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Background: Survival data that are applicable to the current population of adults with congenital heart disease (CHD) are not available.Objectives: Using an alternative survival analysis with age as the primary time scale, we assessed the contemporary survival of adult patients with CHD.Methods: Survival was assessed using prospective data of the national registry of adult patients with CHD of the Netherlands. Survival was stratified by severity and lesion, and compared with a standardised general population.Results: Mean age at inclusion was 37 years, and 49% of the study population was male. During a cumulative prospective follow-up of 90, 270 patient-years in 14, 327 patients, 535 deaths occurred. Median survival was 53.4 (95% CI 49.9 to 60.7), 75.4 (95% CI 72.9 to 79.1) and 84.1 (95% CI 81.9 to 87.0) years for patients with severe, moderate and mild lesions, respectively. Survival of most patients with mild lesions did not differ from the general population, while, as expected, survival of patients with severe and moderate lesions was substantially lower (<0.001).Conclusions: The present study gives insight in the contemporary survival of adults with CHD. This may aid patient counselling, timing of interventions and future research. [ABSTRACT FROM AUTHOR]

Background: Risk factors for adverse clinical outcomes have been identified in patients with repaired tetralogy of Fallot before pulmonary valve replacement (PVR). However, pre-PVR predictors for post-PVR sustained ventricular tachycardia and death have not been identified.Methods: Patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort (International Multicenter TOF Registry), a 4-center international cohort study, who had a comprehensive preoperative evaluation and subsequently underwent PVR were included. Preprocedural clinical, ECG, cardiovascular magnetic resonance, and postoperative outcome data were analyzed. Cox proportional hazards multivariable regression analysis was used to evaluate factors associated with time from pre-PVR cardiovascular magnetic resonance until the primary outcome: death, aborted sudden cardiac death, or sustained ventricular tachycardia.Results: Of the 452 eligible patients (median age at PVR, 25.8 years), 36 (8%) reached the primary outcome (27 deaths, 2 resuscitated death, and 7 sustained ventricular tachycardia) at a median time after PVR of 6.5 years. Cox proportional hazards regression identified pre-PVR right ventricular ejection fraction <40% (hazard ratio, 2.39; 95% CI, 1.18-4.85; P=0.02), right ventricular mass-to-volume ratio ≥0.45 g/mL (hazard ratio, 4.08; 95% CI, 1.57-10.6; P=0.004), and age at PVR ≥28 years (hazard ratio, 3.10; 95% CI, 1.42-6.78; P=0.005) as outcome predictors. In a subgroup analysis of 230 patients with Doppler data, predicted right ventricular systolic pressure ≥40 mm Hg was associated with the primary outcome (hazard ratio, 3.42; 95% CI, 1.09-10.7; P=0.04). Preoperative predictors of a composite secondary outcome, postoperative arrhythmias and heart failure, included older age at PVR, pre-PVR atrial tachyarrhythmias, and a higher left ventricular end-systolic volume index.Conclusions: In this observational investigation of patients with repaired tetralogy of Fallot, an older age at PVR and pre-PVR right ventricular hypertrophy and dysfunction were predictive of a shorter time to postoperative death and sustained ventricular tachycardia. These findings may inform the timing of PVR if confirmed by prospective clinical trials. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac defects considering the prognostic and therapeutic implications. Improved interventional techniques have enabled repair or palliation of most cardiac defects, though a substantial number of patients remain at high risk for PAH after closure. Traditionally, the treatment and management of PAH-CHD patients has been limited to palliative and supportive care, and based on expert opinion rather than clinical trials. Recently, however, the availability of advanced PAH-specific treatment has opened up a new field for the clinical management of this condition. Nevertheless, there is limited evidence on the optimal therapeutic approach for PAH-CHD. Herein, we discuss the current and novel therapeutic options for PAH-CHD as well as highlight several challenges in the clinical management at present. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD), mainly caused by ventricular arrhythmias, is one of the leading causes of mortality in adult congenital heart disease (ACHD) patients. An implantable cardioverter defibrillator (ICD) may prevent SCD, but risk stratification remains challenging. In this review, we will address the current guideline recommendations for ICD implantation in ACHD patients, as well as review a recent study in which the discriminative ability for SCD of these guidelines is evaluated. In this study, the guideline recommendations were applied to patients who died of SCD and living controls. Among SCD cases, 35%-41% of patients were recommended ICD, whereas 16%-17% of controls were recommended ICD. The discriminative ability for SCD of the guidelines was poor, with an area under the receiver operating characteristic curve of 0.61-0.63. Risk stratification for SCD in ACHD patients, therefore, remains to be a work-in-progress. [ABSTRACT FROM AUTHOR]

The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD. [ABSTRACT FROM AUTHOR]

The author reflects on the risk of infective endocarditis (IE) in patients with congenital heart disease (CHD). She reveals that the overall incidence of endocarditis in adults with CHD is 11% per 100,000 person. She notes on the guidelines on IE prophylaxis which emphasized the role of primary prevention. She discusses a study which reports the cumulative incidence and predictors of IE in children 0-18 years old with CHD.

Background: Type D personality, characterized by high levels of negative affectivity and social inhibition, is related to mortality, morbidity, poor health status, quality of life (QoL) and less healthcare utilization in various cardiovascular patient groups. To date, studies in patients with congenital heart disease (CHD) are lacking. Aims: (1) To examine the prevalence of Type D personality in CHD patients; (2) to compare Type D to non-Type D patients with regard to disease severity, functional status, health status and QoL; and (3) to examine the extent to which Type D personality is independently related to healthcare utilization. Methods: A total of 1109 adult CHD patients were included in a questionnaire survey. Due to missing data, 302 patients were excluded. Results: The prevalence of Type D personality was 20.4%. Type D patients reported a poorer functional status, health status and QoL than non-Type D patients (p <0.05). Type D patients reported less healthcare use than non-Type D patients (primary and cardiac outpatient healthcare: adjusted OR=0.56, 95% CI=0.35–0.90; inpatient healthcare: adjusted OR=0.38, 95% CI=0.17–0.83). Results of a post-hoc analysis showed a high prevalence of Type D personality in patients with a poor functional status who did not consult their cardiologist. Conclusion: Type D patients report a poorer functional status, health status and QoL, but less healthcare utilization. In clinical practice, patients should be screened for Type D personality, since social inhibition may prevent them from contacting a healthcare provider in the event of symptom aggravation. [ABSTRACT FROM AUTHOR]

Abstract: Survival of patients with aortic coarctation has dramatically improved after surgical repair became available and the number of patients who were operated and reach adulthood is steadily increasing. However, life expectancy is still not as normal as in unaffected peers. Cardiovascular complications are frequent and require indefinite follow-up. Concern falls chiefly in seven categories: recoarctation, aortic aneurysm formation or aortic dissection, coexisting bicuspid aortic valve, endocarditis, premature coronary atherosclerosis, cerebrovascular accidents and systemic hypertension. In this review, these complications, with particular reference to late hypertension, are discussed and strategies for the clinical management of post-coarctectomy patients are described. [Copyright &y& Elsevier]

Background: Many patients with congenital heart disease have persistent cardiac defects, psychosocial adjustment problems, and a poor quality of life. This study tested the relationship between negative thoughts and adaptation to congenital heart disease. Methods: Eighty-two adult out-Patients with congenital heart disease were divided on the basis of few, moderate or many negative thoughts. Group differences were tested in medical and psychosocial adjustment variables (including negative emotions), and quality of life. Results: Patients with many negative thoughts scored worse on psychosocial adjustment and quality of life, irrespective of severity of cardiac deviation, according to the cardiologist, New York Heart Association classification, number of passed and expected surgery, or use of medication. Conclusion: Negative affect in general, rather than negative thoughts is decisive in psychosocial adjustment and quality of life. Psychological intervention would be helpful for many patients. [ABSTRACT FROM AUTHOR]

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

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. We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. 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). 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). 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. • TGA patients after a successful arterial switch repair have a decreased exercise capacity. • Lower excercise capacity was seen in ASO patients after RVOT intervention compared to patients without RVOT intervention. • RV-arterial coupling emerged as the most sensitive hemodynamic parameter for RV performance after RVOT intervention. [ABSTRACT FROM AUTHOR]

The article discusses research on the role of losartan in reducing aortic disease in patients with Marfan syndrome. It references the study "Marfan Sartan: A Randomized, Double-Blind, Placebo-Controlled Trial" by O. Milleron published in the "European Heart Journal" in 2015. Topics covered include beta-blockade as the prescribed preventive pharmacological treatment.

Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes (physiological vs. pathophysiological). Therefore we studied the course of these parameters and ventricular function in pregnant women with aortic and pulmonary VHD. The cohort comprised 66 pregnant women enrolled in the prospective ZAHARA studies or evaluated by an identical protocol who had pulmonary VHD or aortic VHD (stenosis/prosthetic valve). The control group comprised 46 healthy pregnant women. Echocardiography was performed preconception, during pregnancy and 1 year postpartum. Peak gradient, mean gradient, aortic valve area (AVA)/effective orifice area (EOA), left ventricular ejection fraction (LVEF) and right ventricular function (RVF; TAPSE) were assessed. Peak and mean gradients increased during pregnancy compared to preconception in women with aortic VHD and controls (p < 0.0125), but not in women with pulmonary VHD. AVA/EOA remained unchanged. Preconception and postpartum gradients were comparable in all groups. Mean LVEF was normal in pregnant women with VHD and controls. Mean TAPSE was lower (p < 0.001) in women with pulmonary VHD compared to women with aortic VHD and controls (<20 mm vs. ≥23 mm; p < 0.001). In women with pulmonary VHD a decrease of TAPSE was observed during pregnancy (p = 0.005). Physiological changes during pregnancy lead to increased Doppler gradients in women with aortic VHD. This increase was not found in women with pulmonary VHD, probably caused by impaired RVF. Therefore, evaluation of RVF during pregnancy might be important to prevent underestimation of the degree of stenosis. • Serial changes in Doppler gradients and valve area in aortic and pulmonary valve disease were reported throughout pregnancy • Aortic valve gradients increased during pregnancy and returned to baseline postpartum, valve area remained unchanged • Valve gradients did not change in pregnant women with pulmonary valve disease, likely due to worse right ventricular function • Evaluation of the right ventricle might be important to prevent possible underestimation of the degree of pulmonary stenosis [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Long-Term Nationwide Follow-up Study of Simple Congenital Heart Disease Diagnosed in Otherwise Healthy Children" by M. Olsen and others in the 2016 issue.

Background: We recently reported a novel observation that many patients with equal resting supine right ventricular(RV) and pulmonary artery(PA) systolic pressures develop an RV outflow tract(RVOT) pressure gradient during upright exercise. The current work details the characteristics of patients who develop such an RVOT gradient. Methods: We studied 294 patients (59.7±15.5 years-old, 49% male) referred for clinical invasive cardiopulmonary exercise testing, who did not have a resting RVOT pressure gradient defined by the simultaneously measured peak-to-peak difference between RV and PA systolic pressures. Results: The magnitude of RVOT gradient did not correspond to clinical or hemodynamic findings suggestive of right heart failure; rather, higher gradients were associated with favorable exercise findings. The presence of a high peak RVOT gradient (90th percentile, ≥33mmHg) was associated with male sex (70 vs. 46%, p = 0.01), younger age (43.6±17.7 vs. 61.8±13.9 years, p<0.001), lower peak right atrial pressure (5 [3–7] vs. 8 [4–12]mmHg, p<0.001), higher peak heart rate (159±19 vs. 124±26 beats per minute, p<0.001), and higher peak cardiac index (8.3±2.3 vs. 5.7±1.9 L/min/m2, p<0.001). These associations persisted when treating peak RVOT as a continuous variable and after age and sex adjustment. At peak exercise, patients with a high exercise RVOT gradient had both higher RV systolic pressure (78±11 vs. 66±17 mmHg, p<0.001) and lower PA systolic pressure (34±8 vs. 50±19 mmHg, p<0.001). Conclusions: Development of a systolic RV-PA pressure gradient during upright exercise is not associated with an adverse hemodynamic exercise response and may represent a normal physiologic finding in aerobically fit young people. [ABSTRACT FROM AUTHOR]

The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT. [Display omitted] [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by S. C. Reimold and J. D. Rutherford on valvular heart disease in pregnancy.

Patients with bicuspid aortic valve (BAV) and patients with Marfan syndrome (MFS) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common and distinct pathways of clinical relevance, we compared the histopathological substrates of aortopathy. Ascending aortic wall biopsies were divided in five groups: BAV ( n = 36) and TAV ( n = 23) without and with dilation and non-dilated MFS ( n = 8). General histologic features, apoptosis, the expression of markers for vascular smooth muscle cell (VSMC) maturation, markers predictive for ascending aortic dilation in BAV, and expression of fibrillin-1 were investigated. Both MFS and BAV showed an altered distribution and decreased fibrillin-1 expression in the aorta and a significantly lower level of differentiated VSMC markers. Interestingly, markers predictive for aortic dilation in BAV were not expressed in the MFS aorta. The aorta in MFS was similar to the aorta in dilated TAV with regard to the presence of medial degeneration and apoptosis, while other markers for degeneration and aging like inflammation and progerin expression were low in MFS, comparable to BAV. Both MFS and BAV aortas have immature VSMCs, while MFS and TAV patients have a similar increased rate of medial degeneration. However, the mechanism leading to apoptosis is expected to be different, being fibrillin- 1 mutation induced increased angiotensin-receptor-pathway signaling in MFS and cardiovascular aging and increased progerin in TAV. Our findings could explain why angiotensin inhibition is successful in MFS and less effective in TAV and BAV patients. [ABSTRACT FROM AUTHOR]

The Fontan procedure has been used since 1971 as a palliative treatment for various (functionally) univentricular hearts. The systemic venous blood flows passively to the pulmonary arteries, without passing through a functional ventricle. This results in chronic systemic venous congestion, which may lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. This review discusses possible screening modalities for liver fibrosis and cirrhosis in the Fontan population and proposes a screening protocol. We suggest starting screening for progression of fibrosis and cirrhosis in collaboration with the hepatologist circa 10 years after Fontan completion. The screening programme will consist of a yearly evaluation of liver laboratory tests in conjunction with imaging of the liver with ultrasound or MRI every two years. In case of liver fibrosis or cirrhosis, (reversible) causes should be ruled out (e.g. obstruction in the Fontan circuit). In case of severe fibrosis or cirrhosis, other complications of portal hypertension should be evaluated and screening for hepatocellular carcinoma is required on a regular (6–12 months) basis. As regards hepatocellular carcinoma, treatment should be discussed in a multidisciplinary team, before deciding a treatment modality. [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation >40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort (n = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population (p < 0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population (p = 0.027) or compared with younger MFS patients (p = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain (p = 0.022) and symptoms of depression with unemployment (p = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms. [ABSTRACT FROM AUTHOR]

Background: Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.Methods: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva.Findings: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in β-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042).Interpretation: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery.Funding: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council. [ABSTRACT FROM AUTHOR]

Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyze whether QRS duration, before and after pulmonary valve replacement (PVR), is related to long-term outcome in patients with tetralogy of Fallot (TOF). Background: Key factors that determine outcome after PVR in adult TOF patients are largely unknown. Recognition of such factors assists the identification of patients at increased risk of adverse events. Methods: Adults who previously underwent total correction for TOF (n = 90; age 31.4 ± 10.3 years) and required PVR for pulmonary regurgitation were included. The QRS duration was measured pre-operatively and 6 months after PVR. The post-operative changes in QRS duration were calculated. Adverse events (death, re-PVR, ventricular tachycardia, and symptomatic heart failure) were noted during follow-up. Results: During 5.5 ± 3.5 years of follow-up, 13 adverse events occurred. The 5-year event-free survival rate was 76% for patients with a pre-operative QRS duration >180 ms and 90% in patients with a QRS duration ≤180 ms (p = 0.037). For patients with a post-operative QRS duration >180 ms, 5-year event-free survival was 71%, whereas it was 91% for patients with a post-operative QRS duration ≤180 ms (p = 0.004). After multivariate correction, a post-operative QRS duration >180 ms (hazard ratio: 3.685, 95% confidence interval: 1.104 to 12.304, p < 0.05) and the absence of a reduction in QRS duration post-PVR (hazard ratio: 6.767, 95% confidence interval: 1.704 to 26.878, p < 0.01), was significantly associated with adverse outcome. Conclusions: Severe QRS prolongation, before or after PVR, and the absence of a reduction in QRS duration after PVR, are major determinants of adverse outcome during long-term follow-up of patients with TOF. [ABSTRACT FROM AUTHOR]

Abstract: The population of adult survivors with tetralogy of Fallot (TOF) is growing over the last decades due to improvements in perinatal management, intensive care and surgical techniques. Pulmonary regurgitation (PR) plays a crucial role in the long-term outcome of these patients. Although PR may be tolerated well for many years, eventually it may lead to right ventricular (RV) dilatation, RV dysfunction, exercise intolerance, arrhythmia and sudden cardiac death. Cardiovascular magnetic resonance (CMR) imaging is an important tool in the follow-up of patients after TOF repair, because biventricular volumes and function and PR volume and fraction can be measured with great accuracy and reproducibility. CMR imaging studies have identified risk factors for late adverse outcomes in patients after TOF repair. These include increased RV end-diastolic volume (EDV), reduced left ventricular ejection fraction and abnormal RV outflow tract function. Other applications of CMR include stress imaging, assessment of diastolic function and late gadolinium enhancement, which have provided additional insight in the function of the RV. Timing of pulmonary valve replacement (PVR) is controversial and should balance between the preservation of RV function and the need for subsequent PVR surgery, since the life-span of a homograft is limited. Based on CMR imaging studies, PVR will be considered if the RVEDV reaches a threshold of between 150 and 200ml/m2 in the presence of severe PR. However, timing of PVR should be based on multiple factors, other than RV size and PR fraction alone. [Copyright &y& Elsevier]

Patients with Marfan syndrome have a tall stature, which could be associated with low orthostatic tolerance. Fatigue, a common complaint of these patients, is also related to orthostatic intolerance. Treatment with beta-blockers, to prevent aortic complications, could be a reinforcing factor of both. This study aimed to investigate (1) the relationship between symptoms of orthostatic tolerance and in patients with Marfan syndrome, and (2) whether termination of beta-blocker therapy improves orthostatic tolerance. Symptoms of fatigue and orthostatic complaints were assessed in 49 subjects using questionnaires (MFI-20 and Autonomic Symptoms Profile). Marfan patients have a high level of fatigue and orthostatic complaints when compared to the general population. Fatigue and orthostatic tolerance are significantly correlated. Orthostatic tolerance was assessed in 9 additional subjects by an active-standing test and head-up tilt for 5 minutes, and 24 hours blood pressure monitoring, once during beta-blocker therapy and once after ceasing beta-blockers for 2 weeks. During hemodynamic testing Marfan patients frequently showed Initial Orthostatic Hypotension and an abnormally high initial heart rate response. Ceasing beta-blockers did not affect the initial blood pressure response. Patients with Marfan syndrome are fatigued and have low orthostatic tolerance, which are significantly correlated. Patients could be educated in physical counterpressure maneuvers to increase orthostatic tolerance. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that patients with a congenital heart disease are sensitive regarding heartbeat perception, reflected in enhanced attention for heartbeat, estimation of own heart rate, and a vulnerability to become anxious by listening to heartbeat sounds. Twenty adults with a congenital heart disease, and 20 healthy controls conducted 3 experimental tasks: a concentration task during distraction by heartbeat sounds, own heart rate estimation, and exposure to different patterns of heartbeat sounds. The results showed that patients were more distracted by heartbeat, and were also worse at estimating heart rate than controls. However, heartbeat sounds did not evoke anxiety. In conclusion, patients with a congenital heart disease may differ from controls in heartbeat perception, but there was no support for obsessive monitoring for heartbeat or excessive reactions to heartbeat sounds. [ABSTRACT FROM AUTHOR]

Background: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the Fibrillin-1 gene (FBN1). Here, we undertook the first epigenome-wide association study (EWAS) in patients with MFS aiming at identifying DNA methylation loci associated with MFS phenotypes that may shed light on the disease process. Methods: The Illumina 450 k DNA-methylation array was used on stored peripheral whole-blood samples of 190 patients with MFS originally included in the COMPARE trial. An unbiased genome-wide approach was used, and methylation of CpG-sites across the entire genome was evaluated. Additionally, we investigated CpG-sites across the FBN1-locus (15q21.1) more closely, since this is the gene defective in MFS. Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs) were identified through regression analysis. Associations between methylation levels and aortic diameters and presence or absence of 21 clinical features of MFS at baseline were analyzed. Moreover, associations between aortic diameter change, and the occurrence of clinical events (death any cause, type-A or -B dissection/rupture, or aortic surgery) and methylation levels were analyzed. Results: We identified 28 DMPs that are significantly associated with aortic diameters in patients with MFS. Seven of these DMPs (25%) could be allocated to a gene that was previously associated with cardiovascular diseases (HDAC4, IGF2BP3, CASZ1, SDK1, PCDHGA1, DIO3, PTPRN2). Moreover, we identified seven DMPs that were significantly associated with aortic diameter change and five DMP's that associated with clinical events. No significant associations at p < 10–8 or p < 10–6 were found with any of the non-cardiovascular phenotypic MFS features. Investigating DMRs, clusters were seen mostly on X- and Y, and chromosome 18–22. The remaining DMRs indicated involvement of a large family of protocadherins on chromosome 5, which were not reported in MFS before. Conclusion: This EWAS in patients with MFS has identified a number of methylation loci significantly associated with aortic diameters, aortic dilatation rate and aortic events. Our findings add to the slowly growing literature on the regulation of gene expression in MFS patients. [ABSTRACT FROM AUTHOR]

The mechanisms leading to cardiac remodeling in Marfan syndrome (MFS) are a matter of debate since it could be either due to structural dysfunction of the myocardial extracellular matrix or to increased afterload caused by the dilated aorta. We aim to characterize the presence of abnormal myocardial function in MFS and to investigate its potential association with increased afterload. Aorta, left ventricle (LV) and the postsystolic thickening (PST) were analyzed in echocardiography in Fbn1C1039G/+ mice and in patients with MFS in comparison with wild type (WT) mice and healthy humans. PST was more frequent in MFS than in WT mice (p < 0.05). MFS mice with PST showed larger aorta than those without PST. Patients with MFS showed larger aorta, poorer LV function and a higher prevalence of PST (56%) than did the healthy controls (23%); p = 0.003. Blood pressure was similar. The higher prevalence of PST in an experimental murine model and in MFS patients, regardless of systemic arterial pressure, suggests an increased afterload on the LV myocardium. This finding supports the use of PST as an indicator of myocardial damage and encourage searching for novel early preventive therapy. [ABSTRACT FROM AUTHOR]

Introduction: An increased focus on shared decision-making and patient empowerment in cardiology and on patient outcomes such as quality of life (QoL), depression, and anxiety underline the importance of high-quality patient education. Studies focusing on digital means of patient education performed in other disciplines of medicine demonstrated its positive effect in these areas. Therefore, a review of the current literature was performed to (i) evaluate the status of innovative, digitalized means of patient education in cardiology and (ii) assess the impact of digital patient education on outcome parameters (i.e., patient knowledge (or health literacy), QoL, depression, anxiety, and patient satisfaction). Method: A review of the current literature was performed to evaluate the effect of digitalized patient education for any purpose in the field of cardiology. Medline and EMBASE were searched for articles reporting any digital educational platform used for patient education up to May 2020. The articles were compared on their effect on patient knowledge or health literacy, QoL, depression or anxiety, and patient satisfaction. Results: The initial search yielded 279 articles, 34 of which were retained after applying in, and exclusion criteria. After full-text analysis, the total number of articles remaining was 16. Of these, 6 articles discussed the use of smartphone or tablet applications as a means of patient education, whereas 3 reviewed web-based content, and 7 evaluated the use of video (2 three-dimensional videos, from which one on a virtual reality headset). Conclusion: This review demonstrates that digital patient education increases patient knowledge. Overall, digital education increases QoL and lowers feelings of depression and anxiety. The majority of patients express satisfaction with digital platforms. It remains important that developers of digital patient education platforms remain focused on clear, structured, and comprehensible information presentation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adult patients with congenital heart disease under follow-up often need to undergo diagnostic procedures which expose them to radiation. Aim: To evaluate radiation doses in adult patients with congenital heart disease during follow-up. Methods: Data on diagnostic procedures were used from the European Heart Survey on adult congenital heart disease, a multicenter retrospective cohort study. Lesions included in the survey were Atrial Septal Defect, Ventricular Septal Defect, Fallot, Fontan, Coarctation, Transposition of the Great Arteries, Marfan, and Cyanotic lesions. A total of 4110 patients (52% female) with a mean age of 32 years (range 17–85) were included. The follow-up time ranged from 0 to 72 months, with a median of 61 months. There were a total of 18,403 patient-years of follow-up. During this time, a mean of 4.5 visits per patient took place. Radiation doses were calculated using the number of examinations in each patient''s data file. Effective radiation doses are given in millisievert (mSv). Results: The average cumulative annual effective dose per patient was 0.46 mSv. The relative contributions to these doses were 3% by chest X-rays, 39% by computed tomography scans, 42% by angiography, and 16% by nuclear scans. Effective doses were higher in patients with Fontan, Coarctation, Marfan and Cyanotic lesions, as well as in patients with Atrial Septal Defects. Conclusions: Exposure to radiation during follow-up of patients with adult congenital heart disease mainly stems from computed tomography scans and angiography. Patients with Fontan, Coarctation, Marfan and Cyanotic lesions are more likely to get high doses from computed tomography. In these lesions, therefore, particular care should be taken to use non-ionizing imaging procedures whenever possible. [Copyright &y& Elsevier]

Background Mobile health (mHealth) can improve quality of care and empower cardiac patients. However, large-scale adoption is still lacking, as several challenges continue to be encountered in daily practice. We aimed to explore the mHealth experiences and challenges in cardiac patients, healthcare professionals, healthcare managers and information and communications technology (ICT) developers. Methods A qualitative research was employed where semistructured interviews were conducted in patients, healthcare professionals, managers and ICT developers. We aimed to enrol participants of every stakeholder group, with diversity in sex, age group and occupation. Thematic analysis was used to identify themes reflecting experiences and challenges in mHealth in cardiac patients. Results In total, 24 interviews were conducted in six patients, eight healthcare professionals, five managers and five ICT developers. Monitoring/care at home was reported as important advantage of mHealth (n=20, 83%). Patients valued increase of self-care (n=6, 100%) and remote reassurance (n=6, 100%), but reported medicalisation as important concern (n=4, 67%). Healthcare professionals warned for increased data burden (n=4, 50%). Managers agreed on the importance of device reliability (n=5, 100%) and ICT developers emphasised that the goal of mHealth is to replace care, rather than being supplementary (n=4, 80%). The majority of all participants (n=22, 92%) considered future use of mHealth as promising. Conclusions All stakeholders foresee benefit of mHealth in cardiac patients, especially for remote care and reassurance. Frequently mentioned challenges included the need to replace care with mHealth, rather than adding more workload, and employing reliable devices and applications. If collaboration can be improved and group-specific challenges overcome, success of mHealth in cardiac patients can improve significantly. [ABSTRACT FROM AUTHOR]

22q11.2 Deletion syndrome (22q11.2DS) is common in patients with tetralogy of Fallot (TOF) or pulmonary atresia with ventricular septal defect (PA/VSD) and is associated with worse outcomes in children. Whether this impaired prognosis is also translated into adulthood is unknown, as data in adult patients are limited. We aimed to compare long-term outcomes in adults with TOF or PA/VSD both with and without 22q11.2DS. This study prospectively followed a nationwide multicenter cohort of TOF or PA/VSD patients with genetically confirmed presence or absence of 22q11.2DS, from inclusion in the Dutch national CONCOR registry for adults with congenital heart disease (CHD) onward. Outcome measures included all-cause mortality, cardiac mortality, need for pulmonary valve replacement (PVR), ventricular arrhythmias (VA), pacemaker implantation, and ICD implantation. In total, 479 patients were included (277 (58%) male, median age 28 [IQR; 21–37] years, 62 (13%) with PA/VSD, 34 (7%) with 22q11.2DS). During a median follow-up of 11 [IQR; 6–13] years, 52 (11%) patients died (8 with 22q11.2DS and 44 without 22q11.2DS). Patients with 22q11.2DS had significant decreased survival after 12 years (76% [95% CI; 62–93]) compared to patients without 22q11.2DS (89% [95% CI; 86–92], p = 0.008). 22q11.2DS was associated with increased risk of all-cause mortality and cardiac-mortality, independent of age, sex, and PA/VSD. No association was found between 22q11.2DS and late complications i.e. PVR, VA, pacemaker, or ICD implantation. Adults with TOF or PA/VSD with 22q11.2DS have a significantly worse survival than adults without this deletion. In patients with TOF or PA/VSD, genetic analysis for the presence of 22q11.2DS is important for risk stratification and genetic counseling. • 22q11.2 deletion syndrome is an independent predictor for all-cause mortality. • No differences were seen in risk for late cardiac complications. • Genetic analysis should be considered, as 22q11.2DS is an important risk factor. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) will increasingly determine outcome in the aging adult congenital heart disease (CHD) population. We aimed to determine sex-specific incidence of CAD in adult CHD patients throughout adulthood, compared to the general population. We followed 11,723 adult CHD patients (median age 33 years; 49% male; 57% mild, 34% moderate, 9% severe CHD) from the Dutch CONCOR registry, and two age-sex-matched persons per patient from the general population for first CAD event in national registers (period 2002–2012). Incidence rates were estimated using smoothed hazard functions. CAD risk during follow-up, stratified by CHD severity, was compared using proportional subdistribution hazards regression. In ACHD patients, 103 CAD events (43 women) occurred over 60,456 person-years. Rates per 1000person-years increased from 0.3(95% confidence interval: 0.1–0.6) at age 20 to 5.8(3.7–8.9) at 70 years in female, and from 0.5(0.3–1.0) to 7.8(5.1–11.8) in male patients. Compared to the general population, relative risk was 12.0(2.5–56.3) in women and 4.6(1.7–12.1) in men aged 20 years. Relative risk declined with age, remaining significant up to age ~65 years in women and ~50 years in men. In patients with mild, moderate and severe CHD, CAD risk was 1.3(0.9–1.9), 1.6(1.0–2.5) and 2.9(1.3–6.9) times increased compared to the general population, respectively. We found increased CAD risk in adult CHD patients, with greater relative risk at younger age, in women and those with more severe CHD. These results underline the importance of screening for and treatment of CAD risk factors in these patients. • Coronary artery disease risk was low in adult congenital heart disease patients. • Coronary artery disease risk was increased compared to the general population. • Relative risk was greater at younger age and in women. • Relative risk was greater in those with more severe congenital heart disease. [ABSTRACT FROM AUTHOR]

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. • Gender differences may affect outcome in congenital heart diseases. • Pregnancy can impact on the well-being of patients with congenital heart diseases. • Sex differences in prognosis are due to genetic, morphological, hormonal factors. [ABSTRACT FROM AUTHOR]

Several studies have reported changes in electrocardiographic variables after atrial septal defect (ASD) closure. However no temporal electro-and vectorcardiographic changes have been described from acute to long-term follow-up at different ages. We aimed to study electrical remodeling after percutaneous ASD closure in pediatric and adult patients. ECGs of 69 children and 75 adults (median age 6 [IQR 4–11] years and 45 [IQR 33–54] years, respectively) were retrospectively selected before percutaneous ASD closure and at acute (1–7 days), intermediate (4–14 weeks) and late (6–18 months) follow-up. Apart from electrocardiographic variables, spatial QRS-T angle and ventricular gradient (VG) were derived from mathematically-synthesized vectorcardiograms. In both pediatric and adult patients, the heart rate decreased immediately post-closure, which persisted to late follow-up. The P-wave amplitude also decreased acutely post-closure, but remained unchanged at later follow-up. The PQ duration shortened immediately in children and at intermediate follow-up in adults. The QRS duration and QTc interval decreased at intermediate-term follow-up in both children and adults. In both groups the spatial QRS-T angle decreased at late follow-up. The VG magnitude increased at intermediate follow-up in children and at late follow-up in adults, after an initial decrease in children. In both pediatric and adult ASD patients, electrocardiographic changes mainly occurred directly after ASD closure except for shortening of QRS duration and QTc interval, which occurred at later follow-up. Adults also showed late changes in PQ duration. At 6-to-18 month post-closure, the spatial QRS-T angle decreased, reflecting increased electrocardiographic concordance. The initial acute decrease in VG in children, which was followed by a significant increase, may be the effect of action potential duration dynamics directly after percutaneous ASD closure. • ECG changes mainly occurred directly after ASD closure. • The QRS-T angle decreased after ASD closure, reflecting increased ECG concordance. • The ventricular gradient decreased after ASD closure, followed by an increase. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this prospective randomised controlled trial was to assess whether home-based, self-selected exercise training is safe, results in high compliance and improves exercise capacity in symptomatic adults with congenital heart disease (CHD). Methods Forty adults with moderate or severe CHD (40 ± 12 years, 56% male, New York Heart Association [NYHA] II/III 37/3) were randomly assigned, stratified by CHD complexity, either to home-based exercise training or usual care. The exercise training protocol consisted of three exercise sessions per week for six consecutive months. Patients were free to choose any sports of their preference. Results Thirty-four patients (each randomisation group n = 17) completed the protocol and were analysed. The majority was involved in high-dynamic sports (76%); none had to discontinue the training programme due to exercise-related adverse events. More than 70% adhered to the exercise programme at or above the target training level. Peak VO 2 increased significantly in the exercise group by +1.7 ± 2.7 ml∙kg∙min−1 (p = 0.025), whereas it remained unchanged in the control group by +0.8 ± 2.2 ml∙kg∙min−1 (p = 0.184). No significant changes were found in serum N-Terminal pro-brain natriuretic peptide levels or quality of life in either randomisation group or between groups. Conclusions In symptomatic adults with moderate or severe CHD, home-based exercise training of their preference appeared safe, with good compliance and favourable effects on exercise capacity. Our results demonstrate that it is appropriate to stimulate our patients to regularly perform moderate to vigorous physical activities, in absence of medical restrictions. Highlights • The challenge for both clinicians and symptomatic CHD adults is to ensure safe participation in regular physical activity. • Symptomatic CHD adults have been previously excluded from exercise training trials. • This study is the first RCT to investigate a home-based, self-selected exercise programme in solely symptomatic CHD adults. • Various (strenuous) exercise training could be performed safely at home and without supervision. • Patients should be encouraged to participate in regular moderate to vigorous physical activities. [ABSTRACT FROM AUTHOR]

Abstract Objectives In the VAL-SERVE (Valsartan in Systemic Right Ventricle) trial, three-year valsartan treatment improved systemic ventricular function only in symptomatic patients with congenitally or with an atrial switch corrected transposition of the great arteries. The aim of the current study was to investigate the longer-term clinical outcomes after valsartan treatment. Methods From 2006 to 2009, 88 adults were randomly allocated 1:1 to either valsartan or placebo for three consecutive years. Endpoints were defined as overall survival and freedom from clinical events (arrhythmia, heart failure, tricuspid valve surgery, death). Results Cardiac drug use and median follow-up after trial close-out (8.3 years) was similar between the randomization groups. Six patients (valsartan n = 3, placebo n = 3) died in 364 and 365 person-years (P = 0.999). No difference in the composite or separate clinical endpoints was found between the randomization groups, with corresponding long-term event-free survival rates of 50% and 34%. Nevertheless, in symptomatic patients valsartan significantly reduced the risk for events compared to placebo (HR 0.37, 95% CI 0.17–0.92). Analysis for repeated events and on-treatment analysis with any renin-angiotensin-aldosterone-system-inhibitor did not alter these results. Conclusions Valsartan treatment in systemic RV patients did not result in improved survival at longer-term follow-up, but was associated with decreased risk of events in symptomatic patients. Highlights • Systemic right ventricular failure is a major problem in transposition of the great arteries. • Limited data on heart failure treatment in this patient group are inconclusive. • The study shows a reduction in morbidity in symptomatic patients with angiotensin II receptor blockers. • In line with the previous trial results, valsartan has a favorable treatment effect in symptomatic patients. [ABSTRACT FROM AUTHOR]

Abstract Aims Adult congenital heart disease (ACHD) patients are at increased risk of sudden cardiac death and out-of-hospital cardiac arrest (OHCA). Currently, insufficient data exist on outcome, causes and circumstances of OHCA of ACHD patients resuscitated for OHCA. We investigate these parameters in ACHD patients in comparison to OHCA in the general population. Methods and results We identified ACHD patients with OHCA by linking data from a Dutch nationwide registry of ACHD patients (CONCOR, n = 15,727), and ARREST, a cohort of OHCA cases (n = 17,868). 62 ACHD patients with OHCA were identified. Ventricular septal defect (n = 11), bicuspid aortic valve (n = 10) and atrial septal defect (n = 8) were the most common diagnoses. We included OHCA cases from the general population as controls. ACHD patients were younger than controls (n = 11,624) at the time of OHCA (47 (SD ± 17) years vs. 66 (SD ± 15) years, respectively, p < 0.001), and more often had a shockable initial rhythm (67% vs 40%, respectively, p < 0.001). A cardiac cause of OHCA was identified in 76% of ACHD patients, with only 7% due to myocardial infarction or ischemia. Survival was better in ACHD patients than in controls (44% vs. 19%, p < 0.001), but this difference disappeared after correction for age, gender, witnessed arrest, bystander resuscitation, public location and shockable rhythm. Conclusions OHCA in ACHD patients occurs at young age, is rarely caused by ischemia and occurs mainly in patients with simple congenital defects. Risk stratification efforts should therefore not be restricted to ACHD patients with severe congenital defects. Highlights • Data on OHCA in adult congenital heart disease patients is currently insufficient. • ACHD patients are younger than non-ACHD patients at the time of OHCA. • ACHD patients with OHCA mostly have simple congenital defects. • Survival after OHCA in ACHD patients is better compared to non-ACHD patients. • Survival after OHCA in ACHD is driven by young age and mainly shockable rhythms. [ABSTRACT FROM AUTHOR]

Abstract Background Proximal aortic dilatation in certain congenital heart diseases (CHD) prompts concerns about dissection and consideration of prophylactic surgery. To evaluate contemporary prophylactic practice, we determined incidence of aortic dissection and prophylactic surgery in aortopathy-associated CHD, compared to Marfan syndrom (MFS) and controls. Methods and results We followed patients from the CONCOR adult CHD registry (2002–2015), with a native proximal aorta and aortopathy-associated CHD, comprising bicuspid aortic valve/aortic stenosis ('BAV/AS'; n = 2239) and aortic coarctation/conotruncal defects/univentricular heart/ventricular septal defect ('At-risk CHD'; n = 5439). As reference, we selected MFS (n = 356) and 'Control' (atrial septal defect, pulmonary stenosis; n = 2940) patients. Cumulative incidences of dissection and prophylactic proximal aortic replacement – considered competing events – were determined, and compared corrected for age and sex. Median follow-up was 6.7 years. Ten-year dissection-incidence was 0.3% (95%CI: 0.0–0.7) in BAV/AS and 0.2% (0.0–0.3) in At-risk CHD, both significantly lower than in MFS (4.1%; 1.8–6.4) and similar to Controls (0.1%; 0.0–0.3). Ten-year prophylactic-surgery incidence was 9.3% (7.6–11.0) in BAV/AS and 0.7% (0.5–1.0) in At-risk CHD, both significantly lower than in MFS (21.3%; 16.3–26.3) and higher than in Controls (0.1%; 0.0–0.3). Conclusions In contemporary practice, aortic-dissection incidence is low in adults with aortopathy-associated CHDs, while prophylactic-surgery incidence is high in BAV/AS. To reduce surgical burden, BAV/AS patients could benefit from more individualised prophylactic-surgery algorithms. Highlights • In adults with aortopathy-associated congenital heart disease, aortic dissection risk was lower than in Marfan syndrome. • Prophylactic aortic replacement was frequent in bicuspid aortic valve/aortic stenosis, not in other congenital heart disease. • Many prophylactic aortic replacements in bicuspid aortic valve/aortic stenosis were performed with aortic valve replacement. • Patients with bicuspid aortic valves may benefit from individualised algorithms, to target prophylactic aortic replacement. [ABSTRACT FROM AUTHOR]

Abstract Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the fibrillin-1 gene (FBN1), resulting in aortic aneurysm formation and dissections. Interestingly, variable aortopathy is observed even within MFS families with the same mutation. Thus, additional risk factors determine disease severity. Here, we describe a case of a 2-month-old Fbn1 C1039G/+ MFS mouse with extreme aortic dilatation and increased vascular inflammation, when compared to MFS siblings, which coincided with unilateral renal cystic disease. In addition, this mouse presented with increased serum levels of creatinine, angiotensin-converting enzyme, corticosterone, macrophage chemoattractant protein-1, and interleukin-6, which may have contributed to the vascular pathology. Possibly, cystic kidney disease is associated with aneurysm progression in MFS patients. Therefore, we propose that close monitoring of the presence of renal cysts in MFS patients, during regular vascular imaging of the whole aorta trajectory, may provide insight in the frequency of cystic kidney disease and its potential as a novel indicator of aneurysm progression in MFS patients. Highlights • Renal cysts in Marfan syndrome mouse model are associated with enhanced aortic aneurysm severity. • The excessive aneurysm displayed severe aortic inflammation. • Increased serum levels of creatinine, angiotensin-converting enzyme, corticosterone, and cytokines were measured. • Renal cysts as potential marker for enhanced aneurysm progression. [ABSTRACT FROM AUTHOR]

Background We evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease. Methods Retrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV. Results 52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages ( n  = 19, ≤20 weeks) occurred more frequently in women using anticoagulation ( P  < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used ( n  = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% ( n  = 13), 68% ( n  = 42) and 42% ( n  = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P  < .05), obstetric (59% vs 85%, P  = .02) and fetal/neonatal (34% vs 61%, P  < .05) complication rates than women with biological PHV. This was related to PHV thrombosis ( n  = 3, P  < .02), post-partum hemorrhage ( P  < .02), cesarean section ( P  < .02), low birth weight and small for gestational age (both P  < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups. Conclusion Complications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications. [ABSTRACT FROM AUTHOR]

Objective: To determine whether women delivering preterm have unfavorable cardiovascular profiles as compared with women who deliver at term.Methods: A prospective observational cohort study enrolled 165 women with spontaneous preterm delivery (sPTD) at 24+0 and 36+6 gestational weeks in three perinatal care centers in The Netherlands between August 2012 and August 2014. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, apolipoprotein, glucose, and homocysteine were measured within 24 hours after delivery. Lipids and cardiovascular biochemical risk factors were compared between women with sPTD and an external comparison group of 30 women with term delivery via analysis of covariance.Results: Mean gestational age at delivery was 30.7 ± 3.6 weeks in the sPTD group and 40.3 ± 1.3 weeks in the reference group. Data were adjusted for body mass index, age, and center. As compared with the reference group, total cholesterol and LDL-cholesterol levels were lower and glucose levels were higher among women with sPTD.Conclusion: An association between sPTD and unfavorable lipids and cardiovascular biochemical risk factors was not established. The higher levels of glucose in the sPTD group might be due to increased insulin resistance, which is associated with a higher risk of sPTD. [ABSTRACT FROM AUTHOR]

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