Abstract
Aims
Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl ...(IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients.
Methods and results
A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053).
Conclusions
Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.
It has been demonstrated that atherosclerotic disease progression is contingent upon chronic inflammation. The sequence of events leading up to plaque formation, instability, and eventual plaque ...rupture hinges upon the interaction of proinflammatory cytokines and fat deposition within the coronary vasculature. Over the past decade, a large body of evidence has demonstrated the efficacy of specific anti-inflammatory therapeutics in halting the progression of coronary artery disease. Despite this, these therapeutics have yet to be included in guideline-directed medical therapy regimens. This review will focus on several anti-inflammatories, which have been studied in the context of cardiovascular disease-colchicine, canakinumab, VIA-2291, and methotrexate, and will highlight the potential benefits majority hold in hindering atherosclerosis and cardiovascular disease progression. This holds especially true for individuals already on optimal medical therapy who continue to be at high risk for adverse cardiovascular events.
Coronary artery calcium (CAC) has been demonstrated as a noninvasive, low-cost means of assessing atherosclerotic burden and risk of major cardiovascular events. While it has been previously shown ...that CAC progression predicts all-cause mortality, we sought to quantify this association by examining a large cohort over a follow-up period of 1-22 years.
We studied 3260 persons aged 30-89 years referred by their primary physician for CAC measurement, with a follow-up scan at least 12 months from the initial scan. Receiver operator characteristic (ROC) curves assessed a level of annualized CAC progression that predicted all-cause mortality. Multivariate analyses using Cox proportional hazards models were used to compute hazard ratios and 95% confidence intervals (CIs) for the association between annualized CAC progression and death after adjusting for relevant cardiovascular risk factors.
The average time between scans was 4.7 ± 3.2 years with an additional average of 9.1 ± 4.0 years of follow-up time. The average age of the cohort was 58.1 ± 10.5 years, 70% being male, and 164 deaths occurred. Annualized CAC progression of 20 units optimized sensitivity (58%) and specificity (82%) in ROC curve analysis. Annualized CAC progression of 20 units was significantly associated with mortality while adjusting for age, sex, race, diabetes, hypertension, hyperlipidemia, smoking, baseline CAC level, family history, and time between scans, hazard ratio 1.84 (95% CI, 1.28-2.64) P = 0.001.
Annualized CAC progression of greater than 20 units per year significantly predicts all-cause mortality. This may add clinical value in encouraging close surveillance and aggressive treatment of individuals within this range.
Abstract
Aims
Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ...ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients.
Methods and results
EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40–115 mg/dL, and persistently high triglyceride levels (135–499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (−1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use.
Conclusion
EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial.
ClinicalTrials. govIdentifier
NCT029226027.
Coronary computed tomography angiography has emerged as an important diagnostic modality for evaluation of acute chest pain in the emergency department for patients at low to intermediate risk for ...acute coronary syndromes. Several clinical trials have shown excellent negative predictive value of coronary computed tomography angiography to detect obstructive coronary artery disease. Cardiac biomarkers such as troponins and creatine kinase MB, along with history, electrocardiogram, age, risk factors, troponin score, and Thrombolysis in Myocardial Infarction score should be used in conjunction with coronary computed tomography angiography for safe and rapid discharge of patients from the emergency department. Coronary computed tomography angiography along with high-sensitivity troponin assays could be effective for rapid evaluation of acute chest pain in the emergency department, but high-sensitivity troponins are not always available. Emergency department physicians are not quite comfortable making clinical decisions, especially if the coronary stenosis is in the range of 50% to 70%. In these cases, further evaluation with functional testing, such as nuclear stress testing or stress echocardiogram, is a common approach in many centers; however, newer methods such as fractional flow reserve computed tomography could be safely incorporated in coronary computed tomography angiography to help with clinical decision-making in these scenarios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Prosthetic valve endocarditis can be difficult to diagnose and cause significant morbidity and mortality, especially when no culture data are available to guide therapy. Transthoracic and ...transesophageal echocardiograms, the studies of choice for initial endocarditis evaluation, can be less reliable due to artifact and post-surgical changes. Some less common forms of endocarditis may be difficult to culture and, due to their fastidious nature, may delay the identification of causative organisms. Given the lack of directed antimicrobial treatment, culturenegative prosthetic valve endocarditis is specifically difficult. A wide differential diagnosis is critical to make a timely diagnosis and initiate treatment. Case Presentation: We present a case of a patient presenting with dyspnea which was found to have culture-negative endocarditis requiring mitral and aortic valve replacement that ultimately was complicated with culture-negative prosthetic valve endocarditis. Identifying a culprit organism made appropriate and timely antimicrobial treatment difficult, ultimately resulting in the patient dying from endocarditis complications. Conclusion: A high index of suspicion is needed when managing infective endocarditis, especially when prosthetic valves are involved. Diagnostic accuracy of cultures and echocardiography may be reduced when dealing with prosthetic valve endocarditis; thus, alternative methods of diagnosis may be required to make a timely diagnosis of causative organisms.
Iodixanol is an iso-osmolar non-ionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)-approved iso-osmolar ...agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low-osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. These contrast agents are used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability, and efficacy of iodixanol are reviewed, specifically evaluating the use of CCTA and coronary angiography, including outcome studies, randomized trials, and comparisons to other contrast agents.
Management of patients with stable ischemic heart disease remains challenging, in part due to the inability of non-invasive testing to accurately identify those who may benefit from coronary ...revascularization. For decades, use of functional testing, such as nuclear perfusion imaging, stress echocardiography, and exercise electrocardiography, has remained a pivotal component of algorithms designed to evaluate anginal pain. Over the past several years, however, a growing body of evidence has developed to support anatomical imaging, with special attention given to coronary computed tomography angiography (CCTA) as the more diagnostically and prognostically accurate non-invasive testing modality. The results of several large randomized controlled trials, as well as their subsequent post hoc analyses, have led to the escalation of CCTA as the first-line test in international guidelines for the evaluation of stable chest pain in patients with low-to-intermediate risk of coronary artery disease. Moreover, recognition of CCTA and its role in improving patient outcomes has driven key change in healthcare policy coverage, leading to streamlined reimbursement and the elimination of prior authorization when utilized in the appropriate setting. Given the rapidly accumulating supportive evidence, the next iteration of the American College of Cardiology/American Heart Association guidelines for stable ischemic heart disease should position CCTA as the first-line test in qualifying patients. Here, we review current literature evaluating anatomical and functional imaging, and formulate a discussion on clinical implementation, limitations of currently available data, and direction for CCTA-based future research.
Pseudoaneurysm is a rare but fatal complication of myocardial infarction (MI). With the advances in cardiovascular disease detection and treatments, fatal structural complications post-MI are now ...rare. When they occur, advanced diagnostic modalities can be used for early diagnosis, aiding surgical planning, and improving prognosis. In our case, post-MI left ventricle pseudoaneurysm complicated by hemopericardium was diagnosed using cardiac computed tomography angiography (CCTA). Use of attenuation measurement on CCTA helped diagnose active extravasation into the hemopericardium. This case highlights the high index of suspicion needed for rare but fatal complications post-MI and the utility of CCTA in their management.
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