Sympathetic activation, ventricular repolarization and Ikrblockade: Implications for the antifibrillatory efficacy of potassium channel blocking agents

AbstractObjectives. The aim of the present study was to test, in vivo and in vitro, the influence of adrenergic activation on action potential prolongation induced by the potassium channel blocking agent d-sotalol.Background. d-Sotalol is not effective against myocardial ischemia-dependent ventricular fibrillation in the presence of elevated sympathetic activity. Most potassium channel blockers, such as d-sotalol, affect only one of the two components of Ik(Ikr) but not the other (Iks). Iksis activated by isoproterenol. An unopposed activation of Iksmight account for the loss of anti-fibrillatory effect by d-sotalol in conditions of high sympathetic activity.Methods. In nine anesthetized dogs we tested at constant heart rate (160 to 220 beats/min) the influences of left stellate ganglion stimulation on the monophasic action potential prolongation induced by d-sotalol. In two groups of isolated guinea pig ventricular myocytes we tested the effect of isoproterenol (10−9mol/liter) on the action potential duration at five pacing rates (from 0.5 to 2., Hz) in the absence (n = 6) and in the presence (n = 8) of d-sotalol.Results. In control conditions, both in vivo and in vitro, adrenergic stimulation did not significantly change action potential duration. d-Sotalol prolonged both monophasic action potential duration in dogs and action potential duration of guinea pig ventricular myocytes by 19% to 24%. Adrenergic activation, either left stellate ganglion stimulation in vivo or isoproterenol in vitro, reduced by 40% to 60% the prolongation of action potential duration produced by d-sotalol.Conclusions. Sympathetic activation counteracts the effects of potassium channel blockers on the duration of repolarization and may impair their primary antifibrillatory mechanism. An intriguing clinical implication is that potassium channel blockers may not offer effective protection from malignant ischemic arrhythmias that occur in a setting of elevated sympathetic activity

Prognostic significance of nonsustained ventricular tachycardia in patients receiving cardiac resynchronization therapy for primary prevention: Analysis of the Japan cardiac device treatment registry database

BackgroundWhether nonsustained ventricular tachycardia (NSVT) is a marker of increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be established in patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) for primary prevention.MethodsAmong the follow‐up data of the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2011 and August 2015, information regarding a history of NSVT before the CRT‐D implantation for primary prevention had been registered in 269 patients. Outcomes were compared between two groups with and without NSVT: NSVT group (n = 179) and No NSVT group (n = 90).ResultsThere was no significant difference with regard to age, gender, and NYHA class between the two groups. Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0% in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was 26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival free from heart failure death was reduced in the NSVT group, as compared with the No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A multivariate analysis identified a history of NSVT, anemia, and no use of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin‐receptor blocker (ARB) as predictors of heart failure death.ConclusionsNSVT appears to be a surrogate marker of severe heart failure rather than a substrate for subsequent sustained VTAs in patients with CRT‐D for primary prevention

Outcomes after stepwise ablation for persistent atrial fibrillation in patients with heart failure

AbstractBackgroundThere is limited data regarding the outcomes after stepwise ablation for persistent atrial fibrillation (AF) in patients with heart failure (HF).Methods and resultsPatients without structural heart disease undergoing stepwise ablation for persistent AF (continuous AF≤1 year) were studied (n=108; age, 61±10 years) and 32 patients had a history of HF. The HF patients were further grouped on the basis of left ventricular ejection fraction (LVEF)≤45% (n=15) and >45% (n=17). During a median follow-up period of 2.2 years, repeated ablations were necessary in 65 patients. The proportion of patients that were arrhythmia free 1 year after the last ablation was 67% in patients with LVEF≤45%, 86% in LVEF>45%, and 91% in no HF (p=0.0009). In patients with LVEF≤45%, the AF burden was reduced to less than one paroxysmal episode per month, and patients with and without recurrences both showed significant increases in LVEF over the follow-up period (38±7% to 60±10% and 37±6% to 53±10%, respectively).ConclusionsHF patients with LVEF≤45% had lower chances to remain free from arrhythmias after stepwise ablation for persistent AF than those with LVEF>45%. Nevertheless, LVEF also improved in patients with recurrences, reflecting the observed reduction in AF burden and emphasizing the benefits of ablation

Is head injury characteristic of arrhythmic syncope?

Background: Of the syncope types, arrhythmic syncope is the most life threatening and therefore requires proper treatment. However, the clinical predictors of arrhythmic syncope remain unknown. Some patients with syncope suffer from head injury, a serious side effect whose importance in the differential diagnosis of syncope has not been fully studied. Here, we attempted to identify the clinical characteristics of arrhythmic syncope, including the role played by head injuries. Methods: We studied inpatients referred to the cardiology section for the diagnosis and treatment of syncope. Clinical characteristics including age, sex, incidence of head injury during syncope, and cardiologic studies were evaluated in patients with arrhythmic and non-arrhythmic syncope. Results: Of 5590 inpatients, 273 (4.8%) (170 men; mean age, 61±17 years) suffered a syncopal episode before admission, 119 (43%) of whom were diagnosed with arrhythmic syncope and 30 (11%) of whom were undiagnosed. In multivariate analysis, age >65 years (65% vs. 42%, p<0.005), abnormal electrocardiogram (66% vs. 43%, p<0.01), and the presence of a head injury (31% vs. 16%, p<0.01) were more prevalent in patients with arrhythmic syncope than in patients with non-arrhythmic syncope. Conclusions: Patients with arrhythmic syncope were older, suffered collateral head injuries more frequently, and were more likely to have abnormal electrocardiograms than patients with non-arrhythmic syncope did

A case of an atrial tachycardia originating from an occluded coronary sinus ostium with a persistent left superior vena cava

We present a case of a 37-year-old female who complained of frequent palpitations caused by an atrial tachycardia and atrial premature contractions. Angiography revealed that the coronary sinus was occluded at the ostium and connected to a persistent left superior vena cava. An electrophysiological study and three-dimensional mapping revealed that the origin of the atrial tachycardia and atrial premature contractions was at the coronary sinus ostium in the right atrium. After repeat applications of radiofrequency energy at that site, no further atrial tachycardia or atrial premature contractions were induced by atrial burst pacing. To the best of our knowledge, this is the first report of an atrial tachycardia originating from an occluded coronary sinus ostium