Increased Vulnerability and Distinct Layered Phenotype at Culprit and Nonculprit Lesions in STEMI Versus NSTEMI

ObjectivesThis study aimed to investigate the pancoronary plaque vulnerability (including culprit and nonculprit lesions) and layered phenotype in patients with ST-segment elevation myocardial infarction (STEMI) vs non-STEMI (NSTEMI).BackgroundPancoronary vulnerability should account for distinct clinical manifestations of acute myocardial infarction (AMI). Layered plaque is indicative of previous coronary destabilization and thrombosis.MethodsA total of 464 patients with AMI who underwent 3-vessel optical coherence tomography imaging were consecutively studied and divided into a STEMI group (318 patients; 318 culprit and 1,187 nonculprit plaques) and a NSTEMI group (146 patients; 146 culprit and 560 nonculprit plaques). Patients were followed up for a median period of 2 years.ResultsCompared with NSTEMI, culprit lesions in STEMI had more plaque rupture, thrombus, thin-cap fibroatheroma (TCFA), calcification, macrophage accumulation, and microvessels. The prevalence of plaque rupture (8.2% vs 4.8%; P = 0.018), microvessels (57.5% vs 45.2%; P < 0.001), and calcification (40.7% vs 30.2%; P = 0.003) at nonculprit lesions was higher in STEMI than NSTEMI. The layer area and thickness at the culprit and nonculprit lesions were significantly larger in STEMI than in NSTEMI. Multivariate analyses showed that culprit layer area (odds ratio: 1.443; 95% CI: 1.138-1.830; P = 0.002) was predictive of STEMI (vs NSTEMI), in addition to culprit TCFA, culprit thrombus, and non–left circumflex artery location of the culprit lesion. Although the type of AMI was not related to clinical outcomes, high-sensitivity C-reactive protein, culprit calcified nodule, and nonculprit TCFA predicted the 2-year major adverse cardiovascular events in patients with AMI.ConclusionsPatients with STEMI had increased plaque vulnerability (ie, more plaque rupture and microvessels) and distinct layered phenotype at the culprit and nonculprit lesions compared with patients with NSTEMI. Culprit lesion features of large layer area, TCFA, thrombus, and non–left circumflex artery location predicted the clinical presentation of STEMI.     

Clinical characteristics of liver injury in SARS-CoV-2 Omicron variant- and Omicron subvariant-infected patients

Introduction and ObjectivesLiver injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant- and Omicron subvariant-infected patients is unknown at present, and the aim of this study is to summarize liver injury in these patients.Patients and MethodsIn this study, 460 SARS-CoV-2-infected patients were enrolled. Five severe or critical patients were excluded, and 34 patients were also excluded because liver injury was not considered to be related to SARS-CoV-2 infection. Liver injury was compared between Omicron and non-Omicron variants- and between Omicron subvariant-infected patients; additionally, the clinical data related to liver injury were also analyzed.ResultsAmong the 421 patients enrolled for analysis, liver injury was detected in 76 (18.1%) patients, including 46 Omicron and 30 non-Omicron variant-infected patients. The ratios did not differ between Omicron and non-Omicron variant-, Omicron BA.1, BA.2 and BA.5 subvariant-infected patients (P>0.05). The majority of abnormal parameters of liver function tests were mildly elevated (1-3 × ULN), the most frequently elevated parameter of liver function test was γ-glutamyl transpeptidase (GGT, 9.5%, 40/421), and patients with cholangiocyte or biliary duct injury markers were higher than with hepatocellular injury markers. Multivariate analysis showed that age (>40 years old, OR=1.898, 95% CI=1.058–3.402, P=0.032), sex (male gender, OR=2.031, 95% CI=1.211–3.408, P=0.007), serum amyloid A (SAA) level (>10 mg/ml, OR=3.595, 95% CI=1.840–7.026, P<0.001) and vaccination status (No, OR=2.131, 95% CI=1.089–4.173, P=0.027) were independent factors related to liver injury.ConclusionsLiver injury does not differ between Omicron and non-Omicron variants or between Omicron subvariant-infected patients. The elevations of cholangiocyte or biliary duct injury biomarkers are dominant in SARS-CoV-2-infected patients.     

Advanced glycation end products via skin autofluorescence as potential marker of carotid atherosclerosis in patients with type 2 diabetes

Background and aimsAdvanced glycation end products (AGEs) are reported to be correlated with diabetic vascular complications. This study aimed to investigate the association between AGEs and carotid atherosclerosis (CAS) as a surrogate marker of cardiovascular disease (CVD).Methods and resultsA total of 1006 patients with type 2 diabetes were included. CAS was defined as the presence of carotid arterial atherosclerotic plaque in any of bilateral carotid artery segments measured by ultrasonography. AGEs were measured by the noninvasive skin autofluorescence method. AGE_age index was calculated as AGEs × age/100. Patients with CAS showed a significantly higher AGE_age (P < 0.01), and the prevalence of CAS increased with ascending AGE_age levels (P for trend < 0.001). Logistic regression analysis revealed that AGE_age was significantly positively associated with odds of CAS, and the odds ratios of the presence of CAS across quartiles of AGE_age were 1.00, 3.00 [95% confidence interval (CI) 1.90–4.74], 4.04 (95%CI 2.50–6.53) and 4.99 (95%CI 2.97–8.40) for the multivariable-adjusted model (P for trend <0.001), respectively. In the fully adjusted model, each 5.0 increase in AGE_age was associated with a 0.019 mm increment in carotid intima-media thickness. Furthermore, AGE_age presented an acceptable predictive value for CAS, with an optimal cutoff point of 43.2, and the sensitivity, specificity and area under the curve (AUC) were 74.5% (95%CI 70.7–78.1%), 61.9% (95%CI 57.2–66.4%) and 0.735 (0.706–0.762), respectively.ConclusionAGE_age, the noninvasive measurement of AGEs combined with age is a promising approach for triaging patients at high risk of CVDs.     

Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study

ObjectivesThis study sought to identify morphological predictors of rapid plaque progression.BackgroundTwo patterns of plaque progression have been described: slow linear progression and rapid step-wise progression. The former pattern will cause stable angina when the narrowing reaches a critical threshold, whereas the latter pattern may lead to acute coronary syndromes or sudden cardiac death.MethodsPatients who underwent optical coherence tomography (OCT) imaging during the index procedure and follow-up angiography with a minimum interval of 6 months were selected. Nonculprit lesions with a diameter stenosis of ≥30% on index angiography were assessed. Lesion progression was defined as a decrease of angiographic minimum lumen diameter ≥0.4 mm at follow-up (mean, 7.1 months). Baseline morphological characteristics of plaques with rapid progression were evaluated by OCT. In a subgroup with follow-up OCT imaging for plaques with rapid progression, morphological changes from baseline to follow-up were assessed.ResultsAmong 517 lesions in 248 patients, 50 lesions showed rapid progression. These lesions had a significantly higher prevalence of lipid-rich plaque (76.0% vs. 50.5%, respectively), thin-cap fibroatheroma (TCFA) (20.0% vs. 5.8%, respectively), layered plaque (60.0% vs. 34.0%, respectively), macrophage accumulation (62.0% vs. 42.4%, respectively), microvessel (46.0% vs. 29.1%, respectively), plaque rupture (12.0% vs. 4.7%, respectively), and thrombus (6.0% vs. 1.1%, respectively) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.02 to 4.62; p = 0.045]), TCFA (OR: 5.85; 95% CI: 2.01 to 17.03; p = 0.001), and layered plaque (OR: 2.19; 95% CI: 1.03 to 4.17; p = 0.040) as predictors of subsequent rapid lesion progression. In a subgroup analysis for plaques with rapid progression, a new layer was detected in 25 of 41 plaques (61.0%) at follow-up.ConclusionsLipid-rich plaques, TCFA, and layered plaques were predictors of subsequent rapid plaque progression. A new layer, a signature of previous plaque disruption and healing, was detected in more than half of the lesions with rapid progression at follow-up. (Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538)     

Pancoronary Plaque Characteristics in STEMI Caused by Culprit Plaque Erosion Versus Rupture: 3-Vessel OCT Study

ObjectivesThis study sought to investigate nonculprit plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) presenting with plaque erosion (PE) and plaque rupture (PR). Pancoronary vulnerability was considered at nonculprit sites: 1) the CLIMA (Relationship Between OCT Coronary Plaque Morphology and Clinical Outcome) study (NCT02883088) defined high-risk plaques with simultaneous presence of 4 optical coherence tomography (OCT) features (minimum lumen area <3.5 mm²; fibrous cap thickness [FCT] <75 μm; maximum lipid arc >180º; and macrophage accumulation); and 2) the presence of plaque ruptures or thin-cap fibroatheromas (TCFA).BackgroundPE is a unique clinical entity associated with better outcomes than PR. There is limited evidence regarding pancoronary plaque characteristics of patients with culprit PE versus culprit PR.MethodsBetween October 2016 and September 2018, 523 patients treated by 3-vessel OCT at the time of primary percutaneous intervention were included with 152 patients excluded from final analysis.ResultsOverall, 458 nonculprit plaques were identified in 202 STEMI patients with culprit PE; and 1,027 nonculprit plaques were identified in 321 STEMI patients with culprit PR. At least 1 CLIMA-defined OCT nonculprit high-risk plaque was seen in 11.4% of patients with culprit PE, but twice as many patients were seen with culprit PR (25.2%; p < 0.001). This proportion was also seen when individual high-risk features were analyzed separately. When patients with PE were divided by a heterogeneous substrate (fibrous or lipid-rich plaque) underlying the culprit site, the prevalence of nonculprits with FCT <75 μm, macrophages, and TCFA showed a significant gradient from PE_(Fibrous) to PE_{lipid-rich plaque (LRP)} to PR. Interestingly, nonculprit rupture was rarely found in patients with culprit PE_(Fibrous) (1.9%), although it was exhibited with comparable prevalence in patients with culprit PE_(LRP) (16.3%) versus PR (17.8%). Culprit PE predicted decreased pancoronary vulnerability independent of conventional risk factors.ConclusionsSTEMI patients with culprit PE have a limited pancoronary vulnerability that may explain better outcomes in these patients than in STEMI patients with culprit PR.     

Low vitamin D levels predict left atrial thrombus in nonvalvular atrial fibrillation

Background and aimsWe determined the association between left atrial (LA) thrombus occurrence and a non-classic risk marker, plasma levels of vitamin D, in atrial fibrillation (AF) patients on continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy for ≥4 weeks. Low levels of plasma 25-hydroxy vitamin D (25-OHD) are predictive of fatal stroke. Vitamin D has anticoagulant effects on the coagulation cascade, which are indirectly targeted by NOAC therapy. The impact of plasma levels of vitamin D on the rate of LA thrombus detected by transesophageal echocardiography (TEE) in AF patients is unknown.Methods and resultsWe enrolled 201 (133 female) AF patients who were using continuous NOAC therapy for ≥4 weeks. All patients underwent transthoracic and TEE examination. Serum concentrations of 25-OHD, C-reactive protein (CRP) levels, CHA₂DS₂-VASc scores and parameters, LA size, and left ventricle ejection fraction (LVEF) were examined before the TEE procedure. LA thrombus occurrence was independently associated with serum levels of 25-OHD (OR: 0.884; 95% CI: 0.839–0.932; P < 0.001), LA diameter (OR: 1.120; 95% CI: 1.038–1.209; P = 0.003), and LVEF(OR: 0.944; 95% CI: 0.896–0.995; P = 0.032). Dense spontaneous echo contrast (SEC) presence was also inversely associated with 25-OHD concentrations.ConclusionsLow 25-OHD levels, as a non-classic risk factor, were independently and significantly associated with dense SEC and LA thrombus occurrence in AF patients under NOAC therapy, as well as LA enlargement and decreased LVEF. Further large-scale studies are needed to explain the role of vitamin D deficiency, or efficacy of replacement, on LA thrombus occurrence.     

Association between dairy product consumption and hyperuricemia in an elderly population with metabolic syndrome

Background and aimsThe prevalence of hyperuricemia has increased substantially in recent decades. It has been suggested that it is an independent risk factor for weight gain, hypertension, hypertriglyceridemia, metabolic syndrome (MetS), and cardiovascular disease. Results from epidemiological studies conducted in different study populations have suggested that high consumption of dairy products is associated with a lower risk of developing hyperuricemia. However, this association is still unclear. The aim of the present study is to explore the association of the consumption of total dairy products and their subtypes with the risk of hyperuricemia in an elderly Mediterranean population with MetS.Methods and resultsBaseline cross-sectional analyses were conducted on 6329 men/women (mean age 65 years) with overweight/obesity and MetS from the PREDIMED-Plus cohort. Dairy consumption was assessed using a food frequency questionnaire. Multivariable-adjusted Cox regressions were fitted to analyze the association of quartiles of consumption of total dairy products and their subtypes with the prevalence of hyperuricemia. Participants in the upper quartile of the consumption of total dairy products (multiadjusted prevalence ratio (PR) = 0.84; 95% CI: 0.75–0.94; P-trend 0.02), low-fat dairy products (PR = 0.79; 95% CI: 0.70–0.89; P-trend <0.001), total milk (PR = 0.81; 95% CI: 0.73–0.90; P-trend<0.001), low-fat milk (PR = 0.80; 95% CI: 0.72–0.89; P-trend<0.001, respectively), low-fat yogurt (PR = 0.89; 95% CI: 0.80–0.98; P-trend 0.051), and cheese (PR = 0.86; 95% CI: 0.77–0.96; P-trend 0.003) presented a lower prevalence of hyperuricemia. Whole-fat dairy, fermented dairy, and yogurt consumption were not associated with hyperuricemia.ConclusionsHigh consumption of total dairy products, total milk, low-fat dairy products, low-fat milk, low-fat yogurt, and cheese is associated with a lower risk of hyperuricemia.     

No association between alcohol consumption and risk of atrial fibrillation: A two-sample Mendelian randomization study

Background and aimsAlthough many observational studies have suggested that alcohol intake was associated with incident atrial fibrillation (AF), controversy remains. This study aimed to examine the causal association of alcohol intake with the risk of AF.Methods and resultsTwo-sample Mendelian randomization (MR) analysis was performed to estimate the causal effects of alcohol consumption, alcohol dependence, or alcohol use disorder identification test (AUDIT) scores on AF. Summary data on single nucleotide polymorphisms (SNPs) associated with AF were obtained from a genome-wide association study (GWAS) with up to 1,030,836 participants. The fixed- and random-effect inverse-variance weighted (IVW) methods were used to calculate the overall causal effects. MR analysis revealed nonsignificant association of genetically predicted alcohol consumption with risk of AF using fixed- and random-effect IVW approaches (odds ratio (OR) [95% confidence interval (CI)] = 1.004 [0.796–1.266], P = 0.975; OR [95% CI] = 1.004 [0.766–1.315], P = 0.979). Genetically predicted alcohol dependence was also not causally associated with AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 1.012 [0.978–1.048], P = 0.490; OR [95% CI] = 1.012 [0.991–1.034], P = 0.260). There was no significantly causal association between AUDIT and AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 0.889 [0.433–1.822], P = 0.748; OR [95% CI] = 0.889 [0.309–2.555], P = 0.827). Sensitivity analyses indicated no evidence of pleiotropy and heterogeneity in statistical models.ConclusionsThis MR study did not find evidence of a causal association between alcohol intake and AF.     

Prognostic value of frontal QRS-T angle in predicting survival after primary percutaneous coronary revascularization/coronary artery bypass grafting for ST-elevation myocardial infarction

BackgroundFrontal QRS-T angle (FQRST) has previously been correlated with mortality in patients with stable coronary artery disease, but its role as survival predictor after ST-elevation myocardial infarction (STEMI) remains unknown.MethodsWe evaluated 267 consecutive patients with STEMI undergoing reperfusion or coronary artery bypass grafting. Data assessed included demographics, clinical presentation, electrocardiograms, medical therapy, and one-year mortality.ResultsOf 267 patients, 187 (70%) were males and most (49.4%) patients were Caucasian. All-cause mortality was significantly higher among patients with the highest (101–180°) FQRST [28% vs. 15%, p = 0.02]. Patients with FQRST 1–50° had higher survival (85.6%) compared with FQRST = 51–100° (72.3%) and FQRST = 101–180° (67.9%), [log rank, p = 0.01]. Adjusting for significant variables identified during univariate analysis, FQRST (OR = 2.04 [95% CI: 1.31–13.50]) remained an independent predictor of one-year mortality. FQRST-based risk score (1–50° = 0 points, 51–100° = 2 points, 101–180° = 5 points) had excellent discriminatory ability for one-year mortality when combined with Mayo Clinic Risk Score (C statistic = 0.875 [95%CI: 0.813–0.937]. A high (>4 points) FQRST risk score was associated with greater mortality (32% vs. 19%, p = 0.02) and longer length of stay (6 vs. 2 days, p < 0.001).ConclusionFQRST represents a novel independent predictor of one-year mortality in patients with STEMI undergoing reperfusion. A high FQRST-based risk score was associated with greater mortality and longer length of stay and, after combining with Mayo Clinic Risk Score, improved discriminatory ability for one-year mortality.     

Association between abdominal fat distribution and coronary plaque instability in patients with acute coronary syndrome

Background and aimsThis study aimed to assess possible association of detailed abdominal fat profiles with coronary plaque characteristics in patients with acute coronary syndrome (ACS).Methods and resultsIn 60 patients with ACS, culprit arteries were evaluated at 1-mm intervals (length analyzed: 66 ± 28 mm) by grayscale and integrated backscatter intravascular ultrasound (IB-IVUS) before percutaneous coronary intervention. Standard IVUS indexes (as a volume index: volume/length), plaque components (as percent tissue volume) and fibrous cap thickness (FCT) were assessed by IB-IVUS. Plain abdominal computed tomography was performed to evaluate subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and VAT/SAT ratio. While SAT area only correlated with vessel volume (r = 0.27, p = 0.04), VAT area correlated positively with vessel (r = 0.30, p = 0.02) and plaque (r = 0.33, p = 0.01) volumes and negatively with FCT (r = −0.26, p = 0.049), but not with percent plaque volume and plaque tissue components. In contrast, higher VAT/SAT ratio significantly correlated with higher percent lipid (r = 0.34, p = 0.008) and lower percent fibrous (r = −0.34, p = 0.007) volumes with a trend toward larger percent plaque volume (r = 0.19, p = 0.15), as well as thinner FCT (r = −0.53, p < 0.0001). In the multiple regression analysis, higher VAT/SAT ratio was independently associated with higher percent lipid with lower percent fibrous volumes (p = 0.03 for both) and thinner fibrous cap thickness (p = 0.0001).ConclusionCoronary plaque vulnerability, defined as increased lipid content with thinner fibrous cap thickness, appears to be more related to abnormal abdominal fat distribution, or so-called hidden obesity, compared with visceral or subcutaneous fat amount alone in patients with ACS.     

Outcomes After Transcatheter Aortic Valve Replacement in Bicuspid Versus Tricuspid Anatomy: A Systematic Review and Meta-Analysis

ObjectivesThe aim of this study was to compare the feasibility, safety, and clinical outcomes of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) stenosis.BackgroundAt present, limited observational data exist supporting TAVR in the context of bicuspid anatomy.MethodsPrimary endpoints were 1-year survival and device success. Secondary endpoints included moderate to severe paravalvular leak (PVL) and a composite endpoint of periprocedural complications; incidence rates of individual procedural endpoints were also explored individually.ResultsIn the main analysis, 17 studies and 181,433 patients undergoing TAVR were included, of whom 6,669 (0.27%) had BAV. A secondary analysis of 7,071 matched subjects with similar baseline characteristics was also performed. Device success and 1-year survival rates were similar between subjects with BAV and those with TAV (97% vs 94% [P = 0.55] and 91.3% vs 90.8% [P = 0.22], respectively). In patients with BAV, a trend toward a higher risk for periprocedural complications was observed in our main analysis (risk ratio [RR]: 1.12; 95% CI: 0.99-1.27; P = 0.07) but not in the matched population secondary analysis (RR: 1.00; 95% CI: 0.81-1.24; P = 0.99). The risk for moderate to severe PVL was higher in subjects with BAV (RR: 1.42; 95% CI: 1.29-1.58; P < 0.0001) as well as the incidence of cerebral ischemic events (2.4% vs 1.6%; P = 0.015) and of annular rupture (0.3% vs 0.02%; P = 0.014) in matched subjects.ConclusionsTAVR is a feasible option among selected patients with BAV anatomy, but the higher rates of moderate to severe PVL, annular rupture, and cerebral ischemic events observed in the BAV group warrant caution and further evidence.     

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease

ObjectivesThe aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.BackgroundCoronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.MethodsThis analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).ResultsCPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = –0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = –0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.ConclusionsCalcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)     

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement

BackgroundMyocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood.ObjectivesThe purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR).MethodsThis retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction–confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR.ResultsIn this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003).ConclusionsIn this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.     

Association between the visceral adiposity index and risks of all-cause and cause-specific mortalities in a large cohort: Findings from the UK biobank

Background and aimsThe visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.Methods and resultsIn this large-scale prospective epidemiological study, 357,457 participants (aged 38–73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148–1.255; P < 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150–1.303; P < 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148–1.255; P < 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148–1.255; P < 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.ConclusionIn summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.     

Air Pollution and Coronary Plaque Vulnerability and Instability: An Optical Coherence Tomography Study

ObjectivesWe assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS).BackgroundAir pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated.MethodsPatients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled.ResultsWe included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and Co levels were positively and significantly correlated with serum levels of C-reactive protein.ConclusionsWe provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.     

Neck circumference predicts development of carotid intima-media thickness and carotid plaque: A community-based longitudinal study

Background and aimsCarotid intima-media thickness (C-IMT) is an important index for evaluating subclinical atherosclerosis. Neck circumference (NC), a new anthropometric index of the upper body fat, is closely related to cardiovascular disease (CVD) and CVD risk factors. This study investigated the relationship between NC, C-IMT, and carotid plaque in a community-based cohort.Methods and resultsParticipants recruited from Shanghai communities were followed up for 1.1–2.9 years. All participants underwent anthropometric and biochemical measurements. Elevated NC was defined as NC ≥ 38.5 cm and NC ≥ 34.5 cm in men and women, respectively. Elevated C-IMT, determined by ultrasound, was defined as a level higher than the 75th percentile in the study population (>0.75 mm). In total, 1189 participants without carotid plaque at baseline were included, with an average age of 59.6 ± 7.3 years. After a mean follow-up of 2.1 ± 0.2 years, 203 participants developed carotid plaques. After adjusting for various atherosclerosis risk factors, the logistic regression showed that the higher NC group had a significantly greater risk of developing carotid plaque than the lower NC group (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.12–2.14; P = 0.008). Of those without carotid plaque at follow-up, 495 participants developed elevated C-IMT. Compared to the lower NC group, the higher NC group had a significantly increased risk of elevated C-IMT (OR, 1.49; 95% CI, 1.14–1.95; P = 0.003).ConclusionHigher NC was significantly positively correlated with the risk of carotid plaque and elevated C-IMT.     

Healed Culprit Plaques in Patients With Acute Coronary Syndromes

BackgroundHealed plaques, morphologically characterized by a layered phenotype, are frequently found in subjects with sudden cardiac death. However, in vivo data are lacking.ObjectivesThe purpose of this study was to determine the prevalence, morphological characteristics, and clinical significance of healed culprit plaques in patients with acute coronary syndromes (ACS) using optical coherence tomography (OCT).MethodsA total of 376 ACS patients (252 ST-segment elevation myocardial infarction [MI] and 124 non–ST-segment elevation acute coronary syndrome) who had undergone pre-intervention OCT imaging of the culprit lesion were enrolled. Patients were stratified according to the presence of layered phenotype, defined as layers of different optical density at OCT. Clinical and laboratory data, OCT characteristics, and 1-year outcome were compared between the 2 groups.ResultsAmong 376 patients, 108 (28.7%) healed plaques were identified. Hyperlipidemia, diabetes, and history of MI were more frequent in patients with healed plaques (44.4% vs. 33.2%; p = 0.041; 35.2% vs. 23.5%; p = 0.021; and 15.7% vs. 6.3%; p = 0.009, respectively). High-sensitivity C-reactive protein was significantly higher in patients with healed plaques (median 4.98 mg/l [interquartile range: 1.00 to 11.32 mg/l] vs. 3.00 mg/l [interquartile range: 0.30 to 10.15 mg/l]; p = 0.029). Plaque rupture (64.8% vs. 53.0%; p = 0.039), thin cap fibroatheroma (56.5% vs. 42.5%; p = 0.016), and macrophage accumulation (81.1% vs. 63.4%; p = 0.001) were common in the layered group. OCT also revealed greater area stenosis in plaques with layered phenotype (79.2 ± 9.5% vs. 74.3 ± 14.3%; p = 0.001). The incidence of major adverse cardiovascular events was similar between the 2 groups, except that the all-cause rehospitalization rate was higher among healed plaques (32.7% vs. 16.5%; p = 0.013).ConclusionsHealed plaques, a signature of prior plaque destabilization, were found at the culprit site in more than one-quarter of ACS patients. Such patients more frequently were diabetic, were hyperlipidemic, or had a history of MI. Healed plaques frequently showed OCT features of vulnerability with evidence of local and systemic inflammation. The combination of plaque vulnerability, local inflammation, and greater plaque burden in addition to systemic inflammation may outweigh the protective mechanism of plaque healing and predispose those plaques to develop occlusive thrombus.     

Compositional and functional alterations of gut microbiota in patients with stroke

Background and aimsThere is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied.Methods and resultsWe performed a case–control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions), and TMAO was determined via liquid chromatography–tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08–0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study.ConclusionThis study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.     

Sex Differences in Safety and Effectiveness of LAAO: Insights From the Amulet IDE Trial

BackgroundWomen have higher rates of acute complications after left atrial appendage occlusion (LAAO). However, data on long-term safety and effectiveness are limited.ObjectivesThe aim of this study was to examine sex-specific short- and long-term outcomes after LAAO in the Amulet IDE (Amplatzer? Amulet? LAA Occluder) trial.MethodsThe following outcomes were compared between men and women: in-hospital complications, device-related outcomes (peridevice leak at 45 days and device-related thrombus at 18 months), and long-term clinical outcomes (death, thromboembolism, and bleeding). Subanalyses for the interaction between sex and device type were performed.ResultsA total of 1,833 patients underwent attempted device implantation (917 with the Amulet and 916 with the Watchman), of whom 734 were women (40%). Device success was 97.4% in men and 97.1% in women (P = 0.60). Rates of major in-hospital adverse events were higher in women (4.4% vs 1.9%; P < 0.01), driven by major bleeding (3.7% vs 1.0%; P < 0.01) and pericardial effusion requiring intervention (2.0% vs 0.5%; P < 0.01). Peridevice leak and device-related thrombus were similar in men and women (18.3% vs 18.9% [P = 0.78] and 3.3% vs 5.0% [P = 0.10], respectively). There were no differences between men and women in rates of ischemic stroke or systemic embolism (2.6% vs 2.6%; P = 0.98), transient ischemic attack (1.3% vs 1.6%; P = 0.69), hemorrhagic stroke (0.5% vs 0.4%; P = 0.88), major bleeding (10.1% vs 10.9%; P = 0.49), cardiovascular death (4.3% vs 3.5%; P = 0.45), or all-cause death (8.9% vs 6.9%; P = 0.16).ConclusionsIn the Amulet IDE trial, long-term clinical outcomes including effectiveness following LAAO were comparable in men and women despite the higher rates of in-hospital complications due to major bleeding and pericardial effusion in women. (Amplatzer? Amulet? LAA Occluder Trial [Amulet IDE]; NCT02879448)     

Association of elective cesarean delivery with metabolic measures in childhood: A prospective cohort study in China

Background and aimsCesarean delivery may increase the risk of childhood obesity, a precursor of metabolic syndrome (MetS). We aimed to investigate the association of elective cesarean delivery (ElCD) with MetS and its components in a Chinese birth cohort.Methods and resultsThis cohort included 1467 children (737 delivered by ElCD and 730 by spontaneous vaginal delivery [SVD]) who were followed up at the age of 4–7 years in 2013. MetS was defined as the presence of ≥3 components: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL), high fasting glucose, and hypertension. Of the 1467 children, 93 (6.3%) were categorized as having MetS: 50 (6.8%) delivered by ElCD and 43 (5.9%) by SVD. After multivariable adjustment, ElCD was not associated with MetS (adjusted odds ratio [AOR] 1.15, 95% confidence interval [CI] 0.74, 1.78) or certain components including hypertriglyceridemia, low HDL, and high fasting glucose but was associated with central obesity (AOR 1.33, 95% CI 1.02, 1.72) and hypertension (AOR 1.50, 95% CI 1.15, 1.96), as well as higher levels of total cholesterol (3.43 vs. 3.04 mmol/L; P < 0.001), low-density lipoprotein–cholesterol (1.77 vs. 1.67 mmol/L, P = 0.002), fasting glucose (5.08 vs. 5.02 mmol/L, P = 0.022), systolic (97.57 vs. 94.69 mmHg, P < 0.001)/diastolic blood pressure (63.72 vs. 62.24 mmHg, P < 0.001), and BMI (15.46 vs. 14.83 kg/m², P < 0.001) than SVD.ConclusionsElCD is not associated with MetS in early to middle childhood but is associated with its components including central obesity and hypertension, as well as various continuous indices.