Search

Areas of abnormal or heterogeneous conduction velocity (CV) are important ablation targets for ventricular tachycardias, yet precise assessment of CV in clinical contact mapping remains challenging. Numerous different CV estimation methods have been proposed. This study aimed to compare the automated local activation time (LAT)–independent omnipolar-based CV estimation method termed wave speed (WS) with 4 established LAT-based methods to formally establish the quantitative differences between them. High-density contact maps in patients with structurally normal hearts during sinus rhythm (SR) and ventricular ectopy (VE) were retrospectively analyzed. CV was assessed and compared by 5 methods: omnipolar WS, gradient method, planar wavefront fitting, circular wavefront fitting, and radial basis function. CV variations based on electrogram (EGM) type (unipolar, bipolar, and omnipolar), catheter movement, and surrogate markers for catheter contact were analyzed. The study included 23 patients (47.8% male; 45.7 ± 17.3 years) with 22 SR maps (11 left ventricle, 11 right ventricle) and 16 VE maps (9 left ventricle, 7 right ventricle). The WS algorithm yielded statistically significant higher CV estimates in SR (mean, 1.41 ± 0.18 m/s) and VE (mean, 1.23 ± 0.18 m/s) maps compared with all LAT-based estimation methods, with absolute differences ranging from 0.1 m/s to 0.81 m/s. Median pointwise differences in SR and VE between WS and LAT-based methods were high, ranging from 0.55 ± 0.15 m/s (WS vs planar wavefront fitting) to 0.67 ± 0.16 m/s (WS vs radial basis function). For LAT-based methods, use of unipolar EGMs yielded significantly higher CV estimates than bipolar or omnipolar EGMs in SR. The CV estimation method has an important, statistically significant impact on ventricular CV measurements. Future work will focus on how these differences affect identification of pathologic conduction slowing in scar-related substrate. [Display omitted] [ABSTRACT FROM AUTHOR]

The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events. This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias. This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm. In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13–279.95; P <.001). A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure. [Display omitted] [ABSTRACT FROM AUTHOR]

Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. Genetic testing reports for patients referred to our clinic from 2004–2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy. [ABSTRACT FROM AUTHOR]

This review highlights the links between psychological stress and the neurocircuitry of cardiac–brain interactions leading to arrhythmias. The role of efferent and afferent connections in the heart–brain axis is considered, with the mechanisms by which emotional responses promote arrhythmias illustrated by inherited cardiac conditions. Novel therapeutic targets for intervention in the autonomic nervous system are considered. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and can be challenging to manage. Atrioventricular nodal (AVN) ablation may be an effective management strategy for AF in these patients. The purpose of this study was to assess the efficacy of AVN ablation in HCM patients who have failed medical therapy and/or catheter ablation for AF. A multicenter study with retrospective analysis of a prospectively collated HCM registry was performed. AVN ablation patients were identified. Baseline characteristics and device and procedural indications were collected. Symptoms defined by New York Heart Association and European Heart Rhythm Association classification and echocardiographic findings during follow-up were assessed. Fifty-nine patients were included in the study. Indications for AVN ablation were 6 (10.2%) inappropriate implantable cardioverter-defibrillator shock, 35 (59.3%) ineffective rate control, and 18 (30.5%) to regularize rhythm for symptom improvement. During post-AVN ablation follow-up of 79.4 ± 61.1 months, left ventricular ejection fraction (LVEF) remained stable (pre-LVEF 48.9% ± 12.6% vs post-LVEF 50.1% ± 10.1%; P =.29), even in those without a cardiac resynchronization therapy (CRT) device (pre-LVEF 54.3% ± 8.0% vs post-LVEF 53.8% ± 8.0%; P =.65). Forty-nine patients (83.1%) reported an improvement in symptoms regardless of AF type (17/21 [81.0%] paroxysmal vs 32/38 [84.2%] persistent; P = 1.00), presence of baseline left ventricular impairment (22/26 [84.6%] LVEF ≤50% vs 27/33 [81.8%] LVEF ≥50%; P = 1.00) or CRT device (27/32 [84.4%] CRT vs 22/27 [81.5%] no CRT; P = 1.00). Symptoms improved in 16 patients (89.0%) who underwent AVN ablation to regularize rhythm. AVN ablation improved symptoms without impacting left ventricular function in the majority of patients. The data suggest that AVN ablation is an effective and safe management approach for AF in HCM and should be further evaluated in larger prospective studies. [ABSTRACT FROM AUTHOR]

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs. [ABSTRACT FROM AUTHOR]

Background: Mechanisms sustaining persistent atrial fibrillation (AF) remain uncertain.Objectives: The purpose of this study was to use electrocardiographic imaging (ECGI) mapping to guide localized driver ablation in patients with persistent AF.Methods: Patients undergoing catheter ablation for persistent AF <2 years were included. Patients were enrolled consecutively between 2018 and 2020. ECGI mapping was used to identify focal and rotational potential drivers (PDs). PDs were ablated after pulmonary vein isolation (PVI). The ablation response and freedom from AF/atrial tachycardia (AT) at 1 year were assessed.Results: Forty patients were enrolled. AF terminated with PVI in 8 patients, and 32 underwent ECGI-guided driver ablation. Average procedural duration was 228.8 ± 66.7 minutes, with a total radiofrequency delivery time of 38.9 ± 14.1 minutes. During 1 year of follow-up, the primary endpoint of freedom from AF/AT was achieved in 26 patients (65%). The secondary endpoint of freedom from AF was achieved in 30 patients (75%). AF termination was achieved in 20 of 40 patients (50%). The composite endpoint of an ablation response (AF termination or cycle length slowing ≥10%) occurred in 37 of 40 patients (92.5%). In total, 181 drivers (48 focal and 133 rotational) were ablated, with an ablation response achieved in 59 (32.6%). Focal drivers and drivers with a higher recurrence rate and greater temporal stability were more likely to be associated with an ablation response including AF termination (P <.001).Conclusion: ECGI-guided ablation plus PVI results in high freedom from AF during follow-up and an ablation response in a large proportion of patients. Using driver type and characteristics may facilitate a hierarchical ablation approach. [ABSTRACT FROM AUTHOR]

Background: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear.Objective: The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology.Methods: In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models.Results: Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01-0.38] ms/%; P = .04) and increased local ARI dispersion (effect size -0.13 [-0.23 to -0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01).Conclusion: Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Background: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection.Objective: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population.Methods: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted.Results: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus.Conclusion: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection. [ABSTRACT FROM AUTHOR]

Brugada syndrome is an inherited cardiac condition characterized by a typical electrocardiogram signature of coved-type ST-segment elevation in the right precordial leads and ventricular arrhythmias leading to sudden cardiac death, in the absence of unequivocal structural heart disease. Brugada syndrome specifically affects the right ventricle, which predisposes to cardiac arrest. Besides medical management with quinidine, emerging data indicate that catheter ablation can help reduce the ventricular arrhythmia burden in these patients. This review explores the mechanisms of ventricular arrhythmia, current approaches and evidence for ablating the epicardial arrhythmogenic substrate in this condition. [ABSTRACT FROM AUTHOR]

Background: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT.Objective: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate.Methods: Eighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation-recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively.Results: The origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408-2098) (median, 1st-3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2-10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients.Conclusion: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9–6.1]; P <0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4–6.4]; P =0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6–17.9]; P <0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6–4.1]; P =0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P =0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P =0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P =0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P =0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator%5f876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients. [ABSTRACT FROM AUTHOR]

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has shown favorable outcomes in large registries with broad inclusion criteria. The cohorts reported had less heart disease and fewer comorbidities than standard ICD populations.Objective: The purpose of this study is to characterize acute performance for primary prevention patients with a left ventricular ejection fraction (LVEF) ≤35% (primary prevention ≤35%).Methods: Primary prevention ≤35% patients with no prior documented sustained ventricular tachycardia (VT), pacing indication, end-stage heart failure, or advanced renal failure were prospectively enrolled. Analyses included descriptive statistics, Kaplan-Meier time to event, and multivariable linear and logistic regression.Results: In 1112 of 1116 patients, an S-ICD was successfully implanted (99.6%). Predictors for longer procedure time included 3-incision technique, higher body mass index (BMI), performing defibrillation testing (DFT), imaging, younger age, black race, and European vs North American centers. Patients undergoing DFT (82%) were successfully converted (99.2%; 93.5% converting at ≤65 J). Higher BMI was predictive of failing DFT at ≤65 J. The rate of 30-day freedom from complications was 95.8%. Most complications involved postoperative healing (45%) or interventions after DFT or impedance check (19%).Conclusion: The procedural outcome data of UNTOUCHED reinforce that S-ICD therapy has low perioperative complication rates and high conversion efficacy of induced ventricular fibrillation, even in a higher-risk cohort with low LVEF and more comorbidities than previous S-ICD studies. Higher BMI warrants more careful attention to implant technique. [ABSTRACT FROM AUTHOR]

Background: The relationship between the surface electrocardiogram (ECG) T wave to intracardiac repolarization is poorly understood.Objective: The purpose of this study was to examine the association between intracardiac ventricular repolarization and the T wave on the body surface ECG (SECGTW).Methods: Ten patients with a normal heart (age 35 ± 15 years; 6 men) were studied. Decapolar electrophysiological catheters were placed in the right ventricle (RV) and lateral left ventricle (LV) to record in an apicobasal orientation and in the lateral LV branch of the coronary sinus (CS) for transmural recording. Each catheter (CS, LV, RV) was sequentially paced using an S1-S2 restitution protocol. Intracardiac repolarization time and apicobasal, RV-LV, and transmural repolarization dispersion were correlated with the SECGTW, and a total of 23,946 T waves analyzed.Results: RV endocardial repolarization occurred on the upslope of lead V1, V2, and V3 SECGTW, with sensitivity of 0.89, 0.91, and 0.84 and specificity of 0.67, 0.68, and 0.65, respectively. LV basal endocardial, epicardial, and mid-endocardial repolarization occurred on the upslope of leads V6 and I, with sensitivity of 0.79 and 0.8 and specificity of 0.66 and 0.67, respectively. Differences between the end of the upslope in V1, V2, and V3 vs V6 strongly correlated with right to left dispersion of repolarization (intraclass correlation coefficient 0.81, 0.83, and 0.85, respectively; P <.001). Poor association between the T wave and apicobasal and transmural dispersion of repolarization was seen.Conclusion: The precordial SECGTW reflects regional repolarization differences between right and left heart. These findings have important implications for accurately identifying biomarkers of arrhythmogenic risk in disease. [ABSTRACT FROM AUTHOR]

Background: The comparative efficacy of antiarrhythmic drug (AAD) therapy vs ventricular tachycardia (VT) ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC) is unknown.Objective: We compared outcomes of AAD and/or β-blocker (BB) therapy with those of VT ablation (with AAD/BB) in patients with ARVC who had recurrent VT.Methods: In a multicenter retrospective study, 110 patients with ARVC (mean age 38 ± 17 years; 91[83%] men) with a minimum of 3 VT episodes were included; 77 (70%) were initially treated with AAD/BB and 32 (29%) underwent ablation. Subsequently, 43 of the 77 patients treated with AAD/BB alone also underwent ablation. Overall, 75 patients underwent ablation.Results: When comparing initial AAD/BB therapy (n = 77) and VT ablation (n = 32) after ≥3 VT episodes, a single ablation procedure rendered 35% of patients free of VT at 3 years compared with 28% of AAD/BB-only-treated patients (P = .46). Of the 77 AAD/BB-only-treated patients, 43 subsequently underwent ablation. For all 75 patients who underwent ablation, 56% were VT-free at 3 years after the last ablation procedure. Epicardial ablation was used in 40/75 (53%) and was associated with lower VT recurrence after the last ablation procedure (endocardial/epicardial vs endocardial-only; 71% vs 47% 3-year VT-free survival; P = .05). Importantly, there was no difference in survival free of death or transplantation between the ablation- and AAD/BB-only-treated patients (P = .61).Conclusion: In patients with ARVC and a high VT burden, mortality and transplantation-free survival are not significantly different between drug- and ablation-treated patients. These patients have a high risk of recurrent VT despite drug therapy. Combined endocardial/epicardial ablation is associated with reduced VT recurrence as compared with endocardial-only ablation. [ABSTRACT FROM AUTHOR]

Background: Rate-dependent conduction velocity (CV) slowing is associated with atrial fibrillation (AF) initiation and reentrant mechanisms.Objective: The purpose of this study was to assess the relationship between bipolar voltage, CV dynamics, and AF drivers.Methods: Patients undergoing catheter ablation for persistent AF (<24 months) were enrolled. Unipolar electrograms were recorded with a 64-pole basket catheter during atrial pacing at 4 pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path and correlated with underlying bipolar voltage. CV dynamics within low-voltage zones (LVZs <0.5 mV) were compared to those of non-LVZs (≥0.5 mV) and were correlated to driver sites mapped using CARTOFINDER (Biosense Webster).Results: Eighteen patients were included (age 62 ± 10 years). Mean CV at 600 ms was 1.59 ± 0.13 m/s in non-LVZs vs 0.98 ± 0.23 m/s in LVZs (P <.001). CV decreased incrementally over all 4 PIs in LVZs, whereas in non-LVZs a substantial decrease in CV was only seen between PIs 300-250 ms (0.59 ± 0.09 m/s; P <.001). Rate-dependent CV slowing sites measurements, defined as exhibiting CV reduction ≥20% more than the mean CV reduction seen between PIs 600-250 ms for that voltage zone, were predominantly in LVZs (0.2-0.5 mV; 75.6% ± 15.5%; P <.001). Confirmed rotational drivers were mapped to these sites in 94.1% of cases (sensitivity 94.1%, 95% CI 71.3%-99.9%; specificity 77.9%, 95% CI 74.9%-80.7%).Conclusion: CV dynamics are determined largely by the extent of remodeling. Rate-dependent CV slowing sites are predominantly confined to LVZs (0.2-0.5 mV), and the resultant CV heterogeneity may promote driver formation in AF. [ABSTRACT FROM AUTHOR]

Background: Better characterization of drivers in atrial fibrillation (AF) may facilitate their identification.Objective: The purpose of this study was to demonstrate that certain driver characteristics are associated with greater mechanistic importance in maintaining AF.Methods: Persistent AF was mapped in patients using the CARTOFINDER system with a 64-pole basket catheter to identify and ablate drivers with rotational or focal activity after pulmonary vein isolation. An ablation response was defined as cycle length (CL) slowing ≥30 ms or AF termination. Driver sites with an ablation response were correlated to sites of fastest CL, highest dominant frequency (DF), and greatest organization (lowest cycle length variability [CLV] and highest regularity index [RI]). Parameters predicting AF termination with driver ablation were evaluated.Results: All 29 patients had ≥1 driver identified. Forty-four potential drivers were identified. The predefined ablation response occurred with 39 drivers (89%): 23 rotational and 16 focal. During a 30-second recording, each driver occurred 8.7 ± 5.4 times and completed 3.1 ± 0.9 consecutive repetitions per occurrence. Driver sites correlated best with markers of organization, corresponding to the site of lowest CLV (29/39 [74%]) and highest RI (26/39 [67%]). Correlation with sites of fastest CL and highest DF was poor (17/39 and 15/39, respectively) and depended on driver temporal stability. Greater temporal stability (3.4 ± 0.9 vs 2.7 ± 0.6; P = .001) and driver correlation with sites of lowest CLV and highest RI (both P <.001) predicted AF termination with ablation.Conclusion: Intermittent focal or rotational drivers were identified in all patients. Drivers consistently correlated to organization markers. Greater temporal stability and organization predicted AF termination with driver ablation. [ABSTRACT FROM AUTHOR]

BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. CONCLUSIONS: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. [ABSTRACT FROM AUTHOR]

The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I Na and I Kr . Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls. [ABSTRACT FROM AUTHOR]

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in the young. Improved noninvasive assessment of ARVC and better understanding of the disease substrate are important for improving patient outcomes.Methods and Results: We studied 20 genotyped ARVC patients with a broad spectrum of disease using electrocardiographic imaging (a method for noninvasive cardiac electrophysiology mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration (median, 52 versus 42 ms; P=0.007) and prolonged mean epicardial activation-recovery intervals (a surrogate for local action potential duration; median, 275 versus 241 ms; P=0.014). In these patients, we observed abnormal and varied epicardial activation breakthrough locations and regions of nonuniform conduction and fractionated electrograms. Nonuniform conduction and fractionated electrograms were present in the early concealed phase of ARVC. Electrophysiological abnormalities colocalized with late gadolinium enhancement scar, indicating a relationship with structural disease. Premature ventricular contractions were common in ARVC patients with variable initiation sites in both ventricles. Premature ventricular contraction rate increased with exercise, and within anatomic segments, it correlated with prolonged repolarization, electric markers of scar, and late gadolinium enhancement (all P<0.001).Conclusions: Electrocardiographic imaging reveals electrophysiological substrate properties that differ in ARVC patients compared with healthy controls. A novel mechanistic finding is the presence of repolarization abnormalities in regions where ventricular ectopy originates. The results suggest a potential role for electrocardiographic imaging and late gadolinium enhancement in early diagnosis and noninvasive follow-up of ARVC patients. [ABSTRACT FROM AUTHOR]

Background: The features of the hypertrophic cardiomyopathy (HCM) ECG make it a challenge for subcutaneous implantable cardioverter-defibrillator (S-ICD) screening. We aimed to investigate the causes of screening failure at rest and on exercise to inform optimal S-ICD ECG vector development.Methods and Results: One hundred and thirty-one HCM patients (age, 50±16 years; 92 males and 39 females) with ≥1 HCM risk factor for sudden death underwent S-ICD ECG screening at rest and on exercise. Fifty patients (38%) were ineligible for S-ICD because of screening failure in every lead vector: 33 (66%) failed in the supine position, 12 (24%) failed in the standing position, and 5 (10%) failed on exercise. In patients who could exercise and passed screening at rest, 31 (44%) had 1 vector safety, 16 (23%) had 2 vector safety, and 24 (33%) had 3 vector safety. Increased R:T wave ratio in the S-ICD screening ECG (odds ratio, 4.0; confidence interval, 3.0-5.3; P<0.001) was associated with screening failure, while R/T ratio <3 in aVF (odds ratio, 0.3; confidence interval, 0.12-0.69; P=0.006) and increasing age (odds ratio, 0.97; confidence interval, 0.95-0.99; P=0.03) was associated with reduced screening failure. European Society of Cardiology risk score was higher in those failing screening (risk score 5.5% [interquartile range, 3.2-8.7] in failed versus 4.5% [interquartile range, 2.9-7.4] in passed; P=0.04).Conclusions: HCM patients have a significant incidence of screening failure, which is determined primarily by the increased R:T ratio on the screening ECG and lead aVF. High-risk patients have an increased screening failure rate. Optimization of sensing algorithms is required to ensure that the highest risk HCM patients can benefit from S-ICD implantation. [ABSTRACT FROM AUTHOR]