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Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored., Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA., Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 -10 , OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10 -5 ). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A , which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart., Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A . Genomic and functional data support a causal role of WNT5A at the locus.

Aims: Heart failure is the main threat to long-term health in adults with transposition of the great arteries (TGA) corrected by an atrial switch operation (AtrSO). Current guidelines refrain from recommending heart failure medication in TGA-AtrSO, as there is insufficient data to support the hypothesis that it is beneficial. Medication is therefore prescribed based on personal judgements. We aimed to evaluate medication use in TGA-AtrSO patients and examine the association of use of renin-angiotensin-aldosterone system (RAAS) inhibitors and β-blockers with long-term survival., Methods and Results: We identified 150 TGA-AtrSO patients [median age 30 years (interquartile range 25-35), 63% male] included in the CONCOR registry from five tertiary medical centres with subsequent linkage to the Dutch Dispensed Drug Register for the years 2006-2014. Use of RAAS inhibitors, β-blockers, and diuretics increased with age, from, respectively, 21% [95% confidence interval (CI) 14-40], 12% (95% CI 7-21), and 3% (95% CI 2-7) at age 25, to 49% (95% CI 38-60), 51% (95% CI 38-63), and 41% (95% CI 29-54) at age 45. Time-varying Cox marginal structural models that adjusted for confounding medication showed a lower mortality risk with use of RAAS inhibitors and β-blockers in symptomatic patients [hazard ratio (HR) = 0.13 (95% CI 0.03-0.73); P = 0.020 and HR = 0.12 (95% CI 0.02-0.17); P = 0.019, respectively]. However, in the overall cohort, no benefit of RAAS inhibitors and β-blockers was seen [HR = 0.93 (95% CI 0.24-3.63); P = 0.92 and HR = 0.98 (0.23-4.17); P = 0.98, respectively]., Conclusion: The use of heart failure medication is high in TGA-AtrSO patients, although evidence of its benefit is limited. This study showed lower risk of mortality with use of RAAS inhibitors and β-blockers in symptomatic patients only. These findings can direct future guidelines, supporting use of RAAS inhibitors and β-blockers in symptomatic, but not asymptomatic patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Patients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival. Methods and Results This multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%-9%), 23% (95% CI, 17%-28%), and 5% (95% CI, 2%-8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (<5%), intermediate (5%-20%), and high (>20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82-0.90]). Observed 5- and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients. Conclusions The clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management.

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

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

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

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

Objectives: The aim of this study was to identify which patients with a systemic right ventricle are at risk for clinical events., Background: In patients with congenitally or atrially corrected transposition of the great arteries, worsening of the systemic right ventricle is accompanied by clinical events such as clinical heart failure or the occurrence of arrhythmia., Methods: At baseline, all subjects underwent electrocardiography, echocardiography, cardiopulmonary exercise testing, and cardiovascular magnetic resonance imaging. Clinical events comprised death, vascular events, tricuspid regurgitation requiring surgery, worsening heart failure, and (supra)ventricular arrhythmia. A Cox proportional hazards analysis was used to assess the most valuable determinants of clinical events., Results: A total of 88 patients with a mean age of 33 years were included in the study. Sixty-five percent were men, and 28% had congenitally corrected transposition of the great arteries. During a follow-up period of 4.3 years, 31 patients (35%) experienced 46 clinical events for an annual risk of 12%. Right ventricular end-diastolic volume index measured by means of cardiovascular magnetic resonance imaging or multirow detector computed tomography (hazard ratio: 1.20; p < 0.01) and peak exercise systolic blood pressure (hazard ratio: 0.86; p = 0.02) were the strongest determinants of clinical events. Patients with a right ventricular end-diastolic volume index above 150 ml/m(2) and peak exercise systolic blood pressure below 180 mm Hg were most likely to experience clinical events with an annual event rate of 19% versus 0.9% in patients without these risk factors., Conclusions: Patients with a right ventricular end-diastolic volume index above 150 ml/m(2) and peak exercise systolic blood pressure below 180 mm Hg had a 20-fold higher annual event rate than patients without these risk factors. Regular cardiovascular magnetic resonance imaging and exercise testing are important in the risk assessment of these patients., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively assess aortic dimensions, aortic elasticity, aortic valve competence, and left ventricular (LV) systolic function in patients after the arterial switch operation (ASO) by using magnetic resonance (MR) imaging., Materials and Methods: Informed consent was obtained from all participants for this local ethics committee-approved study. Fifteen patients (11 male patients, four female patients; mean age, 16 years +/- 4 [standard deviation]; imaging performed 16.1 years after surgery +/- 3.7) and 15 age- and sex-matched control subjects (11 male subjects, four female subjects; mean age, 16 years +/- 4) were evaluated. Velocity-encoded MR imaging was used to assess aortic pulse wave velocity (PWV), and a balanced turbo-field-echo sequence was used to assess aortic root distensibility. Standard velocity-encoded and multisection-multiphase imaging sequences were used to assess aortic valve function, systolic LV function, and LV mass. The two-tailed Mann-Whitney U test and Spearman rank correlation coefficient were used for statistical analysis., Results: Patients treated with the ASO showed aortic root dilatation at three predefined levels (mean difference, 5.7-9.4 mm; P < or = .007) and reduced aortic elasticity (PWV of aortic arch, 5.1 m/sec +/- 1.2 vs 3.9 m/sec +/- 0.7, P = .004; aortic root distensibility, [2.2 x 10(-3)] x mm Hg(-1) +/- 1.8 vs [4.9 x 10(-3)] x mm Hg(-1) +/- 2.9, P < .01) compared with control subjects. Minor degrees of aortic regurgitation (AR) were present (AR fraction, 5% +/- 3 in patients vs 1% +/- 1 in control subjects; P < .001). Patients had impaired systolic LV function (LV ejection fraction [LVEF], 51% +/- 6 vs 58% +/- 5 in control subjects; P = .003), in addition to enlarged LV dimensions (end-diastolic volume [EDV], 112 mL/m(2) +/- 13 vs 95 mL/m(2) +/- 16, P = .007; end-systolic volume [ESV], 54 mL/m(2) +/- 11 vs 39 mL/m(2) +/- 7, P < .001). Degree of AR predicted decreased LVEF (r = 0.41, P = .026) and was correlated with increased LV dimensions (LV EDV: r = 0.48, P = .008; LV ESV: r = 0.67, P < .001)., Conclusion: Aortic root dilatation and reduced elasticity of the proximal aorta are frequently observed in patients who have undergone the ASO, in addition to minor degrees of AR, reduced LV systolic function, and increased LV dimensions., (RSNA, 2008)

Aims: To investigate magnitude and determinants of risks during pregnancy in women with Mustard or Senning repair for complete transposition of the great arteries (TGA)., Methods and Results: Using a nationwide registry (CONCOR), 70 women with Senning (23%) or Mustard (77%) repair for TGA were enrolled. A total of 28 patients had 69 pregnancies (two twins), including 17 spontaneous miscarriages and three elective abortions. During 39 of the 49 completed pregnancies, complications were observed. The most important cardiac complication was clinically significant arrhythmia (n=11, 22%), especially occurring in patients with a prior history of arrhythmia. Important general pregnancy complications were preeclampsia (n=5, 10.2%) and pregnancy-induced hypertension (n=4, 8.2%). Obstetric complications included premature rupture of membranes (n=7, 14.3%), premature labour (n=12, 24.4%), premature delivery (n=16, 31.4%), and thrombo-embolic complications (n=2, 4.1%). Mean (singleton) pregnancy duration was 36+/-5 weeks. Eleven of the 51 children (21.6%) were small for gestational age. Foetal and neonatal mortality combined was 11.8% (n=6). No recurrence of congenital heart disease in the offspring was documented., Conclusion: In this largest report on pregnancy in women with atrial-corrected TGA to date, a high incidence of obstetric complications and mortality in the offspring was observed.

Purpose: To prospectively assess regional systemic right ventricular (RV) function at rest and in response to exercise by using magnetic resonance (MR) imaging in patients who have undergone surgical correction at the atrial level for transposition of the great arteries (TGA)., Materials and Methods: Informed consent was obtained, and the medical review board approved this study. In 25 adult patients (mean age, 25.8 years +/- 4.7 [standard deviation]; 13 men) who had undergone correction for TGA (23.4 years +/- 4.9 after surgery) and 11 healthy volunteers (mean age, 27.4 years +/- 2.7; six men), systemic ventricular function was assessed with MR imaging (turbo field echo-planar imaging) at rest and during supine bicycle exercise. Regional wall thickness and wall thickening of the systemic RV were assessed and compared with those of the left ventricle in healthy volunteers by two investigators working together. Regional wall parameters were calculated by using the three-dimensional centerline method. Independent-samples t test and paired-samples t test were used for statistical analysis., Results: Ejection fraction of the systemic RV did not increase after exercise (56% +/- 8 at rest to 55% +/- 7 after exercise, P = .196). Mean RV wall thickening was impaired in patients with TGA at all levels both at rest and in response to exercise (P < .05). Moreover, the free wall and the anterior wall of the systemic RV had a smaller end-systolic thickness and a diminished thickening at rest and after exercise compared with findings in the normal left ventricle (P < .05)., Conclusion: The systemic RV of patients after intraatrial correction for TGA reveals regional functional disturbances at rest and in response to exercise., (RSNA, 2005)

The aim of the study was to evaluate segmental and global right ventricular function at rest and during stress in patients having a systemic morphologically right ventricle. We studied 17 patients after atrial correction for transposition, 13 with congenitally corrected transposition, and 11 age-matched controls using cardiovascular magnetic resonance at rest and during stress with dobutamine given at 15 micrograms per kilogram per minute. Blood was drawn to obtain levels of brain natriuretic peptide. Right ventricular ejection fraction was calculated, and wall-motion and wall-thickening were assessed, in 4 segments of a midventricular slice. The findings for the systemic right ventricle were compared to the left ventricle in controls. Patients with transposition showed a decreased ejection fraction at rest (57 percent versus 69 percent, p equal to 0.005), decreased wall motion of the anterior, lateral and septal wall (p less than 0.01, p less than 0.01, and p less than 0.01) and decreased thickening of the lateral wall (p less than 0.01). Patients with congenitally corrected transposition showed normal ejection fraction, wall thickening, and wall motion at rest. During dobutamine stress, we found no significant differences in wall motion and thickening between the two groups. Ejection fraction, also increased to comparable values during stress, at 67 percent versus 66 percent, p not being significant. In both groups, we observed similarly increased levels of brain natriuretic peptide (p equal to 0.02 and 0.03, respectively). We conclude that only patients with transposition showed segmental wall motion and wall thickening abnormalities at rest. After dobutamine stress, however, segmental and global right ventricular dysfunction was similar in both groups.

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

Background At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations that have the common characteristic that the cardiac morphology is not equipped for sustaining a biventricular circulation. Case summary Here, we present a case of an adult patient after Fontan palliation, illustrative of the complex clinical course and the broad spectrum of complications that can be encountered during follow-up, highlighting the need for a multidisciplinary approach in the clinical care for these patients. Discussion During the surgical Fontan procedure, the inferior vena cava is connected to the pulmonary circulation, after prior connection of the superior vena cava to the pulmonary arterial circulation. The resulting cavopulmonary connection, thus lacking a subpulmonic ventricle, provides non-pulsatile passive flow of oxygen-poor blood from the systemic venous circulation into the lungs, and the functional monoventricle pumps the oxygen-rich pulmonary venous return blood into the aorta. With an operative mortality of <5% and current 30-year survival rates up to 85%, the adult population of patients with a Fontan circulation is growing. This increase in survival is, however, inevitably accompanied by long-term complications affecting multiple organ systems, resulting in decline in cardiovascular performance. Conclusion For optimal treatment, the evaluation in a multidisciplinary team is mandatory, using the specific expertise of the team members to timely detect and address late complications and to support quality of life. [ABSTRACT FROM AUTHOR]

Objective: Pharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.Methods: Data on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.Results: Six-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950-358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%-22%, p<0.001 and -11% to -13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).Conclusions: We describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population. [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]

Background-The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results-We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, ̇vo2peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, -1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3-28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2-14 g; P=0.01) in the placebo group than in the valsartan group. Conclusions-There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. [ABSTRACT FROM AUTHOR]

After atrial correction of transposition of the great arteries (TGA), dysfunction of the systemic right ventricle at rest and during exercise has been reported. Information on changes in systemic right ventricular function during recovery from exercise is lacking. This study evaluates cardiac recovery from supine exercise using magnetic resonance (MR) imaging in patients with asymptomatic TGA after atrial correction. Flow in the ascending aorta, representing stroke volume of the systemic ventricle, was assessed with MR flow mapping in 10 asymptomatic patients with atrially corrected TGA and in 12 controls at rest during exercise and an 8-minute recovery period. In response to exercise, the patients had a smaller increase in heart rate, stroke volume, and cardiac output than did controls. After exercise, no significant difference in halftime of heart rate recovery was observed (patients, 48 +/- 7 seconds; controls, 39 +/- 4 seconds [p >0.05]). In the patients, the time course of stroke volume recovery was significantly different (p <0.001). Stroke volume in the patients, as a percent difference from rest, remained significantly elevated, from 2.5 minutes (+16 +/- 5% vs +7 +/- 6%; p <0.05) to 8 minutes (+4 +/- 7% vs -3 +/- 5%; p <0.05) after exercise. Subsequently, cardiac output remained significantly elevated, from 4.5 minutes (+27 +/- 13% vs +15 +/- 11%; p <0.05) to 7 minutes (+22 +/- 11% vs +12 +/- 12%; p <0.05) after exercise. We conclude that heart rate recovery is within normal limits in patients with atrially corrected TGA. Furthermore, cardiac recovery from exercise, assessed with MR flow mapping, is prolonged in patients with asymptomatic TGA after atrial correction. Abnormal recovery may reflect dysfunction of the systemic right ventricle and an altered metabolic response to exercise. [ABSTRACT FROM AUTHOR]

Data on relational and sexuality issues in adult patients with congenital heart disease (CHD) are scarce. The present study aimed to evaluate relational and sexual behaviors, satisfaction, and functioning in a representative sample of patients with CHD and their partners. In addition, we aimed to evaluate the relation between sexuality parameters and quality of life. Relational and sexuality issues were assessed using a sexuality questionnaire in 133 patients (52% men, 37 ± 13 years old) with CHD (43 with coarctation of the aorta, 42 with transposition of great arteries, 36 with Marfan syndrome, and 12 with Eisenmenger syndrome), and 74 partners. Quality of life was assessed using the Dutch translation of the Medical Outcomes Study Short Form 36-Item Health Survey. Data were compared to an age- and gender-matched control group (n = 3,642). Seventy-one percent of patients with CHD were involved in a relationship, which was significantly less compared to controls (79%, p <0.05). Nonetheless, patients perceived their relationship as more satisfactory compared to controls (p <0.05). Overall, sexual satisfaction was equal in patients compared to controls, although they perceived lower body esteem (p <0.001), decreased sexual esteem (p <0.05), and more distress during sex (p <0.001). Patients reported no more erectile and lubrication problems compared to partners and to controls. We found significant associations between most relational and sexual parameters and quality of life. In conclusion, many aspects of sexuality are affected in adult patients with CHD, whereas their partners remain relatively unaffected. Moreover, sexuality is an important aspect of quality of life in these patients. We advise physicians to be receptive to discuss sexuality issues and provide patients with adequate therapy. [ABSTRACT FROM AUTHOR]