Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease.

BACKGROUND: The number of patients with adult congenital heart disease (ACHD) is rapidly increasing. To optimize patient management, there is a great need to accurately identify high-risk patients. Still, no biomarker has been firmly established as a clinically useful prognostic tool in this group. We studied the association of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitive troponin-T, and growth-differentiation factor 15 with cardiovascular events in ACHD. METHODS: Clinically stable patients with ACHD who routinely visited the outpatient clinic between April 2011 and April 2013 underwent clinical assessment, electrocardiography, echocardiography, and biomarker measurement (NT-proBNP, high-sensitive troponin-T, and growth-differentiation factor 15) at the time of study inclusion. Patients were prospectively followed for the occurrence of cardiovascular events (death, heart failure, hospitalization, arrhythmia, thromboembolic events, and reintervention). Survival curves were derived by the Kaplan-Meier method, and Cox regression was performed to investigate the relation between biomarkers and events with adjustment for multiple clinical and echocardiographic variables. RESULTS: In total, 595 patients were included (median age, 33 years; interquartile range, 25-41 years; 58% male; 90% New York Heart Association class I). Patients were followed during a median of 42 (interquartile range, 37-46) months. Of the 3 evaluated biomarkers, NT-proBNP in the upper quartile (>33.3 pmol/L) was most strongly associated with cardiovascular events (n=165, adjusted hazard ratio, 9.05 [3.24-25.3], P<0.001) and with death or heart failure (n=50, adjusted hazard ratio, 16.0 [2.04-126], P<0.001). When NT-proBNP was analyzed as a continuous variable, similar findings were retrieved. The cumulative proportion of patients with death and heart failure was only 1% in the lowest 2 NT-proBNP quartiles. Elevated NT-proBNP (>14 pmol/L), elevated high-sensitive troponin-T (>14 ng/L), and elevated growth-differentiation factor 15 (>1109 ng/L) identified those patients at highest risk of cardiovascular events (log-rank P<0.0001). CONCLUSIONS: NT-proBNP provides prognostic information beyond a conventional risk marker model in patients with ACHD and can reliably exclude the risk of death and heart failure. Elevated levels of NT-proBNP, high-sensitive troponin-T, and growth-differentiation factor 15 identify patients at highest risk of cardiovascular events. These biomarkers therefore may play an important role in the monitoring and management of patients with ACHD.

Matrix metalloproteinases as candidate biomarkers in adults with congenital heart disease.

Context Matrix metalloproteinases (MMPs) are associated with diastolic dysfunction and heart failure in acquired heart disease. Objective To investigate the role of MMPs as novel biomarkers in clinically stable adults with congenital heart disease. Methods We measured serum MMP-2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 in 425 patients and analysed the association with cardiac function and exercise capacity. Results MMP-2 was significantly associated with exercise capacity, ventilatory efficiency and left ventricular deceleration time, independently of age, sex, body surface area and NT-proBNP. Conclusion MMP-2 may provide new information in the clinical evaluation of adults with congenital heart disease.

Longitudinal development of psychopathology and subjective health status in CHD adults: a 30- to 43-year follow-up in a unique cohort.

OBJECTIVE: To determine longitudinal changes in psychopathology in a cohort of patients 30-43 years after their first cardiac surgery for Congenital Heart Disease (CHD) in childhood, to compare outcomes of the 30- to 43-year follow-up with normative data, and to identify medical predictors for psychopathology. METHODS: This study is the third follow-up of this cohort. The first and second follow-ups of this same cohort were conducted in 1990 and 2001, respectively. At all three follow-ups, psychopathology was assessed with standardised, parallel questionnaires. In 2011, subjective health status was assessed by the Short Form-36. Medical predictor variables were derived from medical examinations and medical records. RESULTS: In this third follow-up, a total of 252 patients participated. Of these, 152 patients participated in all three follow-ups. Over a 30-year period, proportions of patients showing psychopathology decreased significantly. At the 30- to 43-year follow-up, overall outcomes on psychopathology for the CHD sample were similar or even better compared with normative groups. Subjective health status was also better compared with normative data. No differences were found between cardiac diagnostic groups. Medical variables that predicted the course of psychopathology over time were as follows: the scar, as judged by the patient, results of the first cardiac surgery, and the number of hospitalisations. CONCLUSIONS: Over a 30-year period, psychopathology decreased in patients with CHD. Levels of psychopathology in these patients, who are now aged between 30 and 54 years, were comparable or even better than normative data.

Unnatural history of tetralogy of Fallot: prospective follow-up of 40 years after surgical correction.

BACKGROUND: Prospective data on long-term survival and clinical outcome beyond 30 years after surgical correction of tetralogy of Fallot are nonexistent. METHODS AND RESULTS: This longitudinal cohort study consists of the 144 patients with tetralogy of Fallot who underwent surgical repair at <15 years of age between 1968 and 1980 in our center. They are investigated every 10 years. Cumulative survival (data available for 136 patients) was 72% after 40 years. Late mortality was due to heart failure and ventricular fibrillation. Seventy-two of 80 eligible survivors (90%) participated in the third in-hospital investigation, consisting of ECG, Holter, echocardiography, cardiopulmonary exercise testing, N-terminal pro-brain natriuretic peptide measurement, cardiac magnetic resonance (including dobutamine stress testing), and the Short Form-36 questionnaire. Median follow-up was 36 years (range, 31-43 years). Cumulative event-free survival was 25% after 40 years. Subjective health status was comparable to that in the normal Dutch population. Although systolic right and left ventricular function declined, peak exercise capacity remained stable. There was no progression of aortic root dilation. A previous shunt operation, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality (hazard ratio, 2.9, 1.1, and 2.5, respectively). An increase in QRS duration and a deterioration of exercise tolerance and ventricular dysfunction did not predict mortality. Insertion of a transannular patch was a predictor for late arrhythmias (hazard ratio, 4.0; 95% confidence interval, 1.2-13.4). CONCLUSIONS: Although many patients needed a reoperation or developed arrhythmias, late mortality was low, and the clinical condition and subjective health status of most patients remained good. Previous shunt, low temperature during surgery, and early postoperative arrhythmias were found to predict late mortality.

The natural and unnatural history of the Mustard procedure: long-term outcome up to 40 years.

AIMS: To describe long-term survival, clinical outcome and ventricular systolic function in a longitudinally followed cohort of patients after Mustard repair for transposition of the great arteries (TGA). There is serious concern about the long-term outcome after Mustard repair. METHODS AND RESULTS: This longitudinal single-centre study consisted of 91 consecutive patients, who underwent Mustard repair before 1980, at age <15 years, and were evaluated in-hospital every 10 years. Survival status was obtained of 86 patients. Median follow-up was 35 (IQR 34-38) years. Cumulative survival was 84% after 10 years, 80% after 20 years, 77% after 30 years, and 68% after 39 years. Cumulative survival free of events (i.e. heart transplantation, arrhythmias, reintervention, and heart failure) was 19% after 39 years. Reinterventions were mainly required for baffle-related problems. Supraventricular and ventricular arrhythmias occurred in 28 and 6% of the patients, respectively. Pacemaker and/or ICD implantation was performed in 39%. Fifty survivors participated in the current in-hospital investigation including electrocardiography, 2D-echocardiography, cardiopulmonary-exercise testing, NT-proBNP measurement, Holter monitoring, and cardiac magnetic resonance. Right ventricular systolic function was impaired in all but one patient at last follow-up, and 14% developed heart failure in the last decade. NT-proBNP levels [median 31.6 (IQR 22.3-53.2) pmol/L] were elevated in 92% of the patients. Early postoperative arrhythmias were a predictor for late arrhythmias [HR 3.8 (95% CI 1.5-9.5)], and development of heart failure [HR 8.1 (95% CI 2.2-30.7)]. Also older age at operation was a predictor for heart failure [HR 1.26 (95% CI 1.0-1.6)]. CONCLUSION: Long-term survival after Mustard repair is clearly diminished and morbidity is substantial. Early postoperative arrhythmias are a predictor for heart failure and late arrhythmias.

Association between N-terminal pro-brain natriuretic peptide and quality of life in adult patients with congenital heart disease.

AIMS: Advances in medical treatment have resulted in increased life expectancy in congenital heart disease. Consequently, the focus of management has shifted from reducing mortality to reducing long-term morbidity with the goal of improving quality of life. A predictor of quality of life might be N-terminal pro-brain natriuretic peptide, a well-established marker for heart failure. We aimed to determine the association between N-terminal pro-brain natriuretic peptide and quality of life in patients with congenital heart disease. METHODS: We collected blood samples from consecutive patients who were initially operated between 1968 and 1980 (47.8% women; mean age 40.2±5.4 years). The 36-item Short-Form Health Survey was completed to assess subjective health status as a measure of quality of life. Analysis was performed for the entire group and for subgroups defined as simple versus complex congenital heart diseases. Median N-terminal pro-brain natriuretic peptide level was 15.2 pmol/L (overall range 1.3-299.3 pmol/L). N-terminal pro-brain natriuretic peptide levels were associated with the subdomain physical functioning (ß=-0.074, p=0.031). This association remained significant after adjustment for age and sex (ß=-0.071, p=0.038) and after adjustment for age, sex, body mass index, left ventricular function, and renal function (ß=-0.069, p=0.048). In complex congenital heart disease, the association between N-terminal pro-brain natriuretic peptide and physical functioning remained significant in multivariable analysis (ß=-0.076, p=0.046). No associations were found in the simple congenital heart disease group or on the other health status subdomains. CONCLUSION: In adults operated for congenital heart disease, N-terminal pro-brain natriuretic peptide is associated with the subdomain physical, primarily in the complex subgroup.

Heart rate: an accessible risk indicator in adult congenital heart disease.

BACKGROUND: Higher resting heart rate has been described as a risk factor for adverse outcome in healthy individuals and cardiovascular patients. The aim of this study was to evaluate resting heart rate as risk factor in adult congenital heart disease (ACHD). METHODS: In this prospective observational cohort study, patients with moderate or complex ACHD were included at routine outpatient visit. Standard 12-lead ECGs were obtained in rest. Heart rate was obtained from the ECG automatically by the Modular ECG Analysis System (MEANS). The primary endpoint was all-cause mortality and the secondary endpoint was a composite of all-cause mortality and heart failure. Survival was derived using the Kaplan-Meier estimator. Subgroups based on heart rate tertiles were compared by the log-rank test. Cox proportional hazards models were adjusted for clinical factors including age, sex and diagnosis (moderate vs complex ACHD). RESULTS: A total of 556 patients were included (median age 32 years (IQR 24-41), 57.6% male). Mean heart rate was 69±13 bpm. Negative chronotropic medication was used by 74 (13.3%) patients. During a median follow-up of 10.1 (IQR 9.6-10.5) years, 36 patients (6.5%) died and 83 (14.9%) reached the secondary endpoint. Patients with higher heart rates had significantly lower survival and heart failure-free survival. After adjusting for clinical factors, heart rate remained associated with mortality (HR 1.57 per 10 bpm, 95% CI 1.26 to 1.96) and mortality or heart failure (HR 1.33 per 10 bpm, 95% CI 1.13 to 1.57). CONCLUSION: Higher heart rate is associated with lower survival and heart failure-free survival in ACHD.

Long term outcome after surgical ASD-closure at young age: Longitudinal follow-up up to 50 years after surgery.

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.

Blood and Imaging Biomarkers in the Long-term Follow-up of Bicuspid Aortic Valve Patients.

Background: Bicuspid aortic valve (BAV) is a common congenital heart defect. Patients with BAV are at risk for long-term complications such as valve stenosis and regurgitation. This study aimed to investigate sex differences in blood and imaging biomarkers and to describe the long-term prognostic value of blood and echocardiographic biomarkers. Methods: Patients were included from 2 prospective observational cohort studies; they underwent venous blood sampling and transthoracic echocardiography including speckle tracking. Analyzed blood biomarkers were red-cell distribution width (RDW), creatinine, C-reactive protein (CRP), troponin T, N-terminal pro B-type natriuretic peptide (NT-proBNP), and transforming growth factor-beta (TGF-ß). Sex differences were analyzed at baseline. Associations between biomarkers and arrhythmia-free and intervention-free survival were determined by Cox regression, adjusted for age and sex. Results: A total of 182 patients with BAV were included: median age 34; interquartile range [IQR]: 23-46 years; 55.5% male. CRP, NT-proBNP, and RDW were higher in women, whereas creatinine, troponin T and TGF-ß were higher among men. After a median follow-up time of 6.9 (IQR: 6.5-9.9) years, arrhythmia-free and intervention-free survival was, 81.0% and 73.1%, respectively. NT-proBNP was associated with both arrhythmia-free and intervention-free survival (hazard ratio [HR], 1.94, P = 0.005 and HR, 2.06, P = 0.002, respectively). On echocardiography higher left atrial (LA) size, left ventricular end-diastolic diameter (LVEDD), left ventricular (LV) mass index and E/e' ratio were associated with lower arrhythmia-free survival, whereas higher LA size, LV mass index, aortic valve peak velocity, and aortic regurgitation were associated with lower intervention-free survival. Conclusions: Differences were observed in blood biomarkers between men and women with BAV. Besides LV systolic parameters, diastolic LV function and NT-proBNP should have a more prominent role as prognostic markers in clinical care.

Contexte: La bicuspide valvulaire aortique (BVA) est une anomalie cardiaque congénitale fréquente. Les patients atteints d'une BVA présentent des risques de complications à long terme, comme la sténose valvulaire ou la régurgitation valvulaire. Cette étude visait 1) à évaluer les différences entre les sexes en ce qui concerne les biomarqueurs sanguins et les biomarqueurs à l'imagerie; et 2) à décrire la valeur pronostique à long terme des biomarqueurs sanguins et échocardiographiques. Méthodologie: Des patients de 2 études de cohortes observationnelles prospectives ont été inclus dans l'analyse. Des échantillons de sang veineux ont été prélevés, et des échocardiographies transthoraciques, y compris le suivi des marqueurs acoustiques, ont été effectuées. Les biomarqueurs sanguins analysés étaient les suivants : indice de distribution des globules rouges (IDR), créatinine, protéine C-réactive (CRP), troponine T, propeptide natriurétique de type B N-terminal (NT-proBNP) et facteur de croissance transformant ß (TGF-ß). Les différences entre les sexes ont été analysées au départ. Les liens entre les biomarqueurs et la survie sans arythmie et sans intervention ont été déterminés par la régression de Cox, avec correction en fonction de l'âge et du sexe. Résultats: Cent quatre-vingt-deux patients présentant une BVA étaient inclus (âge médian de 34 [écart interquartile : 23-46] ans, 55,5 % hommes). La CRP, la NT-proBNP et l'IDR étaient plus élevées chez les femmes, alors que la créatinine, la troponine T et le TGF-ß étaient plus élevés chez les hommes. Après une période de suivi médiane de 6,9 (écart interquartile : 6,5-9,9) ans, les taux de survie sans arythmie et sans intervention étaient respectivement de 81,0 % et de 73,1 %. La NT-proBNP a été associée à la survie sans arythmie (rapport des risques instantanés [RRI] : 1,94, p = 0,005) et à la survie sans intervention (RRI : 2,06, p = 0,002). À l'échocardiographie, des valeurs élevées pour la taille de l'oreillette gauche, le diamètre télédiastolique du ventricule gauche (VG), l'indice de masse du VG et le rapport E/e' étaient associées à un faible taux de survie sans arythmie, alors que des valeurs élevées pour la taille de l'oreillette gauche, l'indice de masse du VG, la vitesse maximale aortique et la régurgitation aortique étaient associées à un faible taux de survie sans intervention. Conclusions: Les biomarqueurs sanguins variaient en fonction du sexe des personnes présentant une BVA. Outre les paramètres systoliques du VG, la fonction VG diastolique et la NT-proBNP devraient être davantage utilisées comme marqueurs pronostiques en soins cliniques.

Ascending aorta dilatation in patients with bicuspid aortic valve stenosis: a prospective CMR study.

BACKGROUND: The aim of this study was to evaluate the natural progression of aortic dilatation and its association with aortic valve stenosis (AoS) in patients with bicuspid aortic valve (BAV). METHODS: Prospective study of aorta dilatation in patients with BAV and AoS using cardiac magnetic resonance (CMR). Aortic root, ascending aorta, aortic peak velocity, left ventricular systolic and diastolic function and mass were assessed at baseline and at 3-year follow-up. RESULTS: Of the 33 enrolled patients, 5 needed surgery, while 28 patients (17 male; mean age: 31 ± 8 years) completed the study. Aortic diameters significantly increased at the aortic annulus, sinus of Valsalva and tubular ascending aorta levels (P < 0.050). The number of patients with dilated tubular ascending aortas increased from 32 % to 43 %. No significant increase in sino-tubular junction diameter was observed. Aortic peak velocity, ejection fraction and myocardial mass significantly increased while the early/late filling ratio significantly decreased at follow-up (P < 0.050). The progression rate of the ascending aorta diameter correlated weakly with the aortic peak velocity at baseline (R (2) = 0.16, P = 0.040). CONCLUSION: BAV patients with AoS showed a progressive increase of aortic diameters with maximal expression at the level of the tubular ascending aorta. The progression of aortic dilatation correlated weakly with the severity of AoS.

Right ventricular electromechanical dyssynchrony in adults with repaired Tetralogy of Fallot.

Background and purpose: Electromechanical dyssynchrony, manifested by right bundle branch block and regional wall mechanical dysfunction, contributes to inefficient RV function in repaired Tetralogy of Fallot (ToF). This study aims to evaluate the synchronicity of multiple RV walls using two-dimensional multi-plane echocardiography (2D-MPE) in order to augment current understanding of the mechanisms behind RV dyssynchrony. Methods: Sixty-nine adult ToF patients [aged 33 (23-45) years; 61% male] and twenty-five matched healthy controls underwent deformational analysis of the RV lateral, anterior, inferior and septal walls following 2D-MPE acquisitions. RV synchronicity was assessed by the intra-RV deformation delay between each basal RV wall and mid-septal segment in addition to mechanical dispersion calculated across four, six and eight segments (MD). Results: All RV wall-septum delays plus MD-4 and MD-6 indices were significantly greater in ToF patients compared to healthy controls (p < 0.001-0.03). In ToF patients, the lateral and anterior RV walls were last to reach peak deformation and anterior wall longitudinal strain was lower (p = 0.001). Post systolic shortening of at least one RV wall segment was identified in 19 (28%) ToF patients. Despite similar ECG characteristics, lateral and anterior wall-septum delays were significantly longer in patients with greater degrees of dyssynchrony (73 [37-108]ms vs. 37 [0-63]ms, p = 0.006; 91 [52-116]ms vs. 41 [1-69]ms, p = 0.013), although RV ejection fraction (RVEF) was not significantly lower. MD-4 and MD-8 indices displayed moderate negative associations with RVEF, strengthened by inclusion of lateral wall longitudinal strain (r = 0.64/0.65; p ≤0.01). Conclusion: RV dyssynchrony in ToF is characterised by electromechanical delays between the lateral, anterior and septal walls, with anterior wall dysfunction likely associated with surgical repair of the RV outflow tract. Prospectively, 2D-MPE may have an emerging role evaluating RV mechanical response to electrical resynchronisation therapy.

SCUBA Diving in Adult Congenital Heart Disease.

Conventionally, scuba diving has been discouraged for adult patients with congenital heart disease (ACHD). This restrictive sports advice is based on expert opinion in the absence of high-quality diving-specific studies. However, as survival and quality of life in congenital heart disease (CHD) patients have dramatically improved in the last decades, a critical appraisal whether such restrictive sports advice is still applicable is warranted. In this review, the cardiovascular effects of diving are described and a framework for the work-up for ACHD patients wishing to engage in scuba diving is provided. In addition, diving recommendations for specific CHD diagnostic groups are proposed.

Life expectancy and end-of-life communication in adult patients with congenital heart disease, 40-53 years after surgery.

Aims: Although survival of patients with congenital heart disease (CHD) improved significantly over time, life expectancy is still not normal. We aimed to investigate how adult patients, their partners, and treating cardiologists estimated the individual life expectancy of CHD patients. Furthermore, preferences regarding end-of-life (EOL) communication were investigated. Methods and results: In this study, we included 202 patients (age: 50 ± 5) who were operated in childhood (<15 years old) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, or transposition of the great arteries. A specific questionnaire was administered to both the patients and their partners, exploring their perceived life expectancy and EOL wishes. Two cardiologists independently assessed the life expectancy of each patient. Most adults with CHD believed their life expectancy to be normal. However, significant differences were found between estimated life expectancy by the cardiologist and patients (female: P = 0.001, male: P = 0.002) with moderate/severe defects, as well as for males with mild defects (P = 0.011). Regarding EOL communication, 85.1% of the patients reported that they never discussed EOL with a healthcare professional. Compared with patients with mild CHD, significantly more patients with moderate/severe defect discussed EOL with a physician (P = 0.011). The wish to discuss EOL with the cardiologist was reported by 49.3% of the patients and 41.7% of their partners. Conclusion: Adult patients, especially with moderate/severe CHD, perceived their life expectancy as normal, whereas cardiologists had a more pessimistic view than their patients. Increased attention is warranted for discussions on life expectancy and EOL to improve patient-tailored care.

What endocrinologists can do to prevent cardiovascular complications in adults with Prader-Willi syndrome: Lessons from a case series.

Context: Prader-Willi syndrome (PWS) is a complex rare genetic syndrome. Mortality in patients with PWS is 3% per year. In nearly half of the patients, the cause of death is of cardiopulmonary origin. Prevention, diagnosis and treatment of cardiovascular (CV) disease in PWS adults is complicated by the behavioral phenotype, reduced ability to express physical complaints, high pain threshold and obesity. Objective: To describe the challenges in prevention, diagnosis and treatment of CV disease in PWS adults, in order to increase awareness and improve medical care. Methods: Retrospective study of medical records of adults visiting the Dutch PWS reference center. Results: We describe the challenges encountered during diagnosis and treatment of four PWS adults with heart failure. All had pre-existent peripheral edema. CV risk factors in these patients were obesity (n=4), type 2 diabetes mellitus (n=2), hypertension (n=2), hypogonadism (n=3) and sleep apnea (n=2). Remarkably, all patients were younger than 40 years during their first cardiac decompensation. All patients presented with progressive shortness of breath and/or orthopnea and progressive pitting edema. In 117 controls with PWS without CV problems, 31% had leg edema. Conclusion: Diagnosing CV problems in PWS adults is challenging. Peripheral edema is common in PWS adults without CV morbidity, which makes edema in general a poor marker for heart failure. However, when edema is of the pitting kind and progressive, this is a strong predictor of cardiac decompensation. We provide practical recommendations for diagnosing and treating CV problems in this vulnerable patient population.

Quantitative assessment of the entire right ventricle from one acoustic window: An attractive approach in patients with congenital heart disease in daily practice.

BACKGROUND: Right ventricular (RV) function is recognized as an important prognostic factor in adult congenital heart disease (ACHD). The accuracy of established parameters including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC) and tissue Doppler imaging (TDI S') is limited as only a small RV region is reflected. We previously introduced a novel four-view approach with different RV walls visualized from one apical view using electronic plane rotation, also known as iRotate. AIM: To evaluate the entire RV function using electronic plane rotation echocardiography within the spectrum of ACHD compared with healthy subjects. METHODS AND RESULTS: One hundred and forty-two ACHD patients were recruited from the outpatient clinic and 89 healthy subjects. All subjects underwent a transthoracic echocardiogram with evaluation of TAPSE, TDI S' and peak systolic longitudinal RV strain (RV-LS) from all RV walls using the four-view electronic plane rotation model. With exception of TDI S' in inferior coronal view, all parameters were lower in ACHD vs healthy subjects (p < 0.001). Within the ACHD patients, RV strain was lower in anterior (-15.9 ± 4.9) and inferior coronal view (-15.1 ± 4.5) versus lateral (-17.6 ± 5.0) and inferior wall (-17.2 ± 4.7) (p < 0.05). RV-LS values of systemic RV were lower (p < 0.05), but no difference was observed between subpulmonic RV loading conditions. CONCLUSION: The four-view electronic plane rotation model represents a reproducible, easily applicable and complete RV assessment in daily practice. RV function is significantly decreased in the ACHD group using both regional and global assessment parameters. Complete RV strain analysis reveals regional differences.

Clinical outcome of anomalous coronary artery with interarterial course in adults: Single-center experience combined with a systematic review.

BACKGROUND: Anomalous coronary artery originating from the opposite sinus of Vasalva with interarterial course (ACAOS-IAC) is associated with sudden cardiac death (SCD) in young athletes. If identified in adulthood prognosis is usually more benign, resulting in a dilemma regarding revascularization. METHODS: This is a retrospective observational single-center study, including adults with ACAOS-IAC. Medical records between 2012 and 2019 were reviewed for management approach, mortality, cardiac death and coronary related adverse events. Coronary computed tomographic angiography (CCTA) were reviewed. We provide a literature review in regard to clinical outcome. RESULTS: We identified 40 patients with ACAOS-IAC (mean age 51). Presentation was acute in 7/40 (18%). Ischemia detection with single photon emission tomography (SPECT), cardiac magnetic resonance (CMR) or dobutamine stress echocardiography were performed in 25/40 (63%) patients. Ischemia in the vascular territory of the anomaly was present in 2/25 (8%). In 39/40 (98%) patients were treated expectative. During median follow-up of 2.7 years (IQR 1.5-5.3) no cardiovascular death was observed. Mortality occurred in 1/40 (3%) and coronary related adverse events in 2/40 (5%). We identified 20 studies describing 1194 patients. Revascularization was performed in 376/1154 (32.6%) patients. Mortality stratified for clinical management was 23/431 (5.3%) in the non-revascularization versus 16/253 (6.3%) in the revascularization group during 4.0 years follow-up (weighted median). Cause of death was cardiovascular in 10/596 (1.7%) in 4.2 years (weighted median) follow up. CONCLUSIONS: Both revascularization and non-invasive management have good prognosis in adults with ACAOS-IAC during early follow up. There is need for guidelines and long-term surveillance.

Evolution of blood biomarker levels following percutaneous atrial septal defect closure in adults.

BACKGROUND: We sought to assess the effects of percutaneous atrial septal defect (ASD) closure on blood biomarker levels that possibly reflect reverse cardiac remodeling. Therefore, this study investigated temporal changes in six blood biomarkers following percutaneous ASD closure in adults. METHODS: In this prospective observational cohort study, adults with ASD type II scheduled for percutaneous closure were included (2012-2016). NT-proBNP, high-sensitive troponin-T (hs-TnT), high-sensitive C-reactive protein (hs-CRP), red blood cell distribution width (RDW), growth differentiation factor-15 (GDF-15) and galectin-3 were measured one day prior to ASD closure and one day, three months and one year post ASD closure, and changes were evaluated using paired T-tests. Echocardiographic measurements were obtained. RESULTS: Fifty patients were included (median age 50 years, 62% women, 32% NYHA II). At baseline, biomarker levels were elevated in a substantial number of patients; NT-proBNP n = 22 (45%), hs-TnT n = 6 (13%) hs-CRP n = 19 (40%), galectin-3 n = 5 (11%) and GDF n = 10 (23%). One day after ASD closure, significant increases of hs-TnT (median change (Δ) = 12 ng/L), hs-CRP (Δ = 1.9 mg/L), GDF-15(Δ = 129 pg/mL) and RDW (Δ = 0.1%) were observed, and a decrease in galectin-3 (Δ = -1.0 ng/mL). Consequently, 92% had at least one abnormal biomarker directly after closure. At three months biomarker levels returned to baseline, and while echocardiographic measures 1 year post closure were indicative of reverse cardiac remodeling, biomarker levels did not further decrease. CONCLUSION: Percutaneous ASD closure in adults leads to a direct increase in most blood biomarkers, in particular hs-CRP and hs-TnT. After three months, biomarkers returned to baseline levels and remained stable up to one year.

Prognostic value of C-reactive protein in adults with congenital heart disease.

BACKGROUND: High-sensitivity C reactive protein (hs-CRP) has been associated with outcomes in adult congenital heart disease (ACHD). However, its prognostic value beyond N-terminal pro B type natriuretic peptide (NT-proBNP) or troponin T remains unknown. We studied the temporal evolution of hs-CRP, as well as the relation between hs-CRP and adverse clinical outcomes independent of NT-proBNP and troponin T in patients with ACHD. METHODS: In this prospective cohort study, we enrolled 602 patients with ACHD (2011-2013) who underwent baseline and thereafter annual blood sampling during 4 years. Hs-CRP, hs-troponin T and NT-proBNP were measured. The primary endpoint was composed of death or heart failure (HF). Cox regression and Joint Modelling was used to relate 2log hs-CRP levels with the endpoint, with adjustment for baseline characteristics and (repeated) hs-troponin T and NT-proBNP measurements. RESULTS: Hs-CRP was measured at baseline in 591 patients, median age 33 years, 58% men, 90% New York Heart Association I with an average of 4.3 measurements per patient. Median follow-up was 5.9 (IQR 5.3-6.3) years (99.2% complete) and 69 patients met the endpoint. Higher baseline hs-CRP was independently associated with higher risk of death or HF (HR 1.36, 95% CI 1.19 to 1.55). Hs-CRP increased over time prior to death or HF, and repeated hs-CRP measurements were associated with the endpoint, independent of repeated NT-proBNP and hs-troponin T (HR 1.54, 95% CI 1.24 to 1.98). CONCLUSIONS: Hs-CRP carries incremental prognostic value for the risk of death or HF, beyond NT-proBNP and hs-troponin T. Hs-CRP increased prior to the occurrence of HF or death, supporting the role of inflammation in the clinical deterioration of patients with ACHD.

Prognostic Value of Serial High-Sensitivity Troponin T Measurements in Adults With Congenital Heart Disease.

BACKGROUND: Single high-sensitivity troponin T (hs-TnT) measurement is predictive of cardiac events in adults with congenital heart disease (ACHD). We aimed to study the prognostic value of serial hs-TnT measurements in stable patients with ACHD. METHODS: In total, 602 consecutive patients with ACHD were enrolled in this prospective study (2011-2013). Blood sampling was performed at enrollment and thereafter yearly during scheduled visits, up to 4 years. Hs-TnT, N-terminal pro B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured. The composite primary endpoint was defined as all-cause mortality, heart failure, arrhythmia, hospitalization, cardiac (re)interventions, or thromboembolic events. The relationship between changes in serial hs-TnT and the primary endpoint was studied by joint models with adjustment for repeated NT-proBNP and eGFR. RESULTS: In 601 patients (median age, 33 [interquartile range, 25-41] years, 42% women, 90% NYHA I), at least 1 hs-TnT measurement was performed; a mean of 4.3 hs-TnT measurements per patient were collected. After a median follow-up of 5.8 [interquartile range, 5.3-6.3] years, 229 (38.1%) patients reached the primary endpoint. On average, hs-TnT levels increased over time, and more in patients who reached the primary endpoint (P < 0.001). A 2-fold higher hs-TnT was associated with the primary endpoint (unadjusted hazard ratio, 1.62; 95% confidence interval, 1.44-1.82; P < 0.001). The association remained after adjustment for repeated eGFR but not when adjusted for repeated NT-proBNP; repeated NT-proBNP remained associated with the primary endpoint. CONCLUSION: In stable patients with ACHD, hs-TnT levels increased before the occurrence of an event and repeated hs-TnT was associated with the risk of adverse cardiac events. However, repeated hs-TnT was not superior to repeated NT-proBNP.