Plasma levels of sRANKL and OPG are associated with atherogenic cytokines in patients with intermediate cardiovascular risk.

Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are regulators of bone remodeling, but are also considered to play important roles in coronary artery disease (CAD). This study evaluated potential associations of soluble (s) RANKL and OPG with atherosclerosis-relevant cytokines. Blood was collected from 414 individuals who presented to our hospital with intermediate likelihood for CAD for further examination. Plasma concentrations of total sRANKL, OPG, and 20 cytokines were measured using sandwich-type enzyme-linked immunoassays (ELISAs; OPG and sRANKL) and Luminex laser-based fluorescence analysis and correlated with each other. The plasma levels of interferon-γ (IFN-γ) and the T-helper cell 2 cytokines interleukin-4 (IL-4) and IL-13 showed a positive correlation with sRANKL. The association with sRANKL levels was negative for IFN-γ-induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1). The strongest independent association with sRANKL in multivariable analyses was found for IFN-γ (positive) and IP-10 (negative), while IL-13 showed a positive and independent association with OPG plasma levels. OPG and sRANKL plasma levels correlate strongly and independently with specific circulating atherosclerosis-related cytokines in patients with intermediate cardiovascular risk.

Platelet CD40 contributes to enhanced monocyte chemoattractant protein 1 levels in patients with resistant hypertension.

BACKGROUND: Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Although it is acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages. However, recently, platelets were identified as inducing inflammation partly by releasing cytokines. The goal of our study was to evaluate the role of platelets as inflammatory cells in the pathogenesis of EH. METHODS: Thirty-nine patients with EH and 30 healthy normotensive controls have been examined. Expression of platelet CD40 was measured by flow cytometry. Serum levels of monocyte chemoattractant protein 1 (MCP-1) and sCD40L were measured via a multiplexing assay. In in vitro experiments, activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA. RESULTS: Essential hypertension patients showed significantly enhanced MCP-1 levels with highest levels in EH patients with microalbuminuria. EH patients showed increased expression of platelet CD40. In the cell coculture model, activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD40L-dependent manner. EH patients showed elevated sCD40L levels with a positive correlation with MCP-1 levels. CONCLUSIONS: Platelets can contribute to enhanced MCP-1 levels in EH. MCP-1 is markedly elevated in serum of EH patients with highest levels in patients with microalbuminuria, one early sign of renal target organ damage. Further studies are required to test whether MCP-1 blocking or antiplatelet strategies may represent new therapeutic options in preventing hypertensive target organ damage.

Bioresorbable vascular scaffold thrombosis in a consecutive cohort of 550 patients.

OBJECTIVE: To determine the rate of bioresorbable vascular scaffold (BVS) thrombosis in a large, real-world population. BACKGROUND: There is some concern about device thrombosis after percutaneous coronary intervention (PCI) using BVS. No data have been published for PCI using both BVS and metal stents. METHODS: A cohort of 550 consecutive patients who underwent PCI for stable chest pain or acute coronary syndromes with implantation of at least one BVS (Absorb, Abbott Vascular) was systematically followed up by telephone interview and review of medical charts. Data on device thrombosis were retrospectively analyzed in relationship to clinical and angiographic characteristics. RESULTS: Follow-up was achieved in 533 patients (97%, median follow-up 233 days). A total of 964 BVS were implanted in 645 vessels. In addition, 234 metal stents were implanted in 149 patients, including "hybrid intervention" with the combined use of BVS and stents in the same artery in 122 patients. Documented were 15 definite, 1 probable, and 8 possible cases of device thrombosis (rate of definite/probable device thrombosis: 3.0%). Of these, 6 definite and 6 possible thromboses could be unambiguously attributed to BVS (1.1%), whereas a total of 11 definite, 1 probable, and 8 possible thromboses were potentially attributable to BVS (2.3%). Definite device thrombosis occurred in 7/122 patients with "hybrid intervention" (5.7%). CONCLUSIONS: In a large real-world cohort treated with BVS, the rate of scaffold thrombosis was higher than published for randomized trials. A high rate of thrombosis was observed after combined implantation of BVS and stents within one vessel. © 2016 Wiley Periodicals, Inc.

Contrast volume reduction using third generation dual source computed tomography for the evaluation of patients prior to transcatheter aortic valve implantation.

OBJECTIVES: Chronic renal failure is common in patients referred for transcatheter aortic valve implantation (TAVI). CT angiography is recommended and provides crucial information prior to TAVI. We evaluated the feasibility of a reduced contrast volume protocol for pre-procedural CT imaging. METHODS: Forty consecutive patients were examined with prospectively ECG-triggered high-pitch spiral acquisition using a novel third-generation dual-source CT system; 38 ml contrast agent was used. Image quality was graded on a visual scale (1-4). Contrast attenuation was measured at the level of the aortic root and at the iliac bifurcation. RESULTS: Mean patient age was 82 ± 6 years (23 males; 58 %). Mean attenuation/average image quality was 285 ± 60 HU/1.5 at the aortic annulus compared to 289 ± 74 HU/1.8 at the iliac bifurcation (p = 0.77/p = 0.29). Mean estimated effective radiation dose was 2.9 ± 0.3 mSv. A repeat acquisition was necessary in one patient due to image quality. Out of the 35 patients who underwent TAVI, 31 (89 %) patients had no or mild aortic regurgitation. Thirty-two (91 %) patients were discharged successfully. CONCLUSION: Pre-procedural CTA with a total of 38 ml contrast volume is feasible and clinically useful, using third-generation dual-source CT, allowing comprehensive imaging for procedural success. KEY POINTS: • Reduction of contrast agent volume is crucial in patients with chronic renal failure. • Novel third-generation computed tomography helps to reduce contrast agent volume. • Pre-procedural CT allows comprehensive imaging for procedural success before heart valve implantation. • A low-contrast CT protocol is feasible for pre-procedural TAVI planning.

Association of systemic inflammation with epicardial fat and coronary artery calcification.

BACKGROUND: Increased epicardial fat volume (EFV) has been shown to be associated with coronary atherosclerosis. While it is postulated to be an independent risk factor, a possible mechanism is local or systemic inflammation. We analyzed the relationship between coronary atherosclerosis, quantified by coronary calcium in CT, epicardial fat volume and systemic inflammation. METHODS: Using non-enhanced dual-source CT, we quantified epicardial fat volume (EFV) and coronary artery calcium (CAC) in 391 patients who underwent coronary computed tomography for suspected coronary artery disease. In addition to traditional risk factors, serum markers of systemic inflammation were measured (IL-1α, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10,IL-12, IL-13, IL-15, IL-17, IFN-γ, TNF-α, hs-CRP, GM-CS, G-CSF, MCP-1, MIP-1, Eotaxin and IP-10). In 94 patients follow-up data were obtained after 1.9 ± 0.5 years. RESULTS: The 391 patients had a mean age of 60 ± 10 years, and 69 % were males. Mean EFV was 116 ± 50 mL. Median CAC was 12 (IQR 0; 152). CAC and EFV showed a significant correlation (ρ = 0.37; P < 0.001). EFV and CAC were significantly correlated with the traditional risk factors like age, male gender, diabetes, smoking and hypertension. With regard to biomarkers, CAC was significantly associated (negatively) to G-CSF and IL-13. EFV (median binned) was significantly associated (positively) with IP-10 (P = 0.002) and MCP-1 (ρ = 0.037). In follow-up, EFV showed a mean annualized progression of 6 mL (IQR 3; 9) (P < 0.001); CAC progressed by a mean of six Agatston Units (IQR 0; 30). The progression of CAC was significantly correlated with the extent of EFV (P < 0.001) while there was no significant correlation between progression of EFV or CAC with systemic inflammation markers. CONCLUSION: Epicardial fat volume and the baseline extent as well as progression of coronary atherosclerosis-measured by the calcium score-are significantly correlated. While both baseline EFV and CAC displayed significant correlations with systemic inflammation markers, biomarkers were not predictive of the progression of CAC or EFV.

Comparison of Exo-Seal(®) and Angio-Seal (®) for arterial puncture site closure: A randomized, multicenter, single-blind trial.

BACKGROUND: The use of extravascular femoral closure devices in patients undergoing coronary angiography/intervention has not been sufficiently evaluated. We sought to define the impact of an extravascular polyglycolic acid (PGA) plug for the closure of a femoral access site in patients undergoing coronary angiography and/or percutaneous coronary intervention. METHODS: In this prospective, single-blind, multicenter trial we randomly assigned 319 patients to vessel closure with Angio-Seal(®) or Exo-Seal(®). We hypothesized that the use of an extravascular closure device is not inferior to an anchor/plug-mediated device regarding the occurrence of the composite primary endpoint: hematoma > 5 cm, significant groin bleeding (TIMI major bleed), false aneurysm, and device failure. RESULTS: There was no significant difference in patient baseline characteristics or procedural results. After 24 h the primary endpoint occurred in nine patients (5.6 %) in the Angio-Seal(®) group and in 13 patients (8.2 %) inthe Exo-Seal(®) group (p = 0.38). Hematoma > 5 cm was noted in three patients (1.9 %) receiving Angio-Seal(®) vs. two patients (1.3 %) receiving Exo-Seal(®) (p = 0.99). In one patient (0.6 %) of the Exo-Seal(®) group, TIMI major bleeding occurred, requiring transfusion (p = 0.49). There were four (2.5 %) false aneurysms found in patients treated with Angio-Seal(®) and two (1.3 %) in patients treated with Exo-Seal(®) (p = 0.68). There was a trend for a higher incidence of device failure in the Exo-Seal(®) group (1.2 vs. 5.2 %, p = 0.06). At telephone interview after 30 days, there was no significant difference found regarding the events readmission with surgery of puncture site, infection, bleeding, hematoma, or pain. CONCLUSION: In the present study, there were no significant differences found regarding the occurrence of hematoma > 5 cm, major bleeding, false aneurysm, and device failure between Angio-Seal(®) and Exo-Seal(®) 24 h after device implantation.

Epicardial fat and coronary artery calcification in patients on long-term hemodialysis.

INTRODUCTION: Recent studies have shown a significant correlation between increased epicardial fat volume (EFV) and mortality, coronary artery disease events, and measures of coronary atherosclerotic burden, for example, coronary calcium. Patients with chronic kidney disease on hemodialysis have an increased prevalence of coronary atherosclerosis and coronary calcium. The mechanisms underlying both may differ from patients with normal kidney function. Only limited data are available on the relationship between epicardial fat and coronary calcium in these patients. METHODS: Ninety-three consecutive patients (62 men and 31 women; mean age, 55 ± 11 years) with chronic kidney failure on regular hemodialysis underwent computed tomography for coronary calcium scoring as well as assessment of cardiovascular risk factors. Calcium scoring was performed using a low-dose, prospectively ECG-triggered high pitch spiral acquisition protocol (dual-source computed tomography, 280-millisecond (ms) rotation, 2 × 128 × 0.6-mm collimation, 120-kV tube voltage, 80-mA·s tube current). Cross-sectional images were reconstructed with 3.0-mm thickness, 1.5-mm increment, and a medium sharp reconstruction kernel (B35f). Agatston score and EVF were analyzed in a semiautomatic fashion using dedicated software. RESULTS: The mean duration of dialysis was 5.7 years. Of all patients, 93% had arterial hypertension, 66% had hyperlipidemia, 30% were diabetic, and 49.5% were current or prior smokers. The mean body mass index (BMI) was 27 ± 4 kg/m. The mean EFV was 162 ± 80 mL, and the mean coronary artery calcification (CAC) was 765 ± 1391 Agatston units (AU). In univariable and multivariable analysis, EFV was significantly correlated to BMI (P < 0.05) and age (P = 0.021), but not to CAC (P = 0.106). In subanalysis for values binned by median, we also found a significant correlation between EFV (binned) and smoking (P = 0.49) as well as a significant correlation between EFV (binned) and CAC for 46 patients younger than 55 years (median age). CONCLUSION: The epicardial fat volume in patients with chronic kidney disease and on hemodialysis is significantly correlated to BMI, age, and smoking but, with the exception of younger patients, not to the coronary calcium score. Our data suggest that in this special patient cohort, other mechanisms might influence the genesis of coronary calcification.

Impact of telmisartan on the inflammatory state in patients with coronary atherosclerosis--influence on IP-10, TNF-α and MCP-1.

BACKGROUND: Hypertension is one of the most prominent risk factors for coronary artery disease (CAD). Treatment of hypertension is therefore important for reducing cardiovascular events and the progression of atherosclerosis. Several treatment strategies are common in clinical practice for example the use of ACE-blockers or angiotensin receptor II blockers (ARBs), so called sartans. Telmisartan, belonging to the class of ARBs, was shown to exert anti-inflammatory effects besides the blood pressure lowering. METHODS: In this work, two separate substudy groups of hypertensives were compared. 16 patients with arterial hypertension have been treated with telmisartan (initial 40 mg Kinzalmono®) for 7.3 ± 4.4 months. The telmisartan group was compared to a matched control group including 31 hypertensive patients without telmisartan treatment with a follow up period of 1.9 ± 0.5 years. Serum samples from the beginning and the end of follow up were analyzed with Luminex® technology for 26 cytokines and chemokines. The baseline scores of coronary artery calcification (CAC) were gathered by multislice detector computer tomography. RESULTS: After 7 months of telmisartan treatment and 2 years in control patients most of the measured analytes did not change significantly. MCP-1 (P=0.001; P<0.001) was increased significantly in both telmisartan and control group. The relative decrease in IP-10 and TNF-α levels was observed in telmisartan group, as opposed to the increase in control (telmisartan vs. control P=0.048; P=0.01). No linear rank-correlation between measured analytes and the initial CAC was found. CONCLUSION: Telmisartan reduced blood pressure in patients with atherosclerosis and arterial hypertension within a short time period, whereas the inflammatory status of these patients remained largely unchanged. An involvement of telmisartan in the regulation of inflammatory and anti-inflammatory mediators in the context of CAD and CAC is possible, but cannot clearly be assumed based on the present findings.

Association of systemic inflammation markers with the presence and extent of coronary artery calcification.

BACKGROUND: Coronary artery calcification (CAC) is a marker for the presence and extent of coronary atherosclerotic plaques and can be detected non-invasively by multi-detector row CT (MDCT). Well known predictors of CAC are age, gender, and the classical atherogenic risk factors. CAC is associated with atherosclerotic plaque burden, but it is still elusive if atherosclerosis-relevant cytokines and chemokines are also associated with CAC. METHODS: We conducted a clinical study among 455 consecutive individuals who underwent coronary calcium assessment performed by MDCT. Before MDCT, blood was drawn and subsequently analyzed for 20 different atherosclerosis-relevant cytokines and chemokines using a Luminex-laser-based fluorescence analysis. RESULTS: Using univariate analyses, CAC patients revealed significantly higher levels of the chemokines IP-10 (P=0.047) and eotaxin (P=0.031) as compared to non-CAC patients. In multivariate analyses using common thresholds for calcium burden, the three cytokines interleukin-6 (P=0.028), interleukin-8 (P=0.009), and interleukin-13 (P=0.024) were associated with high coronary calcium levels after adjustment for classical variables and risk factors. CONCLUSIONS: In a large group of individuals with atypical chest pain and a low to intermediate likelihood for coronary artery disease elevated plasma levels of IL-6 and reduced levels of IL-8 and IL-13 were predictive for distinct coronary artery calcification. These findings support a specific role of these cytokines in coronary calcification.

Predictive value of the decrease in circulating dendritic cell precursors in stable coronary artery disease.

DCs (dendritic cells) are present in atherosclerotic lesions leading to vascular inflammation, and the number of vascular DCs increases during atherosclerosis. Previously, we have shown that the levels of circulating DCPs (DC precursors) are reduced in acute coronary syndromes through vascular recruitment. In the present study, we have investigated whether DCP levels are also reduced in stable CAD (coronary artery disease). The levels of circulating mDCPs (myeloid DCPs), pDCPs (plasmacytoid DCPs) and tDCP (total DCPs) were investigated using flow cytometry in 290 patients with suspected stable CAD. A coronary angiogram was used to evaluate a CAD score for each patient as follows: (i) CAD excluded (n=57); (ii) early CAD (n=63); (iii) moderate CAD (n=85); and (iv) advanced CAD (n=85). Compared with controls, patients with advanced stable CAD had lower HDL (high-density lipoprotein)-cholesterol (P=0.03) and higher creatinine (P=0.003). In advanced CAD, a significant decrease in circulating mDCPs, pDCPs and tDCPs was observed (each P<0.001). A significant inverse correlation was observed between the CAD score and mDCPs, pDCPs or tDCPs (each P<0.001). Patients who required percutaneous coronary intervention or coronary artery bypass grafting had less circulating mDCPs, pDCPs and tDCPs than controls (each P<0.001). Multiple stepwise logistic regression analysis suggested mDCPs, pDCPs and tDCPs as independent predictors of CAD. In conclusion, we have shown that patients with stable CAD have significantly lower levels of circulating DCPs than healthy individuals. Their decrease appears to be an independent predictor of the presence of, and subsequent therapeutic procedure in, stable CAD.

Outcomes of contemporary interventional therapy of ST elevation infarction in patients older than 75 years.

BACKGROUND: Data on contemporary real-world outcomes of interventional revascularization in patients > or = 75 y of age with ST elevation infarction (STEMI) are limited. METHODS: We analyzed all 504 consecutive patients who underwent angiography for acute STEMI between 1999 and 2005 at our center, and followed them up over one year. Outcomes in patients > or = 75 y of age were compared with younger patients. RESULTS: Patients > or = 75 y of age (n = 115) were majority females (55% versus 21%, p < 0.001), more cases of diabetes (42% versus 27%, p = 0.004), hypertension (78% versus 65%, p = 0.03) and a history of coronary events (25% versus 15%, p = 0.002). Younger patients were more often smokers (63% versus 30%, p < 0.001). After coronary angiography patients > or = 75 y of age underwent less frequent intervention (PCI; 84% versus 93%, p = 0.01). However, if PCI was performed, technical success rates were similar to younger patients (84% versus 86%). The 30-d mortality was 13% versus 6.4% (p = 0.03), but after successful PCI, the 30-d mortality rate was not significantly higher in old patients (7.4% versus 3.9%, p = 0.23). Bleeding complications were very low in both age groups if the radial access route was chosen. Multivariate predictors of 30-d mortality were cardiogenic shock/survived cardiac arrest, ejection fraction < 30%, conservative treatment or unsuccessful PCI (OR 3.01), renal insufficiency, diabetes, and age. One-y mortality was higher in the elderly (24.3% versus 9.9%, p < 0.001). Among 30-d-survivors, only multivessel disease and age were multivariate predictors of 1-y mortality. CONCLUSION: Patients > or = 75 y of age benefit from PCI in STEMI, and failed or unattempted PCI worsens prognosis in the old as well as in younger patients.

Randomized trial of acupuncture to lower blood pressure.

BACKGROUND: Arterial hypertension is a prime cause of morbidity and mortality in the general population. Pharmacological treatment has limitations resulting from drug side effects, costs, and patient compliance. Thus, we investigated whether traditional Chinese medicine acupuncture is able to lower blood pressure. METHODS AND RESULTS: We randomized 160 outpatients (age, 58+/-8 years; 78 men) with uncomplicated arterial hypertension in a single-blind fashion to a 6-week course of active acupuncture or sham acupuncture (22 sessions of 30 minutes' duration). Seventy-eight percent were receiving antihypertensive medication, which remained unchanged. Primary outcome parameters were mean 24-hour ambulatory blood pressure levels after the treatment course and 3 and 6 months later. One hundred forty patients finished the treatment course (72 with active treatment, 68 with sham treatment). There was a significant (P<0.001) difference in posttreatment blood pressures adjusted for baseline values between the active and sham acupuncture groups at the end of treatment. For the primary outcome, the difference between treatment groups amounted to 6.4 mm Hg (95% CI, 3.5 to 9.2) and 3.7 mm Hg (95% CI, 1.6 to 5.8) for 24-hour systolic and diastolic blood pressures, respectively. In the active acupuncture group, mean 24-hour ambulatory systolic and diastolic blood pressures decreased significantly after treatment by 5.4 mm Hg (95% CI, 3.2 to 7.6) and 3.0 mm Hg (95% CI, 1.5 to 4.6), respectively. At 3 and 6 months, mean systolic and diastolic blood pressures returned to pretreatment levels in the active treatment group. CONCLUSIONS: Acupuncture according to traditional Chinese medicine, but not sham acupuncture, after 6 weeks of treatment significantly lowered mean 24-hour ambulatory blood pressures; the effect disappeared after cessation of acupuncture treatment.

Red blood cell omega-3 fatty acids and the risk of ventricular arrhythmias in patients with heart failure.

BACKGROUND: Epidemiological studies support the protective effect of omega-3 fatty acids on sudden cardiac death. However, patients with structural heart disease and an implantable cardioverter defibrillator (ICD) showed no effect or even a proarrhythmic response to fish oil supplementation. Animal studies suggest different electrophysiologic effects of circulating and incorporated omega-3 fatty acids. METHODS: In 102 ICD patients in New York Health Association functional class II or III, the fatty acid composition of red blood cells was analyzed by gas chromatography. The omega-3 index was calculated from eicosapentaenoic acid and docosahexaenoic acid. Patients were followed for 1 year, and ventricular arrhythmias requiring antitachycardic therapy were analyzed. Twenty-five healthy subjects served as control. RESULTS: In ICD patients, the fatty acid profile was significantly altered and the baseline omega-3 index was significantly elevated, as compared to control subjects (5.12% +/- 0.87% vs 4.24% +/- 0.96%, P < .001). Kaplan-Meier estimates of probability of ventricular arrhythmias showed significant differences among quartiles of the omega-3 index. Twelve percent of patients in the lowest quartile had ventricular arrhythmias, as compared to 54% of patients in the highest quartile (P = .022). In a multivariate analysis, the omega-3 index was the only independent predictor for ventricular arrhythmias up to 9 months. At 12 months, a reduced ejection fraction was an additional risk predictor. CONCLUSIONS: In heart failure patients, the red blood cell fatty acid profile is altered. Omega-3 fatty acids are elevated and predict the risk of ventricular arrhythmias.

Chronic development of ischaemic mitral regurgitation during post-infarction remodelling.

BACKGROUND/AIMS: Mitral regurgitation (MR) following myocardial infarction (MI) may be a (sub)acute complication which independently predicts reduced survival. We sought to evaluate the chronic development of MR as potential consequence of left-ventricular (LV) remodelling, the latter being a long-term process. METHODS AND RESULTS: Retrospectively, 103 post-MI patients were included according to a standardised Doppler echocardiogram <3 months following MI (20 +/- 25 days post-MI) and a follow-up examination >6 months after the first examination (5.1 +/- 3.1 years post-MI). Patients were clinically followed up for 7.6 +/- 2.7 years. Group I patients were defined as those showing new development or deterioration in one of three grades of MR, and group II those without this criterion (MR grade acute 0.17 vs. 0.27, p = 0.7, and chronic 1.53 vs. 0.19, p < 0.0001). Patient characteristics were similar in respect of age, gender, size and location of infarction. However, group I patients had coronary artery disease with more vessels involved. With regard to echocardiographic parameters of significantly enlarged LV chamber size in group I vs. group II, the significant decrease in LV performance was more pronounced and occurred concomitant with a higher degree of symptomatic congestive heart failure and greater need for heart failure medications in group I. Mortality in group I patients was 39 versus 9% in group II patients (p = 0.0002), approximating an odds ratio of 6.4697 (95% confidence interval: 2.211-18.931). CONCLUSION: First of all, this retrospective study indicates that MR may be detected in patients after MI during a long-term follow-up most probably due to geometric distortions of LV remodelling resulting in a significantly higher mortality. Since this process is known to become irreversible at a certain point, serial echocardiography may help to detect MR in post-MI patients and thus pave the way for appropriate treatment.

Predictors of Technical Failure in Transradial Coronary Angiography and Intervention.

Transradial access for coronary angiography and intervention is preferred over the femoral approach but can be technically challenging. Identification of predictors of transradial access failure is important, especially in the context of acute coronary syndromes. We therefore retrospectively analyzed 13,095 consecutive patients (66 ± 12 years, 64% male) in whom transradial access was attempted for coronary angiography or intervention to identify predictors of transradial access failure. Angiograms and patient files were systematically reviewed to analyze patient characteristics associated with failure. Transradial access failure rate was 6.8% (909 of 13,095). Patients with transradial access failure were more frequently female (9.5% vs 5.5%; p <0.001), significantly older (68 ± 12 vs 66 ± 12 years, p <0.001), and had a smaller body surface area (1.89 ± 0.21 vs 1.94 ± 0.2 m2; p <0.001). Transradial failure was not significantly more frequent in ST-elevation myocardial infarction versus other patients (8.1% vs 6.9%, p = 0.195). After multivariable adjustment, only female sex (odds ratio [OR] 1.44, p <0.001), higher patient age (OR 1.01/year, p = 0.002), and lower height (OR 0.98/cm, p = 0.004) independently predicted transradial access failure. In conclusion, female sex, higher age, and smaller height independently predict transradial access failure in coronary angiography and intervention. Failure rate in ST-elevation myocardial infarction is not significantly increased.

Influence of Cardiovascular Risk Factors on the Prevalence of Coronary Atherosclerosis in Patients with Angiographically Normal Coronary Arteries.

RATIONALE AND OBJECTIVES: Cardiovascular (CV) disease is predominately influenced by CV risk factors and coronary computed tomography angiography (CTA) is capable of detecting early-stage coronary artery disease. We sought to determine the influence of CV risk factors on the prevalence of nonobstructive atherosclerosis in patients with normal-appearing coronary arteries in invasive coronary angiography (ICA). MATERIALS AND METHODS: In this retrospective analysis, we included 60 consecutive symptomatic patients, having undergone ICA and coronary CTA. Coronary dual source CTA was performed using electrocardiogram-triggered retrospective gated image acquisition at 40%-70% of RR interval (tube voltage 100-120 kV, tube current time product 320-440 mAs, 60 mL contrast, and flow rate 6 mL/s). RESULTS: Out of 60 patients (32 men, mean age 61 ± 11 years) with a normal coronary artery appearance in ICA, 45 (75%) patients showed atherosclerotic plaque in CTA. Plaque was present in 14 of 60 (23%) left main, 41 of 60 (68%) left anterior descending, 21 of 60 (35%) circumflex coronary arteries, and 24 of 60 (40%) right coronary arteries. More than 15% of all coronary artery segments showed detectable plaques. Interobserver agreement ranged from good to very good on a per-patient, per-vessel, and per-segment level. Patients with presence of plaque were significantly older (P = 0.005) and showed higher incidence of arterial hypertension (P = 0.019) as compared to individuals without coronary plaque in dual source computed tomography. CONCLUSIONS: The prevalence of coronary atherosclerosis by CTA is substantial in symptomatic patients with normal invasive coronary angiogram. Hypertension and older age significantly influence the prevalence of atherosclerotic plaque and highlight the importance of risk-modifying therapy.

CT-based analysis of pericoronary adipose tissue density: Relation to cardiovascular risk factors and epicardial adipose tissue volume.

BACKGROUND: Pericoronary adipose tissue (PCAT) can promote atherosclerosis. Metabolically active and inactive PCAT may display different CT densities. However, CT density could be influenced by partial volume effects and image interpolation. OBJECTIVE: To investigate whether PCAT density values in CT displays differences that are larger than those attributable to interpolation and partial volume effects, which would manifest themselves through the relationship between PCAT density and distance from the contrast-enhanced coronary lumen. METHODS: PCAT density analysis was performed (417 non-atherosclerotic segments, 63 patients) using dual-source CT with a threshold-based measurement method. Changes in PCAT density values depending on distance from the contrast-enhanced coronary lumen and the influence of cardiovascular risk profile were analyzed. RESULTS: Mean PCAT density was -78.1 ± 5.6 HU. PCAT density decreased from proximal to distal segments in the LAD (-78.0 ± 7.3 vs. -82.4 ± 7.7 HU; p < 0.001). PCAT density was higher close to the lumen compared to more peripheral locations (-76.0 ± 6.7 vs. -78.5 ± 5.4 HU; p < 0.001). Decreasing PCAT density was significantly associated with higher epicardial adipose tissue (EAT) volume and body mass index. There was a trend of lower PCAT values with a family history of coronary artery disease. CONCLUSION: CT-measured attenuation of PCAT is influenced by EAT volume and body mass index. A decrease of PCAT attenuation with increasing distance from the vessel and from proximal to distal segments may suggest variations in CT density of PCAT due to partial volume effects and image interpolation rather than solely due to differences in tissue composition or metabolic activity.

Influence of ultrasound operating parameters on ultrasound-induced thrombolysis in vitro.

The effect of operating parameters on the thrombolytic potency of ultrasound (US) is important for potential therapeutic applications, but is not fully understood. Fresh human whole-blood thrombi were exposed in vitro to focused US from a diagnostic transducer driven by an impulse generator via an amplifier to vary duration (10 to 60 min), intensity (7 to 90 W/cm(2)), frequency (2 to 4.5 MHz), pulsed wave duty cycle (1:5 to 1:100 and continuous wave mode) and pulse length (100 to 400 micros). Segments of thrombi (498 +/- 73 mg) were submersed and insonated in saline solution. Thrombolytic efficiency was expressed as percentage loss of mass compared with controls (noninsonified thrombi). Ultrasound exposure achieved a significantly higher thrombolysis than no US, 56 +/- 16 % vs. 29 +/- 11 % (n = 232, p < 10(-6)). There was an exponential saturation-type correlation with duration of insonation (r(2) = 0.64) and intensity (r(2) = 0.97), an inverse correlation with US frequency at matched intensities (r(2) = 0.76, p < 10(-5)), a logarithmic relationship with duty cycle in pulsed mode (r(2) = 0.86) and a modest direct effect of pulse length (r(2) = 0.57, p < 10(-5)). Thus, thrombolytic efficiency of US depends directly on duration, intensity, duty cycle and pulse length and inversely, on frequency.

Comparison of intracoronary versus intravenous administration of adenosine for measurement of coronary fractional flow reserve.

BACKGROUND: Measurement of fractional flow reserve (FFR) constitutes the current gold standard to evaluate the hemodynamic significance of coronary stenoses. Limited data validate the intracoronary application of adenosine against standard intravenous infusion. We systematically compared FFR measurements during intracoronary and intravenous application of adenosine about agreement and reproducibility. METHODS AND RESULTS: We included 114 patients with an intermediate degree of stenosis in coronary angiography. Two FFR measurements were performed during intracoronary bolus injection (40 µg for the right and 80 µg for the left coronary artery, FFRic), and 2 FFR measurements during continuous intravenous infusion of adenosine (140 µg/kg per minute, FFRiv). FFR value, the time to reach FFR and patient discomfort (on a subjective scale from 0 for no symptoms to 5 for maximal discomfort) were recorded for each measurement. Mean time to FFR was 100 ± 27 s for continuous intravenous infusion versus 23 ± 14 s for intracoronary bolus administration of adenosine (P < 0.001). Reported discomfort after intracoronary application was significantly lower compared with intravenous adenosine (subjective scale > 0 in 35.1% versus 87.7% of the patients; P < 0.001). Correlation between FFRiv and FFRic was extremely close (r = 0.99; P < 0.001) with no systematic bias in Bland-Altman analysis (bias 0.002 [confidence interval, -0.001 to 0.005]) and low intermethod variability (1.56%). Intramethod variability was not different between intravenous and intracoronary administration (1.47% versus 1.33%; P=0.5). CONCLUSIONS: Intracoronary bolus injection of adenosine (40 µg for the right and 80 µg for the left coronary artery) yields identical FFR results compared with intravenous infusion (140 µg/kg per minute), while requiring less time and offering superior patient comfort.