Objectives This study sought to determine the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) to detect or rule out significant coronary artery disease (CAD). ...Background CTCA is emerging as a noninvasive technique to detect coronary atherosclerosis. Methods We conducted a prospective, multicenter, multivendor study involving 360 symptomatic patients with acute and stable anginal syndromes who were between 50 and 70 years of age and were referred for diagnostic conventional coronary angiography (CCA) from September 2004 through June 2006. All patients underwent a nonenhanced calcium scan and a CTCA, which was compared with CCA. No patients or segments were excluded because of impaired image quality attributable to either coronary motion or calcifications. Patient-, vessel-, and segment-based sensitivities and specificities were calculated to detect or rule out significant CAD, defined as ≥50% lumen diameter reduction. Results The prevalence among patients of having at least 1 significant stenosis was 68%. In a patient-based analysis, the sensitivity for detecting patients with significant CAD was 99% (95% confidence interval CI: 98% to 100%), specificity was 64% (95% CI: 55% to 73%), positive predictive value was 86% (95% CI: 82% to 90%), and negative predictive value was 97% (95% CI: 94% to 100%). In a segment-based analysis, the sensitivity was 88% (95% CI: 85% to 91%), specificity was 90% (95% CI: 89% to 92%), positive predictive value was 47% (95% CI: 44% to 51%), and negative predictive value was 99% (95% CI: 98% to 99%). Conclusions Among patients in whom a decision had already been made to obtain CCA, 64-slice CTCA was reliable for ruling out significant CAD in patients with stable and unstable anginal syndromes. A positive 64-slice CTCA scan often overestimates the severity of atherosclerotic obstructions and requires further testing to guide patient management.
Fat surrounding coronary arteries might aggravate coronary artery disease (CAD). We investigated the relation between epicardial adipose tissue (EAT) and pericoronary fat and coronary atherosclerosis ...and coronary artery calcium (CAC) in patients with suspected CAD and whether this relation is modified by total body weight. This was a cross-sectional study of 128 patients with angina pectoris (61 ± 6 years of age) undergoing coronary angiography. EAT volume and pericoronary fat thickness were measured with cardiac computed tomography. Severity of coronary atherosclerosis was assessed by the number of stenotic (≥50%) coronary vessels; extent of CAC was determined by the Agatston score. Patients were stratified for median total body weight (body mass index BMI 27 kg/m2 ). Overall, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and extent of CAC. In patients with low BMI, those with multivessel disease had increased EAT volume (100 vs 67 cm3 , p = 0.04) and pericoronary fat thickness (9.8 vs 8.4 mm, p = 0.06) compared with those without CAD. Also, patients with severe CAC had increased EAT volume (108.0 vs 69 cm3 , p = 0.02) and pericoronary fat thickness (10.0 vs 8.2 mm, p value = 0.01) compared with those with minimal/absent CAC. In conclusion, EAT and pericoronary fat were not associated with severity of coronary atherosclerosis and CAC in patients with suspected CAD. However, in those with low BMI, increased EAT and pericoronary fat were related to more severe coronary atherosclerosis and CAC. Fat surrounding coronary arteries may be involved in the process of coronary atherosclerosis, although this is different for patients with low and high BMIs.
Objectives This study sought to examine whether exenatide is capable of reducing myocardial infarct size. Background Exenatide is a glucagon-like peptide (GLP)-1 analogue with insulinotropic and ...insulinomimetic properties. Because insulin and GLP-1 have been described as reducing apoptosis, exenatide might confer cardioprotection after acute myocardial infarction (MI). Methods Pigs were randomized to exenatide or phosphate-buffered saline (PBS) treatment after 75 min of coronary artery ligation and subsequent reperfusion. Infarct size was assessed with Evans Blue (Sigma-Aldrich, St. Louis, Missouri) and triphenyltetrazolium chloride. Cardiac function was measured with epicardial ultrasound and conductance catheter-based pressure-volume loops. Western blotting, histology, and activity assays were performed to determine markers of apoptosis/survival and oxidative stress. Results Exenatide reduced myocardial infarct size (32.7 ± 6.4% vs. 53.6 ± 3.9%; p = 0.031) and prevented deterioration of systolic and diastolic cardiac function (systolic wall thickening: 47.3 ± 6.3% vs. 8.1 ± 1.9%, p < 0.001; myocardial stiffness: 0.12 ± 0.06 mm Hg/ml vs. 0.22 ± 0.07 mm Hg/ml; p = 0.004). After exenatide treatment, myocardial phosphorylated Akt and Bcl-2 expression levels were higher compared with those after PBS treatment, and active caspase 3 expression was lower. In addition, fewer cells were terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling-positive. In addition, nuclear oxidative stress as assessed with an 8-hydroxydeoxyguanosine staining was reduced in the exenatide treatment arm, and superoxide dismutase activity and catalase activity were increased. Serum insulin levels increased after exenatide treatment, without affecting glucose levels. Conclusions These data identify exenatide as a potentially effective compound to reduce infarct size in adjunction to reperfusion therapy in patients with acute MI.
The goal of this study was to review the prognostic value of cardiac magnetic resonance (CMR) imaging findings for future cardiovascular events in patients with a recent myocardial infarction (MI) ...and patients with suspected or known coronary artery disease (CAD). Although the diagnostic value of CMR findings is established, the independent prognostic association with future cardiovascular events remains largely unclear. Studies published by February 2013, identified by systematic MEDLINE and EMBASE searches, were reviewed for associations between CMR findings (left ventricular ejection fraction LVEF, wall motion abnormalities WMA, abnormal myocardial perfusion, microvascular obstruction, late gadolinium enhancement, edema, and intramyocardial hemorrhage) and hard events (all-cause mortality, cardiac death, cardiac transplantation, and MI) or major adverse cardiovascular events (MACE) (hard events and other cardiovascular events defined by the authors of the evaluated papers). Fifty-six studies (n = 25,497) were evaluated. For patients with recent MI, too few patients were evaluated to establish associations between CMR findings and hard events. LVEF (range of adjusted hazard ratios HRs: 1.03 to 1.05 per % decrease) was independently associated with MACE. In patients with suspected or known CAD, WMA (adjusted HRs: 1.87 to 2.99), inducible perfusion defects (adjusted HRs: 3.02 to 7.77), LVEF (adjusted HRs: 0.72 to 0.82 per 10% increase), and infarction (adjusted HRs: 2.82 to 9.43) were independently associated with hard events, and the presence of inducible perfusion defects was associated with MACE (adjusted HRs: 1.76 to 3.21). The independent predictor of future cardiovascular events for patients with a recent MI was LVEF, and the predictors for patients with suspected or known CAD were WMA, inducible perfusion defects, LVEF, and presence of infarction.
Abstract Background Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has ...been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. Objectives The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. Methods ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. Results Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. Conclusions Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.
Abstract Aims To compare the extent of cerebral ischemic injury after transcatheter aortic valve replacement (TAVR) with the use of an Embrella Embolic Deflector System versus unprotected TAVR. ...Methods Fifteen patients with severe symptomatic aortic stenosis underwent TAVR with use of the Embrella Embolic Deflector System for cerebral protection. Cerebral diffusion-weighted magnetic resonance imaging (DWI) was performed in all patients at day 4 after the procedure and images were retrospectively compared to 37 patients who had previously undergone TAVR without a protection device (TAVR-only group). Results Successful placement of the Embrella device was achieved in all patients. DWI revealed an increase in the number of ischemic lesions in the Embrella group compared with the TAVR-only group (9.0 vs 5.0, P = .044). The use of the Embrella device was however associated with a significant reduction in single-lesion volume: 9.7 μL 5.8, 18.4 versus 17.8 μL 9.5, 38.7 ( P < .001). Moreover, total infarct volumes of more than 1000 μL were only seen in the TAVR-only group. More lesions occurred in the right side of the brain in the Embrella group, whereas in the TAVR-only group lesions were distributed equally between left and right. One patient in the TAVR-only group suffered from a transient ischemic attack. Postoperative evaluation was clinically uneventful in the Embrella group. Conclusions The use of the Embrella device during TAVR increased the number of cerebral ischemic lesions on postprocedural brain imaging. This increase in number was however accompanied by a significant reduction in single-lesion volume and the absence of large total infarct volumes.
Abstract Objectives The purpose of this study was to investigate the incidence, predictive factors, and effect of post-operative delirium (POD) among patients treated by transcatheter aortic valve ...replacement (TAVR). Background Patients undergoing operations that involve valve replacement appear at higher risk of POD than patients subjected to coronary artery bypass surgery alone. In patients with severe aortic stenosis undergoing TAVR, little is known regarding the potential impact of POD on the clinical outcomes. Methods A retrospective observational cohort study of 268 consecutive patients who underwent TAVR at our institute was conducted. Delirium was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition criteria. The primary outcome of this study was the presence of in-hospital POD after TAVR. Results The incidence of POD after TAVR was 13.4% (n = 36). Of these cases, 18 were associated with post-procedural complications, including major vascular complications/bleeding (n = 4), stroke (n = 3), acute kidney injury (n = 3), atrial fibrillation (n = 4), and infectious disease (n = 4). POD was most frequently diagnosed on the second day after TAVR (interquartile range IQR: 1 to 5 days) and was associated with prolonged in-hospital stay regardless of complications (in uncomplicated TAVR: 6 days IQR: 5 to 10 days vs. 5 days IQR: 4 to 5 days; p < 0.001; and in complicated TAVR: 9 days IQR: 8 to 15 days vs. 6 days IQR: 5 to 9 days; p < 0.001). Predictors of POD were nontransfemoral (transapical/transaortic) access (odds ratio OR: 7.74; 95% confidence interval CI: 3.26 to 18.1), current smoking (OR: 3.99; 95% CI: 1.25 to 12.8), carotid artery disease (OR: 3.88; 95% CI: 1.50 to 10.1), atrial fibrillation (OR: 2.74; 95% CI: 1.17 to 6.37), and age (OR: 1.08; 95% CI: 1.00 to 1.17, per year increase). After a median follow-up of 16 months (IQR: 6 to 27 months), POD remained an independent predictor of mortality in patients undergoing transfemoral TAVR compared with the nontransfemoral TAVR (hazard ratio: 2.81; 95% CI: 1.16 to 6.83 vs. hazard ratio: 0.43; 95% Cl: 0.10 to 1.76), adjusted for possible confounders in a time-dependent Cox-regression model (i.e., age, sex, Logistic EuroSCORE and the occurrence of complications). Conclusions POD after TAVR has an incidence of around 13% and occurs early in the post-operative course. Nontransfemoral access is strongly associated with the occurrence of POD. Patients who develop POD show prolonged in-hospital stay and impaired long-term survival.
Today quantitative information about the type of complications and their incidence during long-term pacemaker (PM) follow-up is scarce.
To assess the incidence and determinants of short- and ...long-term complications after first pacemaker implantation for bradycardia.
A prospective multicenter cohort study (the FOLLOWPACE study) was conducted among 1517 patients receiving a PM between January 2003 and November 2007. The independent association of patient and implantation-procedure characteristics with the incidence of PM complications was analyzed using multivariable Cox regression analysis.
A total of 1517 patients in 23 Dutch PM centers were followed for a mean of 5.8 years (SD 1.1), resulting in 8797 patient-years. Within 2 months, 188 (12.4%) patients developed PM complications. Male gender, age at implantation, body mass index, a history of cerebrovascular accident, congestive heart failure, use of anticoagulant drugs, and passive atrial lead fixation were independent predictors for complications within 2 months, yielding a C-index of 0.62 (95% confidence interval 0.57-0.66). Annual hospital implanting volume did not additionally contribute to the prediction of short-term complications. Thereafter, 140 (9.2%) patients experienced complications, mostly lead-related complications (n = 84). Independent predictors for long-term complications were age, body mass index, hypertension, and a dual-chamber device, yielding a C-index of 0.62 (95% confidence interval 0.57-0.67). The occurrence of a short-term PM complication was not predictive of future PM complications.
Complication incidence in modern pacing therapy is still substantial. Most complications occur early after PM implantation. Although various patient- and procedure-related characteristics are independent predictors for early and late complications, their ability to identify the patient at high risk is rather poor. This relatively high incidence of PM complications and their poor prediction underscores the usefulness of current guidelines for regular follow-up of patients with PM.
Idiopathic ventricular fibrillation (IVF) is a rare primary cardiac arrhythmia syndrome that is diagnosed in a resuscitated cardiac arrest victim, with documented ventricular fibrillation, in whom no ...underlying cause is identified after comprehensive clinical evaluation. In some patients, causative genetic mutations are detected that facilitate patient treatment and follow-up. The feasibility of next-generation sequencing (NGS) has increased with its greater availability and decreasing costs.
The aim of this study was to assess the diagnostic yield of NGS in patients with IVF.
A total of 33 patients initially diagnosed with IVF were included (mean age 53 ± 15 years; 14(42%) men). In all included patients, NGS of 33 genes and the DPP6 haplotype revealed no pathogenic mutations. Genetic screening comprised NGS of a panel of 179 additional genes. Variants with a minor allele frequency of <0.05% were assessed for pathogenicity by using existing mutation databases and in silico predictive algorithms.
In 1 of 33 patients, a likely pathogenic mutation was detected. The added yield of genetic testing with NGS of 179 additional genes is 3% in patients with IVF. In 15% of patients, 1 or multiple variants of uncertain clinical significance were detected.
The added yield of genetic screening of extended NGS panels in patients initially diagnosed with IVF is minimal. Routine analysis of large diagnostic NGS panels is therefore not recommended.
52 Genetic Loci Influencing Myocardial Mass van der Harst, Pim, MD, PhD; Verweij, Niek, PhD; Vogler, Georg, PhD ...
Journal of the American College of Cardiology,
09/2016, Letnik:
68, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Abstract Background Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and ...duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. Objectives This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. Methods We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. Results We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10−8 . These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus . We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. Conclusions Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
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