Aims: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin–angiotensin–aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. Methods and results: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. Conclusions: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Background: The data on the association between serum uric acid (sUA) concentration and outcomes in patients with an ACS are inconsistent and do not focus on patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). The aim of this study was to analyze an association of sUA concentration on admission and outcomes in those patients. Methods: Data from the prospective, single-center registry of patients hospitalized due to NSTE-ACS from January 2006 to December 2016 were analyzed retrospectively. The population was divided into quartiles according to the baseline sUA. The primary outcome was the incidence of all-cause death, non-fatal myocardial infarction, stroke and ACS-driven revascularization at 36 months. Results: Total of 2,824 patients with sUA measured on admission were included in this analysis with a median sUA of 352 µmol/L (5.92 mg/dL). Patients with higher sUA were older and more burdened with cardiovascular risk factors and history of coronary events. The prevalence of multivessel coronary artery disease and left main stenosis was significantly higher in patients with higher sUA. Elevated sUA concentration was associated with significantly worse short-, mid- and long-term outcomes. All-cause mortality was significantly higher in each analyzed period. In the multivariable analysis, sUA elevation was identified as an independent predictor of all-cause mortality at 12-month and 36-month follow-up. Conclusions: Elevated baseline sUA concentration was independently associated with worse mid- and long-term outcomes in patients with NSTE-ACS. Baseline sUA concentration could identify patients with NSTE-ACS at higher risk of more dismal prognosis. Background: The data on the association between serum uric acid (sUA) concentration and outcomes in patients with an ACS are inconsistent and do not focus on patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). The aim of this study was to analyze an association of sUA concentration on admission and outcomes in those patients. Methods: Data from the prospective, single-center registry of patients hospitalized due to NSTE-ACS from January 2006 to December 2016 were analyzed retrospectively. The population was divided into quartiles according to the baseline sUA. The primary outcome was the incidence of all-cause death, non-fatal myocardial infarction, stroke and ACS-driven revascularization at 36 months. Results: Total of 2,824 patients with sUA measured on admission were included in this analysis with a median sUA of 352 µmol/L (5.92 mg/dL). Patients with higher sUA were older and more burdened with cardiovascular risk factors and history of coronary events. The prevalence of multivessel coronary artery disease and left main stenosis was significantly higher in patients with higher sUA. Elevated sUA concentration was associated with significantly worse short-, mid- and long-term outcomes. All-cause mortality was significantly higher in each analyzed period. In the multivariable analysis, sUA elevation was identified as an independent predictor of all-cause mortality at 12-month and 36-month follow-up. Conclusions: Elevated baseline sUA concentration was independently associated with worse mid- and long-term outcomes in patients with NSTE-ACS. Baseline sUA concentration could identify patients with NSTE-ACS at higher risk of more dismal prognosis.

The widespread adoption of leadless pacemakers has introduced new clinical and technical challenges related to device management at end of service and in the setting of device-related complications. While transvenous lead extraction is an established treatment strategy for conventional pacing systems, there is currently no standardized framework for transvenous leadless pacemaker extraction (TLLE). With increasing numbers of leadless pacemakers approaching end of service and expanding indications for leadless pacing, a structured approach to TLLE has become clinically relevant. This review proposes a systematic concept of TLLE, including definitions, clinical indications, procedural strategies, risk assessment, and institutional requirements. Indications for TLLE including device end-of-life, dislocation, interactions, infection, or the need for upgrade to a different device were summarized. Procedural strategies, primarily based on the extraction most frequently from the femoral approach, with the use of snare-based techniques, with the choice of other tools and access tailored to device type, dwell time, fixation mechanism, and degree of encapsulation, have been summarized. Literature findings reporting high success rates were presented, with potential complications, such as cardiac perforation, tamponade, tricuspid valve injury, embolization, and vascular access complications, being summarized as well. Patient selection, pre-procedural imaging have also been evaluated, and factors influencing decision-making, including balance of periprocedural risk against long-term implications of device abandonment have been presented.