Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler

Ischemic Heart Disease Clinical Trial

Official title:

Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05471739
• Other study ID #: 2019/1285
• Status: Completed
• Start date: July 21, 2022
• Est. completion date: October 15, 2022

Study information

• Verified date: March 2023
• Source: Istanbul University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 15, 2022
• Est. primary completion date: September 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Microvascular Disease
• Coronary Microvascular Dysfunction
• Heart Diseases
• Ischemia
• Ischemic Heart Disease
• Microvascular Angina
• Microvascular Coronary Artery Disease
• Myocardial Ischemia
• Non-Obstructive Coronary Atherosclerosis

Locations

Country	Name	City	State
Turkey	Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Istanbul University

Country where clinical trial is conducted

Turkey, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Basal Microvascular Resistance (BMR)		Intraprocedural during coronary angiography
Primary	Hyperemic Microvascular Resistance (HMR)	the ratio of mean distal coronary pressure to average flow velocity	Intraprocedural during coronary angiography
Primary	Coronary Flow Reserve (CFR)	the ratio between coronary blood flow at maximal hyperemia and at baseline condition	Intraprocedural during coronary angiography
Primary	Delta ST	absolute shift of ST segment in IC-ECG record (at J point)	Intraprocedural during coronary angiography
Primary	Delta ST Integral	absolute change in area between ST segment and isoelectric line	Intraprocedural during coronary angiography
Secondary	Resting Average Peak Velocity		Intraprocedural during coronary angiography
Secondary	Hyperemic Average Peak Velocity		Intraprocedural during coronary angiography