Faculty Bibliography

Both aspirin and beta-adrenergic blocking drugs have been shown to reduce the risk of death or acute myocardial infarction (AMI) in patients with unstable angina, but their effect during chronic use on the presentation of acute coronary syndromes is less well defined. Calcium antagonists and oral nitrates are also widely prescribed for patients with coronary disease, but their effect on presentation of acute myocardial ischemia is unknown. We retrospectively examined the effects of prior aspirin and anti-ischemic medical therapy on clinical events in 410 patients hospitalized for unstable angina. Ischemic pain occurred at rest for a duration of 5 to 60 minutes. During hospitalization, 97% of patients received aspirin and all received the direct thrombin inhibitor bivalirudin for at least 72 hours. Despite being older and more likely to have risk factors for coronary disease and poor outcome, patients receiving aspirin before admission were less likely to present with non-Q-wave AMI (5% vs 14% in patients not on aspirin, p = 0.004). Prior beta blocker, calcium antagonist, or nitrate administration did not appear to modify presentation as unstable angina or non-Q-wave AMI. In a multivariate model, the combined incidence of death, AMI not present at enrollment, or recurrent angina was best predicted by age (adjusted odds ratio [95% confidence interval] 2.38 [1.14 to 3.98]) and presence of electrocardiographic changes with pain on presentation (adjusted odds ratio 2.83 [1.50 to 5.35]) but was not related to prior or in-hospital medical therapy. Thus, aspirin but not anti-ischemic therapy before hospitalization of patients with unstable angina was associated with a decreased incidence of non-Q-wave AMI on admission

Chest pain in a patient who has recently had an acute myocardial infarction (MI) may result from ischemia, pulmonary embolism, or pneumonia. Also consider pericarditis as a possible cause. Early postinfarction pericarditis occurs 2 to 4 days following acute MI, primarily in those with transmural infarction; it is usually heralded by low-grade fever and the development of a pericardial friction rub. Dressler's syndrome usually develops 1 to 28 weeks post-MI and is characterized by pleuropericarditis and constitutional symptoms (such as fever, malaise, myalgia, and arthralgia). Give aspirin as first-line therapy for early postinfarction pericarditis. Aspirin is also preferred for patients with Dressler's syndrome, although other NSAIDs (or brief corticosteroid therapy in complicated or refractory cases) may be used.

OBJECTIVES: Women and men enrolled in the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial of unstable angina and non-Q wave myocardial infarction (MI) were evaluated to determine gender differences in characteristics and outcome. BACKGROUND: Coronary heart disease is the leading cause of death for women and men. However, the characteristics and outcome of women compared with men with unstable angina and non-Q wave MI have not been extensively studied. METHODS: The characteristics, outcomes and proportion of 497 women and 976 men with unstable angina and non-Q wave MI at the time of enrollment were compared. When these proportions were noted to be significantly different, we compared them with the 7,731-patient TIMI IIIB Registry, which represents the non-trial, screened population with these syndromes at these centers. RESULTS: For both coronary syndromes, women were older, were less frequently white, had a higher incidence of diabetes and hypertension and were receiving more cardiac medications. The 42-day rate of death and MI in TIMI IIIB was similar for women and men (7.4% vs. 7.5%). Coronary angiography revealed less severe coronary artery disease for women than for men, with absence of critical obstructions in 25% versus 16% and mean ejection fractions 62 +/- 12% versus 57 +/- 13% for women versus men (p < 0.01). Medical management failed in women as often as in men, and rates of cardiac catheterization and percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery were similar for women and men in the conservative strategy arm as well as in the invasive strategy arm. Women in the TIMI IIIB trial had proportionately more unstable angina than did men. The proportion of unstable angina and non-Q wave MI for women was similar in the trial and Registry. However, proportionately more men in the trial had non-Q wave MI than men in the Registry. CONCLUSIONS: 1) Women with each acute coronary syndrome are older than men and have more comorbidity. 2) The outcome with unstable angina and non-Q wave MI is related to severity of illness and not gender. 3) Mortality associated with revascularization for unstable angina and non-Q wave MI was similar for women and men. 4) The proportion of women and men enrolled with each acute coronary syndrome is different. These rates reflect both the prevalence of disease and selection bias owing to trial eligibility criteria and other identified factors

OBJECTIVES: The impact of acute collagen disruption by the disulfide donor, 5,5'-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts. METHODS: Collagen was degraded acutely in 13 isolated, isovolumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control). RESULTS: Collagen content was 3.5 +/- 0.5% of ventricular dry weight in control group compared with 2.1 +/- 0.4% in DTNB group (decrease by 40%, p < 0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86 +/- 17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68 +/- 13% (p < 0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15 +/- 8 mmHg in control and 30 +/- 13 mmHg (p < 0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63 +/- 0.26 in control to 6.07 +/- 0.11 (p < 0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function. CONCLUSIONS: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen

OBJECTIVE--To determine whether an interaction between encainide or flecainide and intercurrent ischaemia could account for the observed increase in cardiac and sudden deaths in the study group in the Cardiac Arrhythmia Suppression Trial (CAST) I. DESIGN--CAST I was a randomised, double blind, placebo controlled study in which patients received the drug which suppressed at least 6 premature ventricular contractions per minute by 80% or episodes of non-sustained ventricular tachycardia by 90%. Arrhythmic sudden death or aborted sudden death were the study end points. Measured secondary end points included recurrent myocardial infarction, new or increasing angina pectoris, congestive heart failure, and syncope. The CAST I database was analysed to determine which of three end points occurred first--cardiac death or cardiac arrest, angina pectoris, or non-fatal recurrent infarction. They were regarded as mutually exclusive end points. The triad of cardiac or sudden arrhythmic death plus congestive heart failure and syncope was similarly analysed. RESULTS--It was assumed that recurrent non-fatal infarction and new or increasing angina pectoris were ischaemic in origin. The sum of these non-fatal ischaemic end points and sudden death were nearly identical in the placebo group (N = 129) and the treatment group (N = 131). The one year event rate in each group was 21%. However, the treatment group had a much greater fatality rate (55 v 17; P < 0.0001) than the placebo group. The same relation was found when the data were examined on the basis of drug exposure rather than intention to treat. The temporal and circadian events were similar in each group and were consistent with an ischaemic pattern. No such patterns emerged from analysis of the presumed non-ischaemic end points of congestive heart failure and syncope. CONCLUSIONS--These data suggest that the interaction between active ischaemia and treatment with encainide or flecainide may have been responsible for the increased mortality seen in the treatment group in CAST I. This conversion of a non-fatal to a fatal event emphasises the need for future antiarrhythmic drugs to be screened in ischaemic models

When initiated a few days after myocardial infarction, angiotensin-converting enzyme inhibition exerts beneficial effects on survival and morbidity in patients with asymptomatic left ventricular systolic dysfunction or symptomatic heart failure. During the acute phase of a myocardial infarction, angiotensin-converting enzyme inhibition appears to be well tolerated, to prevent the development of heart failure in patients with asymptomatic left ventricular systolic dysfunction and to improve the hemodynamic and clinical variables of heart failure when present. Accordingly, early angiotensin-converting enzyme inhibition is clearly indicated in patients with acute myocardial infarction associated with asymptomatic left ventricular dysfunction or clinical evidence of heart failure. Angiotensin-converting enzyme inhibition may also be beneficial when thrombolytic agents fail to restore coronary patency in patients with acute myocardial infarction

BACKGROUND: Cardiogenic shock remains the leading cause of death of patients hospitalized with acute myocardial infarction (MI). This study was conducted to examine (1) the current spectrum of cardiogenic shock, (2) the proportion of patients who are potential candidates for a trial of early revascularization, and (3) the apparent impact of early revascularization on mortality. METHODS AND RESULTS: Nineteen participating centers in the United States and Belgium prospectively registered all patients diagnosed with cardiogenic shock. Two hundred fifty-one patients were registered. The mean age was 67.5 +/- 11.7 years, and 43% were women. Acute mitral regurgitation or ventricular septal rupture was the cause of shock in 8%. Concurrent conditions contributing to the development of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the remaining 214 patients, nonspecific findings on the ECG associated with 'nontransmural' MI were seen in 14%. The median time to shock diagnosis after MI was 8 hours. The overall in-hospital mortality was 66%. Patients clinically selected to undergo cardiac catheterization were significantly younger and had a lower mortality than those not selected (51% versus 85%, P < .0001) even if they were not revascularized (58%). Mortality for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) was 60% (n = 55) and 19% (n = 16) for coronary artery bypass graft surgery (CABG). Sixty percent (n = 150) of registered patients were judged eligible for a trial of early revascularization. Trial-eligible patients were significantly younger (65.4 +/- 11.0 versus 70.6 +/- 11.9 years, P < .001), had an earlier median time to shock onset after MI (6.5 versus 17.5 hours, P = .003), and had lower mortality (62% versus 73%, P = .077) than ineligible patients. CONCLUSIONS: Patients diagnosed with cardiogenic shock complicating acute MI are a heterogeneous group. Those eligible for a trial of early revascularization tended to have lower mortality. Patients selected to undergo cardiac catheterization had lower mortality whether or not they were revascularized. Emergent PTCA and CABG are promising treatment modalities for cardiogenic shock, but biased case selection for treatment may confound the data. Whether PTCA and CABG reduce mortality and which patient subgroups benefit most remain to be determined in a randomized clinical trial

BACKGROUND: Thrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood. METHODS AND RESULTS: In a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration > 120 milliseconds) by 37% (95% CI, -64%, +6%; P = .087) and the filtered QRS duration (105.7 +/- 13.8 versus 108.8 +/- 14.6 milliseconds, P = .05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%, P = .011) of SAECG abnormality and a shorter filtered QRS duration (105.7 +/- 10.9 versus 110.7 +/- 15.9 milliseconds, P = .01). No benefit was seen in patients without ST elevation on ECG. CONCLUSIONS: Late thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit

Left ventricular aneurysm has been associated with increased mortality rates. The Cardiac Arrhythmia Suppression Trial (CAST) database was used prospectively to assess (1) the prognostic significance of left ventricular (LV) aneurysm after myocardial infarction on mortality rates and (2) the relation of LV aneurysm to ventricular arrhythmias and their suppressibility. All patients in the CAST study were enrolled after myocardial infarction. They had > or = 6 ventricular premature depolarizations (VPDs) per hour and ejection fraction < or = 55%; they were enrolled in the study an average of 96 days after the index myocardial infarction. Of 2494 patients with wall motion data, 164 had LV aneurysm, 600 had only dyskinesis, 913 had only akinesis, and 817 had none of these. Radionuclide scan was used in 39%, two-dimensional echocardiography in 30%, and LV angiogram in 31%. Baseline VPDs and nonsustained ventricular tachycardia were similar in all groups. LV aneurysm patients were more frequently eliminated during open-label titration. The incidence of sustained VT during follow-up was only 2.8% for aneurysm patients, a rate that was similar to the other groups. Patients with LV aneurysm had significantly lower survival rates (82% vs 91%) at 16 months after study entry than those without these wall motion abnormalities (p < 0.005). When survival rates were adjusted for ejection fraction there was still a moderately large hazard ratio (1.34) of LV aneurysm that was not statistically significant (p = 0.18). We conclude that (1) the presence of LV aneurysm does not independently worsen prognosis, and (2) older concepts of LV aneurysm and ventricular arrhythmias must be reevaluated