Successful Treatment of Protein-Losing Enteropathy and Plastic Bronchitis by Biphasic Cuirass Ventilation in a Patient with Failing Fontan Circulation.

We present a 16-year-old male patient with hypoplastic left heart syndrome who developed protein-losing enteropathy (PLE) and plastic bronchitis (PB) after a Fontan operation. He received medical therapies, including albumin infusion, unfractionated heparin, and high-dose anti-aldosterone therapy but could not obtain clinical relief. Biphasic cuirass ventilation (BCV) led to expectoration of bronchial casts and prompt resolution of PB. Notably, clinical symptoms related to PLE were dramatically improved after starting BCV. A brief period of BCV increased stroke volume from 26±1.4 to 39±4.0 mL. This case suggests that BCV could be an effective treatment for PLE in patients with failing Fontan circulation.

Pulmonary arterial hypertension associated with bronchopulmonary dysplasia and congenital heart disease in preterm infants. A case report of a preterm infant with recurrent pulmonary hypertension after corrective cardiac surgery and review of the literature.

In preterm infants with congenital heart disease, concomitant bronchopulmonary dysplasia (BPD) is associated with relatively poor clinical outcomes because of the increased pulmonary vascular resistance and adverse effects of inflammation on the damaged lungs, even after surgery. We present herein a 1-year-old female who developed recurrent pulmonary arterial hypertension 6 months after closure of a ventricular septal defect. She was born at 26 weeks of gestation (birth weight, 470 g), and developed BPD requiring oxygen supplementation. Her systemic-to-pulmonary blood flow ratio was 2.1 preoperatively and 1.0 postoperatively, pulmonary arterial pressure was 61/15 (mean 39) mmHg preoperatively and 41/17 (mean 24) mmHg postoperatively, and pulmonary vascular resistance was 4.2 mmHg/L·minute·m(2) preoperatively and 3.6 mmHg/L·minute·m(2) postoperatively. At 1 year of age, echocardiography showed an increase in her estimated right ventricular pressure, indicating worsening pulmonary hypertension. After 3 years of treatment with oxygen supplementation, prostacyclin, and bosentan, her pulmonary arterial pressure improved to the normal range. The pathophysiology of pulmonary arterial hypertension is heterogeneous in preterm infants with congenital heart disease and concomitant BPD. Careful management of these patients is warranted even after corrective cardiac surgery.

Successful control of life-threatening polymorphic ventricular tachycardia by radiofrequency catheter ablation in an infant.

We present a case of a 9-month-old girl in whom malignant polymorphic ventricular tachycardia (VT) was successfully controlled by radiofrequency catheter ablation under guidance with a three-dimensional mapping system. The VTs originated from the left ventricular lateral wall, left ventricular anterior wall, and left ventricular apex. At least six types of VTs were documented during the electrophysiology study. All VTs were successfully controlled after two sessions of radiofrequency catheter ablation, and she was discharged from our hospital on propranolol, mexiletine, flecainide, and aprindine.

GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling.

Congenital heart diseases (CHD) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. Although an improved understanding of the genetic causes of CHD would provide insight into the underlying pathobiology, the genetic etiology of most CHD remains unknown. Here we show that mutations in the gene encoding the transcription factor GATA6 cause CHD characteristic of a severe form of cardiac outflow tract (OFT) defect, namely persistent truncus arteriosus (PTA). Two different GATA6 mutations were identified by systematic genetic analysis using DNA from patients with PTA. Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. Transgenic analysis further suggests that, in the developing heart, the expression of SEMA3C in the OFT/subpulmonary myocardium and PLXNA2 in the cardiac neural crest contributing to the OFT is dependent on GATA transcription factors. Together, our data implicate mutations in GATA6 as genetic causes of CHD involving OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling.

Fatal systemic air embolism in a neonate with absent aortic valve.

A 32-year-old pregnant woman was referred at 33 weeks' gestation for prenatal ultrasound demonstrating fetal hydrops due to absent aortic valve with free aortic valve insufficiency. Elective caesarian section at 34 week's gestation was performed. Surgical intervention was planned immediately after labor at which time mitral valve closure and atrial septostomy using cardiopulmonary bypass would be performed. However, before insertion of the cannula for cardiopulmonary bypass, a gush of air from the right atrium was noted. The surgical procedure was abandoned because systemic air embolism was suspected. The child died 2 h after birth. Autopsy showed absent aortic valve with closed foramen ovale and left-ventricular hypertrophy. Microscopic findings showed pulmonary and systemic lymphangiectasis, which caused the introduction of air into systemic venous system by way of lymphatic duct just after birth.

Outcomes of cardiac surgery in trisomy 18 patients.

OBJECTIVE: The objective was to clarify the outcomes of cardiac surgery in trisomy 18 patients. PATIENTS AND METHODS: We 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. RESULTS: The 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). CONCLUSIONS: Cardiac 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.

GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5.

Congenital heart defects (CHDs) are the most common developmental anomaly and are the leading non-infectious cause of mortality in newborns. Only one causative gene, NKX2-5, has been identified through genetic linkage analysis of pedigrees with non-syndromic CHDs. Here, we show that isolated cardiac septal defects in a large pedigree were linked to chromosome 8p22-23. A heterozygous G296S missense mutation of GATA4, a transcription factor essential for heart formation, was found in all available affected family members but not in any control individuals. This mutation resulted in diminished DNA-binding affinity and transcriptional activity of Gata4. Furthermore, the Gata4 mutation abrogated a physical interaction between Gata4 and TBX5, a T-box protein responsible for a subset of syndromic cardiac septal defects. Conversely, interaction of Gata4 and TBX5 was disrupted by specific human TBX5 missense mutations that cause similar cardiac septal defects. In a second family, we identified a frame-shift mutation of GATA4 (E359del) that was transcriptionally inactive and segregated with cardiac septal defects. These results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5.

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 12.3 +/- 4.3 (6.5-24.4) years of age or 5.9 +/- 2.0 (3.0-11.2) years after total cavopulmonary connection (TCPC). Mean age at the time of TCPC was 6.3 +/- 3.3. 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 lasting >or=60% of the exercise duration, with an amplitude >or=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 (p < 0.05), age at CPX (p < 0.02), weight at CPX (p < 0.02), follow-up duration between TCPC and CPX (p < 0.04), ventricular morphology (p < 0.05), and metabolic equivalents (p < 0.05) and peak minute oxygen uptake (VO(2)) per body weight (p < 0.05). Multivariable analysis showed that EOV was significantly related to peak VO(2) 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 VO(2) 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.

Ventricular efficiency in pregnant women with congenital heart disease.

BACKGROUNDS: Pregnant women with congenital heart disease (CHD) are at risk of cardiovascular events during pregnancy as well as postpartum. The aim of our study is to address the feasibility of echocardiography-derived ventricular-arterial coupling during pregnancy and postpartum among women with CHD. METHODS: In 31 pregnant women with CHD, we performed serial echocardiography at the first and third trimesters, early and late postpartum. The indices of contractility (single-beat determined end-systolic elastance, Eesab) and afterload (effective arterial elastance, Ea) were approximated on the basis of the systemic blood pressure and systemic ventricular volume. The ratio of stroke work and pressure-volume area (SW/PVA) representing ventricular efficiency was also calculated. RESULTS: Age at the delivery was 28 (24-31) years. ZAHARA score was 0.75 (0.75-1.50). Gestational age and birth weight of newborns were 38 (37-39) weeks and 2.73 (2.42-2.92) kg, respectively. Heart rate, systemic ventricular end-diastolic volume and stroke volume significantly increased from the first trimester to the third trimester and reversed postpartum to the values of the first trimester. Eesab and Ea significantly decreased from the first trimester to the third trimester (Eesab; 4.90 [2.86-7.14] vs 3.41 [2.53-4.61] mm Hg/ml, p = 0.0001, Ea; 2.83 [1.74-3.30] vs 2.18 [1.67-2.68] mm Hg/ml, p = 0.0012), and reversed early postpartum parallelly. Ejection fraction and SW/PVA remained unchanged throughout pregnancy and postpartum. CONCLUSIONS: Echocardiography-derived ventricular-arterial coupling is feasible to understand ventricular function in pregnant women with CHD.

Pulmonary arterial resistance and compliance in preterm infants.

BACKGROUND: Preterm birth is known to be associated with an increased risk of pulmonary arterial hypertension, although how preterm birth influences pulmonary hemodynamics has not been fully understood. Pulmonary arterial resistance (Rp) and compliance (Cp) are important factors to assess the pulmonary circulation. The purpose of this study is to clarify the relationship between Rp and Cp in preterm infants. METHODS: We performed cardiac catheterization in 96 infants (50 males) with ventricular septal defect, and compared pulmonary hemodynamic parameters including Rp and Cp between preterm and full-term infants. RESULTS: Thirteen infants were preterm. There were no significant differences in sex, age, preoperative pulmonary arterial pressure, preoperative pulmonary-to-systemic flow ratio, and preoperative Rp between the 2 groups. However, preoperative Cp and resistor-capacitor (RC) time in preterm infants were significantly lower than those in full-term infants (2.1 vs 2.8mL/mmHg/m2 and 0.31 vs 0.36s, respectively; p<0.05 and p<0.01, respectively). Postoperative systolic and mean pulmonary arterial pressures were higher in preterm infants than those in full-term infants (29 vs 25mmHg and 18 vs 14mmHg, respectively; both p<0.01). It was also observed that postoperative Cp was lower in preterm infants, although postoperative Rp remained unchanged. CONCLUSIONS: We demonstrated that preterm infants with pulmonary arterial hypertension had lower Cp than full-term infants, causing a modest increase in pulmonary arterial pressure. It is important to consider the unique pulmonary vasculature characterized by lower Cp, when managing preterm infants with congenital heart disease.

Relationship between pulmonary arterial resistance and compliance among patients with pulmonary arterial hypertension and congenital heart disease.

BACKGROUND: It is unknown whether changes in pulmonary arterial resistance (Rp), pulmonary arterial compliance (Cp), and the product of Rp and Cp (the RC time) in patients with pulmonary arterial hypertension (PAH) are related to an increase in pulmonary blood flow. The aim of this study is to clarify relationships between these parameters before and after corrective surgery among patients with PAH and congenital heart disease. METHODS: We performed cardiac catheter examinations and compared Rp, Cp, and the RC time before and after corrective surgery in 100 infants (53 boys) with PAH related to ventricular septal defect. RESULTS: Median age at surgery was 2.9 (0.6-28.5) months. Preoperative values of the ratio of pulmonary to systemic blood flow (Qp/Qs), systolic pulmonary arterial pressure (PAP), Rp, Cp, and the RC time were 3.5 (2.7-4.3), 65 (56-70) mm Hg, 2.18 (1.64-3.19) Wood unit/m(2), 2.67 (2.01-3.38) mL/mm Hg/m(2), and 0.36 (0.31-0.40) seconds, respectively. Postoperative systolic PAP, Cp, and the RC time were significantly decreased to 26 (23-29) mm Hg, 1.96 (1.77-2.26) mL/mm Hg/m(2), and 0.31 (0.26-0.36) seconds, respectively, although Rp remained unchanged at 2.53 (2.06-3.31) Wood unit/m(2). The relationship between Rp and Cp was inversely related before and after surgery, and the Rp-Cp coupling curve was shifted downward after surgery. In addition, lower preoperative Cp (partial regression coefficient = -3.35; P = .001) and preterm delivery (partial regression coefficient = 6.28; P = .02) were independently related to postoperative higher systolic PAP. CONCLUSIONS: Rp-Cp coupling depends on both the amount of pulmonary blood flow and the condition of the pulmonary vasculature. Lower preoperative Cp is an independent predictive factor to predict higher postoperative pulmonary systolic pressure leading to an increase in right ventricular workload. It is necessary to assess Rp-Cp coupling before surgery among patients with PAH related to congenital heart disease.

Role of TBX1 in human del22q11.2 syndrome.

BACKGROUND: Del22q11.2 syndrome is the most frequent known chromosomal microdeletion syndrome, with an incidence of 1 in 4000-5000 livebirths. It is characterised by a 3-Mb deletion on chromosome 22q11.2, cardiac abnormalities, T-cell deficits, cleft palate facial anomalies, and hypocalcaemia. At least 30 genes have been mapped to the deleted region. However, the association of these genes with the cause of this syndrome is not clearly understood. METHODS: To test for the chromosomal deletion at 22q11.2, we did fluorescence in-situ hybridisation analysis with ten probes on 22q11.2 in 235 unrelated patients with clinically diagnosed del22q11.2 syndrome. To investigate mutations in the coding sequence of TBX1, we also did genetic analysis in 13 patients from ten families who have the 22q11.2 syndrome phenotype but no detectable deletion of 22q11.2. FINDINGS: 96% (225 of 235) of patients had a defined 1.5-3-Mb deletion at 22q11.2. We identified three mutations of TBX1 in two unrelated patients without the 22q11.2 deletion-one with sporadic conotruncal anomaly face syndrome/velocardiofacial syndrome and one with sporadic DiGeorge's syndrome-and in three patients from a family with conotruncal anomaly face syndrome/velocardiofacial syndrome. We did not record these three mutations in 555 healthy controls (1110 chromosomes; p<0.0001). INTERPRETATION: Our results suggest that the TBX1 mutation is responsible for five major phenotypes in del22q11.2 syndrome. Therefore, we conclude that TBX1 is a major genetic determinant of the del22q11.2 syndrome.

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

BACKGROUND: Thrombocytosis 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. METHODS: Enrolled 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. RESULTS: The 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). CONCLUSIONS: Persistent 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.

Clinical features of adult patients with Eisenmenger's syndrome in Japan and Korea.

BACKGROUND: There are few articles on mortality and morbidity of adult patients with Eisenmenger's syndrome (ES) in the current era when disease targeting therapy (DTT) has been available. METHODS AND RESULTS: 198 patients (a median age 35 years, 64% female) with ES who visited the 16 participating institutes in Japan and Korea from 1998 to 2009 were enrolled. Clinical data during adulthood were collected from each institutional chart and analyzed centrally. During a median follow-up of 8 years, 30 patients died including 14 sudden deaths. 89 patients took oral medication of DTT and clinical improvement was observed in 54 of them. However, survival rate in patients taking DTT was not different from those without (87% vs 84%, p=0.55). When the clinical data in between first and last clinic visits were compared in 85 patients, the patients with NYHA >/=III increased from 24% to 48% (p<0.001), SpO2 decreased from 89% to 85% (p=0.008) and hematocrit increased from 51.4% to 52.9% (p=0.04). Non-survivors had poorer NYHA function class, lower body weight (BW), lower body mass index (BMI), and higher serum level of Cr at the first visits than survivors. CONCLUSIONS: Long term survival and clinical status of adult patients with ES remains unsatisfactory even in the current era of DTT. Poor NYHA functional class, low BW, low BMI and high serum level of Cr were related to mortality. DTT therapy improved clinical status in many patients with Eisenmenger's syndrome, but no significant impact on survival could be shown.

Longitudinal growth of the autologous vessels above and below the Gore-Tex graft after the extracardiac conduit Fontan procedure.

OBJECTIVE: Reflecting excellent mid-term outcomes, extracardiac conduit Fontan procedure (ECFP) using Gore-Tex tube graft has been performed with increasing frequency in patients with functional single ventricle. Nevertheless, due to the lack of growth potential of the artificial conduit, the status of the venous pathway along with somatic growth is a continuing concern. In this study, we evaluated the longitudinal growth of the autologous vessels above and below the Gore-Tex graft used in the ECFP. METHODS: This study included 34 patients who had completed cardiac catheterisations at 1 month and 5.1 years after the ECFP. The average age, weight and height at the ECFP were 3.8+/-2.5 years (1.8-12.7 years), 12.7+/-4.6 kg (7.4-33.0 kg) and 92.9+/-16.1cm (72.5-153.5 cm), respectively. We measured the vertical lengths of three different parts angiographically: the length between the confluence point of the innominate vein and the anastomotic site of the conduit to the pulmonary artery (SVC-C), the conduit vertical length (C) and the length between the confluence point of the hepatic vein and the conduit's anastomotic site to the inferior vena cava (IVC-C). RESULTS: We have not observed stenosis or thrombus formation in the conduit or distortion of the conduit or pulmonary artery in any of the cases. No intervention or re-operation related to the extracardiac conduit was required, and laminar flow through the conduit was maintained with efficient Fontan haemodynamics. At 5.1 years after the ECFP, the average weight and height gain were 10.3+/-4.4 kg and 28.5+/-1.9 cm, respectively. The length of SVC-C, C and IVC-C were significantly increased as 124+/-15%, 106+/-7% and 132+/-24%, respectively, compared to the lengths at 1 month after the ECFP. The degree of increase in SVC-C and IVC-C was significantly larger than that in C. CONCLUSIONS: Along with the patient's somatic growth, longitudinal growth of the autologous vessels above and below the Gore-Tex graft was demonstrated to compensate for the lack of growth potential of the artificial graft.

Mid-term follow-up of the status of Gore-Tex graft after extracardiac conduit Fontan procedure.

OBJECTIVE: Extracardiac conduit Fontan procedure (ECFP) using Gore-Tex graft has been performed with increasing frequency for the patients with functional single ventricle. However, lack of growth potential and longevity of the conduit are consistent concerns and main points of criticism of the ECFP. In this study, we investigated the mid-term status of the Gore-Tex graft used in the ECFP by comparing the internal diameter of the graft with the inferior vena cava (IVC) diameter at 1 month and 5.2 years after the ECFP. METHODS: Of 79 patients who underwent ECFP using Gore-Tex graft between November 1997 and December 2007, 33 patients who had completed cardiac catheterization at 1 month (21-73 days) and 5.2 years (3.3-9.6 years) after the ECFP were included in this study. We measured the internal diameter of the Gore-Tex graft and IVC at both catheterizations retrospectively. RESULTS: The size of the Gore-Tex graft used in the ECFP was 16 mm in 17 patients, 18 mm in 9 patients, and 20mm in 7 patients. Laminar flow through the conduits was maintained without any stenosis or kinking of the graft in these 33 patients. No intervention or reoperation related to the extracardiac conduit has been required. There were no significant differences in mean cross-sectional area (CSA) of the conduits at 1 month versus 5.2 years after the ECFP for each conduit size, and no significant changes in the conduit-to-IVC CSA ratio (0.98+/-0.40 vs 0.82+/-0.21 for 16 mm, 1.09+/-0.30 vs 0.92+/-0.33 for 18 mm, and 1.16+/-0.55 vs 0.94+/-0.44 for 20mm conduit). CONCLUSIONS: The conduit CSA and conduit-to-IVC CSA ratio remained unchanged in small caliber grafts down to 16 mm at 5.2 years after the ECFP. However, further investigation is necessary to evaluate the fate of the Gore-Tex graft and late hemodynamics in the patients with small conduits after they achieve full somatic growth.