Hemodynamic Mechanisms of Exercise-Induced Pulmonary Hypertension in Patients with Lymphangioleiomyomatosis: The Role of Exercise Stress Echocardiography

Background: The pathogenesis of pulmonary hypertension (PH) in lymphangioleiomyomatosis (LAM) has not yet been completely clarified. The aim of this study was to conduct a noninvasive evaluation of the main hemodynamic mechanisms of exercise-induced PH in patients with LAM, assessed using exercise stress echocardiography. Methods: Fifteen patients with LAM (mean age, 47 ± 13 years; all women) without resting PH were enrolled in a prospective single-center study and compared with 15 healthy female control subjects (mean age, 45.2 ± 8 years; P =.65). A complete echocardiographic study with Doppler tissue imaging was performed at baseline and during semisupine symptom-limited exercise testing to evaluate (1) left ventricular systolic and diastolic function, (2) right ventricular contractile function, (3) estimated pulmonary capillary wedge pressure, (4) estimated systolic and mean pulmonary artery pressure, and (5) estimated pulmonary vascular resistance. Results: Compared with healthy control subjects, patients with LAM during exercise showed echocardiographic signs of right ventricular overload and right ventricular systolic dysfunction and significant increases in mean pulmonary artery pressure (14.4 ± 6.5 vs 4.2 ± 3.1 mm Hg, P <.0001), pulmonary vascular resistance (+68.3 ± 42.1 vs −0.1 ± 18.3 dyne-sec/cm⁵, P <.0001), and, unexpectedly, pulmonary capillary wedge pressure (+8.3 ± 5.3 vs −0.5 ± 1.3 mm Hg, P <.0001). Conclusions: Exercise-induced PH in patients with LAM could be related not only to hypoxic pulmonary vascular vasoconstriction during exercise (precapillary PH) but also to a significant exercise-induced increase in estimated pulmonary capillary wedge pressure, probably secondary to diastolic dysfunction (postcapillary PH).