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Background: Predicting heart failure events in patients with a systemic right ventricle (sRV) due to transposition of the great arteries (TGA) is important for timely intensification of follow-up. This study assessed the value of strain compared with currently used parameters as predictor for heart failure-free survival in patients with sRV., Methods: In participants of a multicentre trial, speckle-tracking echocardiography (STE) was performed to assess global longitudinal strain (GLS), mechanical dispersion (MD), and postsystolic shortening (PSS). Cox regression was used to determine the association of STE parameters with the combined end point of progression of heart failure and death, compared with cardiovascular magnetic resonance (CMR) and computed tomography (CT) derived parameters., Results: Echocardiograms of 60 patients were analyzed (mean age 34 ± 11 years, 65% male, 35% congenitally corrected TGA). Mean GLS was -13.5 ± 2.9%, median MD was 49 (interquartile range [IQR] 30-76) ms, and 14 patients (23%) had PSS. During a median 8 (IQR 7-9) years, 15 patients (25%) met the end point. GLS, MD, and PSS were all associated with heart failure-free survival in univariable analysis. After correction for age, only GLS (optimal cutoff > -10.5%) and CMR/CT-derived sRV ejection fraction (optimal cutoff < 30%) remained associated with heart failure-free survival: hazard ratio (HR) 8.27, 95% confidence interval (CI) 2.50-27.41 (P < 0.001), and HR 4.34, 95% CI 1.48-12.74 (P = 0.007), respectively). Combining GLS and ejection fraction improved prediction, with patients with both GLS > -10.5% and sRV ejection fraction < 30% at highest risk (HR 19.69, 95% CI 4.90-79.13; P < 0.001)., Conclusions: The predictive value of GLS was similar to that of CMR/CT-derived ejection fraction. The combination of GLS and ejection fraction identified patients at highest risk of heart failure and death. Easily available STE parameters can be used to guide follow-up intensity and can be integrated into future risk prediction scores., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: An anomalous coronary artery is reported in 2% to 23% of patients with tetralogy of Fallot (TOF). Knowledge of coronary anatomy prior to corrective surgery is vital to avoid damage to vessels crossing the right ventricular outflow tract (RVOT). A meta-analysis on the prevalence of anomalous coronary arteries in TOF is lacking to date. Here, an overview of coronary anomalies in TOF is provided and implications for patient management are discussed., Methods: PubMed, Embase and Web of Science were searched. Analysis was done using Revman 5.3 (Cochrane Community, London). The primary analysis focused on the origin and proximal course of the right and left coronary arteries. In addition, the prevalence of large conus arteries and coronary arteriovenous fistulas (CAVF) was calculated., Results: Twenty-eight studies, encompassing 6956 patients, were included; 6% of TOF patients have an anomalous coronary artery. Hereof, 72% cross the RVOT; the majority of the remaining 28% courses behind the aorta. Six percent of patients have a large conus artery and 4% a CAVF. Other coronary anomalies include a left or right coronary artery from the pulmonary trunk or left or right pulmonary artery, coronary tree hypoplasia and anastomoses between coronary and bronchial arteries., Conclusions: The prevalence of coronary anomalies in TOF is 4-6%. In patients with an anomalous coronary artery, 72% cross the RVOT. The combined risk of encountering an anomalous coronary artery or a large conus artery crossing the RVOT is 10.3%. Coronary anatomy should be defined before surgery and the surgical approach adapted accordingly., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

Patients presenting with chest pain suggestive of coronary artery disease (CAD) who at coronary arteriography appear to be free of obstructive disease have presented a diagnostic and therapeutic challenge since the 1970's. Studies in female patient populations have suggested that this is predominantly a women's syndrome usually caused by microvascular endothelial dependent and independent dysfunction. A critical review of the literature focusing on studies including both women and men revealed that apart from a higher incidence of this syndrome in women there are no clinical relevant differences between both sexes. In women a lower coronary flow reserve has been reported but this appears to be mainly due to a higher basal flow. Important questions with regard to the clinical implications of microvascular dysfunction have yet to be resolved in studies involving women as well as men in which a distinction is made between patients with normal coronary arteries and those with nonobstructive disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: In the VAL-SERVE (Valsartan in Systemic Right Ventricle) trial, three-year valsartan treatment improved systemic ventricular function only in symptomatic patients with congenitally or with an atrial switch corrected transposition of the great arteries. The aim of the current study was to investigate the longer-term clinical outcomes after valsartan treatment., Methods: From 2006 to 2009, 88 adults were randomly allocated 1:1 to either valsartan or placebo for three consecutive years. Endpoints were defined as overall survival and freedom from clinical events (arrhythmia, heart failure, tricuspid valve surgery, death)., Results: Cardiac drug use and median follow-up after trial close-out (8.3 years) was similar between the randomization groups. Six patients (valsartan n = 3, placebo n = 3) died in 364 and 365 person-years (P = 0.999). No difference in the composite or separate clinical endpoints was found between the randomization groups, with corresponding long-term event-free survival rates of 50% and 34%. Nevertheless, in symptomatic patients valsartan significantly reduced the risk for events compared to placebo (HR 0.37, 95% CI 0.17-0.92). Analysis for repeated events and on-treatment analysis with any renin-angiotensin-aldosterone-system-inhibitor did not alter these results., Conclusions: Valsartan treatment in systemic RV patients did not result in improved survival at longer-term follow-up, but was associated with decreased risk of events in symptomatic patients., (Copyright © 2018. Published by Elsevier B.V.)

Background: Adult post-coarctectomy patients (CoA) demonstrate increased cardiovascular morbidity and mortality. The carotid intima-media thickness (CIMT), a marker for atherosclerosis, is increased in CoA. The aim was to evaluate the predictive value of CIMT for cardiovascular events., Methods and Results: Consecutive CoA patients were prospectively studied during 10.1±0.7 years follow-up. At baseline and follow-up echocardiography, MRI imaging and CIMT imaging were performed, while cardiovascular events were registered. CIMT data were compared with controls. The composite endpoint included: myocardial infarction, cerebrovascular events (CVAs), and (sudden) cardiac death. 160 CoA patients were studied (median age 31.7 (18-74 years), 64% male). Events occurred in 11 patients (7%), five (3%) with myocardial infarction, four (2.5%) with an ischemic CVA and two (1%) died suddenly. An increased CIMT (≥0.8 mm) (HR=15.44, P=<0.001) was predictive for the occurrence of cardiovascular events. Baseline CIMT was increased in CoA compared to controls (0.64±0.12 mm vs 0.57±0.07 mm, P=0.005). CIMT progression rates were similar (0.0091±0.016 mm/year vs 0.0097±0.018 mm/year, P=0.84). Signs of atherosclerosis occurred significantly earlier in CoA patients., Conclusion: The contemporary cardiovascular event rate in CoA is 11% in 10 years. Atherosclerosis seems to appear earlier in CoA patients as compared to controls. CoA patients with a CIMT exceeding 0.8mm have a fifteen fold higher cardiovascular risk. CIMT seems to be a useful tool for cardiovascular risk assessment in CoA., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: To study the changes over time in biventricular size and function, and clinical parameters in patients after repair of tetralogy of Fallot (TOF) without subsequent pulmonary valve replacement (PVR)., Methods: We prospectively included 78 non-PVR patients (age 20(6-60)years at baseline), who were studied twice with a 5-year interval. Patients underwent magnetic resonance imaging for assessment of biventricular size and function. Exercise testing and electrocardiography were performed to determine peak oxygen uptake (peak VO2) and QRS duration. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was assessed additionally., Results: Pulmonary regurgitation (PR), right ventricular (RV) volumes and QRS duration increased during 5-year follow-up (RV end-diastolic volume (EDV) 130 ± 30 ml/m(2) to 138 ± 34 ml/m(2); QRS 132 ± 27 msec to 139 ± 27 msec); peak VO2 decreased (96 ± 19% to 91 ± 17%). RV ejection fraction, RV effective stroke volume (eff.SV), and NT-proBNP levels remained unchanged. The slope of RVEDV increase was 1.6 ± 3.0 ml/m(2)/year, and depended on RVeff.SV, not on RVEDV, at baseline. Increase in RVEDV correlated with increase in QRS duration over time (r=0.28, p=0.016), and with decrease in RV mass/EDV ratio over time (r=-0.42, p<0.001), not with decrease in peak VO2. In subgroup analysis, patients with larger RVs at baseline showed larger increase in PR during follow-up and larger decrease in NYHA class over time., Conclusions: In TOF patients with moderate RV dilatation, RVEDV increased by 1.6 ± 3.0 ml/m(2)/year, irrespective of RV size at baseline, but depended on RVeff.SV at baseline. Despite limited progression in RV size, unfavourable changes occurred during 5 years follow-up, which suggests there is a need for close follow-up., (© 2013.)

Background: This study aims to investigate indications and complications of permanent cardiac pacing in adults with congenital heart disease (CHD)., Methods and Results: Two-hundred and seventy-four CHD patients were identified who underwent permanent pacemaker implantation between 1972 and 2009. The indication for pacing was acquired sinus node or AV node conduction disease (63%), sinus node or AV node conduction disease after cardiac surgery (28%), and drug/arrhythmia-related indications (9%). Patients with complex CHD received a pacemaker at younger age (23 versus 31 years, p<0.0001) and more often received an epicardial pacing system (51% versus 23%, p<0.0001) compared to those with simple or moderate CHD. Twenty-nine patients (10.6%) had a periprocedural complication during the primary pacemaker implantation (general population: 5.2%). The most common acute complications were lead dysfunction (4.0%), bleeding (2.6%), pocket infection (1.5%) and pneumothorax (1.5%). During a median follow-up of 12 years, pacemaker-related complications requiring intervention occurred in 95 patients (34.6%). The most common late pacemaker-related complications included lead failure (24.8%), pacemaker dysfunction/early battery depletion (5.1%), pacemaker migration (4.7%) and erosion (4.7%). Pacemaker implantation at younger age (<18 years) was an independent predictor of late pacemaker-related complication (adjusted hazard ratio 1.68, 95% confidence interval 1.07 to 2.63, p=0.023)., Conclusions: The risk of periprocedural complications seems higher in the CHD population compared to the general population and more than one-third of CHD patients encountered a pacemaker-related complication during long-term follow-up. This risk increases for those who receive a pacemaker at younger age., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: The arterial switch operation is the current treatment for transposition of the great arteries. Long-term outcome mainly depends on the patency of the transferred coronary arteries. This study assessed the presence of abnormal coronary findings and neoaortic root dilation late after arterial switch operation., Methods: In 30 adult patients after arterial switch operation (22 men, 22 ± 3 years), computed tomography angiography was performed to assess the coronary anatomy and abnormal coronary findings, defined as significant stenosis, interarterial coronary course, and acute angled coronary origins. Neoaortic root dimensions and coronary takeoff height were also assessed., Results: The most common coronary anatomy pattern was found in 24 of 30 patients. Variant anatomy patterns were seen in 6 patients (5 with aberrant circumflex artery, 1 with a single ostium). The prevalence of abnormal coronary findings was higher in patients with variant coronary pattern as compared with patients with common coronary pattern (100% and 29%, respectively; p = 0.003). In particular, an acute angle of the coronary origin was frequently observed. In patients with an acute angle, larger dimensions of the aortic annulus (p = 0.016) and the sinus of Valsalva (p = 0.002) were observed. Moreover, a higher takeoff of the right (p = 0.030) and left (p = 0.002) coronary ostium was noted in patients with acute angles., Conclusions: Abnormal coronary findings were frequently observed in adult patients after arterial switch operation, especially in patients with a variant coronary anatomy pattern. Neoaortic root dilation and a higher coronary takeoff may explain part of the pathophysiology. Long-term follow-up is needed to determine the clinical significance of these findings., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with moderate pulmonary valve restenosis late after relief of severe pulmonary stenosis (PS) may show decreased exercise tolerance. To elucidate the mechanism of decreased exercise tolerance, we evaluated cardiac response to physical and pharmacological stress in these patients and compared results with those of patients with native moderate PS., Methods: Twenty asymptomatic patients with moderate PS were divided into 2 groups: Group I (late after relief of severe PS, n=9), and Group II (no previous intervention, n=11). All patients underwent an exercise test, dobutamine stress (DS) MRI, and delayed contrast enhanced MRI. The response to physical and pharmacological stress was compared between both groups., Results: Group I showed impaired exercise capacity compared to Group II (VO2max=72.8% ± 3.5% vs. 102.5% ± 16.3%, p<0.001). During DS-MRI, RV-SV increased in Group II, but not in Group I (+13 ± 8 ml, -5 ± 8 ml, p<0.001). RV end-diastolic volume decreased significantly in Group I patients (p=0.006) while it did not significantly change in Group II patients. The amount of RV-SV increase (∆ RV-SV) correlated negatively with the period of moderate PS existence and the current PG in Group I (r=-0.82, p=0.007, and r=-0.68, p=0.04, respectively) but not in Group II (r=0.45, p=0.1, and r=0.40, p=0.2, respectively). Furthermore, ∆ RV-SV correlated negatively with the PG before valvuloplasty (r=-0.76, p=0.02)., Conclusion: Impaired exercise capacity in patients with moderate pulmonary restenosis after relief of severe PS is probably caused by inability to increase RV-SV. Disturbed RV filling properties, worsening in time, might play a role., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Aortic valve dysfunction is common in coarctation patients(CoA). Bicuspid aortic valve (BAV) in CoA is associated with aortic valve stenosis (AS), aortic valve regurgitation (AR), and ascending aortic dilatation. The aim of this study was to evaluate the progression of and predictors for aortic valve dysfunction in CoA., Methods: 96 CoA patients prospectively underwent echocardiography twice between 2001 and 2010. AS was defined as an aortic valve gradient ≥ 20 mmHg, AR as none/minor, or moderate/severe. Aortic dilatation as an ascending aortic diameter ≥ 37 mm., Results: All patients (median age 28.0 years, range 17-61 years; male 57%) were followed with a median follow-up of 7.0 years. Sixty patients (63%) had BAV. At baseline 10 patients had AS (10%, 9 BAV), 6 patients AR (6%, 3 BAV) and 11 patients aortic dilatation (11%, 11 BAV). At follow-up 15 patients had AS (15%, 13 BAV) and 12 patients AR. (13%, 8 BAV). Median AS progression was 1.1 mmHg/5 years (range - 13-28). Determinants for AS at follow-up were age (ß=0.20, P=0.01), aortic dilatation (ß=4.6, P=0.03), and baseline aortic valve gradient (ß=0.93, P<0.001). BAV was predictive for AR. (ß=0.91, P=0.049)., Conclusion: Progression of AS in adult CoA patients is mild in this young population. Older age, aortic dilatation and the baseline aortic valve gradient are determinants for AS at follow-up. BAV is predictive for AR. These findings point towards a common embryological pathway of both valvular and aortic disease in CoA., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Aims: Aortic coarctation (CoA) occurs as a "simple" isolated disorder, and in a more "complex" form, combined with associated congenital cardiac abnormalities. Long term outcome of all CoA patients may be complicated by dilatation of the thoracic aorta. The aim of this study was to quantify progressive aortic dilatation, and identify determinants for progressive aortic dilatation., Methods and Results: Cardiovascular Magnetic Resonance Imaging (CMR) and echocardiographic data of 93 CoA patients were analyzed retrospectively on the progression, and determinants, of progressive thoracic aortic dilatation. Outcome of simple- versus complex CoA patients were compared. 93 CoA patients (mean age 39 ± 12 years, male 59%) were followed with CMR (follow-up 5.3 ± 1.8 years). Twenty-eight patients were classified as simple- and 68 as complex CoA. The mean progression rate of thoracic aortic dilatation was highest in the ascending aorta with 2.2 ± 2.0mm/5 years (range 0-7.2mm/5 years). History of VSD (β=1.77, P=0.004) and an increased left ventricular mass index (β=0.02, P=0.04) were associated with progressive ascending aortic dilatation. Complex CoA patients show an increased progression rate compared to simple CoA patients with 2.4mm/5 years versus 1.5mm/5 years respectively. (P=0.03)., Conclusion: Adult post-coarctectomy patients show an increased mean progression rate of ascending aortic dilatation with 2.2mm/5 years. The progression rate of ascending aortic dilatation is increased in complex CoA patients, as compared to simple CoA patients. These findings point towards a more comprehensive genetic subset of patients with an increased risk for progressive ascending aortic dilatation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial enlargement may reflect ventricular diastolic dysfunction. Although patients with tetralogy of Fallot (TOF) have been studied extensively, little is known about atrial size and function. We assessed bi-atrial size and function in patients after TOF repair, and related them to biventricular systolic and diastolic function, and clinical parameters., Methods: 51 Patients (21 ± 8 years) and 30 healthy controls (31 ± 7 years) were included and underwent magnetic resonance imaging to assess bi-atrial and biventricular size, systolic and diastolic function. Patients also underwent exercise testing, and N-terminal prohormone brain natriuretic peptide (NT-proBNP) assessment., Results: In patients, right atrial (RA) minimal volume (34 ± 8 ml/m(2) vs. 28 ± 8 ml/m(2), p=0.001) and late emptying fraction were increased; RA early emptying fraction was decreased. Patients had longer right ventricular (RV) deceleration time (0.24 ± 0.10 vs. 0.13 ± 0.04, p<0.001), reflecting impaired RV relaxation, and larger RV volumes. Patients with end-diastolic forward flow (EDFF) had larger RA and RV size, abnormal RA emptying, higher NT-proBNP levels, higher VE/VCO2 slope (ventilatory response to carbon dioxide production), and the most abnormal LV diastolic function (impaired compliance). Patients with abnormal RA emptying (reservoir function <30% and pump function >24%) had higher NT-proBNP levels and worse exercise capacity. RA minimal volume was associated with RV end-diastolic volume (r=0.35, p=0.013)., Conclusions: In TOF patients with moderate RV dilatation, abnormal bi-atrial function and biventricular diastolic dysfunction are common. Abnormal RA emptying was associated with signs of impaired clinical condition, as was the presence of EDFF. These parameters, together with RA enlargement, could serve as useful markers for clinically relevant RV diastolic dysfunction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Current surgical strategies that aim at preventing pulmonary regurgitation in patients with corrected tetralogy of Fallot (cToF) may result in a certain grade of residual pulmonary stenosis (PS). The clinical implications of a postoperative residual PS in cToF patients remain unclear. Pulmonary valve replacement (PVR) is frequently needed during follow-up of cToF patients. The aim of the current study was to determine the role of residual PS in the need for PVR during follow-up in cToF patients., Methods: cToF patients were included if clinical follow-up after primary surgical correction had taken place for a minimum of 5 years. Patient characteristics, surgical factors, and postoperative factors were reviewed, with a special focus on the transpulmonic systolic gradient. Cox proportional hazards regression analysis was performed to identify predictors of PVR., Results: Of 171 cToF patients, 71 (41.5%) underwent PVR after 24.2 years (interquartile range, 16.8-31.6 years). Year of birth, older age at corrective operation, and patch use significantly predicted PVR during follow-up. By contrast, a mild residual PS in cToF patients (peak systolic gradient, 15-30 mm Hg) independently reduced the risk of PVR, as compared with patients without PS (hazard ratio, 0.47; p=0.02) and with moderate-to-severe PS (hazard ratio, 0.35; p=0.01)., Conclusions: In addition to the known risks factors for PVR, a postoperative mild residual PS reduces the risk of PVR during follow-up of cToF patients. This finding provides clinical evidence for a conservative PS relief during correction of ToF., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesized 1) that long-term ventricular outcome and exercise capacity would be better in patients with isolated pulmonary valve stenosis (PS) treated with balloon pulmonary valvuloplasty (BPV) than in patients operated for tetralogy of Fallot (TOF), and 2) that ventricular outcome and exercise capacity would not be different in PS patients and healthy controls., Methods: We included 21 PS patients after BPV (16.2 ± 5.2 years) and 21 patients operated for TOF (16.6 ± 5.6 years), matching them for gender, age at treatment, and age at study. Patients underwent cardiovascular magnetic resonance (CMR) imaging, exercise testing, 12-lead ECG and 24-hour Holter monitoring for assessment of right ventricular (RV) size and function, pulmonary regurgitation (PR), exercise capacity and electrocardiographic status. Healthy controls for CMR imaging and exercise testing were matched for gender and age at study., Results: RV volumes and PR percentage were significantly larger in TOF patients than in PS patients; biventricular ejection fraction (EF) was not different. PR was mild in most PS patients. RV end-systolic volume was significantly larger in PS patients than in healthy controls; RVEF was significantly lower. Both patient groups had similar exercise test results. Peak workload and VO(2) max. were significantly lower in PS patients than in healthy controls., Conclusions: Longstanding mild PR in PS patients can lead to an enlarged RV, reduced RV function and reduced exercise capacity. Despite more PR and larger RV volumes in TOF patients, exercise capacity and biventricular function are similar in both patient groups., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established., Methods: We designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries., Conclusion: This large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown., Methods: We designed a prospective, multicenter, randomized open label trial to study the effect of bosentan in Fontan patients. The primary endpoint will be the change in maximum exercise capacity (peak V'O2)., Conclusion: We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at (http://www.elsevier.com/locate/withdrawalpolicy., (Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Background: To our knowledge, studies evaluating the quality of life (QoL) in patients with a history of acute pulmonary embolism (PE) are not available, even though QoL is a key outcome component of medical care and a predictor of disease-specific prognosis., Methods: As part of a large follow-up study, the Short Form 36 (SF-36) was presented to consecutive patients who had survived one or more episodes of acute PE. The results of all nine subscales of the SF-36 were compared with sex- and age-adjusted Dutch population norms. Single and multivariate analyses were performed to identify independent determinants of the QoL in our study population., Results: The SF-36 was completed by 392 patients. Except for the health change subscale, patients had substantially lower QoL than population norms on all eight remaining subscales. After multivariate analysis, the time interval between the last thromboembolic episode and study inclusion was inversely related to QoL, and significant determinants of poor QoL were prior PE, age, obesity, active malignancy, and cardiopulmonary comorbid conditions. Regression models that included all identified significant determinants proved to be quite modest predictors for QoL in the individual patient. Awareness of illness, coping mechanisms, and self-management behavior might be additional important indicators of QoL in our study population but require further investigation., Conclusion: We identified several PE- and non-PE-related determinants of QoL in patients with a history of acute PE, which is impaired compared with sex- and age-adjusted population norms. QoL after acute PE should be studied more extensively and added as a standard measure to outcome studies.

Background: The potential use of the ECG for monitoring treatment effects in patients with pulmonary arterial hypertension (PAH) has not been investigated. We evaluated whether the ECG is useful for monitoring treatment response based on changes in pulmonary vascular resistance (PVR)., Methods: An ECG was recorded in 81 PAH patients at the time of diagnostic right heart catheterization and after 1 year of treatment. Patients were treated according to the guidelines. Patients were divided into two groups based on PVR (ie, < 500 or > 500 dyne x s x cm(-5)). A positive treatment response was defined as a > 25% decrease in PVR to an absolute PVR of < 500 dyne x s x cm(-5)., Results: At baseline, the 19 patients with a PVR of < 500 dyne x s x cm(-5) had a significantly lower P amplitude in lead II, a less rightward oriented QRS axis, and a more rightward T axis than the 62 patients with a PVR of > 500 dyne x s x cm(-5). Overall (n = 81), the mean (+/- SD) change in PVR was -143 +/- 360 dyne x s x cm(-5) after 1 year of treatment (p < 0.001). Twelve patients (19%) with a baseline PVR of > 500 dyne x s x cm(-5) were classified as responders. Receiver operating characteristic analysis determined that the P amplitude in lead II (area under the curve [AUC], 0.80; 95% confidence interval [CI], 0.67 to 0.94; p < 0.01), QRS axis (AUC, 0.70; 95% CI, 0.52 to 0.89; p = 0.03), and T axis (AUC, 0.90; 95% CI, 0.82 to 0.97; p < 0.001) were important determinants of treatment response. The presence of a P amplitude in lead II of < 0.175 mV and a T axis of >or= 25 degrees combined had a positive and negative predictive value for treatment response of 0.81 (95% CI, 0.37 to 0.96) and 0.94 (95% CI, 0.86 to 0.99), respectively., Conclusions: Routine ECG evaluation can be an important contribution in the assessment of treatment response in PAH patients.

Background: Pregnancy in women with congenital aortic stenosis (AS) is associated with increased cardiac complications. Data on non-cardiac complications are limited, and this information is crucial for prenatal counselling and perinatal care. The aim of this study was to present the maternal and perinatal outcome of pregnancy in women with congenital AS., Methods: By review of the Dutch CONCOR national registry and a local Belgian tertiary care centre database, 35 women with congenital AS with a history of completed pregnancy before aortic valve replacement were enrolled in this study. Medical history and maternal and perinatal outcome were determined., Results: Thirty-five women had 58 pregnancies resulting in 53 successful pregnancies, three miscarriages, and two abortions. The most serious cardiac complications were heart failure (n=2, 3.8%) and atrial arrhythmia (n=3, 5.7%). Although cardiac complications were present (9.4%), obstetric (22.6%) and perinatal (24.5%) complications were observed more often. A total of six pregnancies (11.3%) were complicated by hypertension-related disorders, including one case of eclampsia. Furthermore, 7 premature births (13.2%) and 7 small-for-gestational-age births (13.2%) were encountered. Pregnancy in women with severe AS was characterized by an increased incidence of heart failure and premature labour, and shorter pregnancy duration. Older women (>30 years) were at increased risk of perinatal events (odds ratio 4.38, 95% confidence interval 1.02 to 18.81)., Conclusions: Pregnancy is generally well tolerated in women with congenital AS. Importantly, an excess of obstetric and perinatal complications was found, requiring more meticulous attention.

Objective: To assess the effect of pulmonary valve replacement (PVR) on the repolarization of patients with tetralogy of Fallot., Background: Pulmonary valve regurgitation may cause right ventricular failure in adult patients with Fallot's tetralogy. In these patients, prolonged depolarization and disturbed repolarization are associated with ventricular arrhythmias and sudden cardiac death., Methods: Thirty Fallot patients (age 32+/-9 years, 19 male) eligible for PVR were studied with cardiac magnetic resonance imaging (CMR) before and 6 months after PVR. Electrocardiograms obtained during initial and follow-up CMR were analyzed and occurrence of ventricular arrhythmias was studied., Results: Right ventricular end-diastolic volume (RV EDV) decreased from 322+/-87 to 215+/-57 ml after PVR (P<0.0001). The spatial QRS-T angle normalized from 117+/-34 to 100+/-35 degrees , P=0.0004 (normal angle <105 degrees). QT dispersion and T-wave complexity did not change significantly. T-wave amplitude decreased from 376+/-121 to 329+/-100 microV (P=0.01). T-wave area decreased from 43+/-15 to 38+/-13 microV s (P=0.02). Decreases in T-wave amplitude and area were most prominent in the right precordial leads overlying the RV. Three patients had sustained ventricular arrhythmias and one patient died suddenly. These patients had a QRS duration >160 ms. No severe ventricular arrhythmias were found in patients with a RV EDV <220 ml, QRS-T angle <100 degrees , QT dispersion <60 ms or T-wave complexity <0.30., Conclusion: Normal repolarization indices may be associated with the absence of severe ventricular arrhythmias. PVR in Fallot patients with dilated right ventricles has a beneficial effect on electrocardiographic indices of repolarization heterogeneity.

Background: Predicting changes in right ventricular (RV) size and function after pulmonary valve replacement (PVR) is important for timely reintervention in adult tetralogy of Fallot patients., Methods: We analyzed the influence of pulmonary regurgitation severity and RV size and function before PVR on the outcome of RV size and function after PVR in 27 adult Fallot patients who had cardiac magnetic resonance imaging before and after PVR. RV dimensions were indexed for body surface area., Results: Pulmonary regurgitation (48% +/- 11% of RV stroke volume) was not related to RV dimensions and function before PVR. Moreover, severity of pulmonary regurgitation did not influence changes in RV dimensions after PVR. The indexed RV end-systolic volume before PVR (mean, 98 mL/m2; range, 52 to 235 mL/m2) best predicted the indexed RV end-systolic volume after PVR (mean, 59 mL/m2; range, 24 to 132 mL/m2, r = 0.78, p < 0.001) and the indexed RV end-diastolic volume after PVR (mean, 107 mL/m2; range, 70 to 170 mL/m2, r = 0.73, p < 0.001). Baseline RV ejection fraction corrected for valvular insufficiencies and shunting (21% +/- 7%) best predicted the RV ejection fraction after PVR (43% +/- 10%, r = 0.77, p < 0.001)., Conclusions: Timing of PVR should be based on indexed RV end-systolic volume and corrected RV ejection fraction rather than on severity of pulmonary regurgitation.

The aim was to validate a magnetic resonance high-resolution, phase-contrast sequence for quantifying flow in small and large vessels and to demonstrate its feasibility to measure flow in coronary artery bypass grafts. A breathhold, echo planar imaging (EPI) sequence was developed and validated in a flow phantom using a fast field echo (FFE) sequence as reference. In 17 volunteers aortic flow was measured using both sequences. In 5 patients flow in the left internal mammary artery (LIMA) and aorta was measured at rest and during adenosine stress, and coronary flow reserve (CFR) was calculated; in 7 patients, vein graft flow velocity was measured. In the flow phantom measurements, the EPI sequence yielded an excellent correlation with the FFE sequence (r = 0.99; p < 0.001 for all parameters). In healthy volunteers, aortic volume flow correlated well (r = 0.88; p < 0.01), with a minor overestimation. It was feasible to measure flow velocity in the LIMA and vein grafts of the 12 patients. The high-resolution, breathhold cardiovascular magnetic resonance velocity-encoded sequence correlated well with a free-breathing, FFE sequence in a flow phantom and in the aortae of healthy volunteers. Using the EPI sequence, it is feasible to measure flow velocity in both LIMA and vein grafts, and in the aorta.

Background: In patients with an intra-atrial correction for transposition of the great arteries (TGA) an abnormal response to stress testing is common. However, hemodynamic responses may vary substantially when different stress tests are used. We compared the hemodynamic response to dobutamine stress with the response to physical exercise in patients and controls., Methods: Thirty-nine patients and 25 age/sex-matched control subjects underwent either dobutamine stress (15 microg/kg/min) or submaximal physical exercise cardiovascular magnetic resonance. End-systolic and end-diastolic right ventricular volumes (ESV; EDV) were determined. Five representative patients underwent both stress tests. For these patients, wall thickening reserve was calculated as systolic wall thickening during stress minus systolic wall thickening at rest., Results: In controls, dobutamine stress and physical exercise showed similar responses: stroke volume, cardiac output, and ejection fraction increased significantly, whereas ESV decreased significantly and EDV was unchanged. In patients, stroke volume did not increase with either dobutamine or exercise (-8.6% vs. 2.9%). Ejection fraction increased significantly with dobutamine (16%, p < 0.001) but tended to decrease during exercise (-2.1%, P = NS). EDV and ESV decreased during dobutamine but were unchanged during exercise. (-22% vs. 5.0%, P < 0.001; -36% vs. 9.0%, P < 0.01 respectively). Wall thickening reserve was higher with dobutamine than with exercise (0.9 mm vs. -0.6 mm, P = 0.02)., Conclusion: Dobutamine stress and physical exercise cannot be used interchangeably for assessment of systolic and diastolic function in patients with an intra-atrial correction for TGA. This may have consequences for the use of different stress CMR approaches in the clinical setting.

Cardiovascular magnetic resonance (CMR) with flow velocity mapping has emerged as a noninvasive method to measure flow in saphenous vein coronary artery bypass grafts. The aim of the current study was to retrospectively test two previously described analysis methods on a large CMR data set and to compare their diagnostic accuracy in detecting diseased vein grafts. In 125 vein grafts of 68 patients, volume flow parameters (volume flow, systolic and diastolic peak flow, diastolic-to-systolic flow ratio at rest and during adenosine stress, and flow reserve) were derived from the velocity maps. Method 1 implemented basal flow < 20 ml/min or flow reserve < 2, yielding a sensitivity and specificity of 70% and 38% in the detection of a diseased graft or recipient vessel. Method 2 used receiver operating characteristic (ROC) curve analysis and implemented all significant volume flow parameters in a logistic regression model, yielding a sensitivity of 74% with a specificity of 68% in the detection of a diseased graft or recipient vessel. Evaluating single and sequential grafts separately, this method yielded a sensitivity and specificity of 79% and 87% for single grafts, and 62% and 94% for sequential grafts in the detection of > or = 50% stenosis in grafts or recipient vessels. Cut-off values were formulated for the respective volume flow parameters, which maximally separate grafts with and without > or = 50% stenosis. Using ROC curve analysis with logistic regression the specificity of the analysis method improved considerably. For the current data set the best results were acquired when single and sequential grafts were separately analyzed.

Purpose: Evaluation of different electrocardiographic criteria for left ventricular hypertrophy (ECG-LVH criteria) using left ventricular mass index (LVMI) determined by magnetic resonance imaging (MRI). In addition, the relation between LVMI regression after aortic valve replacement and corresponding ECG changes regarding LVH was studied., Methods: A group of 31 patients with severe aortic valve disease was studied to assess the presence of ECG-LVH and to measure LVMI and LV end-diastolic volume index (LVEDVI); 13 patients were restudied at 9.8 +/- 2.7 months after aortic valve replacement., Results: Three criteria had a sensitivity of 100% (SV1 + RV5 or RV6 > 3.0 mV; SV1 or SV2 + RV5 > or = 3.5 mV; SV1 or SV2 + RV5 or RV6 > 3.5 mV), at the cost of specificity (50%, 44.4% and 44.4%, respectively). The R in I > 1.4 mV had a specificity of 100%, at the cost of both sensitivity and accuracy (13.6% and 54.5%, respectively). The Romhilt-Estes point score system, using > or = 4 points as cut-off value for LVH, provided the overall best accuracy of 79.5%. The number of Romhilt-Estes points also showed the best correlation with LVMI, both before and after aortic valve replacement (r = 0.81 and r = 0.67, respectively)., Conclusions: Substantial differences in sensitivity, specificity, accuracy, and correlation with LVMI were found among several ECG-LVH criteria. No single criterion performed optimally since the highest sensitivity, specificity, accuracy, and correlation with LVMI were found with different criteria. The present study may therefore contribute to a more targeted use of the existing ECG-LVH criteria.