New heparin dosing recommendations for patients with acute coronary syndromes.

Despite major innovations in antithrombotic and antiplatelet therapy, unfractionated intravenous heparin is widely used to treat acute coronary syndromes. Recommendations for unfractionated heparin dosing in acute myocardial infarction and unstable angina have been issued in two recent American College of Cardiology/American Heart Association guidelines. An initial heparin bolus of 60 U/kg (maximum, 4000 U) followed by a 12-U/kg/h infusion (maximum 1000 U/h) is recommended with alteplase for ST-elevation myocardial infarction. When intravenous heparin is administered for myocardial infarction with non-ST elevation and unstable angina, an initial bolus of 60 to 70 U/kg (maximum, 5000 U) followed by a 12- to 15-U/kg/h infusion is recommended. The goal is to achieve an activated partial thromboplastin time of 50 to 70 seconds. Here, we review these new dosing regimens and explain the rationale for their use. We also review the risk of bleeding with heparin, especially when administered concurrently with aspirin, thrombolytic agents, and glycoprotein IIb/IIIa antagonists, and the relationship between activated partial thromboplastin time and cardiac events.

Augmentation of regional coronary blood flow by intra-aortic balloon counterpulsation in patients with unstable angina.

Intra-aortic balloon counterpulsation is capable of reducing afterload in patients with unstable angina. Whether it is also capable of augmenting coronary blood flow to poststenotic myocardium is controversial. We studied seven patients receiving maximal drug therapy and requiring balloon pumping for unstable angina as balloon volume and assist ratio were altered. All patients had greater than 90% stenosis of the proximal left anterior descending coronary artery. With maximal augmentation (40 cc balloon volume, 1:1 assist ratio) great cardiac vein flow, representing the efflux from the left anterior descending coronary artery bed, rose from a baseline of 52 +/- 20 to 67 +/- 25 ml/min (mean +/- SD, p = .004) and mean aortic diastolic pressure increased from 77 +/- 13 to 99 +/- 33 mm Hg (p = .004). Increased great cardiac vein flow correlated with increased mean aortic diastolic pressure across changes in balloon volumes (off, 20 cc, 30 cc, and 40 cc) and changes in assist ratio (off, 1:4, 1:2, and 1:1) (p = .02). However, the intermediate balloon volumes produced great cardiac vein flows at an intermediate level between full assist and no assist (p less than .05), whereas the intermediate assist ratios did not augment flow. Thus balloon pumping increased flow to a bed fed by collateral vessels or critical stenoses; this increased flow correlated with increased aortic diastolic pressure, indicating probable loss of autoregulatory ability.

Regional coronary blood flow during relief of pacing-induced angina by nitroglycerin. Implications for mechanism of action.

The mechanism for the therapeutic effect of nitroglycerin in stress-induced angina remains controversial; it has been attributed to both increased blood supply to the ischemic myocardium and decreased myocardial oxygen demand. To investigate the contribution of each of these mechanisms, systemic pressures and great cardiac vein flow were measured in 14 patients with single-vessel disease involving the left anterior descending (LAD) coronary artery during the development of pacing-induced angina and after the administration of nitroglycerin while continuing pacing at the angina-provoking rate. Great cardiac vein flow, measured by thermodilution, represents the venous efflux from the LAD territory and therefore provided an index of flow to the poststenotic myocardium. In 11 patients, nitroglycerin was administered systemically (400 to 800 micrograms sublingually or 200 micrograms intravenously); angina was relieved in 10, concomitant with a decrease in both great cardiac vein flow (from 123 +/- 29 to 98 +/- 29 ml/min, p less than 0.001) and mean aortic pressure (from 118 +/- 22 to 104 +/- 22 mm Hg, p less than 0.001). In contrast, when 75 micrograms of nitroglycerin was administered directly into the left main coronary artery of 7 patients, it produced a small increase in great cardiac vein flow (from 108 +/- 32 to 125 +/- 31 ml/min, p = 0.059), no change in aortic pressure, and no relief of angina. This study suggests that nitroglycerin's major beneficial action in pacing-induced angina is unrelated to direct effects on the coronary circulation and is likely related to its cardiac unloading effect.

Electrocardiographic localization of coronary artery narrowings: studies during myocardial ischemia and infarction in patients with one-vessel disease.

To investigate the accuracy of the 12-lead ECG in localizing the site of coronary artery narrowings, we reviewed abnormal ECGs obtained during myocardial infarction, spontaneous angina or exercise stress testing in 134 patients with angiographically documented one-vessel disease. The presence of Q waves, ST-segment elevation and T-wave inversion in leads I, aVL and V1--V4 were all highly correlated with the presence of left anterior descending coronary artery disease (p less than 0.001), and the same ECG findings in leads II, III and aVF were associated with right (RCA) or circumflex coronary artery (LCx) narrowings (p less than 0.001). In contrast, ST depression alone was not useful in predicting the site of coronary artery narrowing. Q waves correctly identified the location of the coronary disease in 98% of cases, ST elevation in 91%, T-wave inversion in 84%, and ST depression in 60%. No electrocardiographic criteria distinguished RCA from LCx disease, even in patients with a right-dominant circulation. These findings should lead to a better understanding of the value and limitations of the 12-lead ECG in localizing coronary artery disease.

Pathogenesis of angina pectoris.

There are two broad classes of angina pectoris, related to two fundamentally different pathogenetic mechanisms: in classic angina, atherosclerotic narrowings limit the ability of the coronary arteries to augment myocardial blood flow in response to increases in demand, and in variant angina, a primary reduction in coronary blood flow occurs, unrelated to changes in demand. Over the last decade, major advances have been made in our understanding of the factors that control coronary blood flow and how they interact in each of the major classes of angina. The present review examines these advances, as well as their relation to the syndromes of rest angina, postprandial angina, and exertional coronary artery spasm. Current knowledge about the mechanisms by which myocardial ischemia produces the sensation of angina is discussed, along with the application of pathogenetic principles to medical therapy.

Limitations of pulmonary wedge V waves in diagnosing mitral regurgitation.

To study the usefulness of large V waves in pulmonary capillary wedge tracings in establishing the diagnosis of mitral regurgitation, data on 1,021 consecutive cardiac catheterizations were reviewed. Wedge tracings were obtained by Swan-Ganz catheterization in 208 patients, usually because of suspected valve disease. One hundred two patients had no trace of mitral regurgitation angiographically, 69 had mild to moderate and 37 had severe regurgitation. V waves were graded as trivial (less than 5), intermediate (5 to 10) or large (10 or more mm Hg above mean wedge pressure). Of 50 patients with large V waves, 18 (36 percent) had no or trace mitral regurgitation; these included 5 with mitral stenosis, 3 with a mitral valve prosthesis, 4 with coronary disease and congestive failure, 2 with aortic valve disease and congestive failure and 2 with a ventricular septal defect. Of 37 patients with severe mitral regurgitation, 16 (43 percent) had large and 12 (32 percent) had trivial V waves. Thus, mitral regurgitation is the most common cause of large V waves; however, large V waves are neither highly sensitive nor specific for severe regurgitation. Increased left atrial compliance may be associated with trivial V waves in the presence of severe regurgitation. Mitral obstruction, congestive heart failure and ventricular septal defect may all be associated with large V waves in the absence of significant mitral regurgitation.