Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers

Ayako Chida, Masaki Shintani, Hisato Yagi, Maya Fujiwara, Yasuko Kojima, Hiroki Sato, Shinichiro Imamura, Masato Yokozawa, Norio Onodera, Hitoshi Horigome, Tomio Kobayashi, Yoshiho Hatai, Tomotaka Nakayama, Hiroyuki Fukushima, Mitsunori Nishiyama, Shouzaburo Doi, Yasuo Ono, Satoshi Yasukouchi, Fukiko Ichida, Kazuto FujimotoShinichi Ohtsuki, Hidetaka Teshima, Tatsuya Kawano, Yuichi Nomura, Hong Gu, Takahiro Ishiwata, Yoshiyuki Furutani, Kei Inai, Tsutomu Saji, Rumiko Matsuoka, Shigeaki Nonoyama, Toshio Nakanishi

Research output: Contribution to journalArticle

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Abstract

Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the activin receptor-like kinase 1 (ALK1) gene have been reported in heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH). However, the relation between clinical characteristics and each gene mutation in IPAH and HPAH is still unclear, especially in childhood. The aim of this study was to determine, in a retrospective study, the influence and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four patients with IPAH or HPAH whose onset of disease was at <16 years of age were included. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p = 0.1205). In conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers.

Original languageEnglish
Pages (from-to)586-593
Number of pages8
JournalAmerican Journal of Cardiology
Volume110
Issue number4
DOIs
Publication statusPublished - 2012 Aug 15

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Type II Bone Morphogenetic Protein Receptors
Activin Receptors
Pulmonary Hypertension
Mutation
Genes
Familial Primary Pulmonary Hypertension
Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Chida, A., Shintani, M., Yagi, H., Fujiwara, M., Kojima, Y., Sato, H., ... Nakanishi, T. (2012). Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers. American Journal of Cardiology, 110(4), 586-593. https://doi.org/10.1016/j.amjcard.2012.04.035

Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers. / Chida, Ayako; Shintani, Masaki; Yagi, Hisato; Fujiwara, Maya; Kojima, Yasuko; Sato, Hiroki; Imamura, Shinichiro; Yokozawa, Masato; Onodera, Norio; Horigome, Hitoshi; Kobayashi, Tomio; Hatai, Yoshiho; Nakayama, Tomotaka; Fukushima, Hiroyuki; Nishiyama, Mitsunori; Doi, Shouzaburo; Ono, Yasuo; Yasukouchi, Satoshi; Ichida, Fukiko; Fujimoto, Kazuto; Ohtsuki, Shinichi; Teshima, Hidetaka; Kawano, Tatsuya; Nomura, Yuichi; Gu, Hong; Ishiwata, Takahiro; Furutani, Yoshiyuki; Inai, Kei; Saji, Tsutomu; Matsuoka, Rumiko; Nonoyama, Shigeaki; Nakanishi, Toshio.

In: American Journal of Cardiology, Vol. 110, No. 4, 15.08.2012, p. 586-593.

Research output: Contribution to journalArticle

Chida, A, Shintani, M, Yagi, H, Fujiwara, M, Kojima, Y, Sato, H, Imamura, S, Yokozawa, M, Onodera, N, Horigome, H, Kobayashi, T, Hatai, Y, Nakayama, T, Fukushima, H, Nishiyama, M, Doi, S, Ono, Y, Yasukouchi, S, Ichida, F, Fujimoto, K, Ohtsuki, S, Teshima, H, Kawano, T, Nomura, Y, Gu, H, Ishiwata, T, Furutani, Y, Inai, K, Saji, T, Matsuoka, R, Nonoyama, S & Nakanishi, T 2012, 'Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers', American Journal of Cardiology, vol. 110, no. 4, pp. 586-593. https://doi.org/10.1016/j.amjcard.2012.04.035
Chida, Ayako ; Shintani, Masaki ; Yagi, Hisato ; Fujiwara, Maya ; Kojima, Yasuko ; Sato, Hiroki ; Imamura, Shinichiro ; Yokozawa, Masato ; Onodera, Norio ; Horigome, Hitoshi ; Kobayashi, Tomio ; Hatai, Yoshiho ; Nakayama, Tomotaka ; Fukushima, Hiroyuki ; Nishiyama, Mitsunori ; Doi, Shouzaburo ; Ono, Yasuo ; Yasukouchi, Satoshi ; Ichida, Fukiko ; Fujimoto, Kazuto ; Ohtsuki, Shinichi ; Teshima, Hidetaka ; Kawano, Tatsuya ; Nomura, Yuichi ; Gu, Hong ; Ishiwata, Takahiro ; Furutani, Yoshiyuki ; Inai, Kei ; Saji, Tsutomu ; Matsuoka, Rumiko ; Nonoyama, Shigeaki ; Nakanishi, Toshio. / Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers. In: American Journal of Cardiology. 2012 ; Vol. 110, No. 4. pp. 586-593.
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abstract = "Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and the activin receptor-like kinase 1 (ALK1) gene have been reported in heritable pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH). However, the relation between clinical characteristics and each gene mutation in IPAH and HPAH is still unclear, especially in childhood. The aim of this study was to determine, in a retrospective study, the influence and clinical outcomes of gene mutations in childhood IPAH and HPAH. Fifty-four patients with IPAH or HPAH whose onset of disease was at <16 years of age were included. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76{\%}. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55{\%} vs 90{\%}, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64{\%}, hazard ratio 5.14, p = 0.1205). In conclusion, patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers.",
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AU - Chida, Ayako

AU - Shintani, Masaki

AU - Yagi, Hisato

AU - Fujiwara, Maya

AU - Kojima, Yasuko

AU - Sato, Hiroki

AU - Imamura, Shinichiro

AU - Yokozawa, Masato

AU - Onodera, Norio

AU - Horigome, Hitoshi

AU - Kobayashi, Tomio

AU - Hatai, Yoshiho

AU - Nakayama, Tomotaka

AU - Fukushima, Hiroyuki

AU - Nishiyama, Mitsunori

AU - Doi, Shouzaburo

AU - Ono, Yasuo

AU - Yasukouchi, Satoshi

AU - Ichida, Fukiko

AU - Fujimoto, Kazuto

AU - Ohtsuki, Shinichi

AU - Teshima, Hidetaka

AU - Kawano, Tatsuya

AU - Nomura, Yuichi

AU - Gu, Hong

AU - Ishiwata, Takahiro

AU - Furutani, Yoshiyuki

AU - Inai, Kei

AU - Saji, Tsutomu

AU - Matsuoka, Rumiko

AU - Nonoyama, Shigeaki

AU - Nakanishi, Toshio

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