Clinical evidence suggests that the lipid-lowering efficacy of statins may be diminished by concurrent β-lactam administration in patients with coronary heart disease (CHD), yet the mechanisms driving this potential drug-drug interaction, particularly the role of gut microbiota as a mediator, remain undefined. To address this gap, we conducted a retrospective analysis of data from a tertiary hospital spanning 5 years, enrolling 436 patients with CHD on statin therapy who had 2 hospital admissions within a 3-month window. Patients were stratified into β-lactam-treated and antibiotic-free cohorts to assess the correlation between β-lactam exposure and statin efficacy. In addition, 16S ribosomal RNA gene sequencing was used to characterize and compare gut microbiota profiles between patients with CHD receiving combined rosuvastatin and β-lactam therapy versus those on rosuvastatin monotherapy. Our findings demonstrated that β-lactam exposure was associated with elevated low-density lipoprotein cholesterol and total cholesterol levels. Both rosuvastatin and β-lactams induced significant alterations in gut microbiota composition, with distinct shifts in bacterial taxa abundances: rosuvastatin increased the relative abundance of Faecalibacterium and Dysosmobacter , whereas β-lactams disrupted the abundance of Faecalibacterium , Roseburia , and Dysosmobacter . Collectively, these results indicate that concomitant β-lactam use impairs rosuvastatin efficacy in patients with CHD, likely through perturbation of gut microbiota composition. Rosuvastatin may exert a portion of its cardioprotective effects through modulation of gut microbiota, and β-lactams may abrogate this benefit by depleting key bacterial taxa linked to statin-mediated lipid regulation. Notably, Dysosmobacter emerges as a potential mediating species in this interaction, supporting a microbiome-dependent mechanism underlying the reduced lipid-lowering efficacy of rosuvastatin during β-lactam coadministration.

Hypertrophic Cardiomyopathy (HCM) is the most commonly inherited cardiomyopathy worldwide, characterized by left ventricular hypertrophy and hypercontractility. Many cases of HCM are due to pathogenic changes in cardiac sarcomere proteins. Traditional therapies including B-blockers, non-dihydropyridine calcium channel blockers and septal reduction therapy have long provided symptomatic relief, but they have not necessarily addressed the disease state at the cellular level. The treatment landscape for HCM has evolved significantly over the last decade with the emergence of new targeted therapies, including a new class of medication called cardiac myosin inhibitors (CMI). CMI therapy represents a paradigm shift in the management of obstructive variants of HCM, offering meaningful improvement in symptoms and cardiac function parameters. CMI therapy remains investigational in the treatment of non-obstructive variants of HCM. This review examines the evolving understanding of HCM and highlights both traditional management strategies and emerging therapies.

Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) that drives a significant residual risk through proatherogenic, proinflammatory, and prothrombotic pathways. However, current mainstay lipid-lowering therapies such as statins have limited efficacy in reducing Lp(a) levels, highlighting a critical therapeutic gap. This review aims to synthesize evidence on the role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in targeting Lp(a). We systematically searched PubMed and Embase for clinical trials and mechanistic studies (2010-2025), using the PRISMA and AMSTAR-2 frameworks to ensure methodological rigor and demonstrated that PCSK9 inhibitors (eg, alirocumab, evolocumab, and tafolecimab) not only reduced low-density lipoprotein (LDL-C) by 55%-60% but also lowered Lp(a) by 20%-30%. The efficacy of these agents varies ethnically, with tafolecimab showing superior performance in East Asian populations, which is partly attributable to the higher prevalence of the PCSK9 R46L loss-of-function allele. Mechanistically, PCSK9 inhibitors lowered Lp(a) levels through 2 pathways: suppression of hepatic synthesis and enhanced plasma clearance. This evidence supports the 2023 ESC guidelines, which issued a Class IIa recommendation for PCSK9 inhibitor use in patients with ASCVD and elevated Lp(a) levels. Given the evolving landscape, further research is warranted to confirm the role of these therapies in precision medicine paradigms for managing Lp(a)-associated risks.

Although S-amlodipine is known to have similar effects in lowering blood pressure and fewer side effects compared to amlodipine (= mixture of S- and R-amlodipine), there are no available data on its impact on long-term cardiovascular prognosis. This retrospective cohort study analyzed claims data from Korean subjects with hypertension treated with either S-amlodipine or amlodipine from 2010 to 2020. Subjects with prior history of cardiovascular disease or stroke were excluded. The composite endpoints of all-cause death, myocardial infarction, and stroke as 3P-major adverse cardiovascular event (MACE) and the composite endpoints of 3P-MACE and heart failure hospitalization as 4P-MACE were assessed. The study included 1:2 propensity score-matched groups of subjects taking S-amlodipine (n = 15,709) and amlodipine (n = 29,951). The mean clinical follow-up duration was 4.9 ± 0.3 years (median 5.0 years). After adjusting for clinical factors, S-amlodipine was associated with a reduced incidence of 3P-MACE (adjusted hazard ratio [aHR], 0.87; 95% confidence interval [CI], 0.81-0.94; P < 0.001), and 4P-MACE (aHR, 0.86; 95% CI, 0.80-0.93; P < 0.001) compared to amlodipine. The better impact of S-amlodipine compared to amlodipine on 3P-MACE and 4P-MACE was also observed in the subgroup analysis based on various clinical factors. S-amlodipine showed better adherence than amlodipine (proportions of days covered ≥ 0.8: 96.7% vs. 91.8%; P < 0.001). In conclusion, S-amlodipine appears to potentially reduce the risk of long-term MACE compared to amlodipine in patients with hypertension who have no history of cardiovascular disease. However, these findings should be interpreted with caution and confirmed through further prospective studies.

Cardiovascular diseases remain the leading cause of global morbidity and mortality, highlighting the urgent need for more efficient, precise, and cost-effective drug development strategies. Traditional drug discovery pipelines face persistent challenges, including elevated expenses, prolonged timelines, and high attrition rates, particularly with the complex pathophysiology of cardiovascular conditions. Artificial intelligence (AI) has emerged as a transformative force capable of addressing these barriers across all stages of cardiovascular drug development. This review explores the integration of AI in target identification, compound screening, drug design, pharmacokinetic and toxicity prediction, and clinical trial optimization. We highlight state-of-the-art AI tools such as large language models (e.g., BioGPT, Geneformer), generative frameworks (e.g., Generative Tensorial Reinforcement Learning (GENTRL), Variational Autoencoders (VAEs), Generative Adversarial Networks (GANs)), and neural ordinary differential equations, illustrating their ability to accelerate drug discovery, personalize therapy, and improve clinical success rates. In the context of clinical trials, platforms such as Trial Pathfinder have been employed to optimize patient recruitment and improve generalizability. Despite these advancements, several challenges persist, particularly those related to data quality, population representativeness, interpretability, and regulatory oversight. Future directions involving the integration of AI with quantum computing, blockchain technology, and precision medicine offer additional opportunities to advance the field. Collectively, these innovations mark a paradigm shift toward faster, safer, and more personalized cardiovascular drug development.

Vericiguat improves outcomes in heart failure (HF) by promoting vasodilation of the systemic and pulmonary arterial beds. Little is known about its impact on pulmonary artery pressure (PAP). We aimed to study this effect using measurements from implanted PAP sensors. A retrospective analysis was performed on patients with HF treated with vericiguat and implanted with CardioMEMS. PAP was followed for 90 days before and after vericiguat initiation. We recorded laboratory values, echocardiographic and hemodynamics before vericiguat initiation. Fifteen patients were included (age 70, 67% men). At baseline, median EF was 27.5%, 42% had RV dysfunction, mildly elevated mean PAP (24 mm Hg) and pulmonary vascular resistance of 1.6 Wood. When comparing the average of measurements 90 days before and after vericiguat, there were no changes in systolic (34 (28-42) versus 33 (30-40), P = 0.4), diastolic (17 (14-20) versus 16 (13-20), P = 0.75), and mean (24 (18-28) versus 23 (19-28), P = 0.55) PAP. We compared average measurements in the 3-week period before starting vericiguat to various 3-week intervals after vericiguat and found no difference. At 90 days, the median loop diuretic dose (Furosemide equivalent) was 40 mg [0-160], compared with 42 mg [0-240] before vericiguat. NTproBNP did not change significantly before and after vericiguat initiation (log(NTproBNP) 3.1 (2.4-3.2) versus 2.9 (2.5-3.1), P = 0.4). In conclusion, vericiguat was well tolerated in stable HF patients with mild pulmonary hypertension, but no significant effect on PAP was observed. Larger studies, including patients with higher PAP, are needed to clarify its impact.

Excessive surgical bleeding is a potential risk in patients taking ticagrelor who must undergo urgent cardiothoracic (CT) surgery before adequate washout of the drug can occur. The DrugSorb-Antithrombotic removal (ATR) device is a polymer sorbent-filled hemoadsorption cartridge that can remove unbound (active) fractions of ticagrelor and ticagrelor active metabolite (TAM) from blood. STAR-T was a randomized double-blind sham-controlled clinical trial investigating whether the intraoperative use of the device could reduce perioperative bleeding complications in patients undergoing CT surgery within 2 days of ticagrelor discontinuation. Blood samples were collected during the study for total drug level measurements because the ability to measure unbound ticagrelor and TAM (0.2% of total levels) requires an ultra-high sensitivity assay, which is not commercially available. A published and validated pharmacokinetic (PK) model was used to explore the effect of the device on unbound ticagrelor/TAM using the total drug concentrations from the study. The model performed well for simulations of total ticagrelor and TAM, which indicated that the unbound concentrations were also appropriate. The model demonstrated that DrugSorb-ATR significantly reduced unbound ticagrelor and TAM concentrations. Linear and logistic regression analyses of summed ticagrelor and TAM concentrations showed that the DrugSorb-ATR device reduced the probability of clinically relevant bleeding in STAR-T because of the reduction in unbound ticagrelor and TAM.

Immune checkpoint inhibitors (ICIs) have successfully revolutionized cancer therapy, but their immune-mediated adverse events include rare, often severe myocarditis. Although dual ICI blockade is associated with increased cardiotoxic risk, little is known about the potential effects of triplet combinations currently under clinical investigation. We developed a coculture model of human cardiomyocytes and human peripheral blood mononuclear cells (hPBMCs) to evaluate immune-mediated cytotoxicity induced by ICIs. HFCs were exposed for 48h to nivolumab plus relatlimab, ipilimumab, or atezolizumab, either alone or in triplet combinations. Cell lysis was quantified by LDH release. Cytokine secretion (IL-2, granzyme B, and additional inflammatory mediators including NLRP3 activation pathway) was measured by ELISA. Digital microscopy was used for morphological assessment. Triplet combinations of nivolumab-relatlimab with ipilimumab or atezolizumab induced significantly higher cardiomyocyte lysis than single agents or doublets ( P < 0.001). This effect correlated with a robust increase in IL-2 and granzyme B secretion, and activation of proinflammatory cytokines and NLRP3 inflammasome-related mediators. Microscopic analyses confirmed immune cell activation and reduced density of HFCs exposed to triplets. Our findings demonstrate that ICI triplets elicit potent immune activation against cardiomyocytes, providing the first preclinical evidence of direct cardiotoxic potential in this setting. These results highlight the need for enhanced clinical surveillance and cardio-oncology monitoring in patients receiving triple ICI combinations, because these regimens expand in clinical practice.

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, exhibits cardioprotective effects; however, the underlying epigenetic and molecular mechanisms remain poorly understood. This study investigated whether DAPA mitigates myocardial ischemia/reperfusion injury (MI/RI) by modulating enhancer of zeste homolog 2 (EZH2), tri-methylation of lysine 27 on histone H3 (H3K27me3), and sirtuin 1 (SIRT1) expression. Wistar rats were randomly assigned to Sham, MI, and MI+DAPA groups (n=12/group). MI groups underwent 30 minutes of left anterior descending coronary artery (LAD) ligation. For 14 days, animals in the MI+DAPA group received orally 1 mg/kg/day DAPA. Heart function, fibrosis, inflammatory factors (TNF-α, NF-κB, IL-1β, IL-6), and oxidative stress were assessed using echocardiography, Masson's trichrome staining, Western blotting, and ELISA respectively. EZH2, H3K27me3, and SIRT1 expressions were also determined by Western blotting 14 days after MI induction. Tissue damage was evaluated using hematoxylin and eosin (H&E) staining. DAPA administration significantly improved MI-induced myocardial damage by decreasing serum levels of LDH, cTnI, and CK-MB. DAPA also improved left ventricular function by increasing ejection fraction (EF) and fractional shortening (FS), decreased left ventricular fibrosis, and reduced myocardial inflammation by improving myocardial TNF-α, NF-κB, IL-1β, IL-6. Additionally, DAPA reduced oxidative stress by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Finally, DAPA downregulated EZH2, reducing H3K27me3 and subsequently increasing SIRT1 levels compared to the MI group. This study's results indicate that DAPA attenuates MI/RI in male rats by modulating epigenetic mechanisms, specifically through EZH2, and H3K27me3 suppression and SIRT1 upregulation, offering novel insights into its cardioprotective potential.