Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure.

Cardiolipin (CL) is responsible for modulation of activities of various enzymes involved in oxidative phosphorylation. Although energy production decreases in heart failure (HF), regulation of cardiolipin during HF development is unknown. Enzymes involved in cardiac cardiolipin synthesis and remodeling were studied in spontaneously hypertensive HF (SHHF) rats, explanted hearts from human HF patients, and nonfailing Sprague Dawley (SD) rats. The biosynthetic enzymes cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate synthase (PGPS) and cardiolipin synthase (CLS) were investigated. Mitochondrial CDS activity and CDS-1 mRNA increased in HF whereas CDS-2 mRNA in SHHF and humans, not in SD rats, decreased. PGPS activity, but not mRNA, increased in SHHF. CLS activity and mRNA decreased in SHHF, but mRNA was not significantly altered in humans. Cardiolipin remodeling enzymes, monolysocardiolipin acyltransferase (MLCL AT) and tafazzin, showed variable changes during HF. MLCL AT activity increased in SHHF. Tafazzin mRNA decreased in SHHF and human HF, but not in SD rats. The gene expression of acyl-CoA: lysocardiolipin acyltransferase-1, an endoplasmic reticulum MLCL AT, remained unaltered in SHHF rats. The results provide mechanisms whereby both cardiolipin biosynthesis and remodeling are altered during HF. Increases in CDS-1, PGPS, and MLCL AT suggest compensatory mechanisms during the development of HF. Human and SD data imply that similar trends may occur in human HF, but not during nonpathological aging, consistent with previous cardiolipin studies.

Devices in heart failure: potential methods for device-based monitoring of congestive heart failure.

Congestive heart failure has long been one of the most serious medical conditions in the United States; in fact, in the United States alone, heart failure accounts for 6.5 million days of hospitalization each year. One important goal of heart-failure therapy is to inhibit the progression of congestive heart failure through pharmacologic and device-based therapies. Therefore, there have been efforts to develop device-based therapies aimed at improving cardiac reserve and optimizing pump function to meet metabolic requirements. The course of congestive heart failure is often worsened by other conditions, including new-onset arrhythmias, ischemia and infarction, valvulopathy, decompensation, end-organ damage, and therapeutic refractoriness, that have an impact on outcomes. The onset of such conditions is sometimes heralded by subtle pathophysiologic changes, and the timely identification of these changes may promote the use of preventive measures. Consequently, device-based methods could in the future have an important role in the timely identification of the subtle pathophysiologic changes associated with congestive heart failure.

The illness experiences of patients and their family members living with congestive heart failure

Purpose. To investigate and understand the illness experiences of patients and their family members living with congestive heart failure (CHF). ^ Design. Focused ethnographic design. ^ Setting. One outpatient cardiology clinic, two outpatient heart failure clinics, and informants' homes in a large metropolitan city located in southeast Texas. ^ Sample. A purposeful sampling technique was used to select a sample of 28 informants. The following somewhat overlapping, sampling strategies were used to implement the purposeful method: criterion; typical case; operational construct; maximum variation; atypical case; opportunistic; and confirming and disconfirming case sampling. ^ Methods. Naturalistic inquiry consisted of data collected from observations, participant observations, and interviews. Open-ended semi-structured illness narrative interviews included questions designed to elicit informant's explanatory models of the illness, which served as a synthesizing framework for the analysis. A thematic analysis process was conducted through domain analysis and construction of data into themes and sub-themes. Credibility was enhanced through informant verification and a process of peer debriefing. ^ Findings. Thematic analysis revealed that patients and their family members living with CHF experience a process of disruption, incoherence, and reconciling. Reconciling emerged as the salient experience described by informants. Sub-themes of reconciling that emerged from the analysis included: struggling; participating in partnerships; finding purpose and meaning in the illness experience; and surrendering. ^ Conclusions. Understanding the experiences described in this study allows for a better understanding of living with CHF in everyday life. Findings from this study suggest that the experience of living with CHF entails more than the medical story can tell. It is important for nurses and other providers to understand the experiences of this population in order to develop appropriate treatment plans in a successful practitioner-patient partnership. ^

Factors affecting the symptom burden in chronic heart failure

Background. Heart failure (HF) is a health problem of epidemic proportions and a clinical syndrome that leads to progressively severe symptoms, which contribute significantly to the burden of the disease. Several factors may affect the symptom burden of patients with HF, including physiological, psychological, and spiritual factors. This study was designed to examine the inter-relationship of physiological, psychological, and spiritual factors affecting symptoms for patients with HF. ^ Objectives. The aims of this study were to examine symptom burden of heart failure patients related to: (1) the physiological factor of brain natriuretic peptide (BNP); (2) the psychological factor of depression; (3) the spiritual factors of self transcendence and purpose in life; and (4) combined effects of physiological, psychological and spiritual factors. One additional aim was to describe symptom intensity related to symptom burden. ^ Methods. A cross-sectional non-experimental correlational design was used to examine factors affecting symptom burden in 105 patients with HF from a southwestern medical center outpatient heart failure clinic. Both men and women were included; average age was 56.6 (SD = 16.86). All measures except BNP were obtained by patient self-report. ^ Results. The mean number of symptoms present was 8.17 (SD = 3.34) with the three most common symptoms being shortness of breath on exertion, fatigue, and weakness. The mean symptom intensity was 365.66 (SD = 199.50) on a summative scale of visual analogue reports for 13 symptoms. The mean BNP level was 292.64 pg/ml (SD = 57 1.11). The prevalence rate for depression was 43.6% with a mean score of 3.48 (SD = 2.75) on the Center for Epidemiological Studies - Depression scale (CES-D 10) scale. In a multivariate analysis, depression was the only significant predictor of symptom burden (r = .474; P < .001), accounting for 18% of the variance. Spirituality had an interaction effect with depression (P ≤ .001), serving as a moderator between depression and symptom burden. ^ Conclusion. HF is a chronic and progressive syndrome characterized by severe symptoms, hospitalizations and disability. Depression is significantly related to symptom burden and this relationship is moderated by spirituality. ^

The role of transforming growth factor beta signaling in cardiac hypertrophy and fibrosis in heart failure

Objective. To determine whether transforming growth factor beta (TGF-β) receptor blockade using an oral antagonist has an effect on cardiac myocyte size in the hearts of transgenic mice with a heart failure phenotype. ^ Methods. In this pilot experimental study, cardiac tissue sections from the hearts of transgenic mice overexpressing tumor necrosis factor (MHCsTNF mice) having a phenotype of heart failure and wild-type mice, treated with an orally available TGF-β receptor antagonist were stained with wheat germ agglutinin to delineate the myocyte cell membrane and imaged using fluorescence microscopy. Using MetaVue software, the cardiac myocyte circumference was traced and the cross sectional area (CSA) of individual myocytes were measured. Measurements were repeated at the epicardial, mid-myocardial and endocardial levels to ensure adequate sampling and to minimize the effect of regional variations in myocyte size. ANOVA testing with post-hoc pairwise comparisons was done to assess any difference between the drug-treated and diluent-treated groups. ^ Results. There were no statistically significant differences in the average myocyte CSA measured at the epicardial, mid-myocardial or endocardial levels between diluent treated littermate control mice, drug treated normal mice, diluent-treated transgenic mice and drug-treated transgenic mice. There was no difference between the average pan-myocardial cross sectional area between any of the four groups mentioned above. ^ Conclusions. TGF-β receptor blockade using oral TGF-β receptor antagonist does not alter myocyte size in MHCsTNF mice that have a phenotype of heart failure. ^

Ambulatory blood pressure and physical activity in heart failure

Background. Ambulatory blood pressure (ABP) measurement is a means of monitoring cardiac function in a noninvasive way, but little is known about ABP in heart failure (HF) patients. Blood pressure (BP) declines during sleep as protection from consistent BP load, a phenomenon termed "dipping." The aims of this study were (1) to compare BP dipping and physical activity between two groups of HF patients with different functional statuses and (2) to determine whether the strength of the association between ambulatory BP and PA is different between these two different functional statuses of HF. ^ Methods. This observational study used repeated measures of ABP and PA over a 24-hour period to investigate the profiles of BP and PA in community-based individuals with HF. ABP was measured every 30 minutes by using a SpaceLabs 90207, and a Basic Motionlogger actigraph was used to measure PA minute by minute. Fifty-six participants completed both BP and physical activity for a 24-hour monitoring period. Functional status was based on New York Heart Association (NYHA) ratings. There were 27 patients with no limitation of PA (NYHA class I HF) and 29 with some limitation of PA but no discomfort at rest (NYHA class II or III HF). The sample consisted of 26 men and 30 women, aged 45 to 91 years (66.96 ± 12.35). ^ Results. Patients with NYHA class I HF had significantly greater dipping percent than those with NYHA class II/III HF after controlling their left ventricular ejection fraction (LVEF). In a mixed model analysis (PROC MIXED, SAS Institute, v 9.1), PA was significantly related to ambulatory systolic and diastolic BP and mean arterial pressure. The strength of the association between PA and ABP readings was not significantly different for the two groups of patients. ^ Conclusions. These preliminary findings demonstrate differences between NYHA class I and class II/III of HF in BP dipping status and ABP but not PA. Longitudinal research is recommended to improve understanding of the influence of disease progression on changes in 24-hour physical activity and BP profiles of this patient population. ^ Key Words. Ambulatory Blood Pressure; Blood Pressure Dipping; Heart Failure; Physical Activity. ^

Persistently elevated troponin I in heart failure patients - a suitable prognosticator and a possible boon to public health?

Baseline elevation of troponin I (TnI) has been associated with worse outcomes in heart failure (HF). However, the prevalence of persistent TnI elevation and its association with clinical outcomes has not been well described. HF is a major public health issue due to its wide prevalence and prognosticators of this condition will have a significant impact on public health. Methods: A retrospective study was performed in 510 patients with an initial HF admission between 2002 to 2004, and all subsequent hospital admissions up to May 2009 were recorded in a de-identified database. Persistent TnI elevation was defined as a level ≥0.05 ng/ml on ≥3 HF admissions. Baseline characteristics, hospital readmissions and all cause mortality were compared between patients with persistent TnI elevation (Persistent), patients with no persistence of TnI (Nonpersistent) and patients who had less than three hospital admissions (admission <3) groups. Also the same data was analyzed using the mean method in which the mean value of all recorded troponin values of each patient was used to define persistence i.e. patients who had a mean troponin level ≥0.05 ng/ml were classified as persistent. Results: Mean age of our cohort was 68.4 years out of which 99.6% subjects were male, 62.4% had ischemic HF. 78.2% had NYHA class III to IV HF, mean LVEF was 25.9%. Persistent elevation of TnI was seen in 26% of the cohort and in 66% of patients with more than 3 hospital admissions. Mean TnI level was 0.67 ± 0.15 ng/ml in the 'Persistent' group. Mean TnI using the mean method was 1.11 ± 7.25 ng/ml. LVEF was significantly lower in persistent group. Hypertension, diabetes, chronic renal insufficiency and mean age did not differ between the two groups. 'Persistent' patients had higher mortality (HR = 1.26, 95% CI = 0.89–1.78, p = 0.199 when unadjusted and HR = 1.29, 95% CI = 0.89–1.86, p = 0.176 when adjusted for race, LVEF and ischemic etiology) HR for mortality in persistent patients was 1.99 (95% CI = 1.06–3.73, p = 0.03) using the mean method. The following results were found in those with ischemic cardiomyopathy (HR = 1.44034, 95% CI = 0.92–2.26, p = 0.113) and (HR = 1.89, 95% CI = 1.01–3.55, p = 0.046) by using the mean method. 2 out of three patients with HF who were readmitted three or more times had persistent elevation of troponin I levels. Patients with chronic persistence of troponin I elevation showed a trend towards lesser survival as compared to patients who did not have chronic persistence, however this did not reach statistical significance. This trend was seen more among ischemic patients than non ischemic patients, but did not reach statistical significance. With the mean method, patients with chronic persistence of troponin I elevation had significantly lesser survival than those without it. Also ischemic patients had significantly lesser survival than non ischemic patients. ^

Secondary left ventricular ejection fraction response to beta blocker therapy in heart failure patients

Chronic β-blocker treatment improves survival and left ventricular ejection fraction (LVEF) in patients with systolic heart failure (HF). Data on whether the improvement in LVEF after β-blocker therapy is sustained for a long term or whether there is a loss in LVEF after an initial gain is not known. Our study sought to determine the prevalence and prognostic role of secondary decline in LVEF in chronic systolic HF patients on β-blocker therapy and characterize these patients. Retrospective chart review of HF hospitalizations fulfilling Framingham Criteria was performed at the MEDVAMC between April 2000 and June 2006. Follow up vital status and recurrent hospitalizations were ascertained until May 2010. Three groups of patients were identified based on LVEF response to beta blockers; group A with secondary decline in LVEF following an initial increase, group B with progressive increase in LVEF and group C with progressive decline in LVEF. Covariate adjusted Cox proportional hazard models were used to examine differences in heart failure re-hospitalizations and all cause mortality between the groups. Twenty five percent (n=27) of patients had a secondary decline in LVEF following an initial gain. The baseline, peak and final LVEF in this group were 27.6±12%, 40.1±14% and 27.4±13% respectively. The mean nadir LVEF after decline was 27.4±13% and this decline occurred at a mean interval of 2.8±1.9 years from the day of beta blocker initiation. These patients were older, more likely to be whites, had advanced heart failure (NYHA class III/IV) more due to a non ischemic etiology compared to groups B & C. They were also more likely to be treated with metoprolol (p=0.03) compared to the other two groups. No significant differences were observed in combined risk of all cause mortality and HF re-hospitalization [hazard ratio 0.80, 95% CI 0.47 to 1.38, p=0.42]. No significant difference was observed in survival estimates between the groups. In conclusion, a late decline in LVEF does occur in a significant proportion of heart failure patients treated with beta blockers, more so in patients treated with metoprolol.^

Racial differences in heart failure with preserved ejection fraction in the ambulatory heart failure population

Racial differences in heart failure with preserved ejection fraction (HFpEF) have rarely been studied in an ambulatory, financially "equal access" cohort, although the majority of such patients are treated as outpatients. ^ Retrospective data was collected from 2,526 patients (2,240 Whites, 286 African American) with HFpEF treated at 153 VA clinics, as part of the VA External Peer Review Program (EPRP) between October 2000 and September 2002. Kaplan Meier curves (stratified by race) were created for time to first heart failure (HF) hospitalization, all cause hospitalization and death and Cox proportional multivariate regression models were constructed to evaluate the effect of race on these outcomes. ^ African American patients were younger (67.7 ± 11.3 vs. 71.2 ± 9.8 years; p < 0.001), had lower prevalence of atrial fibrillation (24.5 % vs. 37%; p <0.001), chronic obstructive pulmonary disease (23.4 % vs. 36.9%, p <0.001), but had higher blood pressure (systolic blood pressure > 120 mm Hg 77.6% vs. 67.8%; p < 0.01), glomerular filtration rate (67.9 ± 31.0 vs. 61.6 ± 22.6 mL/min/1.73 m2; p < 0.001), anemia (56.6% vs. 41.7%; p <0.001) as compared to whites. African Americans were found to have higher risk adjusted rate of HF hospitalization (HR 1.52, 95% CI 1.1 - 2.11; p = 0.01), with no difference in risk-adjusted all cause hospitalization (p = 0.80) and death (p= 0.21). ^ In a financially "equal access" setting of the VA, among ambulatory patients with HFpEF, African Americans have similar rates of mortality and all cause hospitalization but have an increased risk of HF hospitalizations compared to whites.^

Trastuzumab use and risk of congestive heart failure in older breast cancer patients

Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^

Elevated cystatin C & heart failure prognosis a systematic review

Renal insufficiency is one of the most common co-morbidities present in heart failure (HF) patients. It has significant impact on mortality and adverse outcomes. Cystatin C has been shown as a promising marker of renal function. A systematic review of all the published studies evaluating the prognostic role of cystatin C in both acute and chronic HF was undertaken. A comprehensive literature search was conducted involving various terms of 'cystatin C' and 'heart failure' in Pubmed medline and Embase libraries using Scopus database. A total of twelve observational studies were selected in this review for detailed assessment. Six studies were performed in acute HF patients and six were performed in chronic HF patients. Cystatin C was used as a continuous variable, as quartiles/tertiles or as a categorical variable in these studies. Different mortality endpoints were reported in these studies. All twelve studies demonstrated a significant association of cystatin C with mortality. This association was found to be independent of other baseline risk factors that are known to impact HF outcomes. In both acute and chronic HF, cystatin C was not only a strong predictor of outcomes but also a better prognostic marker than creatinine and estimated glomerular filtration rate (eGFR). A combination of cystatin C with other biomarkers such as N terminal pro B- type natriuretic peptide (NT-proBNP) or creatinine also improved the risk stratification. The plausible mechanisms are renal dysfunction, inflammation or a direct effect of cystatin C on ventricular remodeling. Either alone or in combination, cystatin C is a better, accurate and a reliable biomarker for HF prognosis. ^

Citric acid cycle flux and pressure-volume work in the isolated working rat heart

It has been demonstrated previously that the mammalian heart cannot sustain physiologic levels of pressure-volume work if ketone bodies are the only substrates for respiration. In order to determine the metabolic derangement responsible for contractile failure in hearts utilizing ketone bodies, rat hearts were prefused at a near-physiologic workload in a working heart apparatus with acetoacetate and competing or alternate substrates including glucose, lactate, pyruvate, propionate, leucine, isoleucine, valine and acetate. While the pressure-volume work for hearts utilizing glucose was stable for 60 minutes of perfusion, performance fell by 30 minutes for hearts oxidizing acetoacetate as the sole substrate. The tissue content of 2-oxoglutarate and its transamination product, glutamate, were elevated in hearts utilizing acetoacetate while succinyl-CoA was decreased suggesting impaired flux through the citric acid cycle at the level of 2-oxoglutarate dehydrogenase. Further studies indicated that the inhibition of 2-oxoglutarate dehydrogenase developed prior to the onset of contractile failure and that the inhibition of the enzyme may be related to sequestration of the required cofactor, coenzyme A, as the thioesters acetoacetyl-CoA and acetyl-CoA. The contractile failure was not observed when glucose, lactate, pyruvate, propionate, valine or isoleucine were present together with acetoacetate, but the addition of acetate or leucine to acetoacetate did not improve performance indicating that improved performance is not mediated through the provision of additional acetyl-CoA. Furthermore, addition of competing substrates that improved function did not relieve the inhibition of 2-oxoglutarate dehydrogenase and actually resulted in the further accumulation of citric acid cycle intermediates "upstream" of 2-oxoglutarate dehydrogenase (2-oxoglutarate, glutamate, citrate and malate). Studies with (1-$\sp{14}$C) pyruvate indicate that the utilization of ketone bodies is associated with activation of NADP$\sp+$dependent malic enzyme and enrichment of the C4 pool of the citric acid cycle. The results suggest that contractile failure induced by ketone bodies in rat heart results from inhibition of 2-oxoglutarate dehydrogenase and that reversal of contractile failure is dissociated from relief of the inhibition, but rather is due to the entry of carbon units into the citric acid cycle as compounds other than acetyl-CoA. This mechanism of enrichment (anaplerosis) provides oxaloacetate for condensation with acetyl-CoA derived from ketone bodies allowing continued energy production by sustaining flux through a span of the citric acid cycle up to the point of inhibition at 2-oxoglutarate dehydrogenase for energy production thereby producing the reducing equivalents necessary to sustain oxidative phosphorylation. ^

Analysis of recurrent failure times: A time-dependent Yule process approach

Analysis of recurrent events has been widely discussed in medical, health services, insurance, and engineering areas in recent years. This research proposes to use a nonhomogeneous Yule process with the proportional intensity assumption to model the hazard function on recurrent events data and the associated risk factors. This method assumes that repeated events occur for each individual, with given covariates, according to a nonhomogeneous Yule process with intensity function λx(t) = λ 0(t) · exp( x′β). One of the advantages of using a non-homogeneous Yule process for recurrent events is that it assumes that the recurrent rate is proportional to the number of events that occur up to time t. Maximum likelihood estimation is used to provide estimates of the parameters in the model, and a generalized scoring iterative procedure is applied in numerical computation. ^ Model comparisons between the proposed method and other existing recurrent models are addressed by simulation. One example concerning recurrent myocardial infarction events compared between two distinct populations, Mexican-American and Non-Hispanic Whites in the Corpus Christi Heart Project is examined. ^

Exploring race/ethnicity as a risk factor for mortality in newborns following congenital heart surgery at a center of excellence

The purpose of this study was to determine if race/ethnicity was a significant risk factor for hospital mortality in children following congenital heart surgery in a contemporary sample of newborns with congenital heart disease. Unlike previous studies that utilized administrative databases, this study utilized clinical data collected at the point of care to examine racial/ethnic outcome differences in the context of the patients' clinical condition and their overall perioperative experience. A retrospective cohort design was used. The study sample consisted of 316 newborns (<31 days of age) who underwent congenital heart surgery between January 2007 through December 2009. A multivariate logistic regression model was used to determine the impact of race/ethnicity, insurance status, presence of a spatial anomaly, prenatal diagnosis, postoperative sepsis, cardiac arrest, respiratory failure, unplanned reoperation, and total length of stay in the intensive care unit on outcomes following congenital heart surgery in newborns. The study findings showed that the strongest predictors of hospital mortality following congenital heart surgery in this cohort were postoperative cardiac arrest, postoperative respiratory failure, having a spatial anomaly, and total ICU LOS. Race/ethnicity and insurance status were not significant risk factors. The institution where this study was conducted is designated as a center of excellence for congenital heart disease. These centers have state-of-the-art facilities, extensive experience in caring for children with congenital heart disease, and superior outcomes. This study suggests that optimal care delivery for newborns requiring congenital heart surgery at a center of excellence portends exceptional outcomes and this benefit is conferred upon the entire patient population despite the race/ethnicity of the patients. From a public health and health services view, this study also contributes to the overall body of knowledge on racial/ethnic disparities in children with congenital heart defects and puts forward the possibility of a relationship between quality of care and racial/ethnic disparities. Further study is required to examine the impact of race/ethnicity on the long-term outcomes of these children as they encounter the disparate components of the health care delivery system. There is also opportunity to study the role of race/ethnicity on the hospital morbidity in these patients considering current expectations for hospital survival are very high, and much of the current focus for quality improvement rests in minimizing the development of patient morbidities.^