Early vascular aging in adult patients with congenital heart disease.

Many studies have reported that adults with congenital heart disease suffer from hypertension and cardiovascular disease even at younger ages. Therefore, we analyzed early vascular aging, which is defined as pulse wave velocity values higher than the 95th percentile for age and sex, and clarified the relationship between early vascular aging and many parameters related to cardiovascular disorders in adults with congenital heart disease. We enrolled 72 adult patients with congenital heart disease and measured their brachial-ankle pulse wave velocity. Comparing the data between age- and sex-matched controls, patients with a pulse wave velocity higher than the 95th percentile for age and sex were defined as exhibiting early vascular aging. The parameters of patients with and without early vascular aging were compared. Early vascular aging was observed in 15.6% of the patients. Age, systolic blood pressure, diastolic blood pressure, pulse pressure, blood sugar, hemoglobin A1c, uric acid, low-density lipoprotein cholesterol, and triglyceride levels were positive determinants of early vascular aging. Logistic regression analysis proved that systolic blood pressure was a significant determinant of early vascular aging (odds ratio, 1.128, 95% confidence interval, 1.049-1.214; p = 0.001). The prevalence of early vascular aging is high in adult patients with congenital heart disease. Because early vascular aging can damage a patient's vulnerable heart, careful follow-up of blood pressure and pulse wave velocity is essential.

Employment status and contributing factors among adults with congenital heart disease in Japan.

BACKGROUND: Working is an important concern in transitional care for adults with congenital heart disease (ACHD) because work connects people with society. Employment status is correlated with gender, but studies on patient employment by gender have rarely been conducted. This study therefore aimed to examine the employment status of ACHD by gender and to explore the factors influencing this status. METHODS: In this study, 193 Japanese ACHD (mean age: men-33.62 years, women-32.69 years; 89 men, no students included) completed a questionnaire including questions about employment status, an evaluation of hindrances to employment, the Linear Analog Scale to assess quality of life (QOL), and the Satisfaction with Life Scale (SWLS). RESULTS: In the study sample, 13 of 89 (14.6%) men and 13 of 104 (12.5%) women did not have a job. These rates were higher than the national standard rates in Japan (men: 5.0%, women: 2.9%). Of these patients, only one man and one woman listed their illness as a reason for their unemployment. The factors thought to explain unemployment were age for men and disease severity for women (P < 0.05 for both). Unemployed patients had significantly lower QOL and SWLS scores. CONCLUSIONS: Most ACHD can join the workforce but a higher percentage of ACHD do not work and find it challenging to have a career compared with the general population. Moreover, because unemployed patients have low QOL and SWLS scores, obtaining work is crucial to enable these people to have mentally and emotionally stable and fulfilling lives.

Relationship between non-osmotic arginine vasopressin secretion and hemoglobin A1c levels in adult patients with congenital heart disease.

Arginine vasopressin (AVP), which induces vasoconstriction and conserves solute-free water when released during high plasma osmolality, is secreted through 2 mechanisms: osmoregulation and baroregulation. This study aims to clarify the mechanisms and influencing factors for non-osmotic AVP secretion in adult patients with congenital heart disease (CHD). AVP levels were measured in 74 adults with CHD. Non-osmotic AVP secretion was defined as excessive AVP secretion relative to the AVP level inferred from plasma osmolality. Accordingly, 10 patients (13.5%) demonstrated non-osmotic AVP secretion, with AVP levels higher than those in patients without non-osmotic AVP secretion (6.4 ± 3.1 vs. 1.6 ± 0.9 pg/ml; p < 0.0001). Non-osmotic AVP secretion was significantly correlated with diuretic use [odds ratio (OR) 7.227; confidence interval (CI) 1.743-29.962; p = 0.0006], HbA1c level (OR 11.812; CI 1.732-80.548; p = 0.012), and B-type natriuretic peptide (BNP) level (OR 1.007; CI 1.001-1.012; p = 0.022). Multiple logistic regression analysis revealed that there was a significant association between non-osmotic AVP secretion and HbA1c level (OR 9.958; 1.127-87.979; p = 0.0039), and a nearly significant relationship between non-osmotic AVP secretion and BNP (OR 1.006; CI 1.000-1.012; p = 0.056). In conclusion, this study showed that 13.5% of adult patients with CHD demonstrated non-osmotic AVP secretion, which could be correlated with heart failure and insulin resistance. The AVP system might be one of the mechanisms linking heart failure and the onset of type 2 diabetes mellitus in adults with CHD.

Surgical treatment for adult congenital heart disease: consideration for indications and procedures.

The number of the adult patients with congenital heart diseases (ACHD) continues to grow owing to improvement of surgical results and medical management. Corrective surgery for complex CHD does not always mean complete cure. It is not rare that the patients will visit the cardiology institutes because of secondary lesions due to residua or sequela in adults. Some patients with CHD remain unrepairable with different degree of heart failure and pulmonary arterial hypertension. Association of arrhythmias is common in ACHD patients and sometimes critical. We experienced 265 surgical procedures for ACHD patients at our center between 1999 and 2015. Of these procedures, palliative surgery was performed in 3%, palliation to corrective surgery in 6%, primary repair in 57%, and redo surgery in 34%. Hospital mortality within 30 days in this period was 1.1%. Surgery for ACHD patients is safe, beneficial and low-risk treatment; however, tailored procedures for the individual patient are essential to obtain the optimal quality. A comprehensive multidisciplinary approach is required to fulfill this goal.

The cardiac blood supply-workload balance in children.

It is well known that the reflected pressure wave in small children returns earlier than that in adolescent. The reason of early return of the reflected pressure wave in infancy is their height. The short distance between heart and reflection point makes the reflected pressure wave returning to the heart earlier. In adult, the early return (during systole) of the reflected pressure wave means disadvantage to cardiac blood supply-workload balance. The purpose of this study was to clarify whether the early return of the reflected pressure wave in small children impairs the cardiac blood supply-workload balance. This study enrolled 37 small left-to-right shunt patients with normal aortic circulation below 15 years of age. The aortic pressure waveform was recorded using a pressure sensor mounted catheter, and augmentation index and subendocardial viability ratio were calculated. The age of patients was 6.1 ± 3.2 years. The augmentation index was 8.7 ± 14.3 % and the index had a negative correlation with patients' age (r = -0.6243, p < 0.0001). The subendocardial viability ratio, which means the cardiac blood supply-workload balance, was 0.92 ± 0.14 and the index had a positive relationship with patients' age (r = 0.6435, p < 0.0001). The cardiac blood supply-workload balance gradually improves from infancy to young adulthood. One of the causes of the unfavorable cardiac blood supply-workload balance in infancy would be the accelerated aortic pressure wave reflection due to their short height.

Aortic surgery is one of the risk factors for enhancement of pressure wave reflection in adult patients with congenital heart disease.

BACKGROUND: Excessive aortic pressure wave reflection is one of the risk factors of cardiovascular diseases. In some clinical course of congenital heart diseases, the elevated pressure wave reflection has been reported. The purpose of this study is to elucidate the risk factors of the enhanced pressure wave reflection in adult patients with congenital heart disease. METHODS: We enrolled 99 adult (≥20 years) patients with congenital heart disease. We measured their radial pressure augmentation index and examined the relationship between it and various clinical variables. RESULTS: The radial pressure augmentation index was 77.1 ± 19.1% and it had a significant correlation with the history of aorto-pulmonary shunt (t=4.194; p<0.0001), age (t=4.091; p<0.0001), height (t=-3.580; p=0.001) and the history of direct aortic surgery (t=2.253; p=0.027). Forty-four patients (44.4%) demonstrated high radial augmentation index (>1SD of age- and gender matched control) and the determinants of the elevated radial augmentation index were the history of aorto-pulmonary shunt (odds ratio, 21.32; 95% confidence interval, 5.47-83.14; p<0.0001) and the direct aortic surgery (4.18; 1.38-12.72; p=0.012). CONCLUSIONS: The history of aortic surgeries enhances aortic pressure wave reflection in adult patients with congenital heart disease. The enhanced aortic pressure wave reflection is one of the risk factors for cardiovascular diseases. Therefore, the adult patients with congenital heart disease after aortic surgeries should be carefully observed and tightly controlled concerning the risk factors for cardiovascular diseases.

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.

Aortic pressure wave reflection in patients after successful aortic arch repair in early infancy.

Despite the apparently successful surgical repair of aortic coarctation, subsequent cardiovascular complications have sometimes been encountered. Aortic pressure wave reflection is one of the risk factors for developing cardiovascular diseases, and an enhancement of the pressure wave reflection has been reported in patients after aortic arch repair. To clarify this issue, the increase in pressure wave reflection was evaluated in patients <15 years old who underwent aortic arch repair. This study enrolled 35 patients after aortic arch repair in early infancy. All patients underwent cardiac catheterization, and in 20 patients, there was no pressure difference within the repaired aortic arch. The aortic pressure waveforms in patients after successful aortic arch repair were recorded using a pressure sensor-mounted catheter, and the augmentation index in the ascending aorta was calculated. The augmentation index in patients after an aortic arch repair was increased compared with control subjects, although there was no pressure difference between the ascending and descending aorta (P<0.0001). The increase in the augmentation index was correlated with the patient's age (r=0.8932, P<0.0001) and with the left ventricular posterior wall thickness (r=0.4075, P=0.0373). In patients who undergo aortic arch repair, the pressure wave reflection is accelerated, even when the aortic arch repair is 'successful'. This increase is one of the possible causes of left ventricular hypertrophy.

Syndrome of inappropriate secretion of antidiuretic hormone associated with angiotensin-converting enzyme inhibitor administration.

Angiotensin-converting enzyme inhibitors (ACEI's) are an important medication in the treatment of congestive heart failure. However, ACEIs may cause harmful side effects, such as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which is a rare but important side effect. We describe here a case of SIADH associated with ACEI administration in a 6-year-old boy with restrictive cardiomyopathy. After recovery from acute exacerbation of congestive heart failure by tolvaptan administration, an ACEI (cilazapril) was started to decrease the production of angiotensin II, which upregulates serum antidiuretic hormone secretion. The patient's heart failure symptoms worsened, including accumulation of right pleural effusion and ascites, after the initiation of ACEI administration. Cessation of ACEI administration dramatically improved his symptoms. Because it is difficult to distinguish SIADH associated with ACEI from worsening congestive heart failure, the possibility of fluid retention due to ACEI administration should always be considered when this agent is administered to patients with heart failure.

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.

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.

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.

Arrhythmia and reduced heart rate variability during pregnancy in women with congenital heart disease and previous reparative surgery.

OBJECTIVES: Tachyarrhythmia during pregnancy may have an adverse effect on the mother and the fetus. Heart rate variability (HRV) is a significant marker of autonomic nervous function and may predict tachyarrhythmia. HRV and incidence of arrhythmia in women with repaired congenital heart disease (CHD) during pregnancy were examined. METHODS: Twenty-eight patients with repaired CHD (35 pregnancies, age: 26+/-3.5 years at their first pregnancy, 22+/-6.2 years post-repair) and 19 healthy pregnant volunteers (controls, 19 pregnancies, age: 28+/-5.5 years) were enrolled. Holter monitoring and laboratory tests were examined at 28+/-4 weeks of gestation and 22+/-13 weeks postpartum in patients and 28+/-3 weeks of gestation in controls. Time and frequency variables of HRV were analyzed. RESULTS: Compared with controls and postpartum, there was a significantly higher incidence of tachyarrhythmia during pregnancy in women with CHD (4 episodes of supraventricular tachyarrhythmia (SVT) and 5 of non-sustained ventricular tachycardia, P=0.02). HR response in tetralogy of Fallot was impaired (781+/-50 ms, P=0.02). Most of HRV variables were significantly suppressed (average RR 740+/-64 ms, SDRR 99+/-22 ms, low and high frequency domains (341+/-165 ms2 and 256+/-181 ms2) (P<0.05). Reduced SDRR and high frequency domains were observed in patients with tachyarrhythmia. Furthermore, there were increased left ventricular end-diastolic dimensions 48+/-5 mm (P=0.001) and atrial natriuretic peptide levels 33+/-13 pg/ml (P=0.01) in the CHD patients compared with postpartum levels. CONCLUSIONS: Impaired autonomic nervous activity, volume overload of the heart and operative scar all play a contributory role in higher incidence of tachyarrhythmia during pregnancy in patients with repaired CHD compared to healthy pregnant controls. Close monitoring of patients with CHD for tachyarrhythmia during pregnancy is, thus, warranted.

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.

Successful selective intra-arterial thrombolytic therapy for embolic stroke in a patient with asplenia syndrome and unrepaired cyanotic congenital heart disease.

We report successful selective local intra-arterial thrombolytic therapy for thromboembolic occlusion of right middle cerebral artery in a patient with asplenia syndrome and unrepaired cyanotic congenital heart disease.