Introduction and objectives: The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the risk prediction of patients with systemic right ventricles (sRV) is not well defined. The aim of this study was to analyze the prognostic value of NT-proBNP in patients with an sRV. Methods: The prognostic value of NT-proBNP was assessed in 98 patients from the SERVE trial. We used an adjusted Cox proportional hazards model, survival analysis, and c-statistics. The composite primary outcome was the occurrence of clinically relevant arrhythmia, heart failure, or death. Correlations between baseline NT-proBNP values and biventricular volumes and function were assessed by adjusted linear regression models. Results: The median age [interquartile range] at baseline was 39 [32-48] years and 32% were women. The median NT-proBNP was 238 [137-429] ng/L. Baseline NT-proBNP concentrations were significantly higher among the 20 (20%) patients developing the combined primary outcome compared with those who did not (816 [194-1094] vs 205 [122-357]; P=.003). In patients with NT-proBNP concentrations> 75th percentile (> 429 ng/L), we found an exponential increase in the sex- and age-adjusted hazard ratio for the primary outcome. The prognostic value of NT-proBNP was comparable to right ventricular ejection fraction and peak oxygen uptake on exercise testing (c-statistic: 0.71, 0.72, and 0.71, respectively). Conclusions: In patients with sRVs, NT-proBNP concentrations correlate with sRV volumes and function and may serve as a simple tool for predicting adverse outcomes. (c) 2024 Sociedad Espanola de Cardiolog & imath;a. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Objective Residual sequelae after surgical repair of tetralogy of Fallot (rTOF) affect clinical outcome. We investigated the prognostic impact of right ventricular (RV) dyssynchrony in adults with rTOF years after the surgical repair.Methods Patients from the Swiss Adult Congenital HEart disease Registry were included. NT-proBNP levels, echocardiography, exercise testing and MRI data were collected. An offline strain analysis to quantify RV-ventricular and interventricular dyssynchrony was performed. The standard deviation of the time-to-peak shortening (TTP) of six RV segments defined the RV Dyssynchrony Index (RVDI). Maximal difference of TTP between RV and left ventricular segments defined the interventricular shortening delay (IVSD). Predictors of a composite adverse event (arrhythmias, hospitalisation for heart failure and death) were identified by multivariate Cox regression analysis. Their median values were used to create a risk score.Results Out of 285 included patients (mean age 34±14 years), 33 patients (12%) experienced an adverse event during a mean follow-up of 48±21 months. No correlation was found between RVDI, IVSD and clinical events. NT-proBNP, right atrial area and peak heart rate were independent predictors of outcomes. After 4 years-follow-up, no adverse events occurred in patients at low risk (score=0 points), while an adverse event occurred in 62% of patients at high risk (score=3 points, p<0.001).Conclusion In our cohort of adults with rTOF, surrogates of RV dyssynchrony did not correlate with outcomes. A multimodality approach was effective in predicting the risk for adverse events.

Atrial arrhythmias are an important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, the left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study aimed to investigate whether reduced LA strain is associated with SVT in ACHD patients. This retrospective, single-center cohort study collected baseline clinical and echocardiographic data of 206 ACHD patients (157 left heart defect, 49 right heart defect). Patients with sinus rhythm at baseline and a 5-year follow-up (median age 29, IQR 22–41 years) were included. Diagnosis of sustained SVT was determined from clinical reports during the follow-up period. New or recurrent sustained SVT occurred in 16 patients (7.8

Background The determinants and prognostic value of high‐sensitivity cardiac troponin T (hs‐cTnT) among patients with a systemic right ventricle are largely unknown. Methods and Results Ninety‐eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase‐5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs‐cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs‐cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all‐cause death. Median age was 39 (interquartile range, 32–48) years, and 32% were women. Median hs‐cTnT concentration was 7 (interquartile range, 4–11) ng/L. Coefficients of determination for the relationship between hs‐cTnT concentrations and right ventricular end‐systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 ( P =0.046) and −0.381 ( P =0.018), respectively. The sex‐ and age‐adjusted hazard ratio for the primary outcome of hs‐cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14–7.29) and 4.42 (95% CI, 1.21–16.15), respectively. The prognostic performance quantified by the concordance statistics for age‐ and sex‐adjusted models based on hs‐cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61–0.82), 0.72% (95% CI, 0.59–0.84), and 0.71% (95% CI, 0.59–0.83), respectively. Conclusions Hs‐cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end‐systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs‐cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03049540.

Abstract Introduction It is well known, that patients with a systemic (sub-aortic) right ventricle (sRV) for congenitally-corrected transposition of the great arteries (TGA) or with complete TGA after atrial switch operation are more threatened to develop RV dysfunction, relevant supra- and ventricular tachycardia and have a reduced life expectancy. While the randomized, placebo-controlled, double-blinded, multi-centre SERVE trial to investigate the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients showed negative results on the primary end-point RV endsystolic volume (RVESV), aim of this sub-analysis was to evaluate RV global longitudinal strain (GLS), a more sensitive measure of RV function, by cardiac magnetic resonance (CMR) feature tracking (FT) over time, for treatment effect and to investigate whether RV GLS predicts clinical outcome in sRV patients. Methods CMR volumetric RV and FT parameters were analysed (blinded for patient and assessment time and treatment) at baseline and compared to follow-up (FU) after 3 years, or after 1 year in case of withdrawal of the study drug. FT was performed using appropriate software. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of > 4th quartile of RV GLS were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure. Results CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at FU. No treatment effect of tadalafil compared to the placebo was discovered for RV GLS (p=0.26), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over a 3 years FU-time, RV GLS mildly increased (p=0.0023, figure 1). During FU, 14 patients experienced a clinical outcome: 1 death, 4 hospitalisations for heart failure, and 12 clinically relevant arrhythmic events. An RV GLS > -13.4% was associated with adverse clinical outcome (p=0.003, figure 2). Conclusion In patients with a systemic RV, treatment with Tadalafil had no effect on CMR-derived RV global longitudinal strain compared to placebo. RV GLS changed significantly over the 3 years FU-time. A RV GLS value of > -13.4% is associated with adverse clinical outcome in these patients.Figure 1Figure 2

Introducción y objetivos: El objetivo de este estudio es analizar el valor pronóstico de la fracción aminoterminal del péptido natriurético cerebral (NT-proBNP) en pacientes con ventrículo derecho sistémico (VDs).Métodos: El valor pronóstico de la NT-proBNP se evaluó en 98 pacientes del ensayo clínico SERVE. Se empleó un modelo de riesgos proporcionales de Cox ajustado, análisis de supervivencia y estadístico c. El objetivo primario compuesto fue la ocurrencia de arritmia clínicamente relevante, insuficiencia cardiaca o muerte. Como objetivos secundarios se evaluaron las correlaciones entre los valores basales de NT-proBNP y los volúmenes y la función biventriculares mediante modelos de regresión lineal ajustados.Resultados: La mediana [intervalo intercuartílico] de edad al inicio fue de 39 [32-48] años y el 32% eran mujeres. La mediana de NT-proBNP fue de 238 [137-429] ng/l. Las cifras basales de NT-proBNP fueron significativamente más altas entre los 20 pacientes (20%) que cumplían el objetivo primario combinado (816 [194-1.094] frente a 205 [122-357] ng/l; p = 0,003). En pacientes con valores de NT-proBNP superiores al percentil 75 (> 429 ng/l), se halló un aumento exponencial en la razón de riesgos ajustada por sexo y edad para el resultado primario. El valor pronóstico del NT-proBNP fue comparable al de la fracción de eyección del ventrículo derecho y al del consumo máximo de oxígeno en la prueba de esfuerzo (estadístico c, 0,71, 0,72 y 0,71 respectivamente).Conclusiones: En pacientes con VDs, los valores de NT-proBNP se correlacionan con los volúmenes y la función ventriculares y pueden ser un medio útil para la estratificación del riesgo.

Abstract Introduction Invasive studies have shown that patients with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (TGA) or complete TGA after atrial switch procedure possess impaired ventriculo-arterial coupling (VAC) parameters. The randomized, placebo-controlled, double-blinded, multi-centre SERVE trial investigated the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients on RV endsystolic volume (RVESV), with negative results. Aim of this sub-analysis was to evaluate changes of non-invasively assessed VAC parameters over time and for treatment effect. We prospectively analysed whether VAC parameters predict clinical outcome in sRV patients. Methods Volumetric RV parameters and aortic flow were assessed by cardiac magnetic resonance (CMR) and analysed (blinded for patient and assessment time and treatment) at baseline, after 3 years, or after 1 year if the study drug was withdrawed. Parameters were compared with clinical outcome at each visit. Effective arterial elastance Ea was calculated as RV endsystolic pressure (RVesp) / aortic forward flow, with RVesp defined as 0.9 x systolic blood pressure. Right ventricular endsystolic elastance Ees was calculated by RVesp / RVESV, and RV VA-coupling ratio was expressed as Ea/Ees. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of > 4th quartile were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure. Results CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at follow-up (FU). No effect of tadalafil compared to placebo was evident for effective arterial elastance Ea (p=0.35), ventricular endsystolic elastance Ees (p=0.11), VAC Ea/Ees (p=0.82), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over the 3 years FU-time, Ea (p=0.24) and RVEF (p=0.11) did not change, whereas Ees mildly decreased (p=0.0052, fig. 1 A) and Ea/Ees increased (p=0.013, fig. 1 B). During FU, 14 patients experienced a clinical event. An Ees <0.73 mmHg/ml and an Ea/Ees ratio of >1.94 were associated with adverse clinical outcomes (for both p=0.004, fig. 2). Conclusion In sRV patients, treatment with tadalafil had no effect on VAC parameters compared to placebo. CMR-derived ventricular endsystolic elastance (Ees) and Ea/Ees ratio changed over the FU of 3 years and were associated with adverse clinical outcome.Figure 1Figure 2

Introducción y objetivos: Evaluar el impacto del recambio de válvula pulmonar (RVP) en pacientes con tetralogía de Fallot reparada (TFr) en la evolución de los volúmenes y la función biventricular y en los eventos adversos.Métodos: Se identificó a los adultos con TFr del registro SACHER. Se evaluaron los datos seriados de cardiorresonancia magnética, ecocardiografía, capacidad de ejercicio y fracción aminoterminal del propéptido natriurético cerebral (NT-proBNP). El objetivo primario fue la fracción de eyección del ventrículo derecho (FEVD) medida por cardiorresonancia. Los objetivos secundarios fueron los volúmenes biventriculares, la capacidad de ejercicio, los valores de NT-proBNP y el tiempo hasta eventos adversos (arritmia auricular o ventricular, endocarditis). Se analizaron las asociaciones entre el RVP previo y las trayectorias longitudinales de los resultados funcionales y el tiempo hasta los eventos cardiacos adversos con modelos lineales de efectos mixtos y modelos de riesgos proporcionales de Cox respectivamente.Resultados: Se analizó a 308 pacientes (153 con RVP y 155 sin RVP) con 887 visitas de estudio. No se asoció de manera significativa el RVP con la trayectoria de la FEVD (CE = –1,33; IC95%, –5,87 a 3,21; p = 0,566). Se asoció el RVP previo con menor volumen telediastólico del ventrículo derecho, pero no tuvo efecto significativo en la fracción de eyección del ventrículo izquierdo, la capacidad de ejercicio o los valores de NT-proBNP. Se asoció el RVP previo con un riesgo incrementado de arritmias auriculares (HR = 2,09; IC95%, 1,17-3,72; p = 0,012) y endocarditis infecciosa (HR = 12,72; IC95%, 4,69-34,49; p < 0,0001), pero no con un riesgo aumentado de arritmias ventriculares sostenidas (HR = 0,64; IC95%, 0,18-2,27; p = 0,490).Conclusiones: El RVP previo no se asoció de manera significativa con la trayectoria de la FEVD, pero sí con un riesgo aumentado de arritmias auriculares y endocarditis infecciosa.

Background:Adults with a transposition anatomy and a systemic right ventricle (RV) face long-term complications that may impact their quality of life (QoL). Few data are available regarding the QoL in this patient group and its evolution over time. Methods:This study was performed in the SERVE trial's (identifier: NCT03049540) prospective cohort of patients (n = 100) with congenitally corrected transposition of the great arteries (TGA) or dextro-TGA after the atrial switch procedure and a longitudinal follow-up of 3 years. We aimed to describe the longitudinal QoL levels and their predictors. QoL was assessed using the Linear Analog Scale. QoL parameters were collected at baseline, after 12 months, and after 36 months, together with clinical parameters and a questionnaire assessing general self-efficacy (GSE). Results:The mean QoL on the Linear Analog Scale was 79.1 ± 13.6 at baseline, 75.5 ± 14.8 at 1 year, and 79.2 ± 13.6 at 3-year follow-up (P = 0.900). No significant differences in QoL were observed between congenitally corrected TGA or dextro-TGA patients. Cardiopulmonary exercise testing maximum work rate and maximum oxygen uptake, New York Heart Association class, end-diastolic RV volumes, N-terminal pro-B-type natriuretic peptide concentration, and GSE showed significant correlations with QoL levels. Multivariable regression analysis identified GSE value and New York Heart Association class (r 2 = 0.283, P < 0.001) as independent predictors of QoL at baseline. Conclusions:Patients with a systemic RV reported a stable good QoL during 3 years of follow-up. Exercise capacity and self-efficacy were the only independent predictors of QoL. Clinical Trial Registration:NCT03049540.

Abstract Introduction Sequelae or residual lesions after surgical repair of tetralogy of Fallot (rTOF) are inevitable and have an impact on long-term outcome. So far, most of our attention was directed to negative consequences of residual pulmonary regurgitation. Less attention has been paid to the impact of right bundle branch block and intraventricular dyssynchrony on biventricular function, exercise capacity and clinical outcome. Purpose Using the Swiss Adult Congenital HEart disease Registry we aimed to investigate the 5-year clinical course of adults with rTOF late after surgical repair. We used echocardiography strain analysis as surrogate to quantify right and left ventricular dyssynchrony and correlated our findings with routine clinical measures from cardiopulmonary exercise testing, neurohumoral blood work and cardiac magnetic resonance imaging with the aim to identify patients at increased risk for an adverse clinical event. Methods 2D speckle-tracking strain analysis of the right and left ventricle was performed with dedicated software (Tomtec, Germany). RV dyssynchrony index was measured as the standard deviation of time to peak shortening (TTP) in six RV segments. Interventricular shortening delay (IVSD) was defined as the maximal delay of TTP between ventricular segments. We constructed a multivariate model with NT-proBNP, ECG, clinical, imaging and exercise testing variables to predict the composite outcome of all-cause mortality, relevant arrhythmias and hospital admission for decompensated heart failure. Results A total of 285 patients were included. During a mean follow-up of 48±21 months, 33 patient (12 %) suffered an adverse event with a mean time to event of 30 ± 21 months after the baseline visit. RV dyssynchrony index and IVSD did not differ statistically between the groups with and without events (49±31ms vs 41±18ms, p-value 0.21, 130±65ms vs. 103±50ms, p-value 0.9). In the multivariate Cox-regression model, NT-proBNP, right atrial area and peak heart rate at exercise testing were independent predictors of outcome. An integrated risk score with the median values of these 3 variables as cut-off was highly accurate in separating patients at low risk (score 0; n=39) and high risk (score 3; n=38) for an adverse event. After 6 years of follow-up, no patient at low risk (score 0) had an adverse event, while in 62% of patients at high risk (score 3) an adverse event occurred (p<0.001). Conclusion In our cohort of rTOF patients, echocardiographic surrogates of RV dyssynchrony did not correlate with clinical events. An integrated multimodality approach proved to be effective in predicting outcomes.

BACKGROUND:Patients with a systemic right ventricle (RV) have a compromised late outcome caused by ventricular dysfunction. Standard medical heart failure therapy has not been shown to improve RV function and survival in these patients. Phosphodiesterase (PDE)-5 inhibition increases contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with a systemic RV have not been tested.METHODS:The SERVE protocol is a double-blind, randomized placebo-controlled multicenter superiority trial to study the effect of PDE-5 inhibition with Tadalafil on RV volumes and function in patients with either D-transposition of the great arteries repaired with an atrial switch procedure or with congenitally corrected transposition of the great arteries. Tadalafil 20mg or placebo will be given over a study period of 3years. The primary endpoint is the change in mean end-systolic RV volumes from baseline to study end at 3years of follow-up (or at the time of permanent discontinuation of the randomized treatment if stopped before 3- years of follow-up), and will be measured by cardiovascular magnetic resonance imaging (CMR) or by cardiac computed tomography in patients with contraindications for CMR. Secondary endpoints are changes in RV ejection fraction, VO2max and NT-proBNP.CONCLUSION:The objective of this study is to assess the effect of PDE-5 inhibition with Tadalafil on RV size and function, exercise capacity and neurohumoral activation in adults with a systemic RV over a 3-year follow-up period.

INTRODUCTION AND OBJECTIVES:Our aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. METHODS:Adults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. RESULTS:A total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, -1.33; 95%CI, -5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). CONCLUSIONS:Previous PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

A 50-year-old woman with a 2-year history of primary mediastinal large B-cell lym-phoma treated with six chemotherapy cycles EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituxi-mab) underwent follow-up thoracic computed tomography (CT).A moderately sized circumferential pericardial effusion was visualised but no lymphoma recurrence was detected.Past medical history included surgical closure of a type 2 atrial septal defect (ASD) more than 20 years ago.The patient presented herself in good general condition with no clinical signs of tamponade or heart failure.A broad laboratory workup turned out normal and the electrocardiogram showed a sinus rhythm, low QRS and voltage biphasic T waves in I, aVL and V5-V6.

Abstract Introduction Atrial arrhythmias are a common and important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study sought to investigate if LA strain is also a reliable predictor of SVT in the ACHD population. Method We retrospectively obtained baseline clinical and echocardiographic data, including LA function parameters and strain, in 206 ACHD patients. Only patients with sinus rhythm at baseline and 5-years follow-up were included (median age 29, IQR 22–41 years). 157 participants had a left heart defect (aortic stenosis or aortic coarctation, with or without correction) and 49 a right heart defect (Fallot physiology). Diagnosis of sustained SVT was determined from clinical reports during the follow-up period (standard 12-lead ECG, ECG Holter). Results During a median follow-up of 6.2 years, a new or recurrent sustained SVT occurred in 16 patients (7.8%). Patients baseline characteristics are depicted in Table 1. Patients who developed SVT were older, had larger LA dimensions and left ventricular mass, more likely diastolic dysfunction on echo, and a lower peak LA longitudinal strain (PALS). PALS was a good predictor of SVT risk in patients with left and right heart defects with an area under the receiver-operating-curve of 0.857. By Cox regression analysis, patient in the lowest quartile for PALS had a 16.7-fold higher hazard ratio of SVT (95% confidence interval, 4.7 to 59.0, p<0.001) in comparison with the top three quartiles. Overall freedom from arrhythmia after 1, 3 and 5 years of follow-up was 98.1%, 96.1% and 94.2%, respectively. The freedom from SVT as a function of PALS quartiles is shown in Figure 1. Conclusion PALS provides predictive information about the occurrence of SVT in the ACHD population, regardless of the type of the lesion. Including the measurement of LA strain in the follow-up of these patients may permit to better identify patients at risk of future atrial arrhythmias. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Universitätsklinik für Kardiologie, Inselspital Bern

By our case report, we want to bring to light the necessity of further work-up in young patients with syncope, chest pain and dyspnea.

Preprocedural planning and postprocedural evaluation after transcatheter treatment of severe tricuspid regurgitation remain challenging and require further research and standardization. We illustrate the use of multimodality imaging techniques in 3 patients undergoing implantation of a novel custom-made bicaval valved stent for symptomatic treatment of severe tricuspid regurgitation. (Level of Difficulty: Advanced.)