Discriminatory power of a circulating multi-noncoding RNA panel in acute coronary syndrome subtypes: Towards precision detection.

BACKGROUND: Acute Coronary Syndrome (ACS) stands as a significant contributor to cardiovascular mortality, necessitating improved diagnostic tools for early detection and tailored therapeutic interventions. Current diagnostic modalities, exhibit limitations in sensitivity and specificity, urging the quest for novel biomarkers to enhance discrimination of the different stages of ACS including unstable angina, Non-ST-segment Elevation Myocardial Infarction (NSTEMI), and ST-segment Elevation Myocardial Infarction (STEMI). METHODS: This study investigated the potential of a plasma-circulating multi-noncoding RNA (ncRNA) panel, comprising four miRNAs (miR-182-5p, miR-23a-3p, miR-146a-5p, and miR-183-5p) and three lncRNAs (SNHG15, SNHG5, and RMRP), selected based on their intricate involvement in ACS pathogenesis and signaling pathways regulating post-myocardial infarction (MI) processes. The differential expression of these ncRNAs was validated in sera of ACS patients and healthy controls via real-time polymerase chain reaction (RT-PCR). RESULTS: Analysis revealed a marked upregulation of the multi-ncRNAs panel in ACS patients. Notably, miRNA-182-5p and lncRNA-RMRP exhibited exceptional discriminatory power, indicated by the high area under the curve (AUC) values (0.990 and 0.980, respectively). Importantly, this panel displayed superior efficacy in discriminating between STEMI and NSTEMI, outperforming conventional biomarkers like creatine kinase-MB and cardiac troponins. Additionally, the four miRNAs and lncRNA RMRP showcased remarkable proficiency in distinguishing between STEMI and unstable angina. CONCLUSION: The findings underscore the promising potential of the multi-ncRNA panel as a robust tool for early ACS detection, and precise differentiation among ACS subtypes, and as a potential therapeutic target.

Organized thrombus is a frequent underlying feature in culprit lesion morphology in non-ST-elevation myocardial infarction. A study using optical coherence tomography and magnetic resonance imaging.

The concept that the culprit lesion in non-ST segment elevation myocardial infarction (NSTEMI) is caused by sudden plaque rupture with acute thrombus formation has recently been challenged. While angiography is an old gold-standard for culprit identification it merely visualizes the lumen contour. Optical coherence tomography (OCT) provides a detailed view of culprit features. Combined with myocardial edema on cardiac magnetic resonance (CMR), indicating acute ischemia and thus culprit location, we aimed to characterize culprit lesions using OCT. Patients with NSTEMI referred for angiography were prospectively enrolled. OCT was performed on angiographic stenoses ≥50% and on operator-suspected culprit lesions. Hierarchical OCT-culprit identifiers were defined in case of multiple unstable lesions, including OCT-defined thrombus age. An OCT-based definition of an organizing thrombus as corresponding to histological early healing stage was introduced. Lesions were classified as OCT-culprit or non-culprit, and characteristics compared. CMR was performed in a subset of patients. We included 65 patients with 97 lesions, of which 49 patients (75%) had 53 (54%) OCT-culprit lesions. The most common OCT-culprit identifiers were the presence of acute (66%) and organizing thrombus (19%). Plaque rupture was visible in 45% of OCT-culprit lesions. CMR performed in 38 patients revealed myocardial oedema in the corresponding territories of 67% of acute thrombi and 50% of organizing thrombi. A culprit lesion was identified by OCT in 75% patients with NSTEMI. Acute thrombus was the most frequent feature followed by organizing thrombus. Applying specific OCT-criteria to identify the culprit could prove valuable in ambiguous cases.

Differentiation of acute non-ST elevation myocardial infarction and acute infarct-like myocarditis by visual pattern analysis: a head-to-head comparison of different cardiac MR techniques.

OBJECTIVES: Parametric cardiac magnetic resonance (CMR) techniques have improved the diagnosis of pathologies. However, the primary tool for differentiating non-ST elevation myocardial infarction (NSTEMI) from myocarditis is still a visual assessment of conventional signal-intensity-based images. This study aimed at analyzing the ability of parametric compared to conventional techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns. METHODS: Twenty NSTEMI patients, twenty infarct-like myocarditis patients, and twenty controls were examined using cine, T2-weighted CMR (T2w) and late gadolinium enhancement (LGE) imaging and T1/T2 mapping on a 1.5 T scanner. CMR images were presented in random order to two experienced fully blinded observers, who had to assign them to three categories by a visual analysis: NSTEMI, myocarditis, or healthy. RESULTS: The conventional approach (cine, T2w and LGE combined) had the best diagnostic accuracy with 92% (95%CI: 81-97) for NSTEMI and 86% (95%CI: 71-94) for myocarditis. The diagnostic accuracies using T1 maps were 88% (95%CI: 74-95) and 80% (95%CI: 62-91), 84% (95%CI: 67-93) and 74% (95%CI: 54-87) for LGE, and 83% (95%CI: 66-92) and 73% (95%CI: 53-87) for T2w. The accuracies for cine (72% (95%CI: 52-86) and 60% (95%CI: 38-78)) and T2 maps (62% (95%CI: 40-79) and 47% (95%CI: 28-68)) were significantly lower compared to the conventional approach (p < 0.001 and p < 0.0001). CONCLUSIONS: The conventional approach provided a reliable visual discrimination between NSTEMI, myocarditis, and controls. The diagnostic accuracy of a visual pattern analysis of T1 maps was not significantly inferior, whereas the diagnostic accuracy of T2 maps was not sufficient in this context. CLINICAL RELEVANCE STATEMENT: The ability of parametric compared to conventional CMR techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns can avoid potentially unnecessary invasive coronary angiography and help to shorten CMR protocols and to reduce the need of gadolinium contrast agents. KEY POINTS: • A visual differentiation of ischemic from non-ischemic patterns of myocardial injury is reliably achieved by a combination of conventional CMR techniques (cine, T2-weighted and LGE imaging). • There is no significant difference in accuracies between visual pattern analysis on native T1 maps without providing quantitative values and a conventional combined approach for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls. • T2 maps do not provide a sufficient diagnostic accuracy for visual pattern analysis for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls.

FEATURES OF ANATOMICAL LESIONS OF CORONARY ARTERIES DEPENDING ON THE LEVELS OF ST2 AND TROPONIN I IN BLOOD PLASMA IN PATIENTS WITH NSTEMI.

The aim of the study is to evaluate the dependence of associations of ST2, and Troponin I level on the nature of the anatomical lesion of the coronary arteries. We examined 200 patients with NSTEMI aged 38 to 80 years, who were urgently hospitalized in the Vinnytsya Regional Clinical Center of Cardiovascular Pathology. All patients underwent laboratory testing of ST2, and Troponin I level in plasma by enzyme-linked immunosorbent assay on the first day of hospitalization before coronary angiography. In the association of relatively high levels of ST2 and relatively high levels of Troponin I, there is a positive correlation between the degree of coronary arteries damage, while in the association of relatively low levels of ST2 and Troponin I, severe stenotic coronary arteries lesions can be ruled out. Determining the associations of ST2 and Troponin I before coronary angiography allows to predict the degree of stenotic lesions of the coronary arteries and to determine the expected intervention strategy in patients with NSTEMI.

Intracoronary monocyte expression pattern and HDL subfractions after non-ST elevation myocardial infarction.

AIMS: Coronary artery disease (CAD) is described as a range of clinical conditions including myocardial infarction (MI) and unstable angina. Lipid and apolipoprotein profiles together with the study of cholesterol deposit and efflux serve to identify novel pre and post infarct scenarios for the treatment of these patients. In (non-ST elevation myocardial infarction) NSTEMI patients, we analysed both systemic and intracoronary serum ability to accept cholesterol as well as cholesterol efflux capacity (CEC) of monocytes in terms of expression of genes involved in the reverse cholesterol transport (RCT). METHODS AND RESULTS: While HDL-C quantity was similar between systemic and coronary arterial blood, in 21 NSTEMI patients we observed a significant reduction of the preß-HDL fraction and the levels of Apolipoproteins AI, AII, B and E in coronary versus systemic serum. These data are complemented with the observed reduction of CEC. On the contrary, compared to systemic arterial monocytes, in coronary microenvironment of NSTEMI patients after myocardial infarction, the monocytes exhibited a higher mRNA expression of nuclear receptor LXRα and its targets ABCA1 and APOE, which drive cholesterol efflux capacity. CONCLUSION: In this cross-sectional study we observe that in the immediate post infarction period, there is a spontaneous bona fide ligand-induced activation of the LXR driven cholesterol efflux capacity of intracoronary monocytes to overcome the reduced serum ability to accept cholesterol and to inhibit the post-infarction pro-inflammatory local microenvironment.

Retrospective assessment of at-risk myocardium in reperfused acute myocardial infarction patients using contrast-enhanced balanced steady-state free-precession cardiovascular magnetic resonance at 3T with SPECT validation.

BACKGROUND: Contrast-enhanced (CE) steady-state free precession (SSFP) CMR at 1.5T has been shown to be a valuable alternative to T2-based methods for the detection and quantifications of area-at-risk (AAR) in acute myocardial infarction (AMI) patients. However, CE-SSFP's capacity for assessment of AAR at 3T has not been investigated. We examined the clinical utility of CE-SSFP and T2-STIR for the retrospective assessment of AAR at 3T with single-photon-emission-computed tomography (SPECT) validation. MATERIALS AND METHODS: A total of 60 AMI patients (ST-elevation AMI, n = 44;  non-ST-elevation AMI, n = 16) were recruited into the CMR study between 3 and 7 days post revascularization. All patients underwent T2-STIR, CE-bSSFP and late-gadolinium-enhancement CMR. For validation, SPECT images were acquired in a subgroup of patients (n = 30). RESULTS: In 53 of 60 patients (88 %), T2-STIR was of diagnostic quality compared with 54 of 60 (90 %) with CE-SSFP. In a head-to-head per-slice comparison (n = 365), there was no difference in AAR quantified using T2-STIR and CE-SSFP (R2 = 0.92, p < 0.001; bias:-0.4 ± 0.8 cm2, p = 0.46). On a per-patient basis, there was good agreement between CE-SSFP (n = 29) and SPECT (R2 = 0.86, p < 0.001; bias: - 1.3 ± 7.8 %LV, p = 0.39) for AAR determination. T2-STIR also showed good agreement with SPECT for AAR measurement (R2 = 0.81, p < 0.001, bias: 0.5 ± 11.1 %LV, p = 0.81). There was also a strong agreement between CE-SSFP and T2-STIR with respect to the assessment of AAR on per-patient analysis (R2 = 0.84, p < 0.001, bias: - 2.1 ± 10.1 %LV, p = 0.31). CONCLUSIONS: At 3T, both CE-SSFP and T2-STIR can retrospectively quantify the at-risk myocardium with high accuracy.

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Impact of clinical presentations on lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

Optical coherence tomography assessment of macrophages accumulation in non-ST-segment elevation acute coronary syndromes.

AIMS: To investigate in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) the prevalence and the features of optical coherence tomography (OCT)-detected macrophages accumulation in culprit plaques as compared with nonculprit plaques (NCP). METHODS: The study is a post-hoc analysis of a prospective study aimed at evaluating the relationship between aortic inflammation as assessed by F-fluorodeoxyglucose-PET and features of coronary plaque vulnerability as assessed by OCT. We enrolled 32 patients with first NSTE-ACS who successfully underwent three-vessel OCT. RESULTS: The median age was 65 (54-72) years and 27 patients (84%) were men. Culprit plaques were clinically defined. Overall, the rate of lipid plaques and lipid plaques containing macrophages were 6.4 and 4.2 per patient, respectively. Culprit plaques had a smaller minimal luminal area, a higher extension of lipid component and a thinner fibrous cap than NCPs. Macrophages accumulations were more likely found in culprit plaque (84 vs. 61%, P = 0.015) in which they had also a higher circumferential extension. On univariable analysis, macrophages accumulation extension had a higher association with culprit plaques (odds ratio = 4.42; 95% confidence interval; 2.54-9.15, P < 0.001) than the mere presence of macrophages accumulation (odds ratio = 3.36; 95% confidence interval; 1.30-8.66, P = 0.012). Culprit plaques with thrombus had a lower distance between macrophages accumulation and the luminal surface than culprit plaque with no thrombus (0.06 vs. 0.1 mm; P = 0.04). CONCLUSION: In patients with NSTE-ACS, macrophages accumulations are more likely present in culprit plaque in which they disclose also a greater extension compared with those observed in NCP. The distance between macrophages accumulation and the luminal surface is lower in thrombotic culprit plaque than that in nonthrombotic culprit plaque.

Prognostic Value of Psoas Muscle Mass Index in Patients With Non‒ST-Segment‒Elevation Myocardial Infarction: A Prospective Observational Study.

Background Muscle wasting is an important predictor of long-term outcome in patients with cardiovascular disease, but the prognostic value of muscle wasting in patients with non‒ST-segment‒elevation myocardial infarction is not established. The aim of this study is to investigate the prognostic value of muscle wasting, defined by psoas muscle mass index (PMI), in patients with non‒ST-segment‒elevation myocardial infarction. Methods and Results A total of 132 consecutive patients with non‒ST-segment‒elevation myocardial infarction were prospectively enrolled between 2015 and 2018. Primary end point was incidence of cardiovascular events including cardiovascular deaths, non-fatal myocardial infarction, or non-fatal stroke. Cross-sectional area of the psoas muscle at the L3 vertebral level was obtained by computed tomography and PMI was calculated. The median follow-up period was 2.4 years (interquartile range, 1.1-4.0 years). There were 45 cardiovascular events (34%) during the study periods. The optimal cutoff value of PMI to predict cardiovascular events was 772 mm2/m2, as assessed by receiver operating curve analysis. Patients with reduced PMI (PMI<772 mm2/m2) had significantly higher cardiovascular events than those with preserved PMI (PMI≥772 mm2/m2) (48% versus 21%; log-rank test P<0.001). Multivariate Cox proportional hazards model revealed that reduced PMI was a statistically significant predictor of cardiovascular events (hazard ratio, 3.30; 95% CI, 1.70-6.40; P<0.001). Conclusions Muscle wasting defined as PMI is a simple and useful objective marker to predict future cardiovascular outcome in patients with non‒ST-segment‒elevation myocardial infarction. Registration Information URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000013445.

Circulating microparticle concentrations across acute and chronic cardiovascular disease conditions.

Concentrations of different circulating microparticles (MPs) may have clinical and physiological relevance to cardiovascular disease pathologies. PURPOSE: To quantify plasma concentrations of CD31+/CD42b-, CD62E+, and CD34+ MPs across healthy individuals and those with coronary artery disease (CAD) or acute cardiovascular events (non-ST elevation myocardial infarction (NSTEMI)). Fasted blood was obtained from CAD patients (n = 10), NSTEMI patients (n = 13), and healthy older men (n = 15) 60-75 years old. METHODS: CD31+/CD42b-, CD62E+, and CD34+ MPs were isolated from plasma and quantified using flow cytometry. Relationships between MP subtypes, fasting blood lipids, blood glucose, blood pressure, body mass index, and total number of medications were assessed. RESULTS: Concentrations of CD31+/CD42b- MPs were significantly lower in CAD and NSTEMI subjects compared with healthy individuals (p = .02 and .003, respectively). No differences between groups were found for CD62E+ or CD34+ MPs (p > .05 for both). Surprisingly, among all variables assessed, only CD62E+ MP concentrations were positively correlated with triglyceride levels (p = .012) and inversely correlated with SBP (p = .03). CONCLUSIONS: Our findings provide support for the use of different MP subtypes, specifically CD31+/CD42b- MPs, as a potential biomarker of cardiovascular disease. Importantly, results from this study should be looked at in adjunct to previous MP work in CVD conditions as a way of highlighting the complex interactions of variables such as comorbid conditions and medications on MP concentrations.

Clinical Outcomes and Predictors of ST-Elevation Versus Non-ST-Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) can be clinically categorized as ST-segment elevation (STE) and non-ST-segment elevation (NSTE), whose clinical prognosis are poorly understood. The aim of this study was to compare the clinical outcome and their predictors of patients with STE and NSTE in MINOCA population. METHODS: A total of 265 patients with MINOCA (102 with STE, and 163 with NSTE) were consecutively collected. Clinical profile, prognosis, and predictors of all patients were assessed. RESULTS: The proportion of patients with NSTE was greater than patients with STE in MINOCA population. Patients with NSTE were older and more likely to be female and had a higher incidence of atrial fibrillation. Both high density lipoprotein (HDL) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were higher in the NSTE group. Patients with STE were more likely to have a history of smoking and a higher diastolic blood pressure. During the 1-year follow up, there were no differences in the outcomes between the STE and NSTE groups, with no significant differences in mortality and a similar rate of major adverse cardiovascular events (MACE) (20.9% vs 19.3%, P = 0.767). The multivariable predictors of MACE in the NSTE groups were age, lower level of total cholesterol, hypertension, and smoking history, whereas reduced left ventricular ejection fraction, and diabetes mellitus were the multivariable predictors of major adverse cardiac events in the STE group. CONCLUSIONS: There were differences in the clinical profile between STE and NSTE in the MINOCA population, whereas the outcomes during the 1-year follow up were similar. The STE and NSTE groups had different predictive factors for major adverse cardiac events.

Association of trimethylamine N-oxide with coronary atherosclerotic burden in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. MATERIAL AND METHODS: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.

Effect of Levothyroxine on Left Ventricular Ejection Fraction in Patients With Subclinical Hypothyroidism and Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: Thyroid hormones play a key role in modulating myocardial contractility. Subclinical hypothyroidism in patients with acute myocardial infarction is associated with poor prognosis. Objective: To evaluate the effect of levothyroxine treatment on left ventricular function in patients with acute myocardial infarction and subclinical hypothyroidism. Design, Setting, and Participants: A double-blind, randomized clinical trial conducted in 6 hospitals in the United Kingdom. Patients with acute myocardial infarction including ST-segment elevation and non-ST-segment elevation were recruited between February 2015 and December 2016, with the last participant being followed up in December 2017. Interventions: Levothyroxine treatment (n = 46) commencing at 25 µg titrated to aim for serum thyrotropin levels between 0.4 and 2.5 mU/L or identical placebo (n = 49), both provided in capsule form, once daily for 52 weeks. Main Outcomes and Measures: The primary outcome measure was left ventricular ejection fraction at 52 weeks, assessed by magnetic resonance imaging, adjusted for age, sex, type of acute myocardial infarction, affected coronary artery territory, and baseline left ventricular ejection fraction. Secondary measures were left ventricular volumes, infarct size (assessed in a subgroup [n = 60]), adverse events, and patient-reported outcome measures of health status, health-related quality of life, and depression. Results: Among the 95 participants randomized, the mean (SD) age was 63.5 (9.5) years, 72 (76.6%) were men, and 65 (69.1%) had ST-segment elevation myocardial infarction. The median serum thyrotropin level was 5.7 mU/L (interquartile range, 4.8-7.3 mU/L) and the mean (SD) free thyroxine level was 1.14 (0.16) ng/dL. The primary outcome measurements at 52 weeks were available in 85 patients (89.5%). The mean left ventricular ejection fraction at baseline and at 52 weeks was 51.3% and 53.8%, respectively, in the levothyroxine group compared with 54.0% and 56.1%, respectively, in the placebo group (adjusted difference in groups, 0.76% [95% CI, -0.93% to 2.46%]; P = .37). None of the 6 secondary outcomes showed a significant difference between the levothyroxine and placebo treatment groups. There were 15 (33.3%) and 18 (36.7%) cardiovascular adverse events in the levothyroxine and placebo groups, respectively. Conclusions and Relevance: In this preliminary study involving patients with subclinical hypothyroidism and acute myocardial infarction, treatment with levothyroxine, compared with placebo, did not significantly improve left ventricular ejection fraction after 52 weeks. These findings do not support treatment of subclinical hypothyroidism in patients with acute myocardial infarction. Trial Registration: isrctn.org Identifier: http://www.isrctn.com/ISRCTN52505169.

A rare transitory change of the De Winter ST/T-wave complex in a patient with cardiac arrest: A case report.

RATIONALE: The De Winter ST/T-wave complex is a rare and special electrocardiogram (ECG) manifestation in some patients with a total or subtotal occlusion in the proximal left anterior descending (LAD) coronary artery. It mainly appears as an ST-segment superior oblique depression instead of an ST elevation. However, a transitory change of the De Winter ST/T-wave complex has not been reported previously. PATIENT CONCERNS: A 40-year-old man developed sudden precordial dull and unrelieved pain. One hour later, he suddenly lost consciousness when he arrived at the emergency department. After successful cardiopulmonary resuscitation (CPR), 2 ECGs were taken at 22-minute interval, which showed completely different manifestations. The first ECG showed acute inferior-wall ST elevation myocardial infarction (STEMI), while the second ECG showed a De Winter ST/T-wave complex, which indicated acute anterior-wall myocardial infarction. DIAGNOSIS: The patient was diagnosed with acute myocardial infarction. INTERVENTIONS: The patient responded to urgent treatment by percutaneous coronary intervention (PCI). OUTCOMES: It was confirmed that the case was consistent with the main characteristics of a De Winter ST/T-wave complex after PCI. The first ECG was a rare transitory change of the De Winter ST/T-wave complex. The patient was well recovered and discharged. LESSONS: The De Winter ST/T-wave complex is an extremely dangerous and rare ECG manifestation that is not widely recognized at present. Although the mechanism is not very clear, it should be considered as indicating an equivalent risk of STEMI because it may suggest total or subtotal occlusion in the proximal LAD coronary artery. It is believed that in the near future, the mechanism of ECG including its transitory changes, will be fully revealed.

Diagnostic and prognostic value of 2D-Strain in Non-ST Elevation Myocardial Infarction.

BACKGROUND: Strain has shown a promising diagnostic and prognostic value in acute coronary syndromes. With, however, less data in non-ST elevation myocardial infarction (NSEMI). AIM: to evaluate in NSTEMI patients, the ability of strain to predict the severity of the disease, by assessing correlations to established prognostic parameters, and to predict culprit and occluded coronary arteries (CA). Secondary, to determine factors associated to strain changes during follow-up. METHODS: The study was prospective, NSTEMI patients with significant coronary lesion and without significant non-ischaemic disease were included. Angiographic and echocardiographic investigation including global (GLS) and territorial (TLS) longitudinal strain were performed within 24h from admission. Syntax I score was calculated. Severe coronary artery disease (CAD) was defined by left main of three-vessel disease. RESULTS: Seventy NSTEMI patients aged 60.2±10.1 years were enrolled; 61% were smokers, 54% diabetics and 46% hypertensive. 34% had a severe CAD, 7% had an acute coronary occlusion (ACO) and 14% a chronic coronary total occlusion (CTO). GLS >-15.3% predicted a left ventricular ejection fraction (LVEF) <50% with 80% Sensitivity (Se) and 78% Specificity (Sp). GLS was associated to CAD complexity and severity. GLS > -14.1% detected severe CAD with 83% Se and 80%Sp. TLS determined the culprit artery in 74% of cases and TLS > -9.2% predicted ACO with 85% Se and 85% Sp. TLS was also associated to CTO. At a 10 months median follow-up [3-12months], GLS significantly improved, baseline LVEF, GLS, wall motion score index and revascularization were the predictors of this improvement. CONCLUSION: In NSTEMI patients, GLS detected severe CAD and poor myocardial function. TLS predicted the culprit vessel and its occlusion. GLS improvement at midterm was predicted by baseline systolic LV function parameters and myocardial revascularization.

Endothelial Microvesicles Circulating in Peripheral and Coronary Circulation Are Associated With Central Blood Pressure in Coronary Artery Disease.

BACKGROUND: Endothelial microvesicles (EMVs) have emerged as markers of endothelial injury. However, little is known about their levels in the coronary circulation of acute coronary syndrome (ACS) and stable coronary artery disease (CAD). We hypothesized that ACS patients exhibit a more pronounced increase of EMVs both in the peripheral and coronary circulation when compared with CAD. We also investigated possible associations of EMVs with markers preclinical target organ damage. METHODS: We enrolled consecutive eligible patients undergoing coronary angiography. Blood samples were collected from the stem of the left coronary artery and the femoral artery. ΕMVs were measured by a standardized flow cytometry protocol. Central systolic blood pressure (cSBP) was measured invasively and patients' history was recorded. RESULTS: CAD patients exhibited increased levels of EMVs compared with controls. When patients with ACS and stable CAD were compared, the former had significantly increased EMVs in both coronary and peripheral circulation. Importantly, both ACS and CAD patients exhibited increased levels of EMVs in the coronary circulation compared with periphery. In addition, EMVs were associated with cSBP. CONCLUSIONS: EMVs emerge as novel markers of ongoing underlying vascular damage, further augmenting the vicious cycle of inflammation and thrombosis mainly in ACS but also in stable CAD.

DNA Damage and Repair in Patients With Coronary Artery Disease: Correlation With Plaque Morphology Using Optical Coherence Tomography (DECODE Study).

OBJECTIVE: The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology. BACKGROUND: Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity. METHODS: DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography. RESULTS: DNA ligase activity was different across the three groups of patients (control = 119 ±â€¯53, NSTEMI = 115.6 ±â€¯85.1, SA = 81 ±â€¯55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression. CONCLUSION: PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression. Trial Registration Number URL: www.Clinicaltrials.gov; NCT02335086.