A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP.

In the in vitro perfused rectal gland of the dogfish shark (Squalus acanthias), the adenosine analogue 2-chloroadenosine (2Clado) completely and reversibly inhibited forskolin-stimulated chloride secretion with an IC50 of 5 nM. Other A1 receptor agonists including cyclohexyladenosine (CHA), N-ethylcarboxamideadenosine (NECA) and R-phenylisopropyl-adenosine (R-PIA) also completely inhibited forskolin stimulated chloride secretion. The "S" stereoisomer of PIA (S-PIA) was a less potent inhibitor of forskolin stimulated chloride secretion, consistent with the affinity profile of PIA stereoisomers for an A1 receptor. The adenosine receptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline completely blocked the effect of 2Clado to inhibit forskolin-stimulated chloride secretion. When chloride secretion and tissue cyclic (c)AMP content were determined simultaneously in perfused glands, 2Clado completely inhibited secretion but only inhibited forskolin stimulated cAMP accumulation by 34-40%, indicating that the mechanism of inhibition of secretion by 2Clado is at least partially cAMP independent. Consistent with these results, A1 receptor agonists only modestly inhibited (9-15%) forskolin stimulated adenylate cyclase activity and 2Clado markedly inhibited chloride secretion stimulated by a permeant cAMP analogue, 8-chlorophenylthio cAMP (8CPT cAMP). These findings provide the first evidence for a high affinity A1 adenosine receptor that inhibits hormone stimulated ion transport in a model epithelia. A major portion of this inhibition occurs by a mechanism that is independent of the cAMP messenger system.

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.

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.

Autonomic nervous system and sudden cardiac death.

In the United States, sudden cardiac death is a major public health problem, accounting for approximately 300,000 deaths annually. Accurate identification of those patients at highest risk for this event has been problematic. The use of signal-averaged electrocardiography, Holter monitoring and assessment of left ventricular function have been shown to be predictive of future arrhythmic events in patients after a myocardial infarction. However, the clinical utility of these tests has been limited by their low sensitivity and positive predictive value. It has become increasingly clear that the autonomic nervous system is extremely important in the pathogenesis of ventricular arrhythmias and sudden cardiac death. The two most important techniques used to study the autonomic nervous system--heart rate variability and baroreflex sensitivity--are reviewed, and the clinical and experimental data suggesting that these techniques are powerful predictors of future arrhythmic events are discussed in depth.

Use of angiotensin-converting enzyme inhibitors at discharge in patients with acute myocardial infarction in the United States: data from the National Registry of Myocardial Infarction 2.

OBJECTIVES: This study was undertaken to examine recent trends in the use of angiotensin-converting enzyme (ACE) inhibitor therapy in patients discharged after acute myocardial infarction (AMI) and to identify clinical factors associated with ACE inhibitor prescribing patterns. BACKGROUND: Clinical trials have demonstrated a significant mortality benefit in patients treated with ACE inhibitors after AMI. Numerous studies have demonstrated underuse of other beneficial treatments for patients with AMI, such as beta-adrenergic blocking agents, aspirin and immediate reperfusion therapy. METHODS: Demographic, procedural and discharge medication data from 190,015 patients with AMI were collected at 1,470 U.S. hospitals participating in the National Registry of Myocardial Infarction 2. RESULTS: Prescriptions for ACE inhibitor therapy at hospital discharge increased from 25.0% in 1994 to 30.7% in 1996. Patients with a left ventricular ejection fraction < or =40% or evidence of congestive heart failure while in the hospital were discharged with ACE inhibitor treatment 42.6% of the time. Of patients experiencing an anterior wall myocardial infarction and no evidence of heart failure, 26.1% of patients were discharged with this treatment. Of the remaining patients, 15.6% received ACE inhibitors at discharge. ACE inhibitors were prescribed more often to elderly and diabetic patients as well as those requiring intraaortic balloon pump placement. This therapy was given less often to patients who underwent revascularization with coronary angioplasty or coronary artery bypass graft surgery or were treated with calcium channel blocking agents. CONCLUSIONS: Physicians are prescribing ACE inhibitors in patients with myocardial infarction with increasing frequency. Those patients with the greatest expected benefit receive ACE inhibitor treatment most often. However, the majority of even these high risk patients were not discharged with this life-saving therapy.

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.

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.

A comparison of the national registry of myocardial infarction 2 with the cooperative cardiovascular project.

OBJECTIVES: This study was performed to evaluate whether or not the simpler case identification and data abstraction processes used in National Registry of Myocardial Infarction two (NRMI 2) are comparable with the more rigorous processes utilized in the Cooperative Cardiovascular Project (CCP). BACKGROUND: The increased demand for quality of care and outcomes data in hospitalized patients has resulted in a proliferation of databases of varying quality. For patients admitted with myocardial infarction, there are two national databases that attempt to capture critical process and outcome data using different case identification and abstraction processes. METHODS: We compared case ascertainment and data elements collected in Medicare-eligible patients included in the industry-sponsored NRMI 2 with Medicare enrollees included in the Health Care Financing Administration-sponsored CCP who were admitted during identical enrollment periods. Internal and external validity of NRMI 2 was defined using the CCP as the "gold standard." RESULTS: Demographic and procedure use data obtained independently in each database were nearly identical. There was a tendency for NRMI 2 to identify past medical histories such as prior infarct (29% vs. 31%, p < 0.001) or heart failure (21% vs. 25%, p < 0.001) less frequently than the CCP. Hospital mortality was calculated to be higher in NRMI 2 (19.7% vs. 18.1%, p < 0.001) due mostly to the inclusion of noninsured patients 65 years and older in NRMI 2. CONCLUSIONS: We conclude that the simpler case ascertainment and data collection strategies employed by NRMI 2 result in process and outcome measures that are comparable to the more rigorous methods utilized by the CCP. Outcomes that are more difficult to measure from retrospective chart review such as stroke and recurrent myocardial infarction must be interpreted cautiously.

Treatment and outcome of myocardial infarction in hospitals with and without invasive capability. Investigators in the National Registry of Myocardial Infarction.

OBJECTIVES: We sought to determine the extent to which the capability of a hospital to perform invasive cardiovascular procedures influences treatment and outcome of patients admitted with acute myocardial infarction (AMI). BACKGROUND: Patients with AMI are usually transported to the closest hospital. However, relatively few hospitals have the capability for immediate coronary arteriography, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft surgery (CABG), should these interventions be needed. METHODS: The 1,506 hospitals participating in the National Registry of Myocardial Infarction 2 were classified according to their highest level of invasive capability: 1) none (noninvasive, 28.1%); 2) coronary arteriography (cath-capable, 25.2%); 3) coronary angioplasty (PTCA-capable, 7.4%); and 4) bypass surgery (CABG-capable, 39.2%). Treatment and in-hospital outcomes were assessed for 305,812 patients admitted from June 1994 through October 1996. Follow-up through 90 days was ascertained in a subset of 30,402 patients enrolled simultaneously in both the National Registry of Myocardial Infarction (NRMI) 2 and the Cooperative Cardiovascular Project (CCP). RESULTS: The proportion of patients receiving initial reperfusion intervention was only slightly higher at the more invasive hospitals (noninvasive 32.5%, cath-capable 31.2%, PTCA-capable 32.9% and CABG-capable 35.9%, p < 0.001 by chi-square statistic). Among thrombolytic recipients, median door-to-drug time interval differed little among hospital types and ranged from 42 to 45 minutes. At cath-capable, PTCA-capable and CABG-capable hospitals, coronary arteriography was performed in 32.9%, 37.4% and 64.9%, respectively, and PTCA in 0.0%, 5.1% and 31.4%, both p < 0.001 by chi-square statistic. The proportion of patients transferred out to other facilities was 51.0%, 42.2%, 39.9% and 4.4% (p < 0.0001) among noninvasive, cath-capable, PTCA-capable and CABG-capable hospitals, respectively. Among patients in the combined NRMI and CCP data set, mortality at 90 days postinfarction was similar among patients initially admitted to each of the four hospital types. CONCLUSIONS: Although patients with AMI admitted to hospitals without invasive cardiac facilities have a high likelihood of subsequent transfer to other facilities, their likelihood of receiving a reperfusion intervention at the first hospital, their door to thrombolytic drug intervals and their 90-day survival rates are similar to those of patients initially admitted to more invasively equipped hospitals. These data suggest that a policy of initial treatment of myocardial infarction at the closest medical facility is appropriate medical practice.

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.

Postextrasystolic U wave augmentation, a new marker of increased arrhythmic risk in patients without the long QT syndrome.

OBJECTIVES: We attempted to determine the correlation between the presence of postextrasystolic changes in the STU segment and a history of sustained ventricular arrhythmias. BACKGROUND: Postextrasystolic U wave augmentation (a marked increment in U wave amplitude after premature ventricular complexes [PVCs]) is an adverse prognostic sign in the "pause-dependent long QT syndrome." However, the prevalence of postextrasystolic changes in patients without the long QT syndrome is unknown. METHODS: We compared the configuration of the STU segment of the postextrasystolic beat (the sinus beat after a PVC) with the STU configuration during sinus rhythm in three patient groups: 1) 41 patients with spontaneous ventricular tachycardia/fibrillation (VT/VF) (VT/VF group), 2) 63 patients with heart disease and high grade ventricular arrhythmias (control group), and 3) 29 patients with high grade ventricular arrhythmias but no heart disease (reference group). RESULTS: Postextrasystolic T wave changes did not correlate with a history of ventricular tachyarrhythmias. However, postextrasystolic U wave changes were more common among the patients with VT/VF than among control subjects (39% vs. 8.7%, p < 0.001). By logistic multiple regression analysis, a low left ventricular ejection fraction (p < 0.001) and postextrasystolic U wave changes (p < 0.005) were independent predictors of ventricular tachyarrhythmias. CONCLUSIONS: Postextrasystolic T wave changes are common and lack predictive value. Postextrasystolic U wave changes may be a specific marker of a tendency to the development of spontaneous ventricular arrhythmias. Prospective studies should be performed to confirm this association.

Mode of onset of torsade de pointes in congenital long QT syndrome.

OBJECTIVES: We sought to describe the mode of onset of spontaneous torsade de pointes in the congenital long QT syndrome. BACKGROUND: Contemporary classifications of the long QT syndrome (LQTS) refer to the congenital LQTS as "adrenergic dependent" and to the acquired LQTS as "pause dependent." Overlap between these two categories has been recognized, and a subgroup of patients with "idiopathic pause-dependent torsade" has been described. However, it is not known how commonly torsade is preceded by pauses in the congenital LQTS. METHODS: We reviewed the electrocardiograms (ECGs) of all our patients with congenital LQTS evaluated for syncope or sudden death (30 patients). Documentation of the onset of torsade de pointes was available for 15 patients. All these patients had "definitive LQTS" by accepted clinical and ECG criteria. RESULTS: Pause-dependent torsade de pointes was clearly documented in 14 of the 15 patients (95% confidence interval 68% to 100%). The cycle length of the pause leading to torsade was 1.3 +/- 0.2 times longer than the basic cycle length, and most pauses leading to torsade were unequivocally longer than the preceding basic cycle length (80% of pauses were > 80 ms longer than the preceding cycle length). CONCLUSIONS: The "long-short" sequence, which has been recognized as a hallmark of torsade de pointes in the acquired LQTS, plays a major role in the genesis of torsade in the congenital LQTS as well. Our findings have important therapeutic implications regarding the use of pacemakers for prevention of torsade in the congenital LQTS.

Payer status and the utilization of hospital resources in acute myocardial infarction: a report from the National Registry of Myocardial Infarction 2.

BACKGROUND: Prior studies have suggested that payer status may be an important determinant of medical resource utilization and outcome in acute myocardial infarction (AMI). METHODS: A national cohort of 332,221 patients with AMI enrolled from June 1994 to July 1996 were compared within 5 payer groups to ascertain the influence of payer status on hospital resource allocation for AMI in the United States. RESULTS: Medicare comprised the largest proportion (56%), followed by commercial insurance (25%), health maintenance organization (HMO) (10%), uninsured (6%), and Medicaid (3%). Compared with commercially insured patients, Medicare and Medicaid patients received fewer reperfusion therapies, underwent fewer invasive cardiac procedures, and had longer hospitalizations. After adjusting for differences in clinical characteristics, Medicare recipients were as likely as commercially insured patients to receive acute reperfusion therapies or any invasive cardiac procedure. Uninsured and HMO patients tended to utilize hospital resources with intermediate frequency. Medicare recipients aged 65 years or older and the HMO group had similar hospital mortality rates compared with the commercial group (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.96-1.20 and OR, 0.93; 95% CI, 0.83-1.04, respectively), but Medicaid and uninsured groups had higher hospital mortality rates compared with the commercial group (OR, 1.30; 95% CI, 1.14-1.48 and OR, 1.29; 95% CI, 1.12-1.48, respectively). CONCLUSION: This report suggests significant variation by payer status in the management of AMI throughout the United States, but no important differences in mortality among the 3 largest payer groups.

Beta-blocker dosages and mortality after myocardial infarction: data from a large health maintenance organization.

BACKGROUND: Although long-term beta-blocker therapy has been found beneficial in patients after an acute myocardial infarction, these drugs are greatly underused by clinicians. Moreover, the dosages of beta-blockers used in randomized controlled trials appear to be much larger than those routinely prescribed. OBJECTIVE: To determine whether an association exists between the dosage of beta-blockers prescribed after a myocardial infarction and cardiac mortality. METHODS: We performed a retrospective cohort study of 1165 patients who survived an acute myocardial infarction from January 1, 1990, through December 31, 1992. These patients represent a subgroup of the 6851 patients hospitalized at northern California Kaiser Permanente hospitals. RESULTS: Of the 37.7% of patients prescribed beta-blocker therapy, 48.1% were treated with dosages less than 50% of the dosage found to be effective in preventing cardiac death in large randomized clinical trials (lower-dosage therapy). Compared with patients not receiving beta-blockers, those treated with lower-dosage therapy appeared to have a greater reduction in cardiovascular mortality (hazard ratio, 0.33; P=.009) than patients treated with a higher dosage (hazard ratio, 0.82; P=0.51), after adjustment for age, sex, race, disease severity, and comorbidities. CONCLUSIONS: The dosages of beta-blockers shown to be effective in randomized trials are not commonly used in clinical practice, and treatment with lower dosages of beta-blockers was associated with at least as great a reduction in mortality as treatment with higher dosages. This suggests that physicians who are reluctant to prescribe beta-blockers because of the relatively large dosages used in the large prospective clinical trials should be encouraged to prescribe smaller dosages.

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.

Beta blockers prevent cardiac death following a myocardial infarction: so why are so many infarct survivors discharged without beta blockers?

Too often, infarct survivors are discharged from physician's care and/or hospital stay without beta-blocker therapy. This reflects concerns by physicians regarding precipitation of adverse effects. Ironically, many of the infarct survivors not receiving beta blockers could actually derive the greatest benefits from this treatment.

Early use of ACE inhibitors in the treatment of acute myocardial infarction in the United States: experience from the National Registry of Myocardial Infarction 2. National Registry of Myocardial Infarction 2 participants.

This study was undertaken to examine recent trends in the use of angiotensin-converting enzyme (ACE) inhibitors within 24 hours of admission in patients hospitalized for acute myocardial infarction (AMI) and to identify clinical factors associated with ACE inhibitor-prescribing patterns. Demographic, procedural, and acute medication use from 202,438 patients with AMI were collected at 1,470 US hospitals participating in the National Registry of Myocardial Infarction 2 from June 1994 through June 1996. Acute ACE inhibitor use increased from 14.0% in 1994 to 17.3% in 1996. After controlling for all important clinical variables, we found that there was a significant increase in the odds of acute ACE inhibitor treatment over time (odds ratio [OR]1.07 for each 180-day period; 95% confidence intervals [CI] 1.06 to 1.08; p<0.0001). Univariate data suggested that patients treated acutely with ACE inhibitors tended to be older (70.9 vs. 67.2 years) and had lower rates of in-hospital mortality (8.8% vs. 11.0%). Independent predictors of receiving an ACE inhibitor acutely included anterior wall infarction (OR 1.36; 95% CI 1.32 to 1.40), Killip class 2 or 3 (OR 1.77; 95% CI 1.72 to 1.83), prior myocardial infarction (OR 1.33; 95% CI 1.30 to 1.37), prior history of congestive heart failure (OR 1.88; 95% CI 1.82 to 1.95), and diabetes mellitus (OR 1.34; 95% CI 1.30 to 1.38). Physicians are prescribing ACE inhibitors acutely in patients with AMI with increasing frequency. Patients with evidence of congestive heart failure and those with anterior myocardial infarction have the greatest expected benefit from such therapy, and these persons receive such treatment most often. However, most patients hospitalized with AMI do not receive this potentially life-saving therapy.

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.

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.

P-wave morphology during right atrial pacing before and after atrial flutter ablation--a new marker for success.

Fourteen patients with typical atrial flutter underwent pacing from the low lateral right atrium and the proximal coronary sinus in normal sinus rhythm before and after catheter ablation. During low lateral right atrial pacing, a positive change in P-wave morphology in the inferior leads was noted in every patient (n = 12) in whom bidirectional block was achieved; no recurrence was noted in any of these patients.