Christian Pott

Modified phased radiofrequency ablation of atrial fibrillation reduces the number of cerebral microembolic signals.

AIMSnPhased radiofrequency (RF) ablation for atrial fibrillation is associated with an increased number of silent cerebral lesions on magnetic resonance imaging and cerebral microembolic signals (MESs) on transcranial Doppler ultrasound imaging compared with irrigated RF. The increased rate of embolic events may be due to a specific electrical interference of ablation electrodes attributed to the catheter design. The purpose of this study was to elucidate the effect of deactivating the culprit electrodes on cerebral MESs.nnnMETHODS AND RESULTSnTwenty-nine consecutive patients (60 ± 11 years, 10 female) underwent their first pulmonary vein isolation using phased RF energy. Electrode pairs 1 or 5 were deactivated to avoid electrical interference between electrodes 1 and 10 (modified). Detection of MESs by transcranial Doppler ultrasound was performed throughout the procedure to assess cerebral microembolism. Results were compared with the numbers of MESs in 31 patients ablated using all available electrodes (conventional) and to 30 patients undergoing irrigated RF ablation of a previous randomized study. Ablation with modified phased RF was associated with a marked decrease in MESs when compared with conventional phased RF (566 ± 332 vs. 1530 ± 980; P < 0.001). This difference was mainly triggered by the reduction of MES during delivery of phased RF energy, resulting in MES numbers comparable to irrigated RF ablation (646 ± 449; P = 0.7). Total procedure duration as well as time of RF delivery was comparable between phased RF groups. Both times, however, were significantly shorter compared with the irrigated RF group (123 ± 28 vs. 195 ± 38; 15 ± 4 vs. 30 ± 9; P < 0.001, respectively).nnnCONCLUSIONnPulmonary vein isolation with modified phased RF is associated with a decreased number of cerebral microembolism especially during the delivery of ablation impulses, supporting the significance of electrical interference between ablation electrodes 1 and 10. Deactivation of electrode pairs 1 or 5 might increase the safety of this approach without an increase in procedure duration or RF delivery time.

Effects of the β3-Adrenergic Agonist BRL 37344 on Endothelial Nitric Oxide Synthase Phosphorylation and Force of Contraction in Human Failing Myocardium

BACKGROUNDnIn nonfailing myocardium, beta(3)-adrenergic signaling causes a decrease in contractility via endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) release. This study investigates the hypothesis that beta(3)-adrenergic signaling undergoes alterations in failing myocardium.nnnMETHODSnWe compared eNOS- and beta(3)-adrenoceptor expression using Western blot analysis in human nonfailing myocardium versus failing myocardium. With the use of immunohistochemistry, we investigated the distribution of the beta(3)-adrenoceptor protein and eNOS translocation and phosphorylation under basal conditions. beta(3)-adrenergic, eNOS activation, and inotropy were measured in failing myocardium using BRL37344 (BRL, a beta(3)-adrenoceptor agonist).nnnRESULTSnbeta(3)-adrenoceptor expression was increased in failing myocardium. Under basal conditions, Akt- and eNOS(Ser1177) phosphorylation were reduced in failing myocardium. During stimulation with BRL in failing myocardium, a further dephosphorylation of eNOS(Ser1177) and Akt was observed, whereas eNOS(Ser114) phosphorylation was increased. These results suggest a deactivation of eNOS via beta(3)-adrenergic stimulation. Nevertheless, BRL decreased contractility in failing myocardium, but this effect was not observed in the presence of the NO blocker L-NMA. In failing myocardium, the beta(3)-adrenoceptor was predominantly expressed in endothelial cells. In the cardiomyocytes, the beta(3)-adrenoceptor was mainly located at the intercalated disks.nnnCONCLUSIONnIn failing cardiomyocytes, beta(3)-adrenergic stimulation seems to deactivate rather than activate eNOS. At the same time, beta(3)-adrenergic stimulation induced a NO-dependent negative inotropic effect. Because beta(3)-adrenoceptors are expressed mainly in the endothelium in failing myocardium, our observations suggest a paracrine-negative inotropic effect via NO liberation from the cardiac endothelial cells.

Pulmonary vein variants predispose to atrial fibrillation: a case-control study using multislice contrast-enhanced computed tomography

AIMSnPulmonary veins (PV) play a pivotal role in atrial fibrillation (AF). Anatomical variants of PV have been described and related to a higher arrhythmogenic potential. The aim of this study was to compare the prevalence of PV variants and diameters of PV ostia in AF patients and controls.nnnMETHODS AND RESULTSnVariants of PV were defined as right or left common ostia (RCO, LCO), a right middle or right top PV . A long common trunk (LCT) was defined as an LCO with a distance to the first branching ≥ 10 mm. Multislice contrast-enhanced thoracic computed tomography was performed prior to AF ablation in 166 consecutive patients, 47.6% with paroxysmal, 52.4% with persistent AF, as well as in a sex- and age-matched control group without AF, for non-cardiological indications. Images were evaluated by two independent observers. The mean age was 59 ± 10 years, 108 were men (65.1%). A higher prevalence of LCO was found in the AF group: 33.7 vs. 19.9% (P= 0.004), odds ratio (OR) 2.1; 15.4% in patients vs. 10.2% in controls had an LCT (P= 0.14). No differences in other PV variants were found. The ostial diameters were greater in AF-patients (P< 0.001).nnnCONCLUSIONSnTo the best of our knowledge, the present study shows for the first time a higher prevalence of an LCO in patients with AF as compared with controls, with an OR of 2.1. This suggests a pre-disposing role of LCO in the development of AF.

Safety profile of multielectrode-phased radiofrequency pulmonary vein ablation catheter and irrigated radiofrequency catheter

BACKGROUNDnSilent cerebral lesions with the multielectrode-phased radiofrequency (RF) pulmonary vein ablation catheter (PVAC(®)) have recently been investigated. However, comparative data on safety in relation to irrigated RF ablation are missing.nnnMETHODS AND RESULTSnOne hundred and fifty consecutive patients (58 ± 12 years, 56 female) underwent first pulmonary vein isolation (PVI) for atrial fibrillation (61% paroxysmal) using PVAC(®) (PVAC). Procedure data as well as in-hospital complications were compared with 300 matched patients who underwent PVI using irrigated RF (iRF). Procedure duration (148 ± 63 vs. 208 ± 70 min; P < 0.001), RF duration (24 ± 10 vs. 49 ± 25 min; P < 0.001), and fluoroscopy time (21 ± 10 vs. 35 ± 13 min; P < 0.001) were significantly shorter using PVAC. Major complication rates [major bleeding, transitoric ischaemic attack (TIA), and pericardial tamponade] were not significantly different between groups (PVAC, n = 3; 2% vs. iRF n = 17; 6%). Overall complication rate, including minor events, was similar in both groups [n = 21 (14%) vs. n = 48 (16%)]. Most of these were bleeding complications due to vascular access [n = 8 (5.3%) vs. n = 22 (7.3%)], which required surgical intervention in five patients [n = 1 (0.7%) vs. n = 4 (1.3%)]. Pericardial effusion [n = 4 (2.7%) vs. n = 19 (6.3%); pericardial tamponade requiring drainage n = 0 vs. n = 6] occurred more frequently using iRF. Two patients in each group developed a TIA (1.3% vs. 0.6%). Of note, four of five thromboembolic events in the PVAC group (two TIAs and three transient ST elevations during ablation) occurred when all 10 electrodes were used for ablation.nnnCONCLUSIONnPulmonary vein isolation using PVAC as a one-shot-system has a comparable complication rate but a different risk profile. Pericardial effusion and tamponade occurred more frequently using iRF, whereas thromboembolic events were more prevalent using PVAC. Occurrence of clinically relevant thromboembolic events might be reduced by avoidance of electrode 1 and 10 interaction and uninterrupted anticoagulation, whereas contact force sensing for iRF might minimize pericardial effusion.

Electrophysiological profile of vernakalant in an experimental whole-heart model: the absence of proarrhythmia despite significant effect on myocardial repolarization

AIMnThe most recent European Society of Cardiology (ESC) update on atrial fibrillation has introduced vernakalant (VER) for pharmacological cardioversion of atrial fibrillation. The aim of the present study was to investigate the safety profile of VER in a sensitive model of proarrhythmia.nnnMETHODS AND RESULTSnIn 36 Langendorff-perfused rabbit hearts, VER (10, 30 µM, n = 12); ranolazine (RAN, 10, 30 µM, n = 12), or sotalol (SOT, 50; 100 µM, n = 12) were infused after obtaining baseline data. Monophasic action potentials and a 12-lead electrocardiogram showed a significant QT prolongation after application of VER as compared with baseline (10 µM: +25 ms, 30 µM: +50 ms, P < 0.05) accompanied by an increase of action potential duration (APD). The increase in APD90 was accompanied by a more marked increase in effective refractory period (ERP) leading to a significant increase in post-repolarization refractoriness (PRR, 10 µM: +30 ms, 30 µM: +36 ms, P < 0.05). Vernakalant did not affect the dispersion of repolarization. Lowered potassium concentration in bradycardic hearts did not provoke early afterdepolarizations (EADs) or polymorphic ventricular tachycardia (pVT). Comparable results were obtained with RAN. Hundred micromolars of SOT led to an increase in QT interval (+49 ms) and APD90 combined with an increased ERP and PRR (+23 ms). In contrast to VER, 100 µM SOT led to a significant increase in dispersion of repolarization and to the occurrence of EAD in 10 of 12 and pVT in 8 of 12 hearts.nnnCONCLUSIONnIn the present study, application of VER and SOT led to a comparable prolongation of myocardial repolarization. Both drugs increased the PRR. However, VER neither affect the dispersion of repolarization nor induce EAD and therefore did not cause proarrhythmia.

Data on procedural handling and complications of pulmonary vein isolation using the pulmonary vein ablation catheter GOLD

AIMSnThe second-generation multi-electrode-phased radiofrequency pulmonary vein ablation catheter (PVAC GOLD(®)) was redesigned with the intent to improve its safety and efficacy.nnnMETHODS AND RESULTSnUsing a prospectively designed single-centre database, we retrospectively analysed 128 consecutive patients (102 paroxysmal and 43 female) who underwent their first pulmonary vein isolation with the PVAC GOLD(®). The analysis focused on procedural data as well as in-hospital complications. Baseline characteristics of the patient collective were as follows: mean age 57.9 years, mean CHA2DS2-VASC was 1.73 ± 1.30; structural heart disease was present in seven patients. The PVAC GOLD(®) exhibited procedure durations of 123.1 min ± 27.9, duration of energy delivery was 18.3 min ± 11.4, and fluoroscopy duration was 16.0 min ± 7.7. The redesigned catheter shows major complication [major bleeding, transitory ischaemic attack (TIA), and pericardial tamponade] rates of 2.3% (n = 3). The overall rate of adverse events was 5.4% (n = 7). Bleeding complications were observed in three patients (2.3%), in particular there were two cases (1.6%) of minor bleeding and one case (0.8%) of major bleeding. Two patients suffered pericardial effusion, but there was no need for pericardiocentesis. Besides one TIA, there was no other thrombo-embolic event. Furthermore, one case of post-procedural fever was observed. No deaths, stroke, or haemorrhagic shock occurred. Of the 510 pulmonary veins, 508 could be reached with the PVAC GOLD(®) device using a non-steerable long sheath.nnnCONCLUSIONnThe PVAC GOLD(®) seems to have an acceptable safety profile. The handling is comparable with the previous generation PVAC(®).

Ventricular arrhythmias from the mitral annulus: Patient characteristics, electrophysiological findings, ablation, and prognosis

BACKGROUNDnSymptomatic, premature ventricular contractions (PVCs) frequently originate in the right ventricular outflow tract, less frequently in the left ventricular outflow tract, aortic root, or mitral annulus (MA). Little is known about the patient population presenting with MA PVC and/or ventricular tachycardia (VT).nnnOBJECTIVEnTo characterize the subgroup of ventricular arrhythmias arising from the MA.nnnMETHODSnAmong 404 consecutive patients who presented for catheter ablation of idiopathic PVC/VT over a period of 9 years, patients who were found to have an ablation site at the MA were analyzed for clinical and electrophysiological parameters.nnnRESULTSnTwenty-two (5%) patients (mean age 45 ± 18 years; range 16-76 years; 14 [64%] men) had PVC/VT arising from the MA. History of PVC ranged from 2 days in a case with suspected focal myocarditis to 19 years. No patient had severely depressed left ventricular function or significant heart disease, which was determined by echocardiogram, magnetic resonance imaging, and/or coronary angiogram. Sites of origin were distributed around the MA with no preferential area. Ablation was successful in 13 of 16 (81%) patients. One 28-year-old female patient with normal magnetic resonance imaging and no structural heart disease died suddenly 3 months after ablation.nnnCONCLUSIONSnVentricular arrhythmias from the MA represent a rare subgroup of idiopathic PVC/VT. They appear to occur at any age and do not indicate underlying structural heart disease. Catheter ablation has a success rate comparable to that of outflow tract tachycardia. Prognosis remains unclear.

Circumferential pulmonary vein isolation with second-generation multipolar catheter in patients with paroxysmal or persistent atrial fibrillation: Procedural and one-year follow-up results

BACKGROUNDnThere is a lack of procedural and follow-up data on pulmonary vein isolation (PVI) with the second-generation pulmonary vein ablation catheter® (PVAC Gold) in patients with atrial fibrillation (AF). This study provides data on PVI procedures and 1-year follow-up results with PVAC Gold in patients with AF treated in clinical practice.nnnMETHODS AND RESULTSnThree hundred and eighty four patients with documented symptomatic paroxysmal (n=198) or persistent (n=186) AF were included in a non-randomized prospectively designed database. Patients were enrolled consecutively at 2 high-volume centers. Procedural as well as 1year follow-up data were systematically analyzed. Average procedure times±standard deviations were 94±23min and 97±23min, respectively, in patients with paroxysmal and persistent AF. Average fluoroscopy times were 14.7±5.4min and 15.2±5.6min and total application times 18.1±5.0min and 18.8±5.2min, respectively, in the 2 patient cohorts. At 12months, 70.7% (70/99) and 61.9% (70/113) of patients with paroxysmal and persistent AF, respectively, were free from AF. Four early complications occurred. In the group with persistent AF, 1 posterior cerebral infarction occurred 2days after the procedure during initiation of anticoagulation. There was no phrenic nerve palsy or esophageal injury associated with the procedures. No thromboembolic events were recorded during follow-up.nnnCONCLUSIONSnIn patients with paroxysmal or persistent AF, second generation multi-electrode-phased radiofrequency ablation delivers favorable mid-term PVI success rates with few procedure-related or follow-up complications.

Experimental evidence for a severe proarrhythmic potential of levosimendan

BACKGROUNDnThe calcium sensitizer levosimendan is established for therapy of acutely decompensated congestive heart failure. Clinical experience suggests a possible proarrhythmic potential. The aim of the present study was to assess possible proarrhythmic effects and underlying electrophysiological mechanisms.nnnMETHODS AND RESULTSnTen rabbit hearts were isolated and Langendorff-perfused. Thereafter, levosimendan was infused in 3 concentrations (0.5, 1, and 2μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a dose-dependent reduction of QT interval (0.5μM: -27ms, 1μM:-33ms, 2μM: -77ms; p<0.05) and action potential duration at 90% of repolarization (APD90; 0.5μM: -12ms, 1μM: -12ms, 2μM: -20ms). There was no significant increase in dispersion of repolarization. The described abbreviation of myocardial repolarization was accompanied by a significant decrease of effective refractory period (ERP; 0.5μM: -16ms, 1μM: -20ms, 2μM:-27ms; p<0.05). Under baseline conditions, ventricular fibrillation was inducible by programmed stimulation and aggressive burst stimulation in 3 of 10 hearts (4 episodes). After application of 1μM levosimendan, 8 of 10 control hearts were inducible (27 episodes). Of note, in 8 of 10 hearts after infusion of up to 2μM levosimendan, incessant ventricular fibrillation that could not be terminated by multiple external defibrillations occurred.nnnCONCLUSIONnIn the present study, acute infusion of levosimendan resulted in an abbreviation of ventricular repolarization and a reduction of ERP. This led to a significantly elevated inducibility of ventricular fibrillation. In 8 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a proarrhythmic effect of levosimendan and might explain an increased mortality that coincided levosimendan treatment in a few small clinical studies.

Increased sodium/calcium exchanger activity enhances beta-adrenergic–mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model

BACKGROUNDnThe cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown.nnnOBJECTIVEnThe purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function.nnnMETHODSnLangendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 μM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained.nnnRESULTSnAt baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT.nnnCONCLUSIONnThis study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure.