The impact of flow PRA on outcome in pediatric heart recipients in modern era: An analysis of the Pediatric Heart Transplant Study database.

Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA > 20%. Patients with a PRA > 20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%. Patients with higher PRA% determined by SPA were predictive of a positive retrospective cross-match determined by flow cytometric method (P < .001). A PRA > 50% determined by SPA was independently associated with worse overall graft survival after first month of transplant in both unadjusted and adjusted for all other risk factors. In this large multicenter series of pediatric heart transplant recipients, an elevated PRA determined by SPA remains a significant risk factor in the modern era.

The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation.

Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.

Association of race and socioeconomic position with outcomes in pediatric heart transplant recipients.

We assessed the association of socioeconomic (SE) position with graft loss in a multicenter cohort of pediatric heart transplant (HT) recipients. We extracted six SE variables from the US Census 2000 database for the neighborhood of residence of 490 children who underwent their primary HT at participating transplant centers. A composite SE score was derived for each child and four groups (quartiles) compared for graft loss (death or retransplant). Graft loss occurred in 152 children (122 deaths, 30 retransplant). In adjusted analysis, graft loss during the first posttransplant year had a borderline association with the highest SE quartile (HR 1.94, p = 0.05) but not with race. Among 1-year survivors, both black race (HR 1.81, p = 0.02) and the lowest SE quartile (HR 1.77, p = 0.01) predicted subsequent graft loss in adjusted analysis. Among subgroups, the lowest SE quartile was associated with graft loss in white but not in black children. Thus, we found a complex relationship between SE position and graft loss in pediatric HT recipients. The finding of increased risk in the highest SE quartile children during the first year requires further confirmation. Black children and low SE position white children are at increased risk of graft loss after the first year.

Analysis of morbid events and risk factors for death after cardiac transplantation.

Risk factors for death after cardiac transplantation performed at the University of Alabama at Birmingham from January 1981 to July 1985 included (by multivariate analysis) higher calculated preoperative pulmonary vascular resistance (early and constant phases), morphology of cardiomyopathy (versus ischemic heart disease) (constant phase only) and black race (constant phase). Overall actuarial survival was 71% at 1 year and 48% at 3 years (including azathioprine and cyclosporine eras). The hazard function for death was highest immediately after operation and declined rapidly thereafter, merging with a constant phase of risk at about 3 months. The most favorable group for long-term survival was the group of white patients with ischemic heart disease and low pulmonary vascular resistance. When such patients had a pulmonary vascular resistance less than 3 units.m2, the 3 year survival rate exceeded 85%. The most common causes of death were acute rejection (24%) and infection (17%). The risk of infection remained highest during the first several months after any period of augmented immunosuppression.

Fate of infants with hypoplastic left heart syndrome listed for cardiac transplantation: a multicenter study.

BACKGROUND: Infants with hypoplastic left heart syndrome (HLHS) commonly undergo cardiac transplantation as primary management. METHODS: We examined outcomes of primary transplantation for unpalliated HLHS. We analyzed data from the 20 institutions of the Pediatric Heart Transplant Study Group, from January 1, 1993, through December 31, 1998, using actuarial and parametric survival analysis and competing outcomes analysis. RESULTS: During the 6 years studied, 1,234 patients were listed for cardiac transplantation; 262 patients (21.2%) had unpalliated HLHS. The number (and percentage) of patients with HLHS decreased from 58 (27% of patients listed) in 1993 to 30 (14%) in 1998. Overall, 25% of infants with HLHS died while waiting; primary cause of death was cardiac failure (50%). Of the remaining patients awaiting transplantation, 23 (9%) underwent Norwood/Fontan-type surgeries as interim palliation: 52% died. Ultimately, 175 patients underwent cardiac transplantation (67%); 50% received organs by 2 months after listing. Post-transplant actuarial survival was 72% at 5 years, with 76% of deaths (35/46) occurring within 3 months; early mortality was caused primarily by graft failure within the first 30 days after transplantation (in 54%). Among 1-month survivors, survival at 1 and at 5 years was 92% and 85%, respectively. Of the 262 patients listed with unpalliated HLHS, overall survival, taking into account mortality after listing and after transplantation, was 68% at 3 months and 54% at 5 years. CONCLUSIONS: Cardiac transplantation offers good intermediate survival for infants with unpalliated HLHS.

Total lymphoid irradiation in the treatment of early or recurrent heart transplant rejection.

PURPOSE: Recurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection. MATERIALS AND METHODS: Between January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia. RESULTS: The mean posttransplant follow-up is 15 +/- 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67 and 0.07/patient/month (p < 0.001), respectively. The reduced post-TLI rejection frequencies were maintained to 24 months. There was no increase in the frequency of infection after TLI, nor were there any deaths during or immediately following TLI. CONCLUSION: Total lymphoid irradiation is a safe and effective adjunct for prolonged control of early or recurrent cardiac rejection. Bone marrow suppression is transient in nearly all patients and is not associated with an increased incidence of infection. The long-term benefits, possible late deleterious effects, and the potential role of TLI as induction therapy remain to be elucidated.

Early and intermediate-term (10-year) results of surgery for univentricular atrioventricular connection ("single ventricle").

One hundred sixteen patients with "single ventricle" underwent 147 operations between 1967 and July 1982, with an actuarial survival rate (hospital deaths are included in all actuarials) at 10 years of 66%. One hospital death (2%) occurred after 45 primary "classic" shunting operations, and the 10-year actuarial survival was 85%. There were no hospital deaths after atrial septectomy or pulmonary artery banding, and the 10-year actuarial survival rate after these as initial procedures was 76% and 74%, respectively. Thirteen of 36 patients (36%) who underwent ventricular septation between 1967 and November 1, 1983, died in hospital. Among the 13 with the ideal morphologic characteristics of double inlet left ventricle without major associated cardiac anomalies, and without the need for valve replacement or a valved extracardiac conduit, there were no hospital deaths and a late survival rate of 77% (confidence limits 59 to 90%). Sixteen of 73 patients (22%), including those with tricuspid atresia, undergoing the Fontan-type procedure between 1967 and November 1, 1983, died in hospital. Multivariate analysis indicates that cardiac morphologic patterns other than tricuspid atresia are risk factors for hospital death in this group. The 10-year actuarial survival rate among the 73 patients was 71%, but only 1 death (associated with reoperation) occurred more than 2 months after operation. Ninety-seven percent of all surviving patients are in New York Heart Association functional class I or II, as are 100% of those who underwent septation and 96% of those who underwent the Fontan-type procedure.

A comparison of repair and replacement for mitral valve incompetence.

A total of 101 reparative and 389 valve replacement operations, isolated or combined with tricuspid annuloplasty or operations for coronary artery disease, were done for mitral incompetence (1975 to July 1, 1983). The patients undergoing repair as a group were younger and had less hemodynamic and functional derangement than those undergoing replacement. The prevalence of repair was less (p less than 0.001) for two surgeons than for the other four, even when possible differences in patient populations were taken into account by multivariate analysis. Five-year survival rate, including hospital deaths, was 76% after valve repair and 56% after valve replacement (p = 0.005). However, by multivariate analysis, valve replacement rather than repair was only possibly (p = 0.14) a risk factor. (Multivariate analysis in all patients undergoing mitral valve repair in the period 1967 to 1985 [n = 210] did not find the type of annuloplasty to be a risk factor.) The incidence of reoperation was no different after repair or replacement and there was no increase in the risk of reoperation late after repair. Endocarditis early or late after operation occurred in 11 of the 389 patients undergoing mitral replacement and in none of those undergoing repair (p = 0.08). The functional status of the patients was not different between the two groups. These data, and the experience of others, indicate the advantages of repairing rather than replacing the incompetent mitral valve whenever possible.

Microvascular permeability after cardiopulmonary bypass. An experimental study.

UNLABELLED: Microvascular permeability is presumed to increase during cardiopulmonary bypass, but this has not been directly demonstrated. METHOD: Therefore, a controlled experimental study was performed in dogs in which the permeability ratio of the small intestinal microvasculature was determined. Shortly after 120 minutes of cardiopulmonary bypass (experimental group, n = 7) or a sham procedure (control group, n = 7), the superior mesenteric venous pressure was raised in a stepwise fashion until the intestinal lymph/plasma protein concentration stabilized at a minimum value. DATA: Minimal lymph/plasma concentration ratio (permeability ratio) of the total proteins and each of six protein fractions was greater in dogs that had been on bypass than in control dogs (p = 0.01 for total proteins and less than 0.05 for five of the fractions). The variability in this regard was large in both groups, and in some animals subjected to bypass the permeability ratio was more than twice the maximum value for the control group. The increase in permeability ratio was greater for large molecules. Inferences: Cardiopulmonary bypass results in a variable increase in microvascular permeability. This results primarily from an increase in the size of large pores in the microvascular barrier.

The effect of reperfusion pressure on early outcomes after coronary artery bypass grafting. A randomized trial.

Among 60 patients randomly assigned to a reperfusion pressure of 50 mm Hg or one of 75 mm Hg (30 mm Hg during the first 2 minutes in both groups) during initially hyperkalemic, controlled aortic root reperfusion after coronary artery bypass grafting, no in-hospital deaths occurred, no patient received an intraaortic balloon pump, no patient had new Q waves, and creatine kinase MB release was similar in the two groups. Median interval between the beginning of reperfusion and the return of rhythmic cardiac contractions in the 50 mm Hg group was 7 minutes; in the 75 mm Hg group, it was 5 minutes (P = 0.1). The initial reactive hyperemic response was greater in the 75 mm Hg group. There were no believable differences (P < 0.1) between the two groups in postoperative cardiac output, left and right atrial pressure, arterial blood pressure, and prevalence of catecholamine administration.

The size of the pulmonary arteries and the results of the Fontan operation.

All patients (n = 334) undergoing the Fontan operation at the University of Bordeaux, France, and the University of Alabama Medical Center, Birmingham, were entered into a single data base to examine the relation, if any, between size of the pulmonary arteries and outcome. Recent follow-up was made of all patients. The time-related freedom from death or takedown of the Fontan operation was 78% at 1 month, 73% at 6 months, and 72%, 68%, 61%, and 50% at 1, 5, 10, and 15 years after the operation. The hazard function (instantaneous risk of the combined event at each moment in time after the operation) had a rapidly declining early phase that gave way at about 6 months to a late phase of hazard, which began slowly to rise about 8 years after the operation. One of the most powerful risk factors for death or takedown of the Fontan operation was the dimensions of the right and left pulmonary arteries, expressed as a McGoon ratio. By multivariate analysis, the risk of the combined event increased sharply when the McGoon ratio was less than about 1.8, and when the ratio was as low as 1.2 the probability of death or takedown within 30 days of the operation was predicted to be 55% when the right atrium was connected to the pulmonary artery and 34% when connected to the right ventricle. Other risk factors identified were age at operation, the presence of mitral atresia, the degree of main chamber hypertrophy, elevated pulmonary artery pressure, non-use of cardioplegia, global myocardial ischemic time, and attachment of the right atrium to the pulmonary artery rather than to the right ventricle.

Cardiac transplant coronary artery disease. A multivariable analysis of pretransplantation risk factors for disease development and morbid events.

Coronary artery disease after cardiac transplantation is a major obstacle to long-term survival. The development and progression of coronary artery disease after cardiac transplantation was analyzed in 217 consecutive patients undergoing transplantation. The actuarial freedom from any coronary artery disease (by angiography or autopsy) was 81% at 2 years and 20% at 8 years after transplantation. Coronary artery disease was more prevalent in male than female patients (30% versus 50% free of coronary artery disease at 5 years, p = 0.01). By multivariable analysis, pretransplantation risk factors identified for coronary artery disease included pretransplantation positive cytomegalovirus serologic status of the recipient (p = 0.002) and older donor age (p = 0.07). Progression of coronary artery disease was variable in both time of onset and rate. Earlier detection did not result in more rapid progression. Coronary events severe enough for retransplantation (n = 8) and/or death from coronary artery disease (n = 9) occurred in 15 patients, of whom four underwent retransplantation. The actuarial freedom from coronary events was 88% at 5 years and 79% at 8 years. By multivariable analysis, only male recipient (p = 0.05) was a risk factor for coronary events. Seven of the 15 patients (47%) with coronary events died suddenly of coronary artery disease without prior angiographic evidence of severe coronary disease. Coronary artery disease is progressive. Improved surveillance methods are required to detect the disease and institute timely intervention to prevent the occurrence of unanticipated death.

Prophylactic therapy for rejection after cardiac transplantation. A comparison of rabbit antithymocyte globulin and OKT3.

The value of prophylactic monoclonal or polyclonal antibody therapy early after cardiac transplantation is controversial. Between Jan. 1, 1987, and July 1, 1988, 32 consecutive patients underwent cardiac transplantation (cyclosporine, azathioprine, and prednisone maintenance therapy) with either early prophylactic rabbit antithymocyte globulin (n = 17) or monoclonal OKT3 (Ortho Diagnostic Systems, Inc., Raritan, N.J.) (10 days) (n = 15). Follow-up was through Sept. 1, 1988, for morbid events and through Jan. 1, 1989, for survival. All patients (100%) survived the study period (follow-up of 6 to 24 months). The efficacy of rabbit antithymocyte globulin and OKT3 prophylaxis was similar regarding median time (days) to first rejection (16 versus 21 days, p = 0.5), number of rejection episodes during first 2 months (1.5 versus 1.3 days, p = 0.8), and freedom from rejection at 2 months (18% versus 27%, p = 0.8). Early infections were slightly less common in the rabbit antithymocyte globulin group than the OKT3 group (median time to first infection: 318 versus 250 days, p = 0.5; freedom from rejection at 2 months: 82% versus 64%, p = 0.21), although differences were likely due to chance. Cytomegalovirus syndrome was common, with one case of cytomegalovirus pneumonia. T-cell markers during OKT3 treatment did not predict subsequent rejection (within 2 weeks after OKT3) as assessed by mean T3-lymphocyte count during OKT3 use (p = 0.3) or T3-lymphocyte count during the last 3 days of OKT3 use (p = 0.4). Inferences: (1) Prophylactic rabbit antithymocyte globulin or OKT3 with triple-drug immunosuppression yields excellent intermediate survival after heart transplantation. (2) These protocols for rabbit antithymocyte globulin and OKT3 provide similar protection against early rejection with a relatively low risk of early infection. (3) T-cell markers do not predict early rejection after OKT3.

Long-term function of cryopreserved aortic homografts. A ten-year study.

Cryopreserved aortic valve homografts have become an accepted aortic valve substitute, but long-term studies with echocardiographic assessment of valve function are largely unavailable. Between 1981 and January 1, 1991, a total of 178 patients aged 9 months to 80 years (median 46 years) underwent implantation of a cryopreserved aortic valve homograft. Serial two-dimensional Doppler echocardiographic studies were obtained in 149 patients. Overall survival was 91% at 1 year and 85% at 8 years. Survival of patients undergoing isolated primary infracoronary aortic valve replacement was 99% at 1 month and 94% at 8 years. Twelve patients underwent homograft explanation. Freedom from explantation for leaflet degeneration was 95% at 8 years. Freedom from presumed leaflet failure (valve degeneration at explantation or aortic insufficiency grade 3/4 or more without reoperation on echocardiography) was 94% at 5 years and 85% at 8 years. By multivariable analysis younger recipient age was the only risk factor identified for leaflet failure. Ninety-five percent of patients followed up for 4 or more years were in New York Heart Association class I or II.

Analysis and predictors of pulmonary vascular resistance after cardiac transplantation.

Elevated pulmonary vascular resistance is a known risk factor for early death from acute right ventricular failure after orthotopic cardiac transplantation. Patients in whom the elevated pulmonary vascular resistance is due primarily to increased left atrial pressure ("reactive") frequently have normalization of resistance after transplantation, but few studies have detailed the time course and magnitude of these changes. To analyze the response of pulmonary vascular resistance to cardiac transplantation, we analyzed data from 4353 right heart catheterizations on all 182 patients undergoing cardiac transplantation between 1981 and Jan. 1, 1990. Before transplantation 18% of patients had a pulmonary vascular resistance greater than 4 WU, 16% had a pulmonary artery systolic pressure greater than 60 mm Hg, and 16% had a transpulmonary gradient greater than 14 mm Hg. In the overall group of patients, pulmonary vascular resistance (mean value 2.63 WU), transpulmonary gradient (mean value 9.9 mm Hg), and pulmonary artery systolic pressure (mean value 48.0 mm Hg) were normalized within 1 week of cardiac transplantation. In patients with a high preoperative pulmonary vascular resistance (greater than or equal to 4 WU), the resistance fell promptly within 1 week of transplantation but continued to be slightly elevated throughout the period of follow-up. By multiple regression analysis, pulmonary vascular resistance at 1 week and 1 year after transplantation was significantly correlated with the pretransplantation resistance. Pulmonary vascular resistance anytime after transplantation was related to preoperative resistance, body surface area, and pulmonary artery diastolic pressure. Inferences: (1) As a group, cardiac transplant recipients have a normal pulmonary vascular resistance, transpulmonary gradient, and pulmonary artery systolic pressure within 1 week after transplantation with little change thereafter for at least several years. (2) Patients with reversible elevation of pulmonary vascular resistance before cardiac transplantation typically have a reactive and a fixed component. Cardiac transplantation relieves the reactive but not the fixed component. As a result, pulmonary vascular resistance early (within 1 week) and late after transplantation will have fallen but not completely normalized.

Surgery for acute dissection of ascending aorta. Should the arch be included?

Thirty-day and 1-, 5-, 10-, and 20-year overall survivorships among 82 patients undergoing replacement of the ascending aorta with or without the arch for acute aortic dissection between 1968 and May 1989 were 79%, 66%, 56%, 46%, and 30%, respectively. The multivariably determined risk factors for death were the inclusion of the arch in the replacement, the year of the operation, the predissection New York Heart Association functional class, diabetes, and concomitant coronary artery bypass grafting. The current 30-day survivorship predicted by the multivariable equation when the operation involves only the ascending aorta is 97%, and the 10- and 20-year predicted survivorships are 61% and 39%, respectively. When the current era the replacement involves the arch as well as the ascending aorta, the predicted 30-day survivorship is 84%, and the 10- and 20-year ones are 48% and 31%. In 1990 sixteen additional patients (one hospital death) underwent ascending aortic replacement, and six (no hospital deaths) ascending aorta and arch replacement. The predictions for 1990 from the multivariable equation were similar to these actual experiences (Ps for differences were 0.6 and 0.4). Seventy percent of surviving patients with DeBakey type I dissection were free of a second aortic operation for aneurysmal dilation of the distal false channel, but this occurred in none of nine patients in whom an intimal tear in the transverse arch was included in the resection.

The effect of hypothermic circulatory arrest time on cerebral function, morphology, and biochemistry. An experimental study.

Thirty-two pairs (n = 64) of Mongolian gerbils were surface cooled to 18 degrees C and randomly subjected to 0 to 180 minutes of bilateral carotid occlusion in the neck. They were rewarmed after release of the carotid occlusion. After rewarming, one member of each pair was allowed to survive 7 days and then was put to death for brain histologic study; the other was subjected to brain preservation by quick freezing for subsequent biochemical studies. In the survivors, neurologic function was depressed during the 7 subsequent days, and the depression was in direct relation to the time of carotid occlusion (p = 0.0005). The proportion of normal hippocampal neurons decreased in direct proportion to the length of carotid occlusion (p less than 0.0001). The depression in neurologic function and in the proportion of normal neurons was evident when occlusion time exceeded 45 minutes. The proportion of normal neurons was correlated with neurologic function (r = 0.56, p = 0.0001). Cortical adenosine triphosphate (ATP) concentration after brain reperfusion was reduced in comparison with normal and varied inversely with carotid occlusion time (r = -0.84, p less than 0.0001). Alanine (p less than 0.001), lactate (p = 0.01), and pyruvate (p = 0.001) concentrations were elevated, in direct relation to carotid occlusion time. These observations are consistent with other experimental studies of profoundly hypothermic total circulatory arrest and indicate the damaging effect of this modality, particularly when the circulatory arrest time exceeds 45 minutes.

An analysis of valve re-replacement after aortic valve replacement with biologic devices.

Biologic valve re-replacement was examined in a series of 1343 patients who underwent aortic valve replacement at The Prince Charles Hospital, Brisbane, with a cryopreserved or 4 degrees C stored allograft valve or a xenograft valve. A parametric model approach was used to simultaneously model the competing risks of death without re-replacement and re-replacement before death. One hundred eleven patients underwent a first re-replacement for a variety of reasons (69 patients with xenograft valves, 28 patients with 4 degrees C stored allograft valves, and 14 patients with cryopreserved allograft valves). By multivariable analysis younger age at operation was associated with xenograft, 4 degrees C stored allograft, and cryopreserved allograft valve re-replacement. However, this effect was examined in the context of longer survival of younger patients, which increases their exposure to the risk of re-replacement as compared with that in older patients whose decreased survival reduced their probability of requiring valve re-replacement. In patients older than 60 years at the time of aortic valve replacement, the probability of re-replacement (for any reason) before death was similar for xenografts and cryopreserved allograft valves but higher for 4 degrees C stored valves. However, in patients younger than 60 years, the probability of re-replacement at any time during the remainder of the life of the patient was lower with the cryopreserved allograft valve compared with the xenograft valve and 4 degrees C stored allografts.

Evolving trends in risk profiles and causes of death after heart transplantation: a ten-year multi-institutional study.

BACKGROUND: As therapeutic options evolve for advanced heart failure, the appropriate role for cardiac transplantation will require survival analyses that reflect changing trends in causes of death and patient and institutional risk profiles. Results from multi-institutional studies could be used to monitor progress in individual centers. METHODS: Between 1990 and 1999, 7290 patients undergoing cardiac transplantation in 42 institutions entered a formal outcomes study. Changing survival, causes of death, and patient risk profiles were analyzed. Multivariable risk-factor equations were applied to a single institution (300 primary heart transplants) to examine differences in risk-adjusted expected versus observed actuarial outcomes over time. RESULTS: Overall survival in the 42 institutions improved during the decade (P =.02). One- and 3-year cardiac transplant research database survival was as follows: era 1 (1990-1992), 84% and 76%, respectively; era 2 (1993-1995), 85% and 79%, respectively; and era 3 (1996-1999), 85% and 79%, respectively. Causes of death changed over time. Pretransplantation risk profiles increased over time (P =.0001), with increases in reoperations, devices, diabetes, severely ill recipients, pulmonary vascular resistance, sensitization, ischemic times, donor age, and donor inotropic support. Three-year actuarial survival in a single institution was 3% less than risk-adjusted predicted survival in era 1, 1% higher than predicted in era 2, and 7% higher than predicted in era 3. CONCLUSIONS: Survival after cardiac transplantation is gradually improving, despite increasing risk profiles. Further improvement requires periodic re-evaluation of risk profiles and causes of death to target areas of surveillance, therapy, and research. By using these methods, progress at individual institutions can be assessed in a time-related, risk-adjusted manner that also reflects changing institutional experience, expertise, or both.

Pretransplantation risk factors for death after heart transplantation: the Henri Mondor experience.

BACKGROUND AND METHODS: Risk factors for death after primary heart transplantation were identified by analyzing our total experience with 234 patients who underwent transplantation at our institution from May 28, 1979, to May 27, 1996. RESULTS: There were 205 male and 29 female patients. Mean recipient age was 48.5+/-10.9 years (standard deviation). Recipient diagnosis included ischemic cardiomyopathy in 103 (44%), idiopathic cardiomyopathy in 98 (42%), valvular heart disease in 17 (7%), congenital heart disease in 4 (2%), and other diagnoses in 12 (5%) patients. Donor age was 32+/-10.2 years. Graft ischemic time was 138.1+/-51.8 minutes. The operative mortality rate was 23.5%. Actuarial survival estimates for all patients at 1, 5, and 10 years were 62%, 50%, and 44%, respectively. The three most common causes of death (both early and late) after primary heart transplantation were infection (27.4%), acute rejection (18.9%), and early graft failure (17.9%). Multivariate logistic regression analysis identified older recipient age (p = 0.007), higher preoperative pulmonary vascular resistance (p = 0.01), recipient preoperative hepatic insufficiency (p = 0.001), and gender mismatch (p = 0.02) as independent predictors of early death (within 3 months of the procedure). Multivariate proportional hazard regression analysis revealed that recipient idiopathic cardiomyopathy (p = 0.02) and recipient preoperative liver failure (p = 0.01) were independent risk factors for late death (after 3 months). CONCLUSION: These results underscore the importance of adequate recipient selection and recipient/donor matching for short- and long-term survival after primary heart transplantation.