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The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1

Background: The results of pulmonary vein isolation (PVI) are limited by arrhythmia recurrence, which is most often due to failure to effectuate a durable contiguous circumferential transmural lesion around the pulmonary vein ostia., Objective: We sought to determine if enhancing the index ablation line through the use of multiple cryoballoon diameters would be superior to standard ablation with bonus freeze., Methods: We enrolled 226 consecutive patients referred for cryoballoon-based PVI. Patients underwent PVI either with the 28-mm Arctic Front Advance (Medtronic, Minneapolis, Mn) cryoballoon using two 4-minute freezes (standard group) or with the POLARx FIT (Boston Scientific, Marlborough, Ma) cryoballoon using 3-minute freezes in both the 28- and 31-mm-diameter configurations (double stack group). Patients were followed for up to 1 year. The primary outcome was atrial tachyarrhythmia recurrence, with peri-procedural complications, cardioversion, emergency department visit, hospitalization, and repeat ablation being secondary outcomes., Results: A total of 226 patients were included (70% male; 47% with persistent atrial fibrillation [AF]). Patients in the double stack group had a significantly greater freedom from recurrent AF/atrial tachycardia/atrial flutter at 1 year (87.2% vs 68.9%; hazard ratio 0.41; 95% confidence interval 0.24-0.71; P=.008). Periprocedural complications were similar between the groups (5.2% vs 3.4%; P=.50). At 1 year, there was no difference in cardioversion (12.8% vs 20.3%; P=.20), emergency department visit (9.0% vs 15.5%; P=.22), or all-cause hospitalization (1.3% vs 2.7%; P=.66). Significantly less patients treated with double stack underwent repeat ablation (1.3% vs 13.5%; P=.002)., Conclusion: In a mixed cohort of patients with paroxysmal and persistent AF, cryoballoon ablation using the double stack technique is associated with lower rates of AF recurrence, aggregate healthcare utilisation, and lower rates of repeat ablation., Competing Interests: Disclosures Dr Andrade reports personal fees from Medtronic, Boston Scientific, J&J MedTech Kardium, and Abbott. Dr Deyell reports grants and personal fees from J&J MedTech, and Kardium. Dr Macle reports personal fees from Medtronic and grants and personal fees from St. Jude Medical/Abbott and J&J MedTech. The rest of the authors have nothing to disclose., (Copyright © 2025 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Main-group element-mediated C-H activation remains experimentally challenging and the development of clear concepts and design principles has been limited by the increased reactivity of relevant complexes, especially for the heavier elements. Herein, we report that the stibenium ion [( py CDC)Sb][NTf 2 ] 3 (1) ( py CDC=bis-pyridyl carbodicarbene; NTf 2 =bis(trifluoromethanesulfonyl)imide) reacts with acetonitrile in the presence of the base 2,6-di-tert-butylpyridine to enable C(sp 3 )-H bond breaking to generate the stiba-methylene nitrile complex [( py CDC)Sb(CH 2 CN)][NTf 2 ] 2 (2). Kinetic analyses were performed to elucidate the rate dependence for all the substrates involved in the reaction. Computational studies suggest that C-H activation proceeds via a mechanism in which acetonitrile first coordinates to the Sb center through the nitrogen atom in a κ 1 fashion, thereby weakening the C-H bond which can then be deprotonated by base in solution. Further, we show that 1 reacts with terminal alkynes in the presence of 2,6-di-tert-butylpyridine to enable C(sp)-H bond breaking to form stiba-alkynyl adducts of the type [( py CDC)Sb(CCR)][NTf 2 ] 2 (3 a-f). Compound 1 shows excellent specificity for the activation of the terminal C(sp)-H bond even across alkynes with diverse functionality. The resulting stiba-methylene nitrile and stiba-alkynyl adducts react with elemental iodine (I 2 ) to produce iodoacetonitrile and iodoalkynes, while regenerating an Sb trication., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: The long-term natural history of autonomic alterations following catheter ablation of drug-refractory paroxysmal atrial fibrillation is poorly defined., Objectives: The authors sought to define the long-term impact of thermal catheter ablation on the cardiac autonomic system., Methods: The study included 346 patients with drug-refractory paroxysmal atrial fibrillation undergoing pulmonary vein isolation using thermal ablation energy (radiofrequency or cryoballoon ablation). All patients underwent insertion of a Reveal LINQ implantable cardiac monitor prior to ablation. The implantable cardiac monitor continuously recorded physical activity, heart rate variability (HRV) (measured as the standard deviation of the average normal-to-normal), daytime heart rate, and nighttime heart rate (NHR). Longitudinal autonomic data in the 2-month period prior to the date of ablation were compared with the 3 years following ablation., Results: Following ablation, there was a significant decrease in HRV (10-20 ms; P < 0.0001) and significant increases in daytime heart rate and NHR (10 beats/min [P < 0.0001] and 7 beats/min [P < 0.0001], respectively). Changes in autonomic parameters were greatest in the first 3 months following ablation but remained significantly different from baseline for 36 months following ablation. Greater changes in NHR and HRV were associated with improved freedom from recurrent arrhythmia. The type of thermal ablation energy had no influence on the heart rate and autonomic parameters., Conclusions: Pulmonary vein isolation using thermal ablation energy results in significant sustained changes in the heart rate parameters related to autonomic function. These changes are independent of the ablation technology employed and are associated with procedural success. (Cryoballoon vs Irrigated Radiofrequency Catheter Ablation: Double Short vs Standard Exposure Duration [CIRCA-DOSE]; NCT01913522)., Competing Interests: Funding Support and Author Disclosures The CIRCA-DOSE study was funded by a peer-reviewed grant from the Heart and Stroke Foundation of Canada (grant no. G-13-0003121), with additional financial support from Medtronic. Dr Khairy was supported by the André Chagnon Research Chair in Electrophysiology and Congenital Heart Disease. The funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Dr Andrade has received grants and personal fees from Medtronic, grants from Baylis; and personal fees from Biosense Webster. Dr Deyell has received grants from Biosense Webster. Dr Macle has received personal fees from Medtronic; and grants and personal fees from St. Jude Medical/Abbott and Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Holter monitoring may raise suspicion of an underlying catecholaminergic polymorphic ventricular tachycardia (CPVT) diagnosis. Although not a primary investigation for CPVT, Holter monitoring is ubiquitously used as a diagnostic tool in the heart rhythm clinic., Objectives: The objective of this study was to explore Holter monitoring in CPVT diagnosis., Methods: This retrospective cohort study analyzed off-therapy Holter monitoring from 13 ryanodine receptor 2-positive CPVT and 34 healthy patients from the Canadian Hearts in Rhythm Organization national registry. Using the Edwards method, the ratio of ambient-maximum heart rate during Holter monitoring was correlated with exertion level to separate premature ventricular contractions (PVCs) during periods of adrenergic and nonadrenergic stress. A receiver operating characteristic curve analysis determined the optimal threshold for isolating CPVT-induced PVCs during adrenergic states., Results: PVC burden differed between groups (P = 0.001) but was within population norm, suggesting ambient PVCs are uncommon in CPVT. CPVT patients had higher PVC counts than healthy controls (P = 0.002), with a different distribution based on adrenergic state. The optimal threshold for separating PVCs into periods of adrenergic and nonadrenergic stress in CPVT patients was 76% of the maximum heart rate during the monitoring period. Compared with healthy controls, CPVT patients had a higher PVC count, limited to periods of adrenergic stress, defined by >76% maximum heart rate threshold (P = 0.002; area under the receiver operating characteristic curve: 0.84). Below this threshold, there was no significant PVC difference (P = 0.604)., Conclusions: Holter monitor PVC counts alone are inadequate for CPVT diagnosis, owing to the adrenergic nature of the disease. Quantifying PVC prevalence at a heart rate threshold >76% identified CPVT with moderate sensitivity (69%) and high specificity (94%)., Competing Interests: Funding Support and Author Disclosures The study was supported by the Heart in Rhythm Organization (Dr Krahn, Principal Investigator), which receives support from the Canadian Institute of Health Research (RN380020-406814). The authors affirm their complete access to the data and assume entire responsibility for its integrity. All authors have thoroughly reviewed and consented to the manuscript in its current form. Dr Krahn has received support from the Paul Brunes Chair in Heart Rhythm Disorders (Vancouver, British Columbia). Dr Roston has received honoraria from Cardurion Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The SENZA-PDN study evaluated high-frequency 10-kHz spinal cord stimulation (SCS) for the treatment of painful diabetic neuropathy (PDN). Over 24 months, 10-kHz SCS provided sustained pain relief and improved health-related quality of life. This report presents additional outcomes from the SENZA-PDN study, focusing on diabetes-related pain and quality of life outcomes., Methods: The SENZA-PDN study randomized 216 participants with refractory PDN to receive either conventional medical management (CMM) or 10-kHz SCS plus CMM (10-kHz SCS + CMM), allowing crossover after six months if pain relief was insufficient. Postimplantation assessments at 24 months were completed by 142 participants with a permanent 10-kHz SCS implant, comprising 84 initial and 58 crossover recipients. Measures included the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN), Diabetes-Related Quality of Life (DQOL), Global Assessment of Functioning (GAF), and treatment satisfaction., Results: Over 24 months, 10-kHz SCS treatment significantly reduced pain severity by 66.9% ( P < .001; BPI-DPN) and pain interference with mood and daily activities by 65.8% ( P < .001; BPI-DPN). Significant improvements were also observed in overall DQOL score ( P < .001) and GAF score ( P < .001), and 91.5% of participants reported satisfaction with treatment., Conclusions: High-frequency 10-kHz SCS significantly decreased pain severity and provided additional clinically meaningful improvements in DQOL and overall functioning for patients with PDN. The robust and sustained benefits over 24 months, coupled with high participant satisfaction, highlight that 10-kHz SCS is an efficacious and comprehensive therapy for patients with PDN., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: EAP has received consulting fees from Abbott Laboratories, Biotronik, Boston Scientific, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, Presidio Medical, Saluda, and Vertos Medical; research support from Mainstay, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, ReNeuron, Saluda, and SPR; and stock options from neuro42 and SynerFuse. TGS has received research support from Nevro Corp. JAS has received research support from Boston Scientific, Nevro Corp, Saluda Medical, and Vertiflex. MJJ is an employee of Nevro Corp. DRE received a fee from Nevro Corp for the preparation of this manuscript in her capacity as an independent medical writer. JLW has received consulting fees from California Institute for Biomedical Research and Eli Lilly and research support from Nevro Corp. SMS has received research support from Nevro Corp. KA has received consulting fees from Biotronik, Medtronic, Nalu Medical, Nevro Corp, and Saluda Medical, as well as research support from Biotronik, IPM Medical Group, Nevro Corp, Saluda Medical, SPR Therapeutics, and Vivex Biologics. MNG has received consulting fees from Abbott Laboratories, Avanos Medical, Avertis Pharmacy, Boston Scientific, Nevro Corp, and Saluda Medical, as well as research support from Abbott Laboratories, Avanos Medical, Boston Scientific, Nalu Medical, Neuros Medical, Nevro Corp, and Saluda Medical. JX has received research support from the Cleveland Clinic Velosano Program, the National Institutes of Health, the Steve and Melody Golding Foundation, and Nevro Corp. CY has received research support from Nevro Corp. AN has received consulting fees from Aurora Spine, Flowonix, and Nevro Corp, as well as research support from Nevro Corp. DGP has received consulting fees from Abbott Laboratories, AIS Healthcare, Allergan, Amgen, Aurora Spine, CornerLoc, Flowonix, Lundbeck, Pajunk Medical, Saluda Medical, Spark Biomedical, and Vertos Medical; research support from Abbott Laboratories, Aurora Spine, Flowonix, Nevro Corp, and Saluda Medical; speakers’ bureau or honoraria from Abbott Laboratories, Allergan, Amgen, CornerLoc, Lundbeck, Saluda Medical, and Vertos Medical; and stock options from CornerLoc. MJC has received research support from Nevro Corp. VG has received research support from Biotronik, Medtronic, Nevro Corp, PainTEQ, SPR Therapeutics, and St. Jude. RHB has received research support from Nevro Corp. NDM has received consulting fees from Averitas, Nevro Corp, and Salix Pharmaceuticals, as well as research support from Boston Scientific and Nevro Corp. DS has received consulting fees from Abbott Laboratories, Boston Scientific, Flowonix, Medtronic, Nevro Corp, Vertiflex, and Vertos Medical, as well as research support from Abbott Laboratories, Biotronik, Nevro Corp, Vertiflex, and Vertos Medical. SPL has received consulting fees from Nevro Corp and research support from Nevro Corp. DJD has received research support from Nevro Corp, as well as funding for serving as principal investigator of a study supported by SPR Therapeutics paid to his institution. KAS has received research support from Nevro Corp. JHG has received consulting fees from Abbott Laboratories, Saluda Medical, and Stratus Medical. PWW has received research support from Nevro Corp. CEA has received consulting fees from AbbVie, Amgen, Biohaven, Clexio Biosciences, Collegium, Eli Lilly, Elsevier, Flowonix, Gene Pharma, Lundbeck, Nevro Corp, Novartis, Pfizer, SK Life Science, Teva Pharmaceutical, and Vertex, as well as research support from AbbVie, Allergan, Amgen, Daiichi Sankyo, Eli Lilly, Novartis, Teva Pharmaceutical, and Vertex Pharmaceuticals. CEN has received consulting fees from Exelixis, Neurogastrx, and Nevro Corp, as well as research support from Nevro Corp. RST has received consulting fees from Nevro Corp, Medtronic, and Saluda Medical. DLC is an employee of Nevro Corp. NAM has received consulting fees from Nevro Corp, Relievant Medsystems, Saluda Medical, Sollis Therapeutics, and Vertos Medical, as well as research support from Avanos Medical, Mesoblast, Neuros Medical, and Nevro Corp.

Rhodium catalyzed arene alkenylation reactions with arenes and olefins using dioxygen as the direct oxidant (e.g., ACS Catal. 2020 , 10 , 11519), Cu(II) carboxylates (e.g., Science 2015 , 348 , 421; J. Am. Chem. Soc. 2017 , 139 , 5474) or Fe(III) carboxylate clusters (e.g., ACS Catal. 2024, 14 , 10295), in the presence or absence of dioxygen, have been reported. These processes involve heating catalyst precursor [(η 2 -C 2 H 4 ) 2 Rh(μ-OAc)] 2 , olefin, arene, and oxidant at temperatures between 120 and 200 °C. Herein, we report comparative studies of Rh-catalyzed arene alkenylation as a function of oxidant identity. This work includes comparisons of catalysis using Cu(II) carboxylates in the presence and absence of dioxygen, catalysis with only dioxygen as the oxidant, and Fe(III) carboxylates in the presence and absence of dioxygen. We report studies of catalysis with each oxidant including reagent concentration dependencies and kinetic isotope effect experiments using C 6 H 6 or C 6 D 6 and protio- or deutero carboxylic acid. Additionally, we probe ortho/meta/para regioselectivity for reactions of ethylene with monosubstituted arenes and Markovnikov/anti-Markovnikov selectivity with monosubstituted olefins. These studies indicate that the variation of oxidant identity impacts catalyst speciation, the reaction mechanism, and the reaction rate. Consequently, distinct Markovnikov/anti-Markovnikov and ortho/meta/para selectivities are observed for catalysis with each oxidant., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Fe(II) carboxylates react with dioxygen and carboxylic acid to form Fe 6 (μ-OH) 2 (μ 3 -O) 2 (μ-X) 12 (HX) 2 (X = acetate or pivalate), which is an active oxidant for Rh-catalyzed arene alkenylation. Heating (150-200 °C) the catalyst precursor [(η 2 -C 2 H 4 ) 2 Rh(μ-OAc)] 2 with ethylene, benzene, Fe(II) carboxylate, and dioxygen yields styrene >30-fold faster than the reaction with dioxygen in the absence of the Fe(II) carboxylate additive. It is also demonstrated that Fe 6 (μ-OH) 2 (μ 3 -O) 2 (μ-X) 12 (HX) 2 is an active oxidant under anaerobic conditions, and the reduced material can be reoxidized to Fe 6 (μ-OH) 2 (μ 3 -O) 2 (μ-X) 12 (HX) 2 by dioxygen. At optimized conditions, a turnover frequency of ∼0.2 s -1 is achieved. Unlike analogous reactions with Cu(II) carboxylate oxidants, which undergo stoichiometric Cu(II)-mediated production of phenyl esters (e.g., phenyl acetate) as side products at temperatures ≥150 °C, no phenyl ester side product is observed when Fe carboxylate additives are used. Kinetic isotope effect experiments using C 6 H 6 and C 6 D 6 give k H / k D = 3.5(3), while the use of protio or monodeutero pivalic acid reveals a small KIE with k H / k D = 1.19(2). First-order dependencies on Fe(II) carboxylate and dioxygen concentration are observed in addition to complicated kinetic dependencies on the concentration of carboxylic acid and ethylene, both of which inhibit the reaction rate at a high concentration. Mechanistic studies are consistent with irreversible benzene C-H activation, ethylene insertion into the formed Rh-Ph bond, β-hydride elimination, and reaction of Rh-H with Fe 6 (μ-OH) 2 (μ 3 -O) 2 (μ-X) 12 (HX) 2 to regenerate a Rh-carboxylate complex., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Unlike tachyarrhythmias, which are common in pregnancy, there is a paucity of data regarding maternal bradycardias. Our objective was to describe the characteristics, associated conditions, and prognosis of women who develop bradycardia post-partum., Method: We conducted a retrospective chart review of patients referred to the Obstetrical Medicine service at British Columbia Women's Hospital from January 2012 to May 2020 for post-partum maternal bradycardia., Results: Twenty-four patients with post-partum bradycardia were included (age 34.2  ±  4.8 years; heart rate 40.4  ±  8.1 beats per minute; blood pressure 131/72 mm Hg). Sinus bradycardia (79.2%) was the most common rhythm. Dyspnea (29.4%) and chest pain (23.5%) were common symptoms. Mean time to resolution of bradycardia was 3.6  ±  3.8 days. Associated conditions potentially explaining the bradycardia were preeclampsia (54.1%), underlying (16.7%), medications (8.3%), and neuraxial anesthesia (8.3%)., Conclusions: Maternal bradycardia is an uncommon condition complicating the post-partum period, that is generally self-limiting, with the majority only require clinical observation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Surgically repaired Tetralogy of Fallot (rTOF) is associated with progressive right ventricular hypertrophy (RVH) and dilation (RVD). Accurate estimation of RVH/RVD is vital for the ongoing management of this patient population. The utility of the ECG in evaluating patients with rTOF with pre-existing right bundle branch block (RBBB) has not been studied. We aimed to determine the sensitivity/specificity of currently established ECG criteria in detecting RVH/RVD in this patient population., Methods: We included consecutive patients diagnosed with rTOF who underwent CMR performed at our regional referral centre between January 2012 and December 2019. Each CMR was assessed for LVH, LVD, RVH and or RVD. The ECG corresponding to the CMR was then used to determine RVH/LVH for specificity and sensitivity analysis., Results: Our study included 163 consecutive rTOF patients. The specificity for ECG-based criteria for LVH was 100.00% (95% C.I. (87.75, 100.00)), and the sensitivity was 7.19% (95% C.I. (3.15, 12.83)). When RBBB was present, specificity for RVH was 100.00% (95% C.I. (84.56, 100.00)), and sensitivity was 7.69% (95% C.I. (3.75, 13.69)). When RBBB was absent, specificity for RVH was 100.00% (95% C.I. (15.81, 100.00)), and sensitivity was 0.00% (95% C.I. (0.00, 33.63)). A regression model with the entire group of 163 ToF patients, based on the Sokolow-Lyon criterion (sum of R in V1 + S in V5/V6), produced a new suggested criterion for the diagnosis of RVH in patients with rTOF, which was a sum of R in V1 + S in V5/V6 greater than 13.25 mm. This model's sensitivity for RVH detection was 69.1%, and specificity was 36.8%., Conclusions: Standard ECG voltage criteria have poor sensitivity for detecting right and left ventricular chamber hypertrophy and dilatation in patients with rTOF, so current ECG criteria should not be used to monitor RVH/RVD in this patient population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aims: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Insertable cardiac monitors (ICMs) are increasingly used in this population to provide closer monitoring, with the potential for notification systems. However, little is known regarding the psychological impact this information may have on patients. The Abbott Confirm Rx™ ICM has the capability of connecting to the patient's smartphone to enable active participation in their care, as well as two-way communication between the patient and their care providers. This study aimed to explore individuals' experiences of having a smartphone-enabled ICM to monitor for arrhythmias in HCM., Methods and Results: Semi-structured interviews were conducted with 10 participants. Utilizing a grounded theory approach, the interview guide was modified based on emerging themes throughout the study. Reflexive thematic analysis was applied to categorize interview data into codes and overacting themes, with each interview independently coded by two study members. Analysis revealed three key themes: (i) psychological impact, (ii) educational needs, and (iii) technology expectations. Participants reported that receiving feedback from ICM transmissions resulted in improved symptom clarity, providing reassurance, and aiding implantable cardioverter defibrillator decision-making. Some participants reported uncertainty regarding when to send manual transmissions. Lastly, participants reported the app interface did not meet expectations with regard to the amount of data available for patients., Conclusion: Overall, utilizing a smartphone app to facilitate two-way communication of ICM transmissions was well accepted. Future directions include addressing gaps in educational needs and improvements in the patient interface with increased access to data., Competing Interests: Conflict of interest: J.F. reports receiving honorarium from Medtronic. M.W.D. reports receiving honoraria from Abbott. The other authors have no conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Self-administration of investigational intranasal L-type calcium channel blocker etripamil during paroxysmal supraventricular tachycardia (PSVT) appeared safe and well-tolerated in the phase 3 NODE-301 (Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Etripamil Nasal Spray for the Termination of Spontaneous Episodes of Paroxysmal Supraventricular Tachycardia) trial of adults with sustained atrioventricular nodal-dependent PSVT. The NODE-302 open-label extension further characterized etripamil safety and efficacy. Methods and Results Eligible patients were monitored via self-applied cardiac monitoring system for 5 hours after etripamil self-administration. The primary end point was time-to-conversion of positively adjudicated PSVT to sinus rhythm after etripamil treatment. Probability of conversion to sinus rhythm was reported via Kaplan-Meier plot. Adverse events were based on self-reported symptoms and clinical evaluations. Among 169 patients enrolled, 105 self-administered etripamil ≥1 time for perceived PSVT (median [range], 232 [8-584] days' follow-up). Probability of conversion within 30 minutes of etripamil was 60.2% (median time to conversion, 15.5 minutes) among 188 PSVT episodes (92 patients) positively adjudicated as atrioventricular nodal dependent by independent ECG analysis. Among 40 patients who self-treated 2 episodes, 75% had a significantly consistent response by 30 minutes; 9 did not convert on either episode, and 21 converted on both episodes (χ 2 =8.09; P =0.0045). Forty-five of 105 patients (42.9%) had ≥1 treatment-emergent adverse event, generally transient and mild-to-moderate, including nasal congestion (14.3%), nasal discomfort (14.3%), or rhinorrhea (12.4%). No serious cardiac safety events were observed within 24 hours of etripamil. Conclusions In this extension study, investigational etripamil nasal spray was well tolerated for self-treating recurrent episodes of PSVT without medical supervision. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635996.

Aims: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN)., Methods: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment. In total, 142 patients with a 10 kHz SCS system were followed for 24 months, including 84 initial 10 kHz SCS+CMM recipients and 58 crossovers from CMM alone. Assessments included pain intensity, health-related quality of life (HRQoL), sleep, and neurological function. Investigators assessed neurological function via sensory, reflex, and motor tests. They identified a clinically meaningful improvement relative to the baseline assessment if there was a significant persistent improvement in neurological function that impacted the participant's well-being and was attributable to a neurological finding., Results: At 24 months, 10 kHz SCS reduced pain by a mean of 79.9% compared to baseline, with 90.1% of participants experiencing ≥50% pain relief. Participants had significantly improved HRQoL and sleep, and 65.7% demonstrated clinically meaningful neurological improvement. Five (3.2%) SCS systems were explanted due to infection., Conclusions: Over 24 months, 10 kHz SCS provided durable pain relief and significant improvements in HRQoL and sleep. Furthermore, the majority of participants demonstrated neurological improvement. These long-term data support 10 kHz SCS as a safe and highly effective therapy for PDN., Trial Registration: ClincalTrials.gov Identifier, NCT03228420., Competing Interests: Declaration of competing interest Author Erika A. Petersen has received consulting fees from Abbott Laboratories, Biotronik, Boston Scientific, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, Presidio Medical, Saluda, and Vertos Medical, research support from Mainstay, Medtronic Neuromodulation, Nalu Medical, Neuros Medical, Nevro Corp, ReNeuron, Saluda, and SPR, and stock options from neuro42 and SynerFuse. Author Thomas G. Stauss has received research support from Nevro Corp. Author James A. Scowcroft has received research support from Boston Scientific, Nevro Corp, Saluda Medical, and Vertiflex. Author Michael J. Jaasma is an employee of Nevro Corp. Author Elizabeth S. Brooks was an employee of Nevro Corp during her contributions to the work associated with this manuscript. Author Deborah R. Edgar received consulting fees from Nevro in her capacity as an independent medical writer. Author Judith L. White has received consulting fees from California Institute for Biomedical Research and Eli Lilly and research support from Nevro Corp. Author Shawn M. Sills has received research support from Nevro Corp. Author Kasra Amirdelfan has received consulting fees from Biotronik, Medtronic, Nalu Medical, Nevro Corp, and Saluda Medical, as well as research support from Biotronik, IPM Medical Group, Nevro Corp, Saluda Medical, SPR Therapeutics, and Vivex Biologics. Author Maged N. Guirguis has received consulting fees from Abbott Laboratories, Avanos Medical, Avertis Pharmacy, Boston Scientific, Nevro Corp, and Saluda Medical, as well as research support from Abbott Laboratories, Avanos Medical, Boston Scientific, Nalu Medical, Neuros Medical, Nevro Corp, and Saluda Medical. Author Jijun Xu has received research support from the Cleveland Clinic Velosano Program, the National Institutes of Health, the Steve and Melody Golding Foundation, and Nevro Corp. Author Cong Yu has received research support from Nevro Corp. Author Ali Nairizi has received consulting fees from Aurora Spine, Flowonix, and Nevro Corp as well as research support from Nevro Corp. Author Denis G. Patterson has received consulting fees from Abbott Laboratories, AIS Healthcare, Allergan, Amgen, Aurora Spine, CornerLoc, Flowonix, Lundbeck, Pajunk Medical, Saluda Medical, Spark Biomedical, and Vertos Medical, research support from Abbott Laboratories, Aurora Spine, Flowonix, Nevro Corp, and Saluda Medical, speakers’ bureau or honoraria from Abbott Laboratories, Allergan, Amgen, CornerLoc, Lundbeck, Saluda Medical, and Vertos Medical, and stock options from CornerLoc. Author Michael J. Creamer has received research support from Nevro Corp. Author Vincent Galan has received research support from Biotronik, Medtronic, Nevro Corp, PainTEQ, SPR Therapeutics, and St. Jude. Author Richard H. Bundschu has received research support from Nevro Corp. Author Neel D. Mehta has received consulting fees from Averitas, Nevro Corp, and Salix Pharmaceuticals, as well as research support from Boston Scientific and Nevro Corp. Author Dawood Sayed has received consulting fees from Abbott Laboratories, Boston Scientific, Flowonix, Medtronic, Nevro Corp, Vertiflex, and Vertos Medical, as well as research support from Abbott Laboratories, Biotronic, Nevro Corp, Vertiflex, and Vertos Medical. Author Shivanand P. Lad has received consulting fees from Nevro Corp and research support from Nevro Corp. Author David J. DiBenedetto has received research support from Nevro Corp, as well as funding for serving as principal investigator of a study supported by SPR Therapeutics paid to his institution. Author Khalid A. Sethi has received research support from Nevro Corp. Author Johnathan H. Goree has received consulting fees from Abbott Laboratories and Stratus Medical. Author Paul W. Wu has received research support from Nevro Corp. Author Charles E. Argoff has received consulting fees from AbbVie, Amgen, Biohaven, Clexio Biosciences, Collegium, Eli Lilly, Elsevier, Flowonix, Gene Pharma, Lundbeck, Nevro Corp, Novartis, Pfizer, SK Life Science, Teva Pharmaceutical, and Vertex as well as research support from AbbVie, Allergan, Amgen, Daiichi Sankyo, Eli Lilly, Novartis, Teva Pharmaceutical, and Vertex Pharmaceuticals. Author Christian E. Nasr has received consulting fees from Exelixis, Neurogastrx, and Nevro Corp as well as research support from Nevro Corp. Author Rod S. Taylor has received consulting fees from Nevro Corp, Medtronic, and Saluda Medical. Author David L. Caraway is an employee of Nevro Corp. Author Nagy A. Mekhail has received consulting fees from Nevro Corp, Relievant Medsystems, Saluda Medical, Sollis Therapeutics, and Vertos Medical, as well as research support from Avanos Medical, Mesoblast, Neuros Medical, and Nevro Corp., (Copyright © 2023. Published by Elsevier B.V.)

Background: Current inferences about the site of origin (SOO) of premature ventricular complexes (PVC) from the surface ECG have not been subjected to newer data analytic techniques that identify signals that are not recognized by visual inspection., Aims: The objective of this study was to apply data analytics to PVC characteristics., Methods: PVCs from 12-lead ECGs of a consecutive series of 338 individuals were examined by unsupervised machine learning cluster analysis, and indexes were compared to a composite criterion for SOO., Results: Data analytics found that V1S plus V2S ≤ 9.25 of the PVC had a LVOT origin (sensitivity 95.4%; specificity 97.5%). V1R + V2R + V3R > 15.0 (a RBBB configuration) likely had a LVOT origin. PVCs with V1S plus V2S > 12.75 (LBBB configuration) likely had a RVOT origin. PVC with V1S plus V2S > 14.25 (LBBB configuration) and all inferior leads positive likely had a RVOT origin., Conclusion: Newer data analytic techniques provide a non-invasive approach to identifying PVC SOO, which should be useful for the clinician evaluating a 12-lead ECG.

We combine experimental and computational investigations to compare and understand catalytic arene alkenylation using the Pd(II) and Rh(I) precursors Pd(OAc) 2 and [(η 2 -C 2 H 4 ) 2 Rh(μ-OAc)] 2 with arene, olefin, and Cu(II) carboxylate at elevated temperatures (>120 °C). Under specific conditions, previous computational and experimental efforts have identified heterotrimetallic cyclic PdCu 2 (η 2 -C 2 H 4 ) 3 (μ-OPiv) 6 and [(η 2 -C 2 H 4 ) 2 Rh(μ-OPiv) 2 ] 2 (μ-Cu) (OPiv = pivalate) species as likely active catalysts for these processes. Further studies of catalyst speciation suggest a complicated equilibrium between Cu(II)-containing complexes containing one Rh or Pd atom with complexes containing two Rh or Pd atoms. At 120 °C, Rh catalysis produces styrene >20-fold more rapidly than Pd. Also, at 120 °C, Rh is ∼98% selective for styrene formation, while Pd is ∼82% selective. Our studies indicate that Pd catalysis has a higher predilection toward olefin functionalization to form undesired vinyl ester, while Rh catalysis is more selective for arene/olefin coupling. However, at elevated temperatures, Pd converts vinyl ester and arene to vinyl arene, which is proposed to occur through low-valent Pd(0) clusters that are formed in situ. Regardless of arene functionality, the regioselectivity for alkenylation of mono-substituted arenes with the Rh catalyst gives an approximate 2:1 meta / para ratio with minimal ortho C-H activation. In contrast, Pd selectivity is significantly influenced by arene electronics, with electron-rich arenes giving an approximate 1:2:2 ortho / meta/para ratio, while the electron-deficient (α,α,α)-trifluorotoluene gives a 3:1 meta / para ratio with minimal ortho functionalization. Kinetic intermolecular arene ethenylation competition experiments find that Rh reacts most rapidly with benzene, and the rate of mono-substituted arene alkenylation does not correlate with arene electronics. In contrast, with Pd catalysis, electron-rich arenes react more rapidly than benzene, while electron-deficient arenes react less rapidly than benzene. These experimental findings, in combination with computational results, are consistent with the arene C-H activation step for Pd catalysis involving significant η 1 -arenium character due to Pd-mediated electrophilic aromatic substitution character. In contrast, the mechanism for Rh catalysis is not sensitive to arene-substituent electronics, which we propose indicates less electrophilic aromatic substitution character for the Rh-mediated arene C-H activation.

Aims: Same-day discharge is increasingly common after catheter ablation for atrial fibrillation (AF). However, the impact of same-day discharge on healthcare utilization after ablation and whether this differs by ablation modality remains uncertain. We examined the safety, efficacy, and subsequent healthcare utilization of a same-day discharge protocol for AF ablation, including radiofrequency (RF) and cryoballoon ablation, in a contemporary cohort., Methods and Results: All consecutive patients for whom full healthcare utilization data were available at two centres and who underwent AF ablation from 2018 to 2019 were included. Same-day discharge was the default strategy for all patients. The efficacy and safety outcomes were proportions of same-day discharge and readmission/emergency room (ER) visits, and post-discharge complications, respectively. Of the 421 patients who underwent AF ablation (mean 63.3 ± 10.2 years, 33% female), 90.5% (381/421) achieved same-day discharge with no difference between RF and cryoballoon ablation (89.8 vs. 95.1%, adjusted P = 0.327). Readmission ≤30 days occurred in 4.8%, with ER visits ≤30 days seen in 26.1% with no difference between ablation modalities (P = 0.634). Patients admitted overnight were more likely to present to the ER (40.0 vs. 24.7% with same-day discharge, P = 0.036). The overall post-discharge complication rate was low at 4/421 (1.0%), with no difference between ablation modality (P = 0.324) and admission/same-day discharge (P = 0.485)., Conclusion: Same-day discharge can be achieved in a majority of patients undergoing RF or cryoballoon ablation for AF. Healthcare utilization, particularly ER visits, remains high after AF ablation, regardless of ablation modality or same-day discharge., Competing Interests: Conflict of interest: M.W.D. reports honoraria and research funding from Biosense Webster, and honoraria from Medtronic, Abbott, and Boston Scientific. J.G.A. reports research funding and honoraria from Medtronic., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The use of guideline-directed medical therapy (GDMT) is poorly described in patients with heart failure and reduced ejection fraction (HFrEF) with cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillators (ICDs)., Objective: To define the eligibility, uptake, dose, contraindications, and barriers to uptake of contemporary medical therapy in this population., Methods: Retrospective analysis of consecutive adults with ICD and/or CRT attending two Canadian tertiary centre device clinics between 1 March and 31 May 2021., Results: From 1005 device clinic consultations, 227 (22.6%) patients with HFrEF and CRT and/or ICD were included. GDMT eligibility was high: beta-blockers (99.6%), mineralocorticoid receptor antagonists (MRA) (89.0%), angiotensin receptor-neprilysin inhibitors (ARNI) (84.6%), and sodium-glucose cotransporter-2 inhibitors (SGLT2I) (87.7%). Contraindications were rare: beta-blockers (0.4%), MRA (11.0%), ARNI (15.4%), and SGLT2I (12.3%). Uptake of GDMT was high for beta-blockers (97.4%) but low for other medications: MRA (63.0%), ARNI (46.7%), SGLT2I (22.9%). Except for SGLT2I (84.6%) and beta-blockers (57.9%), less than one-half of patients were prescribed target-doses of MRA (10.5%), and ARNI (47.7%). Of the visits, GDMT was already optimal in 16%, electrophysiologists acted in 33% (21% prescribed, 7% ordered investigations, 5% referred to heart function services), and in the remaining visits, optimization was either deferred to another cardiologist (20%) or no plan was mentioned (25%), besides other reasons (4%)., Conclusion: Despite broad eligibility for GDMT in patients with HFrEF and ICD/CRT, significant gaps in prescription and titration exist. Our results highlight the need to embed quality assurance initiatives in cardiac device clinics to improve HFrEF care., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Transseptal puncture to achieve left atrial access is necessary for many cardiac procedures, including atrial fibrillation ablation. More recently, there has been an increasing need for left atrial access using large caliber sheaths, which increases risk of perforation associated with the initial advancement into the left atrium. We compared the effectiveness of a radiofrequency needle-based transseptal system versus conventional needle for transseptal access., Methods: This prospective controlled trial randomized 161 patients with symptomatic paroxysmal atrial fibrillation undergoing cryoballoon pulmonary vein isolation to transseptal access with a commercially available transseptal system (radiofrequency needle plus stiff pigtail wire; RF + Pigtail group) versus conventional transseptal access (standard group). The primary outcome was time required for left atrial access. Secondary outcomes included failure of the assigned transseptal system, radiation exposure, and complications., Results: The median transseptal puncture time was significantly shorter using the radiofrequency needle plus stiff pigtail wire transseptal system compared with conventional transseptal (840 ± 323 vs. 956 ± 407 s, P = 0.0489). Compared to conventional transseptal puncture, fewer transseptal attempts were required (1.0 ± 0.5 RF applications vs. 1.3 ± 0.8 mechanical punctures, P = 0.0123) and the fluoroscopy time was significantly shorter (72.0 [IQR 48.0, 129.0] vs. 93.0 [IQR 60.0, 171.0] s, P = 0.0490) with the radiofrequency needle plus stiff pigtail wire transseptal system. Failure to achieve transseptal LA access with the assigned system was rarely observed (1.3% vs. 5.7%, P = 0.2192). There were no procedural complications observed with either system., Conclusions: The use of a radiofrequency needle plus stiff pigtail wire resulted in shorter time to left atrial access and reduced fluoroscopy time compared to left atrial access using conventional transseptal equipment., Trial Registration: ClinicalTrials.gov identifier NCT03199703., (© 2022. The Author(s).)

Background: The role of cardiac magnetic resonance (CMR) in the evaluation and management of patients with frequent premature ventricular complexes (PVCs) of unknown etiology remains unclear., Objectives: This study evaluated the prevalence and prognostic significance of myocardial abnormalities detected with CMR among patients with frequent PVCs and no known structural heart disease., Methods: This prospective cohort study included consecutive patients with frequent PVCs and a negative initial diagnostic work-up who underwent CMR with late gadolinium enhancement imaging. The clinical outcome was a composite of mortality, ventricular fibrillation, sustained ventricular tachycardia, or reduction in left ventricular ejection fraction of ≥10%., Results: A total of 255 patients were included, of whom 35 (13.7%) had evidence of myocardial abnormality on CMR. Age ≥60 years (odds ratio [OR]: 6.96; 95% CI: 1.30-37.18), multifocal PVCs (OR: 10.90; 95% CI: 3.21-36.97), and non-outflow tract left ventricular PVC origin (OR: 3.00; 95% CI: 1.00-8.95) were independently associated with the presence of a myocardial abnormality on CMR. After a median follow-up of 36 months, the composite outcome occurred in 15 (5.9%) patients. The presence of a myocardial abnormality on CMR was independently associated with the composite outcome (HR: 4.35; 95% CI: 1.34-14.15; P = 0.014)., Conclusions: One in 7 patients with frequent PVCs with no known structural heart disease had myocardial abnormality detected on CMR, and these abnormalities were associated with adverse clinical outcomes. These findings highlight the important role of CMR in the evaluation of patients with frequent PVCs., Competing Interests: Funding Support and Author Disclosures This work was funded in part by the Michael Smith Foundation for Health Research (grant 5967 to Dr Deyell) and the University of British Columbia Division of Cardiology (Dr Deyell). Dr Thibert has received research funding from the University of Ottawa Heart Institute Verged-Beanlands Endowed Research Fellowship. Dr Galson is funded by the British Heart Foundation through a travel fellowship (FS/TF/21/33008). Dr Andrade has received grants and personal fees from Medtronic; has received grants from Baylis; and has received honoraria from Biosense-Webster, Biotronik, and Abbott. Dr Deyell has received research funding from Biosense Webster; and has received honoraria from Biosense Webster, Medtronic, Boston Scientific, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy., Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months., Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were "satisfied" or "very satisfied" with the 10-kHz SCS treatment., Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy., Trial Registration: clincaltrials.gov Identifier: NCT03228420., (© 2022 The Authors.)

Background: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD., Methods: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020., Results: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion ( P <0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days ( P <0.001) after ICD insertion., Conclusions: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Background: Recent evidence has revealed the utility of prolonged arrhythmia detection duration and increased rate cutoff to reduce implantable cardioverter-defibrillator (ICD) therapies. Data on real-world trends in ICD programming and its impact on outcomes are limited., Objective: The purpose of this study was to evaluate trends in ICD programming and its impact on ICD therapy using a large remote monitoring database., Methods: A retrospective analysis of patients with ICD implanted from 2007 to 2018 was conducted using the de-identified Medtronic CareLink database. Data on ICD programming (number of intervals to detection [NID] and therapy rate cutoff) and delivered ICD therapies were collected., Results: Among 210,810 patients, the proportion programmed to a rate cutoff of ≥188 beats/min increased from 41% to 49% and an NID of ≥30/40 increased from 17% to 67% before May 2013 vs after February 2016. Programming to a rate cutoff of ≥188 beats/min, a ventricular fibrillation (VF) NID of ≥30/40, or a combined rate cutoff of ≥188 beats/min and VF NID of ≥30/40 were associated with reductions in ICD therapy. The largest reductions in ICD therapy occurred when the combination of rate cutoff ≥ 188 beats/min and VF NID ≥ 30/40 was programmed (antitachycardia pacing: hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.34-0.36; P < .001; shocks: HR 0.67; 95% CI 0.65-0.69; P < .001; and antitachycardia pacing/shocks: HR 0.43; 95% CI 0.42-0.44; P < .001)., Conclusion: Despite evidence supporting the use of prolonged detection duration and high rate cutoff, implementation of shock reduction programming strategies in real-world clinical practice has been modest. The use of evidence-based ICD programming is associated with reduced ICD shocks over long-term follow-up., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure and reduced ejection fraction (HFrEF) is the predominant indication for cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) implantation. The care gap and opportunity to optimize guideline-directed medical therapy (GDMT) is unclear., Objective: We sought to define uptake, eligibility, dose, and adherence to GDMT in patients with CRT/ICD and HFrEF., Methods: MEDLINE was searched from 2000 to July 2021 for major randomized trials, registries, and cohort studies evaluating GDMT in this population. Thirty-eight studies focused on medical therapy in patients with CRT/ICD devices (CRT = 23, ICD = 11, and both = 4)., Results: In the pivotal device trials, ACEI/ARB and beta-blocker use was high (mean 94%, range 41%-99%; and 83%, range 27%-97%, respectively), but mineralocorticoid receptor antagonists were modest (mean 45%, range 32%-61%), in keeping with guidelines of that era. Similar results were found in observational registries. CRT was associated with beta-blocker uptitration, while the effects on ACEI/ARB were less consistent. For beta blockers, 57%-68% of patients were uptitrated, increasing the mean percent of target dose achieved by 24% from baseline to follow-up. In one study, adherence increased, for ACEI/ARB from 37% to 55% and beta blockers 34% to 58%. Only 1 study assessed potential eligibility at implant for sacubitril-valsartan (72%) or ivabradine (28%), and no study examined sodium-glucose cotransporter-2 inhibitors. Increased uptake, titration, and dose was associated with reduced mortality, hospitalization, and device therapies., Conclusion: Patients with HFrEF and ICD/CRT are undertreated with respect to GDMT, and there is opportunity to optimize therapy to improve morbidity and mortality., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

Importance: Persistently depressed left ventricular ejection fraction (LVEF) after myocardial infarction (MI) is associated with adverse prognosis and directs the use of evidence-based treatments to prevent sudden cardiac death and/or progressive heart failure., Objective: To assess adherence with guideline-recommended LVEF reassessment and to study the evolution of LVEF over 6 months of follow-up., Design, Setting, and Participants: This was a multicenter cohort study at Canadian academic and community hospitals with on-site cardiac catheterization services. Patients with type 1 acute MI and LVEF less than or equal to 45% during the index hospitalization were enrolled between January 2018 and August 2019 and were followed-up for 6 months. Data analysis was performed from May 2020 to September 2021., Exposures: Baseline clinical factors, in-hospital care and LVEF, and site-specific features., Main Outcomes and Measures: The main outcomes were receipt of repeat LVEF assessment by 6 months and the presence of a persistent LVEF reduction at 2 thresholds: LVEF less than or equal to 40%, prompting consideration of additional medical therapy for heart failure, or LVEF less than or equal to 35%, prompting referral for implanted cardioverter defibrillator in addition to medical therapy., Results: This study included 501 patients (mean [SD] age, 63.3 [13.0] years; 113 women [22.6%]). Overall, 370 patients (73.4%) presented with STEMI, and 454 (90.6%) had in-hospital revascularization. The median (IQR) baseline LVEF was 40% (34%-43%). Of 458 patients (91.4%) who completed the 6-month follow-up, 303 (66.2%; 95% CI, 61.7%-70.5%) had LVEF reassessment, with a range of 46.7% to 90.0% across sites (χ213 = 19.6; P = .11). Participants from community hospitals were more likely than those from academic hospitals to undergo LVEF reassessment (73.6% vs 63.2%; χ21 = 4.50; P = .03), as were those with worse LVEF at baseline. Follow-up LVEF improved by an absolute median (IQR) of 8% (3%-15%). However, 103 patients (34.1%) met the definitions of clinically relevant LVEF reduction, including 52 patients (17.2%) with LVEF less than or equal to 35% and 51 patients (16.9%) with LVEF of 35.1% to 40.0%., Conclusions and Relevance: In this cohort study, approximately 1 in 3 patients with at least mild LVEF reduction after acute MI did not undergo indicated LVEF reassessment within 6 months, suggesting that programs to improve the quality of post-MI care should include measures to ensure that indicated repeat cardiac imaging is performed. In those with follow-up imaging, clinically relevant persistent LVEF reduction was identified in more than one-third of patients.

Background: Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) currently relies on arrhythmic burden quantification by 24 or 48-hour Holter monitoring. Whether this approach adequately captures arrhythmic burden, compared with longer-term continuous monitoring, is unclear. We sought to assess the long-term incidence of nonsustained ventricular tachycardia (NSVT) in HCM patients at low or moderate SCD risk, using implantable cardiac monitors (ICMs) paired with a novel Bluetooth-enabled 2-way communication platform., Methods: This prospective, single-arm, observational study enrolled 33 HCM patients. Patients were implanted with an Abbott (Chicago, IL) Confirm Rx ICM and monitored using a protocolized care pathway., Results: A total of 20 patients (60.6%) had ≥ 1 episode of NSVT recorded on the ICM, the majority of whom had previous Holter monitors that did not identify NSVT (60%, n = 12). A total of 71 episodes of NSVT were detected. Median time to first NSVT detection was 76.5 days (range: 0-553 days). A total of 19 patients underwent primary prevention implantable cardioverter defibrillator implantation during an average follow-up of 544 days (range: 42-925 days). A total of 172,112 automatic transmissions were received, and 65 (0.04%) required clinical follow-up. A total of 325 manual transmissions were received and managed. A total of 14 manual transmissions (4.3%) required follow-up, whereas 311 (95.7%) were managed solely with a text message., Conclusions: Surveillance and reporting systems utilizing 2-way communication enabled by novel ICMs are feasible and allow remote management of patients with HCM. Prolonged monitoring with ICMs identified more patients with nonsustained arrythmias than did standard Holter monitoring. In many cases, this information impacted both SCD risk stratification and patient management., (© 2021 The Authors.)

Physicians engaged in cardiovascular implantable electronic device (CIED)-related practice come from diverse training backgrounds with variable degrees of CIED implant training. The objective of the Canadian Heart Rhythm Society Task Force on CIED Implant Training was to establish a common structure and content for training programs in CIED implantation, related activities and maintenance of competency. This executive summary presents the essence of the report with key recommendations included, with the complete version made available in a linked supplement. The goals are to ensure that future generations of CIED implanters are better prepared for continuously evolving CIED practice and quality care for all Canadians., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The Medical Assistance in Dying (MAiD) program has been steadily expanding in Canada, and is expected to continue to do so. There are a substantial number of Canadians with pacemakers and defibrillators, many of whom are potential MAiD recipients. There is a need for review and reflection of standardisation of cardiac device management in MAiD patients, not only because of ethical concerns, but also because of the complexity of management at end of life. This document examines the status and role of cardiac devices (pacemakers and intracardiac defibrillators) and their physiologic interactions and influences during the MAiD process, and provides recommendations for their management., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Introduction: The relative effectiveness of medical therapy compared with a conservative approach of monitoring in patients with idiopathic frequent premature ventricular complexes (PVCs) is uncertain. We evaluated the effectiveness of medical versus conservative therapy for frequent PVCs., Methods: Patients with frequent PVCs (≥5%) were prospectively enrolled in this cohort study between 2016 and 2020. In patients with normal cardiac function and no structural heart disease, those receiving medical therapy were compared with controls without therapy. Patients were followed longitudinally for change in PVC burden and with serial echocardiography., Results: Overall, 120 patients met inclusion criteria (mean: 56.5 ± 14.6 years, 54.2% female) with 53 on beta-blockers or calcium channel blockers (BBs/CCBs), 27 on Class I or III antiarrhythmic drugs (AADs), and 40 patients treated conservatively. Median initial PVC burden ranged from 15.5% to 20.6%. The median relative reduction of PVCs was 32.7%, 30.5%, and 81.3%, in the conservative therapy, BBs/CCBs, and AADs cohorts, respectively. AADs had greater PVC reduction compared with BBs/CCBs (p = 0.017) and conservative therapy (p = 0.045). PVC reduction to <1% was comparable across groups at 35.0%, 17.0%, 33.3%, respectively. Four patients (4/120, 3.3%) developed left ventricular dysfunction. Rates of adverse drug reactions and medication discontinuation were similar between groups, with no serious adverse events noted., Conclusion: In patients with idiopathic frequent PVCs, BB, and CCB have limited effectiveness in PVC reduction. Class I and III AADs have superior effectiveness for medical therapy in symptomatic patients, but only achieved complete PVC resolution suppression in one-third of patients., (© 2021 Wiley Periodicals LLC.)

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments., Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN)., Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated., Interventions: Implanted medical device delivering 10-kHz SCS., Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months., Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001)., Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN., Trial Registration: ClincalTrials.gov Identifier: NCT03228420.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS 2 score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS 2 threshold of ≥ 1 (P < 0.001) and the impact of previous transient ischemic attack/stroke (P = 0.02). Calciphylaxis history affected the decision to prescribe anticoagulation. Specialties differed in thresholds used to consider direct oral anticoagulants for dialysis patients, with nephrologists more likely to prescribe anticoagulation at higher CHADS 2 scores. Our survey demonstrated significant heterogeneity of anticoagulation use for stroke prevention in patients with AF on dialysis. Physician specialty and patient risk profiles contributed to the observed variability. This study reemphasises the need for clinical trials, large observational studies, and consensus guidelines to address evident equipoise., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Rate control medications are foundational in the management of persistent atrial fibrillation (AF). There are no guidelines for adjusting these medications prior to elective direct-current cardioversion (DCCV)., Objective: To derive and validate a preprocedural medication adjustment protocol that maintains peri-DCCV rate control and minimizes risk of postconversion bradycardia, pauses, need for pacing, and cardiopulmonary resuscitation (CPR)., Methods: Consecutive patients with persistent AF awaiting elective DCCV across 2 hospitals were screened for inclusion into derivation, validation, and control cohorts. In the derivation cohort, each patient taking an atrioventricular (AV) nodal blocker had medications adjusted based on heart rate (HR) 2 days before DCCV, and the magnitude of dose adjustment was compared with peri-DCCV HR. The adjustment protocol that achieved the highest percentage of optimal peri-DCCV rate control was tested prospectively in the validation cohort and compared to a standard-of-care control group., Results: The optimal protocol from the derivation cohort (n = 71), based on the 2-day pre-DCCV HR, was to (1) CONTINUE AV nodal blocker for HR ≥ 100 beats per minute (bpm), (2) reduce dose by ONE increment when 80-99 bpm, (3) reduce dose by TWO increments when 60-79 bpm, and (4) HOLD when <60 bpm. In the prospective validation cohort (n = 106), this protocol improved peri-DCCV rate control (82% vs 62%, P < .001) compared to current standard of care (n = 107). There were no conversion pauses ≥5 seconds, need for pacing, or CPR post-DCCV., Conclusion: This simple preprocedural medication adjustment protocol provides an effective strategy of optimizing peri-DCCV rate control in patients with AF., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

Objective: Despite the widespread and increasing use of ambulatory electrocardiography (ECG), there is no consensus on reference ranges for ambulatory electrocardiogram parameters to guide interpretation. We sought to determine population distribution-based reference ranges for parameters measured during ambulatory electrocardiogram in healthy adults, based on existing literature., Methods: We searched multiple databases from 1950 to 2020. Articles reporting original data from ≥24-hour ambulatory electrocardiogram monitoring in healthy adults were included. Data extraction and synthesis were performed according to Meta-analysis of Observational Studies in Epidemiology guidelines. The prevalence/mean and SD for common parameters (sinus pauses, conduction abnormalities and ectopy) were extracted by age group (18-39, 40-59, 60-79 and 80+ years)., Results: We identified 33 studies involving 6466 patients. Sinus pauses of >3 s were rare (pooled prevalence <1%) across all ages. Supraventricular ectopy of >1000/24 hours increased with age, from 0% (95% CI 0% to 0%) in those aged 18-39 years to 6% (95% CI 0% to 17%) in those aged 60-79 years. Episodes of supraventricular tachycardia increased from 3% (95% CI 1% to 6%) in those aged 18-39 years to 28% (95% CI 9% to 52%) in those aged 60-79 years. Ventricular ectopy of >1000/24 hours also increased with age, from 1% (95% CI 0% to 2%) in those aged 18-39 years to 5% (95% CI 1% to 10%) in those aged 60-79 years. Episodes of non-sustained ventricular tachycardia ranged from 0% (95% CI 0% to 1%) in those aged 18-39 years to 2% (95% CI 0% to 5%) in those aged 60-79 years., Conclusion: Despite the limitations of existing published data, this meta-analysis provides evidence-based reference ranges for ambulatory electrocardiogram parameters and highlights significant age-dependent differences that should be taken into account during interpretation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The purpose of this study was to evaluate the efficacy, health care utilization, and safety of a same-day discharge protocol., Background: Catheter ablation of atrial fibrillation (AF) is the most common ablation performed. Increasing volumes of AF ablation are placing demands on hospital resources. In response, our institutions developed a same-day discharge protocol for AF ablation., Methods: This was a multicenter cohort study of all patients undergoing AF ablation from 2010 to 2014 at 2 major centers. The primary efficacy outcome was the proportion of successful same-day discharges. The primary health care utilization outcome was 30-day hospital readmission for any reason. The primary safety outcome was a composite of 30-day death, stroke/transient ischemic attack or embolism, or bleeding requiring hospitalization., Results: A total of 3,054 patients underwent AF ablation from 2010 to 2014 and met inclusion criteria. Same-day discharge was achieved in 79.2% (2,418 of 3,054). Hospital readmission at 30 days was 7.7% for the same-day discharge group, 10.2% for those who remained in the hospital overnight without complications (p = 0.055 for comparison with same-day discharge), and 19.5% (p < 0.001) for those who remained in the hospital with procedural complications (7.7%). Complication rates from discharge to 30 days (excluding immediate procedural complications) were 0.37% for the same-day discharge group, 0.36% (p = 0.999) for those kept overnight without complications, and 2.5% (p = 0.044) for those with initial procedural complications., Conclusions: Same-day discharge after AF ablation is feasible in the majority of patients with use of a standardized protocol. This approach was not associated with higher hospital readmission or complication rates after discharge., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

A comparative study of mesoporous thin films based on SnO 2 (rutile) and TiO 2 (anatase) nanocrystallites sensitized to visible light with [Ru(dtb) 2 (dcb)](PF 6 ) 2 , where dtb = 4,4'-( tert -butyl) 2 -2,2'-bipyridine and dcb = 4,4'-(CO 2 H) 2 -2,2'-bipyridine, in CH 3 CN electrolyte solutions is reported to identify the reason(s) for the low efficiency of SnO 2 -based dye-sensitized solar cells (DSSCs). Pulsed laser excitation resulted in rapid excited state injection ( k inj > 10 8 s -1 ) followed by sensitizer regeneration through iodide oxidation to yield an interfacial charge separated state abbreviated as MO 2 (e - )|Ru + I 3 - . Spectral features associated with I 3 - and the injected electron MO 2 (e - ) were observed as well as a hypsochromic shift of the metal-to-ligand charge-transfer absorption of the sensitizer attributed to an electric field. The field magnitude ranged from 0.008 to 0.39 MV/cm and was dependent on the electrolyte cation (Mg 2+ or Li + ) as well as the oxide material. Average MO 2 (e - ) + I 3 - → recombination rate constants quantified spectroscopically were about 25 times smaller for SnO 2 (6.0 ± 0.14 s -1 ) than for TiO 2 (160 ± 10 s -1 ). Transient photovoltage measurements of operational DSSCs indicated a 78 ms lifetime for electrons injected into SnO 2 compared to 27 ms for TiO 2 ; behavior that is at odds with the view that recombination with I 3 - underlies the low efficiencies of nanocrystalline SnO 2 -based DSSCs. In contrast, the average rate constant for charge recombination with the oxidized sensitizer, MO 2 (e - )|-S + → MO 2 |-S, was about 2 orders of magnitude larger for SnO 2 ( k = 9.8 × 10 4 s -1 ) than for TiO 2 ( k = 1.6 × 10 3 s -1 ). Sensitizer regeneration through iodide oxidation were similar for both oxide materials ( k reg = 6 ± 1 × 10 10 M -1 s -1 ). The data indicate that enhanced efficiency from SnO 2 -based DSSCs can be achieved by identifying alternative redox mediators that enable rapid sensitizer regeneration and by inhibiting recombination of the injected electron with the oxidized sensitizer.

Purpose: The purpose of this study was to evaluate the impact of steerable sheaths on multiple contact force parameters during atrial fibrillation (AF) ablation. Steerable sheaths are commonly used during AF ablation, at an additional cost to standard fixed-curve sheaths. However, there is little data on their incremental value in the era of contact force-guided radiofrequency ablation., Methods: This multi-center cohort study included consecutive patients undergoing index pulmonary vein (PV) isolation with a force-sensing catheter. Operators employed either only steerable or only fixed-curve sheaths. Operators targeted a force of 10-40 g for each ablation lesion. Automated ablation lesion assessment software with standardized settings was employed., Results: Of 85 subjects, 52 and 33 underwent ablation with steerable and fixed-curve sheaths, respectively. The steerable sheath group showed significantly higher average and maximum forces, but predominantly for the right PVs. The proportion of lesions with ≥ 10% of time with less than 10 g of force was lower in the steerable sheath group (adjusted odds ratio 0.56, steerable vs. fixed; 95% confidence interval 0.35, 0.89, p = 0.01). Improved stability was seen in the posterior aspect of both PV pairs. The proportion of RF time-in-target (the proportion of RF time meeting lesion criteria) was not different between the two groups (p = 0.176)., Conclusions: Even with contemporary contact force targets, steerable sheath use in AF ablation is associated with better average and maximum contact force and increased stability in comparison to fixed-curve sheaths.

Cardiac amyloidosis occurs secondarily to the deposition of insoluble protein fibrils in cardiac tissue leading to progressive myocardial dysfunction, clinical heart failure, and arrhythmia. In recent years, increasing awareness and improved screening have resulted in an increased prevalence of cardiac amyloidosis, with contemporary estimates reporting a prevalence of 18-55 cases per 100,000 person-years, accounting for > 13% of heart failure hospitalizations. The arrhythmic manifestations of cardiac amyloidosis can range from conduction-system disease and bradyarrhythmias to atrial fibrillation and sudden cardiac death. Bradyarrhythmias and conduction system disease may occur secondarily to amyloid infiltration, but the timing of pacemaker implantation remains unclear. When available, biventricular pacing should be considered in symptomatic patients, particularly in those expected to receive a high burden of ventricular pacing (> 40%). The management of atrial fibrillation can be challenging, because contemporary agents for rate and rhythm control may be poorly tolerated in patients with cardiac amyloidosis. Patients with cardiac amyloidosis also have a high rate of intracardiac thrombus and should be anticoagulated in the presence of atrial fibrillation (regardless of CHADS 2 score). We generally consider transesophageal echocardiography before cardioversion regardless of anticoagulation status or duration of arrhythmia. Ventricular arrhythmias may also occur in patients with cardiac amyloidosis, and decisions surrounding implantable cardioverter-defibrillator implantation should balance the risks of ventricular arrhythmia and sudden cardiac death with the competing risks of worsening heart failure and noncardiac death. In this review, we cover the primary arrhythmic manifestations of cardiac amyloidosis and discuss their management considerations., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation., Methods: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder., Results: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively ( P =0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively ( P =0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%-100.0%) with CF-RF, 99.9% (interquartile range, 65.3%-100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%-100.0%) with Cryo-2 ( P =0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups ( P =0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure ( P <0.001 vs cryoballoon groups)., Conclusions: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913522.

Objective: The objective of the study was to determine the optimal formula to estimate QT interval adjusting for QRS prolongation during right ventricular (RV) pacing., Methods: This observational study included individuals (n = 43) with a newly implanted permanent ventricular pacemaker, who had a narrow QRS complex before pacemaker insertion. QT interval with RV pacing was related to QT interval before pacemaker implantation. The validation cohort (n = 442) had permanent RV pacing in DDD mode., Results: A new QTc formula was derived utilizing the constants from the relationship between the spline heart rate QT correction (QTcRBK) before and after pacing; specifically, QTcRBK PACED  = QTcRBK × 0.86. The JT interval from paced complexes was highly heart rate (HR) dependent and was not accurate for QT assessment. Previous, QTc formula for paced complexes were not highly correlated with QT before pacing unless a robust HR correction is added. Formulae subtracting a fixed amount from QTc PACED markedly overestimated QTc before pacing., Conclusion: We proposed a new, simple formula for QT estimation in RV pacing. JT interval in paced complexes is highly HR dependent and is not accurate for QT assessment. The new spline approach for HR correction for the QT, once incorporated into some previously proposed formulae, blunts HR dependency and improves prediction of QT before pacing. QTcRBK PACED *0.86 and QTcRBK PACED - (QRS*0.5) demonstrated the best balance of relatively strong correlation to QTc before pacing and accurate QTc prolongation identification. Abnormal QT for QTcRBK PACED *0.86 as defined by the 97.5th and 99th percentile are 469 and 479 ms respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A study of SnO 2 /TiO 2 core/shell films was undertaken to investigate the influences of shell thickness and post deposition sintering on electron localization and transport properties. Electrochemical reduction of the materials resulted in the appearance of a broad visible-near IR absorbance that provided insights into the electronic state(s) within the core/shell structures. As the shell thickness was increased from 0.5 to 5 nm, evidence for the presence of a Sn x Ti 1- x O 2 interfacial state emerged that was physically located between the core and the shell. The lifetime of photoinjected electrons increased with the shell thickness. Electron transport occurred through the SnO 2 core; however, when materials with shell thicknesses ≥2 nm were annealed at 450 °C, a new electron transport pathway through the shell was evident. The data indicate that these materials are best described as SnO 2 /Sn x Ti 1- x O 2 /TiO 2 where electrons preferentially localize in a Sn x Ti 1- x O 2 interfacial state and transport through SnO 2 and annealed TiO 2 (if present). The implications of these results for applications in solar energy conversion are discussed.

Objective: The natural history of frequent premature ventricular complexes (PVCs) in association with preserved left ventricular ejection fraction (LVEF) is uncertain. The optimal management of this population is thus undefined. We studied the outcomes of untreated patients with frequent PVCs and preserved LVEF., Methods: This cohort study prospectively evaluated consecutive patients from 2012 to 2017, with asymptomatic or minimally symptomatic frequent idiopathic PVCs (≥5% PVCs in 24 hours; normal LVEF; no cause identified on comprehensive evaluation). No suppressive therapy (ablation or antiarrhythmic drugs) were used and patients were followed with serial ambulatory ECG monitoring and echocardiography. The primary arrhythmic outcome was reduction in PVC burden to <1% on serial ambulatory monitoring. The primary echocardiographic outcome was a reduction of LVEF to <50%., Results: One hundred patients met inclusion criteria (mean age 51.8 years, 57% female) with a median PVC burden of 18.4%. Reduction to <1% PVCs occurred in 44 of 100 patients (44.0%) at a median of 15.4 months (range 2.6 to 64.3). Recurrence was uncommon (4/44, 9.1%). Four patients (4.3%) with a persistently elevated PVC burden developed left ventricular dysfunction (LVEF <50%) during the follow-up period at a range of 53-71 months. The initial PVC burden did not predict subsequent resolution (HR 1.00(0.97, 1.03); p=0.86)., Conclusions: A strategy of active surveillance is appropriate for the majority of patients with frequent idiopathic PVCs in association with preserved LVEF, owing to the low risk of developing left ventricular systolic dysfunction and the high rate of spontaneous resolution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Implantable cardioverter defibrillator arrhythmia discrimination algorithms often are unable to discriminate ventricular from supraventricular arrhythmias. We sought to evaluate whether the response to antitachycardia pacing (ATP) in patients with an implantable cardioverter defibrillator could further discriminate ventricular from supraventricular arrhythmias in patients receiving ATP., Methods and Results: All episodes of ventricular or supraventricular tachycardia where ATP was delivered in patients enrolled in RAFT (Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Trial) were included. RAFT randomized 1798 patients with New York Heart Association class II/III heart failure, left ventricular ejection fraction ≤30%, and QRS duration of ≥120 ms to a implantable cardioverter defibrillator±cardiac resynchronization therapy. The tachycardia cycle lengths (TCLs) before and after the delivery of ATP and the postpacing intervals were assessed. Overall, 10 916 ATP attempts were reviewed for 8150 tachycardia episodes in 924 patients. After excluding tachycardias where ATP terminated the episode or where the specific mechanism of the tachycardia was uncertain, we analyzed 3676 ATP attempts delivered for 2046 tachycardia episodes in 541 patients. A shorter difference between postpacing interval and TCL (PPI-TCL) was more likely to be associated with ventricular tachycardia than with supraventricular tachyarrhythmia (138.1±104.2 versus 277.4±126.9 ms; p <0.001). Analysis of the receiver operator curve for the PPI-TCL revealed an area under the curve of 0.803 ( p <0.001; 95% confidence interval, 0.784-0.822). The majority of tachycardias with a PPI-TCL >360 ms were supraventricular with a PPI-TCL value of ≤360 ms having a sensitivity of 97.4% and specificity of 28.3% for ventricular tachycardia., Conclusions: The ATP response, specifically the PPI-TCL, can further discriminate ventricular from supraventricular arrhythmias in patients with implantable cardioverter defibrillators when the currently available discriminators fail., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00251251., (© 2018 American Heart Association, Inc.)

[This corrects the article DOI: 10.1371/journal.pone.0169483.].