Citations

ABSTRACT Introduction Lead‐related venous obstruction is a significant complication of chronic indwelling transvenous leads, which poses unique challenges during cardiac device upgrades. Background The anatomical sequelae of venous occlusion are variable and carry important procedural implications. Occlusions can develop in any part of the venous system, but they most often occur in the subclavian and innominate veins, while the superior vena cava is less frequently affected. Methods In this review, we describe approaches to lead‐related venous occlusion providing step‐by‐step procedural guidance. Results Venoplasty, neovascular channel creation are two main techniques for addressing lead‐related venous obstruction. Conclusion Venoplasty in the setting of an indwelling pacemaker or defibrillator leads can be performed safely and effectively. The difficulty of the procedure lies in crossing the obstruction. Familiarity with various tools is needed for a successful outcome.

ABSTRACT Background Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression‐free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints. Methods Two‐arm, superiority‐design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.gov with no date limitation. Trials were required to have a PFS primary endpoint. The study outcomes were the presence of double‐blind designs and blinded independent central review (BICR) for the primary endpoint. Ninety‐five percent credible intervals for binary outcomes were estimated from beta distributions, and multivariable logistic regressions explored associations with trial‐level features. Results After screening, 237 trials were included, enrolling 127,518 patients. A double‐blind design was used in 105 trials (44%, 95% CrI 38%–51%). BICR was used in 111 trials (47%, 95% CrI 41%–53%), including 39 double‐blind trials (16%, 95% CrI 12%–22%). Trials with BICR had higher odds of meeting the primary endpoint (OR 1.84; 95% CI 1.06–3.18; p = 0.03). The PFS assessor identity (central vs. local) or blinding status was not reported in 50 trials (26%, 95% CrI 16%–27%). Trials that met prespecified significance criteria for PFS were more likely to report whether PFS assessors were blinded/unblinded and central/local (OR, 3.05; 95% Cl: 1.60–5.81; p = 0.0007). Conclusions Despite the importance of double blinding in combination with BICR for reducing bias, only a few trials blinded physicians, patients, and primary endpoint assessors. This meta‐epidemiological study illuminates the prevalence of potential assessment biases affecting PFS in Phase III oncology and secondarily emphasizes the need for improved methodology reporting.

Abstract Introduction Alice in Wonderland Syndrome (AIWS) is an uncommon condition manifesting visual and somatosensory disturbances in which patients may perceive objects, including their own bodies, as larger or smaller than they are. In adults, AIWS typically is associated with migraine and epilepsy but has been reported as an adverse effect of topiramate, which is used to treat both illnesses, making it difficult to ascertain whether illness or medication causes altered perceptions. Reported is a case of topiramate-associated AIWS, which adds to the limited reports published on this unique phenomenon. Case Report A 40-year-old woman admitted to a 3-week pain rehabilitation program to treat chronic migraine reported macrosomatognosia that she retrospectively recalled beginning during titration of topiramate. The symptoms of AIWS resolved after the topiramate was discontinued. An assessment with the Naranjo ADR Probability Scale indicated a possible association between topiramate and macrosomatognosia. Discussion In this patient with migraine, the onset of AIWS coincided with titration of topiramate, providing a clue that its emergence may have been an adverse drug reaction rather than the underlying illness. Consistent with previous reports, AIWS resolved shortly after topiramate was discontinued, lending credence to this conclusion. However, the mechanism of AIWS is unknown and may be multifactorial, leaving the possibility that migraine predisposed the patient to develop AIWS from topiramate. Conclusion The long association of AIWS with migraine and epilepsy makes it possible that cases caused by medications used to treat these illnesses, like topiramate, are underreported. Awareness of the temporal relationships between the course of illness and the timing of drug therapy can help guide the recognition of AIWS as a potential adverse event.

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). The treatment course and cardiovascular outcomes of patients who develop new or recurrent AF after CAR-T has yet to be explored. Methods We extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. The endpoint of interest was defined as the first episode of new or recurrent AF during or after CAR-T infusion. Patients with persistent or permanent AF were not counted as events. Tocilizumab use was not counted for patients who had an AF event more than 30 days after CAR-T infusion. Chart review was used to delineate patient treatments and outcomes. Survival analyses techniques were used to define risk of new or recurrent AF. Results There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022, of which 41 had prior history of AF. Overall, there were 10 new and 9 recurrent AF events after CAR T-cell infusion, with a composite cumulative incidence risk of 5.8%. The majority of these events occurred within 30 days of receiving CAR-T (N=14, 73.7%). All events that occurred after 30 days were associated with significant hospitalizations unrelated to CAR-T. Rate control was the preferred method of treatment, with beta blockers being the preferred first-line therapy for both patients on and not on baseline beta blockers (Table). 2 patients were given amiodarone prophylactically prior to CAR-T infusion. Only 1 patient received cardioversion, 15 days after the AF event, but had recurrence shortly thereafter. Only 2 patients were on chronic anticoagulation, and both had history of AF prior to CAR-T. Tocilizumab was given to 9 patients (47.4%) before the onset of AF and not significantly associated to decreased risk of developing new or recurrent AF (HR 1.16, CI 0.47-2.83, P=0.75). Tocilizumab was more likely given to patients with higher cytokine release syndrome and neurotoxicity grading (Figure). There were no myocardial infarctions or strokes. Conclusion Atrial fibrillation is a rare complication of CAR T-cell therapy. Rate-control strategies remain the preferred method of treatment. Very few patients were given anticoagulation, but the incidence of subsequent stroke was negligible. More investigation will need to be undertaken to determine methods of preventing AF in the setting of CAR-T therapy.CAR-T AF Patient Case Series

Abstract Introduction Cancer therapy-related cardiac dysfunction (CTRCD) after anthracycline-based therapy is a dreaded complication due to its significant morbidity and mortality. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) have been shown to improve cardiovascular outcomes in multiple scenarios. However, its potential benefits in patients who develop CTRCD due to anthracycline-based chemotherapy are not well established. Purpose To investigate the benefits of SGLT2i in cancer patients who develop CTRCD secondary to anthracycline-based chemotherapy. Methods All patients who underwent anthracycline therapy between 2002 and 2022 across three tertiary centers and had a diagnosis of moderate or severe CTRCD according to 2022 European Society of Cardiology (ESC) guidelines were evaluated. Baseline characteristics, echocardiograms pre and post chemotherapy, and mortality were reviewed. Kaplan Meier analysis was conducted to compare all-cause and cardiovascular mortality between patients treated with SGLT2i (both patients on chronic SGLT2i who continued their therapy following CTRCD and those who commenced the treatment after CTRCD diagnosis) and those not receiving this therapy. Results In total, 398 patients diagnosed with moderate or severe CTRCD were included; median age was 66.82 (58.07, 74.46) years and 59.29% were males. Among them, 39 (9.80%) received SGLT2i. Mortality rates at 1- and 5-years were significantly lower among patients who were on SGLT2i treatment compared to patients who were not (8.40% vs 46.30%, p= 0.0001 and 17.30% vs 65%, p= 0.0001, respectively) (Figure1). Furthermore, cardiovascular mortality rate at 5 years was significantly lower in patients receiving SGLT2i compared to patients not receiving this therapy (0% vs 11%, p= 0.046). Conclusions SGLT2i may have survival benefit in cancer patients who develop CTRCD secondary to anthracycline-based chemotherapy and might be considered as an adjunctive treatment to improve survival outcomes in this population.Figure 1.Kaplan-Meier Curves

Abstract Background Endocrine therapy has been the mainstay treatment for metastatic hormone receptor-positive / HER2-negative (HR+/HER2-) breast cancer. Given that cell cycle dysregulation and consequent uncontrolled cellular proliferation is a key mechanism behind cancer growth, agents targeting this pathway have been of major therapeutic interest.[1] The cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors palbociclib, ribociclib, and abemaciclib have shown a synergistic effect in combination with endocrine therapy.[2-3] Despite favorable results, post-approval studies have revealed potential concerns for cardiotoxicity. [4] Given this, we sought to characterize the incidence and outcomes of atrial arrhythmia among metastatic HR+/HER2- breast cancer patients who were treated with CDK 4/6 inhibitors at our institution. Purpose To investigate the incidence and risk factors of atrial arrhythmia among hormone receptor-positive/HER2-negative breast cancer patients treated with CDK4/6 inhibitors at our institution. Methods A retrospective cohort study was conducted among 2754 patients ≥18 years of age who received treatment with CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) for an established diagnosis of hormone receptor-positive, HER-2 negative breast cancer between 2015-2024. Patients with new onset atrial fibrillation and/or flutter were identified through chart review. The cumulative incidence of new-onset atrial arrhythmia was estimated using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of atrial arrhythmia. Results A total of 2754 patients was included in the study; 97.3% were female and mean age was 61 years (13). Among these, 101 (3.6%) had a prior history of atrial arrhythmia. The 1-year and 5-year cumulative incidence of new-onset AA were 1.1% and 2.8% respectively (Figure 1). When stratified by specific CDK4/6 inhibitor agents, there was no statistically significant difference. On univariable analysis, age at treatment, hypertension, coronary artery disease, and peripheral vascular disease were associated with new-onset atrial arrhythmia. However, following multivariable adjustment, only age at treatment was statistically significant. Conclusions New-onset atrial arrhythmias may occur during or after CDK4/6 inhibitor use. Older patients appeared to have a higher risk. There were no clear differences in atrial arrhythmia risk between the three CDK4/6 inhibitors.

Abstract Background Patients with cancer treated with immune checkpoint inhibitors are at increased risk of myocardial infarction and ischemic stroke. The mechanism is incompletely understood but may involve accelerated atherosclerosis due to plaque inflammation. Pre-clinical studies may provide insight in these mechanisms. Aim To assess the effects of modulating co-inhibitory immune checkpoint proteins on atherosclerosis progression in animal models. Methods A systematic review was performed in MEDLINE, Embase, Web of Science, and Scopus up to September 2023. Animal studies were included if the effect of modulation of programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and/or lymphocyte-activation gene 3 (LAG-3) on atherosclerotic plaque size was evaluated. Secondary outcomes were plaque composition and systemic inflammation. The ratios of means (RoM) across the studies were pooled in a random effects meta-analysis. Results 1,655 studies were identified of which twelve were included. All studies used an atherosclerotic mouse model (Apoe-/-, Ldlr-/-, or ApoE3*Leiden) and either evaluated pharmacological or genetic modulation of co-inhibitory immune checkpoint proteins. Upon inhibition, atherosclerotic plaque size in the aorta was 49% higher in exposed mice compared to control mice (RoM, 1.49; 95% CI, 1.12-1.82; I2=86%). Plaque composition was predominantly characterized by a greater abundance of CD4+ T cells, CD8+ T cells, and macrophages. Studies stimulating co-inhibitory immune checkpoint proteins corroborated these findings and demonstrated that atherosclerotic plaque size was reduced by 28% in treated mice compared to controls (RoM, 0.72; 95% CI, 0.65-0.80; I2=85%). This reduction was paralleled by a decrease in the number of macrophages and T cells in plaques. Conclusion Immune checkpoint inhibition leads to plaque inflammation and a significant increase in murine atherosclerotic plaque size. These changes may reflect the cause of the increased risk of myocardial infarction and ischemic stroke in patients treated with immune checkpoint inhibitors.

Prostate cancer represents a significant health disparity among Black men, who experience higher rates of both incidence and mortality compared to other racial groups. Understanding the complex interplay of cultural, familial, and socioeconomic factors that shape health behaviors is essential for the development of effective interventions. This study sought to explore the lived experiences of ethnically diverse Black men with prostate cancer, focusing on how cultural context, family history, and spirituality influence health decisions and engagement with care. Through a secondary analysis of existing data, personal narratives from 32 Black prostate cancer survivors, primarily U.S.-born Black men, were examined to identify recurring themes that revealed the multifaceted challenges and motivations these men face. The analysis uncovered eight key themes that reflect a complex landscape, including medical distrust fueled by cultural perceptions and past negative experiences, the dual influence of family history on seeking early care versus hesitation, and the role of spirituality as a guiding force in health decisions. Additionally, financial constraints and limited access to comprehensive health information emerged as critical factors affecting engagement with preventive care. The findings underscore the need for culturally sensitive approaches that acknowledge the diverse experiences of Black men in their prostate cancer journey. By understanding the influence of family dynamics, spirituality, and socioeconomic challenges, future research can create targeted interventions that promote informed decision-making and help reduce disparities in prostate cancer outcomes.

Purpose of review The aim is to summarize the role of sentinel lymph node biopsy (SLN) in surgical staging for endometrial cancer (EC). Recent findings The value of SLN in EC staging continues to be demonstrated in all clinically uterine-confined disease, as SLN matches or improves the diagnostic accuracy of pelvic±para-aortic lymphadenectomy (PLD ± PALD) while reducing recovery time, surgical complications, and risk of lower extremity lymphedema. High diagnostic accuracy allows recommendation of appropriate adjuvant therapy, and recent studies have shown that even patients with high-risk histology may undergo SLN as opposed to PLD ± PALD provided this is combined with appropriate imaging. Debate about the necessity of any lymph node assessment in patients with certain low-risk features continues, with a preponderance of evidence pointing toward universal SLN in patients undergoing surgical staging for EC. In patients with negative SLN and intermediate risk uterine factors, molecular profiling is recommended to augment information gained through surgical assessment. Summary EC surgical staging with SLN is considered standard practice in clinically uterine-confined disease. This approach allows precise treatment recommendations without PLD ± PALD related side effects. The integration of molecular profiling with EC surgical staging will accelerate the benefits of therapeutic advances in EC.