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Background and Aims: Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events.Methods and Results: In this cross-sectional multicenter trial, we enrolled 189 patients with AF who were on oral anticoagulation. The primary endpoint was defined as either the presence of spontaneous echo contrast (SEC), a left atrial appendage (LAA), or a left atrial (LA) thrombus on transesophageal echocardiography. We investigated the association of adipocytokine serum levels with the combined endpoint using logistic regression analysis. Forty-eight individuals (25%) were assigned to group 1 (G1) due to the occurrence of at least one of the components of the combined endpoint (41 [21.7%] SEC, 3 [1.6%] LA thrombus, 13 [6.9%] LAA thrombus), whereas the remaining patients formed group 2 (G2). The BMI, logarithmized (loge) leptin (G1: 2.0 ± 1.3 μg/ml, G2: 2.0 ± 1.1 μg/ml, p = 0.746) and visfatin serum levels (G1: 3.4 ± 0.3 ng/ml, G2: 3.4 ± 0.5 ng/ml, p = 0.900) did not significantly differ between the groups. Conversely, logarithmized adiponectin (G1: 3.3 ± 0.6 ng/ml, G2: 3.1 ± 0.7 ng/ml, p = 0.036) and resistin levels (G1: 1.8 ± 0.5 ng/ml, G2: 1.6 ± 0.5 ng/ml, p = 0.009) were higher in patients with the primary endpoint. Multivariate logistic regression analysis using a score that combined the individual adiponectin and resistin values in each patient corroborated this association.Conclusions: Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk. [ABSTRACT FROM AUTHOR]

Analyzing the 1 H NMR spectrum of d -glucose, the resonance frequencies of the anomeric protons of five d -glucose anomers could be determined in dependence on temperature. Besides, the relative concentrations of all cyclic d -glucose anomers could be quantified. Based on that, thermodynamic parameters were calculated. In addition, ring opening rate constants of all cyclic d -glucose anomers were measured for the first time using 1 H selective blind saturation transfer NMR spectroscopy. The results presented here give rise to the assumption that furanoid anomers highly influence the reactivity of total d -glucose. Finally, the complex anomeric equilibration curves for a freshly prepared solution of crystalline α- d -glucopyranose are presented. Based on that, it is hypothesized that the reactivity of a solution of a reducing sugar in general and d -glucose in particular depends on time until the thermodynamic equilibrium state is reached. [ABSTRACT FROM AUTHOR]

In the search for novel platinum-based anticancer therapeutic agents, we have recently established a structural motif of ( O , S ) bidentate ligands bound to a Pt(II) metal center which is effective against various cancer cell lines. Aiming at further enhancing the cytotoxicity of metal-based drugs, the identification of potential biological targets and elucidation of the mode of action of selected lead compounds is of utmost importance. Here we report our studies on the DNA interaction of three representative Pt(II) complexes of the investigated series, using various model systems and analytical techniques. In detail, CD spectroscopy as well as ESI-MS and MS 2 techniques were applied to gain an overall picture of the binding properties of this class of ( O , S ) bidentate Pt(II) compounds with defined oligonucleotide sequences in single strand, duplex or G-quadruplex form, as well as with the nucleobase 9-methylguanine. On the whole, it was demonstrated that the tested compounds interact with DNA and produce conformational changes of different extents depending on the sequence and structure of the examined oligonucleotide. Guanine was established as the preferential target within the DNA sequence, but in the absence or unavailability of guanines, alternative binding sites can be addressed. The implications of these results are thoroughly discussed. [ABSTRACT FROM AUTHOR]

Quantitative 1 H selective saturation transfer NMR spectroscopy ( 1 H SST qNMR) was used to fully describe the milieu dependent dynamics of the isomeric system of d -erythrose. Thermodynamic activation parameters are calculated for acidic as well as for basic catalysis combining McConnell's modified Bloch equations for the chemical exchange solved for the constraint of saturating the non-hydrated acyclic isomer, the Eyring equation and Hudson's equation for pH dependent catalysis. A detailed mathematical examination describing the milieu dependent dynamics of sugar isomerisation is provided. Thermodynamic data show evidence that photo-catalysed sugar isomerisation as well as degradation has to be considered. Approximations describing the pH and temperature dependence of thermodynamic activation parameters are derived that indicate the possibility of photo-affecting equilibrium constants. Moreover, the results show that isomerisation dynamics are closely related to degradation kinetics and that sugars' reactivities are altered by the concentration of acyclic carbonyl isomer and the sum of its ring closing rate constants. Additionally, it is concluded that sugar solutions show a limited self-stabilising behaviour. [ABSTRACT FROM AUTHOR]

Background Endoscopically detected esophageal lesions (EDELs) have been identified in apparently asymptomatic patients after catheter ablation of atrial fibrillation (AF). The use of esophageal probes to monitor luminal esophageal temperature (LET) during catheter ablation to protect esophageal damage is currently controversial. Objective The purpose of this study was to investigate the impact of the use of esophageal temperature probes during AF catheter ablation on the incidence of EDELs. Methods Eighty consecutive patients (mean age 63.8 ± 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal (n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter ablation were prospectively enrolled. Posterior wall ablation was power limited (≤25 W). In the first 40 patients, LET was monitored continuously (group A), whereas no esophageal temperature probe was used in group B (n = 40 patients). Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency catheter ablation. Results Overall, 13 patients (16%) developed EDELs after AF ablation. The incidence of EDELs was significantly higher in group A than group B (30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher maximal LET during AF ablation than patients without EDEL (40.97 ± 0.92°C vs 40.14 ± 1.1°C, P = .02). Multivariable logistic regression analysis revealed the use of an esophageal temperature probe as the only independent predictor for the development of EDEL (odds ratio 16.7, P < .01). Conclusion The use of esophageal temperature probes in the setting of AF catheter ablation per se appears to be a risk factor for the development of EDEL. [ABSTRACT FROM AUTHOR]

Severe aortic valve stenosis is a common valvular heart disease that is characterized by left ventricular (LV) pressure overload. A lasting effect of pressure overload is LV remodeling, accompanied by concentric hypertrophy and increased myocardial stiffness. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic valve stenosis and high surgical risk. Although TAVI has favorable hemodynamic performance, aortic valve regurgitation (AR) is the most frequent complication because of the specific technique used for implantation of transcatheter valves. During implantation, the calcified native valve is pushed aside, and the prosthesis usually achieves only an incomplete prosthesis apposition. As a consequence, the reported prevalence of moderate and severe AR after TAVI is 6% to 21%, which is considerably higher than that after a surgical valve replacement. Although mild AR probably has minor hemodynamic effects, even moderate AR might result in serious consequences. In moderate and severe AR after TAVI, a normal-sized LV with increased myocardial stiffness has been exposed to volume overload. Because the noncompliant LV is unable to raise end-diastolic volume, the end-diastolic pressure increases, and the forward stroke volume decreases. In recent years, an increasing number of patients have successfully undergone TAVI. Despite encouraging overall results, a substantial number of patients receive neither symptomatic nor prognostic benefits from TAVI. Aortic valve regurgitation has been considered a potential contributor to morbidity and mortality after TAVI. Therefore, various strategies and improvements in valve designs are mandatory to reduce the prevalence of AR after TAVI. [Copyright &y& Elsevier]

Background: Catheter ablation of atrial fibrillation (AF) is complicated by cerebral emboli resulting in acute ischemia. Recently, cerebral ischemic microlesions have been identified with diffusion-weighted magnet resonance imaging (MRI). Objective: The clinical course and longer-term characteristics of these lesions are not known and were investigated in this study. Methods: Of 86 patients, 33 (38%) had new asymptomatic cerebral lesions documented on MRI after catheter ablation for AF; 14 of these 33 (42%) underwent repeat MRI at different time intervals (2 weeks to 1 year) during follow-up, and clinical symptoms as well as size and number of residual lesions were documented. Results: In postablation cerebral MRI, 50 new lesions were identified (3.6 lesions/patient) in 14 patients. No patient presented any neurological symptoms. Distribution of the lesions was predominantly in the left hemisphere (60%) and the cerebellum (26%); 52% of the lesions were small (≤3 mm maximum diameter), 42% were medium (4 to 10 mm) and 3 lesions (6%) had a maximum diameter >10 mm. Follow-up MRI after a median of 3 months revealed 3 residual lesions in 3 of 14 patients corresponding to the large acute postablation lesions (>10 mm). The remaining 47 of 50 (94%) of the small or medium-sized lesions were not detectable at follow-up evaluation. Conclusions: Most asymptomatic cerebral lesions observed acutely after AF ablation procedures were ≤10 mm in diameter. 94% of all lesions healed without scarring at follow-up >2 weeks after ablation. The larger acute lesions produced chronic glial scars. Neither chronic nor acute lesions were associated with neurological symptoms. [Copyright &y& Elsevier]

Background: Atrial fibrillation (AF) is a multifactorial disease of the atria. Objective: We studied the differences in the atrial autonomic innervation pattern in subjects with AF compared with sinus rhythm (SR). Methods: Preparation of postmortem isolated hearts of subjects with documented persistent AF (group A) and SR (group B) included: (1) histological sectioning of predefined areas and quantification of nerve density, and (2) differentiation using immunohistochemistry in adrenergic (sympathetic, tyrosine-hydroxylase antibody), cholinergic (parasympathetic, choline-acetyltransferase antibody) and mixed (adrenergic and cholinergic staining) nerves. Results: Characteristics of subjects in group A (N = 15) and group B (N = 24) did not differ. The mean overall nerve density was similar between groups (A: 0.31 ± 0.25/mm2; B: 0.35 ± 0.25/mm2; P = .87). Nerve density appeared higher in the region of the pulmonary vein ostia and antrum (group A: 0.38 ± 0.21/mm2; group B: 0.32 ± 0.19/mm2,) compared with other locations of the right and left atrium. A total of 2,224 (group A: 685; group B: 1539) nerves were differentiated using immunohistochemistry. There was a high degree of colocalization of adrenergic and cholinergic nerves (group A: 80% mixed staining, group B: 69% mixed staining). In group A hearts there was a significantly lower density of predominantly cholinergic nerves (0.025 ± 0.052/mm2 vs. 0.058 ± 0.099/mm2; P = .008) and a higher density of nerves containing adrenergic components (0.24 ± 0.18/mm2 vs. 0.18 ± 0.17/mm2, P = .046). Conclusion: Overall autonomic nerve density did not differ between atria with persistent AF compared with SR. On a morphological level, we detected a shift toward a lower density of cholinergic nerves and a higher density of nerves containing adrenergic components in AF subjects. [ABSTRACT FROM AUTHOR]

Background: This prospective study was designed to evaluate the hemodynamic results of transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) and the effects on left ventricular function. Methods: From June 2008 to June 2009, consecutive patients with severe symptomatic aortic valve stenosis (aortic valve area <1 cm2) and the indication for TAVI were included. Aortic valve prosthesis was inserted retrograde. Examinations of study patients were performed before, 30 days, and 6 months after TAVI and comprised measurement of B-type natriuretic peptide and echocardiography. Severe prosthesis-patient mismatch was defined as an indexed effective aortic valve area ≤0.65 cm2/m2. Results: In 39 patients, follow-up examinations were performed after TAVI. Severe prosthesis-patient mismatch seldom occurred (n = 1), but mild to moderate aortic valve regurgitation due to paravalvular leaks was common (n = 24, 62%). After 6 months, left ventricular mass index declined (158 ± 46 vs 138 ± 45 g/m2, P = .001), and peak early diastolic mitral annular velocity (E'') and peak systolic mitral annular velocity (S'') increased (P = .004 and P < .001, respectively). B-type natriuretic peptide levels decreased (744 ± 708 at baseline vs 367 ± 273 at 30 days, P = .003, 279 ± 186 pg/mL at 6 months, P = .001). Left ventricular diameters and ejection fraction remained unchanged. Conclusion: Despite the high incidence of paravalvular regurgitation after TAVI, hemodynamic results were favorable. Furthermore, TAVI had positive effects on left ventricular remodeling and improved neurohormonal activity, myocardial hypertrophy, and diastolic function. [Copyright &y& Elsevier]

Abstract: Background: Bone-marrow derived endothelial progenitor cells (CD34+ and VEGFR2+ KDR+ EPC) and endothelial-derived microparticles (CD 31+Annexin V+, EMP; indicator for endothelial apoptosis) were examined in the peripheral blood of 35 male, clinically stable patients with 3-vessel coronary artery disease (CAD). The patients were divided in 2 groups, those with preserved or normal function (n = 17; EF 65 ± 6%) and those with reduced left ventricular (LV) function (n = 18; EF 36 ± 11%). Methods and Results: The number of circulating EPCs was decreased by 25% (P = .07) and the number of EMPs was increased by 109 % (P < .05) in patients with LV dysfunction compared with those with normal or preserved LV function. EPCs were positively correlated (r = 0.24 for patients with LV dysfunction and r = 0.28 for patients with preserved LV function) with endothelial function as assessed by flow-mediated vasodilatation. In contrast, EMPs were inversely correlated (r = –0.42 for patients with LV dysfunction and r = –0.49 for patients with preserved LV function). Conclusions: CAD patients with significant LV dysfunction show an increased index of endothelial cell damage. This decrease (or lack of compensatory elevation) of EPCs may result in a reduced potential for repair and thus contribute at least in part to the pathogenesis of endothelial dysfunction. [Copyright &y& Elsevier]

Abstract: Nucleophosmin mutations of exon 12 (NPM1 mutations) represent the most frequent molecular aberration that can be found in patients with acute myeloid leukaemia (AML) and can be detected in about 35% of AML patients. NPM1 mutations are characterised by four basepair insertions within the region corresponding to the C-terminus of the protein leading to its translocation out of the nucleus. Until now, more than 40 different subsets of mutations have been identified and about 90% of NPM1 mutations are represented by subtype A and B (78% versus 12%, respectively). So far, standard screening of NPM1 mutations using conventional polymerase chain reaction (PCR) followed by capillary electrophoresis is rather time consuming. We established a new method for rapid screening of NPM1 mutations using the fluorescence resonance energy transfer (FRET) principle. Furthermore, based on individual NPM1 mutations type A and B, we designed mutation specific primers to perform a highly sensitive PCR assay that can be applied for the detection of minimal residual disease (MRD). In summary, we demonstrate new methodological approaches for rapid screening of NPM1 mutations as well as for MRD analyses based on the most frequent NPM1 mutations. [Copyright &y& Elsevier]

Abstract: Background: Acute coronary syndrome (ACS) comprises different manifestations of coronary artery disease. Angiograms performed at the time of an ACS may present different coronary morphologies; mostly there are acute vessel occlusions, ruptured atherosclerotic plaques, or thrombotic lesions that require reperfusion therapy. In the presence of intracoronary thrombi localized in the left main coronary artery, the clinical situation is challenging. Hemodynamic situation, symptoms, and rhythm status may change immediately and entail high mortality. Catheter-based therapy and surgical revascularization are associated with a high mortality rate. A noninterventional approach may be chosen in patients with stable hemodynamics and reestablished perfusion. Methods and Patient: We describe a patient with acute ST-elevation myocardial infarction with chest pain and stable hemodynamics. Angiography revealed a large thrombus in the left main coronary artery bifurcation with ostial subtotal narrowing of the circumflex and left anterior descending artery. However, coronary perfusion was maintained. Immediate treatment with the glycoprotein IIb/IIIa inhibitor abciximab was performed. The patient became asymptomatic. Angiography the next day showed no change in thrombus formation, so abciximab infusion was prolonged. Initial elevated enzymes decreased to normal values. Three days later the patient developed a new unstable angina with newly elevated cardiac enzymes. At this time, a thrombolytic agent was administered. Angiography 2 days later demonstrated normal coronaries. Conclusion: This case demonstrates the impact of intracoronary thrombi on repetitive myocardial ischemia and the effectiveness of a noninterventional pharmacological approach for the treatment of acute myocardial infarction due to intracoronary thrombus even in the left main coronary bifurcation. [Copyright &y& Elsevier]

There is abundant evidence now that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; ADMA also causes local vasoconstriction when it is infused intra-arterially. ADMA is increased in plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, and chronic heart failure. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation. In several prospective and cross-sectional studies, ADMA evolved as a marker of cardiovascular risk in certain populations like hemodialysis patients, non-smoking men, or intensive-care patients. The CARDIAC study is a multicenter case–control study designed to address the hypothesis that ADMA may be a suitable and sensitive marker of cardiovascular risk in a large, unselected population of both sexes, and with a broad range of established cardiovascular risk factors. The population included in the CARDIAC study will be prospectively followed for a scheduled follow-up period of 4 years, and the data of the CARDIAC-PRO study will then provide definite evidence whether ADMA may be prospectively determined as a cardiovascular risk factor. [Copyright &y& Elsevier]

Percutaneous thrombin occlusion of pseudoaneurysms complicating invasive coronary interventions has emerged as a useful therapeutic tool. To facilitate thrombin occlusion and make the procedure even more secure, preinjection of echo contrast medium during duplex ultrasound was tested in 132 patients. Complete and immediate occlusion of the pseudoaneurysm was achieved in 99.2% (131 of 132 patients). No complications related to the injection of thrombin were documented. Contrast-enhanced ultrasound-guided thrombin occlusion was a safe and effective therapeutic option. In aneurysms with complex morphology or multiple cavities, preinjection of contrast medium was helpful for documenting the flow pattern. [Copyright &y& Elsevier]

We have shown previously that human epidermal keratinocytes in situ and in vitro constitutively express high levels of the 72-kD heat shock protein (hsp72) and that hsp72 expression in these cells can be further induced with heat treatment. In the present study, we continue our investigation of the ultraviolet (UV) B protective effect of hyperthermic treatment and ask whether hsp72 is a mediator of heat-shock-induced UVB resistance. The results of our experiments demonstrate that heat treatment (42°C for 4 h) before UVB exposure is able to increase significantly the UVB resistance of the epidermal carcinoma cell line A431. Heat-induced UVB resistance was most pronounced if the cells were exposed to UVB immediately after heat treatment. The protective effect was not detectable beyond a recovery period of 12 h. To investigate the role of hsp72 in hyperthermia-induced UVB resistance, we inhibited the expression of this protein using either a specific antisense oligodeoxynucleotide or quercetin, a flavonoid that has been shown to down-regulate hsp expression. Treatment with the oligomer as well as with quercetin significantly increased the susceptibility of A431 to UVB-induced damage and nullified the protective effect of heat preconditioning. A noncomplementary control oligodeoxynucleotide had no significant effect. These results indicate that heat treatment is able to induce a state of increased resistance to the deleterious effects of UVB in human keratinocytes in vitro. hsp72 is a molecular mediator of this protective effect, and its constitutive expression in human epidermal keratinocytes may be an important mechanism for the protection of human epidermis from UVB-induced damage. [ABSTRACT FROM AUTHOR]

Background: The study aims to determine the impact of different lung diseases on morbidity and mortality after transcatheter aortic valve implantation (TAVI).Methods: Transcatheter aortic valve implantation was performed transfemoral or transaxillary with CoreValve prosthesis or Edwards SAPIEN prosthesis in patients with symptomatic severe aortic valve stenosis and high surgical risk. Examinations comprised spirometry, body plethysmography echocardiography, and x-ray before TAVI. The primary study end point was death from any cause after TAVI.Results: During follow-up of 750 ± 538 days, 63 of 212 patients died. Logistic European System for Cardiac Operative Risk Evaluation (hazard risk [HR] 1.032, P < .001), aortic mean gradient (HR 0.96, P < .001), chronic obstructive pulmonary disease (COPD; each degree of COPD: HR 1.436, P = .001), restrictive ventilatory disease (HR 2.252, P = .002), oxygen dependency (HR 3.291, P = .004), and noninvasive ventilation (HR 3.799, P = .005) were independent predictors of long-term mortality. Restrictive ventilatory disease was associated with lower left ventricular ejection fraction, higher B-type natriuretic peptide levels, and pulmonary edema.Conclusion: In patients undergoing TAVI, lung diseases are an independent predictor of all-cause mortality. In particular, oxygen dependency patients and patients with severe COPD and noninvasive ventilation indicate a dismal prognosis. Transcatheter aortic valve implantation seems to have a dubious prognostic benefit in these patients. [ABSTRACT FROM AUTHOR]

Based on theoretical and mechanistical considerations, an equation is presented that describes the observed rate of a pH sensitive reaction. In contrast to the commonly used catalytic catenary, the new approach enables the calculation of non-biased thermodynamic activation parameters. Applying this model, the general acid/base catalysis of the ring opening of β– d –fructopyranose was analyzed polarimetrically. Thereby, it could be shown that acids (bases) catalyze the ring opening of anionic (cationic) sugar species. Since anomerization rate constants correlate with the rate of sugar degradation, catalysts of anomerization will increase the sugar‘s reactivity as well. The most effective catalysts of the ring opening of β– d –fructopyranose in the food relevant pH milieu are weak acids and their conjugated bases. Consequently, the enhanced reactivity of reducing sugars in the presence of amino acids is not solely due to classical Maillard reaction but primarily due to carboxylic acid catalysis of degradation reactions. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The World Health Organization (WHO) recognizes the potential of plants used in secular traditional medicine and considers this an important source of evidence to assess their effectiveness and safety. Brazil is rich in biodiversity and traditional uses based on the Amerindian culture. However, many processes started with the arrival of the Portuguese in the year 1500. The successive economic cycles, for example, led to destruction of native vegetation and an intense cultural erosion. As a consequence, the information about the use of plants in the past centuries are dispersed and without interpretation. In this study a methodology to evidence the traditionality of Brazilian plants was demonstrated using data about barbatimão barks ( Stryphnodendron adstringens (Mart.) Coville - Fabaceae) and Copaiba oleoresin ( Copaifera spp. - Fabaceae) in wound healing, was established. Material and methods Data about use of the plants were recovered from bibliography published between 1576 and 2011. The books (101) were classified using weights, considering the date of publication and the source of Information. Older books that describe primary information received weight 10, while books written more recently and with secondary information received weight 0.4. A score for each category of medicinal use was calculated based on the books weights and the frequency of citation. A review about the current use of both plants was also performed from ethnobotanical studies published in journals. Results and discussion The traditional secular use of barks of barbatimão and oleoresin of copaiba to treat wounds was confirmed based on the historic bibliographic research. The most frequent use of barbatimão in a timeline of 500 years of Brazil’s history, was as astringent, whereas for copaíba was as healing of skin and mucosal lesions. The continuous and current use of these plants to treat wounds, confirmed by recent ethnobotanical studies, is an indicative of the resilience of these remedies and their effectiveness. Conclusion The use of preparations containing barbatimão barks and copaiba oleoresin can be considered effective in the treatment of wounds. Nonetheless, it is necessary to improve the quality of the formulas as established by WHO. [ABSTRACT FROM AUTHOR]

Analyzing classical model reaction systems of Amadori rearrangement products (ARP) it became apparent that the formation of 3-deoxy- d - threo -hexo-2-ulose (3-deoxygalactosone, 3-DGal) during the degradation of ARPs is highly dependent on pH and the amino acid residue of the respective ARP. Based on a detailed analysis of the NMR chemical shifts of the sugar moieties of different ARPs, it could be derived that the formation of 3-DGal is sensitive to the stability of a co-operative hydrogen bond network which involves HO-C3, the deprotonated carboxyl functionality and the protonated amino nitrogen of the amino acid substituent. Participating in this bond network, HO-C3 is partially protonated which facilitates the elimination of water at C3. Based on that, a new mechanism of 3-deoxyglycosone formation is proposed. [ABSTRACT FROM AUTHOR]

Background: Preclinical data suggest beneficial effects of angiotensin II receptor blockers (ARBs) on neointima formation after vascular injury. Preliminary clinical data, however, revealed conflicting results. The AACHEN trial was a double-blind, randomized, placebo-controlled clinical multicenter trial to evaluate the effects of candesartan cilexetil on intimal hyperplasia after coronary stent implantation. Methods: A total of 120 patients (61 ± 9 years, 83% male) were randomized to receive either 32 mg candesartan cilexetil (active) or placebo starting 7 to 14 days before elective coronary stent implantation. A follow-up angiography including intravascular ultrasound assessment of the target lesion was performed 24 ± 2 weeks after stent implantation. The primary end point was defined as the difference in neointimal area between groups as assessed by intravascular ultrasound. Secondary end points included differences in angiographic parameters (ie, restenosis rate) and incidence of major cardiac events. Results: The mean stent length measured 15.0 ± 4.9 mm in the active and 14.6 ± 5.7 mm in the placebo group (P = .81). There was no significant difference in neointimal area between groups (2.1 ± 1.0 vs 2.1 ± 1.5 mm2, P = 1.00), nor were there differences in angiographic end point parameters. Major cardiac event rates were not significantly different between treatment groups (8% vs 11%, P = .75). Conclusions: High-dose candesartan cilexetil therapy in patients with symptomatic coronary artery disease undergoing coronary stent implantation does not reduce clinical event rates, restenosis rates, or neointimal proliferation after elective stent implantation. [Copyright &y& Elsevier]

Background: Asymmetric dimethylarginine (ADMA) plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus, and others. It has been shown that ADMA predicts cardiovascular mortality in patients who have coronary heart disease (CHD). However, the question whether ADMA is an independent risk factor for CHD still remains unresolved. Methods: The CARDIAC study is a multicenter case-control study, designed to detect differences in ADMA plasma levels between patients with CHD and controls from the general population. We included in our analysis 131 cases and 131 controls, matched for age, sex, and body mass index. Results: We found that cases had higher ADMA plasma levels than controls (0.70 μmol/L [0.59-0.87 μmol/L] vs 0.60 μmol/L [0.54-0.69 μmol/L], P < .001). To evaluate the predictive power of ADMA regarding CHD, we calculated 2 multivariate logistic regression models including laboratory parameters and traditional risk factors. The odds ratio for ADMA in the multivariate model including the laboratory characteristics was 2.59 (1.61-4.17; P < .001); the odds ratio for the multivariate model including other risk factors was 6.04 (2.56-14.25; P < .001) for the third tertile (>0.72 μmol/L) versus the first (<0.58 μmol/L). Conclusions: We conclude from the results of our study that ADMA is an independent risk factor for CHD. [Copyright &y& Elsevier]

Background: Correct assessment of the significance of left main stem lesions is of pivotal importance to the patient with coronary artery disease. On the basis of clinical and angiographic information alone, this evaluation often cannot be done reliably. Limited data suggest that coronary pressure-derived fractional flow reserve (FFR) supports decision making in equivocal left main disease. Methods: All patients presenting to our institution between June 1999 and June 2004 with intermediate left main coronary artery disease (40%-80% diameter stenosis by angiography), or in whom left main coronary disease was suspected but could not be quantified angiographically, were included in this prospective single-center follow-up study. If FFR was <0.75 along the left main stem, surgical revascularization was recommended; if FFR was >0.80, medical treatment or percutaneous coronary intervention elsewhere in the coronary tree was chosen. If FFR was in the “gray zone,” between ≥0.75 and ≤0.80 treatment recommendation was dependent on additional individual criteria. Primary end points were freedom from death, myocardial infarction, any coronary revascularization procedure, and stroke. Results: Fifty-one patients (mean age 62.2 ± 9.6 years, 41 male) were included. In 27 patients (53%), coronary artery bypass surgery was performed. The remaining 24 patients (47%) were treated nonsurgically. Mean follow-up was 29 ± 16 months. Estimated survival after 4 years of follow-up was 81% among patients in the surgical group and 100% among patients in the nonsurgical group. Event-free survival was 66% in the surgical group and 69% in the nonsurgical group. Conclusions: Fractional flow reserve is helpful to identify patients with intermediate left main disease in whom deferral of surgical revascularization is associated with excellent survival and low event rates. [Copyright &y& Elsevier]