End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries.

BACKGROUND: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. OBJECTIVES: The authors aimed to determine factors associated with survival in a large cohort of such individuals. METHODS: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). RESULTS: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. CONCLUSIONS: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.

Cardiac MRI predictors of adverse outcomes in adults with a systemic right ventricle.

AIMS: Predicting risk in individuals with a systemic right ventricle (SRV) remains difficult. We assessed the value of cardiac MRI (CMR) for predicting death, heart transplantation (HT), or need for a ventricular assist device (VAD) in adults with D-transposition of the great arteries (DTGA) post Mustard/Senning and in adults with congenitally corrected transposition of the great arteries (ccTGA) at two large academic centres. METHODS AND RESULTS: Between December 1999 and November 2020, 158 adult patients with an SRV underwent CMR. Indexed right ventricular end-diastolic volume (RVEDVI), indexed right ventricular end-systolic volume (RVESVI), right ventricular ejection fraction (RVEF), and right ventricular mass (RV mass) were determined by a core laboratory. Receiver operating curves, area under the curve (AUC), and cut-points maximizing sensitivity and specificity for the endpoint for each CMR parameter were calculated. Over a median of 8.5 years, 21 patients (13%) met a combined endpoint of HT referral, VAD, or death. Each CMR parameter was significantly associated with the endpoint in both cohorts. The AUCs for RVEDVI, RVESVI, RVEF, and RV mass to predict the endpoint were 0.93, 0.90, 0.73, and 0.84 for DTGA and 0.76, 0.74, 0.71, and 0.74 for ccTGA, respectively. Optimized cut-points for RVEDVI were calculated for DTGA and ccTGA and were 132 and 126 mL/m2 , respectively. RVEDVI cut-points were simplified to 130 mL/m2 for survival analysis, which was significantly associated with survival in both cohorts. CONCLUSIONS: Cardiac MRI parameters are associated with an increased risk of death, HT, or VAD in patients with an SRV and should be considered to facilitate risk stratification.

Myocardial Deformation in the Systemic Right Ventricle: Strain Imaging Improves Prediction of the Failing Heart.

BACKGROUND: Predicting heart failure events in patients with a systemic right ventricle (sRV) due to transposition of the great arteries (TGA) is important for timely intensification of follow-up. This study assessed the value of strain compared with currently used parameters as predictor for heart failure-free survival in patients with sRV. METHODS: In participants of a multicentre trial, speckle-tracking echocardiography (STE) was performed to assess global longitudinal strain (GLS), mechanical dispersion (MD), and postsystolic shortening (PSS). Cox regression was used to determine the association of STE parameters with the combined end point of progression of heart failure and death, compared with cardiovascular magnetic resonance (CMR) and computed tomography (CT) derived parameters. RESULTS: Echocardiograms of 60 patients were analyzed (mean age 34 ± 11 years, 65% male, 35% congenitally corrected TGA). Mean GLS was -13.5 ± 2.9%, median MD was 49 (interquartile range [IQR] 30-76) ms, and 14 patients (23%) had PSS. During a median 8 (IQR 7-9) years, 15 patients (25%) met the end point. GLS, MD, and PSS were all associated with heart failure-free survival in univariable analysis. After correction for age, only GLS (optimal cutoff > -10.5%) and CMR/CT-derived sRV ejection fraction (optimal cutoff < 30%) remained associated with heart failure-free survival: hazard ratio (HR) 8.27, 95% confidence interval (CI) 2.50-27.41 (P < 0.001), and HR 4.34, 95% CI 1.48-12.74 (P = 0.007), respectively). Combining GLS and ejection fraction improved prediction, with patients with both GLS > -10.5% and sRV ejection fraction < 30% at highest risk (HR 19.69, 95% CI 4.90-79.13; P < 0.001). CONCLUSIONS: The predictive value of GLS was similar to that of CMR/CT-derived ejection fraction. The combination of GLS and ejection fraction identified patients at highest risk of heart failure and death. Easily available STE parameters can be used to guide follow-up intensity and can be integrated into future risk prediction scores.

Long-term clinical outcomes of valsartan in patients with a systemic right ventricle: Follow-up of a multicenter randomized controlled trial.

OBJECTIVES: In the VAL-SERVE (Valsartan in Systemic Right Ventricle) trial, three-year valsartan treatment improved systemic ventricular function only in symptomatic patients with congenitally or with an atrial switch corrected transposition of the great arteries. The aim of the current study was to investigate the longer-term clinical outcomes after valsartan treatment. METHODS: From 2006 to 2009, 88 adults were randomly allocated 1:1 to either valsartan or placebo for three consecutive years. Endpoints were defined as overall survival and freedom from clinical events (arrhythmia, heart failure, tricuspid valve surgery, death). RESULTS: Cardiac drug use and median follow-up after trial close-out (8.3 years) was similar between the randomization groups. Six patients (valsartan n = 3, placebo n = 3) died in 364 and 365 person-years (P = 0.999). No difference in the composite or separate clinical endpoints was found between the randomization groups, with corresponding long-term event-free survival rates of 50% and 34%. Nevertheless, in symptomatic patients valsartan significantly reduced the risk for events compared to placebo (HR 0.37, 95% CI 0.17-0.92). Analysis for repeated events and on-treatment analysis with any renin-angiotensin-aldosterone-system-inhibitor did not alter these results. CONCLUSIONS: Valsartan treatment in systemic RV patients did not result in improved survival at longer-term follow-up, but was associated with decreased risk of events in symptomatic patients.

Safety and effectiveness of home-based, self-selected exercise training in symptomatic adults with congenital heart disease: A prospective, randomised, controlled trial.

BACKGROUND: The purpose of this prospective randomised controlled trial was to assess whether home-based, self-selected exercise training is safe, results in high compliance and improves exercise capacity in symptomatic adults with congenital heart disease (CHD). METHODS: Forty adults with moderate or severe CHD (40 ±â€¯12 years, 56% male, New York Heart Association [NYHA] II/III 37/3) were randomly assigned, stratified by CHD complexity, either to home-based exercise training or usual care. The exercise training protocol consisted of three exercise sessions per week for six consecutive months. Patients were free to choose any sports of their preference. RESULTS: Thirty-four patients (each randomisation group n = 17) completed the protocol and were analysed. The majority was involved in high-dynamic sports (76%); none had to discontinue the training programme due to exercise-related adverse events. More than 70% adhered to the exercise programme at or above the target training level. Peak VO2 increased significantly in the exercise group by +1.7 ±â€¯2.7 ml∙kg∙min-1 (p = 0.025), whereas it remained unchanged in the control group by +0.8 ±â€¯2.2 ml∙kg∙min-1 (p = 0.184). No significant changes were found in serum N-Terminal pro-brain natriuretic peptide levels or quality of life in either randomisation group or between groups. CONCLUSIONS: In symptomatic adults with moderate or severe CHD, home-based exercise training of their preference appeared safe, with good compliance and favourable effects on exercise capacity. Our results demonstrate that it is appropriate to stimulate our patients to regularly perform moderate to vigorous physical activities, in absence of medical restrictions.

The effect of exercise training in symptomatic patients with grown-up congenital heart disease: a review.

INTRODUCTION: The number of grown-up congenital heart disease (GUCH) patients is steadily increasing. Unfortunately, the majority of these patients suffer from late sequelae, with heart failure being the most common cause of death. Exercise training is beneficial and safe in patients with acquired heart failure, as well as in asymptomatic GUCH patients. However, its effect remains unknown in symptomatic GUCH patients. This could cause reticence on positive sports advice, with possible counterproductive effects. Areas covered: A review of current literature was performed to evaluate the effect of exercise training in symptomatic (NYHA≥2) GUCH patients. The search yielded a mere three studies including symptomatic patients, and another six studies including also patients in NYHA 1 without making clear distinction between the NYHA subgroups. Expert commentary: Suboptimal trial designs, low patient numbers, and homogeneity of investigated cardiac anomalies make this review insufficient to draw definite conclusions. However, all studies describe overall positive effects of exercise training in symptomatic GUCH patients in terms of exercise capacity and quality of life. There were no safety concerns. Larger-scaled, randomized controlled trials are needed to obtain certainty.

The Changing Landscape of Pulmonary Arterial Hypertension in the Adult with Congenital Heart Disease.

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common type of pulmonary arterial hypertension (PAH) and a frequent complication of congenital heart disease (CHD). PAH-CHD represents a heterogeneous patient population and it is important to distinguish between the underlying cardiac defects considering the prognostic and therapeutic implications. Improved interventional techniques have enabled repair or palliation of most cardiac defects, though a substantial number of patients remain at high risk for PAH after closure. Traditionally, the treatment and management of PAH-CHD patients has been limited to palliative and supportive care, and based on expert opinion rather than clinical trials. Recently, however, the availability of advanced PAH-specific treatment has opened up a new field for the clinical management of this condition. Nevertheless, there is limited evidence on the optimal therapeutic approach for PAH-CHD. Herein, we discuss the current and novel therapeutic options for PAH-CHD as well as highlight several challenges in the clinical management at present.