Publications by authors named "Hemal M Nayak"

55 Publications

Atypical pathogens associated with cardiac implantable electronic device infections.

Pacing Clin Electrophysiol 2021 Sep 26;44(9):1549-1561. Epub 2021 Jul 26.

Center for Arrhythmia Care, Heart and Vascular Center, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.

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.
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http://dx.doi.org/10.1111/pace.14311DOI Listing
September 2021

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

Heart Rhythm 2021 Sep 7;18(9):1548-1556. Epub 2021 May 7.

Center for Arrhythmia Care, Pritzker School of Medicine, The University of Chicago Medicine, Chicago, Illinois. Electronic address:

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.
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http://dx.doi.org/10.1016/j.hrthm.2021.05.002DOI Listing
September 2021

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

J Electrocardiol 2021 May-Jun;66:131-135. Epub 2021 Apr 23.

Center for Arrhythmia Care, Heart & Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.04.011DOI Listing
July 2021

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

Ann Noninvasive Electrocardiol 2021 07 3;26(4):e12849. Epub 2021 May 3.

Heart & Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1111/anec.12849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293599PMC
July 2021

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

Pacing Clin Electrophysiol 2021 Aug 16;44(8):1466-1473. Epub 2021 Apr 16.

Center for Arrhythmia Care, Heart and Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, Illinois, USA.

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.
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http://dx.doi.org/10.1111/pace.14243DOI Listing
August 2021

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.

Pacing Clin Electrophysiol 2021 Jun 19;44(6):1047-1053. Epub 2021 Apr 19.

Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.

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.
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http://dx.doi.org/10.1111/pace.14241DOI Listing
June 2021

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

Heart Rhythm 2021 Jun 30;18(6):916-925. Epub 2021 Jan 30.

Center for Arrhythmia Care, Pritzker School of Medicine, The University of Chicago Medicine, Chicago, Illinois; Department of Cardiology, Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:

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 cm vs 104 cm; 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.
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http://dx.doi.org/10.1016/j.hrthm.2021.01.028DOI Listing
June 2021

Indirect and Direct Evidence for 3-D Activation During Left Atrial Flutter: Anatomy of Epicardial Bridging.

JACC Clin Electrophysiol 2020 12;6(14):1812-1823

University of Chicago Pritzker School of Medicine, Center for Arrhythmia Care at the University of Chicago Medicine, Chicago, Illinois, USA. Electronic address:

Objectives: This study sought to describe arrhythmia characteristics using ultra-high density (UHD) mapping of macro-re-entrant left atrial flutter (LAFL) which propagate via epicardial bridging (EB), and highlight regional anatomy that poses challenges to ablation.

Background: Three-dimensional propagation via EB may contribute to the maintenance and complexity of LAFL.

Methods: UHD activation maps of macro-re-entrant LAFL created with a mini-electrode basket catheter were analyzed between June 2015 and March 2020. EB was defined as a region of wave front discontinuity with focal activation distal to an activation gap. Regions of EB were correlated with anatomic structures known to have specialized epicardial bundles. Direct evidence of EB was obtained via percutaneous epicardial access (n = 22) with simultaneous epicardial recordings during endocardial activation gaps.

Results: Among 159 patients who underwent LA endocardial procedures with UHD mapping, 43 patients with 47 macro-re-entrant LAFLs were included in this analysis. Evidence of EB was present in 38% of LAFLs. Four anatomic areas of EB were observed: coronary sinus (17%), vein of Marshall (28%), Bachmann's region (33%), and region of the septopulmonary bundle (22%). All 47 LAFLs were successfully ablated. Percutaneous epicardial mapping yielded direct evidence for EB in 9 patients with LAFL (41%). At 23 ± 13 months, 70% remained free from recurrent LAFL.

Conclusions: In a selected population, UHD mapping demonstrates evidence of EB in 38% of cases of LAFL involving 4 distinct epicardial anatomic regions. Identification of discontinuous 3-dimensional activation patterns with attention to correlative regional LA anatomy may reduce the incidence of ablation failures for complex re-entry.
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http://dx.doi.org/10.1016/j.jacep.2020.09.022DOI Listing
December 2020

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

Heart Rhythm 2021 04 8;18(4):579-588. Epub 2020 Dec 8.

Center for Arrhythmia Care, University of Chicago Medicine, Pritzker School of Medicine, Chicago, Illinois. Electronic address:

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.
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http://dx.doi.org/10.1016/j.hrthm.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026601PMC
April 2021

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

Indian Pacing Electrophysiol J 2021 Mar-Apr;21(2):124-127. Epub 2020 Nov 30.

The University of Chicago Pritzker School of Medicine, Center for Arrhythmia Care, Heart and Vascular Center, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1016/j.ipej.2020.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952771PMC
November 2020

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

Circulation 2021 Jan 10;143(3):212-226. Epub 2020 Nov 10.

The University of Chicago Medicine, Center for Arrhythmia Care, Pritzker School of Medicine, Department of Medicine, Section of Cardiology, IL.

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 (=-0.5, =0.006) and nonischemic cardiomyopathy (=-0.45, =0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length: =-0.46, =0.001, width: =-0.3, =0.047) and predictive of rapid VT termination by a single radiofrequency application (=-0.41, =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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050363DOI Listing
January 2021

Interference of subcutaneous implantable cardioverter defibrillator by deep brain stimulation.

Parkinsonism Relat Disord 2020 12 11;81:75-77. Epub 2020 Oct 11.

Movement Disorder Clinic and Deep Brain Stimulation Program, Department of Neurology, University of Chicago Medicine, Chicago, IL, 60637, USA. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2020.10.018DOI Listing
December 2020

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

Heart Rhythm 2021 01 21;18(1):10-19. Epub 2020 Jul 21.

Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China; Section of Cardiology, Pritzker School of Medicine, The University of Chicago Medicine, Chicago, Illinois. Electronic address:

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 V (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 V, qrS pattern in leads V through V, and pattern break V) 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.
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http://dx.doi.org/10.1016/j.hrthm.2020.07.021DOI Listing
January 2021

Characterization of Lead Adherence Using Intravascular Ultrasound to Assess Difficulty of Transvenous Lead Extraction.

Circ Arrhythm Electrophysiol 2020 08 6;13(8):e007726. Epub 2020 Jul 6.

Department of Medicine, Section of Cardiology, University of Chicago Pritzker School of Medicine, IL.

Background: Clinical factors associated with development of intravascular lead adherence (ILA) are unreliable predictors. Because vascular injury in the superior vena cava-right atrium during transvenous lead extraction is more likely to occur in segments with higher degrees of ILA, reliable and accurate assessment of ILA is warranted. We hypothesized that intravascular ultrasound (IVUS) could accurately visualize and quantify ILA and degree of ILA correlates with transvenous lead extraction difficulty.

Methods: Serial imaging of leads occurred before transvenous lead extraction using IVUS. ILA areas were classified as high or low grade. Degree of extraction difficulty was assessed using 2 metrics and correlated with ILA grade. Lead extraction difficulty was calculated for each patient and compared with IVUS findings.

Results: One hundred fifty-eight vascular segments in 60 patients were analyzed: 141 (89%) low grade versus 17 (11%) high grade. Median extraction time (low=0 versus high grade=97 seconds, <0.001) and median laser pulsations delivered (low=0 versus high grade=5852, <0.001) were significantly higher in high-grade segments. Most patients with low lead extraction difficulty score had low ILA grades. Eighty-six percentage of patients with high lead extraction difficulty score had low IVUS grade, and the degree of transvenous lead extraction difficulty was similar to patients with low IVUS grades and lead extraction difficulty scores.

Conclusions: IVUS is a feasible imaging modality that may be useful in characterizing ILA in the superior vena cava-right atrium region. An ILA grading system using imaging correlates with extraction difficulty. Most patients with clinical factors associated with higher extraction difficulty may exhibit lower ILA and extraction difficulty based on IVUS imaging. Graphic Abstract: A graphic abstract is available for this article.
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http://dx.doi.org/10.1161/CIRCEP.119.007726DOI Listing
August 2020

Transvenous phrenic nerve stimulation for central sleep apnea is safe and effective in patients with concomitant cardiac devices.

Heart Rhythm 2020 12 30;17(12):2029-2036. Epub 2020 Jun 30.

The Ohio State University Wexner Medical Center, Columbus, Ohio.

Background: Central sleep apnea is common in heart failure patients. Transvenous phrenic nerve stimulation (TPNS) requires placing a lead to stimulate the phrenic nerve and activate the diaphragm. Data are lacking concerning the safety and efficacy of TPNS in patients with concomitant cardiovascular implantable electronic devices (CIEDs).

Objective: To report the safety and efficacy of TPNS in patients with concomitant CIEDs.

Methods: In the remedē System Pivotal Trial, 151 patients underwent TPNS device implant. This analysis compared patients with concomitant CIEDs to those without with respect to safety, implant metrics, and efficacy of TPNS. Safety was assessed using incidence of adverse events and device-device interactions. A detailed interaction protocol was followed. Implant metrics included overall TPNS implantation success. Efficacy endpoints included changes in the apnea-hypopnea index (AHI) and quality of life.

Results: Of 151 patients, 64 (42%) had a concomitant CIED. There were no significant differences between the groups with respect to safety. There were 4 CIED oversensing events in 3 patients leading to 1 inappropriate defibrillator shock and delivery of antitachycardia pacing. There was no difference in efficacy between the CIED and non-CIED subgroups receiving TPNS, with both having similar percentages of patients who achieved ≥50% reduction in AHI and quality-of-life improvement.

Conclusion: Concomitant CIED and TPNS therapy is safe. The presence of a concomitant CIED did not seem to impact implant metrics, implantation success, and TPNS efficacy. A detailed interaction protocol should be followed to minimize the incidence of device-device interaction.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.023DOI Listing
December 2020

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

Cardiol Young 2020 Jul 9;30(7):1039-1042. Epub 2020 Jun 9.

Center for Arrhythmia Care, Heart & Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1017/S1047951120001316DOI Listing
July 2020

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

J Electrocardiol 2020 Jul - Aug;61:23-26. Epub 2020 May 18.

Center for Arrhythmia Care, Heart & Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, IL, United States of America.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.05.011DOI Listing
June 2021

Periaortic ventricular tachycardia in structural heart disease: Evidence of localized reentrant mechanisms.

Heart Rhythm 2020 08 21;17(8):1271-1279. Epub 2020 Apr 21.

Center for Arrhythmia Care, Pritzker School of Medicine, The University of Chicago Medicine, Chicago, Illinois. Electronic address:

Background: The mechanisms for scar-related ventricular tachycardia (VT) originating from the periaortic region remain incompletely characterized.

Objective: The purpose of this study was to map the circuits responsible for periaortic VT in high resolution.

Methods: Cases with periaortic VT (2016-2020) were analyzed to characterize the substrate and mechanisms with multielectrode mapping. Periaortic VT was defined as low-voltage and/or deceleration zones within 2 cm of the left ventriculoaortic junction with a corresponding critical site during VT.

Results: Forty-nine periaortic monomorphic VTs were analyzed in 30 patients (25% of all patients with nonischemic cardiomyopathy). Isolated periaortic substrate was observed in 27% of patients, with 73% having concomitant scar, most commonly in the mid-septum (47%). Deceleration zones were equally prevalent on the septal and lateral portions of the periaortic region (87% vs 73%; P = .19). During activation mapping of VT (tachycardia cycle length 392 ± 105 ms), localized reentrant patterns of activation (14 mm [10-17 mm] × 10 mm [7-14 mm]) were demonstrated in 63% and 37% of VTs showed centrifugal activation, consistent with a focal breakout pattern. Ninety-three percent of VTs fulfilled criteria for a reentrant mechanism. Sixty-five percent of reentrant circuits had endocardial activation gaps within the tachycardia cycle length (3-dimensional circuitry), which were associated with higher rates of recurrence as compared with 2-dimensional complete circuits at 1 year (73% vs 37%; P = .028).

Conclusion: Periaortic VTs were observed in 25% of patients with nonischemic cardiomyopathy and scar-related VT. For the first time, localized reentry confined to this anatomically challenging region was demonstrated as the predominant mechanism by high-resolution circuit activation mapping.
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http://dx.doi.org/10.1016/j.hrthm.2020.04.018DOI Listing
August 2020

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

Pacing Clin Electrophysiol 2020 05 2;43(5):527-533. Epub 2020 May 2.

Center for Arrhythmia Care, Heart and Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, Illinois.

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 (I ), 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.
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http://dx.doi.org/10.1111/pace.13913DOI Listing
May 2020

SIDS associated RYR2 p.Arg2267His variant may lack pathogenicity.

J Electrocardiol 2020 May - Jun;60:23-26. Epub 2020 Mar 18.

Center for Arrhythmia Care, Heart & Vascular Center, Pritzker School of Medicine of the University of Chicago, Chicago, IL, United States of America.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.03.007DOI Listing
June 2021

High-Density Grid Catheter for Detailed Mapping of Sinus Rhythm and Scar-Related Ventricular Tachycardia: Comparison With a Linear Duodecapolar Catheter.

JACC Clin Electrophysiol 2020 03 29;6(3):311-323. Epub 2020 Jan 29.

Center for Arrhythmia Care, Pritzker School of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA; Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Objectives: This study aimed to evaluate the feasibility and accuracy of using a novel grid mapping catheter during scar-related ventricular tachycardia (VT) ablation.

Background: Ultra-high-density (UHD) mapping improves identification of local abnormal ventricular activities (LAVAs) and characterization of scar substrates.

Methods: Consecutive patients underwent endocardial and/or epicardial ablation guided by a HD grid mapping catheter. A linear duodecapolar catheter was used in the initial cases for systematic correlation. Isochronal late activation mapping was performed during sinus rhythm to identify deceleration zones, and activation mapping of VT was performed when tolerated.

Results: In 38 patients, 51 electroanatomic maps (left ventricle: 26, epicardium: 21, right ventricle: 4) were created using a grid catheter. LAVAs were identified in 98% of cases and deceleration zones were observed in 86%. High-frequency electrograms with diastolic activation were identified during 44 sustained monomorphic VTs, and the critical isthmus was colocalized to deceleration zones during sinus rhythm in 96% of cases. In 17 cases that underwent sequential mapping with both grid and linear catheters, the low voltage area detected using the grid (HD wave) was significantly smaller, with ratios of 0.61 (<0.5 mV) and 0.81 (<1.5 mV) relative to the duodecapolar catheter.

Conclusions: VT ablation guided by a novel HD grid catheter is safe and feasible for clinical use in human scar-related VT via both endocardial and epicardial approaches. Automated selection of larger bipolar amplitudes among orthogonal pairs consistently displayed smaller low voltage areas than a previously validated linear catheter.
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http://dx.doi.org/10.1016/j.jacep.2019.11.007DOI Listing
March 2020

Simultaneous Endocardial and Epicardial Delineation of 3D Reentrant Ventricular Tachycardia.

J Am Coll Cardiol 2020 03;75(8):884-897

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background: Mechanisms of scar-related ventricular tachycardia (VT) are largely based on computational and animal models that portray a 2-dimensional view.

Objectives: The authors sought to delineate the human VT circuit with a 3-dimensional perspective from recordings obtained by simultaneous endocardial and epicardial mapping.

Methods: High-resolution mapping was performed during 97 procedures in 89 patients with structural heart disease. Circuits were characterized by systematic isochronal analysis to estimate the dimensions of the isthmus and extent of the exit region recorded on both myocardial surfaces.

Results: A total of 151 VT morphologies were mapped, of which 83 underwent simultaneous endocardial and epicardial mapping; 17% of circuits activated in a 2-dimensional plane, restricted to 1 myocardial surface. Three-dimensional activation patterns with nonuniform transmural propagation were observed in 61% of circuits with only 4% showing transmurally uniform activation, and 18% exhibiting focal activation patterns consistent with mid-myocardial reentry. The dimensions of the central isthmus were 17 mm (12 to 28 mm) × 10 mm (9 to 19 mm) with 55% exhibiting a minimal dimension of <1.5 cm. QRS activation was transmural in 63% and located 43 mm (34 to 52 mm) from the central isthmus. On the basis of 6 proposed definitions for epicardial VT, the prevalence of an epicardial circuit ranged from 21% to 80% in ischemic cardiomyopathy and 28% to 77% in nonischemic cardiomyopathy.

Conclusions: A 2D perspective oversimplifies the electrophysiological circuit responsible for reentrant human VT and simultaneous endocardial and epicardial mapping facilitates inferences about mid-myocardial activation. Intricate activation patterns are frequently observed on both myocardial surfaces, and the epicardium is functionally involved in the majority of circuits. Human reentry may exist within isthmus dimensions smaller than 1 cm, whereas QRS activation is often transmural and remote from the critical isthmus target. A 3-dimensional perspective of the VT circuit may enhance the precision of ablative therapy and may support a greater role for adjunctive strategies and technology to address arrhythmogenic tissue harbored in the mid-myocardium and subepicardium.
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http://dx.doi.org/10.1016/j.jacc.2019.12.044DOI Listing
March 2020

Left Ventricular Septal Versus Left Bundle Branch Pacing: A New Beginning in Cardiac Resynchronization Therapy?

J Am Coll Cardiol 2020 02;75(4):360-362

Virginia Commonwealth University Health System, Richmond, Virginia.

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http://dx.doi.org/10.1016/j.jacc.2019.11.041DOI Listing
February 2020

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

Circulation 2019 10 19;140(17):1383-1397. Epub 2019 Sep 19.

Center for Arrhythmia Care, Pritzker School of Medicine, Department of Medicine, Division of Cardiology, University of Chicago, IL (Z.A., D.S., M.R., G.A.U., A.B., S.A.B., Z.F., R.J., T.N., H.L, H.M.N., R.T.).

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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042423DOI Listing
October 2019

Acceleration of a wide complex tachycardia: What is the mechanism?

Heart Rhythm 2019 09;16(9):1443-1445

The University of Chicago Medicine, Center for Arrhythmia Care, Pritzker School of Medicine, Chicago, Illinois. Electronic address:

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http://dx.doi.org/10.1016/j.hrthm.2019.03.031DOI Listing
September 2019

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

Europace 2019 Nov;21(11):1742-1749

Division of Cardiology, Rush University Medical Center, 1717 W. Congress Parkway, Suite 332, Kellogg, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1093/europace/euz229DOI Listing
November 2019

Primary Prevention of Sudden Cardiac Death.

JAMA 2019 07;322(2):161-162

University of Chicago, Chicago, Illinois.

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http://dx.doi.org/10.1001/jama.2019.7662DOI Listing
July 2019

On-treatment comparison between corrective His bundle pacing and biventricular pacing for cardiac resynchronization: A secondary analysis of the His-SYNC Pilot Trial.

Heart Rhythm 2019 12 13;16(12):1797-1807. Epub 2019 May 13.

Center for Arrhythmia Care, The University of Chicago Medicine, Section of Cardiology, Department of Medicine, Pritzker School of Medicine, Chicago, Illinois (Study Coordinating Site). Electronic address:

Background: The His-SYNC pilot trial was the first randomized comparison between His bundle pacing in lieu of a left ventricular lead for cardiac resynchronization therapy (His-CRT) and biventricular pacing (BiV-CRT), but was limited by high rates of crossover.

Objective: To evaluate the results of the His-SYNC pilot trial utilizing treatment-received (TR) and per-protocol (PP) analyses.

Methods: The His-SYNC pilot was a multicenter, prospective, single-blinded, randomized, controlled trial comparing His-CRT vs BiV-CRT in patients meeting standard indications for CRT (eg, NYHA II-IV patients with QRS >120 ms). Crossovers were required based on prespecified criteria. The primary endpoints analyzed included improvement in QRS duration, left ventricular ejection fraction (LVEF), and freedom from cardiovascular (CV) hospitalization and mortality.

Results: Among 41 patients enrolled (aged 64 ± 13 years, 38% female, LVEF 28%, QRS 168 ± 18 ms), 21 were randomized to His-CRT and 20 to BiV-CRT. Crossover occurred in 48% of His-CRT and 26% of BiV-CRT. The most common reason for crossover from His-CRT was inability to correct QRS owing to nonspecific intraventricular conduction delay (n = 5). Patients treated with His-CRT demonstrated greater QRS narrowing compared to BiV (125 ± 22 ms vs 164 ± 25 ms [TR], P < .001;124 ± 19 ms vs 162 ± 24 ms [PP], P < .001). A trend toward higher echocardiographic response was also observed (80 vs 57% [TR], P = .14; 91% vs 54% [PP], P = .078). No significant differences in CV hospitalization or mortality were observed.

Conclusions: Patients receiving His-CRT on-treatment demonstrated superior electrical resynchronization and a trend toward higher echocardiographic response than BiV-CRT. Larger prospective studies may be justifiable with refinements in patient selection and implantation techniques to minimize crossovers.
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http://dx.doi.org/10.1016/j.hrthm.2019.05.009DOI Listing
December 2019
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