Search

Short-coupled idiopathic ventricular fibrillation (SC-IVF) is a rare, life-threatening arrhythmia, accountable for 5–10% of out-of-hospital cardiac arrests (OHCA). Catheter ablation of the short-coupled premature ventricular contraction (PVC) that triggers VF has been shown to prevent VF recurrences in outdated case series. Aim To evaluate the clinical outcome and summarize the recent experience of 3D electrophysiological mapping and radiofrequency catheter ablation (RFCA) of SC-IVFs in a tertiary high-volume referral centre. Methods from January 2016, we enrolled all consecutive patients diagnosed with SC-IVF and treated by RFCA. Structural heart disease was excluded in all patients by means of echocardiography, cardiac magnetic resonance, coronary angiography, and exercise test. Brugada syndrome and long QT syndrome were excluded by Ajmaline and Epinephrine tests, respectively. The CARTO system was used to construct detailed 3D electroanatomic maps of the right and left ventricle. Mapping and ablation were performed with a standard 3.5- irrigated tip catheter. The PVCs were localized by mapping the earliest bipolar electrogram relative to the onset of the ectopic surface QRS (confirmed by QS complex in the unipolar configuration). Pace mapping was used in patients with infrequent PVCs. The origin of PVCs from fascicles/Purkinje network was indicated by initial sharp potentials preceding the ectopic QRS complex. The procedural end point was the abolition of all clinical PVCs. Outcome (freedom from SC-PVCs and VF episodes) was assessed by Holter monitoring and defibrillator memory interrogation. Results eleven consecutive patients [8 men, 3 women; median age 41 (± 5 years)] were enrolled. 10/11 patients (91%) were asymptomatic prior the index VF event, while 1 patient (9%) experienced recurrent syncope. An aborted OHCA was the index event in all patients. Arrhythmic storm was observed at the index presentation in 2 patients (18%). No patient had family history of sudden cardiac death. All patients were implanted with an ICD after the index event. The delay in SC-IVF diagnosis was 3 (± 2 years) from the index event. 2 patients (18%) had ≥ 2 SC-PVC morphologies. The mean coupling interval (CI) of the SC-PVCs ranged from 230 to 330 msec (mean 303 ± 26 msec). The CI/QT ratio ranged from 0.6 to 1 (mean 0.81 ± 0.15). 10 patients underwent RFCA for recurrent VF/ICD shocks and 1 patient for refractory electrical storm. RFCA was based on activation mapping, pace-mapping, and both in 1 (9%), 1 (9%), and 9 (82%) patients, respectively. The sites of ablation were LV Purkinje, RV Purkinje, RV non-Purkinje (RV outflow tract and tricuspid annulus), and LV non-Purkinje (LV Summit) in 3 (27%), 4 (36%), 3 (27%), and 1 (9%) patient, respectively. The first ablation was acutely successful in all patients. 1 patient experienced recurrence of SC-PVCs and VF episodes after 5 days from the first ablation and underwent a second RFCA. There were no peri-procedural complications. After a median follow-up of 22 months (ranging from 6 to 39 months) all patients were free from sustained ventricular arrhythmia recurrences: 10 patients (91%) were free from VF and PVCs; 1 patient (9%) had recurrent SC-PVCs without VF episodes. Conclusions this retrospective study explored the effectiveness of RFCA combined with the advanced electroanatomic mapping in a current cohort of patients with history of OHCA diagnosed with SC-IVF. RFCA of SC-PVCs was safe and highly effective in abolishing VF episodes in all patients.

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.

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.

Quantum networks using photonic channels require control of the interactions between the photons, carrying the information, and the elements comprising the nodes. In this work we theoretically analyse the spectral properties of an optical photon emitted by a solid-state quantum memory, which acts as a converter of a photon absorbed in another frequency range. We determine explicitly the expression connecting the stored and retrieved excitation taking into account possible mode and phase mismatch of the experimental setup. The expression we obtain describes the output field as a function of the input field for a transducer working over a wide range of frequencies, from optical-to-optical to microwave-to-optical. We apply this result to analyse the photon spectrum and the retrieval probability as a function of the optical depth for microwave-to-optical transduction. In the absence of losses, the efficiency of the solid-state quantum transducer is intrinsically determined by the capability of designing the retrieval process as the time-reversal of the storage dynamics., Comment: 14 pages, 4 figures; To appear in Phys Rev A

Quantum Optimal Control is an established field of research which is necessary for the development of Quantum Technologies. In recent years, Machine Learning techniques have been proved usefull to tackle a variety of quantum problems. In particular, Reinforcement Learning has been employed to address typical problems of control of quantum systems. In this tutorial we introduce the methods of Quantum Optimal Control and Reinforcement Learning by applying them to the problem of three-level population transfer. The jupyter notebooks to reproduce some of our results are open-sourced and available on github., Comment: 15 pages, 11 figures

Dynamically probing systems of ultrastrongly coupled light and matter by advanced coherent control have been recently proposed as a unique tool for detecting peculiar quantum features of this regime. Coherence allows in principle on-demand conversion of virtual photons dressing the entangled eigenstates of the system to real ones, with unitary efficiency and remarkable robustness. Here, we study this effect in the presence of decoherence, showing that also in far from ideal regimes is it possible to probe such peculiar features.

openaire: EC/H2020/766900/EU//TEQ Funding Information: Original content from this work may be used under the terms of the . Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. EU H2020 framework through Collaborative Projects TEQ 766900 COST Action CA15220 International Mobility Programme DfE-SFI Investigator Programme 15/IA/2864 Royal Society Wolfson Research Fellowship scheme RSWF\R3\183013 Engineering and Physical Sciences Research Council https://doi.org/10.13039/501100000266 EP/T028106/1 Academy of Finland https://doi.org/10.13039/501100002341 QuantERA grant SiUCs 731473 QuantERA Leverhulme Trust Research Project Grant UltraQute RGP-2018-266 Foundational Questions Institute Fund(“Exploring the fundamental limits set by thermodynamics in the quantum regime”) FQXi-IAF19-06 yes � 2021 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft Creative Commons Attribution 4.0 licence Publisher Copyright: © 2021 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft. We deploy a combination of reinforcement learning-based approaches and more traditional optimization techniques to identify optimal protocols for population transfer in a multi-level system. We constrain our strategy to the case of fixed coupling rates but time-varying detunings, a situation that would simplify considerably the implementation of population transfer in relevant experimental platforms, such as semiconducting and superconducting ones. Our approach is able to explore the space of possible control protocols to reveal the existence of efficient protocols that, remarkably, differ from (and can be superior to) standard Raman, stimulated Raman adiabatic passage or other adiabatic schemes. The new protocols that we identify are robust against both energy losses and dephasing.

Patients with COVID-19 frequently have non-typical ECG changes in the QRS and T-wave morphology. The novel CineECG uses using the mean temporal spatial isochrones (mTSI) to relate the activation and recovery pathway to the cardiac anatomy. The aim of this feasib ility study is to use the novel CineECG to separate normal from abnormal ECGs. The ECGs of 100 normal controls were used to obtain the normal mTSI paths values for the QRS, ST segment and T-wave. These normal CineECG values were used to classify the COVID-19 ECGs as either as normal or abnormal of 107 patients being treatedfor COVID-19 in the University Medical Center Utrecht. The CineECG was able to classify 98% of the normal ECG correctly and 94% of the abnormal ECG in comparison to expert ECG classifications. The ability of the CineECG to relate the ECG to the cardiac anatomy supports the detection of abnormal ECGs. The CineECG might be a novel ECG screening tool to detect potential cardiac involvement of the COVID-19 disease for non-ECG experts.

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.

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.

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. Methods 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 3452 ± 26.4 vs Group 2436.3 ± 28.4 vs Group 1424.4 ± 24.3 ms, respectively; p, Highlights • Only the use of HCQ in combination with AZT causes a significant increase of QT interval. • Older patients are at higher risk of prolonged QT when treated with HCQ with/without AZT. • The use of HCQ alone or in combination with AZT might be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients.

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.

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.

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 2 vs. 20.3 ± 0.8 cm 2 ). 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).

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.

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 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).

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.

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.

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 6months as determined by a blinded observer. Results: Patient characteristics at baseline (NYHA II–III, ejection fraction [EF] 27 ± 6%, QRS 151 ± 17ms) 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 6months, 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.

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.

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)

Attenuated laser pulses are often employed in place for single photons in order to test the efficiency of the elements of a quantum network. In this work we analyse theoretically the dynamics of storage of an attenuated light pulse (where the pulse intensity is at the single photon level) propagating along a transmission line and impinging on the mirror of a high finesse cavity. Storage is realised by the controlled transfer of the photonic excitations into a metastable state of an atom confined inside the cavity and occurs via a Raman transition with a suitably tailored laser pulse, which drives the atom and minimizes reflection at the cavity mirror. We determine the storage efficiency of the weak coherent pulse which is reached by protocols optimized for single-photon storage. We determine the figures of merit and we identify the conditions on an arbitrary pulse for which the storage dynamics approaches the one of a single photon. Our formalism can be extended to arbitrary types of input pulses and to quantum memories composed by spin ensembles, and serves as a basis for identifying the optimal protocols for storage and readout., Comment: 9 pages, 3 figures

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 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.

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).The safety of anesthetic agents in Brugada syndrome (BrS) is under debate.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.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 cmThis 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).

Background Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. Objective The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. Methods Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure–volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. Results Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders ( P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median –25%, interquartile range [IQR] [–39% to –20%] vs median –18%, IQR [–25% to –2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [–1% to 8%], P Conclusion Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

The aim of this article is to understand the natural history of WPW syndrome to prevent sudden death is important to clinicians in establishing accurate prognosis and appropriate treatment. We report our experience on untreated WPW patients purely looking at the natural history of the disease. In a 15-year period (1995-2010), among 11 237 WPW patients referred to our Arrhythmology Department, a total of 1847 selected patients (820 symptomatic) underwent electrophysiological testing without ablation and were followed for a median (25th-75th) follow-up of 8 (5-8) years. During follow-up, malignant arrhythmias (MA) occurred in 16 patients (0.9%) of whom 14 (1.4%) were initially asymptomatic and two (0.2%) symptomatic (P = 0.01). Potentially MA developed in 143 patients (7.7%) without difference between asymptomatic and symptomatic population (P = 0.663). Benign recurrences developed in 295 patients (16%) while ventricular pre-excitation disappeared in 356 patients (19.3%) of whom 155 were initially asymptomatic. All patients were successfully ablated after arrhythmia occurrence. Patients with MA had similar accessory pathways antegrade refractory periods (AP-AERP) (P = 0.064) and more frequently inducible atrioventricular reciprocating tachycardia triggering atrial fibrillation (AVRT-AF) than those with potentially MA (P < 0.001). Symptoms did not predict MA, which were predicted by AP-AERP (HR 0.912, 95% CI 0.887-0.939, P < 0.001) and AVRT-AF (HR 8.306, 95% CI 2.269-30.405, P = 0.001). The natural history of WPW syndrome and the risk of sudden death essentially depend on intrinsic electrophysiological accessory pathway properties rather than on symptoms and electrophysiologic testing is the gold standard to identify patients at risk. The Authors encourage more intensive screening programs to identify asymptomatic patients at risk for prophylactic ablation.

Multipoint LV Pacing Improves Mid-Term CRT Response Introduction Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT. Methods and Results Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: −21.0 ± 13.9 vs. −12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P < 0.001; ΔNYHA: −1.05 ± 0.22 vs. −0.72 ± 0.46 functional classes, P = 0.006). Conclusion PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT.

We theoretically analyse the cooling dynamics of a high-Q mode of a mechanical resonator, when the structure is also an optical cavity and is coupled with a NV center. The NV center is driven by a laser and interacts with the cavity photon field and with the strain field of the mechanical oscillator, while radiation pressure couples mechanical resonator and cavity field. Starting from the full master equation we derive the rate equation for the mechanical resonator's motion, whose coefficients depend on the system parameters and on the noise sources. We then determine the cooling regime, the cooling rate, the asymptotic temperatures, and the spectrum of resonance fluorescence for experimentally relevant parameter regimes. For these parameters, we consider an electronic transition, whose linewidth allows one to perform sideband cooling, and show that the addition of an optical cavity in general does not improve the cooling efficiency. We further show that pure dephasing of the NV center's electronic transitions can lead to an improvement of the cooling efficiency., Comment: 10 pages, 9 figures. To appear in Phys. Rev. A

Nonirrigated magnetic ablation may result in potential char, ineffective lesions, and longer procedure times.This study sought to report the safety and long-term efficacy of irrigated-tip magnetic ablation of atrial fibrillation (AF).Catheter ablation was remotely performed using a new irrigated-tip magnetic catheter (ThermoCool NaviStar-RMT, Biosense Webster, Diamond Bar, CA) in 130 consecutive patients (mean age 59.7 ± 10.5 years) with symptomatic paroxysmal (81 patients) or persistent (49 patients) AF. The radiofrequency (RF) generator was set to fixed power of 30 W. The primary end point of the study was freedom from atrial tachycardia (AT)/AF off antiarrhythmic drugs.The procedure was safely performed in all conventional ablation targets, but crossover to manual catheters was required in 12 patients to complete the mitral isthmus line. The total procedure time was 94.6 ± 15.3 minutes. Impedance values significantly decreased during RF applications (P.001) and the maximum temperature on the catheter tip was 36.4°C ± 0.8°C. The follow-up duration was 15.3 ± 4.9 months. The primary end point was achieved in 66 of 81(81.4%) patients with paroxysmal AF and in 33 of 49 (67.3%) with persistent AF (P = .035, by log-rank test). Patients with paroxysmal AF had higher late AF recurrence (P =.044). Overall, postablation incessant left AT developed in 7 of 130 (5.4%) patients. Major complications were not observed. Left atrial diameter (P.001) and heart failure (P = .032) predicted arrhythmia recurrence after remote irrigated-tip ablation.Remote ablation with irrigated-tip magnetic catheters can be safely and effectively performed in patients with AF, but longer follow-up periods are required to evaluate late AF recurrences.

Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing [MultiPoint™ Pacing (MPP), St. Jude Medical, Sylmar, CA, USA] improves LV function and clinical response relative to conventional CRT in patients receiving a de novo device implant. We hypothesized that patients with a previously implanted conventional CRT device would receive additional benefit by switching to MPP. Patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were programmed to conventional CRT (i.e. biventricular pacing with right ventricular and single LV sites) optimized by intraoperative haemodynamic measurements. After 12 months of conventional therapy, patients were reprogrammed to MPP and re-evaluated at 16 months post-implant. Response to CRT was prospectively defined as reduction in end-systolic volume (ESV) of ≥15% relative to baseline as determined by a blinded observer. Eight patients with an implanted CRT device [New York Heart Association III, ejection fraction (EF) 30 ± 5%, QRS 149 ± 18 ms] received 12 months of conventional CRT and were switched to MPP. After 12 months of conventional CRT, ESV reduction and EF increase relative to baseline were −18 ± 12 and +5 ± 4%, respectively, and six of eight (75%) patients were considered CRT responders. After 4 months of MPP, two of two (100%) patients classified as non-responders to conventional CRT became responders with additional reduction in ESV of −33 and −20% and improvement in EF of +15 and +4%. The remaining six patients classified as responders experienced additional reduction in ESV of −13 ± 21% and improvement in EF of +7 ± 7% after switching to MPP. Multipoint LV pacing may provide additional improvement to LV function in patients receiving conventional CRT.

Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. Methods and Results— Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3–42.3) with implantable cardioverter–defibrillator were enrolled. Low-voltage areas (2 (12.1–24.2) to 28.5 cm 2 (21.6–30.2; P =0.001). Similarly, areas with abnormal electrograms increased after flecainide from 19.0 (17.5–23.6) to 27.3 cm 2 (24.0–31.2; P =0.001). After 23.8 minutes (18.1–28.5) of radiofrequency ablation, abnormal electrograms disappeared, whereas low-voltage areas were replaced by scar areas (2 (19.6–31.0). Substrate elimination resulted in BrS ECG pattern disappearance and no ventricular tachycardia/ventricular fibrillation inducibility without complications. After a median follow-up of 5 months (3.8–5.3), ECG remained normal despite flecainide. Conclusions— In patients with BrS, there is a relationship between abnormal ECG pattern, the extent of abnormal epicardial substrate, and ventricular tachycardia/ventricular fibrillation inducibility. Ablation of the substrate identified in the presence of flecainide can eliminate the BrS phenotype and warrants further study.

We thank Fenici et al for their interest in our experience on the natural history of the Wolff-Parkinson-White (WPW) syndrome.1 The authors, on the basis of their experience, suggest the routine use of ambulatory transesophageal atrial pacing (TEAP) as an intermediate approach to minimize “invasiveness” for risk assessment in the asymptomatic WPW population. It is well known that, unlike invasive electrophysiological testing (EPT), TEAP provides less accurate information about “the real electrophysiological profile of the risk” in WPW patients. Potential limitations are an approximate value of the anterograde refractory period of accessory pathways (APs), no identification of multiple APs, no reproducibility or inducibility of atrial fibrillation, no information on AP …

Background— The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population. Methods and Results— The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually exclusively (13 of 15) in children (median age, 11 years), and was associated with a short accessory pathway antegrade refractory period ( P P P Conclusions— The prognosis of the Wolff-Parkinson-White syndrome essentially depends on intrinsic electrophysiological properties of AP rather than on symptoms. RFA performed during the same procedure after electrophysiological testing is of benefit in improving the long-term outcomes.

Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing in a single coronary sinus branch improves acute LV function. We hypothesized that multipoint pacing (MPP) can improve midterm echocardiographic and clinical response compared with conventional CRT.Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical, Sylmar, CA, USA) were randomized to receive biventricular (BiV) pacing with either conventional LV pacing (CONV group) or MPP (MPP group). For each patient, an optimal pacing configuration for the assigned pacing mode was programmed based on intraoperative pressure-volume (PV) loop measurements. A clinical evaluation and transthoracic echocardiogram were performed before implant (BASELINE) and at 3 months postimplant and analyzed by a blinded observer. A reduction in end-systolic volume (ESV) of ≥15% relative to BASELINE was prospectively defined as response to CRT. Forty-four patients (NYHA Class III, EF 29 ± 6%, QRS duration 152 ± 17 milliseconds) were enrolled and randomized. One patient in the MPP group was lost to follow-up and excluded from further analysis. After 3 months, 11 of 22 (50%) CONV patients and 16 of 21 (76%) MPP patients were classified as responders. ESV reduction, EF increase, and NYHA class reduction relative to BASELINE were significantly greater in the MPP group than in the CONV group (ESV: -21.0 ± 13.9 vs. -12.6 ± 11.1%, P = 0.03; EF: +9.8 ± 5.1 vs. +2.0 ± 7.8 percentage points, P0.001; ΔNYHA: -1.05 ± 0.22 vs. -0.72 ± 0.46 functional classes, P = 0.006).PV loop optimized BiV pacing with MPP resulted in an improved rate of response to CRT.

The superadiabatic quantum driving, producing a perfect adiabatic transfer on a given Hamitonian by introducing an additional Hamiltonian, is theoretically analysed for transfers within a three-level system. Our starting point is the stimulated Raman adiabatic passage, realized through different schemes of laser pulses. We determine the superadiabatic correction for each scheme. The fidelity, robustness and transfer time of all the superadiabatic transfer schemes are discussed. We derive that all superadiabatic corrections are based on a $\pi$- (or near-$\pi$)-area pulse coupling between the initial and final states. The benefits in the protocol robustness overcome the difficulties associated to the actual implementation of the three-level superadiabatic transfer., Comment: 10 pages, 8 figures