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Background: The Netherlands are lacking reliable empirical data in relation to the development of birth and population prevalence of Down syndrome. For the UK and Ireland there are more historical empirical data available. A theory-based model is developed for predicting Down syndrome prevalence in the Netherlands from the 1950s onwards. It is likewise applied to Ireland and the UK for the purpose of validation. Furthermore, a prediction to 2050 is constructed. Materials and Methods: Maternal age births data in the general population, maternal age related risk of Down syndrome, data on selective terminations of Down syndrome pregnancies and mortality rates (from 35 studies from the 1930s until today) were obtained to create this model. Results: For the Netherlands, nowadays birth prevalence is estimated at 14 per 10 000 with around 275 total annual births. The impact of selective abortion is lower than in the UK. Present Dutch Down syndrome population prevalence is estimated, according to this theory-based model, at 7.7 per 10 000 and the grand total at 12 600 individuals. The prevalence of "older" persons with Down syndrome (over 40 years of age) in the Netherlands will reach a peak in 2010, a doubling compared to 1990, implying an increased demand on medical care and counselling. Validity of this theory-based model was examined by comparison with relevant available empirical data from the three countries. The model shows a good fit with historical empirical research, notably four UK and two Irish population prevalence studies and eight birth prevalence studies. Conclusions: A theory-based model for Down syndrome prevalence provides supplementary data in situations with a lack of empirical material and can be used for understanding and predicting long-term developments.

Background Mobile health (mHealth) can improve quality of care and empower cardiac patients. However, large-scale adoption is still lacking, as several challenges continue to be encountered in daily practice. We aimed to explore the mHealth experiences and challenges in cardiac patients, healthcare professionals, healthcare managers and information and communications technology (ICT) developers. Methods A qualitative research was employed where semistructured interviews were conducted in patients, healthcare professionals, managers and ICT developers. We aimed to enrol participants of every stakeholder group, with diversity in sex, age group and occupation. Thematic analysis was used to identify themes reflecting experiences and challenges in mHealth in cardiac patients. Results In total, 24 interviews were conducted in six patients, eight healthcare professionals, five managers and five ICT developers. Monitoring/care at home was reported as important advantage of mHealth (n=20, 83%). Patients valued increase of self-care (n=6, 100%) and remote reassurance (n=6, 100%), but reported medicalisation as important concern (n=4, 67%). Healthcare professionals warned for increased data burden (n=4, 50%). Managers agreed on the importance of device reliability (n=5, 100%) and ICT developers emphasised that the goal of mHealth is to replace care, rather than being supplementary (n=4, 80%). The majority of all participants (n=22, 92%) considered future use of mHealth as promising. Conclusions All stakeholders foresee benefit of mHealth in cardiac patients, especially for remote care and reassurance. Frequently mentioned challenges included the need to replace care with mHealth, rather than adding more workload, and employing reliable devices and applications. If collaboration can be improved and group-specific challenges overcome, success of mHealth in cardiac patients can improve significantly. [ABSTRACT FROM AUTHOR]

Background: Survival data that are applicable to the current population of adults with congenital heart disease (CHD) are not available.Objectives: Using an alternative survival analysis with age as the primary time scale, we assessed the contemporary survival of adult patients with CHD.Methods: Survival was assessed using prospective data of the national registry of adult patients with CHD of the Netherlands. Survival was stratified by severity and lesion, and compared with a standardised general population.Results: Mean age at inclusion was 37 years, and 49% of the study population was male. During a cumulative prospective follow-up of 90, 270 patient-years in 14, 327 patients, 535 deaths occurred. Median survival was 53.4 (95% CI 49.9 to 60.7), 75.4 (95% CI 72.9 to 79.1) and 84.1 (95% CI 81.9 to 87.0) years for patients with severe, moderate and mild lesions, respectively. Survival of most patients with mild lesions did not differ from the general population, while, as expected, survival of patients with severe and moderate lesions was substantially lower (<0.001).Conclusions: The present study gives insight in the contemporary survival of adults with CHD. This may aid patient counselling, timing of interventions and future research. [ABSTRACT FROM AUTHOR]

The article examines the outcome of 136 adults with congenital heart disease in the Netherlands and Belgium after the implantable cardioverter defibrillator (ICD) therapy. Secondary prevention indication, symptomatic nonsustained ventricular tachycardia and coronary artery disease were linked with appropriate ICD shocks. The eight-year survival rates for low-, intermediate- and high-risk patients are also mentioned. About 29% of the patients had 45 complications associated with ICD.

The Netherlands are lacking reliable empirical data in relation to the development of birth and population prevalence of Down syndrome. For the UK and Ireland there are more historical empirical data available. A theory-based model is developed for predicting Down syndrome prevalence in the Netherlands from the 1950s onwards. It is likewise applied to Ireland and the UK for the purpose of validation. Furthermore, a prediction to 2050 is constructed. Maternal age births data in the general population, maternal age related risk of Down syndrome, data on selective terminations of Down syndrome pregnancies and mortality rates (from 35 studies from the 1930s until today) were obtained to create this model. For the Netherlands, nowadays birth prevalence is estimated at 14 per 10 000 with around 275 total annual births. The impact of selective abortion is lower than in the UK. Present Dutch Down syndrome population prevalence is estimated, according to this theory-based model, at 7.7 per 10 000 and the grand total at 12 600 individuals. The prevalence of 'older' persons with Down syndrome (over 40 years of age) in the Netherlands will reach a peak in 2010, a doubling compared to 1990, implying an increased demand on medical care and counselling. Validity of this theory-based model was examined by comparison with relevant available empirical data from the three countries. The model shows a good fit with historical empirical research, notably four UK and two Irish population prevalence studies and eight birth prevalence studies. A theory-based model for Down syndrome prevalence provides supplementary data in situations with a lack of empirical material and can be used for understanding and predicting long-term developments. [ABSTRACT FROM AUTHOR]

Objective To assess the extent and the characteristics of hospital admissions in registered adult patients with congenital heart disease. Design Observational cohort study. Setting The Netherlands. Patients 5798 adult patients with congenital heart disease from the Dutch CONCOR national registry linked to the Dutch National Medical Registration (Prismant). Main outcome measures All hospital admissions from the years 2001 up until 2006. Results During 28⇔990 patient-years, 2908 patients (50%) were admitted to hospital. Median age at admission was 39 years (range 18-86 years); 46% were male. Admission rate in CONCOR patients was high among all ages (range 11-68%) and exceeded that of the general Dutch population two to three times; this difference was most pronounced in the older age groups. Altogether there were 8916 admissions, 5411 (61%) of which were for cardiovascular indications. Among cardiovascular admissions, referrals for arrhythmias were most common (31%). Of 4926 interventions, 2459 (50%) were cardiovascular, most often reparative interventions or cardioversion (53%). Most non-cardiovascular admissions were obstetric. Among defects, univentricular heart and tricuspid atresia had the highest incidence and duration of admission. Conclusions Healthcare utilisation in registered and medically supervised adult patients with congenital heart disease is high and increases with age. Admission rates are at least two times higher than in the general population, and most marked in the older age groups. With the ageing of this population, a major increase in healthcare utilisation is imminent in the near future. Timely preparation of healthcare resources is crucial to sustain optimal care. [ABSTRACT FROM AUTHOR]

Background: In patients with repaired tetralogy of Fallot (rTOF), multiple reoperations or percutaneous interventions after pulmonary valve replacement (PVR) may be necessary due to limited homograft durability. However, data to guide individualised prediction of homograft durability remain scarce. The aim of this study was to provide risk models for RV to pulmonary artery homograft durability.Methods: This retrospective multicentre study included consecutive patients with rTOF who had undergone PVR at an age of >12 years. Homograft dysfunction was defined as at least moderate pulmonary regurgitation (PR) or pulmonary stenosis (PS) (pressure gradient ≥36 mm Hg) as assessed by echocardiography. Reintervention was defined as percutaneous intervention or redo-PVR.Results: A total of 153 patients with rTOF were included (62% male, mean age at PVR 31±11 years, pulmonary homograft 96%, follow-up 9.6 years (IQR 5.9, 13.3)). Average freedom from homograft dysfunction and reintervention after 10 years was 74% and 89%, respectively. In multivariable Cox proportional hazards analysis, postoperative PS ≥20 mm Hg (HR 6.52, 95% CI 3.09 to 13.7), postoperative PR ≥ grade 1 (HR 3.13, 95% CI 1.45 to 6.74) and age at PVR <18 years (HR 3.52, 95% CI 1.64 to 7.53) were independently predictive for homograft dysfunction. In patients without any risk factor, 10-year freedom from homograft dysfunction and reintervention was excellent (91% and 96%, respectively) in contrast to patients with ≥2 risk factors (25% and 73%, respectively).Conclusions: Individualised prediction of homograft durability in patients with rTOF can be guided by early postoperative echocardiography. In adult patients without early postoperative PS or PR, homograft dysfunction and reintervention are unlikely to occur within 10 years, and follow-up may be less stringent. [ABSTRACT FROM AUTHOR]

Background: Although QRS duration >180 ms has prognostic value in adults with tetralogy of Fallot (TOF), its sensitivity to predict mortality is low. Fragmented QRS complexes, a simple measurement on ECG, are related to myocardial fibrosis and dysfunction in patients with TOF. Our objective was to determine whether QRS fragmentation predicts major outcomes in TOF.Methods: This multicentre study included adult patients with TOF from a prospective registry. Notches in the QRS complex in ≥2 contiguous leads on a 12-lead ECG, not related to bundle branch block, were defined as QRS fragmentation, which was classified as none, moderate (≤4 leads) or severe (≥5 leads). The primary and secondary outcomes were all-cause mortality and clinical ventricular arrhythmia, respectively.Results: A total of 794 adult patients with TOF (median age 27 years, 55% male; 52% no QRS fragmentation, 32% moderate, 16% severe) were included. During long-term (median 10.4 years) follow-up, 46 (6%) patients died and 35 (4%) patients had ventricular arrhythmias. Overall, 10-year survival was 98% in patients without fragmented QRS complexes, 93% in patients with moderate QRS fragmentation and 81% in patients with severe QRS fragmentation. In multivariable Cox hazards regression analysis, extent of QRS fragmentation (HR: 2.24/class, 95% CI 1.48 to 3.40, p<0.001) remained independently predictive for mortality, whereas QRS duration was not predictive (p=0.85). The extent of QRS fragmentation was also independently predictive for ventricular arrhythmia (HR: 2.00/class, 95% CI 1.26 to 3.16, p=0.003).Conclusions: The extent of QRS fragmentation is superior to QRS duration in predicting mortality in adult patients with TOF and may be used in risk stratification. [ABSTRACT FROM AUTHOR]

Background: Baffle complications, ie, leakage or stenosis, after an atrial switch operation (AtrSO) for transposition of the great arteries (TGA) are difficult to detect with the use of routine transthoracic echocardiography (TTE). We examined baffle interventions and the prevalence of baffle complications., Methods: This dual-centre study followed TGA-AtrSO patients for the occurrence of baffle interventions. In addition, in 2017-2019, prevalence of baffle complications was determined in patients undergoing routine contrast-enhanced (CE) TTE including various hemodynamic conditions and computed tomography (CT). Baffle leaks were defined as right-to-left shunting on CE-TTE and baffle stenosis as a systemic venous baffle diameter of < 10 mm on CT., Results: In total, 67 TGA-AtrSO patients were followed to a median age of 38 (interquartile range 34-42) years, for a median of 9 (6-13) years. Baffle interventions were documented in 24 patients (36%). Cumulative risk of baffle interventions was 25% after 15 years of follow-up. Prevalence of baffle complications was determined in 29/67 patients. In total, 4 (14%) had patent baffles, 11 (38%) had leakage only, 5 (17%) had stenosis only, and 9 (31%) had both, while 24/29 (84%) were asymptomatic. Although baffle leaks were not associated with clinical characteristics, peak work rate during exercise TTE was lower in patients with vs without stenosis (89 ± 24 W vs 123 ± 21 W; P < 0.001)., Conclusions: Baffle complications are common in TGA-AtrSO. The cumulative risk of baffle interventions was 25% after 15 years of follow-up. CE-TTE uncovered asymptomatic baffle leakage in the majority of patients, especially with examination during exercise. CT revealed baffle stenosis in almost half of the patients, which was associated with decreased exercise tolerance. Awareness of these findings may alter clinical follow-up., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model., Objective: The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD., Methods: The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD., Results: The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95)., Conclusion: The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted., Methods: Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement., Results: 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable., Conclusion: Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Patients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival. Methods and Results This multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%-9%), 23% (95% CI, 17%-28%), and 5% (95% CI, 2%-8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (<5%), intermediate (5%-20%), and high (>20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82-0.90]). Observed 5- and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients. Conclusions The clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management.

Objective: Adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well-defined. The T peak -T end (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non-ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients., Design: From an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention., Outcome Measures: TpTe was measured on a standard 12-lead ECG. The maximum TpTe of all ECG leads (TpTe-max), mean (TpTe-mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis., Results: ECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe-max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe-mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7-12.4, P < .001)., Conclusions: The TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models., (© 2019 The Authors. Congenital Heart Disease published by Wiley Periodicals, Inc.)

Aims: To assess medication use in adult congenital heart disease (ACHD) patients compared to the age- and sex-matched general population, identify patterns of pharmacotherapy, and analyse associations between pharmacotherapy and adverse outcomes in ACHD., Methods and Results: Data of 14 138 ACHD patients from the CONCOR registry [35 (24-48) years, 49% male] and age- and sex-matched referents (1:10 ratio) were extracted from the Dutch Dispensed Drug Register for the years 2006-14. Adult congenital heart disease patients had more cardiovascular and non-cardiovascular drugs than referents (median 3 vs. 1, P < 0.001). Polypharmacy, defined as ≥5 dispensed drug types yearly, was present in 30% of ACHD and 15% of referents {odds ratio [OR] = 2.47 [95% confidence interval (CI) 2.39-2.54]}. Polypharmacy was independently associated with female sex [OR = 1.92 (95% CI 1.88-1.96)], older age [for men: OR = 2.3/10 years (95% CI 2.2-2.4) and for women: OR = 1.6/10 years (95% CI 1.5-1.6); Pinteraction < 0.001], and ACHD severity [mild: OR = 2.51 (95% CI 2.40-2.61), moderate: OR = 3.22 (95% CI 3.06-3.40), severe: OR = 4.87 (95% CI 4.41-5.38)]. Cluster analysis identified three subgroups with distinct medication patterns; a low medication use group (8-year cumulative survival: 98%), and a cardiovascular and comorbidity group with lower survival (92% and 95%, respectively). Cox regression revealed a strong association between polypharmacy and mortality [hazard ratio (HR) = 3.94 (95% CI 3.22-4.81)], corrected for age, sex, and defect severity. Polypharmacy also increased the risk of hospitalization for adverse drug events [HR = 4.58 (95% CI 2.04-10.29)]., Conclusion: Both cardiovascular and non-cardiovascular medication use is high in ACHD with twice as much polypharmacy compared with the matched general population. Patients with polypharmacy had a four-fold increased risk of mortality and adverse drug events. Recognition of distinct medication patterns can help identify patients at highest risk. Drug regimens need repeating evaluation to assess the appropriateness of all prescriptions. More high-quality studies are needed to improve ACHD care with more evidence-based pharmacotherapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study describes the different types of congenital vascular rings according to their anatomy, symptoms, and age at clinical onset and reports the surgical outcomes., Methods: A retrospective observational database study was conducted, reviewing the medical charts of 69 adult survivors with a history of a vascular ring, identified from the Dutch Congenital Cor vitia database., Results: Median age at presentation was 8.5 years (0-53.0 years). Thirty patients (43.5%) had a "left aortic arch with aberrant right subclavian artery," 21 patients (30.4%) a "double aortic arch," and 16 patients (23.2%) a "right aortic arch with aberrant left subclavian artery." The main symptomatology at presentation comprised respiratory symptoms (82.9%). Almost three-quarters of patients were also diagnosed with asthma/bronchial hyperreactivity. Patients with a double aortic arch had more symptoms than patients with a left aortic arch with aberrant right subclavian artery and right aortic arch with aberrant left subclavian artery (P < 0.001), requiring surgery most often (P < 0.001). In patients with childhood onset of symptoms, preoperative spirometry (ie, peak expiratory flows) was more often abnormal as compared with adult patients (P = 0.007). Surgery was performed in 42.0% of all patients at a median age of 17 years (0-63.0 years). Twenty-four (92.3%) of the operated patients showed improvement or complete relief of symptoms shortly after surgery. Of 26 asymptomatic nonoperated patients, 3 patients (11.5%) eventually developed symptoms., Conclusions: The low incidence of vascular rings, their anatomic heterogeneity, and a wide range of common symptoms often lead to misdiagnosis. Clinical awareness is warranted as a large subset of patients could benefit from surgery, even at an adult age., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this prospective randomised controlled trial was to assess whether home-based, self-selected exercise training is safe, results in high compliance and improves exercise capacity in symptomatic adults with congenital heart disease (CHD)., Methods: Forty adults with moderate or severe CHD (40 ± 12 years, 56% male, New York Heart Association [NYHA] II/III 37/3) were randomly assigned, stratified by CHD complexity, either to home-based exercise training or usual care. The exercise training protocol consisted of three exercise sessions per week for six consecutive months. Patients were free to choose any sports of their preference., Results: Thirty-four patients (each randomisation group n = 17) completed the protocol and were analysed. The majority was involved in high-dynamic sports (76%); none had to discontinue the training programme due to exercise-related adverse events. More than 70% adhered to the exercise programme at or above the target training level. Peak VO 2 increased significantly in the exercise group by +1.7 ± 2.7 ml∙kg∙min -1 (p = 0.025), whereas it remained unchanged in the control group by +0.8 ± 2.2 ml∙kg∙min -1 (p = 0.184). No significant changes were found in serum N-Terminal pro-brain natriuretic peptide levels or quality of life in either randomisation group or between groups., Conclusions: In symptomatic adults with moderate or severe CHD, home-based exercise training of their preference appeared safe, with good compliance and favourable effects on exercise capacity. Our results demonstrate that it is appropriate to stimulate our patients to regularly perform moderate to vigorous physical activities, in absence of medical restrictions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Adult congenital heart disease (ACHD) patients are at increased risk of sudden cardiac death and out-of-hospital cardiac arrest (OHCA). Currently, insufficient data exist on outcome, causes and circumstances of OHCA of ACHD patients resuscitated for OHCA. We investigate these parameters in ACHD patients in comparison to OHCA in the general population., Methods and Results: We identified ACHD patients with OHCA by linking data from a Dutch nationwide registry of ACHD patients (CONCOR, n = 15,727), and ARREST, a cohort of OHCA cases (n = 17,868). 62 ACHD patients with OHCA were identified. Ventricular septal defect (n = 11), bicuspid aortic valve (n = 10) and atrial septal defect (n = 8) were the most common diagnoses. We included OHCA cases from the general population as controls. ACHD patients were younger than controls (n = 11,624) at the time of OHCA (47 (SD ± 17) years vs. 66 (SD ± 15) years, respectively, p < 0.001), and more often had a shockable initial rhythm (67% vs 40%, respectively, p < 0.001). A cardiac cause of OHCA was identified in 76% of ACHD patients, with only 7% due to myocardial infarction or ischemia. Survival was better in ACHD patients than in controls (44% vs. 19%, p < 0.001), but this difference disappeared after correction for age, gender, witnessed arrest, bystander resuscitation, public location and shockable rhythm., Conclusions: OHCA in ACHD patients occurs at young age, is rarely caused by ischemia and occurs mainly in patients with simple congenital defects. Risk stratification efforts should therefore not be restricted to ACHD patients with severe congenital defects., (Copyright © 2018. Published by Elsevier B.V.)

Aims: Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients., Methods and Results: From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03)., Conclusions: fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Background: In patients with repaired tetralogy of Fallot (rTOF), multiple reoperations or percutaneous interventions after pulmonary valve replacement (PVR) may be necessary due to limited homograft durability. However, data to guide individualised prediction of homograft durability remain scarce. The aim of this study was to provide risk models for RV to pulmonary artery homograft durability., Methods: This retrospective multicentre study included consecutive patients with rTOF who had undergone PVR at an age of >12 years. Homograft dysfunction was defined as at least moderate pulmonary regurgitation (PR) or pulmonary stenosis (PS) (pressure gradient ≥36 mm Hg) as assessed by echocardiography. Reintervention was defined as percutaneous intervention or redo-PVR., Results: A total of 153 patients with rTOF were included (62% male, mean age at PVR 31±11 years, pulmonary homograft 96%, follow-up 9.6 years (IQR 5.9, 13.3)). Average freedom from homograft dysfunction and reintervention after 10 years was 74% and 89%, respectively. In multivariable Cox proportional hazards analysis, postoperative PS ≥20 mm Hg (HR 6.52, 95% CI 3.09 to 13.7), postoperative PR ≥ grade 1 (HR 3.13, 95% CI 1.45 to 6.74) and age at PVR <18 years (HR 3.52, 95% CI 1.64 to 7.53) were independently predictive for homograft dysfunction. In patients without any risk factor, 10-year freedom from homograft dysfunction and reintervention was excellent (91% and 96%, respectively) in contrast to patients with ≥2 risk factors (25% and 73%, respectively)., Conclusions: Individualised prediction of homograft durability in patients with rTOF can be guided by early postoperative echocardiography. In adult patients without early postoperative PS or PR, homograft dysfunction and reintervention are unlikely to occur within 10 years, and follow-up may be less stringent., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Patients with surgically repaired tetralogy of Fallot (rTOF) may develop functional tricuspid regurgitation (TR) due to annulus dilation. Guidelines suggest pulmonary valve replacement (PVR) in patients with rTOF with progressive TR, but data on clinical outcomes are lacking. Our objective was to determine whether TR was predictive for adverse events after PVR., Methods: In this retrospective, multicenter cohort study, patients with rTOF who had undergone PVR after preoperative echocardiographic assessment of TR grade were included. Preoperative and postoperative imaging data and a composite of adverse clinical events (death, sustained ventricular tachycardia, heart failure, or supraventricular tachycardia) were collected. Multivariate Cox hazards regression analysis was used to determine which factors were predictive for adverse events after PVR., Results: A total of 129 patients (61% men, age at PVR 32.9±10.4 years) were included. The composite endpoint occurred in 39 patients during 8.4±4.2 years of follow-up. In multivariate analysis, severe preoperative TR (HR 2.49, 95% CI 1.11 to 5.52), right ventricular end-systolic volume (HR 1.02/mL/m(2), 95% CI 1.01 to 1.03) and age at PVR (HR 1.07/year, 95% CI 1.04 to 1.09) were predictive for adverse events. Early postoperative TR was not predictive for adverse events (p=0.96). In patients without any risk factor (age >40 years, right ventricular end-systolic volume >90 mL/m(2) or severe TR), 5-year event-free survival was 100% as compared with 61% in patients with two or three risk factors., Conclusions: In patients with rTOF, severe preoperative TR was predictive for adverse events after PVR. Close surveillance is warranted in these patients irrespective of postoperative TR., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Pregnancy is increasingly common in women with congenital heart disease (CHD), but little is known about long-term cardiovascular outcome after pregnancy in these patients. We studied the incidence of cardiovascular events 1-year postpartum and compared cardiac function prepregnancy and 1-year postpartum in women with CHD., Methods: From our national, prospective multicenter cohort study, 172 women were studied. Follow-up with clinical evaluation and echocardiography and NT-proBNP measurement were performed during pregnancy and 12 months postpartum. Cardiovascular events were defined as need for an urgent invasive cardiovascular procedure, heart failure, arrhythmia, thromboembolic events, myocardial infarction, cardiac arrest, cardiac death, endocarditis, and aortic dissection., Results: Cardiovascular events were observed after 11 pregnancies (6.4%). Women with cardiovascular events postpartum had significant higher NT-proBNP values at 20-week gestation (191 [137-288] vs 102.5 [57-167]; P = .049) and 1-year postpartum compared with women without cardiovascular events postpartum (306 [129-592] vs 105 [54-187] pg/mL; P = .014). Women with cardiovascular events during pregnancy were at higher risk for late cardiovascular events (HR 7.1; 95% CI 2.0-25.3; P = .003). In women with cardiovascular events during pregnancy, subpulmonary end-diastolic diameter had significantly increased 1-year postpartum (39.0 [36.0-48.0] to 44.0 [40.0-50.0]; P = .028). No other significant differences were found in cardiac function or size 1-year postpartum compared with preconception values., Conclusions: Cardiovascular events are relatively rare 1 year after pregnancy in women with CHD. Women with cardiovascular events during pregnancy are prone to develop cardiovascular events 1-year postpartum and have increased subpulmonary ventricular diameter compared with preconception values., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Pulmonary arterial hypertension due to congenital heart disease (CHD-PAH) has a poor prognosis. We sought to determine whether the biomarker high-sensitivity troponin T (hsTnT) measured on routine visit at the outpatient clinic is associated with prognosis., Patients: Consecutive adult CHD-PAH (86% Eisenmenger syndrome) patients referred for advanced medical therapy between January 2005 and March 2007 in the Academic Medical Center in Amsterdam. Patients with severe renal impairment were excluded., Main Outcome Measure: The primary outcome was mortality., Results: Of all 31 patients (mean age 45 ± 12 years) with CHD-PAH, eight patients died during a median follow-up of 5.6 (range 1.6 to 6.8) years. A hsTnT level >0.014 μg/L was the 99th percentile cutoff of the normal distribution and therefore defined as elevated. At baseline, elevated levels of hsTnT were found in eight patients (26%). In univariate Cox regression, hsTnT elevated at baseline, NT-pro-BNP and right ventricular function were determinants of death (P < .05 for all). Patients with elevated levels of hsTnT showed a significantly higher mortality rate as compared to patients with normal hsTnT levels (62% vs. 13%, P = .005)., Conclusion: Levels of hsTnT were abnormal in a substantial proportion of CHD-PAH patients. A significant inverse relationship was found between hsTnT and survival., (© 2012 Wiley Periodicals, Inc.)

Supraventricular tachycardias (SVTs) are a major cause of morbidity in adults with congenital heart disease (CHD). Few data exist on safety and efficacy of antiarrhythmic drugs in this population. Our aim was to determine the efficacy of antiarrhythmic drugs in adults with CHD and first-onset SVT on maintaining sinus rhythm after conversion. This was a multicenter retrospective study including adults with CHD and first-onset SVT from January 2008 to January 2011. First-onset SVT occurred in 92 of 7,171 patients without previous SVT (mean age 51 ± 16 years, 57% women). SVTs included atrial fibrillation and flutter in >80% of the patients. Most of these patients had septal defects (50%) and left-sided lesions (21%). The acute management of SVTs resulted in sinus rhythm in 83 patients, and 89% of these patients were instituted on oral antiarrhythmics to prevent SVT recurrence. After a mean follow-up of 2.5 ± 1.4 years, only 45% of the patients were free from SVT. Class III antiarrhythmics (85% sotalol and 15% amiodarone) were associated with a significantly lesser risk of SVT recurrence compared with all other antiarrhythmic drugs (hazard ratio 0.5, 95% confidence interval 0.27 to 0.96, p = 0.036). However, adverse effects of medication occurred in 22% of the patients, mainly in patients taking amiodarone. In conclusion, in adults with CHD and first-onset SVTs, class III antiarrhythmics are more efficacious in maintaining sinus rhythm after cardioversion than other antiarrhythmics. Sotalol may be considered as the first-choice therapy as this is associated with fewer adverse effects than amiodarone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The study objectives were to analyze sex differences in hospital mortality of adult patients with congenital heart disease (CHD) and to determine the impact of health services associated with pregnancy on outcomes in women., Background: The determinants of sex differences in the demographic distribution of CHD are poorly understood., Methods: The Quebec CHD database and the Dutch CONCOR (CONgenital CORvitia) registry were used to identify patients with CHD aged 18 to 65 years who were hospitalized between 1996 and 2005. Regression analyses were used to compare 30-day in-hospital mortality in men versus women and in women aged 18 to 45 years with versus without a pregnancy history, after adjustment for age, CHD severity, comorbidities, and admission diagnosis., Results: Of 39,776 patients followed for 259,741 patient years, 19,099 patients (48%) had 54,195 admissions (62% among women). In those aged 18 to 45 years, 30-day in-hospital mortality was higher in men compared with women with nonpregnancy admissions (adjusted rate ratio: 1.36; 95% confidence interval: 1.02 to 1.81). The adjusted rate ratio for 30-day in-hospital mortality in women with a pregnancy history compared with those without was 0.49 (95% confidence interval: 0.24 to 0.99). A history of pregnancy was not associated with an overall increase in medical encounters., Conclusions: We demonstrated a protective effect of sex on in-hospital mortality in women with CHD of reproductive age that did not correlate with increased medical surveillance. Future studies need to explore other mechanisms to account for our observations. Understanding the determinants of the sex distribution of adults with CHD is important for our ability to predict demographic changes in the population with CHD., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Prevention of aortic dissection and sudden death in patients with Marfan syndrome (MFS) requires accurate diagnosis. MFS is diagnosed by the Ghent criteria, which are primarily based on clinical features of Caucasian MFS populations. We determined whether the Ghent criteria apply to Asian MFS populations., Methods and Results: In this multicenter study, we included 255 adult MFS patients according to the Ghent criteria of 2010. Patients were excluded if they were neither Caucasian nor Asian. The Asian MFS population (n=49) had a smaller body surface area (BSA: 1.8 m² vs. 2.0 m², P<0.001), a more severely affected aortic root (absolute aortic diameter: 42.9 mm vs. 43.3mm, P=0.802; corrected for BSA: 24.9 mm vs. 21.7 mm, P<0.001; Z-score: 4.5 vs. 3.6, P=0.013), and more often a positive systemic score (75.5% vs. 60.0%, P=0.045), but less frequently ectopia lentis (24.5% vs. 48.1%, P=0.004) compared with the Caucasian population (n=206)., Conclusions: The Ghent criteria do not necessarily apply to Asian MFS populations, resulting in a more severely affected cardiovascular system. This may be related to under diagnosis of MFS by multiple factors, including the use of Z-score, and genetic and racial differences. The Ghent criteria should be adapted for Asian populations in order to accurately diagnose MFS.

We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Management of pulmonary atresia with intact ventricular septum is challenging and depends on the severity of right ventricular hypoplasia. Clinical outcomes of biventricular repair seem favorable to univentricular palliation, but data on superiority of biventricular repair regarding exercise capacity are conflicting. We investigated the response to physical and pharmacologic stress in patients with surgically corrected pulmonary atresia with intact ventricular septum., Methods: Sixteen patients (7 patients after univentricular palliation, age 11.8 ± 2.6 years; 7 patients after biventricular repair, age 12.9 ± 2.7 years; and 2 patients after 1.5 ventricular repair, age 12 and 19 years) underwent cardiopulmonary exercise test, dobutamine stress magnetic resonance imaging, and delayed contrast-enhanced magnetic resonance imaging., Results: The univentricular group showed impaired exercise capacity in contrast with normal exercise capacity in the biventricular group. Left ventricular ejection fraction increased in both groups. With dobutamine, left ventricular stroke volume increased only in the biventricular group (+11.3 ± 5.0 mL, P < .001) and not in the univentricular group (-0.04 ± 3.6 mL, P = .9). Heart rate increase was inadequate in the univentricular group. Maximum oxygen consumption and oxygen pulse were strongly correlated with left ventricular stroke volume during stress but not at rest. The results of the 2 patients after 1.5 ventricular repair were comparable to those of the univentricular group. No myocardial fibrosis was detected., Conclusions: Impaired exercise capacity in children and adolescents with pulmonary atresia with intact ventricular septum after univentricular palliation is related to decreased cardiac reserve and inadequate chronotropic response. Young patients with pulmonary atresia with intact ventricular septum after biventricular repair show normal exercise capacity and cardiac reserve., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Circumstances of death have been described for various cardiovascular diseases, but this study is the first for adults with congenital heart disease (CHD)., Methods: Review of medical records and additional information from treating cardiologists and general practitioners, for circumstances of all deaths in a national registry of over 8000 adults with CHD., Results: Of 8595 patients, 231 (2.7%) patients died over 26,500 patient years. Main causes of death were progressive heart failure (26%) and sudden cardiac death (22%). Mortality was highest in the northern, most rural region of the country (p ≤ 0.05). Overall, death occurred out-of-hospital in approximately 35%, but more frequently in rural than in urban areas (55% versus 32%, p ≤ 0.05). Mortality was almost equally distributed throughout the seasons, although fall showed a slightly higher mortality rate. Cardiovascular death occurred suddenly in nearly 40%. Sudden cardiovascular death occurred in 8% during exercise, and most often out-of-hospital (62%). Of non-sudden cardiovascular deaths 18% had occurred out-of-hospital., Conclusion: In adult patients with congenital heart disease, mortality shows substantial regional and subtle seasonal variation. Death usually occurs at rest; approximately 1 of 10 sudden cardiovascular deaths occur during exercise., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Statistics on cause-specific mortality are important for prognostic research. The aim of this study was to assess the utility of the national mortality registry in research on causes of death in adult patients with congenital heart disease (CHD)., Methods: The CONCOR registry of over 10,000 adults with CHD was used to verify the causes of death provided by the WHO guidelines based national mortality registry, by linkage., Results: Of 7277 patients linked to the national mortality registry, 196 (2.4%) were recorded deceased, versus 228 deceased patients (3.1%) recorded in the CONCOR registry, during a follow-up of 25,900 patient years. Median age at death was 48.9 years. Of all deaths in the CONCOR registry, 77% had a cardiovascular origin; nearly 50% were due to progressive heart failure and arrhythmias. The national mortality registry recorded death due to progressive heart failure and arrhythmias in only 8.5%. Moreover, this registry recorded death with an 'unspecified' cause in approximately 30%, primarily containing patients who died due to progressive heart failure and arrhythmias according to their medical records., Conclusion: WHO guidelines based national mortality registries lack the specificity and completeness needed for accurate research on causes of death in adult patients with CHD., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Background: Incidence and prevalence rates for pediatric pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are unknown. This study describes the nationwide epidemiological features of pediatric PH in the Netherlands during a 15-year period and the clinical course of pediatric PAH., Methods and Results: Two registries were used to retrospectively identify children (0-17 years) with PH. Overall, 3263 pediatric patients were identified with PH due to left heart disease (n=160; 5%), lung disease/hypoxemia (n=253; 8%), thromboembolic disease (n=5; <1%), and transient (n=2691; 82%) and progressive (n=154; 5%) PAH. Transient PAH included persistent PH of the newborn and children with congenital heart defects (CHD) and systemic-to-pulmonary shunt, in whom PAH resolved after successful shunt correction. Progressive PAH mainly included idiopathic PAH (n=36; iPAH) and PAH associated with CHD (n=111; PAH-CHD). Pulmonary arterial hypertension associated with CHD represented highly heterogeneous subgroups. Syndromes were frequently present, especially in progressive PAH (n=60; 39%). Survival for PAH-CHD varied depending on the subgroups, some showing better and others showing worse survival than for iPAH. Survival of children with Eisenmenger syndrome appeared worse than reported in adults. For iPAH and PAH-CHD, annual incidence and point prevalence averaged, respectively, 0.7 and 4.4 (iPAH) and 2.2 and 15.6 (PAH-CHD) cases per million children. Compared to studies in adults, iPAH occurred less whereas PAH-CHD occurred more frequently., Conclusions: Pediatric PH is characterized by various age-specific diagnoses, the majority of which comprise transient forms of PAH. Incidence of pediatric iPAH is lower whereas incidence of pediatric PAH-CHD is higher than reported in adults. Pediatric PAH-CHD represents a heterogeneous group with highly variable clinical courses.

Chronic hypertension is a major concern in adults who have undergone resection of coarctation of the aorta (CoA) in childhood. In otherwise healthy subjects, exercise-induced hypertension is prognostic for chronic hypertension; however, the prognostic value in patients with CoA remains unknown. The aim of the present study was to evaluate the predictive value of exercise-induced hypertension for chronic hypertension in these patients. In the present prospective follow-up study, 74 patients with CoA (58% men, age 30.9 ± 9.5 years) underwent ambulatory blood pressure (BP) monitoring and exercise testing twice from 2001 to 2009 with a follow-up period of 6.3 ± 0.8 years. Hypertension was defined as a mean systolic BP ≥140 mm Hg and/or mean diastolic BP ≥90 mm Hg or the need for antihypertensive treatment. Exercise-induced hypertension was defined as a mean systolic BP of <140 mm Hg and peak exercise systolic BP of ≥200 mm Hg. At baseline, 27 patients (36%) were hypertensive, 11 (15%) had exercise-induced hypertension, and 36 (49%) were normotensive. At follow-up, all 27 hypertensive patients remained hypertensive. Of the 11 with exercise-induced hypertension, 7 (64%) had developed chronic hypertension, and 4 (36%) continued to have exercise-induced hypertension. Of the 36 normotensive patients, 7 (19%) had developed hypertension, 12 (33%) had developed exercise-induced hypertension, and 17 (47%) remained normotensive. On multivariate analysis, baseline maximum exercise systolic BP was independently associated with the mean systolic BP at follow-up (β = 0.13, p = 0.005). In conclusion, the maximum exercise systolic BP was a predictor for chronic hypertension in patients with CoA. These findings demonstrate the clinical importance of exercise-induced hypertension and warrant additional study into the long-term consequences of exercise-induced hypertension and the potential beneficial role of early antihypertensive treatment in adult patients after CoA repair with exercise-induced hypertension., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: The risk of infective endocarditis (IE) in adults with congenital heart disease is known to be increased, yet empirical risk estimates are lacking. We sought to predict the occurrence of IE in patients with congenital heart disease at the transition from childhood into adulthood., Methods and Results: We identified patients from the CONCOR national registry for adults with congenital heart disease. Potential predictors included patient characteristics, and complications and interventions in childhood. The outcome measure was the occurrence of IE up to the age of 40 and 60. A prediction model was derived using the Cox proportional hazards model and bootstrapping techniques. The model was transformed into a clinically applicable risk score. Of 10 210 patients, 233 (2.3%) developed adult-onset IE during 220 688 patient-years. Predictors of IE were gender, main congenital heart defect, multiple heart defects, and three types of complications in childhood. Up to the age of 40, patients with a low predicted risk (<3%) had an observed incidence of less than 1%; those with a high predicted risk (≥3%) had an observed incidence of 6%. The model also yielded accurate predictions up to the age of 60., Conclusion: Among young adult patients with congenital heart disease, the use of six simple clinical parameters can accurately predict patients at relatively low or high risk of IE. After confirmation in other cohorts, application of the prediction model may lead to individually tailored medical surveillance and educational counselling, thus averting IE or enabling timely detection in adult patients with congenital heart disease.

Objective: A first step in the delivery of tailored care is answering the following question: does health care meet the needs of patients? Therefore patients' perspective on health care use and their needs was examined. The design used was cross-sectional questionnaire study., Patients: A total of 1109 adult congenital heart defect (CHD) patients attending one of eight Dutch hospitals were randomly selected from a national database (10% of all registered patients)., Main Outcome Measures: Patient reported questionnaires on in- and outpatient health care use during the past year and need for additional care., Results: A total of 66% and 40% of patients had contact with their cardiologist and general practitioner, respectively. Six to 10 percent were hospitalized, operated upon, or visited the emergency room. For the majority, the amount of contact was sufficient. Most patients indicated that the communication skills and expertise of the cardiologist and general practitioner were sufficient, and health care improvements were not necessary. Frequent health care users had a poor functional status and frequent contact with their cardiologist and general practitioner. Patients who want more contact with their cardiologist rated the communication skills of the cardiologist as insufficient., Conclusions: For most patients, the amount and quality of care are both sufficient. Patients who rate the communication skills of the cardiologist as insufficient have need more contact. In addition to the recommended training program as described in the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) guidelines, we recommend the incorporation of communication training. This is the first study to provide insight into health care use and needs of CHD patients in countries with a compulsory health insurance system from the patient perspective., (© 2011 Copyright the Authors. Congenital Heart Disease © 2011 Wiley Periodicals, Inc.)

Aims: Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear., Methods and Results: The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Cox's regression was used to assess mortality predictors. Of 6933 patients, 197 (2.8%) died during a follow-up of 24 865 patient-years. Compared with the general national population, there was excess mortality, particularly in the young. Median age at death was 48.8 years. Of all deaths, 77% had a cardiovascular origin; 45% were due to chronic heart failure (26%, age 51.0 years) or sudden death (19%, age 39.1 years). Age predicted mortality, as did gender, severity of defect, number of interventions, and number of complications [hazard ratio (HR) range 1.1-5.9, P < 0.05]. Several complications predicted all-cause mortality beyond the effects of age, gender, and congenital heart disease severity, i.e. endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (HR range 1.4-3.1, P < 0.05). These risks were similar in patients above and below 40 years of age. Almost all complications predicted death due to heart failure (HR range 2.0-5.1, P < 0.05); conduction disturbances and pulmonary hypertension predicted sudden death (HR range 2.0-4.7, P < 0.05)., Conclusion: Mortality is increased in adults with congenital heart disease, particularly in the young. The vast majority die from cardiovascular causes. Mortality risk, particularly by heart failure, is increased by virtually all complications. Complications are equally hazardous in younger as in older patients.

Background: Marfan syndrome (MFS) is one of the most common systemic disorders of connective tissue with the incidence of approximately 2-3 per 10 000 individuals. Aortic disease, leading to progressive aneurysmal dilatation and dissection is the main cause of morbidity and mortality of Marfan patients. Current treatment (e.g. beta blockers and elective surgery) does postpone but cannot prevent aortic complications in these patients. Recent studies have found transforming growth factor beta (TGF beta) to be involved in the aortic aneurysm formation. Losartan, an angiotensin II type 1 receptor blocker inhibits TGFbeta in a mouse model of Marfan syndrome leading to inhibition of aortic growth. The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome., Methods/design: COMPARE study (COzaar in Marfan Patients Reduces aortic Enlargement) is an open-label, randomized, controlled trial with blinded end-points. Treatment with losartan will be compared with no additional treatment after 3 years of follow-up. We will enroll 330 patients with MFS who will be randomly assigned to receive losartan or not. Patients taking beta-blockers will continue taking their standard treatment. The primary end-point is the largest change in aortic diameter at any aortic level measured by means of MRI. Secondary end-points are change in mortality, incidence of dissection, elective aortic surgery, aortic volume, aortic stiffness and ventricular function. We will also investigate gene and protein expression change in the skin under losartan therapy and create prediction models for losartan-treatment response and aortic dilatation., Discussion: The COMPARE study will provide important evidence of effects of losartan treatment in adult Marfan patient population. We expect losartan to significantly reduce the occurrence and progression of aortic dilatation. This trial investigates a wide spectrum of clinical, genetic and biochemical effects of losartan aiming to provide further insight in the pathogenesis and treatment of Marfan syndrome., Trial Registration: Netherlands Trial Register NTR1423.

Background: Gender differences in prognosis have frequently been reported in cardiovascular disease but less so in congenital heart disease. We investigated whether gender is associated with outcome in adult patients with congenital heart disease., Methods and Results: From the CONgenital CORvitia (CONCOR) national registry for adults with congenital heart disease, 7414 patients were identified. All outcomes before entry into the registry and during subsequent follow-up were recorded, and differences between men and women were analyzed with the underlying congenital heart defect taken into account. Median age at the end of follow-up was 35 years (range, 17 to 91 years); 49.8% were female. No gender difference in mortality was found. Women had a 33% higher risk of pulmonary hypertension (odds ratio [OR]=1.33; 95% CI, 1.07 to 1.65; P=0.01), a 33% lower risk of aortic outcomes (OR=0.67; 95% CI, 0.50 to 0.90; P=0.007), a 47% lower risk of endocarditis (OR=0.53; 95% CI, 0.40 to 0.70; P<0.001), and a 55% lower risk of an implantable cardioverter-defibrillator (OR=0.45; 95% CI, 0.26 to 0.80; P=0.006). Furthermore, the risk of arrhythmias appeared to be lower in women (OR=0.88; 95% CI, 0.77 to 1.02; P=0.08)., Conclusions: The risk of several major cardiac outcomes in adult patients with congenital heart disease appears to vary by gender.

Background: Previous studies have shown that patients with congenital heart disease (ConHD) report a diminished health-related quality of life., Purpose: This study examines the mechanisms by which ConHD affects health-related quality of life. We hypothesize that (1) the relation between trait anxiety and quality of life is mediated by a negative interpretation bias for heart sensations, specifically in ConHD, and that (2) the relation between trait anxiety and interpretation bias is mediated by state anxiety., Method: Sixty-six patients with ConHD and 50 healthy participants read a vignette about a person experiencing ambiguous heart-related sensations. Interpretation bias to these sensations was assessed with the Implicit Models of Illness Questionnaire. Participants completed Spielberger trait and state anxiety questionnaires and the physical subscales of a quality-of-life questionnaire., Results: Path-analysis demonstrated that interpretation bias mediated the relation between trait anxiety and daily functioning. However, trait anxiety and interpretation bias were less influential with respect to gross motor functioning. Moreover, state anxiety mediated the relation between trait anxiety and interpretation bias., Conclusion: These results suggest that patients with ConHD who display both elevated levels of trait and state anxiety exhibit the most pronounced negative interpretation bias for heart sensations and in turn diminished daily functioning.

Introduction: Survival of patients with congenital heart disease has dramatically improved after surgical repair became available 40 years ago. Instead of a mortality of 85% during childhood following the natural course, over 85% of these infants are now expected to reach adulthood. However, data on long-term outcome is scarce due to the lack of large, national registries. Moreover, little is known about the genetic basis of congenital heart defects. In 2000, the Interuniversity Cardiology Institute of the Netherlands and the Netherlands Heart Foundation have taken the initiative to develop a national registry and DNA-bank of patients with congenital heart disease in the Netherlands named CONCOR., Objectives: The aims of the CONCOR project are to facilitate investigation of the prevalence and long-term outcome of specific congenital heart defects and their treatment, to develop an efficient organisational structure for the improvement of healthcare for patients with congenital heart disease, and to allow investigation of the molecular basis of congenital heart defects., Methods: After informed consent, research nurses enter data of participating patients into the CONCOR database using a web application. Data is transferred over the Internet via a secure connection. About 20 ml blood is withdrawn from the patient, and the DNA is isolated and stored. From each participating patient family history on congenital heart disease is obtained., Results: Within two and a half years more than 4200 patients have agreed to participate. More than 99% of the patients that were asked have given their consent to participate in CONCOR. From 60% of these patients DNA has already been obtained. Mean age of the patients included is 34 years; more than 85% of the patients are younger than 45 years. Late complications occur frequently and the incidence increases with advancing age. 18% of the patients are known with supraventricular or ventricular arrhythmias. 2% of the included patients suffered a cerebrovascular accident, 139 (3%) had endocarditis. 6% of the patients has pulmonary hypertension or Eisenmenger syndrome. More than 15% of the patients reported an affected family member with congenital heart disease in the first, second, or third degree. 6% has an affected first-degree relative, and 4% a second-degree relative. Already 10 research projects have started using the CONCOR data and DNA., Conclusion: The population of patients with congenital heart disease is young and rapidly growing. Late complications occur frequently and the incidence increases with advances age. The CONCOR registry and DNA-bank facilitates research on prevalence and long-term outcome and allows investigation of the molecular basis of congenital heart disease.