Browsing by Subject "Ventricular tachycardia"
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Item 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias(Oxford University Press, 2019-08) Cronin, Edmond M.; Bogun, Frank M.; Maury, Philippe; Peichl, Petr; Chen, Minglong; Namboodiri, Narayanan; Aguinaga, Luis; Leite, Luiz Roberto; Al-Khatib, Sana M.; Anter, Elad; Berruezo, Antonio; Callans, David J.; Chung, Mina K.; Cuculich, Phillip; d’Avila, Andre; Deal, Barbara J.; Bella, Paolo Della; Deneke, Thomas; Dickfeld, Timm-Michael; Hadid, Claudio; Haqqani, Haris M.; Kay, G. Neal; Latchamsetty, Rakesh; Marchlinski, Francis; Miller, John M.; Nogami, Akihiko; Patel, Akash R.; Pathak, Rajeev Kumar; Sáenz Morales, Luis C.; Santangeli, Pasquale; Sapp, John L, Jr.; Sarkozy, Andrea; Soejima, Kyoko; Stevenson, William G.; Tedrow, Usha B.; Tzou, Wendy S.; Varma, Niraj; Zeppenfeld, Katja; Medicine, School of MedicineVentricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.Item Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation(American Heart Association, 2021) Raad, Nour; Bittihn, Philip; Cacheux, Marine; Jeong, Dongtak; Ilkan, Zeki; Ceholski, Delaine; Kohlbrenner, Erik; Zhang, Lu; Cai, Chen-Leng; Kranias, Evangelia G.; Hajjar, Roger J.; Stillitano, Francesca; Akar, Fadi G.; Pediatrics, School of MedicineBackground: Arginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLNR14del) has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy. Mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling remain unclear. Methods: To address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLNWT (wildtype [WT], n=12) or the heterozygous human PLNR14del mutation (R14del, n=12) before and after ex vivo challenge with isoproterenol and rapid pacing. Results: Adverse electrophysiological remodeling was evident in the absence of significant structural or hemodynamic changes. R14del hearts exhibited increased arrhythmia susceptibility compared with wildtype. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to β-adrenergic stimulation. A steep repolarization gradient at the left ventricular/right ventricular interface provided the substrate for interventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. Once sustained, these circuits evolved into high-frequency rotors, which in their majority were pinned to the right ventricle. These rotors exhibited unique spatiotemporal dynamics that promoted their increased stability in R14del compared with wildtype hearts. Conclusions: Our findings highlight the crucial role of primary electric remodeling caused by the hPLNR14del mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of PLNR14del induced cardiomyopathy.Item Arrhythmias in Patients With Heart Failure Prescribed Dofetilide or Sotalol(Elsevier, 2024-11-07) Huang, Chien-Yu; Overholser, Brian R.; Sowinski, Kevin M.; Jaynes, Heather A.; Kovacs, Richard J.; Tisdale, James E.; Medicine, School of MedicineBackground: Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced arrhythmias. It is unknown whether HF with preserved ejection fraction (HFpEF) also increases the risk. Objectives: The purpose of this study was to determine if the risk of ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF prescribed dofetilide or sotalol. Methods: Using Medicare claims and pharmacy benefits from 2014 to 2016, we identified patients taking dofetilide or sotalol and non-dofetilide/sotalol users among 3 groups: HFrEF (n = 26,176), HFpEF (n = 33,304), and no HF (n = 580,249). Multinomial propensity score matching was performed. We compared baseline characteristics using Cochran-Mantel-Haenszel statistics and standardized differences, and tested associations of VT and SCA among dofetilide/sotalol users and those with HFpEF, HFrEF, or no HF using a generalized Cox proportional hazards model. Results: VT and SCA occurred 166 (10.68%) and 16 (1.03%) of 1,554 dofetilide/sotalol users with HFpEF, 543 (38.76%) and 40 (2.86%) of 1,401 dofetilide/sotalol users with HFrEF, and 245 (5.06%) and 13 (0.27%) of 4,839 dofetilide/sotalol users without HF. Overall VT risk was increased in HFrEF and HFpEF patients (HR: 7.00 [95% CI: 6.10-8.02] and 1.99 [95% CI: 1.70-2.32], respectively). The risk of VT in patients prescribed dofetilide/sotalol was increased in HFrEF and HFpEF patients (1.53 [95% CI: 1.07-2.20] and 2.34 [95% CI: 1.11-4.95], respectively). While the overall SCA risk was increased in HFrEF and HFpEF patients (5.19 [95% CI: 4.10-6.57] and 2.53 [95% CI: 1.98-3.23], respectively), dofetilide/sotalol use was not associated with an increased SCA risk. Conclusions: In patients with HF who are prescribed dofetilide or sotalol, the risk of VT, but not SCA, was increased.Item Gene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact(Oxford University Press, 2022) Dave, Jaydev; Raad, Nour; Mittal, Nishka; Zhang, Lu; Fargnoli, Anthony; Oh, Jae Gyun; Savoia, Maria Elisabetta; Hansen, Jens; Fava, Marika; Yin, Xiaoke; Theofilatos, Konstantinos; Ceholski, Delaine; Kohlbrenner, Erik; Jeong, Dongtak; Wills, Lauren; Nonnenmacher, Mathieu; Haghighi, Kobra; Costa, Kevin D.; Turnbull, Irene C.; Mayr, Manuel; Cai, Chen-Leng; Kranias, Evangelia G.; Akar, Fadi G.; Hajjar, Roger J.; Stillitano, Francesca; Pediatrics, School of MedicineAims: A mutation in the phospholamban (PLN) gene, leading to deletion of Arg14 (R14del), has been associated with malignant arrhythmias and ventricular dilation. Identifying pre-symptomatic carriers with vulnerable myocardium is crucial because arrhythmia can result in sudden cardiac death, especially in young adults with PLN-R14del mutation. This study aimed at assessing the efficiency and efficacy of in vivo genome editing, using CRISPR/Cas9 and a cardiotropic adeno-associated virus-9 (AAV9), in improving cardiac function in young adult mice expressing the human PLN-R14del. Methods and results: Humanized mice were generated expressing human wild-type (hPLN-WT) or mutant (hPLN-R14del) PLN in the heterozygous state, mimicking human carriers. Cardiac magnetic resonance imaging at 12 weeks of age showed bi-ventricular dilation and increased stroke volume in mutant vs. WT mice, with no deficit in ejection fraction or cardiac output. Challenge of ex vivo hearts with isoproterenol and rapid pacing unmasked higher propensity for sustained ventricular tachycardia (VT) in hPLN-R14del relative to hPLN-WT. Specifically, the VT threshold was significantly reduced (20.3 ± 1.2 Hz in hPLN-R14del vs. 25.7 ± 1.3 Hz in WT, P < 0.01) reflecting higher arrhythmia burden. To inactivate the R14del allele, mice were tail-vein-injected with AAV9.CRISPR/Cas9/gRNA or AAV9 empty capsid (controls). CRISPR-Cas9 efficiency was evaluated by droplet digital polymerase chain reaction and NGS-based amplicon sequencing. In vivo gene editing significantly reduced end-diastolic and stroke volumes in hPLN-R14del CRISPR-treated mice compared to controls. Susceptibility to VT was also reduced, as the VT threshold was significantly increased relative to controls (30.9 ± 2.3 Hz vs. 21.3 ± 1.5 Hz; P < 0.01). Conclusions: This study is the first to show that disruption of hPLN-R14del allele by AAV9-CRISPR/Cas9 improves cardiac function and reduces VT susceptibility in humanized PLN-R14del mice, offering preclinical evidence for translatable approaches to therapeutically suppress the arrhythmogenic phenotype in human patients with PLN-R14del disease.Item IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias(American Society of Hematology, 2021) Gupta, Akash; Fei, Yu-Dong; Kim, Tae Yun; Xie, An; Batai, Ken; Greener, Ian; Tang, Haiyang; Ciftci-Yilmaz, Sultan; Juneman, Elizabeth; Indik, Julia H.; Shi, Guanbin; Christensen, Jared; Gupta, Geetanjali; Hillery, Cheryl; Kansal, Mayank M.; Parikh, Devang S.; Zhou, Tong; Yuan, Jason X-J; Kanthi, Yogendra; Bronk, Peter; Koren, Gideon; Kittles, Rick; Duarte, Julio D.; Garcia, Joe G. N.; Machado, Roberto F.; Dudley, Samuel C.; Choi, Bum-Rak; Desai, Ankit A.; Medicine, School of MedicinePrevious reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes. Administering IL-18 to isolated mouse hearts resulted in VT originating from the right ventricle and further reduced Ito in SCD mouse cardiomyocytes. Sustained IL-18 inhibition via IL-18-binding protein resulted in decreased cardiac fibrosis and NF-κB phosphorylation, improved diastolic function, normalized electrical remodeling, and attenuated IL-18-mediated VT in SCD mice. Patients with SCD and either myocardial fibrosis or increased QTc displayed greater IL18 gene expression in peripheral blood mononuclear cells (PBMCs), and QTc was strongly correlated with plasma IL-18 levels. PBMC-derived IL18 gene expression was increased in patients who did not survive compared with those who did. IL-18 is a mediator of sickle cell cardiomyopathy and VT in mice and a novel therapeutic target in patients at risk for sudden death.Item Pharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy(Elsevier, 2013) Mohamed, Ahmed N.; Abdelhady, Ahmed M.; Spencer, Dustin; Sowinski, Kevin M.; Tisdale, James E.; Overholser, Brian R.; Medicine, School of MedicineProcainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case report describes a patient undergoing CRRT who was administered procainamide for recurring ventricular tachycardia (VT) over approximately a 36 hour period. The patient required increased vasopressor therapy and developed QTc prolongation during procainamide administration. The VT resided following pacemaker adjustments, procainamide administration, and multiple direct current cardioversion attempts. Procainamide and NAPA concentrations were determined over a 120 hour period as part of routine clinical care and a pharmacokinetic (PK) model was developed using NONMEM. The developed PK model was used to simulate several procainamide dosing regimens to optimize therapy during CRRT. Based on the model-based simulations, a 50% reduction in the procainamide maintenance dose (2 mg/min) in CKD patients on CRRT can achieve therapeutic plasma procainamide and combined procainamide/NAPA concentrations.Item Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram(Elsevier, 2017-01) Doytchinova, Anisiia; Hassel, Jonathan L.; Yuan, Yuan; Lin, Hongbo; Yin, Dechun; Adams, David; Straka, Susan; Wright, Keith; Smith, Kimberly; Wagner, David; Shen, Changyu; Salanova, Vicenta; Meshberger, Chad; Chen, Lan S.; Kincaid, John C.; Coffey, Arthur; Wu, Gang; Li, Yan; Kovacs, Richard J.; Everett, Thomas H., IV; Victor, Ronald; Cha, Yong-Mei; Lin, Shien-Fong; Chen, Peng-Sheng; Medicine, School of MedicineBACKGROUND: Sympathetic nerve activity is important to cardiac arrhythmogenesis. OBJECTIVE: The purpose of this study was to develop a method for simultaneous noninvasive recording of skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG) using conventional ECG electrodes. This method (neuECG) can be used to adequately estimate sympathetic tone. METHODS: We recorded neuECG signals from the skin of 56 human subjects. The signals were low-pass filtered to show the ECG and high-pass filtered to show nerve activity. Protocol 1 included 12 healthy volunteers who underwent cold water pressor test and Valsalva maneuver. Protocol 2 included 19 inpatients with epilepsy but without known heart diseases monitored for 24 hours. Protocol 3 included 22 patients admitted with electrical storm and monitored for 39.0 ± 28.2 hours. Protocol 4 included 3 patients who underwent bilateral stellate ganglion blockade with lidocaine injection. RESULTS: In patients without heart diseases, spontaneous nerve discharges were frequently observed at baseline and were associated with heart rate acceleration. SKNA recorded from chest leads (V1-V6) during cold water pressor test and Valsalva maneuver (protocol 1) was invariably higher than during baseline and recovery periods (P < .001). In protocol 2, the average SKNA correlated with heart rate acceleration (r = 0.73 ± 0.14, P < .05) and shortening of QT interval (P < .001). Among 146 spontaneous ventricular tachycardia episodes recorded in 9 patients of protocol 3, 106 episodes (73%) were preceded by SKNA within 30 seconds of onset. Protocol 4 showed that bilateral stellate ganglia blockade by lidocaine inhibited SKNA. CONCLUSION: SKNA is detectable using conventional ECG electrodes in humans and may be useful in estimating sympathetic tone.Item Ventricular tachycardia exacerbated by left bundle branch area pacing(Elsevier, 2023-06-28) Tanawuttiwat, Tanyanan; Kellett, Eric; Das, Mithilesh K.; Fore, Lukas J.; Miller, John M.; Medicine, School of MedicineItem Wide Complex Tachycardia - Ventricular Tachycardia or Not Ventricular Tachycardia, That Remains the Question(2013-04) Garner, John B.; Miller, John M.; Department of Medicine, IU School of MedicineArriving at the correct diagnosis in cases of wide complex tachycardia remains problematic for many clinicians. In this paper, we review the historical development of criteria used to differentiate among the major diagnostic possibilities and compare the strengths and weaknesses of various differentiating algorithms.