Background The optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD) remains uncertain for lack of an adequately powered, randomized trial. The ...FREEDOM trial was designed to compare contemporary coronary artery bypass grafting (CABG) to percutaneous coronary intervention (PCI) with drug-eluting stents in diabetic patients with MVD against a background of optimal medical therapy. Methods A total of 1,900 diabetic participants with MVD were randomized to PCI or CABG worldwide from April 2005 to March 2010. FREEDOM is a superiority trial with a mean follow-up of 4.37 years (minimum 2 years) and 80% power to detect a 27.0% relative reduction. We present the baseline characteristics of patients screened and randomized, and provide a comparison with other MVD trials involving diabetic patients. Results The randomized cohort was 63.1 ± 9.1 years old and 29% female, with a median diabetes duration of 10.2 ± 8.9 years. Most (83%) had 3-vessel disease and on average took 5.5 ± 1.7 vascular medications, with 32% on insulin therapy. Nearly all had hypertension and/or dyslipidemia, and 26% had a prior myocardial infarction. Mean hemoglobin A1c was 7.8 ± 1.7 mg/dL, 29% had low-density lipoprotein <70 mg/dL, and mean systolic blood pressure was 134 ± 20 mm Hg. The mean SYNTAX score was 26.2 with a symmetric distribution. FREEDOM trial participants have baseline characteristics similar to those of contemporary multivessel and diabetes trial cohorts. Conclusions The FREEDOM trial has successfully recruited a high-risk diabetic MVD cohort. Follow-up efforts include aggressive monitoring to optimize background risk factor control. FREEDOM will contribute significantly to the PCI versus CABG debate in diabetic patients with MVD.
Objectives We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle ...anomalies enrolled in the Single Ventricle Reconstruction trial. Methods Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality. Results Analysis included 549 subjects prospectively enrolled from 15 centers; 30-day and hospital mortality were 11.5% (63/549) and 16.0% (88/549), respectively. Independent risk factors for both 30-day and hospital mortality included lower birth weight, genetic abnormality, extracorporeal membrane oxygenation (ECMO) and open sternum on the day of the Norwood procedure. In addition, longer duration of deep hypothermic circulatory arrest was a risk factor for 30-day mortality. Shunt type at the end of the Norwood procedure was not a significant risk factor for 30-day or hospital mortality. Independent risk factors for postoperative renal failure (n = 46), sepsis (n = 93), increased length of ventilation, and hospital length of stay among survivors included genetic abnormality, lower center/surgeon volume, open sternum, and post-Norwood operations. Conclusions Innate patient factors, ECMO, open sternum, and lower center/surgeon volume are important risk factors for postoperative mortality and/or morbidity during the Norwood hospitalization.
Abstract Background The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft ...surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio HR: 1.35, 95% confidence interval CI: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. Conclusions In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes FREEDOM; NCT00086450 ).
Objectives To assess the performance of 3 risk scores from Japan that were developed to predict, in children with Kawasaki disease, resistance to intravenous immunoglobulin (IVIG) treatment. Study ...design We used data from a randomized trial of pulsed steroids for primary treatment of Kawasaki disease to assess operating characteristics of the 3 risk scores, and we examined whether steroid therapy lowers the risk of coronary artery abnormalities in patients prospectively classified as IVIG resistant. Results For comparability with published cohorts, we analyzed the data of 99 patients who were not treated with steroids (16% IVIG-retreated) and identified male sex, lower albumin level, and higher aspartate aminotransferase level as independent risk factors for IVIG resistance. The Kobayashi score was similar in IVIG-resistant and -responsive patients, yielding a sensitivity of 33% and specificity of 87%. There was no interaction of high-risk versus low-risk status by treatment received (steroid versus placebo) with any of the 3 risk score algorithms. Conclusion Risk-scoring systems from Japan have good specificity but low sensitivity for predicting IVIG resistance in a North American cohort. Primary steroid therapy did not improve coronary outcomes in patients prospectively classified as being at high-risk for IVIG resistance.
Abstract Objectives The goal of this single-center series was to assess differences in reintervention by the type of valve used for surgical bioprosthetic pulmonary valve replacement and to identify ...independent predictors of reintervention. Methods Data were retrospectively collected for 611 patients undergoing pulmonary valve replacement from 1996 to 2014. Kaplan–Meier estimation and Cox proportional hazards regression methodologies were used. Results The median age of patients was 17.8 years (interquartile range, 11.9-27.3). The diagnosis was tetralogy of Fallot in 69% of patients. The median follow-up was 3.0 years (interquartile range, 1.1-5.3). Valve types included Sorin Mitroflow (Milan, Italy), 316 (50%; median age 16.5 years); Carpentier-Edwards (Irvine, Calif) Magna/MagnaEase, 223 (35%; median age, 19.3 years); and Carpentier-Edwards Perimount, 72 (11%; median age, 21.9 years). Reintervention occurred in 6.7% of patients (41/633) and was higher in children than adults (hazard ratio, 4.8). Age-adjusted 5-year reintervention rates were Sorin Mitroflow, 13.4%; Carpentier-Edwards Magna/MagnaEase, 2.1%; and Carpentier-Edwards Perimount, 0%. Reintervention was not associated with gender, valve insertion method, or concurrent procedures. The only independent risk factor for reintervention after controlling for age was valve type ( P < .001). The Sorin Mitroflow valve had a shorter time to reintervention than the other 2 valve types (hazard ratios both >7, each P < .001). Differences by valve type did not depend on age (interaction P = .61). Conclusions Bioprosthetic pulmonary valve replacement in patients with congenital heart disease has excellent short-term outcomes, but children have an approximately 5-fold greater risk of reintervention than adults. Independently of age, reintervention rates vary by valve type. These differences may be important in valve selection and follow-up.
Summary Background Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of ...diagnosis. Methods We analysed data from the Pediatric Cardiomyopathy Registry, which collected longitudinal data for 1085 children with hypertrophic cardiomyopathy from 1990 to 2009. Our goal was to understand how patient factors measured at diagnosis predicted the subsequent risk of the primary outcome of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify univariable and multivariable predictors of death or heart transplantation within each causal subgroup. Findings The poorest outcomes were recorded for the 69 children with pure hypertrophic cardiomyopathy with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI 44–69) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI 32–58) at 2 years for the 69 children with mixed hypertrophic and dilated cardiomyopathy and 38% (95% CI 25–51) at 2 years for the 58 children with mixed hypertrophic and restrictive cardiomyopathy. For children diagnosed with hypertrophic cardiomyopathy at younger than 1 year, the rate of death or transplantation was 21% (95% CI 16–27) at 2 years. For children diagnosed with hypertrophic cardiomyopathy and a malformation syndrome, the rate of death or transplantation was 23% (95% CI 12–34) at 2 years. Excellent outcomes were reported for the 407 children who were diagnosed with idiopathic hypertrophic cardiomyopathy at age 1 year or older, with a rate of death or heart transplantation of 3% (95% CI 1–5) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included young age, low weight, presence of congestive heart failure, lower left ventricular fractional shortening, or higher left ventricular end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation was significantly increased when two or more risk factors were present and also as the number of risk factors increased. Interpretation In children with hypertrophic cardiomyopathy, the risk of death or heart transplantation was greatest for those who presented as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as low weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision making and prognosis at the time of diagnosis. Funding US National Institutes of Health and Children's Cardiomyopathy Foundation.
Abstract Background Left ventricular noncompaction (LVNC) is a distinct form of cardiomyopathy characterized by hypertrabeculation of the left ventricle. The LVNC phenotype may occur in isolation or ...with other cardiomyopathy phenotypes. Prognosis is incompletely characterized in children. Methods and Results According to diagnoses from the National Heart, Lung, and Blood Institute–funded Pediatric Cardiomyopathy Registry from 1990 to 2008, 155 of 3,219 children (4.8%) had LVNC. Each LVNC patient was also classified as having an associated echocardiographically diagnosed cardiomyopathy phenotype: dilated (DCM), hypertrophic (HCM), restrictive (RCM), isolated, or indeterminate. The time to death or transplantation differed among the phenotypic groups ( P = .035). Time to listing for cardiac transplantation significantly differed by phenotype ( P < .001), as did time to transplantation ( P = .015). The hazard ratio for death/transplantation (with isolated LVNC as the reference group) was 4.26 (95% confidence interval CI 0.78–23.3) for HCM, 6.35 (95% CI 1.52–26.6) for DCM, and 5.66 (95% CI 1.04–30.9) for the indeterminate phenotype. Most events occurred in the 1st year after diagnosis. Conclusions LVNC is present in at least 5% of children with cardiomyopathy. The specific LVNC-associated cardiomyopathy phenotype predicts the risk of death or transplantation and should inform clinical management.
Background Studies of cardiomyopathy in children with Noonan syndrome (NS) have been primarily small case series or cross-sectional studies with small or no comparison groups. Methods We used the ...Pediatric Cardiomyopathy Registry database to compare the survival experience of children with NS and hypertrophic cardiomyopathy (HCM) with children with idiopathic or familial HCM and to identify clinical and echocardiographic predictors of clinical outcomes. Results Longitudinal data in 74 children with NS and HCM and 792 children with idiopathic or familial isolated HCM were compared. Children with NS were diagnosed with HCM before 6 months old more often (51%) than children with HCM (28%) and were more likely to present with congestive heart failure (CHF) (24% vs 9%). The NS cohort had lower crude survival than the group with other HCM ( P = .03), but survival did not differ after adjustment for CHF and age at diagnosis. Within the NS cohort (1-year survival 78%), a diagnosis of HCM before age 6 months with CHF resulted in 31% 1-year survival. Lower height-for-age z score (hazard ratio 0.26, P = .005) in place of CHF and lower left ventricular fractional shortening z score (hazard ratio 0.79, P = .04) also independently predicted mortality. Conclusions Patients with NS with HCM have a worse risk profile at presentation compared with other children with HCM, resulting in significant early mortality (22% at 1 year). Decreased height-for-age and lower, although still supranormal, left ventricular fractional shortening z score are independent predictors of mortality in patients with NS with HCM. Such patients should have an aggressive therapeutic approach including potential listing for cardiac transplantation.
Objective The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that ...might favor the modified Blalock–Taussig shunt or a right ventricle-to-pulmonary artery shunt. Methods We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. Results Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status ( P = .01), obstructed pulmonary venous return ( P < .001), smaller ascending aorta ( P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome ( P < .001) and lower gestational age ( P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia ( P < .001). The modified Blalock–Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve ( P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not ( P = .43). Conclusions Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock–Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.
Abstract Background Measurement of cerebral venous oxyhemoglobin saturation (ScvO2 ) is considered a gold standard in assessing the adequacy of tissue oxygen delivery (DO2 ) after the stage 1 ...palliation (S1P), with SvO2 <30% often representing severely compromised DO2 . Regional oxygenation index (rSO2 ) based on near-infrared resonance spectroscopy (NIRS) frequently is used to screen for compromised DO2 , although its sensitivity to detect severe abnormalities in SvO2 is uncertain. Methods ScvO2 was measured by co-oximetry from the internal jugular vein as clinically indicated in 73 neonates after S1P. These values were compared with cerebral rSO2 (FORE-SIGHT; CASMED) via mixed effects model linear regression, Bland-Altman analysis, and sensitivity analysis. Because NIRS devices measure a composite of arterial and venous blood, we calculated an rSO2 -based ScvO2 designed to remove arterial contamination from the rSO2 signal: rSO2 -based ScvO2 = (rSO2 − arterial oxygen saturation × 0.3)/0.7. Results Among 520 time-matched pairs of ScvO2 and cerebral rSO2 , the slope of the relationship between rSO2 and ScvO2 (after we adjusted for effects of hemoglobin) was 0.37 ± 0.04 with only modest correlation (r2 = 0.39), and mean bias of +8.26. When ScvO2 was <30%, cerebral rSO2 was <30 in less than 1%, <40 less than 1%, and <50 in 45.7% of data points; specificity of rSO2 in the same range is >99%. Correction of rSO2 for arterial contamination significantly decreased mean bias (+3.03) and improved the sensitivity of rSO2 to detect ScvO2 <30 to 6.5% for rSO2 <30, 29% for rSO2 <40, and 77.4% for rSO2 <50. Conclusions Cerebral rSO2 in isolation should not be used to detect low ScvO2 , because its sensitivity is low, although correction of rSO2 for arterial contamination may improve sensitivity. Cerebral rSO2 of 50 or greater should not be considered reassuring, though values below 30 are specific for low ScvO2.
PDF
