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Background: Identifying bicuspid aortic valve (BAV) patients at risk for cardiac events remains challenging and the role of the electrocardiogram (ECG) has not yet been described. Therefore, this study aims to describe ECG parameters in BAV patients, and investigate their prognostic value., Methods: In this single-center prospective study patients with BAV without a prior aortic valve replacement (AVR) were included. Transthoracic echocardiogram and 12‑lead resting-ECG were obtained. Associations between ECG parameters and the composite endpoint of all-cause mortality and AVR were assessed using Cox-proportional hazard analysis., Results: 120 patients with BAV were included (median age 30 years, 61% male). Median aortic jet velocity was 2.4 m/s [IQR: 1.7-3.4] and 5 patients (4%) had severe aortic regurgitation. All patients were in sinus rhythm. Any ECG abnormality was present in 57 patients (48%). Median PR-interval was 156 [IQR: 138-170] msec. A deviating QRS axis was found in 17 patients (14%) and Cornell criteria for LVH were fulfilled in 20 patients (17%). Repolarization abnormalities were present in 12 patients (10%). Median follow-up duration was 7.0 [6.3-9.8] years, during which 23 patients underwent AVR and 2 patients died. After adjusting for age, a longer PR-interval was associated with worse intervention-free survival (HR 1.02, 95% CI: 1.01-1.04)., Conclusion: Almost half of the patients with BAV had abnormalities on their ECG. Moreover, the PR-interval may be an interesting prognostic marker for intervention-free survival in BAV patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The adult congenital heart disease (ACHD) population is growing and risk prediction is important to predict adverse outcome and consult patients during their lifecourse., Objectives: This study aims to describe the long-term prognostic value of blood biomarkers in ACHD., Methods: In this prospective observational cohort study, 602 patients with moderate or complex ACHD were included (median age 32.5 years [IQR: 24.7-41.2], 42% female, 90% New York Heart Association I). N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive-troponin T, growth differentiation factor 15, high-sensitive-C-reactive protein, suppression of tumorigenicity-2 and galectin-3, as well as full blood count, renal function, LDL, and HDL were measured. Cox models were applied to relate the selected biomarkers with the primary end point of all-cause mortality and secondary end point of mortality or heart failure. Standardized HRs adjusted for relevant prognostic factors, including age, sex, and complexity of diagnosis, were reported., Results: Abnormal biomarker levels were present in 424 (70.4%) patients. During a median follow-up of 10.1 years, 41 (6.8%) patients died and 81 (13.5%) developed heart failure. Associations were observed between the primary and secondary end point and red cell distribution width, NT-proBNP, and growth differentiation factor 15. In a multibiomarker model, only NT-proBNP remained associated with mortality (HR: 2.74; 95% CI: 2.01-3.74). NT-proBNP significantly improved the C-statistic of the clinical prediction model (0.85-0.92). Based on NT-proBNP alone, low-risk patients could be identified. Patients with NT-proBNP <76 ng/L showed a 10-year heart failure-free survival of 98.5%., Conclusions: Blood biomarkers have prognostic value in ACHD. NT-proBNP improves risk prediction and is able to identify low-risk patients. Its routine use should be implemented in ACHD., Competing Interests: This study was supported by a grant from the Dutch Heart Foundation, Den Haag, the Netherlands (grant number 2015T029). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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-β). 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-β 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., (© 2023 The Authors.)

Introduction: The prognosis of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) remains dismal. Better risk prediction is needed. This study investigated the prognostic value of ECG characteristics., Methods: In this single-centre prospective study, consecutive treatment-naïve patients with PAH or CTEPH were included at time of diagnosis. From the 12-lead ECG, obtained at baseline, the following parameters were collected: heart rate (HR), rhythm, QRS axis, conduction times, P-top amplitudes in II, R-top and S-wave amplitudes in V1 and V5 and repolarisation disorders. Associations between the ECG and transplant-free survival was assessed by Kaplan-Meier curves and Cox-proportional hazard regressions., Results: In total, 140 patients were included (median age: 60.7 years, 63.6% female). The ECG was abnormal in 86.2%: sinus rhythm was not present in 9.3%, right QRS axis was observed in 47.8%, mean QRS duration was 101±17 ms. Only 42.5% of the patients had normal repolarisation, 34.5% had right ventricular strain and 14.4% non-specific repolarisation disorders. Over a median follow-up time of 3.49 (IQR: 1.37-6.42) years, 45 patients (32.5%) died or underwent lung transplantation. Transplant-free survival was worse in patients presenting with an abnormal ECG (64.0% vs 86.0%; p=0.037). The following ECG characteristics were associated with all-cause mortality or lung transplantation: heart rate (HR 1.02, 95% CI: 1.00 to 1.05), QRS duration >120 ms (HR 2.61, 95% CI: 1.01 to 6.71) and S-wave amplitude in V5 (HR 1.10, 95% CI: 1.04 to 1.17)., Conclusion: Only 13.8% of patients with PAH and CTEPH presented with a normal ECG, which is associated with favourable outcome. The ECG provides additional prognostic value to current clinical parameters and should be considered in risk prediction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 The Author(s).)

Background Adults with a systemic right ventricle (sRV) have a high risk of cardiac complications. This study aimed to identify prognostic markers in adults with sRV based on clinical evaluation, echocardiography, and blood biomarkers. Methods and Results In this prospective cohort study, consecutive clinically stable adults with sRV caused by Mustard- or congenitally corrected transposition of the great arteries were included (2011-2013). Eighty-six patients were included (age 37±9 years, 65% male, 83% New York Heart Association functional class I, 76% Mustard transposition of the great arteries, 24% congenitally corrected transposition of the great arteries). Venous blood sampling was performed including N-terminal pro B-type natriuretic peptide, high-sensitive-troponin-T, high-sensitivity C-reactive protein, growth differentiation factor-15, galectin-3, red cell distribution width, estimated glomerular filtration rate, and hemoglobin. Besides conventional echocardiographic measurements, longitudinal, circumferential, and radial strain were assessed using strain analysis. During a median follow-up of 5.9 (interquartile range 5.3-6.3) years, 19 (22%) patients died or had heart failure (primary end point) and 29 (34%) patients died or had arrhythmia (secondary end point). Univariable Cox regression analysis was performed using dichotomous or standardized continuous variables. New York Heart Association functional class >I, systolic blood pressure, and most blood biomarkers were associated with the primary and secondary end point (galectin-3 not for primary, N-terminal pro B-type natriuretic peptide and high-sensitivity C-reactive protein not for secondary end point). Growth differentiation factor-15 showed the strongest association with both end points (hazard ratios; 2.44 [95% CI 1.67-3.57, P<0.001], 2.00 [95% CI 1.46-2.73, P<0.001], respectively). End-diastolic basal dimension of the subpulmonary ventricle was associated with both end points (hazard ratio: 1.95 [95% CI 1.34-2.85], P<0.001, 1.70 [95% CI 1.21-2.38, P=0.002], respectively). Concerning strain analysis, only sRV septal strain was associated with the secondary end point (hazard ratio 0.58 [95% CI 0.39-0.86], P=0.006). Conclusions Clinical, conventional echocardiographic, and blood measurements are important markers for risk stratification in adults with a sRV. The value of novel echocardiographic strain analysis seems limited.

Objective: Soluble suppression of tumourigenicity-2 (sST2) is upregulated as response to myocardial stress and may be a potential biomarker for risk stratification in patients with adult congenital heart disease (ACHD). This study aimed to investigate the release of sST2 and its association with cardiovascular events in ACHD., Methods: In this prospective cohort study, 602 consecutive patients with ACHD visiting the outpatient clinic were included (2011-2013). The association between sST2 and a primary composite endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events or cardiac interventions was investigated using multivariable Cox regression., Results: sST2 was measured in 590 (98%) patients (median age 33 [25-41] years, 42% women). After a median follow-up of 5.8 [IQR 5.1-6.2) years, 225 (38.5%) reached the primary endpoint. sST2 was significantly associated with the primary endpoint when adjusted for age, sex, creatinine and N  terminal pro-B type brain natriuretic peptide (NT-proBNP) (HR per twofold higher sST2: 1.28, 95% CI 1.03 to 1.58, p=0.025). This association negated when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.19, 95% CI 0.96 to 1.48, p=0.106). Stratified analysis in complex ACHD did show a significant association between sST2 and the primary endpoint when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.31, 95% CI 1.01 to 1.69, p=0.043). Sex-specific analysis showed an association between sST2 and the primary endpoint in women (HR per twofold higher sST2 1.80, 95% CI 1.30 to 2.49, p<0.001) but not in men (HR per twofold higher sST2 1.19, 95% CI 0.90 to 1.56, p=0.223)., Conclusions: sST2 is a promising novel biomarker in patients with ACHD, specifically in complex ACHD and women. Future research is warranted to elucidate sex-specific and diagnosis-specific differences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Aims: To develop and validate a clinically useful risk prediction tool for patients with adult congenital heart disease (ACHD)., Methods and Results: A risk model was developed in a prospective cohort of 602 patients with moderate/complex ACHD who routinely visited the outpatient clinic of a tertiary care centre in the Netherlands (2011-2013). This model was externally validated in a retrospective cohort of 402 ACHD patients (Czech Republic, 2004-2013). The primary endpoint was the 4-year risk of death, heart failure, or arrhythmia, which occurred in 135 of 602 patients (22%). Model development was performed using multivariable logistic regression. Model performance was assessed with C-statistics and calibration plots. Of the 14 variables that were selected by an expert panel, the final prediction model included age (OR 1.02, 95%CI 1.00-1.03, p = 0.031), congenital diagnosis (OR 1.52, 95%CI 1.03-2.23, p = 0.034), NYHA class (OR 1.74, 95%CI 1.07-2.84, p = 0.026), cardiac medication (OR 2.27, 95%CI 1.56-3.31, p < 0.001), re-intervention (OR 1.41, 95%CI 0.99-2.01, p = 0.060), BMI (OR 1.03, 95%CI 0.99-1.07, p = 0.123), and NT-proBNP (OR 1.63, 95%CI 1.45-1.84, p < 0.001). Calibration-in-the-large was suboptimal, reflected by a lower observed event rate in the validation cohort (17%) than predicted (36%), likely explained by heterogeneity and different treatment strategies. The externally validated C-statistic was 0.78 (95%CI 0.72-0.83), indicating good discriminative ability., Conclusion: The proposed ACHD risk score combines six readily available clinical characteristics and NT-proBNP. This tool is easy to use and can aid in distinguishing high- and low-risk patients, which could further streamline counselling, location of care, and treatment in ACHD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate the prognostic value of six different biomarkers in patients with pulmonary hypertension (PH) and to explore whether a multi-biomarker approach can contribute to a better risk stratification., Methods: In this prospective study, patients with PH were included at the day of the diagnostic right heart catheterization between May 2012 and October 2016. Venous blood sampling included; NT-proBNP, high sensitive troponin-T, high sensitive CRP, galectin-3, red blood cell distribution width and eGFR. Associations between biomarker levels and the primary endpoint (death or lung transplantation) and secondary endpoint (death, lung transplantation or heart failure) were assessed with Cox regression, adjusted for age and sex. Additionally, adjustment for the REVEAL risk score was performed., Results: In total, 106 patients were included (median age 58.7 [IQR 47.0-69.2] years, 64% women, 51% pulmonary arterial hypertension). After a median follow-up duration of 23.9 [IQR 15.1-40.0] months, respectively 29 and 37 patients reached the primary and secondary endpoint. All six biomarkers, except eGFR, were significantly associated with the endpoints. A multi-biomarker approach including the number of elevated biomarkers per patient, demonstrated that patients were at higher risk of adverse events as more biomarker levels were elevated (HR for each extra elevated biomarker; 1.33, 95% CI 1.07-1.64, P = .01). However, a single as well as a combination of multiple biomarkers, did not yield prognostic value independent of the REVEAL risk score., Conclusions: Various biomarkers are associated with the event-free survival in adults with PH. However, risk stratification exclusively based on single or a combination of biomarkers seems not superior to existing risk scores., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Red cell distribution width (RDW) is a standard component of the automated blood count, and is of prognostic value in heart failure and coronary heart disease. We investigated the association between RDW and cardiovascular events in patients with adult congenital heart disease (ACHD)., Methods and Results: In this prospective cohort study, 602 consecutive patients with ACHD who routinely visited the outpatient clinic were enrolled between 2011 and 2013. RDW was measured in fresh venous blood samples at inclusion in 592 patients (median age 33 [IQR 25-41] years, 58% male, 90% NYHA I) and at four annual follow-up visits. During 4.3 [IQR 3.8-4.7] years of follow-up, the primary endpoint (death, heart failure, hospitalization, arrhythmia, thromboembolic events, cardiac intervention) occurred in 196 patients (33%). Median RDW was 13.4 (12.8-14.1)% versus 12.9 (12.5-13.4)% in patients with and without the primary endpoint (P < 0.001). RDW was significantly associated with the endpoint when adjusted for age, sex, clinical risk factors, CRP, and NT-proBNP (HR 1.20; 95% CI 1.06-1.35; P = 0.003). The C-index of the model including RDW was slightly, but significantly (P = 0.005) higher than the model without (0.74, 95% CI 0.70-0.78 versus 0.73, 95% CI 0.69-0.78). Analysis of repeated RDW measurements (n = 2449) did not show an increase in RDW prior to the occurrence of the endpoint., Conclusions: RDW is associated with cardiovascular events in patients with ACHD, independently of age, sex, clinical risk factors, CRP, and NT-proBNP. This readily available biomarker could therefore be considered as an additive biomarker for risk stratification in these patients., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A single NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement is a strong prognostic factor in adult congenital heart disease. This study investigates NT-proBNP profiles within patients with adult congenital heart disease and relates these to cardiovascular events., Methods and Results: In this prospective cohort, 602 patients with adult congenital heart disease were enrolled at the outpatient clinic (years 2011-2013). NT-proBNP was measured at study inclusion in 595 patients (median age 33 [IQR 25-41] years, 58% male, 90% NYHA I) and at subsequent annual visits. The primary end point was defined as death, heart failure, hospitalization, arrhythmia, thromboembolic event, or cardiac intervention; the secondary end point as death or heart failure. Repeated measurements were analyzed using linear mixed models and joint models. During a median follow-up of 4.4 [IQR 3.8-4.8] years, a total of 2424 repeated measurements were collected. Average NT-proBNP increase was 2.9 pmol/L the year before the primary end point (n=199, 34%) and 18.2 pmol/L before the secondary end point (n=58, 10%), compared with 0.3 pmol/L in patients who remained end point-free ( P -value for difference in slope 0.006 and <0.001, respectively). In patients with elevated baseline NT-proBNP (>14 pmol/L, n=315, 53%), repeated measurements were associated with the primary end point (HR per 2-fold higher value 2.08; 95% CI 1.31-3.87; P <0.001) and secondary end point (HR 2.47; 95% CI 1.13-5.70; P =0.017), when adjusted for the baseline measurement., Conclusions: NT-proBNP increased before the occurrence of events, especially in patients who died or developed heart failure. Serial NT-proBNP measurements could be of additional prognostic value in the annual follow-up of patients with adult congenitive heart disease with an elevated NT-proBNP., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: Galectin-3 is an emerging biomarker for risk stratification in patients with heart failure. This study aims to investigate the release of galectin-3 and its association with cardiovascular events in patients with adult congenital heart disease (ACHD)., Methods: In this prospective cohort study, 602 consecutive patients with ACHD who routinely visited the outpatient clinic were enrolled between 2011 and 2013. Galectin-3 was measured in thaw serum by batch analysis. The association between galectin-3 and a primary endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events and cardiac interventions was investigated using multivariable Cox models. Reference values and reproducibility were established by duplicate galectin-3 measurements in 143 healthy controls., Results: Galectin-3 was measured in 591 (98%) patients (median age 33 (25-41) years, 58% male, 90% New York Heart Association (NYHA) class I). Median galectin-3 was 12.7 (range 4.2-45.7) ng/mL and was elevated in 7% of patients. Galectin-3 positively correlated with age, cardiac medication use, NYHA class, loss of sinus rhythm, cardiac dysfunction and N-terminal pro-B-type natriuretic peptide (NT-proBNP). During a median follow-up of 4.4 (IQR 3.9-4.8) years, the primary endpoint occurred in 195 patients (33%). Galectin-3 was significantly associated with the primary endpoint in the univariable analysis (HR per twofold higher value 2.05; 95% CI 1.44 to 2.93, p<0.001). This association was negated after adjustment for NT-proBNP (HR 1.04; 95% CI 0.72 to 1.49, p=0.848)., Conclusions: Galectin-3 is significantly associated with functional capacity, cardiac function and adverse cardiovascular events in patients with ACHD. Nevertheless, the additive value of galectin-3 to a more conventional risk marker such as NT-proBNP seems to be limited., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (© 2016 American Heart Association, Inc.)

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.

Despite successful aortic coarctation (CoA) repair, systemic hypertension often recurs which may influence left ventricular (LV) function. We aimed to detect early LV dysfunction using LV global longitudinal strain (GLS) in adults with repaired CoA, and to identify associations with patient and echocardiographic characteristics. In this cross-sectional study, patients with repaired CoA and healthy controls were recruited prospectively. All subjects underwent echocardiography, ECG and blood sampling within 1 day. With speckle-tracking echocardiography, we assessed LV GLS on the apical four-, three- and two-chamber views. We included 150 subjects: 75 patients (57 % male, age 33.4 ± 12.8 years, age at repair 2.5 [IQR: 0.1-11.1] years) and 75 healthy controls of similar sex and age. LV GLS was lower in patients than in controls (-17.1 ± 2.3 vs. -20.2 ± 1.6 %, P < 0.001). Eighty percent of the patients had a normal LV ejection fraction, but GLS was still lower than in controls (P < 0.001). In patients, GLS correlated with systolic and diastolic blood pressure (r = 0.32, P = 0.009; r = 0.31, P = 0.009), QRS duration (r = 0.34, P = 0.005), left atrial dimension (r = 0.27, P = 0.029), LV mass (r = 0.30, P = 0.014) and LV ejection fraction (r = -0.48, P < 0.001). Patients with either associated cardiac lesions, multiple cardiac interventions or aortic valve replacement had lower GLS than patients without. Although the majority of adults with repaired CoA seem to have a normal systolic LV function, LV GLS was decreased. Higher blood pressure, associated cardiac lesions, and larger left atrial dimension are related with lower GLS. Therefore, LV GLS may be used as objective criterion for early detection of ventricular dysfunction.

Background: Growth-differentiation factor-15 (GDF-15), a cytokine with broad cardiac and non-cardiac activity, has diagnostic and prognostic value in various diseases, including heart failure. We aimed to investigate the release of GDF-15 in adults with congenital heart disease (ConHD), and assess the association with cardiac function and functional capacity., Methods: A total of 587 consecutive adults with ConHD (median age 33 [IQR 25-41] years, 59% men, and 90% NYHA I) underwent electrocardiography, echocardiography, venepuncture and were seen by a cardiologist. A subset of 143 patients underwent bicycle ergometry on the same day., Results: Median plasma GDF-15 was 618 [IQR 487-867] ng/L. In 87 patients (15%), GDF-15 was above the reference value of normal (1109 ng/L). GDF-15 levels were higher in older patients (r=0.367, p<0.001). GDF-15 was higher in patients with elevated pulmonary pressure (median 1114 [IQR 796-2320 ng/L) than in patients with normal pulmonary pressure (median 606 [IQR 481-826] ng/L, p<0.001). GDF-15 correlated positively with NT-proBNP (r=0.445, p<0.001). In multivariate analysis adjusting for age, sex, and NT-proBNP, hs-TnT and hs-CRP, GDF-15 above the reference value was associated with NYHA class (odds ratio for NYHA≥II: 3.5 [95% CI 1.8-6.8], p<0.001), and decreased exercise capacity (odds ratio for workload >85%:0.2 [95% CI 0.06-0.8], p=0.018), but not with systolic ventricular function or ECG rhythm., Conclusions: GDF-15 is elevated in a substantial number of patients and higher in those with elevated pulmonary pressures, regardless of underlying congenital diagnosis. GDF-15 is associated with NYHA class, NT-proBNP and exercise capacity, suggesting the marker has diagnostic and potential prognostic value in adults with ConHD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: Many patients with repaired Tetralogy of Fallot (ToF) have right ventricular (RV) volume overload due to pulmonary regurgitation (PR). We studied the effect of volume overload on global and regional RV and left ventricular (LV) deformation, and their relationships with conventional diagnostic parameters., Methods and Results: In this cross-sectional study, 94 prospectively recruited ToF patients (61% male, age 32.8 ± 9.5 years, age at repair 1.9 [0.8-5.7] years, 39% pulmonary homograft) and 85 healthy controls of similar age and sex underwent echocardiography and electrocardiography. In a subset of patients, cardiac magnetic resonance imaging, bicycle ergometry, and NT-proBNP measurement were performed within the same day. With speckle-tracking echocardiography, we analysed peak systolic global longitudinal strain (GLS), segmental longitudinal strain and strain rate of the RV free wall, LV lateral wall, and septum. Patients had a lower RV free wall strain than controls (-18.1 ± 4.5 vs. -26.5 ± 4.5%, P < 0.001), especially at the apical segment (-15.9 ± 7.4 vs. -28.2 ± 7.7%, P < 0.001), and lower RV strain rate. LV GLS was also lower (-17.4 ± 2.5 vs. -19.6 ± 1.9%, P < 0.001), mainly due to the interventricular septum. Patients with PR >25% had higher LV GLS and RV free wall strain than patients with PR ≤25% (P = 0.004, P = 0.039, respectively). No relationships were found with NT-proBNP or exercise capacity., Conclusion: RV free wall strain and strain rate are decreased in adults late after ToF repair, especially at the apical segment suggesting that apical function is most affected in these RVs. Regarding the LV, septal strain is decreased indicating that RV dysfunction adversely affects LV function, probably by mechanical coupling of the ventricles., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: Late systolic dysfunction of the systemic right ventricle (RV) in patients with transposition of the great arteries (TGA) is of major concern. Right ventricular global longitudinal strain (GLS) might be able to identify early dysfunction., Methods and Results: Adults with TGA after Mustard operation (TGA-Mustard) or congenitally corrected-TGA (ccTGA) underwent echocardiography, electrocardiography, and NT-proBNP measurement. Using speckle-tracking echocardiography, we analysed longitudinal strain and strain rate, and compared findings in both patients groups, to healthy controls and with clinical parameters. We included 42 patients (mean age 37 ± 7 years, 69% male) with a systemic RV [32 TGA-Mustard (34 ± 4 years after corrective surgery) and 10 ccTGA], and 32 healthy controls (mean age 36 ± 11 years). Global longitudinal strain of the systemic RV was lower in patients than GLS of the systemic LV in controls (-14.2 ± 3.5 vs. -20.0 ± 3.0%, P < 0.001). Average LS of the RV lateral wall was lower in patients with TGA-Mustard (-15.5 ± 3.4%) than ccTGA (-18.3 ± 3.6%, P = 0.047). Right ventricular GLS tended to be lower in patients in NYHA class II than I, and correlated with NT-proBNP (r = 0.49, P = 0.001), RV fractional area change (r = -0.39, P = 0.019), RV apex-base-diameter (r = 0.37, P = 0.021), and QRS duration (r = 0.41, P = 0.014)., Conclusion: Global longitudinal strain of the systemic RV in patients is lower than GLS of the systemic LV in healthy controls, especially in the apical segment, and tended to be lower in TGA-Mustard than ccTGA patients. Since RV GLS correlates with RV function, myocardial deformation is useful as a more quantitative tool to measure systemic RV function. Decreased GLS was associated with elevated NT-proBNP and tended to correlate with worsening NYHA class, which strengthens the potential prognostic value of GLS in patients with a systemic RV., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Adult congenital heart disease (ACHD) patients are at risk of late complications including arrhythmias, heart failure and sudden death. High-sensitive troponin-T (hs-TnT) is the standard for diagnosing acute coronary syndrome, but is also associated with cardiac function and prognosis in other cardiac diseases. We aimed to describe hs-TnT level in ACHD patients, and determine its relationship with cardiac function and other biomarkers., Methods: Consecutive ACHD patients, visiting the outpatient clinic, underwent echocardiography, exercise testing and venipuncture on the same day., Results: In total 587 patients were included (median age 33 [IQR 25-41] years, 58% male, 90% NYHA class I). hs-TnT was above the detection limit of 5 ng/L in 241 patients (41%), of whom 47 (8%) had hs-TnT levels above the 99th percentile of normal of 14 ng/L. hs-TnT levels were highest in patients with a systemic RV or pulmonary hypertension. Patients with normal or non-detectable hs-TnT were younger (32 [IQR 24-40] years) than patient with elevated hs-TnT (42 [IQR 36-60] years, p<0.001). The prevalence of hs-TnT ≥14 ng/L was higher in patients with NYHA ≥II (36%, p<0.001), systemic systolic dysfunction (38%, p<0.001), non-sinus rhythm (43%, p<0.001) and elevated pulmonary pressures (39%, p<0.001). hs-TnT was correlated with NT-proBNP (r=0.400, p<0.001)., Conclusions: hs-TnT above the 99th percentile of normal is observed in a non-trivial portion of stable ACHD patients, especially in those with a systemic RV or elevated pulmonary pressures. Since this biomarker of myocardial damage is related to NT-proBNP and ventricular function, its potential predictive value in ACHD patients seems promising and further investigation of underlying mechanisms is warranted., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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 (β=-0.074, p=0.031). This association remained significant after adjustment for age and sex (β=-0.071, p=0.038) and after adjustment for age, sex, body mass index, left ventricular function, and renal function (β=-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 (β=-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.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Amino-terminal B-type natriuretic peptide (NT-proBNP) may detect early cardiac dysfunction in adults with tetralogy of Fallot (ToF) late after corrective surgery. We aimed to determine the value of NT-proBNP in adults with ToF and establish its relationship with echocardiography and exercise capacity., Methods and Results: NT-proBNP measurement, electrocardiography and detailed 2D-echocardiography were performed on the same day in 177 consecutive adults with ToF (mean age 34.6 ± 11.8 years, 58% male, 89% NYHA I, 29.3 ± 8.5 years after surgical correction). Thirty-eight percent of the patients also underwent a cardiopulmonary-exercise test. Median NT-proBNP was 16 [IQR 6.7-33.6] pmol/L, and was elevated in 55%. NT-proBNP correlated with right ventricular (RV) dilatation (r = 0.271, p < 0.001) and RV systolic dysfunction (r = -0.195, p = 0.022), but more strongly with LV systolic dysfunction (r=-0.367, p<0.001), which was present in 69 patients (39%). Moderate or severe pulmonary regurgitation was not associated with higher NT-proBNP. Tricuspid and pulmonary regurgitation peak velocities correlated with NT-proBNP (r = 0.305, p < 0.001 and r = 0.186, p = 0.045, respectively). LV twist was measured with speckle-tracking echocardiography in 71 patients. An abnormal LV twist (20 patients, 28%) was associated with elevated NT-proBNP (p = 0.030). No relationship between NT-proBNP and exercise capacity was found., Conclusions: NT-proBNP levels are elevated in more than 50% of adults with corrected ToF, while they are in stable clinical condition. Higher NT-proBNP is most strongly associated with elevated pulmonary pressures, and with LV dysfunction rather than RV dysfunction. NT-proBNP has the potential to become routine examination in patients with ToF to monitor ventricular function and may be used for timely detection of clinical deterioration., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: Left ventricular (LV) dysfunction is a major determinant of late adverse clinical outcome in adult patients with tetralogy of Fallot (ToF). Therefore, early detection is important. Speckle-tracking echocardiography (STE) has emerged as a quantitative technique to assess LV function. The aim of this study was to evaluate LV rotation and twist with STE in adult ToF patients and their association with right ventricular (RV) and LV dimensions and function, exercise capacity, and NT-proBNP level., Methods: Eighty-two ToF patients and 56 healthy controls matched for age and gender underwent echocardiography, electrocardiography, cardiac magnetic resonance imaging (CMR), bicycle ergometry, and NT-proBNP measurement. For STE, short-axis parasternal views were obtained at the LV base and apex. We analysed LV apical and basal rotation curves and calculated LV twist., Results: Of the 82 ToF patients (55% male, age 33 ± 10 years, 98% NYHA I), 58 (71%) had normal twist, but lower than the controls [12.5 (IQR: 6.6) vs. 16.9 (IQR: 8.2) degrees, P = 0.002] mainly due to decreased apical rotation. Twenty-one (26%) patients had abnormal apical rotation which was associated with larger LV dimensions and decreased systolic biventricular function. Multivariable regression analyses showed positive relations of LV twist with biventricular systolic function measured with echocardiography as well as CMR., Conclusion: The majority of adults with corrected ToF show a reduced LV twist. Strikingly, one-quarter of these patients have an abnormal apical rotation which is associated with decreased systolic LV and RV function. These findings suggest that abnormal apical rotation is a new objective diagnostic criterion for detection of ventricular dysfunction.

Objectives: The aim of this study was to determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in adults with congenital heart disease (CHD) and investigate its relationship with ventricular function and exercise capacity., Background: NT-proBNP may detect early deterioration in cardiac function., Methods: In this cross-sectional study, extensive echocardiography, exercise testing, and NT-proBNP measurements were performed on the same day in consecutive adult patients with CHD., Results: In total, 475 patients were included in this study (mean age of 34 ± 12 years, 57% male, 90% New York Heart Association class I). The median NT-proBNP level was 15.1 pmol/l (interquartile range [IQR]: 7.1 to 31.3 pmol/l), and the NT-proBNP level was >14 pmol/l in 53% of patients. The highest NT-proBNP levels were observed in patients with Fontan circulation (36.1 pmol/l [IQR: 14.4 to 103.8 pmol/l]) and a systemic right ventricle (RV) (31.1 pmol/l [IQR: 21.8 to 56.0 pmol/l]), and the lowest values were seen in patients with aortic coarctation (7.3 pmol/l [IQR: 2.8 to 19.5 pmol/l]). NT-proBNP levels correlated with age (r = 0.39, p < 0.001) and were higher in women (median of 21.7 vs. 10.4 pmol/l; p < 0.001). In patients with aortic stenosis or aortic coarctation, NT-proBNP levels correlated with diastolic function parameters of E/E' ratio (r = 0.40, p < 0.001) and left atrial dimension (r = 0.36, p < 0.001). In patients with a systemic RV, NT-proBNP levels correlated with RV annulus diameter (r = 0.31, p = 0.024). In patients with tetralogy of Fallot, the strongest correlations were observed with left atrial dimension (r = 0.46, p < 0.001) and left ventricular ejection fraction (r = 0.37, p < 0.001). NT-proBNP levels were associated with exercise capacity (n = 198) (maximum workload: β = -0.08, p = 0.021) and peak oxygen uptake (β = -0.012, p = 0.011) in a multivariable regression model adjusted for age and sex., Conclusions: NT-proBNP levels in adults with CHD clearly differ by diagnosis and are related to echocardiographic parameters and exercise capacity. Disease-specific correlations contribute to the understanding of the main hemodynamic problems per diagnosis. Follow-up data are needed to elucidate the additional prognostic value., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Brain natriuretic peptide and N-terminal pro-brain natriuretic peptide are two well-established markers for cardiac failure in acquired heart disease. Nevertheless, the clinical utility of these markers in patients with congenital heart disease remains unclear. Therefore, the aim of this study was to evaluate the diagnostic and prognostic value of these markers in patients with congenital heart disease. A PubMed and EMBASE literature search was executed with focus on the most common simple congenital heart defects, atrial septal defect and ventricular septal defect. Data on brain natriuretic peptide measurement, cardiac function parameters, and follow-up were collected. In patients with atrial or ventricular septal defect, brain natriuretic peptide levels were mildly increased when compared with healthy age-matched controls. Shunt severity and pulmonary artery pressure correlated strongly with natriuretic peptide levels. A clear association between brain natriuretic peptide and functional class was demonstrated. After closure of the defect, a rise in brain natriuretic peptide levels in the first hours to days was observed. After longer follow-up, natriuretic peptide levels decreased and became comparable to pre-procedural values. In conclusion, this systematic review shows that brain natriuretic peptide levels are mildly increased in patients with unrepaired and repaired atrial or ventricular septal defect. Brain natriuretic peptide measurement might be a useful additional tool in the diagnostic work-up of patients with atrial or ventricular septal defect. Further investigation in a larger, prospective study with long-term follow-up is warranted to elucidate the true prognostic value of natriuretic peptides in patients with simple congenital heart disease.

Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-established markers for heart failure in the general population. However, the value of BNP as a diagnostic and prognostic marker for patients with structural congenital heart disease (CHD) is still unclear. Therefore, the purpose of this study was to evaluate the clinical utility of BNP in patients with CHD. We executed a PubMed literature search and included 49 articles that focused on complex congenital heart defects such as tetralogy of Fallot, systemic right ventricle, and univentricular hearts. Data on BNP measurements and cardiac function parameters were extracted. In all patients after correction for tetralogy of Fallot, BNP levels were elevated and correlated significantly with right ventricular end-diastolic dimensions and severity of pulmonary valve regurgitation. Patients with a systemic right ventricle had elevated BNP levels, and positive correlations between BNP and right ventricular function were seen. In patients with a univentricular heart, elevated BNP levels were observed before completion of the Fontan circulation or when patients were symptomatic; a clear association between BNP and New York Heart Association functional class was demonstrated. In conclusion, this review shows an overall increase in BNP values in complex CHD, although differences between types of congenital heart anomaly are present. As BNP values differ widely, conclusions for individual patients should be drawn with caution. Further investigation with sequential BNP measurement in a large, prospective study is warranted to elucidate the prognostic value of BNP assessment in patients with CHD., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We aim to investigate the association between different types of statins, in particular simvastatin and atorvastatin, and long-term mortality after percutaneous coronary intervention (PCI)., Methods and Results: Between 2000 and 2005, a prospective cohort was constituted of 5,647 patients who underwent PCI. Type and doses of statin use were collected after the PCI procedure. Survival status was obtained from municipal civil registries. The primary endpoint was all-cause mortality. Secondary endpoints were cardiac and cancer mortality. Median follow-up was 5.0 years (range three to nine years). During follow-up 738 patients (13.1%) died. In total, 4,970 patients (88%) were on statin therapy four weeks after PCI of whom the majority used either atorvastatin (34%) or simvastatin (29%). Cumulative survival rates at eight years in the atorvastatin group were 83%, and 79% in the simvastatin group (log-rank, p=0.004). After adjustment, statin use was associated with a 50% mortality reduction (HR 0.49, 95% CI 0.40-0.59) and atorvastatin use was associated with lower total mortality than simvastatin use (adjusted HR 0.77, 95% CI 0.61-0.97). This was largely driven by cancer mortality (adjusted HR 0.59, 95% CI 0.38-0.91)., Conclusions: In patients undergoing PCI the use of statins is associated with reduced mortality during prolonged follow-up. Patients using atorvastatin had a 23% lower mortality than those using simvastatin.

Objectives: In a single center experience, we retrospectively evaluated the short-term safety and efficacy of the TandemHeart percutaneous transseptal left ventricular assist (PTVA) system to deliver extracorporeal circulatory support during catheter based treatment of the unprotected left main coronary artery (ULMCA)., Background: Percutaneous Coronary Intervention (PCI) of the ULMCA usually has been restricted to patients who are hemodynamically unstable or ineligible for coronary artery bypass grafting (CABG). High-risk patients for CABG should be considered at increased risk for PCI as well. In these patients the TandemHeart PTVA System (p-LVAD) may provide a valuable safeguard to reduce procedural risks., Methods and Results: Between July 2002 and May 2008 the TandemHeart was used in 9 very high risk patients (Logistic Euro score: 13.64 (7.46-29.67); Syntax score:43 (41-50); Mayo Clinic Risk score (MCRS) 7 (6-8); age: median 65 (range 55-71) undergoing elective PCI for the novo lesions on the ULMCA. All patients were declined for CABG by a heart team. A ''true'' percutaneous insertion technique was used in all patients, technical success rate was 100%. The median (range) time for implementation of circulatory support was 27 min (24-30). A median (range) pump flow up to 4.36 (3.40-5.54) L/min was achieved with significant reduction of left ventricular filling pressures, pulmonary capillary wedge pressure and a small increase of systemic arterial pressures. Median (range) duration of support was 93 min (50.4-102). Successful weaning was achieved in all patients. There was no in hospital death, survival at 6 months was (89%), whereas vascular access site complications were seen in 4 patients (44.4%)., Conclusions: In very high risk PCI, assisted circulation using the TandemHeart-PTVA provides effective, total left ventricular support and may contribute to a reduced procedural risk and improved survival. The rate of device related cardiac and vascular complications was acceptable., ((c) 2009 Wiley-Liss, Inc.)