Search

Background: Silent 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.Methods and Results: One 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.Conclusion: Pulmonary 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. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca2+ overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether ICa blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K+] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block IKr in CHF hearts. After lowering [K+] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of ICa. CONCLUSIONS AND IMPLICATIONS Blockade of ICa was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit [ABSTRACT FROM AUTHOR]

Background: Electrophysiologic characteristics, mapping strategies, and acute success rates of radiofrequency catheter ablation of atriofascicular accessory pathways are well described. However, data on long-term prognosis and predictors for freedom from arrhythmias are lacking.Objective: To report our 20-year single-center experience on ablation of atriofascicular fibers.Method: Between 1992 and 2010, 34 patients with atriofascicular accessory pathways underwent catheter ablation at our institution because of symptomatic antidromic atrioventricular reentrant tachycardias. Radiofrequency procedures were retrospectively analyzed, and patients were followed for recurrences of tachyarrhythmias. Electrocardiograms (before and after ablation and at follow-up) were analyzed for each patient.Results: Successful catheter ablation of the atriofascicular fiber was achieved in 23 (68%) patients. Mechanical block during mapping occurred in 3 (9%) patients, and in 2 of them ablation was performed at the site of mechanical block. Mere modification of conduction properties of the pathway without complete block was achieved in 5 patients (15%). Fast pathway ablation was performed in 2 (6%) of the patients ablated in the early 1990s. During follow-up of 9.3 ± 5.5 years, 24 patients (71%) remained free of tachyarrhythmias, 7 reported significant improvement, and 3 (9%) had no change in symptoms after ablation. Long-term success was identical between patients from the first (1992-1999) and second (2000-2010) decade (12 of 17 [71%] vs 12 of 17 [71%]). It was 87% in those with complete block of the atriofascicular fiber while all patients with mechanical block during mapping reported recurrences. Fast pathway ablation was complicated by complete atrioventricular block in 1 patient, who required pacemaker implantation 18 years after ablation owing to loss of conduction properties of the atriofascicular fiber over the years. On analyzing patients with preexcitation before ablation (n = 16; 47%), we found that the PR interval after ablation was significantly longer only in those without recurrence (162 ± 21 ms vs 134 ± 21 ms; P = .042). None of the other analyzed electrocardiographic parameters, including PR, QRS duration, and preexcitation, had prognostic impact.Conclusion: Acute success of complete ablation of atriofascicular pathways is associated with excellent long-term success (87%). Mere modification of conduction properties of atriofascicular fibers or ablation at the sites of mechanical block are less promising end points of ablation with high recurrence rates. Technical innovations during decades may not further improve long-term outcome in these patients. [ABSTRACT FROM AUTHOR]

Background: Molecular remodeling in heart failure includes slowing of repolarization, leading to proarrhythmia.Objective: To evaluate the effects of Na(+)/Ca(2+) exchanger (NCX) inhibition on repolarization as a novel antiarrhythmic concept in chronic heart failure (CHF).Methods and Results: CHF was induced by rapid ventricular pacing in rabbits. Left ventricular function was assessed by echocardiography. Monophasic action potentials (MAPs) showed a prolongation of repolarization in CHF after atrioventricular block and stimulation at different cycle lengths. Sotalol (100 μM, n = 13) or veratridine (0.5 μM; n = 15) resulted in a further significant increase in the MAP duration. CHF was associated with an increased dispersion of repolarization, as compared with sotalol-treated (+22 ± 7 ms; P < .05) and veratridine-treated (+20 ± 6 ms; P < .05) sham hearts. In the presence of a low potassium concentration, sotalol and veratridine reproducibly induced early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias (VTs). SEA0400 (1 μM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). It suppressed EAD in 6 of 13 sotalol-treated failing hearts and in 9 of 10 veratridine-treated failing hearts, leading to a reduction in VT (60% in sotalol-treated failing hearts and 83% in veratridine-treated failing hearts). Simulations using a mathematical model showed a reduction in the action potential duration and the number of EADs by the NCX block in all subgroups.Conclusions: In an experimental model of CHF, the acute inhibition of NCX (1) reduces the MAP duration, (2) decreases dispersion of repolarization, and (3) suppresses EAD and VT. Our observations indicate for the first time that pharmacological NCX inhibition increases repolarization reserve and protects against VTs in heart failure. [ABSTRACT FROM AUTHOR]

Copyright of Herzschrittmachertherapie und Elektrophysiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: In 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. METHODS: We 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). RESULTS: beta(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. CONCLUSION: In 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. [ABSTRACT FROM AUTHOR]

Background: Long QT syndrome (LQTS) is associated with sudden cardiac death resulting from torsades de pointes (TdP), which are triggered by early afterdepolarizations (EADs). The cardiac Na(+)/Ca(2+) exchanger (NCX) has been suggested to work as a trigger for EADs.Objective: The purpose of this study was to test the hypothesis that inhibition of NCX with a newly developed selective NCX inhibitor (SEA0400) reduces TdP.Methods and Results: In 34 Langendorff-perfused rabbit hearts, the I(Kr)-blocker sotalol (100 microM; n = 18) as well as veratridine (0.5 microM; n = 16), an inhibitor of sodium channel inactivation, led to a significant increase in monophasic action potential (MAP) duration thereby mimicking LQTS2 and LQTS3. In bradycardic hearts, recordings of eight MAPs demonstrated an increased dispersion of repolarization (sotalol: 67%; veratridine: 89%; P <.05). After lowering of potassium concentration, sotalol (56%) and veratridine (63%) induced TdP. Perfusion with SEA0400 (1 microM) suppressed EADs in 15 of 16 sotalol hearts and in seven of 13 veratridine hearts. SEA0400 significantly shortened MAP duration and reduced dispersion of repolarization in both groups (P <.05). This reduced TdP incidence in the sotalol group (100%) and in the veratridine group (77%). To investigate the effects of NCX inhibition on the cellular level, we used a computer model of the rabbit ventricular myocyte. I(Na) and I(Kr) were modified to mimic the effects of veratridine and sotalol, respectively. Consistent with our in vitro experiments, reduction of NCX activity accelerated repolarization of the cellular action potential and prevented EADs.Conclusion: In an intact rabbit heart model of LQT2 and LQT3 as well as in a computer model of the rabbit cardiac myocyte, inhibition of NCX is effective in preventing TdP due to a suppression of EADs, a reversion of action potential prolongation, and a reduction of dispersion of repolarization. Our observations suggest a therapeutic benefit of selective NCX inhibition in LQTS. [ABSTRACT FROM AUTHOR]

1 The present study investigated the effects of the preferential β[sub 3]-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca[sup 2+]-transient and eNOS-activity in human right atrial myocardium. 2 BRL concentration-dependently caused an increase in FOC that was paralleled by an increase in Ca[sup 2+]-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 µM). 3 BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards β[sub ½]-AR. 4 In immunohistochemical experiments BRL (10 µM) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 µM). 5 BRL increased directly detected NO in DAF-staining experiments. This increase was significantly smaller in the presence of the NO-inhibitor L-NAME. 6 The inotropic effects of BRL were not changed in the presence of L-NMA. 7 These results suggest that the inotropic effects of BRL in human atrium are mediated via β[sub ½]AR, whereas the increase of atrial eNOS-activity is due to β[sub 3]-adrenergic stimulation. This increase in eNOS-activity did not influence atrial myocardial contractility. In conclusion, this study shows that β[sub 3]-adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle. [ABSTRACT FROM AUTHOR]

The purine analogs fludarabine (FAMP) and 2-chlorodeoxyadenosine (2-CDA) are highly active in chronic lymphocytic leukemia (CLL). In second-line therapy response rates are in the range of 30 to 60% and exceed 70% when applied to previously untreated patients. While FAMP in particular is thus well established for salvage treatment and can be considered as the present treatment of choice, more data are needed to define the role of purine analogs for first-line therapy. [ABSTRACT FROM AUTHOR]

The development of rapid polymerase chain reaction (PCR) protocols for amplification of rearranged heavy chain immunoglobulin (IgH) gene sequences has facilitated the identification of clonal IgH rearrangements in non-Hodgkin's lymphomas (NHL) and leukemias of B lineage. In the present report we have explored the recently described improved strategy for assessment of clonality of rearranged immunoglobulin heavy chain (IgH) genes in more detail in a series of 101 B cell malignancies and 50 polyclonal controls. The assay is based on an IgH-PCR with an automated fluorescence-based strategy for PCR detection of IgH gene rearrangements. Third complementarity determining region (IgH-CDR3) sequences were amplified using fluorescent dye labeled consensus primers homologous to the corresponding variable (V[H]) and joining (J[H]) gene segments in combination with a thermostable proofreading DNA polymerase. PCR products were size separated on a high resolution polyacrylamide gel and analyzed for clonality by exact size determination and fluorescence quantification in an automated DNA sequencer. PCR findings obtained with the optimized IgH-CDR3-PCR assay showed an overall monoclonality detection rate of 97% (97 of 101 cases with B cell neoplasms). The specificity was 100% as determined by analysis of 50 controls, all of which gave polyclonal PCR results. We found a high rate of monoclonal IgH-CDR3-PCR results not only in the leukemias and diffuse lymphoma but also in the group of follicular lymphoma, where a high rate of false negative results is frequently reported in the literature. In summary, we identified monoclonal IgH-CDR3 junctions in 55 out of 59 cases (93%) with B cell lymphoma and in 42 of 42 (100%) cases with leukemia, immunocytoma and multiple myeloma. The results demonstrate that automated fluorescence detection of IgH-CDR3-PCR products is an ideal tool for detection of clonal and polyclonal lymphoid B cells. In combination with allele-specific primers the procedure may improve current experimental approaches to detect occult malginant B cells during initial staging and follow-up of NHL and ALL patients. [ABSTRACT FROM AUTHOR]