Coronary Microvascular Dysfunction (CMD)

Go Beyond the Angiogram to Get to the Root Cause of Persistent Angina

Overview

CMD Information for Interventional Cardiologists

INOCA Diagnosis and Treatment

How to Diagnose INOCA

The European Association of Percutaneous Cardiovascular Interventions (EAPCI) Expert Consensus Document defines ischemia and no obstructive coronary artery disease (INOCA) and guidance to its diagnosis and management. The document states that, INOCA patients present with a wide spectrum of symptoms and signs that are often misdiagnosed as non-cardiac, leading to under-diagnosis/investigation and under-treatment.¹

Ischemia with non-obstructive coronary arteries graphic

Guidelines Recommend Guidewire-Based Measurements

Both American and European guidelines provide a class IIa recommendation for a physiology wire-based assessment for patients with stable chest pain and/or Ischemia and No Obstructive Coronary Artery Disease (INOCA).^2,3

The AHA/ACC Clinical Practice Guideline³ on chest pain includes Class IIa recommendation for guidewire-based assessment for ischemia and no obstructed coronary artery disease (INOCA) patients.

The ESC guidelines² 2019 were updated accordingly to include an increased focus on microvascular dysfunction.

Guidelines Recommend Guidewire-Based Measurements

CFR = coronary flow reserve; CMR = cardiac magnetic resonance; ECG = electrocardiogram;
FFR = fractional flow reserve; iwFR = instantaneous wave-free ratio; LAD = left anterior descending; PET = position emission tomography.

a Class of recommendation

b Level of evidence

Level-NR: Level (Quality) of Evidence Level B-NR (non-randomized): moderate-quality evidence from 1 or more well-designed, well-executed non-randomized studies, observational studies or registry studies. RCTs. Meta-analyses of such studies.

An updated standardization of Coronary Microvascular Dysfunction (CMD) criteria is provided by the COVADIS group including the cut-off values of CFR < 2.0 and IMR ≥ 25 that characterize CMD.¹

Criteria	Evidence	Diagnostic Parameters
1	Symptoms of myocardial ischaemia^a	Effort or rest angina Exertional dyspnoea
2	Absence of obstructive CAD (<50% diameter reduction or FFR >0.80)	Coronary CTA Invasive coronary angiography
3	Objective evidence of myocardial ischaemia^b	Presence of reversible defect, abnormality or flow reserve on a functional imaging test
4	Evidence of impaired coronary microvascular function	Impaired coronary flow reserve (cut-off <2.0), invasive or noninvasively determined Coronary microvascular spasm, defined as reproduction of symptoms, ischaemic ECG shifts but no epicardial spasm during acetylcholine testing Abnormal coronary microvascular resistance indices (e.g. IMR ≥25)

Kunadian et al. European Heart Journal. 2020; 0:1-21.

Definitive microvascular angina is only diagnosed if criterias 1, 2, 3 and 4 are present.

CAD = coronary artery disease; CCTA = coronary computed tomographic angiography; CFR = coronary flow reserve; ECG = electrocardiogram; FFR = fractional flow reserve; IMR = index of microcirculatory resistance.

a Many patients with heart failure with preserved ejection fraction would fulfil these criteria: dyspnoea, no obstructive CAD and impaired CFR. For this reason, consider measuring LV end-diastolic pressure (normal ≤10 mmHg) and NT-proBNP normal <125 pg/mL.

b Signs of ischaemia may be present but are not necessary. However, evidence of impaired coronary microvascular function should be present.

How to Diagnose CMD with a Comprehensive Physiology Assessment

The PressureWire™ X Guidewire and CoroFlow^‡ Cardiovascular System is a comprehensive solution for assessing both epicardial arteries and the microvasculature.⁴

Diagnosis With Comprehensive Physiology Indices

Colin Berry MD, PhD, Glasgow, UK

The PressureWire™ X Guidewire has pressure and temperature sensors that communicate with the CoroFlow^‡ Cardiovascular System to provide a comprehensive physiology assessment⁴

How to Treat Patients with CMD: Results of the CorMicA Trial

Microvascular angina and vasospastic angina are the two most common causes of INOCA, and both types of angina can be identified with diagnostic testing. The randomized CorMicA trial provides a diagnostic and treatment approach.⁵

The trial protocol assessed patients to determine:

Microvascular angina or CMD—using the PressureWire™ X Guidewire
Vasospastic angina—with acetylcholine testing

The CorMicA results indicate a role for a more thorough investigation of coronary microvascular dysfunction among patients with INOCA, as well as an opportunity to better tailor patient treatment.⁵

CorMicA Trial 1-year RCT Outcomes⁵

INOCA PATIENT MANAGEMENT

The EAPCI Expert Consensus Document¹ defines INOCA and provides guidance to the clinical community on the diagnostic approach and management of INOCA based on existing evidence and best current practices.

Angiotensin-converting enzyme inhibitor = ACEI
Angiotensin receptor blocker = ARB

References

Kunadian, V., et al. EAPCI Expert Consensus. Eur Heart J 2020;0:1-21.
Knuuti, J., et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. European Heart Journal 2020:41,407-477.
Gulati, M., et al. 2021 AHA/ACC Guideline for the Evaluation and Diagnosis of Chest Pain. Circulation 2021;144e368-e454.
PressureWire X Guidewire Instructions for Use (IFU). Refer to IFUs for additional information. CoroFlow Cardiovascular System IFU.
Ford, TJ., et al. 1-year outcomes of angina management guided by invasive coronary function testing (CorMicA). J Am Coll Cardiol Intv. 2020;13:33-45.

MAT-2302513 v1.0

Important Safety Information

Coroventis^‡ CoroFlow^‡ Cardiovascular System

Indications: CoroFlow^‡ is indicated to provide hemodynamic information for use in the diagnosis of patients with cardiovascular diseases.

CoroFlow^‡ is intended for use in catheterization and related cardiovascular specialty laboratories to compute and display various physiological parameters based on the output from one or more measuring devices.

Contraindications: The system has no patient alarm functions. Do not use for cardiac/vital signs monitoring.

Warnings:

If CoroFlow^‡ is used together with 3rd party infusion catheters for assessment of Absolute Flow and Resistance, ensure that the maximum infusion rate per manufacturers instruction is not exceeded or vessel injury may occur.
Do not use the CoroFlow^‡ measurement system if there is reason to believe the system's security has been compromised or if the system was unaccounted for a period of time (i.e. misappropriated, modified or tampered with).
Do not leave the CoroFlow^‡ measurement system unattended when logged in as a PC Administrator
To protect the privacy and security of sensitive information, including electronic protected health information (EPHI), and to protect the integrity of the system itself, the system should be located in a physically secure, access-controlled environment.
To protect the privacy and security of sensitive information, including electronic protected health information (EPHI), the PC on to which CoroFlow^‡ is installed must be configured according to the Installation Instructions in this manual. Failure to configure the PC correctly may result in increased risk for unauthorized release of protected health information. Windows settings include:
- Activation and configuration of restricted user Access
- Activation of Windows Firewall and blocking of network connections
- Activation of Windows Bitlocker drive encryption
- Activation of Windows Secure Boot
- Activation of Windows Anti-Virus scanning
- Activation of Windows update
Use of this equipment adjacent to or stacked with other equipment should be avoided because it could result in improper operation. If such use is necessary, this equipment and the other equipment should be observed to verify that they are operating normally.
Use of accessories, transducers and cables other than those specified or provided by Coroventis^‡ could result in increased electromagnetic emissions or decreased electromagnetic immunity of this equipment and result in improper operation.
Portable RF communications equipment (including peripherals such as antenna cables and external antennas) should be used no closer than 30 cm (12 inches) to any part of CoroFlow^‡, including cables specified by Coroventis^‡. Otherwise, degradation of the performance of this equipment could result.

Precautions:

The PC and CoroHub^‡ shall not be placed within the patient environment (1.5 m from patient).
For operation of other devices used in conjunction with CoroFlow^‡ consult the IFU for each of these devices for details on indication, handling and safety information.
It is recommended to ensure local routines for data backup of stored recordings. CoroFlow^‡ does not create backup of stored data.
Always check minimum performance requirement on PC to ensure compatibility with CoroFlow^‡.
It is recommended to install CoroFlow^‡ on a PC with backup battery to avoid interruption in case of power failure.
Always manually review and confirm valid cursor positions and detected heart beats.
Ensure that Pa and Pd pressure waveforms are aligned in phase and offset after equalization, or indices can be mis-calculated.
Confirm that the correct Wi-Box is selected by manually matching the Wi-Box ID number with the Wi-Box in the lab.
Changing parameter settings outside of default values may affect measurement performance, only for research purposes.
Only to be used by healthcare professionals
Using a network location to store data may cause previously unidentified risks if the network malfunctions
The assembly of medical electrical systems and modifications during the actual service life require evaluation to the requirements according to IEC 60601-1 standard series.
CoroHub^‡ does not have any serviceable parts and require no field maintenance. No modification or tampering with CoroHub^‡ is permitted.
CoroHub^‡ shall not be immersed in liquid.
CoroHub^‡ shall not be used if it has been subject to damage
Direct connection to a non-secure network, like the internet, may interfere with correct operation and/or result in inappropriate access to patient information. Furthermore, it should be noted that reconfiguring a used network may lead to inability to import patient as well as export examination data, ultimately leading to a risk of loss of patient and examination data. To avoid this problem Coroventis^‡ recommends verifying network settings in the system setup after each change.

MAT-2007904 v3.0

PressureWire™ X Guidewire

Indications: The PressureWire™ X Guidewire is indicated to direct a catheter through a blood vessel and to measure physiological parameters in the heart and in the coronary and peripheral blood vessels. Physiological parameters include blood pressure. The PressureWire™ X Guidewire can also measure blood temperature.

Contraindications: This guidewire is contraindicated for use in the cerebral vasculature.

Warnings:

No modification of this device is allowed.
The PressureWire™ X Guidewire is supplied sterile. Discard the guidewire if the pouch is opened or damaged, compromising the sterile barrier. The guidewire is designed for single use only and shall not be reused or resterilized. Adverse effects of using a non-sterile or resterilized guidewire may include, but are not limited to:
- Local and/or systemic infection
- Mechanical damage
- Inaccurate readings
Observe all guidewire movements. Whenever the guidewire is moved or torqued, the tip movement should be examined under fluoroscopy. Never push, withdraw, or torque the guidewire if it meets resistance or without observing corresponding movement of the tip, otherwise vessel/ventricle trauma may occur.
Torquing or excessive manipulation of the guidewire in a sharp bend, against resistance, or repeated attempts to cross a total vessel occlusion may:
- Cause dissection or perforation of blood vessels
- Cause vessel spasm
- Damage and/or fracture the guidewire
When introducing the guidewire, flush the catheter and administer anticoagulation as for a standard catheterization procedure or clotting may occur.
Do not use the guidewire in the ventricles if the patient has a prosthetic mechanical or biological valve. It may result in damage to both the prosthesis and the guidewire, which may cause injury or death.
Use of the PressureWire™ X Guidewire in conjunction with interventional devices with a short rapid exchange may result in a folded or fractured guidewire.
High frequency surgical devices must not be used on a patient at the same time as the guidewire.

Precautions:

The PressureWire™ X Guidewire is a delicate instrument and should be handled carefully.
Make sure that the transmitter is kept dry to ensure accurate pressure and/or temperature readings. Inaccurate readings may necessitate device replacement.
Do not use the guidewire in conjunction with atherectomy catheters. It may damage the guidewire.
Do not withdraw or manipulate the guidewire in a sharp-edged object. It may result in abrasion of the guidewire coating.
Factors that may affect the accuracy of the diagnostic information include, but are not limited to:
- Improper placement of the aortic pressure sensor.
- Failure to achieve maximum coronary and myocardial hyperemia in FFR procedures.
- Blood flow affected by the position of interventional devices, such as balloon catheters.
Guidewire readings may be affected by defibrillation. Rezero the guidewire after defibrillation use.
Do not measure pressure when the guidewire sensor element is in a sharp bend or in contact with atrial or ventricular walls. It might result in pressure artifacts.
Do not use the PressureWire™ X Guidewire together with another guidewire, for so called jailed wire technique, due to difficulty in guidewire withdrawal and possible guidewire entrapment.
Store at room temperature (15°C – 25°C) in a dry and dark place.

Potential Adverse Events: Potential complications which may be encountered during all catheterization procedures include, but are not limited to: vessel dissection or occlusion, perforation, embolus, spasm, local and/or systemic infection, pneumothorax, congestive heart failure, myocardial infarction, hypotension, chest pain, renal insufficiency, serious arrhythmias, or death.

In addition, this device has a coating containing Polyethylene Glycol (PEG); potential allergic reactions (anaphylaxis) may occur during the interventional procedure if the patient is allergic to PEG.

MAT-2103599 v2.0