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Background: Inherent to its geometry, echocardiographic imaging of the systemic right ventricle (RV) is challenging. Therefore, echocardiographic assessment of systemic RV function may not always be feasible and/or reproducible in daily practice. Here, we aim to validate the usefulness of a comprehensive range of 32 echocardiographic measurements of systemic RV function in a longitudinal cohort by serial assessment of their correlations with cardiac magnetic resonance (CMR)-derived systemic RV ejection fraction (RVEF). Methods: A single-center, retrospective cohort study was performed. Adult patients with a systemic RV who underwent a combination of both CMR and echocardiography at two different points in time were included. Off-line analysis of echocardiographic images was blinded to off-line CMR analysis and vice versa. In half of the echocardiograms, measurements were repeated by a second observer blinded to the results of the first. Correlations between echocardiographic and CMR measures were assessed with Pearson's correlation coefficient and interobserver agreement was quantified with intraclass correlation coefficients (ICC). Results: Fourteen patients were included, of which 4 had congenitally corrected transposition of the great arteries (ccTGA) and 10 patients had TGA late after an atrial switch operation. Eight patients (57%) were female. There was a mean of 8 years between the first and second imaging assessment. Only global systemic RV function, fractional area change (FAC), and global longitudinal strain (GLS) were consistently, i.e., at both time points, correlated with CMR-RVEF (global RV function: r = -0.77/ r = -0.63; FAC: r = 0.79/ r = 0.67; GLS: r = -0.73/ r = -0.70, all p -values < 0.05). The ICC of GLS (0.82 at t = 1, p = 0.006, 0.77 at t = 2, p = 0.024) was higher than the ICC of FAC (0.35 at t = 1, p = 0.196, 0.70 at t = 2, p = 0.051) at both time points. Conclusion: GLS appears to be the most robust echocardiographic measurement of systemic RV function with good correlation with CMR-RVEF and reproducibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zandstra, Jongbloed, Widya, ten Harkel, Holman, Mertens, Vliegen, Egorova, Schalij and Kiès.)

Background: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan., Methods and Results: We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (β: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (β: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17)., Conclusions: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Patients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA are prone to heart failure and arrhythmias. This study evaluated feasibility, patient adherence, and satisfaction of a smart technology-based care pathway for heart failure treatment optimization in these patients., Methods and Results: Patients with symptomatic sRV failure eligible for initiation of sacubitril/valsartan were provided with four smartphone compatible devices (blood pressure monitor, weight scale, step counter, and rhythm monitor) and were managed according to a smart technology-based care pathway. Biweekly sacubitril/valsartan titration visits were replaced by electronical visits, patients were advised to continue measurements at least weekly after titration. Data of 24 consecutive sRV patients (median age 47 years, 50% female) who participated in the smart technology-based care pathway were analysed. Median home-hospital distance was 65 km (maximum 227 km). Most patients (20, 83.3%) submitted weekly measurements; 100% submitted prior to electronical visits. Titration conventionally occurs during a hospital visit. By implementing eHealth smart technology, 68 such trips to hospital were replaced by virtual visits facilitated by remote monitoring. An eHealth questionnaire was completed by 22 patients (92%), and 96% expressed satisfaction. After titration, 30 instances of remote adjustment of heart failure medication in addition to scheduled outpatient clinic visits occurred, one (4%) heart failure admission followed, despite ambulant adjustments. Five patients (21%) sent in rhythm registrations ( n  = 17), of these 77% showed sinus rhythm, whereas supraventricular tachycardia was detected in the remaining four registrations., Conclusion: These data suggest that implementation of a smart technology-based care pathway for optimization of medical treatment sRV failure is feasible with high measurement adherence and patient satisfaction., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Objectives: The aim of this study is to describe the significance of symptoms preoperatively and at medium-term follow-up in adolescent and adult patients who underwent surgery of anomalous aortic origin of a coronary artery (AAOCA)., Methods: Consecutive patients who underwent surgery for AAOCA in our tertiary referral centre between 2001 and 2018 were included. Clinical characteristics and symptoms were evaluated and medium-term outcomes were recorded. Symptoms were classified according to the '2019 ESC guidelines on chronic coronary syndromes'., Results: A total of 53 (55% male) patients with mean age of 44 at time of surgery underwent surgical repair of AAOCA. Data on symptoms and events ˃3 months after surgery were available in 34 patients with a median follow-up of 3 years (interquartile range 1.0-5.3). Preoperatively, only 35% patients had typical anginal complaints. After surgical correction of AAOCA, 59% of the patients were free of symptoms, compared to 6% preoperatively (P < 0.001). A total of 3 (9%) patients needed a reoperation/reintervention related to the operated AAOCA. All 3 patients presented postoperatively with novel typical anginal complaints., Conclusions: Adolescent and adult patients with AAOCA present with varying symptoms. Only 35% have typical anginal complaints. Surgical correction of AAOCA reduces the symptoms in the vast majority of patients. One should be aware of potential lesions of the operated coronary artery in patients presenting with typical anginal complaints postoperatively., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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.)

Introduction: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm., Methods: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated., Results: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases., Conclusions: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm., Condensed Abstract: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Maternal heart disease (HD) complicates 1-4 % of pregnancies and is associated with adverse maternal and fetal outcomes. Although vaginal birth is generally recommended in the guidelines, cesarean section (CS) rates in women with HD are often high. Aim of the present study was to evaluate mode of birth and pregnancy outcomes in women with HD in a tertiary care hospital in the Netherlands., Study Design: The study population consisted of 128 consecutive pregnancies in 99 women with HD, managed by a pregnancy heart team between 2012-2017 and ending in births after 24 weeks' gestation. Pregnancy risk was assessed per modified World Health Organization class. Mode of birth (planned and performed) and maternal and fetal complications (cardiovascular events, postpartum hemorrhage, prematurity, small for gestational age and death) were assessed for each pregnancy., Results: Pregnancy risk was classified as modified World Health Organization class I in 23 %, class II in 50 %, class III in 21 % and class IV in 6% of pregnancies. Planned mode of birth was vaginal in 114 pregnancies (89 %) and CS in 14 (11 %; nine for obstetric and five for cardiac indication). An unplanned CS was performed in 18 pregnancies (16 %; 16 for obstetric and two for cardiac indications). Overall mode of birth was vaginal in 75 % and CS in 25 %. Twelve cardiovascular events occurred in eight pregnancies (6 %), postpartum hemorrhage in nine (7 %) and small for gestational age in 14 (11 %). No maternal or fetal deaths occurred., Conclusions: Findings of this study indicate that - given that pregnancies are managed and mode of birth is meticulously planned by a multidisciplinary pregnancy heart team - vaginal birth is a suitable option for women with HD., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2020 Elsevier B.V. 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.)

Ventricular assist device (VAD) implantation is an established treatment modality for patients with end-stage heart failure, and improves symptoms and survival. In the Netherlands, it is not yet routinely considered in patients with congenital heart disease and failing systemic right ventricle (SRV). Recently, a VAD was implanted in 2 SRV patients, one who underwent a Mustard procedure during infancy for transposition of the great arteries (male, 47 years old) and one with a congenitally corrected transposition of the great arteries (male, 54 years old). The first patient is doing well >1 year after implantation; the second patient will be discharged home soon. These examples and other reports demonstrate the feasibility of adopting VAD implantation into routine care for SRV failure. In conclusion, patients with SRV failure may be suitable candidates for VAD implantation: they are relatively young, usually have a preserved subpulmonary left ventricular function, and their specific anatomical and physiological characteristics often make them unsuitable for cardiac transplantation. Therefore it is important to recognise the possibility of VAD implantation early in the process of SRV failure, and to timely refer these patients to a heart failure clinic with experience in VAD implantation in this group of patients for optimisation, screening, and implantation.

Background: Severely increased right ventricular (RV) afterload is considered a contra-indication for orthotopic liver transplantation (OLT). This study assesses the effects of mildly increased RV afterload on long-term outcome after OLT in relation to RV function., Methods: 139 OLT recipients (53±12years, 76% male) were included. Preoperative RV afterload was assessed invasively or, if not available, echocardiographically and categorised as normal, high-normal (mean pulmonary artery pressure [PAP] 20-25mmHg or echocardiographic systolic PAP 35-40mmHg) or mildly elevated (mean PAP 25-35mmHg or systolic PAP 40-50mmHg). The association between level of RV afterload, echocardiographic RV function and postoperative outcome was assessed., Results: Right ventricular afterload was high-normal in 17% and mildly elevated in 12% of patients. Patients with elevated RV afterload had higher echocardiographic RV dimensions and left ventricular filling pressures. RV functional parameters were within normal range and not associated with RV afterload. Increased RV afterload was associated with a higher incidence of postoperative haemodynamic complications (8%, 17%, and 29% for normal, high-normal and mildly elevated RV afterload, respectively, p=0.03) and worse survival (8-year survival 74%, 41% and 37% respectively, p=0.01). Preoperative RV function was not associated with outcome after OLT., Conclusions: Increased RV afterload was associated with increased haemodynamic complications and worse long-term survival in OLT recipients. Right ventricular function in patients with increased RV afterload was within normal range and not associated with postoperative outcome., (Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: This study assessed adult survival and morbidity patterns in patients who underwent atrial correction according to Mustard or Senning for transposition of the great arteries (TGA)., Methods: In 76 adult patients with TGA (59% male) after atrial correction, long-term survival and morbidity were investigated in three periods: early (<15 years postoperatively), midterm (15-30 years postoperatively) and late (>30 years postoperatively)., Results: The Mustard technique was performed in 41 (54%) patients, and the Senning technique was performed in 35 (46%) patients aged 3.1 (IQR: 2.1-3.8) and 1.0 (IQR: 0.6-3.1; p<0.01) years, respectively. Adult survival was 82% at 39.7 (IQR: 35.9-42.4) years postoperatively and exceeded 50 years in four patients. Supraventricular tachycardia (SVT) occurred in 51% of patients. The incidences of ventricular arrhythmia (0%, 8% and 13%; p<0.01), heart failure (0%, 5% and 19%; p<0.01) and surgical reinterventions (0%, 5% and 11%; p=0.01) increased from early to late follow-up. At last follow-up, RV function was depressed in 31 (46%) patients, and New York Heart Association functional class was ≥2 in 34 (48%) patients. Bradyarrhythmia, SVT and ventricular arrhythmia were associated with depressed RV function (OR: 4.47, 95% CI 1.50 to 13.28, p<0.01; OR: 3.74, 95% CI 1.26 to 11.14, p=0.02; OR: 14.40, 95% CI 2.80 to 74.07, p<0.01, respectively) and worse functional capacity (OR: 2.10, 95% CI 0.75 to 5.82, p=0.16; OR: 2.87, 95% CI 1.06 to 7.81, p=0.04; OR: 8.47, 95% CI 1.70 to 42.10, p<0.01, respectively)., Conclusions: In adult patients with TGA, survival was 82% at 39.7 (IQR: 35.9-42.4) years after atrial correction. Morbidity was high and included SVT as most frequent adverse event. Ventricular arrhythmias, heart failure and surgical reinterventions were common during late follow-up. Adverse events were associated with depressed right ventricle function and reduced functional class., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

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.)

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.)

Objectives: In repaired tetralogy of Fallot, surgical pulmonary valve replacement (PVR) is in certain cases required. Our institution reported earlier about 26 patients who received a pulmonary homograft via PVR. To date, we have data from more than 17 years of follow-up. The aim of this retrospective study was to evaluate the late haemodynamic and clinical outcomes in this predefined patient group., Methods: Between 1993 and 2001, 26 patients underwent PVR for pulmonary regurgitation (58% men; 30.4 ± 8.9 years). The rates of mortality and of complications (re-PVR, ablation and cardioverter defibrillator implants) were analysed. Other main study outcomes were haemodynamic parameters determined from cardiovascular magnetic resonance imaging: pulmonary regurgitation; right ventricular (RV) end-diastolic volume; RV ejection fraction; left ventricular (LV) end-diastolic volume; LV ejection fraction; New York Heart Association functional class at the latest follow-up visit; and echocardiographic parameters of the right ventricle., Results: The median follow-up time was 17 ± 1.1 years. Overall freedom from complications was 61.5% (95% confidence interval 47.5-78.6%). One patient died 18 months after surgery of unknown causes. Two patients needed replacement of the homograft at 24 and 39 months after PVR. The indication in both patients was recurrence of severe homograft regurgitation with important RV dilatation. Six patients received an implantable cardioverter defibrillator at a median age of 41 years (interquartile range 36-47); 12 patients experienced supra- and/or ventricular arrhythmias and 6 of these needed ablation. There was no significant deterioration of haemodynamic function or functional class., Conclusions: The patients who underwent PVR exhibited long-term follow-up stabilization of RV function and impressive functional durability of the graft. After a follow-up of 17 years, 23 out of 26 patients (89%) were alive without redo PVR. Event-free survival was good (61.5%).

Background: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension (PH) which is a major cause of death in this population. Echocardiographic (TTE) derived pulmonary arterial pressure (PAP) can be unreliable for the early detection of PH. Previous studies demonstrate that the ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO) can detect PH in a heterogeneous population suspected of PH. The aim of this study is to assess the use of the VG-RVPO as a screening and monitoring instrument of early PH in SSc patients., Methods: Serial ECGs and TTEs from twenty-seven SSc patients who underwent right heart catheterization (RHC) were retrospectively analyzed. The changes in PAP and VG-RVPO over time were studied in patients with and without diagnosed PH., Results: Twenty-four patients (52.5% female, mean age 58.4 years SD 14.3) were studied. In eleven patients PH was confirmed with RHC. In these patients VG-RVPO was significantly higher -8 ± 19 than in patients without PH -23 ± 10 mV·ms, (P < 0.05). In addition, in PH patients the VG-RVPO increased over time in contrast to patients without PH (P < 0.01). The VG was more sensitive to detect disease progression in earlier stages of disease as compared to echocardiographic derived PAP., Conclusions: The VG-RVPO is a sensitive, non-invasive and cost effective tool for early detection of PH in SSc patients. Serial measurements indicate that the VG-RVPO can be used as a follow-up instrument and outperforms TTE to detect early changes in right ventricular pressure over time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves. We present a modification of a relatively simple system introduced in the early 1980s, designated the "Leiden Convention.", Methods: The first step of the Leiden Convention is that the clinician takes position in the nonfacing sinus of the aorta looking toward the pulmonary orifice. The right-hand facing sinus is sinus 1, and the left-hand facing sinus is sinus 2. The coronary branches arising from sinus 1 are annotated proceeding in a counterclockwise fashion toward sinus 2. "Usual" (normal) coronary anatomy would be 1R-2LCx. Given their clinical relevance, single sinus coronary arteries are discussed separately., Results: This system was originally designed and highly applicable in hearts with an altered great artery relationship, such as in the variable and complicated patterns seen in transposition of the great arteries and double outlet right ventricle. The modified system also can be used in cases with normally related great arteries, cases with single sinus coronary arteries, and cases with bicuspid aortic valves., Conclusions: The modified Leiden Convention is not a strict classification but a simple coronary coding system that is broadly applicable., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

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., (© 2017 American Heart Association, Inc.)

Background: Little is known on the clinical course of tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) and which patients are at particular risk. This study aims to determine TR course, characteristics associated with TR progression, and the prognostic relevance of TR in rTOF patients., Methods: In this dualcenter cohort study, rTOF patients from a prospective national registry with ≥1 cardiac magnetic resonance imaging study and ≥2 echocardiograms available were included. Clinical and imaging data were collected. Cox hazards regression analysis was used to assess patient characteristics associated with progression to severe TR and whether severe TR was associated with the combined clinical endpoint of tachyarrhythmia, heart failure, and death, as time-dependent factor., Results: A total of 216 patients were included (57% men, age 34±12years); 11 patients (5%) had severe TR at baseline. During 7.6±3.5years of follow-up, progression to severe TR occurred in 15 patients (7%). NYHA class ≥2 (HR 5.38, 95%-C.I. 1.91-15.16, p=0.001) and moderate baseline TR (HR 13.10, 95%-C.I. 2.95-58.21, p=0.001) were independently associated with progression to severe TR. Adverse events occurred in 47 patients (22%). The occurrence of severe TR was independently associated with adverse events (HR 3.48, 95%-C.I. 1.68-7.21, p=0.001)., Conclusions: In this study, severe TR was present in 12% of adult rTOF patients during 7.6years, and progression to severe TR was most likely in symptomatic patients with moderate baseline TR. In these patients, close surveillance is warranted, because the occurrence of severe TR was associated with worse prognosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background Young patients with congenital heart disease reaching adulthood face mandatory transition to adult cardiology. Their new cardiologist needs to assess the chances of major future events such as surgery. Using a large national registry, we assessed if patient characteristics at the age of 18 years could predict the chance of congenital heart surgery in adulthood. Design and methods Of 10,300 patients from the CONCOR national registry, we used general patient characteristics at age 18 years, underlying congenital heart defect, history of complications, and interventions in childhood as potential predictors of congenital heart surgery occurring from age 18 years up to age 40 and 60 years. Cox regression was used to calculate hazard ratios with 95% confidence intervals. Analyses were performed separately for all congenital heart surgery and for valvular surgery alone. Results Altogether 2427 patients underwent congenital heart surgery after age 18 years, 1389 of whom underwent valvular surgery. Underlying heart defect, male sex, multiple defects, childhood endocarditis, supraventricular arrhythmia, aortic complications and paediatric cardiovascular surgery, independently predicted adult congenital heart surgery. The mean chance of congenital heart surgery was 22% up to age 40 and 43% up to age 60 years; individual chances spanned from 9-68% up to age 40 and from 19-93% up to age 60 years. Conclusion At the time of transition from paediatric to adult cardiology, an easily obtainable set of characteristics of patients with congenital heart disease can meaningfully inform cardiologists about the patient's individual chance of surgery in adulthood. Our findings warrant validation in other cohorts.

Importance: Adults late after total correction of tetralogy of Fallot (TOF) are at risk for major complications. Cardiovascular magnetic resonance (CMR) imaging is recommended to quantify right ventricular (RV) and left ventricular (LV) function. However, a commonly used risk model by Khairy et al requires invasive investigations and lacks CMR imaging to identify high-risk patients., Objective: To implement CMR imaging in noninvasive risk stratification to predict major adverse clinical outcomes., Design, Setting, and Participants: This multicenter study included 575 adult patients with TOF (4.083 patient-years at risk) from a prospective nationwide registry in whom CMR was performed. This study involved 5 tertiary referral centers with a specialized adult congenital heart disease unit. Multivariable Cox hazards regression analysis was performed to determine factors associated with the primary end point. The CMR variables were combined with the noninvasive components of the Khairy et al risk model, and the C statistic of the final noninvasive risk model was determined using bootstrap sampling. The data analysis was conducted from January to December 2016., Main Outcomes and Measures: The composite primary outcome was defined as all-cause mortality or ventricular arrhythmia, defined as aborted cardiac arrest or documented ventricular fibrillation and ventricular tachycardia (lasting ≥30 seconds or recurrent symptomatic)., Results: Of the 575 patients with TOF, 57% were male, and the mean (SD) age was 31 (11) years. During a mean (SD) follow-up of 7.1 (3.5) years, the primary composite end point occurred in 35 patients, including all-cause mortality in 13 patients. Mean (SD) RV ejection fraction (EF) was 44% (10%), and mean (SD) LV EF was 53% (8%). There was a correlation between RV EF and LV EF (R, 0.36; 95% CI, 0.29-0.44; P < .001). Optimal thresholds for ventricular function (RV EF <30%: hazard ratio, 3.90; 95% CI, 1.84-8.26; P < .001 and LV EF <45%: hazard ratio, 3.23; 95% CI, 1.57-6.65; P = .001) were independently predictive in multivariable analysis. Both thresholds were included in a point-based noninvasive risk model (C statistic, 0.75; 95% CI, 0.63-0.85) and combined with the noninvasive components of the Khairy et al risk model., Conclusions and Relevance: In patients with repaired TOF, biventricular dysfunction on CMR imaging was associated with major adverse clinical outcomes. The quantified thresholds (RV EF <30% and LV EF <45%) may be implemented in noninvasive risk stratification.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim was to assess the diagnostic value of the Inverse Dower (INVD)-derived vectorcardiogram (VCG) and the Kors-derived VCG to detect elevated systolic pulmonary artery pressure (SPAP) in suspected pulmonary hypertension (PH)., Methods: In 132 patients, morphologic variables were evaluated by comparing the VCG parameters synthesized by INVD and Kors matrix. Comparison of the diagnostic accuracy of detecting SPAP ≥50mmHg between the matrices was performed by ROC curve analysis and logistic regression analysis., Results: Most VCG parameters differed significantly between INVD and Kors. ROC analysis for detection of SPAP ≥50mmHg by VG projected on the X-axis demonstrated no difference (p=0.99) between INVD (AUC=0.80) and Kors (AUC=0.80). Both the INVD- and Kors-derived VCG provided significant diagnostic information on the presence of SPAP ≥50mmHg (INVD, OR 1.05, 95%CI 1.03-1.07; P<0.001; Kors, OR 1.05, 95%CI 1.03-1.08; P<0.001)., Conclusion: Although there were significant differences in measures of vector morphology, both INVD- and Kors-derived VCG demonstrated equal clinical performance in case of elevated SPAP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In 1816, Laennec discovered that auscultation of the heart and lungs could effectively be performed by placing a hollow cylinder (initially made of a roll of paper) between the chest of the patient and the ear of the examiner. This was the first step in the development of the stethoscope, which was a breakthrough in the diagnosis and management of cardiac and pulmonary patients. Technical improvements of the stethoscope followed and in cardiac patients auscultation soon became a major diagnostic tool. In the second half of the 20th century, new powerful non-invasive diagnostic modalities were developed and the interest in auscultation declined. As a result, the auscultatory skills of students and physicians at all levels of training decreased to a disappointingly low level. We now must decide whether we should stimulate the use of and proficiency in auscultation or if we should accept the further decline and eventual abolishment of this component of the physical examination. Reviewing the literature and taking into consideration the setting in which the patients are presented, including the availability of advanced diagnostic facilities, we conclude that the time-honoured stethoscope, in spite of its limitations, still has potential as a patient-friendly, effective, and economical instrument in medical practice. However, new initiatives are required to train students, physicians and allied health professionals in cardiac auscultation to avoid misinterpretations that may harm the patients and generate extra costs. To be successful such programs will require wide support from the medical community., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objectives: In patients with congenitally corrected transposition of the great arteries (ccTGA) or after atrial (Mustard or Senning) correction for transposition of the great arteries (acTGA), the right ventricle (RV) supports the systemic circulation. The tricuspid valve (TV) (systemic atrioventricular valve) is prone to regurgitation in these patients and this is associated with impending RV failure and decreased survival. This study evaluates mid-term functional improvements, echocardiographic findings and survival after TV surgery in this patient group., Methods: From July 1999 to November 2014, 26 patients (mean age 37.1 ± 12.3 years, 14 females) with ccTGA (n = 15) or acTGA (n = 11) had TV surgery. All patients had RV dysfunction and more-than-moderate TV regurgitation (TR); 14 underwent TV replacement (TVR) and 12 had valvuloplasty (TVP). Main outcomes were New York Heart Association (NYHA) functional class, TR and RV dysfunction at 1 year postoperatively and at latest follow-up. Complications and freedom from the composite end-point of death or recurrent TR were analysed., Results: The median follow-up time was 5.9 years (range, 0-16.1 years). Mean NYHA functional class significantly improved to 1.7 [95% confidence interval (CI): 1.3-2.1] at 1 year (P= 0.004) and was 2.1 (95% CI: 1.7-2.6) at latest follow-up (P= 0.14). TV competence significantly improved to a mean TR grade of 1.1 (95% CI: 0.5-1.7) at latest follow-up (P< 0.001). The mean grade for RV function at latest follow-up was 2.7 (95% CI: 2.3-3.0). Most encountered postoperative complications were arrhythmias and temporary haemodynamic instability due to low cardiac output. Early mortality was 11.5% (n = 3); late mortality was 15.4% (n = 4). Estimated freedom from the composite end-point of death or recurrent TR was 76.9% (95% CI: 55.7-88.9%) at 1 year and 64.8% (95% CI: 43.2-79.9%) at 5 years. In TVP patients, TV function at 1 year and at latest follow-up was significantly worse than in TVR patients (P< 0.001 and P= 0.003, respectively). Also, TVP patients had a significantly lower composite end-point survival curve compared with TVR patients (P= 0.018)., Conclusions: In this patient group, TV surgery showed stabilization of RV function and improvement of NYHA functional class for at least several years. In this series, TVR appears superior to TVP with respect to occurrence of recurrent TR. Early and late mortality after TV surgery is substantial, and we believe that patients with significant TR should be referred earlier for surgery for better outcome., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Elevated systolic pulmonary artery pressure (SPAP) after ST-segment elevation myocardial infarction (STEMI) has been associated with adverse outcome. However, little is known about the development of increased SPAP after STEMI treated with primary percutaneous coronary intervention. The aims of this study were to investigate the incidence and determinants of elevated SPAP (SPAP ≥36 mm Hg at 12 months) after first STEMI and to analyze its prognostic implications. A total of 705 patients (60 ± 12 years; 75% men; left ventricular ejection fraction [LVEF] 47 ± 9%) with first STEMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was available at baseline and 12-month follow-up. Data on all-cause mortality were collected at long-term follow-up. Incident elevated SPAP was present in 5% (n = 38) of patients. Patients with incident elevated SPAP were older (66 ± 12 vs 60 ± 11 years, p = 0.001), had more systemic hypertension (58% vs 30%, p <0.001) and lower LVEF (43 ± 9% vs 48 ± 8%, p <0.001) than their counterparts. Left atrial volume was larger (23 ± 11 vs 18 ± 6 ml/m(2), p = 0.006), and moderate to severe mitral regurgitation was more prevalent in patients with incident elevated SPAP (16% vs 7%, p = 0.05). Independent correlates of incident elevated SPAP at 12-month follow-up were age (odds ratio [OR] 1.04, 95% CI 1.01 to 1.08, p = 0.01), hypertension (OR 2.52, 95% CI 1.23 to 5.14, p = 0.01), baseline LVEF (OR 0.94, 95% CI 0.90 to 0.98, p = 0.003), and baseline left atrial volume (OR 1.08, 95% CI 1.03 to 1.12, p = 0.001). Incident elevated SPAP was independently associated with all-cause mortality (hazard ratio 3.84, 95% CI 1.76 to 8.39, p = 0.001). In conclusion, although the incidence of elevated SPAP after STEMI is low, its presence is independently associated with increased risk of all-cause mortality at follow-up., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Variable coronary anatomy has been described in patients with bicuspid aortic valves (BAVs). This was never specified to BAV morphology, and prognostic relevance of coronary vessel dominance in this patient group is unclear. The purpose of this study was to evaluate valve morphology in relation to coronary artery anatomy and outcome in patients with isolated BAV and with associated aortic coarctation (CoA)., Methods: Coronary anatomy was evaluated in 186 patients with BAV (141 men (79%), 51±14 years) by CT and invasive coronary angiography. Correlation of coronary anatomy was made with BAV morphology and coronary events., Results: Strictly bicuspid valves (without raphe) with left-right cusp fusion (type 1B) had more left dominant coronary systems compared with BAVs with left-right cusp fusion with a raphe (type 1A) (48% vs. 26%, p=0.047) and showed more separate ostia (28% vs. 9%, p=0.016). Type 1B BAVs had more coronary artery disease than patients with type 1A BAV (36% vs. 19%, p=0.047). More left dominance was seen in BAV patients with CoA than in patients without (65% vs. 24%, p<0.05)., Conclusions: The incidence of a left dominant coronary artery system and separate ostia was significantly related to BAVs with left-right fusion without a raphe (type 1B). These patients more often had significant coronary artery disease. In patients with BAV and CoA, left dominancy is more common., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Adults with pulmonary hypertension associated with congenital heart disease (PH-CHD) often have residual shunts. Invasive interventions aim to optimise pulmonary flow and prevent right ventricular failure. However, eligibility for procedures strongly depends on the adaptation potential of the pulmonary vasculature and right ventricle to resultant circulatory changes. Current guidelines are not sufficiently applicable to individual patients, who exhibit great diversity and complexity in cardiac anomalies., Methods and Results: We present four complex adult PH-CHD patients with impaired pulmonary flow, including detailed graphics of the cardiopulmonary circulation. All these patients had an ambiguous indication for shunt intervention. Our local multidisciplinary Grown-Ups with Congenital Heart Disease team reached consensus regarding a patient-tailored invasive treatment strategy, adjacent to relevant guidelines. Interventions improved pulmonary haemodynamics and short-term clinical functioning in all cases., Conclusions: Individual evaluation of disease characteristics is mandatory for tailored interventional treatment in PH-CHD patients, adjacent to relevant guidelines. Both strict registration of cases and multidisciplinary and multicentre collaboration are essential in the quest for optimal therapy in this patient population.

Aims: The right ventricle (RV) remodels early after pulmonary valve replacement (PVR) in tetralogy of Fallot (TOF) patients. Previously reported preoperative thresholds to achieve early postoperative RV normalization were consistently close to 80 mL/m(2) for end-systolic volume (ESV) and 160 mL/m(2) for end-diastolic volume (EDV). Our objective was to determine whether these thresholds were also associated with mid-to-late RV normalization and clinical events., Methods and Results: Out of a multicentre cohort of 157 TOF patients who had undergone PVR, in 65 patients (62% male, age 29 ± 8 years, homograft in 98%) cardiovascular magnetic resonance (CMR) imaging was performed preoperatively and >3 years (6.3 years, interquartile range: 4.9-9.5) postoperatively. Mid-to-late haemodynamic outcome was classified as: 'RV normalization' [RV ejection fraction (EF) > 48% and RV EDV < 108 mL/m(2)] in 14 of 65 (22%) patients, 'intermediate' in 34 of 65 (52%) patients, and 'suboptimal' (RV EF < 45% and RV EDV > 120 mL/m(2)) in 17 of 65 (26%) patients. Preoperative RV ESV < 80 mL/m(2) was strongly associated with favourable mid-to-late haemodynamic outcome in a proportional odds model [common odds ratio (OR): 0.04 for worse class, 95% confidence interval (CI): 0.01-0.17]. During 7.8 ± 4.0 years follow-up after PVR, adverse clinical events (death, sustained ventricular tachycardia, or heart failure) occurred in 18 of 106 (17%) patients with preoperative CMR available. Patients with preoperative RV ESV > 95 mL/m(2) were at increased risk for unfavourable mid-to-late haemodynamic outcome (common OR: 25.5, 95% CI: 5.35-122) and events (hazard ratio: 2.89, 95% CI: 1.03-8.11)., Conclusion: In TOF patients who had undergone PVR, the best preoperative threshold to achieve mid-to-late RV normalization was RV ESV < 80 mL/m(2). Patients with preoperative RV ESV > 95 mL/m(2) were at increased risk for suboptimal haemodynamic outcome and adverse clinical events. Our findings may assist in timing of PVR., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: To deliver adequate care to patients with congenital heart disease (CHD), it is important to know which patients use what type of care. This knowledge is valuable, as modification of these factors may be used as means to regulate healthcare use. Our objective was to examine the predictive value of psychological characteristics for future healthcare use, independent of clinical characteristics., Methods: In total 845 adult CHD-patients participated in a longitudinal questionnaire study, with a two-year follow-up period. Linear regression analyses with negative binomial log link function were performed predicting healthcare used during the previous year. Psychological predictors were Type D personality, quality of life (QoL), depressive symptoms, trait-anxiety, happiness, optimism, and illness perceptions, independent of the number of co-morbidities, disease complexity and functional status. To control for clustering we included the variable type of centre (regional versus tertiary referral)., Results: Patients who reported more healthcare use had a complex defect, a poor functional status, no Type D personality, and a poor QoL. They moreover felt their CHD had a severe impact on their life and believed their CHD could be managed by themselves or treatment., Conclusions: Healthcare use is not entirely determined by disease complexity and functional status but also by psychological patient characteristics. It can by hypothesised that reducing the negative impact experienced and informing patients about strategies to manage their CHD, will modify their future healthcare use. Additional research is necessary to examine this possibility., (© The European Society of Cardiology 2014.)

Background: Pulmonary hypertension (PH) is a leading cause of death in systemic sclerosis (SSc) patients. The current study assessed the ability of the ECG-derived ventricular gradient (VG-RVPO) to detect PH and predict all-cause mortality in PH patients with subtypes of SSc differing in the extent of multi-organ involvement., Methods: ECGs were obtained from 196 patients with limited and 77 patients with diffuse SSc included from our screening programme on cardiac complications. The association of the VG-RVPO with (1) the presence of PH, (2) conventional screening parameters and (3) survival in PH patients was assessed., Results: In limited SSc patients an elevated VG-RVPO corresponded with the presence of PH (-5±12 mV.ms vs -22±16 mV.ms, P<0.01), correlated significantly with conventional screening parameters and had a better diagnostic performance than the presence of a right heart axis (AUC 0.81 vs 0.60; P=0.04). These differences were not observed in patients with diffuse SSc. An elevated VG-RVPO was associated with decreased survival in all SSc patients with PH (3 year survival 30% vs 64%, P=0.02)., Conclusion: An elevated VG-RVPO is associated with PH in limited SSc patients and with decreased survival in all SSc patients with PH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Essentials Predicting chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism is hard. We studied 772 patients with pulmonary embolism who were followed for CTEPH (incidence 2.8%). Logistic regression analysis revealed 7 easily collectable clinical variables that combined predict CTEPH. Our score identifies patients at low (0.38%) or higher (10%) risk of CTEPH., Summary: Introduction Validated risk factors for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) are currently lacking. Methods This is a post hoc patient-level analysis of three large prospective cohorts with a total of 772 consecutive patients with acute PE, without major cardiopulmonary or malignant comorbidities. All underwent echocardiography after a median of 1.5 years. In cases with signs of pulmonary hypertension, additional diagnostic tests to confirm CTEPH were performed. Baseline demographics and clinical characteristics of the acute PE event were included in a multivariable regression analysis. Independent predictors were combined in a clinical prediction score. Results CTEPH was confirmed in 22 patients (2.8%) by right heart catheterization. Unprovoked PE, known hypothyroidism, symptom onset > 2 weeks before PE diagnosis, right ventricular dysfunction on computed tomography or echocardiography, known diabetes mellitus and thrombolytic therapy or embolectomy were independently associated with a CTEPH diagnosis during follow-up. The area under the receiver operating charateristic curve (AUC) of the prediction score including those six variables was 0.89 (95% confidence interval [CI] 0.84-0.94). Sensitivity analysis and bootstrap internal validation confirmed this AUC. Seventy-three per cent of patients were in the low-risk category (CTEPH incidence of 0.38%, 95% CI 0-1.5%) and 27% were in the high-risk category (CTEPH incidence of 10%, 95% CI 6.5-15%). Conclusion The 'CTEPH prediction score' allows for the identification of PE patients with a high risk of CTEPH diagnosis after PE. If externally validated, the score may guide targeting of CTEPH screening to at-risk patients., (© 2015 International Society on Thrombosis and Haemostasis.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: Aberrant origin of the coronary arteries is rare but can be life threatening. It is an important cause of sudden death in athletes and other young adults, and may be treated surgically. Consensus exists that interarterial left coronary artery (LCA) should be surgically repaired. For interarterial right coronary artery (RCA), the discussion remains open. The purpose of this study was to analyse our surgical experience., Methods: From 2001 until 2014, 31 patients were operated for interarterial RCA, interarterial LCA or intraseptal course of the LCA. Twenty-six patients had interarterial RCA, 4 patients interarterial LCA and 1 patient an intraseptal course of the LCA. Median age at operation was 38 years (range 9-66 years). Twenty-eight patients had previous or current symptoms. The most important were a life-threatening event with resuscitation in 3 and myocardial infarction in 3 others. Surgical repair of interarterial RCA consisted of unroofing of the ostium with or without reimplantation in 25 patients and CABG on the RCA with a venous graft in 1 patient. Reconstruction of interarterial LCA consisted of ostium reconstruction of the LCA with a venous patch in 4 patients. The patient with an intraseptal course had a complete release of the LCA out of the septum and reimplantation in the correct coronary sinus. Follow-up was done by analysis of outpatient records, direct patient contact, echocardiography, electrocardiography, CT-angiography and an exercise test., Results: Median follow-up was 6 years (range 0-11 years). One patient was lost to follow-up. No early or late mortality occurred. Three patients had ischaemia with ventricular fibrillation or ventricular tachycardia shortly after surgery. Two were immediately reoperated, 1 had a stent implantation 1.5 months after release of intraseptal LCA. Two of these patients show a slight dysfunction of the left ventricle at follow-up. All other patients are asymptomatic., Conclusions: Surgery for aberrant origin of coronary arteries is safe. There is a risk of cardiac ischaemia shortly after operation, especially in LCA reconstruction. We strongly believe that a slit-like coronary ostium and an intramural aortic course is an absolute indication for surgical repair, also in asymptomatic aberrant RCA., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

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: 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.)

Objectives: Adequate prepregnancy prediction of maternal cardiovascular and offspring risk is important for counselling and management of pregnancy in women with congenital heart disease (CHD). Therefore we performed a study to identify the optimal assessment strategy for estimating the risk of pregnancy in women with CHD., Methods: In this prospective study, we determined the outcomes of 213 pregnancies in 203 women with CHD. The ZAHARA I (Zwangerschap bij Aangeboren HARtAfwijkingen I) and CARPREG (CARdiac disease in PREGnancy) risk scores were calculated for each pregnancy, as was the total number of cardiovascular (TPc) or offspring risk predictors (TPo) from these and other studies combined. Pregnancies were also classified according to the modified WHO classification of maternal cardiovascular risk and according to disease complexity (DC)., Results: Maternal cardiovascular events occurred during 22 pregnancies (10.3%). Offspring events occurred during 77 pregnancies in 81 children (37.3%). Cardiovascular and offspring event rates increased with higher risk scores, higher TPc or TPo, higher WHO class and greater DC. The highest area under the curve (AUC) for maternal cardiovascular risk was achieved by the WHO class (AUC: 0.77, p<0.0001). AUC for the ZAHARA I risk score was 0.71 (p=0.001), and for the CARPREG risk score 0.57 (p=0.32). All models performed insufficiently in predicting offspring events (AUC≤0.6)., Conclusions: The WHO classification is the best available risk assessment model for estimating cardiovascular risk in pregnant women with CHD. None of the offspring prediction models perform adequately in our cohort., (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: Carotid intima-media thickness (CIMT) is a marker for atherosclerosis. Adult post-coarctectomy patients (CoA) demonstrate an increased cardiovascular risk and increased CIMT compared to controls. This study evaluates the effect of high dose statins on the change in CIMT and cardiovascular risk., Methods: We designed a multicenter, prospective, randomized, open label trial with blinded endpoint (PROBE design) to evaluate the effect of three year treatment with atorvastatin 80 mg on CIMT and cardiovascular risk. Primary endpoint was CIMT measured by B mode ultrasonography. Secondary endpoints were mortality and morbidity due to cardiovascular disease and serum lipids., Results: 155 patients (36.3 ± 11.8 years, 96 (62%) male) were randomized (atorvastatin=80, no treatment=75). There was no significant effect of atorvastatin on the change in CIMT (treatment effect -0.005, 95% CI, -0.039-0.029; P=0.76). A significant effect on serum cholesterol and LDL levels was found (- 0.71, 95% CI, - 1.16 to - 0.26; P = 0.002 vs - 0.66, 95% CI - 1.06 to - 0.26; P = 0.001). There was no difference in secondary outcome measures. Baseline CIMT was higher in hypertensive compared to normotensive CoA. (0.69 ± 0.16 mm vs 0.61 ± 0.98 mm; P=0.002). Hypertension (ß=0.043, P=0.031) was the strongest determinant CIMT., Conclusion: Three year treatment with atorvastatin does not lead to a reduction of CIMT and secondary outcome measures, despite a decrease in total cholesterol and LDL levels. Hypertensive CoA demonstrate the highest CIMT and the largest CIMT progression. Blood pressure control should be the main focus in CoA to decrease cardiovascular risk., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Objective: After the arterial switch operation (ASO), disproportional neo-aortic growth during childhood has been reported. Even though it has been suggested neo-aortic dilation will stabilise in adulthood, data are lacking. The aim of this study was to assess the change in neo-aortic dimensions, prevalence of neo-aortic dilation >40 mm and long-term outcome in adults who underwent ASO in childhood., Methods: All 116 ASO patients operated in a tertiary referral centre and born before 1995 were included. Of these, 83 (72%) survived to adulthood (>17 years) and six were lost to follow-up. Neo-aortic measurements performed in adulthood were collected from available echocardiographic, cardiovascular magnetic resonance and CT images. The time trend was analysed using a mixed model, adjusted for imaging modality., Results: Clinical data with at least one measurement of the neo-aortic diameter were available in 77 (93%) adult patients and serial measurements in 65 (78%). At baseline (median age 18.1 years), mean neo-aortic diameter was 36±5 mm. Mean neo-aortic growth was 0.31 mm/year (p<0.001 compared with normal value 0.08 mm/year) and was linear over time. Freedom from neo-aortic dilation beyond a diameter of 40 mm was 23% at 28 years of age. During a mean clinical follow-up in adulthood of 7.2 years (IQR 4.0 to 10.1), 3 (4%) patients underwent neo-aortic replacement. No other neo-aortic complications occurred., Conclusions: In early adulthood, neo-aortic growth was on average linear and did not stabilise over time., (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.)

Pulmonary hypertension has been associated with right ventricular (RV) dyssynchrony which may induce left ventricular (LV) dysfunction and dyssynchrony through ventricular interdependence. The present study evaluated the influence of RV dyssynchrony on LV performance in patients with pulmonary hypertension. One hundred and seven patients with pulmonary hypertension (age 63 ± 14 years, systolic pulmonary arterial pressure 60 ± 19 mmHg) and LV ejection fraction (EF) >35% were evaluated. Ventricular dyssynchrony was assessed with speckle tracking echocardiography and defined as the standard deviation of the time to peak longitudinal strain of six segments of the RV (RV-SD) and the LV (LV-SD) in the apical 4-chamber view. Mean RV-SD and LV-SD assessed with longitudinal strain speckle tracking echocardiography were 51 ± 28 and 47 ± 21 ms, respectively. The patient population was divided according to the median RV-SD value of 49 ms. Patients with RV-SD ≥49 ms had significantly worse NYHA functional class (2.7 ± 0.7 vs. 2.3 ± 0.7, p = 0.004), RV function (tricuspid annular plane systolic excursion: 16 ± 4 vs. 19 ± 4 mm, p < 0.001), LVEF (50 ± 10 vs. 55 ± 8%, p = 0.001), and larger LV-SD (57 ± 18 vs. 36 ± 18 ms, p < 0.001). RV-SD significantly correlated with LV-SD (r = 0.55, p < 0.001) and LVEF (r = -0.23, p = 0.02). Multiple linear regression analysis showed an independent association between RV-SD and LV-SD (β = 0.35, 95%CI 0.21-0.49, p < 0.001). RV dyssynchrony is significantly associated with LV dyssynchrony and reduced LVEF in patients with pulmonary hypertension.

Background and Purpose: Early, preferably noninvasive, detection of pulmonary hypertension improves prognosis. Our study evaluated the diagnostic accuracy of the electrocardiographically derived Butler-Leggett (BL) score and ventricular gradient (VG) to estimate mean pulmonary artery pressure (PAP)., Methods: In 63 patients with suspected pulmonary hypertension, BL score and VG were calculated. The VG was projected on a direction optimized for detection of right ventricular pressure overload (VG-RVPO). BL score and VG-RVPO were entered in multiple linear regression analysis and the diagnostic performance to detect PH (invasively measured mean PAP ≥ 25 mmHg) was assessed with receiver operating characteristic analysis., Results: Both BL score and VG-RVPO correlated significantly with mean PAP (r=0.45 and r=0.61, respectively; P<0.001). Combining BL score and VG-RVPO increased the correlation to 0.67 (P<0.001). The diagnostic performance of this combination for the detection of PH was good with an area under the curve of 0.79 (P<0.001)., Conclusion: Combination of the BL score and VG-RVPO allows for accurate detection of increased PAP., (Copyright © 2014 Elsevier Inc. All rights reserved.)