Assessment of autonomic control of the heart during transient myocardial ischemia.

INTRODUCTION: In the presence of coronary artery obstruction, complex cardiovascular reflexes may lead to changes in heart rate and even to the precipitation of malignant arrhythmias. The autonomic nervous system (ANS) has traditionally been considered to be "balanced" between continuously interacting sympathetic and parasympathetic outflows. The purpose of this study was to assess ANS control of the heart during prolonged coronary balloon occlusion procedures of one of the major coronary arteries. METHODS: R-R intervals were obtained from continuous electrocardiographic data of 90 patients undergoing selective percutaneous coronary interventions (PCI) with balloon inflation periods ranging from 3 to 10 minutes (4.7 ± 1.1 minutes). Three 3-minute stages were chosen: (1) preinflation (baseline), (2) from the start of occlusion (PCI), and (3) immediately post deflation. The dynamics of the ANS was evaluated by heart rate variability analysis using standard time and frequency domain indices and the short-term fractal-like index (α(1)). RESULTS: During PCI, time and frequency domain measures related to vagal control decreased significantly with respect to baseline (significantly in left anterior descending [LAD] artery occlusions). During the postdeflation stage, heart rate variability and high-frequency power increased (P < .01) in the group with right coronary artery occlusions, whereas a marked sympathetic increase, as assessed by an increase (P < .01) of normalized low-frequency power and the low/high-frequency ratio was observed in the LAD group after balloon deflation. Fractal index α(1) decreased during the PCI period but increased significantly after balloon deflation. CONCLUSIONS: Significant changes in autonomic control of heart rate that were a function of the affected artery occurred during and after coronary artery occlusions. Occlusion of the LAD resulted in a significant reduction of vagal activity and a decrease of the short-term fractal index during PCI and a marked sympathetic response after postdeflation. However, a marked increment of vagal activity between the occlusion stage and postdeflation period was found in the right coronary artery group. These results may relate the site of the occlusion and lack of blood supply to different parts of the left ventricle.

Contribution of angiographic and electrocardiographic parameters of reperfusion to prediction of mortality and morbidity after acute ST-elevation myocardial infarction: Insights from the Assessment of Pexelizumab in Acute Myocardial Infarction trial.

BACKGROUND: Reperfusion with primary percutaneous intervention (PCI) in ST-segment elevation myocardial infarction leads to improved clinical outcomes. The contribution angiographic vs electrocardiographic reperfusion parameters confer on prognosis is unclear. METHODS: A prespecified subset of the APEX-AMI trial patients was analyzed by independent angiographic and electrocardiographic core laboratories (n = 1,018). Angiographic reperfusion after PCI and electrocardiogram 30 minutes post-PCI were assessed. RESULTS: Of the 941 patients in the angiographic substudy, 796 (85%) attained post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow 3 and 852 (91%) had TIMI Myocardial Perfusion Grade (TMPG) 2/3. There were 664 (71%) patients with residual ST elevation (ST-E) <2 mm. Ninety-day mortality and death/CHF/shock were lower in patients with TIMI flow 3 vs <3 (1.9% vs 6.2%, P = .002; 5.8% vs 10.4%, P = .044) and those with TMPG 2/3 vs 0/1 (2.0% vs 7.9%, P = .001; 6.0% vs 11.9%, P = .028). Patients with residual ST-E <2 mm had similar rates of mortality as those with > or =2 mm (2.3% vs 3.3%, P = .374) but lower rates of death/CHF/shock (5.2% vs 9.6%, P = .013). After multivariable adjustment, only post-PCI TMPG 2/3 was significantly associated with survival (P = .001), whereas residual ST-E (P = .606) and post-PCI TIMI flow grade (P = .086) were not. Conversely, residual ST-E > or =2 mm (P = .012) rather than angiographic reperfusion was associated with the composite of death/CHF/shock events. CONCLUSION: Angiographic and electrocardiographic estimates of reperfusion with primary PCI in ST-segment elevation myocardial infarction provide different and complementary predictions of morbidity and mortality.

ST-segment recovery and outcome after primary percutaneous coronary intervention for ST-elevation myocardial infarction: insights from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial.

BACKGROUND: Primary percutaneous coronary angioplasty is an effective and widely adopted treatment for acute myocardial infarction. A simple method of determining prognosis after primary percutaneous coronary intervention (PCI) would facilitate appropriate care and expedite hospital discharge. Thus, we determined the prognostic importance of various measures of ST-segment-elevation recovery after primary PCI in a large, contemporary cohort of patients with ST-elevation myocardial infarction. METHODS AND RESULTS: We analyzed ECG data describing the magnitude and extent of ST-segment elevation and deviation before and early after (ie, 30 minutes) primary PCI in the study cohort of 4866 subjects with electrocardiographically high-risk ST-elevation myocardial infarction enrolled in the Assessment of PEXelizumab in Acute Myocardial Infarction (APEX-AMI) trial. Associations among 6 methods for calculating ST-segment recovery, biomarker estimates of infarct size (ie, peak creatine kinase, creatine kinase-MB, and troponin I and T), and prespecified clinical outcomes (ie, rates of 90-day death and 90-day death, heart failure, or shock) were examined. All ST-segment-recovery methods provided strong prognostic information regarding clinical outcomes. A simple ST-segment-recovery method of residual ST-segment elevation measurement in the most affected lead on the post-PCI ECG performed as well as complex methods that required comparison of pre- and post-PCI ECGs or calculation of summed ST-segment deviation in multiple leads (ie, worst-lead residual ST elevation: adjusted hazard ratio for 90-day death rate [reference <1 mm]: 1 to <2 mm, 1.23 [95% CI 0.74 to 2.03]; > or =2 mm, 2.22 [95% CI 1.35 to 3.65], corrected c-index=0.832; 90-day death/congestive heart failure/shock [reference <1 mm]: 1 to <2 mm, 1.55 [95% CI 1.06 to 2.26]; > or =2 mm, 2.33 [95% CI 1.59 to 3.41], corrected c-index=0.802). Biomarker estimates of infarct size declined in association with enhanced ST-segment recovery. CONCLUSIONS: An ECG performed early after primary PCI is a simple, widely available, inexpensive, and powerful prognostic tool applicable to patients with ST-elevation myocardial infarction.

Paramedic transtelephonic communication to cardiologist of clinical and electrocardiographic assessment for rapid reperfusion of ST-elevation myocardial infarction.

BACKGROUND/PURPOSE: We tested the hypothesis that paramedic recognition of ST-elevation myocardial infarction (STEMI) and cardiologist activation of the cardiac catheterization laboratory without transmission of the electrocardiogram reduces door-to-balloon times. METHODS: We studied a consecutive series of patients suspected to have STEMI who were taken to the cardiac catheterization laboratory in the 6-month period before hotline implementation (historical controls) and during the first year of hotline use (intervention group, hotline; emergency medical service patients without hotline, concurrent controls). RESULTS: Emergency medical services activated the hotline 47 times, and 25 patients were subsequently taken to the catheterization laboratory. Patients who received PCI involving hotline use (n = 20) had significantly shorter door-to-balloon times (58 minutes; 25th-75th percentile, 52-73 minutes) than historical controls (n = 15) (112 minutes; 25th-75th percentile, 81-137; P < .0001) and concurrent controls (n = 15) (92 minutes; 25th-75th percentile, 76-112; P = .019). CONCLUSIONS: Paramedic transtelephonic communication to cardiologist of clinical and electrocardiogram assessment resulted in a 54-minute reduction in door-to-balloon time for patients with STEMI.

A cooperative network of trained sites for the conduct of a complex clinical trial: a new concept in multicenter clinical research.

BACKGROUND: The purpose of this report is to present a model of physicians in full-time clinical practice participating as investigators in multicenter clinical trials, sponsored by a pharmaceutical or medical device company. METHODS: This gas-exchange substudy was conducted as a pilot study to establish the feasibility of the 10-member EXERcise testing group of the Duke University Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex multicenter trial using cardiopulmonary exercise testing. An active interchange of information was established involving the principal investigator for the substudy, a dedicated full-time project coordinator, a medical director of the overall EXERDUCCS network site, the project coordinator for the sponsor, and all the participating EXERDUCCS investigators and coordinators. RESULTS: The sponsor set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met this goal. As a result of the successful enrollment and completion of the study and substudy by the EXERDUCCS sites, the sponsor subsequently increased the payment stipends to the sites to compensate for the extra work and expense incurred. CONCLUSIONS: This cooperative experience accomplished several goals: (1) it allowed a complex clinical trial to be successfully completed in a time frame which would not have been possible using only single unconnected sites; (2) it educated the physician-investigators (and their personnel) in exercise cardiopulmonary; and (3) it prepared the sites for future clinical trials involving this methodology.

Electrocardiographic infarct size assessment after thrombolysis: insights from the Acute Myocardial Infarction STudy ADenosine (AMISTAD) trial.

BACKGROUND: Noninvasive methods are needed to evaluate reperfusion success in patients with acute myocardial infarction (MI). The AMISTAD trial was analyzed to compare MI size and myocardial salvage determined by electrocardiogram (ECG) with technetium Tc 99m sestamibi single-photon emission computerized tomography (SPECT) imaging. METHODS: Of 236 patients enrolled in AMISTAD, 166 (70 %) with no ECG confounding factors and no prior MI were included in this analysis. Of these, group 1 (126 patients, 53%) had final infarct size (FIS) available by both ECG and SPECT. Group 2 (56 patients, 24%) had myocardium at risk, FIS, and salvage index (SI) assessed by both SPECT and ECG techniques. Aldrich/Clemmensen scores for myocardium at risk and the Selvester QRS score for final MI size were used. Salvage index was calculated as follows: SI = (myocardium at risk-FIS)/(myocardium at risk). RESULTS: In group 1, FIS was 15% (6, 24) as measured by ECG and 11% (2, 27) as measured by SPECT. In the adenosine group, FIS was 12% (6, 21) and 11% (2, 22). In the placebo group, FIS was 16.5% (7.5, 24) and 11.5% (3.0, 38.5) by ECG and SPECT, respectively. The overall correlation between SPECT and ECG for FIS was 0.58 (P = .0001): 0.60 in the placebo group (P = .0001) and 0.54 (P = .0001) in the adenosine group. In group 2, myocardium at risk was 23% (17, 30) and 26% (10, 50) with ECG and SPECT, respectively (P = .0066). Final infarct size was 17% (6, 21) and 12% (1, 24) (P < .0001). The SI was 29% (-7, 57) and 46% (15, 79) with ECG and SPECT, respectively (P = .0510). CONCLUSIONS: The ECG measurement of infarct size has a moderate relationship with SPECT infarct size measurements in the population with available assessments. This ECG algorithm must further be validated on clinical outcomes.

Prognostic value of predischarge electrocardiographic measurement of infarct size after thrombolysis: insights from GUSTO I Economics and Quality of Life substudy.

BACKGROUND: Current methods for risk stratification after acute myocardial infarction (MI) include several noninvasive studies. In this cost-containment era, the development of low-cost means should be encouraged. We assessed the ability of an electrocardiogram (ECG) MI-sizing score to predict outcomes in patients enrolled in the Economics and Quality of Life (EQOL) sub study of the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries -I (GUSTO-I) trial. METHODS: We classified patients by electrocardiographic Selvester QRS score at hospital discharge: those with a score 0-9 versus > or =10. Endpoints were 30-day and 1-year mortality, resource use, and quality-of-life measures. RESULTS: Patients with a QRS score <10 were well-matched with those with QRS score > or =10 with the exception of a trend to more anterior MI in the higher scored group. Patients with QRS score > or =10 had increased risk of death at 30-days (8.9% vs. 2.9% P < .001), and this difference persisted at 1 year (12.6% vs. 5.4%, P = .001). Recurrent chest pain, use of angiography, and angioplasty were similar during follow-up. However, there was a trend toward less coronary bypass surgery in patients with a QRS score > or =10. Readmission rates were higher at 30 days but similar at 1 year. CONCLUSIONS: Stratification of patients after acute MI by a simple measure of MI size identifies populations with different long-term prognoses; patients with a QRS score > or =10 (approximately 30% of the left ventricle infarcted) at discharge have poorer outcomes in both the short- and long-term. The standard 12-lead ECG provides a simple, economical means of risk stratification at discharge.

Aborted myocardial infarction in patients with ST-segment elevation: insights from the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen-3 Trial Electrocardiographic Substudy.

OBJECTIVES: The investigators undertook a systematic, comprehensive analysis of the therapeutic response and clinical outcomes of reperfusion therapy for acute ST-segment elevation myocardial infarction (STEMI) in 5,470 patients from the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 trial. BACKGROUND: Prompt effective reperfusion therapy for acute STEMI may attenuate major myocardial necrosis. METHODS: We prospectively collected sequential electrocardiographs and clinical data. Aborted myocardial infarction (MI) was defined as maximal creatine kinase < or =2x upper limit of normal coupled with typical evolutionary electrocardiographic changes. RESULTS: Of the patients, 727 (13.3%) had an aborted MI, with the highest frequency (25%) occurring in patients treated <1 h after symptom onset. As compared with MI patients, patients with aborted MI more often had complete ST-segment resolution at 60 min (56.3% vs. 30.2%, p < 0.001) and 180 min (61.5% vs. 53%, p < 0.001); they also had smaller infarct sizes based on QRS score at discharge (2.37 vs. 4.62, p <0.001). Mortality in aborted MI patients compared with those who had true MI was 3.9% versus 4.6% at 30-day and 7.0% versus 7.4% at 1-year. The baseline-adjusted mortality was significantly lower in patients with aborted MI (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.63 to 0.92, p = 0.005 for 30-day and OR 0.70, 95% CI 0.50 to 0.98, p = 0.035 for one year). A very low-risk subset was identified with > or =70% ST-segment resolution at 60 min whose 30-day and 1-year mortality was 1.0% and 2.7%, respectively, compared with 5.9% and 9.3% in aborted MI patients with <70% ST-segment resolution at 60 min (all p < or = 0.002). CONCLUSIONS: Prompt fibrinolytic treatment improved the likelihood of aborted MI. The subgroup with complete 60-min ST-segment resolution had the best clinical outcomes.

Quantitative clinical assessment of chronic anterior myocardial infarction with delayed enhancement magnetic resonance imaging and QRS scoring.

BACKGROUND: Both the regional and global myocardial extent of chronic myocardial infarction (MI) are important prognostic factors for length and quality of life and also crucial for the choice of therapy in patients with ischemic heart disease. Our aim was to develop and validate techniques for comparison between regional and global size of remote anterior MI in the left ventricle quantified with both magnetic resonance imaging (MRI) and electrocardiogram (ECG). METHODS: Delayed-enhancement (DE) MRI was used as a clinical "gold standard" for MI size to evaluate the extent of MI estimated with the commonly available standard 12-lead ECG. A method for comparing global and regional quantifications of MI with DE-MRI and ECG was developed. The Selvester QRS-scoring system was used for estimating MI size electrocardiographically. RESULTS: Twenty-five patients with chronic single anterior MI, documented with DE-MRI, were studied. The best agreement for mean % MI per regional segment of the left ventricle was found in the middle third (26% vs 27%), whereas the most significant discrepancy was found in the apex (56% vs 30%). The global MI size of the left ventricle averaged 21 +/- 9% with DE-MRI and 22% +/- 12% with ECG, with a correlation of r = 0.40 (P <.05). CONCLUSIONS: The current Selvester QRS scoring system performs well for quantifying anterior MI in the mid-regions of the left ventricle. The diagnostic performance of the Selvester QRS-scoring system for quantifying MI in the other regions, particularly the left ventricular apex, can potentially be improved, with DE-MRI as the gold standard.

An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: Results from a randomized trial.

STUDY OBJECTIVE: Conventional emergency department testing strategies for patients with chest pain often do not provide unequivocal diagnosis of acute coronary syndromes. This study was conducted to determine whether the routine use of single photon emission computed tomography (SPECT) imaging at rest and early exercise stress testing to assess intermediate-risk patients with chest pain and no ECG evidence of acute ischemia will lead to earlier discharges, more discriminate use of coronary angiography, and an overall reduction in average costs of care with no adverse clinical outcomes. METHODS: All patients in this study had technetium 99m tetrofosmin SPECT imaging at rest and were randomly assigned to either a conventional (results of the imaging test blinded to the physician) or perfusion imaging-guided (results of the imaging test unblinded to the physician) strategy. Patients in the conventional arm were treated at their physician's discretion. Patients in the perfusion imaging-guided arm were treated according to a predefined protocol based on SPECT imaging test results: coronary angiography after a positive scan result and exercise treadmill testing after a negative scan result. Study endpoints consisted of total in-hospital costs and length of stay. Hospital costs were calculated using hospital department-specific Medicare cost/charge ratios. Length of stay was calculated as total hospital room days billed (regular and intensive care). RESULTS: We enrolled 46 patients, 9 with acute myocardial infarctions. Patients randomly assigned to the perfusion imaging-guided arm had $1,843 (95% confidence interval [CI] $431 to $6,171) lower median in-hospital costs and 2.0-day (95% CI 1.0 to 3.0 days) shorter median lengths of stay but similar rates of in-hospital and 30-day follow up events as patients in the conventional arm. CONCLUSION: An ED chest pain diagnostic strategy incorporating acute resting 99mTc tetrofosmin SPECT imaging and early exercise stress testing may lead to reduced in-hospital costs and decreased length of stay for patients with acute chest pain and nondiagnostic ECGs. [Stowers SA, Eisenstein EL, Wackers FJTh, Berman DS, Blackshear JL, Jones AD Jr, Szymanski TJ Jr, Lam LC, Simons TA, Natale D, Paige KA, Wagner GS. An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms: results from a randomized trial. Ann Emerg Med. January 2000;35:17-25.].