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Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.

Background: In dextro-transposition of the great arteries (dTGA), the aorta and the pulmonary artery are transposed. The present study aimed a three-dimensional speckle-tracking echocardiography-derived determination of volumetric and functional features of the atrium being on the morphologic right side [‘right atrium (RA)] in adult patients with dTGA. Methods: The present study comprised 18 adult dTGA patients, four of whom were excluded due to inferior image quality. From the remaining 14 patients (mean age: 29.7 ± 8.1 years, 9 males), 7 cases underwent Mustard-procedure, while another 7 subjects underwent Senning-procedure. Their results were compared to that of 28 age- and gender-matched healthy subjects (28.8 ± 1.4 years, 20 males). Results: Increased RA volumes respecting the cardiac cycle could be demonstrated in dTGA patients compared to controls. RA stroke volumes (SVs) for reservoir and conduit function were reduced together with impaired RA emptying fractions (EFs) featuring all phases of RA function. Mustard-operated patients showed tendentiously lower RA volumes and increased SVs and EFs respecting the cardiac cycle compared to those of Senning-operated patients suggesting beneficial results for Mustard-procedure. Reduced RA global and mean segmental peak RA strains and RA strains at atrial contraction could be detected in dTGA patients compared to those of controls with tendentiously lower values in Mustard-operated patients compared to those of Senning-operated subjects. Conclusions: Significant RA volumetric and functional abnormalities could be detected in adult dTGA patients following atrial switch repair. While RA volumetric data proved to be better in Mustard-operated patients, RA strains were enhanced in Senning-operated subjects.

Congenital heart defects (CHD) are the most common developmental abnormalities, affecting approximately 0.9% of livebirths. Genetic factors, including copy number variations (CNVs), play an important role in their development. The most common CNVs are found on chromosome 22q11.2. The genomic instability of this region, caused by the eight low copy repeats (LCR A-H), may result in several recurrent and/or rare microdeletions and duplications, including the most common, ∼3 Mb large LCR A-D deletion (classical 22q.11.2 deletion syndrome). We aimed to screen 22q11.2 CNVs in a large Hungarian pediatric and adult CHD cohort, regardless of the type of their CHDs. All the enrolled participants were cardiologically diagnosed with non-syndromic CHDs. A combination of multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis and droplet digital PCR methods were used to comprehensively assess the detected 22q11.2 CNVs in 212 CHD-patients. Additionally, capillary sequencing was performed to detect variants in the TBX1 gene, a cardinal gene located in 22q11.2. Pathogenic CNVs were detected in 5.2% (11/212), VUS in 0.9% and benign CNVs in 1.8% of the overall CHD cohort. In patients with tetralogy of Fallot the rate of pathogenic CNVs was 17% (5/30). Fifty-four percent of all CNVs were typical proximal deletions (LCR A-D). However, nested (LCR A-B) and central deletions (LCR C-D), proximal (LCR A-D) and distal duplications (LCR D-E, LCR D-H, LCR E-H, LCR F-H) and rare combinations of deletions and duplications were also identified. Segregation analysis detected familial occurrence in 18% (2/11) of the pathogenic variants. Based on in-depth clinical information, a detailed phenotype–genotype comparison was performed. No pathogenic variant was identified in the TBX1 gene. Our findings confirmed the previously described large phenotypic diversity in the 22q11.2 CNVs. MLPA proved to be a highly efficient genetic screening method for our CHD-cohort. Our results highlight the necessity for large-scale genetic screening of CHD-patients and the importance of early genetic diagnosis in their clinical management.

Background: In complete or dextro-transposition of the great arteries (dTGA), the aorta and the pulmonary artery are transposed. The present study was designed to examine dTGA-associated left atrial (LA) volumetric and functional abnormalities in adult patients late after repair and to compare their results to those of healthy controls. Methods: The present study consisted of 15 dTGA patients (30.3 ± 8.1 years, 9 males), the patients had Mustard (n = 8) or Senning (n = 7) procedure performed. Their results were compared to those of 36 age- and gender-matched healthy subjects (28.7 ± 1.5 years, 24 males). Results: Increased maximum LA volume and reduced LA emptying fractions respecting the cardiac cycle could be demonstrated in our dTGA patients. LA stroke volumes representing all LA functions were significantly reduced. Peak LA circumferential, longitudinal, and area strains and LA circumferential, longitudinal, and area strains measured at atrial contraction were reduced in our dTGA patients. Most LA strains were reduced in patients having Mustard surgery compared to controls and patients undergoing Senning operation. Conclusions: Significant LA volumetric and functional abnormalities could be demonstrated in adult patients with dTGA late after repair. Senning procedure seems to have more beneficial long-term effects on LA volumetric and functional features as compared to the Mustard procedure.

Abstract Background: Three-dimensional (3D) echocardiography coupled with speckle-tracking echocardiographic (STE) capability is a novel methodology which has been demontrated to be useful for the assessment of left atrial (LA) volumes and functional properties. There is increased scientific interest on myocardial deformation analysis in adult patients with corrected tetralogy of Fallot (cTOF). Objectives: To compare LA volumes, volume-based functional properties and strain parameters between cTOF patients and age- and gender-matched healthy controls. Methods: The study population consisted of 19 consecutive adult patients with cTOF in sinus rhythm nursing at the University of Szeged, Hungary (mean age: 37.9 ± 11.3 years, 8 men, who had repair at the age of 4.1 ± 2.5 years). They all had undergone standard transthoracic two-dimensional Doppler echocardiographic study extended with 3DSTE. Their results were compared to 23 age- and gender-matched healthy controls (mean age: 39.2 ± 10.6 years, 14 men). Results: Increased LA volumes and reduced LA emptying fractions respecting cardiac cycle could be demonstrated in cTOF patients compared to controls. LA stroke volumes featuring all LA functions showed no differences between the 2 groups examined. LA global and mean segmental uni- and multidirectional peak strains featuring LA reservoir function were found to be diminished in adult patients with cTOF as compared to controls. Similarly to peak strains reduced global and mean segmental LA strains at atrial contraction characterizing atrial booster pump function could be demonstrated in cTOF patients as compared to controls. Conclusions: Significant deterioration of all LA functions could be demonstrated in adult patients with cTOF late after repair.