Coarse-Grained Effective Hamiltonian via the Magnus Expansion for a Three-Level System.

Quantum state processing is one of the main tools of quantum technologies. While real systems are complicated and/or may be driven by non-ideal control, they may nevertheless exhibit simple dynamics approximately confined to a low-energy Hilbert subspace. Adiabatic elimination is the simplest approximation scheme allowing us to derive in certain cases an effective Hamiltonian operating in a low-dimensional Hilbert subspace. However, these approximations may present ambiguities and difficulties, hindering a systematic improvement of their accuracy in larger and larger systems. Here, we use the Magnus expansion as a systematic tool to derive ambiguity-free effective Hamiltonians. We show that the validity of the approximations ultimately leverages only on a proper coarse-graining in time of the exact dynamics. We validate the accuracy of the obtained effective Hamiltonians with suitably tailored fidelities of quantum operations.

High-risk Brugada syndrome: factors associated with arrhythmia recurrence and benefits of epicardial ablation in addition to implantable cardioverter defibrillator implantation.

AIMS: This study aims to evaluate the prognostic impact of the arrhythmogenic substrate size in symptomatic Brugada syndrome (BrS) as well as to validate the long-term safety and effectiveness of epicardial radiofrequency ablation (RFA) compared with no-RFA group. METHODS AND RESULTS: In this prospective investigational long-term registry study, 257 selected symptomatic BrS patients with implantable cardioverter defibrillator (ICD) implantation were included. Among them, 206 patients underwent epicardial RFA and were monitored for over 5 years post-ablation (RFA group), while 51 patients received only ICD implantation declining RFA. Primary endpoints included risk factors for ventricular fibrillation (VF) events pre-ablation and freedom from VF events post-ablation. In the RFA group, BrS substrates were identified in the epicardial surface of the right ventricle. During the pre-RFA follow-up period (median 27 months), VF episodes and VF storms were experienced by 53 patients. Independent risk factors included substrate size [hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.08-1.18; P < 0.001], aborted cardiac arrest (HR, 2.98; 95% CI, 1.68-5.28; P < 0.001), and SCN5A variants (HR, 2.22; 95% CI, 1.15-4.27; P = 0.017). In the post-RFA follow-up (median 40 months), the RFA group demonstrated superior outcomes compared with no-RFA (P < 0.001) without major procedure-related complications. CONCLUSION: Our study underscores the role of BrS substrate extent as a crucial prognostic factor for recurrent VF and validates the safety and efficacy of RFA when compared with a no-RFA group. Our findings highlight the importance of ajmaline in guiding epicardial mapping/ablation in symptomatic BrS patients, laying the groundwork for further exploration of non-invasive methods to guide informed clinical decision-making.

Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

Brugada syndrome genetics is associated with phenotype severity.

AIMS: Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. METHODS AND RESULTS: Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. CONCLUSION: In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Novel SCN5A p.V1429M Variant Segregation in a Family with Brugada Syndrome.

Brugada syndrome (BrS) is diagnosed by the presence of an elevated ST-segment and can result in sudden cardiac death. The most commonly found mutated gene is SCN5A, which some argue is the only gene that has been definitively confirmed to cause BrS, while the potential causative effect of other genes is still under debate. While the issue of BrS genetics is currently a hot topic, current knowledge is not able to result in molecular confirmation of over half of BrS cases. Therefore, it is difficult to develop research models with wide potential. Instead, the clinical genetics first need to be better understood. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.4285G>A (p.Val1429Met) in the SCN5A gene, and demonstrate its segregation with BrS, suggesting a pathogenic effect. These results provide the first disease association with this variant and are crucial clinical data to communicate to basic scientists, who could perform functional studies to better understand the molecular effects of this clinically-relevant variant in BrS.

Novel CineECG Derived From Standard 12-Lead ECG Enables Right Ventricle Outflow Tract Localization of Electrical Substrate in Patients With Brugada Syndrome.

BACKGROUND: In Brugada syndrome (BrS), diagnosed in presence of a spontaneous or ajmaline-induced type-1 pattern, ventricular arrhythmias originate from the right ventricle outflow tract (RVOT). We developed a novel CineECG method, obtained by inverse electrocardiogram (ECG) from standard 12-lead ECG, to localize the electrical activity pathway in patients with BrS. METHODS: The CineECG enabled the temporospatial localization of the ECG waveforms, deriving the mean temporospatial isochrone from standard 12-lead ECG. The study sample included (1) 15 patients with spontaneous type-1 Brugada pattern, and (2) 18 patients with ajmaline-induced BrS (at baseline and after ajmaline), in whom epicardial potential duration maps were available; (3) 17 type-3 BrS pattern patients not showing type-1 BrS pattern after ajmaline (ajmaline-negative); (4) 47 normal subjects; (5) 18 patients with right bundle branch block (RBBB). According to CineECG algorithm, each ECG was classified as Normal, Brugada, RBBB, or Undetermined. RESULTS: In patients with spontaneous or ajmaline-induced BrS, CineECG localized the terminal mean temporospatial isochrone forces in the RVOT, congruent with the arrhythmogenic substrate location detected by epicardial potential duration maps. The RVOT location was never observed in normal, RBBB, or ajmaline-negative patients. In most patients with ajmaline-induced BrS (78%), the RVOT location was already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as Normal or Undetermined, all patients with RBBB as RBBB, whereas all patients with spontaneous and ajmaline-induced BrS as Brugada. Compared with standard 12-lead ECG, CineECG at baseline had a 100% positive predictive value and 81% negative predictive value in predicting ajmaline test results. CONCLUSIONS: In patients with spontaneous and ajmaline-induced BrS, the CineECG localized the late QRS activity in the RVOT, a phenomenon never observed in normal, RBBB, or ajmaline-negative patients. The possibility to identify the RVOT as the location of the arrhythmogenic substrate by the noninvasive CineECG, based on the standard 12-lead ECG, opens new prospective for diagnosing patients with BrS.

Optimized three-level quantum transfers based on frequency-modulated optical excitations.

The difficulty in combining high fidelity with fast operation times and robustness against sources of noise is the central challenge of most quantum control problems, with immediate implications for the realization of quantum devices. We theoretically propose a protocol, based on the widespread stimulated Raman adiabatic passage technique, which achieves these objectives for quantum state transfers in generic three-level systems. Our protocol realizes accelerated adiabatic following through the application of additional control fields on the optical excitations. These act along frequency sidebands of the principal adiabatic pulses, dynamically counteracting undesired transitions. The scheme facilitates experimental control, not requiring new hardly-accessible resources. We show numerically that the method is efficient in a very wide set of control parameters, bringing the timescales closer to the quantum speed limit, also in the presence of environmental disturbance. These results hold for complete population transfers and for many applications, e.g., for realizing quantum gates, both for optical and microwave implementations. Furthermore, extensions to adiabatic passage problems in more-level systems are straightforward.

Genotype-Phenotype Correlation in a Family with Brugada Syndrome Harboring the Novel p.Gln371* Nonsense Variant in the SCN5A Gene.

Brugada syndrome (BrS) is marked by coved ST-segment elevation and increased risk of sudden cardiac death. The genetics of this syndrome are elusive in over half of the cases. Variants in the SCN5A gene are the single most common known genetic unifier, accounting for about a third of cases. Research models, such as animal models and cell lines, are limited. In the present study, we report the novel NM_198056.2:c.1111C>T (p.Gln371*) heterozygous variant in the SCN5A gene, as well as its segregation with BrS in a large family. The results herein suggest a pathogenic effect of this variant. Functional studies are certainly warranted to characterize the molecular effects of this variant.

Non-invasive assessment of the arrhythmogenic substrate in Brugada syndrome using signal-averaged electrocardiogram: clinical implications from a prospective clinical trial.

AIMS: Brugada syndrome (BrS) represents a major cause of sudden cardiac death in young individuals. The risk stratification to forecast future life-threatening events is still controversial. Non-invasive assessment of late potentials (LPs) has been proposed as a risk stratification tool. However, their nature in BrS is still undetermined. The purpose of this study is to assess the electrophysiological determinants of non-invasive LPs. METHODS AND RESULTS: Two hundred and fifty consecutive patients with (Group 1, n = 96) and without (Group 2, n = 154) BrS-related symptoms were prospectively enrolled in the registry. Signal-averaged electrocardiogram (SAECG) was performed in all subjects before undergoing epicardial mapping. Group 1 patients exhibited larger arrhythmogenic substrates (AS; 5.8 ± 2.8 vs. 2.6 ± 2.1 cm2, P < 0.001) with more delayed potentials (220.4 ± 46.0 vs. 186.7 ± 42.3 ms, P < 0.001). Late potentials were present in 82/96 (85.4%) Group 1 and in 31/154 (20.1%) Group 2 individuals (P < 0.001). Patients exhibiting LPs had more frequently a spontaneous Type 1 pattern (30.1% vs. 10.9%, P < 0.001), SCN5A mutation (34.5% vs. 21.2%, P = 0.02), and exhibited a larger AS with longer potentials (5.8 ± 2.7 vs. 2.2 ± 1.7 cm2; 231.2 ± 37.3 vs. 213.8 ± 39.0 ms; P < 0.001, respectively). Arrhythmogenic substrate dimension was the strongest predictor of the presence of LPs (odds ratio 1.9; P < 0.001). An AS area of at least 3.5 cm2 identified patients with LPs (area under the curve 0.88, 95% confidence interval 0.843-0.931; P < 0.001) with a sensitivity of 86%, specificity 88%, positive predictive value 85%, and negative predictive value 89%. CONCLUSION: The results of this study support the role of the epicardial AS as an electrophysiological determinant of non-invasive LPs, which may serve as a tool in the non-invasive assessment of the BrS substrate, as SAECG-LPs could be considered an expression of the abnormal epicardial electrical activity.ClinicalTrials.gov number (NCT02641431; NCT03106701).

Novel SCN5A p.W697X Nonsense Mutation Segregation in a Family with Brugada Syndrome.

Brugada syndrome (BrS) is marked by an elevated ST-segment elevation and increased risk of sudden cardiac death. Variants in the SCN5A gene are considered to be molecular confirmation of the syndrome in about one third of cases, while the genetics remain a mystery in about half of the cases, with the remaining cases being attributed to variants in any of a number of genes. Before research models can be developed, it is imperative to understand the genetics in patients. Even data from humans is complicated, since variants in the most common gene in BrS, SCN5A, are associated with a number of pathologies, or could even be considered benign, depending on the variant. Here, we provide crucial human data on a novel NM_198056.2:c.2091G>A (p.Trp697X) point-nonsense heterozygous variant in the SCN5A gene, as well as its segregation with BrS. The results herein suggest a pathogenic effect of this variant. These results could be used as a stepping stone for functional studies to better understand the molecular effects of this variant in BrS.

Comparable clinical characteristics in Brugada syndrome patients harboring SCN5A or novel SCN10A variants.

AIMS: The Brugada syndrome (BrS) is an inherited disease associated with an increased risk of sudden cardiac death. Often, the genetic cause remains undetected. Perhaps due at least in part because the NaV1.8 protein is expressed more in both the central and peripheral nervous systems than in the heart, the SCN10A gene is not included in diagnostic arrhythmia/sudden death panels in the vast majority of cardiogenetics centres. METHODS AND RESULTS: Clinical characteristics were assessed in patients harboring either SCN5A or novel SCN10A variants. Genetic testing was performed using Next Generation Sequencing on genomic DNA. Clinical characteristics, including the arrhythmogenic substrate, in BrS patients harboring novel SCN10A variants and SCN5A variants are comparable. Clinical characteristics, including gender, age, personal history of cardiac arrest/syncope, spontaneous BrS electrocardiogram pattern, family history of sudden death, and arrhythmic substrate are not significantly different between probands harboring SCN10A or SCN5A variants. CONCLUSION: Future studies are warranted to further characterize the role of these specific SCN10A variants.

Novel SCN5A Frameshift Mutation in Brugada Syndrome Associated With Complex Arrhythmic Phenotype.

In this case report, we characterize a novel inherited frameshift mutation c.4700_4701del (p.Phe1567Cysfs*221) in a single copy of the SCN5A gene and its association with Brugada syndrome (BrS). The proband experienced a life-threatening ventricular arrhythmia successfully treated with DC-shock and he also suffered from supraventricular tachycardia. Ajmaline test confirmed the BrS diagnosis. No other mutation nor low frequency variants in the other 23 analyzed genes were detected. The same mutation was found in the father and sister, who were both diagnosed with BrS. We hypothesize that this mutation could be responsible for BrS and potentially linked to supraventricular tachycardias. Further studies are needed to confirm this observation and to assess the clinical relevance of this mutation, in terms of risk-stratification.

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis.

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction.

Multipoint left ventricular pacing improves response to cardiac resynchronization therapy with and without pressure-volume loop optimization: comparison of the long-term efficacy of two different programming strategies.

PURPOSE: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP]) improves long-term LV reverse remodeling, though questions persist about how to program LV pacing vectors and delays. We evaluated if an empirical method of programming MPP vectors and delays between pacing pulses improved CRT response similar to pressure-volume loop (PVL) optimized MPP programming. METHODS: Patients undergoing CRT implant (Quadra Assura MP™ CRT-D and Quartet™ LV lead) received MPP with programmed settings optimized either by PVL measurements at implant (PVL-OPT group) or empirically determined by maximizing the spatial separation between the two cathodes and minimal delays between the three ventricular pacing pulses (MAX-SEP group). CRT response was prospectively defined as a reduction in end-systolic volume (ESV) of ≥ 15% relative to baseline at 6 months as determined by a blinded observer. RESULTS: Patient characteristics at baseline (NYHA II-III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17 ms) were not significantly different between the PVL-OPT (n = 27) and MAX-SEP (n = 26) groups. During the follow-up period, there were no differences in the number of patients requiring reprogramming due to phrenic nerve stimulation or a high threshold for PVL-OPT vs. MAX-SEP (5/27 [19%] vs. 7/26 [27%], p = 0.53). After 6 months, ESV reduction, EF increase, and CRT response rate (RR) were similar for PVL-OPT vs. MAX-SEP (ESV - 20 ± 11 vs. - 22 ± 11%, p = 0.59; EF + 10 ± 4 vs. + 9 ± 7%, p = 0.53; RR 20/27 [74%] vs. 21/26 [81%], p = 0.74), while fewer patients in the PVL-OPT group experienced NYHA class reduction ≥ 2 (4/27 [15%] vs.15/26 [58%], p = 0.002). CONCLUSIONS: Both evaluated methods of MPP programming resulted in similar CRT outcomes. Empirical MPP programming by maximum spatial separation of LV cathodes may be an effective, simple, and non-invasive alternative to pressure-volume optimization.

General Anesthesia Attenuates Brugada Syndrome Phenotype Expression: Clinical Implications From a Prospective Clinical Trial.

OBJECTIVES: This study investigates the electrocardiographic-electrophysiological effects of administration of anesthetic drugs for general anesthesia (GA) in patients with BrS at high risk of sudden cardiac death (SCD). BACKGROUND: The safety of anesthetic agents in Brugada syndrome (BrS) is under debate. METHODS: All consecutive patients with spontaneous type 1 BrS electrocardiographic (ECG) patterns undergoing epicardial ablation of the arrhythmogenic substrate (AS) under GA were enrolled. Anesthesia was induced with single bolus of propofol and maintained with sevofluorane. ECG measurements were collected before, immediately after, and 20 min after induction of GA. Three-dimensional maps during GA and after ajmaline indicated the epicardial AS before ablation. RESULTS: Thirty-six patients with BrS (32 male, 88.9%; mean age 38.8 ± 12.0 years) with a spontaneous type 1 ECG pattern underwent GA. Induction was performed using propofol at mean dose of 1.6 to 2.6 mg/kg (2.1 ± 0.3 mg/kg). Twenty-eight (28 of 36, 77.8%) patients showed a reversion to a nondiagnostic pattern. ST-segment elevation (0.32 ± 0.01 mV vs. 0.19 ± 0.02 mV; p < 0.001) and J-wave amplitude (0.47 ± 0.02 mV vs. 0.31 ± 0.03 mV; p < 0.001) decreased after propofol. The AS area during GA, in the absence of BrS pattern, significantly enlarged after administration of ajmaline (3.6 ± 0.5 cm2 vs. 20.3 ± 0.8 cm2). No patient developed malignant arrhythmias during GA induction and maintenance. CONCLUSIONS: This study shows that GA using single-bolus propofol and volatile anesthetics is safe in high-risk patients with BrS, and it may exert a modulating effect by reducing the manifestation of type 1 BrS pattern and AS in the form of epicardial abnormal ECGs. (Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701).

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome.

BACKGROUND: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. OBJECTIVES: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. METHODS: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome-related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). RESULTS: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. CONCLUSIONS: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701).

Clinical Outcome of Electrophysiologically Guided Ablation for Nonparoxysmal Atrial Fibrillation Using a Novel Real-Time 3-Dimensional Mapping Technique: Results From a Prospective Randomized Trial.

BACKGROUND: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome. METHODS AND RESULTS: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P<0.007). Total radiofrequency duration (P=0.38), mapping (P=0.46), and fluoroscopy times (P=0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group (P=0.03). CONCLUSIONS: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT02571218.

Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome.

BACKGROUND: There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. METHODS AND RESULTS: A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right ventricle epicardium, which were wider in group 1 (P=0.007). AES increased after ajmaline in both groups (P<0.001) and was larger in men (P=0.008). The increase of type-1 ST-segment elevation correlated with AES expansion (r=0.682, P<0.001). Radiofrequency ablation eliminated AES leading to ECG normalization and VT/VF noninducibility in all patients. During a median follow-up of 10 months, the ECG remained normal even after ajmaline in all except 2 patients who underwent a repeated effective procedure for recurrent VF. CONCLUSIONS: In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02641431.

Atrial fibrillation detection using a novel three-vector cardiac implantable monitor: the atrial fibrillation detect study.

AIMS: Continuous rhythm monitoring is valuable for adequate atrial fibrillation (AF) management in the clinical setting. Subcutaneous leadless implantable cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic limitations of the currently available external recording systems, thus resulting in a more accurate patient treatment. The study purpose was to assess the detection performance of a novel three-vector ICM device equipped with a dedicated AF algorithm. METHODS AND RESULTS: Sixty-six patients (86.4% males; mean age 60.4 ± 9.4 years) at risk to present AF episodes, having undergone the novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were enrolled. External 48-h ECG Holter was performed 4 weeks after the device implantation. The automatic ICM AF classification was compared with the manual Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had analysable Holter data, 39/63 (62%) showed at least one true AF episode. All these patients had at least one AF episode stored in the ICM. On Holter monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24, 67%), the ICM confirmed the absence of AF. The AF detection sensitivity and positive predictive value for episodes' analysis were 95.4 and 76.3%, respectively. CONCLUSION: Continuous monitoring using this novel device, equipped with a dedicated detection algorithm, yields an accurate and reliable detection of AF episodes. The ICM is a promising tool for tailoring individual AF patient management. Further long-term prospective studies are necessary to confirm these encouraging results.