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Original Research: Pulmonary Vascular Disease |

Clinical Worsening as Composite Study End Point in Pediatric Pulmonary Arterial HypertensionEnd Points in Pediatric Pulmonary Hypertension

Mark-Jan Ploegstra, MD; Sanne Arjaans, BSc; Willemijn M. H. Zijlstra, BSc; Johannes M. Douwes, MD; Theresia R. Vissia-Kazemier, RN, MANP; Marcus T. R. Roofthooft, MD, PhD; Hans L. Hillege, MD, PhD; Rolf M. F. Berger, MD, PhD
Author and Funding Information

From the Center for Congenital Heart Diseases (Drs Ploegstra, Douwes, Roofthooft, and Berger and Mss Arjaans, Zijlstra, and Vissia-Kazemier), Department of Pediatric Cardiology, Beatrix Children’s Hospital, and the Department of Epidemiology (Dr Hillege), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

CORRESPONDENCE TO: Mark-Jan Ploegstra, MD, Center for Congenital Heart Diseases, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands; e-mail: m.ploegstra@umcg.nl


FOR EDITORIAL COMMENT SEE PAGE 576

Dr Ploegstra and Ms Arjaans contributed equally to this manuscript.

Results from this study were presented at the European Society of Cardiology Congress 2014, August 30, 2014, Barcelona, Spain.

FUNDING/SUPPORT: This study was supported by the Sebald Foundation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):655-666. doi:10.1378/chest.14-3066
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BACKGROUND:  Clinical worsening (CW), an increasingly used composite end point in adult pulmonary arterial hypertension (PAH), has not yet been evaluated in pediatric PAH. This study aims to evaluate the usefulness of CW in pediatric PAH by assessing the event incidence and prognostic value of each separate component of CW and of the composite CW end point.

METHODS:  Seventy pediatric patients with PAH from the Dutch National Network for Pediatric Pulmonary Hypertension, who started PAH-targeted therapy between January 2000 and January 2014, were included in the study and underwent standardized follow-up. The following CW components were prospectively registered: death, lung transplantation (LTx), PAH-related hospitalizations, initiation of IV prostanoids, and functional deterioration (World Health Organization functional-class deterioration, ≥ 15% decrease in 6-min walk distance, or both). The longitudinal event incidence and prognostic value were assessed for each separate component and their combination.

RESULTS:  The end-point components of death, LTx, hospitalizations, initiation of IV prostanoids, and functional deterioration occurred with a longitudinal event rate of 10.1, 2.5, 21.4, 9.4 and 48.1 events per 100 person-years, respectively. The composite CW end point occurred 91.5 times per 100 person-years. The occurrences of either hospitalization, initiation of IV prostanoids, or functional deterioration were predictive of death or LTx (P < .001 for each component). In this cohort, 1-, 3-, and 5-year transplant-free survival was 76%, 64%, and 56%, respectively. Freedom from CW at 1, 3, and 5 years was 43%, 22%, and 17%, respectively.

CONCLUSIONS:  CW occurred with a high event incidence and each of the soft end-point components was predictive of death or LTx. This supports the usefulness of CW as a study end point in clinical trials in pediatric PAH.

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