The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

Cryoballoon ablation of atrial fibrillation is effectively feasible without previous imaging of pulmonary vein anatomy: insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.

Which factors predict the behavior of ventricular extrasystoles in athletes over time?

Spontaneous behavior of ventricular extrasystoles (VE) was analysed. From a database containing 578 athletes with VE, 84 males and 11 females (29.9 ± 18.1 years) having ≥ 100 VE or repetitive VE [ventricular couplets (VC) or ventricular tachycardias (VT)] at first 24-hour Holter electrocardiographic monitoring (24-h-HM) (baseline) and at least 1-year of follow-up (3.1 ± 2.2 years) over the past 10 years were selected. The baseline was compared with the last 24-h-HM to establish DVE (VE reduction of at least 98%/24 h in the absence of VC or VT). SDVE was calculated as standard deviation of the number of VE on serial 24-h-HMs. DVE and SDVE were considered as dependent variables. Independent variables were: age, sex, type of sport, symptoms, baseline VE rate (BVE), baseline VC and VT, VE morphology, VE behavior during the baseline training session, disqualification from competitive sports, echocardiographic abnormalities. DVE occurred in 32 athletes (34%). SDVE varied from 0 to 12,658 VE/24 h (1916 ± 2649.9). Disappearance of VE during the baseline training session (DVET) correlated to DVE (P = 0.0319). BVE directly correlated to SDVE (P = 0.0008). Athletes' VE are highly variable over time, their variability depending on BVE, and they not infrequently tend to disappear. The only useful variable for predicting DVE is DVET.

Post automatic implantable cardioverter defibrillator implant therapies: drugs and ablative techniques.

The aim of this article is to report the evidences about the use of drugs and ablation after implantation of a cardioverter defibrillator. Drugs can be utilized to prevent appropriate and inappropriate shocks, can influence positively or negatively defibrillation threshold, can be useful for the treatment of electrical storm. Ablation can be performed for direct cure of coexisting atrial and ventricular tachyarrhythmias or for AV node modulation. In particular, previous data demonstrate that rescue ventricular tachycardia ablation of drug-refractory electrical storm is possible by a substrate-orientated ablation approach even in patients with complex chronic infarction and various ventricular tachycardias. At the end of this article it is described how remote monitoring, a new very promising technical improvement, can be utilized for deciding, almost in real time, the use of both these therapies or for controlling their efficacy.

Is implantable defibrillator indicated in all patients on cardiac resynchronization therapy?

Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have been introduced during the recent years to improve survival, decrease hospital readmissions and mortality, and to improve functional status and quality of life for patients with heart failure and left ventricular systolic dysfunction (LVSD). Studies which evaluated the use of CRT or ICD alone or compared CRT with CRT-ICD in patients with heart failure and LVSD are listed in this article. The results obtained are already influencing clinical practice in the US, where it has been estimated that 90% of patients receiving a CRT device now are being implanted with an ICD component. However, it is still today debated whether patients with LVSD and heart failure should be routinely offered a CRT-ICD. In fact, there are some issues that still should be solved before to establish indication for CRT-D in all heart failure patients with an indication for CRT: 1) a non complete agreement among the different societies which wrote recommendations for guidelines (a comparative table is reported); 2) a better identification of implantable patients and an amelioration of utilized devices; 3) economic and ethical ramifications of this therapy. Anyway still now the crucial question is: ''Can resynchronization be done in isolation or must be accompanied by an ICD device?''. To answer to this question we can only express which is, in our opinion, the actual position of many physicians who work in the field of pacing and electrophysiology: ''The lesson to be learned is that we still can not predict surely which patient will die of sudden death. Until a method of identifying the high risk patients can be developed, the safest strategy should be to advise a combined ICD-CRT device for patients with indication for CRT''.

Role of natriuretic peptides in heart failure patients with special reference to those on cardiac resynchronization therapy.

In recent years natriuretic peptides (NPs) have emerged as important tools for evaluation of heart failure patients. Since its approval by the Food and Drug Administration (FDA) in November 2000, recent surveys suggest that approximately 83% of hospitals in the US use some type of NP testing. Although NP testing was originally focused on rapid diagnosis of patients presenting to the emergency department with shortness of breath, clinicians regularly look to NPs for diagnosing minimally symptomatic or asymptomatic left ventricular dysfunction, and using NPs levels in clinic to help ascertain when decompensation is present. NP testing is now included in the guidelines for the diagnosis and treatment of chronic heart failure and in the Italian Consensus Document for the clinical use of NPs. Recommendations indicate that assessment of NPs can be considered a reliable rule-out test of heart failure in primary care and in the emergency room even if they stated that the role for treatment monitoring or for prognostic evaluation needs to be determined. In recent years, cardiac resynchronization therapy (CRT) was introduced as a new treatment modality for patients with systolic heart failure and several studies suggest that plasma concentration of NPs ensues as a very useful parameter for evaluating and monitoring patients who undergo CRT. Thus this article aims not only to summarise data concerning NPs measurement in patients with heart failure, but also to indicate how these markers could be utilized in the future to objectively assess effects of CRT (identification of responders). In conclusion, if further studies will confirm above mentioned remarks, it would be possible that NPs evaluation can help to tailor the more suitable therapy for each heart failure patient and, therefore, to reduce the number of failures.

Resynchronization of mitral valve annular segments reduces functional mitral regurgitation in cardiac resynchronization therapy.

AIM: Cardiac resynchronization therapy (CRT) reduces the severity of functional mitral regurgitation (FMR) in patients with heart failure and left bundle branch block. Our hypothesis was that the induction of a more synchronous mitral valve anulus contraction can be a mechanism of FMR reduction in CRT patients. METHODS: An echo tissue Doppler imaging (TDI) examination was performed at baseline and 6 months after biventricular pacing system implant in 30 patients (4 females and 26 males, 74.1+/-6.1 years) with dilatative or ischemic chronic heart failure, NYHA class = or >III, ejection fraction (EF) = or <35% and QRS = or >140 ms. EF, Myocardial Performance Index (MPI), left end-diastolic and systolic volumes (LVEDV, LVESV), mitral regurgitation jet area/left atrial area (JA/LAA), effective regurgitant orifice area (EROA), mitral anulus contraction (MAC) were evaluated. Using TDI, at the 6 left ventricle (LV) basal segments the time to the peak myocardial sustained systolic velocity (Ts) and the standard deviation (SD) of TS were evaluated. RESULTS: At 6 months follow-up NYHA class, EF, MPI were significantly improved, LV volumes were reduced. FMR degree, evaluated both as JA/LAA and EROA, was significantly reduced. This effect was associated with the 6 basal segments resynchronization and with a more effective annular contraction. CONCLUSIONS: Our data show that CRT by resynchronizing left ventricular basal segments produces a more effective mitral valve annulus contraction and contributes to FMR improvement. Further studies need to evaluate if this could be taken into account as new therapeutic perspective of functional mitral valve regurgitation.

Randomized crossover comparison of right atrial appendage pacing versus interatrial septum pacing for prevention of paroxysmal atrial fibrillation in patients with sinus bradycardia.

BACKGROUND: New atrial pacing techniques and overdrive pacing algorithms have been introduced to prevent atrial fibrillation. This study was designed to test the hypotheses that (1) interatrial septum pacing (IASP) at the triangle of Koch would be more effective than right atrial appendage pacing (RAAP) in preventing paroxysmal atrial fibrillation (PAF) in patients with sinus bradycardia and (2) an algorithm (CAP) designed to achieve constant atrial capture would increase the efficacy of rate-responsive atrial pacing. METHODS: We studied 46 patients with PAF and sinus bradycardia implanted with a DDD(R) (Medtronic Thera) pacemaker. Twenty-four patients (6.0 +/- 10.1 PAF episodes/month within 3 months before study) were randomized to RAAP and 22 patients (5.4 +/- 7.1, not significant) to IASP. Within each arm 2 randomized crossover periods of CAP-OFF and CAP-ON function were programed. RESULTS: The PAF episodes per month significantly decreased in the RAAP (CAP-OFF: 2.1 +/- 4.2, P <.05; CAP-ON: 1.9 +/- 3.8, P <.05) and in the IASP group (CAP-OFF: 0.2 +/- 0.5, P <.05; CAP-ON: 0.2 +/- 0.5, P <.05). Values were significantly lower in the IASP group than in the RAAP group in both CAP-OFF (0.2 +/- 0.5 vs 2.1 +/- 4.2, P <.05) and CAP-ON (0.2 +/- 0.5 vs 1.9 +/- 3.8, P <.05) conditions. PAF burden was significantly lower in the IASP than in the RAAP group in CAP-OFF (47 +/- 84 min/d vs 140 +/- 217, P <.05) and in CAP-ON (41 +/- 72 vs 193 +/- 266, P <.05) conditions. No differences were observed within each arm in PAF burden between the 2 crossover CAP programing periods. CONCLUSIONS: Rate-adaptive IASP at the triangle of Koch is more effective than RAAP in preventing PAF in patients with sinus bradycardia. In our sample of patients no additional clinical benefit is furnished by the CAP algorithm.

Altered values of heart rate variability in patients with relapse of atrial fibrillation during the first week after electrical cardioversion: preliminary data.

BACKGROUND: It has not so far been elucidated whether the autonomic nervous system plays a role in the pathogenesis of atrial fibrillation relapse after electrical cardioversion. METHODS: In 40 consecutive patients with atrial fibrillation (22 males, 18 females, mean age 60 +/- 2 years) submitted to successful electrical cardioversion (external in 26 and low-energy internal in 14) we evaluated the heart rate variability (24-hour Holter recording) immediately after restoration of sinus rhythm in order to assess the cardiac sympatho-vagal drive. RESULTS: Patients with atrial fibrillation relapse within the first week of electrical cardioversion were characterized by a significantly higher low/high frequency ratio. CONCLUSIONS: Despite the heterogeneity of the studied population (concerning both the therapy and etiology of atrial fibrillation), our data strongly suggest that the evaluation of the low/high frequency ratio by means of power spectral analysis immediately after electrical cardioversion is a useful tool for the identification of those patients who are prone to atrial fibrillation recurrence. Our conclusions are supported by the finding of high positive and negative predictive values for the low/high frequency ratio both in the 24-hour period and during daytime.

Mapping the organization of atrial fibrillation with basket catheters. Part II: Regional patterns in chronic patients.

The aim of this study was to investigate the spatial patterns of organization of fibrillation in the right atrium using bipolar recordings from a basket catheter in a population of 17 patients with persistent AF. The number of occurrences (NO) (i.e., the number of points laying on the baseline) was used as an objective measure of organization. This parameter significantly matches Wells' criteria for the classification of bipolar recordings during AF. The anatomic correspondence of the splines with eight atrial regions (namely anterior free wall, lateral free wall, posterolateral free wall, posterior free wall, posterior atrial septum, atrial septum, tricuspid valve, and anterior tricuspid valve) was assessed by fluoroscopic projections and electrogram morphology. Each region was further divided into high, mid-high, mid-low, and low segments. It was observed that individual and well-defined patterns of organization characterize the electrical activity of the right atrium in patients with persistent AF. When observed over 10 minutes, these patterns are rather stable in time. In each patient, the NO measurements were significantly different in the various right atrium regions (P < 0.0001 for all patients, Friedman test). The NO averaged over the population was significantly different among the regions (P < 0.001, Kruskal-Wallis test), owing to a common disorganized pattern observed in the tricuspid valve and anterior tricuspid valve regions. When these regions were removed from the analysis, the differences among the remaining regions were not statistically significant (P = 0.77). In conclusion, the quantitative assessment of organization in the entire right atrium showed an individual rather than common distribution. This may have implications in the choice of regions candidate for ablation.

Clinical evaluation of disorganization during atrial fibrillation as a guide to radiofrequency ablation.

Aim of this study was to investigate the spatial patterns of organization of fibrillation in the right atrium using bipolar recordings from a basket catheter. Study population consists of 17 patients with persistent atrial fibrillation (AF), selected a priori for low energy internal cardioversion. Organization was measured by the number of occurrences--i.e. the percentage number of points laying on the baseline--which has been demonstrated to match Wells' criteria for the classification of AF. Well-defined and stable patterns of organization characterize the electrical activity of the right atrium in these patients. The organization in the entire right atrium showed an individual rather than common distribution. This may have implications in the choice of regions candidate for ablation.

Atrioventricular interval optimization in the right atrial appendage and interatrial septum pacing: a comparison between echo and peak endocardial acceleration measurements.

Interatrial septum pacing (IASP) reduces interatrial conduction time and consequently may interfere with atrioventricular delay (AVD) optimization. We studied 14 patients with an implanted BEST Living system device able to measure peak endocardial acceleration (PEA) signal. The aims of our study were to compare the (1) optimal AVD (OAVD) in right atrial appendage pacing (RAAP) and IASP, and (2) OAVD derived by the PEA signal versus OAVD derived by Echo/Doppler evaluation of the left ventricular filling time (LVFT) and cardiac output (CO). Measurements were performed in DDD VDD modes Eight patients (group A) had RAAP and six patients (group B) had IASP. In group A, OAVD measured by LVFT, CO, and PEA was 185 +/- 23 ms, 177 +/- 19 ms, and 192 +/- 23 ms in DDD and 147 +/- 19 ms, 135 +/- 27 ms, and 146 +/- 20 ms in VDD, respectively. OAVD measured by LVFT, CO, and PEA was significantly longer in DDD mode than in VDD (P < 0.01, P < 0.01, P < 0.001). In group B, OAVD measured by LVFT, CO, and PEA was 116 +/- 19 ms, 113 +/- 10 ms, and 130 +/- 30 ms in DDD and 106 +/- 16 ms, 96 +/- 15 ms, and 108 +/- 26 ms in VDD, respectively. No statistical differences were observed between DDD and VDD. Significant correlations between OAVDs PEA derived and OAVDs LVFT and CO derived were observed (r = 0.71, r = 0.69, respectively). When new techniques of atrial stimulation, as IASP, are used an OAVD shorter and similar in VDD and DDD has to be considered. The BEST Living system could provide a valid method to ensure, in every moment, the exact required OAVD to maximize atrial contribution to CO.

Prevention of short term reversible chronic atrial fibrillation by permanent pacing at the triangle of Koch.

OBJECTIVES: The purpose of this study was to investigate if single lead interatrial septum pacing could be effective in maintaining sinus rhythm in patients in whom restoration of sinus rhythm was only possible for a period of 2-24 hours after one or more previous electrical cardioversions, and in whom a sinus bradycardia was documented before arrhythmia restarted. The two hours limit was chosen because it was considered a sufficient time to implant a dual chamber pacemaker. BACKGROUND: Alternative atrial pacing techniques have been demonstrated to be successful in preventing recurrences of atrial fibrillation (AF) in patients with sinus bradycardia. Excluding the AF occurring after only a few sinus beats, at 24 hours from electrical cardioversion an early restart of chronic AF has been reported in 12% to 17% of the patients. METHODS: After sinus rhythm was restored by internal electrical cardioversion, 17 patients, 7 ablated at the AV junction, underwent a dual chamber rate response (DDDR) pacemaker implantation with a screw-in atrial lead placed in the interatrial septum. RESULTS: After a follow-up period of 17+/-5 months (range 12 to 27 months) persistence of sinus rhythm was observed in 11 patients (65%). Six patients (35%) had recurrences of paroxysmal attacks, while five (30%) were totally free of AF. Recurrence of chronic AF was observed in six cases (35%) after 2 days-12 months from implantation. No dislodgements of the atrial lead and no complications were observed at implantation and during follow-up. CONCLUSIONS: Interatrial septum pacing is a safe and feasible technique with a satisfying success rate (65%) in long-term maintaining sinus rhythm in previously unsuccessfully cardioverted patients.

Interatrial septum pacing: a new approach to prevent recurrent atrial fibrillation.

BACKGROUND: There are a variety of approaches to the prevention of atrial fibrillation (AF) with pacing. Aim of this study was to test the safety and feasibility of interatrial septum pacing at the posterior triangle of Koch for AF prevention and to exclude potential arrhythmic effects. MATERIAL AND METHODS: Interatrial septum pacing was performed in 34 patients (21 males, 13 females, mean age 69 +/- 12 years): 9 without a history and clinical evidence of atrial fibrillation (AF) (6 with sinus bradycardia, 2 with second-degree AV block, and 1 with carotid sinus hypersensitivity) and 25 with sinus bradycardia and paroxysmal atrial fibrillation (PAF) (mean symptomatic episodes/month 6.2 +/- 10). In all patients a screw-in bipolar lead was positioned in the interatrial septum superiorly to the coronary sinus. RESULTS: At implant the mean P wave amplitude was 2.5 +/- 1.5 mV, the pacing threshold was 1 +/- 0.6 V and the impedance was 907 +/- 477 Ohm. Mean P wave duration was 118 +/- 17 ms in sinus rhythm and 82 +/- 15 during interatrial septum pacing (p < 0.001). During a mean follow-up period of 10 +/- 7 months, no patients without atrial tachyarrhythmias before implantation experienced AF. During a 9 +/- 6 months follow-up we observed only 2 symptomatic arrhythmia recurrences between AF patients (mean symptomatic episodes/month 0.006 +/- 0.0022) (p < 0.01 vs before implant period). CONCLUSIONS: Our data indicate that interatrial septal pacing is safe and feasible. A significant less incidence of arrhythmic episodes has been observed during follow-up. Further controlled randomized prospective studies are necessary to establish the exact role of this technique respect to conventional or multisite stimulation when patients with paroxysmal AF need to be permanently paced.

Wavelength index at three atrial sites in patients with paroxysmal atrial fibrillation.

The purpose of this study was to evaluate the wavelength index (WLI) at three atrial sites in a group of 23 patients with recurrent episodes of lone paroxysmal atrial fibrillation (LPAF) and a control group (n = 20). All patients underwent programmed atrial stimulation (paced cycle length = 600 ms) at high, medium, and low lateral right atrial wall. P wave duration, sinus cycle length, and corrected sinus node recovery time were not significantly different between the two study groups. WLI was calculated according to the following formulas: atrial effective refractory period (AERP)/duration of atrial extrastimulus electrogram (A2) or AERP/A2 + atrial latency; and atrial functional refractory period (AFRP)/A2. WLI was significantly shorter in LPAF than in the control group at each of the paced atrial sites independently of the formula used. Duration of premature atrial electrogram appeared to play the major role in determining the difference in WLI between patients with paroxysmal atrial fibrillation and the control group.