Higher Incidence of Protein-Losing Enteropathy in Patients with Single Systemic Right Ventricle.

Patients with single ventricle congenital heart disease are at risk of unpredictable protein-losing enteropathy (PLE) after surgical palliation. Based on prior reports of physiologic differences for patients with single morphologic right versus left ventricles, we hypothesized that those with right ventricular morphology would have a higher incidence of PLE. We performed a retrospective review of > 15 million pediatric hospitalizations from the Healthcare Cost and Utilization Project KID 2000-2012 databases for admissions 5-21 years old with ICD-9 codes for hypoplastic left heart syndrome (HLHS) and tricuspid atresia (TA) with and without PLE. Incidence of PLE was compared between those with HLHS and TA. In addition, outcomes and costs were compared between admissions with and without PLE and between HLHS and TA. Of 1623 HLHS admissions, 289 (17.8%) had PLE, and of 926 TA admissions, 58 (5.9%) had PLE (p < 0.001). Admissions with PLE were older compared to those without PLE (12 vs 10 years, p < 0.001) and PLE onset occurred at a younger age for HLHS than TA (11 vs 14 years, p < 0.001). There were no differences in hospital outcomes or costs. Review of this large administrative database suggests a higher incidence of PLE in patients with HLHS and a younger age of onset compared to those with TA. These data suggest that a single systemic right ventricle may be an independent risk factor for developing PLE.

Hospital costs and cost implications of co-morbid conditions for patients with single ventricle in the period through to Fontan completion.

BACKGROUND: Patients undergoing palliative surgeries for single-ventricle conditions are affected by multiple comorbidities or non-cardiac conditions. The prevalence, costs and the cost implications of these conditions have not been assessed. METHODS: Administrative costing records from four hospitals in Australia and New Zealand were linked with the Fontan registry database to analyze the inpatient resource use for co-morbid or non-cardiac conditions. Inpatient costing records from the birth year through to Fontan completion were available for 156 patients. The most frequent primary diagnoses were hypoplastic left heart syndrome (33%), double inlet left ventricle (13%), and tricuspid atresia (12%). RESULTS: During the staged surgical treatment period, children had a mean of 10±6 inpatient admissions and spent 85±64days in hospital. Among these admissions, 3±5 were for non-cardiac conditions, totaling 21±41 inpatient days. Whilst cardiac surgeries were the major reason for resource use (77% of the total cost), other cardiac care that is not surgical contributed 5% and non-cardiac admissions 18% of the total cost. The three most prevalent non-cardiac diagnostic admission categories were 'Respiratory system', 'Digestive system', and 'Ear, nose, mouth and throat', affecting 28%, 21% and 34% of the patients respectively. Multivariate regression estimated that admissions for each of these categories resulted in an increased cost of $34,563 (P=0.08), $52,438 (P=0.05) and $10,525 (P=0.53) per patient respectively for the staged surgical treatment period. CONCLUSIONS: Non-cardiac admissions for single-ventricle patients are common and have substantial resource implications. Further research assessing the causes of admission and extent to which admissions are preventable is warranted.

Right Atrial Dysfunction in the Fetus with Severely Regurgitant Tricuspid Valve Disease: A Potential Source of Cardiovascular Compromise.

BACKGROUND: In severe right heart obstruction (RHO), redistribution of cardiac output to the left ventricle (LV) is well tolerated by the fetal circulation. Although the same should be true of severely regurgitant tricuspid valve disease (rTVD) with reduced or no output from the right ventricle, affected fetuses more frequently develop hydrops or suffer intrauterine demise. We hypothesized that right atrium (RA) function is altered in rTVD but not in RHO, which could contribute to differences in outcomes. METHODS: Multi-institutional retrospective review of fetal echocardiograms performed over a 10-year period on fetuses with rTVD (Ebstein's anomaly, tricuspid valve dysplasia) or RHO (pulmonary atresia/intact ventricular septum, tricuspid atresia) and a healthy fetal control group. Offline velocity vector imaging and Doppler measurements of RA size and function and LV function were made. RESULTS: Thirty-four fetuses with rTVD, 40 with RHO, and 79 controls were compared. The rTVD fetuses had the largest RA size and lowest RA expansion index, fractional area of change, and RA indexed filling and emptying rates compared with fetuses with RHO and controls. The rTVD fetuses had the shortest LV ejection time and increased Tei index with a normal LV ejection fraction. RA dilation (odds ratio, 1.27; 95% CI, 1.05-1.54) and reduced indexed emptying rate (odds ratio, 2.49; 95% CI, 1.07-5.81) were associated with fetal or neonatal demise. CONCLUSIONS: Fetal rTVD is characterized by more severe RA dilation and dysfunction compared with fetal RHO and control groups. RA dysfunction may be an important contributor to reduced ventricular filling and output, potentially playing a critical role in the worsened outcomes observed in fetal rTVD.

Improved long-term outcomes in double-inlet left ventricle and tricuspid atresia with transposed great arteries: systemic outflow tract obstruction present at birth defines long-term outcome.

OBJECTIVES: In 2 subtypes of functional single ventricle, double inlet left ventricle (DILV) and tricuspid atresia with transposed great arteries (TA-TGA), systemic output passes through an outflow chamber before entering the aorta. Intracardiac obstruction to this pathway causing systemic outflow tract obstruction (SOTO) may be present at birth or develop over time. Long-term survival after Fontan has not been defined. We defined outcomes utilizing records from 2 centres that were cross-checked with data from a bi-national Fontan Registry for completeness and accuracy. METHODS: Two hundred and eleven patients were identified, 59 TA-TGA,152 DILV. Median follow-up was 17 years (range 4 days to 49.8 years). The Kaplan-Meier method was used for all of the time to event analyses and the log-rank test was used to compare the time-to-events. Cox proportional hazard models were used to test the association between potential predictors and time-to-event end-points. RESULTS: TA-TGA had reduced survival compared to DILV (cumulative risk of death 28.8% vs 11%, hazard ratio (HR) 3.1 (95% confidence interval (CI) 1.6-6.1), P = 0.001). In both groups, SOTO at birth carried a worse prognosis HR 3.54 (1.36-9.2, P = 0.01). SOTO was not more common in either morphology at birth ( P = 0.20). Periprocedural mortality accounted for 40% of deaths. Fontan was achieved in 82%, DILV were more likely to achieve Fontan than TA-TGA (91% vs 60%, P <0.001). After Fontan there were 9 deaths (4%) with no difference according to morphology. CONCLUSIONS: Patients with TA-TGA have poorer outcomes than those with DILV, affecting survival and likelihood of achieving Fontan. SOTO at birth carries a high risk of mortality suggesting that, when present, initial surgical management should address this.

Risk Factors for Increased Hospital Resource Utilization and In-Hospital Mortality in Adults With Single Ventricle Congenital Heart Disease.

Most patients with single ventricle congenital heart disease are now expected to survive to adulthood. Co-morbid medical conditions (CMCs) are common. We sought to identify risk factors for increased hospital resource utilization and in-hospital mortality in adults with single ventricle. We analyzed data from the 2001 to 2011 Nationwide Inpatient Sample database in patients aged ≥18 years admitted to nonteaching general hospitals (NTGHs), TGHs, and pediatric hospitals (PHs) with either hypoplastic left heart syndrome, tricuspid atresia or common ventricle. National estimates of hospitalizations were calculated. Elixhauser CMCs were identified. Length of stay (LOS), total hospital costs, and effect of CMCs were determined. Age was greater in NTGH (41.5 ± 1.3 years) than in TGH (32.8 ± 0.5) and PH (25.0 ± 0.6; p <0.0001). Adjusted LOS was shorter in NTGH (5.6 days) than in PH (9.7 days; p <0.0001). Adjusted costs were higher in PH ($56,671) than in TGH ($31,934) and NTGH ($18,255; p <0.0001). CMCs are associated with increased LOS (p <0.0001) and costs (p <0.0001). Risk factors for in-hospital mortality included increasing age (odds ratio [OR] 5.250, CI 2.825 to 9.758 for 45- to 64-year old vs 18- to 30-year old), male gender (OR 2.72, CI 1.804 to 4.103]), and the presence of CMC (OR 4.55, CI 2.193 to 9.436) for 2 vs none). No differences in mortality were found among NTGH, TGH, and PH. Cardiovascular procedures were more common in PH hospitalizations and were associated with higher costs and LOS. CMCs increase costs and mortality. In-hospital mortality is increased with age, male gender, and the presence of hypoplastic left heart syndrome.

The Association of H1N1 Pandemic Influenza with Congenital Anomaly Prevalence in Europe: An Ecological Time Series Study.

BACKGROUND: In the context of the European Surveillance of Congenital Anomalies (EUROCAT) surveillance response to the 2009 influenza pandemic, we sought to establish whether there was a detectable increase of congenital anomaly prevalence among pregnancies exposed to influenza seasons in general, and whether any increase was greater during the 2009 pandemic than during other seasons. METHODS: We performed an ecologic time series analysis based on 26,967 pregnancies with nonchromosomal congenital anomaly conceived from January 2007 to March 2011, reported by 15 EUROCAT registries. Analysis was performed for EUROCAT-defined anomaly subgroups, divided by whether there was a prior hypothesis of association with influenza. Influenza season exposure was based on World Health Organization data. Prevalence rate ratios were calculated comparing pregnancies exposed to influenza season during the congenital anomaly-specific critical period for embryo-fetal development to nonexposed pregnancies. RESULTS: There was no evidence for an increased overall prevalence of congenital anomalies among pregnancies exposed to influenza season. We detected an increased prevalence of ventricular septal defect and tricuspid atresia and stenosis during pandemic influenza season 2009, but not during 2007-2011 influenza seasons. For congenital anomalies, where there was no prior hypothesis, the prevalence of tetralogy of Fallot was strongly reduced during influenza seasons. CONCLUSIONS: Our data do not suggest an overall association of pandemic or seasonal influenza with congenital anomaly prevalence. One interpretation is that apparent influenza effects found in previous individual-based studies were confounded by or interacting with other risk factors. The associations of heart anomalies with pandemic influenza could be strain specific.

Consensus on timing of intervention for common congenital heart diseases: part II - cyanotic heart defects.

The purpose of this review/editorial is to discuss how and when to treat the most common cyanotic congenital heart defects (CHDs); the discussion of acyanotic heart defects was presented in a previous editorial. By and large, the indications and timing of intervention are decided by the severity of the lesion. While some patients with acyanotic CHD may not require surgical or transcatheter intervention because of spontaneous resolution of the defect or mildness of the defect, the majority of cyanotic CHD will require intervention, mostly surgical. Total surgical correction is the treatment of choice for tetralogy of Fallot patients although some patients may need to be palliated initially by performing a modified Blalock-Taussig shunt. For transposition of the great arteries, arterial switch (Jatene) procedure is the treatment of choice, although Rastelli procedure is required for patients who have associated ventricular septal defect (VSD) and pulmonary stenosis (PS). Some of these babies may require Prostaglandin E1 infusion and/or balloon atrial septostomy prior to corrective surgery. In tricuspid atresia patients, most babies require palliation at presentation either with a modified Blalock-Taussig shunt or pulmonary artery banding followed later by staged Fontan (bidirectional Glenn followed later by extracardiac conduit Fontan conversion usually with fenestration). Truncus arteriosus babies are treated by closure of VSD along with right ventricle to pulmonary artery conduit; palliative banding of the pulmonary artery is no longer recommended. Total anomalous pulmonary venous connection babies require anastomosis of the common pulmonary vein with the left atrium at presentation. Other defects should also be addressed by staged correction or complete repair depending upon the anatomy/physiology. Feasibility, safety and effectiveness of treatment of cyanotic CHD with currently available medical, transcatheter and surgical methods are well established and should be performed at an appropriate age in order to prevent damage to cardiovascular structures.

Risk factor analysis for second-stage palliation of single ventricle anatomy.

BACKGROUND: Single ventricle hearts can be surgically palliated by a series of operations culminating in the Fontan procedure, which establishes a total cavopulmonary connection. The second-stage procedure creates a physiologic connection between the superior vena cava and the pulmonary artery. METHODS: From 1998 to 2010, 557 patients with single ventricle heart disease underwent second-stage surgical palliation. This cohort was retrospectively analyzed to assess patient outcome by a number of anatomic, physiologic, and procedural factors. The analysis excluded patients undergoing hybrid first-stage procedures. RESULTS: The median age at operation was 165 days (range, 59 days to 49 years). The most common anatomic subtypes were hypoplastic left heart syndrome (52%), tricuspid atresia (12%), unbalanced atrioventricular septal defect (10%), double inlet left ventricle (9%), or other (17%). Left ventricular hypoplasia was present in 70%. A hemi-Fontan procedure was done in 89%, and 11% received a bidirectional Glenn. Concomitant atrioventricular valve repair was necessary in 9%. Early mortality was 4.7%, and 5.9% died after discharge but before Fontan. No early or late deaths occurred in patients with tricuspid atresia and double inlet left ventricle. Multivariate analysis demonstrated ventricular dysfunction, atrioventricular valve regurgitation, and unbalanced atrioventricular septal defect were significant adverse risk factors for survival to Fontan. CONCLUSIONS: Second-stage palliation can be performed at low risk for patients with left ventricular dominance, but significant risk remains for patients with left ventricular hypoplasia and unbalanced atrioventricular septal defect. Atrioventricular valve insufficiency is a persistent problem that has not been neutralized by repair strategies.

Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience.

BACKGROUND: The outcome of prenatally diagnosed tricuspid atresia (TA) is undefined. We sought to characterize clinical and echocardiographic features of fetal TA and to determine factors associated with mortality. METHODS AND RESULTS: All fetuses with TA (n = 88) seen at 3 tertiary care institutions from 1990 to 2005 were reviewed. There were 58 liveborn infants (median gestational age 38 weeks, range 24-40 weeks), 4 in utero demises, 25 terminations of pregnancy, and 1 mother lost to follow-up. Obstruction was present at the pulmonary valve in 27 (45%), aortic valve in 6 (10%), and aortic arch in 15 (25%). Three neonates received compassionate care, 1 died with multiple extracardiac anomalies, 2 were lost to follow-up, and 52 liveborns were actively managed with Blalock-Taussig shunt (23), Norwood palliation (14), pulmonary artery band (10), bidirectional cavopulmonary connection (3), atrial septostomy (1), and right outflow stent (1). Of those actively managed, there were 7 (14%) of 52 who died. Kaplan-Meier estimates of survival were 91% at 1 month, 87% at 6 months, and 83% at 1 year with no subsequent deaths for 13 years. By multivariate analysis, 2 independent factors were associated with an increase in time-related mortality in the actively managed group: presence of chromosomal anomaly or syndrome (P = .005) and use of extracorporeal membrane oxygenation (P = .002). CONCLUSIONS: This is the largest study describing TA in fetus. Compared with published observations of TA diagnosed postnatally, antenatal diagnosis of TA appears to have similar short-term survival in pregnancies surviving to birth.

Cardiac defects in chromosomally normal fetuses with increased nuchal translucency at 10-14 weeks of gestation.

OBJECTIVE: To examine the prevalence, distribution and spectrum of cardiac defects in chromosomally normal fetuses with increased nuchal translucency thickness. PATIENTS AND METHODS: During a 4-year period, targeted fetal echocardiography was used in 353 chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks' gestation. The cardiac scan was performed at 18-22 weeks. In the last 138 cases enrolled, an additional scan at 12-16 weeks was carried out. The follow-up included the findings at necropsy or in the pediatric examination. A complete follow-up was achieved in 97%. RESULTS: Cardiac defects were present in 32 (9.1%) cases, increasing from 5.3% in those with a nuchal translucency thickness of > or = 95th centile (3.9 mm) to 24% when thickness > or = 6 mm (p < 0.001). In 31 cases (97%), the cardiac defect was diagnosed antenatally; in 24 cases (77%) this diagnosis was confirmed later. In the remaining seven cases, the autopsy examination was not available. A wide range of cardiac defects was observed, with the most common being atrioventricular septal defect and tricuspid atresia. CONCLUSIONS: Euploid fetuses with increased nuchal translucency thickness have a significantly increased risk of cardiac defects. This is a marker of different types of heart anomalies and constitutes an additional indication for targeted fetal echocardiography. Most of the cardiac defects can be detected by fetal echocardiography.

Cardiopulmonary function in adult patients late after Fontan repair.

OBJECTIVES: The clinical status and exercise assessment of adult patients late after the Fontan operation were reviewed to determine cardiovascular function. BACKGROUND: The Fontan operation is the final operation for many patients with tricuspid atresia or a single ventricle. Follow-up reports describe most patients to be in Canadian Cardiovascular Society functional class I or II. Objective measures of cardiac performance in the pediatric age group have shown significant dysfunction. METHODS: Forty-seven adult patients were seen late after the Fontan operation at the Toronto Congenital Cardiac Centre for Adults. Thirty of these underwent cycle ergometry to determine maximal exercise capacity. Maximal ventilation, maximal oxygen uptake and anaerobic threshold were determined from a ramp exercise protocol. Ejection fraction at rest and during exercise was measured with gated radionuclide angiography. Results were compared with those of eight normal volunteers. Results are given as mean +/- SD. RESULTS: Thirty patients underwent cardiopulmonary exercise testing 6.7 +/- 3.9 years after a first Fontan operation. Clinically 93% were in functional class I or II. The Fontan group patients had a significantly lower maximal work load (548 +/- 171 vs. 1,094 +/- 190 kilopond-meters, p < 0.00001), anaerobic threshold (11.2 +/- 2.9 vs. 23.6 +/- 4.6 ml/kg per min) and maximal oxygen consumption (14.8 +/- 4.5 vs. 42.1 +/- 10.0 ml/kg per min). Systemic ventricular ejection fraction was lower at rest (38 +/- 12% vs. 58 +/- 7%) and during exercise (40 +/- 15% vs. 70 +/- 8%). CONCLUSIONS: Despite a clinical impression of good function, by objective measures adult patients continue to have significant cardiovascular limitation late after the Fontan operation.