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. 3.7 years;
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.
Objective
Postoperative left ventricular dysfunction is associated with poor prognosis in adults with severe chronic aortic regurgitation and published practice guidelines aim to minimize this risk. ...However, only limited information exists in pediatrics. The goal of this study was to define preoperative risk factors for postoperative left ventricular dysfunction in children with chronic aortic regurgitation.
Methods
Patients fulfilling the following criteria were included in this study: (1) age at preoperative echocardiogram ≤18 years; (2) ≥moderate aortic regurgitation; (3) ≤mild aortic valve stenosis; (4) no additional valve disease/shunt; (5) underwent aortic valve surgery for aortic regurgitation; and (6) available preoperative and ≥6‐month postoperative echocardiograms with adequate information. Primary outcome was postoperative left ventricular dysfunction defined as ejection fraction z‐score < −2.
Results
Median ages at diagnosis and surgery of the 53 eligible patients were 6.9 (0.04–17.2) and 13 years (1.2–22.4), respectively. Compared with patients whose postoperative left ventricular ejection fraction was normal, those with left ventricular ejection fraction z‐score < −2 (n = 10) had significantly higher preoperative left ventricular end‐diastolic and systolic volumes and dimensions and lower indices of systolic function. Preoperative left ventricular ejection fraction z‐score < −1 was the most sensitive (89%; confidence interval CI 52, 100) but least specific (58%; CI 41, 73), whereas left ventricular end‐systolic diameter z‐score ≥ 5 was the most specific (95%; CI 84, 99) but least sensitive (60%; CI 26, 88) outcome identifier. A combination of shortening fraction z‐score < −1 or end‐systolic diameter z‐score ≥ 5 best identified postoperative left ventricular dysfunction with an area of 0.819 under the receiver‐operator characteristic curve.
Conclusion
Lower indices of left ventricular systolic function and severity of dilation identify children at risk for postoperative left ventricular dysfunction after aortic valve surgery. These identifiers are similar to predictors defined in adult patients albeit with different threshold values.
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 20-40 years) with at least 2 local echocardiograms 6 months 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, 19-24 years at first echocardiogram) were included. AoR dilation rate in the entire cohort was 0 to 8 mm/year (median, 0.465; IQR, 0.23-1.45 mm/year). Multiple linear regression analysis showed that baseline AoR stiffness was associated with AoR dilation rate (β = 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, 4.27 cm; IQR, 4.05-4.49 cm vs NSx, 3.73 cm; IQR, 3.37-4.09 cm; 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 (1.63 ± 0.41 mm/year vs 0.38 ± 0.08 mm/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.
Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital ...discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24 hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio OR, 2.3 1.1-5.0, 95% CI, per m/s;
=0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 1.3-14.2;
=0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.
In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions ...normalized as
z
-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (
z
-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA
z
-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was “indicated.” Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2–25% for RL 5, and 0–5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.
M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The ...reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement.
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.
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. The authors propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. The aim of this study was to test the hypothesis that right and left ventricular minute VTI increase predictably with estimated fetal weight and are more reproducible than CO.
Five hundred seventy-one singleton fetuses without cardiovascular pathology between 16 and 36 weeks' gestation were reviewed retrospectively. Twenty-two fetuses with pathology resulting in low- or high-CO 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 of >30°. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter- and intrarater variability were evaluated in a random 10% subset.
Minute VTI and CO measurements were feasible in 67% to 89% of fetuses in this retrospective study. Minute VTI and CO increased with estimated fetal weight nonlinearly (R = 0.61-0.94). The mean inter- and intrarater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (P < .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 used to track fetuses in disease states with low or high CO.
Abstract only Intro: The Pediatric Heart Network (PHN) trial of β-blockers (BB) vs. angiotensin receptor blockers (ARB) for aortic root dilation in Marfan Syndrome showed similar efficacy, but its ...impact on prescribing practices is unknown. We hypothesized there would be an increase in single and combination use of BB and ARB after publication in 2014. Methods: Prescription data (2007-2016) were derived from outpatient encounters (IBM Marketscan) for children and young adults aged 6 mo to 25 yrs diagnosed with Marfan Syndrome who had ≥4 encounters with an adult or pediatric cardiologist or geneticist. Excluding 2014 as washout, data were divided into 2 time periods: 2007-2013 and 2015-2016. Categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug use. We performed interrupted time-series analysis to assess the immediate level change and the change in slope for the prescription trend. We reported odds ratios (OR) and 95% confidence intervals (CI) from logistic regressions with generalized estimating equation methods to account for correlation of prescriptions within subjects. Results: Of 1499 patients (mean age 14.1 yrs, 59% female), BB had a downtrend OR 0.91 (0.89, 0.93), p<0.001 and ARB trended higher OR 1.12 (1.07, 1.18), p<0.001 2007-2013, while combination, ACEI, and no drug use remained stable. There was no immediate effect after publication (2013-2015). Although the trend persisted for BB and ARB use (see Figure), the change in slope was not significant (2015-2016). Combination, ACEI and no drug use remained consistent. Conclusions: In short term follow-up, the impact of the PHN trial on prescription practices for aortic root dilation in Marfan Syndrome in children and young adults did not reach statistical significance. This may be due to early adoption of ARBs with subsequent confirmation of their usefulness. Longer term data are needed to fully explore the trial’s impact on practice change.
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