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.

Circuit Determinants of Ventricular Tachycardia Cycle Length: Characterization of Fast and Unstable Human Ventricular Tachycardia.

BACKGROUND: Fast ventricular tachycardias (VTs) have historically been attributed to shorter path lengths with smaller reentrant circuit dimensions in animal models. The relationship between the dimensions of the reentrant VT circuit and tachycardia cycle length (TCL) has not been examined in humans. This study aimed to analyze the determinants of the rate of human VT with comparison of circuit dimensions and conduction velocity (CV) across a wide range of both stable and unstable VTs delineated by high-resolution mapping. METHODS: Fifty-four VTs with complete circuit delineation (>90% TCL) by high-resolution multielectrode mapping were analyzed in 49 patients (men, 88%; age, 65 years [58-71 years]; nonischemic, 47%). Fast VT was defined as TCL <333 milliseconds (rate >180 bpm). Unstable VT was defined by hemodynamic deterioration with an intrinsic mean arterial pressure <60 mm Hg during a sustained episode. RESULTS: The median TCL of VT was 365 milliseconds (306-443 milliseconds), and 24 fast VTs were characterized. A wide range of CVs was observed within the entrance (0.03-0.55 m/s), common pathway (0.03-0.77 m/s), exit (0.03-0.53 m/s), and outer loop (0.17-1.13 m/s). There were no significant differences in the median dimensions of the isthmus and path length between fast and slow VTs and between unstable and stable VTs. The outer loop CV was the only circuit component that correlated with TCL in both ischemic cardiomyopathy (r=-0.5, P=0.006) and nonischemic cardiomyopathy (r=-0.45, P=0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length: r=-0.46, P=0.001, width: r=-0.3, P=0.047) and predictive of rapid VT termination by a single radiofrequency application (r=-0.41, P=0.023). CONCLUSIONS: Because of a wide spectrum of CV observed within the reentrant path during human VT, the dimensions of the circuit were not predictive of VT cycle length. For the first time, we demonstrate that the CV of the outer loop, rather than isthmus, is the principal determinant of the rate of VT. The size of the circuit was similar between fast and slow VTs and between unstable and stable VTs. Long, continuous electrograms were indicative of spatially confined isthmus dimensions, confirmed by rapid termination of VT during radiofrequency delivery.

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.

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.

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.

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.

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.

Late presentation of recurrent syncope after permanent pacemaker implantation due to Lead-Header malapposition.

Permanent pacemaker (PPM) malfunction due to electrical connection problems such as a loose set screw or lead-header malapposition is extremely rare. We present a patient with complete heart block (CHB) who had PPM malfunction and recurrent syncope, late (14 months) after initial implantation, which was caused by the ventricular lead pin disengagement from the header resulting in oversensing due to noise, pacing inhibition and recurrent syncope. PPM due to lead-header malapposition this late after device implantation has previously not been reported.

Targeted Ablation of Ventricular Tachycardia Guided by Wavefront Discontinuities During Sinus Rhythm: A New Functional Substrate Mapping Strategy.

BACKGROUND: Accurate and expedited identification of scar regions most prone to reentry is needed to guide ventricular tachycardia (VT) ablation. We aimed to prospectively assess outcomes of VT ablation guided primarily by the targeting of deceleration zones (DZ) identified by propagational analysis of ventricular activation during sinus rhythm. METHODS: Patients with scar-related VT were prospectively enrolled in the University of Chicago VT Ablation Registry between 2016 and 2018. Isochronal late activation maps annotated to the latest local electrogram deflection were created with high-density multielectrode mapping catheters. Targeted ablation of DZ (>3 isochrones within 1cm radius) was performed, prioritizing later activated regions with maximal isochronal crowding. When possible, activation mapping of VT was performed, and successful ablation sites were compared with DZ locations for mechanistic correlation. Patients were prospectively followed for VT recurrence and mortality. RESULTS: One hundred twenty patients (median age 65 years [59-71], 15% female, 50% nonischemic, median ejection fraction 31%) underwent 144 ablation procedures for scar-related VT. 57% of patients had previous ablation and epicardial access was employed in 59% of cases. High-density mapping during baseline rhythm was performed (2518 points [1615-3752] endocardial, 5049±2580 points epicardial) and identified an average of 2±1 DZ, which colocalized to successful termination sites in 95% of cases. The median total radiofrequency application duration was 29 min (21-38 min) to target DZ, representing ablation of 18% of the low-voltage area. At 12±10 months, 70% freedom from VT recurrence (80% in ischemic cardiomyopathy and 63% in nonischemic cardiomyopathy) was achieved. The overall survival rate was 87%. CONCLUSIONS: A novel voltage-independent high-density mapping display can identify the functional substrate for VT during sinus rhythm and guide targeted ablation, obviating the need for extensive radiofrequency delivery. Regions with isochronal crowding during the baseline rhythm were predictive of VT termination sites, providing mechanistic evidence that deceleration zones are highly arrhythmogenic, functioning as niduses for reentry.

Intracardiac Delineation of Septal Conduction in Left Bundle-Branch Block Patterns.

BACKGROUND: Septal activation in patients with left bundle-branch block (LBBB) patterns has not been described previously. We performed detailed intracardiac mapping of left septal conduction to assess for the presence and level of complete conduction block (CCB) in the His-Purkinje system. Response to His bundle pacing was assessed in patients with and without CCB in the left bundle. METHODS: Left septal mapping was performed with a linear multielectrode catheter in consecutive patients with LBBB pattern referred for device implantation (n=38) or substrate mapping (n=47). QRS width, His duration, His-ventricular (HV) intervals, and septal conduction patterns were analyzed. The site of CCB was localized to the level of the left-sided His fibers (left intrahisian) or left bundle branch. Patients with ventricular activation preceded by Purkinje potentials were categorized as having intact Purkinje activation. RESULTS: A total of 88 left septal conduction recordings were analyzed in 85 patients: 72 LBBB block pattern and 16 controls (narrow QRS, n=11; right bundle-branch block, n=5). Among patients with LBB block pattern, CCB within the proximal left conduction system was observed in 64% (n=46) and intact Purkinje activation in the remaining 36% (n=26). Intact Purkinje activation was observed in all controls. The site of block in patients with CCB was at the level of the left His bundle in 72% and in the proximal left bundle branch in 28%. His bundle pacing corrected wide QRS in 54% of all patients with LBBB pattern and 85% of those with CCB (94% left intrahisian, 62% proximal left bundle-branch). No patients with intact Purkinje activation demonstrated correction of QRS with His bundle pacing. CCB showed better predictive value (positive predictive value 85%, negative predictive value 100%, sensitivity 100%) than surface ECG criteria for correction with His bundle pacing. CONCLUSIONS: Heterogeneous septal conduction was observed in patients with surface LBBB pattern, ranging from no discrete block to CCB. When block was present, we observed pathology localized within the left-sided His fibers (left intrahisian block), which was most amenable to corrective His bundle pacing by recruitment of latent Purkinje fibers. ECG criteria for LBBB incompletely predicted CCB, and intracardiac data might be useful in refining patient selection for resynchronization therapy.

Ventricular arrhythmia suppression with ivabradine in a patient with catecholaminergic polymorphic ventricular tachycardia refractory to nadolol, flecainide, and sympathectomy.

Conventional treatment strategies for catecholaminergic polymorphic ventricular tachycardia (CPVT) include avoidance of strenuous exercise and competitive sports, drugs such as ß-blockers and flecainide and, cervical sympathectomy. An implantable cardioverter-defibrillator (ICD) has been utilized if the response to these strategies is inadequate; however, ICD use in CPVT patients, in addition to usual complications, is associated with an increased risk of life-threatening electrical storm. Ivabradine is a selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 generated funny current (If ), which has been shown to be efficacious in suppression of inappropriate sinus tachycardia, junctional tachycardia, atrial tachycardia, and ventricular ectopy in humans. We report an 18-year-old male with a severe CPVT phenotype refractory to flecainide, nadolol, and sympathectomy who exhibited suppression of ventricular arrhythmias after initiation of ivabradine. These findings are of importance as ivabradine could be an important add-on therapy in CPVT patients who are drug refractory or are unable to continue conventional therapies at the recommended doses.

SIDS associated RYR2 p.Arg2267His variant may lack pathogenicity.

Sudden infant death syndrome (SIDS) is the sudden death of an infant under 1 year of age that remains unexplained after death scene and medicolegal investigation, including a complete autopsy and clinical history review. The fatal event typically occurs during sleep and heart rhythm during the event is rarely documented. Large series which have utilized molecular autopsy show that long QT syndrome (LQTS) associated cardiac channel mutations contribute to between 5 and 10% of SIDS deaths. In addition, rare novel RYR2 variants have been identified in SIDS victims. Given the lack of a phenotype, the pathogenicity of these variants is inferred from in vitro studies. We report a family with 5 members (mother and 4 children) who are carriers of a rare RYR2 variant (c.6800G > A, p.Arg2267His [Exon: 45], heterozygous) which has previously been identified in a SIDS victim and shown to confer a gain-of-function CPVT phenotype in vitro. All of these 5 family members including the mother (age range 7 to 41 years) have had negative exercise stress tests, echocardiograms and Holter monitors. These findings suggest that caution should be exercised in inferring pathogenicity of rare RYR2 variants based on in vitro functional data which does not always translate to human phenotype.

Marked lateral ST-segment elevation with inferior ST-segment depression in an asymptomatic 12 year-old girl: A normal variant?

Significant ST-segment changes raise concern for myocardial ischemia, cardiomyopathy or myocardial inflammation and therefore, warrant an extensive and often invasive cardiovascular evaluation. We report a 12 year-old asymptomatic African-American girl with marked ST-segment elevation in leads I and aVL and ST-segment depression in inferior leads II, III and aVF. Extensive cardiovascular evaluation did not reveal any abnormality suggesting that these findings, which have previously not been reported, are likely benign, at least in this young girl.

RYR2 p.R169L mutation and left ventricular hypertrophy in a child with emotion-triggered sudden death.

Catecholaminergic polymorphic ventricular tachycardia is a rare (prevalence: 1/10,000) channelopathy characterised by exercise-induced or emotion-triggered ventricular arrhythmias. There is an overall paucity of genotype-phenotype correlation studies in patients with catecholaminergic polymorphic ventricular tachycardia, and in vitro and in vivo effects of individual mutations have not been well characterised. We report an 8-year-old child who carried a mutation in the coding exon 8 of RYR2 (p.R169L) and presented with emotion-triggered sudden cardiac death. He was also found to have left ventricular hypertrophy, a combination which has not been reported before. We discuss the association between genetic variation in RYR2, particularly mutations causing replacement of arginine at position 169 of RYR2 and structural cardiac abnormalities.

How to perform electroanatomic mapping-guided cardiac resynchronization therapy using Carto 3 and ESI NavX three-dimensional mapping systems.

AIMS: To examine the feasibility and safety of a novel protocol for low fluoroscopy, electroanatomic mapping (EAM)-guided Cardiac resynchronization therapy with a defibrillator (CRT-D) implantation and using both EnSite NavX (St. Jude Medical, St. Paul, MN, USA) and Carto 3 (Biosense Webster, Irvine, CA, USA) mapping systems. METHODS AND RESULTS: Twenty consecutive patients underwent CRT implantation using either a conventional fluoroscopic approach (CFA) or EAM-guided lead placement with Carto 3 and EnSite NavX mapping systems. We compared fluoroscopy and procedural times, radiopaque contrast dose, change in QRS duration pre- and post-procedure, and complications in all patients. Fluoroscopy time was 86% lower in the EAM group compared to the conventional group [mean 37.2 min (CFA) vs. 5.5 min (EAM), P = 0.00003]. There was no significant difference in total procedural time [mean 183 min (CFA) vs. 161 min (EAM), P = 0.33] but radiopaque contrast usage was lower in the EAM group [mean 16 mL (CFA) vs. 4 mL (EAM), P = 0.006]. Likewise, there was no significant change in QRS duration with BiV pacing between the groups [mean -13 (CFA) vs. -25 ms (EAM), P = 0.09]. CONCLUSION: Electroanatomic mapping-guided lead placement using either Carto or ESI NavX mapping systems is a feasible alternative to conventional fluoroscopic methods for CRT-D implantation utilizing the protocol described in this study.

A large deletion in RYR2 exon 3 is associated with nadolol and flecainide refractory catecholaminergic polymorphic ventricular tachycardia.

We report a 17-year-old boy with a large RYR2 exon 3 deletion who has a severe catecholaminergic polymorphic ventricular tachycardia (CPVT) phenotype characterized by refractoriness to both nadolol and flecainide which has previously not been reported in this subgroup of CPVT patients. Treatment options in a patient like ours are therefore limited and sympathectomy and implantable cardioverter-defibrillator implantation should be considered early in the treatment course as was done in this patient. In contrast to other CPVT patients who do not usually have structural cardiac abnormalities, these patients are at a high risk of developing left ventricular noncompaction or dilated cardiomyopathy and therefore might benefit from cardiac imaging at regular intervals.

Consequences of Retained Defibrillator and Pacemaker Leads After Heart Transplantation-An Underrecognized Problem.

BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) are common in patients undergoing heart transplantation (HT), and complete removal is not always possible at the time of transplantation. METHODS: We retrospectively assessed the frequency of retained CIED leads and clinical consequences in consecutive HT patients from 2013 to 2016. Clinical outcomes included bacteremia, upper-extremity deep venous thrombosis (UEDVT), lead migration, and inability to perform magnetic resonance imaging (MRI). RESULTS: A total of 138 patients (55 ± 11 years of age, 76% male) were identified; 37 (27%) had retained lead fragments (RLFs) at discharge. Patients with RLFs were older, had longer lead implantation time before HT, and a higher prevalence of dual-coil CIED leads compared with those without RLFs (P < .05 for all). Lead implantation time was identified as an independent predictor for RLFs (P < .05). Patients with RLFs had a higher frequency of DVT compared with the non-RLF group during the 1-year study period (42% vs 21%; P < .04). There was no difference in bacteremia. Fourteen patients (38%) could not undergo clinically indicated MRI. CONCLUSION: RLFs after HT occur commonly and are associated with a higher rate of UEDVT and limit the use of MRI. Although no significant difference was found in the rates of bacteremia between the groups, this finding might be explained by the overall low incidence. Patients with risk factors for RLFs should be identified before transplantation, and complete lead removal should be considered with a multidisciplinary approach.

Impact of high-grade atrioventricular block and cumulative frequent pacing on atrial arrhythmias.

BACKGROUND: The relationship between high-grade atrioventricular block (HGAVB) with cumulative frequent pacing and risk of atrial arrhythmias (AAs) has not been well characterized. We hypothesized HGAVB and pacing may have significant impact on incidence and prevalence of AAs by modulating atrial substrate. OBJECTIVE: To determine impact of HGAVB and pacing on AAs including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). METHODS: All consecutive patients who underwent dual-chamber pacemaker implantation for HGAVB from 2005 to 2011 at the University of Chicago were included. AAs and percent of pacing were detected through device interrogation. Patients' data were collected from electronic medical records and clinic visits. RESULTS: A total of 166 patients (mean age 71 ± 15 years; 54% female, 56% African American) were studied. AF was documented in 27% of patients before pacemaker implantation. During a mean 5.8 ± 2.2 years of follow-up, 47% had device-detected AF, 10% AFL, and 26% AT. New-onset AF was documented in 40 of the 122 patients without prior AF (33%). Continuous (≥ 99%) right ventricular pacing was associated with significantly decreased AF prevalence (34% vs 59%, P = 0.005), and correlated with lower incidence (26% vs 41%, P = 0.22). Pacing suppressed AF in 14% of patients with baseline AF; those patients had lower atrial pacing (3.2% vs 45%, P < 0.0001). Left atrial dilation was the only independent predictor of AF with frequent pacing (P = 0.009). CONCLUSIONS: HGAVB is associated with high incidence and prevalence of AAs with and without pacing. Cumulative frequent (≥99%) ventricular pacing reduces risk of AF in patients with HGAVB.