Abstract
Background
The relationship between clinical outcomes and gene mutations in Chinese pediatric
patients with idiopathic and heritable pulmonary arterial hypertension (PAH) is unclear.
Methods
We retrospectively studied the clinical characteristics and outcomes of pediatric
patients who visited Beijing Anzhen Hospital from September 2008 to December 2018.
Results
Eighty-two pediatric patients were included. Forty-two gene mutations were identified
in 41 patients (50%), including 25 mutations in BMPR2, 5 mutations in ACVRL1, 3 mutations
each in ABCA3 and NOTCH3, 2 mutations each in KCNK3 and HTR2B, 1 mutation in ENG,
and 1 mutation in EIF2AK4. The mean age at diagnosis of PAH was 86.4 ± 55.1 months.
Forty-eight patients (twenty-eight mutation carriers) underwent cardiac catheterization
examinations, with acute vasodilator testing performed simultaneously. Results showed
that mutation carriers demonstrated a higher pulmonary vascular resistance index (P = 0.037). Patients with gene mutations responded poorly to vasodilators (P = 0.001). The 1-, 2-, and 3-year survival rates of mutation noncarriers were 95.1%,
87.8%, and 82.5% respectively; while for mutation carriers, the proportions were 86.6%
(P = 0.216), 63.8% (P = 0.021), and 52.2% (P = 0.010), respectively. Cardiac index was an independent predictor of death (P = 0.005; odds ratio [OR] 2.16, 95% confidence interval [CI] 1.258-3.704), as well
as RAP (P = 0.01; OR 1.26, 95% CI 1.056-1.503).
Conclusions
In our cohort of Chinese pediatric patients, those with an identified gene mutation
demonstrated worse clinical outcomes. Therefore, early gene screening for pediatric
patients with idiopathic and heritable PAH is recommended, and more aggressive treatment
for mutation carriers may be advisable.
Résumé
Contexte
La relation entre les résultats cliniques et les mutations génétiques chez les enfants
chinois atteints d’hypertension artérielle pulmonaire (HTAP) idiopathique et héréditaire
n’est pas bien comprise.
Méthodologie
Nous avons examiné rétrospectivement les caractéristiques et les résultats cliniques
d’enfants qui ont visité l’hôpital Anzhen de Beijing entre septembre 2008 et décembre 2018.
Résultats
Au total, 82 enfants ont été admis dans l’étude. Quarante-deux mutations génétiques
ont été détectées chez 41 patients (50 %), soit 25 mutations de BMPR2, 5 mutations de ACVRL1, 3 mutations chacun de ABCA3 et de NOTCH3, 2 mutations chacun de KCNK3 et de HTR2B, 1 mutation de ENG et 1 mutation de EIF2AK4. L’âge moyen au diagnostic de HTAP s’établissait à 86,4 ± 55,1 mois. Quarante-huit
patients (28 porteurs de mutations) ont subi un examen par cathétérisme cardiaque,
pendant lequel un test de vasodilatation aiguë était réalisé simultanément. Les résultats
révèlent un index de résistance vasculaire pulmonaire plus élevé chez les porteurs
de mutation (p = 0,037). Les patients porteurs d’une mutation génétique ne répondaient pas bien aux vasodilatateurs
(p = 0,001). Les taux de survie à 1 an, 2 ans et 3 ans chez les patients non porteurs
de mutation s’établissaient respectivement à 95,1 %, 87,8 % et 82,5 %; chez les porteurs
de mutation, les taux étaient de 86,6 % (p = 0,216), 63,8 % (p = 0,021) et 52,2 % (p = 0,010), respectivement. L’index cardiaque était un facteur de prédiction indépendant
de décès (p = 0,005; rapport de cotes [RC] de 2,16; intervalle de confiance [IC] à 95 % : de 1,258
à 3,704), ainsi que de pression auriculaire droite (p = 0,01; RC de 1,26; IC à 95 % : de 1,056 à 1,503).
Conclusions
Dans la cohorte d’enfants chinois étudiée, les résultats cliniques étaient moins bons
chez les porteurs d’une mutation génétique. Un dépistage génétique précoce est donc
recommandé chez les enfants atteints de HTAP idiopathique et héréditaire; un traitement
plus énergique pourrait aussi être indiqué chez les porteurs de mutation.
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Article info
Publication history
Published online: August 01, 2019
Accepted:
July 29,
2019
Received:
April 11,
2019
Footnotes
See page 1855 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
