Untitled

Abstract

Abbreviations: CI, cardiac index; iNO, inhaled nitric oxide; iPAH, idiopathic pulmonary arterial hypertension; NYHA, new york heart association; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RHC, right heart catheterization; RV, right ventricular; TAPSE, tricuspidal anular plane systolic excursion; WHO, world health organization; WP, wedge pressure; WU, wood units; 6MWD, 6-minute walking distance IntroductionPulmonary arterial hypertension (PAH) is a progressive disease characterized by an increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) leading to right ventricular failure and ultimately death.1 The past decade has witnessed major advances in PAH management, due to the introduction of specific therapies. Furthermore, oral drugs have been available in the last decade consenting a more wide treatment of the disease among clinicians' community. ET (endothelin)-receptor antagonists and PDE-5 (phosphodiesterase-5) inhibitors showed to improve exercise capacity, NYHA functional class, hemodynamics and progression of disease in several clinical trials.2-6 However, many patients have clinical worsening during oral treatment. Thus, addition of prostanoids represents an important chance to reach clinical improvement for these patients. During a 16-year period of activity in our referral center we treated almost 500 severe PH patients, and near 100 patients were exposed to parenteral prostanoids. In this paper we describe the clinical course of 3 long-term survivor patients (>10years), as they could be considered to have had an exceptional good response to treatment. Case reportsPatient 1 is a 65-year-old woman with idiopathic pulmonary arterial hypertension (iPAH) diagnosed in 1997 after a rapidly progressive reduction of exercise capacity in the last year. At first evaluation at our center, the patient was in NYHA/WHO functional class III, with a reduced effort capacity (six-minute walk distance -6MWD 370meters). ECG showed right ventricular (RV) strain, echocardiography showed marked RV dilatation, with a still preserved systolic function (tricuspidal anular plane systolic excursion -TAPSE 22mm). Right heart catheterization (RHC) revealed a moderate precapillary pulmonary hypertension (mean PAP 42mmHg, wedge pressure -WP 9mm Hg, cardiac index -CI 2.6l/min/m 2 , pulmonary vascular resistance -PVR 7.8WU-Wood Units), with no acute vasoreactivity to inhaled nitric oxide (iNO, 20ppm) (Figure 1). At that time, continuous iv infusion of epoprostenol was the only treatment available, so it was started and up-titrated to the maximum tolerated dosage. During the following months we observed a progressive improvement in clinical status and effort tolerance. After 2years (epoprostenol dose 32ng/kg/ min) she was in class II with a good effort tolerance (6MWD 490m), and a second invasive evaluation documented an improvement of hemodynamics (mPAP 26mmHg, CI 2.9l/min/m 2 , PVR 4.7WU). In the following 15years, s...