Journal of Cardiovascular Pharmacology最新文献

Immune-mediated inflammatory diseases (IMIDs), including axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn's disease (CD), and ulcerative colitis (UC), share overlapping inflammatory pathways and frequently coexist, supporting the relevance of evaluating treatment safety across these conditions. Upadacitinib, a selective Janus kinase 1 inhibitor, is approved for multiple IMIDs; however, concerns regarding major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) have emerged based on class-related safety signals. We conducted systematic review and meta-analysis of randomized controlled trials to assess the risk of MACE and VTE associated with upadacitinib compared with placebo or active comparators in patients with spondyloarthritis (SpA) and inflammatory bowel disease (IBD). A systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified eligible trials. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Eight RCTs comprising 4,433 patients were included, of whom 2,868 received upadacitinib. Across studies, MACE and VTE events were rare in both treatment and control groups. Upadacitinib was not associated with an increased risk of MACE (RR 0.35; 95% CI 0.05-2.19; p = 0.259) or VTE (RR 0.31; 95% CI 0.04-2.55; p = 0.279) in patients with SpA and IBD, with no observed heterogeneity (I2 = 0%). However, the low number of events resulted in wide confidence intervals and limited precision, precluding definitive conclusions regarding cardiovascular and thromboembolic safety. Larger randomized controlled trials and long-term real-world studies are needed to further evaluate these outcomes.

Pericarditis is the most common cardiac manifestation of systemic lupus erythematosus (SLE), yet optimal management remains poorly defined. Glucocorticoids are frequently used but are associated with toxicity and increased recurrence risk. Interleukin-1 (IL-1) inhibition has demonstrated efficacy in recurrent pericarditis, though data in SLE-associated pericarditis is limited. In order to evaluate the clinical impact of IL-1 blockade on the treatment of SLE-associated recurrent pericarditis, we performed a retrospective case series of six patients with SLE-associated recurrent pericarditis treated with the IL-1 inhibitor rilonacept at a tertiary care cardio-rheumatology center. Clinical response, inflammatory markers, imaging findings, and use of concomitant therapies were assessed before and after IL-1 inhibition. Following initiation of rilonacept, all six patients achieved clinical improvement: three (50%) attained complete symptom resolution and three (50%) demonstrated partial symptomatic improvement. C-reactive protein normalized in all four patients with elevated baseline levels. Any post-treatment imaging, available in five of six patients (83.3%), demonstrated objective reduction in pericardial inflammation or effusion in all five. Use of concomitant therapies decreased substantially. IL-1 blockade with rilonacept was associated with clinical and imaging improvement and substantially reduced reliance on glucocorticoids and other anti-inflammatory agents in SLE-associated recurrent pericarditis. These findings support IL-1 inhibition as a targeted, steroid-sparing strategy in refractory disease and further prospective investigation.

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, demonstrates cardioprotective effects in heart failure, and recent trials suggest benefits in acute myocardial infarction (MI). However, the mechanisms underlying its efficacy, particularly its impact on the post-MI inflammatory response, are not fully elucidated. This study aimed to investigate whether EMPA modulates post-MI inflammation and to uncover the underlying molecular pathways. C57BL/6J mice undergoing MI were randomized to receive EMPA or saline for 7 days. EMPA treatment significantly improved survival, reduced fibrosis, and enhanced cardiac function. EMPA attenuated the systemic inflammatory response at day 1 post-MI, as evidenced by lower serum levels of IL-1β, IL-6, and CXCL-1. In the infarcted myocardium at day 1 post-MI, EMPA suppressed infiltration of neutrophils and pro-inflammatory macrophages while increasing anti-inflammatory macrophages. Mechanistically, EMPA upregulated the ketone body metabolic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1), increasing cardiac β-hydroxybutyrate (β-HB) levels, and subsequently inhibited NF-κB p65 phosphorylation. In immortalized bone marrow-derived macrophages, the anti-inflammatory effect of EMPA was mimicked by β-HB and abolished by Bdh1 knockdown, which was rescued by exogenous β-HB. In conclusion, EMPA attenuates maladaptive inflammation and confers cardioprotection after MI, potentially through a BDH1/β-HB/NF-κB pathway in macrophages. This ketone-mediated immunomodulatory axis, primarily defined in vitro, identifies a novel and potential​ pharmacological mechanism of SGLT2 inhibition in the context of post-MI inflammation.

This retrospective multicenter cohort study compared the safety and efficacy of low- versus high-dose colchicine in adult patients with chronic kidney disease (CKD) treated for pericarditis between August 2015 and August 2024. CKD was identified using ICD codes and confirmed by an age- and sex-adjusted estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Patients with recurrent pericarditis or prior colchicine use before admission were excluded. Patients were categorized as receiving high-dose (≥0.6 mg/day) or low-dose (<0.6 mg/day) colchicine. The primary outcomes were colchicine-related adverse effects and a composite of dose reduction or discontinuation. Secondary outcomes included symptom improvement within 72 hours, recurrent pericarditis, and pericardial tamponade within 12 months. A total of 93 patients were included (53 high-dose and 40 low-dose). Idiopathic pericarditis was the most common etiology in both groups. End-stage kidney disease (57.5% vs. 15%) and dialysis (52.5% vs. 13%) were more common in the low-dose group. High-dose colchicine was associated with more gastrointestinal adverse events (39.6% vs. 12.5%, p=0.004), a higher rate of the composite outcome of dose reduction or discontinuation (41.5% vs. 20%, p=0.043), and more frequent dose reduction alone (30.2% vs. 7.5%, p=0.009), while discontinuation rates were similar. Symptom relief, recurrent pericarditis, and pericardial tamponade were comparable between groups. Initial colchicine doses of less than 0.6 mg daily were associated with improved tolerability in patients with CKD and pericarditis.

Abstract: Postural orthostatic tachycardia syndrome (POTS) is a debilitating autonomic disorder characterized by excessive orthostatic tachycardia and significant functional impairment. Conventional therapies, including beta-blockers, often provide incomplete relief or are poorly tolerated. Ivabradine, a selective If channel inhibitor, reduces heart rate without affecting blood pressure or myocardial contractility, making it a promising option, particularly in post-COVID-19 POTS. This systematic review and meta-analysis evaluated the efficacy and safety of ivabradine in patients with POTS. PubMed, Embase, and the Cochrane Library were searched through August 2025 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD420251073600). Eligible studies included randomized controlled trials, observational studies, and case series reporting ivabradine outcomes in POTS. Primary outcomes were changes in standing and supine heart rate; secondary outcomes included symptom burden, quality of life, and adverse events. A random-effects model was used, heterogeneity was assessed through sensitivity analyses, and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Nine studies involving 245 patients were included. Ivabradine significantly reduced standing heart rate (-18.5 bpm; 95% confidence interval -23.3 to -13.8) and supine heart rate (-9.7 bpm; 95% confidence interval -13.4 to -6.1). Symptom improvement particularly palpitations, lightheadedness, and exercise intolerance was consistently reported across classic, pediatric, hyperadrenergic, and post-COVID-19 subgroups. Adverse events were infrequent and mild, most commonly transient visual disturbances, with no reports of severe bradycardia or hypotension. Heterogeneity was high, largely driven by pediatric and post-COVID-19 cohorts. In conclusion, ivabradine seems to provide meaningful heart rate reduction and symptomatic improvement in POTS with a favorable safety profile. However, evidence is limited by small, heterogeneous, predominantly observational studies, underscoring the need for large, multicenter randomized controlled trials.

Abstract: Over 30 million individuals globally are afflicted with heart failure with preserved ejection fraction (HFpEF). Despite this substantial figure, treatment options for HFpEF remain limited. This is largely attributed to the variability in disease features and comorbidities with which patients present in the clinic. A common feature among patients with HFpEF is reduced nitric oxide (NO) bioavailability-a finding which prompted the use of therapeutics targeting the NO signaling pathway in HFpEF preclinical and clinical trials. Although many of these therapeutics were successful in animal models, clinical trials have yielded neutral, negative, or contradictory results. In this review, we will summarize the outcomes of HFpEF clinical trials investigating drugs that target the NO signaling pathway (nitrates, nitrites, soluble guanylyl cyclase stimulators, and phosphodiesterase 5 inhibitors) and discuss potential pitfalls underlying the neutral or negative results, as well as considerations for the design of future studies.

Abstract: Somatostatin and analogues may reduce chest tube (CT) output in chylothorax caused by postcoronary artery bypass grafting (CABG). However, data are limited to case reports and series. This scoping review aimed to describe the efficacy and safety of somatostatin/analogue use in post-CABG chylothorax. We retrieved from PubMed, Embase, and OVID all studies and case reports describing somatostatin/analogue use in adult patients post-CABG for resolution of chylothorax. The primary outcome was time from somatostatin/analogue initiation to daily CT output <100 mL/d. CT duration, need to repeat invasive intervention, and safety events associated with somatostatin/analogues were also analyzed. Somatostatin/analogues were associated with reductions in CT output, but one-third of patients still required pleurodesis or surgical intervention. No safety events were identified. Patients with lower daily CT outputs at the time of somatostatin/analogue initiation were more likely to avoid repeat intervention than those with higher outputs. In conclusion, somatostatin/analogues seem safe and possibly effective in management of post-CABG chylothorax. Future studies should investigate which patients are most likely to benefit from this therapy.

Abstract: The impact of blood pressure (BP) reduction induced by levosimendan infusion on in-hospital mortality in patients with acute heart failure (AHF) and systolic ventricular dysfunction still needs to be clarified. We conducted a retrospective cohort study involving 161 patients hospitalized for AHF and treated with a 24-hour infusion of levosimendan between 2017 and 2024, following a standard protocol. During hospitalization, biometric, clinical, laboratory, and echocardiographic parameters were assessed. The results revealed that the difference in systolic and mean BP before and after levosimendan infusion (delta-SBP and delta-MAP) was significantly associated with higher in-hospital mortality (delta-SBP in survivors: 10.1 ± 19.1 mm Hg vs. in nonsurvivors: 21.4 ± 23.6 mm Hg, P = 0.023; delta-MAP in survivors: 8.8 ± 15.8 mm Hg vs. in nonsurvivors: 17.8 ± 23.3 mm Hg, P = 0.034), regardless of baseline BP values and despite the fact that most patients had absolute values of SBP after levosimendan infusion >90 mm Hg. Multivariable analysis confirmed that a larger reduction in SBP was an independent predictor of in-hospital mortality (OR: 1.053, 95% CI, 1.015-1.092, P = 0.006). Absolute values of SBP after levosimendan infusion (post-SBP) were also independently associated with mortality (OR: 0.942, 95% CI, 0.896-0.990, P = 0.019). However, when the analysis was repeated in a subgroup of subjects with SBP after infusion >90 mm Hg, only delta-SBP remained independently associated with mortality (OR 1.051, 95% CI, 1.009-1.095, P = 0.017). In patients with AHF treated with levosimendan, larger reductions in SBP after therapy are independently associated with in-hospital mortality. Monitoring SBP changes after levosimendan infusion may improve risk stratification and guide clinical decisions.

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy by significantly improving the prognosis of patients with various malignancies. Despite their clinical benefits, ICIs are increasingly recognized for inducing cardiovascular adverse events, including severe toxicities such as myocarditis, which pose substantial challenges in oncology practice. Emerging evidence highlights the gut microbiota as a critical regulator of host immunity, potentially influencing the development and progression of ICI-associated cardiovascular toxicities. This review comprehensively examines the current understanding of the interplay between gut microbiota and ICI-associated cardiovascular adverse events. We systematically analyze the incidence, pathophysiological mechanisms, diagnostic criteria, and prognosis of major cardiovascular toxicities linked to ICIs. Furthermore, we explore the immunomodulatory functions of the gut microbiome that may underlie these adverse events, emphasizing microbiota-mediated systemic immune dysregulation and cardiovascular-specific toxicity pathways. We also discuss future research directions and the clinical implications of integrating gut microbiota modulation into the management of ICI-associated cardiovascular complications. By synthesizing multidisciplinary insights, this review aimed to provide a theoretical foundation and research framework to advance both basic and clinical studies in this emerging field.