Electrophysiological Profile of Different Antiviral Therapies in a Rabbit Whole-Heart Model.

Antiviral therapies for treatment of COVID-19 may be associated with significant proarrhythmic potential. In the present study, the potential cardiotoxic side effects of these therapies were evaluated using a Langendorff model of the isolated rabbit heart. 51 hearts of female rabbits were retrogradely perfused, employing a Langendorff-setup. Eight catheters were placed endo- and epicardially to perform an electrophysiology study, thus obtaining cycle length-dependent action potential duration at 90% of repolarization (APD90), QT intervals and dispersion of repolarization. After generating baseline data, the hearts were assigned to four groups: In group 1 (HXC), hearts were treated with 1 µM hydroxychloroquine. Thereafter, 3 µM hydroxychloroquine were infused additionally. Group 2 (HXC + AZI) was perfused with 3 µM hydroxychloroquine followed by 150 µM azithromycin. In group 3 (LOP) the hearts were perfused with 3 µM lopinavir followed by 5 µM and 10 µM lopinavir. Group 4 (REM) was perfused with 1 µM remdesivir followed by 5 µM and 10 µM remdesivir. Hydroxychloroquine- and azithromycin-based therapies have a significant proarrhythmic potential mediated by action potential prolongation and an increase in dispersion. Lopinavir and remdesivir showed overall significantly less pronounced changes in electrophysiology. In accordance with the reported bradycardic events under remdesivir, it significantly reduced the rate of the ventricular escape rhythm.

Feasibility and efficacy of a novel size adjustable cryoballoon for ablation of atrial fibrillation.

The aim of the present case series was to characterize the feasibility of a novel size adjustable cryoballoon system (PolarX Fit, Boston Scientific, Marlborough, MA, USA). This cryoballoon catheter can be inflated to two different diameters (28 mm and 31 mm) within the same procedure allowing vein adapted PVI. In summary, the novel size adjustable cryoballoon shows similar characteristics as the established versions. The intraprocedural flexibility of balloon size led to employment of the larger variant in the majority of freeze applications. Of note, in all but one procedure, both sizes were employed to ensure optimal occlusion for all veins. This initial series suggests that the size adjustable balloon offers more flexibility of obtain optimal occlusions in particular, in challenging anatomies, including common pulmonary vein ostia.

Electrophysiological Safety Profile of Antiestrogenic Therapies in the Isolated Rabbit Heart.

INTRODUCTION: Hormone-mediated therapies are on the rise and are key therapies in the treatment of some of the most common cancer entities. Proarrhythmic effects have been described in patients treated with SERMs while little to none is known about the electrophysiological effects of the potentially less arrhythmogenic selective estrogen receptor degraders. METHODS: Twenty hearts of female New Zealand White rabbits were excised and retrogradely perfused employing a Langendorff setup. An electrophysiology study was performed to obtain CL-dependent action potential duration at 90% of repolarization (APD90), QT interval, effective refractory period (ERP), and post-repolarization refractoriness (PRR = ERP-APD90). After generating baseline data, the hearts were assigned to two groups and perfused with (n = 10) increasing doses of fulvestrant (1 µM and 5 µM; n = 10) or tamoxifen (2.5 µM and 7.5 µM; n = 10), and the protocol was repeated again. RESULTS: Fulvestrant led to a decrease in APD90 and QT interval and an increased PRR. The inducibility of ventricular tachycardia (VT) episodes was unaltered. Tamoxifen showed similar effects, resulting in a shortened APD90 and QT interval and no increased VT incidence in the setting of a prolonged PRR. CONCLUSION: The present study shows no acute proarrhythmic effect of tamoxifen and fulvestrant in an established whole heart model when employing clinically relevant concentrations.

Evidence-based treatment of atrial fibrillation around the globe: comparison of the latest ESC, AHA/ACC/HRS, and CCS guidelines on the management of atrial fibrillation.

Recent versions of evidence-based guidelines on the management of atrial fibrillation (AF) have been published by the European Society of Cardiology (ESC) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS), the American College of Cardiology, American Heart Association, and the Heart Rhythm Society (AHA/ACC/HRS), and the Canadian Cardiovascular Society/Canadian Heart Rhythm Society (CCS). As all societies refer to the same multicentric and usually multinational studies, the similarities undoubtedly outweigh the differences. Nonetheless, interesting differences can often be found in details, which are usually based on a different assessment of the same study, the availability of data in relation to the publication date and local preferences and availabilities of certain cardiovascular drugs. The following article aims at lining out these similarities and differences.

Impact of different radiation techniques and doses on cardiac implantable electronic devices.

BACKGROUND AND OBJECTIVE: Purpose of this investigation was to get deeper insight into the impact of different radiation techniques and doses on cardiac implantable electric devices (CIEDs). We aimed to mimic a worst-case scenario with very high doses and external radiation being applied directly on the devices. METHODS: Radiation was applied on 21 CIEDs as photon or electron therapy with maximum dose of 150Gy in fractions of 2 -20Gy. CIEDS were put directly into the beam. Brachytherapy was applied with doses of 6Gy to a maximum of 42Gy. Check-ups took place after every fraction and one week after radiation. We calculated the estimated potential risk for the health and survival of patients as well as the risk for CIEDs' loss of function. RESULTS: 28 life- or health-threatening errors occurred during photon therapy, 3/7 devices showed complete loss of function. During electron therapy, 31 potentially patient-threatening errors and 2 losses of function were detected. During brachytherapy, none of the devices showed loss of function but 8 patient-threatening errors occurred. Inadequate shock releases were mostly seen after photon and brachytherapy, random noises occurred more often during electron therapy. The earliest potentially serious error occurred during after 2Gy photon radiation and 6Gy brachytherapy. Losses of function occurred earliest at 80Gy. CONCLUSION: The results underline the warning for precaution concerning CIED patients derived from recommendations in the literature. Our study offers new information especially about the impact of electron radiation and brachytherapy on CIEDs. Risk for the devices to for loss of telemetry or battery capacity might be negligible with normafractionated therapy.

The ECG in sarcoidosis - a marker of cardiac involvement? Current evidence and clinical implications.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients' prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease. We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review. The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.

Ablation of paroxysmal and persistent atrial fibrillation in the very elderly real-world data on safety and efficacy.

BACKGROUND: The role and technique of catheter ablation of atrial fibrillation (AF) in the elderly is unclear. While in young patients pulmonary vein isolation (PVI) has evolved as first option, in older patients decision is often made in favor of drugs as higher complication rates and less benefit are suspected. Therefore, data on PVI of paroxysmal and persistent AF in these patients is still sparse but of eminent importance. HYPOTHESIS: PVI is comparably safe in the very elderly with similar recurrence and complication rates. METHODS: We enrolled all patients (n = 146) aged >75 years who underwent a first PVI over a period of 10 years (2009-2019) from our prospective single-center ablation registry. Mean follow-up time was 231 ± 399 days. RESULTS: Acute ablation success defined as complete PVI and sinus rhythm at the end of the ablation procedure was high (99%). Severe periprocedural complications occurred in 3.3% (stroke/TIA n = 2; 1.3%; pericardial effusion n = 3; 2%). In 4.6% of patients symptomatic sick-sinus-syndrome was unmasked after PVI resulting in pacemaker implantation. There were no deaths related to PVI. Recurrence rate of symptomatic AF was 37.3% resulting in a Re-PVI and/or substrate ablation in 32 pts (20.9%). During follow-up pacemaker implantation plus atrioventricular node ablation was performed in 10 pts (6.8%). There was a trend toward lower recurrence rates with single-shot devices (cryoballoon, multielectrode phased-radiofrequency ablation catheter) than with point-by-point radiofrequency while complication rates did not differ. CONCLUSION: PVI for AF is a feasible treatment option also in patients >75 years with a reasonable success and safety profile. Higher success rates occurred in patients treated with a single-shot device as compared to point-by-point ablation.

Outcome of catheter ablation of supraventricular tachyarrhythmias in cardiac sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of not sufficiently understood origin. Some patients develop cardiac involvement in course of the disease which is mostly responsible for adverse outcome. In addition to complications like high degree atrioventricular (AV) block or ventricular tachyarrhythmias, there is a certain percentage of patients developing atrial tachyarrhythmias. Data is limited and the role of catheter ablation uncertain. Therefore, we studied sarcoid patients who presented with supraventricular tachyarrhythmias. HYPOTHESIS: Treatment and ablation of supraventricular tachycardia could be hampered by inflammation in patients with cardiac sarcoidosis. METHODS: We enrolled 37 consecutive patients with cardiac sarcoidosis who presented with atrial tachyarrhythmias and underwent an electrophysiologic study over a period of 6 years (03/2013-04/2019). In total, 16 catheter ablations for atrial tachyarrhythmias were performed. Mean follow-up duration was 2.5 years. RESULTS: Most common ablation performed was cavo-tricuspid isthmus ablation for typical atrial flutter in seven patients (54%). Pulmonary vein isolation for treatment of atrial fibrillation (AF) was performed in five patients (38%). Two patients received slow-pathway modulation for treatment of recurrent atrioventricular nodal reentry tachycardia (AVNRT). All but two patients with AF had no clinical recurrence during follow-up. Two patients had recurrence of AF but still reported markedly improved european heart rhythm association (EHRA) class. Periprocedural safety was very high. There were no adverse events related to the ablation procedure. One patient died during follow-up in the presence of electrical storm. CONCLUSION: Catheter ablations of supraventricular tachycardias seem to be safe and effective in patients with cardiac sarcoidosis. Outcome is comparable to patients without inflammatory heart disease, although data from larger patient collectives are mandatory to make recommendations in this special entity.

Time-to-isolation-guided cryoballoon ablation reduces oesophageal and mediastinal alterations detected by endoscopic ultrasound: results of the MADE-PVI trial.

AIMS: Cryoballoon ablation is safe and efficient for achieving pulmonary vein isolation (PVI) in atrial fibrillation. Structural oesophago-mediastinal lesions, which seem to be associated with an increased risk of the lethal complication of an atrio-oesophageal fistula, have been described. MADE-PVI (Mediastino-oesophageal Alterations Detected by Endosonography after PVI) aimed at evaluating safety of cryoballoon PVI in relation to two different freeze protocols. As time-to-isolation-(TTI)-guided protocol has been reported to be as effective as conventional 'two freeze protocol', we hypothesized a TTI-guided protocol causes less oesophago-mediastinal lesions. METHODS AND RESULTS: Seventy consecutive patients were scheduled for cryoballoon (2nd generation) PVI employing either a conventional protocol (n = 35: 2 × 180 s per vein) or a TTI-guided approach (n = 35: TTI + 120 s per vein or 1 × 180 s in case TTI could not be measured). Oesophagogastroduodenoscopy and endoscopic ultrasound, assessing oesophago-mediastinal alterations (e.g. ulceration, oedema) were performed blinded prior and post-ablation. Post-interventional mediastinal oedematous alterations were detected in 70% with a mean diameter of 14 mm (±0.9 mm), while only 15% revealed large mediastinal oedema >20 mm. Oesophageal lesions due to PVI occurred in 5%. Freeze protocols had a distinct impact on oesophago-mediastinal alterations as mean diameter and frequency of large oedema were significantly increased in patients after conventional protocol PVI (17 mm vs. 11 mm; 26% vs. 6%). Furthermore, every oesophageal lesion was detected in patients with conventional protocol (9%). No major complication occurred in either group. CONCLUSION: The present prospective study demonstrates a significant impact of freeze protocol on oesophago-mediastinal alterations. A TTI-guided protocol reduces mediastino-oesophageal lesions and may reduce short- and long-term complications of cryoballoon PVI.

Histone deacetylase inhibition by Entinostat for the prevention of electrical and structural remodeling in heart failure.

BACKGROUND: The development of heart failure is accompanied by complex changes in cardiac electrophysiology and functional properties of cardiomyocytes and fibroblasts. Histone deacetylase (HDAC) inhibitors hold great promise for the pharmaceutical therapy of several malignant diseases. Here, we describe novel effects of the class I HDAC inhibitor Entinostat on electrical and structural remodeling in an in vivo model of pacing induced heart failure. METHODS: Rabbits were implanted a pacemaker system, subjected to rapid ventricular pacing and treated with Entinostat or placebo, respectively. Following stimulation, rabbit hearts were explanted and subsequently subjected to electrophysiological studies and further immunohistological analyses of left ventricles. RESULTS: In vivo, rapid ventricular stimulation caused a significant prolongation of monophasic action potential duration compared to sham hearts (from 173 ± 26 ms to 250 ± 41 ms; cycle length 900 ms; p < 0.05) and an increased incidence of Early afterdepolarisations (+ 150%), while treatment with Entinostat in failing hearts could partially prevent this effect (from 250 ± 41 ms to 170 ± 53 ms, p < 0.05; reduction in EAD by 50%). Entinostat treatment partially restored KCNH2 and Cav1.3 gene expressions in failing hearts, and inhibited the development of cardiac fibrosis in vivo. CONCLUSION: In a rabbit model of heart failure, Entinostat diminishes heart failure related prolongation of repolarization and partially restores KCNH2 and Cav1.3 expression. In addition, Entinostat exerts antifibrotic properties both in vitro and in vivo. Thus, Entinostat might be an interesting candidate for the pharmaceutical therapy of heart failure directed against structural and electrical remodeling.

Acute electrophysiologic effects of the polyphenols resveratrol and piceatannol in rabbit atria.

The natural polyphenol resveratrol and its analogue piceatannol have various beneficial effects including antiarrhythmic properties. The aim of the present study was to examine potential electrophysiologic effects in an experimental whole-heart model of atrial fibrillation (AF). Simultaneous infusion of resveratrol (50 µmol/L) or piceatannol (10 µmol/L) in rabbit hearts resulted in an increase in atrial refractory period. Both agents induced a significant slowing of atrial conduction and of intrinsic heart rate. In both groups, a trend toward a reduction in AF and a regularization of AF was observed.

The Transcription Factor ATF4 Promotes Expression of Cell Stress Genes and Cardiomyocyte Death in a Cellular Model of Atrial Fibrillation.

INTRODUCTION: Cardiomyocyte remodelling in atrial fibrillation (AF) has been associated with both oxidative stress and endoplasmic reticulum (ER) stress and is accompanied by a complex transcriptional regulation. Here, we investigated the role the oxidative stress and ER stress responsive bZIP transcription factor ATF4 plays in atrial cardiomyocyte viability and AF induced gene expression. METHODS: HL-1 cardiomyocytes were subjected to rapid field stimulation. Forced expression of ATF4 was achieved by adenoviral gene transfer. Using global gene expression analysis and chromatin immunoprecipitation, ATF4 dependent transcriptional regulation was studied, and tissue specimen of AF patients was analysed by immunohistochemistry. RESULTS: Oxidative stress and ER stress caused a significant reduction in cardiomyocyte viability and were associated with an induction of ATF4. Accordingly, ATF4 was also induced by rapid field stimulation mimicking AF. Forced expression of wild type ATF4 promoted cardiomyocyte death. ATF4 was demonstrated to bind to the promoters of several cell stress genes and to induce the expression of a number of ATF4 dependent stress responsive genes. Moreover, immunohistochemical analyses showed that ATF4 is expressed in the nuclei of cardiomyocytes of tissue specimen obtained from AF patients. CONCLUSION: ATF4 is expressed in human atrial cardiomyocytes and is induced in response to different types of cell stress. High rate electrical field stimulation seems to result in ATF4 induction, and forced expression of ATF4 reduces cardiomyocyte viability.

Direct comparison of the novel automated screening tool (AST) versus the manual screening tool (MST) in patients with already implanted subcutaneous ICD.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has evolved as a valuable alternative to the transvenous ICD, especially in young patients. Unfortunately, some of these patients are ineligible for S-ICD implantation due to specific electrocardiographic features. So far, these patients were identified by mandatory pre-implantation screening using the manual screening tool (MST), which lacks objective value. Therefore, a novel automated screening tool (AST) has been introduced recently for objective screening, which has not been evaluated yet. METHODS/RESULTS: We here first investigate the novel AST, in direct comparison to MST, in 33 consecutive patients with already implanted S-ICD system to compare predicted eligibility by screening tools with true sensing of the S-ICD system. Both screening tools reliably predicted true ineligible single vectors, but also suggested overall ineligibility in a similar fraction of patients (MST: 3.0%; AST: 6.1%), albeit the implanted S-ICD worked flawlessly in these patients. AST did not predict the finally selected sensing vector better than MST. There was a surprising mismatch between AST and MST for the predicted eligibility of single vectors; only in 49% of patients did both screening tools predict eligibility for the same vectors. CONCLUSIONS: The novel AST predicted overall eligibility approximately similar to MST. Both tools predicted ineligibility in a few patients, who were actually eligible. There was a striking mismatch between both screening tools when eligibility of single vectors was predicted. Thus, the AST seems to be a valuable advance, due to its standardized and objective process, but it still lacks specificity.

[Management of inappropriate shocks/T-wave-oversensing in S-ICD®-patients]. / Management von inadäquaten Schocks/T-Wellen-Oversensing bei S-ICD®-Patienten.

Inappropriate shocks are a feared complication after implantable cardioverter-defibrillator (ICD) implantation and have a tremendous impact on quality of life. Inappropriate shocks in patients with subcutaneous ICD (S-ICD®, Boston Scientific, Marlborough, MA, USA) have various underlying causes. This review summarizes the current literature on this topic and lists possible treatment options.

Divergent antiarrhythmic effects of resveratrol and piceatannol in a whole-heart model of long QT syndrome.

BACKGROUND: The polyphenol resveratrol and its metabolite piceatannol have beneficial health effects including antiarrhythmic properties in ischemia/reperfusion. The objective of this study was to determine potential antiarrhythmic effects in acquired long-QT-syndrome (LQTS). METHODS AND RESULTS: 26 rabbit hearts were isolated and Langendorff-perfused. The IKr-blocker sotalol (100µM) was infused to mimic LQTS-2. Hearts were assigned to two groups. Sotalol significantly prolonged action potential duration (APD90) and QT-interval in both groups (group 1:APD90: +18ms, p<0.01;QT: +59ms, p<0.01; group 2: APD90: +22ms, p<0.01; QT: +30ms, p<0.01) and also significantly increased dispersion of repolarization (group 1: +21ms, p<0.01; group 2: +23ms, p<0.01). Thereafter, hearts were additionally perfused either with resveratrol (50µM, group 1, n=14) or with piceatannol (10µM, group 2, n=12). Administration of resveratrol significantly reduced APD90 (-29ms, p<0.01), QT-interval(-60ms, p<0.01) and dispersion of repolarization (-26ms, p<0.01). In contrast, piceatannol did not significantly alter APD90 (±0ms) but shortened QT-interval (-19ms, p<0.01) and increased dispersion of repolarization (+15ms, p<0.01). With sotalol, 7 of 14 bradycardic, AV-blocked hearts in group 1 and 8 of 12 in group 2 showed early afterdepolarizations (EAD) after lowering potassium concentration (p<0.01each). Polymorphic ventricular tachycardia (PVT) occurred in 5 of 14 (p<0.05) and 4 of 12 hearts (p=0.09) with a total number of 42 (p<0.05) and 44 episodes (p=0.07), respectively. Additional infusion of resveratrol reduced EAD (2 of 14, p=0.11) and PVT (1 of 14 hearts, p=0.16, 3 episodes, p<0.05). Piceatannol did not suppress EAD or TdP (EAD in 9 of 12 and TdP in 7 of 12 hearts,50 episodes). CONCLUSION: Resveratrol showed beneficial antiarrhythmic properties in acquired LQTS. Underlying mechanism is a substantial decrease dispersion of repolarization leading to a suppression of triggered activity.

Incidence and management of inadvertent puncture and sheath placement in the aorta during attempted transseptal puncture.

AIMS: Transseptal punctures (TSP) are routinely performed in cardiac interventions requiring access to the left heart. While pericardial effusion/tamponade are well-recognized complications, few data exist on accidental puncture of the aorta and its management and outcome. We therefore analysed our single centre database for this complication. METHODS AND RESULTS: We assessed frequency and outcome of inadvertent aortic puncture during TSP in consecutive patients undergoing ablation procedures between January 2005 and December 2014. During the 10-year period, two inadvertent aortic punctures occurred among 2936 consecutive patients undergoing 4305 TSP (0.07% of patients, 0.05% of TSP) and in one Mustard patient during attempted baffle puncture. The first two patients required left ventricular access for catheter ablation of ventricular tachycardia. In both cases, an 11.5F steerable sheath (inner diameter 8.5F) was accidentally placed in the ascending aorta just above the aortic valve. In the presence of surgical standby, the sheaths were pulled back with a wire left in the aorta. Under careful haemodynamic and echocardiographic observation, this wire was also pulled back 30 min later. None of the patients required a closing device or open heart surgery. None of the patients suffered complications from the accidental aortic puncture and sheath placement. CONCLUSION: Inadvertent aortic puncture and sheath placement are rare complications in patients undergoing TSP for interventional procedures. Leaving a guidewire in place during the observation period may allow introduction of sheaths or other tools in order to control haemodynamic deterioration.

Colchicine Increases Ventricular Vulnerability in an Experimental Whole-Heart Model.

The traditional gout medication colchicine has been reported to effectively prevent atrial fibrillation recurrence after atrial fibrillation ablation or cardiac surgery in a few clinical trials. Severe adverse events have not yet been reported. The aim of the present study was to assess possible direct electrophysiological effects in an experimental whole-heart model. Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, colchicine was administered in two concentrations (1 and 3 µM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a stable QT interval and action potential duration during colchicine infusion. Furthermore, there was no significant increase in dispersion of repolarization. However, colchicine induced a dose-dependent significant decrease of effective refractory period (ERP; 1 µM: -19 ms, 3 µM: -22 ms; p < 0.05). In the present study, acute infusion of colchicine in isolated rabbit hearts resulted in a reduction of ERP in the presence of a stable myocardial repolarization. This led to a significantly elevated inducibility of ventricular fibrillation. In 4 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a pro-arrhythmic or toxic effect of colchicine and underline that further clinical studies on potential adverse effects should be conducted before the drug can be recommended for routine use after atrial fibrillation ablation.

Pulmonary vein reconnection and arrhythmia progression after antral linear catheter ablation of paroxysmal and persistent atrial fibrillation.

BACKGROUND: Assumption of different substrates is the basis for different ablation strategies in patients with paroxysmal and persistent atrial fibrillation (AF). We aimed to investigate pulmonary vein reconnection and influence on progression of initial paroxysmal (pAF) versus persistent atrial fibrillation (perAF). METHODS: Between January 2010 and November 2012, 149 patients (117 men, mean age 59 ± 11 years, range 27-80 years) underwent at least one redo antral pulmonary vein isolation (PVI) using NavX-guided irrigated-tip radiofrequency catheter ablation. We analyzed whether and where reconnection of pulmonary veins was detected, and whether there were differences between patients with pAF and perAF. RESULTS: Of the 149 patients who underwent a redo antral PVI, 80 patients had pAF and 69 had perAF. One, two and three redo PVIs were performed in 149, 26 and 6 patients, respectively. Reconnection of at least one PV was detected in all patients at the second PVI, in 19 of 26 patients (73 %) at the third PVI and 5 of 6 patients (83 %) at the fourth PVI. 20 (29 %) patients with perAF prior to the first PVI had pAF at the second PVI, whereas 15 (19 %) patients with initial pAF had persistent AF at the time of the first redo procedure. From the second to the third PVI, four patients had developed perAF after previous pAF and two with per AF now had pAF. PV reconnection was observed independent of underlying AF type. At the second redo procedure, of those with reconnected veins 12 had pAF and 13 perAF. At the third redo procedure, four patients had pAF and four perAF. CONCLUSION: Most patients with recurrent AF after PVI showed at least one reconnected vein during redo procedures. Reconnection was identified irrespective of the underlying AF type. Progression from pAF to perAF and vice versa was observed irrespective of the initial AF type.

G-CSF therapy reduces myocardial repolarization reserve in the presence of increased arteriogenesis, angiogenesis and connexin 43 expression in an experimental model of pacing-induced heart failure.

G-CSF (granulocyte colony-stimulating factor) treatment has been shown to cause beneficial effects including a reduction of inducible arrhythmias in rodent models of ischemic cardiomyopathy. The aim of the present study was to test whether these effects do also apply to pacing-induced non-ischemic heart failure. In 24 female rabbits, heart failure was induced by rapid ventricular pacing. 24 rabbits were sham operated. The paced rabbits developed a significant decrease of ejection fraction. 11 heart failure rabbits (CHF) and 11 sham-operated (S) rabbits served as controls, whereas 13 sham (S-G-CSF) and 13 heart failure rabbits (CHF-G-CSF) were treated with 10 µg/kg G-CSF s.c. over 17 ± 4 days. G-CSF treatment caused a ~25% increased arterial and capillary density and a ~60% increased connexin 43 expression in failing hearts. In isolated, Langendorff-perfused rabbit hearts eight monophasic action potential recordings showed prolongation of repolarization in CHF as compared with controls in the presence of the QT prolonging agent erythromycin (+33 ± 12 ms; p < 0.01). Moreover, a significant increase in dispersion of repolarization contributed to a significantly higher rate of ventricular tachyarrhythmias in CHF. G-CSF-pre-treated hearts showed a further increase in prolongation of repolarization as compared with S and CHF. The further increase in dispersion of repolarization [S-G-CSF: +23 ± 9 ms (spatial), +13 ± 7 ms (temporal); CHF-G-CSF: +38 ± 14 ms (spatial), +10 ± 4 ms (temporal); p < 0.05 as compared with S and CHF], increased the incidence of ventricular tachyarrhythmias. In summary, chronic G-CSF treatment has moderate beneficial effects on parameters potentially related to hemodynamic function in the non-ischemic rabbit CHF model. However, a significant reduction of repolarization reserve might seriously challenge its suitability as a therapeutic agent for chronic CHF therapy.