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Introduction: Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Objectives: This study compared the long-term efficacy and safety of apixaban with that of uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct current cardioversion (DCC) from June 2014 to September 2016. Methods: We enrolled consecutive patients with persistent nonvalvular AF scheduled to undergo DCC. Patients received apixaban 5 mg or 2.5 mg twice daily (bid) or VKA at therapeutic doses for at least 3 weeks before and 4 weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic, and echocardiographic evaluation at each follow-up visit and were followed-up for 12 months. The primary efficacy endpoint was the composite of stroke/transient ischemic attack and systemic embolism. The primary safety endpoint was major bleeding. Results: After propensity score matching, comparative treatment groups comprised 182 (75.8%) patients receiving apixaban 5 mg bid and 182 receiving VKA. A low incidence of atrial thrombus (0.5%) at TEE was found in both groups. The acute cardioversion success rate was 86.1% in the apixaban group (156/181) and 83.9% in the VKA group (152/181). During the follow-up period, a similarly low incidence of thromboembolic events (1.1%) was reported in both groups; the bleeding safety profile tended to favor apixaban over VKA (1.1 vs. 1.6%; p = 0.3). Conclusions: Newly initiated anticoagulation with apixaban in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy during 12 months of follow-up.

Atrial electromechanical delay (AEMD) is an echocardiographic parameter correlated with the onset of supraventricular arrhythmias in several clinical conditions. Inter-atrial septal pacing in the region of Bachmann’s bundle (BB) has been shown to be safe and feasible in myotonic dystrophy type 1 (DM1) patients, with a low rate of sensing and pacing defects. The aim of this study was to assess the impact of temporary BB pacing compared with right atrial appendage (RAA) pacing on AEMD in DM1 patients undergoing pacemaker (PM) implantation for cardiac rhythm abnormalities. The study enrolled 70 consecutive DM1 patients undergoing PM implantation for cardiac rhythm abnormalities in accordance with the current guidelines. Seventy age- and sex-matched non-DM1 patients undergoing dual-chamber PM implantation for cardiac rhythm abnormalities were used as controls. The atrial pacing lead was temporarily positioned in the RAA and on the right side of the inter-atrial septum in the region of Bachmann’s bundle. For each site (BB and RAA), temporary atrial pacing in the AAI mode was established at 10 beats per minute above the sinus rate and a detailed trans-thoracic echocardiogram with tissue Doppler (TDI) analysis was recorded after at least 10 min of atrial pacing to evaluate AEMD. Temporary RAA pacing did not show statistically significant differences in inter-AEMD (48.2 ± 17.8 vs 50.5 ± 16.5 ms; P = 0.8), intra-left AEMD (43.3 ± 15.5 vs 44.6 ± 15.8 ms; P = 0.1), or intra-right-AEMD (14.1 ± 4.2 vs 15.4 ± 5.8 ms; P = 0.9), in comparison with sinus rhythm. Temporary BB pacing determined a significantly lower inter-AEMD (36.1 ± 17.1 vs 50.5 ± 16.5 ms; P = 0.001) and intra-left AEMD (32.5 ± 15.2 vs 44.6 ± 15.8 ms; P = 0.001) values in comparison with temporary RAA pacing. No statistically significant difference was found in intra-right AEMD (12.2 ± 4.6 vs 15.4 ± 5.8 ms; P = 0.2). In the control group, neither temporary RAA pacing nor temporary BB pacing showed statistically significant differences in inter-AEMD, intra-left AEMD, or intra-right AEMD values in comparison with sinus rhythm. In DM1 patients undergoing dual-chamber PM implantation, atrial pacing in the Bachmann bundle region is associated with significantly lower echocardiographic indices of atrial electromechanical delay (inter-AEMD and intra-left AEMD) in comparison with RAA pacing.

High plasma levels of low density lipoproteins (LDLs) represent one of the major risk factors for cardiovascular disease, as shown by many epidemiological studies. On the other hand, randomized trials designed to address the clinical impact of lipid lowering interventions, have clearly shown that reduction in LDL plasma levels lead to a significant decrease in major cardiovascular events. Based on these observations, pharmacological modulation of LDLs has been highly investigated. Statins, alone or in combination, represent the most powerful agents to date available to reach the LDLs levels suggested by the current guidelines. However, in some patients the recommended LDL reduction is difficult to be achieved because of genetic background (familial hypercholesterolemia), side effects (statin intolerance), or simply because of a non-sufficient response. In the last few years, our understanding of the basic mechanisms involved in the lipoprotein metabolism has progressed significantly. The crucial role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. The main characterized function of PCSK9 relates to the binding to LDL-C receptors (LDLR) in hepatocytes. However, PCSK9 does not interfere with the binding between LDL and its own receptor, but with the ability of the latest to return to the surface of the hepatocyte and bind new LDL molecules. Based on these observations, blocking PCSK-9 may reduce the LDLR clearance, thus increasing the ability of LDLR to remove circulating LDLs. Pharmacological inhibition of this protein has been proposed as new therapeutic approach. The clinical evidence available to date seem to fully support this hypothesis.

Background: The aim of the study was to assess the main determinant of the fall in blood pressure (BP) responsible for the head-up tilt testing-induced syncope. Methods and results: The study involved 200 patients (mean age 42 ± 3; 81 male) with syncope of unknown origin after the first evaluation. According to the response to the diagnostic tilt test, the population study was divided into four groups: Group I with mixed vasovagal syncope; Group II with cardioinhibitory syncope; Group III with vasodepressive syncope; Group IV: 40 patients with clinical syncope but no tilt-induced syncope. Finger arterial BP (Portapres, TNO, Amsterdam, the Netherlands) was recorded during tilt testing. Left ventricular stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were computed from the pressure pulsations (Modelflow, TNO, Amsterdam, the Netherlands). During syncopal phase, the TPR decreased significantly in Group III, and increased in Group I and in Group II. CO decreased in Group I and in Group II and did not change significantly in Group III. SV decreased significantly in all groups. Conclusions: Our data showed that the arterial system appears to be the main determinant of the BP fall in vasodepressive vasovagal syncope; while the impaired constrictive response of the venous system, leading to reduced venous return to the heart, appears to be the main determinant of BP fall in mixed and cardioinhibitory vasovagal syncope. (PACE 2012; 35:739–748)

Aims Paroxysmal atrial arrhythmias occur in myotonic dystrophy type 1 (MD1) patients frequently. Pacemaker (PM) including detailed diagnostic functions may facilitate the diagnosis and management of frequent paroxysmal atrial tachyarrhythmias that may remain undetected during conventional clinical follow-up. Aim of our study was to evaluate the preventive effects of interatrial septum pacing in the Bachmann's Bundle region on atrial fibrillation (AF) in MD1 patients during 12 months follow up period. Methods and results Thirty MD1 patients (age 50.3 ± 7.3; 11 F) who underwent dual chamber PM implantation were randomized at implantation to receive right atrial appendage pacing (16 patients) or Bachmann's bundle pacing (14 patients). No statistically significant difference in the electrical parameters (P wave amplitude, pacing threshold and lead impedance) was found between the two groups at implantation. Patients were followed at 1 month, 3 months, and every 6 months thereafter. They underwent clinical assessment, a standard 12-lead ECG and assessment of device performance at every visit. We counted the number of episodes of atrial arrhythmia occurred during the collection period and the duration of each episode. At 12 months of follow-up, no statistically significant differences in the number of AF episodes or in AF duration were found. Lead parameters remained stable over time and there were no displacements of the electrodes after implantation. Conclusion Implantation of an atrial-active fixation lead on the atrial septum is safe and feasible. However, this study showed no significant difference between septal pacing and high atrial pacing, using the endpoints of AF duration and number of AF episodes.

Aim: We performed a two-year follow-up comparative study of long-term electrical parameters between the right atrial appendage (RAA) and Bachmann’s Bundle (BB) stimulation in myotonic dystrophy type 1 (MD1) patients. Methods: Twenty-five MD1 patients (18 men; age: 54 ± 13 years) with no difference in the electrical parameters between the RAA site and the BB region at implantation were randomized into two groups: in group I (13 patients; age: 52 ± 14 years; four women) the atrial lead was placed in the RAA and in group II (12 patients, age: 56 ± 12 years, three women) the lead was placed in the BB region. Measurements of electrical parameters were recorded at follow-up intervals of 6 weeks and then 12 and 24 months postimplant. Results: There was no statistically significant different in P-wave amplitude, pacing threshold, and impedance values between the two groups at 6 weeks. At 24 months follow-up, the intrinsic P-wave amplitude was 2.05 ± 1.45 mV in the RAA group versus 3.28 ± 1.09 mV in the BB group (P < 0.05); the pacing threshold was 1.85 ± 1.8 V in the RAA group versus 0.50 ± 0.39 V in the BB group (P = 0.03); there were no differences in the atrial impedance between the two groups during the follow-up period. Conclusions: In a direct two-year follow-up comparison between the RAA and BB atrial pacing sites, we showed a statistically significant increased pacing threshold and decreased intrinsic P-wave amplitude during RAA stimulation in MD1 patients. (PACE 2009; 32:1191–1196) Bachmann’s bundle, myotonic dystrophy, pacemaker, arrhythmias, heart block, fibrosis, sensing,pacing, impedance, atrial lead