Fontan circulation and systemic disease - a retrospective cohort analysis over 35 years of follow-up: Fontan systemic disease at 35 years.

BACKGROUND: The Fontan operation provides lifesaving palliation for individuals with single ventricle (SV) physiology. Given recent concerns of systemic disease (SD) for patients with a Fontan circulation, we sought to 1) quantify the increase in SD incidence associated with the Fontan circulation; 2) identify the risk factor of SD; 3) assess the association between SD and mortality in patients with a Fontan circulation. METHODS: A matched retrospective cohort study design was adopted. From the Quebec Congenital Heart Disease (CHD) Database with up to 35 years of follow-up, patients who survived at least 30 days after the Fontan operation were identified. For each Fontan patient, patients with isolated ventricular septal defect (VSD) with the same sex and age were identified and 20 of them were randomly selected to form the control group. The presence of SD was defined as at least one hospitalization due to extra-cardiac complications including liver, respiratory, gastrointestinal or renal disease. Time-to-event analysis including Kaplan-Meier curve analysis and Cox proportional hazard models were conducted to assess the cumulative risk of SD, risk factors of SD, and the association between SD and 10-year mortality. RESULTS: A total of 533 patients with Fontan circulation were identified and matched with 10,280 VSD patients. The cumulative probabilities of SD at 10- and 35-years follow-up were 59.02% and 89.66% in patients with a Fontan circulation, 4-7 times of the probabilities in VSD patients (8.68% and 23.34%, respectively; LogRank tests p<0.0001). In Fontan patients, cardiovascular complications were associated with a 4.1-fold (95% CI: 3.52-4.88) higher risk of developing SD. Multisystem disease (>1 extra-cardiac organ affected) disease was associated with a 3.38-fold (95%CI: 1.73-6.60) increase in 10-year mortality risk when comparing to the absence of SD. CONCLUSIONS: This population-based study demonstrated that patients with a Fontan circulation had increased risk of SD, which in turn led to higher risk of mortality. These findings underscore the need for more systematic surveillance of cardiac and systemic disease for patients after Fontan operation.

Isolating the Effect of Arch Architecture on Aortic Hemodynamics Late After Coarctation Repair: A Computational Study.

Objectives: Effective management of aortic coarctation (CoA) affects long-term cardiovascular outcomes. Full appreciation of CoA hemodynamics is important. This study aimed to analyze the relationship between aortic shape and hemodynamic parameters by means of computational simulations, purposely isolating the morphological variable. Methods: Computational simulations were run in three aortic models. MRI-derived aortic geometries were generated using a statistical shape modeling methodology. Starting from n = 108 patients, the mean aortic configuration was derived in patients without CoA (n = 37, "no-CoA"), with surgically repaired CoA (n = 58, "r-CoA") and with unrepaired CoA (n = 13, "CoA"). As such, the aortic models represented average configurations for each scenario. Key hemodynamic parameters (i.e., pressure drop, aortic velocity, vorticity, wall shear stress WSS, and length and number of strong flow separations in the descending aorta) were measured in the three models at three time points (peak systole, end systole, end diastole). Results: Comparing no-CoA and CoA revealed substantial differences in all hemodynamic parameters. However, simulations revealed significant increases in vorticity at the site of CoA repair, higher WSS in the descending aorta and a 12% increase in power loss, in r-CoA compared to no-CoA, despite no clinically significant narrowing (CoA index >0.8) in the r-CoA model. Conclusions: Small alterations in aortic morphology impact on key hemodynamic indices. This may contribute to explaining phenomena such as persistent hypertension in the absence of any clinically significant narrowing. Whilst cardiovascular events in these patients may be related to hypertension, the role of arch geometry may be a contributory factor.

The use of 3D-printed models in patient communication: a scoping review.

3D models have been used as an asset in many clinical applications and a variety of disciplines, and yet the available literature studying the use of 3D models in communication is limited. This scoping review has been conducted to draw conclusions on the current evidence and learn from previous studies, using this knowledge to inform future work. Our search strategy revealed 269 papers, 19 of which were selected for final inclusion and analysis. When assessing the use of 3D models in doctor-patient communication, there is a need for larger studies and studies including a long-term follow up. Furthermore, there are forms of communication that are yet to be researched and provide a niche that may be beneficial to explore.

Case of placental insufficiency and premature delivery in a Fontan pregnancy: physiological insights and considerations on risk stratification.

OBJECTIVES: The coexistence of two complex physiologies such as Fontan and pregnancy is still not fully understood. We aim to add a unique and essential knowledge to help our colleagues in the management of Fontan patients that undergo pregnancy as well as the fetus and the placenta perfusion. METHODS AND RESULTS: We analyse the coexistence of Fontan and pregnancy physiology on a complex case of a woman with hypoplastic left heart syndrome palliated with a univentricular repair who became pregnant, delivered very prematurely and had atypical placental findings. CONCLUSION: Histopathological analysis of the placenta could help us to refine the understanding of Fontan physiology adaptation during pregnancy, predict women and fetal outcomes as well as to plan a better pre-pregnancy status. However, further evidence is needed in order to reach a more solid and unified conclusion.

Left heart matters in Ebstein's anomaly: the importance of a closer follow up-a case report.

BACKGROUND: Ebstein's anomaly (EA) is mainly thought of as a right heart condition, however, congenital left-sided lesions can co-exist. Therefore, it is paramount to include the left side of the heart as part of a routine investigation in these patients. We present a 57-year-old symptomatic patient with EA and progressive tricuspid regurgitation (TR) associated with acquired left ventricular outflow obstruction (LVOTO). CASE SUMMARY: A 57-year-old women, known to have severe EA presented with shortness of breath and chest pain on exertion secondary to progression of the tricuspid valve regurgitation and right ventricle dilatation leading to a dynamic compression of the left outflow tract requiring surgical intervention. DISCUSSION: Left ventricular obstruction secondary to severe TR and dilation of the right ventricle can present and remain silent at rest but becoming significant on exertion. Therefore, we recommend that all patients with EA and significant TR undergo exercise echocardiography at regular intervals to specifically look for acquired dynamic LVOTO.

Rapid Prototyping Flexible Aortic Models Aids Sizing of Valve Leaflets and Planning the Ozaki Repair.

Two patients with bicuspid aortic valve were selected for aortic valve repair using the Ozaki procedure. Patient-specific models of their aortic roots were generated based on computed tomography data and were 3-dimensional printed using a flexible resin. The models allowed sizing of the valve leaflets and practicing of leaflet suturing. (Level of Difficulty: Advanced.).

Feasibility of Wave Intensity Analysis in Patients With Conotruncal Anomalies Before and After Pregnancy: New Physiological Insights?

Background: Conotruncal anomalies (CTA) are associated with ongoing dilation of the aortic root, as well as increased aortic stiffness, which may relate to intrinsic properties of the aorta. Pregnancy hormones lead to hemodynamic changes and remodeling of the tunica media, resulting in the opposite effect, i.e., increasing distensibility. These changes normalize post-pregnancy in healthy women but have not been fully investigated in CTA patients. Methods: We examined aortic distensibility and ventriculo-arterial coupling before and after pregnancy using cardiovascular magnetic resonance (CMR)-derived wave intensity analysis (WIA). Pre- and post-pregnancy CMR data were retrospectively analyzed. Aortic diameters were measured before, during, and after pregnancy by cardiac ultrasound and before and after pregnancy by CMR. Phase contrast MR flow sequences were used for calculating wave speed (c) and intensity (WI). A matched analysis was performed comparing results before and after pregnancy. Results: Thirteen women (n = 5, transposition of the great arteries; n = 6, tetralogy of Fallot; n = 1, double outlet right ventricle, n = 1, truncus arteriosus) had 19 pregnancies. Median time between delivery and second CMR was 2.3 years (range: 1-6 years). The aortic diameter increased significantly after pregnancy in nine (n = 9) patients by a median of 4 ± 2.3 mm (range: 2-7.0 mm, p = 0.01). There was no difference in c pre-/post-pregnancy (p = 0.73), suggesting that increased compliance, typically observed during pregnancy, does not persist long term. A significant inverse relationship was observed between c and heart rate (HR) after pregnancy (p = 0.01, r = 0.73). There was no significant difference in cardiac output, aortic/pulmonary regurgitation, or WI peaks pre-/post-pregnancy. Conclusions: WIA is feasible in this population and could provide physiological insights in larger cohorts. Aortic distensibility and wave intensity did not change before and after pregnancy in CTA patients, despite an increase in diameter, suggesting that pregnancy did not adversely affect coupling in the long-term.

Determinants of aortic growth rate in patients with bicuspid aortic valve by cardiovascular magnetic resonance.

Objectives: This study aimed to identify determinants of aortic growth rate in bicuspid aortic valve (BAV) patients. We hypothesised that (1) BAV patients with repaired coarctation (CoA) exhibit decreased aortic growth rate, (2) moderate/severe re-coarctation (reCoA) results in increased growth rate, (3) patients with right non-coronary (RN) valve cusps fusion pattern exhibit increased aortic growth rate compared with right-left cusps fusion and type 0 valves. Methods: Starting from n=521 BAV patients with cardiovascular magnetic resonance data, we identified n=145 patients with at least two scans for aortic growth analysis. Indexed areas of the sinuses of Valsalva and ascending aorta (AAo) were calculated from cine images in end-systole and end-diastole. Patients were classified based on dilation phenotype, presence of CoA, aortic valve function and BAV morphotype. Comparisons between groups were performed. Linear regression was carried out to identify associations between risk factors and aortic growth rate. Results: Patients (39±16 years of age, 68% male) had scans 3.7±1.8 years apart; 32 presented with AAo dilation, 18 with aortic root dilation and 32 were overall dilated. Patients with repaired CoA (n=61) showed decreased aortic root growth rate compared with patients without CoA (p≤0.03) regardless of sex or age. ReCoA, aortic stenosis, regurgitation and history of hypertension were not associated with growth rate. RN fusion pattern showed the highest aortic root growth rate and type 0 the smallest (0.30 vs 0.08 cm2/m*year, end-systole, p=0.03). Conclusions: Presence of CoA and cusp fusion morphotype were associated with changes in rate of root dilation in our BAV population.

Long-Term Comparison Between Pulmonary Homograft Versus Bioprosthesis for Pulmonary Valve Replacement in Tetralogy of Fallot.

Background Tetralogy of Fallot repair results in late occurrence of pulmonary regurgitation, which requires pulmonary valve replacement in a large proportion of patients. Both homografts and bioprostheses are used for pulmonary valve replacement as uncertainty remains on which prosthesis should be considered superior. We performed a long-term imaging and clinical comparison between these 2 strategies. Methods and Results We compared echocardiographic and clinical follow-up data of 209 patients with previous tetralogy of Fallot repair who underwent pulmonary valve replacement with homograft (n=75) or bioprosthesis (n=134) between 1995 and 2018 at a tertiary hospital. The primary end point was the composite of pulmonary valve replacement reintervention and structural valve deterioration, defined as a transpulmonary pressure decrease ≥50 mm Hg or pulmonary regurgitation degree of ≥2. Mixed linear model and Cox regression model were used for comparisons. Echocardiographic follow-up duration was longer in the homograft group (8 [interquartile range, 4-12] versus 4 [interquartile range, 3-6] years; P<0.001). At the latest echocardiographic follow-up, homografts showed a significantly lower transpulmonary systolic pressure decrease (16 [interquartile range, 12-25] mm Hg) when compared with bioprostheses (28 [interquartile range, 18-41] mm Hg; mixed model P<0.001) and a similar degree of pulmonary regurgitation (degree 0-4) (1 [interquartile range, 0-2] versus 2 [interquartile range, 0-2]; mixed model P=0.19). At 9 years, freedom from structural valve deterioration and reintervention was 81.6% (95% CI, 71.5%-91.6%) versus 43.4% (95% CI, 23.6%-63.2%) in the homograft and bioprosthesis groups, respectively (adjusted hazard ratio, 0.27; 95% CI, 0.13-0.55; P<0.001). Conclusions When compared with bioprostheses, pulmonary homografts were associated lower transvalvular gradient during follow-up and were associated with a significantly lower risk of reintervention or structural valve degeneration.

Use of 3D Models in the Surgical Decision-Making Process in a Case of Double-Outlet Right Ventricle With Multiple Ventricular Septal Defects.

3D printing has recently become an affordable means of producing bespoke models and parts. This has now been extended to models produced from medical imaging, such as computed tomography (CT). Here we report the production of a selection of 3D models to compliment the available imaging data for a 12-month-old child with double-outlet right ventricle and two ventricular septal defects. The models were produced to assist with case management and surgical planning. We used both stereolithography and polyjet techniques to produce white rigid and flexible color models, respectively. The models were discussed both at the joint multidisciplinary meeting and between surgeon and cardiologist. From the blood pool model the clinicians were able to determine that the position of the coronary arteries meant an arterial switch operation was unlikely to be feasible. The soft myocardium model allowed the clinicians to assess the VSD anatomy and relationship with the aorta. The models, therefore, were of benefit in the development of the surgical plan. It was felt that the clinical situation was stable enough that an immediate intervention was not required, but the timing of any intervention would be dictated by decreasing oxygen saturation. Subsequently, the oxygen saturation of the patient did decrease and the decision was made to intervene. A further model was created to demonstrate the tricuspid apparatus. An arterial switch was ultimately performed without the LeCompte maneuver, the muscular VSD enlarged and baffled into the neo aortic root and the perimembranous VSD closed. At 1 month follow up SO2 was 100%, there was no breathlessness and no echocardiogram changes.

Third time lucky: challenging secundum atrial septal defect.

Secundum atrial septal defect is the most common form of interatrial communication. Atrial septal defects can present in young adults with a variety of clinical presentations, including breathlessness on effort, palpitations, or stroke. Clinical heart failure and resting desaturation are both rarely seen in young patients. We present a case of a young man with a secundum atrial septal defect and a diagnosis of constrictive pericarditis, only made after two attempts at surgical correction of the atrial septal defect, with pericardiectomy at the third attempt and subsequent symptomatic improvement.

Three-Dimensional Printing of Fetal Models of Congenital Heart Disease Derived From Microfocus Computed Tomography: A Case Series.

This article presents a case series of n = 21 models of fetal cardiovascular anatomies obtained from post mortem microfocus computed tomography (micro-CT) data. The case series includes a broad range of diagnoses (e.g., tetralogy of Fallot, hypoplastic left heart syndrome, dextrocardia, double outlet right ventricle, atrio-ventricular septal defect) and cases also had a range of associated extra-cardiac malformations (e.g., VACTERL syndrome, central nervous system anomalies, renal anomalies). All cases were successfully reconstructed from the microfocus computed tomography data, demonstrating the feasibility of the technique and of the protocols, including in-house printing with a desktop 3D printer (Form2, Formlabs). All models were printed in 1:1 scale as well as with the 5-fold magnification, to provide insight into the intra-cardiac structures. Possible uses of the models include education and training.

Physiological stratification in electricity-producing biofilms of Geobacter sulfurreducens.

The elucidation of mechanisms and limitations in electrode respiration by electroactive biofilms is significant for the development of rapidly emerging clean energy production and wastewater treatment technologies. In Geobacter sulfurreducens biofilms, the controlling steps in current production are thought to be the metabolic activity of cells, but still remain to be determined. By quantifying the DNA, RNA, and protein content during the long-term growth of biofilms on polarized graphite electrodes, we show in this work that current production becomes independent of DNA accumulation immediately after a maximal current is achieved. Indeed, the mean respiratory rate of biofilms rapidly decreases after this point, which indicates the progressive accumulation of cells that do not contribute to current production or contribute to a negligible extent. These results support the occurrence of physiological stratification within biofilms as a consequence of respiratory limitations imposed by limited biofilm conductivity.

Nmag_2608, an extracellular ubiquitin-like domain-containing protein from the haloalkaliphilic archaeon Natrialba magadii.

Ubiquitin-like proteins (Ubls) and ubiquitin-like domain-containing proteins (Ulds) found in both eukaryotes and prokaryotes display an ubiquitin fold. We previously characterized a 124-amino acid polypeptide (P400) from the haloalkaliphilic archaeon Natrialba magadii having structural homology with ubiquitin family proteins. The reported N. magadii's genome allowed the identification of the Nmag_2608 gene for the protein containing P400, which belongs to specific orthologs of halophilic organisms. It was found that Nmag_2608 has an N-terminal signal peptide with a lipobox motif characteristic of bacterial lipoproteins. Also, it presents partial identity with the ubiquitin-like domain-containing proteins, soluble ligand binding ß-grasp proteins. Western blots and heterologous expression tests in E. coli evidenced that Nmag_2608 is processed and secreted outside the cell, where it could perform its function. The analysis of Nmag_2608 expression in N. magadii's cells suggests a co-transcription with the adjoining Nmag_2609 gene encoding a protein of the cyclase family. Also, the transcript level decreased in cells grown in low salinity and starved. To conclude, this work reports for the first time an extracellular archaeal protein with an ubiquitin-like domain.