Cardioneuroablation (CNA) is now recognized as a safe and effective method in patients with cardioinhibitory neurocardiogenic syncope (CNCS), especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Several investigations have shown beneficial and very satisfactory results with a standard non-extensive endocardial ablation, aimed at identifying high-amplitude fragmented signals in the right and left atria. Despite this, the current scientific debate is focused about a proposal on an ablative method, even more individualized than CNA (at least as a first approach), considering that a standardized approach, especially in the left atrium, could expose CNCS patients with a good prognosis to an excessive risk of complications. These findings, moving from the concept of CNA to a new concept of 'cardioneuromodulation', opened a new era, aimed at a non-extensive and individualized treatment of different clinical CNCS scenarios or vagally-mediated atrioventricular block or sinus-atrial node dysfunction.

BACKGROUND:Cardioneuroablation (CNA) should focus on the vagal ganglia located in the right atrium close to the sinoatrial and the atrioventricular nodes. OBJECTIVE:The study aimed to evaluate the efficacy and safety of right atrial CNA. METHODS:Patients with severe, asystolic reflex syncope identified by implantable loop recorder (ILR) or tilt testing underwent right atrial CNA and were subsequently monitored using ILR. RESULTS:The population included 28 patients with a mean age of 40.5 ± 13.4 years, of whom 71% were men. Over a median follow-up period of 12.5 months, 8 patients experienced 44 episodes of asystole lasting longer than 3 seconds, as recorded by an ILR. The burden of asystolic episodes significantly reduced from 0.89 episodes per month before CNA (145 over 163 patient-months) to 0.11 episodes per month after CNA (44 over 397 patient-months), with a relative risk reduction of 0.12, P = .0001. Similarly, the burden of syncopal episodes decreased from 0.23 episodes per month before CNA to 0.06 episodes per month after CNA, resulting in an relative risk reduction of 0.24, P = .0001. Median heart rate increased from 75 bpm (interquartile range: 72-79) before ablation to 83 bpm (interquartile range: 78-85) after ablation, lasting up to 9 months post-procedure. No patients experienced complications during the procedure. During follow-up, 2 patients received pacemakers, 1 underwent a redo procedure, and 4 experienced mild transient symptoms: 3 had palpitations and 1 had dyspnea, none requiring therapy. CONCLUSION:Right atrial CNA reduced asystolic episodes by 88% and syncopal episodes by 76% during the mid-term follow-up. Adverse events were infrequent and mild.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered 'gateway' of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

BACKGROUND:Palpitations in athletes are usually benign, but the presence of major cardiac arrhythmias should be ruled out despite the infrequent appraisal of symptoms. External loop recorders (ELR) are promising to identify arrhythmias in these circumstances, but experiences in athletes are lacking. We aimed to investigate the feasibility and diagnostic yield of an ELR in athletes with unexplained palpitations in a cohort study.METHODS:One hundred twenty-two consecutive subjects (61 athletes and 61 sedentary controls) with sporadic palpitations and inconclusive diagnosis were enrolled and equipped with an ELR. Findings were categorized as major and minor arrhythmic findings, non-arrhythmic findings or negative monitoring.RESULTS:Long-term ELR monitoring was feasible in all subjects, with median duration of 12 (11; 15) days. Major arrhythmic events during palpitations were found in 9 (14.8%) athletes: 7 experienced sustained paroxysmal supraventricular tachycardia, and 2 had non sustained ventricular tachycardia. Minor arrhythmic events (premature supraventricular or ventricular beats) were observed in 13 athletes (21.3%). Non-arrhythmic findings (i.e., sinus rhythm or sinus tachycardia) were recorded in 28 athletes (45.9%), whereas 11 (18%) had negative monitoring. In the sedentary group, arrhythmic events were similar for types and frequency to athletes. The diagnostic yield of loop monitoring was 82.8% in the overall population and 82.0% in the athlete's group.CONCLUSIONS:In the management of an athlete symptomatic with unexplained palpitations after 24-hour ECG monitoring and stress test, ELR is an efficient tool to identify major arrhythmic events, which can be present in up to 10% of symptomatic athletes during practice and competition.

Aim The aim of our study was to compare ivabradine versus bisoprolol in the short-term and long-term treatment of inappropriate sinus tachycardia. Methods From this prospective, parallel-group, open-label study, consecutive patients affected by inappropriate sinus tachycardia received ivabradine or bisoprolol and were evaluated with Holter ECG, ECG stress test, European Heart Rhythm Association score and Minnesota Living With Heart Failure Questionnaire at baseline, after 3 and 24 months. Results Overall, 40 patients were enrolled. Baseline parameters were comparable in the ivabradine and bisoprolol subgroups. Two patients had transient phosphenes with ivabradine and two others interrupted the drug after 3 months as they planned to become pregnant. Eight individuals treated with bisoprolol experienced hypotension and weakness, which caused drug discontinuation in five of them. Ivabradine was superior to bisoprolol in reducing Holter ECG mean heart rate (HR) and mean HR during daytime at short- and long-term follow-up. Moreover, ivabradine but not bisoprolol significantly reduced Holter ECG mean HR during night-time as well as maximal and minimal HR and significantly increased the time duration and maximal load reached at ECG stress test. The quality of life questionnaires significantly improved in both subgroups. Conclusion This study suggests that ivabradine is better tolerated than bisoprolol and seems to be superior in controlling the heart rate and improving exercise capacity in a small population of individuals affected by inappropriate sinus tachycardia during a short-term and long-term follow-up.

Several reports have focused on biatrial ganglionated plexi (GP) transcatheter ablation to treat cardioinhibitory neurocardiogenic syncope (CNS). Considering that anatomical studies showed a significant number of GP in the right atrium (RA), we hypothesized that RA “cardioneuroablation” could be an effective treatment for CNS. Eighteen consecutive patients (mean age: 36.9 ± 11.2 years) with severe CNS were submitted to transcatheter ablation of GPs in the RA alone using an anatomical approach. Head up tilt test evaluation was performed during the follow-up period at 6, 12, and 24 months and in case of significant symptoms, while heart rate variability parameters were evaluated at patients discharge at 1, 3, 6, 12, 24, and 36 months after ablation. At a mean follow-up of 34.1 ± 6.1 months, 3 (16.6%) patients experienced syncopal episodes and 5 patients (27.7%) only prodromal episodes. Syncopal and prodromal recurrences were significantly decreased both in overall population (P = 0.001) and in symptomatic patients after ablation (P = 0.003). Heart rate variability analysis showed the loss of autonomic balance secondary to a reincrease of sympathetic tone after the acute phase faster than vagal tone more evident at 12 months (LF/HF vs preablation, P < 0.001) and persistent until 24 months. Finally, a good correlation was observed between symptomatic events and the extension of RF lesions in supero-, middle-, and infero-posterior RA areas (r = 0.73, P = 0.03; r = 0.85, P = 0.02; r = 0.87, P = 0.004, respectively). Cardioneuroablation in the RA can be considered safe and an effective technique to treat CNS episodes.

Aim: The new miniaturized Insertable Cardiac Monitors (mICMs) simplified implant procedure and increased physician and patient acceptance. Besides size reduction, mICM has been provided with fully automatic daily remote transmission capabilities. The aim of this observational study was to assess the efficiency of this new mICM provided with a daily remote monitoring (RM) system in comparison to standard ICM (sICM) followed-up monthly. Methods: A total of 180 patients with an ICM were followed from April 2010 to May 2015: 107 pts with the mICM and 73 pts with sICM. The mICM implantations started on January 2015. The principal indications for total ICM implantation were syncope (68%), pre-syncope (13%) palpitations (13%), AF-management (14%) or suspected AF/cryptogenetic stroke (9%). Results: A significant event was diagnosed in 53.9% of patients (62.6% mICM vs 41.1% sICM). The most frequent event in diagnosed population was tachycardia > 120 bpm in 40.4% of cases (37.3% mICM vs 48.1% sICM). In 36% of patients, asystole > 3 sec or bradycardia < 30 bpm was recorded. Symptoms in absence or with slight variation in rhythm were present in 22.1% of patients. 54.2% of patients did not need any office visits to obtain diagnosis (mICM 69.4% vs sICM 9.5%), 33.7% of patients needed 1 office visit (mICM 25.8% vs sICM 57.1%), 8.4% of patients needed 2 office visits (mICM 1.6% vs sICM 28.6%), 3.6% of patients needed 3 office visits (mICM 3.2% vs sICM 4.8%). The mean time from the start of RM to onset of symptoms was 48.8 days (29.7 days for mICM vs 76.8 days for sICM group). The mean time from the first symptoms to treatment was 3.1 days (2.3 days for mICM vs 4.3 days for sICM). The average of total events has amounted to 1068.2 events (mICM 218.1 vs sICM 2386.6), of which 558.4 false events (mICM 100.7 vs sICM 1268.1). The average of events until the diagnosis has been 119 events (mICM 61.7 vs sICM 263.4), of which 59.2 false events (mICM 18.2 vs sICM 162.3). Conclusion: Automated daily remote monitoring of mICM was associated with presented more diagnostic accuracy than previous model with a minor count of total transmitted events, false events and office visits until diagnosis. The use of mICM allowed to save manpower compared to sICM with substantial economic benefits.

Atrial fibrillation is the most common arrhythmia in clinical practice. Ion channel blocking agents are often characterized by limited long-term efficacy and several side effects. In addition, ablative invasive procedures are neither easily accessible nor always efficacious. The "upstream therapy," which includes angiotensin-converting enzyme inhibitors, aldosterone receptor antagonists, statins, glucocorticoids, and ω-3 poly-unsaturated fatty acids, targets arrhythmia substrate, influencing atrial structural and electrical remodeling that play an essential role in atrial fibrillation induction and maintenance. The mechanisms involved and the most important clinical evidence regarding the upstream therapy influence on atrial fibrillation are presented in this review. Some open questions are also proposed.

Methods and Results: We retrospectively analyzed RM database and hospital files of 99 CRT-D consecutive patients who were visited in the out-patient clinic every 3-4 months; thirty-three patients were in addition controlled remotely with RM (RM group). Kaplan-Meier curves of clinical or device-related AE-free rates were obtained. During a median follow-up of 7 months, clinical AEs were: ventricular and atrial arrhythmias in 14 and 11 patients, low CRT pacing in nine, heart failure, strokes, or death in 15. Device-related AEs were: insufficient pacing/sensing performances in nine patients, lead dislodgement in five. As comparing the RM group with the remaining patients, Kaplan-Meier curves of clinical AEs diverged to significantly different rates: 23.8% (confidence interval [CI] 0.1%-47.5%) in the RM group and 48.7% (21.6-75.7%) in the remaining patients (P = 0.00002), with a hazard ratio of 0.14 (CI 0.06-0.37). Nondivergent Kaplan-Meier curves were obtained for device-related AE-free rates.Conclusion: CRT-D patients followed with quarterly in-office visits without a daily RM system had an 86% higher risk of delayed detection of clinical AEs, during a median follow-up of 7 months. (PACE 2011; 34:208-216).

Ivabradine in IST. We present a case of a 49‐year‐old man with inappropriate sinus tachycardia and ventricular dysfunction. The conventional treatment (ace‐inhibitor and beta‐blockers) was not well tolerated by the patient, so Ivabradine, a specific inhibitor of If current in the sinus node, was started. After 3 months of using this medication, we observed an improvement of ejection fraction and quality of life. (J Cardiovasc Electrophysiol, Vol. pp. 815‐817, July 2010)

BACKGROUND Inappropriate sinus tachycardia (IST) is characterized by an elevated heart rate (HR) at rest and an exaggerated HR response to physical activity or emotional stress. Beta-blockers and calcium channel blockers are the first-line therapy but sometimes are poorly tolerated due to side effects.OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of ivabradine, a selective inhibitor of the I(f) current of the sinoatrial node, in patients affected by IST.METHODS Eighteen consecutive symptomatic patients (2 men and 16 women; mean age 45 +/- 15 years) affected by IST were enrolled in the study. Every patient underwent resting ECG, 24-hour Holter ECG, and exercise ECG at baseline and at 3-month and 6-month follow-up.RESULTS Sixteen patients (14 women; mean age 41 +/- 14 years) completed the study. Holter ECG assessment showed a significant reduction of medium HR (P <.001) and maximal HR (P <.001, basal vs 3-6 months; P = .02, 3 vs 6 months). Minimal HR slightly decreased at 3 months and then stabilized (P = .49, 3 vs 6 months) despite an increased drug dose. Stress test showed a significant decrease at rest (P <.001) and maximal HR (P <.05), suggesting an increased tolerance to physical stress, which was confirmed by a progressive increase of maximal load reached (>100 W) during stress test at 3 months (75%) and 6 months (85%). One patient was excluded because of phosphenes despite dose lowering, and another patient did not complete the protocol.CONCLUSION Ivabradine could represent an effective and safe alternative to calcium channel blockers and beta-blockers for treatment of IST.

Aims: To compare patients with atrial flutter (AFl) and 1:1 atrioventricular conduction (AVC) with patients with AFl and higher AVC.Methods: The characteristics of 19 patients with AFl and 1:1 AVC (group A) were compared with those of 116 consecutive patients with AFl and 2:1 AVC or higher degree AV block (group B).Results: Age, gender, and left ventricular function were similar in the two groups. In group A versus group B, more patients had no structural heart disease (42% vs 17%, P < 0.05) and syncope/presyncope (90% vs 12%, P < 0.05). The AFl cycle length (CL) in group A was longer than in group B (265 +/- 24 ms vs 241 +/- 26 ms, P < 0.01). The transition from AFl with 1:1 to 2:1 AVC or vice versa was associated with small but definite changes in AFl CL, which showed larger variations in response to sympathetic stimulation. In group A patients who were studied off drugs, the atrial-His interval was not different from group B, but maximal atrial pacing rate with 1:1 AVC was faster. In group A, five patients were misdiagnosed as ventricular tachyarrhythmias, and three with a defibrillator received inappropriate shocks. Four patients had ablation of AVC and six had ablation of AFl circuit.Conclusions: The main difference between groups A and B may be an inherent capacity of the AV node for faster conduction, especially in response to increased sympathetic tone. The latter affects not only AVC but also the AFl CL. One should be aware of the different presentations of AFl with 1:1 AVC to avoid misdiagnosis/mismanagement and to consider the diagnosis in patients with narrow or wide QRS tachycardia and rates above 220/min.(PACE 2009; 32:82-90).

Introduction Inappropriate sinus tachycardia (IST) is characterized by an exaggerated increase in heart rate with sinual P wave, in the absence of predisposing conditions. Beta blockers, calcium ch...

Introduction: The elimination of complex fractionated atrial electrograms (CFAEs) has been proposed as a potential target for guiding successful AF substrate ablation. The possibility to efficiently map the atria and rapidly identify CFAEs sites is necessary, before the CFAEs ablation becomes a routine approach. The aims of this study, conducted in patients with persistent and permanent atrial fibrillation (AF), were to analyze by CARTO mapping in the right (RA) and in the left atrium (LA) during AF: (1) the diagnostic accuracy of a new software for CFAEs analysis, (2) the spatial distribution of CFAEs, (3) the regional beat to beat AF intervals (FF).

The prognosis of dilated cardiomyopathy is generally poor. The cause of ventricular dysfunction often cannot be identified. In most cases, the clinical history of cardiomyopathy is irreversible but, in some cases, potentially curable causes may be identified. The development of cardiomyopathy may be correlated to atrial or to ventricular arrhythmias. In this scenario, atrial fibrillation is the most frequent cause of ventricular dysfunction, even if it may also be secondary to heart failure. The diagnosis of tachycardia-induced cardiomyopathy can be made only after the improvement of the left ventricular function once the cardiac frequency has slowed down.