Predictors of AVNRT Recurrence After Slow Pathway Modification.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common regular supraventricular tachycardia (SVT). Slow pathway modification (SPM) is the accepted first line treatment with reported success rates around 95%. Information regarding possible predictors of AVNRT recurrence is scarce.Out of 4170 consecutive patients with SPM in our department from 1993-2018, we identified 78 patients (1.9%) receiving > 1 SPM (69% female, median age 50 years) with a recurrence of AVNRT after a successful SPM. We matched these patients for age, gender and number of radiofrequency applications during first SPM with 78 patients who received one successful SPM in our center without AVNRT recurrence. Both groups were analyzed for possible predictors of a recurrence of AVNRT during long-term follow-up. The recurrence group contained a significantly lower proportion of patients with an occurrence of junctional beats during SPM (69% versus 89%, P = 0.006). Moreover, significantly more cases of previously diagnosed atrial fibrillation/tachycardia (AF/AT; 21% versus 5%, P = 0.007) and inducible AF/AT during electrophysiology study (23% versus 6%, P = 0.006) were present in the recurrence group. While more than half of patients had a recurrence within the first year, in 20% symptoms reappeared ≥ 4 years after ablation.In a small percentage of patients, AVNRT recurs after an initially successful ablation. Interestingly, these patients had significantly fewer junctional beats during ablation and a higher rate of other (inducible) arrhythmias. AVNRT recurrence spanned a considerable timeframe and should remain a differential diagnosis, even years after ablation.

Long-term experience of atrioventricular node ablation in patients with refractory atrial arrhythmias.

Atrial fibrillation and other atrial tachyarrhythmias are increasing with age and concomitant morbidity. First options in symptomatic patients are drug treatment and catheter ablation. Nevertheless, a considerable number of patients suffer from refractory atrial tachyarrhythmias despite treatment. Atrioventricular node ablation (AVNA) may be helpful in many of these patients. Therefore, we investigated AVNA patients with a long-term follow-up. We enrolled 82 patients with a follow-up longer than 1 year receiving AVNA for drug- and ablation-resistant atrial tachyarrhythmias (AA) in a retrospective manner. Mean follow-up duration was 48 ± 24 months. 50% of the patients initially received AVNA to optimize biventricular pacing in cardiac resynchronization therapy, the other 50% because of refractory symptomatic tachyarrhythmias. Persistent AV block was achieved in every patient. Symptom relief and patient satisfaction were high during follow-up. Due to system upgrades there were 63% of patients with a biventricular system during follow-up. In these patients, left-ventricular ejection fraction (LV-EF) increased by 7% (42-49%) after ablation. AVNA is effective in increasing biventricular pacing as well as for symptom relief in patients with refractory atrial tachyarrhythmias. AVNA should be considered as a valuable option in patients with refractory atrial tachyarrhythmias lacking other treatment options.

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.

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.

Antiarrhythmic properties of ivabradine in an experimental model of Short-QT- Syndrome.

The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. Twelve rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1 µmol/L). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32 ms, P<.05) and shortening of action potential duration at 90% of repolarization (APD90; -22 ms, P<.05). The shortening of ventricular repolarization was accompanied by a reduction of effective refractory period (ERP; -20 ms, P<.05). Thereafter, hearts were additionally treated with ivabradine (5 µmol/L) leading to an increase of QT interval (+31 ms, P<.05), APD90 (+15 ms, P<.05) as well as of ERP (+38 ms, P<.05) and post-repolarization refractoriness (PRR, +33 ms, P<.05) as compared with sole pinacidil infusion. Under baseline conditions, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and burst stimulation in 3 of 12 hearts (6 episodes). After application of 1 µmol/L pinacidil, 6 of 12 hearts were inducible (22 episodes). Additional infusion of 5 µmol/L ivabradine led to a significant suppression of VF. Only two episodes could be induced in 1 of 12 hearts. In the present study ivabradine reversed the electrophysiologic effects of pharmacologically simulated short-QT syndrome. Ivabradine demonstrated antiarrhythmic properties based on an increase of both ERP and PRR.

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.

Temperature to time Catch-Up: a novel procedural endpoint to predict durable pulmonary vein isolation after cryoballoon ablation of paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation is a widely used single-shot technique for pulmonary vein isolation (PVI) in the treatment of paroxysmal atrial fibrillation (AF). Procedural endpoints ensuring maximal PVI durability are important. OBJECTIVE: To assess the performance of cryoablation procedural markers to predict long-term PVI. METHODS: In a single center, consecutive patients who underwent redo ablation with high-density mapping for symptomatic AF recurrence after cryoballoon ablation were included and cryoballoon procedural data were collected, including temperature values at 30 and 60 s, time to isolation, nadir temperature and the velocity of temperature decline estimated with the temperature/time catch-up point (T2T-Catch-Up) defined as positive when the freeze temperature in minus degree equals the time in seconds after cryoablation initiation (e.g. - 15 °C in the first 15 s of the ablation impulse). RESULTS: 47 patients (62% male; 58.3 ± 11.2 years) were included. Overall, 38 (80.9%) patients had ≥ 1 reconnected PV. Among 186 PVs, 56 (30.1%; 1.2 per patient on average) were reconnected. Univariate analysis revealed T2T-Catch-Up in 103 (56%) and more frequent in durably isolated than in reconnected PVs (93 [72%] vs 10 [19%], p < 0.0001). Among binary endpoints, T2T-Catch-Up had the highest specificity (82%) and predictive value for durable PVI at redo ablation (90%). In multivariable analyses, absence of T2T-Catch-Up (Odds-ratio 0.12, 95% CI [0.05-0.31], p < 0.0001) and right superior PV (Odds-ratio 3.14, 95% CI [1.27-7.74], p = 0.01) were the only variables independently associated with PV reconnection. CONCLUSION: T2T-Catch-Up, a new and simple cryoballoon procedural endpoint demonstrated excellent predictive value and strong statistical association with durable PVI.

Predictors for major in-hospital complications after catheter ablation of ventricular arrhythmias: validation and modification of the Risk in Ventricular Ablation (RIVA) Score.

OBJECTIVE AND BACKGROUND: Catheter-based treatment of patients with ventricular arrhythmias (VA) reduces VA and mortality in selected patients. With regard to potential risks of catheter ablation, a benefit-risk assessment should be carried out. This can be performed with risk scores such as the recently published "Risk in Ventricular Ablation (RIVA) Score". We sought to validate this score and to test for possible additional predictors in a large database of VT ablations. METHODS AND RESULTS: We analyzed 1964 catheter ablations for VA in patients with (1069; 54.4%) and without (893, 45.6%) structural heart disease (SHD) and observed an overall major adverse event rate of 4.0% with an in-hospital mortality of 1.3% with significantly less complications occurring in patients without structural heart disease (6.5% vs. 1.1%; p ≤ 0.01). The RIVA Score demonstrated to be a valid predictive tool for major in-hospital complications (OR 1.18; 95% CI 1.12, 1.25; p ≤ 0.001). NYHA Class ≥ III (OR 2.5; 95% CI 1.5, 4.2; p < 0.001) and age (OR 1.04; 95% CI 1.02, 1.07; p ≤ 0.001) proved to be additional predictive parameters. Hence, a modified RIVA Score (mRIVA) model was analyzed with a subset of established predictors (SHD, eGFR, epicardial puncture) as well as new predictive parameters (age, NYHA Class ≥ III), that achieved a higher predictive value for major complications compared with the model based on all RIVA variables. CONCLUSION: Adding age and functional heart failure status (NYHA class) as simple clinical parameters to the recently published RIVA Score increases the predictive value for ablation-associated complications in a large VT ablations registry.

[Anatomy of the left ventricle for endocardial ablation]. / Anatomie des linken Ventrikels als Grundlage für endokardiale Ablationen.

As with all cardiac interventions, performing left ventricular ablation requires profound knowledge of cardiac anatomy. The aim of this article is to provide an overview of left ventricular anatomy and to characterize complex and clinically relevant structures from an electrophysiologist-centered perspective. In addition to the different access routes, the trabecular network, the left ventricular outflow tract, and the left ventricular conduction system, complex anatomical structures such as the aortomitral continuity and the left ventricular summit are also explained. In addition, this article offers multiple clinical examples that combine ECG, anatomy, and electrophysiologic study.

[Electromagnetic interference in 3D-mapping procedures]. / Elektromagnetische Interferenzen bei 3-D-Mappingverfahren.

Catheter-based ablation is nowadays a safe and widespread procedure for the treatment of cardiac arrhythmia. This requires exact anatomical knowledge both before and during the examination and is an important prerequisite for targeted treatment. At the beginning of the era of interventional catheter-based treatment, fluoroscopy was the only and usual means of visualization, whereas in the middle of the 1990s continuous 3D-mapping systems were developed for the non-fluoroscopic examination of patients. The correct use of these 3­D systems, which non-fluoroscopically visualize the catheter and mostly identify mechanisms of arrhythmia in great detail, nowadays makes an important contribution to successful interventional catheter treatment of arrhythmia; however, it is not uncommon for patients with ventricular arrhythmia to also carry implanted electronic devices, such as pacemakers, defibrillators or less frequently left ventricular hemodynamic support systems. All implantable devices lead to electromagnetic interferences, which can complicate the diagnostics and treatment during electrophysiological examinations and ablation. This article addresses the adversities and experiences associated with magnet-based 3D systems and implantable electromagnetically active cardiac devices.

Pulmonary Vein Isolation in Obese Compared to Non-Obese Patients: Real-Life Experience from a Large Tertiary Center.

1. Introduction: Pulmonary vein isolation (PVI) is an established procedure used to achieve rhythm control in atrial fibrillation (AF). In obese patients (pts), in whom AF occurs more frequently, a reduced effectiveness of PVI has been observed. Therefore, this study's aim was to compare the long-term efficacy of PVI between obese and non-obese patients. 2. Methods: We enrolled 111 consecutive pts with a body mass index (BMI) of >30 kg/m2 undergoing PVI from our large registry. Procedural data and outcomes were compared with a matched group of 115 non-obese PVI pts and the long-term outcomes were analyzed. 3. Results: Overall follow-up duration was 314 patient-years in the obese and 378 patient-years in the non-obese group. The follow-up rate was 71% in the obese and 76% in the non-obese group. In both groups, their AF-characteristics did not differ significantly, while known risk factors were significantly more prevalent in the obese group. Procedural characteristics were similar in both groups. During follow-up, the obese pts demonstrated significant weight loss compared to the non-obese pts, while at the same time, the overall recurrence rate during follow-up did not differ significantly between both groups (obese: 39.2% and non-obese: 43.7%). PVI related and long-term complications were comparable between both groups. In the univariate analysis, obesity was not found to be associated with an increased AF recurrence risk. 4. Conclusion: These real-life data demonstrate that obese pts may not show higher AF recurrence rates after PVI compared to pts with normal body weight. Furthermore, PVI was found to be safe and effective in obese patients; thus, a BMI alone may not be a criterion for refusal of PVI.

The Incidence, Electrophysiological Characteristics and Ablation Outcome of Left Atrial Tachycardias after Pulmonary Vein Isolation Using Three Different Ablation Technologies.

BACKGROUND: Left atrial tachycardias (LAT) are a well-known outcome of pulmonary vein isolation (PVI). Few data are available on whether the catheter used to perform PVI influences the incidence, as well as the characteristics of post PVI LAT. We present data on LAT following PVI by the following three ablation technologies: (1) phased multi-electrode radiofrequency catheter (PVAC), (2) irrigated single-tip catheter (iRF), and (3) cryoballoon ablation. METHODS: Using a prospectively designed single-center database, we analyzed 650 patients (300 iRF, 150 PVAC, and 200 cryoballoon) with paroxysmal (n = 401) and persistent atrial fibrillation (AF), who underwent their first PVI at our center. RESULTS: The three populations were comparable in their baseline characteristics; however, the cryoballoon group comprised a higher percentage of patients with persistent AF (p = 0.05). The LAT rates were 3.7% in the iRF group (mean follow-up 22 ± 14 months), 0.7% in the PVAC group (mean follow-up 21 ± 14 months), and 4% in the cryoballoon group (mean follow-up 15 ± 8 months). The predominant mechanism of LAT was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in 87% of the patients who underwent 3D mapping. No predictors for LAT occurrence were identified. CONCLUSION: The occurrence of LAT post PVI is rare; the predominant mechanism was macro-reentrant tachycardia. Reconnection of at least one pulmonary vein was observed in nearly all the LAT patients. In our retrospective analysis, the lowest rate of LAT was observed with the PVAC. No predictors for LAT occurrence were identified.

Incidence and Predictors of Left Atrial Appendage Thrombus before Catheter Ablation of Thrombogenic Arrhythmias.

Introduction: Transesophageal echocardiography (TEE) is routinely performed before catheter ablation of atrial tachyarrhythmias to rule out the presence of left atrial thrombi. However, data to support this practice are inconsistent. Methods: We analyzed consecutive pre-procedural TEE in a high-volume electrophysiology center for the presence of left atrial thrombi and a relevant flow reduction in the left atrial appendage (LAA) defined as LAA sludge or LAA emptying velocity (LAAEV) < 20 cm/s. The possible predictors of reduced flow were recorded and compared in a multivariate logistic regression analysis. Results: 1676 TEE were included (1122 before pulmonary vein isolation, 436 before atrial flutter ablation, 166 before other ablations). 543 patients (32%) were female and 991 (59%) were on DOAC. Nine patients (0.5%) had an LAA thrombus on pre-procedural TEE. Ninety-five further patients (5.7%) had a relevant reduction in LAA flow. The underlying rhythm showed a significant association with the presence of LAA thrombus or reduced LAA flow (p = 0.003). Patients in sinus rhythm and cavotricuspid isthmus-dependent atrial flutter exhibited the lowest risk. Additionally, reduced kidney function was associated with a reduction in LAA flow velocities (p = 0.04). Of note, two LAA thrombi occurred in patients in sinus rhythm and six out of nine patients with an LAA thrombus were on vitamin-K antagonists. Conclusions: LAA thrombus is a rare occurrence before an elective catheter ablation. The underlying rhythm and kidney function may serve as markers of a higher likelihood of significantly reduced LAAEV and LAA thrombus.

Usefulness of the MADIT-ICD Benefit Score in a Large Mixed Patient Cohort of Primary Prevention of Sudden Cardiac Death.

Background: Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current guidelines. To help evaluate a patient's individual risk, a new score to predict the benefit of an implantable defibrillator (ICD) for primary prevention, the MADIT-ICD benefit score, has recently been proposed. The score tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death based on data from four previous MADIT trials. We aimed at examining its usefulness in a large single-center register of S-ICD patients with various underlying cardiomyopathies. Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single-center database were included in the analysis (n = 173). During a follow-up of 1227 ± 978 days, 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. There was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n = 29, p = 0.04) to the occurrence of ventricular arrhythmia. However, the occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p = 0.3) in patients with (n = 142, p = 0.19) as well as patients without structural heart disease (n = 31, p = 0.88) and patients with LV-EF < 35%. Of the risk factors included in the risk score calculation, only non-sustained ventricular tachycardias were significantly associated with sustained ventricular arrhythmias (p = 0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p = 0.001, r = 0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI < 23 kg/m2 were key predictors of non-arrhythmic death implemented in the score. Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. In a large S-ICD cohort of primary prevention, the value of the score was limited to patients with ischemic cardiomyopathy. Future research should evaluate the performance of the score in different subgroups and compare it to other risk scores to assess its value for daily clinical practice.

A large-scale chemical screen for regulators of the arginase 1 promoter identifies the soy isoflavone daidzeinas a clinically approved small molecule that can promote neuronal protection or regeneration via a cAMP-independent pathway.

An ideal therapeutic for stroke or spinal cord injury should promote survival and regeneration in the CNS. Arginase 1 (Arg1) has been shown to protect motor neurons from trophic factor deprivation and allow sensory neurons to overcome neurite outgrowth inhibition by myelin proteins. To identify small molecules that capture Arg1's protective and regenerative properties, we screened a hippocampal cell line stably expressing the proximal promoter region of the arginase 1 gene fused to a reporter gene against a library of compounds containing clinically approved drugs. This screen identified daidzein as a transcriptional inducer of Arg1. Both CNS and PNS neurons primed in vitro with daidzein overcame neurite outgrowth inhibition from myelin-associated glycoprotein, which was mirrored by acutely dissociated and cultured sensory neurons primed in vivo by intrathecal or subcutaneous daidzein infusion. Further, daidzein was effective in promoting axonal regeneration in vivo in an optic nerve crush model when given intraocularly without lens damage, or most importantly, when given subcutaneously after injury. Mechanistically, daidzein requires transcription and induction of Arg1 activity for its ability to overcome myelin inhibition. In contrast to canonical Arg1 activators, daidzein increases Arg1 without increasing CREB phosphorylation, suggesting its effects are cAMP-independent. Accordingly, it may circumvent known CNS side effects of some cAMP modulators. Indeed, daidzein appears to be safe as it has been widely consumed in soy products, crosses the blood-brain barrier, and is effective without pretreatment, making it an ideal candidate for development as a therapeutic for spinal cord injury or stroke.

Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation-A Prospective 123I-mIBG-SPECT/CT Imaging Study.

BACKGROUND: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. RESULTS: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. CONCLUSIONS: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

Safe electrophysiologic profile of dexmedetomidine in different experimental arrhythmia models.

Previous studies suggest an impact of dexmedetomidine on cardiac electrophysiology. However, experimental data is sparse. Therefore, purpose of this study was to investigate the influence of dexmedetomidine on different experimental models of proarrhythmia. 50 rabbit hearts were explanted and retrogradely perfused. The first group (n = 12) was treated with dexmedetomidine in ascending concentrations (3, 5 and 10 µM). Dexmedetomidine did not substantially alter action potential duration (APD) but reduced spatial dispersion of repolarization (SDR) and rendered the action potentials rectangular, resulting in no proarrhythmia. In further 12 hearts, erythromycin (300 µM) was administered to simulate long-QT-syndrome-2 (LQT2). Additional treatment with dexmedetomidine reduced SDR, thereby suppressing torsade de pointes. In the third group (n = 14), 0.5 µM veratridine was added to reduce the repolarization reserve. Further administration of dexmedetomidine did not influence APD, SDR or the occurrence of arrhythmias. In the last group (n = 12), a combination of acetylcholine (1 µM) and isoproterenol (1 µM) was used to facilitate atrial fibrillation. Additional treatment with dexmedetomidine prolonged the atrial APD but did not reduce AF episodes. In this study, dexmedetomidine did not significantly alter cardiac repolarization duration and was not proarrhythmic in different models of ventricular and atrial arrhythmias. Of note, dexmedetomidine might be antiarrhythmic in acquired LQT2 by reducing SDR.

Very Long-Term Follow-Up in Cardiac Resynchronization Therapy: Wider Paced QRS Equals Worse Prognosis.

BACKGROUND: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. METHODS AND RESULTS: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4-12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p < 0.01), Δ LV paced-right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p < 0.01), CHA2DS2-Vasc score (p < 0.01), glomerular filtration rate (p < 0.01), coronary artery disease (p < 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p < 0.01), NT-proBNP (p < 0.01), and clinical response to CRT (p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. CONCLUSION: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.

Quantifying Left Atrial Size in the Context of Atrial Fibrillation Ablation: Which Echocardiographic Method Correlates to Outcome of Pulmonary Venous Isolation?

INTRODUCTION: Multiple studies have shown that left atrial (LA) enlargement is a strong predictor of poor outcome after catheter ablation of atrial fibrillation (AF). LA size is commonly approximated as the diameter in the parasternal long axis. It remains unknown whether more precise echocardiographic measurements of LA size allow for better correlation with outcome after pulmonary vein isolation (PVI). METHODS AND RESULTS: We performed a retrospective study of 131 consecutive patients (43 females, 60% paroxysmal AF, mean CHA2DS2-Vasc score 1.6, mean age 61 ± 12 years) referred for PVI. Measurements of the LA were carried out by a single observer in transthoracic echocardiograms (TTE) performed prior to ablation. We calculated diameter of the LA in the parasternal long axis (PLAX), LA area in the 2- as well as 4-Chamber (CH) view. LA volume was computed using the disc summation technique (LAV) and indexed to body surface area (LAVI). Procedural and follow-up data were gathered from a prospective AF database. Ablation was performed exclusively using the second generation cryoballoon by the same operators. Follow-up visits at 3, 6 and 12 months showed freedom from AF in 76%, 73% and 73% respectively. Mean values of LA calculations were LAPLAX: 37.9 mm ± 6.3 mm, 2CH area: 22.5 cm2 ± 6.7 cm2, 4CH area: 21.4 cm2 ± 5.5 cm2, LAV: 73.7 mL ± 26.1 mL and LAVI: 36.2 mL/m2 ± 12.7 mL/m2, respectively. C statistic revealed the best concordance of LAVI with outcome after 12 months (C = 0.67), LAV also exhibited a satisfactory value (C = 0.61) in comparison to surfaces in 2CH (C = 0.59) and 4CH (C = 0.57). PLAX showed the worst correlation (C = 0.51). Additionally, different binary logistic regression models identified three independent predictors of AF outcome after cryoballoon PVI: gender (OR = 0.95 per year; p = 0.01); LAV (OR = 1.3/10mL; p = 0.02) and LAVI (OR = 1.58/10 mL/m2; p = 0.02). In all models, PLAX and area measurements were not predictive. CONCLUSIONS: Our data add further to evidence that LA size lends itself well as a predictor of PVI outcome. LAVI and LAV were independently predictive of rhythm outcome after PVI. This did not hold true for more commonly used measurements, such as PLAX diameter and surfaces of the LA, irrespective of the view chosen.

Improvement of Retinal Microcirculation after Pulmonary Vein Isolation in Patients with Atrial Fibrillation-An Optical Coherence Tomography Angiography Study.

PURPOSE: To evaluate retinal and optic nerve head (ONH) perfusion in patients with atrial fibrillation (AF) before and after catheter ablation of AF with pulmonary vein isolation (PVI). METHODS: 34 eyes of 34 patients with AF and 35 eyes of 35 healthy subjects were included in this study. Flow density data were obtained using spectral-domain OCT-A (RTVue XR Avanti with AngioVue, Optovue, Inc, Fremont, California, USA). The data of the superficial and deep vascular layers of the macula and the ONH (radial peripapillary capillary network, RPC) before and after PVI were extracted and analysed. RESULTS: The flow density in the superficial OCT-angiogram (whole en face) and the ONH (RPC) in patients with AF was significantly lower compared to healthy controls (OCT-A superficial: study group: 48.77 (45.19; 52.12)%; control group: 53.01 (50.00; 54.25)%; p < 0.001; ONH: study group: 51.82 (48.41; 54.03)%; control group: 56.00 (54.35; 57.70)%; p < 0.001;). The flow density in the ONH (RPC) improved significantly in the study group following PVI (before: 51.82 (48.41; 54.03)%; after: 52.49 (50.34; 55.62)%; p = 0.007). CONCLUSIONS: Patients with AF showed altered ocular perfusion as measured using OCTA when compared with healthy controls. Rhythm control using PVI significantly improved ocular perfusion as measured using OCT-A. Non-contact imaging using OCTA provides novel information about the central global microperfusion of patients with AF.