Jun Muneuchi

Pulmonary Hypertension in Patients With Congenital Portosystemic Venous Shunt: A Previously Unrecognized Association

BACKGROUND. Pulmonary arterial hypertension has been reported to be observed in association with acquired portal hypertension. However, the contribution of congenital anomalies occurring in the portal system to the development of pulmonary arterial hypertension remains to be elucidated. METHODS. Nine patients with congenital portosystemic venous shunt were studied from January 1990 through September 2005. RESULTS. Patent ductus venosus was detected in 5 patients, including 3 patients with an absence of the portal vein. The presence of either a gastrorenal or splenorenal shunt was evident in another 4 patients. Six patients had a history of hypergalactosemia with normal enzyme activities, as seen during neonatal screening. Six (66.7%) of the 9 patients were identified to have clinically significant pulmonary arterial hypertension (mean pulmonary artery pressure: 34–79 mm Hg; pulmonary vascular resistances: 5.12–38.07 U). The median age at the onset of pulmonary arterial hypertension was 12 years and 3 months. Histologic studies of lung specimens, which were available in 4 of the 9 patients with congenital portosystemic venous shunt, showed small arterial microthrombotic lesions in 3 patients. This characteristic finding was recognized even in the congenital portosystemic venous shunt patients without PAH. CONCLUSIONS. This study demonstrated thromboembolic pulmonary arterial hypertension to be a crucial complication in congenital portosystemic venous shunt, and this pathologic state may be latently present in patients with pulmonary arterial hypertension of unknown etiology.

Genetic Analysis of MMP Gene Polymorphisms in Patients With Kawasaki Disease

Kawasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis primarily occurring in coronary arteries. Matrix metalloproteinases (MMPs) have been considered to play pathophysiologic roles in the development of coronary artery lesions (CALs); therefore, an evaluation of the genetic contributions of the MMP genes to the development of CALs in KD patients would be beneficial for the prediction of CAL formation. We focused on the known functional single nucleotide polymorphisms (SNPs) in the MMP genes (MMP-2-735C>T, MMP-3-1612 5A/6A, MMP-9-1562C>T, MMP-12-82A>G, and MMP-13-77A>G) and performed the association study between these SNPs and CAL formation in KD. The study population consisted of 44 KD patients with CALs and 92 without CALs and 175 healthy controls. As a result, allele and genotype frequencies of MMP-13-77A>G showed significant differences between KD patients with CALs and without CALs (p = 0.00989 and p = 0.00551, respectively). The estimated frequencies of the G-C haplotype in the MMP-13 gene promoter were significantly lower in KD patients with CALs than in those without CALs. There was no association between other MMP genes and CAL formation. In conclusion, the genetic evaluation by association study demonstrated that the MMP-13 gene, at least in part, contributed to the development of CALs in KD.

Outcomes of cardiac surgery in trisomy 18 patients.

OBJECTIVEnThe objective was to clarify the outcomes of cardiac surgery in trisomy 18 patients.nnnPATIENTS AND METHODSnWe analysed 34 consecutive trisomy 18 patients, of whom 21 were males, with cardiac complications. They were divided into patients who underwent cardiac surgery and those who were conservatively treated. We compared rates of survival and discharge alive between two groups.nnnRESULTSnThe surgery group included nine patients, with six males, who underwent cardiac surgery - intracardiac repair in three patients, pulmonary arterial banding in five patients, and ligation of the ductus in one patient - at median age of 2.2 months, ranging from 0.5 to 9.8, and with median weight of 2.6 kilograms, ranging from 1.5 to 3.2. Cardiac surgery and pre-operative assisted ventilation were hazardous factors leading to death. In the surgery group, cumulative survival rates at 1 month, 6 months, 12 months, and 24 months were 63%, 38%, 25%, and 22%, respectively, compared with 51%, 26%, 9%, and 9% in the conservative group. There was a significant difference (p = 0.002). The cumulative rates of discharge alive at 1 month, 3 months, and 6 months were 0%, 12%, and 65% in the surgery group, which did not differ from the conservative group (p = 0.80).nnnCONCLUSIONSnCardiac surgery contributed to increased survival rate but not the rate of discharge alive in trisomy 18 patients. Cardiac surgery could not prevent all the trisomy 18 patients from death. The indication of cardiac surgery should be carefully individualised to improve the quality of life in trisomy 18 patients and concerned surrounding people.

Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism.

It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and development, and genital and ear anomalies (CHARGE) syndrome patients have DiGeorge sequence showing severe immunodeficiency due to the defect of the thymus. Although the only treatment to achieve immunological recovery for these patients in countries where thymic transplantation is not ethically approved would be hematopoietic cell transplantation, long-term survival has not been obtained in most patients. On the other hand, it is still not clarified whether hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation showing DiGeorge sequence including the defect of T cells accompanied with the aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac anomaly. He received unrelated cord blood transplantation without conditioning at 4xa0months of age. Recovery of T cell number and of proliferative response against mitogens was achieved by peripheral expansion of mature T cells in cord blood without thymic output. Although he is still suffering from severe hypoparathyroidism, he is alive without serious infections for 10xa0months.

Magnetic resonance studies of brain lesions in patients with Kawasaki disease

We evaluated brain lesions in patients with coronary arterial lesions (CAL) as a complication of Kawasaki disease (KD) by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Among 47 patients who underwent coronary angiography for the evaluation of CAL due to KD at Kyushu University Hospital from April 1996 to September 2004, 24 patients were evaluated prospectively by brain MRI and MRA 0.1-21.2 years after the onset of KD. Although most patients had irritability or lethargy, none of them had significant neurological symptoms or signs during the acute phase, except one who showed neck stiffness. In one patient with no apparent neurological symptoms out of the 24 patients, brain MRI and MRA revealed right cerebellar infarction and obliteration of the right posterior inferior cerebellar artery, respectively. These results revealed the presence of cerebrovascular lesion in one of the 24 KD patients with CAL and suggested the need to consider the possibility of brain lesions in severe cases of KD with or without neurological symptoms.

Thrombocytosis in asplenia syndrome with congenital heart disease: A previously unrecognized risk factor for thromboembolism

BACKGROUNDnThrombocytosis and thromboembolic complications occur after splenectomy. However, there is no previous report investigating the presence of thrombocytosis and its association with thromboembolic events in patients having asplenia syndrome with congenital heart disease.nnnMETHODSnEnrolled were 161 consecutive patients with functionally single ventricle who underwent cardiac catheterization between 1997 and 2010. They were divided into two groups: patients having asplenia (Group A, n=46) and patients having no asplenia (Group B, n=115). Aspirin therapy was employed in all patients after surgical interventions except for pulmonary artery banding. We retrospectively reviewed the platelet counts at each seven stage of cardiac catheterization (for pre- and postoperative evaluation of the first palliation, Glenn operation, and Fontan operation, and for late evaluation after Fontan operation), incidence of thromboembolic events, and other possible risk factors for thromboembolism.nnnRESULTSnThe median platelet counts in Group A were consistently higher than those in Group B at any of the seven stages of cardiac catheterizations (p<0.002). The incidence of thromboembolic complications was also higher in Group A than that in Group B (28% vs. 10%, p=0.030). Univariate and multivariate logistic regression analyses showed that a platelet count of more than 550 × 10(9)/L at the first cardiac catheterization was associated with thromboembolic complications (Odds ratio 3.17; p=0.046).nnnCONCLUSIONSnPersistent thrombocytosis is present in patients with asplenia syndrome. It may greatly contribute to the development of thromboembolism during the management of congenital heart disease than expected.

Exertional oscillatory ventilation during cardiopulmonary exercise test in Fontan patients with total cavopulmonary connection.

Exertional oscillatory ventilation (EOV) has been noted during cardiopulmonary exercise testing (CPX) in patients with heart failure. EOV is a predictor of poor prognosis in adult patients with heart failure. The objective of this study was to clarify the incidence and influence of EOV in Fontan patients. Symptom-limited CPX was performed in 36 Fontan patients at 12.3xa0±xa04.3 (6.5–24.4) years of age or 5.9xa0±xa02.0 (3.0–11.2) years after total cavopulmonary connection (TCPC). Mean age at the time of TCPC was 6.3xa0±xa03.3. All 36 TCPC patients were classified as New York Heart Association classification I or II. They also underwent cardiac catheterization subsequently. EOV was defined as cyclic fluctuations in minute ventilation at rest that persist during effort lastingxa0≥60% of the exercise duration, with an amplitudexa0≥15% of the average resting value. EOV was noted in 21 of 36 Fontan patients (58%) with good clinical status. Univariable analysis between Fontan patients with and those without EOV showed significant differences in age at TCPC (pxa0<xa00.05), age at CPX (pxa0<xa00.02), weight at CPX (pxa0<xa00.02), follow-up duration between TCPC and CPX (pxa0<xa00.04), ventricular morphology (pxa0<xa00.05), and metabolic equivalents (pxa0<xa00.05) and peak minute oxygen uptake (VO2) per body weight (pxa0<xa00.05). Multivariable analysis showed that EOV was significantly related to peak VO2 per kilogram. In conclusion, EOV was frequently noted during exercise in Fontan patients with good clinical status. EOV during exercise seems to be related to higher peak VO2 per kilogram and younger age at TCPC, which is a contrary result to those for adult patients with chronic heart failure. EOV is a remarkable phenomenon during exercise to compensate for impaired cardiopulmonary function in Fontan patients.

Myocarditis mimicking acute coronary syndrome following influenza B virus infection: a case report

We present a notable case of a 15-year-old male infected with influenza B virus who showed the clinical manifestations of myocardial ischemia. He was admitted to our hospital with sudden chest pain. He had febrile illness for the past 2 days. Rapid antigen test for influenza revealed positive influenza B virus antigen. The initial electrocardiogram showed elevation of the ST-segments in leads II, II, aVF and reciprocal depression in leads V1 and V2. Serum test showed elevation of creatine kinase and troponin T. Gadlinium-enchanced magnetic resonance imaging, Tl-201 and I-123 beta-methyl-p-iodephenyl-pentadecanoic acid scintigram, coronary angiography revealed no abnormality. Follow-up electrocardiogram showed ST-segment change improvement over the course. Myocarditis associated with influenza B virus seemed to be caused by endothelial impairment and disturbance of microcirculation rather than direct injury to cardiac myocytes.

A novel SCN5A mutation associated with the linker between III and IV domains of Nav1.5 in a neonate with fatal long QT syndrome

A male newborn weighing 2334 g was delivered at 37 weeks of gestation by caesarean section because of prenatal ultrasound findings of fetal hydrops with atrioventricualr block, ventriucular tachycardia (VT), and impaired ventricular function. In spite of the intravenous administration of lidocaine, VT continued. He developed poor perfusion and systemic hypotension. After the intravenous administration of amiodarone, VT was terminated. The electrocardiogram revealed an extremely prolonged corrected QT interval (860 ms) with 2:1 atrioventricular block. Unfortunately, he died 18 h after birth in spite of the administration of lidocaine, beta-blocker and magnesium. Mutational analysis identified a novel heterozygous de novo mutation (F1486del) in SCN5A. This mutation is associated with the IFM motif in the linker between III and IV domains of Na(v)1.5, which serves as an inactivation particle binding within the pore of sodium channels. This report demonstrates an interesting relationship between the clinical phenotype and the location of the mutation in long QT syndrome.

Detectable Silent Calcification in a Regressed Coronary Artery Aneurysm of a Young Adult with a History of Kawasaki Disease

Kawasaki disease is characterized as self-limited vasculites during infancy and childhood. The involvement of coronary arteries occurs in 15% to 20% of patients with Kawasaki disease during the acute phase of the illness [9]. Serial studies of coronary angiography demonstrate that the majority of small to moderate-size coronary artery aneurysms tend to regress within several years. However, large coronary arterial lesions progress to stenosis, complete obstruction, intraarterial thrombi, or calcification, which can lead to fatal myocardial ischemia [2, 3]. Dadlani et al. [4, 5] demonstrated that electron beam computed tomography (CT) could show the evidence of coronary artery calcifications in patients with Kawasaki disease. This imaging method detected coronary artery calcifications in patients with residual coronary arterial lesions, but not in those without such lesions in the longterm follow-up evaluation of Kawasaki disease. We present a case of a young adult with a history of Kawasaki disease in whom coronary artery calcification in a regressed coronary arterial lesion was shown by multislice spiral computed tomography (MSCT). Case Report