Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Echocardiograms over a 10-year follow-up period were reviewed on 26 patients with familial BAV [22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)]. All had a family history of CHD and were recruited from 2005 to 2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long-axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1 ± 5.5 and that was 13.8 ± 6.2 years at the last echocardiogram. Only patients with > 2 echocardiograms in the 10-year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal)-Z score for any segment > 2 or a change in Z score > 2 over follow-up; Group 2 (normal)-Z score < 2 throughout follow-up and change in Z score < 2. Nineteen out of 26 children displayed abnormal aortic growth or dilation of the aorta. BAV with right/left cusp fusion was more frequent in Group 1 (15/18) versus Group 2 (3/7) (p < 0.05). There were no significant differences in gender, aortic valve dysfunction, presence of CoA, family history, cardiac function, presence of left ventricular hypertrophy, or medication use between the 2 groups. In our longitudinal study of children with familial BAV, the majority display evidence of abnormal growth of the ascending aorta during the follow-up period consistent with AscAo and support the extension of current adult guidelines to the pediatric population. While we find that right/left cusp fusion is a risk factor for abnormal aortic growth, additional studies are needed to identify other factors to better select children who require serial screening.

Echocardiographic right ventricular function correlations with cardiac catheterisation data in biventricular congenital heart patients.

BACKGROUND: Newer echocardiographic techniques may allow for more accurate assessment of right ventricular function. Adult studies have correlated these echocardiographic measurements with invasive data, but minimal data exist in the paediatric congenital heart population. The purpose of this study was to evaluate echocardiographic measurements that correlate best with right ventricular systolic and diastolic catheterisation parameters. METHODS: Patients with two-ventricle physiology who underwent simultaneous echocardiogram and cardiac catheterisation were included in this study. Right ventricular systolic echocardiographic data included fractional area change, displacement, tissue Doppler imaging s' wave, global longitudinal strain, and strain rate s' wave. Diastolic echocardiographic data included tricuspid E and A waves, tissue Doppler imaging e' and a' waves, and strain rate e' and a' waves. E/tissue Doppler imaging e', tissue Doppler imaging e'/tissue Doppler imaging a', E/strain rate e', and strain rate e'/strain rate a' ratios were also calculated. Catheterisation dP/dt was used as a marker for systolic function and right ventricular end-diastolic pressure for diastolic function. RESULTS: A total of 32 patients were included in this study. The median age at catheterisation was 3.1 years (0.3-17.6 years). The DP/dt was 493±327 mmHg/second, and the right ventricular end-diastolic pressure was 7.7±2.4 mmHg. There were no significant correlations between catheterisation dP/dt and systolic echocardiographic parameters. Right ventricular end-diastolic pressure correlated significantly with strain rate e' (r=-0.4, p=0.02), strain rate a' (r=-0.5, p=0.03), and E/tissue Doppler imaging e' (r=0.4, p=0.04). CONCLUSION: Catheterisation dP/dt did not correlate with echocardiographic measurements of right ventricular systolic function. Strain rate and tissue Doppler imaging analysis significantly correlated with right ventricular end-diastolic pressure. These values should be further studied to determine whether they may be used as an alternative method to estimate right ventricular end-diastolic pressure in this patient population.

QRS Duration Changes in Patients with Single Ventricle Physiology: Birth to 10 Years.

BACKGROUND: QRS prolongation may be a predictor of mortality in certain forms of congenital heart disease. Minimal data exist describing changes in QRS duration in patients with single ventricles (SVs). The goal was to describe changes in QRS duration in patients with SV and to determine if differences existed between single right ventricle (sRV) versus single left ventricle (sLV) patients. METHODS: Chart review was performed on patients with SV physiology. Patients were divided into sRV and sLV groups. QRS durations were measured monthly for the first 6 months, at 1 year, and then yearly until 10 years. t-tests were used for analysis. RESULTS: One hundred sixty patients were evaluated (95 sRV, 65 sLV). The greatest change in QRS duration for the entire cohort occurred in the first 6 months of life versus 6 months to 10 years of age (1.81 ms/month vs 0.20 ms/month). sRV QRS durations were significantly longer than sLV QRS durations at 1 year (78.9 ± 12.6 ms vs 73.2 ± 11.9 ms), 2 year (81.7 ± 14.7 ms vs 73.4 ± 12.5 ms), 4 year (84.2 ± 12.1 ms vs 77.9 ± 16.4 ms), 6 year (90.8 ± 12.7 ms vs 83.4 ± 13.4 ms), 7 year (90.8 ± 16.5 ms vs 81.2 ± 16.6 ms), and 8 year (96.7 ± 13.6 ms vs 84.8 ± 13.9 ms) time points. CONCLUSION: The greatest change in QRS duration in SV patients occurred in the first 6 months of life when these patients' ventricles were volume loaded. Differences in QRS duration between sRV and sLV patients occurred early in life. Further studies are needed to determine if minimizing volume load early in life decreases the rate of change in QRS duration.

Predictors of ductus arteriosus in-stent stenosis in the hybrid approach to hypoplastic left heart syndrome.

The hybrid approach to palliation of hypoplastic left heart syndrome using pulmonary artery bands, a patent ductus arteriosus (PDA) stent, and atrial septostomy has been well described. One potential complication of hybrid stage 1 palliation is the development of neointimal formation and in-stent stenosis (ISS). This study aimed to identify predictors of ISS development. Patients who underwent hybrid stage 1 palliation between 2002 and 2010 were included in the study. The clinical information included oxygen saturation, weight, vital signs, and medications. Echocardiographic data included ventricular function, degree of tricuspid regurgitation, and velocity through the PDA stent and pulmonary artery bands. Hemodynamic data from interstage catheterizations were similarly noted. Patients who developed clinically significant ISS requiring either transcatheter intervention or early stage 2 repair were compared with those who did not. Of the 66 patients included in the study, 40 were boys (61 %). The median age at hybrid palliation was 7 days (range, 1-93 days), and the median initial weight was 3.2 kg (range, 1.4-5 kg). In 13 patients (20 %), ISS developed. The mean initial weight was significantly greater in the ISS group (3.5 ± 0.5 vs. 3.0 ± 0.6 kg) (p = 0.03). The mean oxygen saturations did not differ significantly between the no-ISS group (82.2 % ± 5.7 %) and the ISS group (81.4 % ± 2.0 %) (p = 0.31). The mean PDA velocities were higher in the ISS group (2.7 ± 0.4 m/s) and increased at a faster rate than in the no-ISS group at (2.4 ± 0.4 m/s) (p = 0.01). The degree of tricuspid regurgitation, ventricular function, and pulmonary artery band gradients shown by echocardiography were similar in the two groups. The development of ISS after hybrid stage 1 palliation can lead to interstage interventions or earlier comprehensive stage 2 repair. Patients with greater initial weight and a lower stent-to-weight ratio are more likely to develop ISS. The cause of ISS is complex, and additional investigation of its etiology currently is ongoing.

Diastolic Dyssynchrony Differences in Patients with Single Right Ventricles vs. Control Patients.

AIMS: Diastolic dyssynchrony is increasingly being recognized as another marker for possible adverse cardiac events. Minimal data exist in hypoplastic left heart syndrome (HLHS) patients. The goal of this study was to determine if there were differences in diastolic dyssynchrony in patients with HLHS vs. control patients. METHODS/RESULTS: Tissue Doppler imaging (TDI) and strain rate (SR) analysis of the right ventricle in HLHS and control patients were performed. Time interval from onset of QRS complex on electrocardiography to peak TDI e' wave was obtained. Differences in intervals were calculated: QRSe'(RV) - QRSe'(IVS) and QRSe'(RV) - QRSe'LV). Time interval from onset of QRS to peak strain rate early diastolic wave (SRe) was obtained for the six-segment model RV. Standard deviation of the six SRe time intervals was calculated. t-tests were performed to determine if differences were present between groups. Sixty patients were studied (35 HLHS, 25 control). There were no significant differences between HLHS and control patients in age (6.5 ± 3.2 years vs. 6.1 ± 2.6 years) or heart rate (91 ± 22 bpm vs. 91 ± 13 bpm), respectively. There were no significant differences between HLHS and control patients in QRSe'(RV) - QRSe'(IVS) (19.9 ± 15.4 ms vs. 23.3 ± 13.6 ms) and QRSe'(RV) - QRSe'(LV) (20.7 ± 13.8 vs. 22.8 ± 14.6 ms), respectively. There was a significant difference in SRe standard deviation between the HLHS and control patients (25.3 ± 12.4 ms vs. 15.5 ± 6.9 ms, P = .0007), respectively. CONCLUSION: Patients with HLHS had increased diastolic dyssynchrony compared with control patients as measured via deformation analysis. Future studies are needed to determine the significance of these findings.

Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background.

Thoracic aortic aneurysms (TAA) are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV) and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/-; Nos3-/- mice. Echocardiographic analysis of Notch1+/-; Nos3-/- mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/-; Nos3-/- mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

Survey of how pediatric cardiologists noninvasively evaluate patients with hypoplastic left heart syndrome.

BACKGROUND: The evaluation of right ventricular (RV) function is important in patients with hypoplastic left heart syndrome (HLHS). Echocardiographic qualitative grading has been the prevalent method used in the past, but newer technologies allowing for quantitative assessment of RV function may have changed this fact. The goal of this study was to determine the current routine noninvasive evaluation of patients with HLHS and what, if any, methods are used to assess systolic and diastolic function in this population. METHODS: Web-based survey was conducted using various listservs. Timing of echocardiograms between surgical stages was assessed. Methods of assessing systolic and diastolic function were evaluated. RESULTS: Two hundred seventy-seven physicians who averaged 12.8 ± 9.6 years removed from training responded. Largest percentage of respondents was echocardiographers (44.2%) in a university-based practice (73.3%) from North America (91.7%). There were 54.3% of respondents who performed echocardiograms monthly between stages I and II, 48.8% who performed echocardiograms every 6 months between stages II and III, and 67.0% who performed echocardiograms annually after stage III procedure. The main method for systolic grading was qualitative grading (95.5%) and for diastolic grading were tricuspid blood inflow velocities (56.8%). Qualitative grading was considered the method of choice for systolic grading for 38.8% of respondents and tissue Doppler velocities was the method of choice for diastolic grading for 35.3% of respondents. There were 4.0% of respondents who routinely perform a cardiac magnetic resonance imaging (cMRI) between stages I and II, 8.0% between stages II and III, and 24.2% after stage III procedure. CONCLUSION: Variability in the noninvasive assessment of the RV in patients with HLHS continues to exist. Qualitative RV systolic assessment was still the predominant method used to assess function despite newer imaging techniques to allow for quantification. Future studies are needed to determine which values are most useful in reviewing function in this complex patient population.