Coronary Microvascular DysfunctionNCT05471739
Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
An observational study of Coronary Microvascular Dysfunction and Coronary Microvascular Disease, run by Istanbul University at 1 site in Turkey (Türkiye).
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronary Microvascular Dysfunction, Coronary Microvascular Disease, Non-Obstructive Coronary Atherosclerosis
- How many people
- 35 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 21 Jul 2022to 15 Oct 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- ≥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.
Who cannot join
- 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
Show all 12Show fewer
- Active Infection
- Morbid Obesity
- Pacemaker (Actively Pacing)
- Peripheral Artery Disease
- Previous CABG
- Chronic Hypoxia due to lung diseases
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology
Istanbul, 34290
About this 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.
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.
Read more
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.
Read the 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:
- Myocardial Perfusion Scan result: whether they relate to (supply blood) ischemic territory.
- 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.
- IC-ECG parameters
- 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
- Medical subject headings
- Microvascular Angina, Myocardial Ischemia
What is being measured
The primary outcome is the main question the study is designed to answer.
Hyperemic Microvascular Resistance (HMR)
the ratio of mean distal coronary pressure to average flow velocity
Measured: Intraprocedural during coronary angiography
Coronary Flow Reserve (CFR)
the ratio between coronary blood flow at maximal hyperemia and at baseline condition
Measured: Intraprocedural during coronary angiography
Delta ST
absolute shift of ST segment in IC-ECG record (at J point)
Measured: Intraprocedural during coronary angiography
Delta ST Integral
absolute change in area between ST segment and isoelectric line
Measured: Intraprocedural during coronary angiography
Secondary outcomes (2)
Resting Average Peak Velocity
Measured: Intraprocedural during coronary angiography
Hyperemic Average Peak Velocity
Measured: Intraprocedural during coronary angiography
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2022
- Study start21 Jul 2022
- Primary completion20 Sep 2022
- Study completion15 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Coronary Microvascular DysfunctionStudies of the same condition, open and under way.
- More trials run by Istanbul UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Murat Sezer, Istanbul University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05471739
- Sponsor's protocol ID
- 2019/1285
- Status last verified
- Mar 2023
- First submitted
- 19 Jul 2022
- Last updated
- 21 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 34593129Ong 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.
PubMed 29031990Kunadian 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.
PubMed 32626906Bigler 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.
PubMed 34125855Cevik E, Tas A, Demirtakan ZG, Damman P, Alan Y, Broyd CJ, Ozcan A, Simsek DH, Sonsoz MR, Royen NV, Perera D, Davies JE, Umman S, Sezer M. Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease. Am Heart J. 2024 Apr;270:62-74. doi: 10.1016/j.ahj.2024.01.003. Epub 2024 Jan 25.
PubMed 38278503Hasdemir H, Tas A, Cevik E, Alan Y, Broyd CJ, Ozcan A, Sonsoz MR, Kara I, Demirtakan ZG, Parker K, Perera D, Umman S, Sezer M. Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison. Open Heart. 2023 Nov 27;10(2):e002437. doi: 10.1136/openhrt-2023-002437.
PubMed 38011991
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simultaneous Assessment of Coronary Microvascular Dysfunction and Ischemia With Non-obstructed Coronary Arteries With Intracoronary Electrocardiogram and Intracoronary Doppler
- ClinicalTrials.gov ID
- NCT05471739
- Acronym / sponsor ID
- 2019/1285
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Istanbul UniversityUniversity, hospital or other
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- 20 Sep 2022 (actual)
- Study completion
- 15 Oct 2022 (actual)
- First posted
- 25 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Myocardial Perfusion Scan result: whether they relate to (supply blood) ischemic territory.
- 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.
- IC-ECG parameters
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- ≥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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hyperemic Microvascular Resistance (HMR)
Time frame: Intraprocedural during coronary angiography
the ratio of mean distal coronary pressure to average flow velocity
Coronary Flow Reserve (CFR)
Time frame: Intraprocedural during coronary angiography
the ratio between coronary blood flow at maximal hyperemia and at baseline condition
Delta ST
Time frame: Intraprocedural during coronary angiography
absolute shift of ST segment in IC-ECG record (at J point)
Delta ST Integral
Time frame: Intraprocedural during coronary angiography
absolute change in area between ST segment and isoelectric line
2 secondary outcomes
Resting Average Peak Velocity
Time frame: Intraprocedural during coronary angiography
Hyperemic Average Peak Velocity
Time frame: Intraprocedural during coronary angiography
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Background: PubMed 34593129Jansen 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.
- Background: PubMed 29031990Ong 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.
- Background: PubMed 32626906Kunadian 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.
- Background: PubMed 34125855Bigler 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.
- Derived from this study: PubMed 38278503Cevik E, Tas A, Demirtakan ZG, Damman P, Alan Y, Broyd CJ, Ozcan A, Simsek DH, Sonsoz MR, Royen NV, Perera D, Davies JE, Umman S, Sezer M. Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease. Am Heart J. 2024 Apr;270:62-74. doi: 10.1016/j.ahj.2024.01.003. Epub 2024 Jan 25.
- Derived from this study: PubMed 38011991Hasdemir H, Tas A, Cevik E, Alan Y, Broyd CJ, Ozcan A, Sonsoz MR, Kara I, Demirtakan ZG, Parker K, Perera D, Umman S, Sezer M. Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison. Open Heart. 2023 Nov 27;10(2):e002437. doi: 10.1136/openhrt-2023-002437.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Microvascular Dysfunction and Coronary Microvascular Disease, run by Istanbul University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hyperemic Microvascular Resistance (HMR) (time frame: Intraprocedural during coronary angiography). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05471739, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.