Melissa A. Daubert

The utility of troponin measurement to detect myocardial infarction: review of the current findings

Myocardial infarction (MI) is defined by the presence of myocardial necrosis in combination with clinical evidence of myocardial ischemia. Cardiac troponins are regulatory proteins within the myocardium that are released into the circulation when damage to the myocyte has occurred. Therefore, serum troponin is an exquisitely sensitive marker of myocardial injury and is necessary for establishing the diagnosis of MI. High-sensitivity troponin assays are improving the diagnostic accuracy and rapid detection of myocardial infarction. The early identification of MI is vital for the institution of anti-thrombotic therapy to limit myocardial damage and preserve cardiac function. Troponin has both diagnostic and prognostic significance in the setting of acute coronary syndrome (ACS). Increased troponin levels in the absence of ACS should prompt an evaluation for an alternative, non-thrombotic mechanism of troponin elevation and direct management at the underlying cause. This review describes the role of troponin in the evaluation of patients with suspected myocardial infarction.

Congenital thoracic vascular anomalies: evaluation with state-of-the-art MR imaging and MDCT.

Congenital thoracic vascular anomalies include embryologic developmental disorders of the thoracic aorta, aortic arch branch arteries, pulmonary arteries, thoracic systemic veins, and pulmonary veins. Diagnostic evaluation of these anomalies in pediatric patients has evolved with innovations in diagnostic imaging technology. State-of-the-art magnetic resonance (MR) imaging, MR angiography multidetector-row computed tomographic (MDCT) angiography, and advanced postprocessing visualization techniques offer accurate and reliable high-resolution two-dimensional and three-dimensional noninvasive anatomic displays for interpretation and clinical management of congenital thoracic vascular anomalies. This article reviews vascular MR imaging, MR angiography, MDCT angiography, and advanced visualization techniques and applications for the assessment of congenital thoracic vascular anomalies, emphasizing clinical embryology and the characteristic imaging findings.

Choice of agreement indices for assessing and improving measurement reproducibility in a core laboratory setting

Clinical core laboratories, such as Echocardiography core laboratories, are increasingly used in clinical studies with imaging outcomes as primary, secondary, or surrogate endpoints. While many factors contribute to the quality of measurements of imaging variables, an essential step in ensuring the value of imaging data includes formal assessment and control of reproducibility via intra-observer and inter-observer reliability. There are many different agreement/reliability indices in the literature. However, different indices may lead to different conclusions and it is not clear which index is the preferred choice as an overall indication of data quality and a tool for providing guidance on improving quality and reliability in a core lab setting. In this paper, we pre-specify the desirable characteristics of an agreement index for assessing and improving reproducibility in a core lab setting; we compare existing agreement indices in terms of these characteristics to choose a preferred index. We conclude that, among the existing indices reviewed, the coverage probability for assessing agreement is the preferred agreement index on the basis of computational simplicity, its ability for rapid identification of discordant measurements to provide guidance for review and retraining, and its consistent evaluation of data quality across multiple reviewers, populations, and continuous/categorical data.

Quality Improvement Implementation: Improving Reproducibility in the Echocardiography Laboratory

BACKGROUND Interpretative variability can adversely affect echocardiographic reliability, but there is no widely accepted method to minimize variability and improve reproducibility. METHODS A continuous quality improvement process was devised that involves testing reproducibility by assessment of measurement differences followed by robust review, retraining, and retesting. Reproducibility was deemed acceptable if ≥80% of all interreader comparisons were within a prespecified acceptable difference. Readers not meeting this standard underwent retraining and retesting until acceptable reproducibility was achieved for the following parameters: left ventricular end-diastolic volume, biplane ejection fraction, mitral and aortic regurgitation, left ventricular outflow tract diameter, peak and mean aortic valve gradients, and aortic valve area. Eight hundred interreader comparisons for evaluation of reproducibility were generated from five readers interpreting 10 echocardiograms per testing cycle. The applicability and efficacy of this method were then evaluated by testing a second larger group of 10 readers and reevaluating reproducibility 1 year later. RESULTS All readers demonstrated acceptable reproducibility for biplane ejection fraction, mitral regurgitation, and peak and mean aortic valve gradients. Acceptable reproducibility for left ventricular end-diastolic volume, aortic regurgitation, and aortic valve area was achieved by four of five readers. No readers attained acceptable reproducibility on initial evaluation of left ventricular outflow tract diameter. After review and retraining, all readers demonstrated acceptable reproducibility, which was maintained on subsequent testing 1 year later. A second larger group of 10 readers was also evaluated and yielded similar results. CONCLUSIONS A continuous quality improvement process was devised that successfully reduced interpretative variability in echocardiography and improved reproducibility that was sustained over time.

Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide

Background Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction. Methods and Results In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ⩽35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg−1·h−1) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (−18 mL; P=0.009) and end-systolic volume (−14 mL; P=0.005) occurred at end infusion in the highest dose cohort. Conclusions This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose–effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464.

Utilization of coronary computed tomography angiography for exclusion of coronary artery disease in ED patients with low- to intermediate-risk chest pain: a 1-year experience ☆

OBJECTIVE We describe our preliminary experience with coronary computed tomography angiography (CCTA) in emergency department (ED) patients with low- to intermediate-risk chest pain. METHODS A convenience cohort of patients with low- to intermediate-risk acute chest pain presenting to a suburban ED in 2009 were prospectively enrolled if the attending physician ordered a CCTA for possible coronary artery disease. Demographic and clinician data were entered into structured data collection sheets required before any imaging. The results of CCTA were classified as normal, nonobstructive (1%-50% stenosis), and obstructive (>50% stenosis). Outcomes included hospital admission and death within a 6-month follow-up period. RESULTS In 2009, 507 patients with ED chest pain had a CCTA while in the ED. The median (interquartile range) age was 54 (47-62) years; 51.5% were female. Thrombolysis in myocardial infarction risk scores were 0 (42.6%), 1 (42.2%), 2 (11.8%), 3 (2.4%), and 4 (1.0%). The results of CCTA were normal (n = 363), nonobstructive (n = 123), and obstructive (n = 21). Admission rates by CCTA results were obstructive (90.5%), nonobstructive (4.9%), and normal (3.0%). None of the patients with normal or nonobstructive CCTA died within the 6-month follow-up period (0%; 95% confidence interval, 0-0.9%). CONCLUSIONS Many ED patients with low- to intermediate-risk chest pain have a normal or nonobstructive CCTA and may be safely discharged from the ED without any associated mortality within the following 6 months.

Heart Disease in Women

Navin C. Nanda, Nurgul Keser, 513 pages. New Delhi, India: Jaypee Brothers Medical Publishing Ltd. 2015.

Computer-aided analysis of 64-slice coronary computed tomography angiography: a comparison with manual interpretation.

184.00, ISBN-13: 978-9351522942 Heart disease is the leading cause of death among women. In comparison with men, women have greater cardiovascular mortality, report more morbidity, and have greater reductions in quality of life. Furthermore, sex disparities in cardiovascular health exist among women of all ages, socioeconomic backgrounds, and racial subgroups, which likely reflect both lingering diagnostic and treatment disparities, and underlying biological sex differences, as well. For example, there is a largely female predominance of stress-induced (Takotsubo) cardiomyopathy after menopause, a greater occurrence of heart failure with preserved ejection fraction, particularly in elderly women, and a higher incidence of rheumatic mitral stenosis among women in developing countries. In addition, after 55 years of age, hypertension is more prevalent in women than in men, particularly in black women. Clinical outcomes also differ by sex. Women with atrial fibrillation have a higher risk of thromboembolic events in comparison with men, and, among individuals younger than 55 years of age, the rate of acute myocardial infarction in the past decade has declined in men, but not in women. As the importance and impact of cardiovascular disease in women is increasingly recognized, we are learning how heart disease is distinct between the sexes, both in its pathophysiology and in our ability to diagnose and treat women. To better understand and appreciate sex differences in cardiovascular disease, there needs to be a compilation of current knowledge and an accessible tool that …

EFFECTS OF A NOVEL TETRAPEPTIDE IN HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF): A PHASE I RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF ELAMIPRETIDE

Coronary computed tomography angiography (CCTA) is increasingly used for the assessment of coronary heart disease (CHD) in symptomatic patients. Software applications have recently been developed to facilitate efficient and accurate analysis of CCTA. This study aims to evaluate the clinical application of computer-aided diagnosis (CAD) software for the detection of significant coronary stenosis on CCTA in populations with low (8%), moderate (13%), and high (27%) CHD prevalence. A total of 341 consecutive patients underwent 64-slice CCTA at 3 clinical sites in the United States. CAD software performed automatic detection of significant coronary lesions (>50% stenosis). CAD results were then compared to the consensus manual interpretation of 2 imaging experts. Data analysis was conducted for each patient and segment. The CAD had 100% sensitivity per patient across all 3 clinical sites. Specificity in the low, moderate, and high CHD prevalence populations was 64%, 41%, and 38%, respectively. The negative predictive value at the 3 clinical sites was 100%. The positive predictive value was 22%, 21%, and 38% for the low, moderate, and high CHD prevalence populations, respectively. This study demonstrates the utility of CAD software in 3 distinct clinical settings. In a low-prevalence population, such as seen in the emergency department, CAD can be used as a Computer-Aided Simple Triage tool to assist in diagnostic delineation of acute chest pain. In a higher prevalence population, CAD software is useful as an adjunct for both the experienced and inexperienced reader.

Treatment of Sleep-Disordered Breathing in Heart Failure Impacts Cardiac Remodeling: Insights from the CAT-HF Trial

Elamipretide is a novel tetrapeptide that targets mitochondrial dysfunction and has the potential to augment cardiac function in HFrEF. To assess the safety of elamipretide, 36 subjects with EF ≤ 35% and stable NYHA Class II-III were randomized (2:1) to a 4-hr IV infusion of elamipretide in 3