Prognostication in Pulmonary Arterial Hypertension with Submaximal Exercise Testing

Vinod Khatri,Augustine Lee,Charles Burger,Jennifer Neal

doi:10.3390/diseases3010015

Vinod Khatri, Augustine Lee + Show 2 more

Open Access

https://doi.org/10.3390/diseases3010015

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Journal: Diseases	Publication Date: Feb 6, 2015
Citations: 3	License type: CC BY 4.0

Affiliation: Mayo Clinic, Northwestern University

Abstract

Introduction: The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Methods: Sixty-five consecutive patients with idiopathic and associated pulmonary arterial hypertension (PAH) underwent right-heart catheterization, echocardiogram, 6MWT and a three-minute SET (Shape-HF™). Analyses explored the association between SET variables and prognosis predicted by the RRRS. Results: Although multiple SET variables correlated with the RRRS on univariate analyses, only VE/VCO2 (ρ = 0.57, p < 0.0001) remained an independent predictor in multivariate analysis (β = 0.05, p = 0.0371). Additionally, the VE/VCO2 was the most discriminatory (area under receiver operating characteristic curve, 0.84) in identifying the highest-risk category (RRRS ≥ 10), with an optimal cut-off of 40.6, resulting in a high sensitivity (92%) and negative-predictive value (97%), but a lower specificity (67%). Conclusion: SETs, particularly the VE/VCO2, appear to have prognostic value when compared to the RRRS. If validated in prospective trials, SET should prove superior to the 6MWT or the RRRS, with significant implications for both future clinical trials and clinical practice.

Highlights

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT)
We examined whether the peak VO2, VE/VCO2 and the partial pressure of carbon dioxide at baseline and at the end of exercise (PETCO2-b, pressures in the end tidal CO2 (PETCO2)-ex) would correlate with the registry risk score (RRRS)
We explored potential cut-offs for the SET variable VE/VCO2 by constructing a receiver-operating characteristic (ROC) curve and its area under the curve (AUC), as well as determining the sensitivity, specificity, predictive values and likelihood ratios (LHR) for the optimal cutoff

Summary

Introduction

The submaximal exercise test (SET), which gives both a measure of exercise tolerance, as well as disease severity, should be a more robust functional and prognostic marker than the six-minute walk test (6MWT). This study aimed to determine the prognostic value of SET as predicted by the validated REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Artery Hypertension Disease Management) registry risk score (RRRS). Long-Term Pulmonary Artery Hypertension Disease Management) cohort helped identify some important independent predictors, as well as a composite scoring system—the REVEAL registry PAH risk score (RRRS)—to help in prognosticating these patients [1,2]. The factors that go into the 6MWT include non-cardiopulmonary factors that have little to do with PAH or right ventricular function (e.g., neurologic disorders, musculoskeletal issues, peripheral arterial disease, conditioning, effort) Despite these and other limitations, the 6MWT has been widely used as an important clinical endpoint of most PAH treatment trials and, has been used regularly in the clinical monitoring and management of PAH patients. A meta-analysis showed that changes in the six-minute walk distance (6MWD) may not correctly predict favorable clinical outcomes [7]

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