Neuregulin-1 in Patient With Different Forms of Cardiovascular Diseases: a Pilot Study
Condition: Heart Failure With Preserved Ejection Fraction; Microvascular Angina; Pulmonary Hypertension; Heart Failure With Reduced Ejection Fraction
MeSH terms: Hypertension, Pulmonary; Hypertension; Heart Failure; Cardiovascular Diseases; Microvascular Angina
Study type: Observational

Summary: 
      This is an observational study of Neuregulin-1 (NRG-1) plasma levels in patients with
      different forms of cardiovascular disease including microvascular angina (MVA), heart failure
      with preserved ejection fraction (HFpEF), as well as, heart failure with reduced ejection
      fraction (HFrEF) and pulmonary hypertension (PH). Investigators intend to identify
      cardiovascular diseases which are characterized by increased circulating NRG-1, considered to
      be a biomarker of therapeutic potential of NRG-1. Participants will undergo blood sampling
      over 3 days following randomisation. Patients demographics and clinical characteristics will
      be recorded and their associations with NRG-1 will be analysed.
    

Detailed description: 
      NRG-1 is a paracrine growth factor with physiological actions in the cardiovascular system
      which is primarily expressed by the endothelium of coronary microvessels. NRG-1 is a natural
      paracrine agonist of the ErbB4 receptor. The NRG-1/ErbB4 system is activated in chronic heart
      failure (HF) and some other chronic diseases, exerting disease mitigation and regenerative
      effects. Recombinant NRG-1 (rhNRG-1) is developed as a drug for HFrEF. Both the preclinical
      and clinical data (phase II and III clinical trials) have demonstrated the favourable effects
      of NRG-1 treatment on the heart. rhNRG-1 effectively enhances the heart function and reverses
      the remodelling of the left ventricle. The levels of circulating NRG-1 were found to
      correlate with outcomes in Stage III and IV CHF. NRG1 appeared to be potentially protective
      Therefore, NRG-1 concentrations are considered to be a biomarker of the therapeutic potential
      of NRG-1. However, little is known about the role of the NRG-1 pathway in other
      cardiovascular diseases (CVDs). This observational study is intended to identify CVDs which
      are characterized by an increase in NRG-1 levels for better positioning the NRG-1 treatment
      in heterogeneous field of CVDs. Based on preclinical data, investigators assume that plasma
      NRG-1 will be altered in patients with microvascular angina, pulmonary hypertension, and
      HFpEF and HFrEF.

      The study intends to enroll twenty patients for each of the 4 study groups and 20 healthy
      controls. We will compare the NRG-1 protein levels in patients and of age-matched healthy
      subjects. Participants will undergo a blood sampling after randomization (+ 3 days) and a 12
      month follow up to assess the outcomes. Demographics, clinical characteristics, laboratory
      values including biomarkers of inflammation and fibrosis, NTproBNP, along with transthoracic
      echo findings and outcomes will be recorded. After the active phase of the research is done,
      we are planning to proceed to observation of the prospective group of patients to verify the
      endpoints.
    

Intervention name(s): Neuregulin-1β level in plasma
Intervention type(s): Diagnostic Test
Intervention description(s): Peripheral blood will be collected after randomization (plus or minus 3 days), the plasma will be assayed for neuregulin-1b, biomarkers of inflammation and fibrosis, NTproBNP
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with a confirmed diagnosis of pulmonary hypertension, microvascular angina, heart
        failure with preserved ejection fraction or heart failure with reduced ejection fraction as
        defined by the diagnostic criteria in respective ESC guidelines
      
Biospecimen description: 
      Blood samples for analysis of neuregulin-1β, NT-proBNP, biomarkers of inflammation and
      fibrosis
    
Keywords: Neuregulin-1; Microvascular Angina,Heart Failure,Pulmonary Hypertension