Impact of congenital heart disease on personality disorders in adulthood.

BACKGROUND AND AIMS: Adults with congenital heart disease (ACHD) constitute an ever-growing patient population characterized by high risks for cardiovascular- and mental disorders. Personality disorders (PDs) are associated with adverse physical and mental health. Studies assessing PD prevalence in ACHD are lacking. METHODS: PD point prevalence was assessed in 210 ACHD by Structured Clinical Interview for Axis-II Personality Disorders (SCID-II) and compared to meta-analytical data from the general population. Depression and anxiety were measured by self-report (Hospital Anxiety and Depression Scale, HADS) and clinician-rating (Montgomery-Åsberg depression rating scale, MADRS). Childhood maltreatment was assessed with the Childhood Trauma Questionnaire and quality-of-life (QOL) with the World Health Organization QOL Scale. RESULTS: PD prevalence was markedly higher in ACHD compared to general population (28.1% vs. 7.7%). Particularly borderline (4.8% vs. 0.9%) and cluster C (i.e. anxious or fearful; 17.1% vs. 3.0%) PDs were overrepresented. PD diagnosis was associated with a surgery age ≤12 years (χ²(1)=7.861, φ=.195, p=.005) and higher childhood trauma levels (U=2583.5, Z=-3.585, p<.001). ACHD with PD reported higher anxiety (HADS-A: U=2116.0, Z=-5.723, p<.001) and depression (HADS-D: U=2254.5, Z=-5.392, p<.001; MADRS: U=2645.0, Z=-4.554, p<.001) levels and lower QOL (U=2538.5, Z=-4.723, p<.001). CONCLUSIONS: PDs, particularly borderline- and cluster C, are significantly more frequent in ACHD compared to general population and associated with depression, anxiety and decreased QOL. Data from the general population suggest an association with adverse cardiometabolic and mental health. To ensure guideline-based treatment, clinicians should be aware of the increased PD risk in ACHD.

Adults with congenital heart disease (ACHD) constitute an ever-growing patient population characterized by an increased cardiovascular disease risk. Personality disorders (PDs) are associated with adverse mental and physical, in particular cardiovascular, health in the general population. Studies assessing PD prevalence in ACHD have been lacking to date. PDs, particularly borderline PD and cluster C (anxious or fearful) PDs, are highly prevalent in ACHD. PDs are associated with heightened levels of anxiety and depression and decreased quality of life in ACHD. Heart surgery before puberty and increased levels of childhood maltreatment are associated with PD diagnosis.

Validation of Phase-Resolved Functional Lung (PREFUL) Magnetic Resonance Imaging Pulse Wave Transit Time Compared to Echocardiography in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary pulse wave transit time (pPTT) is a contrast agent free, vascular imaging biomarker, but has not been validated in chronic obstructive pulmonary disease (COPD). PURPOSE: To validate PREFUL with echocardiographic pPTT as a reference standard and to compare arterial/venous pPTT mapping with spirometry and clinical parameters. STUDY TYPE: Prospective. POPULATION: Twenty-one patients (62% female) with COPD and 44 healthy participants (50% female). FIELD STRENGTH/SEQUENCE: 1.5 T; 2D-spoiled gradient-echo sequence. ASSESSMENT: Three coronal PREFUL MRI slices, echocardiography, and spirometry including forced expiratory volume in 1 second (FEV1, liter) and predicted defined as FEV1 in% divided by the population average FEV1%, were performed. Pulmonary pulse transit time from the main artery to the microvasculature (PREFUL pPTT), to the right upper lobe vein (PREFUL pPTTav , echo pPTTav ), from microvasculature to right upper lobe vein (PREFULvein ) and the ratio of PREFUL pPTT to PREFUL pPTTvein were calculated. Body mass index (BMI), Global Initiative for COPD (GOLD) stage 1-4, disease duration, and cigarette packs smoked per day multiplied by the smoked years (pack years) were computed. STATISTICAL TESTS: Shapiro-Wilk-test, paired-two-sided-t-tests, Bland-Altman-analysis, coefficient of variation, Pearson ρ were applied, pPTT data were compared between 21 subjects from the 44 healthy subjects who were age- and sex-matched to the COPD cohort, P < 0.05 was considered statistically significant. RESULTS: PREFUL pPTTav significantly correlated with echo pPTTav (ρ = 0.95) with 1.85 msec bias, 95% limits of agreement: 55.94 msec, -52.23 msec in all participants (P = 0.59). In the healthy participants, PREFUL and echo pPTTav significantly correlated with age (ρ = 0.81, ρ = 0.78), FEV1 (ρ = -0.47, ρ = -0.34) and BMI (ρ = 0.56, ρ = 0.51). In COPD patients, PREFUL pPTT significantly correlated with FEV1 predicted (ρ = -0.59), GOLD (ρ = 0.53), disease duration (ρ = 0.54), and pack years (ρ = 0.49). DATA CONCLUSION: Arteriovenous PTT measured by PREFUL MRI corresponds precisely to echocardiography and appears to be feasible even in severe COPD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Factors That Influence Adherence to Medication in Adults With Congenital Heart Disease (ACHD).

Objective: Innovative operative and interventional procedures have improved survival in congenital heart disease (CHD), and today more than 90% of these children reach adulthood. Consequently, adherence and psychosocial issues are becoming increasingly important because non-adherence to treatment recommendations worsens morbidity and mortality. This study aimed to identify factors modifying adherence to medication in adult congenital heart disease (ACHD). Methods: This cross-sectional study included 451 outpatients (female 47.9%, average age ± SD: 37.9 ± 12 years) from the ACHD department, who completed a questionnaire assessing medication non-adherence and individual barriers to treatment. Further assessments included psychological well-being (Hospital Anxiety and Depression scale; HADS), childhood traumatization, sociodemographic, and clinical data. Binary logistic regression analysis calculated the impact of these factors on drug adherence. Results: Of the 451 patients 162 participants (35.9%) reported to be non-adherent. In univariate analysis non-adherence to treatment was associated with smoking (P = < 0.001) and internet addiction (P = 0.005). Further factors negatively influencing adherence were the presence of depressive symptoms (P = 0.002), anxiety (P = 0.004), and childhood traumatization (p = 0.002). Factors positively associated with adherence were older age (P = 0.003) and more advanced heart disease as indicated by NYHA class (P = 0.01), elevated NT-proBNP (P = 0.02), device therapy (P = 0.002) and intermittent arrhythmias (P = 0.01). In multivariate analysis especially psychopathological factors such as depression (P = 0.009), anxiety (P = 0.032) and childhood traumatization (P = 0.006) predicted non-adherence. Conclusion: Adherence is a critical issue in the long-term management of ACHD. Identifying modifiable factors that worsen adherence offers the opportunity for targeted interventions. Depressive symptoms, anxiety, and adverse childhood experiences are amenable to psychosocial interventions, as well as cigarette smoking. Our study suggests that a multimodal and interdisciplinary treatment concept for the long-term management of adults with congenital heart disease could be beneficial. Whether it will further improve morbidity and mortality, should be assessed in prospective interventions.

Prevalence of Child Maltreatment in Adults With Congenital Heart Disease and Its Relationship With Psychological Well-Being, Health Behavior, and Current Cardiac Function.

Background: The prevalence of child maltreatment in adults with congenital heart disease (ACHD) has not been assessed so far. Child maltreatment is a major risk factor for unfavorable behavioral, mental, and physical health outcomes and has been associated with decreased quality of life. Given the increased survival time of ACHD, it is essential to assess factors that may worsen the quality of life and interact with classical cardiovascular risk factors and mental well-being. Methods: In a cross-sectional study, 196 ACHD (mean age 35.21 ± 11.24 y, 44,4% female, 55.6% male) completed a thorough psychiatric and cardiac evaluation. Child maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ) and rates were compared to already existing data from the German general population. Further psychological measurements included the WHO Quality of Life Questionnaire, Hospital Anxiety and Depression Scale (HADS) and assessment of lifestyle factors (exercise, smoking, alcohol consumption, body mass index). To identify a relationship between current cardiac function and child maltreatment, we used logistic regression. Results: ACHD reported significantly higher rates of emotional neglect and emotional abuse and sexual abuse and lower rates of physical neglect when compared to the general German population. In addition, total CTQ-scores, emotional abuse, emotional neglect, physical abuse, and sexual abuse correlated with symptoms of depression, anxiety, and negatively correlated with QoL. Furthermore, CTQ scores contributed significantly in predicting higher New York Heart Association (NYHA) scores (p = 0.009). Conclusion: Child maltreatment is more common in ACHD and associated with decreased quality of life and depression and anxiety. Furthermore, we found evidence that self-reported child maltreatment is associated with decreased cardiac function. Given the longer survival time of patients with ACHD, identifying factors that may negatively influence the disease course is essential. The negative consequences of child maltreatment may be the subject of psychosocial interventions that have demonstrated efficacy in treating posttraumatic stress disorders.

Valve-sparing aortic root replacement in adult patients with congenital heart disease.

OBJECTIVES: Aortic root dilatation is frequently observed in patients with congenital heart defects (CHD), but has received little attention in terms of developing a best practice approach for treatment. In this study, we analysed our experience with aortic valve-sparing root replacement in patients following previous operations to repair CHD. METHODS: In this study, we included 7 patients with a history of previous surgery for CHD who underwent aortic valve-sparing operations. The underlying initial defects were tetralogy of Fallot (n = 3), transposition of great arteries (n = 2), coarctation of the aorta (n = 1), and pulmonary atresia with ventricle septum defect (n = 1). The patients' age ranged from 20 to 40 years (mean age 31 ± 6 years). RESULTS: David reimplantation was performed in 6 patients and a Yacoub remodelling procedure was performed in 1 patient. Four patients underwent simultaneous pulmonary valve replacement. The mean interval between the corrective procedure for CHD and the aortic valve-sparing surgery was 26 ± 3 years. There was no operative or late mortality. The patient with transposition of great arteries following an arterial switch operation was re-operated 25 months after the valve-sparing procedure due to severe aortic regurgitation. In all other patients, the aortic valve regurgitation was mild or negligible at the latest follow-up (mean 8.7 years, range 2.1-15.1 years). CONCLUSIONS: Valve-sparing aortic root replacement resulted in good aortic valve function during the first decade of observation in 6 of 7 patients. This approach can offer a viable alternative to root replacement with mechanical or biological prostheses in selected patients following CHD repair.

Eligibility for subcutaneous implantable cardioverter-defibrillator in adults with congenital heart disease.

AIMS: Patients with adult congenital heart disease (ACHD) carry an increased risk for sudden cardiac death. Implantable cardioverter-defibrillator (ICD) therapy may be challenging in these patients due to anatomical barriers, repeated cardiac surgery, or complicated transvenous access. Thus, the subcutaneous ICD (S-ICD) can be a promising alternative in this patient population. Patients with ACHD show significant electrocardiogram (ECG) abnormalities, which could affect S-ICD sensing because it depends on surface ECG. METHODS AND RESULTS: One hundred patients with ACHD were screened for S-ICD eligibility. Standard ECG-based screening test and automated S-ICD screening test were performed in all patients. Sixty-six patients (66%) were male. Underlying congenital heart disease (CHD) was mainly CHD of great complexity (71%) and moderate complexity (29%), including repaired tetralogy of Fallot (20%), which was the most common entity. Thirty-seven patients (37%) already had a pacemaker (23%) or ICD (14%) implanted. Automated screening test identified 83 patients (83%) eligible for S-ICD implantation in either left parasternal position (78%) or right parasternal position (75%). Absence of sinus rhythm, QRS duration, and a paced QRS complex were associated with S-ICD screening failure in univariate analysis. Receiver operating characteristic curve and multivariate analysis revealed a QRS duration ≥148 ms as the only independent predictor for S-ICD screening failure. CONCLUSIONS: Patients with ACHD show satisfactory eligibility rates (83%) for S-ICD implantation utilizing the automated screening test, including patients with CHD of high complexity. S-ICD therapy should be considered with caution in ACHD patients with a QRS duration ≥148 ms and/or need for ventricular pacing.

Increased epicardial adipose tissue in young adults with congenital heart disease comorbid with major depressive disorder.

OBJECTIVE: Congenital heart disease is the most common congenital malformation. In adult congenital heart disease (ACHD), the prevalence of major depressive disorder (MDD) is increased. Beyond its immanent health risks, increased epi­ and paracardial adipose tissue has been described in MDD. Epicardial adipose tissue (EAT) is a fat depot surrounding the heart, and it is hypothesized to be associated with coronary artery disease, left-ventricular dysfunction and atrial fibrillation, being frequent problems in ACHD long-term management. We here examined whether EAT is increased in depressed patients with ACHD. METHODS: Two-hundred and ten ACHD outpatients (mean age 35.5y, 43% female) were included. MDD was diagnosed according to DSM-IV criteria using expert interviews. EAT was measured using echocardiography. Further assessments comprised NT-proBNP, left and right ventricular end-diastolic diameter, left-ventricular ejection fraction, smoking behavior and physical activity. RESULTS: Of 210 patients, 53 (25.2%) were diagnosed with MDD. EAT was increased in depressed ACHD (F = 5.04; df = 1; p = 0.026). Depressed male patients were less physically active (p < 0.05) and smoked more cigarettes (p < 0.05). EAT was positively predicted by depression severity (p = 0.039), body mass index (p < 0.001), and negatively predicted by physical activity (p = 0.019). CONCLUSIONS: The presence of MDD is associated with an increased amount of EAT in ACHD, and is dependent on depression severity. Further, the amount of EAT is at least in part mediated by a more sedentary lifestyle. Given the long-term health risks associated with increased EAT, interventions aiming at increased physical activity, smoking cessation and early identification of comorbid MDD may be recommended in ACHD.

Prediction of heart failure and death in an adult population of Fontan patients.

BACKGROUND: Late Fontan survivors are at high risk to experience heart failure and death. Therefore, the current study sought to investigate the role of non-invasive diagnostics as prognostic markers for failure of the systemic ventricle following Fontan procedure. METHODS: This monocentric, longitudinal observational study included 60 patients with a median age of 24.5 (19-29) years, who were subjected to cardiac magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing, and blood analysis. The primary endpoint of this study was decompensated heart failure with symptoms at rest, peripheral and/or pulmonary edema, and/or death. RESULTS: During a follow-up of 24 months, 5 patients died and 5 patients suffered from decompensated heart failure. Clinical (NYHA class, initial surgery), functional (VO2 peak, ejection fraction, cardiac index), circulating biomarkers (N-terminal pro brain natriuretic peptide), and imaging parameters (end diastolic volume index, end systolic volume index, mass-index, contractility, afterload) were significantly related to the primary endpoint. Multi-variate regression analysis identified afterload as assessed by cardiac magnetic resonance imaging as an independent predictor of the primary endpoint (hazard ratio 1.98, 95% confidence interval 1.19-3.29, p = 0.009). CONCLUSION: We identified distinct parameters of cardiopulmonary exercise testing, cardiac magnetic resonance imaging, and blood testing as markers for future decompensated heart failure and death in patients with Fontan circulation. Importantly, our data also identify increased afterload as an independent predictor for increased morbidity and mortality. This parameter is easy to assess by non-invasive cardiac magnetic resonance imaging. Its modulation may represent a potential therapeutic approach target in these high-risk patients.

Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience.

OBJECTIVES: Decellularized homografts have shown auspicious early results when used for pulmonary valve replacement (PVR) in congenital heart disease. The first clinical application in children was performed in 2002, initially using pre-seeding with endogenous progenitor cells. Since 2005, only non-seeded, fresh decellularized allografts have been implanted after spontaneous recellularization was observed by several groups. METHODS: A matched comparison of decellularized fresh pulmonary homografts (DPHs) implanted for PVR with cryopreserved pulmonary homografts (CHs) and bovine jugular vein conduits (BJVs) was conducted. Patients' age at implantation, the type of congenital malformation, number of previous cardiac operations and number of previous PVRs were considered for matching purposes, using an updated contemporary registry of right ventricular outflow tract conduits (2300 included conduits, >12 000 patient-years). RESULTS: A total of 131 DPHs were implanted for PVR in the period from January 2005 to September 2015. Of the 131, 38 were implanted within prospective trials on DPH from October 2014 onwards and were therefore not analysed within this study. A total of 93 DPH patients (58 males, 35 females) formed the study cohort and were matched to 93 CH and 93 BJV patients. The mean age at DPH implantation was 15.8 ± 10.21 years (CH 15.9 ± 10.4, BJV 15.6 ± 9.9) and the mean DPH diameter was 23.9 mm (CH 23.3 ± 3.6, BJV 19.9 ± 2.9). There was 100% follow-up for DPH, including 905 examinations with a mean follow-up of 4.59 ± 2.76 years (CH 7.4 ± 5.8, BJV 6.4 ± 3.8), amounting to 427.27 patient-years in total (CH 678.3, BJV 553.0). Tetralogy-of-Fallot was the most frequent malformation (DPH 50.5%, CH 54.8%, BJV 68.8%). At 10 years, the rate of freedom of explantation was 100% for DPH, 84.2% for CH (P = 0.01) and 84.3% for BJV (P= 0.01); the rate of freedom from explantation and peak trans-conduit gradient ≥50 mmHg was 86% for DPH, 64% for CH (n.s.) and 49% for BJV (P < 0.001); the rate of freedom from infective endocarditis (IE) was 100% for DPH, 97.3 ± 1.9% within the matched CH patients (P = 0.2) and 94.3 ± 2.8% for BJV patients (P = 0.06). DPH valve annulus diameters converged towards normal Z-values throughout the observation period, in contrast to other valve prostheses (BJV). CONCLUSIONS: Mid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV.

Decellularized aortic homografts for aortic valve and aorta ascendens replacement.

OBJECTIVES: The choice of valve prosthesis for aortic valve replacement (AVR) in young patients is challenging. Decellularized pulmonary homografts (DPHs) have shown excellent results in pulmonary position. Here, we report our early clinical results using decellularized aortic valve homografts (DAHs) for AVR in children and mainly young adults. METHODS: This prospective observational study included all 69 patients (44 males) operated from February 2008 to September 2015, with a mean age of 19.7 ± 14.6 years (range 0.2-65.3 years). In 18 patients, a long DAH was used for simultaneous replacement of a dilated ascending aorta as an extended aortic root replacement (EARR). Four patients received simultaneous pulmonary valve replacement with DPH. RESULTS: Thirty-nine patients (57%) had a total of 62 previous operations. The mean aortic cross-clamp time in isolated cases was 129 ± 41 min. There was 1 conduit-unrelated death. The mean DAH diameter was 22.4 ± 3.7 mm (range, 10-29 mm), the average peak gradient was 14 ± 15 mmHg and the mean aortic regurgitation grade (0.5 = trace, 1 = mild) was 0.6 ± 0.5. The mean effective orifice area (EOA) of 25 mm diameter DAH was 3.07 ± 0.7 cm(2). DAH annulus z-values were 1.1 ± 1.1 at implantation and 0.7 ± 1.3 at the last follow-up. The last mean left ventricle ejection fraction and left ventricle end diastolic volume index was 63 ± 7% and 78 ± 16 ml/m(2) body surface area, respectively. To date, no dilatation has been observed at any level of the graft during follow-up; however, the observational time is short (140.4 years in total, mean 2.0 ± 1.8 years, maximum 7.6 years). One small DAH (10 mm at implantation) had to be explanted due to subvalvular stenosis and developing regurgitation after 4.5 years and was replaced with a 17 mm DAH without complication. No calcification of the explanted graft was noticed intraoperatively and after histological analysis, which revealed extensive recellularization without inflammation. CONCLUSIONS: DAHs withstand systemic circulation, provide outstanding EOA and appear as an alternative to conventional grafts for AVR in young patients. EARR using DAH is a further option in aortic valve disease associated with aorta ascendens dilatation as it avoids the use of any prosthetic material.

Bovine Jugular Veins versus Homografts in the Pulmonary Position: An Analysis across Two Centers and 711 Patients-Conventional Comparisons and Time Status Graphs as a New Approach.

BACKGROUND: Various diseases and diversity in implantation ages, together with evolving diagnostic and therapeutic options, hinder comparative evaluations of long-term outcomes for valved conduits used for reconstruction of the right ventricular outflow tract (RVOT). We combined two common evaluation methods to optimally use information obtained by pooling the raw data from two high volume centers, each with very regular follow-up procedures, with the aim of analyzing durability differences between conventional homografts and bovine jugular veins. PATIENTS AND METHODS: In the period 1985 to 2012, a total of 444 bovine jugular veins and 267 homografts were implanted, and 6,738 postoperative examinations took place. Evaluations included age-stratified Kaplan-Meier analyses, Cox regression models, and time status graphs, the third showing age-group stratified, time-related frequencies of intact, insufficient, stenotic, both insufficient and stenotic, and postinterventional conduits below the freedom from explantation curve. They take into account interventions, explantations, and the nonterminal character of echocardiographic findings. RESULTS: The durability of intact bovine jugular veins in children and young adults is not inferior to that of homografts. Averaged over the first 12 years after implantation, the age groups < 25 years in fact showed advantages for bovine jugular vein recipients. The average fraction of patients younger than 25 years whose conduits were not explanted, postinterventional, stenotic, insufficient, or stenotic and insufficient was at least 10% higher in recipients of bovine jugular veins than in homograft recipients. CONCLUSION: According to the time status graphs, the use of bovine jugular veins for RVOT in patients younger than 25 years appears to lead to superior results when compared with cryopreserved homografts.

Declining cardiopulmonary exercise capacity is not associated with worsening systolic systemic ventricular dysfunction in adults with transposition of great arteries after atrial switch operation.

BACKGROUND/OBJECTIVE: Cardiopulmonary exercise capacity is often reduced in patients with transposition of the great arteries after atrial switch operation. Reduced exercise capacity may be caused by deterioration of systemic right ventricular function over time. This study analyzed serial changes in systemic right ventricular function and cardiopulmonary exercise capacity in young adults with transposition of the great arteries after atrial redirection surgery. METHODS: Twenty-one patients (37% female, mean age 23.2 ± 3.3, mean age at surgery 12.8 ± 14 years) with transposition of the great arteries after atrial switch operation were included in this study. Patients were followed up for a mean period of 39.6 ± 13.1 months. Exercise capacity expressed as peak VO2 max, systemic right ventricular function and subpulmonary left ventricular function assessed by cardiac magnetic resonance imaging and NT-proBNP levels were obtained at baseline and follow-up. Changes in peak VO2 max were correlated to changes in cardiac magnetic resonance imaging and NT-proBNP levels. RESULTS: Baseline peak VO2 max decreased significantly (28.31 ± 5.80 mL/kg/min vs. 25.17 ± 5.71 mL/kg/min, P = .005) on follow-up. Cardiac magnetic resonance imaging parameters of systemic right ventricular ejection fraction as well as subpulmonary left ventricular ejection fraction remained unchanged (44.68 ± 6.59% vs. 45.65 ± 9.60%, P = .54, 60.18 ± 6.29% vs. 61.52 ± 5.30%, P = .35). NT-proBNP levels did not increase (211.7 ± 85.7 ng/mL vs. 261.2 ± 182.2 ng/mL, P = .16). CONCLUSIONS: After atrial switch operation for transposition of the great arteries we observed a declining functional exercise capacity. This was not associated with worsening systemic right ventricular function, suggesting that other factors are contributing to the decline in physical exercise capacity.

Aerobic training in adults after atrial switch procedure for transposition of the great arteries improves exercise capacity without impairing systemic right ventricular function.

BACKGROUND: Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). METHODS: 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. RESULTS: At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. CONCLUSIONS: Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT00837603).

Prognostic value of NT-proBNP in patients with systemic morphological right ventricles: a single-centre experience.

UNLABELLED: In systemic morphological right ventricles after atrial redirection surgery, NT-proBNP is correlated with NYHA-class, ventricular function and subaortic AV-valve regurgitation (TR). The impact of NT-proBNP on adverse clinical outcomes is, however, unknown. METHODS: This prospectively designed, longitudinal, observational study evaluated NT-proBNP in 116 patients (24.9 ± 4.2 years old, NYHA class I/II/III=97/18/1, 71 men) relative to all cardiac causes of hospitalisation, heart failure, transplantation and death. RESULTS: The mean observation time was 7.3 ± 2.4 years. In univariate Cox proportion analysis, the predictors for all causes of hospitalisation (n=41; 35.5%) were NT-proBNP (HR: 5.99; 95%CI: 3.21-11.18), NYHA class (HR: 2.98; 95%CI: 1.62-5.5), ventricular function (HR: 1.96; 95%CI: 1.27-3.02), TR (HR: 2.39; 95%CI: 1.48-3.59), ventricular septal defect repair (HR: 1.29; 95%CI: 1.08-1.53) and a history of supraventricular tachycardia (SVT) (HR: 7.13; 95%CI: 3.74-13.59). In multivariate Cox proportion analysis, NT-proBNP (HR: 3.71; 95%CI: 1.82-7.57), SVT (HR: 4.27; 95%CI: 2.03-8.94) and ventricular septal defect repair (HR: 1.41; 95%CI: 1.15-1.72) remained independently associated with all causes of hospitalisation. For heart failure, transplantation and death, the single predictors were NT-proBNP (HR: 20.67; 95%CI: 4.69-91.78), NYHA class (HR: 6.45; 95%CI: 2.75-15.14), ventricular function (HR: 2.70; 95%CI: 1.48-4.92), TR (HR: 4.11; 95%CI: 1.99-8.47), QRS duration (HR: 2.09; 95%CI: 1.06-4.12) and SVT (HR: 8.00; 95%CI: 2.82-22.69). Multivariate Cox proportion analysis identified NT-proBNP (HR: 6.82; 95%CI: 1.32-35.04) and NYHA class (HR: 6.79; 95%CI: 1.75-26.28). Using ROC curves, the ability of NT-proBNP to detect patients at risk was greater for heart failure, transplantation and death (AUC: 0.944; 95%CI: 0.900-0.988) than for all causes of hospitalisation (AUC: 0.8; 95%CI: 0.713-0.887). CONCLUSION: In systemic right ventricles, NT-proBNP is a useful risk predictor for all causes of hospitalisation and, in particular, for heart failure, transplantation and death. It therefore might be a useful tool for risk assessment in this patient population.

Angiopoietin-2 in adults with congenital heart disease and heart failure.

BACKGROUND: Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied. METHODS: In 91 patients Ang-2 and NT-proBNP were measured and related to New York Heart Association class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Ang-1, VEGF, and sTie2 were also measured. RESULTS: Ang-2 correlates with NYHA class and ventricular dysfunction comparable to NT-proBNP. Further, Ang-2 showed a good correlation with parameters of cardiopulmonary exercise testing. Both, Ang-2 and NT-proBNP identified patients with severely limited cardiopulmonary exercise capacity. Additionally, Ang-2 is elevated in patients with a single ventricle physiology in contrast to NT-proBNP. VEGF, Ang-1, and sTie2 were not correlated with any clinical parameter. CONCLUSION: The performance of Ang-2 as a biomarker for heart failure in ACHD is comparable to NT-proBNP. Its significant elevation in patients with single ventricle physiology indicates potential in this patient group and warrants further studies.

Anomalous intramural course of coronary arteries in congenital heart disease--three case reports and review of the literature.

Anomalies of the coronary arteries are commonly associated with congenital heart disease (CHD). Anomalies include variations in number, shape, and location of the origin, as well as the course of the coronary artery. An intramural course of one of the coronary arteries is a rather rare condition. Most cases of anomalies are of no clinical relevance and are found incidentally during evaluation for other cardiac conditions. However, they become of importance when cardiac surgery/intervention, especially valve replacement, needs to be performed. We conducted a literature review for coronary anomalies with an intramural course in patients with CHD and include three cases from our own clinic. Note that transposition of the great arteries seems to be the condition most frequently associated with an intramural course of one of the coronary arteries. In case of a suspected anomaly, transesophageal echocardiography presents a valuable tool to visualize the origin and course of the coronary artery, as well as the relationship to important anatomical structures like the aortic or pulmonary valve. Alternatively, cardiac magnetic resonance imaging can be used. Although rare, both cardiologists and surgeons need to be aware of intramural courses of coronary arteries to prevent accidental trauma to them and thereby, reducing the risk for the patient.

Long-term morbidity and quality of life after surgical repair of transposition of the great arteries: atrial versus arterial switch operation.

Since a growing number of patients after surgical repair of transposition of the great arteries (TGA) survive until adulthood the focus of attention has shifted to the management of associated long-term morbidity and quality of life (QoL). Therefore, we reviewed all patients that underwent surgical repair of TGA at our institution and compared long-term results after atrial and arterial switch operation. Between 1973 and 2000, a total of 302 patients underwent either atrial switch operation (n=222) or arterial switch operation (n=80). Mean follow-up was 14.5±10.1 years. The arterial switch repair was associated with a higher early mortality whereas long-term survival was comparable between both groups. Postoperative arrhythmias including loss of sinus rhythm and pacemaker implantation occurred significantly more often after atrial switch repair. There was a trend towards a more favourable outcome of the arterial switch group concerning freedom from re-interventions, severe systemic ventricular dysfunction and need for heart failure medication. However, also the arterial switch operation was associated with an increased incidence of loss of sinus rhythm and neo-aortic valve regurgitation during late follow-up. Health related QoL according to the SF-36 questionnaire was not significantly different between both groups and comparable to a healthy population.

Symmetrical dimethylarginine outperforms CKD-EPI and MDRD-derived eGFR for the assessment of renal function in patients with adult congenital heart disease.

BACKGROUND/AIMS: Adults with congenital heart disease exhibit a 3-fold higher mortality in the presence of chronic kidney disease, hence assessment of renal function is crucial in this patient population. Formulas for the estimation of glomerular filtration rate (GFR) have not been evaluated in this patient population. Therefore, this study compares different markers and equations for the estimation of renal function in adults with congenital heart disease. METHODS: Renal function was assessed in 102 patients using the Modification of Diet in Renal Disease (MDRD) equation, the simplified MDRD equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the Cockcroft-Gault formula. Additionally, symmetrical dimethylarginine (SDMA) was measured. Those parameters were compared to cystatin C-derived GFR using the Larsson equation. RESULTS: GFR estimates using the original MDRD (r = 0.465, p < 0.001) and the CKD-EPI equation (r = 0.462, p < 0.001) showed a similar strong correlation with the cystatin C-based eGFR equation, while eGFR using the simplified MDRD equation showed a slightly weaker correlation (r = 0.439, p < 0.001). The Cockcroft-Gault formula showed no correlation at all to the cystatin C-based eGFR (r = 0.144, p = 0.17). The strongest correlation was observed for SDMA and cystatin C-based eGFR (r = -0.552, p < 0.001). CONCLUSION: GFR in adults with congenital heart disease should be estimated using the original MDRD or the CKD-EPI formula. SDMA seems to be a promising marker of renal function for this patient group.