Cardiogenic shock in patients with acute ischemic syndromes with and without ST-segment elevation.

BACKGROUND: Cardiogenic shock is usually considered a sequela of ST-segment elevation myocardial infarction. There are limited prospective data on the incidence and significance of shock in non-ST-segment elevation patients. This study assessed the incidence and outcomes of cardiogenic shock developing after enrollment among patients with and without ST-segment elevation in the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO)-IIb trial. METHODS AND RESULTS: Among 12,084 patients in GUSTO-IIb who did not present with cardiogenic shock, 4092 (34%) had and 7991 (66%) did not have ST-segment elevation on the enrollment ECG. Cardiogenic shock developed in 4.2% of ST-segment elevation patients compared with 2.5% of patients without ST-segment elevation (odds ratio, 0. 581; 95% CI, 0.472 to 0.715; P<0.001). Shock developed significantly later among patients without ST-segment elevation. There were significant differences in baseline characteristics between shock patients with and without ST-segment elevation: Patients without ST-segment elevation were older, more frequently had diabetes mellitus and 3-vessel disease, but had less TIMI grade 0 flow at angiography. Regardless of the initial ECG, mortality was high: 63% among patients with ST-segment elevation and 73% in those without ST-segment elevation. CONCLUSIONS: Cardiogenic shock occurs in the setting of acute ischemic syndromes regardless of whether ST-segment elevation is present. The incidence, patient characteristics, timing, clinical course, and angiographic findings differ between the 2 groups. Mortality from cardiogenic shock is similarly high among patients with and without ST-segment elevation.

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial.

BACKGROUND: A multinational, randomized, placebo-controlled trial (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, PURSUIT) demonstrated that the platelet glycoprotein IIb/IIIa receptor antagonist eptifibatide reduced the incidence of death or myocardial infarction among patients with acute ischemic syndromes without ST-segment elevation. Because of expected differences in practice patterns, a prospectively planned analysis of outcomes as a function of regions of the world was performed. The current study provides a detailed assessment of eptifibatide among the subgroup of patients enrolled within the United States. METHODS AND RESULTS: Patients presenting with chest pain within the previous 24 hours and ischemic ECG changes or creatine kinase-MB elevation were eligible for enrollment. Of the 10 948 patients randomized worldwide, 4035 were enrolled within the United States. Patients were allocated to placebo or eptifibatide infusion for up to 72 to 96 hours. Other medical therapies and revascularization strategies were at the discretion of the treating physician. Eptifibatide reduced the rate of the primary end point of death or myocardial infarction by 30 days from 15.4% to 11.9% (P=0.003) among patients in the United States. The treatment effect was achieved early and maintained over a period of 6 months (18.9% versus 15.2%; P=0.004). Bleeding events were more common in patients receiving eptifibatide but were predominantly associated with invasive procedures. The magnitude of clinical benefit from eptifibatide was greater among patients in the United States than elsewhere in the world. CONCLUSIONS: Platelet glycoprotein IIb/IIIa receptor blockade with eptifibatide reduces the incidence of death or myocardial infarction among patients treated for acute ischemic syndromes without ST-segment elevation within the United States.

Effect of exercise on acute myocardial infarction in rats.

Infarct expansion, the time-related thinning and dilation of an acute transmural infarct, leads to aneurysm formation and cardiac rupture in humans. In this study, the effect of exercise on acute infarct expansion early after myocardial infarction was examined in 129 rats. Ninety rats were exercised on a treadmill for 1.5 hours daily for 1 week beginning on the day of coronary artery ligation; the remaining 39 rats remained in their cages. There was no effect on the prevalence or extent of expansion; specifically, infarct wall thickness, left ventricular diameter and expansion grade (0 to 4+) were similar in the exercise and control rats. There was no difference in infarct size or the number of animals with aneurysmal shape changes in the exercise and control groups. There was no significant difference between the two groups in the histologic finding of intramural hemorrhage, a feature that has been associated with cardiac rupture, and no complete rupture was seen. However, there was a nonsignificant trend toward higher mortality in the exercised group. Thus, the findings of this study suggest that moderate exercise early after myocardial infarction produces no significant detrimental effect on infarct size or left ventricular topography in the rat model.

Indications for immediate angiotensin-converting enzyme inhibition in patients with acute myocardial infarction.

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.

The clinical profile of patients with suspected cardiogenic shock due to predominant left ventricular failure: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We sought to evaluate the frequency of pulmonary congestion and associated clinical and hemodynamic findings in patients with suspected cardiogenic shock (CS). BACKGROUND: The prevalence of pulmonary congestion in the setting of CS is uncertain. METHODS: The 571 SHOCK Trial Registry patients with predominant left ventricular failure (LVF) were divided into four groups: Group A = no pulmonary congestion/no hypoperfusion = 14 (3%), Group B = isolated pulmonary congestion = 32 (6%), Group C = isolated hypoperfusion = 158 (28%) and Group D = congestion with hypoperfusion = 367 (64%). Statistical comparisons between Group C and D only, with regard to patient demographics, hemodynamics, treatment and outcome, were made. RESULTS: A significant proportion of patients with shock had no pulmonary congestion (Group C = 28%, 95% CI, 24% to 31%). Age and gender in this group were similar to Group D. Group C patients were less likely to have a prior MI (p = 0.028), congestive heart failure (p = 0.005) and renal insufficiency (p = 0.032), and the index MI was less likely to be anterior (p = 0.044). Cardiac output, cardiac index and ejection fraction were similar for the two groups but pulmonary capillary wedge pressure was slightly lower for Group C (22 vs. 24 mm Hg, p = 0.012). Treatment with thrombolysis, angioplasty and bypass surgery was similar in the two groups. In-hospital mortality rates for Groups C and D were 70% and 60%, respectively (p = 0.036). After adjustment, this difference was no longer statistically significant (p = 0.153). CONCLUSIONS: Absence of pulmonary congestion at initial clinical evaluation does not exclude a diagnosis of CS due to predominant LVF and is not associated with a better prognosis.

Outcome and profile of women and men presenting with acute coronary syndromes: a report from TIMI IIIB. TIMI Investigators. Thrombolysis in Myocardial Infarction.

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.

Absence of gender differences in clinical outcomes in patients with cardiogenic shock complicating acute myocardial infarction. A report from the SHOCK Trial Registry.

OBJECTIVES: The aim of this study was to assess the impact of gender on clinical course and in-hospital mortality in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). BACKGROUND: Previous studies have demonstrated higher mortality for women compared with men with ST elevation myocardial infarctions and higher rates of CS after AMI. The influence of gender and its interaction with various treatment strategies on clinical outcomes once CS develops is unclear. METHODS: Using the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? (SHOCK) Registry database of 1,190 patients with suspected CS in the setting of AMI, we examined shock etiologies by gender. Among the 884 patients with predominant left ventricular (LV) failure, we compared the patient demographics, angiographic and hemodynamic findings, treatment approaches as well as the clinical outcomes of women versus men. This study had a 97% power to detect a 10% absolute difference in mortality by gender. RESULTS: Left ventricular failure was the most frequent cause of CS for both gender groups. Women in the SHOCK Registry had a significantly higher incidence of mechanical complications including ventricular septal rupture and acute severe mitral regurgitation. Among patients with predominant LV failure, women were, on average, 4.6 years older, had a higher incidence of hypertension, diabetes and a lower cardiac index. The overall mortality rate for the entire cohort was high (61%). After adjustment for differences in patient demographics and treatment approaches, there was no significant difference in in-hospital mortality between the two gender groups (odds ratio = 1.03, 95% confidence interval of 0.73 to 1.43, p = 0.88). Mortality was also similar for women and men who were selected for revascularization (44% vs. 38%, p = 0.244). CONCLUSIONS: Women with CS complicating AMI had more frequent adverse clinical characteristics and mechanical complications. Women derived the same benefit as men from revascularization, and gender was not independently associated with in-hospital mortality in the SHOCK Registry.

Cardiogenic shock complicating acute myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the implications of the timing of onset of cardiogenic shock (CS) after acute myocardial infarction (MI). BACKGROUND: Little information is available about the relationships between timing, clinical substrate, management and outcomes of shock. METHODS: The multinational SHOCK Trial Registry enrolled MI patients with CS from 1993 to 1997. Cardiogenic shock was predominantly attributable to left ventricular (LV) failure in 815 Registry patients for whom temporal data were available. We examined factors related to the timing of shock onset and the relation of temporal onset to in-hospital outcomes. RESULTS: Overall, shock developed a median of 6.2 h after MI symptom onset. Shock onset varied by culprit artery: left main, median 1.7 h; right, 3.5 h; circumflex, 3.9 h; left anterior descending (LAD), 11.0 h; saphenous vein graft, 10.9 h (p = 0.025). Early shock (< 24 h) occurred in 74.1% and was associated with chest pain at shock onset, ST-segment elevation in two or more leads, multiple infarct locations, inferior MI, left main disease and smoking. Late shock (> or = 24 h) was associated with recurrent ischemia, Q waves in two or more leads and LAD culprit vessel. Mortality was higher in patients with early versus late shock (62.6% vs. 53.6%, p = 0.022). CONCLUSIONS: Shock onset after acute MI occurred within 24 h in 74% of the patients with predominant LV failure. Mortality was slightly higher in patients developing shock early rather than later. Many factors influence when shock develops, which has implications for its management.

Cardiogenic shock with non-ST-segment elevation myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?

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.

Diabetes mellitus in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the role of diabetes mellitus in cardiogenic shock (CS) complicating acute myocardial infarction (AMI) in the SHOCK Trial Registry. BACKGROUND: The characteristics, outcomes and optimal treatment of diabetic patients with CS complicating AMI have not been well described. METHODS: Baseline characteristics, clinical and hemodynamic measures, treatment variables, shock etiologies and comorbid conditions were compared for 379 diabetic and 784 nondiabetic patients. Logistic regression was used to examine the association between diabetes and in-hospital mortality, after adjustment for baseline differences. RESULTS: Diabetics were less likely than nondiabetics to undergo thrombolysis (28% vs. 37%; p = 0.002) or attempted revascularization (40% vs. 49%; p = 0.008). The survival benefit for diabetics selected for percutaneous or surgical revascularization (55% vs. 19% without revascularization) was similar to that for nondiabetics (59% vs. 25%). Overall unadjusted in-hospital mortality was significantly higher for diabetics (67% vs. 58%; p = 0.007), but diabetes was only a borderline predictor of mortality after adjustment for baseline and treatment differences (odds ratio for death, 1.36; 95% confidence interval, 1.00 to 1.84; p = 0.051). CONCLUSIONS: Diabetics with CS complicating AMI have a higher-risk profile at baseline, but after adjustment, diabetics have an in-hospital survival rate that is only marginally lower than that of nondiabetics. Diabetics who undergo revascularization derive a survival benefit similar to that of nondiabetics.

Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: Our objective was to define the outcomes of patients with cardiogenic shock (CS) due to severe mitral regurgitation (MR) complicating acute myocardial infarction (AMI). BACKGROUND: Methods for early identification and optimal treatment of such patients have not been defined. METHODS: The SHOCK Trial Registry enrolled 1,190 patients with CS complicating AMI. We compared 1) the cohort with severe mitral regurgitation (MR, n = 98) to the cohort with predominant left ventricular failure (LVF, n = 879), and 2) the MR patients who underwent valve surgery (n = 43) to those who did not (n = 51). RESULTS: Shock developed early after MI in both the MR (median 12.8 h) and LVF (median 6.2 h) cohorts. The MR patients were more often female (52% vs. 37%, p = 0.004) and less likely to have ST elevation at shock diagnosis (41% vs. 63%, p < 0.001). The MR index MI was more frequently inferior (55% vs. 44%, p = 0.039) or posterior (32% vs. 17%, p = 0.002) than that of LVF and much less frequently anterior (34% vs. 59%, p < 0.001). Despite having higher mean LVEF (0.37 vs. 0.30, p = 0.001) the MR cohort had similar in-hospital mortality (55% vs. 61%, p = 0.277). The majority of MR patients did not undergo mitral valve surgery. Those undergoing surgery exhibited higher mean LVEF than those not undergoing surgery; nevertheless, 39% died in hospital. CONCLUSIONS: The data highlight opportunities for early identification and intervention to potentially decrease the devastating mortality and morbidity of severe post-myocardial infarction MR.

Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?

OBJECTIVES: We sought to compare the characteristics and outcomes of patients with acute myocardial infarction (MI) and cardiogenic shock (CS) caused by rupture of the ventricular free wall or tamponade versus shock from other causes. BACKGROUND: Free-wall rupture is a recognized cause of mortality in patients with acute MI. Some of these patients present subacutely, which provides an opportunity for intervention. Recognition of factors that distinguish them from the overall shock cohort would be beneficial. METHODS: The international SHOCK Trial Registry enrolled patients concurrently with the randomized SHOCK Trial. Thirty-six centers consecutively enrolled all patients with suspected CS after MI, regardless of trial eligibility. RESULTS: Of the 1,048 patients studied, 28 (2.7%) had free-wall rupture or tamponade. These patients had less pulmonary edema, less diabetes, less prior MI, and less prior congestive heart failure (all p < 0.05). They more often had new Q waves in two or more leads (51.9% vs. 31.5%, p < 0.04), but MI location and time to shock onset after MI did not differ. Of patients with rupture or tamponade, 75% had pericardial effusions. No hemodynamic characteristics identified patients with rupture/tamponade. Most patients with rupture/tamponade had surgery and/or pericardiocentesis (27/28); their in-hospital survival rate was identical to that of the group overall (39.3%). Women and older patients with rupture/tamponade tended to survive intervention less often. CONCLUSIONS: Free-wall rupture and tamponade may present as CS after MI, and survival after intervention is similar to that of the overall shock cohort. All patients with CS after MI should have echocardiography in order to detect subacute rupture or tamponade and initiate appropriate interventions.

Platelet glycoprotein IIb/IIIa blockade and outcome of cardiogenic shock complicating acute coronary syndromes without persistent ST-segment elevation.

OBJECTIVES: The study examined whether antiplatelet treatment with eptifibatide affected the frequency and outcome of shock among patients in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial who had acute coronary syndromes but not persistent ST-segment elevation. BACKGROUND: Preliminary reports suggest a salutary effect of antiplatelet agents when shock complicates acute myocardial infarction. METHODS: We analyzed the impact of antiplatelet treatment with eptifibatide on the frequency and outcome of cardiogenic shock developing after enrollment. PURSUIT was a double-blind, randomized trial that examined the efficacy of eptifibatide (180 microg/kg bolus + continuous infusion of 2.0 microg/kg/min for < or =96 h) versus placebo among patients who had acute coronary syndromes but not persistent ST-segment elevation. RESULTS: Shock developed in 2.5% of the 9,449 patients at a median (25th, 75th interquartiles) of 94.0 (38, 206) h. Death by 30 days occurred in 65.8% of shock patients. Patients who had acute myocardial infarction upon enrollment had a greater incidence of shock (2.9% vs. 2.1%, p = 0.01), developed shock earlier (40.2% <48 h vs. 20.9%, p = 0.001), and had higher 30-day mortality from shock (77.2% vs. 52.7%, p = 0.001). Randomization to eptifibatide did not affect the occurrence of shock (p = 0.71, adjusted odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.72-1.25). However, shock patients treated with eptifibatide had significantly reduced adjusted odds of 30-day death (p = 0.03, adjusted OR = 0.51, 95% CI = 0.28-0.94). CONCLUSIONS: Patients with shock treated with eptifibatide had significantly reduced adjusted odds of death, suggesting a salutary effect of antiplatelet therapy on shock. This finding warrants verification in specifically designed studies.

Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study.

OBJECTIVES: The purpose of this study was to determine the incidence and demographic characteristics of patients experiencing cardiac rupture after thrombolytic and adjunctive anticoagulant therapy and to identify possible associations between the mechanism of thrombin inhibition (indirect, direct) and the intensity of systemic anticoagulation with its occurrence. BACKGROUND Cardiac rupture is responsible for nearly 15% of all in-hospital deaths among patients with myocardial infarction (MI) given thrombolytic agents. Little is known about specific patient- and treatment-related risk factors. METHODS Patients (n = 3,759) with MI participating in the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9A and B trials received intravenous thrombolytic therapy, aspirin and either heparin (5,000 U bolus, 1,000 to 1,300 U/h infusion) or hirudin (0.1 to 0.6 mg/kg bolus, 0.1 to 0.2 mg/kg/h infusion) for at least 96 h. A diagnosis of cardiac rupture was made clinically in patients with sudden electromechanical dissociation in the absence of preceding congestive heart failure, slowly progressive hemodynamic compromise or malignant ventricular arrhythmias. RESULTS A total of 65 rupture events (1.7%) were reported-all were fatal, and a majority occurred within 48 h of treatment Patients with cardiac rupture were older, of lower body weight and stature and more likely to be female than those without rupture (all p < 0.001). By multivariable analysis, age >70 years (odds ratio [OR] 3.77; 95% confidence interval [CI] 2.06, 6.91), female gender (OR 2.87; 95% CI 1.44, 5.73) and prior angina (OR 1.82; 95% CI 1.05, 3.16) were independently associated with cardiac rupture. Independent predictors of nonrupture death included age >70 years (OR 3.68; 95% CI 2.53, 5.35) and prior MI (OR 2.14; 95%, CI 1.45, 3.17). There was no association between the type of thrombin inhibition, the intensity of anticoagulation and cardiac rapture. CONCLUSIONS Cardiac rupture following thrombolytic therapy tends to occur in older patients and may explain the disproportionately high mortality rate among women in prior dinical trials. Unlike major hemorrhagic complications, there is no evidence that the intensity of anticoagulation associated with heparin or hirudin administration influences the occurrence of rupture.

Predictors of cardiogenic shock after thrombolytic therapy for acute myocardial infarction.

OBJECTIVES: This study characterized clinical factors predictive of cardiogenic shock developing after thrombolytic therapy for acute myocardial infarction (AMI). BACKGROUND: Cardiogenic shock remains a common and ominous complication of AMI. By identifying patients at risk of developing shock, preventive measures may be implemented to avert its development. METHODS: We analyzed baseline variables associated with the development of shock after thrombolytic therapy in the Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. Using a Cox proportional hazards model, we devised a scoring system predicting the risk of shock. This model was then validated in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) cohort. RESULTS: Shock developed in 1,889 patients a median of 11.6 h after enrollment. The major factors associated with increased adjusted risk of shock were age (chi2 = 285, hazard ratio [95% confidence interval] 1.47 [1.40, 1.53]), systolic blood pressure (chi2 = 280), heart rate (chi2 = 225) and Killip class (chi2 = 161, hazard ratio 1.70 [1.52, 1.90] and 2.95 [2.39, 3.63] for Killip II versus I and Killip III versus I, respectively) upon presentation. Together, these four variables accounted for >85% of the predictive information. These findings were transformed into an algorithm with a validated concordance index of 0.758. Applied to the GUSTO-III cohort, the four variables accounted for > 95% of the predictive information, and the validated concordance index was 0.796. CONCLUSIONS: A scoring system accurately predicts the risk of shock after thrombolytic therapy for AMI based primarily on the patient's age and physical examination on presentation.

Angiographic findings and clinical correlates in patients with cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction. BACKGROUND: Patients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking. METHODS: We compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications. RESULTS: Patients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3). CONCLUSIONS: Patients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

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.

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.