In post-operative Tetralogy of Fallot (TOF) patients cMRI data are used for determining right ventricle (RV) dilation to justify the pulmonary valve placement. Echocardiogram analysis of RV volumes has inherent accuracy issues. There are no data exploring the relationship of transthoracic echocardiography tricuspid valve (TV) annulus size and cMRI RV dilation. Retrospective study in post-operative TOF patients. Patients less than 21 years old and with high-quality transthoracic echocardiogram and MRI within 6 months of each other were included. We collected demographic data, type of initial repair, echocardiographic, and cMRI data. A single reviewer measured echocardiogram TV size. Boston z-scores were used. 77 echocardiogram and cMRI pairs were analyzed. Average age was 14 years old. There is not a strong linear relationship between TV z-score and indexed right ventricular end diastolic volume (RVEDVi) (R2 = 0.31). Twenty patients had RVEDVi's of greater than 150 ml/m2. From those 20 patients, 9 patients had a TV z-score of > 2. No patient had a TV z-score > 2 and a normal RVEDVi. For a TV z-score < 2, there was a positive predictive value of 100%, a negative predictive value of 83%, specificity of 100%, and sensitivity of 45%. In our study population, the TV z-score is not sufficient to predict RV dilation. However, TV z-score > 2 has a high positive predictive value for an RVEDVi of > 150 ml/m2. This would suggest that a cMRI should be done if the TV z-score is > 2 on echocardiography.

Heritable connective tissue disorders are a group of diseases, each rare, characterized by various combinations of skin, joint, musculoskeletal, organ, and vascular involvement. Although kidney abnormalities have been reported in some connective tissue disorders, they are rarely a presenting feature. Here we present three patients with prominent kidney phenotypes who were found by whole exome sequencing to have variants in established connective tissue genes associated with Loeys-Dietz syndrome and congenital contractural arachnodactyly. These cases highlight the importance of considering connective tissue disease in children presenting with structural kidney disease and also serves to expand the phenotype of Loeys-Dietz syndrome and possibly congenital contractural arachnodactyly to include cystic kidney disease and cystic kidney dysplasia, respectively.

BACKGROUND:Echo assessment of right ventricular function is difficult due to its complex geometry and regional differences in wall motion. In patients with repaired tetralogy of Fallot, cardiac MRI is the gold standard for assessment of right ventricular function. There is scant data regarding the correlation of echo measures of right ventricular function with cardiac MRI right ventricular function in the paediatric population.METHODS:Echocardiographic measures of regional and global right ventricular function were reviewed in 56 patients with repaired tetralogy of Fallot and 27 patients with structurally normal hearts. These measures were compared to global right ventricular ejection fraction by cardiac MRI.RESULTS:Despite having the same right ventricular ejection fraction by cardiac MRI as normal controls, patients with repaired tetralogy of Fallot had significantly worse global and regional echocardiographic measures of right ventricular function. Right ventricular fractional area change and fractional shortening of the right ventricular outflow tract correlated best with global right ventricular function by MRI. Incorporation of these measures into a regression model allowed accurate prediction of global right ventricular function by cardiac MRI.CONCLUSION:Children with repaired tetralogy of Fallot have abnormal regional and global right ventricular function compared to patients with normal hearts. Despite the presence of patch material, the right ventricular outflow tract significantly contributes to global right ventricular function by cardiac MRI. When incorporated into a model that includes regional and global echocardiographic measures of right ventricular function, right ventricular outflow tract fractional shortening helps predict global right ventricular function by MRI.

Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4–5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt “whole-person health and performance” models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.

OBJECTIVE:Echocardiographic parameters assessing left and right heart function were evaluated in children with established pulmonary hypertension (PH) from bronchopulmonary dysplasia (BPD) to look for correlations with each other, and pulmonary artery pressure (PAPs) from right heart catheterizations (RHC).STUDY DESIGN:Data were retrospectively collected on patients with BPD and PH and correlations were performed between various objective echocardiographic and RHC measurements.RESULTS:A total of 31 patients with BPD were found to have PH by echocardiogram and RHC after chart review. Median age of evaluation was 0.58 years. Correlations were noted between measurements of right heart function, indirect measures of pulmonary artery pressures and left ventricular dimensions. A trend was noted between the tricuspid annular plane systolic excursion obtained at echocardiography and systolic pulmonary artery pressure, obtained during RHC.CONCLUSION:Significant correlations were found between objective echocardiographic measurements of left and right heart function, in patients with PH from BPD.

Fibrosis is commonly described in heart allografts lost late after transplantation. CMR‐derived ECV is a validated measure of DMF in native adult hearts that may predict heart failure and mortality. We explored associations of ECV with histologic myocardial fibrosis and clinical features after pediatric heart transplantation. Twenty‐five recipients (7.0±6.3 years at transplant and 10.7±6.5 years post‐transplant) were prospectively recruited for CMR and BNP measurement at the time of surveillance biopsy. All had normal ejection fractions and lacked heart failure symptoms. Fibrosis was quantified on biopsy after picrosirius red staining as CVF. ECV was quantified using contemporaneous hematocrit on basal and mid‐short‐axis slices. ECV was moderately correlated with CVF (r=.47; P=.019). We found no associations of ECV with hemodynamics, ischemic time, time since transplantation, or number of prior biopsies or acute rejections. Compared to healthy non‐transplant controls, there was no significant difference in ECV (25.1±3.0 vs 23.7±2.0%, P=.09). Log‐transformed BNP was correlated with ECV (recipients: r=.46, P=.02; recipients and controls: r=.45, P=.006). These findings suggest ECV quantifies DMF and relates to biological indicators of cardiac function after pediatric heart transplantation.

Pediatric echocardiography laboratories generally perform transthoracic and transesophageal echocardiographic studies on children from the newborn period through early adulthood. In some cases, older adults with congenital heart disease are also studied in pediatric echocardiography laboratories. Fetal echocardiography is another modality that is often performed in a pediatric laboratory. Establishing and maintaining a pediatric echocardiography laboratory requires attention to structure and organization, space, equipment, staff, and information technology. Quality assessment and patient safety are of the utmost importance and standards are required for each laboratory. It is important to develop standard protocols for the studies performed and to have an environment where interaction between sonographers, trainees, and attending physicians is encouraged. Accreditation of pediatric echocardiography laboratories has also become an important component and helps with the development of standard procedures of operation.

A cardiovascular comorbidity in obese adolescents is increased aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and left ventricular mass (LVM). We investigated in obese adolescents 1) the risk factors associated with aPWV, cIMT and LVM, and 2) the effects of aerobic (AE) versus resistance (RE) exercise alone (without calorie restriction) on aPWV, cIMT, LVM index (LVMI) and cardiometabolic risk factors. Eighty-one obese adolescents (12-18 yrs, BMI ≥95th percentile) were randomized to 3 months of AE (n = 30), RE (n = 27) or a control group (n = 24). Outcome measures included aPWV, cIMT, LVMI, body composition, cardiorespiratory fitness (CRF), blood pressure (BP) and lipids. At baseline, the strongest correlates of aPWV were body weight (r = .31) and diastolic BP (r = .28); of cIMT were body weight (r=0.26) and CRF (r=-0.25); and of LVMI was CRF (r=0.32) after adjusting for sex and race (p < .05 for all). Despite significant reductions in total fat and improvements in CRF in the AE and RE groups, aPWV, cIMT, LVMI, BP, lipids and body weight did not change as compared with controls (p > .05 for all). Interventions of longer duration or together with weight loss may be required to improve these early biomarkers of CVD in obese adolescents.

Background: Late survival after pediatric heart transplantation (HTx) remains poor. Many late deaths are due to “graft failure,” typically in the presence of vasculopathy and diffuse myocardial fibrosis (DMF) - a process associated with ventricular remodeling and heart failure (HF). Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) is a validated measure of DMF in the absence of edema or infiltrative disease, and predicts outcomes of HF and mortality in adults. We hypothesize that ECV is a meaningful biomarker of graft dysfunction following pediatric HTx. Objective: To test the association of ECV with histologic myocardial fibrosis after pediatric HTx. We also explored associations of ECV with hemodynamic, echocardiographic, and serum measures of graft function. Methods: We prospectively enrolled consecutive HTx recipients who were ≥13 years old and ≥9 months post HTx for ECV quantification at the time of surveillance endomyocardial biopsy (EMB). Fibrosis was quantified on EMB by automated image analysis after picrosirius staining and digital scanning. CMR measures of blood and myocardial T1 from basal and mid short axis slices, along with contemporaneous hematocrit, quantified ECV. Results: Nineteen pts (12 male) underwent CMR at a mean age of 18.4 ± 2.8 yrs (range 14.9 - 24.4 yrs) and a mean time after HTx of 10.4 ± 6.6 yrs (1.0 - 20.7 yrs). Four pts were excluded from analysis due to acute rejection (ISHLT grade ≥2R) on concurrent EMB (n=2) or poor quality imaging (n=2). Mean ECV was 27.1 ± 3.8 (20.9 - 32.1). Late gadolinium enhancement was observed in 1 pt. ECV showed moderate correlations with histologic myocardial fibrosis (r=0.61; p=0.02) and serum b-type natriuretic peptide (r=0.66; p=0.008). There was a trend to correlation with pulmonary capillary wedge pressure (r=0.51; p=0.06). We found no associations of ECV with systolic or diastolic function, time after HTx, or graft age. Conclusions: We demonstrate a novel association of ECV with histologic myocardial fibrosis and serum and hemodynamic markers of HF after pediatric HTx. Given prior observations of myocardial fibrosis in chronic graft failure, these findings suggest that ECV may be a relevant, noninvasive marker of graft dysfunction and a potential therapeutic target.

EMB, the gold standard for diagnosis of ACR, poses unique risks in children. Limited cross‐sectional data have associated LV MPI with ACR. We hypothesize that a relative change in MPI from baseline without ACR to the time of ACR will better detect ACR than an absolute threshold LV MPI value. We identified 40 children with ACR ≥60 days post‐transplant matching them by age and time from transplantation to 40 children without ACR. There was a significant increase in LV MPI at time of ACR vs. baseline (0.59 ± 0.17 vs. 0.41 ± 0.11; p < 0.001). There was no difference in LV MPI between baseline and follow‐up (0.41 ± 0.11 vs. 0.42 ± 0.11; p = 0.65). An absolute increase in LV MPI of ≥0.47 had 82.5% sensitivity and 85% specificity for ACR, whereas an increase in LV MPI from baseline of ≥20.4% was 90% sensitive and 100% specific. Serial measurement of LV MPI appears to be a sensitive and specific marker of ACR. LV MPI shows good interobserver agreement and increases at the time of EMB‐proven ACR with subsequent resolution to baseline measurements upon EMB‐proven resolution of ACR. Future studies in larger, prospective cohorts should be undertaken to validate these findings.

DTI indices have been associated with cellular rejection in adult heart transplant recipients, but their predictive value in pediatric recipients is unknown. The purpose of this study was to evaluate DTI measures in the detection of cellular and AMR in pediatric heart transplant recipients. One hundred and forty-eight pediatric heart transplant recipients who had 267 cardiac catheterization procedures with EMB, echocardiogram with DTI, and BNP level performed on the same day were included in the study. For the mitral and tricuspid valves, the ratios (E/E') between the early diastolic inflow velocity by pulsed Doppler (E, m/s) and the early diastolic annular velocity by DTI (E', m/s) were obtained and compared between subjects with and without rejection. Of the 148 recipients, 30 subjects had a total of 37 episodes of rejection: 10 cellular (>or=1B), 17 AMR, and 10 biopsy-negative clinical rejection. Mitral and tricuspid valve E/E' ratios were significantly higher in rejectors than in non-rejectors (5.5 +/- 1.3 vs. 4.4 +/- 1.4, p < 0.001 and 4.9 +/- 2.1 vs. 4.1 +/- 1.5, p < 0.01, respectively). By multivariate linear regression, mitral valve E/E' was an independent predictor of rejection. Mitral and tricuspid valve E/E' <5.0 had 93% and 89% NPV, respectively, for rejection. Mitral and tricuspid valve E/E' ratios <5.0 may be useful non-invasive screening measures to exclude rejection in pediatric heart transplant recipients.

Objective. We sought to identify in utero predictors of postnatal outcomes in fetal patients with pulmonary atresia with intact ventricular septum (PAIVS) or critical pulmonary stenosis.Background: Although PAIVS or critical pulmonary stenosis can be diagnosed in utero by echocardiography, our ability to predict outcomes is limited.Methods: Fetal echocardiograms from 28 patients with PAIVS/critical pulmonary stenosis were retrospectively reviewed. Tricuspid valve (TV) annulus, right and left ventricular internal dimensions, and degree of tricuspid regurgitation were recorded. To establish normal fetal values, echocardiograms; from healthy patients were analyzed in an identical fashion.Results: Both a fetal TV z score of -4 or less beyond 23 weeks of gestation and a fetal TV annulus of 5 mm or less beyond 30 weeks of gestation were predictive of poor postnatal outcomes. in addition, right:left ventricular length or width less than 0.5 and/or die absence of tricuspid regurgitation were predictive of poor outcome.Conclusions. TV annulus size, right:left ventricular ratios, and presence of tricuspid regurgitation on fetal echocardiograms; may aid in guiding prenatal counseling regarding postnatal outcome in PAIVS.

Neonates with double-inlet left ventricle or tricuspid atresia with transposed great arteries and a bulboventricular foramen (BVF) area <2 cm(2)/m(2) develop BVF obstruction. This study examined the outcome of neonates with BVF area between 1 and 2 cm(2)/m(2) whose BVF was bypassed after the neonatal period. We reviewed 29 neonates with double-inlet left ventricles (n = 18) or tricuspid atresia (n = 11) and transposed great arteries. The study group consisted of 9 patients with neonatal BVF areas of 1 to 2 cm(2)/m(2) who did not undergo repair of the BVF obstruction as a neonate. The comparison group consisted of 8 "ideal" patients without BVF obstruction. Precavopulmonary shunt data from cardiac catheterization and echocardiogram and outcomes of the cavopulmonary shunt were compared. Study group patients developed a mild BVF gradient (18 +/- 10 mm Hg by cardiac catheterization) by a mean of 7 months. Left ventricular wall thickness, however, remained in the normal range (4.2 +/- 0.3 mm) and was not statistically different from the comparison group (4.1 +/- 0.4 mm). No difference was found in the precavopulmonary mean pulmonary artery pressure (15 +/- 5 vs 15 +/- 6 mm Hg), transpulmonary gradient (8 +/- 4 vs 8 +/- 5 mm Hg), and left ventricular end-diastolic pressure (7 +/- 2 vs 8 +/- 3 mm Hg). One patient in the study group died from respiratory syncytial virus pneumonia while awaiting cavopulmonary shunt. Neither group had mortality from the cavopulmonary shunt. The lengths of hospital stay were comparable (8.3 +/- 3.7 vs 8.9 +/- 6.0 days). Thus, neonates with BVF area between 1 and 2 cm(2)/m(2) develop mild but hemodynamically insignificant BVF gradient by 7 months of age. This group of patients can be managed safely with relief of BVF obstruction later in infancy.

Radiofrequency catheter ablation (RFCA) is a safe, effective therapy for accessory AV mediated tachycardia requiring precise positioning of the ablation catheter. Palliation of single ventricle with the Glenn or Fontan procedure creates obstacles for correct catheter placement. Transesophageal echocardiography(TEE) has been used to monitor RFCA in children without structural congenital heart disease (CHD) and during interventional catheterization procedures. This report describes our experience with TEE guidance of RFCA in children with palliated single ventricle. Biplane TEE imaging was used to guide mapping and RFCA in 4 children aged 1.5–13 yr. with wt 11–43 kg. Three patients had membranous tricuspid atresia (TA) with WPW and 1 patient had double inlet left ventricle (DILV) with a left atrial ectopic focus. All patients had previously undergone palliation for single ventricle: Glenn shunt (1) or modification of the Fontan procedure (3). On line TEE images guided 1-location of the tricuspid annulus in TA, 2- crossing of a surgically created ASD, 3-retrograde entry of the RV via a Glenn shunt, and 4- retrograde entry of the LV via a Stansel anastomosis. All 4 TEE guided ablations were successful with no early or late complications.

In patients with pulmonary atresia and intact ventricular septum (PA/IVS), the presence of right ventricular to coronary communications (RVCC) dictates surgical management (right ventricular (RV) decompression). Previously, tricuspid valve annulus size-Z score (TV-Z), and RV morphology have been used to predict the presence of RVCC. We hypothesize that pulmonary infundibular diameter better predicts the presence of RVCC than TV-Z score.