David L. Pearle

2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

Elliott M. Antman, MD, FACC, FAHA, Co-Chair*†; Mary Hand, MSPH, RN, FAHA, Co-Chair; Paul W. Armstrong, MD, FACC, FAHA‡§; Eric R. Bates, MD, FACC, FAHA; Lee A. Green, MD, MPH ; Lakshmi K. Halasyamani, MD¶; Judith S. Hochman, MD, FACC, FAHA**; Harlan M. Krumholz, MD, FACC, FAHA††; Gervasio A. Lamas, MD, FACC**; Charles J. Mullany, MB, MS, FACC; David L. Pearle, MD, FACC, FAHA; Michael A. Sloan, MD, FACC; Sidney C. Smith, Jr, MD, FACC, FAHA§§

2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction

Elliott M. Antman, MD, FACC, FAHA, Chair Daniel T. Anbe, MD, FACC, FAHA Paul W. Armstrong, MD, FACC, FAHA Eric R. Bates, MD, FACC, FAHA Lee A. Green, MD, MPH Mary Hand, MSPH, RN, FAHA Judith S. Hochman, MD, FACC, FAHA Harlan M. Krumholz, MD, FACC, FAHA Frederick G. Kushner, MD, FACC, FAHA

Double-Blind, Placebo-Controlled Study of the Effects of Carvedilol in Patients With Moderate to Severe Heart Failure The PRECISE Trial

Background Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. Methods and Results We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction ≤0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n=145) or carvedilol (n=133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P=.014) or by a global assessment of progress judged either by the patient (P=.002) or by the physician (P<.001). In addition, treatment with carvedilol...

Noninvasive detection of coronary artery patency using continuous ST-segment monitoring

Continuous ST-segment Holter recordings were analyzed from 46 patients with acute myocardial infarction (AMI) receiving intracoronary streptokinase (SK) during the first 48 hours of hospitalization. Changes in ST deviation and the time periods of these changes were quantitated and correlated with angiographic evidence of reperfusion. Thirty-six patients had total occlusion of the infarct vessel and 10 had subtotal occlusion. Of the 36 vessels that were totally occluded, 19 were reperfused and 17 were not. In patients in whom reperfusion was successful, an ST steady state was achieved 55 +/- 32 minutes after SK administration. In patients in whom it was not successful, a steady state was achieved in 219 +/- 141 minutes (p less than 0.001). Achievement of steady state within 100 minutes after SK reperfusion indicated successful reperfusion with 89% sensitivity and 82% specificity. All patients with subtotal occlusion achieved an ST steady state before SK infusion. No patient with total occlusion achieved a steady state before SK. Achievement of ST steady state before SK infusion was 100% sensitive and 100% specific for subtotal occlusion at initial angiography. Continuous, quantitative ST-segment analysis is a sensitive and specific noninvasive technique for following coronary artery patency during AMI.

Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure

Objectives. The aim of this study was to assess the efficacy of flosequinan in chronic heart failure. Background. Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic benefits in heart failure, but large scale studies evaluating its clinical efficacy have not been reported. Methods. One hundred ninety-three patients with chronic heart failure (New York Heart Association functional class II or III and left ventricular ejection fraction <40%) receiving digoxin and diuretic drugs were randomly assigned (double-blind) to the addition of flosequinan (100 mg once daily, n = 93) or placebo (n = 100) for 3 months. The clinical status and exercise tolerance of each patient was evaluated at the start of the study and every 2 to 4 weeks during the trial while background therapy remained constant. Results. After 12 weeks, maximal treadmill exercise time increased by 96 s in the flosequinan group but by only 47 s in the placebo group (p = 0.022 for the difference between groups). Maximal oxygen consumption increased by 1.7 ml/kg per in the flosequinan group (n = 17) but by only 0.6 ml/kg per min in the placebo group (n = 23), p = 0.05 between the groups. Symptomatically, 55% of patients receiving flosequinan but only 36% of patients receiving placebo benefited from treatment (p = 0.018). In addition, fewer patients treate with flosequinan had sufficiently severe worsening of heart failure to require a change in medication or withdrawal from the study (p = 0.07). By intention to treat, seven patients in the flosequinan group and two patients in the placebo group died. Conclusions. These findings indicate that flosequinan is an effective drug for patients with chronic heart failure who remain symptomatic despite treatment with digoxin and diuretic drugs. The effect of the drug on survival remains to be determined.

Ventricular arrhythmias during reperfusion

Accelerated idioventricular rhythm has been used as a marker for coronary reperfusion. The incidence of accelerated idioventricular rhythm and ventricular tachycardia was evaluated in 52 consecutive patients undergoing thrombolysis with intracoronary streptokinase during acute myocardial infarction. Complete 12-hour Holter recordings during and after intracoronary streptokinase were obtained in 39 patients. Reperfusion was documented in 17 patients (44%), no reperfusion in 14 (36%), and subtotal occlusion in eight (20%). Accelerated idioventricular rhythm occurred in 83%, 57%, and 63% of patients by group, respectively (p greater than 0.05). Ventricular tachycardia occurred in 100%, 71%, and 100% of patients by group, respectively (p less than 0.05). These data demonstrate that accelerated idioventricular rhythm is not specific for reperfusion and cannot be used as a marker for this event, and that ventricular tachycardia is more common with reperfusion and subtotal occlusion.

Metabolic support during coronary reperfusion

The limitation of infarct size by thrombolysis could potentially be improved by an early metabolic intervention. We therefore evaluated the effects of a 48-hour infusion of glucose-insulin-potassium (GIK) in patients with anterior infarctions. Seventeen patients were randomized to receive intravenous GIK (n = 10) or placebo (n = 7). All patients additionally received streptokinase. Changes in left ventricular function were assessed by comparing the global ejection fractions and the regional infarct area ejection fractions of the first ventriculogram with the 10-day second ventriculogram. There was a significantly greater improvement in the global ejection fraction of patients receiving GIK (increases 0.07 +/- 0.04) than in those randomized to placebo (decreases 0.08 +/- 0.04) (p less than 0.02). There was also a much greater improvement in the area ejection fractions of the group receiving GIK vs the group receiving placebo in the anterolateral (increases 0.24 +/- 0.07 vs decreases 0.02 +/- 0.04 [p less than 0.02]) and diaphragmatic (increases 0.08 +/- 0.08 vs decreases 0.17 +/- 0.05 [p less than 0.005]) segments. Thus in patients with anterior infarctions receiving streptokinase, GIK improves ventricular function and reduces the size of the segmental wall motion abnormality.

Role of the nervous system in experimentally induced arrhythmias.

The purpose of our studies was to examine the role of the nervous system in arrhythmias produced by digitalis overdose and coronary artery occlusion in the cat. This was done by observing the effect of these arrhythmogenic procedures on cardiac efferent neural activity and then determining whether any observed alteration in neural activity contributed to the cardiac rhythm disturbances evoked by digitalis and coronary artery occlusion. Our data indicate that both procedures used to evoke arrhythmias activate each division of the autonomic nervous system. Activation of the sympathetic nervous system resulted in a deleterious effect on cardiac rhythm whereas activation of the parasympathetic nervous system, in general, resulted in a beneficial effect on cardiac rhythm. With coronary occlusion, the role exerted by the nervous system depended on the anatomic location of the involved myocardium. Studies directed at elucidating the mechanisms whereby the nervous system caused cardiac rhythm disturbances indicated that there may be an important difference between the antiarrhythmic efficacy of beta-adrenergic blockade and bilateral stellate ganglionectomy. The latter procedure proved to be a more effective way of removing deleterious sympathetic neural effects on the heart. In conclusion, our findings suggest that the development of new drugs for treating arrhythmias resulting from digitalis and coronary occlusion should be aimed at finding drugs that act to either depress central sympathetic outflow or enhance parasympathetic effects on the ventricle.

2009 Focused updates

Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Co-Chair; Mary Hand, MSPH, RN, FAHA, Co-Chair*; Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Spencer B. King III, MD, MACC, FSCAI, Co-Chair; Jeffrey L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA; Steven R. Bailey, MD, FACC, FSCAI; Eric R. Bates, MD, FACC, FAHA; James C. Blankenship, MD, FACC, FSCAI; Donald E. Casey, Jr, MD, MPH, MBA; Lee A. Green, MD, MPH; Judith S. Hochman, MD, FACC, FAHA; Alice K. Jacobs, MD, FACC, FAHA, FSCAI; Harlan M. Krumholz, MD, SM, FACC, FAHA; Douglass A. Morrison, MD, PhD, FACC, FSCAI; Joseph P. Ornato, MD, FACC, FAHA; David L. Pearle, MD, FACC, FAHA; Eric D. Peterson, MD, MPH, FACC, FAHA; Michael A. Sloan, MD, MS, FACC, FAHA; Patrick L. Whitlow, MD, FACC, FAHA; David O. Williams, MD, FACC, FAHA, FSCAI

Determinants of Cardiac Failure after Coronary Bypass Surgery within 30 Days of Acute Myocardial Infarction

Timing of coronary artery bypass grafting after acute myocardial infarction (MI) is controversial, especially if myocardial function is depressed. Early coronary artery bypass grafting may result in reperfusion injury causing cardiac failure. Delay, however, may risk a second ischemic event. This study was performed to determine if four preoperative factors--time after MI, ejection fraction, ischemia (need for intravenous administration of nitroglycerin), and failure (need for inotropic support)--independently predict postoperative cardiac failure. Postoperative failure was defined as the need for inotropic support or intraaortic balloon pumping. The study group consisted of 145 patients who underwent isolated coronary artery bypass grafting between January, 1980, and July, 1985, within 4 weeks of an acute MI. Postoperatively 38 patients (26%) had cardiac failure. Five patients, all of whom had postoperative cardiac failure, died. Univariate and stepwise logistic regression analyses showed preoperative failure (p = .0001), ejection fraction less than 45% (p = .002), and preoperative ischemia (p = .02) were predictors of postoperative cardiac failure. Time after MI was not found to be an independent predictor (p = .96). We conclude that if ischemia or threatening coronary anatomy is present early after MI and clinical improvement is not occurring, operative intervention should be strongly considered at that time, as it does not appear that delay itself reduces the risk of cardiac failure and may risk a second ischemic event.