Alfredo Trento

Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone.

Coronary artery disease (CAD) has been shown in previous uncontrolled studies to be a limiting factor to long-term survival in patients undergoing cardiac transplantation and who were taking conventional immunosuppressive agents. To study the development of CAD after cardiac transplantation in patients taking the newer immunosuppressive agent cyclosporine, we prospectively performed yearly coronary arteriography on all eligible transplantation patients (first year, 57 patients; second year, 30 patients; third year, 14 patients). The prevalence of CAD by life table analysis was 18% at 1 year, 27% at 2 years, and 44% at 3 years. The occurrence of two or more major rejection episodes was associated (p less than .005) with the development of CAD. In two patients who died of CAD, coronary artery histology revealed subintimal inflammatory cellular infiltration in some lesions. These data demonstrate that the prevalence of CAD rises progressively over time and immunologic factors may be important in its development.

Heart-Lung Transplantation: Lessons Learned and Future Hopes

Since March, 1982, 33 patients have undergone cardiopulmonary transplantation. Nineteen were discharged from the hospital following the operation, and 16 continue to do well. Eight patients have survived 1 year, 5 patients 2 years, and 1 patient 3 years. Often survival has been influenced most by the selection of candidates, as no patient who had undergone a previous sternotomy survived (3 of 3). All 7 early (between 30 and 72 days) and 3 late (145 to 466 days) deaths were related to infection. Methods for ex vivo preservation of the heart-lung bloc have included storage at 4 degrees C, cardiopulmonary bypass and profound hypothermia, and autoperfusion of the heart-lung bloc. The last technique is original and currently is preferred for distant procurement. Because dehiscence of the tracheal anastomosis has occurred in 3 patients, a sutured line is now encircled with a wrap of omentum. Isolated rejection of the lung is frequent in the first three weeks following operation and has been controlled with methylprednisolone. Late survivors have shown a mild restrictive lung disorder that has not progressed between 6 and 24 months. Bronchoalveolar lavage has been useful for diagnosing infection and providing insight into the immunobiology of the transplanted lung. Although mortality and morbidity have been high, the experiences gained through this series will likely result in an improved outlook for future recipients.

Extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock in children

Size limitations and technical barriers prohibit the use of many conventional mechanical circulatory support systems for postcardiotomy ventricular dysfunction in pediatric populations. Extracorporeal membrane oxygenation (ECMO), frequently used to treat neonatal respiratory failure, can provide cardiac support and is effective treatment of postoperative myocardial failure in children. From 1981 to 1987, 10 patients aged 2 days to 5 years were maintained on ECMO for 15 to 144 hours (mean duration, 92 +/- 16 hours) after cardiotomy. Operative procedures included repair of tetralogy of Fallot (2 patients), closure of a ventricular septal defect (2), the Senning procedure for transposition of the great arteries (1 patient), repair of interrupted aortic arch with closure of a ventricular septal defect (1), repair of a partial atrioventricular septal defect (2), closure of a ventricular septal defect with excision of an anomalous muscle bundle (1), and the Fontan procedure (1). Venoarterial ECMO was established in all 10 children. Six patients underwent transthoracic right atrium-ascending aorta cannulation, 3 had right internal jugular vein-right common carotid artery cannulation through a cervical incision, and 1 had right internal jugular vein-left axillary artery cannulation. Eight of the 10 patients were successfully weaned from ECMO, and 7 are long-term survivors. There were 3 deaths; 1 was caused by cardiac and acute renal failure complicated by sepsis two days after decannulation, another occurred 19 days after atrioventricular septal defect repair, and 1 was caused by massive pulmonary hemorrhage. Major hemorrhage developed in 3 patients while on ECMO; 2 required premature decannulation for mediastinal bleeding from operative sites and ultimately survived, and 1 died of respiratory failure as a result of endobronchial bleeding. We conclude that the use of ECMO in pediatric populations for transient postoperative ventricular dysfunction improves survival with limited overall morbidity.

Lessons learned in pediatric heart transplantation

Between February 1, 1982, and June 30, 1988, 32 children underwent cardiac transplantation for treatment of congenital heart disease (10) and other cardiomyopathies (22). The 6-year actuarial survival was a disappointing 36% because of a high perioperative mortality (12 of 32, 37.5%) and because of five late deaths due to uncontrolable rejection. The perioperative mortality was a staggering 60% (6 of 10) for the patients with congenital heart disease. Four of the 6 recipients with congenital heart disease died because of acute failure of the donor right ventricle. This included 2 patients who required reconstruction of the pulmonary arteries for stenosis secondary to previous systemic-to-pulmonary shunts and 2 others in whom the pulmonary vascular resistances were underestimated because of undetected recent pulmonary emboli (1) and complicated pulmonary vascular anatomy (1). Five of the six late deaths were due to rejection-related events, and all were patients with acquired cardiomyopathy.

Clinical experience with the Medtronic-Hall valve prosthesis

Medtronic-Hall valves were implanted during 204 procedures performed between 1982 and 1988. Mean population age was 54.4 years; 96% of patients were in New York Heart Association functional class III or greater. Emergency operations constituted 16% of the procedures. Rheumatic heart disease was the single most common indication for valve replacement. In 18% of patients, operation was performed to replace a previous prosthetic valve. The mean follow-up was 3.2 years. Overall operative mortality was 10.3%, the highest mortality being for double-valve replacements (24%). Valve-related mortality, by position, was 5.3% for aortic valves, 6.0% for mitral valves, and 4.0% for multiple-valve replacements. Actuarial 5-year freedom from events were: survival, 68%; thromboembolism, 90%; prosthetic valve endocarditis, 98%; paravalvular leak, 95%; and reoperation, 92%. Complications with the highest mortality were thromboembolism (36%) and endocarditis (33%). The complication rates in this series are high but the patients were more severely ill than in other reports, and operative survivors experienced a considerable improvement in New York Heart Association functional class.

Extracorporeal Membrane Oxygenation Experience at the University of Pittsburgh

Between January, 1981, and May, 1985, 33 infants suffering from acute cardiorespiratory failure were treated with extracorporeal membrane oxygenation (ECMO) when all other forms of conventional management had failed. Only the patients with respiratory failure that was thought to be reversible were treated. Prolonged conventional respiratory management (more than five days) was considered a contraindication to ECMO support because of irreversible damage to the lungs caused by the barotrauma associated with conventional ventilation. Eighteen of the 33 patients (54%) survived and were discharged from the hospital. Patients with congenital diaphragmatic hernia had a high incidence of fatal bleeding complications (8 of 14). Good results were obtained in the newborns with persistent fetal circulation and meconium aspiration syndrome. We conclude that ECMO markedly improves the survival of newborns with severe respiratory failure who would have a mortality close to 100% with conventional respiratory management.

Asynchronous Rejection of Heart and Lungs Following Cardiopulmonary Transplantation

Eighteen patients have received 19 combined heart-lung allografts since March, 1982. During the maturation of our program of heart-lung transplantation, we have learned that isolated rejection of the lung can occur frequently and that exclusive dependence on the cardiac biopsy can be misleading. Of the 18 patients who received allografts, 10 are the basis for this report. The other patients were excluded because of death from excessive bleeding (1), inadequate lung preservation (2), an inability to differentiate rejection from infection (3), or an absence of rejection of either the heart or the lungs (2). Rejection of the lung was suggested, in the absence of clinical evidence of infection, by the radiographic appearance of a diffuse pulmonary infiltrate. It was confirmed by a prompt response to augmentation of maintenance immunosuppression with an intravenous pulse of methylprednisolone. The presence or absence of cardiac rejection was determined by the standard endomyocardial biopsy. Direct biopsy of the involved lung through a thoracotomy was performed in 4 patients so that a definitive histological diagnosis of rejection would reinforce the anticipated clinical diagnosis. The clinical course in 6 of the 10 patients plus the results of the open lung biopsy in 3 of them suggest that isolated rejection of the lung developed in the absence of cardiac findings. Patients responded within 12 to 24 hours to augmented immunosuppression with a dramatic improvement in the abnormal chest radiograph. In all 10 patients, either isolated lung or synchronous heart and lung rejection episodes were confined to the first six weeks after operation unless a severe alteration in the immunosuppression was made (2 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic abnormalities following cardiac transplantation: Relationship to hypertension and survival

The prevalence and long-term implications of hemodynamic abnormalities seen at 1 year following orthotopic heart transplantation and their relationship to post-transplant hypertension were prospectively evaluated in 82 consecutive asymptomatic recipients taking cyclosporine and prednisone who underwent annual catheterization. Abnormal left ventricular end-diastolic pressure (LVEDP), ejection fraction (EF), and left ventricular end-diastolic pressure-volume ratio (R) were the most prevalent hemodynamic abnormalities (27%, 14%, and 23%, respectively, at 1 year). Patients with abnormal LVEDP or R had higher (p less than 0.05) mean systemic arterial pressure (MAP). During follow-up, hemodynamic abnormalities disappeared in some patients while they developed in some others. Transplant patients with abnormal LVEDP, EF, or R at 1 year who normalized at 2 years had a significant (p less than 0.05) decrease in MAP. Likewise, patients with normal LVEDP, EF, or R at 1 year who subsequently developed abnormalities had a significant (p less than 0.05) increase in MAP. The presence of hemodynamic abnormalities at 1 year was not associated with a poorer survival (mean follow-up 2.6 +/- 1.1 years). In summary, hemodynamic abnormalities in asymptomatic transplant recipients taking cyclosporine and prednisone appear to be related to the level of post-transplant hypertension and do not signify an adverse prognosis over the first 3 years.

Massive Hemoptysis in Patients with Cystic Fibrosis: Three Case Reports and a Protocol for Clinical Management

The clinical management of massive hemoptysis in patients with cystic fibrosis proceeds according to the following paradigm. The site of bleeding is identified by bronchoscopy, ideally under general anesthesia. Then selective bronchial arteriography is performed. If collaterals to the spinal cord are visualized, arterial embolization is abandoned and pulmonary resection is undertaken within the limits of pulmonary function.