Journal of Cardiovascular Pharmacology最新文献

Abstract: Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a proinflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, a recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 men, 40 self-identified Black Americans) with recent hospitalization for HFrEF and systemic inflammation [C-reactive protein (CRP) levels >2 mg/L] who were assigned to anakinra [n = 42 (66.7%)] or placebo [n = 21 (33.3%)] as part of the REDHART2 clinical trial (NCT03797001). Cardiorespiratory fitness was measured as peak oxygen consumption (VO 2peak ). Baseline plasma IL-1Ra levels were 380 [290 to 1046] pg/mL. On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra versus placebo [3994 (3372 to 5000) pg/mL vs. 492 (304 to 1370) pg/mL, P < 0.001]. The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%), and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R = -0.269, P = 0.033 and R=-0.355, P = 0.004, respectively) and no statistically significant correlations with VO 2peak values ( P > 0.05). Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, had a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels, however, showed only a modest correlation with CRP levels and not with VO 2peak.

Abstract: The detrimental effect of gamma radiation on cardiac tissue is an intricate problem in the field of nuclear medicine. Therefore, this study aimed to investigate the potential mechanism of Melissa officinalis (MO) against irradiation (IR)-induced cardiac toxicity using an integrated approach combining phytochemical profiling (HPLC and GC-MS), network pharmacology, molecular docking, and in vivo experimental validation. Phytochemical profiling, network pharmacology, and molecular docking analyses identified ellagic acid as a major bioactive constituent of MO and predicted the NRF2 and MAPK pathways as key targets. For in vivo validation, 24 male Wistar rats were divided into 4 groups: control, MO extract (75 mg/kg/day for 3 weeks), irradiated (5 Gy gamma radiation), and irradiated + MO extract. Cardiac injury was assessed by measuring serum injury biomarkers (ALT, LDH), oxidative stress markers (MDA, GSH, SOD, CAT, and GPx), lipid profile, and gene expression of PGC-1α, β3AR, Na + /K + -ATPase, NRF2, MAPK, and JNK. MO extract significantly attenuated radiation-induced elevations in serum LDH and ALT, reduced lipid peroxidation, restored antioxidant defenses, and was associated with improved transcriptional markers of cardiac metabolism. These effects were mediated through upregulation of NRF2 and downregulation of MAPK and JNK signaling pathways, consistent with network pharmacology predictions. Taken together, these results suggest that MO may represent a promising candidate for mitigating acute radiation-induced biochemical alterations associated with cardiac injury by enhancing cardiac function and mitigating impaired oxidative status. This study revealed that MO could reduce cardiac toxicity in irradiated rats through its antioxidant activity, mediated by the NRF2 and MAPK pathways.

Abstract: The aim of this review was to evaluate the evidence for midodrine as a treatment for patients with postural orthostatic tachycardia syndrome (POTS). We conducted a systematic review of the literature to identify studies which evaluate midodrine treatment in patients with POTS. Random-effects meta-analysis was used to determine the effect of midodrine on symptoms compared with placebo and beta-blockers. A total of 14 studies with 968 patients were included which took place between 2000 and 2017. The proportion of patients who clinically benefited from POTS from 10 studies ranged from 46.2% to 91.3%. Meta-analysis of midodrine versus control for studies of children showed that midodrine had significantly increased odds of symptom response (RR, 1.52; 95% confidence interval, 1.09-2.13, P = 0.01, I 2 = 78%, 4 studies). The pooled result comparing midodrine with beta-blockers in pediatric populations showed that there was a 1.16-fold increase in odds for symptom response compared with beta-blockers (RR, 1.16; 95% confidence interval, 1.02-1.32, P = 0.02, I 2 = 0%, 4 studies). Hypertension was reported in 3 studies to occur in 8.2% of patients (7/85). Gastrointestinal disturbance was reported in 4 studies and it occurred in 3.4% of patients (6/175). The evidence for midodrine efficacy in patients with POTS is limited, particularly in adults. Additional studies are needed to better understand which patients may benefit the most. Midodrine may be considered as a second-line or third-line therapy in patients who remain symptomatic particularly if an enhancement of vascular tone or preload is desired. The use of midodrine in older patients with hypertension should be discouraged.

Abstract: Sinus tachycardia is common after heart transplantation (HTx) and may worsen graft function through increased oxygen demand and remodeling. Ivabradine, a selective If channel inhibitor, lowers heart rate (HR) independently of sympathetic activity. This meta-analysis evaluates its efficacy and safety versus standard care in HTx recipients. A comprehensive search of PubMed, Embase, WoS, Scopus, and Cochrane was conducted through September 2025. Eligible studies included randomized and nonrandomized comparative trials. Data were pooled with a random-effects model to estimate mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes. Six studies, including 852 adult HTx recipients, were included. Ivabradine consistently reduced HR across all time points. Statistical significance was reached at 24 months (MD -16.82 bpm; P = 0.04) and 36 months (MD -12.94 bpm; P = 0.04). A significant reduction was observed in left ventricular mass index (MD -11.10 g/m 2 ; 95% confidence interval -17.15 to -5.06; P < 0.05; I^2 = 0%). While left ventricular mass (LVM) and left ventricular ejection fraction (LVEF) showed trends toward improvement at the final follow-up (MD = -11.23 for LVM and +2.94% for LVEF), neither reached statistical significance ( P = 0.06 and P = 0.48, respectively). No significant differences were found between the ivabradine and control groups regarding all-cause mortality (RR 1.16 at the final follow-up; P = 0.90), graft rejection (RR 1.14; P = 0.87), or systolic blood pressure (MD 0.50 mm Hg; P = 0.83). Ivabradine lowers HR after HTx but shows no clear benefit on mortality, rejection, or ejection fraction. It does not significantly affect blood pressure, supporting its tolerability, particularly when beta-blockers are not tolerated.

Objective: The aim of the study was to investigate the prognostic value of previously established ceramide-phospholipid risk score, CERT2, and its response to lipid-lowering treatments in patients with symptomatic or suspected coronary heart disease.

Approach and results: Selected ceramides and phospholipids were analyzed with a quantitative liquid chromatography-mass spectrometry-based method from plasma or serum samples obtained from the Angiography and Genes study (ANGES, N = 966), and placebo-controlled trials investigating atorvastatin and simvastatin (N = 44) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor RG7652 (N = 78). In the ANGES, the adjusted hazard ratios (95% confidence interval) per SD for the CERT2 risk score were 1.71 (1.42-2.08) for cardiovascular disease death, 1.36 (1.13-1.64) for myocardial infarction, 1.40 (1.20-1.63) for heart failure, 1.23 (1.08-1.40) for atrial fibrillation, 1.09 (0.89-1.33) for stroke, and 1.52 (1.06-2.18) for venous thromboembolism. The median decrease of the CERT2 risk score was 2 points by statin treatment ( P ≤ 0.001) and 3 points by PCSK9 inhibition ( P < 0.001) on the 0-12 scale.

Conclusions: The CERT2 risk score is a significant predictor of cardiovascular outcomes in all-comer patients with symptomatic or suspected coronary heart disease. Treatment with lipid-lowering medication significantly lowers the CERT2 risk score.

Abstract: Severe hypertriglyceridemia (sHTG) is a critical metabolic disorder that substantially elevates the risk of atherosclerotic vascular disease and acute pancreatitis. Despite its clinical significance, many conventional triglyceride-lowering therapies often fail to adequately reduce triglyceride levels or prevent these life-threatening complications. This unmet need has spurred interest in targeting regulatory proteins involved in triglyceride metabolism, such as apolipoprotein C3, a key inhibitor of lipoprotein lipase activity that promotes triglyceride-rich lipoprotein accumulation. Plozasiran, an investigational small interfering RNA therapy, has emerged as a breakthrough in sHTG management by selectively degrading hepatic APOC3 messenger RNA. Indeed, clinical trials demonstrate this drug's robust efficacy in reducing triglyceride levels, concomitant with reduced non-high-density lipoprotein (HDL) cholesterol and apolipoprotein B-key markers of cardiovascular risk. Notably, the Phase III PALISADE trial in familial chylomicronemia syndrome patients revealed plozasiran's potential to mitigate acute pancreatitis risk by normalizing triglyceride levels with a favorable safety profile. Current guidelines emphasize a multimodal approach to sHTG, combining dietary restriction of fats and simple carbohydrates with pharmacotherapy. However, plozasiran's prolonged dosing interval and mechanism-based action position it as a transformative option, particularly for patients refractory to existing treatments. Although long-term cardiovascular outcome data remain pending, its ability to durably modulate APOC3 expression offers new hope for breaking the cycle of dyslipidemia-driven organ damage. As research progresses, this therapy may redefine standards of care for high-risk populations, bridging a critical gap in preventive cardiology and pancreatology.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin agonists are now familiar drugs in obesity, diabetes, heart failure, and cardiovascular prevention. At the same time, a clinically relevant but molecule-specific human literature suggests that selected incretin-based therapies, particularly semaglutide for alcohol-related outcomes, may also modify alcohol use, tobacco use, and selected acute substance-related events. Alcohol currently has the strongest signal. Small randomized studies suggest semaglutide can reduce laboratory alcohol self-administration and craving, whereas an earlier exenatide trial was neutral overall but suggested benefit in participants with obesity. Large registry and EHR studies further associate GLP-1RA exposure with lower alcohol-related hospitalization, lower incident or recurrent alcohol use disorder, and lower alcohol-related event rates. Tobacco evidence is more limited but now includes a pilot smoking-cessation trial with exenatide and a target-trial emulation linking semaglutide with fewer tobacco use disorder-related healthcare encounters. Evidence beyond alcohol and tobacco, and tirzepatide specific evidence, remains preliminary, although lower rates of opioid overdose, alcohol intoxication, and cannabis use disorder have been reported in observational analyses. For cardiologists, the key question is not whether incretin therapies should be viewed as addiction drugs, but whether established cardiometabolic therapies may also modify cardiovascular relevant risk behaviors.

Cardiomyopathy is a major cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Myocardial injury begins during a prolonged subclinical phase while left ventricular ejection fraction (LVEF) remains preserved, suggesting a potential therapeutic window for early cardioprotective intervention. This study evaluated whether cardioprotective pharmacotherapy initiated before overt ventricular dysfunction is associated with improved clinical outcomes in DMD. A systematic review and meta-analysis were conducted following PRISMA guidelines (PROSPERO: CRD420261353435). Randomized trials and observational studies evaluating early cardioprotective therapy were included. Effect estimates were pooled using random-effects models to account for between-study heterogeneity. Fourteen studies including 1,788 patients were included in the review. Early cardioprotective therapy was associated with a significantly reduced risk of death (HR 0.39, 95% CI 0.23-0.65; I2 = 0%; K = 3, N = 958), as well as a lower risk of clinically meaningful cardiac progression (HR 0.36, 95% CI 0.21-0.62; I2 = 21.5%) and progression to overt left ventricular dysfunction (HR 0.41, 95% CI 0.24-0.70; I2 = 12.0%). In contrast, early therapy was not associated with a significant change in short-term left ventricular ejection fraction (mean difference -0.14%, 95% CI -2.57 to 2.29; I2 = 0%). Early cardioprotective therapy initiated prior to overt ventricular dysfunction is associated with lower mortality and reduced progression of cardiomyopathy in Duchenne muscular dystrophy. These findings support the early initiation of cardioprotective therapy during the subclinical phase of Duchenne cardiomyopathy.

The cardiac sarcomere forms the fundamental contractile unit of the myocardium, and its precise structural and regulatory integrity is essential for normal cardiac function. Over the past several decades, advances in functional and structural biology, as well as molecular genetics, have improved our understanding of how sarcomeric protein dysfunction gives rise to inherited cardiomyopathies. This review combines current knowledge on sarcomere-associated hypertrophic cardiomyopathy and dilated cardiomyopathy, focusing on clinical presentation, genetic basis, and the mechanisms that link pathogenic variants to phenotypic manifestations. We highlight how disease-associated variants in sarcomeric genes, such as MYBPC3 , MYH7 , TNNC1 , TNNI3 and TNNT2 , perturb force generation, calcium handling, and myofilament turnover, ultimately driving hypertrophic or dilated phenotypes through distinct, yet overlapping, molecular cascades. Emerging sarcomere-targeted small molecular and gene therapies are discussed, including small-molecule myosin modulators, RNA-based strategies, and in vivo gene-editing approaches aimed at halting or reversing disease progression. These sarcomere-directed precision therapeutics are promising avenues in the treatment of inherited cardiomyopathies and other cardiovascular diseases.