Non-Invasive Coronary Functional Evaluation of Patients With Single-vessel Coronary Artery Disease (NICE-CAD-PCI)
Non-Invasive Coronary Functional Evaluation of Patients With Single-vessel Coronary Artery Disease Treated With Percutaneous Coronary Intervention
Persistent or recurrent angina after successful percutaneous coronary intervention (PCI) remains a common clinical problem, affecting approximately 20-30% of patients despite complete epicardial coronary revascularization. Coronary microvascular dysfunction (CMD) has been proposed as a potential mechanism underlying persistent symptoms and abnormal functional testing after PCI, but it is still unclear whether CMD develops as a consequence of the PCI procedure or represents a pre-existing condition associated with coronary artery disease.
The NICE-CAD-PCI study is a prospective, single-center study designed to investigate coronary microvascular function in patients with stable single-vessel coronary artery disease treated with PCI. Specifically, the study will compare coronary microvascular function in the left anterior descending coronary artery (LAD) territory between patients undergoing PCI of the LAD and patients undergoing PCI of a different coronary artery (right coronary artery or left circumflex artery). This approach aims to clarify whether impaired coronary microvascular function is limited to the treated vascular territory, suggesting a PCI-related effect, or is also present in non-treated territories, supporting the hypothesis of a pre-existing generalized microvascular abnormality.
Within four weeks after PCI, all participants will undergo a comprehensive non-invasive coronary functional evaluation using transthoracic Doppler echocardiography (TTDE) to assess coronary blood flow velocity in the LAD during hyperventilation, cold pressor, and dipyridamole stress tests. Coronary flow reserve and coronary flow responses to the different physiological stimuli will be evaluated as markers of coronary vascular function.
Participants will be followed for six months after PCI to assess the occurrence of clinically driven target lesion revascularization and major adverse cardiovascular events. The study will also explore whether abnormalities detected by non-invasive coronary functional testing are associated with restenosis or adverse clinical outcomes.
The findings of this study may improve the understanding of the mechanisms responsible for persistent symptoms after PCI and contribute to the identification of patients with coronary microvascular dysfunction who may benefit from tailored diagnostic and therapeutic strategies.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Within four weeks after PCI, all enrolled patients will undergo a comprehensive non-invasive coronary functional evaluation using transthoracic Doppler echocardiography (TTDE). After a 10-minute resting period, a complete baseline echocardiographic examination will be performed, including assessment of global and regional left ventricular wall motion. The mid-distal left anterior descending coronary artery (LAD) will then be identified by color Doppler imaging, and peak diastolic coronary blood flow velocity (CBFV) will be measured using pulsed-wave Doppler.
Coronary vascular function will subsequently be assessed using three sequential coronary functional tests performed under continuous 12-lead electrocardiographic monitoring, intermittent blood pressure measurements, and peripheral oxygen saturation monitoring, with a 15-minute recovery interval between tests.
The hyperventilation test will be performed by asking participants to breathe deeply and rapidly at a rate of approximately 30 breaths per minute for 5 minutes. The cold pressor test will consist of immersion of the participant's right hand in ice water for 2 minutes. Finally, dipyridamole will be administered intravenously at a dose of 0.84 mg/kg over 6 minutes to assess endothelium-independent coronary vasodilator capacity.
Coronary blood flow velocity will be measured at baseline and at the peak of each functional test. The ratio between peak and baseline CBFV will be calculated for each stimulus as an index of coronary vascular function. Symptoms, electrocardiographic changes, and inducible regional wall motion abnormalities will also be recorded throughout the examination. Patients receiving beta-blockers or calcium channel blockers will be asked to temporarily discontinue these medications for 48 hours before the study examination.
The primary endpoint is the comparison of coronary flow reserve measured during dipyridamole stress between the LAD and non-LAD groups.
Secondary analyses will evaluate the association between abnormal coronary functional responses and adverse clinical outcomes. Participants will undergo structured clinical follow-up six months after PCI through telephone contact. Information regarding recurrent angina, repeat coronary angiography, target lesion revascularization, myocardial infarction, cardiovascular death, or other cardiovascular events will be collected. Reported events will be verified through review of electronic medical records or hospital documentation whenever available.
The study is powered to detect clinically meaningful differences in coronary flow reserve between the two study groups. Statistical analyses will compare coronary functional parameters between groups using appropriate parametric or non-parametric methods according to data distribution. Multivariable generalized linear models will be used to account for potential confounding variables, while Cox proportional hazards regression analyses will evaluate the relationship between coronary functional abnormalities and six-month clinical outcomes after adjustment for relevant clinical characteristics.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Invasive coronary angiography and PCI performed within the previous 4 weeks from enrollment;
- Obstructive single-vessel CAD (>75% coronary diameter reduction or fractional flow reserve <0.80) treated with PCI.
Exclusion Criteria:
- Presentation as an acute coronary syndrome (i.e. unstable angina or myocardial infarction) or a typical history of variant angina (frequent angina pain at rest with ST-segment elevation at the ECG, caused by recurrent coronary spasm);
- Previous history of specific heart disease, e.g., ischemic (previous percutaneous or surgical myocardial revascularization, myocardial infarction), valvular, congenital heart disease or cardiomyopathy;
- Multivessel coronary artery disease;
- Serious medical conditions, including renal failure (eGFR <30 mL/min), liver diseases, malignancies, and acute or chronic inflammatory diseases;
- Contraindication to dipyridamole;
- Pregnancy;
- Psychological conditions that might interfere with patient co-operation;
- Any condition that, in the judgment of the investigators, would make difficult for the patient to complete the study protocol;
- Refusal to sign the informed consent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Other: LAD group
Patients with stable single-vessel coronary artery disease who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending coronary artery.
All participants undergo non-invasive coronary functional assessment by transthoracic Doppler echocardiography within 4 weeks after PCI and 6-month clinical follow-up.
|
All patients and controls will undergo the following tests during transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, with time intervals of 15 minutes from each other: a) hyperventilation test: the patient is asked to breathe at a rate of 30 respirations per minute, for 5 minutes; b) cold pressor test: the patient puts his/her right hand in ice water for 2 minutes; c) dipyridamole test: intravenous dipyridamole is administered at a dose of 0.84 mg/kg over 6 minutes; Peak diastolic velocity (PDV) of blood flow in the left anterior descending coronary artery will be measured before and at the end of each test by pulsed-wave Doppler, using a GE E95 echocardiographic machine.
The ratio between peak flow velocity of coronary blood flow at peak of each test and the relative basal peak flow velocity of coronary blood flow is taken as the response of coronary blood flow velocity to each test.
|
|
Other: Non-LAD group
Patients with stable single-vessel coronary artery disease who underwent successful percutaneous coronary intervention (PCI) of the right coronary artery or left circumflex artery.
All participants undergo non-invasive coronary functional assessment by transthoracic Doppler echocardiography within 4 weeks after PCI and 6-month clinical follow-up.
|
All patients and controls will undergo the following tests during transthoracic echocardiographic Doppler examination of the left anterior descending coronary artery, with time intervals of 15 minutes from each other: a) hyperventilation test: the patient is asked to breathe at a rate of 30 respirations per minute, for 5 minutes; b) cold pressor test: the patient puts his/her right hand in ice water for 2 minutes; c) dipyridamole test: intravenous dipyridamole is administered at a dose of 0.84 mg/kg over 6 minutes; Peak diastolic velocity (PDV) of blood flow in the left anterior descending coronary artery will be measured before and at the end of each test by pulsed-wave Doppler, using a GE E95 echocardiographic machine.
The ratio between peak flow velocity of coronary blood flow at peak of each test and the relative basal peak flow velocity of coronary blood flow is taken as the response of coronary blood flow velocity to each test.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Difference in coronary flow reserve (CFR) between the LAD and non-LAD groups
Time Frame: Duration of the procedure
|
Coronary flow reserve (CFR) will be measured by transthoracic Doppler echocardiography (TTDE) in the left anterior descending coronary artery during dipyridamole administration.
CFR will be calculated as the ratio between peak hyperemic and baseline diastolic coronary blood flow velocity.
Mean CFR values will be compared between patients undergoing PCI of the LAD (LAD group) and patients undergoing PCI of a non-LAD coronary artery (non-LAD group).
CFR is a dimensionless ratio.
|
Duration of the procedure
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of major adverse cardiovascular events (MACE) according to the presence of functional coronary abnormalities
Time Frame: 6-months after the enrollment.
|
The incidence of major adverse cardiovascular events (MACE) at 6-month follow-up will be assessed according to the presence or absence of functional coronary abnormalities detected by transthoracic Doppler echocardiography (TTDE) during coronary functional testing.
MACE will be defined as a composite of cardiovascular death, myocardial infarction, and target vessel revascularization (percutaneous or surgical).
The outcome will be reported as the number and percentage of patients experiencing at least one MACE during follow-up.
|
6-months after the enrollment.
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 26956
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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