Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
Condition: Coronary Microvascular Dysfunction; Coronary Microvascular Disease; Non-Obstructive Coronary Atherosclerosis; Microvascular Angina; Microvascular Coronary Artery Disease; Ischemic Heart Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Heart Diseases; Atherosclerosis; Microvascular Angina; Ischemia
Study type: Observational

Summary: 
      Coronary Microvascular Dysfunction has been consistently shown to play a considerable role in
      pathophysiology of Ischaemia with non-obstructed coronary arteries (INOCA). While the both
      diagnoses are individually related to remarkably worse outcome, there is no available method
      to simultaneously determine INOCA-CMD endotypes in vessel level, during the invasive
      diagnosis.

      The investigators hereby hypothesize that, combined intracoronary electrocardiogram (IC-ECG)
      (considering the high sensitivity and specificity of IC-ECG for studied vessel-territory) and
      intracoronary doppler can simultaneously and successfully identify vessel specific coronary
      microvascular dysfunction and resulting ischemia, which may potentially enable immediate
      diagnosis and endotyping of CMD-INOCA subgroups during the invasive assessment of first ANOCA
      episode, obviating the need for further ischemia-studies such es SPECT, which have
      considerably higher costs and lower sensitivity.

      Major coronary arteries of patients aged between 18 - 75 without obstructing coronary artery
      disease who have previously documented ischemia with non-obstructed coronary arteries (INOCA)
      via coronary angiogram and myocardial perfusion scan will be evaluated simultaneously with
      IC-ECG and intracoronary Doppler during rest and under adenosine induced hyperaemia.

      Performance of the combined system to identify Coronary Microvascular Dysfunction with
      structural and functional subgroups as defined by abnormal Coronary Flow Reserve (CFR) and
      Hyperemic Microvascular Resistance (HMR) and Ischemia in downstream territories of same
      vessel area (as defined by perfusion scan) is intended to be determined.

      The investigators also intend to interrogate the possible relationship between dynamic
      changes in IC-ECG parameters and invasively obtained intracoronary hemodynamic data.
    

Detailed description: 
      Background and Rationale of Study

      Coronary Microvascular Dysfunction has been consistently shown to play a considerable role in
      pathophysiology of Ischaemia with non-obstructed coronary arteries (INOCA). While the both
      diagnoses are individually related to remarkably worse outcome, there is no available method
      to simultaneously determine INOCA-CMD endotypes in vessel level, during the invasive
      diagnosis.

      Hypothesis

      The investigators hereby hypothesize that, combined intracoronary electrocardiogram (IC-ECG)
      (considering its high sensitivity for ischemia and specificity for studied vessel-territory)
      and intracoronary doppler can simultaneously and successfully identify vessel specific
      coronary microvascular dysfunction and resulting ischemia, which may potentially enable
      immediate diagnosis and endotyping of CMD-INOCA subgroups during the invasive assessment of
      first ANOCA episode, obviating the need for further ischemia-studies such as SPECT, which
      have considerably higher costs and lower sensitivity and requires more hospital visits.

      Study Method

      Major coronary arteries of patients aged between 18 - 75 without obstructing coronary artery
      disease who have previously documented ischaemia with non-obstructed coronary arteries
      (INOCA) via coronary angiogram and myocardial perfusion scan will be evaluated simultaneously
      with IC-ECG and intracoronary Doppler during rest and under adenosine induced hyperaemia
      after obtaining informed consent. Flow (APVr, APVh) data will be collected via intracoronary
      doppler during rest and adenosine induced hyperaemia in concordance with guidelines and
      Coronary Flow Reserve will be determined. Microvascular resistances (HMR, BMR) will be
      calculated with distal pressures and flow data.

      Simultaneous with intracoronary Doppler, IC-ECG records will be obtained during rest and
      hyperaemia. Paper records will be digitized offline in MATLAB environment. Delta ST, Delta ST
      integral, Delta T, Delta T integral will be measured and calculated and quantified as
      continuous values.

      All participants will be go through careful medical evaluation and presence of exclusion
      criteria will be assessed.

      At the end of the data collection period, all available major coronary arteries are expected
      to have:

        1. Myocardial Perfusion Scan result: whether they relate to (supply blood) ischemic
           territory.

        2. Structural/Functional Microvascular Status: (CFR and HMR)

           -Definition of Coronary Microvascular Dysfunction and Subgroups: CMD is defined as CFR <
           2.5. Those with concomitant HMR > 1.9 will be further labeled as structural CMD whereas
           vessels with CFR <2.5 and HMR <1.9 will be labeled as functional CMD.

        3. IC-ECG parameters
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        18 - 75 years old patients with previously documented ischemia with non-obstructed coronary
        arteries and positive ischemia test (myocardial perfusion scan or slow-flow) to be
        enrolled. Patients meeting at least one exclusion criteria won't be enrolled.
      
Keywords: INOCA; ANOCA; CMD; Coronary Microvascular Dysfunction; Ischemia with non-obstructive coronary arteries; Coronary Microvascular Disease; Microvascular Angina