Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure　- A Nationwide Survey in Japan.

BACKGROUND: Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established.Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time. CONCLUSIONS: LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

Fontan completions over 10 years after Glenn procedures.

OBJECTIVE: Despite the broadened indications for Fontan procedure, there are patients who could not proceed to Fontan procedure because of the strict Fontan criteria during the early period. Some patients suffer from post-Glenn complications such as hypoxia, arrhythmia, or fatigue with exertion long after the Glenn procedure. We explored the possibility of Fontan completion for those patients. METHODS: Between 2004 and 2010, five consecutive patients aged between 13 and 31 years (median 21) underwent Fontan completion. These patients had been followed up for more than 10 years (10 to 13, median 11) after Glenn procedure as non-Fontan candidates. We summarise these patients retrospectively in terms of their pre-operative physiological condition, surgical strategy, and problems that these patients hold. RESULTS: Pre-operative catheterisation showed pulmonary vascular resistance ranging from 0.9 to 3.7 (median 2.2), pulmonary to systemic flow ratio of 0.3 to 1.6 (median 0.9), and two patients had significant aortopulmonary collaterals. Extracardiac total cavopulmonary connections were performed in three patients, lateral tunnel total cavopulmonary connection in one patient, and intracardiac total cavopulmonary connection in one patient, without a surgical fenestration. Concomitant surgeries were required including valve surgeries--atrioventricular valve plasty in three patients and tricuspid valve replacement in one patient; systemic outflow tract obstruction release--Damus-Kaye-Stansel procedure in two patients and subaortic stenosis resection in one patient; and anti-arrhythmic therapies--maze procedure in two patients, cryoablation in two patients, and pacemaker implantation in two patients. All patients are now in New York Heart Association category I. CONCLUSION: Patients often suffer from post-Glenn complications. Of those, if they are re-examined carefully, some may have a chance to undergo Fontan completion and benefit from it. Multiple lesions such as atrioventricular valve regurgitation, systemic outflow obstruction, or arrhythmia should be surgically repaired concomitantly.

A case of cough syncope diagnosed by the Valsalva maneuver and cough induction test under invasive arterial pressure measurement.

Following the loss of consciousness during the Valsalva maneuver and cough induction test, real-time arterial pressure measurement could clarify the significant blood pressure decrease in a patient with cough syncope.

Psychosocial factors influencing mental health in adults with congenital heart disease.

BACKGROUND: Although adult congenital heart disease (ACHD) patients encounter unique challenges related to social adaptation and mental health, only minimal research has been conducted on this functioning in Japanese ACHD patients. The aims of this study were to describe aspects of the psychosocial functioning of ACHD patients and to determine the psychosocial factors influencing their mental health. METHODS AND RESULTS: Seventy-two ACHD patients (aged 18-39 years) and 86 control participants (aged 18-39 years) completed the 36-item Short Form Health Survey, a measure of mental health, and 4 self-report questionnaires measuring aspects of psychosocial functioning: Independent-Consciousness, Problem-solving, Locus of Control, and Self-esteem. Compared to the control group, ACHD patients had significantly lower scores for Independence, Problem-solving, and Self-esteem; whereas they had higher scores for Dependence on Parents. To examine the psychosocial factors influencing mental health, a structural equation model was used. The psychosocial factor Problem-solving was found to have the most direct influence on mental health. This factor was associated with Independence and Self-esteem. CONCLUSIONS: ACHD patients in Japan have psychosocial difficulties, and the psychosocial factors influencing patients' mental health are social problem-solving, independence, and self-esteem. The patients have poorer abilities than the control group in all of these areas and hence, they run the risk of developing poor mental health.

Pacemaker implantation for persistent sinus node dysfunction in a patient with COVID-19.

A 46-year-old woman was admitted with coronavirus disease-2019 infection. Symptomatic sinus bradycardia occurred, followed by congestive heart failure. Therapeutics such as isoproterenol, theophylline, and cilostazol could not safely improve her symptoms. She underwent pacemaker implantation 53 days after admission. Atrial pacing remained was at 60% after 6 months.

A rare case with Uhl's anomaly whose hemodynamics largely dependent on right atrial hyper-contraction and a patent foramen ovale - A "double-edged sword" of ventricularized right atrium.

We report the case of a 31-year-old man with Uhl's anomaly. Echocardiography revealed severely enlarged nonfunctioning right ventricle and unusual findings of the premature opening of the pulmonary valve along with substantial forward flow during late-diastole, indicating that pulmonary circulation was largely dependent on compensatory right atrial contraction. Moreover, right-to-left shunt through the patent foramen ovale (PFO) achieved systemic circulation at the expense of severe hypoxia. During accelerated idioventricular rhythm (AIVR) accompanied by ventriculo-atrial (VA) conduction, hypoxemia deteriorated further because of an increased right-to-left shunt through the PFO. We report the case of an adult with Uhl's anomaly whose hemodynamics was largely dependent on the ventricularized right atrium and PFO. Although the unique hemodynamics contributed to his survival into adulthood, detrimental aspects manifested themselves during AIVR with VA conduction like a "double-edged sword." .

Trans-aortic pulmonary vein isolation using magnetic navigation system for paroxysmal atrial fibrillation in a patient with dextrocardia, situs inversus, and inferior vena cava continuity with azygos vein.

A 51-year-old male with dextrocardia and situs inversus underwent catheter ablation for paroxysmal atrial fibrillation. Because the procedure through the trans-septal approach was impossible due to the inferior vena cava continuity with azygos vein, we performed pulmonary vein isolation using magnetic navigation system through the retrograde trans-aortic approach. Superior and inferior left-sided and superior right-sided pulmonary veins could be isolated which was confirmed by the ablation catheter. The patient was free from atrial fibrillation episode at the 12 months follow-up except only one palpitation episode lasting nearly 12 hours at 9 months after the ablation.

Morphological differences in cardiovascular anomalies induced by bis-diamine between Sprague-Dawley and Wistar rats.

It is known that animals show different responses to the same teratogen between different strains. We examined cardiac malformations in Sprague-Dawley (SD) and Wistar rats induced by bis-diamine, which produced conotruncal anomalies and aortic arch malformations in embryos when administered to the dams, to elucidate the morphological differences and pathogenesis in the two strains. Two hundred milligrams of bis-diamine dissolved in 1% gum-tragacanth was administered to pregnant rats on embryonic day (ED) 9.5, 10.5 and 11.5 in each strain. The embryos were removed on ED 20.5. External appearances, cardiovascular morphology and associated anomalies were examined under a dissecting microscope. An immunohistological study with an anti-N-CAM antibody, an excellent marker for neural crest cells, was performed on ED 12.5 embryos. Isolated aortic arch anomalies were common features of malformations induced by bis-diamine in SD rats and intracardiac defects were found in a small number of the embryos. Wistar rats showed more serious cardiovascular anomalies, such as persistent truncus arteriosus and tetralogy of Fallot, especially when dams were treated on ED 10.5 and isolated arch anomalies were significantly less prevalent than in SD rats. Immunohistology demonstrated that there were fewer N-CAM positive cells in the conotruncal region in Wistar rats than in SD rats. Bis-diamine induced more critical cardiovascular malformations in Wistar rats because neural crest cells, which play an important role in conotruncal septation, were more extensively damaged. Different susceptibility to bis-diamine and/or different time of neural crest cell emigration from the hindbrain might explain those morphological differences.

Phonocardiogram in adult patients with tetralogy of Fallot.

BACKGROUND: Right ventricular outflow tract (RVOT) stenosis and pulmonary regurgitation (PR) are important residua and sequelae in adult tetralogy of Fallot (TOF) patients. Auscultation of the heart sound is a useful tool to detect and evaluate these lesions, but there was no previous report regarding heart sound in adult TOF. METHODS: We enrolled consecutive TOF outpatients from January 2013 to October 2013 in our adult congenital heart disease clinic. Phonocardiogram with phono-recording was performed with MES-1000 (Fukuda-Denshi Co., Tokyo, Japan), and compared heart sound with echocardiographic parameters. RESULTS: A total of 30 TOF patients were enrolled [age, 34.7±12.8 years; 14 males (46.7%)]. In all 30 patients, phonocardiography was clearly recorded. Eighteen patients (60.0%) had the single second heart sound, which was more frequently observed before than after pulmonary valve reoperation (75.0% vs 11.1%). The single second heart sound was also associated with PR. In 18/30 (60%), diastolic murmur was associated with moderate PR (p=0.008). In 14/30 (46.7%), systolic murmur was associated with moderate RVOT stenosis (p=0.012). CONCLUSION: Phonocardiogram was a useful tool to detect RVOT lesions. We should listen to heart sound carefully especially focusing on the second heart sound, systolic, and diastolic murmur.

The prevalence and risk factors for cholelithiasis and asymptomatic gallstones in adults with congenital heart disease.

PURPOSE: Cyanosis is considered to be a risk factor for cholelithiasis which is an important complication of cyanotic congenital heart disease (CCHD) in adults. In this study, the prevalence of cholelithiasis and asymptomatic calcium bilirubinate gallstones was evaluated in adults with congenital heart disease (CHD). Furthermore, risk factors for this potentially high risk complication were assessed. MATERIALS AND METHODS: Subjects were derived from 114 consecutive congenital patients who visited our center from May 2008 to January 2009. For analyses of risk factors, we divided them into 4 groups: group A, 15 CCHD patients without reparative surgery (7 men, 31.8 ± 7.0 years old); group B, 41 CCHD patients rendered acyanotic by reparative surgery (21 men, 32.5 ± 11.8 years old); group C, 23 unoperated acyanotic CHD patients (11 men, 42.4 ± 16.4 years old); and group D, 35 patients who were acyanotic before and after operation (18 men, 36.3 ± 14.8 years old). Gallstones were identified by abdominal ultrasound and risk factors were analyzed by a multivariate logistic regression model. RESULTS: Cholecystectomy was performed in 5/114 (4.3%), asymptomatic gallstones were seen in 16/114 (14%), and symptomatic gallstones except for patients after cholecystectomy were seen in 7/114 (6.1%). In group A, 4 (27%) with gallstones underwent cholecystectomy (p<0.01). Non-cholesterol gallstones were observed in 5 patients (33%) in group A, 12 patients (29%) in group B, nobody in group C, and 3 patients (8.6%) in group D. By a multivariate logistic regression model, CCHD by nature regardless of repair, prolonged cyanosis periods, higher frequency of cardiopulmonary bypass (CPB), and lower platelet counts were significant factors predicting gallstones (odds ratio 4.48, 1.08, 3.96, and 0.87, 95% CI, 1.14-17.5, 1.00-1.18, 1.65-9.54, and 0.75-0.99, respectively). CONCLUSIONS: The prevalence of cholelithiasis and asymptomatic gallstones is significantly high in CCHD patients regardless of cardiac repairs. CCHD by nature, prolonged cyanosis durations, high frequency of CPB and low platelet counts have influences on gallstone formation in adults with CHD.

Prevalence of adult patients with congenital heart disease in Japan.

BACKGROUND: Today most patients with congenital heart disease (CHD) can be expected to survive into adulthood. Reports regarding the number of adults with CHD in Japan are scarce. Our study aims to define the number of these adults. MATERIAL AND METHODS: The estimated number of infants born in Japan with major CHDs since 1947 was calculated together with mortality rates. We estimated the number of CHD survivors from data on survival rates of unoperated and postoperative patients. The number of deaths from 1968 to 1997 was analyzed using individual death certificates held by the Japanese Government. RESULTS: In 1967, 163,058 patients with CHD including 53,846 adults were assumed to be alive. From 1968 to 1997, 548,360 patients with CHD were born and 82,919 died. A total of 622,800 patients, including 304,474 children (49%) and 318,326 adults (51%) were estimated to be alive in 1997. From 1997 to 2007, there has been an estimated increase of 9000 adults every year, and in 2007, 409,101 adults are estimated to be alive. CONCLUSIONS: The prevalence in adults with CHD in Japan has explosively increased from 1967 to 2007. There were 409,101 adults with CHD in 2007 with an annual increase of 9000. These data are crucial for planning the establishment in Japan of special facilities and resources necessary for the care of these patients.

Nationwide survey of care facilities for adults with congenital heart disease in Japan.

BACKGROUND: The number of adults with congenital heart disease (CHD) is increasing rapidly, but care programs have not been fully established in Japan. METHODS AND RESULTS: Questionnaires regarding current status and resources of outpatient and in-hospital services, and management of pregnancy in patients with adult CHD (ACHD) were sent to 1,033 training hospitals for board-certified cardiologists. Useful replies were obtained from 458 hospitals (44%). In 417 hospitals (91%), at least 1 patient was followed in the outpatient clinic; however, only 14 hospitals (3%) had specialized outpatient clinics; 354 hospitals (77%) had in-hospital patients, but only 6 hospitals (2%) admitted >50 patients per year. Surgery for ACHD was performed in 232 hospitals (51%), but in 135 of these (58%), the number of operations was <5 per year. Pregnant women with CHD were managed in 157 hospitals (34%), although only 3 hospitals (2%) managed >10 cases per year. CONCLUSIONS: In most hospitals in Japan, a limited number of ACHD patients have been followed up and specialized multi-disciplinary facilities for ACHD need to be established.

Hemiazygos venous additional pulmonary flow for successful total cavo-pulmonary connection.

Patients who underwent only Glenn procedure after being deemed unsuitable candidates for Fontan completion are not small in number, and may develop arterio-venous (AV) pulmonary malformations during the follow-up period. We present the case of a 17-year-old woman with severe systemic desaturation 13 years after Glenn procedure and repair of total anomalous pulmonary venous return. Among other anomalies, the patient disclosed hemiazygos continuation to a persistent left superior vena cava. This case supports the concept that returning flow from the abdominal vein plays an important role in the well-balanced growth of the pulmonary artery and in the inhibition of the pulmonary AV malformation.