First name
Lynn
Middle name
A
Last name
Sleeper

Title

Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1097-6833

Abstract

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension) in a large, multicenter pediatric pulmonary hypertension registry.

STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with and without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome.

RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. Median age of pulmonary hypertension diagnosis in patients with Down syndrome was 0.49 years (IQR 0.21, 1.77), similar to non-Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with or without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%, repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). pulmonary hypertension resolved in 43% after 3 years, associated with pulmonary hypertension diagnosis age <6 months (54% vs 29%, p=0.002) and pre-tricuspid shunt (65% vs 38%, p=0.02). Five-year transplant-free survival was 88% (95% CI: 80-97%). Tracheostomy (HR 3.29, 95% CI 1.61-6.69) and reflux medication use (HR 2.08, 95% CI 1.11-3.90) were independently associated with for a composite outcome of severe pulmonary hypertension.

CONCLUSIONS: Despite high rates of cardiac and respiratory comorbidities that influence pulmonary hypertension severity, children with Down syndrome-associated pulmonary hypertension generally have survival rates similar to children with non-Down syndrome-associated pulmonary hypertension. Pulmonary hypertension resolution is common, but reduced among children with complicated respiratory comorbidities.

DOI

10.1016/j.jpeds.2022.08.027

Alternate Title

J Pediatr

PMID

36027975

Title

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.

Year of Publication

2021

Number of Pages

e017731

Date Published

2021 Apr 28

ISSN Number

2047-9980

Abstract

<p>Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing (=0.005 and =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first-degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01873963.</p>

DOI

10.1161/JAHA.120.017731

Alternate Title

J Am Heart Assoc

PMID

33906374

Title

The impact of pre-implant illness severity on the outcomes of pediatric patients undergoing durable ventricular assist device.

Year of Publication

2020

Date Published

2020 Feb 24

ISSN Number

1557-3117

Abstract

<p><strong>BACKGROUND: </strong>Durable ventricular assist devices (VADs) are increasingly used to treat children with heart failure. Studies demonstrate worse outcomes for those in cardiogenic shock at the time of VAD, but limited data exist on less acutely ill children. We describe the association between illness severity and outcomes in this population.</p>

<p><strong>METHODS: </strong>Data were analyzed from 373 children (aged &lt;19 years) receiving durable VADs from 46 centers in the Pediatric Interagency Registry for Mechanical Circulatory Support. Outcomes were compared by Interagency Registry for Mechanical Circulatory Support (INTERMACS) Patient Profile (PP) and pre-implant characteristics using competing risks methodology.</p>

<p><strong>RESULTS: </strong>Analyses identified 97 patients in cardiogenic shock (PP 1), 222 with progressive decline (PP 2), and 42 stable on inotropes (PP 3). There were 39 infants, 124 were aged 1 to 9 years and 210 were aged 10 to 19 years. A majority had cardiomyopathy and 66 had congenital heart disease (CHD). There were 224 (62%) continuous-flow VADs. Before implant, 40% received mechanical ventilation (MV). Within 6 months post-implant, 57% underwent transplant and 14% died. PP 1 mortality was highest (25% vs 10% for PP 2, hazard ratio [HR]: 2.5, 95% CI: 1.4-4.4, p = 0.02). In PP 1, CHD was an independent mortality risk factor (HR: 2.9, 95% CI: 1.1-7.8, p = 0.03). In PP 2, pulsatile VADs were associated with death (HR: 3.9, 95% CI: 1.6-9.5, p = 0.003). Patients on MV had high mortality (20%-30%) across PP 1 to PP 3 (HR: 3.0 vs no MV, p &lt; 0.001).</p>

<p><strong>CONCLUSIONS: </strong>Children in shock at the time of VAD implant have poor outcomes. MV is associated with increased mortality even in lower acuity INTERMACS profiles. Further study is needed to identify modifiable risk factors in this population.</p>

DOI

10.1016/j.healun.2020.02.011

Alternate Title

J. Heart Lung Transplant.

PMID

32165048

Title

Cardiac Biomarkers in Pediatric Cardiomyopathy: Study Design and Recruitment Results from the Pediatric Cardiomyopathy Registry.

Year of Publication

2019

Number of Pages

1-10

Date Published

2019 Jun

ISSN Number

1058-9813

Abstract

<p><strong>Background: </strong>Cardiomyopathies are a rare cause of pediatric heart disease, but they are one of the leading causes of heart failure admissions, sudden death, and need for heart transplant in childhood. Reports from the Pediatric Cardiomyopathy Registry (PCMR) have shown that almost 40% of children presenting with symptomatic cardiomyopathy either die or undergo heart transplant within 2 years of presentation. Little is known regarding circulating biomarkers as predictors of outcome in pediatric cardiomyopathy.</p>

<p><strong>Study Design: </strong>The Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) study is a multi-center prospective study conducted by the PCMR investigators to identify serum biomarkers for predicting outcome in children with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Patients less than 21 years of age with either DCM or HCM were eligible. Those with DCM were enrolled into cohorts based on time from cardiomyopathy diagnosis: categorized as new onset or chronic. Clinical endpoints included sudden death and progressive heart failure.</p>

<p><strong>Results: </strong>There were 288 children diagnosed at a mean age of 7.2±6.3 years who enrolled in the PCM Biomarkers Study at a median time from diagnosis to enrollment of 1.9 years. There were 80 children enrolled in the new onset DCM cohort, defined as diagnosis at or 12 months prior to enrollment. The median age at diagnosis for the new onset DCM was 1.7 years and median time from diagnosis to enrollment was 0.1 years. There were 141 children enrolled with either chronic DCM or chronic HCM, defined as children ≥2 years from diagnosis to enrollment. Among children with chronic cardiomyopathy, median age at diagnosis was 3.4 years and median time from diagnosis to enrollment was 4.8 years.</p>

<p><strong>Conclusion: </strong>The PCM Biomarkers study is evaluating the predictive value of serum biomarkers to aid in the prognosis and management of children with DCM and HCM. The results will provide valuable information where data are lacking in children.</p>

<p><strong>Clinical Trial Registration NCT01873976: </strong>https://clinicaltrials.gov/ct2/show/NCT01873976?term=PCM+Biomarker&amp;…;

DOI

10.1016/j.ppedcard.2019.02.004

Alternate Title

Prog. Pediatr. Cardiol.

PMID

31745384

Title

Prevalence, predictors, and outcomes of cardiorenal syndrome in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry.

Year of Publication

2015

Number of Pages

2177-88

Date Published

2015 Dec

ISSN Number

1432-198X

Abstract

<p><strong>BACKGROUND: </strong>The association of cardiorenal syndrome (CRS) with mortality in children with dilated cardiomyopathy (DCM) is unknown.</p>

<p><strong>METHODS: </strong>With a modified Schwartz formula, we estimated glomerular filtration rates (eGFR) for children ≥1 year of age with DCM enrolled in the Pediatric Cardiomyopathy Registry at the time of DCM diagnosis and annually thereafter. CRS was defined as an eGFR of &lt;90 mL/min/1.73 m(2). Children with and without CRS were compared on survival and serum creatinine concentrations (SCr). The association between eGFR and echocardiographic measures was assessed with linear mixed-effects regression models.</p>

<p><strong>RESULTS: </strong>Of 285 eligible children with DCM diagnosed at ≥1 year of age, 93 were evaluable. CRS was identified in 57 of these 93 children (61.3%). Mean (standard deviation) eGFR was 62.0 (22.6) mL/min/1.73 m(2) for children with CRS and 108.0 (14.0) for those without (P &lt; 0.001); median SCr concentrations were 0.9 and 0.5 mg/dL, respectively (P &lt; 0.001). The mortality hazard ratio of children with CRS versus those with no CRS was 2.4 (95% confidence interval 0.8-7.4). eGFR was positively correlated with measures of left ventricular function and negatively correlated with age.</p>

<p><strong>CONCLUSIONS: </strong>CRS in children newly diagnosed with DCM may be associated with higher 5-year mortality. Children with DCM, especially those with impaired left ventricular function, should be monitored for renal disease.</p>

DOI

10.1007/s00467-015-3165-8

Alternate Title

Pediatr. Nephrol.

PMID

26210985

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