Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.

Heart transplantation in the young and elderly.

INTRODUCTION: Heart transplantation has become an acceptable treatment in pediatric patients with end-stage heart disease and complex congenital heart disease. The liberalization of recipient eligibility criteria, mainly age, along with the expansion of the donor pool has resulted in the acceptable transplantation of older recipients. METHODS: Between July 1994 and June 1998, 39 pediatric patients aged 16 days to 17.6 years (median 6.68 years) and 123 elderly patients aged 60 to 74.8 years (median 64.1 years) were transplanted at our institution. In the pediatric group, 19 had idiopathic dilated cardiomyopathy (DCM) (46 %), 14 had congenital heart disease (34 %), 4 had other etiologies of cardiomyopathy (10 %), 2 had transplant coronary artery disease (TCAD) (5 %), and 1 each had acute rejection and graft failure. In the elderly group, 71 had ischemic cardiomyopathy (58 %), 38 had DCM (31 %), 9 had other forms of cardiomyopathy (7 %), and 5 had TCAD (4 %). RESULTS: Thirty-day, 1-year, and 4-year survival was 97.4 %, 87.2 %, and 70.9 % for the pediatric group and 92.7 %, 81.3 %, and 79.3 % for the elderly group. One and 4-year freedom from TCAD was 100.0 % and 85.3 % for the pediatric group and 91.9 % and 83.3 % for the elderly group. CONCLUSIONS: [emsp3 ]Orthotopic heart transplantation is effective for the treatment of irreparable congenital and end-stage heart disease. It provides excellent long-term results in both the very young and elderly.

Use of OKT3 for acute myocarditis in infants and children.

Acute viral myocarditis triggers an autoimmune phenomenon that aggressive immunosuppressive therapy with monoclonal OKT3 may suppress. We treated 5 patients, aged 15 months to 16.5 years, who had acute viral myocarditis and left ventricular ejection fraction (LVEF) of 5% to 20%, with a combination immunosuppressive regimen that included OKT3, intravenous immunoglobulin, methylprednisone, cyclosporine, and azathioprine. Within 2 weeks of therapy, all patients demonstrated normalization of LVEF to 50% to 74%, and on mid-term follow-up, we have found no recurrence of heart failure or progression to dilated cardiomyopathy. In patients with severe acute myocarditis, aggressive immunosuppressive regimen based on OKT3 is safe and may inhibit or reverse the immune response, resulting in dramatic improvement in myocardial function.

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Mechanical assist strategy using the BVS 5000i for patients with heart failure.

BACKGROUND: The BVS 5000i external pulsatile assist device is used to support patients with reversible cardiogenic shock. Its low cost and potential for insertion without cardiopulmonary bypass make it an attractive option. METHODS: Nineteen status I patients failing inotropic support were treated with the BVS 5000i with the intention of short-term bridge to transplant. Fourteen patients received left ventricular support whereas 5 received biventricular support. Cardiopulmonary bypass was used in less than 50% of patients. RESULTS: Median support time was 7 days. The 2 myocarditis patients were weaned from support. Twelve patients were transplanted and there were 5 deaths on support. Overall 14 of 19 were transplanted or weaned. One-year survival was 79%. Median hospital stay was 31 days. CONCLUSIONS: The BVS 5000i can be used for short-term mechanical assist toward transplantation in selected patients for whom a donor can be expected soon. The device may provide a cost-effective, short-term strategy to optimize end-organ function before orthotopic heart transplant, particularly for patients who are predictably not ideal to be discharged with implantable left ventricular assist device treatment.

The use of donor hearts with left ventricular hypertrophy.

BACKGROUND: We reviewed 37 patients who received donor hearts with left ventricular hypertrophy (LVH) to determine which factors affected outcomes. METHODS: Thirty-seven patients underwent orthotopic heart transplantation (1994 through 1998) with donor hearts qualified as having LVH by echocardiography (EC) and/or electrocardiogram (ECG). We performed univariate analysis on 18 donor and recipient risk factors for mortality. We calculated 12-month survival curves using Kaplan-Meier estimates and compared them using the log-rank test. A contemporaneous cohort of 221 patients who received optimal hearts within the same institution served as a control for survival. RESULTS: Median follow-up was 18 months (1 to 53). Median recipient age was 58 ye ars (25 to 75), and median donor age was 47 years (12 to 63). Median donor/recipient height and weight ratios were 1.01 (0.9 to 1.19) and 1.16 (0.77 to 2.02), respectively. Two-month survival was 86.4%, and 12-month survival was 73.0%. Survival for the control group was 91. 6% at 2 months and 86.9% at 12 months. Clinically inferior survival curves were observed when donors had known hypertension (n = 17, 95% vs 71% at 2 months, 76% vs 65% at 12 months), ischemia > 180 minutes (n = 18, 95% vs 72% at 2 months, 78% vs 65% at 12 months), LVH by ECG (n = 10, 85% vs 80% at 2 months, 77% vs 56% at 12 months), and greater than mild or unknown ECHO grade (n = 18, 89% vs 72% at 2 months, 84% vs 59% at 12 months, p = 0.11). CONCLUSIONS: Donor hearts with mild LVH may be used selectively, particularly if there are no ECG criteria and if ischemia time is short. Caution is indicated for donors with documented history of hypertension. Precise measurement of LV wall thickness by EC is needed in all donors to estimate severity and to complement ECG interpretation.

Short-term bridge to transplant using the BVS 5000 in a 22-kg child.

The availability of pulsatile mechanical assist devices for bridge to transplant in pediatric patients is limited owing to the patients' small sizes. Pulsatile devices offer potential advantages over nonpulsatile devices but the risk of hypertensive bleeding must be balanced against that of device thrombosis. We describe our experience using the BVS 5000 external pulsatile device in an 8-year old patient with a body surface area of 0.88 m2.

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Generation of functional thymocytes in the human adult.

Reconstituting the immune response will be critical for the survival of HIV-infected individuals once viral load is brought under control. While the adult thymus was previously thought to be relatively inactive, new data suggest it may play a role in T cell reconstitution. We examined thymopoiesis in adults up to 56 years of age and found active T cell receptor (TCR) rearrangement, generating a diverse TCR Vbeta repertoire. The resulting thymocytes are functional and are capable of responding to costimulatory signals. These data demonstrate that the adult thymus remains active late in life and contributes functional T cells to the peripheral lymphoid pool.

Improved survival in patients with acute myocarditis using external pulsatile mechanical ventricular assistance.

BACKGROUND: Acute myocarditis remains a disease with a variable clinical course, from full ventricular recovery to complete heart failure; to date, few cases have been reported that describe the efficacy of temporary mechanical ventricular assistance for its treatment. METHODS: We evaluated the voluntary world registry with the use of an external pulsatile ventricular assist device (the ABIOMED BVS 5000 [BVS]) for acute myocarditis to determine the impact of mechanical ventricular assistance on outcome. Variables analyzed included patient demographics, serum chemistries, and overall hemodynamics prior to BVS, while on BVS support, and after BVS explanation. Postoperative parameters included re-operation, bleeding, respiratory failure, renal failure, and infections, neurologic, or embolic events. RESULTS: Eighteen patients in the ABIOMED world registry underwent BVS implantation for myocarditis; 11 (61.1%) had complete pre-operative and hemodynamic data for analysis. Patients were supported for 13.2 +/- 17.0 days, after which time 7 (63.6%) patients survived to explanation of the device and 2 (18.2%) underwent transplantation. Elevated admission serum chemistries (blood ureanitrogen [BUN], creatinine, transaminases) and hemodynamics (central venous pressure [CVP], mean pulmonary arterial pressure [PAP], pulmonary capillary wedge pressure [PCW], cardiac index [CI], all normalized during the period of device support. Estimated ejection fractions in the 7 explanted patients ranged between 50 to 60% at routine evaluation 3 years after device removal. CONCLUSIONS: Temporary mechanical ventricular assistance represents an efficacious therapy for acute myocarditis in patients with hemodynamic decompensation despite maximal medical therapy. Failure to achieve full ventricular recovery while on device support still allows for other surgical alternatives, including implantation of a long-term implantable ventricular assist device, or cardiac transplantation.

Minimally invasive mechanical cardiac support without extracorporeal membrane oxygenation in children awaiting heart transplantation.

BACKGROUND: Mechanical cardiac assist for small children (< 30 kg) requiring bridge strategy to orthotopic heart transplantation often requires sternotomy for cannulation access to ensure perfusion to the aortic arch. Extracorporeal membrane oxygenation (ECMO) through neck cannulation is an option in very small (< 10 kg) patients, but the risk of stroke is increased in larger children. Another disadvantage is poor decompression of the left atrium, which can cause persistent pulmonary edema. METHODS: Two cases are used to illustrate two methods of avoiding sternotomy during mechanical assist in children with dilated cardiomyopathy. One of these approaches avoids the need for extracorporeal oxygenation. RESULTS: Decompression of the left-sided chambers with a left atrial cannula decreased pulmonary edema and improved pulmonary function. CONCLUSIONS: Pediatric patients with dilated cardiomyopathy may benefit from a left ventricular assist technique using a centrifugal pump, which avoids the neck vessels and sternotomy, as well as ECMO.

Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model.

BACKGROUND: Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed. This study was undertaken to investigate the severity of rewarming ischemia on preservation injury and the possibility of minimizing this by use of leukocyte depletion during initial reperfusion. METHODS: Four experimental groups were tested as follows: neonatal piglet heart-lung blocks were either (1) placed on an isolated, blood-perfused, working heart-lung circuit without intervening ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4 hours. RESULTS: The partial pressure of arterial oxygen and lung compliance were significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/-6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05, respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs 6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p < 0.05, respectively). The WB and leukocyte-depleted groups did not differ significantly from controls for any measured parameter. CONCLUSIONS: This model confirms that rewarming ischemia during lung implantation exacerbates reperfusion injury. Leukocyte-depleted reperfusion as tested for a short period of time (10 minutes) ameliorates this injury and therefore should be considered for clinical lung transplantation.

The University of California at Los Angeles experience in heart transplantation.

In the last decade, the number of patients undergoing heart transplant has steadily increased as a result of expanding indications for this procedure. The limitation on the number of transplants performed has been the number of donor organs available. At UCLA, 900 heart transplant procedures have been performed from 1984-1998. Since 1991, the percent of patients free from rejection and infection in the first year after transplant was 70% and 73%, respectively. Actuarial one-, 3-, and 5-year survival rates are 84%, 76%, and 72%, respectively. Survival of patients aged 60 years and over (n = 105) was comparable to that of patients under age 60. We have been pursuing corticosteroid-free immunosuppression, which has led to a decrease in infection complications. Our work with pravastatin early after transplantation has led to a decrease in clinically severe rejection episodes, which has translated into improved survival. Pravastatin also appears to decrease the development of transplant coronary artery disease and appears to have an adjunct immunosuppressive effect in our heart transplant patients on CsA-based immunosuppression. We have also demonstrated benefit of cardiac rehabilitation early after transplant which should therefore be considered as standard postoperative care. Finally, we have participated and led the multicenter mycophenolate study in demonstrating this drug's effectiveness in improved outcomes in primary heart transplant recipients. Future studies include the use of Rapamycin and interleukin-2 receptor blockers which have been demonstrated in kidney transplantation to significantly reduce rejection. Our program is committed to seek better ways to improve outcome and the quality of life of our heart transplant patients.

Temporary mechanical support with the BVS 5000 assist device during treatment of acute myocarditis.

BACKGROUND: Ventricular support with the BVS 5000 (Abiomed) has been used as temporary circulatory assist for the failing heart. Our purpose is to summarize four cases illustrating the role of mechanical unloading in acute myocarditis. METHODS: Four patients aged 16- to 33-year old presented with congestive heart failure 4 to 20 days after a flu-like syndrome. All patients were in severe cardiogenic shock +/- renal and liver dysfunction. Ejection fraction ranged from 5% to 26%. Indications for ventricular assist were failure of maximal medical treatment with > or = two inotropes +/- intra-aortic balloon pump. Myocardial biopsy revealed acute myocarditis in three patients and severe edema in one despite a characteristic clinical course. Two patients received immunotherapy with OKT3. Biventricular assist was used in three patients and left ventricular assist only was used in one. Mean support time was 8.3 days (7 to 11). RESULTS: All patients had recovery of myocardial function and were discharged from the hospital in good condition. CONCLUSION: The BVS 5000 device provides a safe, simple, and effective method to support the circulation during acute myocarditis. We hypothesize that this may facilitate myocardial recovery by decompressing the distended ventricle. Ventricular assist devices should be used early in the presence of hemodynamic deterioration on maximal medical therapy.

Institutional experience with a protocol of early primary repair of double-outlet right ventricle.

BACKGROUND: Our institution has adopted a protocol of primary repair for all patients with double-outlet right ventricle. METHODS: Since May 1989, 24 consecutive neonates and infants with double-outlet right ventricle and atrioventricular concordance (median age, 4 months) underwent anatomic biventricular repair. One patient (4%) received prior pulmonary artery banding but was still repaired as a neonate at 22 days of age. Twelve patients had a subaortic ventricular septal defect (VSD), 5 patients a subpulmonary VSD, 3 patients doubly committed VSD, and 4 patients a noncommitted VSD. Sixty-nine of 72 associated lesions were repaired simultaneously. Four types of repairs were used: intraventricular rerouting in 16 patients, arterial switch operation with VSD closure into the pulmonary artery in 4 patients, Rastelli-type repair with extracardiac conduit in 3 patients, and the Damus-Kaye-Stansel repair with concomitant repair of aortic arch obstruction in 1 patient. Ventricular septal defect enlargement was necessary in 15 patients. Repair of subpulmonary stenosis and of subaortic stenosis was carried out in 13 and 4 patients, respectively. Three patients underwent simultaneous repair of aortic arch obstruction with no mortality. Two of the patients with noncommitted VSD had simultaneous repair of complete atrioventricular canal and repair of severe pulmonary venous obstruction. RESULTS: The perioperative mortality was 8% (2 patients, and there was one late death (4%). Two patients (9%) underwent early successful reoperations (5 and 8 weeks postoperatively). The two reoperations were for residual VSD (1 patient) and severe mitral regurgitation (1 patient). All 21 survivors are alive at a mean follow-up of 40 months (range, 7 months to 6 years). The estimated 5-year actuarial survival is 88%, with no deaths after 2 months postoperatively. Ninety-five percent of long-term survivors have no restriction of physical activities because of cardiac status and are receiving no cardiac medications. CONCLUSIONS: An institutional protocol of early anatomic biventricular repair of double-outlet right ventricle in infants and neonates achieves excellent survival, making palliative operations unnecessary. Associated lesions should be repaired simultaneously. The complexity of these malformations requires a highly individualized and flexible surgical approach.