Can Pulmonary Arterial Hypertension Be Diagnosed by an Elevated Pulmonary Capillary Wedge Pressure Outside of the Guideline Criteria?Pulmonary Arterial Hypertension Diagnosis FREE TO VIEW

We read with interest the report by Frost and colleagues¹ in a recent issue of CHEST (July 2011) comparing the results of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) with the other registries of pulmonary arterial hypertension (PAH). We are troubled by the inclusion of patients with a pulmonary capillary wedge pressure (PCWP) > 15 mm Hg, a value > 2 SD higher than normal, in this most recent and other publications from the REVEAL Registry.²

Since the 1979 National Institutes of Health registry, a PCWP ≤ 15 mm Hg has been accepted as a requirement for diagnosing PAH by professional societies and for entrance into clinical trials of PAH.³ Of 2,967 subjects in the REVEAL Registry, 239 (8%) had a PCWP > 15 mm Hg, suggesting either a proper diagnosis of pulmonary venous hypertension from unrecognized left-sided heart disease (LHD) or coexistent PAH and LHD. Obesity, female sex, hypertension, sleep apnea, and renal insufficiency, characteristics associated with left-sided heart disease, particularly heart failure with preserved ejection fraction, were more common among subjects with a PCWP > 15 mm Hg.⁴ The primary disease process in these patients may be quite different from that in patients with PAH. Including this heterogeneous population in REVEAL Registry analyses may confound the true picture of PAH.

Risks of inaccurate diagnosis include psychologic stress and adverse effects of therapy. Risks may be higher in patients treated with PAH-specific therapy who have unrecognized LHD. In patients with heart failure with reduced ejection fraction, a trial of epoprostenol was stopped early because of a trend toward increased mortality. Studies of bosentan, enrasentan, tezosentan, and darusentan in heart failure with reduced ejection fraction showed increased transaminases, fluid retention, and hospitalization for heart failure in the treatment arms.⁵ Adequate trials to assess the safety of sildenafil in LHD have not yet been performed. Unrecognized and untreated LHD could result in further preventable morbidity and mortality. Well-designed and executed studies of patients with characteristics of PAH but PCWP > 15 mm Hg are mandatory before the accepted definition of PAH is modified and patients who do not meet these criteria are treated with PAH-specific therapy.