Protamine is frequently used to reverse unfractionated heparin, yet contemporary data on its safety and long-term outcomes in chronic total occlusion percutaneous coronary intervention (CTO PCI)-related perforation are limited. We retrospectively analyzed all CTO PCI procedures performed at a single center between January 2019 and December 2023. Patients who experienced coronary perforation were stratified by protamine administration. Inverse probability of treatment weighting (IPTW) and doubly robust logistic regression were used to adjust for baseline and procedural differences. Clinical end points included protamine-related reactions, cardiac tamponade requiring pericardiocentesis, periprocedural myocardial infarction (MI), acute stent thrombosis, in-hospital all-cause death, and 1-year all-cause death. Among 1503 CTO PCI cases, perforation occurred in 199 patients (13.2%): 108 (54.3%) received protamine and 91 (45.7%) did not. Protamine use increased over time ( P -for-trend <0.001). In-hospital outcomes were comparable between groups, including death (4.6% vs. 4.4%; P > 0.999), pericardiocentesis (8.3% vs. 9.9%; P = 0.806), and periprocedural MI (0.9% vs. 2.2%; P = 0.594). IPTW-adjusted analyses yielded similar results. No acute stent thrombosis or protamine reactions occurred. Doubly robust analysis showed no association between protamine use and in-hospital death (aOR 0.85, 95% CI 0.05-13.86; P = 0.917), pericardiocentesis (aOR 0.45, 95% CI 0.10-1.98; P = 0.294), or either outcome (aOR 0.53, 95% CI 0.21-2.85; P = 0.390). At 1 year, all-cause death remained similar (7.4% vs. 6.6%; P > 0.999), with no association on adjusted analysis (aOR 0.63, 95% CI 0.12-3.40; P = 0.591). Protamine administration for CTO PCI-related perforation seems safe, without evidence of additional clinical benefit compared with no protamine use.

Musculoskeletal adverse reactions (MAEs) caused by statins are the main reason that limits their clinical application. Bempedoic acid provides an alternative treatment option for patients who cannot tolerate statins as a novel oral lipid-lowering drug. The objective of this study was to perform data mining using the FDA Adverse Event Reporting System (FAERS) to realistically observe and systematically summarize bempedoic acid-related MAEs in the real world. The FAERS database from the first quarter of 2020 to the fourth quarter of 2024 was retrospectively queried to characterize reporting of MAEs with bempedoic acid. The association between bempedoic acid and MAEs was evaluated using the reporting odds ratio (ROR) and the Bayesian Confidence Propagation Neural Network, followed by univariate logistic regression to explore factors influencing MAEs. MAEs accounted for 19.64% of the total number of bempedoic acid reports. The median onset time of MAEs with bempedoic acid was 12.5 days. Disproportion analysis showed that myalgia had the strongest AE signal (ROR 30.1[95% CI 24.93-36.35]). Subgroup analyses of age, sex, and weight showed no significant differences in the risk of bempedoic acid-related MAEs. Notably, age >65 years and male patients were significant risk factors for reporting serious MAEs (p<0.001 and p=0.015, respectively). This real-world pharmacovigilance study suggested a significant association between the MAEs and bempedoic acid. Elderly male patients were more likely to develop serious MAEs. Enhanced monitoring is recommended when administering bempedoic acid to high-risk populations.

This study evaluated the clinical efficacy and safety of repeated levosimendan administration, both as monotherapy and in combination with dapagliflozin, in outpatients with chronic heart failure (CHF) and reduced ejection fraction (<40%). We conducted a multicenter, randomized, double-blind, placebo-controlled trial across five outpatient clinics in Moscow, Russia. A total of 393 patients were randomized into three groups: levosimendan (0.1 µg/kg/min, 24-hour infusions every 3 weeks), placebo, and combination therapy (levosimendan plus dapagliflozin 10 mg/day). All patients in the combination group were SGLT2 inhibitor-naïve. The primary outcomes included changes in NT-proBNP levels and hospitalization rates, while secondary outcomes assessed quality of life using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), functional parameters, and safety. Combination therapy produced the greatest clinical benefit, with significant reductions in NT-proBNP (p = 0.03) and hospitalization rates (p = 0.04), and a significantly lower risk of hospitalization or death compared with placebo (HR = 0.58, 95% CI: 0.36-0.92, p = 0.021). Improvements in quality of life were also most pronounced in the combination group, with significant MLHFQ score changes at 3 months (p = 0.02) and 6 months (p = 0.04). Levosimendan monotherapy led to moderate improvements, but effects were consistently smaller than those observed with combination therapy. Safety and tolerability were acceptable across all groups, with no clinically meaningful changes in hematologic or biochemical markers. The combination of levosimendan and dapagliflozin provides superior clinical benefits in CHF outpatients, including reduced hospitalizations and improved quality of life, while maintaining a favorable safety profile.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection that often leads to profound end organ derangement in which vascular system dysfunction plays a critical role. Septic shock is characterized by a pronounced decrease in peripheral vascular resistance, progressive hypotension and lack of response to vasoconstrictors. We have previously shown that sepsis induced cardiac hyporesponsiveness to isoproterenol by a nitric oxide (NO)-dependent mechanism, mediated by increased G protein receptor kinase 2 (GRK2) expression and receptor phosphorylation. In the present report we investigated whether this mechanism is relevant in the vascular system. The contractile response of aortic rings and the in vivo responsiveness to phenylephrine were significantly reduced in septic mice at both 12 and 24 h after cecal ligation and puncture (CLP) surgery. Higher expression of GRK2 and increased phosphorylated GRK2 were detected in the aorta of septic mice along with a reduction in the density of alpha-1 adrenergic receptors. Treatment with the selective NOS-2 inhibitor 1400W prevented vessel hyporesponsiveness, abolished GRK2 expression and activation and preserved alpha-1 adrenergic receptor density. Naïve mouse aorta rings incubated with a NO donor displayed diminished contractile response, and this effect was prevented by a GRK2 inhibitor. Our study showed that during sepsis, NOS-2-derived NO induces and activates GRK2, leading to alpha-1 adrenergic receptor internalization and hyporesponsiveness to vasoconstrictors. Therefore, our findings suggest that GRK2 inhibition is a potential new therapeutic target in sepsis-induced vascular dysfunction.

Fulminant myocarditis (FM) is a critical condition with high mortality. Interleukin-1 (IL-1) is a key mediator of myocardial inflammation. We describe the case of a 19-year-old man with FM, hemodynamic deterioration refractory to standard treatment, and a marked systemic inflammatory response. The introduction of anakinra, an IL-1 receptor antagonist, led to rapid clinical, hemodynamic, and laboratory improvement. A literature review identifies other cases of severe/fulminant myocarditis with hyperinflammation that benefited from IL-1 blockade, despite heterogeneous etiologies. These data suggest that anakinra could be a valuable rescue therapeutic option in selected patients with FM and hyperinflammation. Randomized trials are needed to confirm the role of IL-1 blockade in this high-risk population, focusing on the pharmacology of the immune response.

Cardiovascular disease remains a leading cause of global illness and death, accounting for approximately 17.9 million deaths annually, according to the World Health Organization. There is a growing need for more precise and individualized therapeutic strategies to reduce this burden. Artificial intelligence (AI) has the potential to enhance cardiovascular outcomes by facilitating personalized risk stratification and informing treatment decisions, particularly through advancements in AI-powered cardiovascular imaging and machine learning models. Traditional approaches rely on population-level risk assessments and generalized treatment guidelines, which often fail to capture the complex and diverse nature of individual patient presentations. This review examines the transformative impact of AI-enhanced cardiovascular imaging modalities, including echocardiography, cardiac magnetic resonance imaging, computed tomography angiography, and nuclear cardiology, on optimizing medical therapy. Machine learning algorithms can rapidly and accurately analyze large volumes of imaging data, improving efficiency, standardizing image acquisition and interpretation, reducing inter-observer variability, and increasing diagnostic confidence. By integrating AI with cardiovascular imaging, clinicians can achieve personalized risk assessments, early disease detection, and tailored treatment plans that range from pharmacotherapy to interventions and lifestyle modifications. These advances hold promise for improving outcomes in patients with cardiovascular disease or at risk for its development. The review also addresses current challenges and future directions, highlighting the potential of AI to usher in a new era of individualized cardiovascular care.

The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aimed to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs). Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed through STATA 14.0. This systematic review and network meta-analysis of 13 studies (9248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3%, respectively). Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management. PROSPERO CRD420251145396 ( https://www.crd.york.ac.uk/prospero/ ).

The recent emergence of cardiac myosin inhibitors (CMIs) has established an era of targeted medical therapy for obstructive hypertrophic cardiomyopathy (oHCM), with trials showing decreases in obstructive gradients and improvements in symptoms and exercise capacity. However, not all patients achieve satisfactory responses with CMIs, which can include a "non-response" to medication due to persistent obstruction or continued symptoms despite gradient resolution, or medication failure in cases of discontinuation due to side effects or cost. We present a differential framework for evaluation of CMI non-response or failure, including evaluation for contributors to reduced systolic function, non-oHCM sources of obstruction, or other cardiac and non-cardiac causes of dyspnea. Patients without satisfactory improvement with CMI therapy should undergo a thorough workup according to this framework to identify other potentially addressable concerns that may allow for success with CMIs or indicate other appropriate therapies to address symptoms.