Pearl Zakroysky

Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain

BACKGROUND It is unclear whether an evaluation incorporating coronary computed tomographic angiography (CCTA) is more effective than standard evaluation in the emergency department in patients with symptoms suggestive of acute coronary syndromes. METHODS In this multicenter trial, we randomly assigned patients 40 to 74 years of age with symptoms suggestive of acute coronary syndromes but without ischemic electrocardiographic changes or an initial positive troponin test to early CCTA or to standard evaluation in the emergency department on weekdays during daylight hours between April 2010 and January 2012. The primary end point was length of stay in the hospital. Secondary end points included rates of discharge from the emergency department, major adverse cardiovascular events at 28 days, and cumulative costs. Safety end points were undetected acute coronary syndromes. RESULTS The rate of acute coronary syndromes among 1000 patients with a mean (±SD) age of 54±8 years (47% women) was 8%. After early CCTA, as compared with standard evaluation, the mean length of stay in the hospital was reduced by 7.6 hours (P<0.001) and more patients were discharged directly from the emergency department (47% vs. 12%, P<0.001). There were no undetected acute coronary syndromes and no significant differences in major adverse cardiovascular events at 28 days. After CCTA, there was more downstream testing and higher radiation exposure. The cumulative mean cost of care was similar in the CCTA group and the standard-evaluation group (

Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial

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Use of Coronary Artery Calcium Scanning Beyond Coronary Computed Tomographic Angiography in the Emergency Department Evaluation for Acute Chest Pain The ROMICAT II Trial

4,060, respectively; P=0.65). CONCLUSIONS In patients in the emergency department with symptoms suggestive of acute coronary syndromes, incorporating CCTA into a triage strategy improved the efficiency of clinical decision making, as compared with a standard evaluation in the emergency department, but it resulted in an increase in downstream testing and radiation exposure with no decrease in the overall costs of care. (Funded by the National Heart, Lung, and Blood Institute; ROMICAT-II ClinicalTrials.gov number, NCT01084239.).

Sensitive troponin assays in patients with suspected acute coronary syndrome: Results from the multicenter rule out myocardial infarction using computer assisted tomography II trial

IMPORTANCE Atypical antipsychotic medications are indicated for the treatment of irritability and agitation symptoms in children with autism spectrum disorder (ASD). Unfortunately, these medications are associated with weight gain and metabolic complications that are especially troubling in children and with long-term use. OBJECTIVE To evaluate the efficacy of metformin for weight gain associated with atypical antipsychotic medications in children and adolescents with ASD (defined in the protocol as DSM-IV diagnosis of autistic disorder, Asperger disorder, or pervasive developmental disorder not otherwise specified), aged 6 to 17 years. DESIGN, SETTING, AND PARTICIPANTS A 16-week, double-blind, placebo-controlled, randomized clinical trial was conducted at 4 centers in Toronto, Ontario, Canada; Columbus, Ohio; Pittsburgh, Pennsylvania; and Nashville, Tennessee. In all, 209 potential participants were screened by telephone, 69 individuals provided consent, and 61 participants were randomized to receive metformin or placebo between April 26, 2013, and June 24, 2015. INTERVENTIONS Metformin or matching placebo titrated up to 500 mg twice daily for children aged 6 to 9 years and 850 mg twice daily for those 10 to 17 years. MAIN OUTCOMES AND MEASURES The primary outcome measure was change in body mass index (BMI) z score during 16 weeks of treatment. Secondary outcomes included changes in additional body composition and metabolic variables. Safety, tolerability, and efficacy analyses all used a modified intent-to-treat sample comprising all participants who received at least 1 dose of medication. RESULTS Of the 61 randomized participants, 60 participants initiated treatment (45 [75%] male; mean [SD] age, 12.8 [2.7] years). Metformin reduced BMI z scores from baseline to week 16 significantly more than placebo (difference in 16-week change scores vs placebo, -0.10 [95% CI, -0.16 to -0.04]; P = .003). Statistically significant improvements were also noted in secondary body composition measures (raw BMI, -0.95 [95% CI, -1.46 to -0.45] and raw weight, -2.73 [95% CI, -4.04 to -1.43]) but not in metabolic variables. Overall, metformin was well tolerated. Five participants in the metformin group discontinued treatment owing to adverse events (agitation, 4; sedation, 1). Participants receiving metformin vs placebo experienced gastrointestinal adverse events during a significantly higher percentage of treatment days (25.1% vs 6.8%; P = .005). CONCLUSIONS AND RELEVANCE Metformin may be effective in decreasing weight gain associated with atypical antipsychotic use and is well tolerated by children and adolescents with ASD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01825798.

Potential for coronary CT angiography to tailor medical therapy beyond preventive guideline-based recommendations: Insights from the ROMICAT I trial

Background—Whether a coronary artery calcium (CAC) scan provides added value to coronary computed tomographic angiography (CCTA) in emergency department patients with acute chest pain remains unsettled. We sought to determine the value of CAC scan in patients with acute chest pain undergoing CCTA. Methods and Results—In the multicenter Rule Out Myocardial Infarction using Computer-Assisted Tomography (ROMICAT) II trial, we enrolled low-intermediate risk emergency department patients with symptoms suggesting acute coronary syndrome (ACS). In this prespecified subanalysis of 473 patients (54±8 years, 53% men) who underwent both CAC scanning and CCTA, the ACS rate was 8%. Overall, 53% of patients had CAC=0 of whom 2 (0.8%) developed ACS, whereas 7% had CAC>400 with 49% whom developed ACS. C-statistic of CAC>0 was 0.76, whereas that using the optimal cut point of CAC≥22 was 0.81. Continuous CAC score had lower discriminatory capacity than CCTA (c-statistic, 0.86 versus 0.92; P=0.03). Compared with CCTA alone, there was no benefit combining CAC score with CCTA (c-statistic, 0.93; P=0.88) or with selective CCTA strategies after initial CAC>0 or optimal cut point CAC≥22 (P≥0.09). Mean radiation dose from CAC acquisition was 1.4±0.7 mSv. Higher CAC scores resulted in more nondiagnostic CCTA studies although the majority remained interpretable. Conclusions—In emergency department patients with acute chest pain, CAC score does not provide incremental value beyond CCTA for ACS diagnosis. CAC=0 does not exclude ACS, nor a high CAC score preclude interpretation of CCTA in most patients. Thus, CAC results should not influence the decision to proceed with CCTA, and the decision to perform a CAC scan should be balanced with the additional radiation exposure required. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01084239.

Steroid Exposure, Acute Coronary Syndrome, and Inflammatory Bowel Disease: Insights into the Inflammatory Milieu

BACKGROUND Sensitive troponin (Tn) assays have been developed for the evaluation of patients with suspected acute coronary syndrome (ACS). We sought to compare the performance of a commercially available sensitive Tn I (sTnI) and precommercial highly sTnI (hsTnI) method to conventional Tn (cTn) assays. METHODS Among patients with acute chest pain but normal cTn in the emergency department of 6 centers, sTnI and hsTnI were measured at baseline, 2 and 4 hours after presentation. Diagnostic accuracy of sTnI and hsTnI relative to cTn for diagnosis during index hospitalization as well as their associations with coronary artery disease in patients randomized to coronary computed tomographic angiography (CTA) was assessed. RESULTS Overall, 322 patients were enrolled, of whom 161 had a CTA; 28 had ACS (8.7%), including 21 with unstable angina pectoris (UAP). Both sTnI and hsTnI values at baseline and second draw had significantly higher sensitivity for ACS and UAP than cTn and had significantly greater area under the receiver operator characteristic curve than cTn at first and second draws. Compared with cTn, 29% of ACS cases previously categorized as UAP were reclassified to acute myocardial infarction with sTnI or hsTnI. An hsTnI below limit of detection had 100% negative predictive value for ACS or significant coronary artery stenosis in those randomized to CTA. CONCLUSIONS In patients with acute chest discomfort, use of sTnI and hsTnI methods led to significant improvement in the early diagnostic accuracy for ACS, reclassifying one-third of UAP to myocardial infarction. Very low values for hsTnI excluded underlying coronary artery disease.

Coronary CT Angiography Versus Standard Emergency Department Evaluation for Acute Chest Pain and Diabetic Patients: Is There Benefit With Early Coronary CT Angiography?: Results of the Randomized Comparative Effectiveness ROMICAT II Trial

BACKGROUND Coronary CT angiography (CCTA) is used in the emergency department to rule out acute coronary syndrome in low-intermediate risk patients. OBJECTIVES We evaluated the potential of CCTA to tailor aspirin (ASA) and statin therapy in acute chest pain patients. METHODS We included all patients in the ROMICAT I trial who underwent CCTA before admission. Results of CCTA were blinded to caretakers. We documented ASA and statin therapy at admission and discharge and determined change in medications during hospitalization, agreement of discharge medications with contemporaneous guidelines, and agreement with the presence and severity of coronary artery disease (CAD) as determined by CCTA. RESULTS We included 368 patients (53 ± 12 years; 61% male). Baseline medical therapy at presentation included 27% on ASA and 24% on statin. Most patients who qualified for secondary prevention were on ASA and statin therapy at discharge (95% and 80%, respectively), whereas among those qualifying for primary prevention therapy, only 59% of patients were on aspirin and 33% were on statin at discharge. Excluding secondary prevention patients, among those with CCTA-detected CAD, only 66/131 (50%) were on ASA at discharge and only 53/131 (40%) were on statin. Conversely, in those without CCTA-detected CAD, 54/156 (35%) were on ASA and 20/151 (13%) were on statin at discharge. CONCLUSION There are significant discrepancies between discharge prescription of statin and ASA with the presence and extent of CAD. CCTA presents an efficient opportunity to tailor medical therapy to CAD in patients undergoing CCTA as part of their acute chest pain evaluation.

Use of Coronary Computed Tomographic Angiography Findings to Modify Statin and Aspirin Prescription in Patients With Acute Chest Pain

BACKGROUND Steroids are anti-inflammatory agents commonly used to treat inflammatory bowel disease. Inflammation plays a critical role in the pathophysiology of both inflammatory bowel disease and acute coronary syndrome. We examined the relationship between steroid use in patients with inflammatory bowel disease and acute coronary syndrome. METHODS In 177 patients with inflammatory bowel disease (mean age 67 years, 75% male, 44% Crohns disease, 56% ulcerative colitis), we performed a 1:2 case-control study matched for age, sex, and inflammatory bowel disease type, and compared 59 patients with inflammatory bowel disease with acute coronary syndrome to 118 patients with inflammatory bowel disease without acute coronary syndrome. Steroid use was defined as current or prior exposure. Acute coronary syndrome was defined as myocardial infarction or unstable angina, confirmed by cardiac biomarkers and coronary angiography. RESULTS In patients with inflammatory bowel disease, 34% with acute coronary syndrome had exposure to steroids, vs 58% without acute coronary syndrome (P < .01). Steroid exposure reduced the adjusted odds of acute coronary syndrome by 82% (odds ratio [OR] 0.39; 95% confidence interval [CI], 0.20-0.74; adjusted OR 0.18; 95% CI, 0.06-0.51) in patients with inflammatory bowel disease, 77% in Crohns disease (OR 0.36; 95% CI, 0.14-0.92; adjusted OR 0.23; 95% CI, 0.06-0.98), and 78% in ulcerative colitis (OR 0.41; 95% CI, 0.16-1.04; adjusted OR 0.22; 95% CI, 0.06-0.90). There was no association between other inflammatory bowel disease medications and acute coronary syndrome. CONCLUSIONS In patients with inflammatory bowel disease, steroid use significantly reduces the odds of acute coronary syndrome. These findings provide further mechanistic insight into the inflammatory processes involved in inflammatory bowel disease and acute coronary syndrome.

Utility of Coronary Artery Calcium Scanning Beyond Coronary CT Angiography in the Emergency Department Evaluation for Acute Chest Pain: The ROMICAT II Trial

Background Cardiac computed tomography angiography (CCTA) reduces emergency department length of stay compared with standard evaluation in patients with low‐ and intermediate‐risk acute chest pain. Whether diabetic patients have similar benefits is unknown. Methods and Results In this prespecified analysis of the Rule Out Myocardial Ischemia/Infarction by Computer Assisted Tomography (ROMICAT II) multicenter trial, we randomized 1000 patients (17% diabetic) with symptoms suggestive of acute coronary syndrome to CCTA or standard evaluation. The rate of acute coronary syndrome was 8% in both diabetic and nondiabetic patients (P=1.0). Length of stay was unaffected by the CCTA strategy for diabetic patients (23.9 versus 27.2 hours, P=0.86) but was reduced for nondiabetic patients compared with standard evaluation (8.4 versus 26.5 hours, P<0.0001; P interaction=0.004). CCTA resulted in 3‐fold more direct emergency department discharge in both groups (each P≤0.0001, P interaction=0.27). No difference in hospital admissions was seen between the 2 strategies in diabetic and nondiabetic patients (P interaction=0.09). Both groups had more downstream testing and higher radiation doses with CCTA, but these were highest in diabetic patients (all P interaction≤0.04). Diabetic patients had fewer normal CCTAs than nondiabetic patients (32% versus 50%, P=0.003) and similar normalcy rates with standard evaluation (P=0.70). Notably, 66% of diabetic patients had no or mild stenosis by CCTA with short length of stay comparable to that of nondiabetic patients (P=0.34), whereas those with >50% stenosis had a high prevalence of acute coronary syndrome, invasive coronary angiography, and revascularization. Conclusions Knowledge of coronary anatomy with CCTA is beneficial for diabetic patients and can discriminate between lower risk patients with no or little coronary artery disease who can be discharged immediately and higher risk patients with moderate to severe disease who warrant further workup. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01084239.

Use of Coronary Artery Calcium Scanning Beyond Coronary Computed Tomographic Angiography in the Emergency Department Evaluation for Acute Chest Pain

Coronary CT angiography (CCTA) is used in patients with low-intermediate chest pain presenting to the emergency department for its reliability in excluding acute coronary syndrome (ACS). However, its influence on medication modification in this setting is unclear. We sought to determine whether knowledge of CCTA-based coronary artery disease (CAD) was associated with change in statin and aspirin prescription. We used the CCTA arm of the Rule Out Myocardial Infarction using Computed Angiographic Tomography II multicenter, randomized control trial (R-II) and comparison cohort from the observational Rule Out Myocardial Infarction using Computed Angiographic Tomography I cohort (R-I). In R-II, subjects were randomly assigned to CCTA to guide decision making, whereas in R-I patients underwent CCTA with results blinded to caregivers and managed according to standard care. Our final cohort consisted of 277 subjects from R-I and 370 from R-II. ACS rate was similar (6.9% vs 6.2% respectively, p = 0.75). For subjects with CCTA-detected obstructive CAD without ACS, initiation of statin was significantly greater after disclosure of CCTA results (0% in R-I vs 20% in R-II, p = 0.009). Conversely, for subjects without CCTA-detected CAD, aspirin prescription was lower with disclosure of CCTA results (16% in R-I vs 4.8% in R-II, p = 0.001). However, only 68% of subjects in R-II with obstructive CAD were discharged on statin and 65% on aspirin. In conclusion, physician knowledge of CCTA results leads to improved alignment of aspirin and statin with the presence and severity of CAD although still many patients with CCTA-detected CAD are not discharged on aspirin or statin. Our findings suggest opportunity for practice improvement when CCTA is performed in the emergency department.