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Eisenmenger syndrome is the most severe and extreme phenotype of pulmonary arterial hypertension associated with congenital heart disease. A large nonrestrictive systemic left-to-right shunt triggers the development of pulmonary vascular disease, progressive pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal. Herein, we review the changing epidemiological patterns and pathophysiology of Eisenmenger syndrome. Multiorgan disease is an integral manifestation of Eisenmenger syndrome and includes involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems. Standardized practical guidelines for the assessment, management, risk stratification, and follow-up of this very fragile and vulnerable population are discussed. Multidisciplinary care is the best clinical practice. An approach to the prevention and management of a broad spectrum of complications is provided. Relevant therapeutic questions are discussed, including anticoagulation, noncardiac surgery, physical activity, transplantation, and advanced-care planning (palliative care). Advanced pulmonary arterial hypertension therapies are indicated in patients with Eisenmenger syndrome and World Health Organization functional class II or higher symptoms to improve functional capacity, quality of life, and-less well documented-survival. Specific recommendations regarding monotherapy or combination therapy are provided according to functional class and clinical response. The ultimate challenge for all care providers remains early detection and management of intracardiac and extracardiac shunts, considering that Eisenmenger syndrome is a preventable condition., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Deep learning (DL) algorithms are increasingly used in cardiac imaging. We aimed to investigate the utility of DL algorithms in de-noising transthoracic echocardiographic images and removing acoustic shadowing artefacts specifically in patients with congenital heart disease (CHD). In addition, the performance of DL algorithms trained on CHD samples was compared to models trained entirely on structurally normal hearts. Deep neural network based autoencoders were built for denoising and removal of acoustic shadowing artefacts based on routine echocardiographic apical 4-chamber views and performance was assessed by visual assessment and quantifying cross entropy. 267 subjects (94 TGA and atrial switch and 39 with ccTGA, 10 Ebstein anomaly, 9 with uncorrected AVSD and 115 normal controls; 56.9% male, age 38.9 ± 15.6 years) with routine transthoracic examinations were included. The autoencoders significantly enhanced image quality across diagnostic subgroups (p < 0.005 for all). Models trained on congenital heart samples performed significantly better when exposed to examples from congenital heart disease patients. Our study demonstrates the potential of autoencoders for denoising and artefact removal in patients with congenital heart disease and structurally normal hearts. While models trained entirely on samples from structurally normal hearts perform reasonably in CHD, our data illustrates the value of dedicated image augmentation systems trained specifically on CHD samples.

Background: Several determinants of exercise intolerance in patients with precapillary pulmonary hypertension (PH) due to pulmonary arterial hypertension and/or chronic thromboembolic PH (CTEPH) have been suggested, including diaphragm dysfunction. However, these have rarely been evaluated in a multimodal manner. Methods: Forty-three patients with PH (age 58 ± 17 years, 30% male) and 43 age- and gender-matched controls (age 54 ± 13 years, 30% male) underwent diaphragm function (excursion and thickening) assessment by ultrasound, standard spirometry, arterial blood gas analysis, echocardiographic assessment of pulmonary artery pressure (PAP), assay of amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac magnetic resonance (CMR) imaging to evaluate right ventricular systolic ejection fraction (RVEF). Exercise capacity was determined using the 6-min walk distance (6MWD). Results: Excursion velocity during a sniff maneuver (SniffV, 4.5 ± 1.7 vs. 6.8 ± 2.3 cm/s, P <0.01) and diaphragm thickening ratio (DTR, 1.7 ± 0.5 vs. 2.8 ± 0.8, P <0.01) were significantly lower in PH patients versus controls. PH patients with worse exercise tolerance (6MWD <377 vs. ≥377 m) were characterized by worse SniffV, worse DTR, and higher NT-pro-BNP levels as well as by lower arterial carbon dioxide levels and RVEF, which were all univariate predictors of exercise limitation. On multivariate analysis, the only independent predictors of exercise limitation were RVEF (r = 0.47, P =0.001) and NT-proBNP (r = -0.27, P =0.047). Conclusion: Patients with PH showed diaphragm dysfunction, especially as exercise intolerance progressed. However, diaphragm dysfunction does not independently contribute to exercise intolerance, beyond what can be explained from right heart failure., (© 2019 The Author(s).)

The ESC/ERS guidelines (published at the end of 2015) and other international recommendations defined pulmonary hypertension (PH) by an invasively measured mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. At the 6 th World Symposium on Pulmonary Hypertension in Nice a modification of this hemodynamic definition in the sense of lowering the threshold to > 20 mmHg was proposed. A pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is additionally required for the diagnosis of pre-capillary PH. This modification must be critically reviewed with regard to the underlying rationale and possible consequences. Therefore, a detailed explanation is required. In particular, it must be made clear that this change currently has no influence on the evidence-based and approval-compliant prescription of drugs for the targeted therapy of pulmonary arterial hypertension (PAH)., Competing Interests: S. Rosenkranz: Honorare für Vorträge und/oder Beratertätigkeiten von Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer und United Therapeutics. Forschungsunterstützung an Institutionen von Actelion, Bayer, Novartis, Pfizer und United Therapeutics. G.P. Diller: Forschungsunterstützung und/oder Konferenz-Teilnahme und/oder Honorare für Vorträge und/oder Beratertätigkeit von Actelion, Pfizer, Daiichi-Sankyo, AOP Orphan Therapeuticals. D. Dumitrescu: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, MSD, Novartis, Pfizer, Servier. Forschungsunterstützung an Institution von Actelion. R. Ewert: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Merck, OMT, Pfizer, United Therapeutics. H.A. Ghofrani: Honorare für Vorträge und/oder Konsultationen von Actelion, Bayer, Gilead, GSK, MSD, Novartis, Pfizer und United Therapeutics. E. Grünig: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, GSK, Novartis, Pfizer und United Therapeutics. M. Halank: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, AOP orphan/OMT, Bayer, Gilead, GSK, MSD, Novartis und Pfizer. M. Held: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, Berlin Chemie, Boehringer, GSK, MSD, Novartis, Pfizer, United Therapeutics. H. Kaemmerer: Forschungsunterstützung und/oder Konferenz-Teilnahme und/oder Honorare für Vorträge und/oder Beratertätigkeit von Actelion, Bayer, Pfizer. H. Klose: Honorare für Vorträge und/oder Beratertätigkeiten und Kongressteilnahmeunterstützung von Actelion, Bayer, MSD, GSK, UT, Novartis, OMT und Pfizer; Forschungsunterstützung von GSK, Actelion und Bayer. G. Kovacs: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, MSD, Novartis, Pfizer, Chiesi, Boehringer-Ingelheim. S. Konstantinides: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, Boehringer. I.M. Lang: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, AOP Orphan, Astra-Zeneca, Bayer-Schering, Cordis, Daiichi-Sankyo, Edwards, GSK, Medtronic, Novartis, Pfizer, Servier, United Therapeutics. T.J. Lange: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, AOP orphan/OMT, Bayer, GSK, Pfizer and United Therapeutics. H. Leuchte: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Merck, und Pfizer. E. Mayer: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, MSD und Pfizer. A. Olschewski: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Bayer, GSK, Pfizer. H. Olschewski: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, Bayer, Belerophon, Boehringer, GSK, Menarini, MSD, Novartis, Pfizer, Roche. K.M. Olsson: Honorare für Vorträge und/oder Beratertätigkeiten von Actelion, Bayer, GSK, Pfizer und United Therapeutics. C. Opitz: Keine persönlichen Einkünfte als mögliche Interessenkonflikte. R.T. Schermuly: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Bayer, Gilead, MSD, Novartis, United Therapeutics. W. Seeger: Honorare für Vorträge und/oder Beratertätigkeiten und/oder Forschungsunterstützung an Institutionen von Actelion, Bayer, Pfizer, Novartis. H. Wilkens: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, Boehringer-Ingelheim, GSK, MSD, Novartis, Pfizer und Roche. M.M. Hoeper: Honorare für Beratertätigkeiten und/oder Vorträge von Actelion, Bayer, Gilead, GSK, Merck und Pfizer., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gender differences in the outcome of acquired cardiovascular disease are well known, but available literature on the influence of gender in congenital heart disease (CHD) is limited. Registries have provided valuable, albeit at times conflicting data. Higher mortality rates have been reported in older males with CHD, while sudden cardiac death is more prevalent in young males. However, mortality around surgery for CHD is higher in girls compared to boys, likely due to smaller body size. Women are at higher risk of developing pulmonary arterial hypertension, but at lower risk of adverse aortic outcomes, even though they are less likely to receive aortic surgery. Finally, women have a lower risk of presenting with infective endocarditis compared to men. The underlying reasons for gender differences in CHD can be attributed to genetic, hormonal, behavioural and other causes. The aim of the present paper is to provide an overview of available evidence on gender differences in CHD and their impact on outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: To investigate the utility of novel deep learning (DL) algorithms in recognizing transposition of the great arteries (TGA) after atrial switch procedure or congenitally corrected TGA (ccTGA) based on routine transthoracic echocardiograms. In addition, the ability of DL algorithms for delineation and segmentation of the systemic ventricle was evaluated., Methods and Results: In total, 132 patients (92 TGA and atrial switch and 40 with ccTGA; 60% male, age 38.3 ± 12.1 years) and 67 normal controls (57% male, age 48.5 ± 17.9 years) with routine transthoracic examinations were included. Convolutional neural networks were trained to classify patients by underlying diagnosis and a U-Net design was used to automatically segment the systemic ventricle. Convolutional networks were build based on over 100 000 frames of an apical four-chamber or parasternal short-axis view to detect underlying diagnoses. The DL algorithm had an overall accuracy of 98.0% in detecting the correct diagnosis. The U-Net architecture model correctly identified the systemic ventricle in all individuals and achieved a high performance in segmenting the systemic right or left ventricle (Dice metric between 0.79 and 0.88 depending on diagnosis) when compared with human experts., Conclusion: Our study demonstrates the potential of machine learning algorithms, trained on routine echocardiographic datasets to detect underlying diagnosis in complex congenital heart disease. Automated delineation of the ventricular area was also feasible. These methods may in future allow for the longitudinal, objective, and automated assessment of ventricular function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: The prognostic benefit of atrial septal defect (ASD) closure in adulthood, particularly in advanced age, remains uncertain. The aim of our study was to examine the impact of ASD closure in a contemporary adult cohort on mid to longer term survival as compared with expected survival in the general population., Methods: We study herewith all consecutive patients (≥16 years of age) who underwent ASD closure, catheter or surgical, at our tertiary centre between 2001 and 2012. Furthermore, we compare survival of our ASD closure cohort with expected survival in age and gender-matched general population and standardised mortality ratios (SMR) were calculated., Results: A total of 608 patients (mean age 45.4±16.7 years) underwent ASD closure (catheter 433(71.2%), surgical 175(28.8%)). There was no 30-day mortality and periprocedural complications were low (n=40, 6.6%). During a median follow-up of 6.7 (IQR 4.2-9.3) years 16 (2.6%) patients died; survival was similar to the general population (p=0.80) including patients >40 or >60 years of age at ASD closure (p=0.58 and p=0.64, respectively). There was no survival difference between gender (male: SMR 0.93; 95% CI 0.52 to 1.64, p=0.76; female: SMR 0.99; 95% CI 0.58 to 1.66, p=0.95) or mode of closure compared with general population (catheter: SMR 1.03; 95% CI 0.68 to 1.55, p=0.89; surgical: SMR 0.65; 95% CI 0.22 to 1.88, p=0.38)., Conclusion: Perioperative mortality and morbidity in a large contemporary adult cohort undergoing ASD closure, catheter or surgical, is extremely low. Mid to longer term survival is excellent irrespective of age, gender and mode of closure, and similar to matched general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Women are underrepresented in leading medical positions and academia. The gender-gap in authorship of congenital heart disease (CHD) publications remains unknown. As determinants of gender equity in this field are poorly characterised, we aimed to quantify and characterise publications in CHD and to assess factors associated with female representation in research., Methods and Results: We identified 35 118 CHD publications between 2006 and 2015 for which author gender could be ascertained. Overall, 25.0% of all authors were female. Women accounted for 30.2% and 20.8% of all first and senior authorship positions with great geographic heterogeneity. While globally female first and senior authorship increased by 0.8% and 0.6%/year, some geographic regions showed no improvement in gender representation. Significant predictors of female first authorship on logistic regression analysis were country gross domestic product, human development index, gender inequality index and a female senior author (p<0.0001 for all). Publications with a female lead author tended to be published in journals with a higher impact factor (IF) and to attract more citations compared with those with a male author. Mixed gender authorship was associated with higher IF and number of citations. Women were less disadvantaged when the analysis was confined to original research., Conclusions: While modest improvement in female authorship over time was noted, women remain underrepresented in contemporary academic CHD. Manuscripts with mixed gender authorship had higher IF and more citations. The main predictor of female first authorship was a female senior author. These data should inform policy recommendations regarding gender parity., Competing Interests: Competing interests: None declared.

Background: Increased longevity in patients with congenital heart disease (CHD) is associated with late complications, mainly heart failure, which may not be amenable to redo surgery and become refractory to medical therapy and so, trigger referral for transplantation. We assessed the current role and future prospects of heart and heart-lung transplantation for patients with CHD in England., Methods: We performed a retrospective analysis of hospital episodes for England for 1997-2015, identifying patients with a CHD code (ICD-10 'Q2xx.x'), who underwent heart or heart-lung transplantation., Results: In total, 469 transplants (82.2% heart and 17.8% heart-lung) were performed in 444 patients. Half of patients transplanted had mild or moderate CHD complexity, this percentage increased with time (p=0.001). While overall, more transplantations were performed over the years, the proportion of heart-lung transplants declined (p<0.0001), whereas the proportion of transplants performed in adults remained static. Mortality was high during the first year, especially after heart-lung transplantation, but remained relatively low thereafter. Older age and heart-lung transplantation were strong predictors of death. While an increase in CHD transplants is anticipated, actual numbers in England seem to lag behind the increase in CHD patients with advanced heart failure., Conclusions: The current and future predicted increase in the numbers of CHD transplants does not appear to parallel the expansion of the CHD population, especially in adults. Further investment and changes in policy should be made to enhance the number of donors and increase CHD transplant capacity to address the increasing numbers of potential CHD recipients and optimise transplantation outcomes in this growing population., Competing Interests: Competing interests: MAG and the Royal Brompton Hospital Adult Congenital Centre and Centre for Pulmonary Hypertension have received support from the British Heart Foundation. MAG, GPD and KD acted as consultants for Actelion UK, Pfizer UK and GSK UK and received unrestricted educational grants from Actelion and Pfizer. RAG acted as consultant for Lilly Spain and Pfizer Spain. AK has received an unrestricted research grant from Actelion Global. SJW has received unrestricted educational and research grants from Bayer UK, Pfizer UK, Actelion UK and GSK UK as well as the Pulmonary Hypertension Association (UK)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Congenital heart disease (CHD) is the most common inborn defect. Due to advances in paediatric care, surgical, and catheter procedures the number of adults with CHD has grown remarkably in recent years. Most of these patients, however, have residua from their original operation/s and require life-long care, many of them are subjected to further haemodynamic and electrophysiological interventions during adulthood. While such re-do surgical or catheter interventions together with device therapy and transplantation play a key therapeutic role, increasingly, adults with CHD require drug therapy for late complications namely heart failure (HF), arrhythmias, pulmonary and systemic hypertension, thromboembolic events, etc. Unlike other cardiovascular areas, drug therapy in adult CHD is based on scarce clinical data and remains largely empiric. Consequently, pharmacological therapies are individualized to ameliorate patients' symptoms and/or degree of haemodynamic impairment. Thus far, recommendations have been difficult to make and formalized guidelines on drug therapy are lacking. We review herewith the rationale, limited evidence and knowledge gaps regarding drug therapy in this growing cardiovascular field and discuss pharmacotherapy options in specific conditions namely HF, arrhythmias, thrombosis, pulmonary arterial hypertension, contraception, and pregnancy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: To assess the utility of machine learning algorithms on estimating prognosis and guiding therapy in a large cohort of patients with adult congenital heart disease (ACHD) or pulmonary hypertension at a single, tertiary centre., Methods and Results: We included 10 019 adult patients (age 36.3 ± 17.3 years) under follow-up at our institution between 2000 and 2018. Clinical and demographic data, ECG parameters, cardiopulmonary exercise testing, and selected laboratory markers where collected and included in deep learning (DL) algorithms. Specific DL-models were built based on raw data to categorize diagnostic group, disease complexity, and New York Heart Association (NYHA) class. In addition, models were developed to estimate need for discussion at multidisciplinary team (MDT) meetings and to gauge prognosis of individual patients. Overall, the DL-algorithms-based on over 44 000 medical records-categorized diagnosis, disease complexity, and NYHA class with an accuracy of 91.1%, 97.0%, and 90.6%, respectively in the test sample. Similarly, patient presentation at MDT-meetings was predicted with a test sample accuracy of 90.2%. During a median follow-up time of 8 years, 785 patients died. The automatically derived disease severity-score derived from clinical information was related to survival on Cox analysis independently of demographic, exercise, laboratory, and ECG parameters., Conclusion: We present herewith the utility of machine learning algorithms trained on large datasets to estimate prognosis and potentially to guide therapy in ACHD. Due to the largely automated process involved, these DL-algorithms can easily be scaled to multi-institutional datasets to further improve accuracy and ultimately serve as online based decision-making tools., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: As adult congenital heart disease (ACHD) patients are aging, a high prevalence of cardiovascular risk factors is encountered similar to the general population. Currently, data regarding the primary and secondary prevention of acquired cardiovascular disease in ACHD is lacking., Methods: The German National Register of Congenital Heart Defects was systematically screened for ACHD patients with established cardiovascular risk factors or documented acquired cardiovascular conditions. Data were analyzed with regard to the according medical treatment., Results: Overall, 539 patients were included (mean age 38.4 ± 17.7 years, 49.2% female). Diabetes was present in 57 pts. (10.6%), arterial hypertension in 113 pts. (21.0%), hyperlipidaemia in 81 pts. (15.0%) and obesity in 271 pts. (50.2%). 31 pts. (5.8%) were smokers. Coronary artery disease was established in 16 pts. (3.0%), peripheral vascular disease in 9 pts. (1.7%), and cerebrovascular accidents in 141 pts. (26.2%). Out of the patients with coronary artery disease only 81.3% received antithrombotic treatment. Only 18.8% were prescribed a statin. Of the pts. with peripheral arterial disease, 44.4% received an antiplatelet drug, and only 22.2% were on a statin. Patients with arterial hypertension received antihypertensive drugs in 66.4%., Conclusions: Primary and secondary prevention of acquired cardiovascular disease in ACHD is underutilized. This highlights the importance of educating primary physicians as well as ACHD physicians about the need of primary and secondary prevention for acquired cardiovascular disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The effects of hyperventilation and hyperventilation in the context of periodic breathing (PB) on sympatho-vagal balance (SVB) and hemodynamics in conditions of decreased cardiac output and feedback resetting, such as heart failure (HF) or pulmonary arterial hypertension (PAH), are not completely understood., Objectives: To investigate the effects of voluntary hyperventilation and simulated PB on hemodynamics and SVB in healthy subjects, in patients with systolic HF and reduced or mid-range ejection fraction (HFrEF and HFmrEF) and in patients with PAH., Methods: Study participants (n = 20 per group) underwent non-invasive recording of diastolic blood pressure, heart rate variability (HRV), baroreceptor-reflex sensitivity (BRS), total peripheral resistance index (TPRI) and cardiac index (CI). All measurements were performed at baseline, during voluntary hyperventilation and during simulated PB with different length of the hyperventilation phase., Results: In healthy subjects, voluntary hyperventilation led to a 50% decrease in the mean BRS slope and a 29% increase in CI compared to baseline values (p < 0.01 and p < 0.05). Simulated PB did not alter TPRI or CI and showed heterogeneous effects on BRS, but analysis of dPBV revealed decreased sympathetic drive in healthy volunteers depending on PB cycle length (p < 0.05). In HF patients, hyperventilation did not affect BRS and TPRI but increased the CI by 10% (p < 0.05). In HF patients, simulated PB left all of these parameters unaffected. In PAH patients, voluntary hyperventilation led to a 15% decrease in the high-frequency component of HRV (p < 0.05) and a 5% increase in CI (p < 0.05). Simulated PB exerted neutral effects on both SVB and hemodynamic parameters., Conclusions: Voluntary hyperventilation was associated with sympathetic predominance and CI increase in healthy volunteers, but only with minor hemodynamic and SVB effects in patients with HF and PAH. Simulated PB had positive effects on SVB in healthy volunteers but neutral effects on SVB and hemodynamics in patients with HF or PAH., (© 2019 S. Karger AG, Basel.)

Objectives: To analyze the timing of appearance of conduction abnormalities (CAs) after transcatheter aortic valve implantation (TAVI), to identify predictors of delayed CAs requiring pacemaker (PM) implantation and to provide guidance regarding the duration of telemetry monitoring., Background: How long patients remain at risk of development of CAs requiring PM implantation after TAVI and for how long they should be monitored remains unclear but is crucial when considering early discharge., Methods: Development of CAs was studied in 701 consecutive patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7 days in a single center. After excluding valve-in-valve procedures and patients with previous PM, 606 patients remained for analysis. Predictors of CAs requiring PM and the time of onset of CAs were analyzed., Results: Of 606 patients 76 (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48 h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs within the first 48 h after TAVI., Conclusion: After TAVI using a new-generation balloon-expandable valve, delayed development of CAs requiring PM implantation is not uncommon, even after 5 days. More importantly, 23.5% of patients eventually requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this study. These results question the safety of early discharge and support ECG monitoring for a longer time period. The most optimal way to monitor these patients is yet to be determined., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is an established option for patients with heart failure. Limited data exists on indications and outcome of CRT in contemporary congenital heart disease (CHD) patients., Methods and Results: All patients with CRT registered in the German National Register for Congenital Heart Defects were systematically identified. We analysed data on demographics, type of congenital defect as well as repair, associated conditions, indication for CRT, heart failure medication, combination with a defibrillator or pacemaker and outcome. Overall, 65 patients with CRT were identified. The most common congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected transposition of the great arteries (ccTGA) (n = 9) and double outlet right ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional antibradycardia pacing or ICD indications. Of these, the majority (n = 44) underwent an upgrade to a CRT system to avoid the detrimental consequences of longstanding conventional ventricular single-site pacing, whereas four patients required an ICD due to heart failure and a history of malignant ventricular tachycardia. During a median follow-up of 6.9 years 19 patients developed complications: 16 patients experienced pacemaker lead dysfunction and 3 patients pacemaker infection., Conclusions: The current study based on a large national register for CHD shows that CRT is feasible and can be used as an adjunct in the heart failure treatment of selected CHD patients. Uptake of this therapy proved to be low in this nationwide study and CRT implantation was largely used in patients with a pre-existing pacing indication or those requiring an ICD., (Copyright © 2018. Published by Elsevier B.V.)

In the summer of 2016, delegates from the German Respiratory Society (DGP), the German Society of Cardiology (DGK) and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH in adults associated with congenital heart disease (CHD). As such patients are often complex and require special attention, and the general PAH treatment algorithm in the ESC/ERS guidelines appears too unspecific for CHD, the working group proposes an analogous algorithm for the management of PH-CHD which takes the special features of this patient group into consideration, and includes general measures, supportive therapy, targeted PAH drug therapy as well as interventional and surgical procedures. The detailed results and recommendations of the working group on PH in adults with CHD, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH associated with left heart disease. In this context, the European Guidelines point out that the drugs currently approved to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, sGC stimulators) have not sufficiently been investigated in other forms of PH. However, despite the lack of respective efficacy data, an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. In that sense, the distinction between isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH) and their proper definition may be of particular relevance. The detailed results and recommendations of the working group on PH associated with left heart disease, which were last updated in the spring of 2018, are summarized in this article., (Copyright © 2018. Published by Elsevier B.V.)

Background: In patients with repaired Tetralogy of Fallot (ToF), implantable cardioverter defibrillators (ICD) are considered reasonable in selected adults with multiple risk factors for sudden cardiac death., Patients and Methods: We performed a retrospective cohort study of all 174 patients with repaired ToF who are followed at the University Hospital of Muenster. We analyzed data according to the risk score previously proposed by Khairy and coworkers and patient outcome. We analyzed data separately for patients without previous sustained ventricular tachycardia (VT) (risk stratification group, n = 157) and patients with VT/secondary prevention ICD (n = 17)., Results: In the risk stratification group, a mean of 4 ± 1 risk score parameters were available. All six risk parameters were known in 10%, five in 14%. Risk score increased with availability of parameters. 15 patients with secondary prevention ICD had a mean risk score of 6.3 ± 2.2 (range 2-10). 11 patients of the risk stratification group with primary prevention ICD had a mean risk score 5.8 ± 2.4 (range 3-8). During follow-up of up to 14 years, five patients died (3%): at age 58, two at 69 and two at 76 years., Conclusion: In the majority of patients risk score variables were incomplete, severely limiting its applicability because the true score cannot be calculated. Risk scores were not different between patients with secondary prevention ICD and patients with ICD for primary prevention based on current guidelines. Standardization of follow-up and prospective evaluation of these standards in large prospective patient cohorts is desirable to improve risk stratification in patients with ToF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Electrical dyssynchrony and prolonged QRS duration are common in patients with repaired tetralogy of Fallot (ToF). It has been linked to increased risk of sudden cardiac death and right ventricular (RV) dysfunction. We investigated myocardial dyssynchrony using cardiac magnetic resonance imaging (CMR) and feature tracking analysis (FT) in this setting and compared it to myocardial deformation, conventional parameters of ventricular dysfunction and clinical parameters., Methods and Results: Patients underwent standardized CMR investigations as part of a nationwide study. We prospectively assessed myocardial deformation and analysed regional wall motion abnormalities of the RV and the left ventricle (LV) using CMR-FT. The main measure of dyssynchrony was the maximal time difference (wall motion delay) of the regional strain as a parameter of mechanical biventricular dyssynchrony. In addition, clinical parameters and measures of cardiopulmonary exercise capacity were available. Overall 345 patients were included. Parameters of biventricular wall motion delay correlated significantly with global FT-strain parameters (p < 0.0001 for all imaging planes assessed). Furthermore, we found a significant correlation between circumferential RV motion delay and QRS duration (p = 0.006). Higher LV and RV wall motion delay parameters were also associated with lower peak oxygen consumption (p < 0.05) and a worse LV and RV ejection fraction (p < 0.02)., Conclusions: Assessment of mechanical dyssynchrony is feasible using CMR-FT in ToF patients. Parameters of mechanical dyssynchrony correlate with electrical dyssynchrony, biventricular function and objective exercise capacity in this setting. Due to the weak degree of correlation, however, the clinical significance of these findings remains to be clarified by further studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Congenitally corrected transposition of the great arteries (ccTGA) can occur in isolation, or in combination with other structural cardiac anomalies, most commonly ventricular septal defect, pulmonary stenosis and tricuspid valve disease. Clinical recognition can be challenging, so echocardiography is often the means by which definitive diagnosis is made. The tricuspid valve and right ventricle are on the systemic arterial side of the ccTGA circulation, and are therefore subject to progressive functional deterioration. The natural history of ccTGA is also greatly influenced by the nature and severity of accompanying lesions, some of which require surgical repair. Some management strategies leave the right ventricle as the systemic arterial pump, but carry the risk of worsening heart failure. More complex 'double switch' repairs establish the left ventricle as the systemic pump, and include an atrial baffle to redirect venous return in combination with either arterial switch or Rastelli operation (if a suitable ventricular septal defect permits). Occasionally, the anatomic peculiarities of ccTGA do not allow straightforward biventricular repair, and Fontan palliation is a reasonable option. Regardless of the approach selected, late cardiovascular complications are relatively common, so ongoing outpatient surveillance should be established in an age-appropriate facility with expertise in congenital heart disease care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The systemic right ventricle (SRV) is commonly encountered in congenital heart disease representing a distinctly different model in terms of its anatomic spectrum, adaptation, clinical phenotype, and variable, but overall guarded prognosis. The most common clinical scenarios where an SRV is encountered are complete transposition of the great arteries with previous atrial switch repair, congenitally corrected transposition of the great arteries, double inlet right ventricle mostly with previous Fontan palliation, and hypoplastic left heart syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded prognosis of the SRV in comparison with the systemic left ventricle are multifactorial, including distinct fibromuscular architecture, shape and function, coronary artery supply mismatch, intrinsic abnormalities of the tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV adaptation to pressure or volume overload. Management of the SRV remains an ongoing challenge because SRV dysfunction has implications on short- and long-term outcomes for all patients irrespective of underlying cardiac morphology. SRV dysfunction can be subclinical, underscoring the need for tertiary follow-up and timely management of target hemodynamic lesions. Catheter interventions and surgery have an established role in selected patients. Cardiac resynchronization therapy is increasingly used, whereas pharmacological therapy is largely empirical. Mechanical assist device and heart transplantation remain options in end-stage heart failure when other management strategies have been exhausted. The present report focuses on the SRV with its pathological subtypes, pathophysiology, clinical features, current management strategies, and long-term sequelae. Although our article touches on issues applicable to neonates and children, its main focus is on adults with SRV., (© 2018 American Heart Association, Inc.)

Objectives: Patients with Ebstein's anomaly of the tricuspid valve (EA) are at risk of tachyarrhythmia, congestive heart failure and sudden cardiac death. We sought to determine the value of cardiovascular magnetic resonance (CMR) for predicting these outcomes., Methods: Seventy-nine consecutive adult patients (aged 37±15 years) with unrepaired EA underwent CMR and were followed prospectively for a median 3.4 (range 0.4-10.9) years for clinical outcomes, namely major adverse cardiovascular events (MACEs: sustained ventricular tachycardia/heart failure hospital admission/cardiac transplantation/death) and first-onset atrial tachyarrhythmia (AT)., Results: CMR-derived variables associated with MACE (n=6) were right ventricular (RV) or left ventricular (LV) ejection fraction (EF) (HR 2.06, 95% CI 1.168 to 3.623, p=0.012 and HR 2.35, 95% CI 1.348 to 4.082, p=0.003, respectively), LV stroke volume index (HR 2.82, 95% CI 1.212 to 7.092, p=0.028) and cardiac index (HR 1.71, 95% CI 1.002 to 1.366, p=0.037); all remained significant when tested solely for mortality. History of AT (HR 11.16, 95% CI 1.30 to 95.81, p=0.028) and New York Heart Association class >2 (HR 7.66, 95% CI 1.54 to 38.20, p=0.013) were also associated with MACE; AT preceded all but one MACE, suggesting its potential role as an early marker of adverse outcome (p=0.011).CMR variables associated with first-onset AT (n=17; 21.5%) included RVEF (HR 1.55, 95% CI 1.103 to 2.160, p=0.011), total R/L volume index (HR 1.18, 95% CI 1.06 to 1.32, p=0.002), RV/LV end diastolic volume ratio (HR 1.55, 95% CI 1.14 to 2.10, p=0.005) and apical septal leaflet displacement/total LV septal length (HR 1.03, 95% CI 1.00 to 1.07, p=0.041); the latter two combined enhanced risk prediction (HR 6.12, 95% CI 1.67 to 22.56, p=0.007)., Conclusion: CMR-derived indices carry prognostic information regarding MACE and first-onset AT among adults with unrepaired EA. CMR may be included in the periodic surveillance of these patients., Competing Interests: Competing interests: RR was supported by the Swedish Society of Medicine, Swedish Heart-Lung Foundation and Swedish Society for Medical Research and by the Section of Clinical Physiology, Department of Molecular Medicine and Surgery, at Karolinska Institutet, Stockholm, Sweden. SVB-N was supported by an Intermediate Clinical Research Fellowship from the British Heart Foundation (FS/11/38/28864)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: The New York Heart Association functional classification (NYHA class) is often used to describe the functional capacity of adults with congenital heart disease (ACHD), albeit with limited evidence on its validity in this heterogeneous population. We aimed to validate the NYHA functional classification in ACHD by examining its relation to objective measures of limitation using cardiopulmonary exercise testing (CPET) and mortality., Methods and Results: This study included all ACHD patients who underwent a CPET between 2005 and 2015 at the Royal Brompton, in whom functional capacity was graded according to the NYHA classification. Congenital heart diagnoses were classified according to the Bethesda score. Time to all-cause mortality from CPET was recorded in all 2781 ACHD patients (mean age 33.8 ± 14.2 years) enrolled in the study. There was a strong relation between NYHA class and peak oxygen consumption (peak VO2), ventilation per unit in carbon dioxide production (VE/VCO2) slope and the Bethesda classification (P < 0.0001). Although a large number of 'asymptomatic' (NYHA class 1) patients did not achieve a 'normal' peak VO2, the NYHA class was a strong predictor of mortality, with an 8.7-fold increased mortality risk in class 3 compared with class 1 (hazard ratio 8.68, 95% confidence interval: 5.26-14.35, P < 0.0001)., Conclusion: Despite underestimating the degree of limitation in some ACHD patients, NYHA classification remains a valuable clinical tool. It correlates with objective measures of exercise and the severity of underlying cardiac disease, as well as mid- to long-term mortality and should, thus, be into incorporated the routine assessment and risk stratification of these patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.)

Objective: Infective endocarditis (IE) is associated with significant morbidity and mortality. Patients with adult congenital heart disease (ACHD) have an increased risk of developing IE. The aim of this study is to describe the incidence, predictors of outcome and mortality associated with IE in ACHD in a contemporary cohort., Methods: All episodes of IE in adults with congenital heart disease referred to our tertiary centre between 1999 and 2013 were included in the study. Patients were identified from the hospital database. The diagnosis of endocarditis was established according to the modified Duke criteria. The primary endpoint of the study was endocarditis-associated mortality., Results: There were 164 episodes of IE in 144 patients (male 102, 70.8%). Mean age at presentation was 32.3±22.7 years. Out of these, 43% had a simple, 23% a moderate and 32% a complex lesion. It was at least the second bout of IE in 37 episodes (23%). A predisposing event could be identified in only 26.2% of episodes. Surgical intervention during the same admission was performed in 61 episodes (37.2%). During a median follow-up of 6.7 years (IQR 2.9-11.4), 28 (19.4%) patients died. Out of these, 10 deaths were related to IE (IE mortality 6.9%). On unvariate regression analysis, the development of an abscess (OR: 7.23; 95% CI 1.81 to 28.94, p<0.01) and age (OR: 1.05; 95% CI 1.01 to 1.10, p=0.03) were the only predictors of IE-associated mortality. There was no increase in IE cases at our centre during the period of the study., Conclusions: IE-associated morbidity and mortality in a contemporary cohort of ACHD patients is still high in the current era., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot provides symptomatic benefit and right ventricular (RV) volume reduction. However, data on the rate of ventricular structural and functional adaptation are scarce. We aimed to assess immediate and midterm post-PVR changes and predictors of reverse remoeling., Methods: Fifty-seven patients with repaired tetralogy of Fallot (age ≥16 y; mean age, 35.8±10.1 y; 38 male) undergoing PVR were prospectively recruited for cardiovascular magnetic resonance performed before PVR (pPVR), immediately after PVR (median, 6 d), and midterm after PVR (mPVR; median, 3 y)., Results: There were immediate and midterm reductions in indexed RV end-diastolic volumes and RV end-systolic volumes (RVESVi) (indexed RV end-diastolic volume pPVR versus immediately after PVR versus mPVR, 156.1±41.9 versus 104.9±28.4 versus 104.2±34.4 mL/m 2 ; RVESVi pPVR versus immediately after PVR versus mPVR, 74.9±26.2 versus 57.4±22.7 versus 50.5±21.7 mL/m 2 ; P <0.01). Normal postoperative diastolic and systolic RV volumes (the primary end point) achieved in 70% of patients were predicted by a preoperative indexed RV end-diastolic volume ≤158 mL/m 2 and RVESVi ≤82 mL/m 2 . RVESVi showed a progressive decrease from baseline to immediate to midterm follow-up, indicating ongoing intrinsic RV functional improvement after PVR. Left ventricular ejection fraction improved (pPVR versus mPVR, 59.4±7.6% versus 61.9±6.8%; P <0.01), and right atrial reverse remodeling occurred (pPVR versus mPVR, 15.2±3.4 versus 13.8±3.6 cm 2 /m 2 ; P <0.01). Larger preoperative RV outflow tract scar was associated with a smaller improvement in post-PVR RV/left ventricular ejection fraction. RV ejection fraction and peak oxygen uptake predicted mortality ( P =0.03) over a median of 9.5 years of follow-up., Conclusions: Significant right heart structural reverse remodeling takes place immediately after PVR, followed by a continuing process of further biological remodeling manifested by further reduction in RVESVi. PVR before RVESVi reaches 82 mL/m 2 confers optimal chances of normalization of RV function., (© 2017 The Authors.)

Background: Adults with congenital heart disease (ACHD) have an increased risk for infective endocarditis (IE). In the last decade, the recommendations for IE prophylaxis have changed substantially. The knowledge level of patients about IE and IE prophylaxis has not been studied., Methods: Patients recruited via the German National Register for Congenital Heart Defects were invited to an online survey about IE. Patients were divided into two groups based on ESC guidelines: high IE risk (antibiotic prophylaxis recommended) and low IE risk (prophylaxis not recommended)., Results: Overall, 1458 patients participated and out of these 1211 (age 30.5±11.8years, female=54.2%) with detailed clinical information were further analyzed. 343 patients had a high IE risk, whereas 868 had a low risk. Overall, 74.5% (n=902) stated to know what IE is (low IE risk: 71.3%, high IE risk: 82.5%) Out of these who stated to know what IE is (n=902), 76.5% (n=690) chose the correct answer in a multiple choice question (low IE risk: 76.4%; high IE risk: 76.7%). Antibiotic prophylaxis was known to 66.2% (low IE risk: 59.9%; high IE risk: 82.2%). Out of these who stated to know what antibiotic prophylaxis is (n=802), 83.8% (n=672) chose the correct answer in a multiple choice question (low IE risk: 82.9%; high IE risk: 85.5%)., Conclusions: This study reveals important knowledge gaps regarding IE and antibiotic prophylaxis in ACHD patients. A discussion about IE and antibiotic prophylaxis should take place with every ACHD patient during regular clinical contacts to close this knowledge gap., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Most patients born with CHD nowadays reach adulthood, and thus quality of life, life situation, and state of medical care aspects are gaining importance in the current era. The present study aimed to investigate whether patients' assessment depends on their means of occupation. The findings are expected to be helpful in optimising care and for developing individual treatment plans., Methods: The present study was based on an online survey conducted in cooperation with patient organisations. Participants were recruited from the database of the German National Register for Congenital Heart Defects. In total, 1828 individuals (777 males, 1051 females) took part. Participants were asked to rate aspects such their state of health on a six-tier scale (1=worst specification). Response behaviour was measured against the background of occupational details., Results: Training for or pursuing a profession was found to be significantly associated with participants' rating of five of the six examined aspects (p<0.05). Sex seemed to play an important part in four of the six aspects., Conclusions: An optimal treatment plan for adults with CHD should always consider aspects such as sex and employment status. To work out such an optimal and individual treatment plan for each adult CHD patient, an objective tool to measure patients' actual CHD-specific knowledge precluding socially accepted response bias would be very useful.

Objective: Abnormal body mass index (BMI) is associated with higher mortality in various cardiovascular cohorts. The prognostic implications of BMI in adults with congenital heart disease (ACHD) are unknown. We aim to assess the distribution of BMI and its association with symptoms and survival in the ACHD population., Methods: We included 3069 ACHD patients (median age 32.6 years) under follow-up at our institution between 2001 and 2015. Patients were classified based on BMI as underweight (<18.5), normal weight (18.5-25), overweight (25-30) or obese (>30), and symptoms, exercise capacity and mortality were assessed., Results: Overall, 6.2% of patients were underweight, 51.1% had normal weight, 28.2% were overweight and 14.6% were obese. Higher BMI values were associated with lower all-cause and cardiac mortality on univariable Cox analysis, and this effect persisted after adjustment for age, defect complexity, cyanosis and objective exercise capacity. Higher BMI was especially associated with better prognosis in symptomatic ACHD patients (HR 0.94 (95% CI 0.90 to 0.98), p=0.002) and those with complex underlying cardiac defects (HR 0.96 (95% CI 0.91 to 0.997), p=0.048) In patients with a complex cardiac defect who had repeated weight measurements, weight loss was also associated with a worse survival (HR 1.82 (95% CI 1.02 to 3.24), p=0.04)., Conclusions: ACHD patients with a higher BMI had a lower mortality. The association between BMI and mortality was especially pronounced in symptomatic patients with complex underlying cardiac defects, suggesting that cardiac cachexia may play a role. Indeed, weight loss in complex ACHD patients was linked to an even higher mortality., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Advances in early management of congenital heart disease (CHD) have led to an exponential growth in adults with CHD (ACHD). Many of these patients require cardiac surgery. This study sought to examine outcome and its predictors for ACHD cardiac surgery., Methods: This is an observational cohort study of prospectively collected data on 1090 consecutive adult patients with CHD, undergoing 1130 cardiac operations for CHD at the Royal Brompton Hospital between 2002 and 2011. Early mortality was the primary outcome measure. Midterm to longer-term survival, cumulative incidence of reoperation, other interventions and/or new-onset arrhythmia were secondary outcome measures. Predictors of early/total mortality were identified., Results: Age at surgery was 35±15 years, 53% male, 52.3% were in New York Heart Association (NYHA) class I, 37.2% in class II and 10.4% in class III/IV. Early mortality was 1.77% with independent predictors NYHA class ≥ III, tricuspid annular plane systolic excursion (TAPSE) <15 mm and female gender. Over a mean follow-up of 2.8±2.6 years, 46 patients died. Baseline predictors of total mortality were NYHA class ≥ III, TAPSE <15 mm and non-elective surgery. The number of sternotomies was not independently associated with neither early nor total mortality. At 10 years, probability of survival was 94%. NYHA class among survivors was significantly improved, compared with baseline., Conclusions: Contemporary cardiac surgery for ACHD performed at a single, tertiary reference centre with a multidisciplinary approach is associated with low mortality and improved functional status. Also, our findings emphasise the point that surgery should not be delayed because of reluctance to reoperate only., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: Eisenmenger syndrome (ES) is associated with considerable morbidity and mortality. Therapeutic strategies have changed during the 2000s in conjunction with an emphasis on specialist follow-up. The aim of this study was to determine the cause-specific mortality in ES and evaluate any relevant changes between 1977 and 2015., Methods and Results: This is a retrospective, descriptive multicentre study. A total of 1546 patients (mean age 38.7 ± 15.4 years; 36% male) from 13 countries were included. Cause-specific mortality was examined before and after July 2006, 'early' and 'late', respectively. Over a median follow-up of 6.1 years (interquartile range 2.1-21.5 years) 558 deaths were recorded; cause-specific mortality was identified in 411 (74%) cases. Leading causes of death were heart failure (34%), infection (26%), sudden cardiac death (10%), thromboembolism (8%), haemorrhage (7%), and peri-procedural (7%). Heart failure deaths increased in the 'late' relative to the 'early' era (P = 0.032), whereas death from thromboembolic events and death in relation to cardiac and non-cardiac procedures decreased (P = 0.014, P = 0.014, P = 0.004, respectively). There was an increase in longevity in the 'late' vs. 'early' era (median survival 52.3 vs. 35.2 years, P < 0.001)., Conclusion: The study shows that despite changes in therapy, care, and follow-up of ES in tertiary care centres, all-cause mortality including cardiac remains high. Patients from the 'late' era, however, die later and from chronic rather than acute cardiac causes, primarily heart failure, whereas peri-procedural and deaths due to haemoptysis have become less common. Lifelong vigilance in tertiary centres and further research for ES are clearly needed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: The number of patients with congenital heart disease (CHD) is increasing worldwide and most of them will require cardiac surgery, once or more, during their lifetime. The total volume of cardiac surgery in CHD patients at a national level and the associated mortality and predictors of death associated with surgery are not known. We aimed to investigate the surgical volume and associated mortality in CHD patients in England., Methods: Using a national hospital episode statistics database, we identified all CHD patients undergoing cardiac surgery in England between 1997 and 2015., Results: We evaluated 57,293 patients (median age 11.9years, 46.7% being adult, 56.7% female). There was a linear increase in the number of operations performed per year from 1,717 in 1997 to 5,299 performed in 2014. The most common intervention at the last surgical event was an aortic valve procedure (9,276; 16.2%), followed by repair of atrial septal defect (9,154; 16.0%), ventricular septal defect (7,746; 13.5%), tetralogy of Fallot (3,523; 6.1%) and atrioventricular septal defect (3,330; 5.8%) repair. Associated mortality remained raised up to six months following cardiac surgery. Several parameters were predictive of post-operative mortality, including age, complexity of surgery, need for emergency surgery and socioeconomic status. The relationship of age with mortality was "U"-shaped, and mortality was highest amongst youngest children and adults above 60 years of age., Conclusions: The number of cardiac operations performed in CHD patients in England has been increasing, particularly in adults. Mortality remains raised up to 6-months after surgery and was highest amongst young children and seniors.

Background: The Fontan palliation is associated with numerous complications during long-term. The Fontan conversion operation has been advocated as an option to avoid some of these problems by converting classical Fontan types to modern forms of the circulation. Early mortality of Fontan conversion, however, remains unclear as available reports include limited numbers of patients and the results are heterogeneous., Methods: We reviewed all original articles from 1994 to 2016 reporting Fontan conversion operations. Reports were analysed with specific reference to patient demographics, patient number, concomitant arrhythmia surgery, pacemaker implantation and early mortality., Results: Overall, 37 Fontan conversion studies with a total of 1182 patients were analysed, including 35 single-centre studies and 2 registers. In the 35 single-centre studies the average age at the time of conversion was 21.6years (range 10.2-30.9years). Concomitant arrhythmia operation was performed in 71.6% of patients and concomitant pacemaker implantation procedure was performed in 59.3% of patients. Early mortality varied greatly between publications ranging from 0 to 21%. Based on a random and a fixed effect model mean mortality was 5.3% and 6.2%, respectively. Lower mortality was observed in series including younger patients at the time of conversion (average age<20years, 4.6%) and in the highest volume centre (1.4%)., Conclusion: Fontan conversion carries a substantial mortality risk. However, results vary between centres. Overall, the combination with arrhythmia surgery seems to be associated with lower early mortality especially when patients are referred at an earlier age and are treated at highly experienced centres., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: A growing number of adults with congenital heart disease (ACHD) pose a particular challenge for health care systems across the world. Upon turning into 18 years, under the German national health care system, ACHD patients are required to switch from a pediatric to an adult cardiologist or an ACHD-certified provider. To date, reliable data investigating the treatment situation of ACHD patients in Germany are not available., Materials and Methods: An online survey was conducted in collaboration with patient organizations to address the life situation and the conditions of health care provision for ACHD patients in Germany. ACHD patients were recruited from the database of the National Register for Congenital Heart Defects (NRCHD) and informed about the survey via email, websites, and social networks. A total of 1,828 ACHD patients (1,051 females) participated in this study. The mean age was 31.7 ± 11.7 years. Participants were surveyed about treating physicians and the institution mainly involved in the treatment of their CHD. In addition, participants were asked questions to assess the level of trust toward their treating physician and their familiarity with the term "ACHD-certified provider.", Results: Among the surveyed patients, 25.4% stated that they attended a specific ACHD clinic at a heart center regularly, 32.7% were treated in a private practice setting by a pediatric cardiologist, 32.4% in a private practice (adult) cardiology setting, and 9.5% were treated by an "other physician." Only 24.4% of the male and 29.7% of the female ACHD patients were familiar with the term "ACHD-certified provider.", Conclusion: The transfer from pediatric cardiology to ACHD care requires further attention as many adult patients have not transferred to certified ACHD providers. The question of whether ACHD patients in Germany are offered consistent and adequate care should also be investigated in more detail. The answers regarding the ACHD certification are particularly disappointing and indicative of a large information gap and inadequate education in clinical practice.

Background: Eisenmenger syndrome is associated with substantial morbidity and mortality. There is no consensus, however, on mortality risk stratification. We aimed to investigate survival and predictors of death in a large, contemporary cohort of Eisenmenger syndrome patients., Methods: In a multicenter approach, we identified adults with Eisenmenger syndrome under follow-up between 2000 and 2015. We examined survival and its association with clinical, electrocardiographic, echocardiographic, and laboratory parameters., Results: We studied 1098 patients (median age, 34.4 years; range, 16.1-84.4 years; 65.1% female; 31.9% with Down syndrome). The majority had a posttricuspid defect (n=643, 58.6%), followed by patients with a complex (n=315, 28.7%) and pretricuspid lesion (n=140, 12.7%). Over a median follow-up of 3.1 years (interquartile range, 1.4-5.9), allowing for 4361.6 patient-years observation, 278 patients died and 6 underwent transplantation. Twelve parameters emerged as significant predictors of death on univariable analysis. On multivariable Cox regression analysis, only age (hazard ratio [HR], 1.41/10 years; 95% confidence interval [CI], 1.24-1.59; P <0.001), pretricuspid shunt (HR, 1.56; 95% CI, 1.02-2.39; P =0.041), oxygen saturation at rest (HR, 0.53/10%; 95% CI, 0.43-0.65; P <0.001), presence of sinus rhythm (HR, 0.53; 95% CI, 0.32-0.88; P =0.013), and presence of pericardial effusion (HR, 2.41; 95% CI, 1.59-3.66; P <0.001) remained significant predictors of death., Conclusions: There is significant premature mortality among contemporary adults with Eisenmenger syndrome. We report, herewith, a multivariable mortality risk stratification model based on 5 simple, noninvasive predictors of death in this population., (© 2016 American Heart Association, Inc.)

Background: Controversial results on maternal risk and fetal outcome have been reported in women with aortic stenosis (AS)., Objectives: The authors sought to investigate maternal and fetal outcomes in patients with AS in a large cohort., Methods: The Registry on Pregnancy and Cardiac Disease (ROPAC) is a global, prospective observational registry of women with structural heart disease, providing a uniquely large study population. Data of women with moderate (peak gradient 36 to 63 mm Hg) and severe AS (peak gradient ≥64 mm Hg) were analyzed., Results: Of 2,966 pregnancies in ROPAC, the authors identified 96 women who had at least moderate AS (34 with severe AS). No deaths were observed during pregnancy and in the first week after delivery. However, 20.8% of women were hospitalized for cardiac reasons during pregnancy. This was significantly more common in severe AS compared with moderate AS (35.3% vs. 12.9%; p = 0.02), and reached the highest rate (42.1%) in severe, symptomatic AS. Pregnancy was complicated by heart failure in 6.7% of asymptomatic and 26.3% of symptomatic patients, but could be managed medically, except for 1 patient who was symptomatic before pregnancy and underwent balloon valvotomy. Children of patients with severe AS had a significantly higher percentage of low birth weight (35.0% vs. 6.0%; p = 0.006)., Conclusions: Mortality in pregnant women with AS, including those with severe AS, appears to be close to zero in the current era. Symptomatic and severe AS does, however, carry a substantial risk of heart failure and is associated with high rates of hospitalization for cardiac reasons, although heart failure can nearly always be managed medically. The results highlight the importance of appropriate pre-conceptional patient evaluation and counseling., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Echocardiographic parameters of ventricular deformation of the systemic right ventricle (sRV) predict adverse clinical outcome in patients after atrial repair of transposition of the great arteries (TGA). We assessed myocardial deformation on cardiac MRI (CMR) and correlated these with clinical and conventional CMR parameters in TGA patients., Methods: Retrospective analysis of CMR studies in 91 TGA patients (66% male; mean age 30.1±5.1years) at two tertiary adult congenital heart centers was conducted. Myocardial deformation was assessed by CMR-based feature tracking (FT), providing longitudinal (LS), radial (RS), and circumferential (CS) global strain for the sRV and the subpulmonary left ventricle. A subgroup of optimal TGA was defined (NYHA class I, NT-proBNP <300pg/ml, max. exercise work load ≥100watt, no significant clinical events) as a reference cohort., Results: There was a significant correlation between FT and conventional CMR parameters. Left ventricular ejection fraction (LVEF) correlated significantly with LV LS, RS, and CS (r between 0.24 and 0.34, p values between 0.03 and 0.005). sRVEF correlated with RV CS (r=0.56, p<0.001), and RV RS (r=0.32, p=0.007). QRS duration showed a negative correlation with RV CS (r=-0.53, p<0.001), LV RS (r=-0.34, p=0.008), and LV CS (r=-0.34, p=0.006). Reference values for the novel FT method in clinically optimal TGA patients are provided., Conclusion: Assessment of myocardial function using CMR-based FT is feasible in TGA patients. FT measurements related to important prognostic clinical parameters. Furthermore, we provide for the first time reference values for TGA patients in an optimal clinical status., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To characterise patients with trisomy 21 (Down syndrome, DS) based on the data of the German National Register for Congenital Heart Defects, to identify changes in the availability of surgical therapy over time and to analyse the impact of these changes on developing Eisenmenger syndrome (ES) as well as survival., Methods: Out of 1549 patients with DS with congenital heart disease in the National Register for Congenital Heart Defects, 894 patients (55% female, mean age 17.5 years) had a post-tricuspid shunt lesion (atrioventricular septal defect 69.5%, ventricular septal defect 27.7%, patent arterial duct 2.6%) and were included in the current study., Results: The likelihood of being treated interventionally or surgically before the age of 1 year increased significantly over time. In parallel, the likelihood of developing ES decreased over time (53% birth cohort during 1950s/1960s vs 0.5% birth cohort during 2000-2009, p<0.0001). Overall survival after 1, 10, 20 and 40 years was 96.8%, 94.1%, 92.6% and 75.5%, respectively. Patients with ES had a significantly worse survival compared with those without ES (HR 18.1; 95% CI 7.2 to 45.4; p<0.0001)., Conclusions: The availability of surgical correction was associated with a decrease in the likelihood of developing ES. Patients with DS still have reduced survival prospects compared with the general population, but this effect is largely driven by patients developing ES who still have a very poor prognosis., (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: Systemic right ventricular (RV) dysfunction and sudden cardiac death remain problematic late after Mustard operation for transposition of the great arteries. The exact mechanism for that relationship is likely to be multifactorial including myocardial fibrosis. Doppler echocardiography gives further insights into the role of fibrosis shown by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in late morbidity., Methods and Results: Twenty-two consecutive patients, mean age 28±8years, were studied with 2D echocardiography, and also assessed by LGE CMR. The presence of LGE in 13/22 patients (59%) was related to delayed septal shortening and lengthening (P=0.002 &P=0.049), prolonged systemic RV isovolumic contraction time (P=0.024) and reduced systemic RV free wall and septal excursion (P=0.027 &P=0.005). The systemic RV total isovolumic time was prolonged but not related to extent of LGE. LGE extent was related to markers of electromechanical delay and dyssynchrony (delayed onset of RV free wall shortening and lengthening; r=0.73 &P=0.004 and r=0.62 &P=0.041, respectively, and QRS duration r=0.68, P<0.01) and was inversely related to systolic RV free wall shortening velocity (r=-0.59 &P=0.042). The presence of LGE was also related to lower exercise capacity, ≥mild tricuspid regurgitation and more arrhythmia (P=0.008, P=0.014 and P=0.040). RV free wall excursion and systolic tissue Doppler velocity were related to CMR derived RV ejection fraction (r=0.51, P=0.015, and r=0.77, P=<0.001, respectively)., Conclusion: Post Mustard repair, myocardial fibrosis is related to dyssynchrony, RV long axis dysfunction and tricuspid regurgitation. Echocardiographic measurements of systemic RV function can be confidently used in serial follow-up following Mustard operation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for different forms of PH, and specifically address PH associated with congenital heart disease (CHD). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH in grown-ups with congenital heart disease (GUCH). This article summarizes the results and recommendations of this working group., (© Georg Thieme Verlag KG Stuttgart · New York.)

Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. The present review aims to discuss the clinical applications of invasive and non-invasive diagnostic modalities and to describe the strengths and weaknesses of each technique. Chest radiograph is an inexpensive investigation providing information on pulmonary arterial and hilar dilatation, pruning of peripheral pulmonary arteries and cardiomegaly. Transthoracic two-dimensional and Doppler echocardiography is the most widely used imaging tool. It provides information on cardiac anatomy and an estimate of haemodynamics and biventricular remodelling and function. In addition, echocardiography is valuable in assessing prognosis and monitoring the efficacy of therapy. Structural and functional changes associated with CHD-PAH, mainly affecting the right ventricle and pulmonary circulation, may represent an ideal target for evaluation with cardiac magnetic resonance. This non-invasive imaging modality has a low biological impact. CT plays an important role for patients with limited echocardiographic windows and those who are unable to undergo MRI (claustrophobia, poor compliance, presence of a pacemaker/implantable cardioverter defibrillator). It is the modality of choice for detailed assessment of pulmonary vessel obstruction or thrombosis. Finally, heart catheterisation remains the gold standard for diagnosing and confirming PAH in patients with CHD and for shunt evaluation. The diagnostic assessment of CHD-PAH requires great expertise and a deep knowledge of both CHD and PAH pathophysiology and should take place in a tertiary centre, where multiple data can be appropriately integrated and applied clinically., (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/)