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Atrial fibrillation (AF) and diabetes mellitus (DM) are commonly encountered in clinical practice. Although, the long term macrovascular and microvascular sequela of DM are well validated, the association between the less prevalent type 1 DM (T1DM) and atrial arrhythmogenesis is poorly understood. In the present review we highlight the current experimental and clinical data addressing this complex interaction. Animal studies support that T1DM, characterized by insulin deficiency and glycemic variability, impairs phosphatidylinositol 3‑kinase (PI3K)/protein kinase B signaling pathway. This pathway holds a central role in atrial electrical and structural remodeling responsible for arrhythmia initiation and maintenance. The molecular ''footprint'' of T1DM in atrial myocytes seems to involve a state of increased oxidative stress, impaired glucose transportation, ionic channel dysregulation and eventually fibrosis. On the contrary only a few clinical studies have examined the role of T1DM as an independent risk factor for AF development, and are discussed here. Further research is needed to solidify the real magnitude of this association and to investigate the clinical implications of PI3K molecular signaling pathway in atrial fibrillation management.

Background Radial artery occlusion (RAO) remains the Achilles' heel of transradial coronary procedures. Standard over lower systemic anticoagulation levels are believed to reduce RAO rates but this is ill-supported by scientific evidence. We compared whether standard in comparison with less intensive anticoagulation was superior in preventing vessel closure. Methods and results The two arms of this analysis included 731 pooled patients with the same inclusion and exclusion criteria. We assessed forearm arterial access site occlusion rate by unfractionated heparin (UFH) dose in an individual participant data meta-analysis of this randomized study and of consecutive eligible patients from our previous trial. We randomized 308 consecutive patients undergoing transradial coronary angiography with 5 French (5Fr) catheters without need to crossover to receive 2500 or 5000UFH units. The primary end-point was the ultrasonographically determined vessel occlusion rate. Incident RAOs in the randomized arm were 15.9% vs. 14%, in the low and standard UFH dose, respectively (p=0.7). Corresponding figures for forearm arterial occlusion rates in the pooled population were 13.0% vs. 9.9% (relative risk: 1.3, 95% confidence interval — CI: 0.88–1.98; p=0.2). Procedural and fluoroscopy duration was less than 15 and 3min, respectively. The mean UFH dose difference was 3.52 (95% CI: −0.45 to 7.49) units per kilo body weight between occluded (n=84) and patent forearm arteries (n=647); (p=0.053). Conclusions Incident forearm arterial occlusions were high despite using 5Fr catheters for a short-lasting procedure. Systemic anticoagulation with standard over lower UFH dose did not reduce the frequency of RAOs after coronary angiography.

Background— The autonomic system is an important determinant of atrial arrhythmogenesis. Current evidence indicates that a combined sympathovagal drive is most commonly responsible for eliciting atrial fibrillation (AF) episodes. The purpose of this study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, can lead to a reduction in postablation AF recurrence. Methods and Results— This was a prospective, double-blinded, randomized study of 291 hypertensive patients with symptomatic paroxysmal AF who were scheduled to undergo pulmonary vein isolation. Patients were randomly assigned to receive either moxonidine (0.2–0.4 mg daily) or placebo, along with standard antihypertensive treatment. No significant differences in blood pressure levels were observed between the 2 groups. In the primary outcome analysis, mean recurrence-free survival was 467 days (95% CI, 445–489 days) in the moxonidine group as compared with 409 days (95% CI, 381–437 days) in control subjects (log rank test, P =0.006). The calculated 12-month recurrence rate estimates were 36.9% in the control group and 20.0% in the moxonidine group ( P =0.007). Moxonidine treatment was associated with lower recurrence risk after adjustment for age, body mass index, number of AF episodes in the previous year, and left atrial diameter (adjusted hazard ratio, 0.35 [95% CI, 0.22–0.55]; P Conclusions— Treatment with moxonidine is associated with less AF recurrences after ablation treatment for drug-refractory AF in patients with hypertension. The observed effect does not appear to depend on the antihypertensive action of this agent. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01791699.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide production. The purpose of this study was to assess the correlation between ADMA and treadmill stress test outcome parameters with known prognostic value, in patients with intermediate risk for coronary artery disease (CAD).Study participants were referred for treadmill exercise stress test (EST) due to symptoms of suspected CAD. Participants with prior history of CAD, cerebrovascular events, peripheral artery disease, systemic inflammatory disease or use of anti-inflammatory agents were excluded. ADMA levels were measured before EST.The study prospectively enrolled 209 individuals (165 males, aged 58.1±10.9). A significant negative correlation was detected between ADMA and maximal exercise time (r=-0.556, p0.001), metabolic equivalents (METs) (r=-0.555, p0.001) and Duke treadmill score (DTS) (r=-0.347, p0.001). Subjects who exercised to ≥10 METs (n=114) had lower ADMA levels than those who achieved7 METs (n=30) (0.58±0.06 vs 0.87±0.08μmol/L, p0.001), and those with DTS5 (n=63) had higher ADMA (0.75±0.19 vs 0.64±0.15μmol/L, p0.001) compared to those with DTS ≥5 (n=146). In multivariable analysis, ADMA remained an independent predictor of DTS (R(2)=0.210; beta=-10.5; 95% confidence interval -14.9 to -6.2; adjusted p0.001) and METs (R(2)=0.500; beta -8.5; 95% confidence interval -9.7 to -6.0; adjusted p0.001) after adjustment for age, BMI, gender, diabetes, smoking status, dyslipidemia, hypertension and family history of premature CAD.ADMA is correlated to EST parameters with proven prognostic value. This implies that ADMA itself might be a useful prognosticator in patients with suspected CAD.

There is substantial evidence that the autonomic system plays an important part in the pathogenesis of atrial fibrillation (AF). It appears that, although some patients have a preponderantly sympathetic or vagal overactivation leading to AF, a combined sympathovagal drive is most commonly responsible for AF triggering. The purpose of this hypothesis-generating study was to test whether moxonidine, a centrally acting sympathoinhibitory agent, on top of optimal antihypertensive treatment, can lead to a decrease in AF burden in hypertensive patients with paroxysmal AF. This was a prospective, double-blind, 1-group, crossover study. Hypertensive patients with paroxysmal AF sequentially received treatment with placebo and moxonidine for two 6-week periods, respectively. The change in AF burden (measured as minutes of AF per day in three 48-hour Holter recordings) between the 2 treatment periods was the primary outcome measure. Fifty-six patients (median age 63.5 years, 35 men) were included. During moxonidine treatment, AF burden was reduced from 28.0 min/day (interquartile range [IQR] 15.0 to 57.8) to 16.5 min/day (IQR 4.0 to 36.3; p0.01). European Heart Rhythm Association symptom severity class decreased from a median of 2.0 (IQR 1.0 to 2.0) to 1.0 (IQR 1.0 to 2.0; p = 0.01). Systolic blood pressure levels were similar in the 2 treatment periods, whereas diastolic blood pressure was lower (p0.01) during moxonidine treatment. The most frequent complaint was dry mouth (28.6%). No serious adverse events were recorded. In conclusion, treatment with moxonidine, a centrally acting sympathoinhibitory agent, results in reduction of AF burden and alleviation of AF-related symptoms in hypertensive patients with paroxysmal AF.

Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence.We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint.There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3 pg/mL (IQR 1-4 pg/mL); p=0.01]. sTRAIL gradient was 4 pg/mL (IQR 3-5 pg/mL) in patients without recurrence versus -1 pg/mL (IQR -2-1 pg/mL) in those with recurrence (p0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence.This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.

Objectives This study sought to test the hypothesis that colchicine treatment after percutaneous coronary intervention (PCI) can lead to a decrease in in-stent restenosis (ISR). Background ISR rates are particularly high in certain patient subsets, including diabetic patients, especially when a bare-metal stent (BMS) is used. Pharmacological interventions to decrease ISR could be of clinical relevance. Methods Diabetic patients with contraindication to a drug-eluting stent, undergoing PCI with a BMS, were randomized to receive colchicine 0.5 mg twice daily or placebo for 6 months. Restenosis and neointima formation were studied with angiography and intravascular ultrasound 6 months after the index PCI. Results A total of 196 patients (63.6 ± 7.0 years of age, 128 male) were available for analysis. The angiographic ISR rate was 16% in the colchicine group and 33% in the control group (p = 0.007; odds ratio: 0.38, 95% confidence interval: 0.18 to 0.79). The number needed to treat to avoid 1 case of angiographic ISR was 6 (95% confidence interval: 3.4 to 18.7). The results were similar for IVUS-defined ISR (odds ratio: 0.42; 95% confidence interval: 0.22 to 0.81; number needed to treat = 5). Lumen area loss was 1.6 mm2 (interquartile range: 1.0 to 2.9 mm2) in colchicine-treated patients and 2.9 mm2 (interquartile range: 1.4 to 4.8 mm2) in the control group (p = 0.002). Treatment-related adverse events were largely limited to gastrointestinal symptoms. Conclusions Colchicine is associated with less neointimal hyperplasia and a decreased ISR rate when administered to diabetic patients after PCI with a BMS. This observation may prove useful in patients undergoing PCI in whom implantation of a drug-eluting stent is contraindicated or undesirable.

Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions. The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress. Cardiac ventricular myocytes constitute the major source of BNP-related peptides. Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct. NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney). It has a longer half life than BNP and higher plasma concentration. BNP and NTproBNP tend to be higher in women and lower in obese individuals. They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection. NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP. A cut-off point 300 pg/ml has 99% sensitivity, 60%specificity and NPV 98%for exclusion of acute heart failure. NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD. Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction. Their release is due to myocardial stretch from right ventricular pressure overload.Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.

We hypothesized that uptitration of β blockade and adjustment of pacing parameters to achieve a prevalence of single chamber atrial inhibited rate-responsive (AAIR) pacing in patients with dual-chamber implantable cardioverter--defibrillators (ICDs) would result in maximization of β-blocker dosage and thus decrease appropriate ICD therapies. We included patients with ischemic or dilated cardiomyopathy and implanted ICDs without contraindications to β blockers and atrioventricular conduction disturbances. Two 6-month periods were compared: clinically guided phase (pacing function set at back-up dual-chamber rate-responsive pacing mode at a lower rate of about 40 beats/min) and pacing-guided phase, during which β-blocker dosage was titrated with a target of achieving90% AAIR pacing (lower rate 60 beats/min). Sixty-one patients (64.2 ± 8.3 years old) were included. During the pacing-guided phase the target of ≥90% AAIR pacing was achieved in 80.3% of patients. Mean metoprolol dose during the clinically guided phase was 96.7 ± 29.4 versus 127.0 ± 39.6 mg/day in the pacing-guided phase (p0.001). Appropriate ICD therapies were recorded in 35 patients (57.4%) during the clinically guided phase versus 20 (32.8%) during the pacing-guided phase (p0.001; 1.15 and 0.48 appropriate ICD therapies per patient, respectively, p0.001). In multivariate analysis, AAIR pacing and β-blocker dose were inversely related to appropriate ICD therapies. In conclusion, a pacing-guided approach for maximizing β-blocker doses guided by maximizing AAIR pacing in patients with ICDs may be beneficial compared to the conventional strategy. This pacing-guided approach led to higher daily β-blocker doses, which were correlated to fewer appropriate ICD therapies.

The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs.

CRT and Coronary Flow Reserve. Background: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy. Methods and Results: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non-responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07–0.23, P = 0.001). When comparing responders to non-responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13–0.39; P = 0.002), while in non-responders the difference was 0.04 ± 0.03 (95% confidence interval −0.02 to 0.10; P = 0.168). Conclusion: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT-responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1233-1239, November 2010)

a Cardiology Department and Cardiac Catheterization Laboratory, Athens General Hospital “G. Gennimatas”, Athens, Greece b 1st Department of Cardiology, University of Athens Medical School, Hippokrateion Hospital, Athens, Greece c Department of Cardiology, University of Patras Medical School, Patras, Greece d Cardiac Catheterization Laboratory, Yale-New Haven Hospital, Yale School of Medicine, New Haven, CT, USA

Objective Radial artery spasm may hinder completion of transradial angiography or PCI, leading to access site crossover, prolonged procedure times and complications. The aim of this study was to derive a radial artery spasm risk score in patients undergoing elective percutaneous coronary intervention (PCI), prospectively validate it, and apply it in a real-life clinical setting. Methods The study population consisted of 3 cohorts of patients undergoing elective PCI with transradial access: the derivation cohort (N=1006), the validation cohort (N=576) and the intervention cohort (N=140), consisting of patients with high risk score, in whom intensified spasm-preventive measures were applied. Results Multivariable analysis in the derivation cohort showed that 5 weighted factors could be used to construct a risk score for spasm: body-mass index, height, current smoking, hypertension and peripheral artery disease (c-statistic 0.945, with an optimal cut-off of 4). In the validation cohort, the cut-off of 4 predicted spasm with a sensitivity of 84.5% and a specificity of 74.7%. In the intervention cohort, which included only patients with a spasm-risk score of ≥4, the rate of spasm was drastically reduced (odds ratio 0.32, 95% confidence interval 0.17–0.61), compared to the corresponding high spasm risk subgroup of patients of the validation cohort. Conclusion A spasm risk score can be used to predict radial artery spasm during elective transradial PCI. Using this score, a high spasm risk patient subgroup can be identified, where intensive spasm-preventive measures can lead to a significant reduction in the frequency of spasm.

We sought to test the hypothesis that virtual histology characteristics of the culprit lesion in patients with ST-elevation myocardial infarction are associated with blood flow restoration after thrombolysis.Consecutive patients referred for coronary angiography after successful thrombolysis were included in this correlational cross-sectional study. Evaluation with intravascular ultrasound (IVUS) and virtual histology of the culprit arterial segment was performed in all cases.Forty-eight patients (60.5 ± 10.7 years) were included. TIMI flow grade 3 was found in 24 (50%). Diabetes was strongly associated with lower TIMI flow 3 rate (26.7% vs 60.6%; p = 0.029) and there was a significant difference in the time to thrombolysis (2.0 ± 0.8 hours in those with TIMI flow 3 vs 3.0 ± 0.7 hours in TIMI flow grades 1-2; p0.001). Patients with TIMI flow grades 3 and 1-2 had similar absolute total plaque volume (152.8 ± 59.3mm(3) vs 147.5 ± 92.3mm(3); p = 0.817) and absolute necrotic core (NC) volume (31.2 ± 13.9 mm(3) vs 33.6 ± 23.2mm(3); p = 0.671). However, there were significant differences in the relative NC content, both in proportion to the whole plaque volume (26.3% vs 29.9%; p = 0.016) and as an area fraction at the largest NC site (31.5% vs 40.3%; p0.001).The NC content of atherosclerotic plaques is meaningful for flow restoration after the occurrence of a coronary event. This finding highlights the importance of plaque composition, as studied with virtual histology, not only for the sequence of processes leading to an acute plaque-related event, but also for thrombus formation and lysis, following the occurrence of such an event.

Background Our group previously showed that colchicine treatment is associated with decreased early recurrence rate after ablation for atrial fibrillation (AF). Objective The purpose of this study was to test the mid-term efficacy of colchicine in reducing AF recurrences after a single procedure of pulmonary vein isolation in patients with paroxysmal AF. Assessment of quality-of-life (QOL) changes was a secondary objective. Methods Patients with paroxysmal AF who were scheduled for ablation were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo and were followed for a median of 15 months (with a 3-month blanking period). QOL was assessed with a general-purpose health-related QOL tool (26-item World Health Organization QOL questionnaire) at baseline and after 3 and 12 months. Results Two hundred twenty-three randomized patients underwent ablation, and 206 patients were available for analysis (144 male, age 62.2 ± 5.8 years). AF recurrence rate in the colchicine group was 31.1% (32/103) vs 49.5% (51/103) in the control group ( P = .010), translated in a relative risk reduction of 37% (odds ratio 0.46, 95% confidence interval 0.26–0.81). The number needed to treat was 6 (95% confidence interval 3.2–19.8). Physical domain QOL scores at 12 months were 63.6 ± 13.8 in the colchicine group and 52.5 ± 18.1 in controls, whereas psychological domain scores were 56.1 ± 13.7 vs 44.7 ± 17.3, respectively ( P Conclusion Colchicine treatment after pulmonary vein isolation for paroxysmal AF is associated with lower AF recurrence rates after a single procedure. This reduction is accompanied by corresponding improvements in physical and psychological health-related QOL scores.

The purpose of this study was to test the efficacy of a 6-month course of anti-inflammatory treatment with colchicine in improving functional status of patients with stable chronic heart failure (CHF).CHF has been shown to be associated with inflammatory activation. Inflammation has been designated as a therapeutic target in CHF.Patients with stable CHF were randomly assigned to colchicine (0.5 mg twice daily) or placebo for 6 months. The primary endpoint was the proportion of patients achieving at least one-grade improvement in New York Heart Association class.Two hundred sixty-seven patients were available for final evaluation of the primary endpoint: its rate was 11% in the control group and 14% in the colchicine group (odds ratio: 1.40; 95% confidence interval: 0.67 to 2.93; p = 0.365). The rate of the composite of death or hospital stay for heart failure was 9.4% in the control group, compared with 10.1% in the colchicine group (p = 0.839). The changes in treadmill exercise time with treatment were insignificant and similar in the 2 groups (p = 0.938). C-reactive protein and interleukin-6 were both significantly reduced in the colchicine group (-5.1 mg/l and -4.8 pg/ml, respectively; p 0.001 for both, compared with the control group).According to this prospective, randomized study, anti-inflammatory treatment with colchicine in patients with stable CHF, although effective in reducing inflammation biomarker levels, did not affect in any significant way patient functional status (in terms of New York Heart Association class and objective treadmill exercise tolerance) or the likelihood of death or hospital stay for heart failure.

Background— The ulnar artery is rarely selected for coronary angiography or percutaneous coronary intervention despite the expanding use of the transradial approach. We aimed to establish noninferiority of a default transulnar relative to transradial approach in terms of feasibility and safety. Methods and Results— This was a prospective, randomized, multicenter, parallel-group study involving 902 patients at 5 sites eligible to undergo diagnostic coronary angiography and percutaneous coronary intervention. Patients were randomized in a 1:1 ratio to either transradial approach (reference intervention) or transulnar approach (experimental intervention) regardless of the Allen test results. The primary end point was a composite of cross-over to another arterial access, major adverse cardiovascular events, and major vascular events of the arm at 60 days. The study was prematurely terminated after the first interim analysis because of inferiority of the transulnar approach. Although the difference in the primary end point became inconclusive after adjustment for operator clustering (24.30%; 99.99% confidence interval [CI], −7.98% to 56.58%; P =0.03 at α=0.0001), need for cross-over in the transulnar group remained inferior to transradial access site with a difference of 26.34% (95% CI, 11.96%–40.69%; P =0.004). Conclusions— As a result of higher cross-over rates, a first-line transulnar strategy was proven inferior to the transradial approach for coronary procedures. At present, the transulnar route should not be regarded as an acceptable alternative to the transradial access site. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01364532.

With the advent of transcatheter aortic valve implantation (TAVI), many AS patients, formerly considered inoperable, can receive effective treatment. The relief of the left ventricular pressure overload could lead, in some cases, to the occurrence of dynamic intracavity pressure gradients (DIG) with deleterious clinical impact. This phenomenon resembles the physiology seen in hypertrophic obstructive cardiomyopathy. We report a case in which alcohol septal ablation was used as a bail-out therapy for the acutely developed intracavity obstruction after TAVI. Potential dynamic intracavity gradients should always be excluded in the acutely deteriorated patient postoperatively. Alcohol septal ablation can be considered as a salvage therapeutic tool when other therapies are ineffective to treat subvalvular obstruction.

In this brief report, we present our experience from placing temporary pacing electrodes through peripheral venous access sites, at bedside, in a series of patients needing temporary pacing.Consecutive patients requiring temporary pacing were selected. The median cubital or the basilic vein of the left upper extremity were used for catheterization at the bedside in all cases.25 patients (17 men, age 64.6 ± 11.8) were included. The procedure was successful in 21 cases (84%), 18 of which were completed without the need for fluoroscopic guidance. The pacing leads remained for 4.2 ± 2.2 days. As expected, no serious complications related to venous puncture were observed. Although patients were allowed to be mobilized within the ward and engage in limited movements of the catheterized arm, in only one case was the lead displaced, requiring repositioning.We provide observational evidence that the use of peripheral venous access for temporary pacing lead insertion (with no fluoroscopic guidance, as default strategy) is a safe and feasible choice that might be considered as an alternative to central vein catheterization.

The aim of this study was to test the hypothesis that moderate procedural sedation can reduce the incidence of radial artery spasm.Transradial access for left heart catheterization and percutaneous coronary intervention is increasingly used for emergent and elective procedures, in lieu of the femoral approach. However, increased rates of access site crossover have been reported, with radial artery spasm being a major contributor to this effect.Patients undergoing elective transradial percutaneous coronary intervention were prospectively randomized to receive fentanyl and midazolam during the procedure or no treatment (control subjects). The primary endpoint was angiographically confirmed radial artery spasm. Patient discomfort was quantified with a visual analogue scale.Two thousand thirteen patients (age 64.5 ± 8.4 years) were randomized. Spasm occurred in 2.6% of the treatment group versus 8.3% of control subjects (p0.001; odds ratio [OR]: 0.29). The number needed to treat to avoid 1 case of spasm was 18 (95% confidence interval [CI]: 12.9 to 26.6). The access site crossover rate was 34% lower in the treatment group: 9.9% versus 15.0% (OR: 0.62; 95% CI: 0.48 to 0.82). Patient discomfort visual analogue scale score was 18.8 ± 12.5 in the treatment group versus 27.4 ± 17.4 in control subjects (p0.001). No significant differences were observed in the 30-day rate of death or repeat hospital stay for any cause: 4.6% versus 4.5% (OR: 1.02; 95% CI: 0.67 to 1.56).Routine administration of relatively low doses of an opioid/benzodiazepine combination during transradial interventional procedures is associated with a substantial reduction in the rate of spasm, the need for access site crossover, and the procedure-related level of patient discomfort.

The purpose of the present study was to test the potential of colchicine, an agent with potent anti-inflammatory action, to reduce atrial fibrillation (AF) recurrence after pulmonary vein isolation in patients with paroxysmal AF.Proinflammatory processes induced by AF ablation therapy have been implicated in postablation arrhythmia recurrence.Patients with paroxysmal AF who received radiofrequency ablation treatment were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured on day 1 and on day 4 of treatment.In the 3-month follow-up, recurrence of AF was observed in 27 (33.5%) of 80 patients of the placebo group versus 13 (16%) of 81 patients who received colchicine (odds ratio: 0.38, 95% confidence interval: 0.18 to 0.80). Gastrointestinal side-effects were the most common symptom among patients receiving active treatment. Diarrhea was reported in 7 patients in the colchicine group (8.6%) versus 1 in the placebo group (1.3%, p = 0.03). Colchicine led to higher reductions in CRP and IL-6 levels: the median difference of CRP and IL-6 levels between days 4 and 1 was -0.46 mg/l (interquartile range: -0.78 to 0.08 mg/l) and -0.10 mg/l (-0.30 to 0.10 pg/ml), respectively, in the placebo group versus -1.18 mg/l (-2.35 to -0.46 mg/l) and -0.50 pg/ml (-1.15 to -0.10 pg/ml) in the colchicine group (p0.01 for both comparisons).Colchicine is an effective and safe treatment for prevention of early AF recurrences after pulmonary vein isolation in the absence of antiarrhythmic drug treatment. This effect seems to be associated strongly with a significant decrease in inflammatory mediators, including IL-6 and CRP.

Objectives: Soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) has been shown to exert protective action against atherosclerosis. The aim of this study was to investigate potential associations of coronary sTRAIL levels with indices of in-stent neointimal hyperplasia. Methods: 67 patients who underwent percutaneous coronary intervention with drug-eluting stent were followed up at approximately 12 months with determination of coronary sTRAIL concentration, angiography and intravascular ultrasound evaluation of the stent sites. Results: Mean sTRAIL concentration was 72.2 ± 2.8 pg/ml. sTRAIL was negatively correlated to indices of neointimal hyperplasia and positively correlated to in-stent minimum lumen area (p < 0.001). Neointimal obstruction and maximal in-stent cross-sectional neointima burden in patients in the upper sTRAIL quartile were 3.8 ± 1.2 and 12.6 ± 3.3%, respectively, versus 14.0 ± 0.7 and 49.8 ± 2.7% in the lower quartile (p < 0.001 for both). sTRAIL levels were significantly lower in patients with binary restenosis (48.7 ± 3.0 vs. 75.2 ± 2.9 pg/ml; p < 0.001). In the multivariate analysis, sTRAIL was an independent predictor of neointimal hyperplasia. Conclusion: This study demonstrates a negative association of sTRAIL to in-stent neointima formation. The potential pathophysiologic substrate of this effect implicates modulation of apoptosis in various cell types. These observations should prompt further evaluation of the link between sTRAIL and in-stent restenosis.

Intracardiac echocardiography (ICE) offers the ability to image the left atrium in order to reconstruct a three-dimensional model that can be integrated with electroanatomic data to guide pulmonary vein isolation. We report a case series representing the first-in-Greece experience with the CartoSound module.Patients with paroxysmal or persistent atrial fibrillation (AF) referred for pulmonary vein isolation were included in this case-series. The SoundStar ICE catheter was used to trace left atrial and pulmonary vein contours from the right atrium, the right ventricular outflow tract and the coronary sinus.Eight patients (age 66.3 ± 1.6 years) are presented in this case-series report. Six of them (75%) had paroxysmal AF and the rest were in persistent AF for less than one year. The time for ICE imaging and left atrium three-dimensional reconstruction decreased from a median of 20.5 minutes (interquartile range 19.3-23.3) for the chronologically first four cases to a median of 16.5 minutes (interquartile range 14.517.0) for the chronologically last four cases (p=0.02). The procedure was completed in all cases. No significant periprocedural complications were encountered. Acute success, with restoration of sinus rhythm, was achieved in both patients with persistent AF. Seven of the eight patients (87.5%) were AF-free in 48-hour Holter recordings one week after the procedure.ICE integration into three-dimensional electroanatomic reconstruction of the left atrium provides reliable guidance for pulmonary vein isolation. It appears that this modality is a sound alternative to magnetic resonance and computed tomography image data registration, although randomized comparisons are lacking.

Evidence shows that the soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) may play a protective role against atherosclerosis. This study sought to investigate the potential association of sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology characteristics of coronary plaques.Patients with stable angina or positive for ischaemia non-invasive test were submitted to left cardiac catheterisation. Coronary blood samples were collected and sTRAIL was measured. Coronary arteries with at least one 50% or greater stenosis were studied with IVUS.56 coronary arteries were studied with significant coronary artery disease. Plaque volume per unit of arterial length was 63 ± 5 mm(3)/cm in arteries at the lower quartile of sTRAIL concentration versus 30 ± 4 mm(3)/cm at the upper quartile (p0.001; 95% CI of the difference 19.7 to 46.3 mm(3)/cm). The necrotic core and fibrofatty content of atheromatous plaques were inversely associated with sTRAIL (p0.001). Thin-cap fibroatheromas (TCFA) were discovered in 16 of the 56 arterial segments. The mean sTRAIL concentration in these segments was 56.8 ± 7.5 pg/ml versus 99.9 ± 5.7 pg/ml in those without TCFA (p0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL with the presence of TCFA remained significant in the logistic multivariate analysis (p=0.009).According to the findings of the present study, in addition to coronary artery disease burden, the sTRAIL concentration is also related to the composition of atheromatous plaques. A significant association is demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS-virtual histology prototype of the vulnerable plaque.

Placement of an electrode catheter in the coronary sinus (CS) through the jugular or subclavian vein, as part of electrophysiology (EP) procedures, increases patient discomfort and the possibility of adverse events. We studied the hypothesis that peripheral venous access for CS cannulation, as part of EP procedures, is feasible and can reduce patient discomfort, eliminating central venous access-associated risks. Consecutive patients submitted to EP procedures were randomly assigned to peripheral or central venous access for CS cannulation. If after 30 min from initial needle insertion the CS was still not catheterized, the attempt was considered unsuccessful. Patient level of discomfort was assessed with a visual analog scale (VAS). Success rate was 90% in the peripheral versus 95% in the central venous access group (p = 1.00). No complications related to venous access were observed in the peripheral venous access group, whereas one case of pneumothorax and one case of extensive hematoma in the anterior cervical area were recorded in the central venous access group. Patients submitted to central vein catheterization reported higher VAS scores, 46.8 ± 16.3 versus 36.8 ± 12.9 (p = 0.04). No significant difference was observed in fluoroscopy time needed for CS cannulation (51.1 ± 9.2 s versus 51.4 ± 7.9 s; p = 0.71) between the two groups. This small, randomized study indicates that peripheral venous access for CS catheter placement during EP procedures is feasible, with equivalent success rate to the central venous access approach, and associated with lower levels of self-reported patient discomfort.

The transfemoral approach (TFA) has been the mainstay for arterial access during percutaneous coronary intervention (PCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI). However, the transradial approach (TRA) has been shown to be an equally effective and possibly safer way of performing primary PCI (pPCI).The study population included 98 serially recruited patients who underwent pPCI in our institution. All patients were clinically followed during their hospital stay (6.4 ± 3.1 days).In the 98 patients included in the study, 65 procedures (66.3%) were completed via TRA, whereas the remaining 33 procedures (33.7%) used TFA. Door-to-balloon time was similar (57 ± 19 min vs. 54 ± 15 min, p=ns). Patients in the TRA group were mobilized sooner (28 ± 9 hours vs. 36 ± 13 hours, p0.05). Hospital stay was significantly shorter in the TRA group (6.0 ± 3.2 days vs. 7.1 ± 2.8 days, p0.05). TRA and TFA did not differ significantly as to the incidence of death, non-fatal myocardial infarction or subacute stent thrombosis, but major access-related vascular complications were significantly more frequent in the TFA group (2% vs. 15%, p0.01). Cerebrovascular events did not differ between TRA and TFA.Compared to TFA, TRA seems to be associated with a lower incidence of bleeding complications, as well as earlier mobilization and discharge from hospital. It is conceivable that TRA could become the first choice in the treatment of STEMI patients in the near future, while TFA is kept as an alternative.

As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24-36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia.Two-group open cross-sectional study.Hospitalised patients in cardiology departments of four hospitals.Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level.No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE).Presence of left atrial thrombus on TEE.In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA(2)DS(2)VASc score (p=0.002) and a larger left atrium (p0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016).The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Background: Transradial coronary catheterization has emerged over the last years as a favorable catheterization practice, based on evidence that it is associated with less vascular complications and shorter hospital stays. However, access site crossover appears to be more frequent when the initial route is the transradial one, one of the main reasons being arterial spasm. We hypothesized that radial flow-mediated dilation (FMD) measurements could be used as a preprocedural method to assess the likelihood of arterial spasm. Methods: The study population consisted of patients scheduled for transradial diagnostic catheterization in whom ad hoc percutaneous coronary intervention (PCI) was performed. FMD was measured 1–2 days before PCI. The primary endpoint of the study was operator-defined (operators were blinded as to the FMD results) radial artery spasm. Results: A total of 172 patients (110 male, age 65.3 ± 9) were included. Radial artery spasm was recorded in 13 patients (7.6%). FMD showed a very significant univariate association with the occurrence of spasm (P < 0.001) and was the most important predictor of spasm in the multivariate logistic regression analysis (beta −3.15; P < 0.001), followed by baseline radial artery diameter (P = 0.04), the number of catheters used (P = 0.049) and the administered volume of contrast medium (P = 0.017). Conclusion: Preprocedural FMD is a significant predictor of arterial spasm before elective transradial PCI. It is a low cost, safe, and feasible noninvasive modality, whose results might be taken into account when deciding on the vascular access route for an elective procedure, the size of sheaths or catheters to be used or the intensity of antispasm medication.© 2010 Wiley-Liss, Inc.

The objective of this study was to characterise short-term kinetics of plasma amino-terminal pro-B natriuretic peptide (NT-proBNP) levels in patients with new-onset atrial fibrillation (AF) without heart failure.Prospective cohort study.Emergency departments and inpatient services of three large community hospitals.31 consecutive patients with new-onset atrial fibrillation (24 h before presentation) persisting at least 48 h, without evidence of heart failure.Plasma NT-proBNP levels were obtained at presentation and then 6, 12, 18, and 24 h after presentation. A final sample was obtained 48 h after onset of AF.Mean plasma NT-proBNP levels and 95% CIs (pg/ml) during the 48-h period following onset of AF were: 0-6 h: 636 (395 to 928), 6-12 h: 1364 (951 to 1778), 12-18 h: 1747 (1412 to 2083), 18-24 h: 1901 (1549 to 2253), 24-36 h: 1744 (1423 to 2066) and 36-48 h: 1101 (829 to 1373). Mean time to peak NT-proBNP levels was 16.7 (0.7) h; 29 patients reached their peak levels within 24 h. The mean peak NT-proBNP level was significantly higher than those obtained at 0-6 h and at 36-48 h after onset of AF (p0.001 for both). There was no correlation between ventricular rate and plasma NT-proBNP levels during any time period after onset of AF.In patients with new-onset AF but no clinical or radiographic evidence of heart failure, plasma NT-proBNP levels rise progressively to a peak during the first 24 h and then rapidly fall. This pattern may serve as an aid to assess the time from AF onset.

The effects of radiographic contrast media on markers of complement activation and apoptosis in patients with chronic coronary artery disease (CAD) are unknown. The purpose of this study was to assess the comparative effects of ionic high-osmolar and non-ionic iso-osmolar radiographic contrast media on plasma markers of complement activation and apoptosis in patients with chronic CAD undergoing coronary angiography. Forty-four patients undergoing coronary angiography for chronic CAD were randomly assigned to receive the ionic high-osmolar radiographic contrast agent diatrizoate (Group A), or the non-ionic iso-osmolar contrast agent iodixanol (Group B) during angiography. Complement component 5 (C5a) and apoptotic markers sFas and sFasL were measured just prior to angiography and 1 hour after completion of angiography. Comparison of mean pre- and post-angiography plasma marker levels showed significantly greater increases in plasma levels in Group A than in Group B of C5a (29.30 +/- 5.45 ng/ml for Group A and 0.47 +/- 0.70 ng/ml for Group B (p0.00001), sFas (2.36 +/- 1.63 ng/ml for Group A and 0.23 +/- 0.90 ng/ml for Group B (p0.00001) and sFasL (14.00 +/- 5.41 pg/ml for Group A and 0.01 +/- 1.00 pg/ml for Group B (p0.00001). The results suggest that in patients with chronic CAD, the use of ionic high-osmolar radiographic contrast media during coronary angiography is associated with a more robust inflammatory and apoptotic milieu than that associated with the use of non-ionic iso-osmolar radiographic contrast media.

We sought to determine the potential of remote ischemic periconditioning (RIPC), and its combination with morphine, to reduce reperfusion injury in primary percutaneous coronary interventions.Remote ischemic post-conditioning is implemented by applying cycles of ischemia and reperfusion on a remote organ, which result in release of circulating factors inducing the effects of post-conditioning on the myocardium.A total of 96 patients (59 men) were enrolled. The patients were randomized to groups as follows: 33 to each treatment group (Group A: RIPC; Group B: RIPC and morphine) and 30 to the control group (Group C). Measures of efficacy were achievement of full ST-segment resolution (primary), and reduction of ST-segment deviation score and peak troponin I during hospitalization.A higher proportion of patients in Groups A (73%) and B (82%) achieved full ST-segment resolution after percutaneous coronary intervention, compared with control patients (53%) (p = 0.045). Peak troponin I was lowest in Group B, 103.3 +/- 13.3 ng/ml, in comparison to peak levels in Group A, 166.0 +/- 28.0 ng/ml, and the control group, 255.5 +/- 35.5 ng/ml (p = 0.0006). ST-segment deviation resolution was 87.3 +/- 2.7% in Group B, compared with 69.9 +/- 5.1% in Group A and 53.2 +/- 6.4% in the control group (p = 0.00002). In paired comparisons between groups, Group B did better than the control group in terms of both ST-segment reduction (p = 0.0001) and peak troponin I (p = 0.004), whereas Group A differences from the control group did not achieve statistical significance (p = 0.054 and p = 0.062, respectively).These findings demonstrate a cardioprotective effect of RIPC and morphine during primary percutaneous coronary intervention for the prevention of reperfusion injury. This is in agreement with observations that the beneficial effect of RIPC is inhibited by the opioid receptor blocker naloxone.

A 62-year-old woman was referred for evaluation of recent-onset dyspnoea at rest and a newly found systolic heart murmur, heard best at the apex of the heart. The patient's history was notable for surgical mitral valve replacement 3 years ago, due to severe mitral regurgitation (myxomatous degeneration of the mitral valve). The transthoracic echocardiogram gave the impression of a mitral regurgitant jet, but the acoustic shadow of the prosthesis did not allow adequate evaluation of the regurgitation. A transoesophageal echocardiogram was performed showing a normally functioning mitral prosthesis, with a small periprosthetic leak (Figure 1, upper panel), disproportionate to the patient's symptoms and marked signs of haemolysis. An intracardiac ultrasound study revealed a large paravalvular regurgitant jet, indicating significant periprosthetic regurgitation (Figure 1, lower panel). Intracardiac echocardiography is increasingly being used to guide percutaneous interventions and electrophysiological procedures. The present case suggests a potentially useful widening of the range of intracardiac ultrasound clinical applications, out of the realm of device-closure interventions and electrophysiological procedures. It appears that intracardiac echocardiography could become a second-line alternative to transoesophageal echocardiography, especially in patients with contraindication to the latter.