Improvement in Atrioventricular Conduction Using Cardioneuroablation Performed Immediately after Pulmonary Vein Isolation.

In patients with atrial fibrillation (AF) recurrences after pulmonary vein isolation (PVI), concomitant treatment using anti arrhythmic drugs (AADs) can lead to clinical success. However, patients with atrioventricular (AV) block may not be good candidates for concomitant AAD therapy due to the risk of further worsening of conduction abnormalities. Cardioneuroablation (CNA), as an adjunct to PVI, may offer a solution to this problem. We present a case of a 74-year-old male with paroxysmal AF and first degree AV block in whom CNA following PVI led to PR normalization. The presented case describes an example of CNA utilization in patients with AF undergoing PVI who have concomitant problems with AV conduction and shows that CNA can be sometimes useful in older patients with functional AV block.

Bipolar endo-epicardial RF ablation: Animal feasibility study.

BACKGROUND: Bipolar radiofrequency ablation (B-RFA) is a method used to treat the arrhythmia substrate resistant to unipolar ablation. Few studies have addressed endo-epicardial B-RFA. OBJECTIVE: The aim of the study was to evaluate chronic lesions resulting from endo-epicardial B-RFA and to determine optimal settings for such procedures in an animal model. METHODS: In 7 pigs, up to 5 radiofrequency applications per animal were performed with 2 electrodes placed on both sides of the left ventricular free wall. Current was delivered for 60 seconds by a generator dedicated for B-RFA with power settings of 25, 30, 35, 40, and 50 W. RESULTS: At 12 weeks after ablation, 31 lesions were assessed. Their maximal cross-sectional area ranged from 7.2 to 68 mm2 and correlated with total power delivered (r = 0.53), with temperature increment at the endocardial catheter (r = 0.65), and inversely with temperature decrement at the epicardial catheter (r = 0.54). For power values between 30 and 40 W, the lesion area did not differ significantly (P = .92). Lesion depth ranged from 1.9 to 11 mm and correlated with impedance decrement (r = 0.5). Lesions were transmural in 8 cases. Lesion depth/wall thickness ratio was on average 0.6 ± 0.3, with the smallest value for 25 W (0.5 ± 0.3) and the largest for 50 W (0.8 ± 0.3). Steam pops occurred at a power range of 30-50 W, with an incidence of 1 in 5 applications, with 1 case of fatal tamponade at 40 W. Impedance decrement, endocardial catheter temperature increment, and endocardial electrogram amplitude decrement were greater during applications with steam pops. CONCLUSION: Chronic lesions resulting from endo-epicardial B-RFA appear smaller and less often transmural compared with acute lesions described in the literature. The incidence of steam pops during endo-epicardial B-RFA is relatively high even at low powers.

Bipolar catheter ablation with dedicated radiofrequency system for highly refractory ventricular arrhythmia-Does the rate of success depend on arrhythmia origin?

INTRODUCTION: Despite rapid technological progress, some arrhythmias are still resistant to standard unipolar ablation. These include arrhythmias arising from the base of the heart, cardiac crux, or epicardium. Bipolar radiofrequency ablation (B-RFA) may be useful in some cases, however, data on the efficacy of this approach in various arrhythmia localizations are scarce. The aim of this study was to assess the efficacy of B-RFA in patients with ventricular arrhythmias originating from various locations, occurring refractory to standard unipolar ablation approaches. METHODS: An observational, single center study was conducted over a 30-month period. B-RFA were performed using dedicated radio frequency (RF) generator and electroanatomic mapping system. RESULTS: Twenty-four procedures, in 23 patients with a median (range) of 1 (1-2) previously failed unipolar ablation procedures, were included in the final analysis. There were 12 ablations of ventricular arrhythmias originating from interventricular septum with an acute success rate of 75%, and 12 from left ventricular (LV) summit with an acute success rate of 58%. The midterm success rate (median interquartile range follow-up of 205 days [188-338]) was 66% and 50%, respectively. CONCLUSIONS: B-RFA is a promising method of catheter ablation for refractory cardiac arrhythmias. A higher success rate was observed in ablation for difficult ventricular arrhythmias originating from interventricular septal region than LV summit.

An extension of biorelevant fed-state dissolution tests to clinical pharmacokinetics - A study on gastrointestinal factors influencing rivaroxaban exposure and efficacy in atrial fibrillation patients.

A direct oral anticoagulant rivaroxaban fails to prevent stroke and systemic embolism in one-to-several percent of patients with nonvalvular atrial fibrillation (NVAF), but the reasons are unknown. The study used semi-mechanistic in vitro-in vivo prediction (IVIVP) modeling to explore the reasons for ineffective thrombosis prevention in NVAF patients. Steady-state drug concentrations in plasma were measured at 0 h (Ctrough), 3 h (C3h), and 12 h post-dosing in thirty-four patients treated with 20 mg rivaroxaban daily. The clinical data were compared against "virtual twins" generated with a novel IVIVP model that combined drug dissolution modeling, mechanistic description of gastric drug transit, and population pharmacokinetics defining the variability of drug disposition. The nonresponders had significantly lower C3h and Ctrough than the responders (p < 0.001) and the covariates included in the population pharmacokinetic submodel did not fully explain this difference. Simulations involving varied gastrointestinal parameters in the "virtual twins" revealed that lower small intestinal effective permeability (Peff), rather than a slower stomach emptying rate, could explain low rivaroxaban exposure in the nonresponders. IVIVP modeling was effectively used for exploring pharmacotherapy failure. Low Peff, found as a major determinant of ineffective rivaroxaban treatment, encourages further research to find (pato)physiological factors influencing suboptimal absorption.

Cardioneuroablation for reflex asystolic syncope: Mid-term safety, efficacy, and patient's acceptance.

BACKGROUND: Cardioneuroablation (CNA) is a promising therapy for reflex asystolic syncope; however, convincing data on the mid-term safety and efficacy of this procedure are lacking. OBJECTIVE: The purpose of this study was to assess the mid-term safety, efficacy, and patient acceptance of CNA. METHODS: This prospective observational single-center study included 115 consecutive patients (mean age 39 ± 13 years; 58% female) treated between 2016 and 2022 who completed at least 1-year follow-up. RESULTS: No significant procedure-related acute complications occurred. During median follow-up of 28 months (range 12-75), 95 (83%) remained free from syncope. Of the 20 patients (17%) with syncope recurrence, syncope burden decreased from a mean 17 (median 6.5) to 3.75 (median 2.5) episodes (P = .015). In 9 of 10 patients, pacing system removal was possible. Repeated CNA was needed in 3 patients (3%), whereas pacemaker implantation was performed in 5 (4%). The most frequent mid-term complication of CNA was sinus rhythm acceleration (from 60 ± 14 bpm to 90 ± 16 bpm; P <.0001), which was symptomatic in 31 patients (27%); 8 patients (7%) required chronic beta-blocker and/or ivabradine. Sinus node modification was necessary in 1 patient. Other complaints included dyspnea, chronic chest pain, and decreased exercise capacity, which were mild and reported by 16 patients (14%). Patient acceptance of CNA was very high: 96% stated that it was worth undergoing the procedure. CONCLUSIONS: Mid-term efficacy of CNA exceeds 80%, and acute complications are absent. The most frequent mid-term chronic complication is inappropriate sinus tachycardia, which in 7% required chronic treatment. The procedure is well accepted by patients.

Variability of baroreceptor reflex assessed by tilt table test in a patient undergoing pulmonary vein isolation.

BACKGROUND: The autonomic nervous system (ANS) plays a significant role in atrial fibrillation (AF). Catheter ablation (CA) affects the ANS balance. The assessment of baroreceptor (BR) function is an established method to measure parasympathetic activity; however, it has been rarely used in patients undergoing CA of AF. AIMS: This study is to assess changes in BR function caused by CA and to compare these changes between two different types of CA: point-by-point radiofrequency (RF) versus cryoballoon (CB). METHODS: In this observational, prospective, single center study, 78 patients (25 females, mean age 58 ± 9) with paroxysmal AF and first CA were included: 39 patients (RF group) and 39 (CB group). The BR function was assessed non-invasively using tilt testing and three parameters: event count (BREC) depicting overall BR activity, slope mean depicting BR sensitivity (BRS), and BR effectiveness index (BEI). RESULTS: The groups did not differ in clinical or demographic data. Before CA, tilting caused a marked decrease in BR function parameters in the whole study group (BREC (29 ± 14.0-50.0 vs 28 ± 9.0-44.0, p < 0.068), BRS (10.2 ± 7.1-13.2 vs 5.8 ± 4.9-8.5; p < 0.001), and BEI (52.9 ± 39.9-65.5 vs 39.6 ± 23.6-52.1; p < 0.001), supine vs tilting, respectively). These changes were similar in the both groups. After CA, BR function decreased in the whole group (BREC 12.0 ± 3.0-22.0 vs 6.0 ± 3.0-18.0, p = 0.004; BRS 4.8 ± 3.6-6.8 vs 4.0 ± 3.0-5.8, p = 0.014; BEI 18.7 ± 8.3-27.4 vs 12.0 ± 5.1-21.0, p = 0.009). BREC was significantly more decreased in the CB vs RF. Similar trend was noted for BRS and BEI. CONCLUSIONS: CA significantly affects BR function. These changes were more pronounced following CB rather than RF CA.

Twenty-five years of research on syncope.

Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.

Subclinical Dysfunction of Left Atrial Compliance after Cryoballoon versus Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.

It has been suggested that cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF) may lead to more extensive left atrial (LA) injury than radiofrequency (RF) ablation; however, results are conflicting. We sought to address this issue using modern echocardiographic techniques estimating the LA function after successful CB and RF ablation for PAF. A total of 90 patients (66% males, mean age 57 ± 10 years) successfully treated (no AF recurrences confirmed in serial 4-7 day ECG Holter monitoring) with RF (51%) or CB (49%) ablation for PAF were retrospectively studied. Echocardiography with speckle tracking (STE) was performed before and 12 months after the procedure. The peak longitudinal LA strain (LAS) and strain rate (LASR) during the reservoir (r), conduit (cd), and contraction (ct) phases were measured in sinus rhythm. Analysis of covariance was applied to compare changes in the echocardiographic parameters over time with the baseline measurements as covariance and the type of ablation as the factor. The parallelism of the slopes of the covariance was tested. The LA diameter decreased (38.3 ± 4.1 mm vs. 36.8 ± 3.6 mm, p < 0.001) in the whole study group at 12 months after ablation. The LASRr and LASRcd increased (1.1 ± 0.3 s-¹ vs. 1.3 ± 0.3 s-¹, p < 0.001 and 1.1 ± 0.3 s-¹ vs. 1.2 ± 0.3 s-¹, p < 0.001, respectively) whereas other LA strain parameters remained unchanged in the whole study group at 12 months after ablation. In the analysis of LA function at 12 months after the procedure regarding the mode of ablation, the worsening of parameters reflecting LA compliance was observed in patients with better pre-served baseline values in the CB ablation subgroup. For baseline LAScd >28%, the difference ΔCB - ΔRF was -7.6 (11.7; -3.4), p < 0.001, and for baseline LAScd >16%, ΔCB - ΔRF was -1.8 (-3.2; -0.4), p = 0.014. The traditional Doppler-derived parameter e' showed the same trend-for baseline e' ≥12 cm/s, ΔCB - ΔRF was -1.7 (-2.8; -0.6), p = 0.003. We conclude that worsening of parameters reflecting LA compliance was observed 12 months after CB ablation compared to RF ablation for PAF in patients who underwent a successful procedure and had better-preserved baseline LA function. This might suggest subclinical dysfunction of LA after the CB ablation procedure. The clinical significance of these findings warrants further investigations.

Is catheter-tissue contact force value important for ablation of ventricular arrhythmias originating from the left ventricular papillary muscles?

Background: Good catheter-tissue contact is mandatory to create effective ablation lesions. The minimal contact force value for ablation of arrhythmias originating from the left ventricle is 8.0-10.0 grams but is not known for arrhythmias arising from papillary muscles. Purpose: To analyze contact force values during successful ablation procedures of arrhythmias originating from the left ventricular papillary muscles. Methods: 24 consecutive patients (mean age 57.9 ± 11.9 years, 16 males) underwent ablation of premature ventricular complexes originating from left ventricular papillary muscles with the use of CARTO electro-anatomical system and intracardiac echocardiography. Results: Acute complete abolition of ventricular ectopy was obtained in 23 (96%) patients. The fluoroscopy time was 3.9 ± 3.5 min and procedure duration - 114.8 ± 37.9 min. The mean contact force during successful ablations was 3.0 ± 1.1 grams and 3.18 ± 1.8 grams for antero-lateral and postero-medial papillary muscle, respectively (NS). The mean contact force during a single unsuccessful ablation was 3.0 grams. At control Holter ECG, the mean Ectopy Burden was Reduced in the Antero-Lateral Papillary Muscle Group from 18.0% ± 7.9% to 2.6% ± 2.9% (p = 0.005415) and in the Postero-Medial Papillary Muscle Group - from 34.8% ± 13.7%-1.7% ± 1.3% (p = 0.012694). During Median 27 (IQR: 17-34) Months of Follow-up There one Recurrence of Arrhythmia. Conclusion: The values of contact force for successful ablation of ventricular ectopy originating from the left ventricular papillary muscles may be much lower than those for ablation of other foci which questions the role of contact force measurement when ablating these arrhythmias.

Cardioneuroablation for Reflex Syncope: Efficacy and Effects on Autonomic Cardiac Regulation-A Prospective Randomized Trial.

BACKGROUND: Treatment of cardioinhibitory vasovagal syncope (VVS) is difficult. Recently, cardioneuroablation (CNA) has emerged as a new therapeutic option. OBJECTIVES: This study sought to assess the effects of CNA on syncope recurrences in patients with VVS. METHODS: This study was a prospective, open, randomized, controlled, investigator-initiated trial comparing CNA versus optimal nonpharmacologic therapy in patients with cardioinhibitory VVS. Patients were included if they had documented symptomatic cardioinhibitory or mixed VVS and positive atropine test. CNA was performed using radiofrequency ablation of the ganglionated plexi from the left and right atria. Follow-up lasted 2 years. Primary endpoint was time to first syncope recurrence. Secondary endpoints included changes in sinus rhythm and heart rate variability measured in Holter electrocardiography at baseline and 3, 12, and 24 months after CNA, as well as changes in quality of life at baseline and after completion of follow-up. RESULTS: A total of 48 patients (17 male, mean age 38 ± 10 years, 24 in CNA group, 24 in control group) entered the study. The primary endpoint occurred in 2 patients (8%) from the CNA group versus 13 control patients (54%) (P = 0.0004). After CNA the mean sinus rhythm at 24-hour Holter electrocardiography was significantly faster and heart rate variability parameters significantly changed toward parasympathetic withdrawal compared with baseline values. Quality of life significantly improved in the CNA group (30 ± 10 points vs 10 ± 7 points; P = 0.0001), whereas it remained stable in control patients (31 ± 10 points vs 30 ± 10 points; P = 0.5501). CONCLUSIONS: This is the first randomized study documenting efficacy of CNA in patients with cardioinhibitory VVS. Larger studies are needed to confirm these findings. (Cardioneuroablation for Reflex Syncope [ROMAN]; NCT03903744).

Association Between Left Atrial Appendage Morphology and Function and the Risk of Ischaemic Stroke in Patients with Atrial Fibrillation.

AF is the most common cardiac arrhythmia and has been identified as an independent risk factor for stroke. The European Society of Cardiology guidelines recommend a thromboembolic event risk assessment based on the CHA2DS2-VASc score. However, stroke also occurs in some patients with a low CHA2DS2-VASc score. Therefore, it is necessary to find new factors to improve thromboembolic risk stratification in AF patients. Over 90% of embolic strokes are caused by thrombi originating from the left atrial appendage (LAA). Thus, certain anatomical or functional parameters of the LAA could potentially be used to predict cardioembolic stroke. Studies have suggested that some of these factors, such as LAA morphology, number of LAA lobes, LAA dimensions, LAA volume, distance from the LAA ostium to the first bend of LAA, LAA orifice diameter, extent of LAA trabeculations, LAA takeoff, LAA flow velocity and LAA strain rate, are independently associated with a higher risk of stroke in a population of patients with AF and improve the performance of the CHA2DS2-VASc score. However, the results are conflicting and, so far, no new parameter has been added to the CHA2DS2-VASc score.