Elif Seda Selamet Tierney, MD

Abstract

In this manuscript, we describe the design and rationale of a randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic+resistance) intervention will improve cardiac and physical capacity; muscle mass, strength, and function; and endothelial function. Survival of children with single ventricles beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity which is associated with a greater risk of morbidity and mortality. Furthermore, decreased muscle mass, abnormal muscle function, and endothelial dysfunction in this patient population is known to contribute to disease progression. In adult patients with two ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Despite these known benefits of exercise, pediatric Fontan patients do not exercise routinely due to their chronic condition, perceived restrictions to exercise, and parental overprotection. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Critically, adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or workdays. To overcome these challenges, we utilize live-video conferencing to deliver the supervised exercise sessions. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence, and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. Our ultimate goal is the translation of this model to clinical application as an "exercise prescription" to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality.

View details for DOI 10.1016/j.ahj.2023.02.006

View details for PubMedID 36796574

Abstract

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID-and 61 were KDCOVID+. KDCOVID+patients were older (median 5.5 vs. 3.7years; p<0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p=0.008) and headache (38% vs. 10%; p<0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+patients were more likely to have shock (41% vs. 6%; p<0.001), ICU admission (62% vs. 10%; p<0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p<0.001), and to have received inotropic support (60% vs. 10%; p<0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p=0.63), but KDCOVID+were more likely to have received steroids (85% vs. 35%; p<0.001) and anakinra (60% vs. 10%; p=0.002). KDCOVID-patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p=0.01). KDCOVID+patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

View details for DOI 10.1007/s00246-023-03109-w

View details for PubMedID 36786810

View details for PubMedCentralID PMC9926414

Abstract

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare, delayed hyperinflammatory response to SARS-CoV-2 infection, and causes severe morbidity in the pediatric age group. While MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6-12 years, and specific racial and/or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurological complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein, as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens, are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C versus both acute SARS-CoV-2 infcction and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine -associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

View details for DOI 10.1016/j.cjca.2023.01.002

View details for PubMedID 36626979

Abstract

As we learn more about the novel multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection, the protocols for long-term follow-up have evolved and only some of these protocols have been published. Here, we review the current literature on follow-up guidelines in MIS-C patients.We conducted a PUBMED search of all articles published on "MIS-C" and the term "follow-up" between 2020 and 2022. Inclusion criteria were that (1) the study was an observational study or case series, and (2) the study population included pediatric population who met the diagnostic criteria for MIS-C.There were 206 publications on MIS-C and follow-up in the last 2 years with 11 studies that fit the inclusion criteria. These papers were representing 11 different centers and encompassed a total of 343 participants. Seven of the 11 studies had participants follow-up with their cardiologist within 1 month of discharge. Between 12% and 62% of patients within each study had depressed left ventricular ejection fraction (LVEF) at admission. At the initial follow-up visit, five studies showed a normal LVEF in all patients while the other seven studies showed 2%-13% patients continuing to have depressed LVEF. In eight of the 11 studies, 9%-52% of patients had coronary artery dilation at admission. At their initial follow-up visit, 3%-28% of patients continued to have coronary artery dilation.There is some institutional variation in the outpatient follow-up protocols in patients diagnosed with MIS-C. A standardized follow-up guidelines might be helpful to monitor long-term prognosis of these patients.

View details for DOI 10.3389/fped.2022.1069632

View details for PubMedID 36568433

View details for PubMedCentralID PMC9768426

Abstract

Background Stiffer aortas are associated with a faster rate of aortic root (AoR) dilation and higher risk of aortic dissection in patients with Marfan syndrome. We have previously shown that mild aerobic exercise reduces aortic stiffness and rate of AoR dilation in a Marfan mouse model. In this study, we investigated if these results could be translated to pediatric patients with Marfan syndrome. Methods and Results We enrolled 24 patients with Marfan syndrome aged 8 to 19years to participate in a 6-month physical activity intervention, excluding those with ventricular dysfunction or prior history of aortic surgery. We instructed patients to take 10000 steps per day, tracked by an activity tracker. At baseline and 6 months, we measured AoR dimension, arterial stiffness, endothelial function, physical activity indices, inflammatory biomarkers, and coping scores. Controls consisted of 15 age-matched patients with Marfan syndrome. Twenty-four patients with Marfan syndrome (median age, 14.4years [interquartile range {IQR}, 12.2-16.8], 14 male patients) were enrolled. Baseline assessment demonstrated that the majority of these patients were sedentary and had abnormal arterial health. Twenty-two patients completed the intervention and took an average of 77092177 steps per day (median, 7627 [IQR, 6344-9671]). Patients wore their Garmin trackers at a median of 92.8% (IQR, 84%-97%) of their intervention days. AoR Z score in the intervention group had a significantly lower rate of change per year compared with the controls (rate of change, -0.24 versus +0.008; P=0.01). Conclusions In this clinical intervention in pediatric patients with Marfan syndrome, we demonstrated that a simple physical activity intervention was feasible in this population and has the potential to decrease the AoR dilation rate. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03567460.

View details for DOI 10.1161/JAHA.122.027598

View details for PubMedID 36453629

Abstract

Transthoracic echocardiography (TTE) is an essential tool for diagnosis and management of congenital heart disease. Pediatric echocardiography presents unique challenges including complex anatomy, variable patient cooperation and provider expertise. Diagnostic errors inevitably occur. We designed a collaborative and stepwise quality improvement (QI) process to address diagnostic errors within our laboratory. We retrospectively reviewed medical records to identify diagnostic TTE errors in 100 consecutive cardiac surgery patients 5 years old (July 2020-January 2021). We identified 18 diagnostic errors. Most errors had minor impact (14/18), and 13 were preventable or possibly preventable. We presented these results to our sonographers and faculty and requested input on preventing and managing diagnostic errors. Our root cause analysis based on their responses yielded 7 areas for improvement (imaging, reporting, systems, time, environment, people, QI processes). Our faculty and sonographers chose QI processes and imaging as initial areas for intervention. We defined our SMART goal as a 10% reduction in diagnostic errors. We implemented interventions focused on QI processes. On initial follow up in May 2022, we identified 7 errors in 70 patients (44% reduction in error rate). Utilizing a stepwise and team-based approach, we successfully developed QI initiatives in our echocardiography laboratory. This approach can serve as a model for a collaborative QI process in other institutions.

View details for DOI 10.3390/children9121845

View details for PubMedID 36553289

View details for PubMedCentralID PMC9776848

Abstract

IMPORTANCE: Paediatricians play an integral role in the lifelong care of children with CHD, many of whom will undergo cardiac surgery. There is a paucity of literature for the paediatrician regarding the post-operative care of such patients.OBSERVATIONS: The aim of this manuscript is to summarise essential principles and pertinent lesion-specific context for the care of patients who have undergone surgery or intervention resulting in a biventricular circulation.CONCLUSIONS AND RELEVANCE: Familiarity with common issues following cardiac surgery or intervention, as well as key details regarding specific lesions and surgeries, will aid the paediatrician in providing optimal care for these patients.

View details for DOI 10.1017/S1047951122002955

View details for PubMedID 36165406

Abstract

IMPORTANCE: Single ventricle CHD affects about 5 out of 100,000 newborns, resulting in complex anatomy often requiring multiple, staged palliative surgeries. Paediatricians are an essential part of the team that cares for children with single ventricle CHD. These patients often encounter their paediatrician first when a complication arises, so it is critical to ensure the paediatrician is knowledgeable of these issues to provide optimal care.OBSERVATIONS: We reviewed the subtypes of single ventricle heart disease and the various palliative surgeries these patients undergo. We then searched the literature to detail the general paediatrician's approach to single ventricle patients at different stages of surgical palliation.CONCLUSIONS AND RELEVANCE: Single ventricle patients undergo staged palliation that drastically changes physiology after each intervention. Coordinated care between their paediatrician and cardiologist is requisite to provide excellent care. This review highlights what to expect when these patients are seen by their paediatrician for either well child visits or additional visits for parental or patient concern.

View details for DOI 10.1017/S1047951122002943

View details for PubMedID 36148873

Abstract

Echocardiographic quantification of fetal cardiac output (CO) aids clinical decision-making in the management of various cardiac and extracardiac diseases. Small variability in measuring semilunar valve dimension significantly reduces the reproducibility of the calculated CO. We propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. We hypothesized that right and left ventricular minute VTI increase predictably with estimated fetal weight (EFW) and are more reproducible than CO.571 singleton fetuses without cardiovascular pathology between 16-36 weeks gestation were reviewed retrospectively. 22 fetuses with pathology resulting in low or high cardiac output states were also assessed for comparison. VTI was measured in both ventricular outflow tracts at the level of the semilunar valve, excluding a Doppler insonation angle >30. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter-/intra-rater variability were evaluated in a random 10% subset.Minute VTI and CO measurements were feasible in 67-89% of fetuses in this retrospective study. Minute VTI and CO increased with EFW non-linearly (R=0.61 - 0.94). The mean inter-/intra-rater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (p<0.001 for all).Minute VTI is an easily measured, highly reproducible method of quantifying fetal ventricular systolic function. Variability in calculated CO from valve measurement differences is minimized by solely using VTI. Nomograms of minute VTI provide an efficient and precise assessment of fetal systolic function, and may be utilized to track fetuses in disease states with low or high cardiac output.

View details for DOI 10.1016/j.echo.2022.08.007

View details for PubMedID 35973561

Abstract

Recommendations for management of patients with Kawasaki disease (KD) and coronary artery aneurysms (CAA) include physical activity (PA) promotion. This study aimed to characterize self-reported practices of KD providers to evaluate practice variation in use of cardiopulmonary exercise testing (CPET) and PA recommendations. We developed a REDCap survey with different clinical scenarios of KD patients. It was completed by members of the International Kawasaki Disease Registry (IKDR) and community pediatric cardiologists. Twenty-eight physicians responded; 63% practiced in the US, 63% practiced in an academic setting, 48% were general pediatric cardiologists, and 55% were IKDR members. Most respondents (69%) followed<50 KD patients. The great majority (93%) agreed that patients with no CAA do not require CPET and could be cleared for all PA. For patients with small CAA, 43% of respondents recommended CPET and 75% cleared for all PA if CAAs regressed completely, but only 32% cleared if CAA persisted. For patients with medium CAA, 66% respondents cleared for PA if CAA regressed, and only 7% if CAA persisted; with 66% and 75% recommending CPET, respectively. For patients with large/giant CAA, 81% of respondents recommended CPET. No respondents felt comfortable clearing their patients with persistent large/giant CAA for PA and 19% would restrict from the entire physical education program. There is practice variation in use of CPET in KD patients with CAAs. Providers are hesitant to promote PA in KD patients with CAA despite known benefits and current guidelines.

View details for DOI 10.1007/s00246-022-02984-z

View details for PubMedID 35953605

Abstract

The Pediatric Heart Network (PHN) trial showed similar efficacy of beta-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6months-25years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.16.1years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p<0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p<0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p=0.37] and ARB [OR 1.91 (0.55, 6.69), p=0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

View details for DOI 10.1007/s00246-022-02976-z

View details for PubMedID 35902413

Abstract

BACKGROUND: Intraoperative imaging determines the integrity of surgical repairs. Transoesophageal echocardiography represents standard care for intraoperative imaging in CHD. However, some conditions preclude its use, and epicardial echocardiography is used alternatively. Minimal literature exists on the impact of epicardial echocardiography versus transoesophageal echocardiography. We aimed to evaluate accuracy between the two modalities and hypothesised higher imaging error rates for epicardial echocardiography.METHODS: We retrospectively reviewed all epicardial echocardiograms performed over 16 years and compared them to an age- and procedure-matched, randomly selected transoesophageal echocardiography cohort. We detected un- or misidentified cardiac lesions during the intraoperative imaging and evaluated patient outcomes. Data are presented as a median with a range, or a number with percentages, with comparisons by Wilcoxon two-sample test and Fisher's exact test.RESULTS: Totally, 413 patients comprised the epicardial echocardiography group with 295 transoesophageal echocardiography matches. Rates of imaging discrepancies, re-operation, and incision infection were similar. About 13% of epicardial echocardiography patients had imaging discrepancies versus 16% for transoesophageal (p = 0.2352), the former also had smaller body sizes (p < 0.0001) and more genetic abnormalities (33% versus 19%, p < 0.0001). Death/mechanical support occurred more frequently in epicardial echocardiography patients (16% versus 6%, p < 0.0001), while hospitalisations were longer (25 versus 19 days, p = 0.0003).CONCLUSIONS: Diagnostic accuracy was similar between patients undergoing epicardial echocardiography and transoesophageal echocardiography, while rates of death and mechanical support were increased in this inherently higher risk patient population. Epicardial echocardiography provides a reasonable alternative when transoesophageal echocardiography is not feasible.

View details for DOI 10.1017/S1047951122001536

View details for PubMedID 35747949

Abstract

Objective: Aortic root (AoR) size remains an imperfect predictor of rate of aortic dilation in Marfan syndrome (MFS). Indicators of vascular phenotype such as aortic stiffness have been proposed as additional predictors. In this study we assessed the rate of AoR dilation and stiffness in adult patients with MFS.Methods: We performed a retrospective chart review. We included adult patients with MFS (aged 20-40years) with at least 2 local echocardiograms 6months apart (no aortic surgery in-between). A blinded observer analyzed the echocardiograms. AoR dilation rate and stiffness were calculated.Results: Thirty-two patients (53% women; median age, 21.1; interquartile range [IQR], 19-24years at first echocardiogram) were included. AoR dilation rate in the entire cohort was 0 to 8mm/year (median, 0.465; IQR, 0.23-1.45mm/year). Multiple linear regression analysis showed that baseline AoR stiffness was associated with AoR dilation rate (beta=0.0004; P<.001 for elastic modulus), whereas baseline age and baseline AoR dimension were not. Eighteen of these 32 patients (56%) eventually had AoR surgery (Sx) and 14 did not have surgery (NSx). At baseline, Sx and NSx patients were similar in age. AoR dimension was larger (Sx, 4.27cm; IQR, 4.05-4.49cm vs NSx, 3.73cm; IQR, 3.37-4.09cm; P=.011) and AoR stiffness was higher in Sx patients (beta stiffness index: median, 23.2; IQR, 17.8-28.6 vs median, 15.6; IQR, 11.6-19.7; P=.024). AoR dilation rate was greater in Sx patients, independent of baseline AoR dimension (1.630.41mm/year vs 0.380.08mm/year; P=.01).Conclusions: Our results showed that AoR dilation rate varies among adult patients with MFS and is associated with baseline AoR stiffness, measured by echocardiography. Further studies are warranted to determine how aortic stiffness can be implemented clinically to refine management in patients with MFS.

View details for DOI 10.1016/j.xjon.2022.04.011

View details for PubMedID 36004220

Abstract

PURPOSE: In a large cohort of 373 pediatric patients with Marfan syndrome (MFS) with a severe cardiovascular phenotype, we explored the proportion of patients with MFS with a pathogenic FBN1 variant and analyzed whether the type/location of FBN1 variants was associated with specific clinical characteristics and response to treatment. Patients were recruited on the basis of the following criteria: aortic root z-score > 3, age 6 months to 25 years, no prior or planned surgery, and aortic root diameter < 5 cm.METHODS: Targeted resequencing and deletion/duplication testing of FBN1 and related genes were performed.RESULTS: We identified (likely) pathogenic FBN1 variants in 91% of patients. Ectopia lentis was more frequent in patients with dominant-negative (DN) variants (61%) than in those with haploinsufficient variants (27%). For DN FBN1 variants, the prevalence of ectopia lentis was highest in the N-terminal region (84%) and lowest in the C-terminal region (17%). The association with a more severe cardiovascular phenotype was not restricted to DN variants in the neonatal FBN1 region (exon 25-33) but was also seen in the variants in exons 26 to 49. No difference in the therapeutic response was detected between genotypes.CONCLUSION: Important novel genotype-phenotype associations involving both cardiovascular and extra-cardiovascular manifestations were identified, and existing ones were confirmed. These findings have implications for prognostic counseling of families with MFS.

View details for DOI 10.1016/j.gim.2021.12.015

View details for PubMedID 35058154

Abstract

PURPOSE OF REVIEW: Historically, children with congenital heart disease have been restricted from exercise, contributing to a sedentary lifestyle as well as increased cardiovascular risk factors. Given the large benefits and small risks of exercise in this population, guidelines have recently shifted towards exercise promotion. However, these recommendations have yet not gained traction and children with congenital heart disease continue to live sedentary lives. The purpose of this review is to summarize the current literature on exercise and exercise promotion in this population.RECENT FINDINGS: New literature reinforces the importance of recommending exercise and improving exercise capacity both in congenital heart disease in general and for specific lesions. Exercise recommendations should be individualized based on functional parameters using a structured methodology to approach the evaluation, risk classification, and prescriptions of exercise and physical activity.SUMMARY: Regular exercise is essential for children with congenital heart disease and providers must take an active role in providing exercise recommendations for their patients. Exercise promotion remains a challenge, necessitating novel approaches to promote exercise. Further studies are needed to improve the risk stratification of patients with congenital heart disease, assess the long-term outcomes of specific exercise interventions, and inform individualized recommendations to encourage children with congenital heart disease to safely engage in exercise and establish healthy lifelong habits that will decrease their cardiovascular risk.

View details for DOI 10.1097/HCO.0000000000000931

View details for PubMedID 34608879

Abstract

To test feasibility of tele-clinic visits using parentally-acquired vital signs and focused echocardiographic (echo) images in patients with Marfan syndrome.We included patients with MFS 5-19 years old followed in our clinic. We excluded patients with MFS and history of prior aortic root (AoR) surgery, cardiomyopathy, arrhythmia, or AoR4.5 cm. We trained parents in-person to acquire focused echo images on their children using a hand-held device as well as how to use a stadiometer, scale, blood pressure (BP) machine, and a digital stethoscope. Prior to tele-clinic visits, parents obtained the echo images and vital signs. We compared tele-clinic and on-site clinic visit data. Parental and clinic echoes were independently analyzed.Fifteen patient/parent pairs completed tele-clinic visits, conducted at a median of 7.0 [IQR 3.0-9.9] months from the in-person training session. Parents took a median of 70 [IQR 60-150] minutes to obtain the height, weight, heart rate, BP, cardiac sounds, and echo images prior to tele-clinic visits. Systolic BP was higher on-site than at home (median +13 mmHg, p=0.014). Height, weight, diastolic BP, heart rate, and AoR measurements were similar.This study provides information for implementing tele-clinic visits using parentally-acquired vital signs and echo images in MFS patients. The results show that tele-clinic visits are feasible and that parents were able to obtain focused echo images on their children.

View details for DOI 10.1016/j.jpeds.2021.01.004

View details for PubMedID 33453199

Abstract

To evaluate practice variation in pharmacological management in the International Kawasaki Disease Registry (IKDR).Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described.We included 1,627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z-scores 2.5-4.99 in 848, 5.0-9.99 in 349, and 10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23/30 centers (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and three centers used it in >20% of patients. Non-steroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in large/giant CAA patients. Statins (2.7%, all patients) were mostly used in one center and only in large/giant CAA patients. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their large/giant CAA patients.In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

View details for DOI 10.1016/j.jpeds.2021.08.072

View details for PubMedID 34474088

Abstract

PURPOSE OF REVIEW: Children and adolescents with congenital heart disease (CHD) often have decreased exercise capacity and muscle mass. Exercise has numerous health benefits and can improve exercise capacity and muscle mass. As such, guidelines recommend 60min of daily physical activity in the majority of pediatric CHD patients. Despite these known benefits and guidelines, children and adolescents with CHD often do not exercise regularly. The purpose of this review is to summarize the current literature on exercise in this population.RECENT FINDINGS: With recent advancements in the field, clinical focus in pediatric cardiology has expanded from improving mortality to improving long-term outcomes and quality of life. As part of this paradigm shift, there is ongoing research on safety, impact, and effective delivery of exercise to this population with the overarching goal of promoting an active lifestyle.SUMMARY: Exercise interventions are generally safe, feasible, and beneficial in children and adolescents with CHD. There is growing evidence demonstrating the benefits and utility of exercise as a prescription rather than restriction in pediatric CHD patients. Novel approaches are needed for effective delivery of exercise in this population. Further studies are warranted for assessment of long-term benefits of exercise in pediatric CHD patients.

View details for DOI 10.1097/MOP.0000000000000942

View details for PubMedID 32868597

Abstract

Telehealth is a promising new tool in medicine that has changed the landscape of medical care. The benefits of telehealth technology are immense, including improved access to care and potential savings in monetary and opportunity costs. Current challenges of incorporating telehealth services into regular clinical care include licensure and regulatory barriers, difficulty obtaining insurance reimbursements, and high costs of setting up successful telehealth infrastructures. These challenges threaten telehealth's future scalability and expansion to reach all patients in need.

View details for DOI 10.1016/j.pcl.2020.04.005

View details for PubMedID 32650860

Abstract

BACKGROUND: No guidelines exist for inpatient postoperative transthoracic echocardiographic (TTE) surveillance in congenital heart disease. We prospectively evaluated indications for postoperative TTEs in patients with congenital heart disease to identify areas to improve upon (Phase 1) and then assessed the impact of a simple pilot intervention (Phase 2).METHODS: We included patients with RACHS-1 (Risk Adjustment for Congenital Heart Surgery) scores of 2 and 3 to keep the cohort homogenous. During Phase 1, we collected data prospectively to identify postoperative TTEs for which there were no new findings and no associated clinical management decisions ("potentially redundant" TTEs). During Phase 2, prior to placement of a TTE order, an "Echo Pause" was performed during rounds to prompt review of prior TTE results and indication for the current order. The number of "potentially redundant" TTEs during Phase 1 vs. Phase 2 was compared.RESULTS: During Phase 1, 98 postoperative TTEs were performed on 51 patients. Potentially "redundant" TTEs were identified in two main areas: (a) TTEs ordered to evaluate pericardial effusion and (b) TTEs ordered with the indication of "postoperative," "follow-up," or "discharge" in the setting of a prior complete postoperative TTE and no apparent change in clinical status. During Phase 2, 101 TTEs were performed on 63 patients. The number of "potentially redundant" TTEs decreased from 14/98 (14%) to 5/101 (5%) (P=.026).CONCLUSION: Our results suggest that the number of "potentially redundant" TTEs during inpatient postoperative surveillance of patients with congenital heart disease can be decreased by a simple intervention during rounds such as an "Echo Pause."

View details for DOI 10.1111/echo.14505

View details for PubMedID 31628768

Abstract

The purpose of this article was to review the current literature on psychosocial implications of Marfan syndrome (MFS) and its impact on adolescents, adults, their families and to provide important considerations for providers. Since the previous reviews in 2015, numerous studies have been published that are included in the current review. This literature review was conducted using PubMed, Medline, PsychINFO, ERIC, Web of Science, and Academic Search Premier databases and only articles that studied psychosocial factors that influence MFS patients as adolescents, adults, family members, or their interactions with providers were included in this review. Of the 522 articles reviewed, 41 were selected based on the inclusion and exclusion criteria. All articles were peer-reviewed. MFS has various implications that can impact one's life; studies have shown that MFS causes a negative impact on an individual's formative years, quality of life, reproductive decision-making, work participation, and satisfaction with life. Clinicians and multidisciplinary teams should be aware of these factors to provide support focusing on coping strategies for the patient and their family.

View details for DOI 10.1055/s-0039-1693663

View details for PubMedID 31406616

View details for DOI 10.1161/JAHA.118.011536

View details for Web of Science ID 000484574300022

View details for DOI 10.1016/j.echo.2018.10.007

View details for Web of Science ID 000459902800012

View details for DOI 10.1161/HYPERTENSIONAHA.118.12046

View details for Web of Science ID 000458554900024

View details for DOI 10.1111/petr.13316

View details for Web of Science ID 000457579500010

Abstract

OBJECTIVE: To compare the appropriateness and diagnostic yield of initial outpatient transthoracic echocardiography (TTE) between a community pediatric cardiology practice and an academic children's hospital.STUDY DESIGN: Initial outpatient pediatric TTE ordered by pediatric cardiologists between January and March 2014 at a community practice (Packard Children's Health Alliance [PCHA]; n=238) and an academic tertiary center (Lucile Packard Children's Hospital [LPCH]; n=76) were evaluated based on appropriate use criteria (AUC) released in December 2014. Multivariate logistic regression was used to identify predictors of "rarely appropriate" indications and abnormal TTE findings.RESULTS: Of 314 TTEs, 165 (52.5%) were classified as "appropriate," 40 (12.7%) were classified as "may be appropriate," 100 (31.9%) were classified as "rarely appropriate," and 9 (2.9%) were unclassifiable. The proportion of abnormal findings did not differ between the 2 practice settings (5.3% for LPCH vs 7.6% for PCHA; P=.61). TTEs performed at PCHA were significantly more likely to be "rarely appropriate" (OR, 2.57; 95% CI, 1.28-5.15; P=.008). Children aged <1 year (OR, 1.90; 95% CI, 1.03-3.50; P=.04) and ordering providers with<10 years since the completion of their fellowship (OR, 2.15; 95% CI, 1.20-3.87; P=.01) were associated with "rarely appropriate" indications. "Appropriate" TTEs were associated with abnormal findings (OR, 8.69; 95% CI, 1.77-42.68; P=.008).CONCLUSION: The community practice was independently associated with greater inappropriate ordering of initial outpatient pediatric TTEs compared with the academic practice. The assessment of practice patterns following AUC release should account for physician and practice-related factors that could influence differences in TTE ordering patterns.

View details for DOI 10.1016/j.jpeds.2018.11.057

View details for PubMedID 30661793

Abstract

Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Vascular dysfunction predates clinical presentation of preeclampsia. Therefore, we examined if a nonphysiological hormonal milieu, a modifiable state, affects maternal vascular health in early pregnancy. Blood pressure, endothelial function, circulating endothelial progenitor cell numbers, lipid levels, and corpus luteum (CL) hormones were compared in a prospective cohort of women with infertility history based on number of CL: 0 CL (programmed frozen embryo transfer [FET], N=18); 1 CL (spontaneous conception [N=16] and natural cycle FET [N=12]); or >3 CL associated with in vitro fertilization [N=11]. Women with 0 or >3 CL lacked the drop in mean arterial blood pressure compared with those with 1 CL (both P=0.05). Reactive hyperemia index was impaired in women with 0 CL compared with 1 CL ( P=0.04) while baseline pulse wave amplitude was higher with > 3 CL compared with 1 CL ( P=0.01) or 0 CL ( P=0.01). Comparing only FET cycles, a lower reactive hyperemia index and a higher augmentation index is noted in FETs with suppressed CL compared with FETs in a natural cycle (both P=0.03). The number of angiogenic and nonangiogenic circulating endothelial progenitor cell numbers was lower in the absence of a CL in FETs ( P=0.01 and P=0.03). Vascular health in early pregnancy is altered in women with aberrant numbers of CL (0 or >3) and might represent insufficient cardiovascular adaptation contributing to an increased risk of preeclampsia.

View details for PubMedID 30636549

Abstract

The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function.The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children 18years old distributed equally by age, gender, and race. A core lab used two-dimensional echocardiograms to measure LV dimensions from which a separate data coordinating center calculated LV volumes and systolic functional indices. To evaluate interobserver variability, two independent expert pediatric echocardiographic observers remeasured LV dimensions on a subset of studies, while blinded to calculated volumes and functional indices.Of 3,215 subjects with measurable images, 552 (17%) had a calculated LV shortening fraction (SF)<25% and/or LV ejection fraction (EF)<50%; the subjects were significantly younger and smaller than those with normal values. When the core lab and independent observer measurements were compared, individual LV size parameter intraclass correlation coefficients were high (0.81-0.99), indicating high reproducibility. The intraclass correlation coefficients were lower for SF (0.24) and EF (0.56). Comparing reviewers, 40/56 (71%) of those with an abnormal SF and 36/104 (35%) of those with a normal SF based on core lab measurements were calculated as abnormal from at least one independent observer. In contrast, an abnormal EF was less commonly calculated from the independent observers' repeat measures; only 9/47 (19%) of those with an abnormal EF and 8/113 (7%) of those with a normal EF based on core lab measurements were calculated as abnormal by at least one independent observer.Although blinded measurements of LV size show good reproducibility in healthy children, subsequently calculated LV functional indices reveal significant variability despite qualitatively normal systolic function. This suggests that, in clinical practice, abnormal SF/EF values may result in repeat measures of LV size to match the subjective assessment of function. Abnormal LV functional indices were more prevalent in younger, smaller children.

View details for DOI 10.1016/j.echo.2019.05.025

View details for PubMedID 31351792

Abstract

Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations.This was a multi-center (n=8) retrospective review of TTE reports in children 11 years of age who have had complete TOF repair. We included 10 patients from each participating center (n=80) and scored 2 outpatient follow-up TTE reports on each patient. The adherence rate was based on completeness of TTE reporting elements derived from the guidelines.We reviewed 160 TTE reports on 80 patients. Median age was 4.4 months (IQR 1.5-6.6) and 3.6 years (IQR 1.3-6.4) at the time of complete surgical repair and first TTE report, respectively. The median adherence rate to recommended reporting elements was 61% (IQR 53-70). Of the 160 reports, 9 (7%) were 80% adherent and 40 (25%) were 70% adherent. Quantitative measurements of right ventricular outflow tract (RVOT), right ventricular (RV) size and function, and branch pulmonary arteries were least likely to be reported.Overall adherence to the most recent published imaging guidelines for surveillance of children with repaired TOF patients was suboptimal, especially for reporting of RVOT, RV size and function, and branch pulmonary arteries. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes.

View details for DOI 10.1016/j.ijcard.2019.09.075

View details for PubMedID 31668657

Abstract

To evaluate whether invitro fertilization (IVF) has an effect on the cardiovascular health of offspring.This was a cross-sectional pilot study. We performed vascular health assessment for 17 children aged 10-14years who were conceived via IVF with autologous oocytes at Stanford University. Carotid artery ultrasound evaluated intima-media thickness and stiffness, carotid-femoral pulse wave velocity determined segmental arterial stiffness, and endothelial pulse amplitude testing assessed endothelial function. We compared IVF offspring with control adolescents assessed in the same laboratory, with all comparisons adjusted for age, sex, and race/ethnicity.All participants had normal body mass index and blood pressure. Compared with controls, IVF children had thicker common carotid artery intima-media thickness (0.440.03mm vs 0.380.03mm; P<.01), higher elastic modulus (395.29185.33mm Hg vs 242.7937.69mm Hg; P=.01), higher stiffness (2.650.38 vs 2.280.23; P<.01), and higher peak velocity (142.2931.62cm/s vs 117.7132.69cm/s; P=.04). The mean endothelial pulse amplitude testing reactive hyperemia index was not significantly different between IVF and controls. The mean pulse wave velocity was 4.690.51m/s compared with the controls 4.600.57m/s (P=.11), with 8 (47%) having abnormal values.In an assessment of endothelial function and arterial properties of children conceived via IVF, we found that children conceived via IVF seem to have evidence of abnormal vascular health. Further studies with larger sample size and long-term follow-up are warranted.

View details for DOI 10.1016/j.jpeds.2019.07.033

View details for PubMedID 31443895

Abstract

Although most pregnancies after assisted reproduction are associated with a favorable outcome for the mother and infant, reports of abnormal vascular adaptation in early pregnancy and emerging maternal and perinatal pathology warrant further investigations. Herein we extended our previous work and further examined whether perturbations of blood pressure and endothelial function during the first trimester in conceptions with nonphysiological corpus luteum (CL) numbers would persist through the third trimester of pregnancy and into the postpartum period. We investigated both maternal and perinatal outcomes. Participants were grouped according to CL number and method of conception: 0 CL (programmed autologous frozen-thawed embryo transfer, N=10-18); 1 CL (spontaneous conception [N=16] and natural cycle frozen-thawed embryo transfer [N=12]); or >3 CL associated with autologous fresh embryo transfer [N=8-12]. Augmentation index was higher during the third trimester in the absence of a CL compared to 1 CL (P=0.03) and in frozen-thawed embryo transfer in a programmed compared to a natural cycle (P=0.02). Moreover, baseline pulse-wave amplitude was higher in >3 CL conceptions at all time points (all P<0.05). The incidence of preeclampsia and preeclampsia with severe features was significantly higher in the absence of a CL compared to the presence of one or >3 CL (P=0.045 and P=0.03). Infants from conceptions with >3 CL had lower birth weights (P=0.02) and a higher rate of low birth weight offspring (P=0.008). Deficient vascular adaptation during early gestation in conceptions with nonphysiological CL numbers might predispose women to adverse pregnancy outcomes, for example, preeclampsia.

View details for DOI 10.1161/HYPERTENSIONAHA.119.13779

View details for PubMedID 31838910

Abstract

BACKGROUND: Pediatric heart transplant patients (PedHtx) require frequent monitoring by echocardiography (echo); however, they often live far from hospitals with pediatric echo services, resulting in urgent/emergent transfers to specialized institutions. Our primary objective was to evaluate the feasibility of parental acquisition of echo images to assess left ventricular (LV) systolic function in PedHtx using a handheld echo device. Secondary objectives included retesting for skill maintenance and in patients with decreased LV systolic function.METHODS: During a routine clinic visit, parents received 1-hour training with a handheld echo device to acquire images in parasternal short-axis and apical views. Parents recorded images on their children at training completion and 24hours later at home. An independent echocardiographer assessed clinic, training, and home echos for LV systolic function.RESULTS: Fifteen PedHtx (mean age of 12.6years of age; range, 4.1-16.7) were enrolled. All parents could acquire home images adequate for qualitative assessment of LV systolic function with no discrepancy compared with clinical echos. LV ejection fraction (LVEF) could be calculated (5/6 area-length method) in 86% of training and 43% of home echos with <10% difference in LVEF measurements between home and clinic echos. Five parents repeated home echos >12months later. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in two). Additionally, five heart failure patients with decreased LV systolic function (mean age of 8.6years; range 1.9-15.1) were enrolled. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in one).CONCLUSIONS: Our results suggest that parental home echo acquisition using a handheld echo device is feasible and adequate for qualitative assessment of LV systolic function in PedHtx. However, quantitative assessment of LV systolic function, especially in patients with dysfunction, and retention of the skill set without additional training are suboptimal.

View details for PubMedID 30598367

Abstract

BACKGROUND: Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long-term outcomes and quality of life. We designed a 12- to 16-week diet and exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported.METHODS: Inclusion criteria are as follows: (a) 8-19years old; (b) heart transplant >12months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3months ago; and (d) multi-organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period.RESULTS: A total of 13 participants (15.2 [2.3]years) have been enrolled. Median percent-predicted VO2 max was 56.8 [20.7]% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 [0.325]) and 11 patients had stiff arteries (pulse wave velocity 5.5m/s for 15-19years, 4.5m/s for 8-14years; 5.6 [0.7]m/s). Patients had suboptimal diets (saturated fat: 22.7 [23.8]g/d, sodium: 2771 [1557]mg/d) and were sedentary at a median of 67.5 [13.8]% of their time.CONCLUSIONS: Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non-pharmacologic lifestyle intervention in this patient population.

View details for PubMedID 30393915

Abstract

Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as 10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR]=2.13/each additional criterion, p=0.03) and greater left ventricular end-diastolic dimension z-score (OR=1.47/each 1 unit increase in z-score, p=0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR=1.56/each 1 unit increase in z-score, p=0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.

View details for DOI 10.1016/j.amjcard.2018.07.006

View details for Web of Science ID 000450698500019

View details for PubMedID 30115424

View details for PubMedCentralID PMC6497148

Abstract

Coarctation of the aorta (CoA) can be treated using surgery, balloon angioplasty, or stent implantation. Although short-term results are excellent with all three treatment modalities, long-term cardiovascular (CV) morbidity and mortality remain high, likely due to persistently abnormal vascular function. The effects of treatment modality on long-term vascular function remain uncharacterized. The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities.We will prospectively assess vascular Afunction in large and small arteries fusing multiple noninvasive modalities and compare the results among the three groups of CoA patients previously treated using surgery, balloon angioplasty, or stent implantation after frequency matching for confounding variables. A comprehensive vascular function assessment protocol has been created to be used in 7 centers. Our primary outcome is arterial stiffness measured by arterial tonometry. Inclusion and exclusion criteria have been carefully established after consideration of several potential confounders. Sample size has been calculated for the primary outcome variable.Treatment modalities for CoA may have distinct impact on large and small arterial vascular function. The results of this study will help identify the treatment modality that is associated with the most optimal level of vascular function, which, in the long term, may reduce CV risk.

View details for PubMedID 30271019

View details for PubMedCentralID PMC6146860

Abstract

The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate-corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (-0.2980.139 vs 0.1410.139/year, p=0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618mmHg) predicted a smaller annual decrease in ARz (p 0.001). Upper-quartile aortic-root EM (>914mmHg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p=0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.

View details for DOI 10.1016/j.amjcard.2018.01.016

View details for PubMedID 29631804

Abstract

Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of thegreat arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index 85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n=57). We tested 20 D-TGA patients (16.44.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.780.61 vs. 1.730.54, p=0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

View details for DOI 10.1007/s00246-017-1609-6

View details for PubMedID 28345114

Abstract

In mothers with pre-gestational or gestational diabetes, abnormal arterial stiffness (stiffer arteries) has been reported. The impact of abnormal maternal arterial stiffness on fetal placental and cardiovascular physiology is unknown. The purpose of the study was to determine the impact of maternal diabetes on maternal arterial stiffness and the association with fetal cardiovascular physiology as measured by fetal echocardiography.Between December 2013 and January 2017 we conducted a prospective study on diabetic (otherwise healthy) and non-diabetic, healthy pregnant mothers (at 20-28 gestational weeks and 18-40 years of age) who had a normal fetal cardiac echocardiogram and obstetric ultrasound. Clinical data were collected by means of a patient questionnaire, measurement of blood pressure, height and weight, arterial augmentation index and fetal placental and cardiovascular parameters by fetal echocardiography. Descriptive statistics were calculated. Comparisons were made using parametric and non-parametric tests between controls and diabetic mothers.Twenty-three healthy pregnant controls and 43 diabetic pregnant women (n=22 pre-gestational, n=21 gestational) were included in the study. Maternal arterial augmentation index was higher in those with diabetes compared to healthy controls (12.410.6% versus 4.67.9%; p=0.003). Fetal aortic valve velocity time integral was higher in fetuses whose mothers had diabetes compared to non-diabetic mothers (7.71.9cm versus 6.32.9cm; p=0.022). Left ventricular myocardial performance index was lower in diabetic pregnancies compared to controls (0.400.09 versus; 0.460.11 p=0.02). Umbilical artery resistance index was lower in diabetic pregnancies with hemoglobin A1C levels 6.5% compared to those with HbA1c levels <6.5 (HbA1c 6.5%: 0.690.06, n=15 versus HbA1c <6.5%: 0.760.08, n=21; p=0.009) but not at higher HbA1C cut-offs. A correlation between arterial augmentation index and velocity time integral, myocardial performance index or umbilical artery resistance index was not found.Arterial stiffness is higher in pregnant women with diabetes compared to controls. Fetuses of diabetic mothers show altered cardiovascular parameters with higher velocity time integral and lower left ventricular myocardial performance index, markers of myocardial function. Placental function assessed by umbilical artery resistance was normal despite differences between groups. Arterial stiffness did not correlate with placental or fetal cardiovascular variables. Instead, the findings likely represent a shared response to the environment of abnormal glucose metabolism. The clinical significance of these findings is yet to be determined.

View details for DOI 10.1002/uog.17528

View details for PubMedID 28508434

Abstract

Management of right-dominant atrioventricular septal defect (AVSD) remains a challenge given the spectrum of ventricular hypoplasia. The purpose of this study was to assess whether reported echocardiographic indices and additional measurements were associated with operative strategy in right-dominant AVSD.A blinded observer retrospectively reviewed preoperative echocardiograms of patients who underwent surgery for right-dominant AVSD (January 2000 to July 2013). Ventricular dimensions, atrioventricular valve index (AVVI; left valve area/right valve area), and right ventricular (RV)/left ventricular (RV/LV) inflow angle were measured. A second observer measured a subset of studies to assess agreement. Pearson correlation analysis was performed to examine the relationship between ventricular septal defect size (indexed to body surface area) and RV/LV inflow angle in systole. A separate validation cohort was identified using the same methodology (August 2013 to July 2016).Of 46 patients with right-dominant AVSD (median age, 1day; range, 0-11months), overall survival was 76% at 7years. Twenty-eight patients (61%) underwent single-ventricle palliation and had smaller LV dimensions and volumes, AVVIs (P=.005), and RV/LV inflow angles in systole (P=.007) compared with those who underwent biventricular operations. Three patients undergoing biventricular operations underwent transplantation or died and had lower indexed LV end-diastolic volumes compared with the remaining patients (P=.005). Interobserver agreement for the measured echocardiographic indices was good (intraclass correlation coefficient=0.70-0.95). Ventricular septal defect size and RV/LV inflow angle in systole had astrong negative correlation (r=-0.7, P<.001). In the validation cohort (n=12), RV/LV inflow angle insystole114 yielded sensitivity of 100% and AVVI0.70 yielded sensitivity of 88% for single-ventricle palliation.Mortality remains high among patients with right-dominant AVSD. RV/LV inflow angle in systole and AVVI are reproducible measurements that may be used in conjunction with several echocardiographic parametersto support suitability for a biventricular operation in right-dominant AVSD.

View details for DOI 10.1016/j.echo.2016.10.017

View details for PubMedID 27939051

Abstract

To review current institutional practice and describe factors contributing to variation in inpatient postoperative imaging surveillance after congenital heart surgery.We reviewed records of all children who underwent congenital heart surgery from June to December 2014. Number and primary indications for postoperative transthoracic echocardiograms (TTEs), providers involved, cardiovascular intensive care unit (CVICU) and total hospital length of stay, and Risk-Adjustment for Congenital Heart Surgery-1 scores were recorded.A total of 253 children (age at surgery: 8 months [2 days-19 years]) received 556 postoperative TTEs (median 1 TTE/patient [1-14]), and 23% had 3 TTEs. Fifteen of 556 TTEs (2.7%) revealed a new abnormal finding. The majority of TTEs (59%) were performed in the CVICU (1.51.1 TTEs/week/patient), with evaluation of function as the most common indication (44%). Attending physician practice >10 years was not associated with fewer TTEs (P=.12). Patients with 3 TTEs had higher Risk-Adjustment for Congenital Heart Surgery-1 scores (P=.001), longer CVICU lengths of stay (22 vs 3 days; P<.0001), longer overall hospitalizations (28 vs 7 days; P<.0001), and a higher incidence of mechanical circulatory support (10% vs 0%; P<.0001) than those with <3 TTEs. Eight patients with 3 TTEs did not survive, compared with 3 with <3 TTEs (P=.0004).There was wide intra-institutional variation in echocardiographic use among similar complexity surgeries. Frequency of postoperative echocardiographic surveillance was associated with degree of surgical complexity and severity of postoperative clinical condition. Few studies revealed new abnormal findings. These results may help establish evidence-based guidelines for inpatient echocardiographic surveillance after congenital heart surgery.

View details for DOI 10.1016/j.jpeds.2016.09.061

View details for Web of Science ID 000390028100018

Abstract

Present resource-based relative value unit (RVU) assignment for echocardiography is based on Current Procedural Terminology (CPT) codes, which do not incorporate complexity of diagnosis, time spent for image acquisition, or interpretation of echocardiograms. The objective of this study was to determine whether CPT-based RVU assignment accurately reflects physician effort in performing and interpreting pediatric echocardiographic examinations.Cardiac complexity category (CCC) and physician time for study interpretation of 123 echocardiograms (June to September 2013) were prospectively assigned. Categories included (1) focused effusion/function evaluation, (2) normal anatomy/focused preterm infant studies, (3) acquired heart disease, (4) congenital heart disease excluding single ventricles, (5) single ventricles including heterotaxy syndrome, and (6) hearts on mechanical support. Subsequently, a random sample of echocardiograms (March to August 2013) were retrospectively analyzed, and each study was assigned a CCC and an extrapolated median interpretation time (MIT) on the basis of prospective data collection. Assigned work RVUs based on CPT codes were recorded. Comparisons were made between CCC and time for study interpretation, work RVUs, number of images acquired, and total scan time.A total of 933 echocardiograms were analyzed: 198 (21%), 174 (19%), 98 (11%), 359 (35%), 84 (9%), and 20 (2%) studies in CCCs 1 to 6, respectively. Total scan time, MIT, number of images, and work RVUs were different among CCCs (P<.0001). However, among the more complex studies (CCCs 2-5), work RVUs were similar, while number of images obtained and MIT were different (P<.001). Correlation analysis showed no association between work RVUs and CCC, total scan, or number of images per study. Compared with older patients, work RVUs of studies in children <2years of age were lower, while all other markers of study complexity were higher (P<.05).Current CPT-based assignment of work RVUs does not discriminate study complexity and physician effort. The results of this study highlight the need for a refined system that accurately assesses physician effort in pediatric echocardiography.

View details for DOI 10.1016/j.echo.2016.05.015

View details for PubMedID 27405593

Abstract

Aortic pulse wave velocity (PWV) and augmentation index (AIx) are markers of vascular health and have recently been used in pediatric clinical trials. However, there are limited data on standardization of these measurements in pediatrics. The objective of this study was to prospectively test the feasibility and reproducibility of PWV and AIx in children and adolescents.We performed arterial tonometry on 2 different days within 2 weeks in 40 healthy subjects aged 10-19 years. PWV and AIx were measured in triplicate on each visit.The visits were separated by a mean of 3.083.7 days. We obtained PWV in 77 of 80 (96%) visits and AIx in 76 of 80 (95%) visits in triplicate. Intraclass correlation coefficients (ICCs) for PWV were 0.61 (95% confidence interval (CI) = 0-0.86) when at least 2 measurements and 0.92 (95% CI = 0-1) when 3 measurements were obtained at each visit that met the quality criteria established for adults by the manufacturer (n = 17 and 3 paired visits, respectively). For AIx, ICCs were 0.78 (95% CI = 0.58-0.88) and 0.81 (95% CI = 0.63-0.90) when measurements with an operator index 80, a measure of the quality of the waveform, were included (n = 39 and 36 paired visits, respectively).Arterial applanation tonometry is feasible and reproducible in healthy children and adolescents. AIx has excellent intervisit reproducibility, whereas the intervisit reproducibility of PWV relies on acquisition of multiple measurements that meet quality criteria established for adults. These results have implications for the methodology of future pediatric clinical trials in a population at increasingly higher risk for premature atherosclerosis.

View details for DOI 10.1093/ajh/hpu034

View details for Web of Science ID 000342853700013

Abstract

Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 difference/mean).Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error.This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible.

View details for DOI 10.1016/j.echo.2012.05.004

View details for Web of Science ID 000306657900008

View details for PubMedID 22677278

Abstract

Coronary artery dilation (CAD) and left ventricular systolic dysfunction are recognized complications of Kawasaki Disease (KD). Diastolic function assessed by echocardiography in the KD patient population and its interrelationship to the KD course, systolic dysfunction, and CAD is less well characterized. The purpose of this study was to determine whether diastolic function is impaired in KD patients and whether there are any clinical correlates.All KD patients with an echocardiogram recording of tissue Doppler velocities were included. Patients were analyzed based on CAD (Group I: patients who had CAD during their disease course; Group II: patients who never had CAD). In addition, we compared measures of diastolic function in patients with echocardiograms 0-30 days (n=35) and >30 days (n=72) post-IVIG treatment.116 patients (80 males) were included (mean age, 7.76.7 years; mean time since KD onset, 4.05.6 years). Group I (41 patients, 36%), compared to Group II, had decreased E'(lateral) and longer mitral early deceleration time. E'(lateral) and E'(septal) were significantly decreased in patients 0-30 days vs. >30 days post-IVIG, whereas mitral early deceleration time was not significantly different.Our results demonstrate that there is impaired relaxation in KD patients in the early phase of the disease and in KD patients with CAD during the disease course.

View details for DOI 10.1016/j.ijcard.2009.11.014

View details for PubMedID 19945179

Abstract

To test prospectively the reproducibility and feasibility of endothelial pulse amplitude testing (Endo-PAT), a novel Food and Drug Administration-approved technology, in healthy adolescents.We performed Endo-PAT testing on 2 different days separated by no more than 7 days in 30 healthy fasting adolescents, ages 13 to 19 years, to assess reproducibility and feasibility. The reported level of discomfort, as measured on a pain scale of 1 to 5, was documented.The mean difference in paired Endo-PAT indices was 0.12 (95% CI, -0.09-0.33; P = .24; intraclass correlation coefficient, 0.78), and the within-subject variation of Endo-PAT index was 0.16. The Endo-PAT index on test days 1 and 2 were 1.91 +/- 0.57 and 1.78 +/- 0.51 (mean plus or minus SD), respectively. All attempted studies (100%) were completed (95% CI, 88%-100%), and all completed studies (100%) could be analyzed (95% CI, 88%-100%). The median pain score was 1 on both days.In healthy adolescents, Endo-PAT is feasible and has excellent reproducibility. This technology may provide an easy and reliable means of assessing endothelial function in the pediatric population.

View details for DOI 10.1016/j.jpeds.2008.12.028

View details for Web of Science ID 000266685800030

View details for PubMedID 19217124

Abstract

Severe aortic stenosis in the mid-gestation fetus can progress to hypoplastic left heart syndrome (HLHS). @ In-utero aortic valvuloplasty is an innovative therapy to promote left ventricular growth and function and potentially to prevent HLHS. This study evaluated the effects of mid-gestation fetal balloon aortic valvuloplasty on subsequent fetal left ventricular function and left heart Doppler characteristics.We reviewed fetuses with aortic stenosis that underwent attempted in-utero aortic valvuloplasty between 2000 and 2006. Pre-intervention and the latest post-intervention fetal echocardiograms were analyzed to characterize changes in left heart function and Doppler characteristics in utero.Forty-two fetuses underwent attempted aortic valvuloplasty during the study period, 12 of which were excluded from analysis secondary to inadequate follow-up data, termination or fetal demise. Study fetuses (n = 30) underwent pre-intervention echocardiography at a median gestational age of 23 weeks, and were followed for a median of 66 +/- 23 days post-intervention. In 26 fetuses, aortic valvuloplasty was technically successful. Among these 26, left heart physiology was abnormal pre-intervention and improved or normalized after intervention in most cases: biphasic mitral inflow was present in 5/25 (20%) cases pre-intervention and in 21/23 (91%) post-intervention (P < 0.001); moderate or severe mitral regurgitation was present in 14/26 (54%) cases pre-intervention and in 5/23 (22%) post-intervention (P = 0.02); bidirectional flow across the patent foramen ovale was present in 0/26 cases pre-intervention and in 6/25 (24%) post-intervention (P = 0.01); antegrade flow in the transverse arch was present in 0/25 cases pre-intervention and in 17/26 (65%) post-intervention (P < 0.001). The left ventricular ejection fraction increased from 19 +/- 10% pre-intervention to 39 +/- 14% post-intervention (P < 0.001). These changes were not observed in control fetuses (n = 18).Fetal aortic valvuloplasty, when technically successful, improves left ventricular systolic function and left heart Doppler characteristics.

View details for DOI 10.1002/uog.5132

View details for Web of Science ID 000250732900006

View details for PubMedID 17764106

View details for DOI 10.1016/j.jpeds.2007.05.01

View details for Web of Science ID 000249442800002

View details for PubMedID 17719924

Abstract

This study was designed to assess the frequency and types of genetic variants in CFC1 in children with laterality disorders associated with cardiovascular involvement.Laterality syndromes are estimated to comprise 3% of neonates with congenital cardiac disease. Genetic predisposition in some cases of laterality defects has been suggested by associated chromosomal anomalies and familial aggregation, often within consanguineous families, suggesting autosomal recessive inheritance. Mice with induced homozygous mutations in cfc1, and heterozygous CFC1 mutations in humans, have been associated with laterality defects.Direct sequence analysis of the coding sequence of CFC1 was performed in 42 subjects with laterality defects and congenital cardiac disease.We identified 3 synonymous coding variants, 3 non-synonymous coding variants (N21H, R47Q, and R78W), and 2 intronic variants in CFC1. The N21H variant was observed in 3 of 19 affected Caucasians, and the R47Q variant in another 2. Neither polymorphism was observed in Caucasian controls. Furthermore, all subjects with the N21H polymorphism had double outlet right ventricle. Transmission of both the N21H and R47Q polymorphisms from unaffected parents was demonstrated, and all three non-synonymous variants had significant allele frequencies in unaffected African-American subjects, suggesting that other factors must also contribute to laterality defects.Three non-synonymous variants in CFC1 were identified, the N21H variant being associated with laterality defects in Caucasians, but not fully penetrant. One or more of these non-synonymous missense variants may act as a susceptibility allele in conjunction with other genes, and/or environmental factors, to cause laterality defects.

View details for DOI 10.1017/S1047951107000455

View details for Web of Science ID 000247220000005

View details for PubMedID 17445335

Abstract

To test the hypothesis that chronic beta-blocker therapy in pediatric patients with Marfan syndrome alters the rate of aortic root dilation. Beta-blockade has been advocated as preventive therapy for Marfan syndrome based on reports indicating a decreased rate of aortic root dilation in treated patients.Patients with Marfan syndrome (n = 63) followed at Children's Hospital of Pittsburgh or Children's Hospital of New York-Presbyterian who had > or =18 months of echocardiographic follow-up were studied. All clinical data and 213 serial echocardiograms were reviewed, and aortic root dimensions were measured. Patients were divided into 2 groups for comparison: untreated (n = 34) and treated (n = 29).At study entry, the 2 study groups were comparable in terms of age, sex, body surface area (BSA), aortic root measurements, heart rate, and corresponding z scores. Follow-up duration in each group was similar. At last follow-up, heart rates and heart rate z scores were lower in the treated group. Rates of change of aortic root measurements (P = .52) and the corresponding z scores were not statistically different between the 2 group at the study's end.This study suggests that that beta-blocker therapy does not significantly alter the rate of aortic root dilation in children with Marfan syndrome. Based on these data, the recommendation of lifetime beta-blocker therapy instituted during childhood should be reassessed.

View details for DOI 10.1016/j.jpeds.2006.09.003

View details for Web of Science ID 000243450500018

View details for PubMedID 17188619