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Canadian Journal of Cardiology

Genotypes and Phenotypes of Chinese Pediatric Patients With Idiopathic and Heritable Pulmonary Arterial Hypertension—A Single-Center Study

  • Hong-Sheng Zhang
    Affiliations
    Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China

    Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China
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  • Qian Liu
    Affiliations
    Department of Cardiology, Children’s Hospital of Hebei Province, Hebei, People’s Republic of China
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  • Chun-Mei Piao
    Affiliations
    Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China

    Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Beijing, People’s Republic of China
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  • Yan Zhu
    Affiliations
    Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China
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  • Qiang-Qiang Li
    Affiliations
    Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China
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  • Jie Du
    Correspondence
    Dr Jie Du, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, People’s Republic of China.
    Affiliations
    Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, People’s Republic of China

    Key Laboratory of Remodeling-Related Cardiovascular Diseases, Capital Medical University, Beijing, People’s Republic of China
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  • Hong Gu
    Correspondence
    Corresponding authors: Dr Hong Gu, Pediatric Cardiology Department, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029, People’s Republic of China. Tel.: +86-10-64456498.
    Affiliations
    Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China
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Published:August 01, 2019DOI:https://doi.org/10.1016/j.cjca.2019.07.628

      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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