Richard Nowak

Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea: Results From the BACH (Biomarkers in Acute Heart Failure) Trial

OBJECTIVES Our purpose was to assess the diagnostic utility of mid-regional pro-atrial natriuretic peptide (MR-proANP) for the diagnosis of acute heart failure (AHF) and the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with AHF. BACKGROUND There are some caveats and limitations to natriuretic peptide testing in the acute dyspneic patient. METHODS The BACH (Biomarkers in Acute Heart Failure) trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. A noninferiority test of MR-proANP versus B-type natriuretic peptide (BNP) for diagnosis of AHF and a superiority test of MR-proADM versus BNP for 90-day survival were conducted. Other end points were exploratory. RESULTS MR-proANP (> or =120 pmol/l) proved noninferior to BNP (> or =100 pg/ml) for the diagnosis of AHF (accuracy difference 0.9%). In tests of secondary diagnostic objectives, MR-proANP levels added to the utility of BNP levels in patients with intermediate BNP values and with obesity but not in renal insufficiency, the elderly, or patients with edema. Using cut-off values from receiver-operating characteristic analysis, the accuracy to predict 90-day survival of heart failure patients was 73% (95% confidence interval: 70% to 77%) for MR-proADM and 62% (95% confidence interval: 58% to 66%) for BNP (difference p < 0.001). In adjusted multivariable Cox regression, MR-proADM, but not BNP, carried independent prognostic value (p < 0.001). Results were consistent using NT-proBNP instead of BNP (p < 0.001). None of the biomarkers was able to predict rehospitalization or visits to the emergency department with clinical relevance. CONCLUSIONS MR-proANP is as useful as BNP for AHF diagnosis in dyspneic patients and may provide additional clinical utility when BNP is difficult to interpret. MR-proADM identifies patients with high 90-day mortality risk and adds prognostic value to BNP. (Biomarkers in Acute Heart Failure [BACH]; NCT00537628).

A comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department.

STUDY OBJECTIVE Shock index (SI) (heart rate/systolic blood pressure; normal range, 0.5 to 0.7) and conventional vital signs were compared to identify acute critical illness in the emergency department. DESIGN Quasi-prospective study. PATIENTS Two hundred seventy-five consecutive adults who presented for urgent medical care. INTERVENTIONS Patients had vital signs, SI, and triage priority recorded on arrival in the ED and then their final disposition. RESULTS Two groups were identified retrospectively by the SI; group 1 (41) had an SI of more than 0.9, and group 2 (234) had an SI of less than 0.9 on arrival in the ED. Although both groups had apparently stable vital signs on arrival, group 1 had a significantly higher proportion of patients who were triaged to a priority requiring immediate treatment (23 versus 45; P < .01) and required admission to the hospital (35 versus 105; P < .01) and continued therapy in an ICU (10 versus 13; P < .01). CONCLUSION With apparently stable vital signs, an abnormal elevation of the SI to more than 0.9 was associated with an illness that was treated immediately, admission to the hospital, and intensive therapy on admission. The SI may be useful to evaluate acute critical illness in the ED.

Diagnosis of Acute Aortic Dissection by D-Dimer. The International Registry of Acute Aortic Dissection Substudy on Biomarkers (IRAD-Bio) Experience

Background— D-dimer has been reported to be elevated in acute aortic dissection. Potential use as a “rule-out” marker has been suggested, but concerns remain given that it is elevated in other acute chest diseases, including pulmonary embolism and ischemic heart disease. We evaluated the diagnostic performance of D-dimer testing in a study population of patients with suspected aortic dissection. Methods and Results— In this prospective multicenter study, 220 patients with initial suspicion of having acute aortic dissection were enrolled, of whom 87 were diagnosed with acute aortic dissection and 133 with other final diagnoses, including myocardial infarction, angina, pulmonary embolism, and other uncertain diagnoses. D-dimer was markedly elevated in patients with acute aortic dissection. Analysis according to control disease, type of dissection, and time course showed that the widely used cutoff level of 500 ng/mL for ruling out pulmonary embolism also can reliably rule out aortic dissection, with a negative likelihood ratio of 0.07 throughout the first 24 hours. Conclusion— D-dimer levels may be useful in risk stratifying patients with suspected aortic dissection to rule out aortic dissection if used within the first 24 hours after symptom onset.

Increased 90-Day Mortality in Patients With Acute Heart Failure With Elevated Copeptin Secondary Results From the Biomarkers in Acute Heart Failure (BACH) Study

Background— In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results— The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality ( P <0.001; hazard ratio, 3.85). Mortality was significantly increased in patients with elevated copeptin and hyponatremia ( P <0.001; hazard ratio, 7.36). Combined end points of mortality, readmissions, and emergency department visits were significantly increased in patients with elevated copeptin. There was no correlation between copeptin and sodium ( r =0.047). Conclusions— This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration— URL: . Unique identifier: [NCT00537628][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00537628&atom=%2Fcirchf%2F4%2F5%2F613.atomBackground— In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results— The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality (P<0.001; hazard ratio, 3.85). Mortality was significantly increased in patients with elevated copeptin and hyponatremia (P<0.001; hazard ratio, 7.36). Combined end points of mortality, readmissions, and emergency department visits were significantly increased in patients with elevated copeptin. There was no correlation between copeptin and sodium (r=0.047). Conclusions— This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00537628.

Ballistics: a pathophysiologic examination of the wounding mechanisms of firearms: Part II

Wounds caused by firearms are a frequent occurrence in urban emergency centers. Understanding of the underlying pathophysiologic mechanisms involved in wound production is very important in treatment of these injuries. Part I of this article reports studies on the interaction of projectiles with both the atmosphere and human tissue to produce wounds. Part II will examine the types of wounds formed by specific firearms, and the recent innovations in both weapons and ammunition which are altering the severity of shooting injuries.

Increased 90-Day Mortality in Patients With Acute Heart Failure With Elevated CopeptinClinical Perspective

Background— In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results— The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality ( P <0.001; hazard ratio, 3.85). Mortality was significantly increased in patients with elevated copeptin and hyponatremia ( P <0.001; hazard ratio, 7.36). Combined end points of mortality, readmissions, and emergency department visits were significantly increased in patients with elevated copeptin. There was no correlation between copeptin and sodium ( r =0.047). Conclusions— This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration— URL: . Unique identifier: [NCT00537628][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00537628&atom=%2Fcirchf%2F4%2F5%2F613.atomBackground— In patients with heart failure (HF), increased arginine vasopressin concentrations are associated with more severe disease, making arginine vasopressin an attractive target for therapy. However, AVP is difficult to measure due to its in vitro instability and rapid clearance. Copeptin, the C-terminal segment of preprovasopressin, is a stable and reliable surrogate biomarker for serum arginine vasopressin concentrations. Methods and Results— The Biomarkers in Acute Heart Failure (BACH) trial was a 15-center, diagnostic and prognostic study of 1641 patients with acute dyspnea; 557 patients with acute HF were included in this analysis. Copeptin and other biomarker measurements were performed by a core laboratory at the University of Maryland. Patients were followed for up to 90 days after initial evaluation for the primary end point of all-cause mortality, HF-related readmissions, and HF-related emergency department visits. Patients with copeptin concentrations in the highest quartile had increased 90-day mortality (P<0.001; hazard ratio, 3.85). Mortality was significantly increased in patients with elevated copeptin and hyponatremia (P<0.001; hazard ratio, 7.36). Combined end points of mortality, readmissions, and emergency department visits were significantly increased in patients with elevated copeptin. There was no correlation between copeptin and sodium (r=0.047). Conclusions— This study showed significantly increased 90-day mortality, readmissions, and emergency department visits in patients with elevated copeptin, especially in those with hyponatremia. Copeptin was highly prognostic for 90-day adverse events in patients with acute HF, adding prognostic value to clinical predictors, ser um sodium, and natriuretic peptides. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00537628.

Response of patients with refractory myasthenia gravis to rituximab: a retrospective study

Introduction: Myasthenia gravis, an autoimmune disorder of neuromuscular transmission, is treated by an array of immunomodulating therapies. A variable response is observed with certain patients being medically refractory. Methods: We report the results of 14 refractory generalized myasthenia gravis patients (6 AChR+; 8 MuSK+) treated with rituximab. Results: Sustained clinical improvement was observed in all patients as well as a reduction of conventional immunotherapies. Prednisone dose decreased a mean of 65.1%, 85.7%, and 93.8% after cycle 1, 2, and 3 of rituximab therapy, respectively. A statistically significant reduction in plasma exchange sessions was seen after cycle 1 with all patients being off of plasma exchange after cycle 3. Acetylcholine receptor antibody titers decreased a mean of 52.1% (p = 0.0046) post-cycle 2. Conclusion: Our results support the hypothesis that rituximab is beneficial and well tolerated in managing refractory myasthenia gravis and nearly doubles published cases. We propose that B-cell-directed therapies may become an attractive option and suggest pursuit of a prospective trial.

Identifying Patients for Early Discharge: Performance of Decision Rules Among Patients with Acute Chest Pain

BACKGROUND The HEART score and North American Chest Pain Rule (NACPR) are decision rules designed to identify acute chest pain patients for early discharge without stress testing or cardiac imaging. This study compares the clinical utility of these decision rules combined with serial troponin determinations. METHODS AND RESULTS A secondary analysis was conducted of 1005 participants in the Myeloperoxidase In the Diagnosis of Acute coronary syndromes Study (MIDAS). MIDAS is a prospective observational cohort of Emergency Department (ED) patients enrolled from 18 US sites with symptoms suggestive of acute coronary syndrome (ACS). The ability to identify participants for early discharge and the sensitivity for ACS at 30 days were compared among an unstructured assessment, NACPR, and HEART score, each combined with troponin measures at 0 and 3h. ACS, defined as cardiac death, acute myocardial infarction, or unstable angina, occurred in 22% of the cohort. The unstructured assessment identified 13.5% (95% CI 11.5-16%) of participants for early discharge with 98% (95% CI 95-99%) sensitivity for ACS. The NACPR identified 4.4% (95% CI 3-6%) for early discharge with 100% (95% CI 98-100%) sensitivity for ACS. The HEART score identified 20% (95% CI 18-23%) for early discharge with 99% (95% CI 97-100%) sensitivity for ACS. The HEART score had a net reclassification improvement of 10% (95% CI 8-12%) versus unstructured assessment and 19% (95% CI 17-21%) versus NACPR. CONCLUSIONS The HEART score with 0 and 3 hour serial troponin measures identifies a substantial number of patients for early discharge while maintaining high sensitivity for ACS.

Short-term Mortality Risk in Emergency Department Acute Heart Failure

OBJECTIVES Few tools exist that provide objective accurate prediction of short-term mortality risk in patients presenting with acute heart failure (AHF). The purpose was to describe the accuracy of several biomarkers for predicting short-term death rates in patients diagnosed with AHF in the emergency department (ED). METHODS The Biomarkers in ACute Heart failure (BACH) trial was a prospective, 15-center, international study of patients presenting to the ED with nontraumatic dyspnea. Clinicians were blinded to all investigational markers, except troponin and natriuretic peptides, which used the local hospital reference range. For this secondary analysis, a core lab was used for all markers except troponin. This study evaluated patients diagnosed with AHF by the on-site emergency physician (EP). RESULTS In the 1,641 BACH patients, 466 (28.4%) had an ED diagnosis of AHF, of whom 411 (88.2%) had a final diagnosis of AHF. In the ED-diagnosed HF patients, 59% were male, 69% had a HF history, and 19 (4.1%) died within 14 days of their ED visit. The area under the curve (AUC) for the 14-day mortality receiver operating characteristic (ROC) curve was 0.484 for brain natriuretic peptide (BNP), 0.586 for N-terminal pro-B-type natriuretic peptide (NT-proBNP), 0.755 for troponin (I or T), 0.742 for adrenomedullin (MR-proADM), and 0.803 for copeptin. In combination, MR-proADM and copeptin had the best 14-day mortality prediction (AUC = 0.818), versus all other markers. CONCLUSIONS MR-proADM and copeptin, alone or in combination, may provide superior short-term mortality prediction compared to natriuretic peptides and troponin. Presented results are explorative due to the limited number of events, but validation in larger trials seems promising.

S3 Detection as a Diagnostic and Prognostic Aid in Emergency Department Patients With Acute Dyspnea

STUDY OBJECTIVE Dyspneic emergency department (ED) patients present a diagnostic dilemma. Recent technologic advances have made it possible to capture information about pathologic heart sounds at ECG recording. This study evaluates the effect of an S3 captured by acoustic cardiography on emergency physician diagnostic accuracy and confidence in their diagnosis of acute decompensated heart failure, as well as the patients prognosis. METHODS Dyspneic ED patients older than 40 years who were not dialysis dependent were prospectively enrolled in this multinational study. Treating emergency physicians, initially blinded to all laboratory and acoustic cardiography results, estimated acute decompensated heart failure probability from 0% to 100% on a visual analog scale. The emergency physician repeated the visual analog scale after acoustic cardiography results were provided. Physician diagnostic accuracy for and confidence in acute decompensated heart failure were evaluated against a reference standard diagnosis, as determined by 2 independent cardiologists blinded to acoustic cardiography. Patients were followed through 90 days to determine the relationship of the S3 to adverse events. RESULTS Nine hundred ninety-five patients with acoustic cardiography results were enrolled from March to October 2006 at 7 US and 2 international sites. Median age was 63 years, 55% were men, and 44% were white. The reference diagnosis was acute decompensated heart failure in 41.5%. After initial history and physical examination, the treating physicians initial sensitivity, specificity, and accuracy for acute decompensated heart failure as a possible diagnosis were 89.0% (95% confidence interval [CI] 85.5% to 91.8%), 58.2% (95% CI 54.0% to 62.2%), and 71.0% (95% CI 68.4% to 73.8%), respectively. Acoustic cardiography had an accuracy of 68% (95% CI 65.4% to 71.3%), sensitivity of 40.2% (95% CI 35.5% to 45.1%), and specificity of 88.5% (95% CI 85.5% to 90.9%). Emergency physician confidence and diagnostic accuracy were influenced by adding information about the presence or absence of S3. In a multivariable model, the S3 added no independent prognostic information for 30-day (odds ratio 1.20; 95% CI 0.67 to 2.14) or 90-day events (odds ratio 1.22; 95% CI 0.78 to 1.90). CONCLUSION In patients presenting with acute dyspnea, the acoustic cardiography S3 was specific for acute decompensated heart failure and affected physician confidence but did not improve diagnostic accuracy for acute decompensated heart failure, largely because of its low sensitivity. Further, the acoustic cardiography S3 provided no significant independent prognostic information.