Spatial relationship of organized rotational and focal sources in human atrial fibrillation to autonomic ganglionated plexi.

BACKGROUND: One approach to improve ablation for atrial fibrillation (AF) is to focus on physiological targets including focal or rotational sources or ganglionic plexi (GP). However, the spatial relationship between these potential mechanisms has never been studied. We tested the hypothesis that rotors and focal sources for AF may co-localize with ganglionated plexi (GP). METHODS: We prospectively identified locations of AF rotors and focal sources, and correlated these to GP sites in 97 consecutive patients (age 59.9±11.4, 73% persistent AF). AF was recorded with 64-pole catheters with activation/phase mapping, and related to anatomic GP sites on electroanatomic maps. RESULTS: AF sources arose in 96/97 (99%) patients for 2.6±1.4 sources per patient (left atrium: 1.7±0.9 right atrium: 1.1±0.8), each with an area of 2-3cm2. On area analyses, the probability of an AF source randomly overlapping a GP area was 26%. Left atrial sources were seen in 94 (97%) patients, in whom ≥1 source co-localized with GP in 75 patients (80%; p<0.05). AF sources were more likely to colocalize with left vs right GPs (p<0.05), and colocalization was more likely in patients with higher CHADS2VASc scores (age>65, diabetes; p<0.05). CONCLUSIONS: This is the first study to demonstrate that clinically detected AF focal and rotational sources in the left atrium often colocalize with regions of autonomic innervation. Studies should define if the role of AF sources differs by their anatomical location.

Selection of Antithrombotic Therapy in Patients with Atrial Fibrillation and Percutaneous Coronary Intervention.

BACKGROUND: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy has been shown to effectively prevent stent thrombosis and other ischemic cardiovascular events. The frequent occurrence of atrial fibrillation (AF) and concomitant CAD in the same individuals, suggests that clinicians will encounter many patients treated with PCI who will require anticoagulant treatment for the prevention of the thromboembolic complications of AF. METHODS: In this narrative review we provide an overview and update of evidence regarding antiplatelet therapy in patients with AF undergoing PCI. RESULTS: The combination of dual antiplatelet therapy with anticoagulants may further protect a patient from ischemic complications, at the cost, however, of a several-fold increased bleeding risk. The introduction of novel pharmaceutical agents in both categories implies that there is paucity of data regarding the efficacy and, more importantly, the safety of between-drug combinations. CONCLUSION: Careful consideration of the patient's individual characteristics and assessment of the risk for bleeding and thrombotic events using validated risk prediction tools is of great importance in order to maximize the benefits for each patient, while minimizing the risk for hemorrhage.

Apical vs. non-apical right ventricular pacing in cardiac resynchronization therapy: a meta-analysis.

AIMS: Cardiac resynchronization therapy (CRT) has been shown to improve outcomes in patients with heart failure. The optimal site of right ventricular (RV) stimulation in CRT has not been established. We aimed to conduct a meta-analysis of randomized-controlled trials and observational studies comparing the mid- and long-term effects of RV apical (RVA) and non-apical (RVNA) pacing on CRT outcomes. METHODS: We systematically searched the Cochrane library, EMBASE, and MEDLINE databases for studies evaluating RVA vs. RVNA pacing in CRT with regards to left ventricular end-systolic volume (LVESV) reduction, functional status improvement (defined as ≥1 New York Heart Association class improvement), and the clinical outcome of mortality or cardiovascular hospitalization. Effect estimates [standardized mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI)] were pooled using random-effect models. RESULTS: Twelve studies comprising 2670 patients (1655 with an apical and 1015 with a non-apical RV lead position) were included. In meta-analyses, LVESV reduction and functional status improvement were similar in patients with RVA and RVNA pacing (SMD 0.13, 95% CI: -0.24 to 0.50, P = 0.48; OR 1.08, 95% CI: 0.81 to 1.45, P = 0.60, respectively). Data regarding mortality and hospitalizations could not be pooled due to a small number of relevant studies with significant heterogeneity. CONCLUSION: Our meta-analysis suggests that in CRT patients the effects of RVA or RVNA pacing on LV remodelling and functional status are similar. Mortality and morbidity outcomes with different RV lead positions should be further assessed in randomized clinical trials.

Effect of one-cycle remote ischemic preconditioning to reduce myocardial injury during percutaneous coronary intervention.

Up to 1/3 of percutaneous coronary interventions (PCIs) are complicated by troponin release. Remote ischemic preconditioning (IPC) confers effective cardioprotection; however, a 30-minute remote IPC protocol may be difficult to implement during ad hoc PCI. This study was performed to assess the ability of a brief remote IPC protocol to attenuate cardiac troponin I (cTnI) release after ad hoc PCI. Ninety-four patients undergoing ad hoc PCI for stable coronary artery disease, with undetectable preprocedural cTnI, were recruited and randomized to receive remote IPC (induced by one 5-minute inflation of a blood pressure cuff to 200 mm Hg around the upper arm) or control after the decision for PCI was made. The primary outcome was the difference between cTnI levels 24 hours after PCI and cTnI levels before coronary angiography (ΔcTnI). ΔcTnI in the remote IPC group was significantly lower compared with the control group (0.04 ng/ml [interquartile range 0.01 to 0.14] vs 0.19 ng/ml [interquartile range 0.18 to 0.59], p <0.001). The incidence of PCI-related myocardial infarction (MI) was greater in the control group (42.6% vs 19.1%, p = 0.014). In multivariate analysis, remote IPC was independently associated with ΔcTnI and PCI-related MI. In conclusion, our results suggest that even 1 cycle of remote IPC immediately before ad hoc PCI attenuates periprocedural cTnI release and reduces the incidence of type 4a MI.

Clinical and angiographic characteristics of patients with coronary artery ectasia.

BACKGROUND: The relationship of the extent of coronary artery ectasia (CAE) with coronary blood flow in the major epicardial arteries has not been adequately assessed. This study aimed at investigating the association of the topographical extent of CAE with coronary flow velocity and clinical characteristics in patients with isolated CAE and in patients with coexisting obstructive coronary artery disease (CAD). METHODS: We reviewed 3764 consecutive coronary angiograms performed at Athens Euroclinic and identified patients with CAE according to standard criteria. The topographical extent of ectasia was considered, and coronary flow velocity was determined using the TIMI frame count (TFC). The severity of CAD was assessed using the modified Gensini index and the number of diseased vessels. Clinical data were correlated with TFC and CAD severity analysis. RESULTS: Ectatic lesions were identified in 119 patients. The mean TFC correlated positively with the topographical extent of CAE (rs=0.733, p<0.001). Stepwise multiple linear regression revealed that the topographical extent of CAE and the maximum diameter of the ectatic segment in the corresponding artery are independent predictors of TFC in LAD and RCA. Using multivariate analysis, a history of myocardial infarction was independently associated with CAE extent, and CAD severity. CONCLUSIONS: The extent of ectasia in the coronary vasculature is correlated with coronary flow velocity and associated with clinical presentation independent of coexisting significant coronary stenoses.

Natriuretic Peptides as Predictors of Atrial Fibrillation Recurrences Following Electrical Cardioversion.

Electrical cardioversion (ECV) can be effective in restoring sinus rhythm (SR) in the majority of patients with atrial fibrillation (AF). Several factors that predispose to AF recurrences, such as age, AF duration and left atrial size have been used to guide a decision for cardioversion, but increasing evidence suggests that they may be rather poor markers of left atrial structural remodeling that determines the long-term success of a rhythm control strategy. In this context, the use of easily obtainable biomarkers, such as the levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), to predict AF recurrences may be preferable. Since ANP production is associated with the extent of functional atrial myocardium, and both ANP and BNP reflect atrial pressure and mechanical stretching, these peptides are good candidate biomarkers to assess predisposition to AF recurrences. In this review we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural ANP and BNP levels.

Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients.

AIM: To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in first-degree relatives (FDRs) of Greek PBC patients. METHODS: The presence of antimitochondrial antibodies (AMA) and PBC-specific antinuclear antibodies (ANA) were determined using indirect immunofluorescence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymptomatic for liver-related symptoms FDRs of 44 PBC patients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepatitis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The prevalence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI): 12%-28.1% vs 2.5%, 95% CI: 0.1%-14.7%, P = 0.01; 18.8%, 95% CI: 12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI: 1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio: 3.92, 95% CI: 1.25-12.35, P = 0.02). CONCLUSION: In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.

Adiponectin: a new independent predictor of liver steatosis and response to IFN-alpha treatment in chronic hepatitis C.

OBJECTIVES: To compare serum adiponectin and tumor necrosis factor (TNF)-alpha among patients with viral liver diseases; to investigate associations of serum adiponectin and TNF-alpha with histological or viral characteristics of chronic hepatitis C (CHC); to investigate adiponectin and TNF-alpha alterations during interferon (IFN)-alpha treatment; and to assess the relationship between serum adiponectin and TNF-alpha and response rates to treatment. METHODS: Adiponectin (mug/mL) and TNF-alpha (pg/mL) determinations by enzyme-linked immunosorbent assay (ELISA) in serial samples (before, the middle, the end, and 6 months after the end of treatment) from 83 CHC and 59 chronic hepatitis B (CHB) patients. Forty-three blood donors served as healthy controls. Patients were treated with IFN-alpha (4.5 MU/t.i.w.) for 12 months in CHB cases, and IFN-alpha (3 MU/t.i.w.) plus ribavirin for 6-12 months according to hepatitis C virus (HCV) genotype in CHC cases. RESULTS: After adjustment for gender and body mass index (BMI), HCV genotype 3 overweight patients (BMI > 25 kg/m(2)) had significantly lower adiponectin (7.3 +/- 2.7) at baseline compared with non-3 HCV genotype overweight patients (P < 0.05). Lower adiponectin (HCV genotype 3, P= 0.02 and HCV genotype 1, P= 0.025) and higher TNF-alpha (P= 0.025) at baseline were identified as independent predictors of liver steatosis in CHC patients. Lower adiponectin was also identified as an independent predictor of no virological response at the end of treatment (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.66-0.87, P < 0.001). At the end of IFN-alpha therapy, only HCV genotype 3 patients had significantly higher serum adiponectin (10.4 +/- 6.3) compared with its levels before treatment (8.7 +/- 4.7, P < 0.05). CONCLUSIONS: This study suggests that HCV genotype 3 may directly affect adiponectin. This is further supported by the significant increase in adiponectin at the end of treatment only in HCV genotype 3 patients. Serum adiponectin at baseline appears to be an independent predictor of liver steatosis and for the achievement of end-of-treatment virological response, while serum TNF-alpha at baseline was identified as an independent predictor only of liver steatosis.

Alterations of leptin during IFN-alpha therapy in patients with chronic viral hepatitis.

BACKGROUND/AIMS: Leptin has a particular profibrogenic role in the liver. We investigated whether IFN-alpha influences leptin production in patients with chronic hepatitis B (CHB) and C (CHC). Leptin was determined in serial samples from 63 CHB and 42 CHC IFN-alpha treated patients. Furthermore, we evaluated whether leptin alterations were associated with patients' characteristics. METHODS: Sera were investigated at serial time-points using an enzyme-linked-immunosorbent-assay. Controls consisted of 36 patients with autoimmune liver diseases and 44 healthy patients. RESULTS: Leptin levels before IFN-alpha administration were higher in CHB and CHC compared to healthy (P<0.004) and diseased controls (P=0.0001). In CHB patients, we observed a significant reduction of leptin during IFN-alpha treatment and lasting for up to 6 months after the end of treatment, followed by an increase reaching pretreatment levels at 1.5 years after stopping therapy. The pattern of leptin alterations was similar in CHC patients where leptin's decrease was more pronounced at 6 months after the end of treatment. Biochemical or virological response to treatment was not associated with leptin reduction in both groups. CONCLUSIONS: This study provides information on leptin kinetics during IFN-alpha treatment and follow-up in CHB and CHC patients and suggests IFN-alpha as a potential inhibitor of leptin production.