Clinical Research Directory

Evaluation of the BMPR2-Activin Signaling Pathway in Group II Pulmonary Hypertension.

Previous data from our group showed reduced BMPR2 isoform A in pulmonary hypertension associated with left heart disease (PH-LHD) of valvular origin. Focusing on dysregulation of the BMPR2-activin pathway, a key regulator of vascular homeostasis, this project uses a multimodal approach combining molecular biology, advanced cardiac imaging, and histology. Its aim is to determine the role of the BMPR2-activin pathway in the development and regression of PH-LHD. We will conduct a prospective observational study with 1-year follow-up in 150 heart failure patients of different etiologies undergoing hemodynamic assessment. Clinical parameters, biomarkers, molecular profiles, and hemodynamic/echocardiographic variables will be analyzed. A nested substudy in 40 heart transplant candidates will include thoracic CT for vascular morphometric analysis and histological correlation in explanted hearts versus healthy controls. We will also assess reversibility of vascular remodeling one year after transplantation. Results may redefine PH-LHD classification, enable phenotypic precision-medicine models, guide targeted therapies such as activin inhibitors, and refine transplant criteria in combined pulmonary hypertension.

COMPERA / COMPERA-KIDS

In view of the manifold options for mono- and combination therapy that have now emerged for patients with pulmonary (arterial) hypertension (PH/PAH), controlled clinical trials can only provide part of the information needed for optimal management. In order to gather adequate data on PAH/PH treatment in routine clinical care, the ongoing COMPERA registry prospectively documents consecutive patients with newly initiated treatment of PAH/PAH since May 2007. The internet-based registry fulfills high quality standards through several measures (planned minimum centre contribution of at least 10 patients per year, automated plausibility checks of data at entry, queries, monitoring with source data verification in \>50% of participating centers). It can be applied, among further purposes, for quality assurance: individual centers can confidentially compare their results with the combined outcome of other centers and the recommendations from guidelines. It is expected that the register contributes to optimization of specific drug therapy for PAH and PH. Since July 2013, also children of any age can be documented (COMPERA-KIDS).