Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation using Holter and Heart Rate Variability

ABSTRACT: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation (CNA), the vagal denervation by RF ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after CNA. Additionally, it intends to investigate the arrhythmias behavior after CNA. METHODS - prospective longitudinal study with intra-patient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to CNA, 49(59%) male, 47.3±17 years-old, having vagal paroxysmal atrial fibrillation 58(70%) or neurocardiogenic syncope 25(30%), NYHA Class < II and absence of significant comorbidities. CNA was performed in both atria by interatrial septum puncture, with irrigated conventional catheter and electroanatomic reconstruction. Ablation targeted the neuromiocardial interface by fragmentation mapping (AFNests) using the Velocity Fractionation software, conventional recording and anatomical localization of the ganglionated plexi. There were compared the time and frequency domain of the heart rate variability (HRV) and arrhythmias in 24h Holter pre-, 1-year-post- and 2-year-postCNA. Clinical outpatient follow-up and serial Holter showed 80% asymptomatic cases at 40 months. RESULTS - Time and frequency domain HRV demonstrated significant decrease in all autonomic parameters, showing an important parasympathetic and sympathetic activity reduction at 2 yearspost-CNA (p0.05) suggesting that the reinnervation has halted. There was also an important reduction in all brady- and tachyarrhythmias pre- vs. post-CNA, (p<0.01). CONCLUSIONS ­ There is an important and significant vagal and sympathetic denervation after 2 years of CAN with a significant reduction in brady and tachyarrhythmia in the whole group. There were no complications.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

BACKGROUND: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. METHODS: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). CONCLUSIONS: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Relation of fractionated atrial potentials with the vagal innervation evaluated by extracardiac vagal stimulation during cardioneuroablation

BACKGROUND: Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic vagal denervation through endocardial radiofrequency ablation for these cases. The main challenges are neuromyocardium interface identification and the denervation control and validation. The finding that the AF-Nest (AFN) ablation eliminates the atropine response and decreases RR variability suggests that they are related to the vagal innervation. METHOD: Prospective, controlled, longitudinal, nonrandomized study enrolling 62 patients in 2 groups: AFN group (AFN group 32 patients) with functional or reflex bradyarrhythmias or vagal AF treated with AFN ablation and a control group (30 patients) with anomalous bundles, ventricular premature beats, atrial flutter, atrioventricular nodal reentry, and atrial tachycardia, treated with conventional ablation (non-AFN ablation). In AFN group, ablation delivered at AFN detected by fragmentation/fractionation of the endocardial electrograms and by 3-dimensional anatomic location of the ganglionated plexus. Vagal response was evaluated before, during, and postablation by 5 s noncontact vagal stimulation at the jugular foramen, through the internal jugular veins (extracardiac vagal stimulation [ECVS]), analyzing 15 s mean heart rate, longest RR, pauses, and atrioventricular block. All patients had current guidelines arrhythmia ablation indication. RESULTS: Preablation ECVS induced sinus pauses, asystole, and transient atrioventricular block in both groups showing a strong vagal response (P=0.96). Postablation ECVS in the AFN group showed complete abolishment of the cardiac vagal response in all cases (pre/postablation ECVS=P<0.0001), demonstrating robust vagal denervation. However, in the control group, vagal response remained practically unchanged postablation (P=0.35), showing that non-AFN ablation promotes no significant denervation. CONCLUSIONS: AFN ablation causes significant vagal denervation. Non-AFN ablation causes no significant vagal denervation. These results suggest that AFNs are intrinsically related to vagal innervation. ECVS was fundamental to stepwise vagal denervation validation during cardioneuroablation. Visual Overview A visual overview is available for this article.

Relation of Fractionated Atrial Potentials With the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation During Cardioneuroablation.

BACKGROUND: Vagal hyperactivity is directly related to several clinical conditions as reflex/functional bradyarrhythmias and vagal atrial fibrillation (AF). Cardioneuroablation provides therapeutic vagal denervation through endocardial radiofrequency ablation for these cases. The main challenges are neuromyocardium interface identification and the denervation control and validation. The finding that the AF-Nest (AFN) ablation eliminates the atropine response and decreases RR variability suggests that they are related to the vagal innervation. METHOD: Prospective, controlled, longitudinal, nonrandomized study enrolling 62 patients in 2 groups: AFN group (AFN group 32 patients) with functional or reflex bradyarrhythmias or vagal AF treated with AFN ablation and a control group (30 patients) with anomalous bundles, ventricular premature beats, atrial flutter, atrioventricular nodal reentry, and atrial tachycardia, treated with conventional ablation (non-AFN ablation). In AFN group, ablation delivered at AFN detected by fragmentation/fractionation of the endocardial electrograms and by 3-dimensional anatomic location of the ganglionated plexus. Vagal response was evaluated before, during, and postablation by 5 s noncontact vagal stimulation at the jugular foramen, through the internal jugular veins (extracardiac vagal stimulation [ECVS]), analyzing 15 s mean heart rate, longest RR, pauses, and atrioventricular block. All patients had current guidelines arrhythmia ablation indication. RESULTS: Preablation ECVS induced sinus pauses, asystole, and transient atrioventricular block in both groups showing a strong vagal response (P=0.96). Postablation ECVS in the AFN group showed complete abolishment of the cardiac vagal response in all cases (pre/postablation ECVS=P<0.0001), demonstrating robust vagal denervation. However, in the control group, vagal response remained practically unchanged postablation (P=0.35), showing that non-AFN ablation promotes no significant denervation. CONCLUSIONS: AFN ablation causes significant vagal denervation. Non-AFN ablation causes no significant vagal denervation. These results suggest that AFNs are intrinsically related to vagal innervation. ECVS was fundamental to stepwise vagal denervation validation during cardioneuroablation. Visual Overview A visual overview is available for this article.

Utilidade da estimulação vagal extracardíaca na elucidação de feixes anômalos ocultos durante ablação e estudo eletrofisiológico / Usefulness of extracardiac vagal stimulation in elucidating occult anomalous bundles during ablation and electrophysiological study

Confirmar se a condução ventrículoatrial [CVA] ocorre por via normal ou anômala [VA] é fundamental no diagnóstico e ablação [ABL] de taquicardias supraventriculares [TSV]. Neste estudo propomos uma alternativa de confirmar a presença de VAs ocultas, através da estimulação vagal extracardíaca [EVEC] considerando que esta bloqueia a condução pelo nó AV. MÉTODOS: 26 pcts, 27,9±15anos, 15(57,7%) sexo feminino, portadores de TSV: reentrada nodal [RN] 5(19%) e reentrada AV [RAV] 21(81%) com ou sem pré-excitação, submetidos à ABL por RF. A partir da punção femoral e veias jugulares internas D ou E, um cateter foi avançado até o nível do maxilar superior para EVEC(30Hz/50µs/0,5 a 1V/kg até 70V) sem contato com o vago. A CVA foi testada com e sem EVEC durante estimulação ventricular[EV], pré e pós-ABL. RESULTADOS: Em todos os casos, foi possível obter intensa ação vagal com supressão reversível do nó sinusal e nó AV. Antes da ABL, a CVA estava presente em todos os casos e foi bloqueada pela EVEC apenas nos casos sem VAs. Após a ABL, a CVA foi completamente bloqueada pela EVEC em todos os casos, mas reapareceu em um pct de RN. Em todos pct de RAV, a CVA não foi bloqueada pela EVEC pré-ABL, mas desapareceu ou foi bloqueada pela EVEC pós-ABL (tabela). CONCLUSÃO: O bloqueio da CVA por EVEC sugere ausência ou eliminação com sucesso de vias anômalas. O ressurgimento da CVA resistente à EVEC pós-ABL em uma RN pode ser explicado pela denervação nodal AV pela ABL do 3º gânglio cardíaco durante ABL da via lenta. Estes dados sugerem que a EVEC pode ser muito útil para revelar VAs anômalas septais difíceis que se confundem com a CVA por vias normais. (AU)

Ablation of "Background Tachycardia" in Long Standing Atrial Fibrillation: Improving the Outcomes by Unmasking a Residual Atrial Fibrillation Perpetuator.

BACKGROUND: Catheter ablation of long-standing persistent AF (LSAF) remains challenging. Since AF-Nest (AFN) description, we have observed that a stable, protected, fast source firing, namely "Background Tachycardia"(BT), could be hidden beneath the chaotic AF. Following pulmonary vein isolation (PVI)+AFN ablation one or more BT may arise or be induced in 30-40% of patients, which could be the culprit forAF maintenance and ablation recurrences. METHODS AND RESULTS: We studied 114 patients, from 322 sequential LSAF regular ablations, having spontaneous or induced residual BT after EGM-guided PVI+AFN ablation of LSAF; 55.6±11y/o, 97males (85.1%), EF=65.5±8%, LA=42.8±6.7mm. Macroreentrant tachycardias were excluded. Pre-ablationAF 12-leads ECG Digital processing(DP) and spectral analysis(SA) was performed searching for BT before AF ablation and its correlation with BT during ablation.After PVI, 38.1±9 AFN sites/patient and 135 sustained BTs (1-3, 1.2±0.5/patient) were ablated. BT cycle length(CL) was 246.3±37.3ms. In 79 patients presenting suitable DP for SA, the BT-CL was 241.6±34.3ms with intra procedure BT-CL correlation r=0.83/p<0.01. Following BT ablation, AF could not be induced. During FU of 13→60 months(22.8±12m), AF freedom for BT RF(+) vs. BT RF(-) groups were 77.9% vs. 56.4% (p=0.009), respectively. There was no significant complication. CONCLUSION: BT ablation following PVI and AFN ablation improved long-term outcomes ofLSAF ablation. BT is likely due to sustained microreentry, protected during AF by entry block. BT can be suspected by spectral analysis of the pre-ablation ECG and is likely one important AF perpetuator by causing electrical resonance of the AFN. This ablation strategy warrants randomized, multicenter investigation.

Simplified Method for Vagal Effect Evaluation in Cardiac Ablation and Electrophysiological Procedures.

OBJECTIVES: The aim of this study is to show a simplified reversible approach to investigate and confirm vagal denervation at any time during the ablation procedure without autonomic residual effect. BACKGROUND: Parasympathetic denervation has been increasingly applied in ablation procedures such as in vagal-related atrial fibrillation and cardioneuroablation. This method proposes an easy way to study the vagal effect and to confirm its elimination following parasympathetic denervation through vagal stimulation (VS) by an electrophysiological catheter placed in the internal jugular vein. METHODS: A prospective controlled study including 64 patients without significant cardiopathy (48 male [75.0%], age 46.4 ± 16.4 years) who had a well-defined RF ablation indication for symptomatic arrhythmias, comprising a "denervation group" (DG), with indication for ablation with parasympathetic denervation (vagal-related atrial fibrillation or severe cardioinhibitory syncope) and a "control group" (CG), with ablation indication without parasympathetic denervation (accessory pathway or ventricular arrhythmia). By using a neurostimulator, both groups underwent non simultaneous bilateral VS (8 to 12 s, frequency: 30 Hz, pulse width: 50 µs, amplitude: 0.5 to 1 V/kg up to 70 V) through the internal jugular vein pre- and post-ablation. RESULTS: Significant cardioinhibition was achieved pre-ablation in all cases (pause of 11.5 ± 1.9 s in DG vs. 11.4 ± 2.1 s in CG; p = 0.79). Eight patients (12.5%) presented catheter progression difficulty in 1 jugular vein (2 right, 6 left); however, the contralateral VS was adequate for cardioinhibition. After ablation, the cardioinhibition was reproduced only in CG (pause of 11.2 ± 2.2 s) as in DG it was entirely eliminated. There was no significant difference between pre- and post-ablation cardioinhibition in CG (p = 0.84). There was no complication (follow-up 8.8 ± 5 months). CONCLUSIONS: The vagal stimulation was feasible, easy, and reliable, and showed no complications. It may be repeated during the procedure to control the denervation degree without residual effect. It could be a suitable tool for vagal denervation confirmation or autonomic tests during electrophysiological studies. Ablation without parasympathetic denervation did not change the vagal response.

Syncopal high-degree AV block treated with catheter RF ablation without pacemaker implantation.

A 23-year-old-female patient had undergone a very successful gastric banding surgery to treat obesity. Six months later she began to present recurrent syncope due to very frequent, intermittent high-degree AV block referred to as pacemaker implantation. The electrophysiological study showed impaired AV nodal conduction but the His-Purkinje conduction was preserved. Partial catheter radiofrequency ablation of the cardiac autonomic nervous system guided by spectral endocardial mapping (cardioneuroablation) was performed. The electrophysiological parameters were normalized. Holter recordings were normal and the patient was asymptomatic with normal life without pacemaker implantation in a follow-up 21 months later.

A new treatment for atrial fibrillation based on spectral analysis to guide the catheter RF-ablation.

BACKGROUND: By studying the spectrum of atrial potentials by fast Fourier transform (FFT) we have found two types of atrial muscle: the compact (CM) and the fibrillar (FM) myocardium. The former presents normal in-phase conduction inferring a great number of cellular connections, long-lasting refractoriness and leftward FFT-shift. The latter shows anisotropic out-of-phase conduction, fewer cellular connections, short refractoriness and a segmented right-FFT-shift. The compact is the normal predominant muscle and the fibrillar is different and may be neural input, vein insertion, interatrial (1A) septum, left atrial (LA) roof, etc. or pathological tissue, being so by loss of cellular connections this is a possible mechanism for conversion of compact into fibrillar-like myocardium. During atrial fibrillation (AF), clusters of FM (AF nests) present higher frequencies than any surrounding tissue. PURPOSE: The purpose was to describe a new method for paroxysmal AF RF-ablation targeting AF nests. METHOD: Forty patients, six control and 34 having idiopathic drug-refractory paroxysmal or persistent AF were studied and treated. Two catheters were placed in the LA by transseptal approach. RF (30-40 J/60-70 degrees C) was applied to all sites outside the pulmonary veins (PV) presenting right-FFT-shift (AF nests). RESULTS: Numerous AF nests were found in 34/34 AF patients and only in 1/6 controls (only in this case it was possible to induce AF despite an absence of AF history). The main FM sites were: LA roof, LA septum, close to the insertion of the superior PV, near the insertion of the inferior PV, LA posterior wall, RA near the superior vena cava insertion, RA lateral and anterior wall and the right IA septum. Ablation of all AF nests near PV insertions resulted in 35 PV isolations. After 9.9 +/- 5 months only two AF patients presented relapse of a different AF form (coarse AF) which was very well controlled with medication previously ineffective. The AF was more frequent as the ratio FM/CM increased. CONCLUSIONS: The RF-ablation of AF nests decreasing the fibrillar/compact myocardium ratio eliminated 94% of the paroxysmal AF in patients in the FU of 9.9 +/- 5 months. The AF nests may be easily identified by spectral analysis and seem to be the real AF substrate. Paroxysmal AF may be cured or controlled by applying RF in several places outside the PV and, thereby, avoiding PV stenosis.