Integrated Diagnostics Characterization of Right Ventricular Diastolic Flow Dynamics in Pulmonary Arterial Hypertension
Condition: Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Hypertension
Study type: Observational

Summary: 
      Pulmonary hypertension (PH) is a condition in which high blood pressure develops in the lungs
      and right side of the heart. People with PH suffer from shortness of breath, chest pain,
      heart failure, heart rhythm problems, and fainting. PH is diagnosed using a test called a
      cardiac catheterization where blood pressure is measured directly using a tube placed in the
      right side of the heart and lung arteries. Because a cardiac catheterization is invasive,
      researchers are investigating ways to diagnose PH using imaging tests that are not invasive.
      The study will evaluate whether or not a magnetic resonance image (MRI) of the heart, and
      blood tests can detect PH.
    

Detailed description: 
      The adaptive changes that result from chronic pressure overload in pulmonary arterial
      hypertension (PAH) lead to myocardial hypertrophy, stiffening, and right ventricular
      diastolic dysfunction (RVDD). A growing body of evidence has identified RVDD as an important
      prognostic indicator for PAH.1 Diagnosis of RVDD relies upon 1) elevated brain natriuretic
      peptide (BNP), which correctly identifies RVDD in the PAH population but remains a
      nonspecific marker, and 2) echocardiography, as defined by reduced early (E') tricuspid
      annular velocity, elevated ratio of early filling tricuspid inflow peak velocity to E'
      (E/E'), and prolonged relaxation time (RT). 2 However, the right ventricle's unusual anatomy
      and susceptibility to altered loading conditions have raised questions about the ability of
      echo indices to accurately reflect complex diastolic mechanics. The development of a robust
      non-invasive application for RV diastolic assessment may improve the understanding,
      diagnosis, and management of RVDD and therefore PAH.

      Similar to the left ventricle, rheological analysis of right ventricular inflow in canine
      models has identified the formation of diastolic vortex rings.3 Vortex rings develop from
      high velocity diastolic jet emanating from the valvular annulus interacting with stationary
      blood in the ventricle. Vortex ring formation time has successfully identified left
      ventricular diastolic dysfunction.4 Numerous additional vortex properties exist, including
      depth, transverse position, length, width, and sphericity index, that offer novel and robust
      diastolic flow characterization with the potential incremental diagnostic value to existing
      echo parameters. Vortex formation and analysis in RVDD has yet to be studied.

      Vortex measurement can be performed using dimensional (4D) (time-resolved three-dimensional)
      cardiac MRI (CMR). 4D CMR captures the complex multidirectional nature of flow through
      volumetric rendering of fluid vectors and velocity using blood flow streamlines and particle
      traces. In contrast to echocardiography, 4D CMR is not limited by poor acoustic windows
      commonly seen in patients with respiratory disease and PAH, making it an ideal noninvasive
      modality for vortex characterization.

      The biological adaptations resulting from chronic pressure overload in PAH might be
      correlated to the blood levels of different categories of biomarkers. They might play a role
      in the screening, diagnosis, monitoring or prognosis of patients with PAH and RVDD. Special
      mention can be made to the natriuretic peptides (BNP, NT-proBNP) based on their clinical
      value as hemodynamic markers in congestive heart failure. Cardiac markers of necrosis
      (asTroponin-I, and particularly the high sensitivity assays) might identify even minimal
      areas with such myocardial cell damage. The biological evaluation of cardiac fibrosis, might
      be assessed by markers of fibrosis, as Hyaluronic acid (HA), Procollagen III amino terminal
      peptide (PIIINP) and Tissue inhibitor of metalloproteinase 1 (TIMP-1). The potential role of
      the inflammatory component, can be evaluated with MPO (myeloperoxidase, pro-inflammatory
      enzyme), IL-6 (pro-inflammatory cytokine), C-RP (C-reactive protein)

      The present study aims to:

        1. Characterize and quantify RV vortex flow in normal subjects and PAH subjects with RVDD

        2. Assess the feasibility of 4D CMR right ventricular diastolic vortex analysis for
           diagnosis of RVDD Hypothesis: 4D CMR vortex analysis accurately identifies RVDD, and the
           information provided by biomarkers helps by adding diagnostic information.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        specialist clinics community
      
Biospecimen description: 
      plasma, serum
    
Keywords: pulmonary hypertension; cardiac magnetic resonance imaging; Characterize and quantify RV vortex flow; Assess feasibility of cardiac MR for RVDD diagnosis; Biomarker information to help diagnose