Safety and Efficacy of Bosentan in Patients With Diastolic Heart Failure and Secondary Pulmonary Hypertension

Inclusion Criteria:

• Clinically signs or history of congestive heart failure NYHA II-III (Fatigue, dyspneaon exertion, lung crepitations, pulmonary edema, ankle and or lower leg swelling,jugular pressure enhancement, hepatomegaly)

• Echocardiographic signs of diastolic dysfunction (heart failure with normal ejectionfraction)

• Right ventricle enlargement with pulmonary hypertension

• 6 minute walking distance > 150 m < 400 m

• Right Heart Catheterization: Mean PAP > 25 mmHg, PCWP > 15 mmHg Echocardiographic requirements for definition of heart failure with normal ejectionfraction

• E/E` > 15, or

• E/E` > 8 + NTpBNP > 220 pg/ml, or

• E/E` > 8 + E:A < 0.5 + DT > 280 ms or

• Ard-Ad > 30 ms or

• atrial enlargement or

• atrial fibrillation

• NTpBNP > 220 pg/ml + combination

• IVRT - IVRTm < 0 septal und lateral Echocardiographic requirements for pulmonary hypertension and right ventricle dysfunction

• RVEDD > 30 mm short axis parasternal, and

• one of the following:

• Tricuspid valve regurgitation velocity (TRV) > 3 m/s;

• RV-annular systolic velocity < 10 cm/sec (TDI)

• TAPSE < 18 mm

Exclusion Criteria:

• Patients who are not on guideline conform treatments for cardiovascular disease.

• Left ventricle systolic dysfunction (EF < 50 %), aortic stenosis with peak gradient (instantane) > 40 mm Hg,moderate and severe aortic insufficiency

• moderate and severe mitral regurgitation,

• acute coronary disease, stable coronary artery disease or peripheral vascular diseaselimiting exercise.

• Other causes of pulmonary - artery - hypertension:

• relevant obstructive ventilatory disease > grade II (lung functions tests)

• collagen disease (Tests: MSCT and ANA, ANCA),

• chronic thrombo- embolic pulmonary arterial hypertension (MSCT),

• sleep disorder.

• HIV, HCV, HBV infection.

• Drug related PAH.

• Orthopaedic disease, immobility, inability to perform 6MWT and cancer.

• Liver disease Child-Pugh B and C, three fold above normal elevated liver enzymes,

• anaemia Hb < 10 mg/dl,

• other specific treatment of pulmonary arterial hypertension including other endothelinreceptor blockers, phosphodiesterase inhibitors, prostaglandins and L-arginin

• drug therapy with glibenclamide, rifampicin, tacrolimus, sirolimus, cyclosporine A

• known adverse reactions to bosentan and

• pregnancy and lactation