David E. Fixler

Mortality Resulting From Congenital Heart Disease Among Children and Adults in the United States, 1999 to 2006

Background— Previous reports suggest that mortality resulting from congenital heart disease (CHD) among infants and young children has been decreasing. There is little population-based information on CHD mortality trends and patterns among older children and adults. Methods and Results— We used data from death certificates filed in the United States from 1999 to 2006 to calculate annual CHD mortality by age at death, race-ethnicity, and sex. To calculate mortality rates for individuals ≥1 year of age, population counts from the US Census were used in the denominator; for infant mortality, live birth counts were used. From 1999 to 2006, there were 41 494 CHD-related deaths and 27 960 deaths resulting from CHD (age-standardized mortality rates, 1.78 and 1.20 per 100 000, respectively). During this period, mortality resulting from CHD declined 24.1% overall. Mortality resulting from CHD significantly declined among all race-ethnicities studied. However, disparities persisted; overall and among infants, mortality resulting from CHD was consistently higher among non-Hispanic blacks compared with non-Hispanic whites. Infant mortality accounted for 48.1% of all mortality resulting from CHD; among those who survived the first year of life, 76.1% of deaths occurred during adulthood (≥18 years of age). Conclusions— CHD mortality continued to decline among both children and adults; however, differences between race-ethnicities persisted. A large proportion of CHD-related mortality occurred during infancy, although significant CHD mortality occurred during adulthood, indicating the need for adult CHD specialty management.

Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.

Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocardial ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordil) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and modified the reduction in the reflow phenomenon to the subendocardial portion of the ischemic area. Thus, both an increase in coronary vascular resistance and a significant reduction in reflow to the subendocardial portion of the ischemic area occur in the canine heart after 120 minutes of myocardial ischemia. Moreover, the increase in coronary vascular resistance can be prevented and the reduction in reflow to the subendocardial portion of the ischemic area can be modified by the administration of hypertonic mannitol.

Ethnicity and socioeconomic status: impact on the diagnosis of congenital heart disease.

OBJECTIVES The purpose of this study was to estimate the prevalence rates of specific cardiac defects for three ethnic groups and to determine the effects of ethnicity, family income and household education level on the timing of referral for pediatric cardiac care. BACKGROUND Previous studies examining ethnic differences in rates of congenital heart disease were based on hospital referrals or were limited to diagnoses made in the 1st year of life. These limitations may lead to potential biases in the ascertainment of cases. The present study is population based and includes patients diagnosed after the 1st year of life. METHODS Cases of congenital heart disease were enumerated among 379,561 liveborn infants to black, white and Mexican-American residents in Dallas County, Texas. Diagnosis was made on the basis of examination by a pediatric cardiologist, two-dimensional echocardiographic studies, cardiac catheterization or observations at operation or at autopsy. Ethnicity, median family income and household educational level were determined from birth certificate information. RESULTS White children had higher prevalence rates for aortic stenosis, endocardial cushion defect and ventricular septal defect. Mexican-American children had the lowest rate for hypoplastic left heart syndrome. The median age at referral to a pediatric cardiologist was 1.9 months for blacks, 2.1 months for whites and 2.2 months for Mexican-Americans. Stratifying the cases by median family income and household educational level failed to show any significant relation to age at referral. CONCLUSIONS Prevalence rates of specific cardiac defects vary among black, white and Mexican-American children, probably reflecting different genetic and environmental backgrounds. The timing of referral for pediatric cardiac care, however, was not related to ethnicity, median family income or household educational level.

Prenatal Diagnosis, Birth Location, Surgical Center, and Neonatal Mortality in Infants With Hypoplastic Left Heart Syndrome

Background— Most studies have not demonstrated improved survival after prenatal diagnosis of critical congenital heart disease, including hypoplastic left heart syndrome (HLHS). However, the effect of delivery near a cardiac surgical center (CSC), the recommended action after prenatal diagnosis, on HLHS mortality has been poorly investigated. Methods and Results— Using Texas Birth Defects Registry data, 1999 through 2007, which monitored >3.4 million births, we investigated the association between distance (calculated driving time) from birth center to CSC and neonatal mortality in 463 infants with HLHS. Infants with extracardiac birth defects or genetic disorders were excluded. The associations between prenatal diagnosis, CSC HLHS volume, and mortality were also examined. Neonatal mortality in infants born <10 minutes from a CSC was 21.0%, 10 to 90 minutes 25.2%, and >90 minutes 39.6% (P for trend <0.001). Prenatal diagnosis alone was not associated with improved survival (P=0.14). In multivariable analysis, birth >90 minutes from a CSC remained associated with increased mortality (odds ratio, 2.03; 95% confidence interval, 1.19–3.45), compared with <10 minutes. In subanalysis, birth >90 minutes from a CSC was associated with higher pretransport mortality (odds ratio, 6.69; 95% confidence interval, 2.52–17.74) and birth 10 to 90 minutes with higher presurgical mortality (odds ratio, 4.45; 95% confidence interval, 1.17–17.00). Higher surgical mortality was associated with lower CSC HLHS volume (odds ratio per 10 patients, 0.88; 95% confidence interval, 0.84–0.91). Conclusions— Infants with HLHS born far from a CSC have increased neonatal mortality, and most of this mortality is presurgical. Efforts to improve prenatal diagnosis of HLHS and subsequent delivery near a large volume CSC may significantly improve neonatal HLHS survival.

Respiratory syncytial virus infection in children with congenital heart disease: A review

This paper reviews recent changes in morbidity and mortality of respiratory syncytial virus (RSV) infection in infants with congenital heart disease. Mortality since the late 1970s has declined substantially, from approximately 37% to 3%. Although the frequency of admission to intensive care units has declined from approximately 60% to 30%, the frequency for mechanical ventilatory support has not changed significantly. Because mortality dropped prior to the widespread use of ribavirin, it is difficult to ascribe the improvement to this therapy. In infants with congenital heart disease (CHD), nosocomial infection remains a significant problem, accounting for approximately 33% of the RSV cases. Some authors report significant reductions in hospital-acquired RSV by use of gloves and gowns for contacts with infectious cases. Efforts at primary prevention have encountered problems with development of an RSV vacine. Preliminary data from studies of passive immunization using immune globulins with high RSV antibody titers suggest that this therapy may reduce the severity of RSV infection in infants with serious heart disease.

Late Detection of Critical Congenital Heart Disease Among US Infants: Estimation of the Potential Impact of Proposed Universal Screening Using Pulse Oximetry

IMPORTANCE Critical congenital heart disease (CCHD) was added to the Recommended Uniform Screening Panel for Newborns in the United States in 2011. Many states have recently adopted or are considering requirements for universal CCHD screening through pulse oximetry in birth hospitals. Limited previous research is directly applicable to the question of how many US infants with CCHD might be identified through screening. OBJECTIVES To estimate the proportion of US infants with late detection of CCHD (>3 days after birth) based on existing clinical practice and to investigate factors associated with late detection. DESIGN, SETTING, AND PARTICIPANTS Descriptive and multivariable analysis. Data were obtained from a multisite population-based study of birth defects in the United States, the National Birth Defects Prevention Study (NBDPS). We included all live-born infants with estimated dates of delivery from January 1, 1998, through December 31, 2007, and nonsyndromic, clinically verified CCHD conditions potentially detectable through screening via pulse oximetry. MAIN OUTCOMES AND MEASURES The main outcome measure was the proportion of infants with late detection of CCHD through echocardiography or at autopsy under the assumption that universal screening at birth hospitals might reduce the number of such late diagnoses. Secondary outcome measures included prevalence ratios for associations between selected demographic and clinical factors and late detection of CCHD. RESULTS Of 3746 live-born infants with nonsyndromic CCHD, late detection occurred in 1106 (29.5% [95% CI, 28.1%-31.0%]), including 6 (0.2%) (0.1%-0.4%) first receiving a diagnosis at autopsy more than 3 days after birth. Late detection varied by CCHD type from 9 of 120 infants (7.5% [95% CI, 3.5%-13.8%]) with pulmonary atresia to 497 of 801 (62.0% [58.7%-65.4%]) with coarctation of the aorta. In multivariable analysis, late detection varied significantly by CCHD type and study site, and infants with extracardiac defects were significantly less likely to have late detection of CCHD (adjusted prevalence ratio, 0.58 [95% CI, 0.49-0.69]). CONCLUSIONS AND RELEVANCE We estimate that 29.5% of live-born infants with nonsyndromic CCHD in the NBDPS received a diagnosis more than 3 days after birth and therefore might have benefited from routine CCHD screening at birth hospitals. The number of infants in whom CCHD was detected through screening likely varies by several factors, including CCHD type. Additional population-based studies of screening in practice are needed.

Mortality in First 5 Years in Infants With Functional Single Ventricle Born in Texas, 1996 to 2003

Background— Infants with functional single ventricle have a high risk of death during the early years of life. Studies have reported improvement in postoperative survival, but they do not include preoperative deaths or those occurring before transfer. The purpose of this population-based study was to estimate 5-year survival in infants with functional single ventricle, to define factors associated with survival, and to estimate improvement in outcome. Methods and Results— Patients with hypoplastic left heart syndrome, pulmonary atresia intact ventricular septum, single ventricle, and tricuspid atresia born in 1996 to 2003 were identified from the Texas Birth Defects Registry and linked to state and national birth and death vital records. We examined the effects of defect type, birth era, birth weight, gestational age, maternal race/ethnicity, extracardiac anomalies, sex, and maternal age and education on survival. Five-year survival varied by defect type: hypoplastic left heart syndrome, 38.0% (95% confidence interval, 32.6 to 43.5); single ventricle, 56.1% (95% confidence interval, 49.9 to 61.7); pulmonary atresia intact ventricular septum, 55.7% (95% confidence interval, 45.8 to 64.4); and tricuspid atresia, 74.6% (95% confidence interval, 62.4 to 83.4). The presence of extracardiac defects increased the adjusted risk of death by 84%. Non-Hispanic blacks had an adjusted risk of death that was 41% higher than that for non-Hispanic whites, and Hispanics had a 26% higher risk. Patients born in 2001 to 2003 had a 47% lower risk than those born in 1996 to 2000. Conclusions— This population-based study demonstrates significant improvement in overall 5-year survival, particularly in cases of hypoplastic left heart syndrome and single ventricle. Additional studies are needed to determine the factors causing racial/ethnic and regional differences in outcome.

Hemodynamic alterations during septal or right ventricular ischemia in dogs.

This study indicates that in dogs, ischemic injury to just the ventricular septum has little effect on left ventricular function. The data demonstrate that ischemic injury to either the right ventricular free wall or the ventricular septum alters right ventricular function and/or compliance, suggesting that both regions play a role in maintaining right ventricular performance. That septal contraction supports right ventricular function may explain why in earlier studies, right ventricular pressure development and output were little affected by severe injury to the free wall.

The Importance of the Muscle and Ventilatory Blood Pumps During Exercise in Patients Without a Subpulmonary Ventricle (Fontan Operation)

OBJECTIVES The aim of this study was to determine the relative contribution of the muscle and ventilatory pumps to stroke volume in patients without a subpulmonic ventricle. BACKGROUND In patients with Fontan circulation, it is unclear how venous return is augmented to increase stroke volume and cardiac output during exercise. METHODS Cardiac output (acetylene rebreathing), heart rate (electrocardiography), oxygen uptake (Douglas bag technique), and ventilation were measured in 9 patients age 15.8 ± 6 years at 6.1 ± 1.8 years after Fontan operation and 8 matched controls. Data were obtained at rest, after 3 min of steady-state exercise (Ex) on a cycle ergometer at 50% of individual working capacity, during unloaded cycling at 0 W (muscle pump alone), during unloaded cycling with isocapnic hyperpnea (muscle and ventilatory pump), during Ex plus an inspiratory load of 12.8 ± 1.5 cm water, and during Ex plus an expiratory load of 12.8 ± 1.6 cm water. RESULTS In Fontan patients, the largest increases in stroke volume and stroke volume index were during zero-resistance cycling. An additional increase with submaximal exercise occurred in controls only. During Ex plus expiratory load, stroke volume indexes were reduced to baseline, non-exercise levels in Fontan patients, without significant changes in controls. CONCLUSIONS With Fontan circulation increases in cardiac output and stroke volume during Ex were due to the muscle pump, with a small additional contribution by the ventilatory pump. An increase in intrathoracic pressure played a deleterious role in Fontan circulation by decreasing systemic venous return and stroke volume.

Pulse Oximetry Screening at 4 Hours of Age to Detect Critical Congenital Heart Defects

OBJECTIVE. The purpose of this prospective study was to assess the feasibility and reliability of pulse oximetry screening to detect critical congenital heart defects in a newborn nursery. METHODS. The study was performed in a large urban hospital with an exclusively inborn population. Stable neonates who had a gestational age of ≥35 weeks and birth weight of ≥2100 g and in whom a critical congenital heart defect was not suspected were admitted to the newborn nursery. When the 4-hour pulse oximetry reading was <96%, pulse oximetry was repeated at discharge, and when the pulse oximetry reading remained at persistently <96%, echocardiography was performed. RESULTS. Of 15299 admissions to newborn nursery during the 12-month study period, 15233 (99.6%) neonates were screened with 4-hour pulse oximetry. Pulse oximetry readings were ≥96% for 14374 (94.4%) neonates; 77 were subsequently evaluated before discharge for cardiac defects on the basis of clinical examination. Seventy-six were normal, and 1 had tetralogy of Fallot with discontinuous pulmonary arteries. Pulse oximetry readings at 4 hours were <96% in 859 (5.6%); 768 were rescreened at discharge, and 767 neonates had a pulse oximetry reading at ≥96%. One neonate had persistently low pulse oximetry at discharge; echocardiography was normal. Although 3 neonates with a critical congenital heart defect had a 4-hour pulse oximetry reading of <96%, all developed signs and/or symptoms of a cardiac defect and received a diagnosis on the basis of clinical findings, not screening results. CONCLUSIONS. All neonates with a critical congenital heart defect were detected clinically, and no cases of critical congenital heart defect were detected by pulse oximetry screening. These results indicate that pulse oximetry screening does not improve detection of critical congenital heart defects above and beyond clinical observation and assessment. Our findings do not support a recommendation for routine pulse oximetry screening in seemingly healthy neonates.