Advocacy at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

BACKGROUND: The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. METHODS: The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis. RESULTS: Of 95 included patients, 47 patients received 150 mg losartan daily (age, 38.0±12.4 years; 74% male), and 48 patients received placebo (age, 40.6±11.4 years; 63% male). Overall, RV EF did not change in patients allocated to losartan (n=42) (44.4±5.1% to 45.2±5.0%) and placebo (n=46) (43.2±6.3% to 43.6±6.9%). Losartan did not significantly improve RV EF in comparison with placebo (+0.51%; 95% confidence interval, -1.0 to +2.0; P=0.50). No significant treatment effects were found on secondary outcomes: left ventricular EF, peak aerobic exercise capacity, and N-terminal pro-brain natriuretic peptide (P>0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EF<40%, pulmonary valve replacement, or QRS fragmentation. However, in a post hoc analysis, losartan was associated with improved RV EF in a subgroup (n=30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4; P=0.045). CONCLUSIONS: Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

Anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS), fractional flow reserve- and intravascular ultrasound-guided management in adult patients.

OBJECTIVES: To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the evaluation of patients with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS). BACKGROUND: ACAOS of the right and left coronary are rare, but may lead to symptoms and impose a risk for sudden cardiac death, depending on several anatomical features. Assessment and risk estimation is challenging in (nonathlete) adults, especially if they present without symptoms or with atypical complaints. METHODS: The team retrospectively studied 30 consecutive patients with ACAOS with interarterial course, who received IVUS- and FFR-guided treatment at our institution between October 2010 and September 2017. RESULTS: FFR was abnormal in only seven patients. IVUS showed the typical slit-like anatomy of the orifice in 23 patients. Based on FFR and/or IVUS results, in conjunction with the clinical presentation, clinical decision was made. A decision for intervention was made if at least two out of three entities were abnormal. Intervention implied unroofing of the coronary artery (n = 10) or coronary artery bypass grafting (n = 1). In all other patients a conservative strategy was followed. No adverse events occurred in the total population after a median of 37 (0-62) months of follow-up. CONCLUSIONS: Conservative treatment may be justifiable in adult patients with ACAOS in the presence of normal FFR and nonsuspicious symptoms, despite the presence of an interarterial course and/or slitlike orifice on IVUS. We recommend the use of FFR and IVUS in the standard work-up for adult patients with ACAOS and propose the use of a flowchart to aid in decision-making.

Tricuspid flow and regurgitation in congenital heart disease and pulmonary hypertension: comparison of 4D flow cardiovascular magnetic resonance and echocardiography.

BACKGROUND: Tricuspid valve (TV) regurgitation (TR) is a common complication of pulmonary hypertension and right-sided congenital heart disease, associated with increased morbidity and mortality. Estimation of TR severity by echocardiography and conventional cardiovasvular magnetic resonance (CMR) is not well validated and has high variability. 4D velocity-encoded (4D-flow) CMR was used to measure tricuspid flow in patients with complex right ventricular (RV) geometry and varying degrees of TR. The aims of the present study were: 1) to assess accuracy of 4D-flow CMR across the TV by comparing 4D-flow CMR derived TV effective flow to 2D-flow derived effective flow across the pulmonary valve (PV); 2) to assess TV 4D-flow CMR reproducibility, and 3) to compare TR grade by 4D-flow CMR to TR grade by echocardiography. METHODS: TR was assessed by both 4D-flow CMR and echocardiography in 21 healthy subjects (41.2 ± 10.5 yrs., female 7 (33%)) and 67 RV pressure-load patients (42.7 ± 17.0 yrs., female 32 (48%)). The CMR protocol included 4D-flow CMR measurement across the TV, 2D-flow measurement across the PV and conventional planimetric measurements. TR grading on echocardiographic images was performed based on the international recommendations. Bland-Altman analysis and intra-class correlation coefficients (ICC) were used to asses correlations and agreement. RESULTS: TV effective flow measured by 4D-flow CMR showed good correlation and agreement with PV effective flow measured by 2D-flow CMR with ICC = 0.899 (p < 0.001) and mean difference of -1.79 ml [limits of agreement -20.39 to 16.81] (p = 0.084). Intra-observer agreement for effective flow (ICC = 0.981; mean difference - 1.51 ml [-12.88 to 9.86]) and regurgitant fraction (ICC = 0.910; mean difference 1.08% [-7.90; 10.06]) was good. Inter-observer agreement for effective flow (ICC = 0.935; mean difference 2.12 ml [-15.24 to 19.48]) and regurgitant fraction (ICC = 0.968; mean difference 1.10% [-7.96 to 5.76]) were comparable. In 25/65 (38.5%) TR grade differed by at least 1 grade using 4D-flow CMR compared to echocardiography. CONCLUSION: TV effective flow derived from 4D-flow CMR showed excellent correlation to PV effective flow derived from 2D-flow CMR, and was reproducible to measure TV flow and regurgitation. Twenty-five out of 65 patients (38.5%) were classified differently by at least one TR grade using 4D-flow CMR compared to echocardiography.

Left ventricular function and exercise capacity after arterial switch operation for transposition of the great arteries: a systematic review and meta-analysis.

BACKGROUND: The arterial switch operation for transposition of the great arteries was initially believed to be an anatomical correction. Recent evidence shows reduced exercise capacity and left ventricular function in varying degrees in the long term after an arterial switch operation. OBJECTIVE: To perform a meta-analysis on long-term exercise capacity and left ventricular ejection fraction after an arterial switch operation. METHODS: A literature search was performed to cover all studies on patients who had undergone a minimum of 6 years of follow-up that reported either left ventricular ejection fraction, peak oxygen uptake, peak workload, and/or peak heart rate. A meta-analysis was performed if more than three studies reported the outcome of interest. RESULTS: A total of 21 studies reported on the outcomes of interest. Oxygen uptake was consistently lower in patients who had undergone an arterial switch operation compared with healthy controls, with a pooled average peak oxygen uptake of 87.5±2.9% of predicted. The peak heart rate was also lower compared with that of controls, at 92±2% of predicted. Peak workload was significantly reduced in two studies. Pooled left ventricular ejection fraction was normal at 60.7±7.2%. CONCLUSION: Exercise capacity is reduced and left ventricular ejection fraction is preserved in the long term after an arterial switch operation for transposition of the great arteries.

Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin-angiotensin-aldosterone system (REDEFINE) trial: Rationale and design of a randomized, double-blind, placebo-controlled clinical trial.

Renin-angiotensin-aldosterone system (RAAS) inhibition with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors is beneficial in patients with acquired left ventricular dysfunction. Adult patients with tetralogy of Fallot (TOF) with right ventricular (RV) dysfunction are at high risk for heart failure, arrhythmias, and sudden cardiac death. However, the efficacy of RAAS inhibition has not been established in these patients. METHODS: The REDEFINE is an investigator-initiated, multicenter, prospective, randomized, double-blind, placebo-controlled trial to study the effects of the angiotensin II receptor blocker losartan (target dosage of 150 mg once daily) in adult patients with TOF. Patients with RV dysfunction in the absence of severe valvular dysfunction are eligible for inclusion. The primary end point is the change in RV ejection fraction after 18 to 24 months, as measured by cardiovascular magnetic resonance imaging. In addition, laboratory measurements, echocardiography, and cardiopulmonary exercise testing are performed. CONCLUSION: The REDEFINE trial will study the effects of RAAS inhibition with losartan in TOF patients with RV dysfunction.

Regional right ventricular remodeling and function in children with idiopathic pulmonary arterial hypertension vs those with pulmonary valve stenosis: Insights into mechanics of right ventricular dysfunction.

BACKGROUND: Right ventricular (RV) pressure overload in the context of pulmonary stenosis (PS) has a much better prognosis than in the context of idiopathic pulmonary arterial hypertension (iPAH), which may be related to differences in global and regional RV remodeling and systolic function. We compared RV mechanics in children with PS to those with iPAH, aiming to identify mechanisms and markers of RV dysfunction. METHODS: Eighteen controls, 18 iPAH and 16 PS patients were retrospectively studied. Age, BSA, and sex distribution were comparable. Two-dimensional echocardiography, blood flow and tissue Doppler, and longitudinal RV deformation were analyzed. ANCOVA-including RV systolic pressure (RVSP) and length as covariates-was used to compare patient groups. RESULTS: RV systolic pressure was higher in iPAH vs PS (96.8±25.4 vs 75.4±18.9 mm Hg, P=.011). Compared to controls, PS patients showed mild dilation (P<.01) and decreased longitudinal deformation (P<.001) at the RV apex. Compared to both PS and controls, iPAH patients showed marked spherical RV dilation (P<.001), reduced global, RV free wall and septal longitudinal deformation (iPAH -22.07%±4.35% vs controls -28.18%±1.69%; -9.98%±4.30% vs -17.45%±2.52%; P<.001) and RV postsystolic shortening (P<.001). RV transverse shortening (radial performance) was increased in PS (31.75%±10.35%; P<.001) but reduced in iPAH (-1.62%±11.11% vs controls 12.00%±7.74%; P<.001). CONCLUSION: Children with iPAH demonstrate adverse global and regional RV remodeling and mechanics compared to those with PS. Mechanisms of RV systolic dysfunction in iPAH include decreased longitudinal deformation, decreased or absent transverse shortening, and postsystolic shortening. These markers may be useful to identify children at risk of RV failure.

Secundum atrial septal defect is associated with reduced survival in adult men.

AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients. METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43). CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.

Unnatural history of tetralogy of Fallot: prospective follow-up of 40 years after surgical correction.

BACKGROUND: Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. METHODS AND RESULTS: This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31-43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2-13.4). CONCLUSIONS: Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.

Advances in cardiac magnetic resonance imaging of congenital heart disease.

Due to advances in cardiac surgery, survival of patients with congenital heart disease has increased considerably during the past decades. Many of these patients require repeated cardiovascular magnetic resonance imaging to assess cardiac anatomy and function. In the past decade, technological advances have enabled faster and more robust cardiovascular magnetic resonance with improved image quality and spatial as well as temporal resolution. This review aims to provide an overview of advances in cardiovascular magnetic resonance hardware and acquisition techniques relevant to both pediatric and adult patients with congenital heart disease and discusses the techniques used to assess function, anatomy, flow and tissue characterization.

The natural and unnatural history of the Mustard procedure: long-term outcome up to 40 years.

AIMS: To describe long-term survival, clinical outcome and ventricular systolic function in a longitudinally followed cohort of patients after Mustard repair for transposition of the great arteries (TGA). There is serious concern about the long-term outcome after Mustard repair. METHODS AND RESULTS: This longitudinal single-centre study consisted of 91 consecutive patients, who underwent Mustard repair before 1980, at age <15 years, and were evaluated in-hospital every 10 years. Survival status was obtained of 86 patients. Median follow-up was 35 (IQR 34-38) years. Cumulative survival was 84% after 10 years, 80% after 20 years, 77% after 30 years, and 68% after 39 years. Cumulative survival free of events (i.e. heart transplantation, arrhythmias, reintervention, and heart failure) was 19% after 39 years. Reinterventions were mainly required for baffle-related problems. Supraventricular and ventricular arrhythmias occurred in 28 and 6% of the patients, respectively. Pacemaker and/or ICD implantation was performed in 39%. Fifty survivors participated in the current in-hospital investigation including electrocardiography, 2D-echocardiography, cardiopulmonary-exercise testing, NT-proBNP measurement, Holter monitoring, and cardiac magnetic resonance. Right ventricular systolic function was impaired in all but one patient at last follow-up, and 14% developed heart failure in the last decade. NT-proBNP levels [median 31.6 (IQR 22.3-53.2) pmol/L] were elevated in 92% of the patients. Early postoperative arrhythmias were a predictor for late arrhythmias [HR 3.8 (95% CI 1.5-9.5)], and development of heart failure [HR 8.1 (95% CI 2.2-30.7)]. Also older age at operation was a predictor for heart failure [HR 1.26 (95% CI 1.0-1.6)]. CONCLUSION: Long-term survival after Mustard repair is clearly diminished and morbidity is substantial. Early postoperative arrhythmias are a predictor for heart failure and late arrhythmias.

Common genetic variants improve risk stratification after the atrial switch operation for transposition of the great arteries.

BACKGROUND: Clinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients. METHODS AND RESULTS: This multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24-35] years) for 13 (IQR 9-16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant (p < 1 × 10-8) locus and 18 suggestive loci (p < 1 × 10-5). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10-5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17-1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone (p = 2 × 10-16, C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5-20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively. CONCLUSIONS: Common genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial.

The prevalence of adult congenital heart disease, results from a systematic review and evidence based calculation.

PURPOSE: The prevalence of adult patients with congenital heart disease (CHD) has been reported with a high degree of variability. Prevalence estimates have been calculated using birth rate, birth prevalence, and assumed survival and derived from large administrative databases. To report more robust prevalence estimate, we performed a systematic review for studies concerning CHD prevalence in adults. Moreover, to diminish bias of calculated estimates, we conducted an evidence-based calculation for the Netherlands. METHODS: A systematic database search was performed to identify reports on the prevalence of adult CHD. Bicuspid aortic valve, mitral valve prolapse, Marfan syndrome, cardiomyopathy, congenital arrhythmia, and spontaneously closed defects were excluded. In addition, CHD prevalence was calculated using birth rate, birth prevalence, and survival estimates. RESULTS: Our search yielded 10 publications on the prevalence of CHD in adults. Four reported results from population wide cross-sectional data, whereas in 6, prevalence was calculated. Mean prevalence reported by empirical studies was 3,562 per million when unspecified lesions were included and 2,297 per million when these were excluded. Mean prevalence derived from calculation was 3,536. Our calculated estimate was 3,228 per million adults. Taking these estimates as well as the limitations inherent to their derivation into consideration, the prevalence of CHD in the adult population is approximately 3,000 per million adults. CONCLUSION: This systematic review presents a comprehensive overview of publications on the prevalence of CHD in adults. The best available evidence suggests that overall prevalence of CHD in the adult population is in the region of 3,000 per million.

Turning 18 with congenital heart disease: prediction of infective endocarditis based on a large population.

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.

Baffle Complications in Adults After Atrial Switch for Transposition of the Great Arteries.

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.

Medication in adults after atrial switch for transposition of the great arteries: clinical practice and recommendations.

AIMS: Heart failure is the main threat to long-term health in adults with transposition of the great arteries (TGA) corrected by an atrial switch operation (AtrSO). Current guidelines refrain from recommending heart failure medication in TGA-AtrSO, as there is insufficient data to support the hypothesis that it is beneficial. Medication is therefore prescribed based on personal judgements. We aimed to evaluate medication use in TGA-AtrSO patients and examine the association of use of renin-angiotensin-aldosterone system (RAAS) inhibitors and ß-blockers with long-term survival. METHODS AND RESULTS: We identified 150 TGA-AtrSO patients [median age 30 years (interquartile range 25-35), 63% male] included in the CONCOR registry from five tertiary medical centres with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006-2014. Use of RAAS inhibitors, ß-blockers, and diuretics increased with age, from, respectively, 21% [95% confidence interval (CI) 14-40], 12% (95% CI 7-21), and 3% (95% CI 2-7) at age 25, to 49% (95% CI 38-60), 51% (95% CI 38-63), and 41% (95% CI 29-54) at age 45. Time-varying Cox marginal structural models that adjusted for confounding medication showed a lower mortality risk with use of RAAS inhibitors and ß-blockers in symptomatic patients [hazard ratio (HR) = 0.13 (95% CI 0.03-0.73); P = 0.020 and HR = 0.12 (95% CI 0.02-0.17); P = 0.019, respectively]. However, in the overall cohort, no benefit of RAAS inhibitors and ß-blockers was seen [HR = 0.93 (95% CI 0.24-3.63); P = 0.92 and HR = 0.98 (0.23-4.17); P = 0.98, respectively]. CONCLUSION: The use of heart failure medication is high in TGA-AtrSO patients, although evidence of its benefit is limited. This study showed lower risk of mortality with use of RAAS inhibitors and ß-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and ß-blockers in symptomatic, but not asymptomatic patients.

Right ventricular quantification in clinical practice: two-dimensional vs. three-dimensional echocardiography compared with cardiac magnetic resonance imaging.

AIMS: To establish the additional value of three-dimensional echocardiography (3D echo) for assessment of right ventricular (RV) size and function in patients with congenital heart disease (CHD) in everyday clinical practice, the accuracy and reproducibility of 3D echo were compared with conventional two-dimensional echocardiography (2D echo) and cardiac magnetic resonance (CMR) imaging as reference. METHODS AND RESULTS: Patients with CHD and primarily affected right ventricles (n = 62), patients with CHD and primarily affected left ventricles (LV group, n = 27), and healthy controls (n = 31) were studied. 2D echo-, 3D echo- and CMR data sets were obtained. Moderate correlations were found between RV dimensions by 2D echo and CMR-derived RV end-diastolic volumes (r = 0.32-0.77). The correlations between RV volumes obtained by 3D echo and CMR imaging were better (r = 0.71-0.97) than the 2D echo-derived correlations (P < 0.001). Only the 2D echo-derived RV inlet diameter correlated better in healthy controls than in the RV group. Receiver operating characteristic curve analysis revealed that 3D echo-derived end-diastolic volume best identified RV dysfunction (sensitivity 95% and specificity 100%). The 3D echo-derived measurements were as reproducible as the 2D echo-derived measurements (n = 37, coefficients of variation ranging from 5 to 19%), with tricuspid annular plane systolic excursion being the most reproducible measurement (coefficient of variation of 6%). CONCLUSION: 3D echo improved quantitative RV size and function assessment compared with 2D echo in patients as well as in healthy controls. Everyday clinical use of 3D echo for RV assessment can be reality with the currently available software and provides incremental benefit in assessment of the right ventricle.

Mortality in adult congenital heart disease.

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.

Clinical Course Long After Atrial Switch: A Novel Risk Score for Major Clinical Events.

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.