Endocrine therapy is the main treatment for hormone receptor-positive (HR+) breast cancer. However, advanced tumors develop resistance to endocrine therapy, rendering it ineffective as the disease progresses. There are several molecular mechanisms of primary and secondary endocrine resistance. Resistance can develop due to either alteration of the estrogen receptor pathway (e.g., ESR1 mutations) or upstream growth factors signaling pathways (e.g., PI3K/Akt/mTOR pathway). Despite progress in the development of molecularly targeted anticancer therapies, the emergence of resistance remains a major limitation and an area of unmet need. In this article, we review the mechanisms of acquired endocrine resistance in HR+ advanced breast cancer and discuss current and future investigational therapeutic approaches.

Background: Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety. This study sought to determine the causes of early mortality (≤90 days) after AF ablation. Methods: We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available. Results: A total of 6723 patients were included in the study. The 90-day all-cause mortality rate was 0.22% (n=15). Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06% (n=4). Conclusions: AF ablation procedure has a 90-day mortality of 0.22%, and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was low at 0.06%. Further studies are required to investigate causes and risk factors associated with sudden death in this patient population.

Cardiac sarcoidosis (CS) is characterized by various arrhythmic manifestations ranging from catastrophic sudden cardiac death secondary to ventricular arrhythmia, severe conduction disease, sinus node dysfunction, and atrial fibrillation. The management of CS is complex and includes not only addressing the arrhythmia but also controlling the myocardial inflammation resultant from the autoimmune reaction. Arrhythmic manifestations of CS carry significant prognostic implications and invariably affect long-term survival in these patients. In this review, we focus on management of arrhythmic manifestation of cardiac sarcoidosis as well as risk stratification for sudden cardiac death in these patients.

Cardiac resynchronization therapy with defibrillator therapy (CRT-D) has revolutionized the treatment of heart failure with reduced ejection fraction (EF) among a select group of patients with wide QRS. While outcomes in the short- and medium-term post-CRT have been extensively reported, data on very long-term outcomes (10+ years) are limited. The authors aimed to study outcomes of CRT over very long terms of 10+ years. We retrospectively reviewed the records of patients who underwent CRT-D at the Mayo Clinic between January 2001 and September 2022. All patients with an EF ≤35%, QRS ≥120 ms, and CRT-D were included in the analysis. The primary endpoint was all-cause mortality. Double matching-propensity matching followed by univariate and multivariable survival analyses-was conducted using accelerated failure models with a log-logistic distribution. Time ratios (TRs) representing the change in survival for a unit increment change in that variable were reported. Among a matched cohort of 610 patients, post-CRT-D implantation, the average survival was 16.1 years for patients with nonischemic cardiomyopathy (NICM) and 9.1 years for patients with ischemic cardiomyopathy. NICM was associated with increased survival in both univariate (TR: 1.92; P < 0.001) and multivariable (TR: 1.43; P = 0.014) analyses. Other independent predictors of increased survival post-CRT included baseline left bundle branch block morphology, decreasing age, higher left ventricular EF, female gender, and absence of the following comorbidities: atrial fibrillation, type 2 diabetes mellitus, and chronic kidney disease 3 or higher. Our data suggest that over the very long term (>10 years), patients with NICM had significantly higher survival post-CRT than patients with ischemic cardiomyopathy.

Introduction: Ventricular tachycardia storm or electrical storm (ES) is a common complication following left ventricular assist device (LVAD) implantation. The factors contributing to ES and outcomes are less studied. The study aimed to determine the factors associated with ES and the probability of survival in patients undergoing LVAD in three tertiary centers over a span of 15 years.Methods: We performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2006 to December 31, 2020. ES was defined as ≥3 episodes of sustained ventricular tachycardia over a period of 24 h with no identifiable reversible cause. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed.Results: A total of 883 patients who underwent LVAD implantation were included in our study. ES occurred in 7% (n = 61) of patients with a median of 13 days (interquartile range [IQR]: 5–297 days) following surgery. We found 57% of patients (n = 35) developed ES within 30 days, while 43% (n = 26) patients developed ES at a median of 545 (IQR 152–1032) days after surgery. Following ES, 26% of patients died within 1 year. Patients with ES had a significant association with a history of ventricular arrhythmias and implantable cardioverter defibrillator (ICD) shocks before the procedure. ES was significantly associated with reduced survival compared to patients without ES (hazards ratio [HR]: 1.92, 95% CI: 1.39–2.64, p < .001).Conclusion: Following LVAD implantation, the rate of ES was 7% with majority of ES occurring within 30 days of LVAD. Risk factors for ES included pre‐implant history of ventricular arrhythmias and ICD shock. ES was significantly associated with reduced survival compared to patients without ES.