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Mitochondrial dysfunction plays a critical role in the development and exacerbation of heart failure (HF). Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, influences cardiac energy metabolism. The present study investigated the relationship between serum Drp1 levels and the prognosis of patients with HF across a broad spectrum. Serum Drp1 concentrations were measured using ELISA. The primary outcome was the risk of composite major adverse cardiac events (MACEs), which included instances of cardiac death and HF-related readmissions. To assess the prognostic significance of serum Drp1, a receiver operating characteristic curve was constructed to predict MACE-free survival. Additionally, an optimal threshold value for Drp1 was determined and was used to stratify patients into different risk categories. A total of 256 HF patients were finally included and categorized into two groups based on their serum Drp1 levels, labeled as the low (Drp1 ≤2.66 ng/ml, n=101) and high group (Drp1 >2.66 ng/ml, n=155). Patients with low serum Drp1 concentrations showed impaired heart structure and function, as assessed by echocardiography. The 6-month follow-up results indicated that patients with reduced Drp1 concentrations faced a substantially increased risk of MACEs (21.1% vs. 2.8%; P<0.001). The present study revealed that diminished serum Drp1 concentrations could potentially act as a predictive marker for the prognosis of HF in a broad patient population.
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Background: Acute kidney injury (AKI) is common after cardiac interventional procedures. The prevalence and clinical outcome of AKI in patients with acute myocardial infarction (AMI) after undergoing intra-aortic balloon pump (IABP) implantation remains unknown. The aim of this study was to investigate the incidence, risk factors, and prognosis of AKI in specific patient populations. Methods: We retrospectively reviewed 319 patients with AMI between January 2017 and December 2021 and who had successfully received IABP implantation. The diagnostic and staging criteria used for AKI were based on guidelines from "Kidney Disease Improving Global Outcomes". The composite endpoint included all-cause mortality, recurrent myocardial infarction, rehospitalization for heart failure, and target vessel revascularization. Results: A total of 139 patients (43.6%) developed AKI after receiving IABP implantation. These patients showed a higher incidence of major adverse cardiovascular events (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.06-2.26, p = 0.022) and an increased risk of all-cause mortality (HR: 1.62, 95% CI: 1.07-2.44, p = 0.019). Multivariable regression models found that antibiotic use (odds ratio [OR]: 2.07, 95% CI: 1.14-3.74, p = 0.016), duration of IABP use (OR: 1.24, 95% CI: 1.11-1.39, p < 0.001) and initial serum creatinine (SCr) (OR: 1.01, 95% CI: 1.0-1.01, p = 0.01) were independent risk factors for AKI, whereas emergency percutaneous coronary intervention was a protective factor (OR: 0.35, 95% CI: 0.18-0.69, p = 0.003). Conclusions: AMI patients who received IABP implantation are at high risk of AKI. Close monitoring of these patients is critical, including the assessment of renal function before and after IABP implantation. Additional preventive measures are needed to reduce the risk of AKI in these patients.
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Background: Dynamin-related protein 1 (Drp1) has been demonstrated as a crucial role in mediating the programed cell death and cardiac metabolism through its regulatory of mitophagy in animal studies. However, the clinical values of Drp1 for human cardiac disease remain unknown. This study is aimed to evaluate the diagnostic and prognostic values of serum Drp1 in these patients with heart failure (HF). Methods: The enzyme linked immunosorbent assay (ELISA) was used for measuring serum Drp1 concentrations in 85 cases of HF with preserved ejection fraction (HFpEF) and 86 cases of HF with reduced ejection fraction (HFrEF). The diagnostic value of Drp1 was evaluated using the receiver operating characteristic (ROC) analysis. The composite endpoint was consisted of cardiac death and rehospitalization for HF, and the association between Drp1 and clinical outcomes were further determined. Results: Serum Drp1 concentrations were much higher in HFpEF than that in HFrEF (4.2 ± 3.7 ng/mL vs. 2.6 ± 2.2 ng/mL, p = 0.001) and the ROC analysis demonstrated it as a potential diagnostic biomarker for distinction of the HF phenotypes, with an optimal cutoff point of 3.5 ng/mL (area under the curve (AUC) = 0.659, sensitivity: 45.9%, specificity: 83.7%). Kaplan-Meier survival analysis indicated that a low serum concentration of Drp1 (cut-off value = 2.5 ng/mL, AUC = 0.738) was in relation to poor prognosis of HF. Moreover, binary logistic regression analysis identified the low serum concentration of Drp1 as an independent risk predictor for rehospitalization (odds ratio (OR) = 6.574, p = 0.001) and a composite endpoint (OR = 5.927, p = 0.001). Conclusions: Our findings suggested that low serum concentrations of Drp1 might serve as a predicting biomarker for distinction of HF phenotypes and overall prognosis of HF.
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Objective: Dapagliflozin (DAPA) has been reported to have significant cardiac protective effects on heart failure (HF). However, the dose and time, as well as the underlying mechanisms, for DAPA treatment in acute myocardial infarction (AMI) remain controversial. The aim of this study aimed to assess the efficacy and safety of DAPA treatment along with an increased concentration gradient for AMI and explore the potential mechanisms. Methods: Non-diabetic Sprague-Dawley rats were used for establishing AMI models and then were treated with three different concentrations of DAPA [0.5 mg/kg, 1 mg/kg and 1.5 mg/kg, described as AMI+DAPA Low, AMI+DAPA Medium (Med) and AMI+DAPA High, respectively] for six weeks from the onsetting of AMI. Echocardiography, histological staining and Western blot were performed to assess the relevant cardiac protective effects. Mitochondrial biogenesis and myocardial apoptosis were evaluated via the electron microscopy and TUNEL assay, respectively, as well as the Immunoblotting. In vitro, H9c2 cells were subjected to hypoxic treatment to assess the efficacy of DAPA on mitochondrial biogenesis and apoptosis. Results: The medium dose of DAPA treatment could significantly reduce the infarct size (P < 0.01) and the echocardiography results showed that the MI-induced damage in cardiac function got partly repaired, showing no significant difference in left ventricle ejection fraction (LVEF) versus the Sham group (Sham vs AMI+DAPA Med group: 70.47% vs 61.73%). The Western blotting results confirmed the relevant benefits and the underlying mechanisms might be through the activation of PGAM5/Drp1 signaling pathway to normalize the mitochondrial fission and reduce cardiomyocyte apoptosis. Moreover, a medium dose of DAPA treatment could avoid increased damage to the bladder endothelium following higher treatment doses. Conclusion: Appropriate dose of DAPA treatment could improve the cardiac remodeling and reduce the cardiomyocyte apoptosis after AMI, without increased damage to bladder endothelium, which might be more preferred for MI patients without diabetes.
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Dinámicas Mitocondriales , Infarto del Miocardio , Animales , Apoptosis , Compuestos de Bencidrilo , Glucósidos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
WHAT IS KNOWN AND OBJECTIVE: It is well known that high in-stent thrombotic risk due to the superimposition of a platelet-rich thrombus was considered as the main origin of major adverse cardiac events after stent implantation. The clinical management of antiplatelet therapy strategy after percutaneous coronary intervention (PCI) remains controversial. This study is sought to explore the efficacy and safety of a maintained P2Y12 inhibitor monotherapy after shorter-duration of dual antiplatelet therapy (DAPT) in these patients. METHODS: Medline, Google Scholar, Web of Science, and the Cochrane Controlled Trials Registry were searched online for retrieving eligible citations. A composite of all-cause death, myocardial infarction (MI) and stroke was defined as major adverse cardio- and cerebro-vascular events (MACCE), which is analysed as the primary efficacy endpoint. The risk of bleeding events was chosen as safety endpoint. RESULTS: Five randomized clinical trials (RCT) with 32,143 patients were finally analysed. A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT cloud not only reduce the incidence of MACCE [odds ratios (OR): 0.89, 95% confidence intervals (CI): 0.79-0.99, p = 0.037], but also the bleeding risk (OR 0.61, 95% CI: 0.44-0.85, p = 0.003). No higher incidence of any ischaemic events, including MI, stroke or definite stent thrombosis (ST) was observed with respect to this new antiplatelet therapy option. CONCLUSIONS: A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT was suggested as a more preferable antiplatelet therapy option in patients undergoing coronary drug-eluting stents (DES) placement. Larger and more powerful randomized trials with precise sub-analyses are still necessary for further confirming these relevant benefits.
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Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Trombosis , Quimioterapia Combinada , Stents Liberadores de Fármacos/efectos adversos , Humanos , Infarto del Miocardio/tratamiento farmacológico , Intervención Coronaria Percutánea/métodos , Inhibidores de Agregación Plaquetaria/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Trombosis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: The efficacy and safety of ticagrelor following percutaneous coronary intervention for patients with acute coronary syndrome remains unclear. This study sought to evaluate clinical outcomes of ticagrelor as part of dual-antiplatelet treatment for these patients. METHODS: PubMed, MEDLINE, Embase, and other Internet sources were searched for eligible citations. The primary end point was major adverse cardiovascular and cerebrovascular events, consisting of cardiovascular death, myocardial infarction, and stroke. The secondary end point was the occurrence of definite/probable stent thrombosis (ST). The risk of bleeding was chosen to be the safety end point. RESULTS: Eleven clinical trials - six randomized trials and five observational trials - were finally analyzed. A tendency toward reduction in the risk of major adverse cardiovascular and cerebrovascular events was observed only with respect to ticagrelor (OR 0.83, 95% CI 0.66-1.03; P=0.091), which might have resulted from the lower risk of cardiovascular death (OR 0.78, 95% CI 0.68-0.89; P<0.001). The overall incidence of ST differed significantly between the ticagrelor group and the clopidogrel group (OR 0.74, 95% CI 0.59-0.93; P=0.009), but the risk of bleeding, regardless of major or minor bleeding, increased significantly. CONCLUSION: As part of dual-antiplatelet treatment following percutaneous coronary intervention, ticagrelor significantly reduced the risk of cardiovascular death and ST in acute coronary syndrome patients, but at the cost of bleeding. More powerful relevant randomized trials are still warranted to guide clinical decision-making.
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Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/cirugía , Clopidogrel/uso terapéutico , Intervención Coronaria Percutánea , Ticagrelor/uso terapéutico , Clopidogrel/administración & dosificación , Humanos , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Ticagrelor/administración & dosificaciónRESUMEN
MicroRNA-210 (miRNA-210) has been reported to be associated with angiogenesis and may serve important roles in acute myocardial infarction (AMI), which remain unclear. The present study sought to evaluate the efficacy of miRNA210 in AMI and to examine the potential associated mechanisms. AMI models were established in SpragueDawley rats. The expression of miRNA210 was upregulated via transfection with lentivirusmediated agonists and quantitative analysis was performed using the reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Immunoblotting and RTqPCR were separately used to detect the expression levels of hepatocyte growth factor (HGF) in heart samples, while only the protein expression level of ßmyosin heavy chain (ßMHC) was assessed. The expression of HGF in human umbilical vein endothelial cells under hypoxic conditions was silenced by transfecting with small interfering RNA, as demonstrated by the determination of associated protein expression levels. The microvessel density (MVD) of the infarcted myocardium was selected to be the angiogenesis efficacy endpoint, which was evaluated by platelet endothelial cell adhesion molecule immunostaining. Markedly increased expression of HGF was observed among the AMI rats receiving miRNA210 agonists, demonstrated via quantitative analyses using RTqPCR or western blotting. Promotion of angiogenesis was observed with the increased MVD. Improved cardiac function in the rats was subsequently noted, as they exhibited improved left ventricular fractional shortening and left ventricular ejection fraction percentages, which may result from improved cardiac contractility indicated by attenuating the increase in ßMHC protein expression. Overexpression of miRNA210 appeared to be an advantageous therapeutic tool for treating AMI, primarily due to its promoting effects on angiogenesis in the infarcted myocardium by stimulating HGF expression and inducing improved left ventricular remodeling, leading to improved cardiac function.
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MicroARNs/genética , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Neovascularización Patológica/genética , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Ecocardiografía , Regulación de la Expresión Génica , Pruebas de Función Cardíaca , Factor de Crecimiento de Hepatocito/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Infarto del Miocardio/fisiopatología , RatasRESUMEN
OBJECTIVE: The effects of intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation in patients with complex coronary artery lesions remains to be controversial. This study sought to evaluate the outcomes of IVUS guidance in these patients. METHODS: The EMBASE, Medline, and other internet sources were searched for relevant articles. The primary endpoint was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction (MI), and target-vessel revascularization (TVR). The incidence of definite/probable stent thrombosis (ST) was analyzed as the safety endpoint. RESULTS: Fifteen clinical trials involving 8.084 patients were analyzed. MACE risk was significantly decreased following IVUS-guided DES implantation compared with coronary angiography (CAG) guidance (odds ratio [OR] 0.63, 95% confidence intervals [CI]: 0.53-0.73, p<0.001), which might mainly result from the lower all-cause mortality risk (OR 0.52, 95% CI: 0.40-0.67, p<0.001), MI (OR 0.70, 95% CI: 0.56-0.86, p=0.001), and TVR (OR 0.53, 95% CI: 0.40-0.70, p<0.001). The subgroup analyses indicated better outcomes of IVUS guidance in DES implantation for these patients with left main disease or bifurcation lesions. CONCLUSION: IVUS guidance in DES implantation is associated with a significant reduction in MACE risk in patients with complex lesions, particularly those with left main disease or bifurcation lesions. More large and powerful randomized trials are still warranted to guide stenting decision making.
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Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Ensayos Clínicos como Asunto , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Humanos , Intervención Coronaria Percutánea , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: The optimal antiplatelet regimen after in-coronary intervention among patients presenting with complex coronary artery lesions or acute coronary syndrome (ACS) has remained unclear. This study sought to evaluate the clinical outcomes of triple antiplatelet treatment (TAPT) (cilostazol added to aspirin plus clopidogrel) in these patients. METHODS: The PubMed, EMBASE, MEDLINE, and other Internet sources were searched for relevant articles. The primary end point was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction, and target vessel revascularization. The incidence of definite/probable stent thrombosis and bleeding were analyzed as the safety end points. RESULTS: Eleven clinical trials involving 9,553 patients were analyzed. The risk of MACE was significantly decreased following TAPT after stent implantation in the ACS subgroup (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.61-0.85; P<0.001), which might mainly result from the lower risk of all-cause mortality in this subset (OR: 0.62; 95% CI: 0.48-0.80; P<0.001). The risk of bleeding was not increased with respect to TAPT. CONCLUSION: TAPT after stent implantation was associated with feasible benefits on reducing the risk of MACE, especially on reducing the incidence of all-cause mortality among patients suffering from ACS, without higher incidence of bleeding. Larger and more powerful randomized trials are still warranted to prove the superiority of TAPT for such patients.
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Stents/efectos adversos , Ensayos Clínicos como Asunto , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The effects of intra-aortic balloon pump (IABP) usage in patients with acute myocardial infarction remain controversial. This study sought to evaluate the outcomes of IABP usage in these patients. METHODS: Medline, EMBASE, and other internet sources were searched for relevant clinical trials. The primary efficacy endpoints (in-hospital, midterm, and long-term mortality) and secondary endpoints (reinfarction, recurrent ischemia, and new heart failure in the hospital) as well as safety endpoints (severe bleeding requiring blood transfusion and stroke in-hospital) were subsequently analyzed. RESULTS: Thirty-three clinical trials involving 18,889 patients were identified. The risk of long-term mortality in patients suffering from acute myocardial infarction was significantly decreased following IABP use (odds ratio [OR] 0.66, 95% confidence interval [CI]: 0.48-0.91, P=0.010). Both in-hospital and midterm mortality did not differ significantly between the IABP use group and no IABP use group (in-hospital: OR 0.87, 95% CI: 0.59-1.28, P=0.479; midterm: OR 1.12, 95% CI: 0.53-2.38, P=0.768). IABP insertion was not associated with the risk reduction of reinfarction, recurrent ischemia, or new heart failure. However, IABP use increased the risk of severe bleeding requiring blood transfusion (OR 2.05, 95% CI: 1.29-3.25, P=0.002) and stroke (OR 1.71, 95% CI: 1.04-2.82, P=0.035). In the thrombolytic therapy and cardiogenic shock subgroups, reduced mortality rates following IABP use were observed. CONCLUSION: IABP insertion is associated with feasible benefits with respect to long-term survival rates in patients suffering from acute myocardial infarction, particularly those suffering from cardiogenic shock and receiving thrombolytic therapy, but at the cost of higher incidence of severe bleeding and stroke.
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The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation. Medline, the Cochrane Library, and other Internet sources were searched for clinical trials comparing the efficacy and safety of triple vs dual therapy for patients taking OAC after coronary stenting. Sixteen eligible trials including 9185 patients were identified. The risks of major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.82-1.39, P = 0.65), all-cause mortality (OR: 0.98, 95% CI: 0.76-1.27, P = 0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77-1.31, P = 0.97), and stent thrombosis (OR: 0.91, 95% CI: 0.49-1.69, P = 0.75) were similar between triple and dual therapy. Compared with dual therapy, triple therapy was associated with a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35-0.94, P = 0.03) but with higher major bleeding (OR: 1.52, 95% CI: 1.11-2.10, P = 0.01) and minor bleeding (OR: 1.59, 95% CI: 1.05-2.42, P = 0.03). Subgroup analysis indicated there were similar ischemic stroke and major bleeding outcomes between triple therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel was associated with similar efficacy and safety outcomes compared with triple therapy. Triple therapy could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events.