Forty-year survival after Glenn procedure without Fontan procedure in patients with single ventricle.

OBJECTIVES: There are no data on long-term outcomes beyond 30 years after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology. Hence, this study aimed to clarify the very long-term outcomes of these patients. METHODS: This single-centre, retrospective cohort study investigated the clinical outcomes of patients with single-ventricle physiology who underwent the Glenn procedure between 1970 and 1999. Those who underwent the subsequent Fontan procedure were excluded. The primary outcome was all-cause death. The secondary outcome was a composite of all-cause death, arrhythmic events, neurological events or infective endocarditis. The prognostic factors associated with the long-term outcomes were also evaluated. RESULTS: In total, 36 patients were enrolled (median age at Glenn procedure: 6.2 years, 56% male). During a median follow-up of 17.6 years (interquartile range: 6.1-33.4), 21 patients died and 29 experienced the composite outcome. The 20-, 30- and 40-year overall survival after the Glenn procedure was 51.2%, 44.4% and 40.3%, respectively. The 20-, 30- and 40-year event-free survival was 36.0%, 25.5% and 14.5%, respectively. Patients with dominant left ventricular morphology had better overall survival than those with dominant right ventricular morphology (hazard ratio: 0.24, 95% confidence interval: 0.08-0.76, P = 0.014). None of the patients had liver cirrhosis but 1 had protein-losing enteropathy. CONCLUSIONS: The 40-year overall survival after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology was 40.3%. Dominant left ventricular morphology may be associated with better long-term overall survival than dominant right ventricular morphology.

Relationship between the Amount of Menstrual Flow and Cardiac Status in Women with Fontan Circulation.

A high prevalence of heavy menstrual bleeding (HMB) has been reported in women with Fontan circulation. Cyanosis has been reported to contribute to HMB, and menstruation has been suggested to affect cardiac status in women with congenital heart disease. This study aimed to evaluate the relationship between the amount of menstrual flow and cardiac status in women with Fontan circulation.Twenty women who had undergone the Fontan procedure were prospectively investigated and the amount of their menstrual flow was evaluated using a questionnaire. Participants were divided into two groups-small and large menstrual bleeding groups-and their clinical data, including the results of hematological tests and echocardiographic findings, were evaluated.One (5%) woman showed primary amenorrhea. Eight of the remaining 19 (42%) women were included in the large menstrual bleeding group. Women with large menstrual bleeding showed a significantly higher hematocrit level (47.1% [36.2%-50.3%] versus 42.1% [35.3%-44.9%], P = 0.006) and longer QRS duration (106 [92-172] ms versus 88 [78-140] ms, P = 0.008), as well as a lower fractional area change (37.4% [35.6%-47.2%] versus 47.0% [38.2%-55.7%], P = 0.010) and global longitudinal strain (-10.5% [-14.9% to -6.6%] versus -13.9% [-20.5% to -7.8%], P = 0.041) of the dominant ventricle on echocardiography, than women with small bleeding.Erythrocytosis, longer QRS duration, and reduced ventricular function were related to increased menstrual bleeding in women with Fontan circulation. These functions may be interrelated with the amount of menstrual flow in such women.

Relationship between right and left ventricular diastolic dysfunction assessed by 2-dimensional speckle-tracking echocardiography in adults with repaired tetralogy of Fallot.

Several studies have reported a correlation between right ventricular (RV) and left ventricular (LV) systolic dysfunction in adults with repaired tetralogy of Fallot (TOF). However, data are lacking regarding the relationship between RV and LV diastolic dysfunction assessed by 2-dimensional speckle-tracking echocardiography. We studied 69 adults with repaired TOF (mean age 34 years, 61% male) who had been regularly followed up and had routinely undergone echocardiography. In addition to conventional echocardiography, global longitudinal strain (GLS) and early diastolic strain rate (SRe) of both ventricles were assessed using 2-dimensional speckle-tracking echocardiography. Results were compared with 30 age- and sex-matched controls. RV and LV GLS were decreased in TOF patients compared with controls (- 18.4 ± 3.3% vs. -23.5 ± 4.2%, p < 0.001 and - 16.0 ± 3.8% vs. -20.0 ± 3.0%, p < 0.001, respectively). RV and LV SRe were also decreased in TOF patients compared with controls (1.22 ± 0.34 sec- 1 vs. 1.47 ± 0.41 sec- 1, p = 0.003 and 1.29 ± 0.42 sec- 1 vs. 1.63 ± 0.42 sec- 1, p < 0.001, respectively). A correlation between RV and LV SRe was found in TOF patients (r = 0.43, p < 0.001) as well as between RV and LV GLS (r = 0.45, p < 0.001). Two-dimensional speckle-tracking echocardiography reveals subclinical RV and LV diastolic dysfunction in adults with repaired TOF. A correlation is observed between RV and LV diastolic dysfunction as well as between RV and LV systolic dysfunction.

CRT in a congenital heart disease patient with interventricular dyssynchrony due to an RV conduction delay.

We encountered a unique pattern of cardiac dyssynchrony in a patient with complex congenital heart disease (heterotaxy syndrome) with a biventricular physiology and systemic left ventricle (LV). On speckle tracking echocardiography, dyssynchrony was not detected within the LV, but was noted in an interventricular fashion between the LV and right ventricle (RV). An electrophysiologic study revealed a conduction delay in the subpulmonary RV. Cardiac resynchronization therapy provided reverse cardiac remodeling and an excellent result in our patient by placing the pacing leads around the dyssynchronous lesion.

Extremely short setting of optimal sensed atrioventricular interval in patients after Fontan procedure with implanted dual-chamber pacemaker.

BACKGROUND: Atrioventricular interval optimisation is important in patients with dual-chamber pacing, especially with heart failure. In patients with CHD, especially in those with Fontan circulation, the systemic atrial contraction is supposed to be more important than in patients without structural heart disease. METHODS: We retrospectively evaluated two patients after Fontan procedure with dual-chamber pacemaker with a unique setting of optimal sensed atrioventricular interval. RESULTS: The optimal sensed atrioventricular interval determined by echocardiogram was extremely short sensed atrioventricular interval at 25 and 30 ms in both cases; however, the actual P wave and ventricular pacing interval showed 180 and 140 ms, respectively. In both cases, the atrial epicardial leads were implanted on the opposite site of the origin of their own atrial rhythm. The time differences between sensed atrioventricular interval and actual P wave and ventricular pacing interval occurred because of the site of the epicardial atrial pacing leads and the intra-atrial conduction delay. CONCLUSION: We need to consider the origin of the atrial rhythm, the site of the epicardial atrial lead, and the atrial conduction delay by using electrocardiogram and X-ray when we set the optimal sensed atrioventricular interval in complicated CHD.

Evaluating the response to cardiac resynchronization therapy performed with a new ventricular morphology-based strategy for congenital heart disease.

BACKGROUND: In cardiac resynchronization therapy (CRT) for patients with congenital heart disease (CHD) and a ventricular morphology other than a systemic left ventricle (LV), we previously proposed pacing sites that are different from those used for a systemic LV. The leads should be placed laterally on opposite sides of both ventricles in patients with short-axis dyssynchrony and a single ventricular physiology with two ventricles, whereas they should be placed at the farthest sites along the longitudinal direction in the right ventricle (RV) in patients with long-axis dyssynchrony of the RV. Moreover, in patients with interventricular dyssynchrony and a biventricular physiology with a systemic RV, they should be placed at sites that both ventricles can contract simultaneously. We retrospectively investigated 27 consecutive procedures in 24 patients with CHD who underwent CRT to evaluate the effectiveness of a new ventricular morphology-based CRT strategy. The responder rate was 63% (17/27). The reasons for a non-response to CRT in 10 cases were as follows: non-optimal lead positions during CRT, 4; no systemic ventricular conduction delay or heart failure symptoms before the CRT, 5; short follow-up periods after the CRT, 2; and an extremely dilated systemic RV, 1. The responder rate became 88% (14/16), after excluding the procedures without a ventricular conduction delay or heart failure symptoms and those with non-optimal lead positions. This new strategy for CRT can provide favorable results for CHD patients with a systemic ventricular conduction delay and heart failure.

Continuous infusion of lipo-prostaglandin E1 for Takayasu's arteritis with heart failure in an 11-month-old baby: a case report.

BACKGROUND: Takayasu's arteritis is extremely rare in children aged below 6 years. At the onset of Takayasu's arteritis in children, symptoms are varied but differ from those in adults. Corticosteroids are the mainstay of treatment for preventing irreversible vascular damage but there is no standard treatment for progressive vascular stenosis. CASE PRESENTATION: A Japanese 11-month-old baby boy presented with Takayasu's arteritis and heart failure, possibly due to afterload mismatch caused by high blood pressure. Computed tomography was performed and revealed thoracic and abdominal aortic aneurysms. It also revealed severe celiac artery stenosis and bilateral renal artery stenosis. Prednisolone was initiated as first-line therapy. The fever resolved, and C-reactive protein levels returned to normal. Although his general condition improved, deterioration of vascular lesions was evident. Celiac artery occlusion, severe right renal artery stenosis, and new superior mesenteric artery stenosis were observed. We decided to use a continuous infusion of lipo-prostaglandin E1 for prevention of branch stenosis of his abdominal aorta. The progression of vascular stenosis was stopped and our patient's cardiac function gradually improved. CONCLUSIONS: A differential diagnosis of heart failure with high blood pressure should be considered in babies. The progression of vascular stenosis may be suppressed by lipo-prostaglandin E1.

Starnes procedure for severe left atrioventricular valve regurgitation.

We present the case of a 19-day-old girl with incomplete atrioventricular septal defect, muscular ventricular septal defect, and severe left atrioventricular valve regurgitation. We attempted biventricular repair with left atrioventricular valve repair; however, we could not control the regurgitation. Moreover, the commercially available prosthetic valve was too large to implant. Thus we switched intraoperatively to a univentricular repair. We successfully performed patch closure of the left atrioventricular valve (Starnes procedure), Damus-Kaye-Stansel anastomosis, and a systemic-to-pulmonary artery shunt.

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function.

Loss-of-function mutations in filamin A (FLNA) cause an X-linked dominant disorder with multiple organ involvement. Affected females present with periventricular nodular heterotopia (PVNH), cardiovascular complications, thrombocytopenia and Ehlers-Danlos syndrome. These mutations are typically lethal to males, and rare male survivors suffer from failure to thrive, PVNH, and severe cardiovascular and gastrointestinal complications. Here we report two surviving male siblings with a loss-of-function mutation in FLNA. They presented with multiple complications, including valvulopathy, intestinal malrotation and chronic intestinal pseudo-obstruction (CIPO). However, these siblings had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. Trio-based whole-exome sequencing revealed a 4-bp deletion in exon 40 that was predicted to cause a lethal premature protein truncation. However, molecular investigations revealed that the mutation induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses. This study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA.

Living-donor liver transplantation for congenital biliary atresia with porto-pulmonary hypertension and moderate or severe pulmonary arterial hypertension: Kyoto University experience.

Porto-pulmonary hypertension with moderate or severe pulmonary arterial hypertension (PAH) is viewed as a contraindication to liver transplantation (LT) because of associated poor outcomes; however, patients with biliary atresia (BA) are generally good candidates for LT. Ten patients with moderate/severe PAH underwent living-donor liver transplantation (LDLT) at our institution; eight of these patients had BA and were the focus of this study. Preoperative therapies, including prostaglandin (PG)I2 , were introduced. When mean pulmonary arterial pressure (mPAP) after treatment was <40 mmHg or initial mPAP without therapy was <35 mmHg, we performed an acute volume challenge test to evaluate right ventricular function. LDLT was performed when mPAP after anesthetic induction was confirmed at ≤35 mmHg. Six patients had favorable responses to preoperative treatment and catheter testing, but two patients showed poor responses. The two patients with poor responses had poor clinical courses with unstable mPAP after LDLT. The other six patients had successful courses with well-controlled mPAP, and PGI2 was withdrawn or weaned following LDLT. Survival did not significantly differ between the eight BA recipients with moderate/severe PAH and 77 age-matched BA recipients without PAH from the same time period. LDLT has major benefits for BA patients with well-controlled PAH.

Ventricular septal defect complicated by infantile lobar emphysema.

An infant with ventricular septal defect, atrial septal defect, and Down syndrome (trisomy 21) was referred to our institution. The patient gradually developed infantile lobar emphysema of the right upper lobe and became dependent on mechanical ventilator support. When the patient was five months of age, we successfully performed a total correction of cardiac anomalies combined with a right upper lobectomy. The resection of the right upper lobe was performed under cardiopulmonary bypass through a median sternotomy. There was no major airway bleeding or mediastinitis. The patient was extubated on postoperative day 12 and discharged on postoperative day 29.

Single-lobe lung transplantation for rapidly deteriorating pulmonary venoocclusive disease.

Pulmonary venoocclusive disease, classified as a subgroup of pulmonary arterial hypertension, is known to show poor prognosis and lung transplantation is the only possible treatment. Single living-donor lobar lung transplantation is a unique method of treatment, mostly for small children, and size matching is the most important factor to conduct single living-donor lobar lung transplantation safely. We report a successful single living-donor lobar lung transplantation for a 6-year-old girl with pulmonary venoocclusive disease who received the graft from her mother. Preoperatively, the recipient was intubated under deep sedation because of repeated episodes of pulmonary edema due to rapidly deteriorating pulmonary venoocclusive disease.

Pulmonary atresia with ventricular septal defect and pulmonary sequestration.

A 5-day-old girl who had pulmonary atresia with ventricular septal defect, patent ductus arteriosus, intralobar pulmonary sequestration of the right lower lobe, and retroesophageal innominate vein, was referred to our institution. We successfully performed a systemic-to-pulmonary shunt. During cardiopulmonary bypass, the arteries supplying the sequestrated lung were ligated above the diaphragm through the median sternotomy, without a thoracotomy. The postoperative course was uneventful, and we avoided the potential complications of lung infection and ventricular overload.

Left pulmonary artery banding to repair ipsilateral diffuse pulmonary arteriovenous fistula.

Congenital pulmonary arteriovenous fistula (PAVF) is a rare disease which causes hypoxemia by shunting deoxygenated blood from the pulmonary artery into pulmonary venous return. Lung transplantation is the most effective therapy to treat severe, diffuse PAVF. However, the availability of lungs for transplantation is limited in most parts in the world. For patients with diffuse PAVF affecting only one side of the lungs, ipsilateral pulmonary artery banding (PAB) is an effective treatment, but not yet standard of care. We report successful treatment of a patient with diffuse left-sided PAVF with PAB. We believe that PAB is an effective therapy for severe unilateral PAVF and may serve as a bridge to lung transplantation.

Living-donor liver transplantation for moderate or severe porto-pulmonary hypertension accompanied by pulmonary arterial hypertension: a single-centre experience over 2 decades in Japan.

BACKGROUND: Candidates for orthotopic liver transplantation (OLT) often have porto-pulmonary hypertension (PPHTN) with pulmonary arterial hypertension (PAH). Poor outcomes of PPHTN contraindicate OLT. There are no guidelines for living-donor liver transplantation (LDLT) in PPHTN patients. METHODS: We present our experiences of LDLT in six patients with moderate or severe PPHTN, along with our institutional guidelines. Three had liver cirrhosis and three were non-cirrhotic. Catheterization studies were undertaken before, during and after LDLT, and the mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance and total peripheral resistance (TPR) were monitored. RESULTS: The results showed significant differences in CO and TPR between cirrhotic and non-cirrhotic patients before, during and after LDLT. Cirrhotic patients showed systemic hyperdynamic state. Two cirrhotic patients showed poor responses to pre-transplant treatment, and continued to have increased PAH and poor clinical courses after LDLT. LDLT has an advantage of flexible timing of LT. Currently in our institution, PPHTN patients with mPAP <40 mmHg are registered for LDLT after treatment and catheterization. However, LDLT is performed when mPAP is ≤35 mmHg, leading to improved outcomes. CONCLUSION: PPHTN patients with well-controlled PAH, or secondary PAH resulting from porto-systemic shunts, may be appropriate candidates for LDLT after careful considerations.

Lasting 18F-DOPA PET uptake after clinical remission of the focal form of congenital hyperinsulinism.

BACKGROUND: Positron emission tomography (PET) using (18)F-DOPA is a useful tool for detecting the focal forms of congenital hyperinsulinism. (18)F-DOPA is taken up by aromatic L-amino acid decarboxylase in pancreatic ß-cells. However, the role of this enzyme in insulin secretion is unknown. SUBJECTS AND METHODS: A Japanese boy who presented with symptomatic hyperinsulinemic hypoglycemia at the age of 2 days and spontaneous resolution at 1 year and 10 months was subjected to mutational analysis and repeated (18)F-DOPA PET scans. RESULTS: Mutational analysis revealed a paternally inherited monoallelic mutation, c.4186G>T (p.D1396Y), in the ABCC8 gene, and an (18)F-DOPA PET scan revealed focal uptake in the body of the pancreas. The patient was successfully treated with frequent feeding. A follow-up PET scan revealed virtually identical uptake to that observed previously. However, in the arterial stimulation-venous sampling procedure, no significant insulin release was observed. He was placed on a normal diet, and no hypoglycemia recurrence was observed. CONCLUSION: This case demonstrates two important findings. Firstly, the uptake of (18)F-DOPA does not correlate with the insulin-secreting capacity of the lesion. Secondly, clinical remission could be a functional process not necessarily accompanied by the apoptotic death of abnormal ß-cells.