Development of quality indicators of transfer and transition in adolescents and young adults with congenital heart disease.

BACKGROUND: Quality indicators are crucial in evaluating and comparing the quality of healthcare services. In the case of congenital heart disease, transition programmes for adolescents have been recommended to ensure uninterrupted healthcare and lifelong care. It is necessary to establish quality indicators in order to facilitate the evaluation of programme quality and to allow comparison between different centres. The objective of this study is therefore to develop a set of quality indicators for the transition of adolescents with congenital heart disease. METHODS: The RAND/UCLA appropriateness method was employed in a four-step process to develop a set of quality indicators. First, a literature search was conducted on the dimensions of transitional care, based on which a preliminary set of quality indicators was developed. Second, experts were contacted, and an expert panel was established. Third, the panel members were asked to rate the appropriateness of the quality indicators in a two-round process. Finally, in the fourth step, we evaluated the data by measuring the median and Disagreement Index. RESULTS: The expert panel consisted of 16 members, congenital cardiologists, nurses, transition experts, patients and research experts. The preliminary set of quality indicators comprised 16 items, categorized in process and structure criteria. Based on the panel's feedback, the set was refined to 12 quality indicators, which were rated as relevant and feasible. CONCLUSIONS: This study represents the first attempt to develop quality indicators for transitional care services for adolescents with congenital heart disease. The set of 12 quality indicators was developed based on existing evidence and expert opinion. Further testing is needed to assess the feasibility of these quality indicators in daily practice. If successfully implemented, these quality indicators could allow comparison and facilitate benchmarking of transitional care services for adolescents with congenital heart disease.

Coronavirus disease 2019 in adults with congenital heart disease: a position paper from the ESC working group of adult congenital heart disease, and the International Society for Adult Congenital Heart Disease.

We are witnessing an unparalleled pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated with coronavirus disease 2019 (COVID-19). Current data show that SARS-CoV-2 results in mild flu-like symptoms in the majority of healthy and young patients affected. Nevertheless, the severity of COVID-19 respiratory syndrome and the risk of adverse or catastrophic outcomes are increased in patients with pre-existing cardiovascular disease. Patients with adult congenital heart disease (ACHD)-by definition-have underlying cardiovascular disease. Many patients with ACHD are also afflicted with residual haemodynamic lesions such as valve dysfunction, diminished ventricular function, arrhythmias or cyanosis, have extracardiac comorbidities, and face additional challenges regarding pregnancy. Currently, there are emerging data of the effect of COVID-19 on ACHD patients, but many aspects, especially risk stratification and treatment considerations, remain unclear. In this article, we aim to discuss the broad impact of COVID-19 on ACHD patients, focusing specifically on pathophysiology, risk stratification for work, self-isolation, hospitalization, impact on pregnancy, psychosocial health, and longer-term implications for the provision of ACHD care.

Impact of a structured patient education programme on early diagnosis of prosthetic pulmonary valve endocarditis.

BACKGROUND: Infective endocarditis is a major threat after prosthetic pulmonary valve replacement. Early diagnosis may improve outcomes. METHODS: A structured patient education programme for prevention and early diagnosis of infective endocarditis was developed at our institution since 2016. Time delay between onset of symptoms of prosthetic pulmonary valve endocarditis and its diagnosis (defined as initiation of appropriate high-dose intravenous antibiotic treatment) was compared for patients presenting before (cohort 1) and after (cohort 2) initiation of the patient education programme. RESULTS: Between 2008-2019, 26 patients (median age 24.9, range: 16.8-62.0 years, 73% male) were diagnosed with prosthetic pulmonary valve endocarditis, 13 patients (cohort 1) before (1.7 cases/year) and 13 patients (cohort 2) after June 2016 (3.7 cases/year). There were no differences in baseline characteristics or clinical presentation between the study cohorts. Overall, the median delay between onset of symptoms and diagnosis of infective endocarditis was 6 days (range: 0-133 days) with a significantly longer delay among patients in cohort 1, compared to cohort 2 (25 days, range: 5-133 days versus 3 days, range: 0-13 days, p < 0.0001). A delay of >7 days was documented in 11/13 patients (85%) in cohort 1 as compared to 1/13 (8%) in cohort 2 (p < 0.001). Need for urgent valve replacement or permanent deterioration of prosthetic valve function was higher in cohort 1, compared to cohort 2 (11/13, 85% versus 5/13, 39%; p = 0.041). CONCLUSIONS: Prosthetic pulmonary valve endocarditis is increasingly recognised. A structured patient education programme may improve early diagnosis and clinical outcomes.

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

[2020 ESC guidelines on treatment of adult congenital heart disease (ACHD)]. / ESC-Leitlinie 2020 zur Behandlung von Erwachsenen mit angeborenem Herzfehler (ACHD).

The new guidelines of the European Society of Cardiology (ESC) on treatment of adult congenital heart disease (ACHD) were published in August 2020. The previous recommendations from 2010 were adapted to reflect the diagnostic and therapeutic progress made in the past 10 years. The recommendations are nearly exclusively based on an evidence level C (consensus of opinion of experts or knowledge from small studies, retrospective studies or registries). This is not surprising considering the heterogeneous patient population with a multitude of cardiac defects and repair strategies performed in the past. The cohort of ACHD patients is steadily growing in numbers and is becoming older due to reduced perioperative morbidity and mortality and further medical progress. Therefore, the current guidelines do not focus solely on the acute treatment of cardiac problems but also address the importance of a comprehensive longitudinal follow-up for a chronic, lifelong disorder. On a defect-specific level, progress in the past decade in arrhythmia diagnosis and management, percutaneous interventions and the treatment of pulmonary arterial hypertension have led to many revised or new recommendations. Finally, the 2020 guidelines also address for the first time the management of coronary anomalies.

Recommendations for advance care planning in adults with congenital heart disease: a position paper from the ESC Working Group of Adult Congenital Heart Disease, the Association of Cardiovascular Nursing and Allied Professions (ACNAP), the European Association for Palliative Care (EAPC), and the International Society for Adult Congenital Heart Disease (ISACHD).

Survival prospects in adults with congenital heart disease (CHD), although improved in recent decades, still remain below expectations for the general population. Patients and their loved ones benefit from preparation for both unexpected and predictable deaths, sometimes preceded by a prolonged period of declining health. Hence, advance care planning (ACP) is an integral part of comprehensive care for adults with CHD. This position paper summarizes evidence regarding benefits of and patients' preferences for ACP and provides practical advice regarding the implementation of ACP processes within clinical adult CHD practice. We suggest that ACP be delivered as a structured process across different stages, with content dependent upon the anticipated disease progression. We acknowledge potential barriers to initiate ACP discussions and emphasize the importance of a sensitive and situation-specific communication style. Conclusions presented in this article reflect agreed expert opinions and include both patient and provider perspectives.

Adolescents' with congenital heart disease and their parents' experiences of a nurse-led transition program. An interpretive phenomenological study / Wie Eltern und ihre Kinder die pflegegeleitete Transitionssprechstunde für Adoleszente mit angeborenen Herzfehlern erleben. Eine interpretierende phänomenologische Studie

Background: Up to 90 % of patients with congenital heart disease (CHD) now reach adulthood. To avoid lapses in care during the change from pediatric to adult care, a nurse-led transition program (TP) was implemented at a Swiss University Hospital. Aim: This study explored the experiences and expectations of adolescents with CHD and their parents regarding a nurse-led TP. Method: This qualitative study used an interpretive, phenomenological approach. Individual interviews were conducted with seven adolescent CHD patients in the transition period and their parents (six mothers, two fathers). Analysis followed an iterative process. Results: For most study participants, the transfer from pediatric to adult medicine as part of the TP went smoothly. They experienced the TP positively. Patients valued the provision of a constant contact person to provide CHD-related information; parents welcomed the support of an informed, neutral clinician for their children. To varying degrees, adolescents were willing to take over self-responsibility; conversely, parents found it difficult to turn their responsibility over to their children. Parents wished to give the adolescent as much time as needed to act responsibility on their own. Conclusions: A transition program is a key element for establishing a continuous care in adolescents with a chronic disease. It facilitates the parents' process of allowing their youths to assume increasing responsibility for their own health.

Long-term data from the Swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

Prognostic value of right ventricular dyssynchrony in adults with repaired tetralogy of Fallot.

OBJECTIVE: Residual sequelae after surgical repair of tetralogy of Fallot (rTOF) affect clinical outcome. We investigated the prognostic impact of right ventricular (RV) dyssynchrony in adults with rTOF years after the surgical repair. METHODS: Patients from the Swiss Adult Congenital HEart disease Registry were included. NT-proBNP levels, echocardiography, exercise testing and MRI data were collected. An offline strain analysis to quantify RV-ventricular and interventricular dyssynchrony was performed. The standard deviation of the time-to-peak shortening (TTP) of six RV segments defined the RV Dyssynchrony Index (RVDI). Maximal difference of TTP between RV and left ventricular segments defined the interventricular shortening delay (IVSD). Predictors of a composite adverse event (arrhythmias, hospitalisation for heart failure and death) were identified by multivariate Cox regression analysis. Their median values were used to create a risk score. RESULTS: Out of 285 included patients (mean age 34±14 years), 33 patients (12%) experienced an adverse event during a mean follow-up of 48±21 months. No correlation was found between RVDI, IVSD and clinical events. NT-proBNP, right atrial area and peak heart rate were independent predictors of outcomes. After 4 years-follow-up, no adverse events occurred in patients at low risk (score=0 points), while an adverse event occurred in 62% of patients at high risk (score=3 points, p<0.001). CONCLUSION: In our cohort of adults with rTOF, surrogates of RV dyssynchrony did not correlate with outcomes. A multimodality approach was effective in predicting the risk for adverse events.

Association of reduced peak left atrial strain with supraventricular arrhythmia in adults with congenital heart disease.

Atrial arrhythmias are an important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, the left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study aimed to investigate whether reduced LA strain is associated with SVT in ACHD patients. This retrospective, single-center cohort study collected baseline clinical and echocardiographic data of 206 ACHD patients (157 left heart defect, 49 right heart defect). Patients with sinus rhythm at baseline and a 5-year follow-up (median age 29, IQR 22-41 years) were included. Diagnosis of sustained SVT was determined from clinical reports during the follow-up period. New or recurrent sustained SVT occurred in 16 patients (7.8%, median follow-up of 6.2 years). Patients who developed SVT were older, more likely to have diastolic dysfunction, and had larger LA dimensions, left ventricular mass, and a lower peak LA longitudinal strain (PALS). Lower PALS was associated with higher risk of SVT in patients with left and right heart defects. Patients in the lowest quartile for PALS had a 15.9-fold higher hazard ratio of SVT (95% confidence interval, 4.5 to 56.0, p < 0.001) in comparison with the top three quartiles. PALS provides information about the occurrence of SVT in the ACHD population. Including measurement of LA strain in the follow-up of these patients may allow to better identify patients at risk of future atrial arrhythmias.

NT-proBNP in systemic right ventricles: a new cutoff level for risk stratification?

INTRODUCTION AND OBJECTIVES: The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the risk prediction of patients with systemic right ventricles (sRV) is not well defined. The aim of this study was to analyze the prognostic value of NT-proBNP in patients with an sRV. METHODS: The prognostic value of NT-proBNP was assessed in 98 patients from the SERVE trial. We used an adjusted Cox proportional hazards model, survival analysis, and c-statistics. The composite primary outcome was the occurrence of clinically relevant arrhythmia, heart failure, or death. Correlations between baseline NT-proBNP values and biventricular volumes and function were assessed by adjusted linear regression models. RESULTS: The median age [interquartile range] at baseline was 39 [32-48] years and 32% were women. The median NT-proBNP was 238 [137-429] ng/L. Baseline NT-proBNP concentrations were significantly higher among the 20 (20%) patients developing the combined primary outcome compared with those who did not (816 [194-1094] vs 205 [122-357]; P=.003). In patients with NT-proBNP concentrations> 75th percentile (> 429 ng/L), we found an exponential increase in the sex- and age-adjusted hazard ratio for the primary outcome. The prognostic value of NT-proBNP was comparable to right ventricular ejection fraction and peak oxygen uptake on exercise testing (c-statistic: 0.71, 0.72, and 0.71, respectively). CONCLUSIONS: In patients with sRVs, NT-proBNP concentrations correlate with sRV volumes and function and may serve as a simple tool for predicting adverse outcomes.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Impact of pulmonary valve replacement on ventricular function and cardiac events in patients with tetralogy of Fallot. A retrospective cohort study.

INTRODUCTION AND OBJECTIVES: Our aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. METHODS: Adults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. RESULTS: A total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, -1.33; 95%CI, -5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). CONCLUSIONS: Previous PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Arrhythmias and Clinical Outcomes in a Swiss Multicenter Cohort of Patients With Dextro-Transposition of the Great Arteries and Atrial Switch.

Background Data on the incidence of arrhythmias, associated cardiac interventions, and outcome in patients with dextro-transposition of the great arteries and atrial switch are scarce. Methods and Results In this multicenter analysis, we included adult patients with dextro-transposition of the great arteries and atrial switch regularly followed up at 3 Swiss tertiary care hospitals. The primary outcome was a composite of left ventricular assist device, heart transplantation, and death. The secondary outcome was occurrence of ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. We identified 207 patients (34% women; median age at last follow-up, 35 years) with dextro-transposition of the great arteries and atrial switch. Arrhythmias occurred in 97 patients (47%) at a median age of 22 years. A pacemaker or an implantable cardioverter-defibrillator was implanted in 39 (19%) and 13 (6%) patients, respectively, and 33 (16%) patients underwent a total of 51 ablation procedures to target 60 intra-atrial re-entry tachycardias, 4 atrioventricular nodal re-entry tachycardias, and 1 atrial fibrillation. The primary outcome occurred in 21 patients (10%), and the secondary outcome occurred in 18 patients (9%); both were more common in patients with concomitant ventricular septum defect than in those without (hazard ratio [HR], 3.06 [95% CI, 1.29-7.27], P=0.011; and HR, 3.62 [95% CI, 1.43-9.18], P=0.007, respectively). Conclusions In patients with dextro-transposition of the great arteries and atrial switch reaching adulthood, arrhythmias occur in almost half of patients, and associated rhythm interventions are frequent. One-tenth of those patients do not survive until the age of 35 years free from left ventricular assist device or heart transplantation, and the outcome is worse in patients with concomitant ventricular septum defect.

Determinants of Advanced Liver Fibrosis in Adult Patients After Fontan Palliation: Usefulness of Ultrasound Transient Elastography.

BACKGROUND: Fontan-associated liver disease is an increasing concern. Our aim was to assess prevalence and predictors of advanced liver fibrosis with a specific focus on utility of liver stiffness measurement by ultrasound transient elastography. METHODS: A total of 97 adult Fontan patients (55% male, median age: 23.1 years, interquartile range [IQR]: 18.7-30.6); 92 (95%) were evaluated with transient elastography, and 50 (52%) underwent transjugular liver biopsy. Advanced liver fibrosis was defined as congestive hepatic fibrosis score 3 or 4. RESULTS: Only 4 patients (4%) had liver stiffness values < 10 kilopascal (kPa). Liver-stiffness measurements correlated weakly with peak oxygen uptake on exercise testing and Fontan pressure but not with Model for End-Stage Liver Disease excluding INR (MELD-XI) score or spleen size. Serial follow-up liver stiffness measurements in 73 clinically stable patients showed large variability among individual patients. Advanced liver fibrosis was present in 35 of 50 (70%) patients on liver biopsy and was associated to MELD-XI-Score ≥ 11 and splenomegaly but not to liver-stiffness measurements. Advanced liver fibrosis was not associated with patient age or time since Fontan operation but with younger age at completion of Fontan (3.7 years, IQR: 2.3-6.3 vs 6.8 years; IQR: 3.5-12.1; P = 0.037). CONCLUSIONS: In our cohort, advanced liver fibrosis was present in the majority of adult Fontan patients. Liver stiffness as measured by transient elastography was not associated with the degree of liver fibrosis. Because of its high variability on serial measurements, it seems not to be useful for clinical decision making. The unexpected finding that younger age at completion of Fontan was associated with advanced liver fibrosis merits further evaluation.

Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function. A multicentre, double-blind, randomized, placebo-controlled trial: SERVE.

AIMS: In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end-systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N-terminal pro-B-type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 years of follow-up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular end-systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval -4.3 to 11.0, p = 0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo group. CONCLUSIONS: In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a 3-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles.

The coronavirus disease pandemic among adult congenital heart disease patients and the lessons learnt - results of a prospective multicenter european registry.

Background: At the beginning of the COVID-19 pandemic, professionals in charge of particularly vulnerable populations, such as adult congenital heart disease (ACHD) patients, were confronted with difficult decision-making. We aimed to assess changes in risk stratification and outcomes of ACHD patients suffering from COVID-19 between March 2020 and April 2021. Methods and results: Risk stratification among ACHD experts (before and after the first outcome data were available) was assessed by means of questionnaires. In addition, COVID-19 cases and the corresponding patient characteristics were recorded among participating centres. Predictors for the outcome of interest (complicated disease course) were assessed by means of multivariable logistic regression models calculated with cluster-robust standard errors. When assessing the importance of general and ACHD specific risk factors for a complicated disease course, their overall importance and the corresponding risk perception among ACHD experts decreased over time. Overall, 638 patients (n = 168 during the first wave and n = 470 during the subsequent waves) were included (median age 34 years, 52% women). Main independent predictors for a complicated disease course were male sex, increasing age, a BMI >25 kg/m2, having ≥2 comorbidities, suffering from a cyanotic heart disease or having suffered COVID-19 in the first wave vs. subsequent waves. Conclusions: Apart from cyanotic heart disease, general risk factors for poor outcome in case of COVID-19 reported in the general population are equally important among ACHD patients. Risk perception among ACHD experts decreased during the course of the pandemic.

COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease.

Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.