Influence of myopotential interference on the Wavelet discrimination algorithm in implantable cardioverter-defibrillator

Background: Wavelet is a morphology-based algorithm for detecting ventricular tachycardia. The electrogram (EGM) source of the Wavelet algorithm is nominally programmed with the Can-RV coil configuration, which records a far-field ventricular potential. Therefore, it may be influenced by myopotential interference. Methods: We performed a retrospective review of 40 outpatients who had an implantable cardioverter-defibrillator (LCD) with the Wavelet algorithm. The percent-match score of the Wavelet algorithm was measured during the isometric chest press by pressing the palms together. We classified patients with percent-match scores below 70% due to myopotential interference as positive morphology change, and those with 70% or more as negative morphology change. Stored episodes of tachycardia were evaluated during the follow-up. Results: The number of patients in the positive morphology change group was 22 (55%). Amplitude of the Can-RV coil EGM was lower in the positive morphology change group compared to that in the negative group (3.9 +/- 1.3 mV vs. 7.4 +/- 1.6 mV, P=0.0015). The cut-off value of the Can-RV coil EGM was 5 mV (area under curve, 0.89). Inappropriate detections caused by myopotential interference occurred in two patients (5%) during a mean follow-up period of 49 months, and one of them received an inappropriate LCD shock. These patients had exhibited positive morphology change. Conclusions: The Wavelet algorithm is influenced by myopotential interference when the Can-RV coil EGM is less than 5 mV

A Dipeptidyl Peptidase-4 Inhibitor, Des-Fluoro-Sitagliptin, Improves Endothelial Function and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E–Deficient Mice

ObjectivesThe aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS).BackgroundThe new class of anti–type 2 diabetes drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1.MethodsEndothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic rings and atherosclerotic lesion development in the entire aorta in apolipoprotein E–deficient mice fed a high-fat diet with or without DFS, and the antiatherogenic effects of DFS were investigated in cultured human macrophages and endothelial cells. Plasma levels of active GLP-1 were measured in patients with or without coronary artery disease.ResultsDFS significantly improved endothelial dysfunction (89.9 ± 3.9% vs. 79.2 ± 4.3% relaxation at 10−4 mol/l acetylcholine, p < 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% [15.6% to 25.8%] vs. 24.6% [19.3% to 34.6%], p < 0.01) compared with vehicle treatment. In cultured human macrophages, DFS significantly increased GLP-1-induced cytosolic levels of cyclic adenosine monophosphate compared with GLP-1 alone, resulted in inhibiting phosphorylation of c-jun N-terminal kinase and extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B p65 nuclear translocation through the cyclic adenosine monophosphate/protein kinase A pathway, and suppressed proinflammatory cytokines (i.e., interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha) and monocyte chemoattractant protein-1 production in response to lipopolysaccharide. DFS-enhanced GLP-1 activity sustained endothelial nitric oxide synthase phosphorylation and decreased endothelial senescence and apoptosis compared with GLP-1 alone. In the human study, fasting levels of active GLP-1 were significantly lower in patients with coronary artery disease than those without (3.10 pmol/l [2.40 to 3.62 pmol/l] vs. 4.00 pmol/l [3.10 to 5.90 pmol/l], p < 0.001).ConclusionsA DPP-4 inhibitor, DFS, exhibited antiatherogenic effects through augmenting GLP-1 activity in macrophages and endothelium

Pleomorphic ventricular tachycardia originating from Purkinje fiber network of left anterior fascicle

A 55-year old woman with recurrent syncope and palpitation experienced polymorphic ventricular tachycardia (VT) and more than three monomorphic VTs with a right bundle branch block configuration, either inferior-, middle-, and superior-axis. During the pleomorphic VT, the diastolic potential (dp) was recorded at the antero-lateral left ventricle. Changes in the QRS morphology were associated with the time between dp and onset of QRS complex (dp-V interval), and prolongation of dp-V interval terminated the VT. In addition, the delayed potentials were seen during sinus rhythm around this area. Delivery of radiofrequency current targeting the delayed potentials abolished all the VTs. Different exits from relatively large area of slow conduction in the left anterior fascicle might have produced the pleomorphic VTs

Unique preferential conduction within the isolated septal substrate in a patient with ventricular tachycardia complicated with non-ischemic dilated cardiomyopathy

We describe the case of a 67-year-old woman with non-ischemic dilated cardiomyopathy who underwent successful radiofrequency catheter ablation for ventricular tachycardia (VT) originated from the isolated ventricular septal substrate. Pacemapping exhibited either left, identical to clinical VT, or right bundle branch block like wide QRS morphology. Time interval from the stimulus to QRS onset (St-QRS) was prolonged at the center of the substrate, while St-QRS at the border was shortened. Difference in the morphology of pacemapping was dependent on whether or not the pacing stimulus could propagate directly into the right ventricle due to the possible intramural conduction disturbance. (C) 2013 Elsevier Inc. All rights reserved

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes

The objective of this study was to investigate the mechanisms of increase in the efficacy of ATP-sensitive K+ channel (K-ATP) openings by hypo-osmotic stress. The whole-cell K-ATP currents (I-K,I-ATP) stimulated by 100 mu mol/L pinacidil, a K+ channel opening drug, were significantly augmented during hypo-osmotic stress (189 mOsmol/L) compared with normal conditions (303 mOsmol/L). The EC50 and E-max value for pinacidil-activated I-K,I-ATP (measured at 0 mV) was 154 mu mol/L and 844 pA, respectively, in normal solution and 16.6 mu mol/L and 1266 pA, respectively, in hypo-osmotic solution. Augmentation of I-K,I-ATP during hypo-osmotic stress was attenuated by wortmannin (50 mu mol/L), an inhibitor of phosphatidylinositol 3- and 4-kinases, but not by (i) phalloidin (30 mu mol/L), an actin filament stabilizer, (ii) the absence of Ca2+ from the internal and external solutions, and (iii) the presence of creatine phosphate (3 mmol/L), which affects creatine kinase regulation of the K-ATP channels. In the single-channel recordings, an inside-out patch was made after approximately 5 min exposure of the myocyte to hypo-osmotic solution. However, the IC50 value for ATP under such conditions was not different from that obtained in normal osmotic solution. In conclusion, hypo-osmotic stress could augment cardiac I-K,I-ATP through intracellular mechanisms involving the phosphatidylinositol kinase pathway

Characteristics of idiopathic ventricular tachycardia originating above the pulmonary valve

Panoptic studies of ventricular tachycardia (VT) originating above the pulmonary valve are scarce. The purpose of this study is to clarify the characteristic of idiopathic VT arising above pulmonary valve. We analyzed 15 consecutive patients with idiopathic VT that was successfully abolished by catheter ablation at the right ventricular outflow tract (RVOT-VT, n = 11) and above the pulmonary valve (PA-VT, n = 4). Incidence of syncope was higher in PA-VT than RVOT-VT (100 vs 27 %, P < 0.05) and polymorphic VT was also more prevalent in PA-VT (75 vs 0 %, P < 0.05). The coupling interval (315 ± 29 vs 449 ± 32 ms, mean ± SE) at the onset of VT and minimum cycle length (CL) (192 ± 13 vs 344 ± 37 ms) during VT were shorter in PA-VT (both P < 0.05). Among 12-lead ECG parameters, only R-wave amplitude in lead II was different between groups (2.05 ± 0.17 mV in PA-VT vs 1.44 ± 0.05 mV in RVOT-VT, P < 0.005). At the successful ablation site, the activation time from the onset of QRS complex did not differ between groups (-37 ± 3 vs -31 ± 4, P = 0.405), whereas, the amplitude of intracardiac electrograms was significantly lower in PA-VT (0.83 ± 0.38 mV vs 2.39 ± 0.36 mV, P < 0.05). Although the number of patients in this study is limited, VT originating above the pulmonary valve demonstrated rapid excitation and often degenerated into polymorphic VT, suggesting its malignant electrophysiological characteristics

Long-term reliability of the defibrillator lead inserted by the extrathoracic subclavian puncture

Background: As the transvenous defibrillator lead is fragile and its failure may cause a life-threatening event, reliable insertion techniques are required. While the extrathoracic puncture has been introduced to avoid subclavian crush syndrome, the reports on the long-term defibrillator lead survival using this approach, especially the comparison with the cephalic cutdown (CD), remain scarce. We aimed to evaluate the long-term survival of the transvenous defibrillator lead inserted by the extrathoracic subclavian puncture (ESCP) compared with CD. Methods: Between 1998 and 2011, 324 consecutive patients who underwent an implantable cardioverter-defibrillator (ICD) implantation in Hokkaido University Hospital were included. ICD leads were inserted by CD from 1998 to 2003 and by contrast venography-guided ESCP thereafter. Lead failure was defined as a nonphysiologic high-rate oversensing with abnormal lead impedance or highly elevated sensing and pacing threshold. Results: Of 324 patients, CD was used in 37 (11%) and ESCP in 287 patients (89%). During the median follow-up of 6.2 years (IQR:3.2-8.3), 7 leads (2 in CD and 5 leads in ESCP group) failed. All patients with lead failure in ESCP group were implanted with either SJM Riata (n = 1) or Medtronic Fidelis lead (n = 4). Five-year lead survival was 93.8% (CI95%:77.3-98.4%) in CD compared with 99.1% (CI95%:96.6-99.8%) in ESCP group (P = 0.903). Univariate Cox regression analysis showed that the use of Fidelis or Riata lead was the strong predictor of the ICD lead failure (HR 13.8, CI95%:2.9-96.5; P = 0.001). Conclusions: Contrast venography-guided extrathoracic puncture ensures the reliable long-term survival in the transvenous defibrillator leads

Predictors and Proarrhythmic Consequences of Inappropriate Implantable Cardioverter-Defibrillator Therapy

Background: Despite the benefits of implantable cardioverter-defibrillator (ICD) therapy, inappropriate shocks can lead to multiple adverse effects. The aim of this study was to clarify the predictors of inappropriate ICD shocks and their proarrhythmic consequences. Methods and Results: We retrospectively studied 316 consecutive patients who underwent ICD implantation from December 2000 to December 2011. Of them, 70 (22%) experienced inappropriate ICD shocks without proarrhythmia requiring some intervention; 2 patients (0.6%) had proarrhythmic inappropriate ICD therapy by antitachycardia pacing (ATP), thereby calculated to be 0.18% of patients per year. However, they did not have syncope from this inappropriate ATP. Multivariate analysis identified younger age (≤56 years: hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.02-2.77, P=0.043), paroxysmal atrial fibrillation (HR 3.00, 95% CI 1.64-5.31, P=0.0002), stroke (HR 2.23, 95% CI 1.11-4.47, P=0.024), and no diuretic use (HR 1.72, 95% CI 1.03-2.93, P=0.039) as independent predictors of the occurrence of inappropriate ICD shocks. Conclusions: Young age, paroxysmal atrial fibrillation, stroke, and no use of diuretics were independently associated with inappropriate ICD shocks. Proarrhythmic inappropriate ICD therapy was observed with an annual incidence of 0.18% by ATP

Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII

Sustained ventricular arrhythmias (SVAs) lead to sudden cardiac death, for which β- adrenoreceptor blockers are effective. We hypothesized that electrophysiological changes and arrhythmias by β- adrenoreceptor stimulation are crucially related to activation of small-conductance calcium-activated potassium (SK) channels via the increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs). The latter served as a model of left ventricular hypertrophy. We performed dual optical mapping of action potentials and Ca2+ transients, and the effects of isoproterenol and apamin, an SK channel blocker, were evaluated in the Langendorff-perfused hearts. Action potential duration was abbreviated by isoproterenol (100 nM) in both WKY rats and SHRs. In contrast, the CaMKII activity was increased by isoproterenol only in SHRs. In the presence of isoproterenol, apamin prolonged the action potential duration only in SHRs (n = 10, from 116.6 ± 5.05 ms to 125.4 ± 3.80 ms, P = 0.011), which was prevented by KN-93, a CaMKII inhibitor. Increase in Ca2+ transients and shortening of Ca2+ transient duration by isoproterenol were similarly observed in both animals, which was not affected by apamin. Apamin reduced the isoproterenol-induced SVAs and maximal slope of action potential duration restitution curve specifically in SHRs. In conclusion, β- adrenoreceptor stimulation creates arrhythmogenic substrates via the CaMKII-dependent activation of SK channels in cardiac hypertrophy