Acute Myocardial Infarction
Conditions
Keywords
Acute Myocardial Infarction, STEMI, Post Conditioning, Primary Percutaneous Coronary Intervention
Brief summary
This study will evaluate change in heart muscle function from baseline to three months and twelve months in participants who present with a heart attack and a completely occluded coronary artery. These subjects will be randomized to receive standard Percutaneous transluminal coronary angioplasty (PTCA)/Stenting to open the artery or routine PTCA/Stenting plus post conditioning. Post conditioning commences immediately upon reperfusion using four cycles of thirty second inflations with a standard angioplasty balloon followed by a thirty seconds of reperfusion. The investigators hypothesize that Postconditioning reduces the size of the heart attack when utilized with successful primary Angioplasty/stent.
Detailed description
Single center study involving 140 patients randomized to Post Conditioning + Percutaneous coronary intervention (PCI) versus routine PCI during their ST-Elevation Myocardial Infarction (STEMI, Heart Attack) presentation. The Post Conditioning protocol consists of performing four, 30-second PTCA (Angioplasty) balloon occlusions followed by 30-seconds of reperfusion over a total of 4 minutes. The first balloon inflation occurs immediately after an angioplasty guidewire is placed through the obstruction in the artery. Following this protocol the vessel is stented as part of the usual practice for treatment of STEMI. No other treatment differences will occur between the two groups and all patients will receive the usual post-STEMI care. Patients in both groups will receive a cardiac MRI 3-5 days following their STEMI for measurement of heart attack size and heart muscle function, among other measures. Patients will undergo collection of blood for creatine kinase (CK)-MB and troponin I every 8 hours for 24 hours following PCI. All patients will be followed by phone follow-up visits to review history and major adverse cardiac event (MACE) (death, recurrent STEMI, repeat revascularization, arrhythmias, implantable cardioverter-defibrillator (ICD) placement and hospitalization for congestive heart failure (CHF)). All patients will be required to take P2Y12 inhibitors and aspirin for the duration of the trial. All patients will be treated with angiotensin-converting enzyme inhibitor (ACE-I), beta blockers and statins.
Interventions
PROCEDUREPost Conditioning + Primary PCI
Four, 30-second PTCA balloon occlusions followed by 30-seconds of reperfusion over a total of 4 minutes, in addition to Percutaneous Coronary Intervention as clinically indicated.
PROCEDUREStandard Primary PCI
Routine Percutaneous Coronary Intervention as clinically indicated.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Minneapolis Heart Institute Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years old, \< 80 years old * Able to give informed consent * Able to undergo cMRl (cardiac magnetic resonance imaging * ST-segment elevation infarction with 100% occlusion of a major epicardial vessel (\> 2.5 mm) * No angiographic evidence of collateral flow distal to occluded artery * Ischemic duration between 1.0 and 6 hours * Thrombolysis in myocardial infarction (TIMI) 3 Flow following PCI
Exclusion criteria
* Visible collateral blood flow to the distal vasculature of the occluded vessel * Previous Coronary Artery Bypass Graft surgery * Previous q-wave myocardial infarction in the same territory * Inability to give informed consent * Inability to undergo cMRl * Life expectancy less than one year * History of Non-compliance or alcohol or drug addiction * Patients with cardiogenic shock, cardiac arrest, hypothermia on presentation * Chronic dialysis or significant renal insufficiency (Creatinine Clearance \< 35 mI/mm/i .73 m2) * TIMI Flow \> 0 on presentation * Ischemic Time \> 6 hours or \< 1.0 hours * Presence of significant valvular heart disease (\>mod Aortic Stenosis, \>2+ Mitral Regurgitation) * Known Left Ventricular systolic dysfunction (Left Ventricular Ejection Fraction \< 50% prior to STEMI)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI) | Day 3-5 post-PCI | Infarct size was quantified by delayed, contrast-enhanced MRI |
| Myocardial Salvage Index (MSI) on Baseline cMRI | Day 3-5 post-PCI | The myocardial salvage index (MSI) was calculated using the formula: MSI = (AAR - Infarct size) / AAR X 100 % where quantitative estimation of myocardium at risk (AAR) was measured as the hyperintense region on T2- weighted imaging. Measurements were performed using the QMass software package (Medis mc, Raleigh NC) by a single investigator who was blinded to treatment. The endocardial and epicardial borders were manually identified and the regions of interest (edema or scar) were automated as 2 standard deviations above the mean density of the myocardium. |
| Micro Vascular Obstruction (MVO) on Baseline cMRI | Day 3-5 post-PCI | High T1 imaging was utilized for the determination of the presence or absence of MVO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl | baseline | LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. |
| Global Left Ventricular Ejection Fraction | baseline | — |
| Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl | baseline | LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. |
| Infarct Size by Peak Troponin | over first 72 hour post PCI | — |
| Infarct Size by Peak Creatine Kinase (CK) | over first 72 hours post PCI | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Post Conditioning + PCI Post Conditioning + Primary PCI: Four, 30-second PTCA balloon occlusions followed by 30-seconds of reperfusion over a total of 4 minutes, in addition to Percutaneous Coronary Intervention as clinically indicated. | 54 |
| Standard PCI Standard Primary PCI: Routine Percutaneous Coronary Intervention as clinically indicated. | 49 |
| Total | 103 |
Baseline characteristics
| Characteristic | Post Conditioning + PCI | Total | Standard PCI |
|---|---|---|---|
| Age, Continuous | 59.8 Years STANDARD_DEVIATION 10 | 59.9 Years STANDARD_DEVIATION 9.8 | 60.0 Years STANDARD_DEVIATION 9.7 |
| Current Smoker No | 26 Participants | 44 Participants | 18 Participants |
| Current Smoker Unknown | 0 Participants | 1 Participants | 1 Participants |
| Current Smoker Yes | 28 Participants | 58 Participants | 30 Participants |
| Diabetes Diabetes | 10 Participants | 19 Participants | 9 Participants |
| Diabetes No Diabetes | 44 Participants | 84 Participants | 40 Participants |
| Ejection Fraction | 50.3 Percent of blood ejected STANDARD_DEVIATION 10 | 50.2 Percent of blood ejected STANDARD_DEVIATION 10 | 50.1 Percent of blood ejected STANDARD_DEVIATION 10.1 |
| Family History of Myocardial Infarction No | 36 Participants | 62 Participants | 26 Participants |
| Family History of Myocardial Infarction Yes | 18 Participants | 41 Participants | 23 Participants |
| History of Stroke No | 53 Participants | 102 Participants | 49 Participants |
| History of Stroke Yes | 1 Participants | 1 Participants | 0 Participants |
| Hyperlipidemia Dyslipidemia | 33 Participants | 59 Participants | 26 Participants |
| Hyperlipidemia No Dylsipidemia | 21 Participants | 44 Participants | 23 Participants |
| Hypertension Hypertension | 29 Participants | 51 Participants | 22 Participants |
| Hypertension No Hypertension | 25 Participants | 52 Participants | 27 Participants |
| Infarct related artery LAD | 22 Participants | 39 Participants | 17 Participants |
| Infarct related artery LCx | 4 Participants | 7 Participants | 3 Participants |
| Infarct related artery Multiple Arteries | 3 Participants | 4 Participants | 1 Participants |
| Infarct related artery RCA | 25 Participants | 53 Participants | 28 Participants |
| Ischemic Duration | 144 Minutes | 146 Minutes | 158 Minutes |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 48 Participants | 94 Participants | 46 Participants |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Male | 48 Participants | 87 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 1 / 49 |
| other Total, other adverse events | 13 / 54 | 7 / 49 |
| serious Total, serious adverse events | 2 / 54 | 2 / 49 |
Outcome results
Primary
Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI)
Infarct size was quantified by delayed, contrast-enhanced MRI
Time frame: Day 3-5 post-PCI
Population: There were 12 patients whose MRI data were not usable, including 6 in the post conditioning + PCI group and 6 in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI) | 20.1 ml |
| Standard PCI | Infarct Size on Baseline Cardiac Magnetic Resonance Imaging (cMRI) | 21.0 ml |
p-value: 0.9Kruskal-Wallis
Primary
Micro Vascular Obstruction (MVO) on Baseline cMRI
High T1 imaging was utilized for the determination of the presence or absence of MVO.
Time frame: Day 3-5 post-PCI
Population: There were 8 patients in which were unable to determine the presence or absence of MVO, including 4 in the post conditioning + PCI group and 4 in the standard PCI group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post Conditioning + PCI | Micro Vascular Obstruction (MVO) on Baseline cMRI | 31 Participants |
| Standard PCI | Micro Vascular Obstruction (MVO) on Baseline cMRI | 25 Participants |
p-value: 0.45Chi-squared
Primary
Myocardial Salvage Index (MSI) on Baseline cMRI
The myocardial salvage index (MSI) was calculated using the formula: MSI = (AAR - Infarct size) / AAR X 100 % where quantitative estimation of myocardium at risk (AAR) was measured as the hyperintense region on T2- weighted imaging. Measurements were performed using the QMass software package (Medis mc, Raleigh NC) by a single investigator who was blinded to treatment. The endocardial and epicardial borders were manually identified and the regions of interest (edema or scar) were automated as 2 standard deviations above the mean density of the myocardium.
Time frame: Day 3-5 post-PCI
Population: There were 18 patients we were unable to obtain myocardial salvage indexes for, including 10 in the post conditioning + PCI group and 8 in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Myocardial Salvage Index (MSI) on Baseline cMRI | 32.6 (%) |
| Standard PCI | Myocardial Salvage Index (MSI) on Baseline cMRI | 32.7 (%) |
p-value: 0.81Kruskal-Wallis
Secondary
Global Left Ventricular Ejection Fraction
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post Conditioning + PCI | Global Left Ventricular Ejection Fraction | 55.1 Percent | Standard Deviation 10.8 |
| Standard PCI | Global Left Ventricular Ejection Fraction | 54.0 Percent | Standard Deviation 9.5 |
p-value: 0.58t-test, 2 sided
Secondary
Infarct Size by Peak Creatine Kinase (CK)
Time frame: over first 72 hours post PCI
Population: There was 1 patient who did not have a CK lab test done in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Infarct Size by Peak Creatine Kinase (CK) | 1701 IU/L |
| Standard PCI | Infarct Size by Peak Creatine Kinase (CK) | 1619 IU/L |
p-value: 1Kruskal-Wallis
Secondary
Infarct Size by Peak Troponin
Time frame: over first 72 hour post PCI
Population: There were 31 patients who did not have a troponin drawn within the specified study protocol window, including 10 in the post conditioning + PCI group and 21 in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Infarct Size by Peak Troponin | 19.63 ng/ml |
| Standard PCI | Infarct Size by Peak Troponin | 14.44 ng/ml |
p-value: 0.86Kruskal-Wallis
Secondary
Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl
LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole.
Time frame: baseline
Population: There were 4 patients who did not have an LVEDV measurement done, including 2 in the post conditioning + PCI group and 2 in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl | 149 mL |
| Standard PCI | Left Ventricular Remodeling (Left Ventricular End Diastolic Volume - LVEDV) as Measured by cMRl | 147 mL |
p-value: 0.58Kruskal-Wallis
Secondary
Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl
LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole, and the beginning of filling, or diastole.
Time frame: baseline
Population: There were 4 patients who did not have an LVESV measurement done, including 2 in the post conditioning + PCI group and 2 in the standard PCI group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Post Conditioning + PCI | Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl | 70 mL |
| Standard PCI | Left Ventricular Remodeling (Left Ventricular End Systolic Volume - LVESV) as Measured by cMRl | 65 mL |
p-value: 0.77Kruskal-Wallis