The impact of arrhythmias in acute heart failure.

BACKGROUND: Arrhythmias are common in chronic heart failure and affect outcomes. The incidence and significance of new arrhythmias in acute heart failure, however, are largely unknown. METHODS AND RESULTS: The Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations study randomized 949 patients with decompensated heart failure to receive intravenous milrinone or placebo. In the study, patients were divided into 2 groups based on the occurrence of a new arrhythmic event during their index hospitalization and analyzed for outcome. There were 59 new arrhythmic events occurring in 6% of the population. Of these, 49% were atrial fibrillation/flutter. The primary endpoint of days hospitalized for cardiovascular causes within 60 days after randomization was 30.9+/-22.7 for those in the arrhythmia group and 11.3+/-12.7 days for those with no arrhythmias (P=.0001). Mortality during index hospitalization was 26% in the arrhythmia group and 1.8% in the no arrhythmia group (P=.001). Death or hospitalization at 60 days was also worse in the arrhythmia group (35 versus 8.2%, P=.0001; 57 versus 34%, P=.001, respectively). Cox proportional hazard analysis identified new arrhythmias as an independent risk factor for the primary endpoint and death at 60 days. CONCLUSION: New arrhythmia during an exacerbation of heart failure identifies a high-risk group with higher intrahospital and 60-day morbidity and mortality.

Use of bedside activated partial thromboplastin time monitor to adjust heparin dosing after thrombolysis for acute myocardial infarction: results of GUSTO-I. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

BACKGROUND: The safety and efficacy of bedside monitors of activated partial thromboplastin time (aPTT) have not been examined in a large population receiving intravenous heparin after thrombolytic treatment for acute myocardial infarction. We compared outcomes among patients monitored with these devices versus standard monitoring methods. METHODS AND RESULTS: Investigators chose the bedside device (n = 1713 patients) or their standard method (n = 26,162) for all aPTT measurements at their sites. Clinical outcomes at 30 days, 1-year mortality rate, and aPTT levels at 6, 12, and 24 hours were compared. Bedside-monitored patients had significantly less moderate/severe bleeding (10% vs 12%, P < .01), fewer transfusions (7% vs 11%, P < .001), and a smaller decrease in hematocrit (5.5% vs 6.7%, P < .001) but significantly more recurrent ischemia (22% vs 20%, P = .01). Fewer bedside-monitored patients had subtherapeutic aPTT levels at 12 and 24 hours. Among patients with subtherapeutic levels at 6 and 12 hours, more bedside-monitored patients had therapeutic levels when next monitored. After adjustment for baseline differences, no significant difference in mortality rate was observed in bedside-monitored patients at 30 days (4.3% vs 4.8%, P = .27) and at 1 year (7.1% vs 7.7%, P = .38). The groups had similar rates of reinfarction, shock, heart failure, and stroke. CONCLUSIONS: This prospective substudy supports the use of bedside monitoring of heparin anticoagulation after thrombolysis.

Prognostic significance of the initial electrocardiogram in patients with acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

CONTEXT: Early risk stratification of patients with myocardial infarction is critical to determine optimum treatment strategies and enhance outcomes, but knowledge of the prognostic importance of the initial electrocardiogram (ECG) is limited. OBJECTIVE: To assess the independent value of the initial ECG for short-term risk stratification after acute myocardial infarction. DESIGN: Retrospective analysis of the Global Utilization of Streptokinase and t-PA (alteplase) for Occluded Coronary Arteries (GUSTO-I) clinical trial database. SETTING: A total of 1081 hospitals in 15 countries. PATIENTS: From the 41 021 patients enrolled in the overall study, we selected those who presented within 6 hours of chest pain onset with ST-segment elevation and no confounding factors (paced rhythms, ventricular rhythms, or left bundle-branch block) on the ECG performed before thrombolysis was administered (n=34 166). MAIN OUTCOME MEASURE: Ability of initial ECG to predict all-cause mortality at 30 days. RESULTS: Most ECG variables were associated with 30-day mortality in a univariable analysis. In a multivariable analysis combining the initial ECG variables and clinical predictors of mortality, the sum of the absolute ST-segment deviation (both ST elevation and ST depression: odds ratio [OR], 1.53; 95% confidence interval [CI], 1.38-1.69), ECG, heart rate (OR, 1.49; 95% CI, 1.41-1.59), QRS duration (for anterior infarct: OR, 1.55; 95% CI, 1.43-1.68), and ECG evidence of prior infarction (for new inferior infarct: OR, 2.47; 95% CI, 2.02-3.00) were the strongest ECG predictors of mortality. A nomogram based on the multivariable model produced excellent discrimination of 30-day mortality (C-index, 0.830). CONCLUSIONS: In patients presenting with myocardial infarction accompanied by ST-segment elevation, components of the initial ECG help predict 30-day mortality. This information should be valuable in early risk stratification, when the opportunity to reduce mortality is greatest, and may help in assessing outcomes adjusted for patient risk.

Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.

We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.

Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: results in 16,521 patients.

OBJECTIVES: We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. BACKGROUND: Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately quantified, partly because of small sample sizes and methodologic limitations in previous studies. METHODS: We examined the clinical and angiographic outcomes of 16,521 patients with an acute inferior myocardial infarction who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) study. Patients were classified into those without precordial ST segment depression (n = 6,422 [38.9%]), those with ST segment depression in leads V1 to V3 only (n = 5,850 [35.4%]), those with ST segment depression in leads V4 to V6 only (n = 876 [5.3%]) and those with ST segment depression in both leads V1 to V3 and leads V4 to V6 (n = 3,373 [20.4%]) on initial electrocardiography. Outcome measures included postinfarction complications (second- or third-degree heart block, congestive heart failure or shock) and 30-day and 1-year mortality. RESULTS: Patients with precordial ST segment depression had larger infarctions, more postinfarction complications and a higher mortality rate than those without precordial ST segment depression (4.7% vs. 3.2% at 30 days; 5.0% vs. 3.4% at 1 year; both p < 0.001), regardless of whether ST segment depression was noted in leads V1 to V6 or in leads V4 to V6. The magnitude of precordial ST segment depression (sum of leads V1 to V6) added significant independent prognostic information after adjustment for clinical risk factors; the risk of 30-day mortality increased by 36% for every 0.5 mV of precordial ST segment depression. CONCLUSIONS: Assessment of the magnitude of precordial ST segment depression is useful for acute risk stratification in patients with an inferior myocardial infarction.

Gas chromatographic determination of methamphetamine and its metabolite amphetamine in human plasma and urine following conversion to N-propyl derivatives.

A gas chromatographic method for the simultaneous determination of methamphetamine and its metabolite amphetamine in human plasma and urine is described. The method utilizes reductive alkylation with propionaldehyde and sodium borohydride to produce N-propyl derivatives, which have excellent chromatographic properties. Structural analogs of the analytes, p-methylmethamphetamine and p-methylamphetamine, are used as internal standards. The method has good precision and accuracy for concentrations ranging from less than 10 ng/ml to 5000 ng/ml and has been used to measure plasma concentrations as part of a pharmacokinetic/pharmacodynamic study of methamphetamine in humans.

Depressive Disorder in Older Medical Inpatients on General Medicine and Cardiology Services at a University Teaching Hospital.

The authors examined the prevalence, characteristics, and correlates of depressive disorder among medical inpatients age 60 or over at a private teaching hospital. Seventy-six of 129 patients admitted to the general medicine and cardiology services at Duke University Hospital were screened for depressive disorder using DSM-III-R criteria. Depressive disorders were diagnosed in 34.2% of patients: major depression in 13.2%, adjustment disorder in 11.8%, depression not otherwise specified in 5.3%, organic mood disorder in 1.3%, and uncomplicated bereavement in 2.6%. Of patients with major depression, all had symptoms of mild-to-moderate severity. The most common presenting symptoms were insomnia, psychomotor agitation, difficulty concentrating, and loss of energy. Depression was more prevalent among women, general medicine patients, staff (vs. private) patients, and those who were functionally disabled or had multiple serious medical conditions. When other patient characteristics were controlled, however, only health factors were independently associated with depression.

"Paralogs", sorbent families for protein separations.

Novel peptide-based (paralog) sorbents are evaluated with respect to performance, reproducibility and reusability in a 96-well test plate screening format, and to utility in protein separations. The results demonstrate that this approach to constructing sorbents provides a new and generally applicable set of tools for separating proteins.

Thyroglobulin structure-function: the effect of iodination on the structure of human thyroglobulin.

Thyroglobulin of very low iodine content has been prepared from a single non-toxic human goitre. The initial iodine content of the protein (0.038%) has been increased to levels of 0.16% and 0.85% by in vitro treatment with thyroid peroxidase and the resulting proteins studied with respect to their intrinsic fluorescence, circular dichroism spectra and binding of the hydrophobic probe 1,8-anilinonaphthalene sulfonic acid (ANS). While significant differences were observed between levels of iodination in both the ANS binding and intrinsic fluorescence of the thyroglobulin, no significant differences in the near and far UV circular dichroism spectra of the protein as a function of iodine content were observed. These data suggest that, the iodination of thyroglobulin effects specific areas of the protein without significant disruption of its overall secondary structure.