Immunoadsorption in Patients With Pulmonary Hypertension

Randomized, Prospective Investigation on the Effects of Immunoadsorption on Pulmonary Vascular Resistance in Patients With Pulmonary Hypertension

The purpose of this study is to investigate, if Immunoadsorption of autoantibodies with subsequent substitution of immunoglobulins is able to improve haemodynamics in patients with pulmonary hypertension.

Increased pulmonary precapillary vascular resistance due to vasoconstriction and vasoproliferative processes is the basic pathophysiological mechanism in the development of pulmonary hypertension (PH). In patients with pulmonary arterial hypertension (PH) production of endothelin-1 (ET-1) is increased and elevated ET-1 plasma levels correlate with PH severity As recently shown Autoantibodies against the Endothelin-1 Typ A and Angiotensin II Typ-1 Receptor, which have a high Incidence in PH-Patients, may also play an important role in the pathophysiology of PH (Dandel et al.). The concept of this study is that the elimination of these autoantibodies by Immunoadsorption with protein A may improve haemodynamics and patient wellbeing. Immunoglobulins are substituted after Immunoadsorption to minimize infection risk.

pulmonary hypertension, autoantibodies, immunoadsorption, immunoglobulin substitution, right ventricular function

Immunoadsorption with protein-A columns on five consecutive days with subsequent human polyclonal immunoglobulin G substitution after day 5 (0,5g /kg bodyweight)

The extend of change of pulmonary vascular resistance over the observation period will be compared between the 2 groups (treatment versus control group).

TAPSE=excursion of the lateral tricuspid annulus (measured in m-mode). the extend of cange of TAPSE over the observationperiod will be compared between the 2 groups (treatment vs. controlgroup)

NYHA = functional capacity. The extent of change of NYHA-class over the observation period will be compared between the 2 groups (treatment versus control group).

nt pro BNP = B-type natriuretic peptide. The extent of change of nt-pro BNP over the observation period will be compared between the 2 groups (treatment versus control group).

The extent of change of peak oxygen uptake over the observation period will be compared between the 2 groups (treatment versus control group).

The extent of change of 6-min walktest over the observation period will be compared between the 2 groups (treatment versus control group).

The extent of change of ET-1 TYP A Receptor Autoantibody level over the observation period will be compared between the 2 groups (treatment versus control group).

PAPs = systolic pulmonalarterial pressure estimated by maximal flow velocity of tricuspid regurgitant jet (continues doppler). The extent of change of PAPs over the observation period will be compared between the 2 groups (treatment versus control group).

S´lat. TR Annulus = systolic velocity of the lateral tricuspid annulus measured by tissue doppler. The extent of change of S´ lat. TR Annulus over the observation period will be compared between the 2 groups (treatment versus control group).

AT right ventricular outflow = acceleration time of right ventricular outflow, measured by pulsed wave doppler echocardiography. The extent of change of AT over the observation period will be compared between the 2 groups (treatment versus control group).

Inclusion Criteria: pulmonary hypertension (PH) NYHA II-IV medical treatment of PH respective to current guidelines 18 years or older written informed consent of the patient Exclusion Criteria: pulmonary hypertension due to left ventricular dysfunction decompensated heart failure need for Catecholamines active infection pregnancy malign tumor disease other secondary disease with life expectancy < 1 year refusal by the patient