Immune cellular components and signaling pathways in the tumor microenvironment.

During the past decade there has been a revolution in cancer therapeutics by the emergence of antibody-based and cell-based immunotherapies that modulate immune responses against tumors. These new therapies have extended and improved the therapeutic efficacy of chemo-radiotherapy and have offered treatment options to patients who are no longer responding to these classic anti-cancer treatments. Unfortunately, tumor eradication and long-lasting responses are observed in a small fraction of patients, whereas the majority of patients respond only transiently. These outcomes indicate that the maximum potential of immunotherapy has not been reached due to incomplete knowledge of the cellular and molecular mechanisms that guide the development of successful anti-tumor immunity and its failure. In this review, we discuss recent discoveries about the immune cellular composition of the tumor microenvironment (TME) and the role of key signaling mechanisms that compromise the function of immune cells leading to cancer immune escape.

Determinants of acute irreversible electroporation lesion characteristics after pulsed field ablation: the role of voltage, contact, and adipose interference.

AIMS: Pulsed field ablation (PFA) is a non-thermal ablative approach in which cardiomyocyte death is obtained through irreversible electroporation (IRE). Data correlating the biophysical characteristics of IRE and lesion characteristics are limited. The aim of this study was to assess the effect of different procedural parameters [voltage, number of cycles (NoCs), and contact] on lesion characteristics in a vegetal and animal model for IRE. METHODS AND RESULTS: Two hundred and four Russet potatoes were used. Pulsed field ablation lesions were delivered on 3 cm cored potato specimens using a multi-electrode circular catheter with its dedicated IRE generator. Different voltage (from 300 to 1200 V) and NoC (from 1 to 5×) protocols were used. The impact of 0.5 and 1 mm catheter-to-specimen distances was tested. A swine animal model was then used to validate the results observed in the vegetable model. The association between voltage, the NoCs, distance, and lesion depth was assessed through linear regression. An almost perfect linear association between lesion depth and voltage was observed (R2 = 0.95; P < 0.001). A similarly linear relationship was observed between the NoCs and the lesion depth (R2 = 0.73; P < 0.001). Compared with controls at full contact, a significant dampening on lesion depth was observed at 0.5 mm distance (1000 V 2×: 2.11 ± 0.12 vs. 0.36 ± 0.04, P < 0.001; 2.63 ± 0.10 vs. 0.43 ± 0.08, P < 0.001). No lesions were observed at 1.0 mm distance. CONCLUSION: In a vegetal and animal model for IRE assessment, PFA lesion characteristics were found to be strongly dependent on voltage settings and the NoCs, with a quasi-linear relationship. The lack of catheter contact was associated with a dampening in lesion depth.

Long-term clinical outcomes of cardiac sympathetic denervation in patients with refractory ventricular arrhythmias.

BACKGROUND: Cardiac sympathetic denervation (CSD) is a useful therapeutic option in patients with structural heart disease (SHD) and ventricular tachycardia (VT) who are otherwise refractory to standard antiarrhythmic drug (AAD) therapy or catheter ablation (CA). In this study, we sought to retrospectively analyze the long-term outcomes of CSD in patients with refractory VT and/or VT storm with a majority of the patients being taken up for CSD ahead of CA. METHODS: We included consecutive patients with SHD who underwent CBD from 2010 to 2019 owing to refractory VT. A complete response to CSD was defined as a greater than 75% reduction in the frequency of ICD shocks for VT. RESULTS: A total of 65 patients (50 male, 15 female) were included. The underlying VT substrate was ischemic heart disease (IHD) in 30 (46.2%) patients while the remaining 35 (53.8%) patients had other nonischemic causes. The mean duration of follow-up was 27 ± 24 months. A complete response to CSD was achieved in 47 (72.3%) patients. There was a significant decline in the number of implantable cardioverter-defibrillator (ICD) or external defibrillator shocks post-CSD (24 ± 37 vs. 2 ± 4, p < .01). Freedom from a combined endpoint of ICD shock or death at 2 years was 51.5%. An advanced New York Heart Association class (III and IV) was the only parameter found to be associated with this combined endpoint. CONCLUSION: The current retrospective analysis re-emphasizes the role of surgical CSD and explores its role ahead of CA in the treatment of patients with refractory VT or VT storm.

Trans-nasal high-flow dehumidified air in acute migraine headaches: A randomized controlled trial.

BACKGROUND: Intranasal high flow of dehumidified (dry) air results in evaporative cooling of nasal passages. In this randomized clinical trial, we investigated the effect of dry gas induced nasal cooling on migraine headaches. METHODS: In this single-blind study, acute migraineurs were randomized to either nasal high-flow dry oxygen, dry air, humidified oxygen or humidified air (control) at 15 L/min for 15 min. All gases were delivered at 37°C. Severity of headache and other migraine associated symptoms (International Classification for Headache Disorders, 3rd edition criteria) were recorded before and after therapy. The primary endpoint was change in pain scores, while changes in nausea, photosensitivity and sound sensitivity scores served as secondary endpoints. A linear regression model was employed to estimate the impact of individual treatment components and their individual interactions. RESULTS: Fifty-one patients (48 ± 15 years of age, 82% women) were enrolled. When compared to the control arm (humidified air), all therapeutic arms showed a significantly greater reduction in pain scores (primary endpoint) at 2 h of therapy with dry oxygen (-1.6 [95% CI -2.3, -0.9]), dry air (-1.7 [95% CI -2.6, -0.7)]), and humidified oxygen (-2.3 [95% CI -3.5, -1.1]). A significantly greater reduction in 2-h photosensitivity scores was also noted in all therapeutic arms (-1.8 [95% CI -3.2, -0.4], dry oxygen; -1.7 [95% CI -2.9, -0.4], dry air; (-2.1 [95% CI -3.6, -0.6], humidified oxygen) as compared to controls. The presence of oxygen and dryness were independently associated with significant reductions in pain and photosensitivity scores. No adverse events were reported. CONCLUSION: Trans-nasal high-flow dry gas therapy may have a role in reducing migraine associated pain.Clinical Trial registration: NCT04129567.

Safety and Feasibility of a Novel Transnasal Cooling Device to Induce Normothermia in Febrile Cerebrovascular Patients.

BACKGROUND: Inducing normothermia with surface cooling temperature modulating devices (TMDs) is cumbersome and often associated with significant shivering. We tested the safety and feasibility of a novel transnasal evaporative cooling device to induce and maintain normothermia in febrile patients following ischemic and hemorrhagic stroke. METHODS: A single-center study utilizing the CoolStat® transnasal cooling device was used to achieve core temperature reduction in mechanically ventilated stroke patients with fever (T ≥ 38.3 C) refractory to acetaminophen by inducing an evaporative cooling energy exchange in the nasal turbinates thru a high flow of dehumidified air into the nasal cavity and out through the mouth. Continuous temperature measurements were obtained from tympanic and core (esophageal or bladder) temperature monitors. Safety assessments included continuous monitoring for hypertension, tachycardia, and raised intracranial pressure (when monitored). Otolaryngology (ENT) evaluations were monitored for any device-related nasal mucosal injury with a pre- and post-visual examination. Shivering was assessed every 30 min using the Bedside Shivering Assessment Scale (BSAS). Duration of device use was limited to 8 h, at which time patients were transitioned to routine care for temperature management. RESULTS: Ten subjects (median age: 54 years, BMI: 32.5 kg/m2, 60% men) were enrolled with normothermia achieved in 90% of subjects. One subject did not achieve normothermia and was later refractory to other TMDs. Median baseline temperature was 38.5 ± 0.1 C, with a reduction noted by 4 h (38.5 ± 0.1 vs 37.3 ± 0.8, P < 0.001) and sustained at 8 h (38.5 ± 0.1 vs 37.1 ± 0.7, P = 0.001). Time to normothermia was 2.6 ± 1.9 h. The median BSAS was 0 (range 0-1) with only 4 episodes necessitating meperidine across 76 h of study monitoring. No treatment was discontinued due to safety concerns. ENT evaluations noted no device-related adverse findings. CONCLUSIONS: Inducing normothermia with a novel transnasal TMD appears to be safe, feasible and not associated with significant shivering. A multicenter trial testing the ability of the CoolStat to maintain normothermia for 24 h is currently underway.

Esophageal injury associated with catheter ablation for atrial fibrillation: Determinants of risk and protective strategies.

Catheter ablation has become an important element in the management of atrial fibrillation. Several technical advances allowed for better safety profiles and lower recurrence rates, leading to an increasing number of ablations worldwide. Despite that, major complications are still reported, and esophageal thermal injury remains a significant concern as atrioesophageal fistula (AEF) is often fatal. Recognition of the mechanisms involved in the process of esophageal lesion formation and the identification of the main determinants of risk have set the grounds for the development and improvement of different esophageal protective strategies. More sensitive esophageal temperature monitoring, safer ablation parameters and catheters, and different energy sources appear to collectively reduce the risk of esophageal thermal injury. Adjunctive measures such as the prophylactic use of proton-pump inhibitors, as well as esophageal cooling or deviation devices, have emerged as complementary methods with variable but promising results. Nevertheless, as a multifactorial problem, no single esophageal protective measure has proven to be sufficiently effective to eliminate the risk, and further investigation is still warranted. Early screening in the patients at risk and prompt intervention in the cases of AEF are important risk modifiers and yield better outcomes.

Exponential Rise of Fungal Infection Reported in Rajkot Civil Hospital in Covid Pandemic Era: A Retrospective Study.

Mucormycosis is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes. Mucormycosis is an aggressive, life-threatening infection requiring prompt diagnosis and early treatment. Wide spread use of steroid and higher antibiotics may cause immune irregulation in post covid patients. A hallmark of mucormycosis infection is the presence of extensive angioinvasion with resultant vessel thrombosis and tissue necrosis. We reported exponential rising cases of fungal infection in covid pandemic era. Here we published epidemiological data of 773 fungal infected cases operated in ENT department of PDU Medical college, Rajkot in 2021. We have documented patients demographic data with comorbidity, paranasal sinuses with orbital, palatal and cerebral involvement, evaluation method, surgical and post surgical management protocol which we followed in our institute to treat all cases. We got promising result in terms of survival and less morbidity. Early presentation, less comorbidity, proper evaluation and immediate debridement with systemic antifungal coverage for adequate duration proved to be mainstay treatment of fungal infection in covid pandemic era.

Parapharyngeal Lipoma Extending to Skull Base: A Case Report with Surgical Approaches.

Parapharyngeal lipoma with skull base extension is rare tumor found in head and neck region. We report a case of 66 years old female patient with left side face swelling extending to neck. On clinical examination, it was found soft, non-tender, mobile swelling present over left side pre-auricular region. It was extending from pretragal area superiorly to left submandibular region inferiorly. CECT neck and fine needle aspiration cytology was done to know the benign nature of disease. It suggest tumor extending from skull base to C6 vertebral level in parapharyngeal space. Tumor was excised via Trans parotid-transcervical approach. Parapharyngeal lipomas are confined to either the prestyloid or post styloid compartments. We report an unusual parapharyngeal lipoma involving both the compartments of the parapharyngeal space.

The role of ROS in tumor infiltrating immune cells and cancer immunotherapy.

Reactive oxygen species (ROS) are a group of short-lived highly reactive molecules formed intracellularly from molecular oxygen. ROS can alter biochemical, transcriptional, and epigenetic programs and have an indispensable role in cellular function. In immune cells, ROS are mediators of specialized functions such as phagocytosis, antigen presentation, activation, cytolysis, and differentiation. ROS have a fundamental role in the tumor microenvironment (TME) where they are produced by immune cell-intrinsic and -extrinsic mechanisms. ROS can act as a double-edged sword with short exposures leading to activation in various innate and adaptative immune cells, and prolonged exposures, unopposed by redox balancing antioxidants leading to exhaustion, immunosuppression, and unresponsiveness to cancer immunotherapy. Due to its plasticity and impact on the anti-tumor function of immune cells, attempts are currently in process to harness ROS biology with the purpose to improve contemporary strategies of cancer immunotherapy. Here, we provide a short overview how ROS and various antioxidant systems impact on the function of innate and adaptive immune system cells with emphasis on the TME and immune-based therapies for cancer.

Ansel Mucormycosis Staging and Outcome Evaluation Score: Our Experience in Soaring Stage of Mucormycosis.

To propose Mucormycosis staging and Outcome evaluation score. (i) To provide method of conveying clinical experience to others without ambiguity. (ii) To facilitate an estimation of prognosis. (iii) To provide useful information for treatment decision. Retrospective observational study. Tertiary care center, Rajkot. 556 confirmed operated case of mucormycosis. It was a single center observational study of 556 confirmed cases of mucormycosis. In suspected cases of fungal infection, clinical symptoms were noted along with covid history and comorbid condition. Clinical findings were noted after nasal endoscopy. Rest neurological examination was done to rule out CNS involvement. Representative sample from nasal mucosa sent for microbiological examination. MRI PNS with Brain and Orbit was advised. After surgery, specimen was sent for histopathological confirmation. We reported most common age group was 51-60 years. 52% cases presented early with only nasal involvement and 1.8% cases with late cerebral involvement presentation. From recorded all above findings we have described this diseases progression in 4 components limited to nasal, orbital, palate and/or skull base, cerebral involvement. It is bases on anatomical progression on clinical and radiological findings. Considering all four components, staging system is designed that includes stage I to stage Vb. Outcome evaluation score designed to consider factors like patient's age, comorbidity, stage of disease while presentation, IV antifungal coverage and patient's psychological condition. Our clinical and radiological diagnostic staging and outcome evaluation score may helpful for others for early and better management of mucormycosis.

Quality assessment of cardiac magnetic resonance myocardial scar imaging prior to ventricular arrhythmia ablation.

High-resolution scar characterization using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) is useful for guiding ventricular arrhythmia (VA) treatment. However, imaging study quality may be degraded by breath-holding difficulties, arrhythmias, and implantable cardioverter-defibrillators (ICDs). We evaluated the effect of image quality on left ventricle (LV) base to apex scar interpretation in pre-VA ablation LGE-CMR. 43 consecutive patients referred for VA ablation underwent gradient-recalled-echo LGE-CMR. In ICD patients (n = 24), wide-bandwidth inversion-recovery suppressed ICD artifacts. In non-ICD patients, single-shot steady-state free-precession LGE-CMR could also be performed to reduce respiratory motion/arrhythmia artifacts. Study quality was assessed for adequate/limited scar interpretation due to cardiac/respiratory motion artifacts, ICD-related artifacts, and image contrast. 28% of non-ICD patients had studies where image quality limited scar interpretation in at least one image compared to 71% of ICD patient studies (p = 0.012). A median of five image slices had limited quality per ICD patient study, compared to 0 images per non-ICD patient study. Poorer quality in ICD patients was largely due to motion-related artifacts (54% ICD vs 6% non-ICD studies, p = 0.001) as well as ICD-related image artifacts (25% of studies). In VA ablation patients with ICDs, conventional CMR protocols frequently have image slices with limited scar interpretation, which can limit whole-heart scar assessment. Motion artifacts contribute to suboptimal image quality, particularly in ICD patients. Improved methods for motion and ICD artifact suppression may better delineate high-resolution LGE scar features of interest for guiding VA ablation.

Intersection of Race and Socioeconomic Status on Concussion Recovery among NCAA Student-Athletes: A CARE Consortium Study.

PURPOSE: The objectives of this study are to 1) describe collegiate student-athlete (SA) race and household income and 2) evaluate time to normal academic performance (i.e., return to learn (RTL)), initiation of the return to play (iRTP) protocol, RTP protocol duration, and time to unrestricted RTP (URTP) after sustaining sport-related concussion (SRC). METHODS: Data were collected between 2014 and 2020 by the Concussion Assessment, Research, and Education Consortium. Baseline data were used to characterize participant demographics ( N = 22,819) and post-SRC outcomes ( n = 5485 SRC) in time to RTL ( n = 1724) and RTP outcomes ( n = 2646) by race. Descriptive statistics and nonparametric tests examined differences across race by demographic and injury characteristics. Kaplan-Meier curves estimated median days to RTL, iRTP protocol, RTP protocol completion, and URTP by race and covariate measures. Multivariable Cox proportional hazards regression assessed the effect of race on risk of RTL and RTP recovery time points. RESULTS: SA largely identified as White (75%) followed by Black (14%), multiracial (7%), and Asian (3%). More than half (53%) of all SA reported a household income of >$120,000, whereas 41% of Black SA reported a household income <$60,000. Race was not associated with relative risk of RTL or iRTP but was associated with RTP protocol completion and URTP. Non-Black/non-White SA were 17% less likely (adjusted hazard ratio = 0.83; 95% confidence interval = 0.71, 0.97) to complete the RTP protocol, and Black SA were 17% more likely (adjusted hazard ratio = 1.17; 95% confidence interval = 1.05, 1.31) to reach the URTP time point compared with White SA. CONCLUSIONS: The present findings suggest collegiate SA enrolled in the Concussion Assessment, Research, and Education Consortium are primarily White and come from household incomes well above the US median. Race was not associated with RTL or iRTP but was associated with RTP protocol duration and total time to URTP. Clinicians should be conscientious of how their implicit or preconceived biases may influence SRC management among National Collegiate Athletic Association SA.

Driver Mutations Dictate the Immunologic Landscape and Response to Checkpoint Immunotherapy of Glioblastoma.

The composition of the tumor immune microenvironment (TIME) is considered a key determinant of patients' response to immunotherapy. The mechanisms underlying TIME formation and development over time are poorly understood. Glioblastoma (GBM) is a lethal primary brain cancer for which there are no curative treatments. GBMs are immunologically heterogeneous and impervious to checkpoint blockade immunotherapies. Utilizing clinically relevant genetic mouse models of GBM, we identified distinct immune landscapes associated with expression of EGFR wild-type and mutant EGFRvIII cancer driver mutations. Over time, accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) was more pronounced in EGFRvIII-driven GBMs and was correlated with resistance to PD-1 and CTLA-4 combination checkpoint blockade immunotherapy. We determined that GBM-secreted CXCL1/2/3 and PMN-MDSC-expressed CXCR2 formed an axis regulating output of PMN-MDSCs from the bone marrow leading to systemic increase in these cells in the spleen and GBM tumor-draining lymph nodes. Pharmacologic targeting of this axis induced a systemic decrease in the numbers of PMN-MDSC, facilitated responses to PD-1 and CTLA-4 combination checkpoint blocking immunotherapy, and prolonged survival in mice bearing EGFRvIII-driven GBM. Our results uncover a relationship between cancer driver mutations, TIME composition, and sensitivity to checkpoint blockade in GBM and support the stratification of patients with GBM for checkpoint blockade therapy based on integrated genotypic and immunologic profiles.

Randomized Clinical Trial to Evaluate an Atrial Fibrillation Stroke Prevention Shared Decision-Making Pathway.

Background Oral anticoagulation reduces stroke and disability in atrial fibrillation (AF) but is underused. We evaluated the effects of a novel patient-clinician shared decision-making (SDM) tool in reducing oral anticoagulation patient's decisional conflict as compared with usual care. Methods and Results We designed and evaluated a new digital decision aid in a multicenter, randomized, comparative effectiveness trial, ENHANCE-AF (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention). The digital AF shared decision-making toolkit was developed using patient-centered design with clear health communication principles (eg, meaningful images, limited text). Available in English and Spanish, the toolkit included the following: (1) a brief animated video; (2) interactive questions with answers; (3) a quiz to check on understanding; (4) a worksheet to be used by the patient during the encounter; and (5) an online guide for clinicians. The study population included English or Spanish speakers with nonvalvular AF and a CHA2DS2-VASc stroke score ≥1 for men or ≥2 for women. Participants were randomized in a 1:1 ratio to either usual care or the shared decision-making toolkit. The primary end point was the validated 16-item Decision Conflict Scale at 1 month. Secondary outcomes included Decision Conflict Scale at 6 months and the 10-item Decision Regret Scale at 1 and 6 months as well as a weighted average of Mann-Whitney U-statistics for both the Decision Conflict Scale and the Decision Regret Scale. A total of 1001 participants were enrolled and followed at 5 different sites in the United States between December 18, 2019, and August 17, 2022. The mean patient age was 69±10 years (40% women, 16.9% Black, 4.5% Hispanic, 3.6% Asian), and 50% of participants had CHA2DS2-VASc scores ≥3 (men) or ≥4 (women). The primary end point at 1 month showed a clinically meaningful reduction in decisional conflict: a 7-point difference in median scores between the 2 arms (16.4 versus 9.4; Mann-Whitney U-statistics=0.550; P=0.007). For the secondary end point of 1-month Decision Regret Scale, the difference in median scores between arms was 5 points in the direction of less decisional regret (P=0.078). The treatment effects lessened over time: at 6 months the difference in medians was 4.7 points for Decision Conflict Scale (P=0.060) and 0 points for Decision Regret Scale (P=0.35). Conclusions Implementation of a novel shared decision-making toolkit (afibguide.com; afibguide.com/clinician) achieved significantly lower decisional conflict compared with usual care in patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096781.

The evolving role of tissue-resident memory T cells in infections and cancer.

Resident memory T cells (TRM) form a distinct type of T memory cells that stably resides in tissues. TRM form an integral part of the immune sensing network and have the ability to control local immune homeostasis and participate in immune responses mediated by pathogens, cancer, and possibly autoantigens during autoimmunity. TRM express residence gene signatures, functional properties of both memory and effector cells, and remarkable plasticity. TRM have a well-established role in pathogen immunity, whereas their role in antitumor immune responses and immunotherapy is currently evolving. As TRM form the most abundant T memory cell population in nonlymphoid tissues, they are attractive targets for therapeutic exploitation. Here, we provide a concise review of the development and physiological role of CD8+ TRM, their involvement in diseases, and their potential therapeutic exploitation.

Exploring the Utility of Crutch Force Sensors to Predict User Intent in Assistive Lower Limb Exoskeletons.

The adoption of assistive lower limb exoskeletons in built environments is reliant on the further development of these devices to handle the varied conditions experienced in everyday life. The required development includes more varied and flexible gait patterns, but also appropriate user interfaces to enable fluid gait. This work explores the properties of an algorithm used to predict user intent based on sensors onboard a user-balanced robotic exoskeleton system. Specifically, classification algorithms built with different input data sets are compared - with varying detail of the interaction forces between the crutches and the ground, and the duration of the data sample used to make the prediction. Data were collected with one able-bodied participant using an exoskeleton, training three independent classifiers corresponding to different exoskeleton states. The results indicate the value of including information about the interaction forces between the crutches and the ground in improving prediction accuracy, with increasing prediction window also generally resulting in an increase in prediction accuracy. Whilst no categorical recommendation can be made with respect to either parameter, these results provide a baseline which can be used in conjunction deliberate consideration of the costs associated with implementation.

Effects of High-Flow Transesophageal Dry Air on Core Temperature: A Novel Method of Therapeutic Hypothermia.

Therapeutic hypothermia (TH) is one of the few proven neuroprotective modalities in clinical practice. However, current methods to achieve TH are suboptimal. We investigated a novel esophageal device that utilizes high-flow transesophageal dry air to achieve TH via evaporating cooling. Seven Yorkshire pigs (n = 7) underwent hypothermia therapy using a novel esophageal device that compartmentalizes a segment of esophagus through which high-flow dry air freely circulates in and out of the esophagus. Efficacy (primary objective) and safety (secondary objective) were evaluated in all animals. Safety assessment was divided into two sequential phases: (1) acute safety assessment (n = 5; terminal studies) to evaluate adverse events occurring during therapy, and (2) chronic safety assessment (n = 2; survival studies) to evaluate adverse events associated with therapy within 1 week of follow-up. After 1 hour of esophageal cooling (mean airflow rate = 64.2 ± 3.5 L/min), a significant reduction in rectal temperature was observed (37.3 ± 0.2°C → 36.3 ± 0.4°C, p = 0.002). The mean rectal temperature reduction was 1 ± 0.4°C. In none of the seven animals was oral or pharyngeal mucosa injury identified at postprocedural visual examination. In the two animals that survived, no reduction of food ingestion, signs of swallowing dysfunction or discomfort, or evidence of gastrointestinal bleeding was observed during the 1-week follow-up period. Open-chest visual inspection in those two animals did not show damage to the esophageal mucosa or surrounding structures. A novel esophageal device, utilizing high-flow transesophageal dry air, was able to efficiently induce hypothermia despite external heating. Therapy was well-tolerated, and no acute or chronic complications were found.

Long-Term Outcomes of Bilateral Cardiac Sympathetic Denervation for Refractory Ventricular Tachycardia.

OBJECTIVES: This study sought to explore the long-term arrhythmic outcomes of bilateral cardiac sympathetic denervation (BCSD). BACKGROUND: BCSD has been associated with improved arrhythmic outcomes in patients with refractory ventricular arrhythmias. However, whether BCSD antiarrhythmic effects are sustained long after the procedure is still uncertain. METHODS: We included consecutive patients who underwent BCSD because of refractory ventricular tachycardia (VT) and had at least 18 months of follow-up. VT recurrence after BCSD was evaluated to assess arrhythmic outcomes. The occurrence of VT episodes within the first 12 weeks after the procedure was assessed to explore the impact of early VT recurrence on late arrhythmia-free survival. RESULTS: Twenty patients (42 ± 16 years; 55% male) were included in the analysis. Nineteen (95%) patients had structural heart disease (left ventricular ejection fraction: 0.46 ± 0.14). Class I or class III drugs failed for all patients, and the mean number of VT ablation procedures was 2.5 ± 1.6. Over a mean follow-up of 1,300 ± 321 days (median: 1,276 days [Interquartile range (IQR): 1,181 to 1,480 days), 11 (55%) patients remained VT free after sympathectomy. Freedom from sustained VT or implantable cardioverter-defibrillator shock was 60% (95% confidence interval: 0.35 to 0.77) and 54.5% (95% confidence interval: 0.31 to 0.73) after BCSD at 1 and 4 years. Early VT recurrence was not associated with worse late arrhythmia-free survival rates. CONCLUSIONS: BCSD was associated with longstanding antiarrhythmic effects in patients with refractory ventricular arrhythmias. The occurrence of VT episodes early after the procedure was not associated with worse late arrhythmic outcomes.

Prospective Multicenter Assessment of a New Intraprocedural Automated System for Localizing Idiopathic Ventricular Arrhythmia Origins.

OBJECTIVES: The objective of this study was to present a new system, the Automatic Arrhythmia Origin Localization (AAOL) system, which used incomplete electroanatomic mapping (EAM) for localization of idiopathic ventricular arrhythmia (IVA) origin on the patient-specific geometry of left ventricular, right ventricular, and neighboring vessels. The study assessed the accuracy of the system in localizing IVA source sites on cardiac structures where pace mapping is challenging. BACKGROUND: An intraprocedural automated site of origin localization system was previously developed to identify the origin of early left ventricular activation by using 12-lead electrocardiograms (ECGs). However, it has limitations, as it could not identify the site of origin in the right ventricle and relied on acquiring a complete EAM. METHODS: Twenty patients undergoing IVA catheter ablation had a 12-lead ECG recorded during clinical arrhythmia and during pacing at various locations identified on EAM geometries. The new system combined 3-lead (III, V2, and V6) 120-ms QRS integrals and patient-specific EAM geometry with pace mapping to predict the site of earliest ventricular activation. The predicted site was projected onto EAM geometry. RESULTS: Twenty-three IVA origin sites were clinically identified by activation mapping and/or pace mapping (8, right ventricle; 15, left ventricle, including 8 from the posteromedial papillary muscle, 2 from the aortic root, and 1 from the distal coronary sinus). The new system achieved a mean localization accuracy of 3.6 mm for the 23 mapped IVAs. CONCLUSIONS: The new intraprocedural AAOL system achieved accurate localization of IVA origin in ventricles and neighboring vessels, which could facilitate ablation procedures for patients with IVAs.

Assessment of an ECG-Based System for Localizing Ventricular Arrhythmias in Patients With Structural Heart Disease.

Background We have previously developed an intraprocedural automatic arrhythmia-origin localization (AAOL) system to identify idiopathic ventricular arrhythmia origins in real time using a 3-lead ECG. The objective was to assess the localization accuracy of ventricular tachycardia (VT) exit and premature ventricular contraction (PVC) origin sites in patients with structural heart disease using the AAOL system. Methods and Results In retrospective and prospective case series studies, a total of 42 patients who underwent VT/PVC ablation in the setting of structural heart disease were recruited at 2 different centers. The AAOL system combines 120-ms QRS integrals of 3 leads (III, V2, V6) with pace mapping to predict VT exit/PVC origin site and projects that site onto the patient-specific electroanatomic mapping surface. VT exit/PVC origin sites were clinically identified by activation mapping and/or pace mapping. The localization error of the VT exit/PVC origin site was assessed by the distance between the clinically identified site and the estimated site. In the retrospective study of 19 patients with structural heart disease, the AAOL system achieved a mean localization accuracy of 6.5±2.6 mm for 25 induced VTs. In the prospective study with 23 patients, mean localization accuracy was 5.9±2.6 mm for 26 VT exit and PVC origin sites. There was no difference in mean localization error in epicardial sites compared with endocardial sites using the AAOL system (6.0 versus 5.8 mm, P=0.895). Conclusions The AAOL system achieved accurate localization of VT exit/PVC origin sites in patients with structural heart disease; its performance is superior to current systems, and thus, it promises to have potential clinical utility.