Juan Calderón-Colmenero

Background: Fontan-associated liver disease (FALD) develops as a consequence of chronic systemic venous congestion, which alters hepatic hemodynamics and promotes sinusoidal congestion, inflammation, and fibrosis. Our objective was to evaluate liver changes using magnetic resonance imaging (MRI) in patients with a Fontan circuit. Methods: We conducted a retrospective study including patients who underwent the Fontan procedure between January 2005 and December 2019 and were evaluated using T1, T2 and apparent diffusion coefficient mapping. Patients were classified into two groups: none-to-mild FALD (≤5 points) and moderate-to-severe FALD (≥6 points). FALD severity was characterized, and logistic regression analysis was performed to evaluate the association between the variables of interest and the outcome. The discriminative performance of quantitative MRI parameters was also assessed using ROC curves. Results: Thirty-nine patients were included, with a median age at surgery of 9.3 years (IQR 5.9–10.8); 61.5% (n = 24) were female. The most frequent diagnosis was tricuspid atresia (51.3%, n = 20), and the Fontan procedures were mainly performed using an extracardiac conduit (97.4%, n = 38). No factors were significantly associated with moderate-to-severe FALD. T1 mapping of segment I demonstrated the highest discriminative performance (AUC = 0.771; 95% CI: 0.500–1.000), with a cutoff value of >734 ms, yielding a sensitivity of 83.3% (95% CI: 43.65–99.15) and a specificity of 75% (95% CI: 57.89–86.75). Conclusions: After 10 years of follow-up, 15% had moderate-to-severe FALD. T1 mapping of segment I demonstrated the highest discriminative performance, with a sensitivity greater than 80% for identifying moderate-to-severe FALD.

Congenital Heart Diseases (CHDs) are a heterogeneous group of structural abnormalities affecting the heart and major arteries, which are present in at least 1% of births worldwide. Studies have linked CHD to both genetic and environmental factors. In this regard, it has been demonstrated that changes in the epigenetic pattern impact the expression of key genes involved in proper cardiac development. Therefore, it is suggested that aberrant epigenetic mechanisms may contribute to the development of these pathologies. Here, we review and summarize the main epigenetic mechanisms involved in CHD. Moreover, cardiac development and the importance of the environment and CHD are also addressed.

Background: Fontan circulation maintains an elevated venous pressure; this promotes venous and lymphatic congestion and may lead to late circuit failure. Our objective was to determine the association between thoracic lymphatic perfusion patterns assessed by magnetic resonance imaging and late Fontan failure. Methodology: A retrospective study was performed. We included patients who underwent the Fontan procedure between January 2005 and December 2019 and who were evaluated with lymphatic mapping using magnetic resonance imaging. Lymphatic abnormalities were classified into four types. The prevalence of late failure was determined, and logistic regression analysis was performed to establish the association between the variables of interest and the outcome. Results: Fifty-four patients were included with a mean age at surgery of 8.8 years ± 3.5 years; 42.6% (n = 23) were men. The most frequent diagnosis was tricuspid atresia (50%, n = 27), and the Fontan procedures were mainly performed using an extracardiac conduit (96.3%, n = 52). The prevalence of late Fontan failure was 35.2%. The lymphatic perfusion patterns observed were Type 1 in 25.9% (n = 14), Type 2 in 46.3% (n = 25), Type 3 in 25.9% (n = 14), and Type 4 in 1.8% (n = 1), with no differences in relation to late failure. (p = 0.42). The age at surgery was found to be a factor associated with the late Fontan failure (OR: 1.23; 95% CI: 1.02–1.48; p = 0.02). Conclusions: One-third of patients with Fontan circulation may experience late failure, not significantly associated with lymphatic changes, but when the total cavopulmonary connection is completed at an older age.

Congenital heart diseases (CHDs) are a group of complex diseases characterized by structural and functional malformations during development in the human heart; they represent an important problem for public health worldwide. Within these malformations, septal defects such as ventricular (VSD) and atrial septal defects (ASD) are the most common forms of CHDs. Studies have reported that CHDs are the result of genetic and environmental factors. Here, we review and summarize the role of genetics involved in cardiogenesis and congenital cardiac septal defects. Moreover, treatment regarding these congenital cardiac septal defects is also addressed.

Background: Down syndrome is the most common chromosomal abnormality, it is associated with a wide variety of congenital heart defects, being considered as clinical elements of high infant morbidity and mortality. Objective: To describe the clinical outcomes of patients with Down syndrome undergoing surgery and interventionism as treatment for congenital heart disease at this Institution. Material and methods: 368 patients with Down syndrome and associated congenital heart disease were diagnosed. The variables studied were weight, stature, sex, age, type of heart disease, corrective procedure, length of stay in the hospital and intensive care unit, morbidity and mortality. Results: 368 pediatric patients underwent surgical or interventional correction. Of which 197 (54%) were female, the median age was 24 months (interquartile range [IQR]: 14-48) in the surgical group and 36 months (IQR: 17-85) in the interventional group. The most frequent congenital heart diseases were: PCA (31%), IVC (28%), CAV (20%), ASD (16%) and tetralogy of Fallot with 4% respectively. Hospital stay was 9 days (IQR: 7-15) in the surgical group and 3 days (IQR: 2-5) in the hemodynamic group. Morbidities were postoperative infection in 30 patients (14%) and complete atrioventricular block in 19 patients (9%). Overall mortality including both surgical and interventional was 2%. Conclusions: The therapeutic, surgical and interventional results in children with Down syndrome and congenital heart disease have improved very satisfactorily. The lower prevalence of the atrioventricular canal in the Mexican population is noteworthy. It is essential to carry out a cardiological evaluation of children with Down syndrome and those with congenital heart disease to correct them in a timely manner to promote survival and quality of life.

Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2–9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock–Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Right atrial isomerism (RAI) is a complex entity whose treatment and outcome are heterogeneous. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted; it included patients diagnosed with RAI who underwent cardiac surgery; their follow-up was from January 1, 2010 to March 31, 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients with RAI were included, the median age was 4 years (IQR 2-9.2), and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock‐Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). The use of inhaled nitric oxide was a marker of postoperative mortality in critically ill patients (OR: 10.33; 95% CI: 1.04 - 102.08; p = 0.02). The overall survival was 86.8%, with a better outcome in those who did not require reintubation (Log Rank, p < 0.01). The survival of RAI was similar to other centers of reference. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

This chapter aimed to determine whether a correlation exists between S100B serum levels and clinical background variables at the pre-operative period of pediatric patients with congenital heart disease. S100B is a calcium-binding protein, belonging to the S100 family proteins which are characterized by their high solubility and, currently, comprises 21 members which are expressed in a cell-specific manner. S100B protein has been proposed as a brain injury biomarker in several clinical scenarios. We designed a prospective case-control study that included all pediatric patients (one month to 18 years old), with congenital heart disease, admitted at our institution for surgical treatment, in a 3 month period of time. We studied 44 patients at the pre-operative period and divided them in two groups: 20 with clinical neurological background and 24 without them. Clinical pediatric neurological background variables were obtained, and serum levels of S100B protein were measured using the ELISA “sandwich” technique. The cut-off for S100B serum level in patients with clinical neurological background variables was 16 pg/ml, with sensibility and specificity values of 70% and 70.8%, respectively. S100B protein levels greater than 16 pg/ ml correlated with clinical neurological background variables (p=0.014, OR=2.556, and 95% CI=1.205 - 5.418). Neurological clinical background variables before operation may modify operative resilience and the risk of neurological complications. S100B protein appears to be the potential biomarker that we are looking for establishing neurological morbidity risk at the preoperative period of surgery for congenital heart disease, due its correlation with clinical neurological background, as shown in this study. Despite the need of more evidences, our results support a strong trend to consider S100B protein as a potential biomarker of clinical neurological background in pediatric patients with congenital heart disease at the pre-operative period, because its serum levels > 16pg/ml may predict neurological damage at a reliably and costless way before surgery, allowing the clinicians for a more accurate neurological support postoperatively in order to improve results.

The TBX20 gene has a key role during cardiogenesis, and it has been related to epigenetic mechanisms in congenital heart disease (CHD). The purpose of this study was to assess the association between DNA methylation status and congenital septal defects. The DNA methylation of seven CpG sites in the TBX20 gene promoter was analyzed through pyrosequencing as a quantitative method in 48 patients with congenital septal defects and 104 individuals with patent ductus arteriosus (PDA). The average methylation was higher in patients than in PDA (p < 0.001). High methylation levels were associated with a higher risk of congenital septal defects (OR = 4.59, 95% CI = 1.57–13.44, p = 0.005). The ROC curve analysis indicated that methylation of the TBX20 gene could be considered a risk marker for congenital septal defects (AUC = 0.682; 95% CI = 0.58–0.77; p < 0.001). The analysis of environmental risk factors in patients with septal defects and PDA showed an association between the consumption of vitamins (OR = 0.10; 95% CI = 0.01–0.98; p = 0.048) and maternal infections (OR = 3.10; 95% CI = 1.26–7.60; p = 0.013). These results suggest that differences in DNA methylation of the TBX20 gene can be associated with septal defects.

Background: Heart failure in the adult with adult congenital heart disease (ACHD) is a current topic due to its association with high morbidity and mortality and has been implicated as the leading cause of death in these kinds of patients. Purpose: This study reports experience of patients with ACHD and Acute Heart Failure (AHF) hospitalized at a teaching center specialized in cardiovascular disease in Latin America. Methods: A retrospective cohort study of patients with AHF who were hospitalized in the coronary care unit of a Latin-American teaching hospital from January 2006 to December 2018. Patients with ACHD were identified and their clinical characteristics and in-hospital evolution were analyzed. Results: During the study period, of 7,759 patients admitted with AHF, 181 (2.3%) had ACHD. Their median age was 34 years and 53.6% were men. Patients were grouped as follows: (Group I) left to right shunt 51.4%, (Group II) left ventricular outflow tract obstruction 17.7%, (Group III) outflow tract obstruction of the right ventricle 7.2%, (Group IV) conotronchal anomalies 3.9% and (Group V) miscellaneous group 19.9%. In general, history of previous surgery was in 28.2%, the frequency was higher in Group I and Group III (38.5% and 31.3%, respectively). Overall, all-cause in-hospital mortality was higher among patients with AHF- ACHD compared with patients without ACHD with AHF (23.2% vs. 17.8%; p=0.05). Unadjusted in-hospital mortality was not significant different across the five groups (21.5%, 28.1%, 7.7%, 42.9% and 25.0% for Group I, Group II, Group III, Group IV and Group V, respectively; p=0.41) (Figure 1). Conclusions: Adult patients with congenital heart disease and acute heart failure are a challenge in clinical and surgical management that entails a high in-hospital mortality. A high percentage of these patients are candidates for surgical treatment. Funding Acknowledgement: Type of funding sources: None. Figure 1