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

• Status: Completed
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Heart failure is a major medical and socioeconomic problem in western industrial countries, especially with aging populations. Heart failure with normal left ventricle systolic function (heart failure with preserved ejection fraction, HFPEF, heart failure with normal ejection fraction, HFNEF) are common causes of hospitalization mainly in the elderly population and are frequently associated with pulmonary hypertension. It is commonly seen, that patients with left heart disease and pulmonary hypertension with right ventricle dysfunction have a worse prognosis.

The investigators hypothesize, that an additional treatment with Bosentan in this patients will improve their exercise capacity, symptoms, hemodynamics and quality of life.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Teaching Hospital Hall in Tirol
• Treatments: Bosentan

Criteria

Inclusion Criteria:

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

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

• 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 ejection fraction

• 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 disease limiting 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 endothelin receptor 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