The population of patients with a systemic right ventricle (sRV) in biventricular circulation includes those who have undergone an atrial switch operation for destro-transposition of the great arteries (d-TGA) and those with congenitally corrected transposition of the great arteries (ccTGA). Despite the life expectancy of these patients is significantly increased, the long-term prognosis remains suboptimal due to late complications such as heart failure, arrhythmias, and premature death. These patients, therefore, need a close follow-up to early identify predictive factors of adverse outcomes and to implement all preventive therapeutic strategies. This review analyzes the late complications of adult patients with an sRV and TGA and clarifies which are risk factors for adverse prognosis and which are the therapeutic strategies that improve the long-term outcomes. For prognostic purposes, it is necessary to monitor sRV size and function, the tricuspid valve regurgitation, the functional class, the occurrence of syncope, the QRS duration, N-terminal pro B-type natriuretic peptide levels, and the development of arrhythmias. Furthermore, pregnancy should be discouraged in women with risk factors. Tricuspid valve replacement/repair, biventricular pacing, and implantable cardioverter defibrillator are the most important therapeutic strategies that have been shown, when used correctly, to improve long-term outcomes.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, classically characterized by right ventricular outflow tract obstruction, ventricular septal defect, overriding aorta, and right ventricular hypertrophy. Recent advances in molecular and genomic research indicate that TOF is part of a phenotypic continuum encompassing Trilogy, Tetralogy, and Pentalogy of Fallot, in which the variability of anatomical presentation reflects shared genetic and epigenetic mechanisms with highly variable penetrance and expressivity. Variants in NOTCH1, FLT4, KDR, GATA6, and TBX1 highlight key pathways in conotruncal development and endothelial–mesenchymal transition, yet these well-known genes explain only a fraction of the genetic landscape. Emerging studies have identified additional candidate genes and networks involved in cardiac morphogenesis, including transcriptional regulators, signaling mediators, chromatin-remodeling factors, and splicing-associated genes such as PUF60 and DVL3. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA expression, further modulate phenotypic expressivity and contribute to variability along the Trilogy–Tetralogy–Pentalogy spectrum. This review integrates current genomic and clinical evidence to provide a comprehensive overview of the molecular architecture of Fallot-type conotruncal malformations, emphasizing the interplay between genetic and epigenetic mechanisms, genotype–phenotype correlations, and implications for diagnosis, risk stratification, counseling, and personalized management in the era of precision cardiology.

The Venus P-Valve is a novel self-expanding prosthesis designed for transcatheter pulmonary valve implantation (TPVI) in patients with severe pulmonary regurgitation and dilated right ventricular outflow tracts. This case series assessed the incidence of subclinical leaflet thrombosis, defined as hypoattenuated leaflet thickening (HALT), and reduced leaflet motion 6 months after TPVI in 7 patients treated between January and April 2023. HALT was detected via computed tomography angiography in 71% of patients, primarily affecting the right cusp. Despite the high incidence of HALT, no significant valve dysfunctions or adverse clinical events were documented. Patients with HALT were treated with oral anticoagulation, resulting in a reduction of HALT at follow-up. These findings underscore the uncertainty regarding the short-term clinical relevance of HALT and reduced leaflet motion, emphasizing the need for individualized antithrombotic strategies. Larger studies are required to evaluate the long-term impact and optimal therapeutic approach for patients undergoing TPVI with the Venus P-Valve.