Yuling Fu

Acute Coronary Syndromes in the GUSTO-IIb Trial Prognostic Insights and Impact of Recurrent Ischemia

Background—Recurrent ischemia after an acute coronary syndrome portends an unfavorable outcome and has major resource-use implications. This issue has not been studied systematically among the spectrum of patients with acute coronary presentations, encompassing those with and without ST-segment elevation. Methods and Results—We assessed the 1-year prognosis of the 12 142 patients enrolled in the GUSTO-IIb trial by the presence (n54125) or absence (n58001) of ST-segment elevation. This latter group was further categorized into those with baseline myocardial infarction (n53513) or unstable angina (n54488). We also assessed the incidence of recurrent ischemia and its impact on outcomes. Recurrent ischemia was significantly rarer in those with ST-segment elevation (23%) than in those without (35%; P,0.001). Mortality at 30 days was greater among patients with ST-segment elevation (6.1% versus 3.8%; P,0.001) but less so at 6 months; by 1 year, mortality did not differ significantly (9.6% versus 8.8%). Patients with non‐ST-segment-elevation infarction had higher rates of reinfarction at 6 months (9.8% versus 6.2%) and higher 6-month (8.8% versus 5.0%) and 1-year mortality rates (11.1% versus 7.0%) than such patients who had unstable angina. Conclusions—Refractory ischemia was associated with an approximate doubling of mortality among patients with ST-segment elevation and a near tripling of risk among those without ST elevation. This study highlights not only the substantial increase in late mortality and reinfarction with non‐ST-segment-elevation infarction but also the opportunities for better triage and application of therapeutic strategies for patients with recurrent ischemia. (Circulation. 1998;98:1860-1868.)

Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial

AIMS To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention (PCI) and its association with 90-day outcomes. METHODS AND RESULTS We examined the incidence, propensity for, and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infarction patients with multi-vessel coronary artery disease (MVD). Of the 5373 patients who underwent primary PCI in the APEX-AMI trial, 2201 had MVD. Of those, 217 (9.9%) underwent non-infarct-related arteries (IRA) PCI, whereas 1984 (90.1%) underwent PCI of the IRA alone. Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group (12.5 vs. 5.6%, P (log-rank) < 0.001 and 17.4 vs. 12.0%, P (log-rank) = 0.020, respectively). After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI, this procedure remained independently associated with an increased hazard of 90-day mortality [adjusted hazard ratio 2.44, 95% CI (1.55-3.83), P < 0.001]. CONCLUSION Non-culprit coronary interventions were performed at the time of primary PCI in 10% of MVD patients and were significantly associated with increased mortality. Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients. Prospective randomized study of this issue may be warranted.

Prognostic value of ST segment depression in acute coronary syndromes: insights from PARAGON-A applied to GUSTO-IIb ☆

Objectives Our objectives were to develop a risk-stratification model addressing the importance of the magnitude and distribution of ST segment depression in predicting long-term outcomes and to validate the model in an analogous patient population. Background Although patients without ST segment elevation presenting with acute coronary syndromes represent an increasingly frequent population admitted to coronary care units, little attention has been paid to quantifying their ST segment abnormalities. Methods ST segment depression was categorized into three groups: 1) no ST segment depression; 2) 1-mm ST segment depression in two contiguous leads; and 3) ST segment depression > or =2 mm in two contiguous leads. A logistic regression model was developed using Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A) data to assess the prognostic value of the extent and distribution of ST segment depression in predicting one-year mortality. The model was validated using the non-ST segment elevation population in Global Use of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO-IIb). Results ST segment depression was the strongest predictor of one-year mortality, accounting for 35% of the models predictive power. Patients with ST segment depression > or =2 mm were approximately 6 times (odds ratio [OR] 5.73, 95% confidence interval [CI] 2.8 to 11.6) more likely to die within one year than patients with no ST segment depression. On validation, the model showed good discriminatory power (c-index = 0.75). Patients with ST segment depression > or =2 mm in more than one region were almost 10 times more likely to die within one year than patients with no ST segment depression. Conclusions These data provide new evidence supporting the powerful prognostic value of the baseline electrocardiogram and, in particular, the magnitude and distribution of ST segment depression in predicting unfavorable events.

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]; ≥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]; ≥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.

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients.

OBJECTIVES Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each markers relative prognostic utility. BACKGROUND The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml. RESULTS Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.

Incidence, distribution, and prognostic impact of occluded culprit arteries among patients with non–ST-elevation acute coronary syndromes undergoing diagnostic angiography

BACKGROUND Because acute occlusion of coronary arteries supplying the inferolateral myocardium frequently eludes standard 12-lead electrocardiogram (ECG) diagnosis, these patients may present as non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS We examined culprit artery occlusion among 1,957 NSTE-ACS patients in the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network trial who underwent diagnostic coronary angiography. We compared baseline characteristics, electrocardiographic findings, in-hospital treatment, and long-term outcomes between patients with and without occluded culprit arteries. RESULTS The culprit artery was occluded in 528 (27%) patients. Culprit lesions were more frequently identified in the inferolateral territory among patients with an occluded culprit artery (63%) compared with those with a nonoccluded artery (45%, P < .0001). Patients with an occluded culprit artery were younger, more often male, and more likely to have had a prior myocardial infarction. Despite similar in-hospital treatment, patients with an occluded culprit artery had larger infarcts (median peak creatine kinase-MB 4.3 vs 2.1 x upper limit of normal, P < .0001) and higher risk-adjusted 6-month mortality (hazard ratio 1.72, 95% CI 1.07-2.79). CONCLUSIONS More than 25% of NSTE-ACS patients had an occluded culprit artery on angiography. These patients may represent ST-segment elevation myocardial infarction equivalents; thus, improved early risk stratification techniques would help more rapidly triage these high-risk patients to an early invasive management strategy.

International differences in evolution of early discharge after acute myocardial infarction.

BACKGROUND Early discharge of low-risk patients with acute myocardial infarction is feasible and can be achieved at no additional risk of adverse events. We aimed to identify the extent to which countries have taken advantage of the opportunity for early discharge. METHODS The study population consisted of 54174 patients enrolled in GUSTO-I, GUSTO-III, and ASSENT-2 studies (enrollment period 1990-98) in the USA, Canada, Australia, New Zealand, Belgium, France, Germany, Spain, and Poland. We identified patients with uncomplicated acute myocardial infarction who were eligible for early discharge on the basis of previously established criteria, and assessed the extent to which these patients were discharged early--defined as discharged alive within 4 days of admission. The economic consequences (defined as potentially unnecessary hospital days consumed per 100 patients enrolled) were also investigated. FINDINGS Patients in all European countries had significantly longer stays than did those from non-European countries. Over the study period, the number of eligible patients discharged on or before day 4 increased in the USA, Canada, Australia, and New Zealand. Despite this increase, no more than 40% of patients who were eligible for early discharge were actually discharged early. The rate of early discharge of eligible patients was consistently low (<2%) in Belgium, France, Germany, Spain, and Poland. In ASSENT-2, which is the most recent trial in this study, the number of potentially unnecessary hospital days (per 100 patients enrolled) ranged from 65 in New Zealand to 839 in Germany. INTERPRETATION Despite more than a decade of research, there is still a lot of variation between countries in international length-of-stay patterns in acute myocardial infarction. The potential for more efficient discharge of low-risk patients exists in all countries investigated, but was especially evident in the European countries included in the study (Belgium, France, Germany, Spain, and Poland).

Canadian-American Differences in the Management of Acute Coronary Syndromes in the GUSTO IIb Trial One-Year Follow-Up of Patients Without ST-Segment Elevation

BackgroundLittle information exists concerning practice patterns between Canada and the United States in the management of myocardial infarction (MI) patients without ST-segment elevation and unstable angina. Methods and ResultsWe examined the practice patterns and 1-year outcomes of 2250 US and 922 Canadian patients without ST-elevation acute coronary syndromes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial. The US hospitals more commonly had on-site facilities for angiography and revascularization. These procedures were performed more often and sooner in the United States than Canada, whereas Canadian patients were more likely to undergo noninvasive stress testing. The length of initial hospital stay was 1 day longer for Canadian than US patients. Recurrent and refractory ischemia was more common in Canada. One-year mortality was comparable between the 2 countries. However, at 6 months, even after baseline differences were accounted for, the (re)MI rate was significantly higher in Canadian than US patients with unstable angina (8.8% versus 5.8%, P =0.039), as was the composite rate of death or (re)MI (13.1% versus 9.1%, P =0.016). ConclusionsOne-year mortality was comparable between Canada and the United States in both MI and unstable angina cohorts despite higher intervention rates in the United States. However, outcomes at 6 months among patients with unstable angina differed. Whereas more frequent coronary interventions were not associated with reduced recurrent MI or death among MI patients without ST elevation, they may favorably affect outcomes in patients with unstable angina.

Baseline Q-Wave Surpasses Time From Symptom Onset as a Prognostic Marker in ST-Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention

OBJECTIVES We assessed the incremental value of baseline Q waves over time from symptom onset as a marker of clinical outcome in ST-segment elevation myocardial infarction (STEMI). BACKGROUND Time from symptom onset is a central focus in STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG) has been suggested to be of incremental value to time from symptom onset in evaluating clinical outcomes. METHODS We evaluated baseline Q waves and ST-segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in 4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90-day mortality; and the composite of death, congestive heart failure (CHF), or cardiogenic shock were assessed. RESULTS Fifty-six percent of patients had baseline Q waves: they were older, more frequently male and diabetic, and had a more advanced Killip class. Patients with baseline Q waves had greater mortality and a higher composite rate of death, CHF, and shock versus patients without baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality and the composite outcome were lowest among those randomized < or =3 h without baseline Q waves. After multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF. CONCLUSIONS Baseline Q waves in STEMI patients treated with primary PCI provide an independent prognostic marker of clinical outcome. These data might be useful in designing future clinical trials as well as in evaluating patients for triage and potential transfer for planned primary PCI. (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX-AMI]; NCT00091637).

Differentiating ST Elevation Myocardial Infarction and Nonischemic Causes of ST Elevation by Analyzing the Presenting Electrocardiogram

Guidelines recommend that patients with suggestive symptoms of myocardial ischemia and ST-segment elevation (STE) in > or =2 adjacent electrocardiographic leads should receive immediate reperfusion therapy. Novel strategies aimed to reduce door-to-balloon time, such as prehospital wireless electrocardiographic transmission, may be dependent on the interpretation accuracy of the electrocardiogram (ECG) readers. We assessed the ability of experienced electrocardiographers to differentiate among STE, acute STE myocardial infarction (STEMI), and nonischemic STE (NISTE). A total of 116 consecutive ECGs showing STE were studied. Fifteen experienced cardiologists were asked to decide, based on the ECG and assuming that the patient had compatible symptoms, whether they would send each patient for primary percutaneous coronary intervention (PPCI). If NISTE was chosen, the reader selected 1 or more 12 possible options to explain the choice. Of 116 patients, only 8 had STEMI. The percentage of ECGs for which PPCI was recommended for the patient by the individual readers varied widely (7.8% to 33%). There was no significant difference between the North American and Other Countries readers (p = 0.13). The sensitivity and specificity of the individual readers ranged from 50% to 100% (average 75%) and 73% to 97% (average 85%), respectively. There were broad inconsistencies among the readers in the chosen reasons used to classify NISTE. In conclusion, we found wide variations among experienced electrocardiographers in reading ECGs with STE and differentiating STEMI with need for PPCI from NISTE. There is a need to revise our current electrocardiographic criteria for differentiating STEMI from NISTE.