Browsing by Subject "Acute Coronary Syndrome"
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Item Open Access Acute Coronary Syndrome: Diagnosis and Initial Management.(American family physician, 2024-01) Nohria, Raman; Viera, Anthony JAcute coronary syndrome (ACS) is defined as reduced blood flow to the coronary myocardium manifesting as ST-segment elevation myocardial infarction or non-ST-segment elevation ACS, which includes unstable angina and non-ST-segment elevation myocardial infarction. Common risk factors include being at least 65 years of age or a current smoker or having hypertension, diabetes mellitus, hyperlipidemia, a body mass index greater than 25 kg per m2, or a family history of premature coronary artery disease. Symptoms most predictive of ACS include chest discomfort that is substernal or spreading to the arms or jaw. However, chest pain that can be reproduced with palpation or varies with breathing or position is less likely to signify ACS. Having a prior abnormal cardiac stress test result indicates increased risk. Electrocardiography changes that predict ACS include ST depression, ST elevation, T-wave inversion, or presence of Q waves. No validated clinical decision tool is available to rule out ACS in the outpatient setting. Elevated troponin levels without ST-segment elevation on electrocardiography suggest non-ST-segment elevation ACS. Patients with ACS should receive coronary angiography with percutaneous or surgical revascularization. Other important management considerations include initiation of dual antiplatelet therapy and parenteral anticoagulation, statin therapy, beta-blocker therapy, and sodium-glucose cotransporter-2 inhibitor therapy. Additional interventions shown to reduce mortality in patients who have had a recent myocardial infarction include smoking cessation, annual influenza vaccination, and cardiac rehabilitation.Item Open Access Association of Perceived Health Competence With Cardiac Rehabilitation Initiation.(Journal of cardiopulmonary rehabilitation and prevention, 2023-03) Hu, Jiun-Ruey; Huang, Shi; Bosworth, Hayden B; Freedland, Kenneth E; Mayberry, Lindsay S; Kripalani, Sunil; Wallston, Kenneth A; Roumie, Christianne L; Bachmann, Justin M; Vanderbilt Inpatient Cohort Study (VICS)Purpose
Cardiac rehabilitation (CR), a program of supervised exercise and cardiovascular risk management, is widely underutilized. Psychological factors such as perceived health competence, or belief in one's ability to achieve health-related goals, may play a role in CR initiation. The aim of this study was to evaluate the association of perceived health competence with CR initiation among patients hospitalized for acute coronary syndrome (ACS) after adjusting for demographic, clinical, and psychosocial characteristics.Methods
The Vanderbilt Inpatient Cohort Study (VICS) characterized the effect of psychosocial characteristics on post-discharge outcomes in ACS inpatients hospitalized from 2011 to 2015. The primary outcome for this analysis was participation in an outpatient CR program. The primary predictor was the two-item Perceived Health Competence Scale (PHCS-2), which yields a score from 2 to 10 (higher scores indicate greater perceived health competence). Multiple logistic regression was used to evaluate the relationship between the PHCS-2 and CR initiation.Results
A total of 1809 VICS participants (median age: 61 yr, 39% female) with ACS were studied, of whom 294 (16%) initiated CR. The PHCS-2 was associated with a higher odds of CR initiation (OR = 1.15/point increase: 95% CI, 1.06-1.26, P = .001) after adjusting for covariates. Participants with comorbid heart failure had a lower odds of CR initiation (OR = 0.31: 95% CI, 0.16-0.60, P < .001) as did current smokers (OR = 0.64: 95% CI, 0.43-0.96, P = .030).Conclusion
Perceived health competence is associated with outpatient CR initiation in patients hospitalized with ACS. Interventions designed to support perceived health competence may be useful for improving CR participation.Item Open Access Efficacy of High-Sensitivity Troponin T in Identifying Very-Low-Risk Patients With Possible Acute Coronary Syndrome.(JAMA cardiology, 2018-02) Peacock, W Frank; Baumann, Brigette M; Bruton, Deborah; Davis, Thomas E; Handy, Beverly; Jones, Christopher W; Hollander, Judd E; Limkakeng, Alexander T; Mehrotra, Abhi; Than, Martin; Ziegler, Andre; Dinkel, CarinaImportance:Physicians need information on how to use the first available high-sensitivity troponin (hsTnT) assay in the United States to identify patients at very low risk for 30-day adverse cardiac events (ACE). Objective:To determine whether a negative hsTnT assay at 0 and 3 hours following emergency department presentation could identify patients at less than 1% risk of a 30-day ACE. Design, Setting, and Participants:A prospective, observational study at 15 emergency departments in the United States between 2011 and 2015 that included individuals 21 years and older, presenting to the emergency department with suspected acute coronary syndrome. Of 1690 eligible individuals, 15 (no cardiac troponin T measurement) and 320 (missing a 0-hour or 3-hour sample) were excluded from the analyses. Exposures:Serial hsTnT measurements (fifth-generation Roche Elecsys hsTnT assay). Main Outcomes and Measures:Serial blood samples from each patient were collected after emergency department presentation (once identified as a potential patient with acute coronary syndrome) and 3 hours, 6 to 9 hours, and 12 to 24 hours later. Adverse cardiac events were defined as myocardial infarction, urgent revascularization, or death. The upper reference level for the hsTnT assay, defined as the 99th percentile, was established as 19 ng/L in a separate healthy US cohort. Patients were considered ruled out for acute myocardial infarction if their hsTnT level at 0 hours and 3 hours was less than the upper reference level. Gold standard diagnoses were determined by a clinical end point committee. Evaluation of assay clinical performance for acute myocardial infarction rule-out was prespecified; the hypothesis regarding 30-day ACE was formulated after data collection. Results:In 1301 healthy volunteers (50.4% women; median age, 48 years), the upper reference level was 19 ng/L. In 1600 patients with suspected acute coronary syndrome (48.4% women; median age, 55 years), a single hsTnTlevel less than 6 ng/L at baseline had a negative predictive value for AMI of 99.4%. In 974 patients (77.1%) with both 0-hour and 3-hour hsTnT levels of 19 ng/L or less, the negative predictive value for 30-day ACE was 99.3% (95% CI, 99.1-99.6). Using sex-specific cutpoints, C statistics for women (0.952) and men (0.962) were similar for acute myocardial infarction. Conclusions and Relevance:A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.Item Open Access Emergency physician high pretest probability for acute coronary syndrome correlates with adverse cardiovascular outcomes.(Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2009-08) Chandra, Abhinav; Lindsell, Christopher J; Limkakeng, Alexander; Diercks, Deborah B; Hoekstra, James W; Hollander, Judd E; Kirk, J Douglas; Peacock, W Frank; Gibler, W Brian; Pollack, Charles V; EMCREG i*trACS InvestigatorsOBJECTIVES: The value of unstructured physician estimate of risk for disease processes, other than acute coronary syndrome (ACS), has been demonstrated. The authors sought to evaluate the predictive value of unstructured physician estimate of risk for ACS in emergency department (ED) patients without obvious initial evidence of a cardiac event. METHODS: This was a post hoc secondary analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i*trACS), a prospectively collected multicenter data registry of patients over the age of 18 years presenting to the ED with symptoms of ACS between 1999 and 2001. In this registry, following patient history, physical exam, and electrocardiogram (ECG), the unstructured treating physician estimate of risk was recorded. A 30-day follow-up and a medical record review were used to determine rates of adverse cardiac events, death, myocardial infarction (MI), or revascularization procedure. The analysis included all patients with nondiagnostic ECG changes, normal initial biomarkers, and a non-MI initial impression from the registry and excluded those without complete data or who were lost to follow-up. Data were stratified by unstructured physician risk estimate: noncardiac, low risk, high risk, or unstable angina. RESULTS: Of 15,608 unique patients in the registry, 10,145 met inclusion/exclusion criteria. Patients were defined as having unstable angina in 6.0% of cases; high risk, 23.5% of cases; low risk, 44.2%; and noncardiac, 26.3% of cases. Adverse cardiac event rates had an inverse relationship, decreasing from 22.0% (95% confidence interval [CI] = 18.8% to 25.6%) for unstable angina, 10.2% (95% CI = 9.0% to 11.5%) for those stratified as high risk, 2.2% (95% CI = 1.8% to 2.6%) for low risk, and to 1.8% (95% CI = 1.4% to 2.4%) for noncardiac. The relative risk (RR) of an adverse cardiac event for those with an initial label of unstable angina compared to those with a low-risk designation was 10.2 (95% CI = 8.0 to 13.0). The RR of an event for those with a high-risk initial impression compared to those with a low-risk initial impression was 4.7 (95% CI = 3.8 to 5.9). The risk of an event among those with a low-risk initial impression was the same as for those with a noncardiac initial impression (RR = 0.83, 95% CI = 0.6 to 1.2). CONCLUSIONS: In ED patients without obvious initial evidence of a cardiac event, unstructured emergency physician (EP) estimate of risk correlates with adverse cardiac outcomes.Item Open Access Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod.(Drug Des Devel Ther, 2015) Kragholm, Kristian; Newby, Laura Kristin; Melloni, ChiaraEach year, despite optimal use of recommended acute and secondary prevention therapies, 4%-5% of patients with acute coronary syndrome (ACS) experience relapse of ACS or other cardiovascular events including stroke, heart failure, or sudden cardiac death after the index ACS. The sudden atherosclerotic plaque rupture leading to an ACS event is often accompanied by inflammation, which is thought to be a key pathogenic pathway to these excess cardiovascular events. Losmapimod is a novel, oral p38 mitogen-activated protein kinase (MAPK) inhibitor that targets MAPKs activated in macrophages, myocardium, and endothelial cells that occur as a part of global coronary vascular inflammation following plaque rupture. This review aims to 1) discuss the pathophysiological pathways through which p38 MAPKs may play key roles in initiation and progression of inflammatory disease and how losmapimod is thought to counteract these p38 MAPKs, and 2) to describe the efficacy and safety data for losmapimod obtained from preclinical studies and randomized controlled trials that support the hypothesis that it has promise as a treatment for patients with ACS.Item Open Access Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions.(Chinese medical journal, 2018-02) Zhao, Xue-Yan; Li, Jian-Xin; Tang, Xiao-Fang; Xian, Ying; Xu, Jing-Jing; Song, Ying; Jiang, Lin; Xu, Lian-Jun; Chen, Jue; Zhang, Yin; Song, Lei; Gao, Li-Jian; Gao, Zhan; Zhang, Jun; Wu, Yuan; Qiao, Shu-Bin; Yang, Yue-Jin; Gao, Run-Lin; Xu, Bo; Yuan, Jin-QingBACKGROUND:There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. METHODS:We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. RESULTS:During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. CONCLUSIONS:CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.Item Open Access Evaluation of T-Wave Morphology in Patients With Left Bundle Branch Block and Suspected Acute Coronary Syndrome.(The Journal of emergency medicine, 2016-09) Meyers, H Pendell; Jaffa, Elias; Smith, Stephen W; Drake, Weiying; Limkakeng, Alexander TT-wave morphology in the setting of left bundle branch block (LBBB) has been proposed as an indicator of myocardial ischemia.We sought to identify T-wave morphology findings in patients with LBBB that predict non-ST-segment elevation myocardial infarction (NSTEMI). We hypothesized that two or more contiguous leads with concordant T waves would be predictive of NSTEMI.This was a retrospective cohort study performed by chart review in a tertiary care center emergency department. We identified a consecutive cohort who presented with LBBB and symptoms consistent with acute coronary syndrome. Exclusion criteria were diastolic blood pressure > 120 mm Hg, heart rate > 130 beats/min, positive pressure ventilation, potassium > 5.5 mEq/L, and cardiac arrest without prearrest electrocardiogram (ECG) available. We collected ECGs and classified T waves into five categories based on morphology, blinded to clinical outcome. Clinical outcome data were collected blinded to ECG findings. Those with ECG diagnostic of STEMI by modified Sgarbossa criteria were excluded from the primary analysis, which was sensitivity and specificity of two or more contiguous leads with concordant T waves for NSTEMI.There were 246 patients included. Mean age was 73 years; 160 (65%) were female, and 32 had myocardial infarction. Thirty percent had two or more contiguous precordial leads with partially or completely concordant T waves. For NSTEMI, the sensitivity and specificity of this finding were 19% (95% confidence interval [CI] 8-37) and 68% (95% CI 61-74).We found no clinically useful relationship between T-wave concordance and myocardial infarction in our patient population. Future investigation of LBBB T-wave morphology should focus on alternative populations and findings.Item Open Access Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction.(The American journal of emergency medicine, 2022-06) Limkakeng, Alexander T; Hertz, Julian; Lerebours, Reginald; Kuchibhatla, Maragatha; McCord, James; Singer, Adam J; Apple, Fred S; Peacock, William F; Christenson, Robert H; Nowak, Richard MItem Open Access Impact of renal dysfunction on acute coronary syndrome evaluation in observation unit patients.(Am J Emerg Med, 2010-07) Limkakeng, Alexander T; Chandra, AbhinavOBJECTIVES: The impact of renal disease on risk stratification of patients at low risk for potential acute coronary syndrome has not been well defined. The objective of this study was to document the prevalence of renal dysfunction and assess the association between renal impairment and abnormal cardiac evaluation in observation unit (OU) patients. METHODS: Retrospective cohort study at an academic medical center OU. Data were abstracted using predetermined definitions of data outcomes by trained abstractors. Patients had symptoms consistent with acute coronary syndrome and did not have obvious evidence of acute MI or ischemia on electrocardiogram, unstable vital signs, abnormal cardiac markers, serious arrhythmias, or uncontrollable chest pain. Observation patients received serial cardiac markers and electrocardiograms, with the majority receiving stress testing at treating physician discretion. Patients were stratified by glomerular filtration rates (GFR) at cut-off points of less than 60 and less than 90 mL/min per 1.73 m(2). Odds ratios were calculated for stress test findings of inducible ischemia or hospital admission. RESULTS: Five hundred and twenty-nine out of 545 patients had complete data and were enrolled. Sixty-nine (13%) patients had a GFR of less than 60 and 300 (56%) patients had a GFR of less than 90. An abnormal cardiac evaluation was found in 64 (12%) patients, of whom 31 (49%) had some renal impairment. The odds ratio of an abnormal cardiac evaluation with a GFR of less than 90 is 1.65 (95% confidence interval, 0.95-2.88) and 1.65 (95% confidence interval, 0.83-3.28) for GFR less than 60. CONCLUSIONS: Renal dysfunction is common in OU patients. In these patients, renal dysfunction did not confer higher risk for abnormal cardiac evaluation.Item Open Access Lifetime cost-effectiveness analysis of ticagrelor in patients with acute coronary syndromes based on the PLATO trial: a Singapore healthcare perspective.(Singapore medical journal, 2013-03) Chin, Chee Tang; Mellstrom, Carl; Chua, Terrance Siang Jin; Matchar, David BruceIntroduction
Ticagrelor is a novel antiplatelet drug developed to reduce atherothrombosis. The PLATO trial compared ticagrelor and aspirin to clopidogrel and aspirin in patients with acute coronary syndromes (ACS). Ticagrelor was found to be superior in the primary composite endpoint of cardiovascular death, myocardial infarction or stroke, without increasing major bleeding events. The current study estimates the lifetime cost-effectiveness of ticagrelor relative to generic clopidogrel from a Singapore public healthcare perspective.Methods
This study used a two-part cost-effectiveness model. The first part was a 12-month decision tree (using PLATO trial data) to estimate the rates of major cardiovascular events, healthcare costs and health-related quality of life. The second part was a Markov model estimating lifetime quality-adjusted survival and costs conditional on events during the initial 12 months. Daily drug costs applied were SGD 1.05 (generic clopidogrel) and SGD 6.00 (ticagrelor). Cost per quality-adjusted life years (QALY) was estimated from a Singapore public healthcare perspective using life tables and short-term costs from Singapore, and long-term costs from South Korea. Deterministic and probabilistic sensitivity analyses were performed.Results
Ticagrelor was associated with a lifetime QALY gain of 0.13, primarily driven by lower mortality. The resulting incremental cost per QALY gained was SGD 10,136.00. Probabilistic sensitivity analysis indicated that ticagrelor had a > 99% probability of being cost-effective, given the lower recommended WHO willingness-to-pay threshold of one GDP/capita per QALY.Conclusion
Based on PLATO trial data, one-year treatment with ticagrelor versus generic clopidogrel in patients with ACS, relative to WHO reference standards, is cost-effective from a Singapore public healthcare perspective.Item Open Access Lower likelihood of cardiac procedures after acute coronary syndrome in patients with human immunodeficiency virus/acquired immunodeficiency syndrome.(Medicine, 2018-02) Clement, Meredith E; Lin, Li; Navar, Ann Marie; Okeke, Nwora Lance; Naggie, Susanna; Douglas, Pamela SCardiovascular disease (CVD) is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected adults; however, this population may be less likely to receive interventions during hospitalization for acute coronary syndrome (ACS). The degree to which this disparity can be attributed to poorly controlled HIV infection is unknown.In this large cohort study, we used the National Inpatient Sample (NIS) to compare rates of cardiac procedures among patients with asymptomatic HIV-infection, symptomatic acquired immunodeficiency syndrome (AIDS), and uninfected adults hospitalized with ACS from 2009 to 2012. Multivariable analysis was used to compare procedure rates by HIV status, with appropriate weighting to account for NIS sampling design including stratification and hospital clustering.The dataset included 1,091,759 ACS hospitalizations, 0.35% of which (n = 3783) were in HIV-infected patients. Patients with symptomatic AIDS, asymptomatic HIV, and uninfected patients differed by sex, race, and income status. Overall rates of cardiac catheterization and revascularization were 53.3% and 37.4%, respectively. In multivariable regression, we found that relative to uninfected patients, those with symptomatic AIDS were less likely to undergo catheterization (odds ratio [OR] 0.48, confidence interval [CI] 0.43-0.55), percutaneous coronary intervention (OR 0.69, CI 0.59-0.79), and coronary artery bypass grafting (0.75, CI 0.61-0.93). No difference was seen for those with asymptomatic HIV relative to uninfected patients (OR 0.93, CI 0.81-1.07; OR 1.06, CI 0.93-1.21; OR 0.88, CI 0.72-1.06, respectively).We found that lower rates of cardiovascular procedures in HIV-infected patients were primarily driven by less frequent procedures in those with AIDS.Item Open Access Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge: a randomized clinical trial.(JAMA internal medicine, 2014-02) Ho, P Michael; Lambert-Kerzner, Anne; Carey, Evan P; Fahdi, Ibrahim E; Bryson, Chris L; Melnyk, S Dee; Bosworth, Hayden B; Radcliff, Tiffany; Davis, Ryan; Mun, Howard; Weaver, Jennifer; Barnett, Casey; Barón, Anna; Del Giacco, Eric JImportance
Adherence to cardioprotective medication regimens in the year after hospitalization for acute coronary syndrome (ACS) is poor.Objective
To test a multifaceted intervention to improve adherence to cardiac medications.Design, setting, and participants
In this randomized clinical trial, 253 patients from 4 Department of Veterans Affairs medical centers located in Denver (Colorado), Seattle (Washington); Durham (North Carolina), and Little Rock (Arkansas) admitted with ACS were randomized to the multifaceted intervention (INT) or usual care (UC) prior to discharge.Interventions
The INT lasted for 1 year following discharge and comprised (1) pharmacist-led medication reconciliation and tailoring; (2) patient education; (3) collaborative care between pharmacist and a patient's primary care clinician and/or cardiologist; and (4) 2 types of voice messaging (educational and medication refill reminder calls).Main outcomes and measures
The primary outcome of interest was proportion of patients adherent to medication regimens based on a mean proportion of days covered (PDC) greater than 0.80 in the year after hospital discharge using pharmacy refill data for 4 cardioprotective medications (clopidogrel, β-blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [statins], and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ACEI/ARB]). Secondary outcomes included achievement of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level targets. RESULTS Of 253 patients, 241 (95.3%) completed the study (122 in INT and 119 in UC). In the INT group, 89.3% of patients were adherent compared with 73.9% in the UC group (P = .003). Mean PDC was higher in the INT group (0.94 vs 0.87; P< .001). A greater proportion of intervention patients were adherent to clopidogrel (86.8% vs 70.7%; P = .03), statins (93.2% vs 71.3%; P < .001), and ACEI/ARB (93.1% vs 81.7%; P = .03) but not β-blockers (88.1% vs 84.8%; P = .59). There were no statistically significant differences in the proportion of patients who achieved BP and LDL-C level goals.Conclusions and relevance
A multifaceted intervention comprising pharmacist-led medication reconciliation and tailoring, patient education, collaborative care between pharmacist and patients' primary care clinician and/or cardiologist, and voice messaging increased adherence to medication regimens in the year after ACS hospital discharge without improving BP and LDL-C levels. Understanding the impact of such improvement in adherence on clinical outcomes is needed prior to broader dissemination of the program.Trial registration
clinicaltrials.gov Identifier: NCT00903032.Item Open Access Novel antiplatelet agent ticagrelor in the management of acute coronary syndrome.(Journal of interventional cardiology, 2011-06) Ramaraj, Radhakrishnan; Movahed, Mohammad Reza; Hashemzadeh, MehrnooshCurrent clinical guidelines recommend dual antiplatelet agents namely aspirin and clopidogrel for the treatment of patients suffering from acute coronary syndrome (ACS). But the efficacy of clopidogrel is variable as it is a pro-drug, which has to be metabolized to become an active drug thus exhibiting variable platelet inhibition, increases risk of bleeding, stent thrombosis, and ischemia. To overcome this limitation, prasugrel was developed with increased antiplatelet activity thereby reducing the risk of myocardial ischemia and stent thrombosis. This action of prasugrel was associated with an increased risk of major bleeding. Finally, a novel reversible and direct-acting oral adenosine diphosphate (ADP) receptor antagonist, ticagrelor was developed that showed consistent and increased P2Y12 inhibition with similar incidence of bleeding but greater reduction in cardiac events compared to clopidogrel. The focus of this article is to review ticagrelor as a new class of P2Y12 inhibitor.Item Open Access Patient-centered adherence intervention after acute coronary syndrome hospitalization.(Circulation. Cardiovascular quality and outcomes, 2012-07) Lambert-Kerzner, Anne; Del Giacco, Eric J; Fahdi, Ibrahim E; Bryson, Chris L; Melnyk, S Dee; Bosworth, Hayden B; Davis, Ryan; Mun, Howard; Weaver, Jennifer; Barnett, Casey; Radcliff, Tiffany; Hubbard, Amanda; Bosket, Kevin D; Carey, Evan; Virchow, Allison; Mihalko-Corbitt, Renee; Kaufman, Amy; Marchant-Miros, Kathy; Ho, P Michael; Multifaceted Intervention to Improve Cardiac Medication Adherence and Secondary Prevention Measures (Medication) Study InvestigatorsBackground
Adherence to cardioprotective medications in the year after acute coronary syndrome hospitalization is generally poor and is associated with increased risk of rehospitalization and mortality. Few interventions have specifically targeted this high-risk patient population to improve medication adherence. We hypothesize that a multifaceted patient-centered intervention could improve adherence to cardioprotective medications.Methods and results
To evaluate this intervention, we propose enrolling 280 patients with a recent acute coronary syndrome event into a multicenter randomized, controlled trial. The intervention comprises 4 main components: (1) pharmacist-led medication reconciliation and tailoring; (2) patient education; (3) collaborative care between pharmacist and primary care provider/cardiologist; and (4) 2 types of voice messaging (educational and medication refill reminder calls). Patients in the intervention arm will visit with the study pharmacist ≈1 week post-hospital discharge. The pharmacist will work with the patient and collaborate with providers to reconcile medication issues. Voice messages will augment the educational process and remind patients to refill their cardioprotective medications. The study will compare the intervention versus usual care for 12 months. The primary outcome of interest is adherence using the ReComp method. Secondary and tertiary outcomes include achievement of targets for blood pressure and low-density lipoprotein, and reduction in the combined cardiovascular end points of myocardial infarction hospitalization, coronary revascularization, and all-cause mortality. Finally, we will also evaluate the cost-effectiveness of the intervention compared with usual care.Conclusions
If the intervention is effective in improving medication adherence and demonstrating a lower cost, the intervention has the potential to improve cardiovascular outcomes in this high-risk patient population.Item Open Access Pilot study of myocardial ischemia-induced metabolomic changes in emergency department patients undergoing stress testing.(PloS one, 2019-01) Limkakeng, Alexander T; Henao, Ricardo; Voora, Deepak; O'Connell, Thomas; Griffin, Michelle; Tsalik, Ephraim L; Shah, Svati; Woods, Christopher W; Ginsburg, Geoffrey SBACKGROUND:The heart is a metabolically active organ, and plasma acylcarnitines are associated with long-term risk for myocardial infarction. We hypothesized that myocardial ischemia from cardiac stress testing will produce dynamic changes in acylcarnitine and amino acid levels compared to levels seen in matched control patients with normal stress tests. METHODS:We analyzed targeted metabolomic profiles in a pilot study of 20 case patients with inducible ischemia on stress testing from an existing prospectively collected repository of 357 consecutive patients presenting with symptoms of Acute Coronary Syndrome (ACS) in an Emergency Department (ED) observation unit between November 2012 and September 2014. We selected 20 controls matched on age, sex, and body-mass index (BMI). A peripheral blood sample was drawn <1 hour before stress testing and 2 hours after stress testing on each patient. We assayed 60 select acylcarnitines and amino acids by tandem mass spectrometry (MS/MS) using a Quattro Micro instrument (Waters Corporation, Milford, MA). Metabolite values were log transformed for skew. We then performed bivariable analysis for stress test outcome and both individual timepoint metabolite concentrations and stress-delta metabolite ratios (T2/T0). False discovery rates (FDR) were calculated for 60 metabolites while controlling for age, sex, and BMI. We built multivariable regularized linear models to predict stress test outcome from metabolomics data at times 0, 2 hours, and log ratio between these two. We used leave-one-out cross-validation to estimate the performance characteristics of the model. RESULTS:Nine of our 20 case subjects were male. Cases' average age was 55.8, with an average BMI 29.5. Bivariable analysis identified 5 metabolites associated with positive stress tests (FDR < 0.2): alanine, C14:1-OH, C16:1, C18:2, C20:4. The multivariable regularized linear models built on T0 and T2 had Area Under the ROC Curve (AUC-ROC) between 0.5 and 0.55, however, the log(T2/T0) model yielded 0.625 AUC, with 65% sensitivity and 60% specificity. The top metabolites selected by the model were: Ala, Arg, C12-OH/C10-DC, C14:1-OH, C16:1, C18:2, C18:1, C20:4 and C18:1-DC. CONCLUSIONS:Stress-delta metabolite analysis of patients undergoing stress testing is feasible. Future studies with a larger sample size are warranted.Item Open Access Rapidly progressing mycotic aortic aneurysm masquerading as acute coronary syndrome.(The Canadian journal of cardiology, 2013-12) Chhabra, Lovely; Kruger, Mihaela A; Kuraganti, Gayatri; Eltibi, Rami; Mamidala, Suresh; Bajaj, Rishi; Belur, Akhila; Rapose, Alwyn; Hannan, JosephMycotic aortic aneurysms are rare. The most common cause of a mycotic aortic aneurysm is bacterial seeding in a diseased or injured aortic intima with subsequent arteritis. Because the clinical presentation of mycotic aortic aneurysms can be quite variable, the diagnosis hence can often be quite challenging. We herewith report an interesting case study in which the patient with a mycotic aortic aneurysm presented with the clinical picture masquerading as an acute coronary syndrome. The scenario reiterates the fact that despite the availability of accurate noninvasive imaging techniques, strong clinical suspicion might be imperative for the diagnosis of mycotic aneurysms.Item Open Access Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.(Journal of the American Heart Association, 2016-11-04) Cornel, Jan H; Ohman, E Magnus; Neely, Benjamin; Jakubowski, Joseph A; Bhatt, Deepak L; White, Harvey D; Ardissino, Diego; Fox, Keith AA; Prabhakaran, Dorairaj; Armstrong, Paul W; Erlinge, David; Tantry, Udaya S; Gurbel, Paul A; Roe, Matthew TThe relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3-level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10-unit decrease) were not independently associated with the 2-level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3-level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001).Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.Item Open Access Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial.(Clinical chemistry, 2012-01) Kohli, Payal; Bonaca, Marc P; Kakkar, Rahul; Kudinova, Anastacia Y; Scirica, Benjamin M; Sabatine, Marc S; Murphy, Sabina A; Braunwald, Eugene; Lee, Richard T; Morrow, David AObjective
We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.Background
Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.Methods
We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.Results
Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).Conclusions
ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.Item Open Access Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome.(Blood, 2012-11-29) Funderburg, Nicholas T; Zidar, David A; Shive, Carey; Lioi, Anthony; Mudd, Joseph; Musselwhite, Laura W; Simon, Daniel I; Costa, Marco A; Rodriguez, Benigno; Sieg, Scott F; Lederman, Michael MThe mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.Item Open Access Simplified Predictive Instrument to Rule Out Acute Coronary Syndromes in a High-Risk Population.(J Am Heart Assoc, 2015-12-14) Fanaroff, Alexander C; Schulteis, Ryan D; Pieper, Karen S; Rao, Sunil V; Newby, L KristinBACKGROUND: It is unclear whether diagnostic protocols based on cardiac markers to identify low-risk chest pain patients suitable for early release from the emergency department can be applied to patients older than 65 years or with traditional cardiac risk factors. METHODS AND RESULTS: In a single-center retrospective study of 231 consecutive patients with high-risk factor burden in which a first cardiac troponin (cTn) level was measured in the emergency department and a second cTn sample was drawn 4 to 14 hours later, we compared the performance of a modified 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Using Contemporary Troponins as the Only Biomarker (ADAPT) rule to a new risk classification scheme that identifies patients as low risk if they have no known coronary artery disease, a nonischemic electrocardiogram, and 2 cTn levels below the assay's limit of detection. Demographic and outcome data were abstracted through chart review. The median age of our population was 64 years, and 75% had Thrombosis In Myocardial Infarction risk score ≥2. Using our risk classification rule, 53 (23%) patients were low risk with a negative predictive value for 30-day cardiac events of 98%. Applying a modified ADAPT rule to our cohort, 18 (8%) patients were identified as low risk with a negative predictive value of 100%. In a sensitivity analysis, the negative predictive value of our risk algorithm did not change when we relied only on undetectable baseline cTn and eliminated the second cTn assessment. CONCLUSIONS: If confirmed in prospective studies, this less-restrictive risk classification strategy could be used to safely identify chest pain patients with more traditional cardiac risk factors for early emergency department release.