Amanda Stebbins

Cardiorenal Interactions: Insights From the ESCAPE Trial

OBJECTIVES We examined the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) database to understand the impact and pathophysiology of renal dysfunction in patients hospitalized with advanced decompensated heart failure (HF). BACKGROUND Baseline renal insufficiency (RI) (estimated glomerular filtration rate [eGFR] <60 ml/min) and worsening renal function (WRF) (upward arrow serum creatinine [SCr] >or=0.3 mg/dl) during treatment of decompensated HF are associated with adverse outcomes. METHODS We used a Cox proportional hazards model to evaluate the impact of renal function on 6-month outcomes. Renal parameters were correlated with hemodynamic measurements. The impact of a strategy using pulmonary artery catheter (PAC) guidance on WRF and outcomes in patients with baseline RI was compared with treatment based on clinical assessment alone. RESULTS Baseline and discharge RI, but not WRF, were associated with an increased risk of death and death or rehospitalization. Among the hemodynamic parameters measured in patients randomized to the PAC arm (n = 194), only right atrial pressure correlated weakly with baseline SCr (r = 0.165, p = 0.03). There was no correlation between baseline hemodynamics or change in hemodynamics and WRF. A PAC-guided strategy was associated with less average increase in creatinine but did not decrease the incidence of defined WRF during hospitalization or affect renal function after discharge relative to clinical assessment alone. CONCLUSIONS Among patients with advanced decompensated HF, baseline RI impacts outcomes more than WRF. Poor forward flow alone does not appear to account for the development of RI or WRF in these patients. The addition of hemodynamic monitoring to clinical assessment does not prevent WRF or improve renal function after discharge.

Atrial Fibrillation in the Setting of Acute Myocardial Infarction: The GUSTO-I Experience

OBJECTIVES We examined the clinical predictors and angiographic and clinical outcomes associated with atrial fibrillation in the setting of acute myocardial infarction (MI). BACKGROUND This condition has been studied primarily in prethrombolytic era small trials. METHODS We compared baseline clinical characteristics, short-term clinical and angiographic outcomes and 1-year mortality of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with atrial fibrillation on admission electrocardiography (n = 1,026 [2.5%]) or after enrollment (n = 3,254 [7.9%]) and those without atrial fibrillation (n = 36,611 [89.6%]). Univariable and multivariable analyses were used to assess relations between baseline factors and the development of atrial fibrillation. RESULTS Patients with any atrial fibrillation more often had three-vessel coronary artery disease and initial Thrombolysis in Myocardial Infarction (TIMI) grade < 3 flow than those without the arrhythmia. In-hospital stroke was increased in patients with atrial fibrillation (3.1% vs. 1.3%, p = 0.0001), mainly ischemic stroke (1.8% vs. 0.5%, p = 0.0001). Significant multivariable predictors of later atrial fibrillation included advanced age, higher peak creatine kinase levels, worse Killip class and increased heart rate. The unadjusted mortality rate was significantly higher at 30 days (14.3% vs. 6.2%, p = 0.0001) and at 1 year (21.5% vs. 8.6%, p < 0.0001) in patients with atrial fibrillation. The adjusted 30-day mortality rate remained significantly higher with any (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2 to 1.4) or later (OR 1.4, 95% CI 1.3 to 1.5) atrial fibrillation but not with baseline atrial fibrillation (OR 1.1, 95% CI 0.88 to 1.3). CONCLUSIONS Atrial fibrillation in the setting of acute MI independently predicts stroke and 30-day mortality. More aggressive treatment strategies in this subgroup may be warranted and deserve further study.

Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention

Cardiovascular disease (CVD) is the leading cause of mortality in women. Differences in pathophysiology, diagnosis, and treatment of women with cardiovascular disease compared with men have become a major focus during the past decades. Guideline of CVD prevention in women drew heavily on the results of randomized clinical trials (RCT). However, data from RCT in women was limited, leading to concerns of women been underrepresented in clinical trials from which guidelines were generated. During the past several years, researchers, physicians, and regulators have made substantial efforts to improve understanding of the sex difference in CVD and to recognize the importance of heart disease in women. The purpose of this review is to evaluate contemporary sex differences in CVD disease management, current representation of women in RCT, and examine factors that may improve women’s representation and quality of care in CVD prevention in women.

Impact of an Aggressive Invasive Catheterization and Revascularization Strategy on Mortality in Patients With Cardiogenic Shock in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) Trial An Observational Study

BACKGROUND Although retrospective analyses have revealed an association between survival and coronary angiography and angioplasty in patients with acute myocardial infarction complicated by cardiogenic shock, the degree to which bias in the selection of patients to undergo these procedures contributes to this observation remains unclear. METHODS AND RESULTS We studied 2200 patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial with acute myocardial infarction complicated by cardiogenic shock (systolic blood pressure < 90 mm Hg for > or = 1 hour) who survived > or = 1 hour after the onset of shock to determine the influence of an aggressive strategy of early angiography (within 24 hours of shock onset) and coronary angioplasty or bypass surgery, if appropriate, on survival. Revascularization was not protocol mandated but was selected by the attending physicians. Shock was present on admission in 11% and developed after admission in 89% of shock patients. The 30-day mortality was 38% in the 406 patients who underwent early angiography and were referred within 24 hours for angioplasty (n = 175), bypass surgery (n = 36), angioplasty and bypass surgery (n = 22), or neither (late or no revascularization, n = 173) compared with 62% in the 1794 patients who did not (P = .0001). However, there were important differences in the baseline characteristics of the two groups, including younger age (63 versus 68 years, P = .0001), less prior infarction (19% versus 27%, P = .001), and a shorter time to thrombolytic therapy (2.9 versus 3.2 hours, P = .0001) in patients treated with an aggressive strategy. Using multivariate logistic regression analysis to adjust for differences in baseline characteristics, an aggressive strategy was independently associated with reduced 30-day mortality (odds ratio, 0.43 [confidence interval, 0.34 to 0.54], P = .0001). CONCLUSIONS An aggressive strategy of early angiography (and revascularization when appropriate) is associated with a reduction in mortality in patients with acute myocardial infarction and cardiogenic shock who receive thrombolytic therapy.

Facilitation of Early percutaneous coronary intervention after reteplase with or without abciximab in acute Myocardial Infarction: Results from the SPEED (GUSTO-4 pilot) trial

OBJECTIVES We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.

Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: Observations from the GUSTO-I study

OBJECTIVES We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.

Sustained Ventricular Arrhythmias in Patients Receiving Thrombolytic Therapy Incidence and Outcomes

BACKGROUND Sustained ventricular tachycardia (VT) and fibrillation (VF) occur in up to 20% of patients with acute myocardial infarction (MI) and have been associated with a poor prognosis. The relationships among the type of arrhythmia (VT versus VF or both), time of VT/VF occurrence, use of thrombolytic agents, and eventual outcome are unclear. METHODS AND RESULTS In the GUSTO-I study, we examined variables associated with the occurrence of VT/VF and its impact on mortality. Of the 40 895 patients with ventricular arrhythmia data, 4188 (10.2%) had sustained VT, VF, or both. Older age, systemic hypertension, previous MI, Killip class, anterior infarct, and depressed ejection fraction were associated with a higher risk of sustained VT and VF (P<0.001). In-hospital and 30-day mortality rates were higher among patients with sustained VT/VF than among patients without sustained ventricular arrhythmias (P<0.001). Both early (<2 days) and late (>2 days) occurrences of sustained VT and VF were associated with a higher risk of later mortality (P<0. 001). In addition, patients with both VT and VF had worse outcomes than those with either VT or VF alone (P<0.001). Among patients who survived hospitalization, no significant difference was found in 30-day mortality between the VT/VF and no VT/VF groups. However, after 1 year, the mortality rate was significantly higher in the VT alone and VT/VF groups (P<0.0001). CONCLUSIONS Despite the use of thrombolytic therapy, both early and late occurrences of sustained VT or VF continue to have a negative impact on patient outcome; patients with both VT and VF had the worst outcome; and among patients who survived hospitalization, the 1-year mortality rate was significantly higher in those who experienced VT alone or VT and VF.

Atenolol Use and Clinical Outcomes After Thrombolysis for Acute Myocardial Infarction: The GUSTO-I Experience

OBJECTIVES We assessed the use and effects of acute intravenous and later oral atenolol treatment in a prospectively planned post hoc analysis of the GUSTO-I dataset. BACKGROUND Early intravenous beta blockade is generally recommended after myocardial infarction, especially for patients with tachycardia and/or hypertension and those without heart failure. METHODS Besides one of four thrombolytic strategies, patients without hypotension, bradycardia or signs of heart failure were to receive atenolol 5 mg intravenously as soon as possible, another 5 mg intravenously 10 min later and 50 to 100 mg orally daily during hospitalization. We compared the 30-day mortality of patients given no atenolol (n=10,073), any atenolol (n=30,771), any intravenous atenolol (n=18,200), only oral atenolol (n=12,545) and both intravenous and oral drug (n=16,406), after controlling for baseline differences and for early deaths (before oral atenolol could be given). RESULTS Patients given any atenolol had a lower baseline risk than those not given atenolol. Adjusted 30-day mortality was significantly lower in atenolol-treated patients, but patients treated with intravenous and oral atenolol treatment vs. oral treatment alone were more likely to die (odds ratio, 1.3; 95% confidence interval, 1.0 to 1.5; p=0.02). Subgroups had similar rates of stroke, intracranial hemorrhage and reinfarction, but intravenous atenolol use was associated with more heart failure, shock, recurrent ischemia and pacemaker use than oral atenolol use. CONCLUSIONS Although atenolol appears to improve outcomes after thrombolysis for myocardial infarction, early intravenous atenolol seems of limited value. The best approach for most patients may be to begin oral atenolol once stable.

Risk stratification with a point-of-care cardiac troponin T test in acute myocardial infarction☆

Troponin T has been used successfully to risk stratify patients with acute coronary syndromes, but the utility of this approach using a rapid bedside assay in patients undergoing thrombolysis for ST-segment elevation acute myocardial infarction has not been assessed in a large population. We assessed whether a point-of-care, qualitative troponin T test at enrollment could independently risk-stratify patients randomized to receive alteplase or reteplase in the GUSTO-III trial. Complete troponin T data were available for 12,666 patients (84%) enrolled at 550 hospitals. The primary end point was mortality at 30 days, and the predictive ability of an elevated baseline troponin T level was analyzed (after adjustment for baseline characteristics) with multiple logistic regression. Patients with an elevated troponin T result at enrollment (8.9%) had significantly higher mortality at 30 days (unadjusted 15.7% vs 6.2% for negative patients; p = 0.001), which persisted even after adjustment for age, heart rate, location of infarction, Killip class, and systolic blood pressure. In a multivariable regression model, a positive troponin T result added independently to the prediction of 30-day mortality (chi-square 46, p = 0.001). A positive result with qualitative troponin T testing on admission is an independent marker of higher 30-day mortality. Troponin T testing could be a valuable addition to the evaluation strategy for patients with acute myocardial infarction.

Diabetic Retinopathy Should Not Be a Contraindication to Thrombolytic Therapy for Acute Myocardial Infarction: Review of Ocular Hemorrhage Incidence and Location in the GUSTO-I Trial

OBJECTIVES This study sought to evaluate the incidence of ocular hemorrhage in patients with and without diabetes after thrombolytic therapy for acute myocardial infarction. BACKGROUND Ocular hemorrhage after thrombolysis has been reported rarely. However, there is concern that the risk is increased in patients with diabetes. In fact, diabetic hemorrhagic retinopathy has been identified as a contraindication to thrombolytic therapy without clear evidence that these patients have an increased risk for ocular hemorrhage. METHODS We identified all suspected ocular hemorrhages from bleeding complications reported in patients enrolled in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I trial. Additional information was collected on a one-page data form. We compared the incidence and location of ocular hemorrhages in patients with and without diabetes. RESULTS There were 40,899 patients (99.7%) with information about diabetic history and ocular bleeding. Twelve patients (0.03%) had an ocular hemorrhage. Intraocular hemorrhage was confirmed in only one patient. There were 6,011 patients (15%) with diabetes, of whom only 1 had an ocular hemorrhage (eyelid hematoma after a documented fall). The upper 95% confidence intervals for the incidence of intraocular hemorrhage in patients with and without diabetes were 0.05% and 0.006%, respectively. CONCLUSIONS Ocular hemorrhage and, more important, intraocular hemorrhage after thrombolytic therapy for acute myocardial infarction is extremely uncommon. The calculated upper 95% confidence interval for the incidence of intraocular hemorrhage in patients with diabetes was only 0.05%. We conclude that diabetic retinopathy should not be considered a contraindication to thrombolysis in patients with an acute myocardial infarction.