Benefits of early rhythm control of atrial fibrillation.

In contrast to current guidelines and earlier trials, recent studies demonstrated superiority of rhythm- over rate-control and challenged the strategy of "rate versus rhythm" therapy in patients with atrial fibrillation. These newer studies have started to shift the use of rhythm-control therapy from the symptom-driven therapy of current guidelines to a risk-reducing strategy aimed at restoring and maintaining sinus rhythm. This review discusses recent data and presents an overview on the current discourse: The concept of early rhythm control seems attractive. Patients with rhythm control may undergo less atrial remodeling compared to those with rate control. In addition, in EAST-AFNET 4 an outcome-reducing effect of rhythm control was achieved by delivering therapy with relatively few complications early after the initial AF diagnosis. Successful rhythm control therapy and most likely reduced AF burden, estimated by the presence of sinus rhythm at 12 months after randomization, explained most of the reduction in cardiovascular outcomes achieved by rhythm control. However, it is too early to call for early rhythm control for all AF patients. Rhythm control may raise concerns regarding the generalizability of trial results in routine practice involving important questions on the definition of "early" and "successful", and the relevant issue of antiarrhythmic drugs versus catheter ablation. Further information is required to select patients who will benefit from an early ablative or non-ablative rhythm management.

Pre-procedural proton pump inhibition is associated with fewer peri-oesophageal lesions after cryoballoon pulmonary vein isolation.

Pulmonary vein isolation (PVI) using cryoenergy is safe and efficient for treatment of atrial fibrillation (AF). Pre-existing upper gastrointestinal (GI) pathologies have been shown to increase the risk for AF. Therefore, this study aimed at assessing incidental pathologies of the upper GI tract in patients scheduled for PVI and to analyse the impact of patients' characteristics on PVI safety outcome. In 71 AF patients, who participated in the MADE-PVI trial, oesophagogastroduodenoscopy and endosonography were prospectively performed directly before and the day after PVI to assess pre-existing upper GI pathologies and post-interventional occurrence of PVI-associated lesions. Subgroup analysis of the MADE-PVI trial identified clinically relevant incidental findings in 53 patients (74.6%) with age > 50 years being a significant risk factor. Pre-existing reflux oesophagitis increased risk for PVI-associated mediastinal oedema, while patients already treated with proton pump inhibitors (PPI) had significantly fewer mediastinal oedema. Our results suggest that AF patients with pre-existing reflux oesophagitis are at higher risk for PVI-associated mediastinal lesions, which is decreased in patients with constant PPI-treatment prior to PVI. Since PVI-associated mediastinal lesions are regarded as surrogate parameter for an increased risk of the fatal complication of an oesophago-atrial fistula, our findings hint at a beneficial effect of pre-interventional prophylactic PPI-treatment to reduce risk for PVI-associated complications.German Clinical Trials Register (DRKS00016006; date of registration: 17/12/2018).

Remaining challenges in catheter ablation of accessory pathways: rare entity of coronary sinus diverticulum-associated pathways.

INTRODUCTION: A limited number of case reports of coronary sinus (CS) diverticula complicating catheter ablation have been published. METHODS AND RESULTS: We retrospectively analysed 2245 patients who underwent ablation of an accessory pathway (AP) at our institution between 1/11/1993 and 31/10/2016. Eight patients (0.36%) were found to have a CS diverticulum in venography. APs showed a mean antegrade conduction time of 276 ± 23 ms (range 220-310 ms) and a mean retrograde conduction of 301 ± 45 ms (230-350 ms). Four patients had 1 (n = 2), 2 (n = 1), or 3 (n = 1) previously failed ablation attempts. Pathways could not be ablated with a conventional 4 mm tip catheter in 7 of 8 cases. In seven patients, ablation was successful, in two using an 8-mm ablation catheter, in two using cryoablation, and in the remaining three with an irrigated tip ablation catheter. After failed femoral approach, one 9-year-old female was successfully ablated via the right jugular vein. In one 75-year-old female, ablation was not successful. During a mean follow-up of 8.9 ± 6.4 years, all patients remained free of recurrences. CONCLUSION: In inferoseptal pathways, especially with previous failed ablation attempts, venographies of the CS should be performed. After successful ablation long-term prognosis is excellent.

Device updates successfully reduce T­wave oversensing and inappropriate shocks in subcutaneous ICD patients.

AIMS: To analyse the impact of device and software updates on the prevention of T­wave oversensing (TWOS) and inappropriate shocks (IS) in subcutaneous ICD (S-ICD) patients. BACKGROUND: TWOS is a feared complication after implantation. It may lead to harmful IS. To date, specific strategies to reduce these events are lacking. METHODS: In this retrospective single-centre trial we analysed 146 S­ICD patients who were implanted between 2010 and 2016. In all eligible consecutive patients (n = 139), follow-up of at least 6 weeks was studied. The incidence of TWOS/IS was analysed in patients receiving a 2nd generation S­ICD (Emblem-S-ICD) between 2014 and 2016 (Emblem). Their outcome was compared with a control group (SQ) treated with the SQ1010 device between 2010 and 2014, who were followed up for a maximum of 2 years. Furthermore, to test if the software update SMR8 reduces inappropriate shocks in the SQ1010-S-ICD population, the incidence of TWOS/IS was evaluated before and after update installation. RESULTS: Basic characteristics and indications for S­ICD implantation were similar in both groups. However, the cumulative incidence of TWOS/IS was significantly decreased in Emblem vs. SQ (SQ: 15.4%, n = 14/91 vs. Emblem 4.2%, n = 2/48; p = 0.049). Furthermore, with regards to the SQ population we also observed a trend towards a significant reduction of TWOS/IS after installation of the software update SMR8 in 2014 (before update: 13.4%, n = 11/82 vs. after update: 4.6%, 3/65, p = 0.07). CONCLUSION: 2nd generation devices but probably also the SMR8 software update reduce the incidence of TWOS/IS in S­ICD patients.

Application of the Bogossian formula for evaluation of the QT interval in pacemaker patients with stimulated left bundle branch block.

BACKGROUND: The presence of left bundle branch block (LBBB) represents a particular challenge in properly measuring the QT interval. Here we demonstrate the applicability of the "Bogossian formula" in pacemaker patients with LBBB due to apical or nonapical right ventricular (RV) pacing and preserved left ventricular function. METHODS: A total of 163 patients with a cardiac one- or two-chamber pacemaker were included in this prospective, multicentre observational study. Twelve-lead ECG recordings were obtained during both intrinsic rhythm and RV pacing with induced LBBB. The QT interval measured during LBBB was corrected using the Bogossian formula to obtain the "modified QT" (QTm). The QTmc interval was calculated with the Bazett formula, and this was compared with the QTc interval during intrinsic rhythm. RESULTS: Eighty-three patients (78 ± 9 years; male n = 83) with apical and eighty patients (71 ± 13 years; male n = 80) with non-apical RV pacing were included in this study. In the apical group the QTmc was determined to be 444 ± 39 ms in paced rhythm and the QTc interval 413 ± 36 ms in intrinsic rhythm. In the non-apical group these values were 430 ± 34 ms in paced and 416 ± 32 ms in intrinsic rhythm. CONCLUSION: The Bogossian formula is a reliable tool for QTc interval evaluation in pacemaker patients with LBBB due to apical or non-apical RV pacing. However, an overestimation of 30 ms should be included in the calculation.

Comparing learning curves of two established "single-shot" devices for ablation of atrial fibrillation.

PURPOSE: We compared the contour of learning curves of two "single-shot" devices used for pulmonary vein isolation (PVI) for safety and procedural data. METHODS: We performed a retrospective analysis comparing the first 60 PVI performed at our center using a pulmonary vein ablation catheter (PVAC) array (39 male, mean age 57 years, 42 paroxysmal AF) to the first 60 first PVI using the Cryoballoon (44 male, mean age 59 years, 22 paroxysmal AF). Both groups were further divided into tertiles, where T1 regroups the first 20 ablations, T2 the following 20, and T3 the last 20 ablations. RESULTS: The mean total procedure time was reduced by 24 min between T1 and T3 for the PVAC and 15 min for the Cryoballoon (p = 0.01). Fluoroscopy increased by 5 min, total ablation time was reduced by 7 min for PVAC (p = 0.02), and both times decreased respectively by 7 and 1 min for the Cryoballoon (p = ns). In the PVAC group, a mean rate of 0.16 (T1: n = 5; T2: n = 2; T3: n = 3) complications was observed while a rate of 0.16 (T1: n = 2; T2: n = 3; T3: n = 4) occurred in the CRYO group (p = ns). Severe complications defined as stroke, pericardial tamponade with need of pericardiocentesis and phrenic nerve palsy occurred in n = 4 in both groups (6.6%). CONCLUSIONS: With either of the systems, no significant differences in the effect of the learning curve on the occurrence of adverse events were observed. However, the PVAC array seemed to have a steeper learning curve for procedure, as well as fluoroscopy time.

Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice.

AIMS: In atrial fibrillation, increased function of the Na+/Ca2+-exchanger (NCX) is one among several electrical remodeling mechanisms. METHODS/RESULTS: Using the patch-clamp- and Ca2+ imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2+ extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18±0.05; WTOE:0.02±0.02; p<0.001). Using the same protocol, a DAD triggered an sAP by tendency less often in KO vs. WTKO (p=0.06) and significantly less often under a more aggressive proarrhythmic protocol (ratio sAP/DAD: KO:0.01±0.003; WT KO: 0.12±0.05; p=0.007). The DAD amplitude was increased in OE vs. WTOE and decreased in KO vs. WTKO. There were no differences in SR-Ca2+-load, the number of spontaneous Ca2+-release-events or IKACh/IK1. CONCLUSIONS: Atrial myocytes with increased NCX expression exhibited increased vulnerability towards sAPs while atriomyocytes with reduced NCX expression were protected. The underlying mechanism consists of a modification of the DAD-amplitude by the level of NCX-activity. Thus, although the number of spontaneous Ca2+-releases and therefore DADs is unaltered, the higher DAD-amplitude in OE made a transgression of the voltage-threshold of an sAP more likely. These findings indicate that the level of NCX activity could influence triggered activity in atrial myocytes independent of possible remodeling processes.

[Catheter ablation of electrical storm: ready for prime time?]. / Katheterablation bei elektrischem Sturm: Was sagen die Studien?

Electrical storm is an increasingly recognized clinical entity. It is generally defined as the occurrence of ≥ 3 episodes of potentially life-threatening ventricular arrhythmias during a time span of 24 h. Apart from pharmacological treatment options, catheter ablation remains a relatively novel, promising addition to the armamentarium of the cardiologist. Here, we will review the study data on ablation of patients with electrical storm.

Late sodium current inhibition: the most promising antiarrhythmic principle in the near future?

Ranolazine has primarily been developed and so far approved as an antianginal drug. However, it also has potentially interesting and relevant antiarrhythmic properties. Its antiarrhythmic effects are mainly based on the blockade of sodium currents, in particular of the late sodium current. Experimental and clinical studies have revealed an antiarrhythmic effect of ranolazine in atrial fibrillation as chronic or "pill in the pocket" therapy. Of note, this effect was preserved in the setting of chronic heart failure. Furthermore, an antiarrhythmic effect has also been shown in experimental models of ventricular tachyarrhythmias. In addition, prevention of ventricular tachyarrhythmias has been demonstrated in patients with structural heart disease. A few late sodium current inhibitors are evaluated for antiarrhythmic properties in experimental studies. However, randomized clinical data is not yet available for these recently developed agents and larger controlled trials are necessary before recommending ranozaline as a novel antiarrhythmic drug.

Panic attacks and supraventricular tachycardias: the chicken or the egg?

Panic attacks occur in about 2 % of the population. Symptoms include a racing or pounding heart beat, chest pain, dizziness, light-headedness, nausea, difficulty in breathing, tingling or numbness in the hands, flushes or chills, dreamlike sensations or perceptual distortions. The symptoms of paroxysmal supraventricular tachycardia (PSVT) may be similar. A PSVT is often difficult to document on the ECG since it has often ceased before the patient comes to medical attention. Besides, a tachycardia may still be present and even be documented but interpreted as a phenomenon secondary to the panic attack. In addition, ECG abnormalities between episodes can often not be identified. The evidence that in some patients paroxysmal SVT is the cause, but not the consequence of a panic attack, is based on observations that catheter ablation was able to cure patients presenting with panic disorders. To better establish the prevalence of SVT as the underlying mechanism of a panic attack, there is a need for prospective studies and/or registries. Whereas gastric ulcer has in some patients changed from a psychosomatic disorder to an infectious disease, we may hypothesise that a certain proportion of panic disorders may mutate into an underlying arrhythmia rather than a primary psychiatric disorder.

[Catecholaminergic polymorphic ventricular tachycardia]. / Katecholaminerge polymorphe ventrikuläre Tachykardien.

Catecholaminergic polymorphic ventricular tachycardia (PCVT) is a rare, congenital ventricular tachyarrhythmia which occurs in the setting of adrenergic activation. It potentially leads to syncope and/or sudden cardiac death (SCD). PCVT represents one of the most dangerous congenital ion channel diseases. Mutations of the ryanodine receptor gene (RYR2), the calsequestrin gene (CASQ2), and the triadin gene (TRDN) have been identified as an underlying correlate. ß-Blockers are employed as therapy and are sometimes combined with class IC antiarrhythmic drugs, or calcium antagonists of the verapamil type. ICD implantation is recommended in case of persisting syncope in the presence of ß-blocker therapy or survived SCD. Left thoracic sympathectomy represents a subsidiary interventional therapy for individual cases. In addition, modifications of the patient's lifestyle including avoidance of physical stress and heart rates> 120/min are recommended.

[Atrial fibrillation : new anticoagulants and antiarrhythmic drugs]. / Vorhofflimmern : Neue Antiarrhythmika und Antikoagulanzien.

Atrial fibrillation is the most common form of arrhythmia and one of the most frequent causes of ischemic stroke. Several new anticoagulants have recently been introduced as alternatives to vitamin-K antagonists for prophylaxis of ischemic stroke and tested in phase-3 studies for efficacy and safety. Identifying patients who will profit in particular from the new anticoagulant therapy is crucial to the clinical application of these drugs. Vernakalant and dronedarone are new antiarrhythmic drugs for rhythm control of atrial fibrillation. However, therapeutic efficacy of the new agents still has to be proven.

Blockade of I(Ca) suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure.

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) 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 I(Kr) 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 I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) 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 http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x.

APFIM investigations on site occupancies of the ternary alloying elements Cr, Fe, and Re in NiAl.

The site occupancies of the transition metals Cr, Fe, and Re dissolved in NiAl of stoichiometric composition have been determined by atomic layer resolved atom probe field-ion microscopy (APFIM). The investigations were supported by X-ray diffraction studies to evaluate the lattice parameters. These are influenced by atomic size effects and constitutional lattice defects like Ni antistructure atoms in the Al sublattice and vacancies in the Ni sublattice. The APFIM results were compared with ALCHEMI data and calculated site preference energies published in the literature. Chromium additions to stoichiometric NiAl with 0.8 at% in solid solution exhibit a strong preference for Al sites. The lattice parameter of NiAl(Cr) solid solution is decreased. Iron atoms dissolved in higher concentrations of 5 at % in NiAl are almost equally distributed within both sublattices. They are possessing a weak preference for Al sites, which causes a lattice expansion of NiAl(Fe) solid solution. ALCHEMI results and site preference energy data show a strong site preference of Cr atoms for the Al sublattice. In contrast, iron atoms exhibit a weak site preference for Ni sites depending upon the stoichiometry of the NiAl host lattice. Re solutes in low concentrations of about 0.2 at % in NiAl possess a strong site preference for the Ni sublattice. The increase of the lattice parameter of NiAl(Re) is due to the pronounced size effect of Re atoms. For these species no ALCHEMI and site preference energy data are available in the literature.

Compression behaviour of elastically anisotropic polycrystals using energy-dispersive X-ray diffraction.

The compression behaviour of a foil of Cu3Au in a pressure medium of NaCl has been studied by energy-dispersive X-ray diffraction in a diamond-anvil cell. Evidence from stress analysis and peak broadening of the foil (the most extreme example of a non-ideal powder) throws light on the compression of powders under non-hydrostatic conditions. A complete pressure cycle, including re-pressurization after pressure release, shows that significant plastic deformation takes place which results in large deviations from a (hydrostatic) equation of state. The origin of the deformations is traced to shear stresses transmitted to the sample through the pressure medium.