Clinical trial NCT05471739: Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
Official title: Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Microvascular Dysfunction
Coronary Microvascular Disease
Non-Obstructive Coronary Atherosclerosis
Microvascular Angina
Microvascular Coronary Artery Disease
Ischemic Heart Disease
Keywords: INOCA
ANOCA
CMD
Coronary Microvascular Dysfunction
Ischemia with non-obstructive coronary arteries
Coronary Microvascular Disease
Microvascular Angina
Lead sponsor: Istanbul University
Sponsor class: OTHER
First posted: 2022-07-25
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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.

Brief 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

Eligibility criteria: 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

Primary outcomes:
measure: Hyperemic Microvascular Resistance (HMR)
timeFrame: Intraprocedural during coronary angiography
measure: Coronary Flow Reserve (CFR)
timeFrame: Intraprocedural during coronary angiography
measure: Delta ST
timeFrame: Intraprocedural during coronary angiography
measure: Delta ST Integral
timeFrame: Intraprocedural during coronary angiography
Secondary outcomes:
measure: Resting Average Peak Velocity
timeFrame: Intraprocedural during coronary angiography
measure: Hyperemic Average Peak Velocity
timeFrame: Intraprocedural during coronary angiography
Other outcomes:
measure: Basal Microvascular Resistance (BMR)
timeFrame: Intraprocedural during coronary angiography
Locations:
city: Istanbul
country: Turkey
facility: Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology
Study officials:
References:
citation: Jansen TPJ, Konst RE, Elias-Smale SE, van den Oord SC, Ong P, de Vos AMJ, van de Hoef TP, Paradies V, Smits PC, van Royen N, Damman P. Assessing Microvascular Dysfunction in Angina With Unobstructed Coronary Arteries: JACC Review Topic of the Week. J Am Coll Cardiol. 2021 Oct 5;78(14):1471-1479. doi: 10.1016/j.jacc.2021.08.028.
citation: Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018 Jan 1;250:16-20. doi: 10.1016/j.ijcard.2017.08.068. Epub 2017 Sep 8.
citation: Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S, Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R, Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020 Oct 1;41(37):3504-3520. doi: 10.1093/eurheartj/ehaa503.
citation: Bigler MR, Seiler C. Detection of myocardial ischemia by intracoronary ECG using convolutional neural networks. PLoS One. 2021 Jun 14;16(6):e0253200. doi: 10.1371/journal.pone.0253200. eCollection 2021.