Sudden out-of-hospital cardiac arrest in pediatric patients in Kyushu area in Japan.

BACKGROUND: It is well-known that a neurologically favorable outcome of out-of-hospital cardiac arrest (OHCA) is associated with the presence of bystander-initiated cardiopulmonary resuscitation (bystander CPR) and use of an automated external defibrillator. However, little is known about the effect of the presence of pre-existing conditions, prior activity, and locations on the outcome of pediatric OHCA. METHODS: We analyzed the data from questionnaires about pediatric patients with OHCA aged from 3 days to 19 years in the Kyushu area in Japan between 2012 and 2016. RESULTS: A total of 594 OHCA cases were collected. The numbers of OHCA cases and the rate of 1 month survival with a favorable neurological outcome during sleeping, swimming / bathing, and exercise were 192 (1.0%), 83 (32.5%), and 44 (65.9%), respectively. When an OHCA occurred at school (n = 56), 88% of children / adolescents received bystander CPR, but when it occurred at home (n = 390), 15% received bystander CPR. Cardiovascular (n = 61), suicide (n = 61), and neurological / neuromuscular (n = 44) diseases were three major pre-existing conditions. The OHCA of cardiovascular disease was associated with exercise (24/61) and mainly occurred at school (22/61). The OHCA of neurological / neuromuscular disease was associated with swimming/bathing (15/44) and mainly occurred during bathing at home (12/44). Multivariate regression analysis showed that the presence of bystander CPR (P < 0.001) and occurrence of OHCA at school (P < 0.001) were independently predictive of a favorable outcome in pediatric OHCA. CONCLUSION: The outcome was different among pre-existing conditions, prior activity, and location of OHCA. These findings might be useful for preventing OHCA and improving the outcome of pediatric OHCA.

Detection of Pediatric Pulmonary Arterial Hypertension by School Electrocardiography Mass Screening.

Rationale: To detect pulmonary arterial hypertension (PAH) at any early stage is a promising approach to optimize the outcome. Objectives: To investigate the impact of school ECG-based screening on detecting idiopathic or heritable (I/H)-PAH in the general pediatric population. Methods: This was a nationwide survey of patients with I/H-PAH newly diagnosed at 3 months to 18 years of age in Japan during 2005-2012. Measurements and Main Results: Eighty-seven eligible patients (age range, 1-16 yr) were recruited. Among 68 (78%) patients diagnosed at greater than or equal to 6 years of age (the age of the first ECG-based screening), 28 (41%) were detected by the ECG-based screening (screening group) and 40 (59%) were recognized by their symptoms (n = 37) or coincidental occasions (n = 3; nonscreening group). In the screening group, the proportion of patients in World Health Organization functional class I/II at diagnosis was higher (96% vs. 60%; P < 0.001), plasma brain natriuretic peptide level was lower (149 ± 290 vs. 398 ± 559 pg/ml; P = 0.045), and 6-minute-walk distance was longer (420 ± 109 vs. 327 ± 104 m; P < 0.001) than the nonscreening group, despite similar values in mean pulmonary artery pressure (58 ± 17 vs. 61 ± 17 mm Hg; P = 0.42) and pulmonary vascular resistance index (18 ± 8 vs. 21 ± 11 Wood units ⋅ m2; P = 0.24) between groups. The proportion of patients on intravenous epoprostenol at the final visit was lower in the screening group than the nonscreening group (14% vs. 50; P = 0.004). Conclusions: These findings suggest that the ECG-based screening detects a unique subpopulation of pediatric patients with I/H-PAH that is associated with already established pulmonary hypertension but without obvious right heart failure and warrants investigating the prognostic significance of this system.

Usefulness of Liver Stiffness on Ultrasound Shear-Wave Elastography for the Evaluation of Central Venous Pressure in Children With Heart Diseases.

BACKGROUND: Liver stiffness on ultrasound shear-wave elastography (SWE) reflects central venous pressure (CVP) in adult patients with heart failure, but the association of liver stiffness on SWE with CVP in pediatric patients is not clear. The present study evaluated whether liver stiffness on SWE is useful as a non-invasive indicator of CVP in pediatric patients.Methods and Results:Liver stiffness was measured using ultrasound SWE in 79 patients aged <20 years with congenital heart diseases. None of the patients was found to have liver disease. Correlations between liver stiffness and other clinical variables, including CVP, were analyzed. CVP was the only factor independently and significantly correlated with liver stiffness in multivariate analysis. However, variables related to hepatic fibrosis did not correlate with liver stiffness. CONCLUSIONS: Liver stiffness on ultrasound SWE is useful as a non-invasive indicator of CVP in children with heart diseases.

Real-world use of intravascular ultrasound in Japan: a report from contemporary multicenter PCI registry.

Clinical trial data suggest that intravascular ultrasound (IVUS) may improve clinical outcomes after PCI. The aim of this study was to investigate the safety of IVUS in its broader use for percutaneous coronary intervention (PCI). A total of 11,570 consecutive patients undergoing PCI between 2008 and 2014 in Japan were analyzed. Associations between IVUS use, PCI-related complications were assessed with logistic regression and propensity score matching analyses. Subgroup analysis was performed in elective PCI patients. IVUS was used in 84.8% of patients (N = 9814; IVUS group); its use was almost universal in elective PCIs (90.8 vs. 81.7% in urgent/emergent PCIs, P < 0.001). The non-IVUS group were older (68.7 ± 11.4 vs. 67.9 ± 10.8 years, P = 0.004), with more comorbid conditions. The non-IVUS group had smaller stent lumens (2.97 ± 0.42 mm vs. 3.09 ± 0.45 mm, P < 0.001) and a higher proportion of plain old balloon angioplasty. After matching, a lower rate of flow-impairing coronary dissections was observed in the IVUS group, although this was limited only to elective PCIs, not among urgent/emergent PCIs (non-IVUS vs. IVUS; 2.7% vs. 1.0%, P = 0.018, 0.7% vs. 1.2%, P = 0.32, respectively). With a multivariate logistic regression analysis, IVUS use remained an independent predictor to reduce risk of flow impairing severe coronary dissection among elective PCIs (odds ratio 0.38, 95% confidence interval 0.22-0.66: P = 0.001). In this Japanese PCI registry, IVUS was used extensively during the study period, particularly in elective cases. Using IVUS was associated with a lower event rate of flow-impairing coronary dissections that was limited to elective PCIs, not among urgent/emergent PCIs, without increasing PCI-related complications.

Efficacy of Sports Club Activities on Exercise Tolerance Among Japanese Middle and High School Children and Adolescents After Fontan Procedure.

The exercise tolerance of Fontan patients is poorer than that of healthy people. Some previous studies reported that exercise tolerance can be improved in this population by cardiac rehabilitation. This study aimed to determine the factors associated with peak oxygen uptake (VO2) and to subsequently clarify the correlation between participation in sports club activities and variables related to exercise tolerance. Cardiopulmonary exercise tests were performed by 115 Fontan patients aged between 6 and 20 years. The patients completed questionnaires on their daily physical activities including participation in extracurricular sports clubs in middle (junior high school) and high school. Peak VO2 had a significant negative correlation with age and a positive correlation with hemoglobin, stroke volume, and resting tidal volume in the entire study group. Additionally, the sports club participants who were middle and high school students had significantly higher peak VO2 and resting tidal volume. Exercise habits including participation in sports club activities may promote exercise tolerance by improving respiratory function in Fontan adolescents.

Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease.

Congenital heart disease (CHD) is the most common birth defect occurring in humans and some transcriptional factors have been identified as causative. However, additional mutation analysis of these genes is necessary to develop effective diagnostic and medical treatment methods. We conducted sequence analysis of the coding regions of NKX2.5, GATA4, TBX1, TBX5, TBX20, CFC1 and ZIC3 in 111 Japanese patients with non-syndromic CHD and 9 of their relatives. All patient samples were also analyzed by multiplex ligation-dependent probe amplification using probes involved in chromosome deletion related to CHD. Five novel variations of TBX5, GATA4 and TBX20 were detected in 6 of the patients, whereas none were found in 200 controls. The TBX5 variation p.Pro108Thr, located in the T-box domain, was identified in a patient with tricuspid atresia, an exon-intron boundary variation of GATA4 (IVS4+5G>A) was detected in a Tetralogy of Fallot patient and an 8p23 microdeletion was detected in one patient with atrioventricular septal defect and psychomotor delay. A total of seven non-synonymous polymorphisms were found in the patients and controls. Accumulation of novel variations of genes involving the cardiac development may be required for better understanding of CHD.

Favorable Effects of Oxygen Inhalation in Patients After Bidirectional Glenn Procedure as Assessed by Cardiovascular Magnetic Resonance Flow Measurement.

BACKGROUND: Home oxygen therapy (HOT) is used to adapt patients to the bidirectional Glenn (BDG) physiology. However, the precise cardiovascular effect of oxygen inhalation is still unknown. We used phase-contrast MRI to evaluate the cardiovascular effects of oxygen inhalation in young patients with BDG physiology. METHODS AND RESULTS: The 56 sessions of cardiac MRI were performed in 36 patients with BDG circulation. Oxygen saturation (SpO2) and heart rate (HR) were monitored under both room air and nasal 100% oxygen inhalation, and the blood flow volumes of the ascending aorta (AA), superior vena cava (SVC), and inferior vena cava (IVC) were measured by phase-contrast MRI. Systemic-to-pulmonary collateral flow (SPCF) volumes were calculated by subtracting the sum of flow volumes through the SVC and IVC from the flow volume through the AA, and used for further comparative examination. Under nasal oxygen inhalation, SpO2significantly increased from 82% to 89%, while HR decreased from 115 to 110 beats/min. AA (5.0 vs. 4.9 L·min(-1)·m(-2)), SVC (1.85 vs. 1.77 L·min(-1)·m(-2)), and systemic blood flow volume (=SVC+IVC) significantly decreased (3.60 vs. 3.46 L·min(-1)·m(-2)). In contrast, SPCF and the pulmonary-to-systemic blood flow ratio (Qp/Qs) remained unchanged. CONCLUSIONS: Oxygen inhalation improved arterial blood oxygenation and lowered HR in patients with BDG circulation without an increase in Qp/Qs. HOT would be protective of the cardiovascular system in patients with BDG circulation. (Circ J 2016; 80: 1378-1385).

Effect of Smoking Status on Clinical Outcome and Efficacy of Clopidogrel in Acute Coronary Syndrome.

BACKGROUND: The "smoker's paradox" is an otherwise unexplained phenomenon in which the mortality of smokers after acute myocardial infarction is reduced, contrary to expectations. It has been suggested that an association with antiplatelet agents exists, but the true mechanism remains largely unidentified. METHODS AND RESULTS: The analysis included 6,195 consecutive patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome, registered in the Japanese multicenter PCI registry. Smokers were significantly younger and had less comorbidity than non-smokers. Unadjusted in-hospital mortality rate, general complication rate, and bleeding complication rate were lower in smokers than in non-smokers. After adjustment, the trend persisted and smoking was not associated with overall mortality (odds ratio [OR], 0.90; 95% confidence interval [CI]: 0.61-1.34; P=0.62), and was associated with lower overall (P=0.032) and bleeding complication events (P=0.040). Clopidogrel effectively reduced the occurrence of in-hospital complications and major adverse cardiac events in smokers compared with non-smokers (OR, 0.55; 95% CI: 0.53-0.98 vs. OR, 1.20; 95% CI: 0.87-1.67; and OR, 0.37; 95% CI: 0.20-0.70 vs. OR, 1.48; 95% CI: 0.90-2.43, respectively). CONCLUSIONS: The smoker's paradox was largely explained by confounding factors related to the lower risk profile of smokers, and they benefited from a positive modification of the efficacy of clopidogrel. (Circ J 2016; 80: 1590-1599).

Evaluation of echogenicity of the heart in Kawasaki disease.

Pathologic studies of the heart in patients with Kawasaki disease (KD) revealed vasculitis, valvulitis, myocarditis, and pericarditis. However, there have been no studies on the quantitative determination of multi-site echogenicity of the heart in KD patients. It is also undetermined whether the degree of echogenicity of each site of the heart in patients with KD might be related to the response to intravenous immunoglobulin (IVIG) treatment. In 81 KD patients and 30 control subjects, we prospectively analyzed echogenicity of the heart. Echogenicity was measured in four sites: coronary artery wall (CAW), mitral valve (MV), papillary muscle (PM), and ascending aortic wall (AAo wall) by the calibrated integrated backscatters (cIBs). The cIB values of all measurement sites at acute phase in KD patients were significantly higher than those in control subjects (KD patients vs control subjects; CAW, 19.8 ± 6.2 dB vs 14.5 ± 2.0 dB, p < 0.05; MV, 23.3 ± 5.3 dB vs 16.0 ± 3.3 dB, p < 0.05; PM, 22.4 ± 5.1 dB vs 12.7 ± 1.9 dB, p < 0.05; AAo wall, 25.3 ± 5.6 dB vs 18.3 ± 3.4 dB, p < 0.05). The cIB values of CAW at the acute phase in IVIG nonresponders were significantly higher than those in responders. Conclusion: Echogenicity of the heart in KD patients at the acute phase increased not only in the coronary artery wall but also in other parts of the heart. Echogenicity of CAW might be helpful in determining the unresponsiveness of IVIG treatment.

Incidence of periprocedural myocardial infarction and cardiac biomarker testing after percutaneous coronary intervention in Japan: results from a multicenter registry.

Periprocedural myocardial infarction (pMI) is an important complication associated with percutaneous coronary intervention (PCI). However, data on the frequency of biomarker testing and the incidence of pMI remain unclear. Using the multicenter Japan Cardiovascular Database, we identified 2182 patients who underwent PCI without preprocedural cardiac biomarker elevation (silent ischemia, stable angina, or unstable angina without biomarker elevation) from September 2008 to August 2011. Of these, 550 patients (25.2 %) underwent cardiac biomarker testing within 6-24 h after PCI. The incidence of pMI was 2.7 % among all identified patients and 7.5 % among those who underwent cardiac marker testing. Of note, cardiac biomarker testing was performed more frequently than no testing in patients with a higher risk profile such as unstable angina (32.7 vs 24.7 %, P < 0.001), higher symptom scaling (28.2 vs 22.5 %, P = 0.008), urgent or emergent procedures (19.3 vs 15.0 %, P = 0.022 or 4.2 vs 1.0 %, P < 0.001, respectively), and type C lesion (31.3 vs 25.2 %, P = 0.006). Presentation with silent ischemia (odds ratio = 1.51, 95 % confidence interval (CI) 1.16-1.97) and nonemergent PCIs (odds ratio = 3.45, 95 % CI 1.79-6.67) were associated with no postprocedural cardiac biomarker testing. The real-world multicenter PCI registry in Japan revealed an incidence of 2.7 % for pMI; however, cardiac biomarkers were assessed in only 25.2 % of patients after PCI. The results suggest an underuse of postprocedural biomarker testing and room for procedural quality improvement, particularly in cases of silent ischemia and nonemergent cases.

Muscle squeezing immediately after coronary reperfusion therapy using postconditioning with lactate-enriched blood.

BACKGROUND: We recently reported a new approach for cardioprotection, postconditioning with lactate-enriched blood (PCLeB), and a patient with ST-segment elevation myocardial infarction (STEMI), in whom muscle squeezing of the culprit coronary artery was observed immediately after reperfusion with PCLeB. In this study, we examined the prevalence of muscle squeezing immediately after reperfusion in patients with anterior STEMI treated using PCLeB. METHODS AND RESULTS: PCLeB is a modified postconditioning protocol that comprises intermittent reperfusion and timely coronary injections of lactated Ringer's solution. We treated 30 consecutive patients with anterior STEMI using PCLeB. Among the 30 patients, 4 patients exhibited muscle squeezing of the left anterior descending artery (LAD) immediately after reperfusion. We performed follow-up coronary angiography in 23 patients and found another patient who exhibited muscle squeezing of the LAD. Thus, of 30 patients, 5 were confirmed to have myocardial bridging and 4 exhibited muscle squeezing immediately after reperfusion with PCLeB. No patient died or experienced re-hospitalization for heart failure or recurrent ischemic events at 6 months except for one patient with malignancy. CONCLUSION: Muscle squeezing immediately after reperfusion therapy is not a rare phenomenon in patients with anterior STEMI treated using PCLeB.

Evaluation of coronary artery variations using dual-source coronary computed tomography angiography in neonates with transposition of the great arteries.

OBJECTIVE: The purpose of this study was to investigate whether the origins and courses of the coronary arteries could be better assessed using ECG-gated dual-source computed tomography (CT) than with echocardiography in neonates with transposition of the great arteries (TGA). METHODS: A total of 17 neonates within 14 days old who underwent both echocardiography and retrospective ECG-gated coronary CT angiography were retrospectively reviewed. The patients were sedated and intubated during CT examinations, and CT images were obtained with a breath-hold. CT images were reconstructed by multiple cardiac phases, and the coronary artery assessment was performed in the most static phase. Coronary anomalies were classified by Shaher's classification and validated by surgical findings. RESULTS: CT correctly classified 16 of 17 cases (Shaher type 1: 7, type 2: 4, type 9: 3, type 3: 1, type 4: 2), whereas echocardiography classified only 8 of 17 cases correctly. Dual-source CT had a significantly higher diagnostic ability than echocardiography (p = 0.0078). CONCLUSION: Dual-source coronary CT angiography has a higher diagnostic ability than echocardiography in the assessment of the origins and courses of the coronary arteries in neonates with TGA.

Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction.

The beneficial effects of reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) is attenuated by reperfusion injury. No approach has been proven successful in preventing this injury in the clinical setting to date. Meanwhile, a novel approach for cardioprotection in patients with STEMI, i.e., postconditioning with lactate-enriched blood (PCLeB), has recently been reported. PCLeB is a modification of the original protocol of postconditioning, aimed at increasing the delay in the recovery from tissue acidosis produced during ischemia. This was sought to achieve controlled reperfusion with tissue oxygenation and minimal lactate washout. In this modified postconditioning protocol, the duration of each brief reperfusion is gradually increased in a stepwise manner from 10 to 60 s. Each brief ischemic period lasts for 60 s. At the end of each brief reperfusion, injection of lactated Ringer's solution (20-30 mL) is performed directly into the culprit coronary artery immediately before the balloon inflation and the balloon is quickly inflated at the lesion site, so that the lactate is trapped inside the ischemic myocardium during each brief repetitive ischemic period. After seven cycles of balloon inflation and deflation, full reperfusion is performed. Stenting is performed thereafter, and the percutaneous coronary intervention is completed. Excellent in-hospital and 6 month outcomes in a limited number of patients with STEMI treated using PCLeB have already been reported. This method article provides a detailed description of each step of the PCLeB procedures.

Outcome of patients with functional single ventricular heart after pacemaker implantation: What makes it poor, and what can we do?

BACKGROUND: Pacemaker implantation in patients with single ventricle is associated with poor outcomes. OBJECTIVE: The purpose of this study was to determine the reasons for the poor outcomes of pacemaker implantation. METHODS: We performed a retrospective chart review of patients with single ventricle who had undergone permanent pacemaker implantation. Patients were categorized into 3 groups based on the site of pacing and the proportion of ventricular pacing (VP) as follows: (1) atrial pacing group with atrial pacing only (n = 11); (2) low VP group with low daily VP proportion (<50%; n = 12); and (3) high VP group with high daily VP proportion (≥50%; n = 15). Pacing leads were placed at the epicardium in all patients. RESULTS: No patients in the atrial pacing or low VP groups died, whereas the survival rate in the high VP group was 58.9% and 39.3% at 10 and 20 years, respectively, after pacemaker implantation. Among the post-Fontan patients, plasma brain natriuretic peptide (BNP) levels significantly increased with the proportion of VP: 11.7, 20.3, and 28.4 pg/mL in the atrial pacing, low VP, and high VP groups, respectively (P = 0.04). In the high VP group, the plasma BNP level was significantly lower in patients with an apical pacing lead than in those with a nonapical pacing lead (27.0 pg/mL vs 82.8 pg/mL, respectively; P = .03). CONCLUSION: A higher proportion of VP was associated with poor outcome and higher plasma BNP levels, probably due to ventricular dyssynchrony. In epicardial ventricular pacing, apical pacing is better to avoid the increase in ventricular stress and plasma BNP level.

A Novel Double Side Branch Protection Technique for a Left Main Trifurcation Lesion: Simultaneous Jailed Balloon and Jailed Corsair Technique.

Percutaneous coronary intervention for left main trifurcation disease is challenging. Although side branch protection techniques such as the jailed balloon technique and jailed Corsair technique are the established methods for treatment of coronary bifurcation lesions, little is known regarding the application and feasibility of these techniques for left main trifurcation disease. We herein describe a 72-year-old man with angina pectoris who was successfully treated with percutaneous coronary stent implantation for a left main trifurcation lesion. In this case, we performed a novel double side branch protection technique, the simultaneous jailed balloon and jailed Corsair technique, with a single 8 Fr guiding catheter. This is the first case report to highlight the feasibility and efficacy of combined use of the jailed balloon and jailed Corsair techniques during percutaneous coronary intervention for left main trifurcation disease.

Effects of body habitus on contrast-induced acute kidney injury after percutaneous coronary intervention.

BACKGROUND: Limiting the contrast volume to creatinine clearance (V/CrCl) ratio is crucial for preventing contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). However, the incidence of CI-AKI and the distribution of V/CrCl ratios may vary according to patient body habitus. OBJECTIVE: We aimed to identify the clinical factors predicting CI-AKI in patients with different body mass indexes (BMIs). METHODS: We evaluated 8782 consecutive patients undergoing PCI and who were registered in a large Japanese database. CI-AKI was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%. The effect of the V/CrCl ratio relative to CI-AKI incidence was evaluated within the low- (≤25 kg/m2) and high- (>25 kg/m2) BMI groups, with a V/CrCl ratio > 3 considered to be a risk factor for CI-AKI. RESULTS: A V/CrCl ratio > 3 was predictive of CI-AKI, regardless of BMI (low-BMI group: odds ratio [OR], 1.77 [1.42-2.21]; P < 0.001; high-BMI group: OR, 1.67 [1.22-2.29]; P = 0.001). The relationship between BMI and CI-AKI followed a reverse J-curve relationship, although baseline renal dysfunction (creatinine clearance <60 mL/min, 46.9% vs. 21.5%) and V/CrCl ratio > 3 (37.3% vs. 20.4%) were predominant in the low-BMI group. Indeed, low BMI was a significant predictor of a V/CrCl ratio > 3 (OR per unit decrease in BMI, 1.08 [1.05-1.10]; P < 0.001). CONCLUSIONS: A V/CrCl ratio > 3 was strongly associated with the occurrence of CI-AKI. Importantly, we also identified a tendency for physicians to use higher V/CrCl ratios in lean patients. Thus, recognizing this trend may provide a therapeutic target for reducing the incidence of CI-AKI.

Cardiac Ventricular Contractile Responses to Chronically Increased Afterload Secondary to Right Ventricular Outflow Obstruction in Patients With Tetralogy of Fallot.

We examined the adaptive mechanism of the pulmonary ventricle (PV) in response to increased afterload secondary to pulmonary stenosis in tetralogy of Fallot (TOF, n = 47) and congenitally corrected transposition of the great arteries (cCTGA, n = 18), where the PV is morphologically different. We also elucidated the effects of such adaptation on systemic ventricular (SV) function. PV contractility, assessed by dp/dtmax, showed significant positive correlations with PV pressure (r = 0.82, p <0.01 for TOF and r = 0.78, p <0.01 for cCTGA) and pulmonary-to-systemic ventricular pressure ratio (r = 0.70, p <0.01 for TOF and r = 0.76, p <0.01 for cCTGA) in patients with both TOF and cCTGA. Notably, the slopes of these correlations were significantly higher in cCTGA than in TOF (p <0.01), suggesting enhanced contractile responses in cCTGA. Moreover, SV dp/dtmax showed significant positive correlations with PV dp/dtmax in patients with both TOF and cCTGA (r = 0.67, p <0.01 and r = 0.61, p <0.01, respectively), indicating positive ventricular-ventricular interaction. In this relationship, the slopes of correlations were significantly higher in TOF than in cCTGA (p = 0.024). These results, indicating different behaviors of PV contractile physiology and its interaction with the SV, may have important therapeutic implications when considering medical, catheter, and surgical interventions for pulmonary stenosis in these diseases. The results may also offer the potential for a new approach for improvement of prognosis, especially in cCTGA.

Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports.

Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for.