Tarek Alsaied

Strategies for thromboprophylaxis in Fontan circulation: a meta-analysis

Background The Fontan circulation is associated with an increased risk of thromboembolic events (TEs). As many as 25% of these thrombotic events result in fatality. More subtle adverse effects on the pulmonary circulation from embolic thrombi may further impair adequate functioning of the circuit. Despite these well-documented phenomena, the most optimal approaches to thromboprophylaxis are still not clearly defined. Objective A meta-analysis of published trials in English on PubMed and Cochrane libraries that evaluated the role of using TE prophylaxis in patients who underwent the Fontan procedure was conducted. Methods 10 studies with a total number of 1200 patients with an average follow-up time of 7.1 years were identified. A random effect model was used. Results The incidence of TE was significantly less in patients who received TE prophylaxis (using either aspirin or warfarin) compared with patients who did not receive TE prophylaxis (OR 0.425, 95% CI 0.194 to 0.929, p<0.01, I2=37%). The incidence of TE was significantly lower in patients who received aspirin compared with no TE prophylaxis (OR 0.363, 95% CI 0.177 to 0.744, p<0.01, I2=0%) and who received warfarin compared with no TE prophylaxis (OR 0.327, 95% CI 0.168 to 0.634, p<0.01, I2=2.5%). There was no significant difference in incidence of TE between warfarin and aspirin (OR 0.936, 95% CI 0.609 to 1.438, p=0.54, I2=0%). Furthermore, there was no significant difference in incidence of early TE (within 6 months of the operation) or late TE (>6 months) between patients receiving warfarin and aspirin (OR 0.784, 95% CI 0.310 to 1.982, p=0.37, I2=8%) and (OR 0.776, 95% CI 0.249 to 2.42, p=0.3, I2=45%), respectively. When only total cavopulmonary connection patients were included, there was again no difference between warfarin and aspirin in the incidence of TE (OR 0.813, 95% CI 0.471 to 1.401, p=0.34, I2=11%). Conclusions This study shows a significantly lower incidence of TE after Fontan procedure if either aspirin or warfarin is used. This meta-analysis suggests no significant difference in incidence of early or late TE in patients receiving aspirin compared with warfarin.

Factors associated with long-term mortality after Fontan procedures: a systematic review.

Background Despite an ageing Fontan population, data on late outcomes are still scarce. Reported outcome measures and determinants vary greatly between studies making comprehensive appraisal of mortality hazard challenging. Methods We conducted a systematic review to evaluate causes and factors associated with late mortality in patients with Fontan circulation. Late mortality was defined as mortality beyond the first postoperative year. Studies were included if they had ≥90 patients or ≥20 late mortalities and/or transplants. Studies with overlapping patients were rationalised to include only the most recent studies to avoid duplication. Results From 28 studies, a total of 6707 patients with an average follow-up time of 8.23±5.42 years was identified. There were 1000 deaths. Causes of late death were reported in 697 cases. The five most common causes were heart/Fontan failure (22%), arrhythmia (16%), respiratory failure (15%), renal disease (12%) and thrombosis/bleeding (10%). Factors associated with late mortality were evaluated and classified into 9 categories. Conclusions Causes and factors associated with late mortality after the Fontan operation are summarised in this study. The presented information will aid in identifying patients at highest risk for mortality and guide our risk stratification efforts in this patient population.

Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia.

Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 ± 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 ± 0.08 vs 0.26 ± 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 ± 0.07 vs 0.37 ± 0.04, P = .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 ± 261 vs 33 ± 33 pg/mL, P = .04) but lower hemoglobin (8.4 ± 0.3 vs 10.9 ± 1.4 g/dL, P = .004) compared with participants with normal diastolic function. Participants with the highest ECV values (≥0.40) were more likely to have diastolic dysfunction (P = .003) and increased left atrial volume (57 ± 11 vs 46 ± 12 mL/m2, P = .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r = -0.46, P = .03) and NT-proBNP (r = 0.62, P = .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

Does Congenital Heart Disease Affect Neurodevelopmental Outcomes in Children with Down Syndrome

OBJECTIVE The impact that congenital heart disease (CHD) has on the neurodevelopment of children with Down syndrome (DS) is unknown and potentially has implications for targeted early intervention. This study assessed the relationship between CHD that required surgery in the first year of life and neurodevelopmental, behavioral and emotional functioning outcomes in children with DS. METHODS A retrospective chart review of 1092 children (0-18 years) with DS who visited a single institution from 8/08-8/13 was performed. Children who underwent at least one of nine neurodevelopmental (cognitive, language, developmental) or academic tests were included in the analysis (N = 178). Cohort was age-divided into infants/toddlers (0-2 years), preschoolers (3-5 years), and school age/adolescent (6-18 years). Test scores of children with DS who underwent cardiac surgery in the first year of life were compared to children with DS without CHD. T test, chi-square and Mann Whitney U tests were used where appropriate. RESULTS Infants/toddlers with cardiac surgery had lower scores for receptive (P = .01), expressive (P = .021) and composite language (P < .001) compared to those with no CHD. Preschoolers with cardiac surgery had lower language scores and lower visual motor scores, although not statistically significant. In school age children with cardiac surgery there were no differences in IQ scores, language scores, or academic achievement scores compared to those without CHD. Also at school-age there was no difference in the incidence of ADHD, executive function or on internalizing and externalizing behavior scores. CONCLUSION Children with DS undergoing cardiac surgery during the first year demonstrated poorer neurodevelopmental outcomes as infants/toddler but had no difference at school age compared to children with DS without CHD. These results will guide early interventions to optimize neurodevelopmental outcomes in children with DS and will help with family counseling after CHD repair.

Fetal Origins of Adult Cardiac Disease: A Novel Approach to Prevent Fetal Growth Restriction Induced Cardiac Dysfunction Using Insulin Like Growth Factor.

Background:Fetal growth restriction (FGR) is a risk factor for adult cardiovascular disease. Intraplacental gene transfer of human insulin-like growth factor-1 (IGF-1) corrects birth weight in our mouse model of FGR. This study addresses long term effects of FGR on cardiac function and the potential preventive effect of IGF-1.Study design:Laparotomy was performed on pregnant C57BL/6J mice at embryonic day 18 and pups were divided into three groups: Sham operated; FGR (induced by mesenteric uterine artery ligation); treatment (intraplacental injection of IGF-1 after uterine artery ligation). Pups were followed until 32 wk of life. Transthoracic echocardiography was performed starting at 12 wk.Results:Systolic cardiac function was significantly impaired in the FGR group with reduced fractional shortening compared with sham and treatment group starting at week 12 of life (20 ± 4 vs. 31 ± 5 vs. 32 ± 5, respectively, n = 12 for each group; P < 0.001) with no difference between the sham and treatment groups.Conclusion:Intraplacental gene transfer of IGF-1 prevents FGR induced cardiac dysfunction. This suggests that in utero therapy may positively impact cardiac remodeling and prevent adult cardiovascular disease.

Predicting long-term mortality after Fontan procedures: A risk score based on 6707 patients from 28 studies

BACKGROUND Reported long-term outcome measures vary greatly between studies in Fontan patients making comprehensive appraisal of mortality hazard challenging. We sought to create a clinical risk score to assist monitoring of Fontan patients in the outpatient setting. METHODS A systematic review was conducted to evaluate risk factors for long-term (beyond the first postoperative year) mortality in Fontan patients. Studies were eligible for inclusion if ≥90 patients were included or ≥20 long-term mortalities we reported. Risk factors for long-term mortality were determined. The pooled hazard ratios were used to create components of a clinical score for long-term mortality using meta-analysis techniques. RESULTS Twenty-eight studies were included. The total number of patients was 6707 with an average follow-up of 8.23 ± 5.42 years. There were 1000 deaths. Thirty-five risk factors for late mortality were identified and classified into 9 categories and their relative hazards were used to derive the initial components of a weighted, practical and clinically based Fontan risk score (ranging from 0 to 100). The final score included 8 risk factors: anatomic risk factors, elevated preoperative pulmonary artery pressure, atriopulmonary Fontan, heart failure symptoms, arrhythmia, moderate/severe ventricular dysfunction or atrioventricular valve regurgitation, protein losing enteropathy, and end organ disease (cirrhosis or renal insufficiency). CONCLUSION In patients with Fontan circulation, the influence of readily available risk factors can be quantified in an integer score to predict long-term mortality. Prospective validation and refinement of this risk score will be undertaken.

Time in therapeutic range as a marker for thrombotic and bleeding outcomes in Fontan patients.

Fontan patients managed with warfarin are at risk not only for thrombotic events, but also for bleeding episodes as a consequence of anticoagulation treatment. The aim of this study was to determine whether time spent in patient specified therapeutic range (TTR), when managed in a cardiology-based pharmacist managed anticoagulation clinic (PMAC), is a useful target metric for monitoring, as well as improving outcomes. A single center retrospective review was conducted evaluating TTR of all Fontan patients (n = 45) on warfarin managed in our outpatient cardiology pharmacist managed anticoagulation clinic (PMAC) during a 19 month time frame. The primary outcome was time spent within, above, and below therapeutic range. Secondary outcomes were thrombotic event (TE) incidence pre- and post PMAC enrollment and bleeding event incidence during PMAC management. Of the Fontan patients included, 55.6% were male and the median age at latest anticoagulation clinic follow-up was 19 years (IQR 13, 29). A composite 52.9 patient years of warfarin therapy was evaluated during the study time frame. The mean TTR for patients was 84.1 ± 5.2%. The most frequent reasons for non-therapeutic INRs were diet changes (42.8%), medication non-compliance (13.7%), and drug interactions (8.8%). Only one TE occurred during the study time frame. The incidence of TE in this population was decreased after PMAC enrollment (1 per 52.9 patient year versus 1 event per 17.4 patient year; p < 0.0002). Two major bleeds that required emergency department visit occurred during this time, none were cerebral or gastrointestinal. In Fontan patients anticoagulated with warfarin, a greater than 80% TTR can be achieved in a PMAC. Such high time in therapeutic range was associated with excellent outcomes, despite the obvious complexity of this population.

Effect of fetal hemodynamics on growth in fetuses with single ventricle or transposition of the great arteries

As birth weight is a critical predictor of outcome in neonates with congenital heart defect (CHD), the common problem of poor fetal growth in this population is clinically important. However, it is not well understood and the impact of fetal hemodynamics on fetal growth and birth weight in those with CHD has not been assessed. In this study, we sought to evaluate the association between combined cardiac output (CCO) and fetal middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices (PIs) and fetal growth in different subgroups of CHD, and to study the effects of fetal hemodynamics on late gestational weight gain. We hypothesized that fetuses with CHD will have lower CCO and be smaller at birth.

Variations in rotation of the aortic root and membranous septum with implications for transcatheter valve implantation

Objective It is intuitive to suggest that knowledge of the variation in the anatomy of the aortic root may influence the outcomes of transcatheter implantation of the aortic valve (TAVI). We have now assessed such variation. Methods We used 26 specimens of normal hearts and 78 CT data sets of adults with a mean age of 64±15 years to measure the dimensions of the membranous septum and to assess any influence played by rotation of the aortic root, inferring the relationship to the atrioventricular conduction axis. Results The aortic root was positioned centrally in the majority of both cohorts, although with significant variability. For the cadaveric hearts, 14 roots were central (54%), 4 clockwise-rotated (15%) and 8 counterclockwise-rotated (31%). In the adult CT cohort, 44 were central (56%), 21 clockwise-rotated (27%) and 13 counterclockwise-rotated (17%). A mean angle of 15.5° was measured relative to the right fibrous trigone in the adult CT cohort, with a range of −32° to 44.7°. The dimensions of the membranous septum were independent of rotation. Fibrous continuity between the membranous septum and the right fibrous trigone increased with counterclockwise to clockwise rotation, implying variation in the relationship to the atrioventricular conduction axis. Conclusions The central fibrous body is wider, providing greater fibrous support, in the setting of clockwise rotation of the aortic root. Individuals with this pattern may be more vulnerable to conduction damage following TAVI. Knowledge of such variation may prove invaluable for risk stratification.

International medical graduates in cardiology fellowship: brain drain or brain gain?

It was graduation day for 1 of the biggest and most prestigious pediatric residency programs in the country. Families came from every state to see their children graduate. Omar’s family could not join him from overseas today, as they were not able to get the visa in time. The big news today was