Natasha Clayton

Rule-In and Rule-Out of Myocardial Infarction Using Cardiac Troponin and Glycemic Biomarkers in Patients with Symptoms Suggestive of Acute Coronary Syndrome

BACKGROUND Early rule-in/rule-out of myocardial infarction (MI) in patients presenting to the emergency department (ED) is important for patient care and resource allocation. Given that dysglycemia is a strong risk factor for MI, we sought to explore and compare different combinations of cardiac troponin (cTn) cutoffs with glycemic markers for the early rule-in/rule-out of MI. METHODS We included ED patients (n = 1137) with symptoms suggestive of acute coronary syndrome (ACS) who had cTnI, high-sensitivity cTnI (hs-cTnI), hs-cTnT, glucose, and hemoglobin A1c (Hb A1c) measurements. We derived rule-in/rule-out algorithms using different combinations of ROC-derived and literature cutoffs for rule-in and rule-out of MI within 7 days after presentation. These algorithms were then tested for MI/cardiovascular death and ACS/cardiovascular death at 7 days. ROC curves, sensitivity, specificity, likelihood ratios, positive and negative predictive values (PPV and NPV), and CIs were determined for various biomarker combinations. RESULTS MI was diagnosed in 133 patients (11.7%; 95% CI, 9.8-13.8). The algorithms that included cTn and glucose produced the greatest number of patients ruled out/ruled in for MI and yielded sensitivity ≥99%, NPV ≥99.5%, specificity ≥99%, and PPV ≥80%. This diagnostic performance was maintained for MI/cardiovascular death but not for ACS/cardiovascular death. The addition of hemoglobin A1c (Hb A1c) (≥6.5%) to these algorithms did not change these estimates; however, 50 patients with previously unknown diabetes may have been identified if Hb A1c was measured. CONCLUSIONS Algorithms incorporating glucose with cTn may lead to an earlier MI diagnosis and rule-out for MI/cardiovascular death. Addition of Hb A1c into these algorithms allows for identification of diabetes. Future studies extending these findings are needed for ACS/cardiovascular death. ClinicalTrials.gov identifier: NCT01994577.

Economic Considerations of Early Rule-In/Rule-Out Algorithms for The Diagnosis of Myocardial Infarction in The Emergency Department Using Cardiac Troponin and Glycemic Biomarkers

BACKGROUND We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS). METHODS We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A1c (Hb A1c) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative). RESULTS Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly. CONCLUSIONS Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs.

High-Sensitivity Cardiac Troponin Risk Cutoffs for Acute Cardiac Outcomes at Emergency Department Presentation

The optimal high-sensitivity cardiac troponin (hs-cTn) cutoffs for determining risk in patients who present with acute coronary syndrome symptoms are unknown. In 1137 emergency department patients we calculated adjusted relative risks for a composite outcome (myocardial infarction, unstable angina, heart failure, ventricular arrhythmia, or cardiovascular death) within 7 days for the presentation of hs-cTnT (Roche) and hs-cTnI (Abbott) assay concentrations on the basis of literature cutoffs. Patients with hs-cTn concentrations ≥ 14 ng/L had an adjusted relative risk of 4.9 for the composite outcome, with different hs-cTnT/hs-cTnI concentration ranges yielding higher risks. A common low-risk cutoff of 14 ng/L may be used for hs-cTn with higher cutoffs identifying high-risk patients.

A laboratory score at presentation to rule-out serious cardiac outcomes or death in patients presenting with symptoms suggestive of acute coronary syndrome

BACKGROUND We evaluated whether a low high-sensitivity cardiac troponin (hs-cTn) cutoff combined with glucose, red cell distribution width (RDW), and the estimated glomerular filtration rate (eGFR) can be used to rule-out a serious cardiac outcome or death in patients presenting with symptoms suggestive of acute coronary syndrome (ACS). METHODS This was a prospective observational emergency department (ED) study enrolling consecutive patients presenting with symptoms suggestive of ACS (ClinicalTrials.gov: NCT01994577). The primary outcome was a 7-day composite of myocardial infarction, unstable angina, decompensated congestive heart failure, serious ventricular cardiac arrhythmia, or death. A laboratory score combining glucose, RDW, eGFR with hs-cTnT (Roche) or hs-cTnI (Abbott) was compared to hs-cTn alone using the limit of detection (LoD; hs-cTnT<5ng/l/hs-cTnI<2ng/l) as the cutoff. A benchmark of >99% sensitivity was used to assess the laboratory panel with hs-cTn versus the LoD alone to identify low-risk patients suitable for discharge. RESULTS A total of 1095 patients (n=267 composite-outcomes) had measurements of glucose, RDW, eGFR, hs-cTnT, and hs-cTnI at presentation. Applying the hs-cTn LoD alone as the cutoff missed 5 composite-outcomes (sensitivity=98.1%), however the addition of the laboratory panel to the hs-cTn LoD increased the sensitivity to >99% with approximately 10% of the population identified as low-risk. The percentage of low-risk patients was increased to 15% (1 composite-outcome missed) when employing a low measurable hs-cTnI cutoff with the laboratory panel (laboratory score<2 points). CONCLUSION A laboratory score with hs-cTn may identify low-risk patients suitable for ED discharge at presentation.

The General Public’s Willingness to Pay for Tax Increases to Support Unrestricted Access to an Alzheimer’s Disease Medication

AbstractBackground: Alzheimer’s disease (AD) is a neurodegenerative disorder highlighted by progressive declines in cognitive and functional abilities. Objective: Our objective was to assess the general public’s maximum willingness to pay MWTP for an increase in annual personal income taxes to fund unrestricted access to AD medications. Methods: We randomly recruited 500 Canadians nationally and used computer-assisted telephone interviewing to administer a questionnaire. The questionnaire contained four ‘efficacy’ scenarios describing an AD medication as capable of symptomatically treating cognitive decline or modifying disease progression. The scenarios also described the medication as having no adverse effects or a 30% chance of adverse effects. We randomized participants to order of scenarios and willingness-to-pay bid values; MWTP for each scenario was the highest accepted bid for that scenario. We conducted linear regression and bootstrap sensitivity analyses to investigate potential determinants of MWTP. Results: Mean MWTP was highest for the ‘disease modification/no adverse effects’ scenario (

Performance of high-sensitivity cardiac troponin in the emergency department for myocardial infarction and a composite cardiac outcome across different estimated glomerular filtration rates

Can130.26) and lowest for the ‘symptomatic treatment/30% chance of adverse effects’ scenario (

Caregivers’ willingness-to-pay for Alzheimer’s disease medications in Canada

Can99.16). Bootstrap analyses indicated none of our potential determinants (e.g. age, sex) were associated with participants’ MWTP. Conclusions: The general public is willing to pay higher income taxes to fund unrestricted access to AD (especially disease-modifying) medications. Consequently, the public should favour placing new AD medications on public drug plans. As far as we are aware, no other study has elicited the general public’s willingness to pay for AD medications.

High-sensitivity cardiac troponin concentrations at emergency department presentation in females and males with an acute cardiac outcome

BACKGROUND Clinicians regularly observe increased high-sensitivity cardiac troponin (hs-cTn) concentrations in patients with low estimated glomerular filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome (ACS) from increased hs-cTn results across a range of eGFR. The objective of this study was to determined the optimal hs-cTn concentrations for acute myocardial infarction (MI) and a composite cardiovascular outcome across different eGFR ranges and to assess the utility of a low hs-cTn cutoff to rule-out events. METHODS We undertook an observational study in the emergency department of patients (n = 1212) with symptoms suggestive of ACS who had an eGFR and at least one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a composite of MI, unstable angina, congestive heart failure, serious ventricular cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed across different eGFR ranges (<30,30-59,60-89,≥90 ml/min/1.73m2) by spearman correlation, ROC-curve analyses, and sensitivity and negative predictive value (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6 ng/l) for the outcomes. RESULTS Both hs-cTnI and hs-cTnT concentrations were negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR≥90. CONCLUSION The test performance for hs-cTn for diagnosing or ruling-out an acute cardiac event varies per the eGFR. Accurate risk stratification requires knowledge of the eGFR.

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department

We studied caregivers’ willingness-to-pay for Alzheimer’s disease drug therapy. We recruited 216 caregivers of persons with mild or moderate Alzheimer’s disease and presented them with four scenarios describing a hypothetical Alzheimer’s disease medication. The scenarios described the medication as capable of either treating the symptoms of disease or modifying the course of disease. The scenarios also presented two different probabilities of adverse effects occurrence, i.e. 0% or 30%. Most caregivers said they would pay out-of-pocket for the medication, with support for such payment ranging from 68% to 93%, depending on the specific scenario. The highest level of support was for the ‘disease modifying and no adverse effects’ scenario, while the lowest level was for the ‘symptom treatment and 30% chance of adverse effects’ scenario. On average, caregivers’ monthly willingness-to-pay out-of-pocket for the medication ranged from

A COMPARISON OF HEALTH UTILITY SCORES CALCULATED USING UNITED KINGDOM AND CANADIAN PREFERENCE WEIGHTS IN AN ALZHEIMER'S DISEASE SAMPLE

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