Chest
Volume 141, Issue 3, March 2012, Pages 642-650
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Original Research
Pulmonary Vascular Disease
Validation of the Pulmonary Hypertension Connection Equation for Survival Prediction in Pulmonary Arterial Hypertension

https://doi.org/10.1378/chest.11-0969Get rights and content

Objective

The pulmonary hypertension connection (PHC) equation predicts contemporary survival in idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension (PAH). The aim of this study is to validate the PHC equation in a prospective PAH population cohort and compare its predictability with the French equation.

Methods

We compared the rates of actual survival in patients prospectively followed for up to 3.5 years in four double-blind, randomized trials and their open-label extension studies with predicted survival calculated using the PHC equation [(P(t) = e(–A(x,y,z)t), A(x,y,z) = e(–1.270-0.0148x + 0.0402y − 0.361z), where P(t) is the probability of survival, t the time interval in years, x the mean pulmonary artery pressure, y the mean right atrial pressure, and z the cardiac index] and the French equation in patients with idiopathic, heritable, and anorexigen-associated PAH (n = 449).

Results

Mean age was 44 ± 15 years, 77% were women, and 80% had World Health Organization (WHO) functional class III/IV symptoms. The mean 6-min walk distance (6MWD) was 354 ± 95 m. The baseline hemodynamics were as follows: mean right atrial pressure 10 ± 6 mm Hg, mean pulmonary artery pressure 59 ± 15 mm Hg, and cardiac output 4.1 ± 1.5 L/min. The 1-, 2-, and 3-year Kaplan-Meier survival rates were 89%, 80%, and 70%, respectively; the nonadjusted survival rates were 91%, 87%, and 84%, respectively. The expected survival predicted by both the PHC and the French equations was similar to the actual observed Kaplan-Meier survival and was within its 95% confidence limits. The PHC equation also performed well when used in patients with WHO functional class III/IV, cardiac output < 4 L/min, or 6MWD < 380 m.

Conclusion

Risk prediction equations (PHC and French) accurately predicted survival and may be useful for risk estimation in patients with idiopathic, heritable, and anorexigen-associated PAH in large cohort studies. Their use for survival prediction for individual patients needs further study.

Section snippets

Study Population

Patients included in these analyses were enrolled in four double-blind randomized controlled trials and their associated open-label extension study arms13, 14, 15, 16, 17 that investigated two prostaglandin analogs (treprostinil and beraprost) in PAH. Detailed inclusion and exclusion criteria for these clinical trials have been reported previously.13, 14, 15, 16, 17 Briefly, patients were eligible for these clinical trials only if they met the following entry criteria: New York Heart

Baseline Characteristics

A total of 694 patients with PAH were included in these clinical trials. The mean age was 44 ± 15 years. Eighty-one percent (n = 559) were women. A majority of patients were WHO FC III or IV (81%, n = 560). Of the 694 patients, 449 patients had IPAH, HPAH, or anorexigen-associated PAH (65%); 114 patients had connective tissue disease-associated PAH (16%), 122 patients had congenital heart disease-associated PAH (18%), and nine patients had other associated PAH (1%). The mean 6MWD at baseline

Discussion

The PHC equation accurately predicted survival in a prospective IPAH, HPAH, and anorexigen-associated PAH population cohort. This was true despite multiple enrollment criteria and disease severity. The accurate prediction of survival by both the PHC equation and the French equation in this independent cohort supports their use as a survival comparator in the general population cohort studies. The PHC equation also performed well in the subset analyses (1) in sick patients with WHO FC III and

Acknowledgments

Author contributions: Dr Thenappan takes responsibility for the integrity of the work.

Dr Thenappan: contributed to study design, data analyses, and drafting of the manuscript.

Ms Glassner: contributed to drafting the manuscript and manuscript revisions.

Dr Gomberg-Maitland: contributed to study design, data analyses, drafting of manuscript, and manuscript revisions.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Actelion, Gilead,

References (20)

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Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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