Lynn A. Sleeper

Comparison of shunt types in the Norwood procedure for single-ventricle lesions.

BACKGROUND The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies. METHODS Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age. RESULTS Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02). CONCLUSIONS In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.)

Prediction of Adverse Outcomes in Children with Sickle Cell Disease

BACKGROUND The ability to identify infants with sickle cell anemia who are likely to have severe complications later in life would permit accurate prognostication and tailoring of therapy to match disease-related risks and facilitate planning of clinical trials. We attempted to define the features of such babies by following the clinical course of 392 children with sickle cell disease from infancy to about the age of 10 years. METHODS We analyzed the records of 392 infants who received the diagnosis of homozygous sickle cell anemia or sickle cell-Beta(0)-thalassemia before the age of six months and for whom comprehensive clinical and laboratory data were recorded prospectively; data were available for a mean (+/-SD) of 10.0+/-4.8 years. Results obtained before the age of two years were evaluated to determine whether they predicted the outcome later in life. RESULTS Of the 392 infants in the cohort, 70 (18 percent) subsequently had an adverse outcome, defined as death (18 patients [26 percent]), stroke (25 [36 percent]) frequent pain (17 [24 percent]), or recurrent acute chest syndrome (10 [14 percent]). Using multivariate analysis, we found three statistically significant predictors of an adverse outcome: an episode of dactylitis before the age of one year (relative risk of an adverse outcome, 2.55; 95 percent confidence interval, 1.39 to 4.67), a hemoglobin level of less than 7 g per deciliter (relative risk, 2.47; 95 percent confidence interval, 1.14 to 5.33), and leukocytosis in the absence of infection (relative risk, 1.80; 95 percent confidence interval, 1.05 to 3.09). CONCLUSIONS Three easily identifiable manifestations of sickle cell disease that may appear in the first two years of life (dactylitis, severe anemia, and leukocytosis) can help to predict the possibility of severe sickle cell disease later in life.

Decreased muscarinic receptor binding in the arcuate nucleus in Sudden Infant Death Syndrome

Muscarinic cholinergic activity in the human arcuate nucleus at the ventral medullary surface is postulated to be involved in cardiopulmonary control. A significant decrease in [3H]quinuclidinyl benzilate binding to muscarinic receptors in the arcuate nucleus is now shown to occur in sudden infant death syndrome (SIDS) infants, compared to infants dying acutely of known causes. In infants with chronic oxygenation abnormalities, binding is low in other nuclei, as well as in the arcuate nucleus. The binding deficit in the arcuate nucleus of SIDS infants might contribute to a failure of responses to cardiopulmonary challenges during sleep.

Contemporary Outcomes After the Fontan Procedure: A Pediatric Heart Network Multicenter Study

OBJECTIVES We characterized a large cohort of children who had a Fontan procedure, with measures of functional health status, ventricular size and function, exercise capacity, heart rhythm, and brain natriuretic peptide (BNP). BACKGROUND The characteristics of contemporary Fontan survivors are not well described. METHODS We enrolled 546 children (age 6 to 18 years, mean 11.9 years) and compared them within pre-specified anatomic and procedure subgroups. History and outcome measures were obtained within a 3-month period. RESULTS Predominant ventricular morphology was 49% left ventricular (LV), 34% right ventricular (RV), and 19% mixed. Ejection fraction (EF) was normal for 73% of subjects; diastolic function grade was normal for 28%. Child Health Questionnaire mean summary scores were lower than for control subjects; however, over 80% of subjects were in the normal range. Brain natriuretic peptide concentration ranged from <4 to 652 pg/ml (median 13 pg/ml). Mean percent predicted peak O2 consumption was 65% and decreased with age. Ejection fraction and EF Z score were lowest, and semilunar and atrioventricular (AV) valve regurgitation were more prevalent in the RV subgroup. Older age at Fontan was associated with more severe AV valve regurgitation. Most outcomes were not associated with a superior cavopulmonary connection before Fontan. CONCLUSIONS Measures of ventricular systolic function and functional health status, although lower on average in the cohort compared with control subjects, were in the majority of subjects within 2 standard deviations of the mean for control subjects. Right ventricular morphology was associated with poorer ventricular and valvular function. Effective strategies to preserve ventricular and valvular function, particularly for patients with RV morphology, are needed.

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction : A report from the shock trial Registry

OBJECTIVES We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.

Epidemiology and Cause-Specific Outcome of Hypertrophic Cardiomyopathy in Children Findings From the Pediatric Cardiomyopathy Registry

Background— Current information on the epidemiology and outcomes of hypertrophic cardiomyopathy (HCM) in children is limited by disease diversity and small case series. Methods and Results— The Pediatric Cardiomyopathy Registry has collected prospective and retrospective data on children diagnosed with HCM since 1990. We identified the various causes of HCM in childhood and determined the relationship between outcomes, cause, and age at presentation. Of 855 patients <18 years of age with HCM, 8.7% (n=74) had inborn errors of metabolism, 9.0% (n=77) had malformation syndromes, 7.5% (n=64) had neuromuscular disorders, and 74.2% (n=634) had idiopathic HCM. Children with HCM associated with inborn errors of metabolism and malformation syndromes have significantly worse survival than the other 2 groups. Patients with idiopathic HCM diagnosed before 1 year of age (n=227) had worse survival from the time of diagnosis than those diagnosed after 1 year of age (n=407). Patients with idiopathic HCM who survived to at least 1 year of age, however, had an annual mortality rate of 1% that was similar regardless of whether they were diagnosed before or after 1 year of age. Conclusions— In children, HCM is a diverse disorder with outcomes that depend largely on cause and age. Patients presenting before 1 year of age have the broadest spectrum of causes and the poorest outcome. In those children with idiopathic HCM who survive beyond age 1, however, survival is independent of age at diagnosis, with an annual mortality rate (1%) that is much lower than previously reported in children and is not different from has been found in population-based studies in adults.

Sickle cell disease as a cause of osteonecrosis of the femoral head.

BACKGROUND AND METHODS Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later. RESULTS At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation. CONCLUSIONS Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry☆

OBJECTIVES We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting.

Atenolol versus Losartan in Children and Young Adults With Marfan's Syndrome

BACKGROUND Aortic-root dissection is the leading cause of death in Marfans syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfans syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS Among children and young adults with Marfans syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

Percutaneous coronary intervention for cardiogenic shock in the SHOCK trial

OBJECTIVES We examined the clinical, angiographic, and procedural characteristics determining survival after percutaneous coronary intervention (PCI) for cardiogenic shock. BACKGROUND The SHOCK (SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?) trial prospectively enrolled patients with shock complicating acute myocardial infarction (MI). Patients were randomized to a strategy of early revascularization or initial medical stabilization. METHODS Patients randomized to early revascularization underwent PCI or bypass surgery on the basis of predefined clinical criteria. Patients randomized to early revascularization who underwent PCI and had angiographic films available for analysis are the subject of this report (n = 82). RESULTS The median time from MI to PCI was 11 h. The majority of patients had occluded culprit arteries (Thrombolysis In Myocardial Infarction [TIMI] grade 0 or 1 flow in 62%) and multivessel disease (81%). One-year mortality in PCI patients was 50%. Mortality was 39% if PCI was successful but 85% if unsuccessful (p < 0.001). Mortality was 38% if TIMI flow grade 3 was achieved, 55% with TIMI grade 2 flow, and 100% with TIMI grade 0 or 1 flow (p < 0.001). Mortality was 67% if severe mitral regurgitation was documented. Independent correlates of mortality were as follows: increasing age (p < 0.001), lower systolic blood pressure (p = 0.009), increasing time from randomization to PCI (p = 0.019), lower post-PCI TIMI flow (0/1 vs. 2/3) (p < 0.001), and multivessel PCI (p = 0.040). CONCLUSIONS Restoration of coronary blood flow is a major predictor of survival in cardiogenic shock. Benefit appears to extend beyond the generally accepted 12-h post-infarction window. Surgery should be considered in shock patients with severe mitral insufficiency or multivessel disease not amenable to relatively complete percutaneous revascularization.