BACKGROUND:Type 2 myocardial infarction and myocardial injury are common in clinical practice, but long-term consequences are uncertain. We aimed to define long-term outcomes and explore risk ...stratification in patients with type 2 myocardial infarction and myocardial injury.
METHODS:We identified consecutive patients (n=2122) with elevated cardiac troponin I concentrations (≥0.05 µg/L) at a tertiary cardiac center. All diagnoses were adjudicated as per the universal definition of myocardial infarction. The primary outcome was all-cause death. Secondary outcomes included major adverse cardiovascular events (eg, nonfatal myocardial infarction or cardiovascular death) and noncardiovascular death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models.
RESULTS:The adjudicated index diagnosis was type 1 or 2 myocardial infarction or myocardial injury in 1171 (55.2%), 429 (20.2%), and 522 (24.6%) patients, respectively. At 5 years, all-cause death rates were higher in those with type 2 myocardial infarction (62.5%) or myocardial injury (72.4%) compared with type 1 myocardial infarction (36.7%). The majority of excess deaths in those with type 2 myocardial infarction or myocardial injury were because of noncardiovascular causes (hazard ratio, 2.32; 95% confidence interval, 1.92–2.81 versus type 1 myocardial infarction). Despite this finding, the observed crude major adverse cardiovascular event rates were similar between groups (30.6% versus 32.6%), with differences apparent after adjustment for covariates (hazard ratio, 0.82; 95% confidence interval, 0.69–0.96). Coronary heart disease was an independent predictor of major adverse cardiovascular events in those with type 2 myocardial infarction or myocardial injury (hazard ratio, 1.71; 95% confidence interval, 1.31–2.24).
CONCLUSIONS:Despite an excess in noncardiovascular death, patients with type 2 myocardial infarction or myocardial injury have a similar crude rate of major adverse cardiovascular events as those with type 1 myocardial infarction. Identifying underlying coronary heart disease in this vulnerable population may help target therapies that could modify future risk.
Advances in imaging technology have driven the rapid expansion in the use of CT in the assessment of coronary atherosclerotic plaque. Based on a rapidly growing evidence base, current guidelines ...recommend coronary CT angiography as the first‐line diagnostic test for patients presenting with stable chest pain. There is a growing need to refine current methods for diagnosis and risk stratification to improve the individualisation of preventative therapies. Imaging assessments of high‐risk plaque with CT can be used to differentiate stable from unstable patterns of coronary atherosclerosis and potentially to improve patient risk stratification. This review will focus on coronary imaging with CT with a specific focus on the detection of coronary atherosclerosis, high‐risk plaque features, and the implications for patient management.
Cycle-consistent generative adversarial network (CycleGAN) has been widely used for cross-domain medical image synthesis tasks particularly due to its ability to deal with unpaired data. However, ...most CycleGAN-based synthesis methods cannot achieve good alignment between the synthesized images and data from the source domain, even with additional image alignment losses. This is because the CycleGAN generator network can encode the relative deformations and noises associated to different domains. This can be detrimental for the downstream applications that rely on the synthesized images, such as generating pseudo-CT for PET-MR attenuation correction. In this paper, we present a deformation invariant cycle-consistency model that can filter out these domain-specific deformation. The deformation is globally parameterized by thin-plate-spline (TPS), and locally learned by modified deformable convolutional layers. Robustness to domain-specific deformations has been evaluated through experiments on multi-sequence brain MR data and multi-modality abdominal CT and MR data. Experiment results demonstrated that our method can achieve better alignment between the source and target data while maintaining superior image quality of signal compared to several state-of-the-art CycleGAN-based methods.
•Novel DiCyc architecture filters out domain-specific deformations.•The deformable layers are modified for less parameters and faster convergence.•Expectation–maximization training with 2-forward-1-backward back propagation.•New cycle-consistency and image alignment losses with less conflicted gradients.•An ablation study visualizes the trade-off between image alignment and quality.
Abstract Background In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography ...(CCTA). Objectives The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. Methods In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. Results Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios HRs: 0.39 95% confidence interval (CI): 0.23 to 0.68; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 95% CI: 1.08 to 1.55; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 95% CI: 3.12 to 5.20; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 95% CI: 0.28 to 0.88; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621). Conclusions In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial SCOT-HEART; NCT01149590 )
Calcific aortic stenosis, a relatively common problem in the elderly, has been found to be associated with atherosclerosis and hypercholesterolemia. This study found that, contrary to expectations, ...intensive lipid-lowering therapy with atorvastatin, which reduced low-density lipoprotein cholesterol levels to a mean of 63±23 mg per deciliter, had no effect on the progression of aortic stenosis (as measured by the aortic-jet velocity) or on aortic-valve calcification (as measured by helical computed tomographic scanning).
Intensive lipid-lowering therapy with atorvastatin had no effect on the progression of aortic stenosis or on aortic-valve calcification.
In the Western world, calcific aortic stenosis is the most common form of valvular heart disease, and its incidence increases with age such that 3 percent of adults over 75 years of age have aortic stenosis.
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It is a gradually progressive disease, characterized by a long asymptomatic phase, lasting several decades, followed by a shorter symptomatic phase associated with severe narrowing of the orifice of the aortic valve. Once symptoms occur, the prognosis is poor and surgery is usually mandated. Calcific aortic stenosis is now the leading indication for valve replacement in North America and Europe. However, there are currently . . .
High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway ...with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients.
Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary
yndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease.
The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9-98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0-99.9;
<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (
<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease.
Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile.
URL: http://clinicaltrials.gov. Unique identifier: NCT01852123.
Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the ...basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques.
BACKGROUND—Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, ...and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology.
METHODS AND RESULTS—Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (EnsemblRP11-94A24.1), which we termed smooth muscle–induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein.
CONCLUSIONS—These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies.
The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We ...used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG).
In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent 18F-NaF and 18F-FDG PET-CT, and invasive coronary angiography. 18F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of 18F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction.
In 37 (93%) patients with myocardial infarction, the highest coronary 18F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 IQR 1·40–2·25 vs highest non-culprit 1·24 1·06–1·38, p<0·0001). By contrast, coronary 18F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 1·40–2·13 vs 1·58 1·28–2·01, p=0·34). Marked 18F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal 18F-NaF uptake (maximum tissue-to-background ratio 1·90 IQR 1·61–2·17) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 1·09–1·19 vs 1·01 0·94–1·06; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% 21–29 vs 18% 14–22, p=0·001).
18F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease.
Chief Scientist Office Scotland and British Heart Foundation.
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