Cardiovascular Drugs and Therapy最新文献

Purpose: Hydrogen sulfide (H₂S) secreted by perivascular adipose tissue (PVAT) is a critical vasodilator, which might be involved during the pathogenesis of hypertension. The present study aimed to investigate the exact role of H₂S on the regulation of PVAT anti-contraction by long-term exercise in obesity hypertension.

Methods: After the establishment of obesity hypertension (24 weeks) through a high-fat diet, male Sprague-Dawley rats were randomly assigned to control group (HC), exercise group (HE), cystathionine γ-lyase (CSE) blocking group (HCB), and exercise combined with CSE blocking group (HEB). Exercise and CSE inhibitor regimens were performed throughout 13 weeks.

Results: After 13 weeks of intervention, blood pressure was significantly decreased by long-term exercise (HC vs. HE, P < 0.05) but not by exercise combined with the CSE inhibitor regimen. Meanwhile, the CSE inhibitor significantly blocked the production of H₂S in PVAT even after exercise (HE vs. HEB, P < 0.05). Furthermore, long-term exercise altered the expressions of voltage-dependent K⁺ (K_v) channel subunits 7 (KCNQs), which were diminished by CSE inhibition in mesenteric arteries. As for vascular tension assessment, after incubation with or without KCNQ opener (retigabine), the anti-contractile effect of PVAT (with or without transferred bath solution of PVAT) was significantly enhanced by long-term exercise and eliminated by the CSE inhibitor regimen (P < 0.05); KCNQ inhibitor (XE991) blunted this effect except for HE.

Conclusions: These results collectively suggest that endogenous H₂S is a strong regulator of the anti-contractile effect of PVAT in obesity hypertension by long-term exercise, and KCNQ in the resistance artery might be involved during this process but not the only target channel mediated by H₂S.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improved knowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management of cardiac risk. Although most reviews focus on the cardiotoxic effect of a specific individual chemotherapeutic agent, the aim of our review is to provide comprehensive insight into various agents that induced cardiotoxicity and their underlying mechanisms. Characterization of these mechanisms are underpinned by research on animal models and clinical studies. In order to gain insight into these complex mechanisms, we emphasize the role of inflammatory processes and oxidative stress on chemotherapy-induced cardiac changes. A better understanding and identification of the interplay between chemotherapy and inflammatory/oxidative processes hold some promise to prevent or at least mitigate cardiotoxicity-associated morbidity and mortality among cancer survivors.

Introduction: This study aims to compare the addition of SGLT2 inhibitors or doubling the diuretic dose in patients receiving treatment with beta-blockers, angiotensin-converting enzyme inhibitors (ACEi), or angiotensin receptor blockers (ARB), as well as mineralocorticoid receptor antagonists (MRA), for heart failure with reduced ejection fraction (HFrEF) who present to the emergency department with decompensated heart failure.

Methods: This study is a single-center and prospective analysis. A total of 980 decompensated heart failure (HFrEF) patients receiving optimal medical therapy (OMT) according to the 2021 European heart failure guidelines were randomized in a 2:1 ratio into the furosemide and empagliflozin treatment arms. The analysis includes patient clinical characteristics, laboratory results, and echocardiographic data. Factors influencing rehospitalization were identified through multivariate Cox regression analysis. Log-rank analysis was employed to assess factors affecting rehospitalization.

Results: The mean age of the patients was 67.9 years, with 52.1% being men. There was no significant impact of demographic, clinical, or echocardiographic factors on rehospitalization at 1 month; only the effect of treatment subgroups on rehospitalization was observed (p = 0.039). Significant echocardiographic and clinical improvements were seen in both treatment arms. The empagliflozin group exhibited significant improvements in 6-min walk distance, heart rate, body weight, NT-pro BNP levels, and eGFR level compared to the furosemide group. The rate of rehospitalization in the first month was significantly lower in those receiving empagliflozin (28.7%) compared to those receiving a double dose of furosemide (40.2%) (log-rank p = 0.013).

Discussion and conclusion: This study provides valuable insights into the management of decompensated HFrEF and demonstrates that SGLT2 inhibitors offer benefits beyond glycemic control in this patient group. The significant reduction in rehospitalization rates and improvements in echocardiographic parameters underscore the potential of SGLT2 inhibitors in reducing acute heart failure episodes.

Purpose: To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI).

Methods: Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart.

Results: The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/β-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2.

Conclusion: LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/β-catenin signaling pathway and then promoting the LSG neuronal apoptosis.

Purpose: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release.

Methods: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice.

Results: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils.

Conclusion: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Purpose: In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined.

Methods: Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation. Patients were stratified by concurrent MR: moderate/severe (PVR + MR) vs. mild/none (PVR - MR). Cumulative incidence functions and Fine-Gray competing risk regression were performed to assess the effect of MR on heart transplant rates and overall survival during index LVAD support.

Results: Of 644 LVAD recipients, 232 (171 HeartMate II, 59 HeartWare, 2 HeartMate III) had baseline PVR > 3 Woods units; of these, 124 (53%) were INTERMACS 1-2, and 133 (57%) had moderate/severe MR (≥ 3 +). Patients with PVR + MR had larger a baseline left ventricular end-diastolic diameter than patients with PVR - MR (87.9 ± 38.2 mm vs. 75.9 ± 38.0 mm; P = 0.02). Median clinical follow-up was 18.8 months (interquartile range: 4.7-36.4 months). Moderate/severe MR was associated with lower mortality rates during index LVAD support (adjusted hazard ratio 0.64, 95% CI 0.41-0.98; P = 0.045) and higher heart transplant rates (adjusted odds ratio 2.86, 95% CI 1.31-6.25; P = 0.009). No differences in stroke, gastrointestinal bleeding, or right heart failure rates were observed.

Conclusions: Among LVAD recipients with elevated preoperative PVR, those with moderate/severe MR had better overall survival and higher transplant rates than those with mild/no MR. These hypothesis-generating findings could be explained by incremental LVAD benefits resulting from reduction of MR and better LV unloading in a subset of patients with larger ventricles at baseline. In patients with preoperative elevated PVR, MR severity may be a prognostic sign that can inform patient selection for end-stage heart failure therapy.

Aims: The present meta-analysis focused on investigating whether bivalirudin plus post-PCI infusion was safer and more effective than heparin monotherapy in patients who developed ST-segment elevation myocardial infarction (STEMI) and who underwent primary percutaneous coronary intervention (PCI).

Methods: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were systemically searched to identify randomized controlled trials (RCTs) comparing bivalirudin and heparin for treating STEMI patients who underwent primary PCI. The Cochrane quality assessment tool was used to assess the quality of the enrolled studies. The primary and secondary outcomes included net adverse clinical events (NACEs, comprising all-cause death or major bleeding), major adverse cardiovascular events (MACEs, comprising all-cause death, stroke, MI, and TVR), in-stent thrombosis (IST), and bleeding of Bleeding Academic Research Consortium (BARC) types 2, 3, and 5.

Results: The four RCTs, comprising 10,695 events, included 5350 patients who received bivalirudin combined with post-PCI infusion and 5345 patients who received heparin monotherapy. Compared with those in the heparin group, the number of NACEs (RR 0.84, 95% CI 0.73-0.96, P = 0.009), MACEs (RR 0.82, 95% CI 0.67-0.99, P = 0.04), and ISTs (RR 0.66, 95% CI 0.49-0.91, P < 0.0001) in the bivalirudin group was significantly lower. There were no significant differences in all-cause death, cardiac death, stroke, MI, TVR, or BARC type 2, 3, or 5 bleeding between the two groups.

Conclusion: In STEMI patients undergoing primary PCI, bivalirudin plus post-PCI infusion significantly reduced the incidence of NACEs, MACEs, and ISTs compared with heparin monotherapy, without increasing the risk of MI or TVR. Bivalirudin may also contribute to a potential reduction in stroke, death, and BARC type 2, 3, and 5 bleeding rates.

Purpose: Intermediate-high-risk pulmonary embolism (IHR PE) is a challenging form of embolism obstruction that causes right ventricular (RV) dysfunction. The optimal management of IHR PE has not been established. This single-center prospective, observational study aimed to evaluate the efficacy and safety of complex catheter-directed therapy (CDT) - catheter-directed mechanical aspiration thrombectomy (CDMT) supplemented with catheter-directed thrombolysis (hybrid CDT) in comparison to CDMT alone for IHR PE.

Methods: A propensity score based on the pulmonary embolism severity index class and Miller obstruction index (MOI) was calculated, and 21 hybrid CDT cases (mean age 54.8 (14.7) years, 9/21 women) were matched with 21 CDMT cases (mean age 58.8 (14.9) years, 13/21 women). The baseline demographics, clinical, and treatment characteristics were analyzed.

Results: No significant differences were detected regarding baseline demographics and PE severity parameters. Hybrid CDT demonstrated a higher reduction in mean pulmonary artery pressure (mPAP) (hybrid CDT: median mPAP reduction 8 mmHg (IQR: 6-10 mmHg) vs CDMT: median mPAP reduction 6 mmHg (IQR: 4-7 mmHg); P = 0.019), MOI score (hybrid CDT: median change - 5 points (IQR: 5-6 points) vs CDMT median change - 3 points (IQR: 3-5 points); P = 0.019), and median RV: left ventricular ratio (hybrid CDT: median change 0.4 (IQR: 0.3-0.45) vs CDMT median change 0.26 (IQR: 0.2-0.4); P = 0.007). No major bleeding was observed. Both the hybrid CDT and CDMT alone treatments are safe and effective in managing IHR PE.

Conclusions: Hybrid CDT is a promising technique for the management of IHR PE with insufficient thrombus load reduction by CDMT.

Trial registration: NCT0447356-registration date 16 July 2020.

Background: New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for managing NOAF in this population is uncertain.

Methods: This retrospective cohort study utilized deidentified patient data from the TriNetX Research Network. Patients with TAVR and NOAF were stratified into a rhythm control cohort if they were treated with antiarrhythmics, received AF ablation, or underwent cardioversion within 1 year of AF diagnosis. A rate control cohort was similarly defined by the absence of rhythm control strategies and treatment with a beta blocker, calcium channel blocker, or digoxin. After 1:1 propensity score matching, the Kaplan-Meier survival analysis and Cox proportional hazard ratios (HRs) were used to compare outcomes at 7 years of follow-up.

Results: We identified 569 patients in each cohort following propensity matching. At 7 years, the primary composite outcome of all-cause death, myocardial infarction, cerebrovascular accident, and heart failure hospitalization was not significantly different between the rhythm and rate control cohorts (HR 0.99, 95% CI 0.83-1.18). The individual components of the primary outcome in addition to all-cause hospitalization were also similar between the groups.

Conclusions: Similar outcomes were seen among patients receiving an early rhythm or rate control strategy to manage NOAF after TAVR. The attenuated benefits of an early rhythm control strategy observed in this setting may be due to the overall high burden of comorbidities and advanced age of these patients.