Transposition Complexes Research Articles

AFM-based force spectroscopy unravels stepwise formation of the DNA transposition complex in the widespread Tn3 family mobile genetic elements.

Transposon Tn4430 belongs to a widespread family of bacterial transposons, the Tn3 family, which plays a prevalent role in the dissemination of antibiotic resistance among pathogens. Despite recent data on the structural architecture of the transposition complex, the molecular mechanisms underlying the replicative transposition of these elements are still poorly understood. Here, we use force-distance curve-based atomic force microscopy to probe the binding of the TnpA transposase of Tn4430 to DNA molecules containing one or two transposon ends and to extract the thermodynamic and kinetic parameters of transposition complex assembly. Comparing wild-type TnpA with previously isolated deregulated TnpA mutants supports a stepwise pathway for transposition complex formation and activation during which TnpA first binds as a dimer to a single transposon end and then undergoes a structural transition that enables it to bind the second end cooperatively and to become activated for transposition catalysis, the latter step occurring at a much faster rate for the TnpA mutants. Our study thus provides an unprecedented approach to probe the dynamic of a complex DNA processing machinery at the single-particle level.

One-stage repair of transposition complex and interrupted aortic arch in children.

A transposition complex with an interrupted aortic arch (IAA) is rare and surgically challenging because of its anatomical diversity and complexity. Herein, we aimed to present our 20-year experience with one-stage arterial switch surgery associated with IAA repair. From January 2000 to April 2017, 11 patients were diagnosed with transposition complex and IAA and underwent one-stage repair at our center. These patients were retrospectively reviewed. Two patients had transposition of the great arteries, while the others had double outlet right ventricles, of whom eight had subpulmonary ventricular septal defects (VSDs; Taussig-Bing anomalies), and one had a noncommitted VSD. In terms of the IAA, three patients underwent repair by extended end-to-end anastomosis, and one 16-mm prosthetic vascular graft was replaced in an elder patient. The remaining patients underwent autologous pericardial patch enlargement. All the variables were summarized and reported with descriptive statistics. Three early deaths occurred in this study. The median follow-up time was approximately 5 years (range: 3-14 years). No late deaths were reported. Only one patient required percutaneous re-intervention for recurrent coarctation. Moderate aortic regurgitation was observed in three patients. However, there was no requirement for aortic valvuloplasty or valve replacement. One patient had more than moderate tricuspid regurgitation. The other survivors are presently healthy. Although one-stage repair for transposition complex and IAA still has non-negligible mortality even in older children, the late outcomes of survivors are acceptable. Owing to the high rate of valve regurgitation, closer follow-up is necessary for these patients.

Invited commentary to one-stage repair of transposition complex and interrupted aortic arch in children.

The management of patients with transposition complex in combination with an interrupted aortic arch (IAA) presents a technical challenge to the surgeon to decide which is the best approach to correct both defects. This is a rare disorder and with significant variation in anatomic arrangements deciding on the ideal surgical repair. Over time, a single-stage approach to repair has become standard.

Characteristics of hospital admissions associated with implantable cardioverter defibrillator placement among adults with congenital heart disease

BackgroundCharacteristics of hospitalizations including healthcare utilization for adult patients with congenital heart disease (ACHD) at the time of implantable cardioverter defibrillator (ICD) placement has not been well studied. MethodsWe analyzed data from the 2002–2014 United States National Inpatient Sample (NIS). ICD implantation, CHD, complications, and indications for admissions were determined based on diagnostic codes among adults. Propensity score matching was performed, based on age, sex and in-hospital mortality index with a 10:1 ratio between adults without CHD and those with CHD, to determine relative healthcare utilization attributable to CHD. ResultsACHD accounted for 136,509 ± 3488 admissions of which 1451 ± 121 admissions (1.1 ± 0.06%) were associated with an ICD placement. ICD placement occurred most frequently among patients with TOF, VSD, and transposition complexes usually in the context of a dysrhythmia. Compared to those without CHD, ACHD patients had higher adjusted total hospital charges ($147,002 ± 5516 vs $132,455 ± 2182; p < 0.001), length of stay (6.2 ± 0.5 vs 5.2 ± 0.1 days; p < 0.001), lower readmission score (5.5 ± 0.5 vs 9.7 ± 0.1; p = 0.04) and a higher complication rate (13.4% vs 8.3%; p < 0.001). Dysrhythmias were more frequently the primary diagnosis for admission in the ACHD cohort (63% vs 38%; p < 0.001). ConclusionCompared to a matched non-CHD population, ACHD patients had greater healthcare utilization and had more frequent complications. The reasons underlying this difference bear investigation to improve care quality.

Applications of the Bacteriophage Mu In Vitro Transposition Reaction and Genome Manipulation via Electroporation of DNA Transposition Complexes.

The capacity of transposable elements to insert into the genomes has been harnessed during the past decades to various in vitro and in vivo applications. This chapter describes in detail the general protocols and principles applicable for the Mu in vitro transposition reaction as well as the assembly of DNA transposition complexes that can be electroporated into bacterial cells to accomplish efficient gene delivery. These techniques with their modifications potentiate various gene and genome modification applications, which are discussed briefly here, and the reader is referred to the original publications for further details.

Multi-institutional evaluation of the indications and radiation dose of functional cardiovascular computed tomography (CCT) imaging in congenital heart disease.

Ventricular volumes and ejection fraction are often used in clinical decision making in patients with congenital heart disease (CHD). The referral diagnosis, radiation exposure and image quality of functional cardiac computed tomography (CT) in a relatively large cohort of patients of CHD has not been reported. This is a retrospective evaluation of functional CT studies performed in CHD patients from three institutions (1/2007–3/2013). Patient and scanner characteristics, radiation dose estimates and image quality were compared. Two hundred ninety-eight functional CT studies were evaluated. The most common referral diagnosis were tetralogy of Fallot (33 %), transposition complexes(24 %) single ventricle heart disease (15 %), and left sided obstruction (15 %). The reason for cardiac CT was presence of pacemaker (60 %), need for detailed coronary artery imaging (18 %), metallic artifact inC MR(12 %), evaluation of prosthetic valve function (4 %), and claustrophobia or BMI too large for the available MR scanner (6 %). 266(89.3 %) scans allowed quantification of ventricular function,25 (8.4 %) scans allowed qualitative assessment of function, and 7 (2.3 %) of the scans were non-diagnostic for functional analysis. Median DLP was 399 mGy cm (186,614), and median effective dose was 5.5 mSv (2.6, 8.5).Radiation dose and image quality varied across institutions.Cardiac CT function imaging can be performed in patients with congenital heart disease when CMR is contraindicated or has poor image quality. Radiation dose and image quality varies across institutions.

Multi-institutional evaluation of the indications and radiation dose of functional cardiovascular computed tomography (CCT) imaging in congenital heart disease.

Ventricular volumes and ejection fraction are often used in clinical decision making in patients with congenital heart disease (CHD). The referral diagnosis, radiation exposure and image quality of functional cardiac computed tomography (CT) in a relatively large cohort of patients of CHD has not been reported. This is a retrospective evaluation of functional CT studies performed in CHD patients from three institutions (1/2007-3/2013). Patient and scanner characteristics, radiation dose estimates and image quality were compared. Two hundred ninety-eight functional CT studies were evaluated. The most common referral diagnosis were tetralogy of Fallot (33%), transposition complexes (24%) single ventricle heart disease (15%), and left sided obstruction (15%). The reason for cardiac CT was presence of pacemaker (60%), need for detailed coronary artery imaging (18%), metallic artifact in CMR (12%), evaluation of prosthetic valve function (4%), and claustrophobia or BMI too large for the available MR scanner (6%). 266 (89.3%) scans allowed quantification of ventricular function, 25 (8.4%) scans allowed qualitative assessment of function, and 7 (2.3%) of the scans were non-diagnostic for functional analysis. Median DLP was 399mGycm (186, 614), and median effective dose was 5.5mSv (2.6, 8.5). Radiation dose and image quality varied across institutions. Cardiac CT function imaging can be performed in patients with congenital heart disease when CMR is contraindicated or has poor image quality. Radiation dose and image quality varies across institutions.

Transposition Complex with Aortic Arch Obstruction: Outcomes of One-Stage Repair Over 10Years.

The surgical management of transposition complex with aortic arch obstruction remains technically demanding due to anatomic complexity. Even in the recent surgical era, there are centers that address this anomaly with a staged strategy. This report presents our experiences with a one-stage repair of transposition complexes with aortic arch obstructions more than the last 10 years. Since 2003, 19 patients with a transposition of the great arteries (TGA, 2 patients) or a double outlet of the right ventricle (DORV, 17 patients) and aortic arch obstruction have undergone one-stage repair of their anomalies. The mean age was 6.7 ± 2.3 days, and the mean body weight was 3.4 ± 0.3 kg. The 2 patients with TGA exhibited coarctation of the aorta. The 17 patients with DORV all exhibited the Taussig–Bing type. The great artery relationships were anteroposterior in 4 patients (21.1 %). The coronary artery anatomies were usual (1LCx; 2R) in 8 patients (42.1 %). There were 2 early deaths (10.5 %). Seven patients (36.8 %) required percutaneous interventions. One patient required re-operation for pulmonary valvar stenosis and left pulmonary artery patch angioplasty. The overall survival was 84.2 %. The freedom from mortality was 83.5 % at 5 years, and the freedom from intervention was 54.4 % at 5 years. The one-stage repair of transposition complexes with aortic arch obstructions resulted in an acceptable survival rate and a relatively high incidence of postoperative catheter interventions. Postoperative catheter interventions are highly effective. Transposition complexes combined with aortic arch obstructions can be managed by one-stage repair with good early and midterm results.

Transposons Tn10 and Tn5.

The study of the bacterial transposons Tn10 and Tn5 has provided a wealth of information regarding steps in nonreplicative DNA transposition, transpososome dynamics and structure, as well as mechanisms employed to regulate transposition. The focus of ongoing research on these transposons is mainly on host regulation and the use of the Tn10 antisense system as a platform to develop riboregulators for applications in synthetic biology. Over the past decade two new regulators of both Tn10 and Tn5 transposition have been identified, namely H-NS and Hfq proteins. These are both global regulators of gene expression in enteric bacteria with functions linked to stress-response pathways and virulence and potentially could link the Tn10 and Tn5 systems (and thus the transfer of antibiotic resistance genes) to environmental cues. Work summarized here is consistent with the H-NS protein working directly on transposition complexes to upregulate both Tn10 and Tn5 transposition. In contrast, evidence is discussed that is consistent with Hfq working at the level of transposase expression to downregulate both systems. With regard to Tn10 and synthetic biology, some recent work that incorporates the Tn10 antisense RNA into both transcriptional and translational riboswitches is summarized.

Management of adults with cyanotic congenital heart disease

### Learning objectives Great advances in medicine, in particular surgical and interventional advances, for the treatment of cyanotic congenital heart disease (CCHD) and early detection of large septal defects, have...

PO-0024 Clinical Course Features Of Newborns With Congenital Heart Defects: 15 Years’ Experience Of Our Centre

Aim A retrospective cohort study was made as well as a comparative analysis of the medical and surgery results of newborns with congenital heart defects (CHD). Materials 2440 newborns (median: 8 days [IQR:2–18 days], 3.25 kg [IQR:0,85–6,5 kg]) underwent surgical repair in the Bakoulev SCCVS between 1999 and 2013. At the time of corrective surgery 1104 (51%) patients were up to 7 days old with critical CHD (median:2,9 kg [IQR:0,85–5,1 kg]). Among them 526(48%) were 1 day old. All newborns were divided into two groups by the number of surgical repairs performed per year: group 1-up to 100 patients (1999–2004,n = 305), and group 2–more than 100 patients (2005–2013,n = 2135). The survival analysis was made according to Kaplan and Meier method (K-M). Results The CHD range was primarily represented by aortic obstructive lesions (622–25,5%), transposition complexes (488–20%), tetralogy of Fallot complexes (193–7,9%), critical pulmonary stenosis/atresia with intact septum (183–7,5%) and others. 47% undergone complete repair of CHD. The following risk factors (n = 6) for increased post-operative mortality by multivariate analysis (p = 0.0001) were identified. Progressive deteriorate on of the surgical results survival increased with number of risk factors, regardless of their combination (ROC-curve: AUS=0.8073, K-M p = 0.00001). 22 diagnostic/treatment strategies of critical neonates with CHD were developed. Over a period of study the capacity of surgery care was expanded (p.001), including complete repair CHD (42% vs 49%,p = 0.01). Morbidity of critical neonates decreased in both preoperative (21% vs 0,01% p = 0.0002) and postoperative period (K-M p = 0.000001). Actuarial survival rate was improved both for neonates undergoing palliative surgery (p = 0.0003) and complete repair (p = 0.000001).

An assay to monitor the activity of DNA transposition complexes yields a general quality control measure for transpositional recombination reactions.

Transposon-based technologies have many applications in molecular biology and can be used for gene delivery into prokaryotic and eukaryotic cells. Common transpositional activity measurement assays suitable for many types of transposons would be beneficial, as diverse transposon systems could be compared for their performance attributes. Therefore, we developed a general-purpose assay to enable and standardize the activity measurement for DNA transposition complexes (transpososomes), using phage Mu transposition as a test platform. This assay quantifies transpositional recombination efficiency and is based on an in vitro transposition reaction with a target plasmid carrying a lethal ccdB gene. If transposition targets ccdB, this gene becomes inactivated, enabling plasmid-receiving Escherichia coli cells to survive and to be scored as colonies on selection plates. The assay was validated with 3 mini-Mu transposons varying in size and differing in their marker gene constitution. Tests with different amounts of transposon DNA provided a linear response and yielded a 10-fold operational range for the assay. The colony formation capacity was linearly correlated with the competence status of the E.coli cells, enabling normalization of experimental data obtained with different batches of recipient cells. The developed assay can now be used to directly compare transpososome activities with all types of mini-Mu transposons, regardless of their aimed use. Furthermore, the assay should be directly applicable to other transposition-based systems with a functional in vitro reaction, and it provides a dependable quality control measure that previously has been lacking but is highly important for the evaluation of current and emerging transposon-based applications.

Recovery of respiratory gas exchange after exercise in adults with congenital heart disease

BackgroundDelayed gas exchange kinetics in the early recovery period after exercise testing has been reported in children and adults with congenital heart disease (ACHD). Our objective was to compare early and late phase recovery kinetics in three groups of ACHD-patients. MethodsSixty-seven adults with complex ACHD (33 repaired tetralogy of Fallot, 19 Fontan operations, and 15 transposition complexes) and 10 healthy controls underwent symptom-limited cardiopulmonary exercise testing measuring gas-exchange kinetics over a 10minute recovery period. Changes within the first minute of recovery and late changes, characterized as the time to reach 50% of peak values (T1/2), were compared between groups. ResultsRecovery of VO2 in early and late recoveries was significantly delayed in all ACHD-patients compared to controls without significant differences between patient groups. VO2-recovery at 1min compared between patients and controls was −7.2±4.0 versus −17.0±4.5ml·kg·min−1 and T1/2 VO2 was 147±62 versus 66±23s (p<0.0001 for both comparisons). Similar changes were observed for VCO2-recovery. Peak VO2 (ml·kg·min−1) demonstrated strong correlation with VO2-recovery at 1min (ml·kg·min−1, r=0.90) and moderate correlation with T1/2 VO2 (r=−0.70). ConclusionGas exchange recovery after exercise testing is prolonged in ACHD-patients, independent of the congenital heart lesion but related to peak aerobic capacity, particularly recovery kinetics within the first minute. Recovery kinetics at 1min is a useful and easily obtained clinical measure that warrants further study as a prognostic measure.

Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010.

Our objective was to obtain contemporary lifetime estimates of congenital heart disease (CHD) prevalence using population-based data sources up to year 2010. The Quebec CHD database contains 28 years of longitudinal data on all individuals with CHD from 1983 to 2010. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular hearts. We used latent class bayesian models combining case definitions from physician claims, hospitalization, and surgical data to obtain point and interval prevalence estimates of CHD in the first year of life, in children (<18 years of age) and in adults. We identified 107 559 CHD patients from 1983 to 2010. Prevalence of CHD in the first year of life was 8.21 per 1000 live births (95% confidence interval, 7.47-9.02) from 1998 to 2005. In 2010, overall prevalence of CHD was 13.11 per 1000 (95% confidence interval, 12.43-13.81) in children and 6.12 per 1000 (95% confidence interval, 5.69-6.57) in adults. CHD prevalence increased by 11% in children and 57% in adults from 2000 to 2010. Prevalence in the severe CHD subgroup increased by 19% (95% confidence interval, 17%-21%) in children and 55% (51%-62%) in adults. By 2010, adults accounted for 66% of the entire CHD population. With an increase of >50% in CHD prevalence since 2000, by 2010 adults accounted for two thirds of patients with severe and other forms of CHD in the general population. Our findings should inform allocation of resources and the planning of workforce needs for the predominantly adult CHD population.

Development of a high-efficient transformation system of Bacillus pumilus strain DX01 to facilitate gene isolation via gfp-tagged insertional mutagenesis and visualize bacterial colonization of rice roots

A Tn5 transposition vector, pMOD-tet-egfp, was constructed and used for the random insertional mutagenesis of Bacillus pumilus. Various parameters were investigated to increase the transformation efficiency B. pumilus DX01 via Tn5 transposition complexes (transposome): bacterial growth phase, type of electroporation buffer, electric field strength, and recovery medium. Transformation efficiency was up to 3 × 10(4) transformants/μg of DNA under the optimized electroporation conditions, and a total of 1,467 gfp-tagged transformants were obtained. Fluorescence-activated cell sorting analysis showed that all gfp-tagged bacterial cells expressed GFP, indicating that foreign DNA has been successfully integrated into the genome of B. pumilus and expressed. Finally, flanking DNA sequences were isolated from several transformants and colonization of rice roots by B. pumilus DX01 was also studied. The method developed here will be useful for creating an insertion mutant library of gram-positive bacteria, thus facilitating their molecular genetic and cytological studies.

Identification of basepairs within Tn5 termini that are critical sfor H-NS binding to the transpososome and regulation of Tn5 transposition

BackgroundThe H-NS protein is a global regulator of gene expression in bacteria and can also bind transposition complexes (transpososomes). In Tn5 transposition H-NS promotes transpososome assembly in vitro and disruption of the hns gene causes a modest decrease in Tn5 transposition (three- to five-fold). This is consistent with H-NS acting as a positive regulator of Tn5 transposition. Molecular determinants for H-NS binding to the Tn5 transpososome have not been determined, nor has the strength of the interaction been established. There is also uncertainty as to whether H-NS regulates Tn5 transposition in vivo through an interaction with the transposition machinery as disruption of the hns gene has pleiotropic effects on Escherichia coli, the organism used in this study.ResultsIn the current work we have further examined determinants for H-NS binding to the Tn5 transpososome through both mutational studies on Tn5 termini (or 'transposon ends') and protein-protein cross-linking analysis. We identify mutations in two different segments of the transposon ends that abrogate H-NS binding and characterize the affinity of H-NS for wild type transposon ends in the context of the transpososome. We also show that H-NS forms cross-links with the Tn5 transposase protein specifically in the transpososome, an observation consistent with the two proteins occupying overlapping binding sites in the transposon ends. Finally, we make use of the end mutations to test the idea that H-NS exerts its impact on Tn5 transposition in vivo by binding directly to the transpososome. Consistent with this possibility, we show that two different end mutations reduce the sensitivity of the Tn5 system to H-NS regulation.ConclusionsH-NS typically regulates cellular functions through its potent transcriptional repressor function. Work presented here provides support for an alternative mechanism of H-NS-based regulation, and adds to our understanding of how bacterial transposition can be regulated.

Incidence and Predictors of Sudden Cardiac Arrest in Adults With Congenital Heart Defects Repaired Before Adult Life

Many adult survivors of repaired congenital heart disease (CHD) are at premature risk of death. Sudden cardiac arrest (SCA) is 1 of the leading causes of death but little is known about determinants for SCA in adults with repaired lesions. We sought to determine incidence and risk factors for SCA in a study population of 936 adults with previously repaired CHD who had completed follow-up at a single tertiary center during a mean period of 9 ± 7 years. Mean age at first examination in our institution was 21 ± 7 years. Diagnostic categories included tetralogy of Fallot (216), coarctation of the aorta (157), transposition complexes (99), single ventricle (55), and other CHD (409). During a total follow-up of 8,387 person-years, 22 patients (2.6 per 1,000 person-years) presented with SCA. Incidence of SCA varied widely between specific lesions; the highest incidence was observed in transposition complexes (10 per 1,000 person-years). Independent predictors of SCA were retrospectively identified using multivariate Cox proportional hazard modeling. Age at initial examination and severely impaired subaortic ventricular systolic function were independent risk factors for SCA (severe subaortic ventricular systolic dysfunction, adjusted hazard ratio 29, 95% confidence interval 11 to 72, p <0.001). SCA occurred in 23% of patients with severe subaortic ventricular systolic dysfunction versus 0.7% of patients with nonsevere decreased subaortic ventricular function (p <0.001). In conclusion, severe subaortic ventricular systolic dysfunction is a dominant multivariate predictor of SCA in an unselected population of adult survivors after surgery for CHD. Our data support the consideration of primary prevention strategies in these patients.

Right ventricular outflow repair: the aortic autograft technique procures the best late results in the transposition complex☆

After treatment of transposition of the great arteries (TGA), ventricular septal defect (VSD), pulmonary stenosis, or atresia by various surgical procedures, two main problems led to reoperation: RV-PA conduit or connection stenosis and subaortic stenosis. We report here our mid- and long-term experience of a technique described in 1997 using a segment of aortic autograft as a RV-PA conduit. Between 1993 and 2005, 25 patients with TGA, VSD, PS, or atresia were corrected with a technique using an intra-ventricular rerouting with conal septum resection (as in reconstruction-endo-ventriculaire (REV)) and interposition of tubular segment of autograft aorta between RV and PA without Lecompte maneuver (as in Rastelli), using in some cases an additional monocusp patch. The patient's age at correction ranged from 2.5 months to 11 years (mean 2.2 years); seven patients were under 1 year and 13 had a previous shunt procedure. Patients were regularly followed by two-dimensional (2D) annual echocardiogram, occasionally by catheterization and more recently by MNR. There was one postoperative death essentially due to RV failure. There was one late death after 15 years. There were 23 long-term survivors with a mean follow-up of 12.8 years. All patients were in class I category and all of them were in sinus rhythm. Three of them needed a reoperation at 4, 5, and 6 years for subaortic stenosis and one of them with abnormal chordae in the left ventricle (LV) outflow, Only one patient needed a reoperation for RV-PA stenosis, 13 years after correction done at age 2.5 months, the autograft tissue not being implied and found normal at histology. Mean RV pressure by echo at last follow-up was 41 mm Hg. Ten patients exhibit a mild-to-moderate pulmonary regurgitation. Freedom from reoperation for RV-PA obstruction is 90% at 10 and 15 years. Compared with all other techniques (Rastelli, REV, and Nikaidoh) our autograft technique provides the best-reported outcome for RV-PA outflow freedom from reoperation, the aortic segment employed being a living tissue susceptible to growth. However, it remains most often a long-term valveless procedure and does not avoid occasional unexpected LV-AO stenosis.

In Vitro Recombination and Inverted Terminal Repeat Binding Activities of the Mcmar1 Transposase

The Mcmar1 mariner element (MLE) presents some intriguing features with two large, perfectly conserved, 355 bp inverted terminal repeats (ITRs) containing two 28 bp direct repeats (DRs). The presence of a complete ORF in Mcmar1 makes it possible to explore the transposition of this unusual MLE. Mcmar1 transposase (MCMAR1) was purified, and in vitro transposition assays showed that it is able to promote ITR-dependent DNA cleavages and recombination events, which correspond to plasmid fusions and transpositions with imprecise ends. Further analyses indicated that MCMAR1 is able to interact with the 355 bp ITR through two DRs: the EDR (external DR) is a high-affinity binding site for MCMAR1, whereas the IDR (internal DR) is a low-affinity binding site. The main complex detected within the EDR contained a transposase dimer and only one DNA molecule. We hypothesize that the inability of MCMAR1 to promote precise in vitro transposition events could be due to mutations in its ORF sequence or to the specific features of transposase binding to the ITR. Indeed, the ITR region spanning from EDR to IDR resembles a MITE and could be bent by specific host factors. This suggests that the assembly of the transposition complex is more complex than that of those involved in the mobility of the Mos1 and Himar1 mariner elements.

The Right Heart in Adults With Congenital Heart Disease

Right ventricular dysfunction is not uncommon in adults with congenital heart disease. In congenital heart disease, unlike acquired heart disease, the right ventricle is not always the subpulmonary ventricle: it may support the systemic circulation as it does in patients with transposition complexes. The result is chronic right ventricular pressure overload. In contrast, pulmonary valve regurgitation -a frequent problem after surgical repair of the tetralogy of Fallot- imposes a volume overload on the right ventricle. Over time, both conditions may lead to right ventricular dysfunction and often this becomes a major clinical concern. Clearly, a thorough understanding of right ventricular anatomy and physiology is a necessity for those caring for patients with congenital heart disease. This article provides an overview of right ventricular morphology and the adverse effects of right ventricular dysfunction in adults with congenital heart disease.