Editorial [Chronic Thromboembolic Pulmonary Hypertension-Therapeutic Options]

The pulmonary circulation is normally a low-pressure, low resistance circuit due to its large cross-sectional area and high capacitance. Pulmonary hypertension is defined as a mean pulmonary arterial pressure >25 mm Hg at rest or 30 mm Hg at exercise at catheterization. Chronic thromboembolic pulmonary disease is a cause of pulmonary hypertension [1-9]. The condition is defined by absence of thrombus resolution after one or more episodes of acute pulmonary event that causes sustained obstruction of the pulmonary arteries and subsequent pulmonary hypertension. The extent of vascular obstruction is the major determinant of chronic thromboembolic pulmonary hypertension (CTEPH). Although exact incidence of CTEPH is not known with certainty, it is generally estimated to affect no more than 0.5% of embolic survivors [10-11]. However, it is felt that this condition is under diagnosed, and one well-executed prospective longitudinal study found the incidence to be 3.8% after two years of acute pulmonary embolism [12]. Preliminary reports suggested that an underlying hypercoagulable state may be responsible for the development of CTEPH [13, 14]. Once pulmonary hypertension develops, the prognosis is poor, and this prognosis worsens in the absence of intracardiac shunt. In fact, once mean pulmonary artery pressure in patients with chronic thromboembolic disease exceed 50 mm hg, the 5 year mortality approaches 90% [15]. In view of the severity of disease, and poor prognosis the therapy is urgently needed. CTEPH can be effectively treated by pulmonary thrombendarterectomy (PTE) [16-21]. At The University of California-San Diego Medical Center, the perioperative mortality rate in the 1181 patients who underwent PTE through 1999 was 8.6% overall. Survival has continued to improve over time, with a mortality of 15.8 percent before 1990, 7.2 percent between 1990 and 1999, and 4.4 percent between 1998 and 2002 [22]. Among the survivors of PTE, they observed immediate dramatic improvement in pulmonary artery pressure from 46 mm Hg preoperative to 28 mm Hg post operative, and pulmonary vascular resistance decreasing from 901 (dynes x sec x cm-5) to 261 (dynes x sec x cm-5) [23,24]. In this issue of Current Respiratory Medicine Reviews, Hans-Jurgen Seyfarth and coworkers [25], review in detail the different therapies in patients with CTEPH. Hans-Jurgen Seyfarth and colleagues raised important questions regarding the role of alternate therapies (mainly medical therapies) for the patients who are deemed not to be candidate for PTE. These authors present an excellent review regarding current medical therapies for patients with CTEPH. There are several small studies reviewed in the article by Hans-Jurgen Seyfarth [25]. The role of Beraprost in patients with CTEPH, for example, was marginal though minimal survival benefit was seen. However, some of these studies have very few patients and response was not as adequate [26, 27]. Studies on inhaled Iloprost for patient with CTEPH who cannot go for PTE has been described, moreover a role for bridging therapy has been considered prior to PTE [28]. In a study by Kramm and coworkers [29], preoperative use of inhaled Iloprost significantly increased cardiac index, and reduced mean pulmonary artery pressure and pulmonary vascular resistance, which in turn could reduce the risk of pulmonary reperfusion injury following PTE. The continuous intravenous epoprostenol for CTEPH has also been studied, which has shown to have promising result both as perioperative bridging as well as for distal lesions. There are few studies, as mentioned in article by Hans-Jurgen Seyfarth et al. regarding the role of phosphodiesterase 5-inhibitors and endothelin receptor antagonists, as well as combination therapy with inhaled Iloprost and sildenafil, and another study with addition of bosentan in patients who are being treated with Iloprost [30, 31]. These studies once again had very small number of patients. In addition to medical therapy, balloon angioplasties (BAP) have been used in the treatment for CTEPH. 18 patients evaluated for BAP for CTEPH underwent intervention. Distally surgically inaccessible disease was present in 16 patients; 9 were deemed “nonsurgical” on additional referral to other national centers for PTE. Proximal disease with severe concomitant medical illness was present in 2 patients; the proximal disease with morbid obesity in one and a combination of severe coronary artery disease and chronic obstructive pulmonary disease in other. 16 of 18 patients remained alive at an average of 34.2 months after initial catheterization. Average NYHA class improved from 3.3 preoperatively to 1.8 post-operatives, and 6 minute walking capacity increased from 209 yards preoperatively to 497 yards post-operative [32].........