Elimination of Benign Ventricular Premature Beats or Ventricular Tachycardia with Catheter Ablation versus Two Different Optimal Antiarrhythmic Drug Treatment Regimens (Sotalol or Verapamil/Flecainide).

BACKGROUND: Symptomatic idiopathic ventricular arrhythmias (VA), including premature beats (VPB) and nonsustained ventricular tachycardia (VT) are commonly encountered arrhythmias. Although these VA are usually benign, their treatment can be a challenge to primary and secondary health care providers. Mainstay treatment is comprised of antiarrhythmic drugs (AAD) and, in case of drug intolerance or failure, patients are referred for catheter ablation to tertiary health care centers. These patients require extensive medical attention and drug regimens usually have disappointing results. A direct comparison between the efficacy of the most potent AAD and primary catheter ablation in these patients is lacking. The ECTOPIA trial will evaluate the efficacy of 2 pharmacological strategies and 1 interventional approach to: suppress the VA burden, improve the quality of life (QoL), and safety. HYPOTHESIS: We hypothesize that flecainide/verapamil combination and catheter ablation are both superior to sotalol in suppressing VA in patients with symptomatic idiopathic VA. STUDY DESIGN: The Elimination of Ventricular Premature Beats with Catheter Ablation versus Optimal Antiarrhythmic Drug Treatment (ECTOPIA) trial is a randomized, multicenter, prospective clinical trial to compare the efficacy of catheter ablation versus optimal AAD treatment with sotalol or flecainide/verapamil. One hundred eighty patients with frequent symptomatic VA in the absence of structural heart disease or underlying cardiac ischemia who are eligible for catheter ablation with an identifiable monomorphic VA origin with a burden ≥5% on 24-h ambulatory rhythm monitoring will be included. Patients will be randomized in a 1:1:1 fashion. The primary endpoint is defined as >80% reduction of the VA burden on 24-h ambulatory Holter monitoring. After reaching the primary endpoint, patients randomized to one of the 2 AAD arms will undergo a cross-over to the other AAD treatment arm to explore differences in drug efficacy and QoL in individual patients. Due to the use of different AAD (with and without ß-blocking characteristics) we will be able to explore the influence of alterations in sympathetic tone on VA burden reduction in different subgroups. Finally, this study will assess the safety of treatment with 2 different AAD and ablation of VA.

[Efficacy of Shensong Yangxin Capsules in treating bradycardia combined with premature beat: a systematic review and Meta-analysis of randomized clinical trials].

To analyze the efficacy and safety of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Databases, such as CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, ClinicalTrials were retrieved by computers for relevant randomized controlled trials of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Two researchers independently screened out the literatures, extracted data according to the inclusion criteria, and applied the Risk of Bias assessment tool in assessing the methodological quality. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 9 randomized controlled trials including 706 subjects were included. The intervention measure was the single administration with Shensong Yangxin Capsules, and the control measure was the blank control. The results showed that Shensong Yangxin Capsules had an obvious effect on average heart rate(MD=6.59, 95%CI[3.87, 9.31], I~2=90%), premature beat efficacy(RR=1.72, 95%CI[1.53, 1.93], I~2=0%), heart rate efficacy(RR=1.74, 95%CI[1.40, 2.17], I~2=47%), and objective efficacy(RR=1.50, 95%CI[1.31, 1.70], I~2=31%). Eight studies reported safety events, with no significant adverse reaction. In conclusion, the single administration with Shensong Yangxin Capsules may have a certain effect in improving heart rate, controlling premature beats and alleviating clinical symptoms in patients with bradycardia combined with premature beat, with no obvious adverse reaction. Shensong Yangxin Capsules can be used in clinic. This potential conclusion needs to be confirmed in future trials using rigorous methodology.

Dantrolene suppresses ventricular ectopy and arrhythmogenicity with acute myocardial infarction in a langendorff-perfused pacing-induced heart failure rabbit model.

INTRODUCTION: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking. METHODS AND RESULTS: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 µM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed. CONCLUSION: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility.

Ventricular fibrillation in loop recorder memories in a patient with early repolarization syndrome.

We report the first documentation of spontaneous ventricular fibrillation by a loop recorder in a patient with an ECG pattern of early repolarization (ER) in the inferior leads and presenting with syncope.

Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram.

We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle.

Electrophysiological and pharmacological characteristics of triggered activity elicited in guinea-pig pulmonary vein myocardium.

The pulmonary vein is known as an important source of ectopic beats, initiating frequent paroxysms of atrial fibrillation. We analyzed electrophysiological and pharmacological characteristics of triggered activity elicited in the isolated pulmonary vein from the guinea pig. Immediately after the termination of train stimulation (pacing cycle length of 100 ms), spontaneous activities accompanied with phase-4 depolarization were detected in 43 out of 45 pulmonary vein preparations. Such triggered activities were not observed in the isolated left atrium. The incidence of triggered activity was higher at a shorter pacing cycle length (100 - 200 ms), and the coupling interval was shorter at a shorter pacing cycle length. Verapamil (1 µM), ryanodine (0.1 µM), and pilsicainide (10 µM) suppressed the occurrence of triggered activities. The resting membrane potential of the pulmonary vein myocardium was more positive than that of the left atrium. Carbachol (0.3 µM) hyperpolarized the resting membrane potential and completely inhibited the occurrence of triggered activities. These results suggest that the pulmonary veins have more arrhythmogenic features than the left atrium, possibly through lower resting membrane potential. The electrophysiological and pharmacological characteristics of triggered activity elicited in the pulmonary vein myocardium were similar to those previously reported using ventricular tissues.

[Current role of amiodarone in antiarrhythmic therapy]. / Aktueller Stellenwert von Amiodaron in der antiarrhythmischen Therapie.

Decades after its registration, amiodarone is still regarded as the most effective antiarrhythmic drug available for the treatment of tachyarrhythmias. Amiodarone is classified as a class III antiarrhythmic drug. In addition to the prolongation of cardiac repolarization, its leading pharmacologic features are sodium and calcium channel block, nonselective ß-adrenergic inhibition as well as high lipophilicity and a very long plasma half-life. In patients with paroxysmal atrial fibrillation, amiodarone is the most effective antiarrhythmic drug in maintaining sinus rhythm. Furthermore, it prevents ventricular arrhythmias, such as frequent ventricular extrasystoles or nonsustained runs of ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation. In patients with increased risk for sudden cardiac death, e.g., with severely depressed left ventricular function, amiodarone is a highly effective and safe antiarrhythmic drug. In addition, amiodarone has been shown to reduce the number of appropriate and inappropriate shocks in patients with an implantable cardioverter-defibrillator. During long-term amiodarone treatment, typical side effects including corneal microdeposits, blue-gray skin discoloration, photosensitivity, hypothyroidism, hyperthyroidism, peripheral neuropathy, optical neuritis and hepatotoxicity accrue. Upon cessation of medication, these are almost always reversible. Irreversible, severe adverse effects, such as pulmonary toxicity, are very rare under the currently used maintenance dose of 200 mg/day. With regard to its side effect profile, an adequate follow-up of patients including laboratory values, lung function tests, and visual acuity is necessary.

Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores.

We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 microM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5-yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.

RSD1235 blocks late INa and suppresses early afterdepolarizations and torsades de pointes induced by class III agents.

OBJECTIVE: RSD1235 is a novel antiarrhythmic drug with atria-selective electrophysiological actions on Na(+) and K(+) currents. The mechanism for its protection of ventricular repolarization was assessed by its action on Purkinje fibers, and by block of late sodium current active during repolarization. Further, RSD1235's ability to reverse the pro-arrhythmic actions of the class III agents dofetilide and clofilium was assessed in isolated Purkinje fibers and an in vivo model of torsades de pointes (TdP). METHODS: Action potential and early after-depolarization (EAD) recordings were made from in situ and isolated rabbit Purkinje fibers at 37 degrees C using floating sharp microelectrodes; late I(Na) was recorded using a whole-cell patch clamp technique of Nav1.5 expressed in HEK cells at 22 degrees C; In vivo, anesthetized methoxamine-sensitized rabbits were used to test the ability of RSD1235 to suppress clofilium-induced TdP. RESULTS: RSD1235 (0.5-30 microM) had minor dose-dependent effects on action potential duration (APD) at 50% and 90% repolarization in Purkinje fibers, but pre-treatment significantly attenuated the APD-prolonging effects of dofetilide (300 nM). EADs induced by 300 nM dofetilide were terminated by 30 microM RSD1235 in all experiments (n=7). RSD1235 blocked a late component of Na current (I(Na)), which can produce inward currents contributing to EAD formation. RSD1235 pre-treatment (1 micromol/kg/min) or acute infusions prevented/terminated TdP induced by clofilium in 8 of 9 rabbits, and reduced the duration of TdP episodes from 71 +/- 23 s in control to 17 +/- 7 and 14 +/- 14 s at infusion rates of 0.3 and 1.0 micromol/kg/min, respectively (n = 9, p < 0.001). CONCLUSION: RSD1235 itself has minor actions on repolarization in Purkinje fibers, but can reverse the AP-prolonging actions of class III agents and terminate arrhythmias in a model of TdP. We suggest that these protective actions of RSD1235 may result, at least in part, from its ability to inhibit late I(Na) during action potential repolarization.

Extrasystoles: side effect of kangaroo care?

OBJECTIVE: To present an unpublished reason for an arrhythmic electrocardiogram (ECG) recording during kangaroo care in a preterm infant. DESIGN: Case report. PATIENT: Preterm infant. MEASUREMENTS AND MAIN RESULTS: A preterm infant exhibited cardiac arrhythmia on the ECG monitor during kangaroo care, leading to interruption of kangarooing. Arrhythmia disappeared after placing the baby back into the incubator. The most likely reasons for arrhythmia were excluded. However, arrhythmia reappeared upon continuation of kangaroo care. ECG monitoring revealed the reason for the monitoring error. CONCLUSIONS: ECG monitoring during kangaroo care should cause error because of superimposed electric activity from the parent. Oxygen saturation represents a more reliable method of monitoring during kangaroo care.

TCM treatment of extrasystole with huanglian shengmai yin--a report of 357 cases.

The previous experimental studies have demonstrated that addition of Huang Qi ([symbol: see text] Radix Astragali) to the formulated recipe Sheng Mai Yin ([symbol: see text] Decoction for Pulse-activation) exerts the effects of strengthening the myodynamia, increasing the coronary flow, improving myocardial metabolism, and resisting the arrhythmia. The active component of Huang Lian ([symbol: see text] Rhizoma Coptidis) can prolong the myocardial action potential and antagonize the chloroform-, aconitine-, barium chloride-, epinephrine- or coronary ligation-induced arrhythmia by blocking the calcium channel. Ku Shen ([symbol: see text] Radix Sophorae Flavescentis) contains matrine and flavones, which act as quinidine to decrease the excitability of the myocardium, prolong the refractory period, and inhibit the ectopic cardiac rhythm. And Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) has the action of improving the ischemic state of the myocardium by dilating the coronary vessels. In conclusion, the definite therapeutic effects of Huang Lian Sheng Mai Yin in treating ventricular, atrial and nodal arrhythmia suggests that the prescription is rational and accords with the therapeutic principle of TCM. Except discomfort in the gastric cavity and poor appetite experienced by some patients, there is no toxic or adverse reaction.

Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine.

The ventricular tachyarrhythmias associated with the LQT3 syndrome are typically bradycardia-dependent. However, some episodes can be associated with exercise or emotional stress, suggesting a different arrhythmogenic mechanism when sympathetic activity predominates. This study examined the potential arrhythmogenic mechanisms during periods of autonomically mediated transient heart rate acceleration in a canine anthopleurin-A model of LQT3 syndrome. Using plunge needle electrodes, transmural unipolar electrograms of the left ventricle were recorded from endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) sites. The activation-recovery interval (ARI) was measured to estimate local refractoriness. The cardiac cycle length was gradually shortened by cessation of vagal stimulation (vagal stimulation protocol (VSP)), and intramural electrograms and onset mode of ventricular tachyarrhythmias were analyzed in 7 experiments. The VSP was performed 8 times before and 5 times after administration of mexiletine in each experiment. Before mexiletine, vagal stimulation slowed the heart rate and created large transmural ARI dispersion because of a greater ARI prolongation at Mid rather than Epi/Endo sites. After cessation of vagal stimulation, unipolar electrograms started to show ARI alternans and ventricular premature beats developed sporadically. Sustained ventricular tachyarrhythmias were induced in 12 of the 56 trials of the VSP. Initiation of ventricular tachyarrhythmias was associated with delayed conduction at Mid/Endo sites. Mexiletine attenuated transmural ARI dispersion, and neither ARI alternans nor ventricular tachyarrhythmias was observed during all 35 trials of the VSP after mexiletine administration. Heart rate acceleration induced by an abrupt shift to a state of predominant sympathetic activity enhances arrhythmias in this LQT3 model. Mexiletine homogenizes ventricular repolarization, suppresses premature complexes and was antiarrhythmic during ventricular tachyarrhythmias induced by the VSP.

[Use of plasmapheresis in the treatment of drug-resistant cardiac arrhythmias]. / Ispol'zovanie plazmafereza pri lechenii narushenii ritma serdtsa, rezistentnykh k lekarstvennoi terapii.

AIM: To study the therapeutical efficiency of plasmapheresis (PA) in patients with drug-resistant cardiac arrhythmias (CA) and its mechanisms. MATERIALS AND METHODS: Discrete PA sessions were carried out in 56 patients with drug-resistant CA: paroxysmal atrial arrhythmia (AA), ventricular and supraventricular premature contractions, supraventricular tachycardia of various etiology. Biochemical blood values, coagulographic parameters, lipid peroxidation (LPO), the spectrum of nonesterified fatty acids (NEFA), the level of medium-sized molecules were determined, ECG monitoring, EchoCG, and left ventricular radioisotope computed tomography were performed before and after a PA session. RESULTS: PA was effective in 50% of cases. The duration of its effect averaged 3.0 (1.25-5.0) months. PA was more beneficial for patients with IHD, AA with normal left atrial dimensions, and hyperlipidemia. The duration of the effect was significantly higher when antiarrhythmic drug therapy was continued after PA. Due to PA, there were significant decreases in the blood concentrations of cholesterol, medium-sized molecules, malonic dialdehyde (MDA) and in the proportion of polyunsaturated NEFA. The antiarrhythmic effect was associated with the decreases in MDA and NEFA, with a tendency for a reduction in the rate of chemiluminescence. CONCLUSION: PA may be used in the treatment of drug-resistant CA. The most significant mechanism of its antiarrhythmic activity is to recover sensitivity to antiarrhythmics. The intrinsic antiarrhythmic activity may be associated with its effect on NEFA metabolism and LPO; however, its mechanisms await further studies.

[Clinical and experimental study of effect of yangxin fumai oral liquid in treating patients with extrasystole].

OBJECTIVE: To evaluate the therapeutic effect of Yangxin Fumai Oral Liquid (YFOL), a Chinese herbal medicine for nourishing heart and restoring pulse, in treating patients with extrasystole. METHODS: The effect of YFOL was observed in treating 30 patients with different kinds of extrasystole and compared with that in 30 patients treated by propafenone. The effect of YFOL on experimental arrhythmia was studied in animals as well. RESULTS: Clinical observation showed that the effect of YFOL against extrasystole in the two groups was similar, but the YFOL group showed better effect in symptom improvement (P < 0.01) with no marked side-effects. Experimental study showed that YFOL could reduce the chloroform induced ventricular fibrillation occurrence in mice, delay the initiating time of ventricular extrasystole, tachycardia and fibrillation induced by aconitine, BaCl2 and coronary artery ligation in rats, or shorten the lasting time of arrhythmia, reduce the attacking rate of ventricular extrasystole. There was significant difference in comparing with the control group (P < 0.05, P < 0.01). CONCLUSION: YFOL is a good and convenient Chinese herbal preparation for different kinds of extrasystole with low toxic and side-effects in clinical practice.

Effect of phenylephrine on focal atrial fibrillation originating in the pulmonary veins and superior vena cava.

OBJECTIVES: This study was aimed at evaluating the effects of phenylephrine infusion on the occurrence of focal atrial fibrillation (AF). BACKGROUND: Paroxysmal AF can be initiated by ectopic atrial beats originating in the pulmonary vein (PV) or superior vena cava (SVC). The effect of change in autonomic tone on this focal AF is unknown. METHODS: This study included 12 patients with frequent bursts of AF documented by 24-h Holter monitoring. The number and coupling interval of spontaneous ectopic activity and bursts of AF were evaluated for 1 min before and after phenylephrine (2 to 3 microg/kg) injection. RESULTS: After detailed mapping, four patients had a focus located in the left superior PV, six in the right superior PV and two in the SVC. In 10 patients with AF foci originating in the PVs, the frequency of ectopic activity (19.5 +/- 27.4 vs. 11.4 +/- 22.9 beats/min, p = 0.059) was reduced as well as AF bursts (14 +/- 3 vs. 1.8 +/- 2.7 bursts/min, p = 0.005) before versus after phenylephrine injection; the minimal coupling interval of ectopic activity and AF bursts became longer compared with baseline. The maximal percent increase in sinus cycle length after phenylephrine injection was significantly greater in patients with complete suppression of AF compared with those with partial suppression (43 +/- 19 vs. 14 +/- 5%, p = 0.01). However, no significant effect of phenylephrine on AF originating in the SVC was found. CONCLUSIONS: Change in autonomic tone induced by phenylephrine injection was effective in suppressing focal AF originating in the PVs but not in the SVC.