Angina, Stable, Angina, Unstable, Coronary Artery Disease, Coronary Stenosis
Conditions
Brief summary
This is a pilot study designed to assess the relationship between iFR (instantaneous wave-free ratio) pullback and the distribution of coronary atheroma/stenoses as assessed by Quantitative Coronary Angiography (QCA) post angiographically successful PCI (Percutaneous Coronary Intervention).
Detailed description
DEFINE-PCI is a multi-center, prospective, non-significant risk study in up to 25 centers in USA and internationally. Consented subjects with CAD (Coronary Artery Disease) who undergo physiologic lesion assessment with iFR\<0.90 in at least 1 coronary artery are eligible for participation. After successful PCI to all culprit lesions based on angiographic assessment of the treating physician, a blinded post-PCI iFR and iFR pullback will be performed. The proportion of patients with impaired post-PCI iFR will be assessed, and the number of patients in whom ischemia could theoretically be normalized with further PCI determined. Additionally, the association between the post-PCI iFR results and cardiovascular events and clinical symptoms will be assessed. Follow-up will be at 1, 6 and 12 months, including administration of quality of life questionnaires.
Interventions
DIAGNOSTIC_TESTiFR pullback
iFR pullback assessment post angiographically successful PCI
Sponsors
Duke Clinical Research Institute
Cardiovascular Research Foundation, New York
Volcano Corporation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must be \> 18 years old 2. Subjects presenting with stable angina, silent ischemia or non-ST-elevation ACS (acute coronary syndrome) (unstable angina or biomarker positive) 3. Single vessel CAD with at least 2 separate lesions (≥10 mm apart) of ≥40% stenosis or a single long lesion of ≥20mm OR multi-vessel CAD, defined as at least 2 vessels with ≥40% stenosis 4. Pre-PCI iFR performed in all vessels intended for PCI 5. Pre-PCI iFR of \<0.90 of at least 1 stenosis 6. Subjects are able and willing to comply with scheduled visits and tests and to provide informed consent.
Exclusion criteria
1. Pregnant or planning to become pregnant for the duration of the study 2. Acute STEMI (ST-elevated Myocardial Infarction) within the past 7 days 3. Cardiogenic shock (sustained (\>10 min) systolic blood pressure \< 90 mmHg in absence of inotropic support or the presence of an intra-aortic balloon pump). 4. Ionotropic or temporary pacing requirement 5. Sustained ventricular arrhythmias 6. Prior CABG (Coronary Artery Bypass Graft) 7. Known ejection fraction ≤30% 8. Chronic Total Occlusion (CTO) 9. Known severe mitral or aortic stenosis. 10. Any known medical comorbidity resulting in life expectancy \< 12 months. 11. Participation in any investigational study that has not yet reached its primary endpoint. 12. Known severe renal insufficiency (eGFR \<30 ml/min/1.72 m2). 13. TIMI flow \<3 at baseline 14. Intra-coronary thrombus on baseline angiography
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Residual Ischemia (iFR <0.90) | end of procedure/intervention | Residual ischemia is defined as iFR measurement \<0.90 after operator-assessed angiographically successful PCI (residual diameter stenosis \<50% in any treated lesion in the target vessel) This outcome describes the number of participants that had a residual ischemia (defined as iFR\<0.90) after a PCI that appeared to be successful based on angiography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Target Vessel Revascularization | 12 month | Ischemia-driven target vessel revascularization at one year |
| Recurrent Ischemia | 12 month | Recurrent ischemia at one-year |
| Cardiac Events | 12 months | Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI |
| Target Vessel Failure | 12 months | Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization |
| Quality of Life Change From Baseline to 12 Months Follow-up | 12 months | Quality of life (assessed by the Seattle Angina Questionnaire) at baseline, 30-days, 6 months and 1 year (12 months). Minimum score is 0 and maximum score is 100, with a high score representing a more positive quality of life score. Outcome is the change in score from baseline to 12 months follow-up. |
| Target Vessel MI | 12 month | Target vessel Myocardial infarction at one year |
| Correlation Between iFR and Angiographic Visual Interpretation | at the end of the procedure/intervention | Correlation between iFR \<0.90 and coronary stenosis \>50% assessed by visual interpretation. This was tested using generalized estimating equations for logistic regression to account for the correlation of observations from the same subject. An absolute value of exactly 1 implies that a linear equation describes the relationship between iFR and visual interpretation of the angiography. Outcome reports how well the iFR value and the visual interpretation are in agreement (for example, when iFR \<0.90 and coronary stenosis \>50% assessed by visual interpretation the correlation is 1). |
| Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI | Procedural | Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI |
| Differentiation | End of procedure /intervention | Differentiation of the cause for impaired iFR |
| Delta iFR | at the end of the procedure/intervention | Predictors of delta iFR before and after PCI, or predictors of impaired iFR Outcome is presented as the odds ratio (OR) that the post-PCI iFR will be \<0.90. An OR \> 1 means greater odds that the post-PCI iFR is \<0.90, OR = 1 means there is no association, and OR \< 1 means there is a lower odds that the post-PCI iFR is \<0.90. |
| Cardiac Mortality | 12 months | All-cause and cardiac mortality at one year |
Countries
Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diagnostic Test: iFR Pullback iFR (instantaneous wave free ratio) pullback assessment post angiographically successful PCI | 500 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 32 |
| Overall Study | Other | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Diagnostic Test: iFR Pullback | — |
|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 9.9 | — |
| BMI (Body Mass Index) | 30.8 kg/m^2 STANDARD_DEVIATION 8.8 | — |
| Diabetes Mellitus | 169 Participants | — |
| Hyperlipidemia | 351 Participants | — |
| Hypertension | 383 Participants | — |
| Insulin treated diabetes | 48 Participants | — |
| Left ventricular ejection fraction (%) | 56.3 % of blood ejected with each contraction STANDARD_DEVIATION 9 | — |
| NSTEMI (Non-ST Elevated Myocardial Infarction) | 85 Participants | — |
| Prior Myocardial Infarction | 134 Participants | — |
| Prior Percutaneous Coronary Intervention (PCI) | 227 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Recent STEMI (ST Elevated MI) (>7days) | 21 Participants | — |
| Renal disease | 39 Participants | — |
| Sex: Female, Male Female | 121 Participants | — |
| Sex: Female, Male Male | 379 Participants | — |
| Silent Ischemia | 27 Participants | — |
| Smoker | 83 Participants | — |
| Stable angina | 212 Participants | — |
| Unstable Angina | 155 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 467 |
| other Total, other adverse events | 0 / 467 |
| serious Total, serious adverse events | 12 / 467 |
Outcome results
Primary
Number of Participants With Residual Ischemia (iFR <0.90)
Residual ischemia is defined as iFR measurement \<0.90 after operator-assessed angiographically successful PCI (residual diameter stenosis \<50% in any treated lesion in the target vessel) This outcome describes the number of participants that had a residual ischemia (defined as iFR\<0.90) after a PCI that appeared to be successful based on angiography.
Time frame: end of procedure/intervention
Population: Total vessels/units (535) in participant population (467)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Number of Participants With Residual Ischemia (iFR <0.90) | 112 participants |
Secondary
Cardiac Events
Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI
Time frame: 12 months
Population: The total number of participants was divided in two groups based on their post-PCI iFR result. (see primary endpoint) The total number of participants still in study at one year is 467.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Cardiac Events | 9 Participants |
| iFR < 0.90 | Cardiac Events | 3 Participants |
Secondary
Cardiac Mortality
All-cause and cardiac mortality at one year
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Cardiac Mortality | 0 Participants |
| iFR < 0.90 | Cardiac Mortality | 0 Participants |
Secondary
Correlation Between iFR and Angiographic Visual Interpretation
Correlation between iFR \<0.90 and coronary stenosis \>50% assessed by visual interpretation. This was tested using generalized estimating equations for logistic regression to account for the correlation of observations from the same subject. An absolute value of exactly 1 implies that a linear equation describes the relationship between iFR and visual interpretation of the angiography. Outcome reports how well the iFR value and the visual interpretation are in agreement (for example, when iFR \<0.90 and coronary stenosis \>50% assessed by visual interpretation the correlation is 1).
Time frame: at the end of the procedure/intervention
Population: The correlation calculation was performed on the total number of analyzable participants with a post-PCI iFR pullback assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Correlation Between iFR and Angiographic Visual Interpretation | 0.03 coefficient of determination (R2) |
Secondary
Delta iFR
Predictors of delta iFR before and after PCI, or predictors of impaired iFR Outcome is presented as the odds ratio (OR) that the post-PCI iFR will be \<0.90. An OR \> 1 means greater odds that the post-PCI iFR is \<0.90, OR = 1 means there is no association, and OR \< 1 means there is a lower odds that the post-PCI iFR is \<0.90.
Time frame: at the end of the procedure/intervention
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Delta iFR | pre-PCI reference vessel diameter | 0.32 Odds ratio |
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Delta iFR | lesion location in left anterior descending coronary artery | 5.65 Odds ratio |
Secondary
Differentiation
Differentiation of the cause for impaired iFR
Time frame: End of procedure /intervention
Population: Number of vessels in which residual ischemia (post-PCI iFR \<0.90) after angiographically successful PCI
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Differentiation | single or multiple residual focal lesions | 93 vessels |
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Differentiation | diffuse disease | 21 vessels |
Secondary
Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI
Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI
Time frame: Procedural
Population: This analysis assumes that all focal lesions with post-PCI iFR \<0.90 were successfully treated with additional PCI. Using the cutoff of iFR \<0.90, the outcome is the number of participants that would remain, or not have been treated, because the iFR measurements are under 0.90.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI | 23 Participants |
Secondary
Quality of Life Change From Baseline to 12 Months Follow-up
Quality of life (assessed by the Seattle Angina Questionnaire) at baseline, 30-days, 6 months and 1 year (12 months). Minimum score is 0 and maximum score is 100, with a high score representing a more positive quality of life score. Outcome is the change in score from baseline to 12 months follow-up.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Quality of Life Change From Baseline to 12 Months Follow-up | 21.42 units on a scale | Standard Deviation 24.99 |
| iFR < 0.90 | Quality of Life Change From Baseline to 12 Months Follow-up | 20.73 units on a scale | Standard Deviation 21.83 |
Secondary
Recurrent Ischemia
Recurrent ischemia at one-year
Time frame: 12 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Recurrent Ischemia | 6 Participants |
| iFR < 0.90 | Recurrent Ischemia | 1 Participants |
Secondary
Target Vessel Failure
Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization
Time frame: 12 months
Population: The total number of participants was divided in two groups based on their post-PCI iFR result. (see primary endpoint) The total number of participants still in study at one year is 467.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Target Vessel Failure | 4 Participants |
| iFR < 0.90 | Target Vessel Failure | 2 Participants |
Secondary
Target Vessel MI
Target vessel Myocardial infarction at one year
Time frame: 12 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Target Vessel MI | 4 Participants |
| iFR < 0.90 | Target Vessel MI | 2 Participants |
Secondary
Target Vessel Revascularization
Ischemia-driven target vessel revascularization at one year
Time frame: 12 month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants With Analyzable iFR Pullback Assessment Post Angiographically Successful PCI | Target Vessel Revascularization | 10 Participants |
| iFR < 0.90 | Target Vessel Revascularization | 3 Participants |