Models and Molecular Mechanisms of World Health Organization Group 2 to 4 Pulmonary Hypertension.

Abstract

Pulmonary hypertension (PH) is defined as a resting mean pulmonary artery (PA) pressure (mPAP) ≥25 mm Hg, which is roughly double the normal mPAP.1 The breadth and inclusivity of this definition is problematic for several reasons. First, PH is a heterogeneous syndrome with variable etiologies, therapies, and prognosis. Thus, a diagnosis of PH does not guide therapy, although it does portend poor prognosis. Second, mPAP is rarely measured directly because this requires right heart catheterization. In clinical practice, right ventricular (RV) systolic pressure (RVSP) is usually estimated from noninvasive Doppler measurement of the peak velocity of a tricuspid regurgitation jet using the Bernoulli equation. This estimate is fraught with difficulties, including inaccuracy and an intrinsic inability to distinguish whether PH is caused by pulmonary vascular disease versus left ventricular (LV) diastolic dysfunction. Although pulmonary vascular disease can be identified and mPAP calculated from the PA Doppler signal (by measuring PA acceleration time2; Figure 1), this simple measurement is often omitted. Figure 1. Group 3 pulmonary hypertension case: 68-year-old male with moderately severe chronic obstructive pulmonary disease and obstructive sleep apnea. A , ECG showed sinus tachycardia with first-degree atrial ventricular block. Note right axis deviation and right ventricular hypertrophy with S1Q3T3 pattern. B , Ventilation perfusion (VQ) scan did not demonstrate VQ mismatch. No evidence of pulmonary embolism. C , Posterior anterior (PA) and lateral chest x-ray. Evidence of right ventricle (RV) enlargement (arrows indicate enlarged right pulmonary artery on PA view and loss of retrosternal airspace on lateral view). D , Apical 4-chamber view on ultrasound demonstrating RV and right atrial (RA) enlargement. E ,Parasternal short axis view on ultrasound showing mild septal flattening (arrow), a sign of RV pressure/volume overload. F ,Pulse wave Doppler of the pulmonic valve demonstrates severe pulmonary hypertension. The Doppler signal is early peaking, …