First name
Catherine
Middle name
M
Last name
Avitabile

Title

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

Year of Publication

2022

Number of Pages

1246-1254

Date Published

06/2022

ISSN Number

1476-5543

Abstract

OBJECTIVE: To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH).

STUDY DESIGN: Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood.

RESULT: After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001].

CONCLUSION: In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.

DOI

10.1038/s41372-022-01421-6

Alternate Title

J Perinatol

PMID

35676536

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

Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension.

Year of Publication

2022

Number of Pages

458-466

Date Published

09/2022

ISSN Number

1468-2052

Abstract

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.

DOI

10.1136/archdischild-2021-322617

Alternate Title

Arch Dis Child Fetal Neonatal Ed

PMID

34952853

Title

A multifaceted approach to the management of plastic bronchitis after cavopulmonary palliation.

Year of Publication

2014

Number of Pages

634-40

Date Published

2014 Aug

ISSN Number

1552-6259

Abstract

<p><strong>BACKGROUND: </strong>Plastic bronchitis is a rare, potentially life-threatening complication after Fontan operation. Hemodynamic alterations (elevated central venous pressure and low cardiac output) likely contribute to the formation of tracheobronchial casts composed of inflammatory debris, mucin, and fibrin. Pathologic studies of cast composition support medical treatment with fibrinolytics such as inhaled tissue plasminogen activator (t-PA).</p>

<p><strong>METHODS: </strong>This was a retrospective case series of medical, surgical, and catheter-based treatment of patients with plastic bronchitis after cavopulmonary palliation.</p>

<p><strong>RESULTS: </strong>Included were 14 patients (86% male, 93% white). Median age at Fontan operation was 2.7 years (range, 1.2 to 4.1 years), with median interval to plastic bronchitis presentation of 1.5 years (range, 9 days to 15.4 years). Cast composition was available for 11 patients (79%) and included fibrin deposits in 7. All patients were treated with pulmonary vasodilators, and 13 (93%) were treated with inhaled t-PA. Hemodynamically significant lesions in the Fontan pathway were addressed by catheter-based (n=9) and surgical (n=3) interventions. Three patients (21%) underwent heart transplantation. Median follow-up was 2.7 years (range, 0.6 to 8.7 years). Symptoms improved, such that 6 of 13 patients (46%) were weaned off t-PA. Rare or episodic casts are successfully managed with outpatient t-PA in most of the other patients. Of the 3 patients who underwent heart transplant, 2 are asymptomatic and 1 has recurrent casts in the setting of elevated filling pressures and rejection.</p>

<p><strong>CONCLUSIONS: </strong>A systematic step-wise algorithm that includes optimization of hemodynamics, aggressive pulmonary vasodilation, and inhaled t-PA is an effective treatment strategy for patients with plastic bronchitis after cavopulmonary connection.</p>

DOI

10.1016/j.athoracsur.2014.04.015

Alternate Title

Ann Thorac Surg

PMID

24841545

Title

Exercise capacity in the Fontan circulation.

Year of Publication

2013

Number of Pages

824-30

Date Published

2013 Dec

ISSN Number

1467-1107

Abstract

<p>The Fontan operation can create a stable circulation from childhood through early adulthood. However, the absence of a sub-pulmonary pumping chamber leads to a physiology in which exercise capacity is limited and decreases with age starting in adolescence. The limitation in exercise capacity is more pronounced at peak levels of exercise, but is still present during more modest levels of activity. The underlying causes of exercise impairment relate to both central cardiovascular factors (oxygen delivery) and peripheral factors (oxygen extraction). Interventions to improve cardiac preload and to improve lean muscle mass may help to improve exercise capacity and, perhaps, will alter the "natural history" of the progressive decline.</p>

DOI

10.1017/S1047951113001649

Alternate Title

Cardiol Young

PMID

24401254

Title

Children with protein-losing enteropathy after the Fontan operation are at risk for abnormal bone mineral density.

Year of Publication

2012

Number of Pages

1264-8

Date Published

2012 Dec

ISSN Number

1432-1971

Abstract

<p>Protein-losing enteropathy (PLE) is a rare but potentially devastating complication of single-ventricle physiology after the Fontan operation. Although abnormal bone mineral density (BMD) is a known complication of chronic disease and congenital heart disease, no reports have described BMD in patients with PLE. This study investigated a cross-sectional sample of children and young adults with a confirmed diagnosis of PLE. Serum levels of 25(OH)D, calcium, total protein, and albumin were recorded from the first outpatient encounter with each subject. Corrected calcium (cCa) was calculated from the serum calcium and albumin levels. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD, and z-scores were generated using appropriate software. DXA results were available for 12 patients (eight males and four females). The age at DXA ranged from 7.2 to 25.2 years. The mean z-score was -1.73 standard deviation (SD) for the entire cohort, with 42 % z-scores below -2 SDs. Serum 25(OH)D levels were abnormal in 58 % of the patients. There was a positive correlation between cCa and DXA z-score and a negative correlation between total protein and DXA z-score. Patients receiving corticosteroid therapy had a significantly lower DXA z-score than those not receiving corticosteroids (-3.15 vs. -0.31; p = 0.02). Children with PLE are at risk for abnormal BMD compared with age- and sex-matched control subjects. In the study cohort, corticosteroid exposure, a marker of disease severity, appeared to be associated with decreased BMD. Routine bone health screening is warranted for children with PLE, particularly those receiving corticosteroid therapy.</p>

DOI

10.1007/s00246-012-0290-z

Alternate Title

Pediatr Cardiol

PMID

22434509

Title

Tricuspid annular plane systolic excursion does not correlate with right ventricular ejection fraction in patients with hypoplastic left heart syndrome after Fontan palliation.

Year of Publication

2014

Number of Pages

1253-8

Date Published

2014 Oct

ISSN Number

1432-1971

Abstract

<p>Tricuspid annular plane systolic excursion (TAPSE) reflects longitudinal myocardial shortening, the main component of right ventricular (RV) contraction in normal hearts. To date, TAPSE has not been extensively studied in patients with hypoplastic left heart syndrome (HLHS) and systemic RVs after Fontan palliation. This retrospective study investigated HLHS patients after Fontan with cardiac magnetic resonance (CMR) performed between 1 January 2010 and 1 August 2012 and transthoracic echocardiogram (TTE) performed within 6 months of CMR. The maximal apical displacement of the lateral tricuspid valve annulus was measured on CMR (using four-chamber cine images) and on TTE (using two-dimensional apical views). To create TTE-TAPSE z-scores, published reference data were used. Intra- and interobserver variability was tested with analysis of variance. Inter-technique agreement of TTE and CMR was tested with Bland-Altman analysis. In this study, 30 CMRs and TTEs from 29 patients were analyzed. The age at CMR was 14.1 ± 7.1 years, performed 11.9 ± 7.8 years after Fontan. For CMR-TAPSE, the intraclass correlation coefficients for inter- and intraobserver variability were 0.89 and 0.91, respectively. The TAPSE measurements were 0.57 ± 0.2 cm on CMR and 0.70 ± 0.2 cm on TTE (TTE-TAPSE z score, -8.7 ± 1.0). The mean difference in TAPSE between CMR and TTE was -0.13 cm [95 % confidence interval (CI) -0.21 to -0.05], with 95 % limits of agreement (-0.55 to 0.29 cm). The study showed no association between CMR-TAPSE and RVEF (R = 0.08; p = 0.67). In patients with HLHS after Fontan, TAPSE is reproducible on CMR and TTE, with good agreement between the two imaging methods. Diminished TAPSE suggests impaired longitudinal shortening in the systemic RV. However, TAPSE is not a surrogate for RVEF in this study population.</p>

DOI

10.1007/s00246-014-0924-4

Alternate Title

Pediatr Cardiol

PMID

24840648

Title

Marked skeletal muscle deficits are associated with 6-minute walk distance in paediatric pulmonary hypertension.

Year of Publication

2021

Number of Pages

1426-1433

Date Published

2021 Sep

ISSN Number

1467-1107

Abstract

<p><strong>BACKGROUND: </strong>Poor growth is common in children with pulmonary hypertension; however, skeletal muscle deficits have not been described and the association between muscle deficits and functional status is unknown.</p>

<p><strong>METHODS: </strong>Patients aged 8-18 years with pulmonary hypertension (diagnostic Groups 1, 2, or 3) and World Health Organization functional class I or II underwent dual-energy absorptiometry to measure leg lean mass Z-score (a surrogate for skeletal muscle). Muscle strength was assessed using dynamometry. Physical activity questionnaires were administered. Clinical data, including 6-minute walk distance, were reviewed. Relationships between skeletal muscle, physical activity score, and 6-minute walk distance were assessed by correlations and linear regression.</p>

<p><strong>RESULTS: </strong>Sixteen patients (12.1 ± 3.2 years, 50% female, 56% Group 1, 56% functional class II) were enrolled. Leg lean mass Z-score was significantly less than reference data (-1.40 ± 1.12 versus 0.0 ± 0.9, p &lt; 0.001) and worse in those with functional class II versus I (-2.10 ± 0.83 versus -0.50 ± 0.73, p &lt; 0.01). Leg lean mass Z-score was positively associated with right ventricular systolic function by tricuspid annular plane systolic Z-score (r = 0.54, p = 0.03) and negatively associated with indexed pulmonary vascular resistance (r = -0.78, p &lt; 0.001). Leg lean mass Z-score and forearm strength were positively associated with physical activity score. When physical activity score was held constant, leg lean mass Z-score independently predicted 6-minute walk distance (R2 = 0.39, p = 0.03).</p>

<p><strong>CONCLUSIONS: </strong>Youth with pulmonary hypertension demonstrate marked skeletal muscle deficits in association with exercise intolerance. Future studies should investigate whether low leg lean mass is a marker of disease severity or an independent target that can be improved.</p>

DOI

10.1017/S1047951121000342

Alternate Title

Cardiol Young

PMID

33568240

Title

Inhaled Nitric Oxide Is Associated with Improved Oxygenation in a Subpopulation of Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension.

Year of Publication

2020

Number of Pages

167-172

Date Published

2020 04

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVES: </strong>To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders.</p>

<p><strong>STUDY DESIGN: </strong>We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO &gt;20&nbsp;mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate.</p>

<p><strong>RESULTS: </strong>During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n&nbsp;=&nbsp;90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO (51&nbsp;±&nbsp;3 vs 123&nbsp;±&nbsp;7&nbsp;mm Hg, P &lt; .01), alveolar-arterial gradient (422&nbsp;±&nbsp;30 vs 327&nbsp;±&nbsp;27&nbsp;mm Hg, P &lt; .01), and PaO to FiO ratio (82&nbsp;±&nbsp;10 vs 199&nbsp;±&nbsp;15&nbsp;mm Hg, P &lt; .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P&nbsp;=&nbsp;.03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P&nbsp;=&nbsp;.02).</p>

<p><strong>CONCLUSIONS: </strong>iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function.</p>

DOI

10.1016/j.jpeds.2019.09.052

Alternate Title

J Pediatr

PMID

31706636

Title

Accuracy of Brain Natriuretic Peptide for Diagnosing Pulmonary Hypertension in Severe Bronchopulmonary Dysplasia.

Year of Publication

2019

Number of Pages

147-153

Date Published

2019

ISSN Number

1661-7819

Abstract

<p><strong>BACKGROUND: </strong>Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown.</p>

<p><strong>OBJECTIVE: </strong>The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born &lt;32 weeks' gestation with sBPD.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure &gt;½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP.</p>

<p><strong>RESULTS: </strong>Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39-290] vs. 35 [20-76], p &lt; 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66-0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%).</p>

<p><strong>CONCLUSIONS: </strong>BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.</p>

DOI

10.1159/000499082

Alternate Title

Neonatology

PMID

31096210

WATCH THIS PAGE

Subscription is not available for this page.