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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.annemergmed.2009.01.006 Byline: Luke K. Hermann (a), Scott D. Weingart (b), W. Lane Duvall (c), Milena J. Henzlova (c) Abstract: This is a study designed to evaluate the utility of routine provocative cardiac testing in low-risk young adult (younger than 40 years) patients evaluated for an acute coronary syndrome in an emergency department (ED) setting. Author Affiliation: (a) Department of Emergency Medicine, Division of Emergency Critical Care, Mount Sinai School of Medicine, New York, NY (b) Department of Emergency Medicine, Elmhurst Hospital, New York, NY (c) Division of Cardiology, Department of Internal Medicine, Mount Sinai School of Medicine, New York, NY Article History: Received 24 October 2008; Revised 12 December 2008; Accepted 7 January 2009 Article Note: (footnote) Supervising editor: Keith A. Marill, MD, Author contributions: LKH conceived of the study, supervised data collection, and drafted the article. SDW provided significant revisions to the article, including the structure and content of the discussion and conclusions segments. WLD designed and implemented the data collection instrument that provided background patient information. WLD and MJH assisted with revisions to the article. MJH provided access to the results of all cardiac studies. LKH takes responsibility for the paper as a whole., Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement., Publication date: Available online February 23, 2009., Reprints not available from the authors.

Fifty-four year-old man with recent history of myocardial infarction and a percutaneous coronary intervention who suffered a ventricular fibrillation arrest at home. He was resuscitated in the field. His heart rhythm was in atrial fibrillation. The cardiac catheterization showed a patent stent from his previous myocardial infarction and no new occlusions. He subsequently underwent hypothermia protocol using the Alsius CoolGard 3000 Temperature Control System and Icy Catheter. Heparin drip was started for atrial fibrillation 36 hours after catheter insertion and became therapeutic 2 hours before the end of cooling maintenance phase. Heparin drip was stopped 4 hours into the rewarming phase because of spontaneous conversion to sinus rhythm. Subcutaneous heparin was resumed for deep venous thrombosis prophylaxis. He was extubated to room air after hypothermia protocol. The cooling catheter was removed 88 hours after insertion. Within 1 minute of catheter removal, his oxygen saturation dropped to 80%. Transthoracic echocardiogram showed a mobile thrombus in the right atrium prolapsing into the right ventricle. Computer tomography angiography of the chest confirmed a large saddle embolus. Ninety minutes later, patient went into cardiac arrest with pulseless electrical activity while he was being considered for surgical embolectomy, but he could not be resuscitated. The temporal relationship of the catheter removal and his acute clinical decompensation led to believe that this was an intravascular cooling catheter (ICC)-related event. Providers should be cognizant of the complications of central venous catheters such as thrombosis formation, as it could lead to fatal pulmonary embolism. Physicians should promote frequent assessment of the access site(s) during routine physical examinations and potentially use point of care vascular ultrasound in high-risk cases to rule out a catheter-associated thrombus before catheter removal.

Stress-first approaches to myocardial perfusion imaging provide diagnostically and prognostically accurate perfusion data equivalent to a full rest-stress study while saving time in the imaging laboratory and reducing the radiation exposure to patients and laboratory staff. Unfortunately, implementing a stress-first approach in a nuclear cardiology laboratory involves significant challenges such as the need for attenuation correction, triage of patients to an appropriate protocol, real-time review of stress images, and consideration of differential reimbursement. Despite it being best practice for both the patient and the laboratory, these impediments have kept the proportions of studies performed stress-first relatively unchanged in North America and world-wide in the last 10 years.

Purpose:Enzyme replacement therapy with olipudase alfa (recombinant human acid sphingomyelinase) is being developed for Niemann–Pick disease type B (NPD B).Methods:A single-center, open-label, nonrandomized, single-ascending-dose trial evaluated the safety of intravenous olipudase alfa (0.03–1.0?mg/kg) in 11 adults with NPD B. Patients were monitored in the hospital for 72?h after infusion and had follow-up visits on days 14 and 28.Results:Plasma ceramide, a product of sphingomyelin catabolism by olipudase alfa, showed dose-dependent elevations by 6?h postdose, or postinfusion. No serious adverse drug reactions (ADRs) occurred during the study. Acute phase reaction-type ADRs, as evidenced by elevated inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin-8, and calcitonin) and constitutional symptoms (fever, pain, nausea, and/or vomiting) emerged 12–24?h following doses =0.3?mg/kg olipudase alfa. Three patients experienced hyperbilirubinemia. The study was terminated after a patient dosed at 1?mg/kg exhibited severe hyperbilirubinemia; he was subsequently diagnosed with Gilbert syndrome.Conclusion:The maximum tolerated dose of olipudase alfa in adults with NPD B was 0.6?mg/kg. First-dose ADRs were likely induced by elevated concentrations of ceramide (or its downstream derivatives) generated by the catabolism of accumulated sphingomyelin. Within-patient dose escalation to slowly catabolize sphingomyelin stores may be a strategy to mitigate first-dose ADRs in patients with NPD B.Genet Med 18 1, 34–40.

IMPORTANCE The American Heart Association recommends routine provocative cardiac testing in accelerated diagnostic protocols for coronary ischemia. The diagnostic and therapeutic yield of this approach are unknown. OBJECTIVE To assess the yield of routine provocative cardiac testing in an emergency department–based chest pain unit. DESIGN AND SETTING We examined a prospectively collected database of patients evaluated for possible acute coronary syndrome between March 4, 2004, and May 15, 2010, in the emergency department–based chest pain unit of an urban academic tertiary care center. PARTICIPANTS Patients with signs or symptoms of possible acute coronary syndrome and without an ischemic electrocardiography result or a positive biomarker were enrolled in the database. EXPOSURES All patients were evaluated by exercise stress testing or myocardial perfusion imaging. MAIN OUTCOMES AND MEASURES Demographic and clinical features, results of routine provocative cardiac testing and angiography, and therapeutic interventions were recorded. Diagnostic yield (true-positive rate) was calculated, and the potential therapeutic yield of invasive therapy was assessed through blinded, structured medical record review using American Heart Association designations (class I, IIa, IIb, or lower) for the potential benefit from percutaneous intervention. RESULTS In total, 4181 patients were enrolled in the study. Chest pain was initially reported in 93.5%, most (73.2%) were at intermediate risk for coronary artery disease, and 37.6% were male. Routine provocative cardiac testing was positive for coronary ischemia in 470 (11.2%), of whom 123 underwent coronary angiography. Obstructive disease was confirmed in 63 of 123 (51.2% true positive), and 28 (0.7% overall) had findings consistent with the potential benefit from revascularization (American Heart Association class I or IIa). CONCLUSIONS AND RELEVANCE In an emergency department–based chest pain unit, routine provocative cardiac testing generated a small therapeutic yield, new diagnoses of coronary artery disease were uncommon, and false-positive results were common.

Cardiovascular risk might be reduced by targeted changes in both low density and high density lipoprotein cholesterol (LDL-C and HDL-C). This dual strategy will require a well tolerated, effective regimen, as well as a better understanding of how HDL-C may be targeted.