Citations

Abstract Introduction High-power short-duration (HPSD) ablation has emerged as a promising alternative to conventional power delivery (CPD) for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF). However, its efficacy, procedural efficiency, and safety profile remain uncertain. Methods PubMed, Embase, Cochrane Library and ClinicalTrials.Gov databases were systematically searched for randomized controlled trials (RCTs) comparing HPSD with CPD ablation for PVI in patients with AF. Random-effects models were used to pool hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI). Results Seven RCTs with 1,006 patients (514 HPSD, 489 CPD) were included. No significant differences were found in freedom from arrhythmia during the follow-up period (HR 0.77; 95% CI 0.41–1.45; p=0.424). AF recurrence did not differ (RR 0.94; 95% CI 0.65–1.36; p=0.733) between groups. HPSD had a significantly shorter procedural (MD -22.61 min; 95% CI -33.18, -12.04; p<0.001) and RF ablation (MD -15.70 min; 95% CI -20.86, -10.55; p<0.001) times, with comparable fluoroscopy time (MD 0 min; 95% CI -0.44, 0.45; p=0.99) between groups. Conclusion In patients with AF undergoing PVI, HPSD did not increase freedom from arrhythmia as compared with CPD ablation, however it was associated with shorter procedure and RF ablation times. These findings suggest that HPSD may be a more efficient approach without compromising clinical outcomes.

ABSTRACT Background High‐power short‐duration (HPSD) ablation has emerged as a promising alternative to conventional power delivery (CPD) for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF), though its efficacy, procedural efficiency, and safety profile remain uncertain. Aims To evaluate and compare the efficacy, procedural efficiency, and safety of HPSD versus CPD ablation strategies for PVI in patients with AF through a systematic review and meta‐analysis of randomized controlled trials (RCTs). Materials and Methods PubMed, Embase, Cochrane Library, and ClinicalTrials.Gov databases were systematically searched for RCTs comparing HPSD with CPD ablation for PVI in patients with AF. Random‐effects models were used to pool hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI). R version 4.4.2 was used for statistical analysis. Results Eight RCTs with 1094 patients (558 undergoing HPSD and 536 undergoing CPD ablation) were included. No significant differences were found in freedom from arrhythmia during the follow‐up period (HR: 0.77; 95% CI: 0.41–1.45; p = 0.424). AF recurrence did not differ (RR: 0.83; 95% CI: 0.59–1.16; p = 0.268) between groups. HPSD had a significantly shorter procedural (mean difference [MD]: −21.93 min; 95% CI: −31.34, −12.53; p < 0.001) and RF ablation times (MD: −13.87 min; 95% CI: −19.46, −8.27; p < 0.001). No differences were observed in fluoroscopy time and first‐pass isolation for right and left pulmonary veins. There was no difference in esophageal lesion rates, pericardial, or neurological complications, but there was a higher incidence of steam pops in HPSD (RR: 3.42; 95% CI: 1.45–8.09; p = 0.005). Discussion Although HPSD ablation did not significantly improve freedom from arrhythmia or reduce AF recurrence compared to CPD, it demonstrated enhanced procedural efficiency, with shorter procedure and RF ablation times. Despite the higher rate of steam pops, the overall safety profile was similar between both groups. Conclusion High‐power short‐duration ablation for pulmonary vein isolation in atrial fibrillation demonstrated comparable efficacy and safety to conventional power delivery, with the added benefit of shorter procedure and RF ablation times. However, HPSD ablation was associated with increased occurrence of steam pops.

Introduction: High-power short-duration (HPSD) ablation has emerged as a promising alternative to conventional power delivery (CPD) for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF). However, its efficacy, procedural efficiency, and safety profile remain uncertain. Methods: PubMed, Embase, Cochrane Library and ClinicalTrials.Gov databases were systematically searched for randomized controlled trials (RCTs) comparing HPSD with CPD ablation for PVI in patients with AF. Random-effects models were used to pool hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI). R version 4.4.2 was used for statistical analysis. Results: Seven RCTs with 1,006 patients (514 HPSD, 489 CPD) were included. No significant differences were found in freedom from arrhythmia during the follow-up period (HR 0.77; 95% CI 0.41–1.45; p=0.424). AF recurrence did not differ (RR 0.94; 95% CI 0.65–1.36; p=0.733) between groups. HPSD had a significantly shorter procedural (MD -22.61 min; 95% CI -33.18, -12.04; p<0.001) and RF ablation times (MD -15.70 min; 95% CI -20.86, -10.55; p<0.001). No differences were observed in fluoroscopy time and first-pass isolation for right and left pulmonary veins. There was no difference in esophageal lesion rates, pericardial, or neurological complications, but there was a higher incidence of steam pops in HPSD (RR 3.42; 95% CI 1.45–8.09; p=0.005). Conclusion: In patients with AF undergoing PVI, HPSD did not increase freedom from arrhythmia as compared with CPD ablation, however it was associated with shorter procedure and RF ablation times with a similar safety profile.

ABSTRACTBackgroundAnemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.MethodsWe comprehensively searched PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through March 2024 and conducted a prognostic systematic review and meta‐analysis. All analyses were performed using R V. 4.3.1. This meta‐analysis was registered at PROSPERO (CRD42024556023).ResultsWe included 23 studies comprising 286,781 patients for analysis. Anemia had a significant association with an 84% increase in risk of major bleeding (HR: 1.84 with 95% CI [1.59, 2.13], p < 0.01), a 32% increase in the risk of intracranial hemorrhage (HR: 1.32 with 95% CI [1.10, 1.58], p < 0.01), a 98% increase in the risk of gastrointestinal bleeding (HR: 1.98 with 95% CI [1.67, 2.35], p < 0.01), and a 91% increase in the risk of all‐cause mortality (HR: 1.91 with 95% CI [1.46, 2.51], p < 0.01). However, the impact of anemia did not significantly affect the risk of stroke, transient ischemic stroke (TIA), or systemic embolism (HR: 1.07 with 95% CI [0.93, 1.22], p = 0.36).ConclusionAnemia was significantly associated with an increased risk of major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all‐cause mortality. However, anemia did not significantly impact stroke, TIA, or systemic embolism.

Significance Statement There is no standardized desensitization regimen for kidney transplant candidates. CD38, expressed by plasma cells, could be targeted for desensitization to deplete plasma cells producing alloantibodies and donor-specific antibodies. Few studies and case reports are available regarding the use of CD38 antibodies for desensitization in patients awaiting kidney transplant. This study shows that isatuximab, a CD38-targeting therapy, was well tolerated in kidney transplant candidates, with a durable decrease in anti-HLA antibodies and partial desensitization activity. The short treatment period and long follow-up of this study allowed for the understanding of the mechanism and timing for any antibody rebound. Isatuximab could be further investigated as an option for adjunct therapy to existing desensitization for patients on the kidney transplant waitlist. Background Patients with calculated panel reactive antibody (cPRA) ≥80.00%, particularly those with cPRA ≥99.90%, are considered highly sensitized and underserved by the Kidney Allocation System. Desensitization removes circulating reactive antibodies and/or suppresses antibody production to increase the chances of a negative crossmatch. CD38 is expressed highly on plasma cells, thus is a potential target for desensitization. Methods This was an open-label single-arm phase 1/2 study investigating the safety, pharmacokinetics, and preliminary efficacy of isatuximab in patients awaiting kidney transplantation. There were two cohorts, cohorts A and B, which enrolled cPRA ≥99.90% and 80.00% to <99.90%, respectively. Results Twenty-three patients (12 cohort A, 11 cohort B) received isatuximab 10 mg/kg weekly for 4 weeks then every 2 weeks for 8 weeks. Isatuximab was well tolerated with pharmacokinetic and pharmacodynamic profiles that indicated similar exposure to multiple myeloma trials. It resulted in decreases in CD38 + plasmablasts, plasma cells, and NK cells and significant reductions in HLA-specific IgG-producing memory B cells. Overall response rate, on the basis of a predefined composite desensitization end point, was 83.3% and 81.8% in cohorts A and B. Most responders had decreases in anti-HLA antibodies that were maintained for 26 weeks after the last dose. Overall, cPRA values were minimally affected, however, with only 9/23 patients (39%) having cPRA decreases to target levels. By study cutoff (median follow-up of 68 weeks), six patients received transplant offers, of which four were accepted. Conclusions In this open-label trial, isatuximab was well tolerated and resulted in a durable decrease in anti-HLA antibodies with partial desensitization activity. Clinical Trial registration number NCT04294459.

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.