Objectives This study sought to determine whether epicardial fat volume predicts coronary events in the general population. Background Epicardial adipose tissue (EAT) is suggested to promote plaque ...development in the coronary artery tree. Methods We quantified EAT volume in participants from the prospective population-based Heinz Nixdorf Recall cohort study free of cardiovascular disease. Incident coronary events were assessed during a follow-up period of 8.0 ± 1.5 years. Multivariable association of EAT with cardiovascular risk factors, coronary artery calcification (CAC), and coronary events was assessed using regression analysis. Results From the overall 4,093 participants (age 59.4 years, 47% male), 130 subjects developed a fatal or nonfatal coronary event. Incidence of coronary events increased by quartile of EAT (0.9% vs. 4.7% for 1st and 4th quartile, respectively, p < 0.001). Doubling of EAT was associated with a 1.5-fold risk of coronary events when adjusting for cardiovascular risk factors (hazard ratio HR 95% confidence interval (CI): 1.54 1.09 to 2.19), which remained unaltered after further adjustment for CAC score (HR 95% CI: 1.50 1.07 to 2.11). For discrimination of subjects with events from those without, we observed a trend for improvement of Harrell's C and explained variance by EAT over traditional cardiovascular risk factors, which, however, did not reach statistical significance (0.720 to 0.730 for risk factors alone and with EAT added, respectively, p = 0.10, R2 = 2.73% to R2 = 2.92%, time-dependent integrated discrimination improvement = 0.196%). Conclusions Epicardial fat is associated with fatal and nonfatal coronary events in the general population independent of traditional cardiovascular risk factors and complements information from cardiac computed tomography above the CAC score.
Abstract Objectives The aim of this study was to assess the difference in indication for statin therapy by European Society of Cardiology (ESC) versus American Heart Association/American College of ...Cardiology (AHA/ACC) guidelines and to quantify the potential additional role of coronary artery calcification (CAC) score over updated guidelines in a primary prevention cohort. Background Recently, ESC and AHA/ACC updated the guidelines regarding statin therapy in primary prevention. Methods In 3,745 subjects (59 ± 8 years of age, 47% men) from the population based longitudinal Heinz Nixdorf Recall cohort study without cardiovascular disease or lipid-lowering therapy at baseline CAC score was assessed between 2000 and 2003. Subjects remained unaware of their initial CAC score. Statin indication was determined according to 2012 ESC and 2013 AHA/ACC guidelines based on subjects individual baseline characteristics. Results The frequency of statin recommendation was lower according to ESC compared to AHA/ACC guidelines (34% vs. 56%; p < 0.0001), whereas low CAC score (<100) was common in subjects with statin indication by both guidelines (59% for ESC, 62% for AHA/ACC). During 10.4 ± 2.0 years of follow-up, 131 myocardial infarctions occurred. For ESC recommendations, CAC score differentiated risk for subjects without (1.0 95% confidence interval (CI): 0.4 to 1.5 vs. 6.5 95% CI: 4.1 to 8.9 coronary events per 1,000 person-years for CAC 0 vs. ≥100) and with statin indication (2.6 95% CI: 0.6 to 4.7 vs. 9.9 95% CI: 7.3 to 12.5 per 1,000 person-years for CAC 0 vs. ≥100). Likewise, CAC score stratified proportions experiencing events subjects with statin indication according to AHA/ACC (2.7 95% CI: 1.1 to 4.2 vs. 9.1 95% CI: 7.0 to 11.0 per 1,000 person-years for CAC 0 vs. ≥100), whereas event rate in subjects without statin indication was low (1.1 95% CI: 0.65 to 1.68 per 1,000 person-years). Conclusions Current ESC and AHA/ACC guidelines lead to markedly different recommendation regarding statin therapy in a German primary prevention cohort. Quantification of CAC score in addition to the guidelines improves stratification between subjects at high versus low risk for coronary events, indicating that CAC scoring may help to match intensified risk factor modification to atherosclerotic plaque burden as well as actual risk while avoiding therapy in subjects with low coronary atherosclerosis that have low 10-year event rate.
Valve-in-Valve Transcatheter Aortic Valve Implantation for Degenerated Bioprosthetic Heart Valves Holger Eggebrecht, Ulrich Schäfer, Hendrik Treede, Peter Boekstegers, Jörg Babin-Ebell, Markus ...Ferrari, Helge Möllmann, Helmut Baumgartner, Thierry Carrel, Philipp Kahlert, Philipp Lange, Thomas Walther, Raimund Erbel, Rajendra H. Mehta, Matthias Thielmann Multicenter data from 47 patients aged 64 to 97 years undergoing transfemoral (n = 25) or transapical (n = 22) valve-in-valve (viv) transcatheter aortic valve implantation (TAVI) for degenerated surgically implanted bioprosthetic heart valves were analyzed. Procedural success was obtained in all patients. Vascular access complications occurred in 6 (13%). Five (11%) patients required new pacemaker implantation. Valvular function was excellent with respect to valve competence, but increased transvalvular gradients ≥20 mm Hg were noted in 44%. Mortality at 30 days was 17% (1 procedural and 7 post-procedural deaths). Valve-in-valve TAVI can be performed with high technical success rates, acceptable post-procedural valvular function, and excellent functional improvement.
Between 43,000 and 47,000 people die annually in the United States from diseases of the aorta and its branches and continues to increase. For the thoracic aorta, these diseases are increasingly ...treated by stent-grafting. No prospective randomized study exists comparing stent-grafting and open surgical treatment, including for disease subgroups. Currently, one stent-graft device is approved by the Food and Drug Administration for descending thoracic aortic aneurysms although two new devices are expected to obtain FDA approval in 2008. Stent-graft devices are used “off label” or under physician Investigational Device Exemption studies for other indications such as traumatic rupture of the aorta and aortic dissection. Early first-generation devices suffered from problems such as stroke with insertion, ascending aortic dissection or aortic penetration from struts, vascular injury, graft collapse, endovascular leaks, graft material failure, continued aneurysm expansion or rupture, and migration or kinking; however, the newer iterations coming to market have been considerably improved. Although the devices have been tested in pulse duplicators out to 10 years, long-term durability is not known, particularly in young patients. The long-term consequences of repeated computed tomography scans for checking device integrity and positioning on the risk of irradiation-induced cancer remains of concern in young patients. This document (1) reviews the natural history of aortic disease, indications for repair, outcomes after conventional open surgery, currently available devices, and insights from outcomes of randomized studies using stent-grafts for abdominal aortic aneurysm surgery, the latter having been treated for a longer time by stent-grafts; and (2) offers suggestions for treatment.
Purpose Transcatheter aortic valve implantation (TAVI) results in the dislodgement of debris with risk of cerebral lesions or stroke. The EMBOL-X protection device (Edwards Lifesciences, Irvine, CA) ...is positioned within the ascending aorta to capture such debris. Description Between July 2012 and April 2014 we randomly assigned 30 high-risk patients to undergo transaortic TAVI with the SAPIEN XT prosthesis (Edwards Lifesciences) combined with either the EMBOL-X device (group-1, n = 14) or without (group-2, n = 16). Periprocedural cerebral lesions were assessed by diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and within 7 days post-procedurally. Evaluation New foci of restricted diffusion on cerebral DW-MRI were found in 69% in group-2 and 50% in group-1. Lesion size was smaller in patients treated with the EMBOL-X device than in those without (88 ± 60 vs 168 ± 217 mm3 , p = 0.27, t = 1.2, degrees of freedom = 10). Transaortic TAVI patients treated with the EMBOL-X device had significantly smaller lesion volumes in the supply region of the middle cerebral artery (33 ± 29 vs 76 ± 67 mm3 , p = 0.04). There were no neurologic events after transaortic TAVI. Conclusions The intraaortic protection device seems to reduce both the incidence and the volume of new cerebral lesions ( ClinicalTrials.gov number, NCT01735513 ).
Early- and Long-Term Intravascular Ultrasound and Angiographic Findings After Bioabsorbable Magnesium Stent Implantation in Human Coronary Arteries Ron Waksman, Raimund Erbel, Carlo Di Mario, Jozef ...Bartunek, Bernard de Bruyne, Franz R. Eberli, Paul Erne, Michael Haude, Mark Horrigan, Charles Ilsley, Dirk Böse, Hans Bonnier, Jacques Koolen, Thomas F. Lüscher, Neil J. Weissman, on behalf of the PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting with Absorbable Metal Stents) Investigators This study aimed to evaluate the degradation rate and the long-term vascular responses to the absorbable metal stent (AMS) as seen by series of angiographic and intravascular ultrasound (IVUS) studies. We concluded that IVUS imaging supports the safety profile of AMS with degradation at 4 months and durability of the results without any early or late adverse findings. Slower degradation is warranted to provide sufficient radial force to eliminate early recoil and improve long-term patency rates of the AMS.
Objectives This study sought to identify risk factors for thrombus formation on the Amplatzer Cardiac Plug (ACP) (St. Jude Medical, St. Paul, Minnesota) after left atrial appendage occlusion. ...Background Left atrial appendage occlusion with the ACP aims to reduce the risk of embolic stroke and bleeding complications associated with vitamin K antagonists in patients with atrial fibrillation. Methods We performed transesophageal echocardiography before discharge and after 3, 6, and 12 months in 34 patients with atrial fibrillation undergoing ACP implantation and receiving dual antiplatelet therapy. Clinical, echocardiographic, and hemostaseological parameters were retrospectively analyzed to identify risk factors for thrombus formation. Results Three patients had thrombi before discharge, 3 more at the 3-month follow-up. No differences were found in left atrial volume, left atrial appendage velocity, spontaneous echo contrast, transmitral gradient, or mitral regurgitation between patients without or with thrombi. CHADS2 (Congestion, Hypertension, Age, Diabetes, and Stroke) score (2.0 ± 1.1 vs. 4.3 ± 1.0), CHA2 DS2 -VASc (CHADS2 plus Vascular Disease and Sex Category) score (5.2 ± 1.3 vs. 6.8 ± 0.8), and pre-interventional platelet count (215.9 ± 63.9/nl vs. 282.5 ± 84.4/nl) were higher and ejection fraction (50.6 ± 11.4% vs. 39.7 ± 10.6%) lower in those with thrombi. Factor 2, factor 5, or methylenetetrahydrofolate reductase mutations and genetic variants associated with reduced clopidogrel activity were not more frequent in patients with thrombi. Conclusions Transesophageal echocardiography identified 17.6% of patients with thrombus formation on the ACP despite dual antiplatelet therapy. CHADS2 and CHA2 DS2 -VASc scores, platelet count, and ejection fraction are risk factors for such thrombus formation.
Abstract Background Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also ...associated with other diseases or traits. Objectives This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. Methods In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. Results We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 ( KCNJ13-GIGYF2 ), 6p21 ( C2 ), 11p15 ( MRVI1-CTR9 ), 12q13 ( LRP1 ), 12q24 ( SCARB1 ), and 16q13 ( CETP ). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10−4 with a range of other diseases/traits. Conclusions We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
Background The risk of clinically apparent, periprocedural stroke after thoracic endovascular aortic repair (TEVAR) due to dislodgement and embolization of aortic debris from intravascular ...manipulation of guidewires, catheters, and large-bore delivery systems ranges between 2% and 6% and has been associated with increased postoperative mortality. The rate of clinically silent cerebral ischemia is yet unknown, but may be even higher. Methods Nineteen patients (13 male, 6 female) who underwent TEVAR were included into this descriptive study. Periprocedural apparent and silent cerebral ischemia was assessed by daily clinical neurologic assessment and serial cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and 5 days (median, interquartile range: 3.5) after the procedure. Results The TEVAR was successful in all patients without immediate clinically apparent neurologic deficits. Postinterventional cerebral DW-MRI detected a total of 29 new foci of restricted diffusion in 12 of 19 TEVAR patients (63%). Lesions were usually multiple (1 to 6 lesions per patient) and ranged in size between 15 mm3 and 300 mm3 ; 16 lesions were found in the left hemisphere, 13 lesions in the right hemisphere. Overstenting of the left subclavian artery was performed in 8 cases, but was not associated with lateralization of lesions. There were no additional apparent neurologic events during the in-hospital period. Conclusions Thoracic endovascular aortic repair resulted in a high incidence of new foci of restricted diffusion on cerebral DW-MRI in a pattern suggestive of periprocedural embolization. Although multiple lesions per patients were found, these lesions were not associated with apparent neurologic deficits during the in-hospital period. Further developments in TEVAR should be directed toward reducing the risk of periprocedural cerebral embolization.
Objectives This study sought to determine whether the evaluation of the combined presence of coronary artery calcium (CAC) and high-sensitivity C-reactive protein (hsCRP) improves discrimination and ...stratification of hard coronary events and all-cause mortality in the general population. Background Coronary atherosclerosis is a chronic inflammatory disease. Both hsCRP as a measure of inflammation and CAC as a measure of coronary plaque burden have been shown to improve risk appraisal. Methods Framingham risk variables, hsCRP, and CAC were measured in 3,966 subjects without known coronary artery disease or acute inflammation. After 5 years, incident coronary deaths, nonfatal myocardial infarction, and all-cause mortality were determined. Results CAC and hsCRP independently predicted 91 coronary events (adjusted hazard ratios HRs: log2 (CAC+1) = 1.25 95% confidence interval (CI): 1.16 to 1.34, p < 0.0001; hsCRP = 1.11 95% CI: 1.02 to 1.21, p = 0.019) and 130 deaths (adjusted HRs: log2 (CAC+1) = 1.12 95% CI: 1.06 to 1.19, p < 0.0001; hsCRP = 1.11 95% CI: 1.04 to 1.19, p = 0.004). For coronary events, net reclassification improvement (NRI) was 23.8% (p = 0.0007) for CAC and 10.5% (p = 0.026) for hsCRP. Adding CAC to Framingham risk variables and hsCRP further improved discrimination of coronary risk but not vice versa. Among persons without CAC, those with hsCRP >3 mg/l versus <3 mg/l had a significantly higher coronary risk (p = 0.006). For all-cause mortality, integrated discrimination improvement (IDI) was positive when CAC or hsCRP were added to age and sex (+0.51%, p < 0.001 and +0.43%, p = 0.012, respectively). Adjusted HRs in the highest versus lowest category of a risk index derived from established CAC and hsCRP thresholds (i.e., CAC = 100 and hsCRP = 3 mg/l) were 5.92 (95% CI: 3.14 to 11.16) for coronary events and 3.02 (95% CI: 1.82 to 5.01) for all-cause mortality (p < 0.0001 each). The adjusted HR for coronary events in intermediate risk subjects was 6.98 (95% CI: 2.47 to 19.73), p < 0.001. Conclusions The risk of coronary events and all-cause mortality that is mediated by the presence of coronary atherosclerosis and systemic inflammation can be estimated by CAC and hsCRP. An improvement in coronary risk prediction and discrimination was predominantly driven by CAC, whereas hsCRP appears to have a role especially in persons with very low CAC scores.
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