Heart failure in congenital heart disease: management options and clinical challenges

Introduction: The population of adults with congenital heart disease (ACHD) is rapidly expanding and one of the major complications is heart failure. Timely diagnosis and treatment are crucial, but strong evidence for effectiveness of heart failure treatment in ACHD is currently lacking. Components of the medical history, physical examination and further diagnostic tests including ECG, echocardiography, cardiac magnetic resonance imaging, exercise testing, and biomarkers can identify patients at risk for early mortality or heart failure. Areas covered: Although the number of studies guiding evidence-based treatment are expanding, many clinical questions have not been completely answered yet. Therefore, in this review we provide an overview of current available insights in epidemiology, diagnosis, risk stratification and treatment options in ACHD patients, including non-medical therapies and advanced care planning. Expert Opinion: We strongly advocate expanding current use of biomarkers in the diagnostic process and timely initiation of discussing advanced treatment options and advanced care planning with patients and their loved ones. More research in multi-center collaborations is needed to study all aspects of care of adult congenital heart disease patients

The Prognostic Value of Soluble ST2 in Adults with Pulmonary Hypertension

Soluble ST2 (sST2) is upregulated in response to myocardial stress and may serve as biomarker in adults with pulmonary hypertension (PH). This prospective cohort study investigated sST2 levels and its association with echocardiographic and hemodynamic measures, and adverse clinical outcomes in adults with PH of different etiologies. sST2 was measured during the diagnostic right heart catheterization for PH, in adult patients enrolled between May 2012 and October 2016. PH due to left heart failure was excluded. The association between sST2 and a primary endpoint composed of death or lung transplantation and a secondary composite endpoint including death, lung transplantation or heart failure, was investigated using Cox regression with adjustment for NT-proBNP. In total 104 patients were included (median age was 59 years, 66% woman, 51% pulmonary arterial hypertension). Median sST2 was 28 [IQR 20–46] ng/mL. Higher sST2 was associated with worse right ventricular dysfunction and higher mean pulmonary and right atrial pressures. Median follow-up was 3.3 [IQR 2.3–4.6] years. The primary and secondary endpoint occurred in 33 (31.7%) and 43 (41.3%) patients, respectively. sST2 was significantly associated with both endpoints (HR per 2-fold higher value 1.53, 95%CI 1.12–2.07, p = 0.007 and 1.45, 95%CI 1.10–1.90, p = 0.008, respectively). However, after adjustment for NT-proBNP, both associations did not reach statistical significance. In conclusions, higher sST2 levels are associated with more severe PH and right ventricular dysfunction and yields prognostic value in adults with PH, although not independently of NT-proBNP

Prognostic value of soluble ST2 in adults with congenital heart disease

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 wi

Systolic and diastolic strain measurements show left ventricular dysfunction in women with Turner syndrome

Aim: This study aimed to describe the systolic left ventricular global longitudinal strain (LvGLS) and left ventricular peak early diastolic strain rate (Sre) in adult women with Turner syndrome (TS) and to determine its relationship with exercise capacity and clinical parameters. Methods: In this cross-sectional cohort study, consecutively included adult TS women underwent an electrocardiogram, transthoracic echocardiogram (TTE) and cardiopulmonary exercise test (CPET) on the same day. LvGLS and Sre were measured using 2D speckle tracking analysis (STE) and compared with age-matched healthy female controls. Results: Ninety-four adult women ( age 36 +/- 13 years) with TS and 32 healthy age-matched female controls were included. Women with TS had a significantly impaired/reduced systolic LvGLS (-17.82 +/- 2.98% vs. -21.80 +/- 1.85%, p 0.001), compared to healthy female controls. Furthermore, TS women had reduced diastolic function as measured by conventional echocardiographic parameters: A higher A-wave ( p < 0.001), lower E/A-ratio (p = 0.001), longer deceleration time (p = 0.006), and a higher E/E'-ratio (p < 0.001). Women with TS also had a significantly reduced maximal workload (p = 0.033), reduced oxygen uptake (p < 0.001) and a reduced maximal heart rate (p < 0.001) during exercise. Multivariable linear regression analysis revealed that Age, karyotype and QT-duration were significantly associated with Sre, but not with LvGLS, in the TS population. Conclusion: Systolic and diastolic strain and exercise capacity were significantly reduced in TS women compared to healthy women. No correlation between strain itself and exercise capacity could be demonstrated, but correlations with conventional TTE parameters and baseline characteristics were found.Cardiolog

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.Contexte : Le dosage unique de la troponine T hypersensible (hs-TnT) est predictif d ’ev enements cardiaques chez les adultes atteints de cardiopathie congenitale. Notre objectif etait d ’etudier la valeur pro- nostique du dosage seriel de la hs-TnT chez des patients adultes atteints de cardiopathie congenitale qui pr esentaient un etat stable. Methodologie : Au total, 602 patients adultes atteints de cardiopathie congenitale ont et e inscrits cons ecutivement à cette etude prospective (2011-2013). Les prelèvements sanguins ont et e effectu es au moment de l’inscription et chaque annee par la suite au cours des visites prevues, jusqu ’à la quatrième annee. La hs-TnT, le propeptide natriuretique de type B N-terminal (NT-proBNP) et le taux de filtration glomerulaire estim e (TFGe) ont et e mesur es. Le paramètre d’evaluation principal regroupait les d ecès toutes causes confondues, l’insuffisance cardiaque, l’arythmie cardiaque, les hospitalisations, les (re)interventions cardiaques et les ev enements thromboemboliques. La relation entre les variations des taux seriels de hs-TnT et le paramètre d’evaluation principal a et e etudi ee à l ’aide de modèles conjoints corriges pour tenir compte de la mesure r ep et ee du taux de NT-proBNP et du TFGe. Resultats : Chez 601 patients (âge median : 33 ans [intervalle inter- quartile : 25-41 ans], 42 % de sexe feminin, 90 % pr esentant une maladie de classe I de la NYHA), au moins un dosage de la hs-TnT a et e effectu e; les investigateurs ont effectu e, en moyenne, 4,3 dosages de la hs-TnT par patient. Au terme d’un suivi median de 5,8 ans [intervalle interquartile : 5,3-6,3 ans], le paramètre d’evaluation prin- cipal a et e atteint chez 229 (38,1 %) patients. E

Exploring the Prognostic Value of Novel Markers in Adults With a Systemic Right Ventricle

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 b

Differences in Trial and Real-world Populations in the Dutch Castration-resistant Prostate Cancer Registry

__Background:__ Trials in castration-resistant prostate cancer (CRPC) treatment have shown improved outcomes, including survival. However, as trial populations are selected, results may not be representative for the real-world population. The aim of this study was to assess the differences between patients treated in a clinical trial versus standard care during the course of CRPC in a real-world CRPC population. __Design, setting, and participants:__ Castration-resistant Prostate Cancer Registry is a population-based, observational, retrospective registry. CRPC patients from 20 hospitals in the Netherlands have been included from 2010 to 2013. __Outcome measurements and statistical analysis:__ Baseline characteristics, systemic treatment, and overall survival were the main outcomes. Descriptive statistics, multivariate Cox regression, and multiple imputations with the Monte Carlo Markov Chain method were used. __Results and limitations:__ In total, 1524 patients were enrolled of which 203 patients had participated in trials at any time. The median follow-up period was 23 mo. Patients in the trial group were significantly younger and had less comorbidities. Docetaxel treatment was more freque

Risk Stratification in Adult Congenital Heart Disease: A blood biomarker-based approach

This thesis provides novel insights in the prognostic value of blood biomarkers and what role blood biomarkers can play in the risk stratification of adults with congenital heart disease and adults with pulmonary hypertension

Prognostic value of soluble ST2 in adults with congenital heart disease

textabstractObjective 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