Rejection and infection after pediatric cardiac transplantation

Cardiac transplantation has only recently become an accepted therapeutic modality for children and adolescents with end-stage cardiomyopathy. Long-term survival, the incidence of rejection, and the incidence of infection are still being defined. From 1985 to 1989, 21 children aged 6 months to 19 years (average age, 11.2 years) underwent cardiac transplantation at our institutions. Eighteen survived the operative period and have been followed for 5 to 49 months (average follow-up, 24 months). All operative survivors have received triple-drug immunosuppression consisting of cyclosporine, azathioprine, and prednisone. During follow-up, 7 patients have been treated on 12 occasions for rejection as documented by endomyocardial biopsy. Eight (67%) of the 12 episodes of rejection occurred in the presence of subtherapeutic cyclosporine levels. Two of the 7 patients treated for rejection have subsequently died of ongoing cardiac rejection and arrhythmia. There have been no perioperative or late deaths from infection. Bacterial sepsis was identified and treated twice during follow-up, viral infections on five occasions, and fungal infection once. Actuarial 1-year survival and 3-year survival of the 18 operative survivors are 94% and 78%, respectively. In the first 7 months after cardiac transplantation, 73% of patients were free from rejection and 83% were free from serious bloodborne infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart- and heart-lung transplantation in children

Since January 1987, 16 prepubertal children have undergone heart (13) or heart-lung (3) transplantation. Immunosuppression included cyclosporine and azathioprine and excluded steroids except in case of rejection. The indications for heart transplantation were hypoplastic left heart syndrome (4 infants, mean age = 2 months), congenital heart disease (4 patients, mean age = 5.7 years) and cardiomyopathy (5 patients, mean age = 2.8 years). There were 4 early deaths (acute graft failure in 2, pulmonary hypertension in 1, infection in 1) and 1 late death (heart failure at 3 months). The 8 survivors had a mean follow-up of 12 months (range 1-19 months). Late complications were minimal. There were 4 episodes of rejection in 2 patients. There was no infection, normal somatic growth and no systemic hypertension. Renal function remained within normal limits although mild-to-moderate tubulointerstitial lesions were found in 4 renal biopsies. Three children (9-11 years old) underwent heart-lung transplantation. The early postoperative course was difficult with 6 episodes of rejection and 5 infections. One patient died at 3 months from infectious complications. One child has a complete rehabilitation 8 months posttransplantation. The last patient is clinically well at 7 months but has a residual tracheal stenosis. The long-term fate of these children, and particularly the long-term effects of cyclosporine therapy are unknown. Heart and heart-lung transplantation remain under investigation but may be reasonable approaches for infants and children with end-stage cardiac and/or pulmonary disease.     

The changing face of cardiac transplantation: the Washington University Program, 1985-1987

Since January, 1985, 59 patients have undergone 62 heart transplantations at Washington University School of Medicine. The experience in this program serves as a useful microcosm of the field of cardiac transplantation as a whole to demonstrate certain trends that are becoming evident. Of the patients, 47% had coronary artery disease compared with 40% with cardiomyopathy. Fourteen patients (24%) were 55 years old or older at the time of transplantation. Sixteen patients (27%) required mechanical support of respiration or circulation or both prior to transplantation. Six patients were maintained with a left ventricular or biventricular assist device, and all survived; 1 patient received extracorporeal membrane oxygenation and lived; 7 patients were maintained with an intraaortic balloon pump, 6 of whom survived; and 2 were maintained with a mechanical ventilator and survived. The preoperative waiting period averaged 51 days for the group as a whole. Status-3 patients experienced an average 81-day waiting period, and those in blood group O waited 155 days. In contrast, critically ill patients (status 0) underwent transplantation within an average of 9 days. Actuarial survival at 12 months for all patients, operative survivors, patients age 55 years old or more, and patients bridged to transplantation was 87%, 92%, 84%, and 87%, respectively. Utilizing the combination therapy of cyclosporine, azathioprine, and prednisone introduced by one of us in 1983 and administered to all patients in this series, 50% of patients were rejection free and 56% were infection free at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neonatal cardiac transplantation. Intermediate-term results and incidence of rejection. Loma Linda University Pediatric Heart Transplant Group.

Early age at cardiac transplantation may favor successful engrafting with minimal chronic immunosuppression. Fifty-two newborns underwent orthotopic heart transplantation; 47 (90%) survived the operation, and 44 (85%) were late survivors. Actuarial survival was 92% at 1 month, 86% at 1 year, and 84% at 5 years. Forty-four infants who survived 12 weeks and the corresponding 100 rejection episodes were analyzed. Mean follow-up was 2.2 years. The mean number of rejections per year of follow-up was 1.2. No episodes of rejection were identified in six patients. Seven patients had a late rejection episode more than 1 year after transplantation, and only one had a late rejection episode after 2 years. Neonatal cardiac transplantation is effective and durable therapy for uncorrectable heart disease. Intermediate-term results are excellent. Severe rejection is uncommon, and few episodes occur after 1 year of follow-up.     

Mid-term follow up results of Japanese heart transplant patients operated in UCLA Medical Center.

Japanese candidates have been accepted for heart transplantation by the UCLA Medical Center in the US since 1993 due to the lack of donors available from brain-dead patients. OBJECTIVES AND METHODS: We monitored to patients who underwent such heart transplantation and have been seen at the out-patient clinic at Tokyo Women's Medical University following transplantation. Pre-operative diagnosis was dilated cardiomyopathy in all patients. One patient underwent Novacor implantation as a bridge to heart transplant. All patients underwent cardiac echocardiography and cardiac catheterization including intraluminal echography. RESULTS: All patients survived with an actuarial survival curve of 100% at 1 year, 100% at 3 years and 87% at 5 years in 4.15 years of average follow-up. Two patients died due to liver dysfunction and cerebral emboli. The postoperative functional status of patients was New York Heart Association classification I in 8 (100%). Immunosuppressive therapies included triple drug therapy using either cyclosporin or tacrolimus. The incidence of acute rejection (/pt) exceeding grade 3 was 4% within three months, 3.5% in 3-6 months, and no significant rejection episode more than 6 months after transplantation. Posttransplantation coronary artery disease was seen in 2 patients, but no progression was seen after diltiazem therapy. CONCLUSION: Our postoperative follow-up after cardiac transplantation appears to be satisfactory.     

Intermediate term results of infant orthotopic cardiac transplantation from two centers

Orthotopic cardiac transplantation has become established for selected infants with severe forms of congenital heart disease. This study reviews the combined experience and intermediate term results of infants undergoing orthotopic cardiac transplantation from Children's Memorial Hospital, Chicago, and Kosair Children's Hospital, Louisville. From June 1986 through December 1989, 20 orthotopic cardiac transplantations were performed in 19 patients. Sixteen patients had variants of hypoplastic left heart syndrome. One infant had anomalous origin of the left coronary artery with severe ischemic cardiomyopathy. Two infants had aortic stenosis with endocardial fibroelastosis, and one had extracorporeal membrane oxygenation as a bridge to transplantation. Immunosuppression included cyclosporine, azathioprine (Imuran), and corticosteroids with an effort to wean the patients from steroids by 6 months to 2 years. Three early deaths resulted--from technical errors in two patients and from hyperacute rejection in one patient at 3 days. Four late deaths have occurred. Two patients died at 2 and 13 months of acute rejection. One patient died at 15 months of acute rejection after retransplantation. One patient died at 7 months of respiratory syncytial viral pneumonia. The remaining 12 patients are surviving 5 to 47 months (means 20 months) after orthotopic cardiac transplantation. Rejection surveillance in the first 6 months is by clinical signs supplemented by echocardiography, electrocardiography, and cell cycle analysis; endomyocardial biopsy is used after 6 months of age. For the cumulative series, 24 episodes of suspected rejection have been treated during 277 at-risk patient months with intravenous methylprednisolone (Solu-Medrol) (n = 18) and monoclonal antibody (OKT3) (n = 6), for an incidence of 1.04 episodes of rejection per patient per year. Serious posttransplantation infections including endocarditis, catheter sepsis, meningitis, and colonic perforation were successfully treated in four patients. Subjectively, their quality of life is excellent as shown by normal growth and developmental milestones and a low hospital readmission rate (1.4 episodes per patient per year). These encouraging intermediate term results warrant continued application of infant orthotopic cardiac transplantation for severe forms of congenital heart disease.     

Cardiac transplantation for hypertrophic cardiomyopathy: a valid therapeutic option.

BACKGROUND: Hypertrophic cardiomyopathy is a rare indication for cardiac transplantation, with only anecdotal reports in the literature. Transplantation has been proposed to patients with hypertrophic cardiomyopathy who remained symptomatic despite optimal medical treatment or who progressed to congestive heart failure, and when conventional surgical correction was not or was no longer possible. In this report, we analyze the clinical results of cardiac transplantation in these patients. METHODS: We retrospectively reviewed complete clinical data and prospectively gathered complete follow-up data for 14 patients who underwent orthotopic cardiac transplantation for hypertrophic cardiomyopathy at the Montreal Heart Institute and Ste-Justine Hospital between 1984 and 2001. RESULTS: Ten male (71.4%, 5 adults and 5 children) and 4 female (28.6%, 2 adults and 2 children) patients underwent heart transplantation for hypertrophic cardiomyopathy. The median age of the recipients in the pediatric group was 13 years (range, 6-16) and was 40 years (range, 22-46) in the adult group. Median duration of follow-up was 9.5 years (mean, 8.8 +/- 4.8 years; range, 1-18) and was 100% complete. We found no operative mortality and found 2 late deaths related to coronary graft atherosclerosis. Long-term survival at 5, 10, and 15 years was 100%, 85%, and 64%, respectively. Freedom from acute rejection at 1, 5, and 10 years was 73%, 32%, and 9%, respectively. The remaining 11 survivors exhibit few symptoms and are currently in New York Heart Association Class I or II. CONCLUSIONS: Cardiac transplantation is a valid therapeutic option for patients with symptomatic hypertrophic cardiomyopathy who do not respond to optimal medical management and who are not candidates for conventional surgical treatment. The long-term outcome is excellent in these patients.     

Heart transplantation in children: an international survey

A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor.     

Heterotopic heart transplantation--a means to increase donor availability

From November 1985 to August 1989, 105 patients underwent heart transplantation at our institution of whom 8 (7%) underwent heterotopic heart transplantation (HHTx). There were 7 males and 1 female with a mean age of 49 +/- 6 years (range, 41-58 years), 7 of whom had ischaemic cardiomyopathy and 1 had dilated cardiomyopathy. The indications for HHTx were gross donor/recipient size mismatch, unreliable donor heart, elevated pulmonary vascular resistance and the need for urgent transplantation or their combination. HHTx was performed as a left ventricular bypass in 6 patients and as biventricular bypass in 2 combined with various surgical procedures on the native heart in 5. There was one perioperative death with a mean follow-up of the survivors of 17 +/- 10 months (range, 6-30 months). Comparison of preoperative and postoperative (1 year) 2-D echocardiographic studies of the native heart showed haemodynamic stability of the latter with no substantial changes in left ventricular ejection fraction and cardiac index, while left ventricular end-diastolic volume tended to increase in 2 patients. In conclusion, preservation of the native heart allows recovery or growth of a graft considered unsuitable for orthotopic transplantation. Our experience confirms that HHTx may still be considered a valuable alternative to orthotopic transplantation in selected patients, thus expanding donor utilization.     

Surgical spectrum of aortic stenosis in children: a thirty-year experience with 257 children

Aortic stenosis accounts for 5 to 6% of infants and children seen for surgical repair of congenital heart disease. The clinical presentation and reported results of operation for aortic stenosis are highly variable. This retrospective review was undertaken to assess our operative mortality and the degree of gradient reduction afforded by each of several surgical techniques used to treat aortic stenosis in children over a 30-year period. Two hundred fifty-seven patients ranging in age from 1 day to 19 years were operated on between 1957 and 1986. The indication for operation included asymptomatic patients with gradients greater than 50 mm Hg to patients in profound cardiogenic shock. The operative mortality for children older than 6 months was 4%, whereas neonates seen with critical aortic stenosis had a 60% mortality. The late mortality was 2%. Eighty percent of surviving patients to date have undergone cardiac catheterization after repair. This shows an overall reduction of 57 mm Hg in the left ventricular-aortic gradient. Patients with supravalvular aortic stenosis and discrete subvalvular aortic stenosis as well as patients undergoing aortic valve replacement showed a reduction in or elimination of associated aortic insufficiency, whereas patients undergoing aortic valvotomy or neonates having valvotomy had a significant increase in demonstrable aortic insufficiency. The incidence of third-degree heart block or cerebral emboli following operation for aortic stenosis was less than 1%. However, the incidence of late bacterial endocarditis following repair was nearly 5%; six of eleven cases occurred in the group with discrete subvalvular aortic stenosis. Twenty-nine (13%) of the 223 long-term survivors have undergone a subsequent procedure for relief of residual or recurrent obstruction; 12 have had insertion of an aortic valve prosthesis, 12 have had insertion of an apicoaortic conduit, and 6 have required repeat aortic valvotomy. These data demonstrate the low operative mortality and excellent hemodynamic benefit of surgical relief of single-level aortic stenosis in children older than neonates. Conduits placed for complex obstructions or operative procedures in neonates have acceptable hemodynamic benefits, but operative mortality remains high.     

Rescue cardiac transplantation for early failure of the Fontan-type circulation in children

OBJECTIVE: Early failure of the Fontan-type circulation is a potentially fatal complication. We review our experience with cardiac transplantation in children presenting with end-stage heart failure in this scenario. METHODS: We performed a retrospective review. Between 1985 and 2003, 6 children aged less than 16 years were referred for cardiac transplantation. The indication for cardiac transplantation was end-stage cardiac failure early after the completion of the Fontan-type operation. RESULTS: All 6 patients listed for transplantation underwent cardiac transplantation; the median interval to transplantation from the operation was 36 days (range, 6-180 days). Four patients had undergone the Fontan procedure, and 2 had one-and-a-half-ventricle repair. All 6 patients were ventilated and inotrope dependent, with varying degrees of multiorgan dysfunction. One patient was bridged to transplantation with extracorporeal membrane oxygenation. The median age at transplantation was 7.1 years (range, 3-12.5 years), and weight was 18.9 kg (range, 11-35 kg). One patient died on the operating table (graft failure and hemorrhage). In 5 survivors the median intensive care unit stay was 10 days (range, 8-61 days). On follow-up of 6 to 81 months, there have been no subsequent deaths, and the quality of life in survivors is good. CONCLUSION: Rescue cardiac transplantation in the setting of an early failure of the Fontan-type circulation and end-stage cardiac failure is an effective treatment option and can be performed with acceptable early mortality and encouraging short-term to medium-term results.     

Accelerated coronary atherosclerosis after cardiac transplantation: major threat to long-term survival

Accelerated coronary atherosclerosis (ACA) has been documented at autopsy and was noted at coronary angiography in seven patients, 11 to 48 months after cardiac transplantation. To delineate the importance of this problem, the risk factors and the therapeutic approaches in 7 patients who had ACA after heart transplantation were compared with those in 28 patients free of ACA at annual coronary angiography. Ischemic cardiomyopathy was the preoperative diagnosis in all but one patient in the ACA group. The age of the transplant recipients, total myocardial ischemic times and arterial blood pressures at follow-up were similar in both groups. Donor age averaged 31 +/- 3 years in the ACA group and 22 +/- 1 years in patients free of ACA. Preoperative cholesterol, triglyceride and high-density lipoprotein levels were lower in ACA-free patients and the low-density lipoprotein level was higher. At the last follow-up visit, serum lipid levels were similar in both groups. The incidence of acute rejection and of infection was slightly, but not significantly, higher in patients with ACA. The actuarial survival of ACA patients 4 years after transplantation was 30% +/- 20% compared with 100% for patients free of ACA (p less than 0.01). Actuarial rates of freedom from ACA and from death due to ACA were 73% +/- 11% and 81% +/- 11% respectively. Stepwise discriminant analysis showed that older donors and higher pretransplant triglyceride levels were independently related to the development of ACA after cardiac transplantation. In conclusion ACA remains an important cause of late death after heart transplantation. Although therapeutic measures are limited, prevention should focus on strict control of serum lipid levels after transplantation.     

Mechanical Support and Medical Therapy Reverse Heart Failure in Infants and Children

Most infants and children implanted with ventricular assist devices (VADs) go on to cardiac transplantation. Recovery of dilated cardiomyopathies with the combination left ventricular decompression with a VAD and treatment with maximal medical therapy has been possible in some adults, and may be more feasible in infants and children. We used pulsatile and continuous flow VADs and the total artificial heart (TAH) as bridges to transplantation or to recovery. Candidates for native heart recovery were treated with maximal medical therapy for congestive heart failure and short‐term dobutamine prior to weaning off device support. Since 1997, 28 infants and children, ages 1 month to 16 years, were implanted for durations of 3–107 days (mean 27). Eighteen received left VADs (LVAD), seven biventricular assist devices (BiVADs), and three TAHs. Device‐related mortality was 7/28 (25%), leaving 21/28 (75%) surviving to transplantation or weaning from device support and 20/28 (71%) discharged from the hospital and currently surviving for 2 months to 9 years. Ten of 11 transplant recipients (90%) have survived 2 to 9 years. All 10 with recovered hearts are alive and well for 2 months to 5 years. Eight of 12 (67%) LVAD patients with dilated hearts recovered. None of the recovery patients were over 6 years old. Infants and children who have failed inotropic therapy may be treated with an LVAD and medical therapy for congestive heart failure anticipating native heart recovery. A variety of devices have been tried. All small LVADs yielded comparable results. Larger and older children also have a chance of recovery, but our experience with them is too small except to note that they do well with larger devices and transplantation.     

Left ventricular assist devices as bridge to heart transplantation: The Niguarda Experience

BACKGROUND: Congestive heart failure is the leading cause of death in Western countries. Heart transplantation currently is the only accepted therapy for patients with end-stage heart failure, but the supply of donor hearts is inadequate, and different mechanical circulatory support systems have been investigated as bridges to heart transplant. METHODS: Since April 1992, 53 patients (47 men, 6 women, aged 12 to 61 years) received left ventricle mechanical circulatory support as bridge to heart transplant. The two principal devices used were: the Novacor LVAS in 31 patients and the DeBakey VAD in 11 patients. RESULTS: All patients survived the operation. Mean duration of LVAD support was 2.8 +/- 5.6 months. Thirty-seven patients (71.1%) underwent heart transplantation. Twelve major bleeding episodes occurred in nine patients (16.9%). Globally, major and minor neurologic events occurred in 13 patients (24.5%). Ten patients (19.9%) assisted with the Novacor Wearable LVAS device were discharged at home while waiting for heart transplant (HTx). The mean follow-up of the 34 discharged transplanted patients was 45.3 +/- 37 months. Actuarial survival of transplanted patients while on LVAD was 91.0 +/- 4.9% and 83.4 +/- 8.5% at 1 and 5 years, respectively. No differences in post-transplant long-term survival and rejection and allograft vasculopathy occurred between patients transplanted with or without LVAD implanted. CONCLUSIONS: LVAD therapy proved to be effective in bridging patients with end-stage heart failure to HTx. While on LVAD support, patients assisted with implantable wearable devices could be discharged at home, ameliorating their quality of life. The excellent survival rate after HTx is concomitant with a low incidence of rejection and cardiac allograft vasculopathy.     

Cardiac transplantation in pediatric patients: fifteen-year experience of a single center

Background

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.

Methods

Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 ± 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.

Results

Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 ± 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.

Conclusions

Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.     

Heart transplantation in patients seventy years of age and older: A comparative analysis of outcome

OBJECTIVE: Advanced age has traditionally been considered a contraindication for heart transplantation because of the reported adverse effect of increased age on long-term survival. However, as the field of transplantation continues to evolve, the criteria regarding the recipient's upper age limit have been expanded and older patients are being considered as potential candidates. We analyzed the outcome of heart transplantation in patients 70 years of age and older and compared these results with those in younger patients (<70 years) over a 4-year period. METHOD: We retrospectively analyzed the results of 15 patients 70 years of age and older who underwent heart transplantation between November 1994 and May 1999 and compared them with results in 98 younger patients undergoing transplantation during the same period RESULTS: The older age group had a higher preoperative left ventricular ejection fraction (P =.02), higher incidence of female donors (P =.02), and longer cardiac allograft ischemic time (P =.01). No differences were found regarding incidence of diabetes mellitus, donor age, donor/recipient weight ratio, and mismatch (<0.80). The 30-day or to-discharge operative mortality was similar in both groups (0% in the older vs 5.1% in younger patients). Actuarial survival at 1 year and 4 years was not statistically different between the older and younger patients (93.3% +/- 6.4% vs 88.3% +/- 3.3% and 73.5% +/- 13.6% vs 69.1% +/- 5.8%, respectively). The length of intensive care unit stay and total post-transplantation hospital stay, incidence of rejection, and incidence of cytomegalovirus infection were similar between the groups. CONCLUSIONS: Heart transplantation in selected patients 70 years of age and older can be performed as successfully as in younger patients (<70 years of age) with similar morbidity, mortality, and intermediate-term survival. Advanced age as defined (> or =70 years) should not be an exclusion criterion for heart transplantation. The risks and benefits of transplant surgery should be applied individually in a selective fashion.     

Neurologic complications of heart transplantation in children.

Neurologic complications can add significant morbidity to otherwise successful orthotopic heart transplantations in children. Complications have been reported to occur in up to 50% of children undergoing heart transplantation. The purpose of this study was to identify the prevalence and outcome of neurologic complications of heart transplantation in children. We reviewed all children who received orthotopic heart transplantation at Texas Children's Hospital from November 1984 to November 1990. Twenty-two patients (ages, 3 weeks to 17 years; mean, 8.5 years) underwent heart transplantation using cardiopulmonary bypass with moderate hypothermia. For analysis, we compared results during the first 3 years of our experience, 1984 through 1987 (group 1), to 1987 through 1990 (group 2). Survival was 45% (5 of 11 patients) for group 1 and 73% (8 of 11 patients) for group 2. A neurologic complication was defined as a change in the neurologic examination and/or status. Neurologic complications included seizures (6 of 22 patients), strokes (3 of 22 patients), unresponsiveness (3 of 22 patients), and change in mental status (2 of 22 patients). Early (within 2 weeks after operation) neurologic complications occurred in 45% (10 of 22 patients), were persistent (sequelae lasting more than 4 months) in 27% (6 of 22 patients), and resulted in death in 9% (2 of 22 patients). Late (after 2 weeks after operation) neurologic complications occurred in 23% (5 of 22 patients), were persistent in 9% (2 of 22 patients), and have occurred in only two survivors. Neurologic factors were not responsible for the cause of death in group 2. No neurologic complications (early or late) were seen in 1 of 11 patients in group 1 as compared with 7 of 11 patients in group 2 (p < 0.015). Serious neurologic morbidity decreased between the two groups after preoperative cyclosporine was avoided and postoperative hypertension was controlled. All survivors are functioning at age-appropriate levels. Although neurologic complications may be frequent, long-term neurologic disability in survivors is rare.     

Clinical experience with the Novacor ventricular assist system. Bridge to transplantation and the transition to permanent application

At Stanford University, a Novacor left ventricular assist system (Baxter Healthcare Corporation, Novacor Division, Oakland, Calif.) was placed as a bridge to heart transplantation in 13 patients. During the hospitalization preceding device implantation, all patients were receiving inotropic support for biventricular failure, 11 had pulmonary edema, 6 had life-threatening ventricular arrhythmias, 5 had liver dysfunction with coagulopathy, and 2 had renal failure necessitating artificial support. The mean cardiac index before implantation of the Novacor system was 1.5. All survivors with the Novacor device had a dramatic increase in cardiac output (mean cardiac index = 3.1). One patient with cardiac allograft rejection died during implantation of the left ventricular assist system. Two patients died of pulmonary sepsis and multiorgan failure after the device was implanted. All patients who had the Novacor device implanted for more than 7 days were able to walk and ride stationary bicycles while awaiting transplantation. Ten patients (77%) underwent successful heart transplantation after a mean of 18 days' support with the Novacor device. One patient died of presumed sepsis 2 days after transplantation. Nine patients (90%) are alive 4 months to 6 years after transplantation. In the overall United States experience, 68 patients (as of May 1990) have had a Novacor left ventricular assist device implanted. Five were still being supported, 39 had received a transplant (62%), and 35 patients (90%) survived the transplant hospitalization (1 died later). No instances of device failure have occurred. Overall, the Novacor assist system provided effective bridging to transplantation, with posttransplant survival similar to results after routine transplantation. Modifications and improvements based on this clinical experience have been made in the areas of patient selection, techniques of operative placement, postoperative management, and design of the assist system. Isolated left heart support with a fully implantable left ventricular assist system will be offered as an alternative to heart transplantation for selected patients by 1992.     

Long-term results of heart transplantation in patients older than 60 years

BACKGROUND: Advanced age has been traditionally considered a relative contraindication for heart transplantation. Older patients are now considered as potential candidates for heart transplantation. The objective of this study was to evaluate the long-term results of heart transplantation in patients older than 60 years. METHODS: Between 1986 and 2001, 81 patients aged between 60 and 70 years (mean, 63 +/- 2 years) underwent heart transplantation. These patients were compared with 403 adult recipients younger than 60 years (mean, 47 +/- 11 years) who underwent transplantation during the same period. RESULTS: Thirty-day mortality was 6% (5/81) and 6% (25/403) in the older and younger patients, respectively (P = NS). Actuarial survival at 1, 5, and 10 years was 88% +/- 4% versus 83% +/- 2%, 75% +/- 5% versus 69% +/- 2%, and 50% +/- 9% versus 51% +/- 3% in the older and younger patients, respectively (P = NS). Older patients had significantly fewer rejection episodes (P =.003). Freedom from allograft coronary artery disease at 1, 5, and 10 years was 98% +/- 2% versus 92% +/- 2%, 85% +/- 6% versus 76% +/- 3%, and 81% +/- 7% versus 68% +/- 3% (P =.1). The incidences of infectious complication, cytomegalovirus infection, and posttransplant lymphoproliferative disorder were similar between the 2 groups, but older recipients were more likely to have a nonposttransplant lymphoproliferative disorder cancer (P =.002). Age at transplantation was not identified as an independent risk factor for early and late death. CONCLUSION: Heart transplantation in selected patients aged 60 years and older results in survival comparable with that of younger patients. Older patients have a lower risk of rejection but an increased risk of development of a nonposttransplant lymphoproliferative disorder cancer. Advanced age per se should not be considered as an exclusion criterion for transplantation.     

Coronary revascularization rather than cardiac transplantation for chronic ischemic cardiomyopathy.

Patients with very poor ventricular function have been thought to be highly vulnerable to elective myocardial revascularization. Ischemic cardiomyopathy is now the major indication for cardiac transplantation. The 2-year survival of medically treated patients with ejection fractions less than 20%, but who are not sufficiently symptomatic for cardiac transplantation, is less than 25%. At our institution we have taken an aggressive approach by using myocardial revascularization for chronic ischemic cardiomyopathy. Between 1983 and 1988, 39 patients with preoperative ejection fractions less than 20% underwent coronary artery bypass. Patients were excluded if they had valvular heart disease other than mild to moderate mitral regurgitation, required resection of a left ventricular aneurysm, or required emergency operation for acute coronary occlusion. Mean age was 63.3 years (range, 43 to 80 years) and 31 were men. Mean preoperative ejection fraction was 18.3% (range, 10% to 20%) and the mean preoperative left ventricular end diastolic pressure was 22 mm Hg (range, 8 mm Hg to 38 mm Hg). There was one operative death (2.6%). Mean follow-up was 21 months (range, 3 to 60 months) with eight late deaths (a total mortality rate of 21%). Seven deaths were due to arrhythmias. Three patients continued to have severe heart failure, one of whom underwent successful cardiac transplantation. By life table analysis, there was a 3-year survival rate of 83%. With the present shortage of cardiac transplant donors, myocardial revascularization for ischemic cardiomyopathy is a reasonably effective means for preserving residual ventricular function.