Novel Phenotypic Effects of a Rare SCN5A (c.2482C>T) Mutation.

In a familial cohort with 8 heterozygous carriers of a rare pathogenic SCN5A mutation (c.2482C>T), 4 female mutation carriers manifested with fetal ventricular tachycardia and 2:1 atrioventricular block. One presented with multifocal ectopic premature Purkinje-related complexes-like phenotype and atrial fibrillation later in life. These novel findings inform the need for robust fetal monitoring of mutation carriers.

Identification of Human Ventricular Tachycardia Demarcated by Fixed Lines of Conduction Block in a 3-Dimensional Hyperboloid Circuit.

BACKGROUND: The circuit boundaries for reentrant ventricular tachycardia (VT) have been historically conceptualized within a 2-dimensional (2D) construct, with their fixed or functional nature unresolved. This study aimed to examine the correlation between localized lines of conduction block (LOB) evident during baseline rhythm with lateral isthmus boundaries that 3-dimensionally constrain the VT isthmus as a hyperboloid structure. METHODS: A total of 175 VT activation maps were correlated with isochronal late activation maps during baseline rhythm in 106 patients who underwent catheter ablation for scar-related VT from 3 centers (42% nonischemic cardiomyopathy). An overt LOB was defined by a deceleration zone with split potentials (≥20 ms isoelectric segment) during baseline rhythm. A novel application of pacing within deceleration zone (≥600 ms) was implemented to unmask a concealed LOB not evident during baseline rhythm. LOB identified during baseline rhythm or pacing were correlated with isthmus boundaries during VT. RESULTS: Among 202 deceleration zones analyzed during baseline rhythm, an overt LOB was evident in 47%. When differential pacing was performed in 38 deceleration zones without overt LOB, an underlying concealed LOB was exposed in 84%. In 152 VT activation maps (2D=53, 3-dimensional [3D]=99), 69% of lateral boundaries colocalized with an LOB in 2D activation patterns, and the depth boundary during 3D VT colocalized with an LOB in 79%. In VT circuits with isthmus regions that colocalized with a U-shaped LOB (n=28), the boundary invariably served as both lateral boundaries in 2D and 3D. Overall, 74% of isthmus boundaries were identifiable as fixed LOB during baseline rhythm or differential pacing. CONCLUSIONS: The majority of VT circuit boundaries can be identified as fixed LOB from intrinsic or paced activation during sinus rhythm. Analysis of activation while pacing within the scar substrate is a novel technique that may unmask concealed LOB, previously interpreted to be functional in nature. An LOB from the perspective of a myocardial surface is frequently associated with intramural conduction, supporting the existence of a 3D hyperboloid VT circuit structure. Catheter ablation may be simplified to targeting both sides around an identified LOB during sinus rhythm.

Variations in Atrial Fibrillation Ablation Use and Charges in a Modern Cohort of Medicare Beneficiaries.

Catheter ablation of atrial fibrillation (CAF) is increasingly being used in the United States. This study aimed to identify variations in CAF use among Medicare beneficiaries (MBs) over a 6-year period (2013 to 2019). Using the Center of Medicare and Medicaid Services database, a 100% sample of MBs who underwent CAF from 2013 to 2019 was included. We stratified CAF use data geographically (Northeast, South, West, and Midwest) and identified the number of CAFs per 100,000 MBs, number of electrophysiologists performing CAFs per 100,000 MBs, number of CAFs per individual electrophysiologist, and average submitted charge for CAF. In addition, we stratified the data per urban versus rural areas and gender of the operator. We found that the mean atrial fibrillation (AF) prevalence, rates of CAFs, number of electrophysiologists performing CAFs, and number of CAFs per electrophysiologist have increased steadily in all regions. The mean AF prevalence was different among regions, with the highest prevalence in the Northeast (p <0.001); however, there was a pattern of higher CAFs rates in the West and the South (p ≥0.057). The number of electrophysiologists performing CAFs was not different among regions; however, the number of CAFs per electrophysiologist was higher in the West and the South (p <0.001). The average submitted charge for CAF has decreased over years and was the lowest in the West and the South (p <0.001). There was no major difference in these variables regarding operator gender. In conclusion, there are significant variations in CAF use among MBs in the United States according to geographic and urban versus rural regions. These variations have the potential to impact the outcomes in MBs diagnosed with AF.

Population-Level Impact of the Guidelines Update on Patient Selection and Outcomes After Cardiac Resynchronization Therapy.

OBJECTIVES: This study sought to analyze the impact of the American College of Cardiology, American Heart Association, and Heart Rhythm Society (ACC/AHA/HRS) guidelines for cardiac resynchronization therapy with defibrillator (CRT-D) update on utilization and efficacy of CRT-D. BACKGROUND: In September 2012, the ACC/AHA/HRS guidelines for CRT-D were modified to include left bundle branch block (LBBB) as a Class I indication. METHODS: The IBM Watson MarketScan Database was queried between January 1, 2003, and December 31, 2018, for CRT-D implants or upgrades. The primary outcome was heart failure (HF) hospitalization following left ventricular lead implant. Secondary outcomes included all-cause mortality and device-related lead revision. RESULTS: A total of 27,238 patients were analyzed: 18,384 pre-update and 8,854 post-update. Mean age was 69 ± 11 years, 73% men, and 98% with history of HF hospitalization. The proportion of patients with LBBB increased from 29% to 55% (P < 0.001) after the update. Patients receiving CRT-D post-update demonstrated a greater prevalence of comorbidities, including atrial fibrillation (47% vs 40%; P < 0.001), diabetes mellitus (45% vs 39%; P < 0.001), chronic kidney disease (24% vs 15%; P < 0.001), and HF hospitalization in the year before CRT-D (40% vs 37%; P < 0.001). Despite greater baseline comorbidities, HF hospitalization significantly declined post-update (HR: 0.89; P < 0.001). Multivariate predictors of reduced HF hospitalization included angiotensin receptor neprilysin inhibitor prescription (HR: 0.48; P < 0.001) and presence of LBBB (HR: 0.71; P < 0.001). All-cause mortality was not significantly different between the 2 groups, and fewer lead revisions were noted post-update (0.6% vs 1.7%; P < 0.001). CONCLUSIONS: The revised 2012 guidelines led to an increased proportion of LBBB patients receiving CRT-D at the population-level. This change was associated with reduced HF hospitalization, despite broadening therapy to patients with more comorbid conditions.

Empiric ablation of polymorphic ventricular tachycardia/fibrillation in the absence of a mappable trigger: Prospective feasibility and efficacy of pacemap matching to defibrillator electrograms.

BACKGROUND: Catheter ablation strategies for ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PMVT) are not established when spontaneous triggers are rare or absent. OBJECTIVE: The purpose of this study was to report the feasibility and efficacy of a novel empiric ablation strategy of pacemapping to stored implantable cardioverter-defibrillator (ICD) template electrograms (SITE) of the clinical premature ventricular contraction (PVC) trigger. METHODS: Fifteen patients with drug-refractory VF/PMVT receiving defibrillator shocks without identifiable and mappable PVC triggers were prospectively analyzed. The protocol incorporated systematic pacemapping from known arrhythmogenic sites (moderator band/right ventricular [RV] papillary muscles, left conduction system/Purkinje network, outflow tracts) with real-time comparison between the paced ICD electrogram (EGM) morphology and SITE. RESULTS: Regions within the left Purkinje network yielded the best pacemap match for the SITE of the clinical PVC trigger in 55% of ablation targets (left posterior fascicle 6, left septal fascicle 1, left anterior fascicle 5), followed by the RV moderator band region in 14% (n = 3), RV papillary muscles in 13% (n = 3), periaortic region in 14% (n = 3), and left ventricular anterolateral papillary muscle in 4% (n = 1). Freedom from ICD therapies off antiarrhythmic drug (AAD) was 64% at 6 months and 48% at 12 months. Shock burden was reduced from 4 (2-6) to 0 (0-1) (P = .001), and use of AADs was reduced from 2 (1-2) to 0 (0-1) (P = .001). CONCLUSION: In the absence of a mappable trigger, an empiric strategy of interrogating the Purkinje network, papillary muscles, and outflow tract regions by pacemap matching with SITE of the clinical PVC is feasible to guide ablation. A significant reduction in VF/PMVT therapy burden and AAD utilization was observed after a single procedure.

Impact of physiological pacing on functional mitral regurgitation in systolic dysfunction: Initial echocardiographic remodeling findings after His bundle pacing.

BACKGROUND: Although His bundle pacing (HBP) has been shown to improve left ventricular ejection fraction (LVEF), its impact on mitral regurgitation (MR) remains uncertain. OBJECTIVES: The aim of this study was to evaluate change in functional MR after HBP in patients with left ventricular (LV) systolic dysfunction. METHODS: Paired echocardiograms were retrospectively assessed in patients with reduced LVEF (<50%) undergoing HBP for pacing or resynchronization. The primary outcomes assessed were change in MR, LVEF, LV volumes, and valve geometry pre- and post-HBP. MR reduction was characterized as a decline in ≥1 MR grade post-HBP in patients with ≥grade 3 MR at baseline. RESULTS: Thirty patients were analyzed: age 68 ± 15 years, 73% male, LVEF 32% ± 10%, 38% coronary artery disease, 33% history of atrial fibrillation. Baseline QRS was 162 ± 31 ms: 33% left bundle branch block, 37% right bundle branch block, 17% paced, and 13% narrow QRS. Significant reductions in LV end-systolic volume (122 mL [73-152 mL] to 89 mL [71-122 mL], P = .006) and increase in LV ejection fraction (31% [25%-37%] to 39% [30%-49%], P < .001) were observed after HBP. Ten patients had grade 3 or 4 MR at baseline, with reduction in MR observed in 7. In patients with at least grade 3 MR at baseline, reduction in LV volumes, improved mitral valve geometry, and greater LV contractility were associated with MR reduction. Greater reduction in paced QRS width was present in MR responders compared to non-MR responders (-40% vs -25%, P = .04). CONCLUSIONS: In this initial detailed echocardiographic analysis in patients with LV systolic dysfunction, HBP reduced functional MR through favorable ventricular remodeling.

Atypical pathogens associated with cardiac implantable electronic device infections.

BACKGROUND: Cardiovascular implantable electronic device (CIED) infections are associated with significant morbidity and mortality making the identification of the causative organism critical. The vast majority of CIED infections are caused by Staphylococcal species. CIED infections associated with atypical pathogens are rare and have not been systematically investigated. The objective of this study is to characterize the clinical course, management and outcome in patients with CIED infection secondary to atypical pathogens. METHODS: Medical records of all patients who underwent CIED system extraction at the University of Chicago Medical Center between January 2010 and November 2020 were retrospectively reviewed to identify patients with CIED infection. Demographic, clinical, infection-related and outcome data were collected. CIED infections were divided into typical and atypical groups based on the pathogens isolated. RESULTS: Among 356 CIED extraction procedures, 130 (37%) were performed for CIED infection. Atypical pathogens were found in 5.4% (n = 7) and included Pantoea species (n = 2), Kocuria species (n = 1), Cutibacterium acnes (n = 1), Corynebacterium tuberculostearicum (n = 1), Corynebacterium striatum (n = 1), Stenotrophomonas maltophilia (n = 1), and Pseudozyma ahidis (n = 1). All patients with atypical CIED infections were successfully treated with total system removal and tailored antibiotic therapy. There were no infection-related deaths. CONCLUSIONS: CIED infections with atypical pathogens were rare and associated with good outcome if diagnosed early and treated with total system removal and tailored antimicrobial therapy. Atypical pathogens cultured from blood, tissue or hardware in patients with CIED infection should be considered pathogens and not contaminants.

Double loop ventricular tachycardia activation patterns with single loop mechanisms: Asymmetric entrainment responses during "pseudo-figure-of-eight" reentry.

BACKGROUND: The classical paradigm of scar-related reentrant ventricular tachycardia (VT) features a circuit with a double loop figure-of-eight (F8) activation pattern. OBJECTIVE: The purpose of this study was to interrogate VT circuits with F8 activation patterns by entrainment mapping to differentiate an active loop from a passive loop. METHODS: Sixty VT circuits with >90% of tachycardia cycle length delineated in high resolution were retrospectively analyzed in 55 patients (nonischemic 49%). A pseudo-F8 VT circuit was defined as a double loop activation pattern driven by a single loop mechanism with a passive loop that yields a long postpacing interval (postpacing interval - tachycardia cycle length ≥ 30 ms). RESULTS: Single loop activation patterns were observed in 33% (n = 20). Of 40 circuits with F8 patterns by activation mapping, 20 were studied with entrainment mapping, where a passive loop was identified by a long postpacing interval in 50%. In 6 circuits where entrainment mapping was performed from both outer loop regions, all demonstrated asymmetric responses to entrainment, confirming a single loop mechanism. Entrainment from both lateral margins of the common pathway (n = 7) demonstrated an asymmetric response in 29%. In all pseudo-F8 circuits (n = 10), the shorter loop functioned as the active loop and ablation targeting the active loop side of the isthmus resulted in VT termination with a single radiofrequency application. CONCLUSION: In a selected cohort, single loop mechanisms are more prevalent than double loop reentry in reentrant human VT. Half of VT circuits with double loop activation patterns can be demonstrated to be sustained by a single active loop mechanism by entrainment mapping. Ablation targeting the shorter active loop resulted in rapid termination during radiofrequency application.

A novel familial SCN5A exon 20 deletion is associated with a heterogeneous phenotype.

The SCN5A gene, located on chromosome 3p21, has 28 exons and is a member of the human voltage-gated sodium channel gene family. Genetic variation in SCN5A is associated with a diverse range of phenotypes. Due to incomplete penetrance, delayed expression, inherent low signal-to-noise ratio, and marked phenotypic heterogeneity, rare novel variants in SCN5A could be misinterpreted. Hence, defining the phenotypic characteristics of these rare SCN5A variants in humans is of importance. We describe the phenotypic heterogeneity noted in 4 familial carriers of a rare, previously unreported, large deletion in exon 20 of SCN5A (c.3667-?_c.3840C +?del) and discuss the mechanisms that underlie this heterogeneity.

PR interval prolongation is significantly associated with aortic root abscess: An age- and gender-matched study.

BACKGROUND: Electrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age- and gender-matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis. METHODS: Patients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12-lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre- and post-admission PR interval, was the primary outcome of interest. The patients in the ARA group were age- and gender-matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed. RESULTS: Eighteen patients with surgically confirmed ARA were enrolled. These patients were age- and gender-matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (-5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003). CONCLUSIONS: The findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement.

Resting electrocardiographic differences in ventricular repolarization between children and young adults with congenital heart disease and those with a structurally normal heart are diminished by exercise.

OBJECTIVE: Exercise-induced repolarization changes have not been systematically evaluated in children and young adults with congenital heart disease (CHD). We carried out this study to assess the QTc responses during exercise in children and young adults (≤ 21 years) with CHD with comparison to those with structurally normal hearts. METHODS: Baseline QRS duration, calculated baseline QTc, QTc at 4 min of recovery and delta QTc was measured in 360 exercise stress tests which were performed in 360 subjects (137 stress tests in patients with CHD [CHD group] and 223 stress tests in patients with structurally normal hearts). The effects of presence of CHD and potential confounders on primary outcome measure, change in QTc (delta QTc), and secondary outcome measures (QTc at baseline and QTc at 4 min of recovery) were determined using multiple linear regression analyses. RESULTS: The baseline QTc and the QTc at 4 min of recovery in the CHD group was longer than patients with structurally normal hearts (respective p values = .00 and .001). No significant difference was noted in delta QTc between the CHD and structurally normal heart groups. CONCLUSIONS: While patients with CHD had a longer QRS duration and QTc interval at baseline than those with structurally normal hearts, these differences did not persist or augment with exercise.

Isolated left bundle branch block in the young: case reports and review of literature.

Isolated left bundle branch block (LBBB) aberrancy is exceedingly rare in the young and its clinical and genetic determinants remain poorly characterized. Furthermore, there is conflicting data on its natural history in the pediatric age group patients. We report the rare phenotype of isolated typical LBBB aberrancy in two healthy children, one of whom carried a likely pathogenic mutation in the coding exon 1 of NKX2-5 (p.Q22R, c.65A > G, rs201442000). Our findings suggest that isolated LBBB aberrancy could be non-progressive in some children, at least in the short term. However, given the paucity of data on this entity, we recommend continued long-term surveillance.

Spatial and transmural properties of the reentrant ventricular tachycardia circuit in arrhythmogenic right ventricular cardiomyopathy: Simultaneous epicardial and endocardial recordings.

BACKGROUND: While advances in the characterization of the structural substrate in arrhythmogenic right ventricular cardiomyopathy (ARVC) have been made, the ventricular tachycardia (VT) circuit remains incompletely described. OBJECTIVE: The purpose of this study was to delineate the reentrant VT circuit with simultaneous epicardial and endocardial mapping (SEEM) in ARVC. METHODS: Twenty-three consecutive patients with ARVC and VT underwent SEEM at 4 centers between 2014 and 2020. Retrospective analysis was performed on combined isochronal activation maps. RESULTS: Of the 30 VT circuits, 24 were delineated with SEEM (956 [341-1843] endocardial points and 1763 [882-3054] epicardial points). The apex and outflow tract rarely harbored VT circuits, with 50% distributed in the inferior wall and 43% in the free wall. The entire tachycardia cycle length was recorded from the epicardium in 71% of circuits. In all circuits, a large proportion of the tachycardia cycle length was recorded from the epicardium relative to the endocardium. Localized epicardial reentry was observed in 35% of patients (14 mm × 15 mm), which was associated with smaller endocardial low voltage area (39 cm2 vs 104 cm2; P = .002) and preserved right ventricular ejection fraction (35% vs 25%; P = .046) compared with those with larger circuit dimensions. Seventy percent of termination sites were achieved from the epicardium. CONCLUSION: High-resolution recordings from both myocardial surfaces confirm a consistent predominance of epicardial participation during reentry in ARVC. Only the perivalvular inflow region of the "triangle of dysplasia" had a strong propensity to harbor VT circuits, with the greatest proportion located in the inferior wall. Localized epicardial reentry may be a manifestation of earlier stage disease with a relative paucity of endocardial substrate.

Left ventricular summit arrhythmias with an abrupt V3 transition: Anatomy of the aortic interleaflet triangle vantage point.

BACKGROUND: While early precordial electrocardiographic (ECG) characteristics are useful to differentiate left-sided from the right-sided outflow tract ventricular arrhythmia (OTVA), few patterns predict an origin from the septal margin of the left ventricular (LV) summit. OBJECTIVE: The purpose of this study was to report mapping and ablation characteristics of a new ECG pattern with left bundle branch morphology and an abrupt R-wave transition in lead V3 (ATV3). METHODS: Over a 3-year period, 78 consecutive patients (mean age 57±15 years; 35% female) with OTVA were referred for mapping and ablation. Twenty patients (26%) exhibited an ATV3 pattern, of whom 65% failed prior ablation. RESULTS: Ninety-two percent of patients with ATV3 that underwent simultaneous epicardial and endocardial mapping demonstrated an intramural or epicardial site of origin. Eighty percent of OTVA with ATV3 was eliminated by ablation from the vantage point of the interleaflet triangle below the right-left coronary junction. The ATV3 pattern showed higher sensitivity, specificity, predictive value, and accuracy than validated ECG criteria (notch or "w" pattern in lead V1, qrS pattern in leads V1 through V3, and pattern break V2) for predicting successful ablation in the region of the anterior LV ostium. At 12±11 months, freedom from ventricular arrhythmia recurrence was 89% and 82% in the ATV3 and control groups, respectively. CONCLUSION: ATV3 is a simple and distinct ECG pattern indicative of a site of origin from the septal margin of the LV summit. The right-left aortic interleaflet triangle vantage point was effective to eliminate OTVA with ATV3 that overwhelmingly exhibited the earliest activation from the epicardium or mid-myocardium. Test characteristics for ATV3 were superior to ECG patterns validated for the anterior LV ostium.

Prognostic value of cardiac magnetic resonance septal late gadolinium enhancement patterns for periaortic ventricular tachycardia ablation: Heterogeneity of the anteroseptal substrate in nonischemic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) from the anteroseptal subtype of nonischemic cardiomyopathy has a high probability of recurrence after catheter ablation. OBJECTIVE: The purpose of this study was to determine the predictive value of septal scar patterns by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) on ablation outcomes in patients with VT arising from an anteroseptal substrate. METHODS: Patients with periaortic VT arising from an anteroseptal substrate with preprocedural wideband LGE-CMR were divided into 2 groups by the degree of longitudinal septal LGE extension as full-length septal (≥80% anteroposterior length) or partial septal (<80% anteroposterior length). Septal LGE volumes were quantified in those with and without VT recurrence. RESULTS: Among 234 patients referred for scar-related VT ablation between 2017 and 2020, 25 patients (92% male; age 64 ± 8 years) and a total of 108 VTs were analyzed. A greater number of VT morphologies were induced in patients with full-length septal LGE compared to partial septal LGE (median [interquartile range]: 5 [3-9] vs 2 [1-4]; P = .005). Patients with VT recurrence had larger septal LGE volumes compared to those without recurrence (11.4 mL [8.8-13.9] vs 4.2 mL [0-9.5]; P = .012). At median follow-up of 16 months (5-22), overall freedom from VT recurrence was 52% and significantly higher in patients with partial septal LGE than in those with full-length septal LGE (80% vs 20%; P = .005). CONCLUSION: VT originating from an anteroseptal substrate is associated with heterogeneous patterns and extent of CMR septal scar. Preprocedural imaging may substratify this challenging patient population for the propensity for multiple induced VT morphologies and recurrence after catheter ablation.