Hybrid Stenting of Pulmonary Venous Baffle Stenosis: Subxiphoid Approach in Transposition of the Great Arteries.

A 31-year-old woman with transposition of the great arteries status post-Senning operation presents with severe pulmonary venous baffle obstruction. Both standards of care (percutaneous stenting or open repair) were deemed suboptimal and/or high risk. A multidisciplinary, hybrid approach via subxiphoid incision, guided by 3-dimensional modeling, provided a lower risk and minimally invasive intervention.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation.

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy. The purpose of this study is to evaluate the effects of udenafil on vital signs in the cohort of patients enrolled in the FUEL trial. This international, multicenter, randomized, double-blind, placebo-controlled trial of udenafil included adolescents with single ventricle congenital heart disease who had undergone Fontan palliation. Changes in vital signs (heart rate [HR], systolic [SBP] and diastolic blood pressure [DBP]) were compared both to subject baseline and between the treatment and the placebo groups. Additional exploratory analyses were performed to evaluate changes in vital signs for prespecified subpopulations believed to be most sensitive to udenafil initiation. Baseline characteristics were similar between the treatment and placebo cohorts (n = 200 for each). The groups demonstrated a decrease in HR, SBP, and DBP 2 hours after drug/placebo administration, except SBP in the placebo group. There was an increase in SBP from baseline to after 6-min walk test in the treatment and placebo groups, and the treatment group showed an increase in HR (87.4 ± 15.0 to 93.1 ± 19.4 beats/min, p <0.01) after exercise. When comparing changes from baseline to the 26-week study visit, small decreases in both SBP (-1.9 ± 12.3 mm Hg, p = 0.03) and DBP (-3.0 ± 9.6 mm Hg, p <0.01) were seen in the treatment group. There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration.

Association of cardiovascular magnetic resonance diastolic indices with arrhythmia in repaired Tetralogy of Fallot.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality. METHODS: Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations. RESULTS: One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 [0.24-0.80], p = 0.007) and total arrhythmia (OR 0.56 [0.37-0.92], p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality. CONCLUSIONS: Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia.

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants.

BACKGROUND: The FUEL trial (Fontan Udenafil Exercise Longitudinal) demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle function in this cohort has not been studied. METHODS: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus right ventricle/other) and baseline value. RESULTS: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (P=0.03, adjusted mean difference [SE] of changes between groups -0.03[0.01]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve regurgitation, and higher annular s' and e' velocity). CONCLUSIONS: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort. REGISTRATION: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.

Metabolomic Profiling of Adults with Congenital Heart Disease.

Metabolomic analysis may provide an integrated assessment in genetically and pathologically heterogeneous populations. We used metabolomic analysis to gain mechanistic insight into the small and diverse population of adults with congenital heart disease (ACHD). Consecutive ACHD patients seen at a single institution were enrolled. Clinical variables and whole blood were collected at regular clinical visits. Stored plasma samples were analyzed for the concentrations of 674 metabolites and metabolic markers using mass spectrometry with internal standards. These samples were compared to 28 simultaneously assessed healthy non-ACHD controls. Principal component analysis and multivariable regression modeling were used to identify metabolites associated with clinical outcomes in ACHD. Plasma from ACHD and healthy control patients differed in the concentrations of multiple metabolites. Differences between control and ACHD were greater in number and in degree than those between ACHD anatomic groups. A metabolite cluster containing amino acids and metabolites of amino acids correlated with negative clinical outcomes across all anatomic groups. Metabolites in the arginine metabolic pathway, betaine, dehydroepiandrosterone, cystine, 1-methylhistidine, serotonin and bile acids were associated with specific clinical outcomes. Metabolic markers of disease may both be useful as biomarkers for disease activity and suggest etiologically related pathways as possible targets for disease-modifying intervention.

Sizing Up Fontan Failure: Association with Increasing Weight in Adulthood.

Obesity has become increasingly recognized in adults with Fontan palliation, yet the relationship between weight changes in adulthood and Fontan failure is not clearly defined. We hypothesize that increasing weight in adulthood among Fontan patients is associated with the development of Fontan failure. Single-center data from adults with Fontan palliation who were not in Fontan failure at their first clinic visit in adulthood and who received ongoing care were retrospectively collected. Fontan failure was defined as death, transplant, diagnosis of protein losing enteropathy, predicted peak VO2 less than 50%, or new loop diuretic requirement. Anthropometric data including weight and BMI were collected. Change in weight was compared between those that developed Fontan failure, and those that remained failure-free. To estimate the association between weight change during adulthood and the risk of developing Fontan failure, a survival analysis using multiple Cox's proportional hazards regression model was performed. Overall, 104 patients were included in the analysis. Those that developed Fontan failure had a larger associated median weight gain than those who remained failure-free (7.8 kg vs. 4.9 kg, respectively; p = 0.011). In multivariable Cox regression analysis, increased weight during adulthood was associated with increased likelihood of developing Fontan failure (HR 1.36; CI 1.07-1.73; p = 0.011). Weight gain in adulthood is associated with the development of Fontan failure.

More than the heart: Hepatic, renal, and cardiac dysfunction in adult Fontan patients.

SETTING: Fontan-associated liver disease universally affects adults with single ventricle heart disease. Chronic kidney disease is also highly prevalent in adult Fontan patients. In this study, we evaluate the relationship of Fontan hemodynamics invasively and noninvasively with extra-cardiac dysfunction as measured by MELD and MELD-XI. OBJECTIVE: We hypothesize that invasive and noninvasive measures of Fontan circuit congestion and ventricular dysfunction are associated with increased MELD and MELD-XI scores. DESIGN: Single-center data from adults with Fontan palliation who had ongoing care, including cardiac catheterization, were retrospectively collected. Hemodynamic data from cardiac catheterization and echocardiographic assessment of ventricular and atrioventricular valve function were tested for association with serum creatinine, MELD, and MELD-XI. Linear regression was used to perform multivariable analysis in the echocardiogram cohort. RESULTS: Fifty-seven patients had congruent lab and catheterization data for analysis. Sixty-three and sixty-nine patients had congruent lab and echocardiogram data for MELD and MELD-XI, respectively. Of the hemodynamic variables analyzed, only decreased systemic oxygen saturation had significant correlation with elevated MELD and MELD-XI (P = .045). Patients with moderately or severely reduced ejection fraction by echocardiogram had significantly higher MELD and MELD-XI scores compared to those with normal or mildly depressed systolic ventricular function (P = .008 and P < .001 for MELD and MELD-XI, respectively). Significant differences in creatinine were also found among the ventricular dysfunction groups (P = .02). CONCLUSIONS: In adults following Fontan palliation, systolic ventricular dysfunction and decreased oxygen saturation were associated with hepatic and renal dysfunction as assessed by elevated serum creatinine, MELD, and MELD-XI scores.