Sympathetic toggled paroxysmal atrial fibrillation and recurrent premature atrial contractions in ambulatory patients.

BACKGROUND: Autonomic nerve activity is important in the mechanisms of paroxysmal atrial fibrillation (PAF). OBJECTIVE: The purpose of this study was to test the hypothesis that a single burst of skin sympathetic nerve activity (SKNA) can toggle on and off PAF or premature atrial contraction (PAC) clusters. METHODS: Simultaneous recording of SKNA and electrocardiogram (neuECG) recording was performed over 7 days in patients with PAF. RESULTS: In study 1, 8 patients (7 men and 1 woman; age 62 ± 8 years) had 124 episodes of PAF. An SKNA burst toggled both on and off PAF in 8 episodes (6.5%) (type 1), toggled on but not off in 12 episodes (9.7%) (type 2), and toggled on a PAC cluster followed by PAF in 4 episodes (3.2%) (type 3). The duration of these PAF episodes was <10 minutes. The remaining 100 episodes (80.6%) were associated with active SKNA bursts throughout PAF (type 4) and lasted longer than type 1 (P = .0185) and type 2 (P = .0027) PAF. There were 47 PAC clusters. Among them, 24 (51.1%) were toggled on and off, and 23 (48.9%) were toggled on but not off by an SKNA burst. In study 2, 17 patients (9 men and 8 women; age 58 ± 12 years) had <10 minutes of PAF (4, 8, 0, and 31 of types 1, 2, 3, and 4, respectively). There were significant circadian variations of all types of PAF. CONCLUSION: A single SKNA burst can toggle short-duration PAF and PAC cluster episodes on and off. The absence of continued SKNA after the onset might have affected the maintenance of these arrhythmias.

Sarcoma in patients with Lynch syndrome and response to immunotherapy.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant genetic predisposition to multiple malignancies and is characterized by deficient DNA mismatch repair. Increased incidence of sarcomas is not formally ascribed to LS; however, increasing evidence suggests a preponderance of these malignancies in affected families. Sarcomas typically possess a low tumor mutational burden and incite a poor immune infiltrate, thereby rendering them poorly responsive to immunotherapy. METHODS: We searched the University of California, Los Angeles (UCLA) sarcoma program database for patients with a diagnosis of sarcoma and LS from 2016 to 2023. Three such patients were identified and all three were treated with PD1 blockade. RESULTS: We present three cases of LS-associated sarcomas (two soft tissue sarcoma and one osteosarcoma) with increased tumor mutational burdens. These patients were each treated with an anti-PD1 antibody and experienced a response far superior to that reported for non-LS-associated sarcomas. CONCLUSIONS: Increased mutational burden and immune infiltrate are observed for sarcomas associated with LS. Although unselected patients with sarcoma have demonstrated poor response rates to immunotherapy, our findings suggest that patients with Lynch-associated sarcomas are more likely to respond to treatment with anti-PD1. These patients should be given consideration for immunotherapy.

False Tendons in the Left Ventricle: Implications for Successful Ablation of Left Posterior Fascicular Tachycardias.

BACKGROUND: The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear. OBJECTIVES: The purpose of this study is to describe the endocavitary substrate of the re-entrant loop of LPF-VT. METHODS: A total of 26 consecutive patients with LPF-VT underwent an electrophysiology study and radiofrequency ablation. RESULTS: Intracardiac echocardiography imaging observed a 100% prevalence of false tendons (FTs) at the left posterior septal region in all patients, and 3 different types of FTs could be classified according to their location. In 22 patients, a P1 potential could be recorded via the multielectrode catheter from a FT. In 4 patients without a recorded P1 during LPF-VT, the earliest P2 potentials were recorded from a FT in 3 patients, and from a muscular connection between 2 posteromedial papillary muscles in 1 patient. Catheter ablation focused on the FTs with P1 or earliest P2 (in patients without P1) was successful in all 26 patients. After 19 ± 8.5 months of follow-up, no patients had recurrence of LPF-VT. CONCLUSIONS: FTs provide an electroanatomical substrate for LPF-VT and a "culprit FT" may be identified as the critical structure bridging the macro-re-entrant loop. Targeting the "culprit FT" is a novel anatomical ablation strategy that results in long-term arrhythmia-free survival.

Novel algorithms improve arrhythmia detection accuracy in insertable cardiac monitors.

INTRODUCTION: Insertable cardiac monitors (ICMs) are commonly used to diagnose cardiac arrhythmias. False detections in the latest ICM systems remain an issue, primarily due to inaccurate R-wave sensing. New discrimination algorithms were developed and tested to reduce false detections of atrial fibrillation (AF), pause, and tachycardia episodes in ICMs. METHODS: Stored electrograms (EGMs) of AF, pause, and tachycardia episodes detected by Abbott Confirm Rx™ ICMs were extracted from the Merlin.net™ Patient Care Network, and manually adjudicated to establish independent training and testing datasets. New discrimination algorithms were developed to reject false episodes due to inaccurate R-wave sensing, P-wave identification, and R-R interval patterns. The performance of these new algorithms was quantified by false positive reduction (FPR) and true positive maintenance (TPM), relative to the existing algorithms. RESULTS: The new AF detection algorithm was trained on 5911 EGMs from 744 devices, resulting in 66.9% FPR and 97.8% TPM. In the testing data set of 1354 EGMs from 119 devices, this algorithm achieved 45.8% FPR and 97.0% TPM. The new pause algorithm was trained on 7178 EGMs from 1490 devices, resulting in 70.9% FPR and 98.7% TPM. In the testing data set of 1442 EGMs from 340 devices, this algorithm achieved 74.4% FPR and 99.3% TPM. The new tachycardia algorithm was trained on 520 EGMs from 204 devices, resulting in 57.0% FPR and 96.6% TPM. In the testing data set of 459 EGMs from 237 devices, this algorithm achieved 57.9% FPR and 96.5% TPM. CONCLUSION: The new algorithms substantially reduced false AF, pause, and tachycardia episodes while maintaining the majority of true arrhythmia episodes detected by the Abbott ICM algorithms that exist today. Implementing these algorithms in the next-generation ICM systems may lead to improved detection accuracy, in-clinic efficiency, and device battery longevity.

Cancer-Associated B Cells in Sarcoma.

Despite being one of the first types of cancers studied that hinted at a major role of the immune system in pro- and anti-tumor biology, little is known about the immune microenvironment in sarcoma. Few types of sarcoma have shown major responses to immunotherapy, and its rarity and heterogeneity makes it challenging to study. With limited systemic treatment options, further understanding of the underlying mechanisms in sarcoma immunity may prove crucial in advancing sarcoma care. While great strides have been made in the field of immunotherapy over the last few decades, most of these efforts have focused on harnessing the T cell response, with little attention on the role B cells may play in the tumor microenvironment. A growing body of evidence suggests that B cells have both pro- and anti-tumoral effects in a large variety of cancers, and in the age of bioinformatics and multi-omic analysis, the complexity of the humoral response is just being appreciated. This review explores what is currently known about the role of B cells in sarcoma, including understanding the various B cell populations associated with sarcoma, the organization of intra-tumoral B cells in tertiary lymphoid structures, recent trials in immunotherapy in sarcoma, intra-tumoral immunoglobulin, the pro-tumor effects of B cells, and exciting future areas for research.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Reduction of opioid use after orthopedic surgery: a scoping review.

BACKGROUND: The opioid epidemic is one of the biggest public health crises of our time, and overprescribing of opioids after surgery has the potential to lead to long-term use. The purpose of this review was to identify and summarize the available evidence on interventions aimed at reducing opioid use after orthopedic surgery. METHODS: We searched CENTRAL, Embase and Medline from inception until August 2019 for studies comparing interventions aimed at reducing opioid use after orthopedic surgery to a control group. We recorded demographic data and data on intervention success, and recorded or calculated percent opioid reduction compared to control. RESULTS: We included 141 studies (20 963 patients) in the review, of which 113 (80.1%) were randomized controlled trials (RCTs), 6 (4.3%) were prospective cohort studies, 16 (11.4%) were retrospective cohort studies, 5 (3.6%) were case reports, and 1 (0.7%) was a case series. The majority of studies (95 [67.4%]) had a follow-up duration of 2 days or less. Interventions included the use of local anesthetics and/or nerve blocks (42 studies [29.8%]), nonsteroidal anti-inflammatory drugs (31 [22.0%]), neuropathic pain medications (9 [6.4%]) and multimodal analgesic combinations (25 [17.7%]. In 127 studies (90.1%), a significant decrease in postoperative opioid consumption compared to the control intervention was reported; the median opioid reduction in these studies was 39.7% (range 5%-100%). Despite these reductions in opioid use, the effect on pain scores and on incidence of adverse effects was inconsistent. CONCLUSION: There is a large body of evidence from randomized trials showing the promise of a variety of interventions for reducing opioid use after orthopedic surgery. Rigorously designed RCTs are needed to determine the ideal interventions or combination of interventions for reducing opioid use, for the good of patients, medicine and society.

A Systematic Review of Outcome Measures in Orthopaedic Trauma Trials: What Are We Measuring?

Purpose: The objectives of this study are to describe the outcome measures used in orthopaedic fracture care trials, with a particular focus on patient-reported outcome measures (PROMs), and to determine which study characteristics are associated with number of citations. Methods: We retrieved randomized clinical trials on fracture care between 2012 and 2017 from Embase, Medline and CENTRAL databases. Data collected included study characteristics (e.g., region, design, setting, sample size) and outcome measures (e.g., primary variable, measurement perspective, use of PROMs, study results and number of citations). Results: We identified a total of 8,580 articles in the initial search. After title screening, abstract screening and full-text review, we included 416 articles for analysis. 58.4% (243) of the studies clearly defined a primary outcome measure and 56.3% (234) reported sample size justifications for outcome selection. The most common primary outcome reported was a visual analogue scale for pain; used in 21 of the 243 (8.6%) studies that defined a primary outcome. At least one PROM was used in 68.5% (285) of the papers included. Conclusions: A large proportion of studies reporting on PROMs for orthopaedic trauma patients do not provide key information on the outcome selection process; a step of utmost importance in and the designing and reporting of RCTs. There is substantial heterogeneity in the selection of PROMs for fracture care trials, which limits the ability to compare and summarize across studies. Future research in fracture care should strive towards improving the reporting of informative PROMs, with rationale that demonstrates understating of the injury, intervention and patient values. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00667-8.

The Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Knee Arthroplasty.

BACKGROUND: The prevalence and outcomes of unexpected positive intraoperative cultures (UPC) in presumed aseptic revision total knee arthroplasty (TKA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondly, we aimed to compare the infection-free implant survival between cohorts based on number of UPCs and antibiotic treatment. METHODS: We reviewed our institutional database from 2006 to 2019 for all TKA revisions (n = 1795) to identify all presumed aseptic TKA revisions with intraoperative culture(s). After exclusions, 775 revisions were eligible and those with UPC were included in the Kaplan-Meier analysis to determine infection-free implant survival for the cohorts. RESULTS: The prevalence of UPC was 9.8%. The 2- and 5-year infection-free survival was 97.4% and 95.3%, respectively. The 5-year infection-free survival from the same microorganism as the UPC was 98.7%. Infection-free survival was similar for the 1 versus ≥2 UPC cohorts (P = .416), however was poorer for the cohort treated with antibiotics (P = .021). Only one of 3 subsequent PJI-related implant failures was caused by the same microorganism (polymicrobial) as the UPC. There were no subsequent infections in patients with a single UPC not treated with antibiotics. CONCLUSIONS: The prevalence of UPC was 9.8% and the infection-free implant survival is excellent. Infection-free survivorship from PJI caused by the same UPC microorganism is outstanding. Comparisons between cohorts must be interpreted with caution due to study limitations. A single UPC in patents without other signs of infection does not require antibiotic treatment. LEVEL OF EVIDENCE: IV.

Atrial fibrillation mechanisms before and after pulmonary vein isolation characterized by noncontact charge density mapping.

BACKGROUND: The interaction of the pulmonary vein (PV) and putative nonpulmonary triggers of atrial fibrillation (AF) remains unclear and has yet to translate into patient-tailored ablation strategies. OBJECTIVE: The purpose of this study was to use noncontact mapping to detail the global conduction patterns in paroxysmal and persistent AF and how they are modified during PV ablation. METHODS: Forty patients during AF ablation underwent mapping using a noncontact catheter (AcQMap, Acutus Medical, Inc., Carlsbad, CA) before and after PV isolation (PVI). Propagation history maps were analyzed postprocedure for each patient to categorize conduction patterns into focal, organized reentrant, and disorganized patterns (F-Patterns, O-Patterns, and D-Patterns, respectively). RESULTS: Activation patterns identified by using a noncontact mapping system can be subclassified from 3 main patterns into subtypes (macroreentrant and localized reentrant [MR and LR] subtypes and disorganized 1 and disorganized 2 [D1 and D2] subtypes). Persistent AF demonstrated more D-Patterns and less O-Patterns and F-Patterns than did paroxysmal AF. In addition, patients with PAF inducible after PVI demonstrated a higher region number and higher prevalence of MR subtypes than did those noninducible. PVs remained the critical region and included almost one-third of all patterns across any AF types. PVI was effective to eliminate PV-related functional phenotypes and affected recurrence with other patterns. CONCLUSION: Activation patterns identified using AcQMap can be classified into 3 main patterns (F-Patterns, O-Patterns, and D-Patterns) as well as subtypes (MR and LR subtypes and D1 and D2 subtypes). PerAF was different from PAF in demonstrating a higher region number and higher prevalence of D-Patterns but a lower region number and lower prevalence of O-Patterns and F-Patterns.

Biological substrate modification suppresses ventricular arrhythmias in a porcine model of chronic ischaemic cardiomyopathy.

AIMS: Cardiomyopathy patients are prone to ventricular arrhythmias (VA) and sudden cardiac death. Current therapies to prevent VA include radiofrequency ablation to destroy slowly conducting pathways of viable myocardium which support re-entry. Here, we tested the reverse concept, namely that boosting local tissue viability in zones of slow conduction might eliminate slow conduction and suppress VA in ischaemic cardiomyopathy. METHODS AND RESULTS: Exosomes are extracellular vesicles laden with bioactive cargo. Exosomes secreted by cardiosphere-derived cells (CDCEXO) reduce scar and improve heart function after intramyocardial delivery. In a VA-prone porcine model of ischaemic cardiomyopathy, we injected CDCEXO or vehicle into zones of delayed conduction defined by electroanatomic mapping. Up to 1-month post-injection, CDCEXO, but not the vehicle, decreased myocardial scar, suppressed slowly conducting electrical pathways, and inhibited VA induction by programmed electrical stimulation. In silico reconstruction of electrical activity based on magnetic resonance images accurately reproduced the suppression of VA inducibility by CDCEXO. Strong anti-fibrotic effects of CDCEXO, evident histologically and by proteomic analysis from pig hearts, were confirmed in a co-culture assay of cardiomyocytes and fibroblasts. CONCLUSION: Biological substrate modification by exosome injection may be worth developing as a non-destructive alternative to conventional ablation for the prevention of recurrent ventricular tachyarrhythmias.

Administration of Adenosine Triphosphate Provides Additional Value Over Programmed Electrophysiologic Study in Confirmation of Successful Ablation of Atrioventricular Accessory Pathways.

Objectives: To study the benefit of adenosine triphosphate (ATP) in evaluating ablation endpoints of accessory pathways (AP) and subsequent long-term prognosis. Methods: We reviewed consecutive patients with supraventricular tachycardias due to APs that underwent radiofrequency catheter ablation (RFCA) from January 2016 to September 2018 in our center. The patients were divided into two groups: the ATP group (who had passed both the ATP test and PES after ablation as the endpoint) and the non-ATP group (who had passed PES only after ablation as the endpoint). We reviewed the patients' intra-cardiac electrograms and analyzed their long-term outcomes. Results: In total, 1,343 patients underwent successful RFCA. There were 215 patients in the ATP group with one lost to follow-up. There were 1,128 patients in the non-ATP group with 39 lost to follow-up. Twenty-three patients in the ATP group demonstrated additional electrophysiological entities due to ATP administration, including reappearance of the ablated APs in 16 patients, discovery of PES-undetected APs in 5, induction of atrial fibrillation in 5, premature atrial contractions in 1, and premature ventricular contractions in another. During the 7 to 39 months (average 24.4 ± 9.5 months) follow-up, the recurrence rate was 8.41% (18/214) in the ATP group and 6.80% (74/1,084) in the non-ATP group. In subjects with recurrence, 14 patients (14/18 = 77.8%) in the ATP group and 50 patients (50/74 = 67.6%) in the non-ATP group accepted redo ablations. Among the ATP-group, all the 14 redo APs were the old ones as before. Among the non-ATP-group, redo ablations confirmed that 39 APs were the old ones, while 20 APs were newly detected ones which had been missed previously. The difference in recurrent AP locations confirmed by redo procedures between the two groups was significant (p = 0.008). In the non-ATP group, 20 (40%) of redo cases were proven to have multiple APs, while 33 (3.3%) cases who did not suffer from recurrence had multiple APs. Existences of multiple APs in recurred cases were significantly higher than that in non-recurred ones in the non-ATP group (p < 0.001), while there was no such difference in the ATP group (p = 0.114). Conclusions: The existence of multiple APs was more common in recurrent cases if ATP was not used for confirmation of ablation endpoints. ATP probably has additional value over PES alone by detecting weak AP conductions. ATP can evoke atrial and ventricular arrhythmias.

Delayed repolarization and ventricular tachycardia in patients with heart failure and preserved ejection fraction.

Sudden death is the most common mode of mortality in patients with heart failure and preserved ejection fraction (HFpEF). Ventricular arrhythmias (VA) have been suspected as the etiology but the supporting evidence in patients with HFpEF is scarce. We sought to investigate VA prevalence, and to determine if VA are associated with prolonged repolarization, in patients with HFpEF. In a retrospective case-control study design, Cedars-Sinai patients who underwent prolonged ambulatory electrocardiographic monitoring (Zio Patch) between 2016 and 2018 were screened for a clinical diagnosis of HFpEF. Patients with normal diastolic and systolic function who underwent Zio Patch monitoring were also reviewed as controls. Multivariable logistic regression was used to compare the prevalence of rhythm disturbances in patients with and without HFpEF. Ventricular tachycardia (VT) was more prevalent in patients with HFpEF (37% vs. 16% in controls, p = 0.001). Most episodes were non-sustained except for one case of sustained VT in a patient with HFpEF. Covariate-adjusted logistic regression including HFpEF diagnosis, age, sex, body mass index, and the presence of comorbidities revealed that only HFpEF was associated with increased risk of VT (relative risk 2.86, p = 0.023). Subgroup-analyses revealed an association between increased QTc interval and risk of VT (460 ± 38 ms in HFpEF patients with VT vs. 445 ± 28 ms in HFpEF patients without VT, p = 0.03). Non-sustained VT was more prevalent in patients with HFpEF compared to patients without HFpEF, and QTc interval prolongation was associated with VT in HFpEF.

Prevalence and Outcomes of Unexpected Positive Intraoperative Cultures in Presumed Aseptic Revision Hip Arthroplasty.

BACKGROUND: The prevalence and outcomes of unexpected positive cultures (UPCs) of specimens taken during presumed aseptic revision total hip arthroplasty (THA) are unclear. The purpose of this study was to determine the prevalence of UPC and infection-free implant survival in this patient population. Secondary aims included identifying factors associated with subsequent infection-related failure in patients with UPC. METHODS: We reviewed all THA revisions (n = 2,288) performed at our institution from 2006 to 2019. Presumed aseptic revision THAs with intraoperative culture(s) were eligible (n = 1,196), and those with UPC were included in a Kaplan-Meier analysis to determine the infection-free implant survival and in Cox regression analysis to identify factors associated with infection-related failure. RESULTS: UPC(s) were documented for 9.2% (110) of 1,196 aseptic THA revisions. The 2- and 5-year infection-free implant survival in the entire UPC cohort was 93.1% (95% confidence interval [CI] = 90.5% to 95.7%) and 86.8% (95% CI = 82.9% to 90.7%), respectively. The 2- and 5-year infection-free survival with failure due to infection with the same microorganism as identified in the UPC as the end point was 95.8% (95% CI = 93.7% to 97.9%) and 94.3% (95% CI = 91.7% to 96.9%), respectively. Subsequent infection-related failures caused by the same microorganism as identified in the UPC were more likely to occur after revisions with ≥2 UPCs than after those with 1 UPC (p = 0.024). Revision due to adverse metal reaction was a risk factor for subsequent infection-related failure (hazard ratio [HR] = 14.49, 95% CI = 2.69 to 78.04). Patients with a single UPC who were not treated with antibiotics had no subsequent periprosthetic joint infections (PJIs) caused by the same microorganism as identified in the UPC. CONCLUSIONS: The prevalence of UPC was 9.2%, and the infection-free implant survival in patients with UPC is encouraging. Implant survival free of PJI caused by the same microorganism as identified in the UPC was excellent. Aseptic revision for adverse metal reaction was a risk factor for subsequent PJI in patients with UPC. No patient with a single UPC who was not treated with antibiotics developed PJI caused by the UPC-identified microorganism, suggesting that in the absence of other signs of infection a single UPC does not warrant antibiotic treatment. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Catheter ablation for atrial tachycardias: How to interpret the unclear activation map?

BACKGROUND: Post-ablation atrial tachycardias (ATs) are characterized by low-voltage signals that challenge current mapping methods. In this study, we analyzed common mistakes during activation mapping and delineated a mapping strategy for correct interpretation of tachycardia mechanisms in patients with challenging underlying substrate. METHODS AND RESULTS: Thirty-one patients referred for AT ablation were selected for the study. Three types of incorrect activation patterns were identified, which were referred to as unrecognized block line (pseudo-macroreentry and pseudo-fig-8 reentry), incorrect activation timing window of interest (WOI) (chaotic activation), and mis-annotation of complex signals (multiple sites of "early meets late"). Pseudo-macroreentry and chaotic activation occur in focal or localized reentry AT with the error related to the WOI selection (four cases), incorrect annotation of local activation time (six cases), or a previous line of atrial block in (seven cases). Pseudo-fig-8 reentry (five cases) and multiple sites of "early meets late" (nine cases) occur in macroreentrant AT with blocked areas and low-voltage atrial substrate. All ATs were successfully eliminated at the origin site. CONCLUSIONS: We delineated a series of ATs in the setting of a disordered pattern of activation mapping encountered in patients after previous extensive ablation or atriotomy. The algorithm proposed rapidly corrects the activation map and identifies the mechanism of the AT.