Faculty Bibliography

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

Recently, it has been demonstrated in multiple clinical research studies that non-Q-wave myocardial infarction shares many of the features of unstable angina pectoris and that both diseases initially are managed similarly. Important new antiplatelet drugs (glycoprotein IIb-IIIa inhibitors) and antithrombin agents (low-molecular-weight heparin) are currently recommended for patients with unstable angina pectoris/non-ST-segment elevation MI who are at high or intermediate risk on the basis of symptoms, electrocardiographic findings, and the presence or absence of serum markers (eg, troponin I, troponin T, and creatine kinase-MB). This review provides important information concerning the results of clinical studies of glycoprotein IIb-IIIa inhibitors (tirofiban hydrochloride and eptifibatide) when used with unfractionated heparin in patients with this syndrome or with low-molecular weight heparin (enoxaparin sodium) in similar patients. The Thrombolysis in Myocardial Infarction IIIB, Veterans Affairs Non-Q-Wave Infarction Studies in Hospital, and Fast Revascularization During Instability in Coronary Artery Disease II studies evaluating a conservative, ischemia-guided approach vs an early aggressive approach to such patients are presented, with a practical algorithm for treating such patients

AIMS: We analysed time trends in patient characteristics, management, and outcomes of cardiogenic shock complicating acute myocardial infarction in the international, prospective SHOCK Trial Registry and pre-study Registry. BACKGROUND: Despite therapeutic advances in its management, the incidence and high mortality of this complication has remained unchanged for decades. However, in recent years mortality was reported to decrease in one community concomitant with increasing use of revascularization. METHODS: Thirty-six centres registered 1380 patients with suspected cardiogenic shock complicating acute myocardial infarction from January 1992 to August 1997. Patient and myocardial infarction characteristics, haemodynamics, medications, procedure use, and vital status at discharge were recorded. RESULTS: In all, 79% of patients had shock due to predominant pump failure (non-mechanical aetiology). The aetiology, patient profile, and clinical characteristics of cardiogenic shock did not differ over time, except for increases in the incidence of prior bypass surgery (P=0.054) and transfers to tertiary centres (P=0.008). In all, 44% underwent revascularization (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%). The revascularization rate increased over time (P=0.006) with a significant decrease in the time to revascularization (P=0.033). The use of Swan-Ganz catheterization decreased over time (P=0.018), as did the mean length of hospitalization (P=0.034). Overall in-hospital mortality was high (63%) but decreased over time in all patients (P=0.004) and those with pump failure (P=0.018). Mortality was lower for patients who underwent revascularization compared to those who were not revascularized (41% vs 79%, P<0.001). CONCLUSIONS: Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate, but mortality decreased significantly from 1992 to 1997. This partly reflects the greater use of revascularization, which was associated with better outcomes. The reported international trend towards shorter admissions for myocardial infarction was also observed in this cohort

BACKGROUND: Controversy exists regarding the timing of thrombolytic administration and rupture rate. METHODS: Hospital records at St. Luke's-Roosevelt Hospital of the 4 study patients were reviewed and compared with those of 41 patients from a group of 537 patients concurrently admitted with a diagnosis of myocardial infarction (MI). RESULTS: Four patients experienced ventricular free wall rupture after having a MI between November 17, 1993, and July 28, 1995. All received tissue plasminogen activator. In 1 patient, pericardial effusion associated with a pseudoaneurysm was discovered in the operating room. The 3 others developed clinical pericardial tamponade before surgery. All 4 patients survived and left the hospital on postoperative days 10, 11, 11, and 82, respectively. During this same time period, 537 patients were admitted with MI, 41 of whom died; the study's 4 patients were compared with these 41. CONCLUSIONS: These data demonstrate that rupture of the ventricular free wall can occur early after thrombolytic therapy and may have a subacute course. Prompt diagnosis and surgery offer excellent chances of surviving this fatal condition

OBJECTIVES: We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND: Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS: We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS: Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS: There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting

OBJECTIVES: We sought to determine the outcomes of patients with cardiogenic shock (CS) complicating non-ST-segment elevation acute myocardial infarction (MI). BACKGROUND: Such patients represent a high-risk (ST-segment depression) or low-risk (normal or nonspecific electrocardiographic findings) group for whom optimal therapy, particularly in the setting of shock, is unknown. METHODS: We assessed characteristics and outcomes of 881 patients with CS due to predominant left ventricular (LV) dysfunction in the SHOCK Trial Registry. RESULTS: Patients with non-ST-segment elevation MI (n = 152) were significantly older and had significantly more prior MI, heart failure, azotemia, bypass surgery, and peripheral vascular disease than patients with ST-elevation MI (n = 729). On average, the groups had similar in-hospital LV ejection fractions (approximately 30%), but patients with non-ST-elevation MI had a lower highest creatine kinase and were more likely to have triple-vessel disease. Among patients selected for coronary angiography, the left circumflex artery was the culprit vessel in 34.6% of non-ST-elevation versus 13.4% of ST-elevation MI patients (p = 0.001). Despite having more recurrent ischemia (25.7% vs. 17.4%, p = 0.058), non-ST-elevation patients underwent angiography less often (52.6% vs. 64.1%, p = 0.010). The proportion undergoing revascularization was similar (36.8% for non-ST-elevation vs. 41.9% ST-elevation MI, p = 0.277). In-hospital mortality also was similar in the two groups (62.5% for non-ST-elevation vs. 60.4% ST-elevation MI). After adjustment, ST-segment elevation MI did not independently predict in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 0.83 to 2.02; p = 0.252). CONCLUSIONS: Patients with CS and non-ST-segment elevation MI have a higher-risk profile than shock patients with ST-segment elevation, but similar in-hospital mortality. More recurrent ischemia and less angiography represent opportunities for earlier intervention, and early reperfusion therapy for circumflex artery occlusion should be considered when non-ST-elevation MI causes CS

BACKGROUND: Cardiogenic shock is usually characterized by inadequate cardiac output and sustained hypotension. However, following a large myocardial infarction, peripheral hypoperfusion can occur with relatively well maintained systolic blood pressure, a condition known as nonhypotensive cardiogenic shock. The aim of this study was to determine the characteristics of patients with this condition. METHODS: The SHOCK trial registry prospectively enrolled patients with suspected cardiogenic shock complicating acute myocardial infarction. We identified a group of 49 patients who presented with nonhypotensive shock, defined as clinical evidence of peripheral hypoperfusion with a systolic blood pressure >90 mm Hg without vasopressor circulatory support. Clinical characteristics, hemodynamic data, and outcomes in these patients were compared with a group of 943 patients with classic cardiogenic shock with hypotension. The age, gender, and distributions of coronary risk factors were similar in both groups. RESULTS: Patients with nonhypotensive shock were more likely to have an anterior wall myocardial infarction (71% versus 53%, P = 0.03). Both groups of patients had similar rates of treatment with thrombolytic therapy, angioplasty, and bypass surgery. Patients with nonhypotensive shock had an in-hospital mortality rate of 43% as compared with a rate of 66% among patients who had classic cardiogenic shock with hypotension (P = 0.001). Mortality among 76 patients who presented with a systolic blood pressure <90 mm Hg but no hypoperfusion was 26%. CONCLUSIONS: Even in the presence of normal blood pressure, clinical signs of peripheral hypoperfusion, which may be subtle, are associated with a substantial risk of in-hospital death following acute myocardial infarction

OBJECTIVES: We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis. BACKGROUND: The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism. METHODS: The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective. RESULTS: The ACE inhibitor was started 3.2+/-1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m2 (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients. CONCLUSIONS: We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI