Pre-implant predictors of inappropriate shocks with the third-generation subcutaneous implantable cardioverter defibrillator.

AIMS: Despite recent improvements, inappropriate shocks emitted by implanted subcutaneous implantable cardioverter defibrillators (S-ICDs) remain a challenge in 'real-life' practice. We aimed to study the pre-implant factors associated with inappropriate shocks for the latest generation of S-ICDs. METHODS AND RESULTS: Three-hundred patients implanted with the third-generation S-ICD system for primary or secondary prevention between January 2017 and March 2020 were included in this multicentre retrospective observational study. A follow-up of at least 6 months and pre-implant screening procedure data were mandatory for inclusion. During a mean follow-up of 22.8 (±11.4) months, 37 patients (12.3%) received appropriate S-ICD shock therapy, whereas 26 patients (8.7%) experienced inappropriate shocks (incidence 4.9 per 100 patient years). The total number of inappropriate shock episodes was 48, with nine patients experiencing multiple episodes. The causes of inappropriate shocks included supraventricular arrhythmias (34.6%) and cardiac (30.7%) or extra-cardiac noise (38.4%) oversensing. Using multivariate analysis, we explored the independent factors associated with inappropriate shocks. These were the availability of less than three sensing vectors during pre-implant screening [hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.11-0.93; P = 0.035], low QRS/T wave ratio in Lead I (for a threshold <3; HR, 4.79; 95% CI, 2.00-11.49; P < 0.001), history of supraventricular tachycardia (HR, 8.67; 95% CI, 2.80-26.7; P < 0.001), and being overweight (body mass index > 25; HR, 2.66; 95% CI, 1.10-6.45; P = 0.03). CONCLUSION: Automatic pre-implant screening data are a useful quantitative predictor of inappropriate shocks. Electrocardiogram features should be taken into consideration along with other clinical factors to identify patients at high risk of inappropriate shocks.

Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome.

AIMS: Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores. METHODS AND RESULTS: A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67-0.79) and 0.71 (0.61-0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P < 0.01). No statistical difference was found in intermediate-risk patients (score 2-4). The Shanghai score does not allow to better stratify the risk of SCA. CONCLUSIONS: In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient.

The emergence of Staphylococcus aureus as the primary cause of cardiac device-related infective endocarditis.

BACKGROUND: Increasing use of cardiovascular implantable electronic devices (CIED), as permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), or cardiac resynchronization therapy (CRT), is associated with the emergence of CIED-related infective endocarditis (CIED-IE). We aimed to characterize CIED-IE profile, temporal trends, and prognostic factors. METHODS: CIED-IE diagnosed at Rennes University Hospital during years 1992-2017 were identified through computerized database, and included if they presented all of the following: (1) clinical signs of infection; (2) microbiological documentation through blood and/or CIED lead cultures; (3) lead or valve vegetation, or definite IE according to Duke criteria. Data were retrospectively extracted from medical charts. The cohort was categorized in three periods: 1992-1999, 2000-2008, and 2009-2017. RESULTS: We included 199 patients (51 women, 148 men, median age 73 years [interquartile range, 64-79]), with CIED-IE: 158 PPMs (79%), 24 ICD (12%), and 17 CRT (9%). Main pathogens were coagulase-negative staphylococci (CoNS: n = 86, 43%), Staphylococcus aureus (n = 60, 30%), and other Gram-positive cocci (n = 28, 14%). Temporal trends were remarkable for the decline in CoNS (P = 0.002), and the emergence of S. aureus as the primary cause of CIED-IE (24/63 in 2009-2017, 38%). Factors independently associated with one-year mortality were chronic obstructive pulmonary disease (COPD: hazard ratio 3.84 [1.03-6.02], P = 0.03), left-sided endocarditis (HR 2.25 [1.09-4.65], P = 0.03), pathogens other than CoNS (HR 3.16 [1.19-8.39], P = 0.02), and CIED removal/reimplantation (HR 0.41 [0.20-0.83], P = 0.01). CONCLUSIONS: S. aureus has emerged as the primary cause of CIED-IE. Left-sided endocarditis, COPD, pathogens other than CoNS, and no CIED removal/reimplantation are independent risk factors for one-year mortality.

CRT-Pacemaker Versus CRT-Defibrillator Who Needs Sudden Cardiac Death Protection?

PURPOSE OF THE REVIEW: Patients with cardiomyopathy and impaired left ventricular (LV) ejection fraction are at risk of sudden cardiac death (SCD). In selected heart failure patients, cardiac resynchronization therapy (CRT) provides LV reverse remodeling and improves the cellular and molecular function leading to a reduced risk of ventricular arrhythmia and SCD. Consequently, some CRT candidates may not need concomitant ICD therapy. This review aimed at focusing on the residual risk of SCD in patients receiving CRT and discussing the requirement of a concomitant ICD therapy in CRT candidates. RECENT FINDINGS: New imaging diagnostic tools may be helpful to accurately predict patient with a residual risk of SCD and who required a CRT-D implantation. Recent data highlighted that cardiac computed tomography (CT) or myocardial scar tissue analysis using contrast-enhanced cardiac magnetic resonance (CMR) was able to predict the occurrence of VA in patients with bi-ventricular pacing. Cardiac imaging and specifically myocardial scar analysis seem promising to evaluate the risk of SCD following bi-ventricular pacing and will probably be of great help in the future to accurately identify those who needs concomitant defibrillator's protection.

Radiofrequency ablation of right ventricular tachycardia in patients with no femoral access: safety and efficacy of a superior approach.

AIMS: Ventricular tachycardia (VT) ablation has been proven to be effective and safe to avoid arrhythmia recurrences in patients with repaired congenital heart disease (CHD). However, some of these patients may present right ventricular (RV) access issues [agenesia or thrombosis of inferior vena cava (IVC)], making impossible to access the right ventricle through an inferior approach. In such patients, only a superior approach would theoretically be feasible. METHODS AND RESULTS: All VT ablations performed through a jugular or subclavian approach in CHD patients between 2012 and 2017 were included. Among 247 patients scheduled for VT ablation, two patients underwent three VT ablation procedures via a superior approach for due to the inability to access the right ventricle through a conventional IVC access (IVC interruption with azygos continuation in one patient and IVC thrombosis in the other). Ablation was performed using a three-dimensional system through a superior approach, using a subclavian access in both cases. A redo ablation had to be performed in the first patient using a jugular approach. Large curve catheters were used to facilitate RV outflow tract access. Supposed critical isthmuses could be localized and ablated. Patients remained free from arrhythmias during follow-up. CONCLUSION: In patients with repaired CHD and 'no femoral access', ablation of RV tachycardia can be performed using a subclavian or a jugular approach. Mapping may be challenging, requiring large curve catheters. Conventional isthmuses can be mapped and ablated successfully, and such patients should not be denied radiofrequency ablation.

The second generation cryoballoon has improved durable isolation of left but not right pulmonary veins: new insights from a multicentre study.

Aims: Pulmonary vein isolation (PVI) using second-generation cryoballoon (CB2) is associated with improved outcomes compared with first generation (CB1). We aimed at investigating the characteristics of left and right PV reconnections after CB1 and CB2 ablations in patients with clinical recurrences requiring redo ablation. Methods and results: From 2010 to 2016, 776 patients underwent 28-mm cryoballoon PVI for symptomatic paroxysmal atrial fibrillation (AF) in 3 centres, 279 with CB1 and 497 with CB2. Among them, 94 patients (12.1%) had symptomatic AF recurrences requiring a redo ablation [43 (15.4%) CB1 and 51 (10.3%) CB2]. The benefit of CB2 over CB1 was compared for each PV. Durable PVI was confirmed in 7 CB1 (16.3%) and 14 CB2 (27.4%) patients, and 2.7 ± 2.1 and 1.4 ± 1.4 gaps per patient were found, respectively (P = 0.002). Significantly more left superior and left inferior PVs were found to be isolated in CB2 compared with CB1 group (78.4% vs. 48.8%, P = 0.005 and 78.4% vs. 46.5%, P = 0.003, respectively) while the rate of durable right superior and right inferior PVs isolation were similar (68.6% vs. 60.5%, P = 0.542 and 66.7% vs. 55.8%, P = 0.387, respectively). Significantly fewer gaps were found in left PVs in CB2 patients, while there was no significant difference for right PVs. Gaps localization was similar in both groups. Conclusion: Fewer reconnection gaps are observed during redo ablations of paroxysmal AF in patients primarily ablated with CB2. This difference is driven by less reconnection gaps observed in both left PVs, while no difference was observed for right PVs.

Sex Differences in Autonomic Response to Exercise Testing in Patients with Brugada Syndrome.

INTRODUCTION: Cardiac events in patients with Brugada syndrome (BS) typically occur at rest and mainly during sleep, suggesting that changes in autonomic modulation play an important role in the arrhythmogenesis of the disease. Moreover, sex differences in clinical manifestations of BS have been reported, identifying male patients with worse prognosis. The aim of our work was to assess and compare, according to sex, autonomic response to exercise in a clinical series including 105 BS patients. METHOD: Standard 12-lead electrocardiogram recordings were collected during a physical stress test divided into four phases: warm-up, incremental exercise, active recovery, and passive recovery. Spectral non-stationary heart rate variability indicators were extracted by means of a smoothed pseudo Wigner-Ville distribution approach that adapts frequency bands to respiratory information. These indicators were then averaged in non-overlapped windows of 1 min for each patient to compare groups at each minute of the physical stress test. RESULTS: From the last minute of warm-up and until the third minute of incremental exercise, asymptomatic male patients presented significantly greater low-frequency (LF) values ([Formula: see text]: p = 0.015;[Formula: see text]: p = 0.024; [Formula: see text]: p = 0.011; [Formula: see text]: p = 0.002) than asymptomatic females. Conversely, asymptomatic women showed increased vagal modulation during the first minutes of incremental exercise ([Formula: see text]: p = 0.031; [Formula: see text]: p = 0.001). However, no significant differences were observed between symptomatic male and female patients. CONCLUSION: As previously reported in healthy subjects, enhanced parasympathetic and decreased sympathetic tones appear to be not only greater in women but also defensive during cardiac stress. Based on the results, asymptomatic patients presented same-sex tendencies. However, we observed that symptomatic males developed a more female-like autonomic modulation, probably related to a more protective autonomic response to exercise. These results could be a step forward toward the understanding of the autonomic function in BS along with a potential impact on risk stratification.

Avoiding non-responders to cardiac resynchronization therapy: a practical guide.

Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ∼30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidisciplinary efforts to overcome. Progress has, thus far, been slowed by several factors, ranging from a lack of consensus regarding the definition of NR and technological limitations to the delivery of therapy. We critically review the various endpoints that have been used in landmark clinical trials of CRT, and the variability in response rates that has been observed as a result of these different investigational designs, different sample populations enrolled and different means of therapy delivered, including new means of multisite and left ventricular endocardial simulation. Precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF. Potentially reversible causes of NR to CRT are reviewed, with emphasis on loss of biventricular stimulation due to competing arrhythmias. The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio. These objectives require collaborative efforts by the HF team, the electrophysiologists and the cardiac imaging experts.

Heart rate variability and repolarization characteristics in symptomatic and asymptomatic Brugada syndrome.

AIM: Modulation of ST-segment elevation (STE) and tachyarrhythmic events by the autonomic nervous system (ANS) has been reported in patients with Brugada syndrome (BS). This study examined and compared the autonomic characteristics and STE in symptomatic vs. asymptomatic patients with BS. METHODS AND RESULT: We studied 40 symptomatic and 78 asymptomatic patients (mean age = 46.1 ± 13.7 years; 88 men) who underwent 24 h, 12-lead electrocardiograms, and exercise and a head-up tilt tests. Heart rate variability was examined and STE was measured at 5 points between 100 and 140 ms after the onset of 1 min averaged QRS complexes, and the type 1 Brugada pattern was automatically identified. 'Type 1 Brugada burden' was the percentage of averaged type 1 complexes. All measurements were made over 24 h, and during day and night times. During daytime, the variation coefficients of standard deviation of normal-to-normal intervals were 39.0 ± 12.3 vs. 34.1 ± 14.5 ms (P< 0.05) and high frequency normalized units were 39.9 ± 16.9 vs. 33.9 ± 16.2% (P< 0.05) in symptomatic vs. asymptomatic patients, respectively. ST-segment elevation was similar in symptomatic and asymptomatic patients at all time points. The type 1 Brugada burden in V2 was 38.7 ± 33.6% in the symptomatic vs. 24.3 ± 35.2% in the asymptomatic sample, a statistically non-significant difference. CONCLUSION: This analysis of ANS did not identify sensitive predictors of arrhythmic events in patients with BS. We observed, however, greater fluctuations in sinus node response to ANS in symptomatic patients. The type 1 Brugada electrocardiographic pattern was not as reliable a predictor of arrhythmic risk as previously reported.

Defining nonvalvular atrial fibrillation: A quest for clarification.

Non-vitamin K oral anticoagulants (NOACs) are currently recommended for patients with nonvalvular atrial fibrillation since the publication of the 4 major pivotal trials evaluating the efficacy and safety of factor IIa and factor Xa inhibitors. The definition of nonvalvular atrial fibrillation is unclear, varying from one trial to another and even between North American and European guidelines, which is a source of uncertainties in clinical practice. However, many patients with atrial fibrillation present signs of valvular involvement, and clarification of this term is needed to not deny NOACs to patients based on the wrong perception that they may have valvular atrial fibrillation. The currently unique contraindications to NOACs are patients with mechanical heart valves and those with moderate-to-severe mitral stenosis, as stated by the recent 2015 position paper of the European Heart Rhythm Association. Patients with native heart valve involvement, regardless of their severity, are suitable for NOAC therapy. Patients with bioprosthetic heart valves and mitral valve repair may be suitable for NOACs except for the first 3 and the first 3-6 months postoperatively, respectively. Patients with transaortic valve implantation or percutaneous transluminal aortic valvuloplasty are also considered as being eligible for NOACs, although the bleeding risk has to be carefully considered in this population often requiring a combination with antiplatelet therapy. Future studies are warranted to increase the level of evidence of use of NOACs, particularly in patients with transaortic valve implantation and valvular surgery, and to determine whether they could be used in the future in the only 2 remaining contraindications.

Personalized screening before subcutaneous cardioverter-defibrillator implantation: Usefulness and outcomes in clinical practice-the S-ICD screening SIS prospective study.

BACKGROUND: Electrocardiographic screening before subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure. OBJECTIVE: The objectives of the SIS study were to assess to what extent a personalized screening method improves eligibility for S-ICD implantation and to evaluate the inappropriate shock rate after such screening success. METHODS: All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 and January 2022. In case of traditional screening failure, patients received a second personalized screening. If at least 1 vector was positive, the personalized screening was considered successful, and the patient was eligible for implantation. RESULTS: The study included 474 patients (mean age, 50.4 ± 14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n = 466; P = .002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after 1-year follow-up, 3 of the 7 patients (43%) implanted with personalized screening experienced inappropriate shock vs 18 of the 427 patients (4.2%) with traditional screening and S-ICD implantation (P = .003). CONCLUSION: Traditional S-ICD screening was successful in our study in a high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended. CLINICALTRIALS: gov identifier: NCT04101253.

Expanding indications for resynchronization therapy.

Cardiac resynchronization therapy (CRT) is one of the major advances in the treatment of patients with chronic heart failure due to impaired left ventricular ejection fraction. Current guidelines recommend with the highest levels of recommendation and evidence CRT in patients with low ejection fraction wide QRS, LBBB, and mild to severe heart failure (New York Heart Association class II to IV). However, other patients might benefit from CRT. This is the case for patients with permanent atrial fibrillation, patients conventional pacemaker indication, patients with mildly impaired left ventricular function (>35 %), or asymptomatic patients (NYHA I). We will discuss in this manuscript each new potential indication for CRT.

Multivariate ensemble classification for the prediction of symptoms in patients with Brugada syndrome.

Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients. Graphical abstract Pipeline for feature selection and predictive modeling of symptoms in Brugada syndrome.

Ablation of multifocal premature ventricular contractions using automated pace-mapping software.

INTRODUCTION AND OBJECTIVES: Ablation of multifocal premature ventricular complexes (PVCs) is challenging. Activation mapping can be performed for the predominant morphology, but may be useless for other less prevalent ones. We aimed to describe the efficacy of an automated pace-mapping software-based ablation strategy for ablating the site of origin of multiple PVC locations. METHODS: Consecutive patients referred for ablation of multifocal PVCs were prospectively enrolled. Spontaneous PVC templates were recorded and a detailed pace-mapping map was generated to spot the site of origin of PVCs. RESULTS: A total of 47 PVCs were targeted in 21 patients (five and 16 patients with three or two PVCs morphologies each, respectively). Detailed pace-mapping comprising 73.5±41.6 different pacing locations was performed (best matching 97.2% [IQR 95.9-98.3%] similar to the clinical PVC). Activation points were acquired if possible, although ablation was only based on pace-mapping in 13 (27.6%) foci. Complete acute procedural success was obtained in 14 (66.7%) patients, while one PVC morphology was deliberately not ablated in five patients (23.8%). After 12.3±9.4 months of follow-up, PVC burden decreased from 24.4±10.4% to 5.6±5.0% (p<0.001). Interestingly, patients with acute procedural failures or with some PVCs deliberately not targeted during the procedure also experienced a significant decrease in PVC burden (30.0±8.9% to 11.9±3.5%, p=0.002). CONCLUSION: Quantitative morphology-matching software can be used to obtain a detailed map identifying the site of origin of each single PVC, and successful ablation can be performed at these sites, even if activation points cannot be obtained due to the paucity of ectopic beats.

Septal versus apical pacing sites in permanent right ventricular pacing: The multicentre prospective SEPTAL-PM study.

BACKGROUND: The optimal right ventricular pacing site for patients requiring pacemaker implantation for permanent atrioventricular block is a matter of debate. Long-term right ventricular apical pacing has been associated with left ventricular ejection fraction impairment and heart failure. Right ventricular septal pacing has been proposed as an alternative. AIM: The aim of this randomized prospective multicentre trial was to compare left ventricular remodelling and outcomes between right ventricular apical and septal pacing after mid-term follow-up. METHODS: Patients requiring pacemaker implantation for high-degree atrioventricular block were enrolled and randomized in a 1:1 fashion to receive a right ventricular apical or septal lead. RESULTS: A total of 141 patients were included, 69 in the septal group and 72 in the apical group. Both groups exhibited similar left ventricular ejection fractions after 18 months of follow-up (septal 57.1±11.9% vs. apical 57.4±13.4%), and left ventricular ejection fraction variation was similar in the two groups at the end of follow-up (septal -1.5±13.2% vs. apical 0.3±13.3%). Additionally, left ventricular volume, quality of life and 6-minute walk distance were similar in the two groups. However, patients in the septal group were more likely to be asymptomatic, with a significantly lower concentration of N-terminal prohormone of brain natriuretic peptide. Lastly, lead position did not impact 18-month survival. CONCLUSION: Pacing from the right ventricular apex does not have any detrimental effect on left ventricular systolic function compared with septal pacing over an 18-month period.

Electrophysiological Study-Guided Permanent Pacemaker Implantation in Patients With Conduction Disturbances Following Transcatheter Aortic Valve Implantation.

Conduction disturbances remain common following transcatheter aortic valve implantation (TAVI). Aside from high-degree atrioventricular block (HAVB), their optimal management remains elusive. Invasive electrophysiological studies (EPS) may help stratify patients at low or high risk of HAVB allowing for an early discharge or permanent pacemaker (PPM) implantation among patients with conduction disturbances. We evaluated the safety and diagnostic performances of an EPS-guided PPM implantation strategy among TAVI recipients with conduction disturbances not representing absolute indications for PPM. All patients who underwent TAVI at a single expert center from June 2017 to July 2020 who underwent an EPS during the index hospitalization were included in the present study. False negative outcomes were defined as patients discharged without PPM implantation who required PPM for HAVB within 6 months of the initial EPS. False positive outcomes were defined as patients discharged with a PPM with a ventricular pacing percentage <1% at follow-up. A total of 78 patients were included (median age 83.5, 39% female), among whom 35 patients (45%) received a PPM following EPS. The sensitivity, specificity, positive and negative predictive values of the EPS-guided PPM implantation strategy were 100%, 89.6%, 81.5%, and 100%, respectively. Six patients suffered a mechanical HAVB during EPS and received a PPM. These 6 patients showed PPM dependency at follow-up. In conclusion, an EPS-guided PPM implantation strategy for managing post-TAVI conduction disturbances appears effective to identify patients who can be safely discharged without PPM implantation.

Dynamic changes in ventricular depolarization during exercise in patients with Brugada syndrome.

Brugada syndrome (BS) is a genetic pathological condition associated with a high risk for sudden cardiac death (SCD). Ventricular depolarization disorders have been suggested as a potential electrophysiological mechanism associated with high SCD risk on patients with BS. This paper aims to characterize the dynamic changes of ventricular depolarization observed during physical exercise in symptomatic and asymptomatic BS patients. To this end, cardiac ventricular depolarization features were automatically extracted from 12-lead ECG recordings acquired during standardized exercise stress test in 110 BS patients, of whom 25 were symptomatic. Conventional parameters were evaluated, including QRS duration, R and S wave amplitudes ([Formula: see text], [Formula: see text]), as well as QRS morphological features, such as up-stroke and down-stroke slopes of the R and S waves ([Formula: see text], [Formula: see text] and [Formula: see text]). The effects of physical exercise and recovery on the dynamics of these markers were assessed in both BS populations. Features showing significantly different dynamics between the studied groups were used alone and in combination with the clinical characteristics of the patients in a logistic regression analysis. Results show larger changes in the second half of the QRS complex through [Formula: see text] and [Formula: see text] measured in the right precordial leads for asymptomatic patients, especially during recovery, when the vagal tone is more pronounced. Multivariate analysis involving both types of features resulted in a reduced model of three relevant features ([Formula: see text] in lead V2, Sex and heart rate recovery, HRR), which achieved a suitable discrimination performance between groups; sensitivity = 80% and specificity = 75% (AUC = 83%). However, after controlling the model for possible confounding factors, only one feature ([Formula: see text]) remained meaningful. This adjusted model significantly improved the overall discrimination performance by up to: sensitivity = 84% and specificity = 100% (AUC = 94%). The study highlights the importance of physical exercise test to unmask differentiated behaviors between symptomatic and asymptomatic BS patients through depolarization dynamic analysis. This analysis together with the obtained model may help to identify asymptomatic patients at low or high risk of future cardiac events, but it should be confirmed by further prospective studies.