Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study.

BACKGROUND: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD). METHODS: An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6 months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire). RESULTS: In total, 530 ACHD patients (mean age 47 SD 15 years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 [IQR 0.0-2.0] year, thromboembolic event rate was 1.0% [95%CI 0.4-2.0] (n = 6) per year, with 1.1% [95%CI 0.5-2.2] (n = 7) annualized rate of major bleeding and 6.3% [95%CI 4.5-8.5] (n = 37) annualized rate of minor bleeding. Adherence was sufficient during 2 years follow-up in 80-93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (n = 33), QoL improved in 6 out of 8 domains (p ≪ 0.05). CONCLUSIONS: Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.

Hepatic fibrosis and cirrhosis in the Fontan circulation: a detailed morphological study.

AIMS: To describe the histological features of the liver in patients with a Fontan circulation. METHODS: Specimens from liver biopsies carried out as part of preoperative assessment prior to extracardiac cavopulmonary conversion of an older style Fontan were examined and scored semi-quantitatively for pertinent histological features. To support the use of the scoring, biopsy specimens were also ranked by eye for severity to allow correlation with assigned scores. RESULTS: Liver biopsy specimens from 18 patients with a Fontan circulation were assessed. All specimens showed sinusoidal fibrosis. In 17 cases there was at least fibrous spur formation, with 14 showing bridging fibrosis and 2 showing frank cirrhosis. In 17 cases at least some of the dense or sinusoidal fibrosis was orcein positive, although a larger proportion of the dense fibrous bands were orcein positive compared with the sinusoidal component. All specimens showed marked sinusoidal dilatation, and 14 showed bile ductular proliferation; 1 showed minimal iron deposition, and 1 showed mild lobular lymphocytic inflammation. There was no cholestasis or evidence of hepatocellular damage. Similar appearances were observed in 2 patients with severe tricuspid regurgitation. DISCUSSION: The histological features of the liver in patients with a Fontan circulation are similar to those described in cardiac sclerosis. Sinusoidal dilatation and sinusoidal fibrosis are marked in the Fontan series. The presence of a significant amount of orcein negative sinusoidal fibrosis suggests there may be a remediable component, although the dense fibrous bands are predominantly orcein positive, suggesting chronicity and permanence. No inflammation or hepatocellular damage is evident, suggesting that fibrosis may be mediated by a non-inflammatory mechanism.

Creation and enlargement of atrial defects in congenital heart disease.

Transcatheter creation and enlargement of interatrial defects (IAD) may improve hemodynamics; however, procedural outcomes have not been well defined. Hospital records were reviewed for children who underwent percutaneous procedures to create and enlarge an IAD and were grouped as follows: (1) right and (2) left heart obstructive lesions, (3) left atrial (LA) decompression during left heart assist, (4) failing Fontan circulation, and (5) miscellaneous. Forty-five children (mean age, 3.4 +/- 4.7 years; 30 (67%) male) were identified. In group 1 (n = 6), all achieved endpoints of right atrial (RA) decompression (n = 2), improved left ventricular filling (n = 3), or improved arterial saturations (n = 1). In group 2 (n = 18), mean LA pressure decreased (21 +/- 6 to 13 +/- 5 mmHg, p < 0.001) and arterial saturations increased (61 +/- 13% to 78 +/- 11%, p < 0.001). All except 2 patients achieved definitive repair, further palliation (n = 9), or heart transplantation (HTX) (n = 7). In group 3 (n = 5), the LA was decompressed (21 to 13 mmHg, p = 0.03) in all, and all except 1 patient survived to HTX (n = 2) or full recovery (n = 2). In group 4 (n = 11), of 7 patients with a low cardiac output syndrome after surgery, despite improved atrial shunting, 3 died and 1 required a HTX. In group 5 (n = 5), RA decompression (n = 1) or improved arterial saturation (n = 4) was achieved in all. Overall, 5-year HTX free survival was 75%. Mechanical ventilation before the procedure (p < 0.001), the need for a blade septostomy (p = 0.002), and higher LA pressures after the procedure (p = 0.04) independently predicted mortality or the requirement for HTX. Transcatheter optimization of an atrial communication can help optimize treatment strategies and has a low procedural risk.

Low pressure giant pulmonary artery aneurysms in the adult: natural history and management strategies.

OBJECTIVE: To describe aspects of the natural history and pathophysiology of giant low pressure pulmonary artery aneurysms and to propose potential surgical strategies. DESIGN: Cross sectional retrospective review. SETTING: Supraregional tertiary referral centre. PATIENTS: All adult patients referred for assessment of giant pulmonary artery aneurysm retrospectively identified from the Mayo Adult Congenital Heart Disease Clinic database. METHODS: Patient data were reviewed from hospital records, including echocardiograms, magnetic resonance images, radiographs, and histology slides. RESULTS: Four patients were identified with a median age of 52 years (range 37-64 years). Presenting symptoms were effort related dyspnoea, chest discomfort, and hoarseness in one patient. All patients had pulmonary regurgitation and clinical evidence of right ventricular enlargement in association with a pulsatile mass at the upper left sternal edge. Transthoracic echocardiography showed the giant pulmonary artery aneurysm involving the main pulmonary artery and proximal branches, and confirmed severe pulmonary regurgitation in all patients. None of the patients had intimal tearing, medial dissection, or pulmonary arterial rupture. The pulmonary valve was replaced to relieve symptoms and preserve right ventricular function. Pulmonary arterial histology showed medial degeneration of elastic fibres with accumulation of basophilic ground substance. CONCLUSIONS: Rupture or dissection of these low pressure aneurysms is rare. The timing of surgical intervention should be determined by changes in right ventricular size and function resulting from pulmonary regurgitation or pulmonary stenosis, and not the size of the aneurysm.

Cardiopulmonary exercise performance in adult survivors of the Mustard procedure.

Most patients with the Mustard procedure are now adults. To date, however, there have been few reports on resting and exercise hemodynamics in a large population of adults with this circulation. The aim of this study is to describe such parameters in one of the largest and oldest populations of adults with the Mustard procedure. The database of the University of Toronto Congenital Cardiac Centre for Adults was examined to identify 84 adults with the Mustard procedure who have undergone cardiopulmonary exercise tests. Magnetic resonance imaging and echocardiography studies were obtained in order to assess right ventricular size, function and baseline hemodynamics. Patients achieved lower maximum uptake of oxygen, maximal heart rate, forced vital capacity, forced expiratory volume in 1 second, and oxygen saturations at maximal exercise compared to a healthy population. Magnetic resonance imaging showed significantly different right ventricular ejection fractions between patients and controls. There were no effects of operative variables or preoperative hemodynamics on current exercise capacity. Patients after the Mustard procedure have subnormal exercise capacities. Factors such as chronotropic incompetence, peripheral deconditioning, and impaired lung function may be responsible for these results.

Factors associated with self-perceived state of health in adolescents with congenital cardiac disease attending paediatric cardiologic clinics.

The purpose of our study was to determine the ways in which adolescents with congenital cardiac disease believed that the condition had affected their life, and how these views were related to their perceived health. Interviews were conducted with a series of 37 adolescents, 17 girls and 20 boys, aged from 11 to 18, as they attended the clinics of 4 paediatric cardiologists in a teaching hospital in the United Kingdom. Transcripts of the interviews were analysed for recurring themes. A questionnaire was formed consisting of a set of questions for each theme, and additional items eliciting "perceived health", and administered to a second series of 74 adolescents, 40 boys and 34 girls, who were again aged from 11 to 18 years. Slightly less than half (46%) perceived their health as either "good" or "very good", and one-third (33%) rated it as "average". The majority (66%) felt themselves to be "the same" as, or only very slightly "different" from, their peers. The assessment of the seriousness of their condition by the adolescents, the degree to which they saw themselves as different from others, and their perceived health, were not related to the "complexity of the underlying medical condition" as rated by their physician. It was the psychosocial themes, such as exclusion from activities or the effect of the condition on relationships, that were most strongly related to the perception of their health by the adolescents. Improved education of parents, teachers and peers, and attendance at classes for cardiac rehabilitation, might help to ameliorate some of these problems.

The Fontan procedure in adults.

SETTING: Tertiary adult congenital cardiac referral centre. DESIGN: Retrospective cross sectional analysis. OBJECTIVES: To report our 20 year experience with adult Fontan operations, and to compare late outcome in patients with single ventricle with definitive aortopulmonary or cavopulmonary shunt palliation. PATIENTS AND MAIN OUTCOME MEASURES: Patients older than 18 years undergoing Fontan operation between 1 January 1982 and 31 December 1998 were identified. Mortality and late outcome were derived from hospital records. These patients were compared with a cohort of 50 adults with single ventricle who had not undergone a Fontan operation. RESULTS: 61 adults, median age 36 years (range 18-47 years), with a median follow up of 10 years (range 0-21 years) were identified. Actuarial survival was 80% at one year, 76% at five years, 72% at 10 years, and 67% at 15 years. Compared with before the Fontan operation, more patients were in New York Heart Association (NYHA) functional class I or II at the latest follow up (80% v 58%, p < 0.001). Systolic ventricular function deteriorated during follow up such that 34% had moderate to severe ventricular dysfunction at the latest follow up compared with 5% before Fontan (p < 0.001). Arrhythmia increased with time (10% before Fontan v 57% after 10 years, p < 0.001). Fontan patients had improved NYHA functional class, ventricular function, atrioventricular regurgitation, and fewer arrhythmias than the non-Fontan group at the latest follow up. CONCLUSION: The Fontan operation in adults has acceptable early and late mortality. Functional class, systolic ventricular function, atrioventricular regurgitation, and arrhythmia deteriorate late after surgery but to a lesser degree than in non-Fontan patients with a single ventricle.

Right ventricular form and function after percutaneous atrial septal defect device closure.

OBJECTIVES: We sought to assess the right heart's response to percutaneous device closure of moderate sized atrial septal defects (ASDs) in adults over a one-year follow-up period. BACKGROUND: Percutaneous ASD device closure is a safe and effective means of reducing or eliminating interatrial shunting. The response of the adult's right heart to device closure is incompletely understood. METHODS: Forty consecutive patients had 40 device implantations (32 with the CardioSeal implant and 8 with the Amplatzer device). The patients were assessed with echocardiography, chest radiography and electrocardiography before the procedure and at 1, 6 and 12 months. RESULTS: The mean ASD size was 13+/-4 mm, and the device size ranged from 33 to 40 mm for CardioSeal and 12 to 36 mm for Amplatzer. At one month, heart size (49% vs. 46%), four-chamber right ventricular (RV) size (45 vs. 41 mm), paradoxical septal motion (60% vs. 5%), QRS duration (125 vs. 119 ms), PR interval (181 vs. 155 ms) and echocardiographically determined pulmonary artery systolic pressure decreased significantly and was maintained at 12-month follow-up. At six months, right atrial length decreased from 50 to 47 mm. At one year, 29% of patients had persistent RV enlargement. CONCLUSIONS: Right heart morphology undergoes rapid improvement within one month of defect closure, with associated mechanoelectrical benefit. A small number of patients had persistent RV enlargement or pulmonary hypertension, or both, at one year. Our data support the application of transcatheter methods in achieving excellent hemodynamic and anatomic outcomes.

Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure.

Angiotensin-converting enzyme inhibitors had no significant effect on cardiopulmonary exercise function in 14 patients who had undergone a Mustard operation for transposition of the great arteries. In some patients aerobic capacity improved and maximum systolic blood pressure decreased.

Lung function and aerobic capacity in adult patients following modified Fontan procedure.

OBJECTIVE: To examine cardiopulmonary performance in 52 adult patients with a Fontan circulation. DESIGN: Retrospective cohort study. Values of maximum oxygen uptake (VO(2)max), maximum heart rate (HRmax), forced vital capacity (FVC), and forced expiratory volume in one second (FEV(1)) were compared with predictive values for different age groups. Patients were further subdivided into those with a pulmonary artery connection (RA-PA) or right atrium to right ventricle conduit (RA-RV). RESULTS: At late follow up (median 10 years, range 1 to 26 years), patients with Fontan circulation had greatly diminished VO(2)max, HRmax, FVC, and FEV(1) compared with predicted values. Early age at surgery had a positive impact on aerobic capacity. The FEV(1):FVC ratio indicated restrictive lung function. No differences were found with respect to any variable between patients with RA-PA connections and those with RA-RV connections. CONCLUSIONS: Patients with a Fontan circulation have greatly diminished values of aerobic capacity and a restrictive pattern of lung function. Patients with an early surgical procedure obtained higher values of VO(2)max. The theoretical benefits of including the right ventricle in a Fontan circulation were not apparent.

Aerobic capacity in adults with various congenital heart diseases.

As an increasing number of patients with congenital heart disease reach adulthood, more information is needed regarding outcomes. The first signs of impaired heart function may appear during exercise testing. The aim of the present study was to establish mean values for maximal oxygen uptake in adults with various congenital heart diseases. Patients from 6 major diagnostic groups were identified, including patients with atrial septal defect (ASD, n = 93), transposition of the great arteries corrected with the Mustard procedure (n = 84), congenitally corrected transposition of the great arteries (CCTGA, n = 41), Tetralogy of Fallot (n = 168), Ebstein's anomaly (n = 37), and Modified Fontan procedure (n = 52). Diminished maximal oxygen uptake was found in all diagnostic groups across age compared with healthy subjects. A significant decrease in maximal oxygen uptake with aging was found in those with ASD (p <0.0001), CCTGA (p = 0.01), and Tetralogy of Fallot (p <0.0001). There was no significant decline, however, in Ebstein's anomaly (p = 0.270), Fontan procedure (p = 0.182), and in the Mustard patients (p = 0.188). All patients achieved significantly lower heart rates than predicted (mean for all groups, p <0.0001). Forced vital capacity values (3.51 L, mean SD +/- 1.02) were lower than predicted values (4.10 L, mean SD +/- 0.90, p <0.0001) for all patients groups except those with ASD. Mean values, however, were within the accepted 20% range of variance. This study showed diminished aerobic capacity in all diagnostic groups when compared with a healthy population. The maximal oxygen uptake values across age groups can be used as reference values in patients with similar diagnoses and as the basis for further research.

Exercise capacity in adult patients with congenitally corrected transposition of the great arteries.

OBJECTIVE: To examine cardiopulmonary values, static lung function, and ejection fraction in adult patients with congenitally corrected transposition of the great arteries (CCTGA). PATIENTS AND METHODS: 41 patients who had undergone static lung function testing and cardiopulmonary exercise tests with measurements of ejection fraction were identified at the Toronto Congenital Cardiac Centre for Adults. RESULTS: Aerobic capacity in patients with CCTGA was severely diminished, varying from 30-50% of the results achieved by healthy subjects. Normal values of right ventricular and left ventricular ejection fraction were found. However, the systemic right ventricular ejection fraction increased by 2% from rest to exercise, as opposed to the expected > 5% increase in a healthy population. The pulmonary left ventricular ejection fraction decreased by 2% at peak exercise. CONCLUSION: Diminished values of heart rate, forced expiratory volume in one second (FEV(1)), forced vital capacity, and systolic blood pressure compared to the predicted values may contribute to the reduced maximal oxygen uptake (VO(2)max) found in patients with CCTGA. In addition, a limited increase in systolic right ventricular ejection fraction and a decrease in pulmonary left ventricle contractility suggest a dysfunction of both ventricles.

Illness understanding in children and adolescents with heart disease.

AIMS: To evaluate illness knowledge and understanding in children and adolescents with congenital and acquired heart disease, and whether the degree of understanding is related to age, sex, or complexity of the heart disease. DESIGN: Prospective cohort study. SETTING: Tertiary paediatric cardiac centre. METHODS: Patients' understanding of their congenital heart disease was assessed in a representative sample of volunteers aged between 7-18 years using semistructured interviews based upon Leventhal's illness representation model. RESULTS: 63 of 69 interviews were suitable for analysis. There were similar numbers of boys and girls and a wide distribution of heart defects. Only 30% of patients had a good understanding of their illness; 77% did not know the medical name of their condition, and 33% had a wrong or poor understanding of their illness. Understanding was unrelated to age, sex, or the nature of the heart disease. Understanding of illness duration was significantly related to age, but not to sex or to the nature of the disease. CONCLUSIONS: Illness understanding is poor in children and adolescents with heart disease, and many have an entirely wrong concept of their disease. Intensified efforts to ensure better patient and parental understanding are needed.

Dystrophic calcification of the fetal myocardium.

Intramural cardiac masses were detected antenatally in three fetuses by echocardiography. The masses were initially thought to be rhabdomyomas. All three pregnancies were terminated and histology showed dystrophic calcification in all, with no evidence of tumour. Therefore, dystrophic calcification of the fetal myocardium may have a similar appearance to single or multiple rhabdomyomas. This should be considered when counselling parents after detection of masses in the fetal heart, particularly when considering the risk of associated tuberous sclerosis.

Haemolysis following implantation of duct occlusion coils.

OBJECTIVES: To describe the incidence and management of haemolysis after transcatheter coil occlusion of the arterial duct. DESIGN: Prospective clinical and echocardiographic follow up of patients who have undergone implantation of the Cook detachable duct occlusion coil. SETTING: Tertiary paediatric cardiac centre. PATIENTS: Five cases of haemolysis (two girls aged 6 and 11 months; three boys aged 6, 17, and 14 months) from a series of 137 duct coil implantations. MAIN OUTCOME MEASURES: The occurrence of clinically significant haemolysis after implantation of duct occlusion coils and resolution of haematuria after completion of duct occlusion. RESULTS: Haemolysis was detected in five of 137 procedures following implantation of Cook detachable duct coils. Four patients became symptomatic 12 hours after the procedure but in one haemolysis was detected three months later. Resolution of ongoing haemolysis was achieved within 48 hours of detection with further coil implantations, but haematuria persisted for up to 10 days. In one patient the extensive destruction of erythrocytes resulted in acute renal failure requiring peritoneal dialysis. CONCLUSIONS: Haemolysis is an important complication after duct coil implantation. It occurred in 3.6% of 137 procedures in this series and is most likely to occur in young patients with relatively large ducts. Further coil implantation to occlude the duct completely is not only successful but technically relatively straightforward and should be undertaken early if major complications such as severe anaemia and renal failure are to be avoided.