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Introduction: Scar substrate in nonischemic cardiomyopathy (NICM) patients is often difficult to identify. Advances in cardiac imaging, especially using late iodine-enhanced computed tomography (LIE-CT), allow better characterization of scars giving rise to ventricular tachycardia (VT). Currently, there are limited data on clinical correlates of CT-derived scar substrates in NICM. We sought assess the relationship between scar location on LIE-CT and outcomes after radiofrequency catheter ablation (RFCA) in NICM patients with VT., Methods: From 2020 to 2022, consecutive patients with NICM undergoing VT RFCA with integration of cardiac CT scar modeling (inHeart, Pessac, France) were included at two US tertiary care centers. The CT protocol included both arterial-enhanced imaging for anatomical modeling and LIE-CT for scar assessment. The distribution of substrate on CT was analyzed in relation to patient outcomes, with primary endpoints being VT recurrence and the need for repeat ablation procedure., Results: Sixty patients were included (age 64 ± 12 years, 90% men). Over a median follow-up of 120 days (interquartile range [IQR]: 41-365), repeat ablation procedures were required in 32 (53%). VT recurrence occurred in 46 (77%), with a median time to recurrence of 40 days (IQR: 8-65). CT-derived total scar volume positively correlated with intrinsic QRS duration (r = .34, p = 0.008). Septal scar was found on CT in 34 (57%), and lateral scar in 40 (7%). On univariate logistic regression, septal scar was associated with increased odds of repeat ablation (odds ratio [OR]: 2.9 [1.0-8.4]; p = 0.046), while lateral scar was not (OR: 0.9 [0.3-2.7]; p = 0.855). Septal scar better predicted VT recurrence when compared to lateral scar, but neither were statistically significant (septal scar OR: 3.0 [0.9-10.7]; p = 0.078; lateral scar OR: 1.7 [0.5-5.9]; p = 0.391)., Conclusion: In this tertiary care referral population, patients with NICM undergoing VT catheter ablation with septal LIE-CT have nearly threefold increased risk of need for repeat ablation., (© 2024 Wiley Periodicals LLC.)

Background: Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators., Methods: The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA., Results: The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3 years after enrollment., Conclusions: There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The authors describe 3 patients presenting with cardiac sarcoidosis (CS) flare and ventricular tachycardia (VT) storm following infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. COVID-19-related cardiac manifestations can vary and include arrythmias, myocarditis, and exacerbation of underlying cardiovascular disease. The exact mechanism of myocardial involvement is not clear but may include abnormal host immune response and direct myocardial injury, thereby predisposing to enhanced arrhythmic risk. Arrhythmias account for 20% of COVID-19-related complications with ventricular arrythmias occurring in 5.9% of cases. Further studies are needed to better understand mechanisms underlying the intersection between COVID-19 infection and inflammatory cardiomyopathies., Competing Interests: Funding Support and Author Disclosures Dr John was supported by the Pierce Family Fellowship. Dr Winterfield has received institutional research support from Abbott Medical and Biosense Webster; and has received consulting fees from Abbott Medical, Biosense Webster, Thermedical, and Biotronik. Dr Houston has received institutional research support from Medtronic Inc and CVRx; and has received consulting fees from Edwards Lifesciences and Medtronic. Dr Tedrow has received consulting fees from Biosense Webster and Thermedical Inch; has served on an advisory board for Biosense Webster; and has received honoraria for educational courses from Biosense Webster, Boston Scientific, Medtronic, and Abbott medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The PAINESD (Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA functional class, Ejection fraction, Storm, Diabetes mellitus) risk score has been validated as a predictor of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing ventricular tachycardia (VT) ablation. Whether the addition of total scar volume (TSV) determined by preprocedure computed tomography imaging provides additional risk stratification has not been previously investigated., Objectives: The purpose of this study was to evaluate the impact of TSV on the risk of AHD and its adjunctive benefit to the PAINESD score newly modified as Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA class, Ejection fraction, Storm, Scar volume, Diabetes mellitus (PAINES2D) based on the addition of scar volumes., Methods: This was a retrospective analysis of all index VT ablations at a quaternary care center from 2017 to 2022. Associations between TSV and AHD were evaluated among patients with structural heart disease., Results: Among 61 patients with TSV data, 13 (21%) had periprocedural AHD. TSV and PAINESD were independently associated with AHD risk. Both TSV and PAINESD were associated with AHD (P = 0.016 vs P = 0.053, respectively). The highest TSV tertile (≥37.30 mL) showed significant association with AHD (P = 0.018; OR: 4.80) compared to the other tertiles. The PAINESD and PAINES2D scores had significant impact on AHD (P = 0.046 and P = 0.010, respectively). The PAINES2D score had a greater impact on AHD compared to PAINESD (area under the curve: 0.73; P = 0.011; 95% CI: 0.56-0.91 and area under the curve: 0.67; P = 0.058; 95% CI: 0.49-0.85, respectively)., Conclusions: Addition of TSV to a modified PAINESD score, PAINES2D, enhances risk prediction of AHD. Further prospective study is needed to assess benefit in various cardiomyopathy populations undergoing VT ablation., Competing Interests: Funding Support and Author Disclosures Dr Tedford has consulting relationships with Medtronic, Abbott Medical, Aria CV Inc, Acceleron, Alleviant, CareDx, Cytokinetics, Itamar, Edwards LifeSciences, Eidos Therapeutics, Lexicon Pharmaceuticals, Gradient, and United Therapeutics; is the national principal investigator for the RIGHT-FLOW clinical trial (Edwards); serves on Steering Committee for Merck and Abbott and a Research Advisory Board for Abiomed; and also does hemodynamic core lab work for Merck. Dr Gold hasconsultation relationships with Medtronic, Boston Scientific, CVRX, EBR, and Abbott Medical. Dr Field has received research funding from Medtronic, Abbott Medical, and Biosense Webster. Dr Schoepf has received institutional research support and honoraria for speaking and consulting from Bayer, ElucidBio, Guerbet, HeartFlow, Inc, Keya Medical, and Siemens Healthineers. Dr Cochet is a cofounder of inHEART Medical. Dr Jaïs is a cofounder of inHEART Medical. Dr Santangeli has consultation relationships with Boston Scientific, Abbott Medical, and Biosense Webster. Dr Winterfield has received institutional research support from Abbott Medical and Biosense Webster; and has consultation relationships with Abbott Medical, Biosense Webster, Thermedical, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Advanced cardiac imaging is an important component in pre-procedural planning for ventricular tachycardia (VT) ablations. inHEART's proprietary software, inHEART Models, and its academic version, Multimodality Platform for Specific Imaging in Cardiology (MUSIC), provide detailed characterization of anatomical structures and scars., Areas Covered: This review highlights the current overview of the market and offers insight into inHEART Models and MUSIC and its application during VT ablations with supporting case examples. An overview of the clinical profile and regulatory status of inHEART Models, and other competing technologies, such as Automatic Detection of Arrhythmia Substrate (ADAS) 3D software and Catheter Precision's View into Ventricular Onset (VIVO), are also discussed., Expert Opinion: inHEART and MUSIC utilization has increased over the last few years and continues to establish its presence as an important aspect of VT ablations. Its unique proprietary software sets itself apart from others in the field. The introduction of dual source-photon counting detector computed tomography (PCD-CT) is expected to make significant advancements in the field and take imaging to a new level. inHEART's continued research in cardiac imaging and digital technology is expected to increase as is its global presence in the electrophysiology (EP) community.

Background: High-power, short-duration (HPSD) radiofrequency ablation (RFA) reduces procedure time; however, safety and efficacy thresholds vary with catheter design., Objective: The study sought to determine optimal HPSD ablation conditions with a novel flexible-tipped, contact force-sensing RFA catheter., Methods: RFA lesions were created in thigh muscle (16 swine) over a range of conditions (51-82 W, 2-40 g, 8-40 mL/min irrigation). An intracardiac study was performed (12 swine) to characterize steam pop thresholds. Lesions were created in a second intracardiac study (14 swine, n = 290 pulmonary vein isolation [PVI] lesions) with combinations of radiofrequency power, duration, and contact force. PVI was tested, animals were sacrificed, and lesions were measured., Results: The likelihood of coagulation formation in the thigh model was <20% when power was ≤79 W, when contact force was ≤40 g, when duration was ≤11 seconds, and when irrigation rates were 8 to 40 mL/min. The impact of contact force on lesion safety and efficacy was more pronounced using HPSD (60 W/8 seconds) compared with conventional ablation (30 W/45 seconds) ( P = .038). During PVI, focal atrial lesions ranged in width from 4.2 to 12.5 mm and were transmural 80.8% of the time. PVI was achieved in 13 of 14 veins. Logistic regression identified that the optimal parameters for radiofrequency application were 60 to 70 W with a duration <8 seconds and <15 g contact force., Conclusions: Optimal HPSD lesions with this this flexible-tipped, force-sensing RFA catheter were created at 60 to 70 W for <8 seconds with <15 g contact force. Chronic studies are ongoing to assess radiofrequency parameter refinements and long-term lesion durability using these conditions., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Ventricular tachycardia (VT) ablation of mid- or epicardial substrate is difficult and requires a creative approach in patients with a history of coronary bypass that precludes percutaneous epicardial catheter manipulation. The coronary venous system (CVS) provides limited access to the epicardial surface of the heart. The objective of this study is to assess the feasibility, safety, and efficacy of epicardial mapping and ablation of VT substrates from the CVS in patients with history of coronary bypass., Methods: Patients undergoing VT ablation at our institution were retrospectively reviewed. Those who had basal to mid ventricular substrate based on computed tomography imaging and history of coronary bypass were included. Endocardial and CVS mapping and ablation was performed in standard fashion using 3D electroanatomic mapping. The primary endpoint was defined as VT circuit elimination, termination, non-inducibility, or perturbation of the circuit., Results: Of 192 consecutive VT ablations from 2017 to 2020, 35 (18%) had a history of coronary bypass and basal to the mid-ventricular substrate by imaging. There were no significant characteristic differences between the endocardial only (n = 19) vs endocardial + CVS (n = 16) groups. In 14 (88%) of patients undergoing CVS mapping, the VT circuit was identified to be within access from the epicardial surface. Ablation was attempted in 8 (57%) of these patients, and the primary endpoint was reached in 88% of those undergoing CVS ablation. There were no complications related to CVS ablation., Conclusion: Mapping and ablation of mid- or epicardial VT circuits from the CVS branches are feasible and safe and may be helpful in the treatment of VT in patients who are otherwise not candidates for percutaneous epicardial ablation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Conventional contact-based electroanatomic mapping is poorly suited for rapid or dynamic ventricular arrhythmias. Whole-chamber charge density (CD) mapping could efficiently characterize complex ventricular tachyarrhythmias and yield insights into their underlying mechanisms., Objective: The purpose of this study was to evaluate the feasibility and accuracy of noncontact whole-chamber left ventricular (LV) CD mapping and to characterize CD activation patterns during sinus rhythm, ventricular pacing, and ventricular fibrillation (VF)., Methods: Ischemic scar as defined by CD amplitude thresholds was compared to late gadolinium enhancement criteria on magnetic resonance imaging using an iterative closest point algorithm. Electrograms recorded at sites of tissue contact were compared to the nearest noncontact CD-derived electrograms to calculate signal morphology cross-correlations and time differences. Regions of consistently slow conduction were examined relative to areas of scar and to localized irregular activation (LIA) during VF., Results: Areas under receiver operating characteristic curves (AUCs) of CD-defined dense and total LV scar were 0.92 ± 0.03 and 0.87 ± 0.06, with accuracies of 0.86 ± 0.03 and 0.80 ± 0.05, respectively. Morphology cross-correlation between 8677 contact and corresponding noncontact electrograms was 0.93 ± 0.10, with a mean time difference of 2.5 ± 5.6 ms. Areas of consistently slow conduction tended to occur at scar borders and exhibited spatial agreement with LIA during VF (AUC 0.90 ± 0.02)., Conclusion: Noncontact LV CD mapping can accurately delineate ischemic scar. CD-derived ventricular electrograms correlate strongly with conventional contact-based electrograms. Regions with consistently slow conduction are often at scar borders and tend to harbor LIA during VF., (Copyright © 2022. Published by Elsevier Inc.)

Background: Ablation Index (AI) is a multiparametric quality marker to assess the durability of radiofrequency (RF) lesions. The comparative effectiveness and safety of AI versus time-based energy dosing for ablation of ventricular arrhythmias are unknown., Objective: We compared AI and time-based RF dosing strategies in the left ventricles (LVs) of freshly harvested porcine hearts., Methods: Ablation was performed in vitro with an open-irrigated ablation catheter (Thermocool ST/SF), 40 W, contact force 10-15 g. Tissue samples were stained in triphenyltetrazolium chloride for the measurement of lesion dimensions., Results: A total of 560 lesions were performed (AI-group: [n = 360]; time-group: [n = 200]). Using normal saline (NS) (n = 280), growth in lesion depth slowed after 30 s and AI > 550 in comparison to width, volume, and magnitude of impedance drops which continued to increase with longer RF duration. Risk of steam pop (SP) was higher for RF > 30 s (RF < 30 s:1 SP [2.5%] vs. RF > 30 s: 15 SP [25%]; p = .002) or AI targets >550 (AI: 350-550: 2 SP [2%] vs. AI 600-750: 15 SP [19%]; p = .001). Using half-normal saline (HNS) (n = 280), lesion dimension and impedance drops were larger and growth in lesion depth slowed earlier (AI: 500). Risk of SPs was higher above AI 550 (AI: 350-550: 7 [7%] SPs vs. AI 600-750: 28 [35%] SPs; p < .00001). While codependent variables, correlation between AI and time was modest-to-strong but decreased with longer RF duration., Conclusion: In this ex vivo study, AI was a better predictor of lesion dimensions than ablation time and magnitude of impedance drop in the LV using NS and HNS irrigation. AI targets above 550 led to a higher risk of SPs. Future trials are required to verify these findings., (© 2022 Wiley Periodicals LLC.)

Introduction: Catheter ablation (CA) of frequent premature ventricular contractions (PVC) is increasingly performed in older patients as the population ages. The aim of this study was to assess the impact of age on procedural characteristics, safety and efficacy on PVC ablations., Methods: Consecutive patients with symptomatic PVCs undergoing CA between 2015 and 2020 were evaluated. Acute ablation success was defined as the elimination of PVCs at the end of the procedure. Sustained success was defined as an elimination of symptoms, and ≥80% reduction of PVC burden determined by Holter-electrocardiogram during long-term follow. Patients were sub-grouped based on age (<65 vs. ≥65 years)., Results: A total of 114 patients were enrolled (median age 64 years, 71% males) and followed up for a median duration of 228 days. Baseline and procedural data were similar in both age groups. A left-sided origin of PVCs was more frequently observed in the elderly patient group compared to younger patients (83% vs. 67%; p = .04). The median procedure time was significantly shorter in elderly patients (160 vs. 193 min; p = .02). The rates of both acute (86% vs. 92%; p = .32) and sustained success (70% vs. 71%; p = .90) were similar between groups. Complications rates (3.7%) did not differ between the two groups., Conclusion: In a large series of patients with a variety of underlying arrhythmia substrates, similar rates of acute procedural success, complications, and ventricular arrhythmia-free-survival were observed after CA of PVCs. Older age alone should not be a reason to withhold CA of PVCs., (© 2021 Wiley Periodicals LLC.)

Catheter-based ablation techniques have a well-established role in atrial fibrillation (AF) management. The prevalence and impact of AF is increasing globally, thus mandating an emphasis on improving ablation techniques through innovation. One key area of ongoing evolution in this field is the use of laser energy to perform pulmonary vein isolation during AF catheter ablation. While laser use is not as widespread as other ablation techniques, such as radiofrequency ablation and cryoballoon ablation, advancements in product design and procedural protocols have demonstrated laser balloon ablation to be equally safe and effective compared to these other modalities. Additionally, strategies to improve procedural efficiency and decrease radiation exposure through low fluoroscopy protocols make this technology an increasingly promising and exciting option.

Competing Interests: The authors report no conflicts of interest for the published content.

Aim: To compare outcomes among patients with implantable cardioverter defibrillator/cardiac resynchronization therapy-defibrillator undergoing outpatient ventricular tachycardia (VT) catheter ablation using intracardiac echocardiography (ICE) versus no ICE. Patients & methods: Patients were classified into ICE (n = 1143)/non-ICE (n = 1677) groups based on ICE procedure codes. Patients in each group were propensity matched on study covariates. Survival analyses were used to assess outcomes. To examine residual confounding, falsification outcomes were evaluated. Results: ICE patients had a 24% lower risk of all-cause readmissions, 24% lower risk of cardiovascular-related and 20% lower risk of VT-related readmissions compared with non-ICE patients. Falsification analyses for ICE use association were nonsignificant. Conclusion: Patients with implantable cardioverter defibrillator/cardiac resynchronization therapy-defibrillator undergoing VT ablation with ICE use had significantly lower likelihood of VT-related readmission.

Introduction: By providing real-time monitoring of catheter-tissue interface and for complications, intracardiac echocardiography (ICE) during catheter ablation for ventricular tachycardia (VT) may improve outcomes. To test this hypothesis, we compared 12-month readmission rates (all-cause, cardiovascular [CV]-related, and VT-related), repeat ablation, and complications among patients with VT with structural heart disease undergoing ablation with versus without ICE., Methods and Results: Using the 2008-2017 IBM MarketScan Commercial and Medicare Supplemental databases, patients with a history of implantable cardioverter defibrillator/cardiac resynchronization therapy (ICD/CRT-D) who underwent VT ablation with and without ICE use were identified. Propensity matching was performed and regression analysis was used to compare outcomes. After matching, 1324 patients were identified (ICE: 662; non-ICE: 662). The rate of 12-month VT-related readmission (18.13% vs 22.51%; P < .05) and repeat VT ablation (14.35% vs 19.34%; P = .02) postindex discharge were lower among patients in the ICE group compared with the non-ICE group, with a 24% lower risk of 12-month VT-related readmission (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.58-0.99) and a 30% lower risk of repeat ablation (OR, 0.70; 95% CI, 0.52-0.93) vs non-ICE group. The 12-month all-cause (44.56% vs 43.20%; P = .62) and CV-related readmissions (35.20% vs 32.93%; P = 0.38) and complication rates were not significantly different between the two groups., Conclusions: VT ablation using ICE was associated with a lower likelihood of 12-month VT-related readmission and repeat ablation compared with non-ICE patients., (© 2019 Wiley Periodicals, Inc.)

Background: Catheter ablation of ventricular tachycardia (VT) has been shown to reduce the number of recurrent shocks in patients with an implantable cardioverter-defibrillator (ICD). However, how VT ablation affects postprocedural medical and pharmaceutical usage remains unclear., Objective: The purpose of this study was to investigate changes in health care resource utilization (HCRU) after VT ablation., Methods: This large-scale, real-world, retrospective study used the MarketScan databases to identify patients in the United States with an ICD or cardiac resynchronization therapy-defibrillator (CRT-D) undergoing VT ablation. We calculated cumulative medical and pharmaceutical expenditures, office visits, hospitalizations, and emergency room (ER) visits in the 1-year periods before and after ablation., Results: A total of 523 patients met the study inclusion criteria. After VT ablation, median annual cardiac rhythm-related medical expenditures decreased by $5,408. Moreover, the percentage of patients with at least 1 cardiac rhythm-related hospitalization and ER visit decreased from 53% and 41% before ablation to 28% and 26% after ablation, respectively. Similar changes were observed in the number of all-cause hospitalizations and ER visits, but there were no significant changes in all-cause medical expenditures. During the year before VT ablation, there was an increasing rate of health care resource utilization, followed by drastic slowing after ablation., Conclusion: This retrospective study demonstrated that catheter ablation seems to reduce hospitalization and overall health care utilization in VT patients with an ICD or CRT-D in place., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Next-generation catheters have been developed to reduce irrigation volume and preserve power delivery. A novel design uses a flexible tip (FlexAbility™ catheter) that directs flow to the contact surface. Because of recent safety issues with new catheters, we undertook a study in a canine heart with 3 irrigated catheters to compare efficacy and safety., Methods: Endocardial ablation was performed by 2 independent operators in 12 anesthetized canines with the FlexAbility (St. Jude Medical), ThermoCool™ (Biosense Webster), and ThermoCool™ SF (Biosense Webster) catheters. Endocardial RF lesions were delivered with each catheter in all 4 chambers of each animal for 52 ± 16 seconds. Each chamber was randomized to receive ablation from one catheter with recording of safety events. Cardiac pathology was performed with triphenyl tetrazolium chloride stain., Results: Average lesion dimensions were not significantly different between the 3 catheters. FlexAbility™ demonstrated a lower risk of steam pops relative to ThermoCool SF (P-value = 0.013) despite equal mean power and radiofrequency time. High-temperature generator shutdowns were observed with FlexAbility™ but not with either ThermoCool catheter. High-temperature shutdowns were associated with larger average impedance drops (28.5 ohms vs. 19 ohms) without compromising lesion size., Conclusions: The FlexAbility™ tip is safe and effective with no significant difference in lesion sizes compared to both standard ThermoCool and ThermoCool SF. FlexAbility™ has a significantly lower risk of steam pops compared to ThermoCool SF in a beating heart as defined predominantly by an abrupt rise of impedance., (© 2015 Wiley Periodicals, Inc.)

Purpose of Review: Drug-refractory ventricular tachycardia in the setting of structural heart disease results in frequent implantable cardioverter defibrillator therapies and an increased risk of heart failure. Management requires catheter ablation procedures for effective suppression of the arrhythmia., Recent Findings: Imaging and electroanatomic mapping technologies provide new insights into the myocardial structural abnormalities responsible for ventricular tachycardia. Integration of imaging data with three-dimensional mapping systems coupled with improved targeting of abnormal electrical signals may improve the ablation outcomes. New ablation tools show promise for the effective ablation of previously unreachable myocardial ventricular tachycardia circuits., Summary: Catheter ablation procedures have evolved over the last 2 decades. Improved technology may contribute to more widespread utilization of catheter ablation in the future.

Background: Immunoreactive signal for the desmosomal protein plakoglobin (γ-catenin) is reduced at cardiac intercalated disks in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a highly arrhythmogenic condition caused by mutations in genes encoding desmosomal proteins. Previously, we observed a false-positive case in which plakoglobin signal was reduced in a patient initially believed to have ARVC but who actually had cardiac sarcoidosis. Sarcoidosis can masquerade clinically as ARVC but has not been previously associated with altered desmosomal proteins., Methods and Results: We observed marked reduction in immunoreactive signal for plakoglobin at cardiac myocyte junctions in patients with sarcoidosis and giant cell myocarditis, both highly arrhythmogenic forms of myocarditis associated with granulomatous inflammation. In contrast, plakoglobin signal was not depressed in lymphocytic (nongranulomatous) myocarditis. To determine whether cytokines might promote dislocation of plakoglobin from desmosomes, we incubated cultures of neonatal rat ventricular myocytes with selected inflammatory mediators. Brief exposure to low concentrations of interleukin (IL)-17, tumor necrosis factor-α (TNF-α), and IL-6 (cytokines implicated in granulomatous myocarditis) caused translocation of plakoglobin from cell-cell junctions to intracellular sites, whereas other potent cytokines implicated in nongranulomatous myocarditis had no effect, even at much higher concentrations. We also observed myocardial expression of IL-17 and TNF-α and elevated levels of serum inflammatory mediators, including IL-6R, IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1β, in patients with ARVC (all P<0.0001 compared with controls)., Conclusions: The results suggest novel disease mechanisms involving desmosomal proteins in granulomatous myocarditis and implicate cytokines, perhaps derived in part from the myocardium, in disruption of desmosomal proteins and arrhythmogenesis in ARVC.

Objective: Demonstrate a case report involving successful use of lipid emulsion therapy for intractable cardiac arrest due to lidocaine toxicity., Data Source: Lipid emulsion therapy has been shown to be effective in treating the cardiotoxic effects of such drugs as bupivacaine, verapamil, propranolol, and clomipramine as mentioned in a 2009 editorial in Critical Care Medicine by Jeffrey Bent. The mechanism of action of lipid emulsion therapy is not well defined and has been postulated to work by both a "lipid sink," decreasing circulating amounts of drugs to the periphery, or through a direct "energy source" to the myocardium. We present a case report of a patient successfully resuscitated with lipid emulsion therapy after prolonged and intractable lidocaine toxicity. Lidocaine is generally considered much less cardiotoxic than other local anesthetics and is used commonly as infusions for intractable ventricular arrhythmias., Conclusion: This case demonstrates the need to consider lipid emulsion therapy in the advanced cardiac life support algorithm for lidocaine toxicity as well as other lipid soluble drug intoxications.

Type 2 diabetes mellitus (DM) is increasing around the world, and the public health impact of DM, driven largely by cardiovascular disease complications, underpins the importance of continued efforts toward primary prevention of DM. Only a few interventions have been shown to prevent DM, with none of them yet proven to improve cardiovascular risk commensurately. Accumulating evidence suggest that drugs that block the renin-angiotensin-aldosterone system (RAAS), many of which have proven cardiovascular disease (CVD) benefit, also have favourable effects on parameters of glucose metabolism and incident diabetes. Here we review the evidence accumulated to date from animal studies, clinical mechanistic studies and clinical trials regarding the effect of RAAS inhibition and incident DM.

The gating modifier toxins are a large family of protein toxins that modify either activation or inactivation of voltage-gated ion channels. omega-Aga-IVA is a gating modifier toxin from spider venom that inhibits voltage-gated Ca(2+) channels by shifting activation to more depolarized voltages. We identified two Glu residues near the COOH-terminal edge of S3 in the alpha(1A) Ca(2+) channel (one in repeat I and the other in repeat IV) that align with Glu residues previously implicated in forming the binding sites for gating modifier toxins on K(+) and Na(+) channels. We found that mutation of the Glu residue in repeat I of the Ca(2+) channel had no significant effect on inhibition by omega-Aga-IVA, whereas the equivalent mutation of the Glu in repeat IV disrupted inhibition by the toxin. These results suggest that the COOH-terminal end of S3 within repeat IV contributes to forming a receptor for omega-Aga-IVA. The strong predictive value of previous mapping studies for K(+) and Na(+) channel toxins argues for a conserved binding motif for gating modifier toxins within the voltage-sensing domains of voltage-gated ion channels.