Seasonal variations of ventricular arrhythmia clusters in defibrillator recipients

BACKGROUND: Clustering ventricular arrhythmias are the consequence of acute ventricular electrical instability and represent a challenge in the management of the growing number of patients with an implantable cardioverter-defibrillator (ICD). Triggering factors can rarely be identified. OBJECTIVES: Several studies have revealed seasonal variations in the frequency of cardiovascular events and life-threatening arrhythmias, and we sought to establish whether seasonal factors may exacerbate ventricular electrical instability leading to arrhythmia clusters and electrical storm. METHODS: Two hundred and fourteen consecutive defibrillator recipients were followed-up during 3.3 +/- 2.2 years. Arrhythmia cluster was defined as the occurrence of three or more arrhythmic events triggering appropriate defibrillator therapies within 2 weeks. Time intervals between two clusters were calculated for each month and each season, and were compared using Kruskal-Wallis test and Wilcoxon-Mann-Whitney test with Bonferroni adjustment. RESULTS: During a follow-up of 698 patient years, 98 arrhythmia clusters were observed in 51 patients; clustering ventricular arrhythmias were associated with temporal variables; they occurred more frequently in the winter and spring months than during the summer and fall. Accordingly, the time intervals between two clusters were significantly shorter during winter and spring (median and 95% CI): winter 16 (5-19), spring 11.5 (7-25), summer 34.5 (15-55), fall 50.5 (19-65), P = 0.0041. CONCLUSION: There are important seasonal variations in the incidence of arrhythmia clusters in ICD recipients. Whether these variations are related to environmental factors, change in physical activity, or psychological factors requires further study.

Prediction of arrhythmic events after myocardial infarction based on signal-averaged electrocardiogram and ejection fraction

Trials on implantable cardioverter-defibrillators (ICD) for patients after acute myocardial infarction (AMI) have highlighted the need for risk assessment of arrhythmic events (AE). The aim of this study was to evaluate risk predictors based on a novel approach of interpreting signal-averaged electrocardiogram (SAECG) and ejection fraction (EF).

Gender differences in patients referred for atrial fibrillation management to a tertiary center

BACKGROUND: Atrial fibrillation (AF) ablation is less frequently performed in women than in men. Although the prevalence of AF is slightly higher in men, this does not fully account for the lower number of AF ablations performed in women. This study sought to examine the effect of gender on referral for AF and subsequent AF management. METHODS: Consecutive patients referred to our tertiary arrhythmia outpatient clinic for AF management were retrospectively analyzed. RESULTS: Of 264 patients referred, only 27% were women. Women were older than men (63 +/- 9 vs 58 +/- 11 years, P = 0.002), more often had paroxysmal AF (78% vs 63% in men, P = 0.022), and women more frequently complained about palpitations (71% vs 49%, P = 0.002). In addition, they had more often experienced amiodarone side effects than men (56% vs 36%, P = 0.046). In this referred population, there was no difference in the proportion of women and men undergoing AF ablation immediately following the initial evaluation (21% vs 25%, P = ns), at any time during the follow-up (38% vs 44%, P = ns), and there was no difference in the proportion of patients undergoing atrioventricular node ablation in both sexes (6% of women vs 3% of men, P = ns). CONCLUSIONS: There is an important difference in the proportion of men and women referred for management of AF in a specialized outpatient arrhythmia clinic, with women being referred three times less often than men. However, there is no gender-related difference in the subsequent treatment decisions. These findings emphasize the importance of focusing on management of symptomatic AF in women.

Long-term outcome of ablative therapy of postoperative supraventricular tachycardias in patients with univentricular heart: a European multicenter study

BACKGROUND: Catheter ablation has evolved as a possible curative treatment modality for supraventricular tachycardias (SVT) in patients with univentricular heart. However, the long-term outcome of ablation procedures is unknown. We evaluated the procedural and long-term outcome of ablative therapy of late postoperative SVT in patients with univentricular heart. METHODS AND RESULTS: Patients with univentricular heart (n=19, 11 male; age, 29+/-9 years) referred for ablation of SVT were studied. Ablation was guided by 3D electroanatomic mapping in all but 2 procedures. A total of 41 SVT were diagnosed as intra-atrial reentrant tachycardia (n=30; cycle length, 310+/-68 ms), typical atrial flutter (n=4; cycle length, 288+/-42 ms), focal atrial tachycardia (n=6; cycle length, 400+/-60 ms), and atrial fibrillation (n=1). Ablation was successful in 73% of intra-atrial reentrant tachycardia, 75% of atrial flutter, and all focal atrial tachycardia and focal atrial fibrillation. During the follow-up period of 53+/-34 months, 2 patients were lost to follow-up, 3 died of heart failure, 2 underwent heart transplantation, and 1 underwent conduit replacement. Of the remaining group, 8 had sinus rhythm and 3 had SVT. CONCLUSIONS: Focal and reentrant mechanisms underlie postoperative SVT in patients with univentricular heart. Successive SVT developing over time may be caused by different mechanisms. Ablative therapy is potentially curative, with a procedural success rate of 78%. In patients who had multiple ablation procedures, the SVT originated from different atrial sites, suggesting that these new SVT were caused by progressive atrial disease. Despite recurrent SVT, sinus rhythm at the end of the follow-up period was achieved in 72%.

Termination of Ventricular Tachycardia with Antitachycardia Pacing after Ineffective Shock Therapy in an ICD Recipient with Hypertrophic Cardiomyopathy

Implantable Cardioverter Defibrillator (ICD) implantation is the only established therapy for primary or secondary prevention of sudden cardiac death in patients with Hypertrophic Cardiomyopathy (HCM). Ineffectiveness of shock therapy for the termination of potentially fatal ventricular arrhythmias in ICD recipients is rare in the presence of appropriate arrhythmia detection by the device. We report the case of a 48-year-old woman with HCM and a single chamber ICD, who received five inefficient high-energy (35 Joules) shocks for the termination of an appropriately detected episode of Ventricular Tachycardia (VT). The episode was safely terminated with a subsequent application of Antitachycardia Pacing (ATP) by the device. At the following ICD control, an acceptable defibrillation threshold was detected.

Ventricular tachycardia arising from the aortomitral continuity in structural heart disease: characteristics and therapeutic considerations for an anatomically challenging area of origin

BACKGROUND: The aortomitral continuity (AMC) has been described as a site of origin for ventricular tachycardias (VT) in structurally normal hearts. There is a paucity of data on the contribution of this region to VTs in patients with structural heart disease. METHODS AND RESULTS: Data from 550 consecutive patients undergoing catheter ablation for VT associated with structural heart disease were reviewed. Twenty-one (3.8%) had a VT involving the peri-AMC region (age, 62.7+/-11 years; median left ventricular ejection fraction, 43.6+/-17%). Structural heart disease was ischemic in 7 (33%), dilated cardiomyopathy in 10 (47.6%), and valvular cardiomyopathy in 4 (19%) patients, respectively. After 1.9+/-0.8 catheter ablation procedures (including 3 transcoronary ethanol ablations) the peri-AMC VT was not inducible in 19 patients. The remaining 2 patients underwent cryosurgical ablation. Our first catheter ablation procedure was less often successful (66.7%) for peri-AMC VTs compared with that for 246 VTs originating from the LV free wall (81.4%, P=0.03). During a mean follow-up of 1.9+/-2.1 years, 12 (57.1%) patients remained free of VT, peri-AMC VT recurred in 7 patients, and 1 patient had recurrent VT from a remote location. Three patients died. Analysis of 50 normal coronary angiograms demonstrated an early septal branch supplying the peri-AMC area in 58% of cases that is a potential target for ethanol ablation. CONCLUSIONS: VTs involving the peri-AMC region occur in patients with structural heart disease and appear to be more difficult to ablate compared with VTs originating from the free LV wall. This region provides unique challenges for radiofrequency ablation, but cryosurgery and transcoronary alcohol ablation appear feasible in some cases.

Erythropoietin enhances oxygenation in critically perfused tissue through modulation of nitric oxide synthase

The aim of this study was to investigate the effect of human recombinant erythropoietin (EPO) on the microcirculation and oxygenation of critically ischemic tissue and to elucidate the role of endothelial NO synthase in EPO-mediated tissue protection. Island flaps were dissected from the back skin of anesthetized male Syrian golden hamsters including a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. Before ischemia, animals received an injection of epoetin beta at a dose of 5,000 U/kg body weight with (n = 7) or without (n = 7) blocking NO synthase by 30 mg/kg body weight L-NAME (Nomega-nitro-L-arginine methyl ester hydrochloride). Saline-treated animals served as control (n = 7). Ischemic tissue damage was characterized by severe hypoperfusion and inflammation, hypoxia, and accumulation of apoptotic cell nuclei after 5 h of collateralization. Erythropoietin pretreatment increased arteriolar and venular blood flow by 33% and 37%, respectively (P < 0.05), and attenuated leukocytic inflammation by approximately 75% (P < 0.05). Furthermore, partial tissue oxygen tension in the ischemic tissue increased from 8.2 to 15.8 mmHg (P < 0.05), which was paralleled by a 21% increased density of patent capillaries (P < 0.05) and a 50% reduced apoptotic cell count (P < 0.05). The improved microcirculation and oxygenation were associated with a 2.2-fold (P < 0.05) increase of endothelial NO synthase protein expression. Of interest, L-NAME completely abolished all the beneficial effects of EPO pretreatment. Our study demonstrates that, in critically ischemic and hypoxic collateralized tissue, EPO pretreatment improves tissue perfusion and oxygenation in vivo. This effect may be attributed to NO-dependent vasodilative effects and anti-inflammatory actions on the altered vascular endothelium.

Reducing Myofibroblast Arrhythmogeneicity by Pharmacological Targeting of Their Cytoskeleton

Introduction: Slow conduction and ectopic activity are key elements of cardiac arrhythmogenesis. Both anomalies can be caused by myofibroblasts (MFBs) following establishment of heterocellular gap junctional coupling with cardiomyocytes. Because MFBs are characterized by the expression of {alpha}-smooth muscle actin ({alpha}-SMA) containing stress fibers, we investigated whether pharmacological interference with stress fiber formation might affect myofibroblast arrhythmogenicity. Methods: Experiments were done with patterned growth strands of neonatal rat ventricular cardiomyocytes coated with cardiac MFBs. Impulse propagation characteristics were measured optically using voltage sensitive dyes. Electrophysiological characteristics of single MFBs were assessed using patch clamp techniques. Actin polymerization was inhibited by latrunculin B (LtB). Data are given as mean±S.D. (n=5 to 22). Results: As assessed by immunocytochemistry, exposure of MFBs to LtB (0.3–10 µmol/L) profoundly disrupted stress fiber formation. This led, within minutes, to a dramatic change in cell morphology with MFBs assuming an astrocyte-like shape. In pure cardiomyocyte preparations, LtB had negligible effects on impulse conduction velocity ({theta}) and maximal action potential upstroke velocities (dV/dtmax). In contrast, LtB applied to MFB coated cardiomyocyte strands substantially increased {theta} from 247±32 to 371±26 mm/s and dV/dtmax from 40±7 to 81±1 %APA/ms, i.e., to values similar to those of pure cardiomyocyte strands (342±13 mm/s; 82±1 %APA/ms). Moreover, LtB at 1 µmol/L completely abolished MFB induced ectopic activity. LtB induced normalization of electrophysiologic parameters can be explained by the finding that LtB hyperpolarized MFBs from –25 mV to –50 mV, thus limiting their depolarizing effect on cardiomyocytes which was shown before to cause slow conduction and ectopic activity. Conclusions: Pharmacological interference with the cytoskeleton of cardiac MFBs alters their electrophysiological phenotype to such an extent that detrimental effects on cardiomyocyte electrophysiology are completely abolished. This observation might form a basis for the development of therapeutic strategies aimed at limiting the arrhythmogenic potential of MFBs.