In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a ...modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.
Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, -3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45-0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07-4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81-1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02-3.69); and >1 year, 2.48 (95% confidence interval, 1.28-4.80).
By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time.
http://www.clinicaltrials.gov. Unique identifier: NCT00115934.
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.
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.
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).
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.)
The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart ...Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.
Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as ...damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.
To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.
Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.
Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled).
Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status.
No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% 95% CI, -9.6% to 1.1%; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% 95% CI, -10.2% to 2.7%; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% 95% CI, -10.4% to -0.5%; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications.
Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.
clinicaltrials.gov Identifier: NCT01545232.
Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to ...describe associations of diastolic function with current clinical status.
Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored.
DFG was calculable in 326 of 546 subjects (60%) (mean age, 11.7 ± 3.3 years). Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3 diastolic function. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (P < .001); this association remained significant when using Z scores adjusted for age (P < .001). DFG was associated with achieving maximal effort on exercise testing (P = .004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3. No additional significant associations of DFG with laboratory or clinical measures were identified.
Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but few clinically or statistically significant associations were found. This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles.
Although newborn screening for critical congenital heart disease (CCHD) was recommended by the US Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and ...Children to promote early detection, it was deemed by the Secretary of the HHS as not ready for adoption pending an implementation plan from HHS agencies.
To develop strategies for the implementation of safe, effective, and efficient screening.
A work group was convened with members selected by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children, the American Academy of Pediatrics, the American College of Cardiology Foundation, and the American Heart Association.
On the basis of published and unpublished data, the work group made recommendations for a standardized approach to screening and diagnostic follow-up. Key issues for future research and evaluation were identified.
The work-group members found sufficient evidence to begin screening for low blood oxygen saturation through the use of pulse-oximetry monitoring to detect CCHD in well-infant and intermediate care nurseries. Research is needed regarding screening in special populations (eg, at high altitude) and to evaluate service infrastructure and delivery strategies (eg, telemedicine) for nurseries without on-site echocardiography. Public health agencies will have an important role in quality assurance and surveillance. Central to the effectiveness of screening will be the development of a national technical assistance center to coordinate implementation and evaluation of newborn screening for CCHD.
Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder. We assessed the effects of ...antioxidant supplementation with vitamins C and E, initiated early in pregnancy, on the risk of serious adverse maternal, fetal, and neonatal outcomes related to pregnancy-associated hypertension.
We conducted a multicenter, randomized, double-blind trial involving nulliparous women who were at low risk for preeclampsia. Women were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the 9th and 16th weeks of pregnancy. The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death.
A total of 10,154 women underwent randomization. The two groups were similar with respect to baseline characteristics and adherence to the study drug. Outcome data were available for 9969 women. There was no significant difference between the vitamin and placebo groups in the rates of the primary outcome (6.1% and 5.7%, respectively; relative risk in the vitamin group, 1.07; 95% confidence interval CI, 0.91 to 1.25) or in the rates of preeclampsia (7.2% and 6.7%, respectively; relative risk, 1.07; 95% CI, 0.93 to 1.24). Rates of adverse perinatal outcomes did not differ significantly between the groups.
Vitamin C and E supplementation initiated in the 9th to 16th week of pregnancy in an unselected cohort of low-risk, nulliparous women did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension (ClinicalTrials.gov number, NCT00135707).
Objectives The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified ...Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths. Methods There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event. Results The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome. Conclusions In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate.
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