Journal of the American College of Cardiology, 2010
Category: Cardiomyopathies/Myocarditis/Pericardial Disease Background: Hemodynamic assessment can... more Category: Cardiomyopathies/Myocarditis/Pericardial Disease Background: Hemodynamic assessment can be particularly challenging in overweight and obese patients with heart failure as the physical exam often limits the ability to assess filling pressures. This presents a need for a non-invasive test such as serum BNP to assist in hemodynamic evaluation. We compared the relationship between BNP levels and PCWP in lean, overweight, and obese patients.
Background-Impedance cardiography (ICG) is a noninvasive modality that utilizes changes in impeda... more Background-Impedance cardiography (ICG) is a noninvasive modality that utilizes changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure (HF) is uncertain.
Journal of the American College of Cardiology, Mar 1, 2010
Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective ... more Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. The ESCAPE Risk Model and Discharge Score Key Words: heart failure y risk stratification y discharge risk model.
Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure.... more Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure <or=15 and right atrial pressure <or=8 mm Hg. Patients were randomized to PAC or CLIN during hospitalization with chronic heart failure and mean left ventricular ejection fraction 20%, and at least 1 symptom and 1 sign of congestion. MR and mitral flow patterns, measured blinded to therapy and timepoint, were available at baseline and discharge in 133 patients, and at 3 months in 104 patients. Changes in MR and related transmitral flow patterns were compared between PAC and CLIN patients. Jugular venous pressure, edema, and weights decreased similarly during therapy in the hospital for both groups. In PAC but not in CL...
Journal of the American College of Cardiology, 2010
Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective ... more Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. The ESCAPE Risk Model and Discharge Score Key Words: heart failure y risk stratification y discharge risk model.
Journal of the American College of Cardiology, 2001
We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic... more We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic complications and to determine the relationship of angiographically evident complications to elevations of creatine kinase-MB (CK-MB) enzyme levels during percutaneous coronary intervention. In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, eptifibatide during coronary intervention was associated with decreased ischemic complications at 48 h and 30 days. Patients (n = 2,064) were randomized to placebo versus eptifibatide (two 180 microg/kg boluses 10 min apart and as a continuous infusion of 2 microg/kg per min) during percutaneous coronary stenting. Angiographic complications including major dissection, distal embolization, residual thrombus, abrupt closure, residual stenosis &amp;amp;gt;50% and side-branch occlusion were prospectively recorded by the operator. Creatine kinase-MB levels were measured after the procedure and every 6 h thereafter. The incidence of angiographic complications and CK-MB elevation was determined for eptifibatide versus placebo groups. Eptifibatide-treated patients demonstrated nonsignificant trends toward fewer angiographic complications (10 vs. 12% for placebo patients, p = 0.13) and, for patients with angiographic complications, fewer subsequent CK-MB elevations (43 vs. 50% for placebo patients, p = 0.31). In patients without any angiographic complications, the incidence of CK-MB elevation &amp;amp;gt;3 times the normal was 7% with placebo and 4% with eptifibatide (p = 0.003). Eptifibatide during nonurgent coronary stent intervention only minimally (and insignificantly) reduces the incidence of angiographic complications and subsequent CK-MB elevations in patients developing an angiographic complication. The greater effect is to reduce myocardial infarction in patients undergoing otherwise uneventful coronary stent implantation as well as in the overall study population.
Journal of the American College of Cardiology, 2004
Background: Cardiac rupture is responsible for about 15% of all in-hospital deaths among patients... more Background: Cardiac rupture is responsible for about 15% of all in-hospital deaths among patients with acute myocardial infarction (AMI). However, information regarding the clinical profile and pathological features of this fatal complication is limited. Methods: We studied 53 consecutive patients with AMI (M/F; 32/21, age; 73±7 [mean±SD] years), who died of ventricular septal and free wall rupture between 1978 and 2002. The diagnosis was made based on postmortem histological examination. Fortytwo patients (80%) were without previous infarction and 44 patients (84%) were hypertensive. Results: Cardiac rupture occurred acutely within 48 hours of AMI onset in 20 patients (38%). Also, it occurred 6-8 days after the onset of AMI in 17 patients (32%), in whom immunohistochemical studies revealed accumulation of inflammatory cells and activation of matrix metalloproteinases at the rupture site. AMI-related artery was the left anterior descending artery in 37 patients (70%), the right coronary artery in 13 patients (25%) and the left circumflex artery in 3 patients (5%). In most patients (n=48, 91%), the AMIrelated vessel was totally or subtotally occluded. Since 1993, the era in which the reperfusion therapy has been developed, the total number of rupture patients has been decreasing, but the percentage of those with hemorrhagic infarction has been increasing; 1978-82, n=12 (17%); 1983-87, n=14 (29%); 1988-92, n=14 (36%); 1993-97, n=7 (57%); 1998-2002, n=6 (50%). Conclusions: These findings indicate the potential importance of revascularization of the AMI-related artery to reduce the risk of cardiac rupture. Histologically, sustained inflammatory responses with metalloprotease activation may contribute to modulating the wound-healing process following infarction.
In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiv... more In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was no difference in days alive and out of the hospital for patients with decompensated heart failure randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial patients, whereas measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs 6 days, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and higher 6-month mortality (34% vs 20%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) than trial patients. The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials.
Background: Previous reports using invasive techniques like the pulmonary artery catheter and the... more Background: Previous reports using invasive techniques like the pulmonary artery catheter and the Implantable Hemodynamic Monitor have established the superiority of invasive management over clinical assessment for the detection of rising filling pressures and prevention of resultant hospitalizations in patients with advanced heart failure (HF). To examine this issue in patients with mild to moderate HF, we employed a previously validated noninvasive technology (VeriCor Ò ), which measures left ventricular end-diastolic pressure (LVEDP) by an analysis of the arterial waveform during the expiratory strain phase of a valsalva maneuver. Methods: Clinical assessment (history and physical findings) was documented in 77 ambulatory patients with mild to moderate (NYHA class I-III) HF who presented to the HF clinic at VA Boston Healthcare System. This was followed by VeriCor testing to measure the LVEDP. All patients were managed on a standard HF regimen without the knowledge of the LVEDP readings and were followed by the same clinical providers. After a 12 month follow-up, clinical information and rate of hospitalization were examined. Results: Patients with an LVEDP # 20 mmHg were considered to be adequately managed (Group I), while those with LVEDPs O 20 mmHg were considered to be sub-optimally treated (Group II). The distributions of age, race, etiology of HF and left ventricular ejection fraction were not significantly different in the two groups. Both groups were treated with comparable standard HF regimens. Of the 77 patients deemed adequately treated by clinical assessment alone, a significant number (61%, p ! 0.01) were noted to have LVEDP O 20 mmHg (21e35 mmHg, mean 25.7 þ/À 3.6mmHg). Of the 19 reported hospitalizations during follow-up, 18 (95%, P ! 0.0001) were in Group II (LVEDP O 20mmHg). Conclusions: a) Clinical assessment failed to recognize high LVEDP levels (21 to 35 mmHg) that put HF patients at increased risk of hospitalization (18-times higher than in patients with LVEDPs ! 20mmHg). b) By accurately identifying LVEDP levels and guiding HF treatment, non-invasive hemodynamic monitoring using the VeriCor technology may reduce hospitalizations and related costs.
Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). Th... more Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). This study assessed whether rapid-assay B-type natriuretic peptide (BNP) and troponin I predicts length of stay and mortality and correlates with pulmonary artery catheter (PAC)-derived hemodynamics in patients hospitalized with acute HF. There were 141 nonconsecutive patients in this prospective cohort study of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), a randomized trial testing PACs in 433 patients with severe decompensated HF. Biomarkers were drawn at baseline and discharge and when the first, second, and final hemodynamics were obtained in 69 patients randomly assigned to PACs. Cox analysis was used to model mortality, length of stay, and rehospitalization, and Pearson's correlations were used to describe the relation among BNP, troponin I, and PAC-derived hemodynamics. The median (25th percentile, 75th percentile) BNP levels were 783 pg/ml (329, 1,565) at baseline and 468 pg/ml (240, 946) at discharge. After treatment for HF, the median BNP level decreased by 144 pg/ml (؊653, 55; p ؍ 0.004). Patients with baseline BNP levels >1,500 pg/ml had greater mortality at 6 months and almost twice the length of stay as patients with BNP levels <500 pg/ml (10.1 vs 5.7 days, p ؍ 0.002). Troponin I did not predict these outcomes. First BNP correlated modestly with first right atrial pressure (r ؍ 0.47, p ؍ 0.005) and first pulmonary capillary wedge pressure (r ؍ 0.54, p ؍ 0.001). Final BNP correlated modestly with final right atrial pressure (r ؍ 0.63, p ؍ 0.001). In conclusion, patients with BNP >1,500 pg/ml had greater mortality and longer length of stay than patients with BNP <500 pg/ml. BNP decreased after hospitalization, but correlated modestly with PAC-derived hemodynamics. Rapid-assay BNP may provide information that helps physicians decide when to pursue more aggressive and invasive therapies.
The association of weight loss achieved through various decongestive strategies with clinical out... more The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.
Little is known about the prognostic value of leukocyte count on admission for patients with ches... more Little is known about the prognostic value of leukocyte count on admission for patients with chest pain. In total, 1,461 patients who presented to the emergency department with non-ST-segment elevation chest pain were studied by clinical history, electrocardiography, serial troponin I determination, and leukocyte count on admission. End points were 1-year mortality and major events (mortality or infarction). Overall patient distribution by quartiles of leukocyte count showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for other risk factors, the fourth quartile cut-off value (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml) predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p = 0.0001) but not major events (p = 0.07). When analysis was performed to assess troponin status, in the subgroup with increased troponin (n = 634, 16% mortality), a leukocyte count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml was related to mortality (hazard ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no differences in mortality between patients with or without a leukocyte count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight overlap (p = 0.9). Further, in the subgroup with normal troponin levels, leukocyte count was not significantly different between patients with or without ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not associated with mortality in patients with ST depression (p = 0.7). In conclusion, leukocyte count on admission is predictive of mortality in patients with chest pain and non-ST-segment elevation myocardial infarction. However, in the absence of myocardial necrosis, leukocyte count lacks prognostic value.
Background Treatment of decompensated heart failure often includes the use of intravenous vasoact... more Background Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined.
for the ESCAPE Investigators Stanford and San Francisco, CA; Durham, NC; and Atlanta, GA Backgrou... more for the ESCAPE Investigators Stanford and San Francisco, CA; Durham, NC; and Atlanta, GA Background Pulmonary hypertension has been shown to predict hospitalizations and mortality in patients with heart failure. We aimed to define the prevalence of mixed pulmonary hypertension (MPH; mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure N15 mm Hg, and pulmonary vascular resistance ≥3 Wood units), identify clinical predictors of MPH, and determine whether MPH predicts adverse outcomes in patients hospitalized with severe heart failure.
Background Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hos... more Background Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hospitalized for decompensated heart failure (HF). We assessed whether elevated TnT levels are associated with the severity, etiology, and prognosis of HF in stable, ambulatory patients.
Stroke is a rare but serious event that complicates the course of patients with acute coronary sy... more Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.
Journal of the American College of Cardiology, 2010
Category: Cardiomyopathies/Myocarditis/Pericardial Disease Background: Hemodynamic assessment can... more Category: Cardiomyopathies/Myocarditis/Pericardial Disease Background: Hemodynamic assessment can be particularly challenging in overweight and obese patients with heart failure as the physical exam often limits the ability to assess filling pressures. This presents a need for a non-invasive test such as serum BNP to assist in hemodynamic evaluation. We compared the relationship between BNP levels and PCWP in lean, overweight, and obese patients.
Background-Impedance cardiography (ICG) is a noninvasive modality that utilizes changes in impeda... more Background-Impedance cardiography (ICG) is a noninvasive modality that utilizes changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure (HF) is uncertain.
Journal of the American College of Cardiology, Mar 1, 2010
Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective ... more Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. The ESCAPE Risk Model and Discharge Score Key Words: heart failure y risk stratification y discharge risk model.
Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure.... more Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure <or=15 and right atrial pressure <or=8 mm Hg. Patients were randomized to PAC or CLIN during hospitalization with chronic heart failure and mean left ventricular ejection fraction 20%, and at least 1 symptom and 1 sign of congestion. MR and mitral flow patterns, measured blinded to therapy and timepoint, were available at baseline and discharge in 133 patients, and at 3 months in 104 patients. Changes in MR and related transmitral flow patterns were compared between PAC and CLIN patients. Jugular venous pressure, edema, and weights decreased similarly during therapy in the hospital for both groups. In PAC but not in CL...
Journal of the American College of Cardiology, 2010
Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective ... more Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. The ESCAPE Risk Model and Discharge Score Key Words: heart failure y risk stratification y discharge risk model.
Journal of the American College of Cardiology, 2001
We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic... more We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic complications and to determine the relationship of angiographically evident complications to elevations of creatine kinase-MB (CK-MB) enzyme levels during percutaneous coronary intervention. In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, eptifibatide during coronary intervention was associated with decreased ischemic complications at 48 h and 30 days. Patients (n = 2,064) were randomized to placebo versus eptifibatide (two 180 microg/kg boluses 10 min apart and as a continuous infusion of 2 microg/kg per min) during percutaneous coronary stenting. Angiographic complications including major dissection, distal embolization, residual thrombus, abrupt closure, residual stenosis &amp;amp;gt;50% and side-branch occlusion were prospectively recorded by the operator. Creatine kinase-MB levels were measured after the procedure and every 6 h thereafter. The incidence of angiographic complications and CK-MB elevation was determined for eptifibatide versus placebo groups. Eptifibatide-treated patients demonstrated nonsignificant trends toward fewer angiographic complications (10 vs. 12% for placebo patients, p = 0.13) and, for patients with angiographic complications, fewer subsequent CK-MB elevations (43 vs. 50% for placebo patients, p = 0.31). In patients without any angiographic complications, the incidence of CK-MB elevation &amp;amp;gt;3 times the normal was 7% with placebo and 4% with eptifibatide (p = 0.003). Eptifibatide during nonurgent coronary stent intervention only minimally (and insignificantly) reduces the incidence of angiographic complications and subsequent CK-MB elevations in patients developing an angiographic complication. The greater effect is to reduce myocardial infarction in patients undergoing otherwise uneventful coronary stent implantation as well as in the overall study population.
Journal of the American College of Cardiology, 2004
Background: Cardiac rupture is responsible for about 15% of all in-hospital deaths among patients... more Background: Cardiac rupture is responsible for about 15% of all in-hospital deaths among patients with acute myocardial infarction (AMI). However, information regarding the clinical profile and pathological features of this fatal complication is limited. Methods: We studied 53 consecutive patients with AMI (M/F; 32/21, age; 73±7 [mean±SD] years), who died of ventricular septal and free wall rupture between 1978 and 2002. The diagnosis was made based on postmortem histological examination. Fortytwo patients (80%) were without previous infarction and 44 patients (84%) were hypertensive. Results: Cardiac rupture occurred acutely within 48 hours of AMI onset in 20 patients (38%). Also, it occurred 6-8 days after the onset of AMI in 17 patients (32%), in whom immunohistochemical studies revealed accumulation of inflammatory cells and activation of matrix metalloproteinases at the rupture site. AMI-related artery was the left anterior descending artery in 37 patients (70%), the right coronary artery in 13 patients (25%) and the left circumflex artery in 3 patients (5%). In most patients (n=48, 91%), the AMIrelated vessel was totally or subtotally occluded. Since 1993, the era in which the reperfusion therapy has been developed, the total number of rupture patients has been decreasing, but the percentage of those with hemorrhagic infarction has been increasing; 1978-82, n=12 (17%); 1983-87, n=14 (29%); 1988-92, n=14 (36%); 1993-97, n=7 (57%); 1998-2002, n=6 (50%). Conclusions: These findings indicate the potential importance of revascularization of the AMI-related artery to reduce the risk of cardiac rupture. Histologically, sustained inflammatory responses with metalloprotease activation may contribute to modulating the wound-healing process following infarction.
In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiv... more In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), there was no difference in days alive and out of the hospital for patients with decompensated heart failure randomly assigned to therapy guided by pulmonary artery catheter (PAC) plus clinical assessment versus clinical assessment alone. The external validity of these findings is debated. ESCAPE sites enrolled 439 patients receiving PAC without randomization in a prospective registry. Baseline characteristics, pertinent trial exclusion criteria, reasons for PAC use, hemodynamics, and complications were collected. Survival was determined from the National Death Index and the Alberta Registry. On average, registry patients had lower blood pressure, worse renal function, less neurohormonal antagonist therapy, and higher use of intravenous inotropes compared with trial patients. Although clinical assessment anticipated less volume overload and greater hypoperfusion among the registry population, measured filling pressures were similarly elevated in the registry and trial patients, whereas measured perfusion was slightly higher among registry patients. Registry patients had longer hospitalization (13 vs 6 days, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and higher 6-month mortality (34% vs 20%, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) than trial patients. The decision to use PAC without randomization identified a population with higher disease severity and risk of mortality. This prospective registry highlights the complex context of patient selection for randomized trials.
Background: Previous reports using invasive techniques like the pulmonary artery catheter and the... more Background: Previous reports using invasive techniques like the pulmonary artery catheter and the Implantable Hemodynamic Monitor have established the superiority of invasive management over clinical assessment for the detection of rising filling pressures and prevention of resultant hospitalizations in patients with advanced heart failure (HF). To examine this issue in patients with mild to moderate HF, we employed a previously validated noninvasive technology (VeriCor Ò ), which measures left ventricular end-diastolic pressure (LVEDP) by an analysis of the arterial waveform during the expiratory strain phase of a valsalva maneuver. Methods: Clinical assessment (history and physical findings) was documented in 77 ambulatory patients with mild to moderate (NYHA class I-III) HF who presented to the HF clinic at VA Boston Healthcare System. This was followed by VeriCor testing to measure the LVEDP. All patients were managed on a standard HF regimen without the knowledge of the LVEDP readings and were followed by the same clinical providers. After a 12 month follow-up, clinical information and rate of hospitalization were examined. Results: Patients with an LVEDP # 20 mmHg were considered to be adequately managed (Group I), while those with LVEDPs O 20 mmHg were considered to be sub-optimally treated (Group II). The distributions of age, race, etiology of HF and left ventricular ejection fraction were not significantly different in the two groups. Both groups were treated with comparable standard HF regimens. Of the 77 patients deemed adequately treated by clinical assessment alone, a significant number (61%, p ! 0.01) were noted to have LVEDP O 20 mmHg (21e35 mmHg, mean 25.7 þ/À 3.6mmHg). Of the 19 reported hospitalizations during follow-up, 18 (95%, P ! 0.0001) were in Group II (LVEDP O 20mmHg). Conclusions: a) Clinical assessment failed to recognize high LVEDP levels (21 to 35 mmHg) that put HF patients at increased risk of hospitalization (18-times higher than in patients with LVEDPs ! 20mmHg). b) By accurately identifying LVEDP levels and guiding HF treatment, non-invasive hemodynamic monitoring using the VeriCor technology may reduce hospitalizations and related costs.
Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). Th... more Rapid-assay biomarkers may predict outcomes in patients with decompensated heart failure (HF). This study assessed whether rapid-assay B-type natriuretic peptide (BNP) and troponin I predicts length of stay and mortality and correlates with pulmonary artery catheter (PAC)-derived hemodynamics in patients hospitalized with acute HF. There were 141 nonconsecutive patients in this prospective cohort study of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE), a randomized trial testing PACs in 433 patients with severe decompensated HF. Biomarkers were drawn at baseline and discharge and when the first, second, and final hemodynamics were obtained in 69 patients randomly assigned to PACs. Cox analysis was used to model mortality, length of stay, and rehospitalization, and Pearson's correlations were used to describe the relation among BNP, troponin I, and PAC-derived hemodynamics. The median (25th percentile, 75th percentile) BNP levels were 783 pg/ml (329, 1,565) at baseline and 468 pg/ml (240, 946) at discharge. After treatment for HF, the median BNP level decreased by 144 pg/ml (؊653, 55; p ؍ 0.004). Patients with baseline BNP levels >1,500 pg/ml had greater mortality at 6 months and almost twice the length of stay as patients with BNP levels <500 pg/ml (10.1 vs 5.7 days, p ؍ 0.002). Troponin I did not predict these outcomes. First BNP correlated modestly with first right atrial pressure (r ؍ 0.47, p ؍ 0.005) and first pulmonary capillary wedge pressure (r ؍ 0.54, p ؍ 0.001). Final BNP correlated modestly with final right atrial pressure (r ؍ 0.63, p ؍ 0.001). In conclusion, patients with BNP >1,500 pg/ml had greater mortality and longer length of stay than patients with BNP <500 pg/ml. BNP decreased after hospitalization, but correlated modestly with PAC-derived hemodynamics. Rapid-assay BNP may provide information that helps physicians decide when to pursue more aggressive and invasive therapies.
The association of weight loss achieved through various decongestive strategies with clinical out... more The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.
Little is known about the prognostic value of leukocyte count on admission for patients with ches... more Little is known about the prognostic value of leukocyte count on admission for patients with chest pain. In total, 1,461 patients who presented to the emergency department with non-ST-segment elevation chest pain were studied by clinical history, electrocardiography, serial troponin I determination, and leukocyte count on admission. End points were 1-year mortality and major events (mortality or infarction). Overall patient distribution by quartiles of leukocyte count showed increased mortality (6%, 7%, 6%, and 17%, p = 0.0001) and major events (13%, 13%, 15%, and 24%, p = 0.0001) in the fourth quartile. After adjustment for other risk factors, the fourth quartile cut-off value (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml) predicted mortality (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p = 0.0001) but not major events (p = 0.07). When analysis was performed to assess troponin status, in the subgroup with increased troponin (n = 634, 16% mortality), a leukocyte count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml was related to mortality (hazard ratio 2.2, 95% confidence interval 1.5 to 3.4, p = 0.0001). However, in the subgroup with normal troponin levels (n = 827, 4.2% mortality), there were no differences in mortality between patients with or without a leukocyte count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10,000 cells/ml (4.4% vs 4.2%, p = 0.8), with survival curves showing a tight overlap (p = 0.9). Further, in the subgroup with normal troponin levels, leukocyte count was not significantly different between patients with or without ST depression (7,969 +/- 2,171 vs 8,108 +/- 2,356 cells/ml, p = 0.6) and was not associated with mortality in patients with ST depression (p = 0.7). In conclusion, leukocyte count on admission is predictive of mortality in patients with chest pain and non-ST-segment elevation myocardial infarction. However, in the absence of myocardial necrosis, leukocyte count lacks prognostic value.
Background Treatment of decompensated heart failure often includes the use of intravenous vasoact... more Background Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined.
for the ESCAPE Investigators Stanford and San Francisco, CA; Durham, NC; and Atlanta, GA Backgrou... more for the ESCAPE Investigators Stanford and San Francisco, CA; Durham, NC; and Atlanta, GA Background Pulmonary hypertension has been shown to predict hospitalizations and mortality in patients with heart failure. We aimed to define the prevalence of mixed pulmonary hypertension (MPH; mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure N15 mm Hg, and pulmonary vascular resistance ≥3 Wood units), identify clinical predictors of MPH, and determine whether MPH predicts adverse outcomes in patients hospitalized with severe heart failure.
Background Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hos... more Background Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hospitalized for decompensated heart failure (HF). We assessed whether elevated TnT levels are associated with the severity, etiology, and prognosis of HF in stable, ambulatory patients.
Stroke is a rare but serious event that complicates the course of patients with acute coronary sy... more Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.
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