Hans Pankau

Long-Term Bosentan in Chronic Thromboembolic Pulmonary Hypertension

Background: There is no approved pharmacological treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not suitable for pulmonary endarterectomy (PEA). Objective: The study investigates the effect of the dual endothelin receptor antagonist bosentan on exercise tolerance (6-min walking distance, 6MWD) and right ventricular function (Tei index) in patients with CTEPH over 24 months. Methods: Twelve consecutive patients (5 males and 7 females) with CTEPH not eligible for PEA or following partial or complete failure of PEA were included in a non-randomized, open-label prospective study. All patients were WHO class III. They were included, if progressive pulmonary hypertension was diagnosed despite best supportive treatment. Bosentan was started at 62.5 mg b.i.d. and increased to the final dose of 125 mg b.i.d. Results: 6MWD and the Tei index were assessed every 6 months. We observed a significant increase in 6MWD from 319 ± 85.0 m at baseline to 391 ± 76.9 m at 6 months and a significant decrease in the Tei index from 0.39 ± 0.10 at baseline to 0.34 ± 0.08 at 6 months. This improvement was maintained over 24 months (6 MWD: 381 ± 101 m; Tei index: 0.31 ± 0.03). Six patients exhibited an improvement in WHO class at 6, 12 and 18 months, 5 demonstrated improvement at the 24-month follow-up. The remainder were stable throughout the study period. Conclusion: This is the first study demonstrating a long-term beneficial effect of bosentan on exercise tolerance (6MWD) and right heart function (Tei index) in CTEPH.

Acute Improved Hemodynamics following Inhaled Iloprost in Chronic Thromboembolic Pulmonary Hypertension

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a potential consequence to pulmonary embolism. The histologic picture is similar to idiopathic pulmonary hypertension (IPAH) suggesting that vascular remodeling also contributes to CTEPH. The treatment of choice is pulmonary endarterectomy. However, this treatment option is not adequate for all patients with CTEPH. Currently, no data exist on standard vasodilative therapy for CTEPH. Intravenous and oral prostanoids, both well-known vasodilators in IPAH, have been used with promising results, whereas the same has not been consistently observed for inhaled iloprost. Objective: In this study, we examined acute hemodynamic effects of inhaled iloprost in patients with CTEPH. Methods: In a prospective study, right heart catheterization was performed in 20 patients (mean age 56 years, New York Heart Association class II–IV) at the time of diagnosis of CTEPH. Pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac output (CO), mean systemic arterial pressure (MAP) and oxygen partial pressure (PaO2) were obtained before and 20 min after inhaling 5 µg iloprost. Subsequently, all patients were evaluated for pulmonary endarterectomy. Six patients were eligible for surgery. Results: Significant changes in pulmonary and systemic hemodynamics were observed following the inhalation of iloprost (before to after inhalation): PVR: 1,057 ± 404.3 to 821.3 ± 294.3 dyn·s·cm–5, p < 0.0001; mPAP: 50.55 ± 8.43 to 45.75 ± 8.09 mm Hg, p = 0.0002; CO: 3.66 ± 1.05 to 4.05 ± 0.91 l/min, p < 0.0106. MAP and PaO2 decreased significantly (MAP: 94.15 ± 11.58 to 89.45 ± 14.29 mm Hg, p = 0.0111; PaO2: 7.33 ± 1.17 to 6.64 ± 1.25 kPa, p = 0.0260). Conclusions: Hemodynamic changes directly following inhalation of iloprost suggest a significant contribution of a reversible component of vasoconstriction to pulmonary arterial hypertension in patients with CTEPH.

Prolonged oral L-carnitine substitution increases bicycle ergometer performance in patients with severe, ischemically induced cardiac insufficiency

Summary. Acute and chronic L-carnitine application exerts protective effects in a number of cardiac diseases. These favourable effects are attributed to improvements of the energy metabolism and have been found both in animal experiments and in man. In order to investigate the effect of long-time oral L-carnitine substitution on physical performance, 41 patients suffering from class NYHA II or III cardiac insufficiency were recruited for a clinical study. Following the double-blind, randomized, placebo-controlled design of the study, 20 patients were given 3 × 1g L-carnitine daily for 120 days whereas the control group (21 patients) received placebo. Bicycle ergometer tests were used to determine maximum performance, systolic and diastolic blood pressure, heart rate, and ST changes. Four series of tests were carried out: on day 0 (before the first substrate application), on the 60th and the 120th day (during L-carnitine or placebo application), and on the 180th day (60 days after the end of substitution). A significant improvement in performance (significantly higher maximum performance during bicycle ergometry) could be found within the carnitine group on the 60th and 120th day of L-carnitine application; and haemodynamical parameters showed a tendency to improve, too. These effects, which were attributed to L-carnitine, could be detected even 60 days after the end of substitution. No corresponding changes were found in the placebo group.The findings presented in this paper support suggestions of other authors that L-carnitine in combination with the usual medication (digitalis, β-blockers, calcium antagonists, nitrates) improves performance and effort tolerance in patients with cardiac insufficiency. Moreover, the findings suggest a favourable long-term effect, which lasts beyond the actual L-carnitine application, on the performance of patients with advanced cardiac insufficiency.

Exercise dependence of N-terminal pro-brain natriuretic peptide in patients with precapillary pulmonary hypertension.

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by cardiac ventricular myocytes upon pressure and volume overload and is a prognostic marker to monitor the severity of precapillary pulmonary hypertension and the extent of right heart failure. Objectives: The impact of physical exercise on NT-proBNP levels in patients with left heart disease was demonstrated previously. No data regarding patients with isolated right heart failure and the influence of acute exercise on NT-proBNP serum levels exist. Methods: Twenty patients with precapillary pulmonary hypertension were examined. Hemodynamic parameters were measured during right heart catheterization. Serum NT-proBNP of patients was measured at rest, after a 6-min walking test, during ergospirometry and during recovery, all within 7 h. Significant differences in sequential NT-proBNP values, relative changes compared to values at rest and the correlation between NT-proBNP and obtained parameters were assessed. Results: At rest, the mean serum level of NT-proBNP was 1,278 ± 998 pg/ml. The mean level of NT-proBNP at maximal exercise was increased (1,592 ± 1,219 pg/ml), whereas serum levels decreased slightly during recovery (1,518 ± 1,170 pg/ml). The relative increase of serum NT-proBNP during exercise correlated with pulmonary vascular resistance (r = 0.45; p = 0.026) and cardiac output (r = –0.5; p = 0.015). Conclusions: In this study, we demonstrated acute changes in NT-proBNP levels due to physical exercise in a small group of patients with precapillary pulmonary hypertension. Our results also confirm the predominant usefulness of NT-proBNP as an intraindividual parameter of right heart load.

Contents Vol. 84, 2012

J. Hammer, Basel F.J.F. Herth, Heidelberg J. Johnston, Vancouver, B.C. C. Kroegel, Jena F. Kummer, Vienna P.N. Mathur, Indianapolis, Ind. M. Miravitlles, Barcelona J. Müller-Quernheim, Freiburg L.P. Nicod, Lausanne M. Noppen, Brussels D. Olivieri, Parma C. Page, London W. Randerath, Solingen S. Siddiqui, Leicester T. Terashima, Ichikawa O.S. Usmani, London S. van Eeden, Vancouver, B.C. K. Yasufuku, Toronto, Ont. Official Journal of