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Outcomes of idiopathic pulmonary arterial hypertension in Japanese children: a retrospective cohort study

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A Correction to this article was published on 01 June 2021

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Abstract

Recently, targeted therapy has been developed for idiopathic pulmonary arterial hypertension (IPAH). Studies evaluating the prognosis of IPAH have been conducted in adults. However, there is no nationwide survey of pediatric patients with IPAH regarding the long-term prognosis in Japan. Therefore, we investigated the clinical outcomes of Japanese pediatric patients with IPAH and risk factors for a poor prognosis. This multi-center, retrospective cohort study included pediatric patients with IPAH under the age of 15 years, who were gleaned from the nationwide network of Japanese Society of Pediatric Cardiology and Cardiac Surgery (JSPCCS). The questionnaire was sent to members of JSPCCS in 2015. Patients who were diagnosed with IPAH from 1994 to 2014 were included. The primary endpoint was death or lung transplantation. Ninety-five patients were finally enrolled. Both the mean age at diagnosis and the mean follow-up duration were 7 years. Ninety-five percent of patients had received targeted therapy for IPAH during follow-up. The overall 1, 3, 5, and 10-year event free rate, estimated using Kaplan–Meier survival estimate, was 96, 91, 83, and 74%, respectively. The prognosis was significantly poorer in patients with increased right ventricular systolic pressure (RVp), mean pulmonary artery pressure (mPAP) (≥ 52 mmHg), cardiothoracic ratio (≥ 55%), and levels of B-type natriuretic peptide (BNP) during follow-up (≥ 300 pg/mL) than in those without these parameters. In conclusion, in Japanese children with IPAH, the event-free rate for death or lung transplantation was found to be good. Greater RVp, mPAP, BNP levels during follow-up, and cardiothoracic ratio may be predictive indicators for a poor prognosis.

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References

  1. D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, Levy PS, Pietra GG, Reid LM, Reeves JT, Rich S, Vreim CE, Williams GW, Wu M (1991) Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115:343–349

    Article  CAS  Google Scholar 

  2. Barst RJ, Maislin Greg M, Fishman AP (1999) Vasodilator therapy for primary pulmonary hypertension in children. Circulation 99:1197–1208

    Article  CAS  Google Scholar 

  3. Tamura Y, Kumamaru H, Satoh T, Miyata H, Ogawa A, Tanabe N, Hatano M, Yao A, Abe K, Tsujino I, Fukuda K, Kimura H, Kuwana M, Matsubara H, Tatsumi K, Japan PH Registry (JAPHR) Network (2017) Effectiveness and outcome of pulmonary arterial hypertension-specific therapy in Japanese patients with pulmonary arteria hypertension. Circ J 82:275–282

    Article  Google Scholar 

  4. Ogawa A, Satoh T, Tamura Y, Fukuda K, Matsubara H (2017) Survival of Japanese patients with idiopathic/heritable pulmonary arterial hypertension. Am J Cardiol 119:1479–1484

    Article  Google Scholar 

  5. Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD (2012) Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 125:113–122

    Article  Google Scholar 

  6. 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, Yasukochi S, Ichida F, Fujimoto K, Ohtsuki S, Teshima H, Kawano T, Nomura Y, Gu H, Ishiwata T, Furutani Y, Inai K, Saaji T, Matsuoka R, Nonoyama S, Nakanishi T (2012) Outcomes of childhood pulmonary arterial hypertension in BMPR2 and ALK1 mutation carriers. Am J Cardiol 110:586–593

    Article  CAS  Google Scholar 

  7. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing Z, Krowka MJ, Langleben D, Nakanishi N, Souza R (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43-54

    Article  Google Scholar 

  8. Bernstein D (2020) Laboratory cardiac evaluation. In: Kliegman RM, St Geme III JW, Blum NJ, Shah SS, Tasker RC, Wilson KM (eds) Nelson Textbook of Pediatrics, Edition 21 Elsevier, Philadelphia, p2354–2355

  9. Saji T (2013) Update on pediatric pulmonary arterial hypertension. Differences and similarities to adult disease. Circ J 77:2639–2650

    Article  CAS  Google Scholar 

  10. Moledina S, Hislop AA, Foster H, Schulze-Neick I, Haworth SG (2010) Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart 96:1401–1406

    Article  CAS  Google Scholar 

  11. Sawada H, Mitani Y, Nakayama T, Fukushima H, Kogaki S, Igarashi T, Ichida F, Ono Y, Nakanishi T, Doi S, Ishikawa S, Matsushima M, Yamada O, Saji T (2019) Detection of pediatric pulmonary arterial hypertension by school electrocardiography mass screening. Am J Respir Crit Care Med 199:1397–1406

    Article  Google Scholar 

  12. Barst RJ, Ivy DD, Gaitan G, Szatmari A, Rudzinski A, Garcia AE, Sastry BK, Pulido T, Layton GR (2012) A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 125:324–334

    Article  CAS  Google Scholar 

  13. Rosenzweig EB, Ivy DD, Widlitz A, Doran A, Claussen LR, Yung D, Abman SH, Morganti A, Nguyen N, Barst RJ (2005) Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 46:697–704

    Article  CAS  Google Scholar 

  14. Beghetti M (2009) Bosentan in pediatric patients with pulmonary arterial hypertension. Curr Vasc Pharmacol 7:225–233

    Article  CAS  Google Scholar 

  15. Nakayama T, Shimada H, Takatsuki S, Hoshida H, Ishikita T, Matsuura H, Saji T (2007) Efficacy and limitations of continuous intravenous epoprostenol therapy for idiopathic pulmonary arterial hypertension in Japanese children. Circ J 71:1785–1790

    Article  Google Scholar 

  16. Zijlstra WMH, Douwes JM, Rosenzweig EB, Schokker S, Krishnan U, Roofthooft MTR, Miller-Reed K, Hillege HL, Ivy D, Berger RF (2014) Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies. J Am Coll Cardiol 63:2159–2169

    Article  Google Scholar 

  17. Hansmann G (2017) Pulmonary hypertension in infants, children, and young adults. J Am Coll Cardiol 69:2551–2569

    Article  Google Scholar 

  18. Ivy DD, Abman SH, Barst RJ, Berger RM, Bonnet D, Fleming TR, Haworth SG, Raj JU, Rosenzweig EB, Schulze Neick I, Steinhorn RH, Beghetti M (2013) Pediatric pulmonary hypertension. J Am Coll Cardiol 62:D117-126

    Article  Google Scholar 

  19. Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, Naeije R, Newman J, Oudiz RJ, Provencher S, Torbicki A, Voelkel NF, Hassoun PM (2013) Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 62:D22-33

    Article  Google Scholar 

  20. Ploegstra MJ, Roofthooft MT, Douwes JM, Bartelds B, Elzenga NJ, van de Weerd D, Hillege HL, Berger RM (2014) Echocardiography in pediatric pulmonary arterial hypertension: early study on assessing disease severity and predicting outcome. Circ Cardiovasc Imaging 8:e000878

    PubMed  Google Scholar 

  21. Yung D, Widlitz AC, Rosenzweig EB, Kerstein D, Maislin G, Barst RJ (2004) Outcomes in children with idiopathic pulmonary arterial hypertension. Circulation 110:660–665

    Article  Google Scholar 

  22. Douwes JM, Humpl T, Bonnet D, Beghetti M, Ivy DD, Berger RMF (2016) Acute vasodilator response in pediatric pulmonary arterial hypertension. J Am Coll Cardiol 67:1312–1323

    Article  Google Scholar 

  23. Sitbon O, Humbert M, Ioos JXV (2005) Long-term response to calcium channel blochers in idiopathic pulmonary arterial hypertension. Circulation 111:3105–3111

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the following participants who replied to the questionnaire; Tomotaka Nakayama, Satoshi Ikehara, Department of Pediatrics, Toho University Omori Medical Center; Daiji Takeuchi, Ayaka Chida, Yoshiyuki Furutani, Department of Pediatric Cardiology, Tokyo Women's Medical University; Department of Pediatrics; Shozaburo Doi, Yoshichika Maeda, Department of Pediatrics, Tokyo Medical and Dental University; Nozomi Kitazawa, Nagano Chuo Hospital; Hitoshi Horigome, Department of Child Health, Faculty of Medicine, University of Tsukuba; Satoshi Sakai, Cardiovascular Division, Faculty of Medicine, University of Tsukuba; Masaki Mitomo, Nobuo Momoi. Department of Pediatrics, Fukushima medical University; Takanari Fujii, Cardiovascular Center, Showa University Northern Yokohama Hospital; Gaku izumi, Atsuhito Takeda, Masato Yokozawa, Department of Peditrics, Hokkaido University; Fukiko Ichida, Department of Pediatrics, University of Toyama; Somura Jyunpei, Ouki Furukawa, Department of Pediatrics, Shiga University of Medical Science; Manatomo Toyono, Shunsuke Shimada, Department of pediatrics, Akita University; Tomio Kobayashi, Division of Cardiology, Gunma Children's Medical Center.; Shinichi Otsuki, Takahiro Eitoku, Maiko Kondo, Department of Pediatrics, Okayama University; Yashunobu Hayabuchi, Department of Pediatrics, University of Tokushima; Kosei Araki, Hiroyuki Fukushima, Department of Pediatrics, Keio University School of Medicine; Hirotaka Oki, Tokyo Metropolitan Children’s Medical Center, Department of Cardiology; Masaki Yamamoto, Department of Pediatrics, Kochi University; Teshima Hideki, National Hospital Organization Nagasaki Medical Center; Mamoru Ayusawa, Hiroshi Kanamaru, Department of Pediatrics, Nihon University School of Medicine; Norio Onodera, Division of Pediatrics, Iwate Prefectural Kitakami Hospital; Nomura Yuichi, Department of Pediatrics, Kagoshima University; Mitsunori Nishiyama, Department of Pediatrics, Sakakibara Heart Institute; Satoko Takei, Department of Pediatrics; Showa University Fujigaoka Hospital; Satoshi Yasukochi, Department of Cardiology, Nagano Children’s Hospital; Kazuto Fujimoto, Department of Pediatrics, Japanese Red Cross Society Kyoto Daini Hospital; Takahiro Ishiwata, Department of Pediatrics, National Defense Medical College; Tatsuya Kawano, Department of Pediatrics, Oita University; Yasuo Ono, Department of Cardiology, Shizuoka Children's Hospital; Hideaki Nakamura, Department of Cardiology, Kanagawa Children's Medical Center; and Manaki Sasaki, Department of Pediatrics, Hakodate Central General Hospital.

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This study was conducted by the epidemiological survey committee of Japanese Society of Pediatric Cardiology and Cardiovascular Surgery (JSPCCS) and the committee was financially supported by JSPCCS.

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Authors and Affiliations

  1. Department of Pediatric Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan

    Kenji Miyamoto, Kei Inai, Yoshiyuki Furutani & Toshio Nakanishi

  2. Department of Strategy and Management, Clinical Research Center, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

    Tohru Kobayashi

  3. Department of Cardiology, Tokyo Metropolitan Children’s Medical Center, Musashidai 2-8-29,, Fuchu-shi, Tokyo, 183-8561, Japan

    Jun Maeda

  4. Department of Pediatrics, Keio Medical University, Shinjuku-ku, Tokyo, Japan

    Jun Maeda & Hiroyuki Yamagishi

  5. Department of Pediatrics, Toho University Omori Medical Center, Ota-ku, Tokyo, Japan

    Shinichi Takatsuki

  6. Department of Pediatrics, Kouchi Medical School, Nankoku City, Kochi, Japan

    Tomotaka Nakayama

  7. Department of Pediatrics, School of Medicine, Dokkyo Medical University, Shimotoga, Tochigi, 321-0293, Japan

    Kenji Miyamoto

  8. Department of Pediatrics, School of Medicine, International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita, Chiba, 286-8520, Japan

    Toshio Nakanishi

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  1. Kenji Miyamoto
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  2. Kei Inai
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  4. Jun Maeda
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  7. Yoshiyuki Furutani
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  8. Hiroyuki Yamagishi
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  9. Toshio Nakanishi
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Correspondence to Jun Maeda or Toshio Nakanishi.

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The Medical Ethics Committee of Tokyo Women’s Medical University, Clinical Study #3035.

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Miyamoto, K., Inai, K., Kobayashi, T. et al. Outcomes of idiopathic pulmonary arterial hypertension in Japanese children: a retrospective cohort study. Heart Vessels 36, 1392–1399 (2021). https://doi.org/10.1007/s00380-021-01806-1

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  • DOI: https://doi.org/10.1007/s00380-021-01806-1

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