Clifford L. Cua

Hybrid Approach for Hypoplastic Left Heart Syndrome: Intermediate Results After the Learning Curve

BACKGROUND Lessons learned during the development of a novel hybrid approach have resulted in a reliable, reproducible alternative treatment for hypoplastic left heart syndrome (HLHS). Herein we report our results using this hybrid approach in a uniform risk cohort. METHODS This is a review of prospectively collected data on patients treated for HLHS using a hybrid approach (n = 40) between July 2002 and June 2007. The hybrid approach includes pulmonary artery bands, a ductal stent, and atrial septostomy as a neonate, comprehensive stage 2 procedure resulting in Glenn shunt physiology at six months and Fontan completion at two years. RESULTS Forty patients had a hybrid stage 1 with 36 undergoing a comprehensive stage 2 procedure. Fifteen patients have completed the Fontan procedure with 17 pending. Overall survival was 82.5% (33 of 40). The seven deaths included one at stage 1, two between stages 1 and 2, three at stage 2, and one between stages 2 and 3. One patient had successful heart transplantation during the interstage period. CONCLUSIONS The hybrid approach can yield acceptable intermediate results that are comparable with a traditional Norwood strategy. Potential advantages of the hybrid approach include the avoidance of circulatory arrest and shifting the major surgical stage to later in life. These data provide the platform for a prospective trial comparing these two surgical options to assess whether there is less cumulative impact with the hybrid approach, thereby improving end organ function, quality, and quantity of life.

Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient

Objective: Hyperglycemia in critical care populations has been shown to be a risk factor for increased morbidity and mortality. Minimal data exist in postoperative pediatric cardiac patients. The goal of this study was to determine whether hyperglycemia in the postoperative period was associated with increased morbidity or mortality. Design: Retrospective chart review. Setting: Tertiary care, free-standing pediatric medical center with a dedicated cardiac intensive care unit. Patients: We included 184 patients <1 yr of age who underwent cardiac surgery requiring cardiopulmonary bypass from October 2002 to August 2004. Patients with a weight <2 kg, a preoperative diagnosis of diabetes, preoperative extracorporeal membrane oxygenation support, solid organ transplant recipients, and preoperative renal or liver insufficiency were excluded. Interventions: None. Measurements and Main Results: Age was 4.3 ± 3.2 months and weight was 4.9 ± 1.7 kg at surgery. Duration of hyperglycemia was significantly longer in patients with renal insufficiency (p = .029), liver insufficiency (p = .006), infection (p < .002), central nervous system event (p = .038), extracorporeal membrane oxygenation use (p < .001), and death (p < .002). Duration of hyperglycemia was also significantly associated with increased intensive care (p < .001) and hospital (p < .001) stay and longer ventilator use (p < .001). Peak glucose levels were significantly different in patients with renal insufficiency (p < .001), infection (p = .002), central nervous system event (p = .01), and mortality (p < .001). Conclusions: Hyperglycemia in the postoperative period was associated with increased morbidity and mortality in postoperative pediatric cardiac patient. Strict glycemic control may improve outcomes in this patient population.

Increased Incidence of Idiopathic Persistent Pulmonary Hypertension in Down Syndrome Neonates

Down syndrome (DS) patients have an increased risk of developing pulmonary hypertension later in life compared to age-matched controls. The goal of this study was to determine if the incidence of persistent pulmonary hypertension of the newborn (PPHN) is also higher in neonatal DS patients compared to the general population. A retrospective chart review of DS patients admitted during a 3-year period to the neonatal intensive care unit was performed. DS patients with meconium aspiration syndrome, pulmonary infections, or pulmonary space-occupying lesions were excluded. DS patients were divided into four groups based on treatment and consisted of no intervention (A), supplemental oxygen (B,) mechanical ventilation use (C), and inhaled nitric oxide administration (D). Group D was defined as having PPHN. z test of the difference between sample and known population, chi-square, t-test, and analysis of variance with Tukey adjusted post hoc test were used for analysis. p < 0.05 was considered significant. A total of 58 patients met inclusion criteria. Twenty-four DS patients were in group A, 17 in group B, 10 in group C, and 7 in group D. There was no difference between the four groups for gender (males: 10, 5, 5, and 5, respectively), gestational age (36.4, 38.2, 36.4, and 36.4 weeks, respectively), weight (2.8, 3.0, 2.4, and 3.0 kg, respectively), or the presence of congenital heart defects (17, 10, 6, and 1, respectively). The estimated number of DS patients born in the state of Ohio during this period was 598; therefore, the incidence of PPHN in DS was 1.2%. The reported incidence of PPHN is 0.1%. The Reported incidence of PPHN was significantly lower versus the incidence of PPHN in DS (z = 2.7, p = 0.007). It was concluded that DS patients have an increased incidence of PPHN compared to historical controls regardless of baseline demographics.

Early postoperative outcomes in a series of infants with hypoplastic left heart syndrome undergoing stage I palliation operation with either modified Blalock-Taussig shunt or right ventricle to pulmonary artery conduit.

Objective: Previous publications using nonconcurrent series of patients indicate improved survival for patients with hypoplastic left heart syndrome (HLHS) undergoing stage I palliation with a right ventricle to pulmonary artery conduit (NW-RVPA) vs. a modified Blalock-Taussig shunt (NW-BT). We compared postoperative outcomes in a concurrent series of patients with HLHS undergoing an NW-BT procedure vs. NW-RVPA procedure. Design: Perioperative data from 66 consecutive patients who underwent NW-BT (n = 37) or NW-RVPA (n = 29) procedures were retrospectively analyzed. Setting: Cardiac intensive care unit in a tertiary pediatric hospital. Patients: Charts were reviewed for all patients with the diagnosis of HLHS undergoing the NW-BT or NW-RVPA procedure between January 2002 and December 2003. Results: Cardiopulmonary bypass time was longer in the NW-BT group than in the NW-RVPA group (152.5 ± 52.0 vs. 134.5 ± 36.1 mins; p = .04). Postoperative diastolic pressures were higher and the Pao2 to Fio2 ratio profiles were lower for the NW-RVPA group over the first 72 hrs. Time to sternal closure (2 [1–6] vs. 4 [2–41] days; p = .01), duration of mechanical ventilation (113 [49–386] vs. 136 [84–764] hrs; p = .01), time to establish enteral feeds (4 [2–8] vs. 5 [3–22] days; p = .01), length of intensive care unit stay (11 [7–55] vs. 15 [8–90] days; p = .04), and length of hospital stay (16 [11–67] vs. 27 [12–126] days; p = .01) were shorter in the NW-RVPA group. Postoperative mortality was not significantly different between the NW-RVPA group (7%) and NW-BT group (11%). Conclusion: At an experienced institution with low stage I palliation mortality for HLHS, there were no differences in early morbidity and mortality between the NW-RVPA and NW-BT procedures. The primary advantage of the NW-RVPA procedure may be faster recovery following surgery and earlier discharge from the hospital.

Variation in folate pathway genes contributes to risk of congenital heart defects among individuals with Down syndrome

Cardiac abnormalities are one of the most common congenital defects observed in individuals with Down syndrome. Considerable research has implicated both folate deficiency and genetic variation in folate pathway genes with birth defects, including both congenital heart defects (CHD) and Down syndrome (DS). Here, we test variation in folate pathway genes for a role in the major DS‐associated CHD atrioventricular septal defect (AVSD). In a group of 121 case families (mother, father, and proband with DS and AVSD) and 122 control families (mother, father, and proband with DS and no CHD), tag SNPs were genotyped in and around five folate pathway genes: 5,10‐methylenetetrahyrdofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), cystathionine β‐synthase (CBS), and the reduced folate carrier (SLC19A1, RFC1). SLC19A1 was found to be associated with AVSD using a multilocus allele‐sharing test. Individual SNP tests also showed nominally significant associations with odds ratios of between 1.34 and 3.78, depending on the SNP and genetic model. Interestingly, all marginally significant SNPs in SLC19A1 are in strong linkage disequilibrium (r2≥0.8) with the nonsynonymous coding SNP rs1051266 (c.80A>G), which has previously been associated with nonsyndromic cases of CHD. In addition to SLC19A1, the known functional polymorphism MTHFR c.1298A was over‐transmitted to cases with AVSD (P=0.05) and under‐transmitted to controls (P=0.02). We conclude, therefore, that disruption of the folate pathway contributes to the incidence of AVSD among individuals with DS. Genet. Epidemiol. 34: 603–612, 2010.

An Excess of Deleterious Variants in VEGF-A Pathway Genes in Down-Syndrome-Associated Atrioventricular Septal Defects

About half of people with trisomy 21 have a congenital heart defect (CHD), whereas the remainder have a structurally normal heart, demonstrating that trisomy 21 is a significant risk factor but is not causal for abnormal heart development. Atrioventricular septal defects (AVSD) are the most commonly occurring heart defects in Down syndrome (DS), and ∼65% of all AVSD is associated with DS. We used a candidate-gene approach among individuals with DS and complete AVSD (cases = 141) and DS with no CHD (controls = 141) to determine whether rare genetic variants in genes involved in atrioventricular valvuloseptal morphogenesis contribute to AVSD in this sensitized population. We found a significant excess (p < 0.0001) of variants predicted to be deleterious in cases compared to controls. At the most stringent level of filtering, we found potentially damaging variants in nearly 20% of cases but fewer than 3% of controls. The variants with the highest probability of being damaging in cases only were found in six genes: COL6A1, COL6A2, CRELD1, FBLN2, FRZB, and GATA5. Several of the case-specific variants were recurrent in unrelated individuals, occurring in 10% of cases studied. No variants with an equal probability of being damaging were found in controls, demonstrating a highly specific association with AVSD. Of note, all of these genes are in the VEGF-A pathway, even though the candidate genes analyzed in this study represented numerous biochemical and developmental pathways, suggesting that rare variants in the VEGF-A pathway might contribute to the genetic underpinnings of AVSD in humans.

Two-dimensional speckle strain and dyssynchrony in single right ventricles versus normal right ventricles.

BACKGROUND Patients with single-right ventricle (RV) physiology are at increased risk for myocardial dysfunction and mechanical dyssynchrony. Newer echocardiographic modalities may be better able to quantitate right ventricular function in this unique population. The aim of this study was to use two-dimensional speckle analysis of strain and strain rate to quantify systolic function and dyssynchrony in single-RV post-Fontan patients and compare them with values for controls. METHODS Patients with single RV who underwent Fontan palliation and patients with normal biventricular anatomy were studied. Two-dimensional speckle echocardiography was used to measure strain, strain rate, time to peak, and longitudinal displacement in a 6-segment model of the RV. Independent t tests were used to compare group means. P values < .05 were considered significant. RESULTS Thirteen patients were studied in each group. There was no significant difference in age between single-RV patients and controls (6.60 +/- 2.07 vs 5.75 +/- 1.83 years, respectively). Single-RV strain values were significantly lower in all 6 segments compared with values in controls (basal interventricular septum [IVS], -14.28 +/- 7.78% vs -22.00 +/- 2.36%; mid IVS, -17.70 +/- 4.54% vs -22.99 +/- 2.71%; apical IVS, -19.46 +/- 4.97% vs -25.42 +/- 4.06%; basal RV, -22.40 +/- 5.7% vs -41.42 +/- 5.42%; mid RV, -21.20 +/- 3.21% vs -39.67 +/- 6.04%; apical RV, -20.70 +/- 4.90% vs -33.68 +/- 3.90%). Systolic strain rate and longitudinal displacement were also lower in the free wall and apical IVS in single-RV patients compared with controls. The modified Yu index for strain time to peak was longer in the single-RV patients (43.16 +/- 13.63 vs 21.72 +/- 7.25 ms). CONCLUSION Significant differences in strain analysis between single-RV patients and patients with biventricular physiology exist at a relatively young age. Future studies are needed to determine the clinical significance of these differences.

Differences in Tissue Doppler Imaging Between Single Ventricles After the Fontan Operation and Normal Controls

Tissue Doppler imaging measurements could be used to quantitate ventricular function in patients with systemic single ventricles. The objective of the present study was to measure the tissue doppler imaging-derived indexes of function and dyssynchrony in patients with single ventricular physiology and compare these values with those from control patients. Echocardiograms were performed in patients with single left or right ventricular physiology and control patients. Measurements were made of the free walls at the level of the atrioventricular annulus. Differences were assessed with one-way analysis of variance. Post hoc comparisons were performed with a Tukey adjustment. No significant difference was present in age among the control (5.75 +/- 1.73 years, n = 16), single left ventricle (7.07 +/- 2.81 years, n = 12), or single right ventricle (6.25 +/- 2.2 years, n = 14) groups. The single right ventricular free wall peak systolic annular, peak early diastolic annular, and peak late diastolic annular velocities were significantly lower and the myocardial performance index and interval to mechanical activation greater compared to the controls. The single left ventricular free wall peak systolic annular, peak early diastolic annular, and peak late diastolic annular velocities were also significantly lower and the myocardial performance index and interval to mechanical activation greater compared to controls. In conclusion, significant decreases in systolic and diastolic function, as well as differences in dyssynchrony, using tissue Doppler imaging exist in patients with single ventricular physiology compared to control patients.

Two-dimensional speckle strain and dyssynchrony in single left ventricles vs. normal left ventricles.

BACKGROUND Patients with single left ventricle (LV) physiology maybe at increased risk for myocardial dysfunction and mechanical dyssynchrony. Newer echocardiographic modalities may be able to better quantitate LV function in this unique population. Our objective was to use 2D-speckle analysis of strain and strain rate to quantify systolic function and dyssynchrony in single LV post-Fontan patients and compare them to control LV patients. METHODS Patients with single LV status post-Fontan procedure and patients with normal biventricular anatomy were studied. Two-dimensional speckle echocardiography was used to measure strain, strain rate, time to peak, and longitudinal displacement in a six-segment model of the LV. Independent t-tests were used to compare group means. RESULTS Twelve patients with single LV physiology and thirteen control patients were studied. There was no significant difference in ages for the single LV patients vs. control patients (7.1 + 2.8 years vs. 5.7 + 1.8 years). Single LV strain values were significantly lower in four of the six segments compared with control LV (mid interventricular septal [IVS]: -19.3 + 6.4% vs. -23.8 + 3.5%, apical IVS: -20.8 + 5.4% vs. -27.4 + 4.7%, basal LV: -20.6 + 6.6% vs. -25.8 + 3.4%, and apical LV: -21.0 + 6.2% vs. -26.1 + 4.3%). Longitudinal displacement was lower for all three segments of the IVS for the single LV vs. control LV. Modified Yu index for strain and strain rate time to peak was longer in the single LV patients vs. controls (51.2 + 18.2 ms vs. 27.9 + 8.0 ms and 90.2 + 24.2 ms vs. 52.5 + 23.7 ms, respectively). CONCLUSION Significant differences in strain analysis between single LV patients vs. control patients with normal biventricular physiology exist at a relatively young age. Future studies are needed to determine the significance of these differences.

A comparison of the Vasotrac with invasive arterial blood pressure monitoring in children after pediatric cardiac surgery.

The Vasotrac is a device that provides near-continuous and noninvasive arterial blood pressure monitoring and may be an alternative to direct intraarterial measurement. It has been evaluated in adult patients, but minimal information is available for pediatric patients. We evaluated agreement between measurements of arterial blood pressure and heart rate obtained from the Vasotrac versus an arterial catheter in a pediatric population. Children undergoing corrective cardiac surgery were enrolled. Simultaneous arterial blood pressure measurements were obtained postoperatively from the Vasotrac unit and an arterial catheter. Bland-Altman plots were constructed to assess agreement. Paired correlation analysis, bias, and precision calculations were performed. Sixteen patients, mean age 10.1 ± 2.3 yr and weight 34.6 ± 11.9 kg, were enrolled. Four-thousand-one- hundred- two paired measurements were obtained. Arterial blood pressures measured noninvasively correlated with catheter measurements with Pearson r values of 0.90, 0.80, and 0.91 for systolic, diastolic, and mean arterial blood pressures, respectively (all P < 0.001). There was excellent agreement between arterial blood pressure measurement methods. Absolute mean differences based on mixed-model regression with 95% confidence intervals were 4.0 mm Hg (3.0–5.0 mm Hg), 4.3 mm Hg (3.1–5.5 mm Hg), and 3.5 mm Hg (2.5–4.0 mm Hg) for systolic blood pressure, diastolic blood pressure, and mean blood pressure, respectively. Arterial blood pressure measurements obtained from the Vasotrac agreed well with invasive arterial monitoring in pediatric patients.