Baseline Quality-of-Life of Caregivers of Patients With Heart Failure Prior to Advanced Therapies: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT) Study.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ2 tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R2 = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

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.

An essential role for Fas ligand in transplantation tolerance induced by donor bone marrow.

Medawar and co-workers originally demonstrated that injection of donor bone marrow (DBM) into immuno-incompetent neonatal rodents could induce tolerance to grafts from animals of the same strain as the bone marrow donor. Induction of tolerance in this manner can also be accomplished in mature mice, dogs and monkeys if the resident T-cell populations in the recipient are depleted by a polyclonal antithymocyte globulin or an anti-T cell immunotoxin. The molecular mechanisms by which bone marrow cells mediate the induction of tolerance remain uncertain. Here we examined a well-established adult mouse model of antithymocyte globulin and DBM treatment and show that expression of functional Fas ligand (FasL, also CD95L) on the injected bone marrow cells is required for tolerance induction. The results indicate that a state of microchimerism per se is insufficient for the induction of tolerance in T cell-depleted transplant recipients. Moreover, the results are consistent with the hypothesis that tolerance induced by DBM involves an apoptotic process leading to deletion of graft-reactive cells.

Preoperative anthropomorphic radiographic measurements can predict postoperative pancreatic fistula formation following pancreatoduodenectomy.

BACKGROUND: Postoperative pancreatic fistulae (POPF) are a major contributing factor to pancreatoduodenectomy-associated morbidity. Established risk calculators mostly rely on subjective or intraoperative assessments. We hypothesized that various objective preoperatively determined computed tomography (CT) measurements could predict POPF as well as validated models and allow for more informed operative consent in high-risk patients. METHODS: Patients undergoing elective pancreatoduodenectomies between January 2013 and April 2018 were identified in a prospective database. Comparative statistical analyses and multivariable logistic regression models were generated to predict POPF development. Model performance was tested with receiver operating characteristics (ROC) curves. Pancreatic neck attenuation (Hounsfield units) was measured in triplicate by pancreatic protocol CT (venous phase, coronal plane) anterior to the portal vein. A pancreatic density index (PDI) was created to adjust for differences in contrast timing by dividing the mean of these measurements by the portal vein attenuation. Total areas of subcutaneous fat and skeletal muscle were calculated at the L3 vertebral level on axial CT. Pancreatic duct (PD) diameter was determined by CT. RESULTS: In the study period 220 patients had elective pancreatoduodenectomies with 35 (16%) developing a POPF of any grade. Multivariable regression analysis revealed that demographics (age, sex, and race) were not associated with POPF, yet patients resected for pancreatic adenocarcinoma or chronic pancreatitis were less likely to develop a POPF (10 vs. 24%; p = 0.004). ROC curves were created using various combinations of gland texture, body mass index, skeletal muscle index, sarcopenia, PDI, PD diameter, and subcutaneous fat area indexed for height (SFI). A model replacing gland texture with SFI and PDI (AUC 0.844) had similar predictive performance as the established model (p = 0.169). CONCLUSION: A combination of preoperative objective CT measurements can adequately predict POPF and is comparable to established models relying on subjective intraoperative variables. Validation in a larger dataset would allow for better preoperative stratification of high-risk patients and improve informed consent among this patient population.

Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

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.

Outcome of listing for cardiac transplantation for failed Fontan: a multi-institutional study.

BACKGROUND: The Fontan procedure is a successful palliation for children with single-ventricle physiology; however, many will eventually require heart transplantation. The purpose of this study was to determine risk factors for death awaiting transplantation and to examine results after transplantation in Fontan patients. METHODS AND RESULTS: A retrospective, multi-institutional review was performed of 97 Fontan patients <18 years of age listed at 17 Pediatric Heart Transplant Study centers from 1993 to 2001. Mean age at listing was 9.7 years (0.5 to 17.9 years); 25% were <4 years old; 53% were United Network for Organ Sharing status 1; 18% required ventilator support. Pretransplantation survival was 78% at 6 months and 74% at 12 months and was similar to 243 children with other congenital heart disease (CHD) and 747 children without congenital heart disease (No-CHD), who were also awaiting transplantation. Patients who were younger, status 1, had shorter interval since Fontan, or were on a ventilator were more likely to die while waiting. At 6 months, the probability of receiving a transplant was similar for status 1 and 2 (65% versus 68%); however, the probability of death was higher for status 1 (22% versus 5%). Seventy patients underwent transplantation. Survival was 76% at 1 year, 70% at 3 years, and 68% at 5 years, slightly less than CHD and No-CHD patients. Causes of death included infection (30%), graft failure (17%), rejection (13%), sudden death (13%), and graft coronary artery disease (9%). Protein-losing enteropathy (present in 34 patients) resolved in all who survived >30 days after transplantation. CONCLUSIONS: Heart transplantation is an effective therapy for pediatric patients with a failed Fontan. Although early posttransplantation survival is slightly lower than other patients with CHD, long-term results are encouraging, and protein-losing enteropathy can be expected to resolve.

Intermediate septal accessory pathways: electrocardiographic characteristics, electrophysiologic observations and their surgical implications.

Intermediate septal accessory pathways are located in close proximity to the atrioventricular (AV) node and His bundle, have unique features that distinguish them from typical anterior and posterior accessory pathways and have been associated with a high risk for unsuccessful pathway division and the production of complete AV block after surgery. Between July 1986 and May 1990, 4 of 70 patients (3 men and 1 woman; mean age 33 +/- 13 years) undergoing surgery for accessory pathway division were found to have an intermediate septal accessory pathway. The presenting arrhythmia was atrial fibrillation with rapid anterograde conduction over the accessory pathway in two patients and recurrent orthodromic reciprocating tachycardia in two patients. In all patients, the delta wave on the electrocardiogram (ECG) was inverted in lead V1, but two patterns of delta wave configuration were observed. In three patients (type 1 intermediate septal accessory pathway), the delta wave was upright in lead II, inverted in lead III and isoelectric in lead a VF; the transition from a negative to an upright delta wave occurred in lead V2. The fourth patient exhibited a different delta wave pattern (type 2 intermediate septal accessory pathway). The delta wave was upright in each of leads II, III and aVF; the transition from a negative to an upright delta wave occurred at lead V3. Intraoperative electrophysiologic study localized the atrial insertion of type 1 pathways to the midpoint of Koch's triangle close to the AV node.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery to right ventricle fistula in heart transplant recipients: a complication of endomyocardial biopsy.

In a series of 74 heart transplant recipients undergoing annual coronary angiography, a coronary artery to right ventricle fistula was observed in 4 patients, an incidence rate of 5.4%, which is much higher than the expected incidence of congenital coronary artery fistula (0.1% to 0.2%). A traumatic origin of the fistulas is unlikely because none of the heart donors had evidence of chest trauma. An endomyocardial biopsy-related etiology of the fistulas is postulated. All fistulas were located in the biopsy sampling area. Patients with a fistula underwent more biopsies before the diagnosis compared with patients without a fistula (20 +/- 11 versus 14 +/- 6, p = 0.05). At least one large arteriole (diameter greater than 0.16 mm) was found on pathologic examination of the biopsy specimens from each of the patients with a fistula (100%) but in only 2 (16.7%) (p less than 0.01) of 12 randomly selected patients without a fistula. The size of the fistula appears to be hemodynamically insignificant in all four patients, judging from angiographic size, normal intracardiac pressures and normal cardiac output values at rest. The diagnosis of a coronary artery to right ventricle fistula is possible and should be entertained at the time of coronary angiography of heart transplant recipients. The clinical significance of the finding is unclear. As long as endomyocardial biopsy remains the diagnostic method of identifying tissue rejection, prevention of the described complication is unlikely.

Combined automatic implantable cardioverter-defibrillator and pacemaker systems: implantation techniques and follow-up.

The automatic implantable cardioverter-defibrillator (AICD) effectively prevents death due to ventricular tachycardia or ventricular fibrillation. Some patients who need an AICD also require cardiac pacing to treat symptomatic bradycardia, bradycardia after defibrillation, or to provide a rate floor to reduce the frequency of bradycardia-related ventricular arrhythmias. Some patients also can benefit from antitachycardia pacing. A mapping technique to implant a pacemaker and AICD sensing leads is presented. For patients with a pacemaker who later need an AICD, the left ventricle is mapped with use of the AICD rate-sensing electrodes to identify a site at which the minimal pacemaker stimulus and maximal ventricular electrogram amplitudes are recorded. An external cardioverter-defibrillator that has amplifiers similar to those in the AICD is used to monitor the rate-sensing electrogram. For patients with an implanted AICD, pacemaker implantation is undertaken by mapping the right ventricle with the pacemaker lead while the AICD is in standby mode; the AICD beep monitor is then used to determine a site where pacemaker stimulus detection by the AICD does not occur. Eight patients underwent implantation of a combined AICD-pacemaker system (four ventricular antitachycardia pacemakers, three ventricular demand pacemakers and one atrial demand pacemaker). Neither inhibition of AICD arrhythmia detection nor double counting occurred. Satisfactory AICD-pacemaker function was shown in all patients postoperatively, and no pacemaker malfunction was observed. Thus, with currently available technology, a combined AICD-pacemaker system can be implanted with satisfactory function of both devices and without adverse device-device interactions.

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.

Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis.

To assess the usefulness of transesophageal echocardiography in the evaluation of proximal coronary artery stenosis, 111 consecutive patients (mean age 61 years) who had intraoperative transesophageal echocardiography and coronary angiography within 1 week of surgery were studied. Transesophageal echocardiography visualized the entire length of the left main artery (0.2 to 2.2 cm, mean 0.93), 0.2 to 2.2 cm of the proximal left anterior descending artery and 0.1 to 3.4 cm of the proximal left circumflex artery in 103 patients (93%) and 0.1 to 4.6 cm of the proximal right coronary artery in 55 patients (49%). In the coronary artery segments visualized by echocardiography and compared with the corresponding angiographic segments, transesophageal echocardiography correctly identified 23 (96%) of 24 left main stenoses, 11 (78%) of 14 stenoses involving the left anterior descending artery, 6 (75%) of 8 left circumflex stenoses and all 7 stenoses (100%) of the right coronary artery. In all seven patients with ostial stenosis (left main artery in five and right coronary artery in two), the condition was correctly diagnosed by this technique. The sensitivity and specificity of transesophageal echocardiography in the overall evaluation of proximal coronary artery stenosis as customarily defined by angiography were 96% and 99% for the left main artery, 48% and 99% for the left anterior descending artery, 67% and 100% for the left circumflex artery and 37% and 100% for the right coronary artery, respectively. The distance of the stenotic lesion from the origin of the vessel by transesophageal echocardiography also correlated well with that measured by angiography (r = 0.63 to 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a central site of action to explain the negative chronotropic effect of atropine: studies on the human transplanted heart.

The chronotropic response to atropine is biphasic; low doses cause slowing of the sinus rate and high doses cause acceleration. Although it is accepted that atropine functions as a competitive antagonist at high doses, the mechanism of the negative chronotropic response at low doses is controversial. Specifically, it is unclear whether the effect is mediated centrally or peripherally. Since at the time of cardiac replacement all central nervous system connections to the heart are severed, the transplanted heart is a unique model for separating these effects. Graded doses of atropine sulfate (0.5, 1.0, 2.0, 4.0, 8.0 and 40.0 micrograms/kg body weight) were administered to 12 human heart transplant recipients to test the hypothesis that the bradycardiac effect of low dose atropine is centrally mediated. The baseline sinus cycle lengths of the decentralized donor and innervated native sinus nodes were 694 +/- 20 and 733 +/- 27 ms, respectively. At the 0.5 and 1.0 microgram/kg doses, the cycle lengths of the native sinus node increased by 29.1 +/- 13.5 and 23.1 +/- 14.2 ms, respectively. At the 2.0 micrograms/kg dose the sinus cycle length again shortened to control. At the maximal dose of atropine the sinus cycle length shortened by 138.3 +/- 29.7 ms compared with control. In contrast, the decentralized donor sinus node exhibited a flat dose response to atropine. High dose atropine (40 micrograms/kg) caused no change in the donor heart's atrial effective refractory period, corrected sinus node recovery time, or sinoatrial conduction time measured by either the Strauss or the Narula method.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of endocardial and epicardial programmed stimulation for the induction of ventricular tachycardia.

Twenty-seven patients who had pairs of stainless steel wire electrodes placed on the right and the left ventricle during cardiac surgery underwent both epicardial and endocardial programmed ventricular stimulation to assess the inducibility of ventricular tachycardia. Twenty-six of the patients had coronary artery disease and were studied to evaluate map-guided surgery for treatment of ventricular arrhythmias. Burst ventricular pacing and up to three ventricular extrastimuli coupled to two drive train cycle lengths were delivered from the right and left ventricular epicardial wire electrodes and from endocardial catheter electrodes placed at the apex and outflow tract of the right ventricle. Ventricular tachycardia was reproducibly induced in three patients by both endocardial and epicardial stimulation. In one patient ventricular tachycardia was reproducibly induced by epicardial stimulation, but nonreproducible, nonsustained ventricular tachycardia was induced by endocardial stimulation. Ventricular tachycardia remained inducible by both endocardial and epicardial stimulation in three instances (two patients) during drug therapy. A negative study (less than 10 consecutive ventricular beats induced) was obtained in 23 patients by both endocardial and epicardial stimulation. The patients were followed up for 12 to 43 months (average 31). Sudden death or documented ventricular tachycardia occurred in two of the three patients with a positive study by both endocardial and epicardial stimulation. Nineteen (83%) of the 23 patients with concordantly negative studies remained free of arrhythmias. On the basis of concordant results of endocardial and epicardial stimulation (p = 0.001) these results suggest that epicardial stimulation of the right and the left ventricle is an acceptable method to assess the postoperative inducibility of ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?

BACKGROUND: Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven. METHODS: To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736). RESULTS: By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5%, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was <2%. Specific patient sub-sets that received a survival benefit in the current era with induction included younger patients of black race with >/=4 HLA mismatches and long-term (>6 months) support on a ventricular assist device (VAD). CONCLUSIONS: Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.

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.

Azathioprine hypersensitivity. Case report and review of the literature.

Fever in a transplant recipient is an important sign of graft rejection or infection. Rarely, fever may result from an immunosuppressive agent used to prevent graft rejection. A case of fever, rigors, arthralgias, and myalgias is reported in a cardiac transplant recipient in whom azathioprine therapy was recently begun. These findings resolved on discontinuation of the azathioprine, recurred on rechallenge, and were most consistent with a hypersensitivity reaction. The clinical spectrum of reported azathioprine hypersensitivity reactions is reviewed.

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.