Hiroyuki Aotsuka

Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect.

Recently, GATA4 and NKX2.5 were reported as the disease genes of atrial septal defect (ASD) but the relationship between the locations of their mutations and phenotypes is not clear. We analyzed GATA4 and NKX2.5 mutations in 16 familial ASD cases, including four probands with atrioventricular conduction disturbance (AV block) and two with pulmonary stenosis (PS), by PCR and direct sequencing, and examined their phenotypes clinically. Five mutations, including two GATA4 and three NKX2.5 mutations, were identified in 31.3% of the probands with ASD, and three of them were novel. The two GATA4 mutations in the probands without AV block were S52F and E359Xfs (c.1075delG) that was reported previously, and three NKX2.5 mutations in the probands with AV block were A88Xfs (c.262delG), R190C, and T178M. Additionally, we observed some remarkable phenotypes, i.e., dextrocardia with E359Xfs (c.1075delG) and cribriform type ASD with R190C, both of which are expected to be clues for further investigations. Furthermore, progressive, most severe AV block was closely related with a missense mutation in a homeodomain or with a nonsense/frame‐shift mutation of NKX2.5 for which classification has not been clearly proposed. This pinpoints essential sites of NKX2.5 in the development of the conduction system.

Measurement of ventricular volumes by cine magnetic resonance imaging in complex congenital heart disease with morphologically abnormal ventricles

This study assessed the validity of cine magnetic resonance imaging (MRI) for measuring right and left ventricular volumes by using Simpsons rule in children with complex congenital heart disease. Forty-five patients with complex congenital heart disease (average age 2.6 years) and 10 controls (average age 2.3 years) were evaluated. The whole heart was encompassed by contiguous transverse sections. Ventricular volumes were calculated by adding luminal areas determined in each section at end diastole and end systole. End-diastolic and end-systolic volumes by MRI in both groups correlated well with those by ventriculography (r>0.89). Comparison of the ejection fraction in both ventricles in both groups yielded a good correlation between MRI and ventriculography (r>0.67). MRI technique in both groups had low intraobserver and interobserver variation (<6%). Cine MRI provides a suitable noninvasive means of quantifying ventricular volume in children with complex congenital heart disease.

Quantification of collateral aortopulmonary flow in patients subsequent to construction of bidirectional cavopulmonary shunts

OBJECTIVES We sought to provide a new method for quantifying collateral aortopulmonary flow in patients subsequent to construction of a bidirectional cavopulmonary shunt, and to clarify the clinical advantages of the new method. METHODS We performed lung perfusion scintigraphy and cardiac catheterization in 10 patients subsequent to construction of a bidirectional cavopulmonary shunt. First, the ratio of collateral to systemic flow was determined by whole-body images of lung perfusion scintigraphy, dividing the total lung count by the total body count minus the total lung count. Second, we integrated lung perfusion scintigraphy and cardiac catheterization data using a formula derived from the Fick principle, taking the ratio of pulmonary to systemic flow to be 1 plus the ratio calculated above and multiplied by the systemic saturation minus the inferior caval venous saturation divided by the pulmonary venous saturation minus the inferior caval venous saturation. Finally, the amount of collateral flow was obtained from the ratio of pulmonary to systemic flow. We evaluated the impact of collateral flow on the calculation of pulmonary vascular resistance. RESULTS The median age at bidirectional cavopulmonary shunt was 1.41 years, and the median age at catheterization was 2.33 years. The mean amount of collateral flow was 1.75 +/- 0.46 litres/min/m(2). The pulmonary vascular resistance calculated without considering the collateral flow was overestimated by an average of 57 +/- 23%, compared to the resistance calculated with our new method. CONCLUSIONS The use of scintigraphy combined with catheterization allows accurate determination of aortopulmonary collateral flow, and avoids overestimation of pulmonary vascular resistance in these candidates for the Fontan circulation.

Magnetic resonace imaging of heterotaxia in infants

OBJECTIVES This study assessed the usefulness and safety of magnetic resonance imaging (MRI) for systematically diagnosing heterotaxia in infants. BACKGROUND Although it is important to diagnose and treat infants with heterotaxia, which is associated with viscerobronchial cardiovascular anomalies, systematic diagnosis of these anomalies by a single imaging technique is difficult. METHODS Twenty patients with heterotaxia were evaluated. The infants ranged in age from 21 days to 12 months (average 5.2 months, average body weight 4.3 kg). Electrocardiographically gated MRI was performed by spin echo imaging techniques operating at 0.5 tesla. RESULTS In all 20 patients, MRI results were sufficient to evaluate these anomalies without serious complications. In 17 patients, neither a spleen nor splenules were detected, but in 3 patients, a polymorphous spleen was visualized. In all 20 patients, bronchial anatomies were clearly visualized (bilateral eparterial bronchi in 14 patients, bilateral hyparterial bronchi in 2 and normal bronchial patterns in 4). Additionally, in a comparison of 149 observations of cardiovascular anatomy by MRI with those by angiography, discrepancies were found in only 10 observations (6.7%). CONCLUSIONS Magnetic resonance imaging was found to be safe and very useful for the systematic diagnosis of heterotaxia in infants.

Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

Abstract. The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r2×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSVD: RSVD= TSV − FSV) and regurgitant fraction (RF: RF = RSVD/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSVD (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m2) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.

B-type natriuretic peptide at the early stage of univentricular circulation reflects inadequate adaptation to volume overload

BACKGROUND Recent studies showed that children with univentricular heart have elevated plasma B-type natriuretic peptide (BNP) levels prior to bidirectional cavopulmonary anastomosis (BDCPA). However, it remains to be established whether BNP levels reflect the degree of hemodynamic overload and relate to long-term outcome in univentricular circulation. METHODS Fifty one consecutive children with functionally univentricular heart prior to BDCPA were studied. All patients underwent cardiac catheterization and BNP measurement. Ventricular end-systolic wall stress (ESWS) and end-diastolic wall stress (EDWS) were calculated from cardiac catheterization data. RESULTS Median age was 1.1 years and 34% were female. Median BNP concentration was 90.4 pg/ml. Patients with high BNP (≥ 100 pg/ml) had higher pulmonary to systemic flow ratio (p = 0.014), a greater end-diastolic volume (p=0.009), more severe atrioventricular valve regurgitation (p= 0.02) and lower ventricular mass to end-diastolic volume ratio (p=0.006). BNP levels strongly related to EDWS (r = 0.75, p< 0.0001) and ESWS (r = 0.63, p < 0.0001). During median follow-up period of 3.2 years, 15 patients died and one underwent heart transplantation for refractory heart failure. On multivariate Cox regression analysis, high BNP concentration was an independent predictor of death or transplantation (HR 3.05, CI: 1.06-8.83, p = 0.04). CONCLUSIONS High BNP concentration at the first palliative stage towards Fontan circulation reflects high wall stress due to high volume load and insufficient ventricular hypertrophy. Moreover, high BNP levels at this stage were independently related to long-term outcome. BNP may be used as a guide to identify patients with high workload due to inadequate adaptation to hemodynamic load, who are at high risk.

Portosystemic Shunt with Polysplenia and Hypoplastic Left Heart Syndrome

We report a unique case of portosystemic shunt with polysplenia and hypoplastic left heart syndrome. The abnormal vessel connected the right renal vein and the splenic vein. The shunt flow was from the systemic vein to the portal vein before the Fontan-type operation, but it reversed and ran from portal vein to systemic vein after the Fontan-type operation.

Anomalous origin of both pulmonary arteries from the ascending aorta with a nonbranching main pulmonary artery arising from the right ventricle

SummaryA 3-month-old boy, mildly cyanosed and tachypneic, was found by cineangiography to have a nonbranching main pulmonary artery arising from the right ventricle and connecting to the descending aorta via a large persistent ductus arteriosus. The left and right pulmonary arteries arose as a common “trunk,” before branching, from the ascending aorta. Complete surgical correction was performed at 7-months of age. Subsequent cardiac catheterization has demonstrated normal pressures and blood oxygen saturation in all right-heart chambers and the great arteries.

Intracardiac Fontan procedure for heterotaxy syndrome with complex systemic and pulmonary venous anomalies

OBJECTIVE The extracardiac conduit procedure is widely used for patients with heterotaxy syndrome with complex systemic and pulmonary venous anomalies; however, it lacks conduit-growth potential and requires long-term anticoagulation. We present the intracardiac Fontan procedure, which eliminates the above-mentioned disadvantages. PATIENTS AND METHODS Twenty-four patients (mean age, 4.1 years; weight, 13.0 kg) with heterotaxy syndrome underwent intracardiac Fontan operations between March 1995 and March 2008. In each patient, the anomalous systemic venous return with the isolated hepatic vein was redirected to the pulmonary artery using an intra-atrial baffle without obstructing the pulmonary venous pathway; this was accomplished by anterior (n=5), lateral (n=15) or posterior tunnel methods (n=4), depending on the anatomical relationship of the systemic and pulmonary venous pathways. RESULTS There was one (4%) in-hospital and two (8%) late deaths in total. Five (21%) patients underwent re-operation for either pulmonary venous obstruction or supraventricular tachycardia. The actuarial 12-year survival was 86% (the Kaplan-Meier survival plot). The freedom from re-operation at 10 years was 77%. Anticoagulation was not required except for two patients (8%) who had prosthetic valves and coagulation disorder. Obstruction of the systemic venous pathway was not observed in any patient; however, five (20%) patients had clinically significant postoperative arrhythmias. At the final follow-up, all survivors were categorised as the New York Heart Association class I. CONCLUSIONS Aided by detailed preoperative anatomical and physiological diagnoses, intracardiac Fontan procedures were technically feasible in patients with complex systemic and pulmonary venous anomalies. The specific cardiac anatomy in these patients warranted this procedure; however, taking into consideration the improved outcomes of the modified Fontan procedure, this method should be performed with deliberation.

Systematic diagnostic method using magnetic resonance imaging to analyze viscero-bronchial-cardiovascular anomalies in pediatric patients with congenital heart disease

Segmental analysis of magnetic resonance imaging (MRI) was performed in 300 patients with congenital heart disease (CHD) (182 cyanotic CHD and 118 acyanotic CHD), between 20 days and 18 years of age. The usefulness of MRI in systematic diagnosis of CHD, which had previously been documented by angiography and echocardiography, was assessed. Electrocardiographyically gated MRI was performed by spin echo and gradient refocused imaging techniques operating at 0.5 tesla. In all 300 patients, not only cardiovascular anomalies of CHD but also viscerobronchial-cardiovascular anomalies were clearly visualized without serious complications due to MRI. In comparing 300 major cardiac anomalies and 1477 segments of the vein, the atrium, the ventricle, and the great arteries visualized by MRI and angiography, discrepancies were found in 7 anomalies (2.3%), and 22 segments (1.5%), respectively. Finally, in 86% (26/30) of patients manifesting atrioventricular valve regurgitation (AVVR), which had been evaluated by echocardiography, the AVVR was also detected on MRI. Based on these findings, segmental analysis of cardiac MRI was found to be safe and useful for systematic diagnosis of viscero-bronchial-cardiovascular anomalies in pediatric patients with CHD.