Arrhythmia, Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Infarction, Ventricular Fibrillation
Conditions
Keywords
Stents, myocardial infarction
Brief summary
The purpose of this study is to determine if opening blocked arteries with heart balloons and stents prevents heart rhythm problems in individuals 3 to 28 days after a heart attack.
Detailed description
BACKGROUND: There is now unequivocal evidence that early coronary reperfusion using either thrombolytics or primary angioplasty results in a long-term mortality reduction among individuals who have had a heart attack. The benefit of early reperfusion (less than 6 hours after the heart attack) was initially attributed to myocardial salvage and the resultant preservation of left ventricular function. However, it is now known that the survival benefit associated with thrombolytic therapy is not consistently associated with a major improvement in left ventricular ejection fraction (LVEF). These observations led to the formulation of the late open artery hypothesis, which suggests that clinical outcomes can potentially be improved by late reperfusion after a heart attack. Observational clinical studies have suggested that late patency of the infarct-related artery (IRA) after thrombolysis is associated with a survival benefit that is independent of LVEF and therefore cannot be solely explained by salvage of myocardium. Definitive proof of the late open artery hypothesis is currently lacking, however, because previous studies that have evaluated late percutaneous transluminal coronary angioplasty (PTCA) of occluded IRAs after a heart attack have produced conflicting results. These findings led to the organization of the Occluded Artery Trial (OAT), an international, NHLBI-funded, randomized trial of 2,200 participants. OAT is testing the hypothesis that mechanical reperfusion of an occluded IRA with PTCA and percutaneous coronary intervention (PCI) 3 to 28 days after a heart attack in high-risk individuals will reduce mortality, recurrent heart attacks, and hospitalization for class IV congestive heart failure. Enhancement of electrical stability is one of the major mechanisms that has been proposed to explain the association of an open IRA with an improved prognosis independent of myocardial salvage. DESIGN NARRATIVE: This study is an ancillary study of OAT. It will characterize the effects of late PCI of occluded IRAs on the most important and clinically relevant noninvasive markers of vulnerability to malignant ventricular arrhythmias: heart rate variability, T wave variability, and signal-averaged electrocardiography. These analyses will be performed in 300 participants at baseline, 30 days, and 1 year following a heart attack in order to determine the effects of late PCI on the autonomic nervous system, ventricular repolarization, and ventricular conduction abnormalities.
Interventions
PROCEDUREPCI
DRUGOptimal Medical Therapy
Guideline-directed drug therapies after MI
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Has experienced a heart attack 3 to 28 days prior to study entry * Persistently occluded IRA defined as either: 1) Thrombolysis in Myocardial Infarction (TIMI) 0, with no flow beyond the site of occlusion; or 2) TIMI 1, with penetration of dye beyond the site of occlusion without dye reaching the distal vessel * LVEF less than 50% or proximal occlusion in a large vessel * Normal sinus rhythm * QRS duration less than 120 ms * Able to return for follow-up assessment of arrhythmia markers one month and one year after study entry
Exclusion criteria
* Has a clinical indication for revascularization (post-heart attack angina at rest; significant inducible ischemia; or significant left main or triple vessel disease requiring PTCA or CABG) * Current serious illness or condition that limits 3-year survival * Severe valvular disease * Chronic total occlusion * New York Heart Association Class III-IV congestive heart failure * Prior left ventricular aneurysm in the recent heart attack location * Is a poor candidate for PTCA/stent on the basis of angiographic or clinical criteria * Cannot medically survive anticoagulation during PTCA/stent or antiplatelet therapy after stent * Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-termed Fractal Scaling Exponent (Alpha 1) | Baseline, one year | Nonlinear measurement of heart rate variability, change between baseline and 1 year is the primary outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T-wave Variability | Baseline and one year | Variability in T wave morphology, change between baseline and one year |
| Filtered QRS Duration | Baseline and one year | Signal-averaged ECG |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PCI+Optimal Medical Therapy PCI with angioplasty and stenting of the infarct-related artery and optimal medical therapy
PCI
Optimal Medical Therapy: Guideline-directed drug therapies after MI | 149 |
| Optimal Medical Therapy Optimal medical therapy alone
Optimal Medical Therapy: Guideline-directed drug therapies after MI | 151 |
| Total | 300 |
Baseline characteristics
| Characteristic | Optimal Medical Therapy | Total | PCI+Optimal Medical Therapy |
|---|---|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 10.5 | 57.4 years STANDARD_DEVIATION 10.5 | 57.2 years STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 3 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 | 30 Participants | 61 Participants | 31 Participants |
| Race (NIH/OMB) White | 117 Participants | 232 Participants | 115 Participants |
| Sex: Female, Male Female | 24 Participants | 62 Participants | 38 Participants |
| Sex: Female, Male Male | 127 Participants | 238 Participants | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 149 | 0 / 151 |
| serious Total, serious adverse events | 0 / 149 | 0 / 151 |
Outcome results
Primary
Short-termed Fractal Scaling Exponent (Alpha 1)
Nonlinear measurement of heart rate variability, change between baseline and 1 year is the primary outcome.
Time frame: Baseline, one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI+Optimal Medical Therapy | Short-termed Fractal Scaling Exponent (Alpha 1) | 0.01 unit-less | Standard Deviation 0.34 |
| Optimal Medical Therapy | Short-termed Fractal Scaling Exponent (Alpha 1) | -0.03 unit-less | Standard Deviation 0.32 |
Comparison: The planned sample size of 300 subjects was chosen to provide 80% power to detect a clinically relevant difference of 0.1 in the change in α1 from baseline to 1 year between the 2 treatment groups on the basis of data from prior studies that indicated that baseline levels of α1 would be 1.0 with a common SD of 0.2.p-value: 0.3495% CI: [-0.12, 0.04]t-test, 2 sided
Secondary
Filtered QRS Duration
Signal-averaged ECG
Time frame: Baseline and one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI+Optimal Medical Therapy | Filtered QRS Duration | 1.5 Milliseconds | Standard Deviation 12.4 |
| Optimal Medical Therapy | Filtered QRS Duration | 3.7 Milliseconds | Standard Deviation 11.8 |
p-value: 0.2395% CI: [-1.4, 5.9]t-test, 2 sided
Secondary
T-wave Variability
Variability in T wave morphology, change between baseline and one year
Time frame: Baseline and one year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI+Optimal Medical Therapy | T-wave Variability | -6.3 Microvolts | Standard Deviation 25.1 |
| Optimal Medical Therapy | T-wave Variability | -3.4 Microvolts | Standard Deviation 31 |
p-value: 0.4595% CI: [-4.8, 10.7]t-test, 2 sided