Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

Safety of the weight-adjusted dosing regimen of tenecteplase in the ASSENT-Trial.

The results of the ASsessment of Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial revealed that tenecteplase (TNK) is equivalent to tissue plasminogen activator (t-PA) for treating myocardial infarction. Because careful consideration of safety is important with all agents, including the newer bolus therapies, and across a range of doses, this study evaluated the safety of TNK compared with t-PA across a range of weight and dose categories. The 5 doses of TNK ranged from 30 to 50 mg and were adjusted for estimated weight. Rates of death and intracranial hemorrhage were determined among patients receiving TNK and t-PA in ASSENT-2, stratified by categories of estimated weight corresponding to each TNK dose. Respective rates of death with TNK versus t-PA were not significantly different in any estimated weight category: <60 kg (12.54% vs 11.46%), 60 to 69 kg (8.22% vs. 8.97%), 70 to 79 kg (5.57% vs 5.48%), 80 to 89 kg (4.66% vs 5.36%), and > or =90 kg (4.91% vs. 3.96%, all p > or =0.26). Respective rates of intracranial hemorrhage were also not significantly different: <60 kg (2.20% vs. 2.29%), 60 to 69 kg (0.97% vs. 1.33%), 70 to 79 kg (1.15% vs. 1.10%), 80 to 89 kg (0.73% vs 0.49%), and > or =90 kg (0.47% vs 0.47%, all p > or =0.33). Adjustment for small baseline differences in this randomized sample did not change the results. Thus, across the range of estimated weight categories corresponding to each TNK dose, TNK is as safe and effective as t-PA.

Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.

BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.

The association between white blood cell count and acute myocardial infarction mortality in patients > or =65 years of age: findings from the cooperative cardiovascular project.

OBJECTIVES: The purpose of the study was to examine the association between white blood cell (WBC) count on admission and 30-day mortality in patients with acute myocardial infarction (AMI). BACKGROUND: Elevations in WBC count have been associated with the development of AMI and with long-term mortality in patients with coronary artery disease. However, the relationship between WBC count and prognosis following AMI is less clear. METHODS: Using the Cooperative Cardiovascular Project database, we evaluated 153,213 patients > or = 65 years of age admitted with AMI. RESULTS: An increasing WBC count is associated with a significantly higher risk of in-hospital events, in-hospital mortality and 30-day mortality. Relative to those patients in the lowest quintile, patients in the highest quintile were three times more likely to die at 30 days (10.3% vs. 32.3%; p < 0.001). After adjustment for confounding factors, WBC count was found to be a strong independent predictor of 30-day mortality (odds ratio = 2.37; 95% confidence interval 2.25 to 2.49, p = 0.0001 for the highest quintile of WBC count). CONCLUSIONS: White blood cell count within 24 h of admission for an AMI is a strong and independent predictor of in-hospital and 30-day mortality as well as in-hospital clinical events. Although the mechanism of the association remains speculative, the results of this study have important clinical implications for risk-stratifying patients with AMI.

Use of reperfusion therapies in elderly patients with acute myocardial infarction.

Almost one-third of patients with acute myocardial infarction (AMI) are aged >75 years, and this proportion is expected to increase as the population ages. Mortality and complication rates are particularly high in the elderly, yet reperfusion therapies, including thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA), are under-utilised among eligible patients. There is a concern, whether real or perceived, that the risks of such therapies may outweigh the potential benefits. Presently, there are no randomised clinical trials of thrombolytic therapy in the elderly that definitively assess its efficacy in patients aged >75 years. In the meta-analysis of randomised trials by the Fibrinolytic Therapy Trialists, thrombolysis was associated with a mortality reduction among patients aged >75 years, though this reduction did not meet formal statistical significance. Because the point estimates for mortality reduction were in the direction that favoured use of thrombolytic therapy, the American Heart Association/American College of Cardiology AMI guidelines recommend thrombolysis as a Class 2a therapy in this age group. Observational studies using data from the Cooperative Cardiovascular Project database and the National Registry of Myocardial Infarction have recently cast some doubt on the benefit of thrombolysis among the elderly, but definitive answers from a randomised trial are still lacking. Meanwhile, primary PTCA, which has been compared to thrombolysis in both trial and observational settings, appears to offer the mortality benefit of reperfusion with lower stroke rates. Since primary PTCA is not widely available, efforts must be made to maximise available therapies in the elderly. Early diagnosis is essential, as is prompt reperfusion among eligible patients, since delay is so strongly associated with mortality with both thrombolysis and PTCA. Finally, newer, more fibrin-specific thrombolytics may decrease the bleeding risk associated with thrombolytic therapy.

Underutilization of reperfusion therapy in eligible African Americans with acute myocardial infarction: Role of presentation and evaluation characteristics.

BACKGROUND: Immediate reperfusion therapy to restore coronary blood flow is recommended for all eligible patients with acute myocardial infarction. However, reperfusion therapy is reportedly underutilized among African Americans, even when they are eligible. Reasons for the lack of use have not been fully explored. METHODS: We examined the demographic, clinical, and treatment data of 10,469 African Americans with acute myocardial infarction who were eligible for reperfusion therapy, enrolled in the National Registry of Myocardial Infarction-2 from June 1994 through March 1998. RESULTS: The mean age was 62.58 (+/-14.4) years, and 44.7% were female. Although eligible, 47% of the African Americans in this study did not receive reperfusion therapy. In a multivariate analysis, the absence of chest pain at presentation (odds ratio [OR] 0.31, 95% CI 0.26-0.37) and initial admission diagnoses other than definite myocardial infarction (OR for receipt of reperfusion <0.12) were the strongest predictors of lack of early reperfusion therapy. Progressive delays in hospital arrival and hospital evaluation predicted a lower likelihood of early reperfusion. Prior stroke (OR 0.63, 95% CI 0.50-0.78), myocardial infarction (OR 0.75, 95% CI 0.65-0.86), and congestive heart failure (OR 0.49, 95% CI 0.40-0.60) were all associated with lack of reperfusion therapy. CONCLUSION: Almost half of eligible African American patients with myocardial infarction did not receive reperfusion therapy. Potential reasons may include atypical presentation, patient and institutional delay, and underappreciation of myocardial infarction by care providers. Strategies to address these factors may improve the rate of use of reperfusion therapy.

Application of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3.

CONTEXT: The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-elevation myocardial infarction (STEMI) is a simple integer score for bedside risk assessment of patients with STEMI. Developed and validated in multiple clinical trials of fibrinolysis, the risk score has not been validated in a community-based population. OBJECTIVE: To validate the TIMI risk score in a population of STEMI patients reflective of contemporary practice. DESIGN, SETTING, AND PARTICIPANTS: The risk score was evaluated among 84 029 patients with STEMI from the National Registry of Myocardial Infarction 3 (NRMI 3), which collected data on consecutive patients with myocardial infarction (MI) from 1529 US hospitals between April 1998 and June 2000. MAIN OUTCOME MEASURES: Ability of the TIMI risk score to correctly predict risk of death in terms of model discrimination (c statistic) and calibration (agreement of predicted and observed death rates). RESULTS: Patients in NRMI 3 tended to be older, to be more often female, and to have a history of coronary disease more often than those in the derivation set. Forty-eight percent received reperfusion therapy. The TIMI risk score revealed a significant graded increase in mortality with rising score (range, 1.1%-30.0%; P<.001 for trend). The risk score showed strong prognostic capacity overall (c = 0.74 vs 0.78 in derivation set) and among patients receiving acute reperfusion therapy (c = 0.79). Predictive behavior of the risk score was similar between fibrinolytic-treated patients (n = 23 960; c = 0.79) and primary percutaneous coronary intervention patients (n = 15 348; c = 0.80). In contrast, among patients not receiving reperfusion therapy, the risk score underestimated death rates and offered lower discriminatory capacity (c = 0.65). CONCLUSIONS: Sufficiently simple to be practical at the bedside and effective for risk assessment across a spectrum of patients, the TIMI risk score may be useful in triage and treatment of patients with STEMI who are treated with reperfusion therapy.

The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: data from the National Registry of Myocardial Infarction 2.

BACKGROUND: Cardiogenic shock complicating acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized with AMI. Although several studies have demonstrated the importance of establishing and maintaining a patent infarct-related artery, it remains unclear as to whether intra-aortic balloon counterpulsation (IABP) provides incremental benefit to reperfusion therapy. The purpose of this study was to determine whether IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in a large AMI registry. METHODS: We evaluated patients participating in the National Registry of Myocardial Infarction 2 who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). RESULTS: The mean age of patients in the study was 72 years, 54% were men, and the majority were white. The overall mortality rate in all patients who had cardiogenic shock or in whom cardiogenic shock developed was 70%. IABP was used in 7268 (31%) patients. IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% vs 49%) but was not associated with any benefit in patients treated with primary angioplasty (45% vs 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72 to 0.93). CONCLUSIONS: Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy.

Death or nonfatal stroke in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction 2.

In a retrospective cohort of patients treated in community hospitals, tissue plasminogen activator (t-PA) was associated with decreased odds of in-hospital death or nonfatal stroke. However, the relative benefit was less evident in older patients and women, and some older subgroups did not benefit from treatment.

Microvascular dysfunction in acute myocardial infarction: focus on the roles of platelet and inflammatory mediators in the no-reflow phenomenon.

Recent interest has shifted from infarct artery patency to microvascular perfusion in the evaluation of patients with acute myocardial infarction (AMI). Microvascular dysfunction occurs in a substantial proportion of patients, despite aggressive therapy with thrombolytic agents and/or percutaneous mechanical revascularization techniques. Patients with impaired microvascular perfusion after immediate reperfusion therapy have an adverse clinical prognosis. Recent studies have extended our understanding of the pathophysiology of this so-called no-reflow phenomenon, focusing on the critical roles of platelet and inflammatory mediators leading to microvascular obstruction and reperfusion injury. Moving beyond the Thrombolysis in Myocardial Infarction (TIMI) flow grade system, new techniques have been developed to assess microvascular perfusion, including TIMI frame counting, angiographic myocardial perfusion grading, myocardial contrast echocardiography, Doppler flow wire studies, nuclear scintigraphy, and magnetic resonance imaging. Armed with a greater understanding of the primary mediators of microvascular dysfunction, these tools may identify improved therapy directed at optimizing myocardial perfusion in patients with AMI.

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris.

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 microg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 +/- 4.0 vs 54.9 +/- 4.1, p = 0.03) and a 14% improvement in severity (41.5 +/- 3.2 vs 35.7 +/- 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Intracranial hemorrhage rates and effect of immediate beta-blocker use in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction-2.

In acute myocardial infarction (AMI), immediate beta-blocker therapy reduces the incidence of reinfarction and recurrent chest pain in patients receiving tissue plasminogen activator (t-PA). Data from the Thrombolysis in Myocardial Infarction (TIMI)-2 trial also raises the possibility that such therapy may reduce the rate of intracranial hemorrhage (ICH). We reviewed data obtained from 60,329 patients treated with t-PA who were enrolled in the National Registry of Myocardial Infarction 2. Of the 60,329 in the study cohort, 23,749 patients (39.4%) were treated with immediate beta-blocker therapy and 542 patients (0.9%) developed an ICH. In a multivariate model that included all covariates known to be associated with the development of ICH, immediate beta-blocker therapy was associated with a 31% reduction in the ICH rate (odds ratio 0.69, 95% confidence intervals 0.57 to 0.84). Thus, in the present study, the use of immediate beta-blocker therapy in patients with AMI treated with t-PA was associated with a significant reduction in ICH. This finding supports the observations made in the TIMI 2 trial and serves to reinforce the recommendations made by the American College of Cardiology/American Heart Association task force that immediate beta-blocker therapy should be administered to all patients with AMI who do not have contraindications to this therapy.

Association between white blood cell count, epicardial blood flow, myocardial perfusion, and clinical outcomes in the setting of acute myocardial infarction: a thrombolysis in myocardial infarction 10 substudy.

BACKGROUND: Elevation of the white blood cell (WBC) count during acute myocardial infarction (AMI) is associated with adverse outcomes. We examined the relationship between the WBC count and angiographic findings to gain insight into this relationship. Results and Methods-We evaluated data from 975 patients in the Thrombolysis In Myocardial Infarction (TIMI) 10A and 10B trials. Patients with a closed artery at 60 and 90 minutes had higher a WBC count than patients with an open artery (P:=0.02). Likewise, the presence of angiographically apparent thrombus was associated with a higher WBC count (11.5+/-5.2x10(9)/L, n=290, versus 10.7+/-3. 5x10(9)/L, n=648; P=0.008). In addition, a higher WBC count was associated with poorer TIMI myocardial perfusion grades (4-way P=0.04). Mortality rates were higher in patients with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 4.9% for WBC count 5 to 10x10(9)/L, 3.8% for WBC count 10 to 15x10(9)/L, 10.4% for WBC count >15x10(9)/L; P=0.03). The development of new congestive heart failure or shock was also associated with a higher WBC count (0% for WBC count 0 to 5x10(9)/L, 5.2% for WBC count 5 to 10x10(9)/L, 6.1% for WBC count 10 to 15x10(9)/L, 17.1% for WBC count >15x10(9)/L; P<0.001), an observation that remained significant in a multivariable model that adjusted for potential confounding variables (odds ratio 1.21, P=0.002). CONCLUSIONS: Elevation in WBC count was associated with reduced epicardial blood flow and myocardial perfusion, thromboresistance (arteries open later and have a greater thrombus burden), and a higher incidence of new congestive heart failure and death. These observations provide a potential explanation for the higher mortality rate observed among AMI patients with elevated WBC counts and helps explain the growing body of literature that links inflammation and cardiovascular disease.

Treatment and outcomes of left bundle-branch block patients with myocardial infarction who present without chest pain. National Registry of Myocardial Infarction 2 Investigators.

OBJECTIVES: We sought to determine the importance of chest pain on presentation as a predictor of in-hospital treatment and mortality in myocardial infarction (MI) patients with left bundle-branch block (LBBB). BACKGROUND: Left bundle-branch block patients have a high mortality after MI but are unlikely to receive reperfusion therapy despite evidence from clinical trials demonstrating the efficacy of thrombolytic therapy. Nearly half of MI patients with LBBB present without chest pain. METHODS: We studied the clinical features, treatment and in-hospital survival of 29,585 patients with LBBB enrolled in the National Registry of MI 2 June 1994 through March 1998). Multivariate logistic regression was used to assess the independent effect of chest pain on reperfusion decisions and in-hospital mortality. RESULTS: Left bundle-branch block patients with chest pain were greater than five-fold more likely to receive reperfusion therapy (13.6% vs. 2.6%) than LBBB patients without chest pain; they were also more likely to receive aspirin, beta-adrenergic blocking agents, heparin and nitrates (all p < 0.0001). Unadjusted in-hospital mortality was 18% in patients with chest pain and 27% in patients without chest pain. Adjusting for patient characteristics reduced the odds ratio associated with the absence of chest pain from 1.47 (95% confidence interval: 1.41 to 1.54) to 1.21 (95% confidence interval: 1.12 to 1.30). The remainder of the mortality difference was caused by the undertreatment of patients without chest pain, particularly the low utilization of aspirin and beta-blockers. CONCLUSIONS: Left bundle-branch block patients with MI who present without chest pain are less likely to receive optimal therapy and are at increased risk of death. Prompt recognition and treatment of this high-risk subgroup should improve survival.

Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain.

CONTEXT: Although chest pain is widely considered a key symptom in the diagnosis of myocardial infarction (MI), not all patients with MI present with chest pain. The extent to which this phenomenon occurs is largely unknown. OBJECTIVES: To determine the frequency with which patients with MI present without chest pain and to examine their subsequent management and outcome. DESIGN: Prospective observational study. SETTING AND PATIENTS: A total of 434,877 patients with confirmed MI enrolled June 1994 to March 1998 in the National Registry of Myocardial Infarction 2, which includes 1674 hospitals in the United States. MAIN OUTCOME MEASURES: Prevalence of presentation without chest pain; clinical characteristics, treatment, and mortality among MI patients without chest pain vs those with chest pain. RESULTS: Of all patients diagnosed as having MI, 142,445 (33%) did not have chest pain on presentation to the hospital. This group of MI patients was, on average, 7 years older than those with chest pain (74.2 vs 66.9 years), with a higher proportion of women (49.0% vs 38.0%) and patients with diabetes mellitus (32.6% vs 25. 4%) or prior heart failure (26.4% vs 12.3%). Also, MI patients without chest pain had a longer delay before hospital presentation (mean, 7.9 vs 5.3 hours), were less likely to be diagnosed as having confirmed MI at the time of admission (22.2% vs 50.3%), and were less likely to receive thrombolysis or primary angioplasty (25.3% vs 74.0%), aspirin (60.4% vs 84.5%), beta-blockers (28.0% vs 48.0%), or heparin (53.4% vs 83.2%). Myocardial infarction patients without chest pain had a 23.3% in-hospital mortality rate compared with 9.3% among patients with chest pain (adjusted odds ratio for mortality, 2. 21 [95% confidence interval, 2.17-2.26]). CONCLUSIONS: Our results suggest that patients without chest pain on presentation represent a large segment of the MI population and are at increased risk for delays in seeking medical attention, less aggressive treatments, and in-hospital mortality. JAMA. 2000;283:3223-3229

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

OBJECTIVE: To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. DESIGN: The literature on the "congenital long QT" was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. RESULTS: Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were "pause dependent"; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (

The volume of primary angioplasty procedures and survival after acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators.

BACKGROUND: There is an inverse relation between mortality from cardiovascular causes and the number of elective cardiac procedures (coronary angioplasty, stenting, or coronary bypass surgery) performed by individual practitioners or hospitals. However, it is not known whether patients with acute myocardial infarction fare better at centers where more patients undergo primary angioplasty or thrombolytic therapy than at centers with lower volumes. METHODS: We analyzed data from the National Registry of Myocardial Infarction to determine the relation between the number of patients receiving reperfusion therapy (primary angioplasty or thrombolytic therapy) and subsequent in-hospital mortality. A total of 450 hospitals were divided into quartiles according to the volume of primary angioplasty. Multiple logistic-regression models were used to determine whether the volume of primary angioplasty procedures was an independent predictor of in-hospital mortality among patients undergoing this procedure. Similar analyses were performed for patients receiving thrombolytic therapy at 516 hospitals. RESULTS: In-hospital mortality was 28 percent lower among patients who underwent primary angioplasty at hospitals with the highest volume than among those who underwent angioplasty at hospitals with the lowest volume (adjusted relative risk, 0.72; 95 percent confidence interval, 0.60 to 0.87; P<0.001). This lower rate, which represented 2.0 fewer deaths per 100 patients treated, was independent of the total volume of patients with myocardial infarction at each hospital, year of admission, and use or nonuse of adjunctive pharmacologic therapies. There was no significant relation between the volume of thrombolytic interventions and in-hospital mortality among patients who received thrombolytic therapy (7.0 percent for patients in the highest-volume hospitals vs. 6.9 percent for those in the lowest-volume hospitals, P=0.36). CONCLUSIONS: Among hospitals in the United States that have full interventional capabilities, a higher volume of angioplasty procedures is associated with a lower mortality rate among patients undergoing primary angioplasty, but there is no association between volume and mortality for thrombolytic therapy.