of treatment, with mediastinal and peritoneal irrigation and parenteral antibiotics, before undergoing a successful heart transplantation 12 weeks after placement of the left ventricular assist device.

Cardiac transplantation in situs inversus.

Transplantation of the heart was successfully performed in a patient with situs inversus of the viscera and atria. Anatomic constants common to all patients allowed the left atrium, pulmonary artery, and aorta to be joined as usual in the transplant operation. Systemic venous reconstruction was the crux of the operation. A composite superior vena cava was reconstructed on the right side from the recipient translocated superior vena cava, donor superior vena cava and innominate vein, and recipient in situ pericardium. The inferior vena cava was rerouted from the left side across the midline to the right through a composite conduit consisting of the recipient night atrium and in situ pericardium over the diaphragm. These reconstructed venous passageways have remained patent and unobstructed for 1 1/2 years after the operation.

Coronary artery bypass surgery: emerging trends in mortality.

In a consecutive series of 4,697 patients undergoing coronary artery bypass surgery, these risk factors were found to be significant for increased postoperative mortality: age greater than 70, female sex, unstable angina, prior myocardial infarction, hypertension, diabetes mellitus, and ejection fraction less than .40. A comparison by year (1980-1988) revealed a steadily increasing incidence of these risk factors. Future analysis of coronary artery bypass mortality should include risk-factor stratification.

Cardiac transplantation in a regional center: goals and results at two years.

Cardiac transplantation moved from the realm of an investigational procedure to a therapeutic modality in the early 1980s. While one-year survival of 80 percent or greater can be expected, close follow-up is required to monitor for rejection, infection, and other late complications. With the need for close surveillance, both short and long-term, improved patient access to the transplantation center based on geographic proximity allows enhanced care by the original transplant team.

An avoidable pitfall in donor selection for heart transplantation. Utah Heart Transplant Program.

Evaluation of potential donors for heart transplantation is an important part of any heart transplantation program. Standard guidelines are being refined constantly to expand the donor pool. We present a case of carbon monoxide poisoning that led to severe myocardial damage in the transplanted heart.

Cardiac transplantation: goals and two-year results.

Results of cardiac transplantation have improved steadily following the first successful operation in 1967. However, rejection, infection, hypertension, hypercholesterolemia and accelerated coronary artery disease remain important late problems after successful heart transplantation. Facilitated patient access to the transplant center based upon geographic proximity to the home, family, and primary care physicians leads to enhanced care by allowing the original transplant team to remain actively involved with ease in the long-term follow-up. With this goal in mind, a cardiac transplantation center was developed with emphasis on developing an organized approach to providing care for patients with refractory congestive heart failure in the Virginia, West Virginia, Washington, D.C., Maryland, and Delaware area. Twenty-one of the 22 patients (95.4 per cent) survived and resumed active lives one to 26 months following heart transplantation. Forty-four rejection episodes occurred and were treated successfully, primarily on an outpatient basis. Only six infections were serious enough to require readmission to Fairfax Hospital, but all responded completely to treatment. Cardiac transplantation at a center focusing on regional patient care is not only less costly and more comfortable for patients and their families, but the continuity of care and comprehensive management of late complications can lead to improved long-term survival rates.

Major abdominal complications following cardiac transplantation. Utah Transplantation Affiliated Hospitals Cardiac Transplant Program.

Serious complications involving the alimentary tract are commonly reported following cardiac transplantation, and may be associated with significant morbidity and mortality. The aim of this report was to review the incidence, severity, and outcome of abdominal complications in our heart transplant population in whom we used corticosteroid-sparing protocols for immunosuppression. From March 1985 through September 1988, 178 patients underwent 185 cardiac transplants. Twenty-six cardiac transplant recipients (15%) sustained 33 major abdominal complications, including gastrointestinal bleeding (n = 8), pancreatitis (n = 8), bowel perforation (n = 6), cholecystitis (n = 4), and miscellaneous other problems (n = 7). Operative therapy was required in 61% of cases. No deaths were caused by the gastrointestinal complications of their operative management. Corticosteroid-sparing immunosuppression may be responsible for the low incidence of abdominal morbidity, and early, aggressive surgical intervention may reduce subsequent mortality.

OKT3 monoclonal antibody given for ten versus fourteen days as immunosuppressive prophylaxis in heart transplantation.

We have previously reported that murine antihuman monoclonal antibody OKT3 (Orthoclone OKT3) given for 14 days after heart transplantation is effective as immunosuppressive prophylaxis. The optimal protocol for OKT3 prophylaxis in heart transplantation is unknown, particularly the duration of OKT3 therapy. We conducted a consecutively allocated overlapping 6-month study with 68 heart transplant patients, comparing 14-day OKT3 (n = 34) to 10-day OKT3 treatment (n = 34). Both protocols included OKT3 given beginning 24 to 48 hours after operation, cyclosporine beginning on postoperative day 3, low-dosage steroids and azathioprine to prevent antibody production to OKT3, and a steroid pulse plus randomization to plus or minus vincristine after stopping OKT3. Pretransplant characteristics including age, sex, cause of congestive heart failure, and absence of positive pretransplant crossmatch were similar between the two groups. Although the infection rate was not significantly different between the two groups and mortality (one patient in each group) did not differ, 14-day prophylaxis decreased the number of treated rejection episodes per patient for the 6-month study (1.59 +/- 0.18 versus 2.24 +/- 0.19, p = 0.016). A 14-day course of OKT3 also decreased the risk of rejection during the 6-month follow-up period (p less than 0.05). In addition to having a decreased number of rejection episodes, patients in the 14-day protocol were also more likely to be withdrawn from maintenance steroids (79% versus 53%, p = 0.02). In conclusion, a measurable dose response efficacy can be demonstrated for 14-day versus 10-day OKT3 prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)