Hypertension, Pulmonary Clinical Trial
Official title:
Endothelin Receptor Blockade in Heart Failure With Diastolic Dysfunction and Pulmonary Hypertension
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.
Heart Failure with preserved ejection fraction is with more than 50% of cases the most
common form of heart failure. Typically patients are elderly women with arterial
hypertension. Mortality, hospitalization rates due to heart failure and in-hospital
complications do not differ significantly from patients with systolic heart failure. However
there are some subgroups of HFPEF-patients with a worse prognosis, for example up to 30% of
patients develop secondary pulmonary hypertension and thus right ventricle dysfunction.
Increased right-ventricle systolic pressure is associated with increased mortality in
patients with all forms of heart failure.
There is a lack of evidence about HFPEF. Drugs for treating systolic heart failure showed no
improvement in mortality and prognosis. Diuretics are just able to relieve symptoms. There
are no clinical trials concerning HFPEF with secondary pulmonary hypertension.
The endothelin system is not only activated in PAH, but also in pulmonary venous
hypertension and congestive heart failure, where ET-1 levels rise with the severity of
secondary pulmonary hypertension. Pulmonary congestion leads to endothelial dysfunction that
results in increased levels of Endothelin-1 (ET-1).
ET-1 is a potent vasoconstrictor. In pulmonary arterial vessels the ETA receptor is the
predominant receptor (ratio of ETA to ET B = 9:1), which is responsible for vasoconstriction
and remodeling of the pulmonal vasculature. In heart failure the ETA receptor is
upregulated. Elevated plasma ET-1 levels correlate with pulmonary artery pressure (PAP),
pulmonary vascular resistance (PVR) and inversely with peak exercise capacity.
Recent clinical and laboratory findings indicate comparable pathophysiological mechanisms in
pulmonary hypertension secondary to left ventricular dysfunction and pulmonary arterial
hypertension. Yet, despite an expanding application in pulmonary artery hypertension,
according to current opinion, the oral dual endothelin (ETA/ETB) antagonist bosentan is not
indicated for PVH caused by left ventricle / left atrial pressure overload and preserved
systolic function. However, there are several studies which show some effects of pulmonary
vessel dilating drugs in PAH and left ventricle dysfunction.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
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