Reanalysis of putative ovarian follicles suggests that Early Cretaceous birds were feeding not breeding.

We address the identity of putative ovarian follicles in Early Cretaceous bird fossils from the Jehol Biota (China), whose identification has previously been challenged. For the first time, we present a link to the botanical fossil record, showing that the "follicles" of some enantiornithine fossils resemble plant propagules from the Jehol Biota, which belong to Carpolithes multiseminalis. The botanical affinities of this "form-taxon" are currently unresolved, but we note that C. multiseminalis propagules resemble propagules associated with cone-like organs described as Strobilites taxusoides, which in turn are possibly associated with sterile foliage allocated to Liaoningcladus. Laser-Stimulated Fluorescence imaging furthermore reveals different intensities of fluorescence of "follicles" associated with a skeleton of the confuciusornithid Eoconfuciusornis zhengi, with a non-fluorescent circular micro-pattern indicating carbonaceous (or originally carbonaceous) matter. This is inconsistent with the interpretation of these structures as ovarian follicles. We therefore reaffirm that the "follicles" represent ingested food items, and even though the exact nature of the Eoconfuciusornis stomach contents remains elusive, at least some enantiornithines ingested plant propagules.

Delayed occurrence of an accelerated idioventricular rhythm with alternating bundle branch block after myocardial infarction as predictor of sudden cardiac arrest: a case report.

BACKGROUND: Accelerated idioventricular rhythm (AIVR) is known as reperfusion arrhythmia in the setting of acute myocardial infarction (AMI). In healthy individuals, it is usually considered to be benign. Alternating bundle branch block (ABBB) often progresses to complete atrioventricular block requiring permanent pacemaker implantation. We report a case of delayed appearance of AIVR following myocardial infarction (MI) in combination with ABBB as precursor of sudden cardiac arrest due to ventricular fibrillation (VF). CASE SUMMARY: A 62-year-old male with pre-existing left bundle branch block (LBBB) was admitted with an acute non-ST segment elevation MI. He underwent successful percutaneous coronary intervention (PCI) of a subtotal proximal left anterior descending artery (LAD) stenosis. Before and after PCI the electrocardiogram (ECG) demonstrated sinus rhythm with LBBB. The patient was discharged 5 days after PCI, left ventricular function at this time was moderately reduced (ejection fraction of 40%). After another 5 days, the patient was admitted for elective cardiac rehabilitation. At this time, the ECG demonstrated an AIVR with right bundle branch block morphology. Due to ABBB, the patient was scheduled for permanent pacemaker implantation. Before pacemaker implantation could take place, the patient developed a sudden cardiac arrest due to VF and was successfully resuscitated. A follow-up coronary angiography revealed no novel lesions. A cardiac resynchronization therapy defibrillator was implanted for secondary prevention of sudden cardiac death. DISCUSSION: Delayed occurrence of AIVR in combination with ABBB following AMI could be a predictor of sudden cardiac death. These patients are probably at high risk for malignant ventricular arrhythmias.

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.

Overexpression of the Na+ /Ca2+ exchanger influences ouabain-mediated spontaneous Ca2+ activity but not positive inotropy.

Administration of digitalis in heart failure (HF) increases quality of life but does not carry a prognostic benefit. Digitalis is an indirect inhibitor of the Na+ /Ca2+ exchanger (NCX), which is overexpressed in HF. We therefore used the cardiac glycoside ouabain in Ca2+ imaging experiments and patch-clamp experiments in isolated ventricular myocytes from nonfailing transgenic NCX overexpressor mice (OE). In field-stimulated myocytes, ouabain (1-100 µm) increased the amplitude of the Ca2+ transient in OE and wild-type (WT) similarly. Ouabain-mediated spontaneous Ca2+ -activity was significantly more pronounced in OE compared to WT myocytes at higher concentrations (100 µm). Also, at very high concentrations (1000 µm) of ouabain, the number of cells with hypercontraction leading to cell death was higher in OE. Ouabain (10 µm) shortened the action potential duration in both genotypes. Our findings suggest that the proarrhythmic but not the inotropic effects of cardiac glycosides are enhanced by increased NCX expression. This may offer an explanation for the observed lack of prognostic benefit but increased quality of life in HF, which is accompanied by NCX upregulation.

Distinct Occurrence of Proarrhythmic Afterdepolarizations in Atrial Versus Ventricular Cardiomyocytes: Implications for Translational Research on Atrial Arrhythmia.

Background: Principal mechanisms of arrhythmia have been derived from ventricular but not atrial cardiomyocytes of animal models despite higher prevalence of atrial arrhythmia (e.g., atrial fibrillation). Due to significant ultrastructural and functional differences, a simple transfer of ventricular proneness toward arrhythmia to atrial arrhythmia is critical. The use of murine models in arrhythmia research is widespread, despite known translational limitations. We here directly compare atrial and ventricular mechanisms of arrhythmia to identify critical differences that should be considered in murine models for development of antiarrhythmic strategies for atrial arrhythmia. Methods and Results: Isolated murine atrial and ventricular myocytes were analyzed by wide field microscopy and subjected to a proarrhythmic protocol during patch-clamp experiments. As expected, the spindle shaped atrial myocytes showed decreased cell area and membrane capacitance compared to the rectangular shaped ventricular myocytes. Though delayed afterdepolarizations (DADs) could be evoked in a similar fraction of both cell types (80% of cells each), these led significantly more often to the occurrence of spontaneous action potentials (sAPs) in ventricular myocytes. Interestingly, numerous early afterdepolarizations (EADs) were observed in the majority of ventricular myocytes, but there was no EAD in any atrial myocyte (EADs per cell; atrial myocytes: 0 ± 0; n = 25/12 animals; ventricular myocytes: 1.5 [0-43]; n = 20/12 animals; p < 0.05). At the same time, the action potential duration to 90% decay (APD90) was unaltered and the APD50 even increased in atrial versus ventricular myocytes. However, the depolarizing L-type Ca2+ current (ICa) and Na+/Ca2+-exchanger inward current (INCX) were significantly smaller in atrial versus ventricular myocytes. Conclusion: In mice, atrial myocytes exhibit a substantially distinct occurrence of proarrhythmic afterdepolarizations compared to ventricular myocytes, since they are in a similar manner susceptible to DADs but interestingly seem to be protected against EADs and show less sAPs. Key factors in the generation of EADs like ICa and INCX were significantly reduced in atrial versus ventricular myocytes, which may offer a mechanistic explanation for the observed protection against EADs. These findings may be of relevance for current studies on atrial level in murine models to develop targeted strategies for the treatment of atrial arrhythmia.

Occurrence of primarily noninducible atrioventricular nodal reentry tachycardia after radiofrequency delivery in the slow pathway region during empirical slow pathway modulation.

BACKGROUND: The first-line therapy for atrioventricular nodal reentry tachycardia (AVNRT) is catheter-based slow pathway modulation. If AVNRT is not inducible during an electrophysiological study, an empirical slow pathway modulation (ESPM) may be considered in patients with dual atrioventricular nodal physiology and/or a typical electrocardiogram (ECG). METHODS: We screened 149 symptomatic patients who underwent ESPM in our department between 1993 and 2013. All patients fulfilled the following criteria: (1) either dual atrioventricular nodal (AVN) physiology with up to 2 AVN echo beats or characteristic ECG documentation or both, (2) noninducibility of AVNRT by programmed stimulation, and (3) completion of a telephone questionnaire for long-term follow-up. Out of this population we retrospectively investigated 13 patients who were primarily noninducible but in whom an AVNRT occurred during or after radiofrequency (RF) delivery. RESULTS: When AVNRT occurred, the procedure lost its empirical character, and RF delivery was continued until the procedural endpoint of noninducibility of AVNRT. This endpoint was reached in all but one patient (92%). After a follow-up of 73 ± 15 months, this patient was the only one who reported no benefit from the procedure. CONCLUSIONS: Out of 149 initially noninducible patients, a considerable number (9%) exhibited AVNRT during or after RF delivery. These patients crossed over from empirical to controlled slow pathway modulation resulting in a good clinical outcome. Our observations should encourage electrophysiologists to repeat programmed stimulation even after initial empirical RF delivery to retest for inducibility.

The Effects of SEA0400 on Ca2+ Transient Amplitude and Proarrhythmia Depend on the Na+/Ca2+ Exchanger Expression Level in Murine Models.

Background/Objective: The cardiac Na+/Ca2+ exchanger (NCX) has been identified as a promising target to counter arrhythmia in previous studies investigating the benefit of NCX inhibition. However, the consequences of NCX inhibition have not been investigated in the setting of altered NCX expression and function, which is essential, since major cardiac diseases (heart failure/atrial fibrillation) exhibit NCX upregulation. Thus, we here investigated the effects of the NCX inhibitor SEA0400 on the Ca2+ transient amplitude and on proarrhythmia in homozygous NCX overexpressor (OE) and heterozygous NCX knockout (hetKO) mice compared to corresponding wild-types (WTOE/WThetKO). Methods/Results: Ca2+ transients of field-stimulated isolated ventricular cardiomyocytes were recorded with fluo-4-AM or indo-1-AM. SEA0400 (1 µM) significantly reduced NCX forward mode function in all mouse lines. SEA0400 (1 µM) significantly increased the amplitude of field-stimulated Ca2+ transients in WTOE, WThetKO, and hetKO, but not in OE (% of basal; OE = 98.7 ± 5.0; WTOE = 137.8 ± 5.2*; WThetKO = 126.3 ± 6.0*; hetKO = 140.6 ± 12.8*; *p < 0.05 vs. basal). SEA0400 (1 µM) significantly reduced the number of proarrhythmic spontaneous Ca2+ transients (sCR) in OE, but increased it in WTOE, WThetKO and hetKO (sCR per cell; basal/+SEA0400; OE = 12.5/3.7; WTOE = 0.2/2.4; WThetKO = 1.3/8.8; hetKO = 0.2/5.5) and induced Ca2+ overload with subsequent cell death in hetKO. Conclusion: The effects of SEA0400 on Ca2+ transient amplitude and the occurrence of spontaneous Ca2+ transients as a proxy measure for inotropy and cellular proarrhythmia depend on the NCX expression level. The antiarrhythmic effect of SEA0400 in conditions of increased NCX expression promotes the therapeutic concept of NCX inhibition in heart failure/atrial fibrillation. Conversely, in conditions of reduced NCX expression, SEA0400 suppressed the NCX function below a critical level leading to adverse Ca2+ accumulation as reflected by an increase in Ca2+ transient amplitude, proarrhythmia and cell death. Thus, the remaining NCX function under inhibition may be a critical factor determining the inotropic and antiarrhythmic efficacy of SEA0400.

Patients' and procedural characteristics of AV-block during slow pathway modulation for AVNRT-single center 10year experience.

BACKGROUND: Permanent AV-block is a recognized and feared complication of slow pathway modulation for AVNRT. We aimed to assess incidence of transient and permanent AV-block as well as consequences of transient AV-block in a large contemporary AVNRT ablation cohort. METHODS: We searched our single center prospective ablation database for occurrence of transient and permanent AV-block during slow pathway modulation between January 2004 and October 2015. We analyzed patients' and procedural characteristics as well as outcome of patients in whom transient or permanent AV-block occurred. RESULTS: Of 9170 patients who underwent a catheter ablation at our institution between January 2004 and October 2015, 2101 patients (64% women, mean age 50±18years) underwent slow pathway modulation. In three patients, permanent AV-block occurred during RF application. Additional two patients had transient AV-block that recovered (after a few minutes and 25min), but recurred within two days of the procedure. All five patients underwent dual chamber pacemaker implantation (0.2%). Transient AV-block related to RF delivery occurred in 44 patients (2%). Transient mechanical AV-block occurred in additional 17 patients (0.8%). In 12 patients, ablation was continued despite transient AV-block. One of these patients developed permanent AV-block. CONCLUSION: Permanent AV-block following slow pathway modulation is a rare event, occurring in 0.2% of patients in a large contemporary single center cohort. Transient AV-block is more frequent (2%).

Increased sodium/calcium exchanger activity enhances beta-adrenergic-mediated increase in heart rate: Whole-heart study in a homozygous sodium/calcium exchanger overexpressor mouse model.

BACKGROUND: The cardiac sodium/calcium (Na+/Ca2+) exchanger (NCX) contributes to diastolic depolarization in cardiac pacemaker cells. Increased NCX activity has been found in heart failure and atrial fibrillation. The influence of increased NCX activity on resting heart rate, beta-adrenergic-mediated increase in heart rate, and cardiac conduction properties is unknown. OBJECTIVE: The purpose of this study was to investigate the influence of NCX overexpression in a homozygous transgenic whole-heart mouse model (NCX-OE) on sinus and AV nodal function. METHODS: Langendorff-perfused, beating whole hearts of NCX-OE and the corresponding wild-type (WT) were studied ± isoproterenol (ISO; 0.2 µM). Epicardial ECG, AV nodal Wenckebach cycle length (AVN-WCL), and retrograde AVN-WCL were obtained. RESULTS: At baseline, basal heart rate was unaltered between NCX-OE and WT (WT: cycle length [CL] 177.6 ± 40.0 ms, no. of hearts [n] = 20; NCX-OE: CL 185.9 ± 30.5 ms, n = 18; P = .21). In the presence of ISO, NCX-OE exhibited a significantly higher heart rate compared to WT (WT: CL 133.4 ± 13.4 ms, n = 20; NCX-OE: CL 117.7 ± 14.2 ms, n = 18; P <.001). ISO led to a significant shortening of the anterograde and retrograde AVN-WCL without differences between NCX-OE and WT. CONCLUSION: This study is the first to demonstrate that increased NCX activity enhances beta-adrenergic increase of heart rate. Mechanistically, increased NCX inward mode activity may promote acceleration of diastolic depolarization in sinus nodal pacemaker cells, thus enhancing chronotropy in NCX-OE. These findings suggest a novel potential therapeutic target for heart rate control in the presence of increased NCX activity, such as heart failure.

Circumferential pulmonary vein isolation with second-generation multipolar catheter in patients with paroxysmal or persistent atrial fibrillation: Procedural and one-year follow-up results.

BACKGROUND: There is a lack of procedural and follow-up data on pulmonary vein isolation (PVI) with the second-generation pulmonary vein ablation catheter® (PVAC Gold) in patients with atrial fibrillation (AF). This study provides data on PVI procedures and 1-year follow-up results with PVAC Gold in patients with AF treated in clinical practice. METHODS AND RESULTS: Three hundred and eighty four patients with documented symptomatic paroxysmal (n=198) or persistent (n=186) AF were included in a non-randomized prospectively designed database. Patients were enrolled consecutively at 2 high-volume centers. Procedural as well as 1year follow-up data were systematically analyzed. Average procedure times±standard deviations were 94±23min and 97±23min, respectively, in patients with paroxysmal and persistent AF. Average fluoroscopy times were 14.7±5.4min and 15.2±5.6min and total application times 18.1±5.0min and 18.8±5.2min, respectively, in the 2 patient cohorts. At 12months, 70.7% (70/99) and 61.9% (70/113) of patients with paroxysmal and persistent AF, respectively, were free from AF. Four early complications occurred. In the group with persistent AF, 1 posterior cerebral infarction occurred 2days after the procedure during initiation of anticoagulation. There was no phrenic nerve palsy or esophageal injury associated with the procedures. No thromboembolic events were recorded during follow-up. CONCLUSIONS: In patients with paroxysmal or persistent AF, second generation multi-electrode-phased radiofrequency ablation delivers favorable mid-term PVI success rates with few procedure-related or follow-up complications.

Eobowenia gen. nov. from the Early Cretaceous of Patagonia: indication for an early divergence of Bowenia?

BACKGROUND: Even if they are considered the quintessential "living fossils", the fossil record of the extant genera of the Cycadales is quite poor, and only extends as far back as the Cenozoic. This lack of data represents a huge hindrance for the reconstruction of the recent history of this important group. Among extant genera, Bowenia (or cuticles resembling those of extant Bowenia) has been recorded in sediments from the Late Cretaceous and the Eocene of Australia, but its phylogenetic placement and the inference from molecular dating still imply a long ghost lineage for this genus. RESULTS: We re-examine the fossil foliage Almargemia incrassata from the Lower Cretaceous Anfiteatro de Ticó Formation in Patagonia, Argentina, in the light of a comparative cuticular analysis of extant Zamiaceae. We identify important differences with the other member of the genus, viz. A. dentata, and bring to light some interesting characters shared exclusively between A. incrassata and extant Bowenia. We interpret our results to necessitate the erection of the new genus Eobowenia to accommodate the fossil leaf earlier assigned as Almargemia incrassata. We then perfom phylogenetic analyses, including the first combined morphological and molecular analysis of the Cycadales, that indicate that the newly erected genus could be related to extant Bowenia. CONCLUSION: Eobowenia incrassata could represent an important clue for the understanding of evolution and biogeography of the extant genus Bowenia, as the presence of Eobowenia in Patagonia is yet another piece of the biogeographic puzzle that links southern South America with Australasia.

Effective suppression of atrial fibrillation by ivabradine: Novel target for an established drug?

BACKGROUND: Ivabradine is an inhibitor of mixed Na+-K+-currents and routinely administered in chronic heart failure. Clinical studies reported divergent trends regarding proarrhythmic and antiarrhythmic effects in atrial fibrillation (AF). METHODS AND RESULTS: In 12 isolated rabbit hearts AF was induced in 7 of 12 hearts (13 episodes) under baseline conditions by a standardized protocol employing atrial burst pacing. Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Monophasic action potential recordings showed a decrease of atrial action potential duration (aAPD,-37ms, p<0.05) and atrial effective refractory period (aERP;-39ms, p<0.05) after infusion of both acetycholine (1µM) and isoproterenol (1µM) as compared with baseline. This led to induction of AF in 11 of 12 hearts (124 episodes). Simultaneous infusion of ivabradine (3µM) led to a significant reduction of AF (6 of 11 hearts, 63 episodes). Ivabradine induced an increase of aAPD (+9ms) and aERP (+30ms, p<0.05) leading to a marked increase of atrial post-repolarization refractoriness (aPRR), defined as the difference of aERP and aAPD (+21ms, p<0.05). Results were compared to 10 rabbits treated with flecainide. Flecainide treatment also induced a significant increase of aPRR and resulted in induction of AF in 6 of 10 hearts (58 episodes) while 9 of 10 hearts were inducible during sole treatment with acetylcholine and isoproterenol (129 episodes). CONCLUSION: In the present experimental study, administration of ivabradine reduced inducibility of AF and therefore may represent a supplemental therapeutic option in AF. Of note, its antiarrhythmic efficacy was comparable to the established agent flecainide.

Routine 18F-FDG PET/CT does not detect inflammation in the left atrium in patients with atrial fibrillation.

Increasing evidence supports a role of inflammation in the development of atrial fibrillation (AF). However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce. In this study, we used 18-Fluor-Deoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) to determine atrial inflammation in patients with and without AF. Retrospectively, 18F-FDG PET/CT scans were analyzed. 37 patients with a history of AF were compared to an age and sex matched control group with no history of AF. Standardized uptake values were obtained in the atrial walls, in the left ventricular wall, and in the right ventricular blood pool, respectively. Target to background ratios (TBR) were determined in the atrial and left ventricular walls and compared between the two groups. TBR values of the left atrial wall were slightly but not significantly higher in patients with AF (1.21 ± 0.27) compared to those without AF (1.14 ± 0.29; p = 0.85). Likewise, a weak but not significant difference was observed in signal intensities in the right atrial wall between patients in the AF (1.14 ± 0.45) and the control group (0.96 ± 0.2; p = 0.41). TBR values of the left ventricular myocardium did not differ between the groups; no significant correlation was found between the TBR in the left and right atrial wall and blood glucose levels. 18F-FDG PET/CT performed under routine conditions did not detect a significant difference in inflammatory activity in the left or right atrium between patients with and without AF. Contrary to previous reports, these results therefore do not clearly support a role for ongoing atrial inflammation in patients with AF. Prospective clinical studies using myocardial glucose uptake suppression strategies may be helpful to clarify these issues.

Effective suppression of atrial fibrillation by the antihistaminic agent antazoline: First experimental insights into a novel antiarrhythmic agent.

INTRODUCTION: The antihistaminic antazoline (ANT) was reported to be highly effective and safe for rapid conversion of atrial fibrillation (AF). We therefore analyzed underlying mechanisms in an experimental whole-heart model. METHODS AND RESULTS: Isolated and retrogradely perfused rabbit hearts underwent a standardized protocol employing atrial burst pacing-induced AF in five of 20 hearts under baseline conditions (seven episodes). Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Two monophasic action potential recordings on the left- and two on the right atrial epicardium showed a decrease in atrial action potential duration (aAPD, -25 msec, P<.05) and atrial effective refractory period (aERP; -52 msec, P<.01) after infusion of acetylcholine (1 µmol/L) and isoproterenol (1 µmol/L). This led to induction of AF in 14 of 20 hearts (145 episodes). Simultaneous infusion of ANT (20 µmol/L) led to a complete suppression of AF in all inducible hearts. Treatment with ANT also led to a significant increase in aAPD (+41 msec, P<.01) and aERP (+74 msec, P<.05), leading to a marked increase in atrial postrepolarization refractoriness (aPRR, +33 msec, P<.01). Results were compared to 13 rabbits treated with flecainide. Flecainide induced a significant increase in aPRR and resulted in induction of AF in seven of 13 hearts (51 episodes) while 11 of 13 hearts were inducible with acetylcholine and isoproterenol (93 episodes). CONCLUSION: Administration of ANT was highly effective in suppressing AF. The antiarrhythmic effect could be explained by a significant increase in postrepolarization refractoriness as a result of a more marked increase in aERP as compared with aAPD.

Slow pathway modification in patients presenting with only two consecutive AV nodal echo beats.

BACKGROUND: Slow pathway modification (SPM) is the therapy of choice for AV-nodal reentry tachycardia (AVNRT). When AVNRT is not inducible, empirical ablation can be considered, however, the outcome in patients with two AV nodal echo beats (AVNEBs) is unknown. METHODS: Out of a population of 3003 patients who underwent slow pathway modification at our institution between 1993 and 2013, we retrospectively included 32 patients with a history of symptomatic tachycardia, lack of paroxysmal supraventricular tachycardia (pSVT) inducibility but occurrence of two AVNEBs. RESULTS: pSVT documentation by electrocardiography (ECG) was present in 20 patients. The procedural endpoint was inducibility of less than two AVNEBs. This was reached in 31 (97%) patients. Long-term success was assessed by a telephone questionnaire (follow-up time 63±9 months). A total 94% of the patients benefited from the procedure (59% freedom from symptoms; 34% improvement in symptoms). Among those patients in whom ECG documentation was not present, 100% benefited (58% freedom from symptoms, 42% improvement). CONCLUSION: This is the first collective analysis of a group of patients presenting with symptoms of pSVT and inducibility of only two AVNEBs. Procedural success and clinical long-term follow-up were in the range of the reported success rates of slow pathway modification of inducible AVNRT, independent of whether ECG documentation was present. Thus, SPM is a safe and effective therapy in patients with two AVNEBs.

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.

Experimental evidence for a severe proarrhythmic potential of levosimendan.

BACKGROUND: The calcium sensitizer levosimendan is established for therapy of acutely decompensated congestive heart failure. Clinical experience suggests a possible proarrhythmic potential. The aim of the present study was to assess possible proarrhythmic effects and underlying electrophysiological mechanisms. METHODS AND RESULTS: Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, levosimendan was infused in 3 concentrations (0.5, 1, and 2µM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a dose-dependent reduction of QT interval (0.5µM: -27ms, 1µM:-33ms, 2µM: -77ms; p<0.05) and action potential duration at 90% of repolarization (APD90; 0.5µM: -12ms, 1µM: -12ms, 2µM: -20ms). There was no significant increase in dispersion of repolarization. The described abbreviation of myocardial repolarization was accompanied by a significant decrease of effective refractory period (ERP; 0.5µM: -16ms, 1µM: -20ms, 2µM:-27ms; p<0.05). Under baseline conditions, ventricular fibrillation was inducible by programmed stimulation and aggressive burst stimulation in 3 of 10 hearts (4 episodes). After application of 1µM levosimendan, 8 of 10 control hearts were inducible (27 episodes). Of note, in 8 of 10 hearts after infusion of up to 2µM levosimendan, incessant ventricular fibrillation that could not be terminated by multiple external defibrillations occurred. CONCLUSION: In the present study, acute infusion of levosimendan resulted in an abbreviation of ventricular repolarization and a reduction of ERP. This led to a significantly elevated inducibility of ventricular fibrillation. In 8 of 10 hearts, incessant ventricular fibrillation occurred. These results suggest a proarrhythmic effect of levosimendan and might explain an increased mortality that coincided levosimendan treatment in a few small clinical studies.

Antiarrhythmic effect of vernakalant in an experimental model of Long-QT-syndrome.

AIMS: The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS). METHODS AND RESULTS: Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0.5 µM, n = 14) after obtaining baseline data. Thereafter, vernakalant (10 µM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT. CONCLUSION: Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms.

Severe proarrhythmic potential of risperidone compared to quetiapine in an experimental whole-heart model of proarrhythmia.

In several case reports, proarrhythmic effects of antipsychotic drugs have been reported. The aim of the present study was to investigate if application of risperidone or quetiapine has the potential to provoke polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In 24 isolated rabbit hearts, risperidone (5 and 10 µM, n = 12) or quetiapine (5 and 10 µM, n = 12) was infused after obtaining baseline data. Eight endocardial and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant QT prolongation after application of risperidone as compared with baseline (5 µM: +29 ms, 10 µM: +35 ms, p < 0.01) accompanied by an increase of action potential duration. Administration of risperidone also significantly increased spatial dispersion of repolarization (5 µM: +16 ms, 4 µM: +19 ms; p < 0.05) as well as temporal dispersion of repolarization. Lowering of potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EADs) in 8 of 12 hearts and polymorphic ventricular tachycardia resembling torsade de pointes in 6 of 12 hearts (10 µM, 49 episodes). The results were compared with hearts treated with quetiapine (5 and 10 µM). Quetiapine led to an increase in QT interval (5 µM: +10 ms; 10 µM: +28 ms; p < 0.05) and a similar increase of APD90. However, treatment with quetiapine did not result in significant alterations of spatial and temporal dispersion of repolarization. No ventricular arrhythmias were observed in this group. In the present study, quetiapine demonstrated a safe electrophysiologic profile despite significant QT prolongation. In contrast, risperidone led to a more marked prolongation of myocardial repolarization combined with a more marked increase of dispersion of repolarization.