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.

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

Inclusion Criteria:

• ≥1 previous episode of typical angina pectoris with normal coronary angiograms (Angina with Non-obstructed Coronary Arteries)
• positive myocardial perfusion scan (MPS) for ischemia or slow-flow.

Exclusion Criteria:

• obstructive epicardial coronary artery disease of at least 1 coronary artery in angiogram
• lung disease causing severe bronchospasm
• NYHA III - IV Heart Failure
• Bundle Branch Block
• Hb < 10 g/dL
• Active Malignancy
• Active Infection
• Morbid Obesity
• Pacemaker (Actively Pacing)
• Peripheral Artery Disease
• Previous CABG
• Chronic Hypoxia due to lung diseases

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.