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

Antiarrhythmic Effect of Ranolazine in Combination with Selective NCX-Inhibition in an Experimental Model of Atrial Fibrillation

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF

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

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

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 practic

Outcome of catheter ablation in the very elderly-insights from a large matched analysis

Background: Ablation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected. Hypothesis: We hypothesized that different kind of ablations can be performed safely regardless of the pts age. Methods: We enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re-entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in-hospital complications were analyzed. Results: The analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60-80, 40-60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40-60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred. Conclusion: Ablation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients

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