A new antiinflammatory compound, leumedin, inhibits modification of low density lipoprotein and the resulting monocyte transmigration into the subendothelial space of cocultures of human aortic wall cells.

Addition of leumedin, N-[9H-(2,7-dimethylfluorenyl-9-methoxy) carbon]-L-leucine at 30-60 microM together with LDL almost completely prevented the induction of monocyte chemotactic protein mRNA, reduced monocyte chemotactic protein 1 levels by 84%, and inhibited monocyte migration into the subendothelial space of cocultures of human aortic wall cells by < or = 98%. LDL incubated with leumedin formed a stable complex that remained intact even after refloating in an ultracentrifuge. Leumedin at 50 microM did not change conjugated diene formation during coculture modification of LDL or Cu++ catalyzed oxidation of LDL. Unlike LDL from control rabbits, LDL isolated from rabbits that were injected with 20 mg/kg leumedin was remarkably resistant to modification by the coculture and did not induce monocyte migration to a significant degree. Moreover, HDL isolated from rabbits injected with leumedin was far more effective in protecting against LDL modification by the artery wall cocultures than HDL from control rabbits. We conclude that leumedins can associate with lipoproteins in vivo, rendering LDL resistant to biological modification and markedly amplifying the protective capacity of HDL against in vitro LDL oxidation by artery wall cells.

Monocyte migration into the subendothelial space of a coculture of adult human aortic endothelial and smooth muscle cells.

Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were isolated and used to form a multilayer of EC-SMC separated by a layer of collagen. SMC and/or collagen layers exerted minimal effects on Na+ transport but impeded the transport of LDL. The presence of an endothelial monolayer markedly reduced the transport of Na+ and LDL. When monocytes were presented to the complete coculture, in the absence of added chemoattractant, one monocyte entered the subendothelial space for every one to three EC present. In contrast, neither collagen nor SMC plus collagen nor EC plus collagen induced comparable monocyte migration. Despite massive migration of monocytes into the coculture, no significant alteration in Na+ transport was observed. LDL transport into the preparation during massive monocyte migration increased modestly, but this was far less than the amount of LDL transported in the absence of an endothelial monolayer. We conclude that (a) the endothelial monolayer was the principal permeability barrier, (b) a substantial migration of monocytes occurred in the absence of added chemoattractant when both EC and SMC were present in the coculture, (c) endothelial barrier function was largely maintained after monocyte migration; and (d) these experiments indicate the need to study all three cell types (monocytes, EC, and SMC) together to understand the complex interactions that occur between these cells.

Recipient mononuclear cell recognition and adhesion to graft endothelium after human cardiac transplantation. Lymphocyte recognition leads to monocyte adhesion.

Transendothelial migration of mononuclear cells is crucial in the development of allograft rejection and transplant coronary disease. Adhesion of circulating cells to endothelium is the initial step in transendothelial migration. Human aortic endothelial cell cultures were established from aortic tissue harvested at the time of organ donation for cardiac transplantation which allowed specific recipient mononuclear cell-graft endothelial interactions to be studied. Confluent untreated endothelial cells were incubated with recipient mononuclear cells for 15 min to assess adhesion. Adhesion of recipient mononuclear cells to endothelium derived from their graft was threefold higher than adhesion to nonspecific endothelium (93 +/- 20 vs. 30 +/- 11 cells/high power field, P < 0.005). Graft-specific adhesion was inhibited by preincubation of the endothelium with antibodies to class I HLA (34 +/- 16 cells/high power field, P < 0.005). Immunofluorescence performed after adhesion showed that 73 +/- 6% of both specific and nonspecific adherent cells were monocytes. The use of purified lymphocyte and monocyte preparations showed that graft-specific lymphocytes induce unrelated monocytes to become adherent. These results suggest that lymphocytes are primed in vivo to recognize endothelium derived from their graft which leads to a rapid increase in lymphocyte and monocyte adhesion. Such allo-recognition may involve endothelial class I HLA molecules.

Interaction of monocytes with cocultures of human aortic wall cells involves interleukins 1 and 6 with marked increases in connexin43 message.

Medium from cocultures of human aortic endothelial cells (HAEC) and smooth muscle cells (HASMC) taken from the same donor contained approximately two- to fourfold more macrophage colony-stimulating factor, granulocyte/macrophage colony-stimulating factor, and up to 5.1-fold more transforming growth factor beta than could be accounted for by the sum of the activities of media from equivalent numbers of HAEC and HASMC cultured separately. After pulse labeling, immunoprecipitated [35S]fibronectin and [14C]collagen were also found to be substantially increased in the coculture compared to the sum of HAEC and HASMC cultured separately. The cocultivation of HAEC and HASMC resulted in a 2.7-fold increase in connexin43 messenger RNA. When direct physical contact between HAEC and HASMC was prevented by a membrane that was permeable to medium, the levels of [35S]fibronectin and [14C]collagen in the coculture were significantly reduced. Monocytes cultured alone contained low levels of [35S]fibronectin and [14C]collagen but when added to the coculture there was up to a 22-fold increase in [35S]fibronectin and a 1.9-fold increase in [14C]collagen compared to the coculture alone. The increase in fibronectin was prevented in the presence of neutralizing antibody to interleukin 1 and antibody to interleukin 6 by 45% and 67%, respectively. Addition of monocytes to cocultures also induced the levels of mRNA for connexin43 by 2.8-fold. We conclude that the interaction of HAEC, HASMC, and monocytes in coculture can result in marked increases in the levels of several biologically important molecules and that increased gap junction formation between the cells and interleukins 1 and 6 may be partially responsible for these changes.

Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.

Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.

Donor brain death mechanisms and outcomes after heart transplantation.

We sought to explore whether the cause of donor brain death influenced recipient outcomes after cardiac transplantation. In retrospect, 358 consecutive donors provided cardiac allografts to adult patients undergoing orthotopic heart transplantation at a single urban US medical center from January 2000 through December 2005. Alternate recipients were excluded. Mechanism and cause of donor brain injury and death were divided into five categories: anoxia (nontraumatic) (n=36), blunt head trauma (n=220), penetrating head trauma (n=83), brain tumor/infection (n=7), and cerebrovascular event (n=12). The five subgroups were categorized as traumatic or nontraumatic. The end points of the study were causes of early and late mortality, survival, and rejection rate. There were 59 deaths in the 6-year period. Total and short-term recipient mortality were found to be statistically higher among heart transplant recipients when the donors suffered from traumatic brain death compared to those whose brain death etiology was nontraumatic (P=.045, P=.033, respectively). Rejection rate was similar in all groups (P=.497). In conclusion, donor traumatic brain death was found to be a valid risk factor for recipient mortality after heart transplantation. Caution should be used when evaluating such donors, particularly in the presence of other risk factors.

Ethnicity as a predictor of graft longevity and recipient mortality in heart transplantation.

BACKGROUND: There is a dearth of data about the effect of donor and recipient ethnicity on survival and rejection rate after clinical heart transplantation, although the subject had been partly studied before. We compared the mortality and rejection rate among different ethnic groups at our institution. METHODS: In retrospect, 525 consecutive donors provided cardiac allografts to adult and pediatric patients undergoing orthotropic heart transplantation at a single, urban US medical center between 2000 and 2005. Donors and recipients were categorized according to ethnicity: African American, Asian, Caucasian, Hispanic, and Others (Indian, Mediterranean/Arabic, Afghans). Donor and recipient ethnicity-as an independent factor and the interaction between them-were examined as a risk factor for mortality and rejection after heart transplantation. Mean follow-up period was 3.2+/-1.9 years (range, 0.1 to 6.6). All recipients received triple immunosuppression consisting of a calcineurin inhibitor, an antiproliferative agent, and steroids. No patients received induction immunotherapy. The end points of the study were early and late mortality, rejection rate, and rejection-free survival time. RESULTS: The overall mortality was 17.3% (91 patients). Recipient mortality rate according to donor race was: African American, 23.1%; Asian, 11.1%; Caucasian, 18.7%; and Hispanic, 14.6%. No statistical significance was found, although the mortality differences presented. Recipient mortality with regard to recipients ethnicity was: African American, 22.2%; Asian, 6.3%; Caucasian, 18%; Hispanic, 18.9%; and others 40% (P=.048). Donor-recipient race match was not found as a risk factor influencing mortality as the matched group mortality was 17.5% comparing with the mismatched group mortality of 17.8% (P=.874). The overall rejection rate was 3.8% (20 rejection events). Rejection rate according donor race was: African American, 7.7%; Asian, 10.7%; Caucasian, 4%; and Hispanic, 1.3% (P=.027). Rejection rate with respect to recipients ethnicity was: African American, 0; Asian, 3.2%; Caucasian, 4.4%; Hispanic, 2.7%; and others, 20% with no statistical significance (P=.236). Donor recipient race match was not found as a risk factor influencing rejection rate (P=.58). CONCLUSIONS: Recipients' ethnicity was found as a significant risk factor for mortality. Rejection rate were found higher among the African American donors and significantly lower in the Hispanic donors. Significantly lower mortality rate was found among Asian recipients. Donor-recipient race match did not influence the mortality or rejection rate.

Is third-time heart retransplantation justifiable?

Since repeat heart transplantation traditionally carries higher risk than primary engraftment, we tested the hypothesis that third-time cardiac allograft transplantation is associated with prohibitive mortality and morbidity. The cohort of all third-time cardiac retransplants performed at our institution (n=3) and reported to UNOS from 1987 to 2002 (n=10) was reviewed. The primary endpoints were early and late mortality. Extending the study frame through 2003 captures a total of 5 and 15 third-time heart transplant recipients in UCLA and UNOS databases, respectively. Of the 15 patients undergoing third-time retransplants, preoperatively one was ventricular assist device-dependent, four were on intravenous inotropes, and two had creatinine levels greater than 2.5. Additionally, four were male recipients of female donor hearts and the mean donor ischemic time was 2.6 hours. One patient was diagnosed with acute allograft rejection, 13 with coronary artery vasculopathy/chronic rejection, and one with primary graft failure. At our institution, five patients underwent a third heart transplant. There was no early or hospital mortality. One patient died late from transplant coronary artery disease and another following a fourth allograft. The mortality rate for third-time heart allograft recipients is acceptable. These results are influenced by small sample size, younger age, case selection, and operations at select, high-volume institutions with significant experience.

Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses.

BACKGROUND: Great arteries in congenital heart disease (CHD) may dilate, become aneurysmal, or rupture. Little is known about medial abnormalities in these arterial walls. Accordingly, we studied 18 types of CHD in patients from neonates to older adults. METHODS AND RESULTS: Intraoperative biopsies from ascending aorta, paracoarctation aorta, truncus arteriosus, and pulmonary trunk in 86 patients were supplemented by 16 necropsy specimens. The 102 patients were 3 weeks to 81 years old (average, 32+/-6 years). Biopsies were examined by light (LM) and electron (EM) microscopy; necropsy specimens by LM. Positive aortic controls were from 15 Marfan patients. Negative aortic controls were from 11 coronary artery disease patients and 1 transplant donor. Nine biopsies from acquired trileaflet aortic stenosis were compared with biopsies from bicuspid aortic stenosis. Negative pulmonary trunk controls were from 7 coronary artery disease patients. A grading system consisted of negative controls and grades 1, 2, and 3 (positive controls) based on LM and EM examination of medial constituents. CONCLUSIONS: Medial abnormalities in ascending aorta, paracoarctation aorta, truncus arteriosus, and pulmonary trunk were prevalent in patients with a variety of forms of CHD encompassing a wide age range. Aortic abnormalities may predispose to dilatation, aneurysm, and rupture. Pulmonary trunk abnormalities may predispose to dilatation and aneurysm; hypertensive aneurysms may rupture. Pivotal questions are whether these abnormalities are inherent or acquired, whether CHD plays a causal or facilitating role, and whether genetic determinants are operative.

Use of a venous assist device after repair of complex lesions of the right heart.

Sixteen patients underwent hemodynamic evaluation of a venous assist device after complex operations on the right side of the heart. The device consists of an inflatable abdominal binder attached to a Jobst extremity pump causing intermittent external compression of the abdomen. In addition, six of these patients were evaluated using total lower body compression for comparison. Modifications of the Fontan procedure were performed in 14 patients, mitral valve anuloplasty and tricuspid valve replacement in 1 patient and reconstruction of the right ventricular outflow tract for treatment of pulmonary atresia with intact septum in 1 patient. The patients' ages ranged from 23 months to 31 years (mean 10.7 +/- 1.8 years). Systemic blood pressure, right and left atrial pressures, heart rate and arterial-mixed venous oxygen saturation difference were recorded in each patient with and without the device in place. With the venous assist device, mean systolic pressure increased from 95 +/- 4 to 122 +/- 3 mm Hg (p less than 0.05) and diastolic pressure rose from 57 +/- 3 to 70 +/- 3 mm Hg (p less than 0.05). Left atrial pressure increased from 7 +/- 1 to 15 +/- 1 mm Hg and right atrial pressure from 15 +/- 1 to 23 +/- 1 mm Hg (both p less than 0.05). In addition, arterial-mixed venous oxygen saturation difference decreased from 29% without the device to 23% with the device in place (p less than 0.05). Total lower body compression gave similar results to intermittent abdominal compression alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical options for complex transposition of the great arteries.

Between September 1976 and November 1987, 53 patients underwent surgical treatment by the same surgeon for "complex transposition of the great arteries" with ventricular septal defect or severe left ventricular outflow tract obstruction, or both. Six patients with transposition and left ventricular outflow tract obstruction underwent atrial rerouting and direct relief of the left ventricular outflow tract obstruction. Twenty-two patients presented with transposition plus ventricular septal defect; 15 of these patients underwent atrial rerouting and ventricular septal defect closure and 7 underwent an arterial switch procedure. Twenty-five patients presented with transposition plus ventricular septal defect and left ventricular outflow tract obstruction, 23 of whom underwent a Rastelli procedure. There were one early death (mortality rate 1.9%; 90% confidence limits 0-7%) and three late deaths (mortality rate 5.8%) during a mean follow-up period of 42 months (range 2 to 124). These results show that 1) atrial rerouting is an appropriate surgical procedure for transposition of the great arteries with left ventricular outflow tract obstruction; 2) the arterial switch procedure provides excellent early correction of transposition with ventricular septal defect and is currently the preferred procedure for this lesion; and 3) the Rastelli procedure can be performed with a low early mortality rate and excellent long-term results for transposition with ventricular septal defect and left ventricular outflow tract obstruction.

Subaortic obstruction in complex congenital heart disease: management by proximal pulmonary artery to ascending aorta end to side anastomosis.

Six patients with univentricular heart and one patient with d-transposition of the great arteries had transection of the main pulmonary artery with an end to side anastomosis of the main pulmonary artery to the ascending aorta to relieve subaortic obstruction. Two operations were performed as a palliative procedure within the first 6 months of life and five were performed as part of a definitive repair (four modified Fontan procedures and one repair of transposition of the great arteries with ventricular septal defect). There was one surgical death (14%) occurring 1 day postoperatively from low cardiac output. The remaining six patients are doing well 1 to 19 months postoperatively (mean 11.4 months). The proximal pulmonary artery to ascending aorta end to side anastomosis is an effective means of bypassing subaortic obstruction associated with complex congenital heart disease.

Factors influencing survival of patients with heterotaxy syndrome undergoing the Fontan procedure.

OBJECTIVES: This study was undertaken to determine those factors that may influence survival in patients with heterotaxy syndrome undergoing the Fontan procedure. BACKGROUND: The Fontan procedure remains the preferred palliative procedure for patients with heterotaxy syndrome. Although the mortality rate has improved for patients without this syndrome undergoing the Fontan procedure, it remains high for patients with heterotaxy syndrome. METHODS: The medical records of 20 consecutive pediatric patients with asplenia (n = 12) and polysplenia (n = 8) who underwent the Fontan procedure between January 1, 1986 and December 31, 1990 were reviewed. Anatomic and hemodynamic data were collected, as well as data on types of surgical palliative procedures and on outcome of the Fontan procedure. RESULTS: There were two early and two late deaths for a total mortality rate of 20% in the patients with heterotaxy syndrome, as compared with 8.5% for the patients without this syndrome who underwent the Fontan procedure during the same time period. Factors that significantly increased the risk of the Fontan procedure in these patients were 1) preoperative findings of greater than mild atrioventricular valve regurgitation, b) hypoplastic pulmonary arteries, and c) mean pulmonary artery pressure greater than or equal to 15 mm Hg after 6 months of age. Systemic and pulmonary venous anomalies coupled with single-ventricle anatomy were not significant risk factors for determining a poor outcome of the Fontan procedure. CONCLUSIONS: This study suggests that the outcome of the Fontan procedure in patients with heterotaxy syndrome may be improved by early protection of the pulmonary vascular bed, despite the existence of other cardiac anomalies.

Repair of conotruncal abnormalities with the use of the valved conduit: improved early and midterm results with the cryopreserved homograft.

Repair of complex cardiac lesions has been facilitated by the availability of valved conduits to reestablish right ventricular to pulmonary artery continuity. From 1977 to June 1991, 148 patients underwent repair with insertion of a conduit. Their mean age was 6.6 years (11 days to 45 years). The diagnosis was transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction in 51, truncus arteriosus in 36, pulmonary atresia with ventricular septal defect in 25, tetralogy of Fallot in 19, double-outlet right ventricle in 10, pulmonary atresia with intact ventricular septum in 6 and atrioventricular canal with pulmonary atresia in 1. A Dacron porcine-valved conduit was used in 37, a homograft conduit in 106 and a nonvalved conduit in 5. There were 13 early deaths overall (8.8%); 8 (22%) of the early deaths occurred in the 37 patients who received a Dacron graft, 4 (3.8%) occurred in the 106 patients who received a homograft and 1 occurred in a patient with a nonvalved Gore-Tex conduit. An additional patient underwent orthotopic heart transplantation in the early postoperative period. In 117 patients operated on from January 1985 to June 1991 the early mortality rate was 2.6% (3 of 117). Among 28 patients receiving a Dacron porcine-valved graft there were two late deaths (7.1%) after a mean follow-up interval of 93 months, and 8 patients required reoperation for conduit obstruction. Among 102 homograft recipients there were two late deaths (1.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Bubble contrast echocardiography in detecting pulmonary arteriovenous shunting in children with univentricular heart after cavopulmonary anastomosis.

OBJECTIVES: We sought to compare bubble contrast echocardiography and pulmonary angiography in detecting pulmonary arteriovenous malformation (PAVM) in children with cavopulmonary anastomosis (CPA), and to examine anatomic and physiologic variables associated with the development of PAVM. BACKGROUND: Development of PAVM in patients with CPA may cause profound cyanosis. Pulmonary arteriovenous malformation has been traditionally diagnosed by pulmonary angiography with reported incidence of 20% to 25% in patients with CPA. METHODS: Fourteen patients (age 1.1 to 12.6 years) with any forms of CPA and normal pulmonary venous drainage formed the study population. All patients underwent cardiac catheterization and pulmonary angiography. Bubble contrast echocardiographic studies were performed with injection of 10 ml of agitated saline solution into branch pulmonary arteries. Transthoracic echocardiograms using an apical view were performed to assess the appearance of bubble contrast in the systemic ventricles. We compared the results of pulmonary angiograms and contrast echocardiograms, and findings of contrast echocardiograms between lungs with hepatic venous blood flow and lungs without hepatic venous blood. RESULTS: Ten of the 14 patients (71%) had positive contrast echocardiographic studies, compared with three (21%) detected by pulmonary angiograms (p = 0.01). No difference was found in pulmonary artery pressure, transpulmonary gradient or presence of heterotaxy syndrome between patients with positive contrast echocardiographic studies and patients with negative studies. However, patients with positive contrast echocardiograms tended to have lower oxygen saturation (81%) and higher hemoglobin (16.4 g/dl) compared with patients with negative studies (88% and 14.7 g/dl, p = 0.10 and p = 0.18 respectively). Patients with Glenn shunt or unidirectional Fontan had higher incidence of PAVM (10/11) compared with patients with classic or lateral tunnel Fontan (0/3, p = 0.01). All 12 lungs with no perfusion of hepatic venous blood had positive contrast echocardiographic studies. Lungs with no hepatic venous blood flow were more likely to develop PAVM compared with lungs with hepatic venous blood flow (12/12 and 3/16 respectively, p < 0.01). CONCLUSIONS: Bubble contrast echocardiography is more sensitive in detecting PAVM compared with pulmonary angiography. The prevalence of PAVM in patients with CPA may be much higher than what had been reported previously. Lungs with no hepatic venous blood flow are more likely to develop PAVM than lungs with hepatic venous blood flow.

Benefits of early surgical repair in fixed subaortic stenosis.

OBJECTIVES: We sought to determine whether early resection can improve outcome in fixed subaortic stenosis. BACKGROUND: The diagnosis of subaortic stenosis (SAS) is often made before significant gradients occur. Whereas resection is the accepted treatment, it remains uncertain whether surgical intervention at this early stage can reduce the incidence of recurrence or influence the progression of aortic valve damage. METHODS: Follow-up was available for 75 of 83 consecutive patients operated on for fixed SAS; the average duration of follow-up was 6.7 years. The lesion was discrete in 68 patients (91%) and of a tunnel type in 7, with associated ventricular septal defect in 28 (37%). All underwent transaortic resection. RESULTS: There were no deaths. There were 18 recurrences of SAS in 15 patients (20%). Thirteen patients (17%) underwent 17 reoperations for recurrence or aortic valve disease. The cumulative hazard of recurrence was 8.9%, 16.1% and 29.4% +/- 2.3% (mean +/- SEM), and the hazard of events, including recurrence and reoperation, was 9.2%, 18.4% and 35.1% +/- 3.5% at 2, 5 and 10 years, respectively. Residual end-operative left ventricular outflow tract (LVOT) gradients (> 10 mm Hg, n = 8) and tunnel lesions were univariate predictors of recurrence (p = 0.0006 and p = 0.003, respectively). Multivariate predictors included higher preoperative LVOT gradient (p < 10(-4)) and younger patient age (p = 0.002). Only two recurrences (0.87 per 100 patient-years of follow-up) were noted in patients with a preoperative peak LVOT gradient < or = 40 mm Hg (n = 40), whereas higher gradients (n = 35) were associated with a greater than sevenfold recurrence rate (6.45 events per 100 patient-years, p = 0.002). The aortic valve required concomitant repair in 17 cases in the high gradient group (48.6%) but in only 8 in the low gradient group (20%, p = 0.018). Despite relief of the obstruction, progressive aortic regurgitation was noted at follow-up after 14 procedures in the high gradient group (40%) but after only 5 procedures in the low gradient group (12.5%, p = 0.014). CONCLUSIONS: The data suggest that surgical resection of fixed subaortic stenosis before the development of a significant (> 40 mm Hg) outflow tract gradient may prevent recurrence, reoperation and secondary progressive aortic valve disease.

Is intravenous glucocorticoid therapy better than an oral regimen for asymptomatic cardiac rejection? A randomized trial.

OBJECTIVES: This study assessed whether treatment with oral prednisone (bolus plus tapered doses) is comparable to intravenous methylprednisolone sodium succinate (Solu-Medrol) therapy in patients with asymptomatic moderate cardiac allograft rejection episodes without hemodynamic compromise. BACKGROUND: Intravenous Solu-Medrol therapy is frequently administered for moderate rejection episodes after heart transplantation but has not previously been compared with an oral prednisone therapy for asymptomatic cardiac rejection in a randomized trial. Compared with oral prednisone therapy, the administration of intravenous Solu-Medrol is more costly and resource intensive, and it can require loss of work time for patients and the family members who accompany them to treatment. METHODS: Forty-one heart transplant patients with 43 episodes of asymptomatic moderate cardiac rejection were randomized to receive 3 days of 1,000 mg of intravenous Solu-Medrol (20 episodes) or prednisone as a bolus dose of 100 mg orally for 3 days, tapering to the previous maintenance dosage over 14 days (23 episodes). Follow-up endomyocardial biopsies were performed at 2 and 4 weeks. Infectious complications were monitored and the cost of the two forms of therapy was assessed. RESULTS: Resolution of moderate rejection occurred within 4 weeks in 19 (95%) of 20 patients treated with intravenous steroids and in 21 (91%) of 23 patients treated with oral prednisone. No significant difference in infectious complications occurred between the two groups in the ensuing 3 months after therapy. The cost of the oral prednisone therapy was $6.30 compared with the cost of $180 to $966 for administration of intravenous Solu-Medrol. CONCLUSIONS: Oral prednisone (bolus plus tapered doses) appears to be as effective and to have similar infectious complication rates as intravenous Solu-Medrol for the treatment of asymptomatic cardiac rejection. The convenience and lower cost of oral prednisone therapy may warrant its routine use for this type of cardiac rejection.

Effect of late postoperative atrial septal defect closure on hemodynamic function in patients with a Lateral tunnel Fontan procedure.

OBJECTIVES: The aim of this study was to evaluate prospectively the effect of late atrial septal defect closure on cardiac output and oxygen delivery in patients who have undergone the Fontan procedure. BACKGROUND: An adjustable atrial septal defect is incorporated in patients undergoing the Fontan procedure who have increased pulmonary vascular resistance or poor ventricular function, or both. After the Fontan procedure, the atrial septal defect is test occluded. Patients with mean right atrial and pulmonary artery pressures > 15 mm Hg are discharged with the atrial septal defect open. METHODS: Twelve patients (20 months to 12 years old) underwent evaluation and closure of the atrial septal defect at a mean interval of 3.8 months (range 1 to 18) after the Fontan procedure. Each patient underwent full right and left heart catheterization. Cardiac output was obtained using the cine-volume method. The study included six patients with a high transpulmonary gradient or poor ventricular function preoperatively, or both (high risk group) and six who had only borderline increased pulmonary vascular resistance (low risk group). Patients in both groups had a mean right atrial pressure > 15 mm Hg when the atrial defect was test occluded in the first week after the Fontan procedure. RESULTS: All results are given as mean value +/- SD. Ventricular end-diastolic pressure was significantly lower (p = 0.03) with the atrial septal defect open in low risk patients (6 +/- 3 mm Hg) than in high risk patients (10 +/- 3 mm Hg). With the atrial septal defect open, low risk patients had a significantly higher (p = 0.04) cardiac index (4.87 +/- 0.81 liters/min per m2) than the high risk patients (3.96 +/- 0.47 liters/min per m2). There was no significant difference (p = 0.14) in cardiac index between the two groups with occlusion of the atrial septal defect. Oxygen delivery was also significantly higher (p < 0.05) with the atrial septal defect open in low risk patients (836 +/- 99 ml/min per m2) than in high risk patients (704 +/- 106 ml/min per m2). There was no significant difference (p = 0.89) in oxygen delivery between the two groups with occlusion of the atrial septal defect. With the atrial septal defect open, the interatrial gradient was not significantly different in low risk patients (4 +/- 1 mm Hg) from that in high risk patients (4 +/- 1 mm Hg). CONCLUSIONS: These data show that an interatrial communication results in increased postoperative systemic perfusion and oxygen delivery in patients with good diastolic ventricular function after the Fontan procedure.

Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens.

Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1-year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year.

Amiodarone therapy does not compromise subsequent heart transplantation.

OBJECTIVES: The objective of this study was to determine the frequency of pulmonary complications, feasibility of early hospital discharge and requirements for postoperative inotropic and chronotropic support in patients receiving amiodarone therapy before heart transplantation. BACKGROUND: Although many patients waiting for heart transplantation will die of arrhythmias before a donor heart is found, the use of amiodarone has been limited by concern about increased complications in the perioperative period. METHODS: The 29 patients receiving amiodarone at the time of heart transplantation at University of California, Los Angeles Medical Center between October 1986 and September 1990 were compared with 29 control recipients to evaluate postoperative morbidity. Patients were receiving amiodarone for recurrent ventricular tachyarrhythmias (n = 11), atrial fibrillation (n = 2) or complex ventricular ectopic activity (n = 16). The average daily dose was 360 +/- 230 mg/day for an average of 11 +/- 22 months before transplantation. Amiodarone and control groups had a similar ejection fraction (0.18 +/- 0.07 vs. 0.20 +/- 0.08), frequency of coronary disease, age and gender. There were three more status I patients in the control group. OKT3 was given to only two patients receiving amiodarone and 12 control patients at high risk for renal dysfunction. RESULTS: Postoperatively, the duration of assisted ventilation was 21 +/- 19 h after amiodarone therapy versus 26 +/- 2 h in the control group (20 +/- 18 h vs. 15 +/- 9 h after excluding patients receiving OKT3), discharge arterial oxygen saturation was > 95% in both groups. Two patients in the amiodarone group with a smoking history of > 100 pack-years developed bilateral pulmonary infiltrates of brief duration. Although patients receiving amiodarone required atrial pacing more frequently (eight vs. two patients) and had a lower heart rate at discharge (75 +/- 18 vs. 86 +/- 11 beats/min), the duration of inotropic support (2.1 +/- 1.5 vs. 3.5 +/- 2.5 days) and of hospital stay (10 +/- 3 vs. 15 +/- 10 days) was not higher in the amiodarone than in the control group. The mortality rate at 30 days was similar in the two groups (6.8% vs. 3.4%, p = NS). CONCLUSIONS: Amiodarone therapy before heart transplantation may contribute to occasional pulmonary complications but does not significantly increase perioperative morbidity or mortality with the regimens used in this retrospective study.