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AIMS: Improvement in left ventricular ejection fraction (impEF) often presents in contemporary acute myocardial infarction (AMI) patients. New-onset atrial fibrillation (NOAF) during AMI is an important predictor of subsequential heart failure (HF), while its impact on the trajectory of post-MI left ventricular ejection fraction (LVEF) and prognostic implication in patients with and without impEF remains undetermined. We aimed to investigate the prognostic impacts of NOAF in AMI patients with and without impEF. METHODS AND RESULTS: Consecutive AMI patients without a prior history of AF between February 2014 and March 2018 with baseline LVEF ≤ 40% and had ≥1 LVEF measurement after baseline were included. ImpEF was defined as a baseline LVEF ≤ 40% and a re-evaluation showed both LVEF > 40% and an absolute increase of LVEF ≥ 10%. Persistently reduced EF (prEF) was defined as the second measurement of LVEF either ≤40% or an absolute increase of LVEF < 10%. The primary endpoint was a major adverse cardiac event (MACE) that was composed of cardiovascular death and HF hospitalization. Cox regression analysis and competing risk analysis were performed to assess the association of post-MI NOAF with MACE. Among 293 patients (mean age: 66.6 ± 11.3 years, 79.2% of males), 145 (49.5%) had impEF and 67 (22.9%) developed NOAF. Higher heart rate (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.73-0.97; P = 0.015), prior MI (OR: 0.25, 95% CI: 0.09-0.69; P = 0.008), and STEMI (OR: 0.40, 95% CI: 0.21-0.77; P = 0.006) were independent predictors of post-MI impEF. Within up to 5 years of follow-up, there were 22 (15.2%) and 53 (35.8%) MACE in patients with impEF and prEF, respectively. NOAF was an independent predictor of MACE in patients with impEF (hazard ratio [HR]: 7.34, 95% CI: 2.49-21.59; P < 0.001) but not in those with prEF (HR: 0.78, 95% CI: 0.39-1.55; P = 0.483) after multivariable adjustment. Similar results were obtained when accounting for the competing risk of all-cause death (subdistribution HR and 95% CIs in impEF and prEF were 6.47 [2.32-18.09] and 0.79 [0.39-1.61], respectively). CONCLUSIONS: The NOAF was associated with an increased risk of cardiovascular outcomes in AMI patients with impEF.
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BACKGROUND: It is well-known that systemic inflammation plays a crucial role in the pathogenesis and prognosis of acute myocardial infarction (AMI). The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a novel index that is used for the characterization of the severity of systemic inflammation. Recent studies have identified the high SII level as an independent predictor of poor outcomes in patients with AMI. We aimed to investigate the prognostic implications of SII in AMI patients with and without diabetes mellitus (DM). METHODS: We included 2111 patients with AMI from February 2014 to March 2018. Multivariable Cox regression analyses were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death and cardiovascular (CV) death. Multiple imputation was used for missing covariates. RESULTS: Of 2111 patients (mean age: 65.2 ± 12.2 years, 77.5% were males) analyzed, 789 (37.4%) had DM. Generalized additive model analyses showed that as the SII increased, the C-reactive protein and peak TnT elevated while the LVEF declined, and these associations were similar in patients with and without DM. During a median of 2.5 years of follow-up, 210 all-cause deaths and 154 CV deaths occurred. When treating the SII as a continuous variable, a higher log-transformed SII was significantly associated with increased all-cause mortality (HR: 1.57, 95%CI: 1.02-2.43) and CV mortality (HR: 1.85, 95%CI 1.12-3.05), and such an association was also significant in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.90 [1.40-6.01] and 3.28 [1.43-7.57], respectively) while not significant in the nondiabetics (Pinteraction for all-cause death and CV death were 0.019 and 0.049, respectively). Additionally, compared to patients with the lowest tertiles of SII, those with the highest tertiles of SII possessed significantly higher all-cause mortality (HR: 1.82, 95%CI 1.19-2.79) and CV mortality (HR: 1.82, 95%CI 1.19-2.79) after multivariable adjustment, and this relationship remained pronounced in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.00 [1.13-3.55] and 2.09 [1.10-3.98], respectively) but was not observed in the nondiabetics (HRs and 95%CIs for all-cause death and CV death were 1.21 [0.75-1.97] and 1.60 [0.89-2.90], respectively). Our restricted cubic splines analyses indicated a pronounced linear association between SII and mortality only in diabetics. CONCLUSIONS: In AMI patients with DM, high SII is an independent predictor of poor survival and may be helpful for patient's risk stratification.
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Diabetes Mellitus , Infarto del Miocardio , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Pronóstico , Infarto del Miocardio/diagnóstico , Inflamación/diagnóstico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Sistema de RegistrosRESUMEN
AIMS: To investigate the predictive value and prognostic impact of stress hyperglycemia ratio (SHR) for new-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI). MATERIALS AND METHODS: This retrospective study included 2145 AMI patients without AF history between February 2014 and March 2018. SHR was calculated using fasting blood glucose (mmol/L)/[1.59*HbA1c (%)-2.59]. The association between SHR and post-MI NOAF was assessed with multivariable logistic regression analyses. The primary outcome was a composite of cardiac death, heart failure hospitalisation, recurrent MI, and ischaemic stroke (MACE). Cox regression-adjusted hazard ratios with 95% confidence intervals (CI) were estimated for MACE. RESULTS: A total of 245 (11.4%) patients developed NOAF. In the multivariable logistic regression analyses, SHR (each 10% increase) was significantly associated with increased risks of NOAF in the whole population (OR: 1.05, 95% CI: 1.01-1.10), particularly in non-diabetic individuals (OR:1.08, 95% CI: 1.01-1.17). During a median follow-up of 2.7 years, 370 (18.5%) MACEs were recorded. The optimal cut-off value of SHR for MACE prediction was 1.119. Patients with both high SHR (≥1.119) and NOAF possessed the highest risk of MACE compared to those with neither high SHR nor NOAF after multivariable adjustment (HR: 2.18, 95% CI: 1.39-3.42), especially for diabetics (HR: 2.63, 95% CI: 1.41-4.91). Similar findings were observed using competing-risk models. CONCLUSIONS: SHR is an independent predictor of post-MI NOAF in non-diabetic individuals. Diabetic patients with both high SHR and NOAF had the highest risk of MACE, suggesting that therapies targeting SHR may be considered in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03533543.
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Fibrilación Atrial , Isquemia Encefálica , Hiperglucemia , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Isquemia Encefálica/complicaciones , Factores de Riesgo , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Hospitales , Hiperglucemia/complicacionesRESUMEN
AIMS: The 4S-AF scheme (Stroke risk [St], Symptom severity [Sy], Severity of atrial fibrillation burden [Sb], Substrate [Su]) is a novel approach for the holistic characterization of AF. We aimed to investigate the prognostic implications of the 4S-AF scheme score in acute myocardial infarction (AMI) patients with new-onset atrial fibrillation (NOAF). METHODS: We included 262 patients with post-MI NOAF who had complete data for the 4S-AF scheme evaluation between February 2014 and March 2018. The 4S-AF scheme score was calculated as a sum of each domain with a maximum of 9. The primary outcome was all-cause death. RESULTS: Of 262 patients (66.0% males, mean age 74.5 ± 10.4 years) were analyzed. The mean 4S-AF scheme score was 5.0 ± 1.6. There were 62 (27.3%) all-cause deaths within a median follow-up of 2.6 years. According to multivariable Cox regression models, each 1-point increase in the 4S-AF scheme score was significantly associated with 39% increased all-cause mortality (HR: 1.39, 95% CI: 1.16-1.67, P<0.001), which was mainly driven by the Sb (HR: 1.43, 95%CI: 1.05-1.95, P = 0.025) and Su (HR: 1.53, 95%CI: 1.17-2.02, P = 0.002) domains. Adding the 4S-AF scheme score on top of the Global Registry of Acute Coronary Events score could significantly improve its discriminative capability (C-index from 0.713 to 0.761, P = 0.039) and reclassification performance (continuous net reclassification improvement: 41.0% [95%CI: 12.5-69.6]; integrated discrimination improvement: 5.1% [95%CI: 2.2-8.1]) for all-cause mortality. CONCLUSIONS: Characterization of NOAF using the 4S-AF scheme aids in the risk stratification of AMI patients with NOAF.
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Fibrilación Atrial , Infarto del Miocardio , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Pronóstico , Fibrilación Atrial/complicaciones , Factores de Riesgo , Infarto del Miocardio/epidemiología , Sistema de RegistrosRESUMEN
Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.
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Fibrilación Atrial , Remodelación Atrial , Infarto del Miocardio , Ratones , Animales , Conexina 43/metabolismo , Fibrilación Atrial/genética , Infarto del Miocardio/patología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Estrés Oxidativo , Ratones Noqueados , Inflamación/genética , Inflamación/complicacionesRESUMEN
Macrophage polarization followed by myocardial infarction (MI) is essential for wound healing. Tripartite motif-containing protein 21 (TRIM21), a member of E3 ubiquitin ligases, is emerging as a mediator in cardiac injury and heart failure. However, its function in modulating post-MI macrophage polarization remains elusive. Here, we detected that the levels of TRIM21 significantly increased in macrophages of wild-type (WT) mice after MI. In contrast, MI was ameliorated in TRIM21 knockout (TRIM21-/-) mice with improved cardiac remodeling, characterized by a marked decrease in mortality, decreased infarct size, and improved cardiac function compared with WT-MI mice. Notably, TRIM21 deficiency impeded the post-MI apoptosis and DNA damage in the hearts of mice. Consistently, the accumulation of M1 phenotype macrophages in the infarcted tissues was significantly reduced with TRIM21 deletion. Mechanistically, the deletion of TRIM21 orchestrated the process of M1 macrophage polarization at least partly via a PI3K/Akt signaling pathway. Overall, we identify TRIM21 drives the inflammatory response and cardiac remodeling by stimulating M1 macrophage polarization through a PI3K/Akt signaling pathway post-MI.
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Lesiones Cardíacas , Infarto del Miocardio , Ratones , Animales , Remodelación Ventricular , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Infarto del Miocardio/metabolismo , Macrófagos/metabolismo , Lesiones Cardíacas/metabolismoRESUMEN
BACKGROUND AND AIMS: Stress hyperglycemia ratio (SHR) is associated with increased in-hospital morbidity and mortality in patients with acute myocardial infarction (AMI). We aimed to investigate the impact of stress "hyperglycemia" on long-term mortality after AMI in patients with and without diabetes mellitus (DM). METHODS AND RESULTS: We included 2089 patients with AMI between February 2014 and March 2018. SHR was measured with the fasting glucose divided by the estimated average glucose derived from glycosylated hemoglobin (HbA1c). The primary endpoint was all-cause death. Of 2 089 patients (mean age: 65.7 ± 12.4, 76.7% were men) analyzed, 796 (38.1%) had DM. Over a median follow-up of 2.7 years, 141 (6.7%) and 150 (7.2%) all-cause deaths occurred in the diabetic and nondiabetic cohorts, respectively. Compared with participants with low SHR (<1.24 in DM; <1.14 in non-DM), the hazard ratios and 95% confidence intervals for those with high SHR (≥1.24 in DM; ≥1.14 in non-DM) for all-cause mortality were 2.23 (1.54-3.23) and 1.79 (1.15-2.78); for cardiovascular mortality were 2.42 (1.63-3.59) and 2.10 (1.32-3.35) in DM and non-DM subjects, respectively. The mortality prediction was improved in the diabetic individuals with the incorporation of SHR into the Global Registry of Acute Coronary Events (GRACE) score, showing an increase in a continuous net reclassification index of 0.184 (95%CI: 0.003-0.365) and an absolute integrated discrimination improvement of 0.014 (95%CI: 0.002-0.025). CONCLUSION: The improvement in the prediction of long-term mortality beyond the GRACE score indicates the potential of SHR as a biomarker for post-MI risk stratification among patients with DM. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT03533543.
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Diabetes Mellitus , Hiperglucemia , Infarto del Miocardio , Biomarcadores , Glucemia/metabolismo , Femenino , Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Pronóstico , Factores de RiesgoRESUMEN
Oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction exerts an essential role in the development of atherosclerosis. Protein Z-dependent protease inhibitor (ZPI), a member of the serine protease inhibitor superfamily, could inhibit the function of activated coagulation factor X (FXa) via interaction with protein Z (PZ). Studies have pointed out that ZPI was statistically related to atherosclerotic diseases, which may have a robust cardiovascular protective effect. However, the underlying mechanism of ZPI on ox-LDL-mediated endothelial injury requires further elucidation. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 µg/ml) and ZPI (10 µg/ml). Cell viability was measured by the Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis, oxidative stress, and endothelial-to-mesenchymal transition (EndMT) were analyzed by immunofluorescence (IF). Cell migration was measured using a wound-healing assay. Quantitative real-time polymerase chain reaction and western blot analysis were performed to determine messenger RNA and protein expression. Ox-LDL (100 µg/ml, 48 h) significantly reduced cell viability and migration, increased EndMT, inflammation, apoptosis, and oxidative stress. The related protein expression of phosphatidylinositol 3 kinase/protein kinase B (Pi3k/Akt) signal pathway in HUVECs was also simultaneously decreased. We also discovered that ZPI treatment could prevent ox-LDL-mediated endothelial injury through the improvement of cell viability and alleviation of apoptosis, oxidative stress, EndMT, and inflammation. Thus, the protective effect of ZPI on HUVECs may be mediated by activation of the Pi3k/Akt signal pathway. ZPI may exert an important protective role in HUVECs dysfunction triggered by ox-LDL via activation of the Pi3k/Akt signal pathway. Therefore, ZPI may possess potential therapeutic effects on atherosclerotic endothelial injury-related diseases.
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Aterosclerosis , Fosfatidilinositol 3-Quinasas , Apoptosis , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Purpose: The prognostic impact of new-onset atrial fibrillation (NOAF) among different heart failure (HF) subtypes including HF with preserved (HFpEF, ejection fraction [EF] ≥50%), mid-range (HFmrEF, EF 40%~49%), and reduced (HFrEF, EF <40%) EF following acute myocardial infarction (AMI) remains unclear. We aimed to investigate the incidence and prognostic implication of post-MI NOAF across HF subtypes. Patients and Methods: We included 1413 patients with post-MI HF (743 with HFpEF, 342 with HFmrEF and 328 with HFrEF) between February 2014 and March 2018. NOAF was considered as patients without a preexisting AF who developed AF during the AMI hospitalization. The primary endpoint was all-cause mortality. Results: Of 1413 patients (mean age 66.8 ± 12.6 years, 72.9% men) analyzed, 200 (14.2%) developed post-MI NOAF. Patients with HFrEF were more likely to experience NOAF compared to those with HFmrEF or HFrEF (18.9%, 13.7% and 12.2% in HFrEF, HFmrEF and HFpEF, respectively; p for trend = 0.006). During a median follow-up of 28.5 months, 192 patients died (70 with HFrEF, 35 with HFmrEF and 87 with HFpEF) and 195 patients experienced HF rehospitalization (79 with HFrEF, 37 with HFmrEF and 79 with HFpEF). After multivariable adjustment, NOAF was independently associated with all-cause mortality (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.03-3.12) only in the HFrEF group compared to sinus rhythm (SR), whereas an increased risk of HF rehospitalization was found in all HF subtypes, particularly in HFmrEF (HR: 5.08, 95% CI: 2.29-11.25) and HFpEF (HR: 2.83 95% CI: 1.64-4.90). Conclusion: In patients with post-MI HF, NOAF carried a worse prognosis for all-cause death in the HFrEF group and for HF rehospitalization in all HF subtypes.
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Fibrilación Atrial , Insuficiencia Cardíaca , Infarto del Miocardio , Anciano , Fibrilación Atrial/complicaciones , Causas de Muerte , Femenino , Humanos , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Pronóstico , Sistema de Registros , Volumen SistólicoRESUMEN
Dissolved organic matter (DOM) is a diverse and highly complex mixture of organic macromolecules, and thus plays a central role in aquatic ecosystems. However, responses of components and sources of DOM to hydrological processes and trophic levels (nutrient stoichiometric ratios) are poorly understood, particularly in monsoonal headwater streams of Asia that are vulnerable to catchment physical characteristics. In this study, the excitation - emission matrix florescence spectroscopy coupled with parallel factor analysis (EEM-PARAFAC) was used to explore the DOM characters in a headwater stream, where seasonal rainfalls and nutrient levels vary largely. The EEM-PARAFAC modelling identified one autochthonous protein-like fluorescence substance (C1) and two allochthonous fulvic- and humic-like fluorescence compounds (C2 and C3). The allochthonous compounds dominated the overall DOM signal in the headwaters. The hydrological seasonality coupled with nutrients was key in modulating headwater DOM sources and components. Seasonal rainfall events contributed more allochthonous terrestrial-derived DOM flushing into river waters, resulting in higher fulvic- and humic-like organic matter (C2 + C3) in the wet season. In the dry season, longer water residence time accompanying with higher C:P stoichiometric ratio was responsible for higher autochthonous microbial- and plant-derived DOM (tryptophan and tyrosine fractions), also reflected by higher C1, biological index (BIX) and freshness index (ß:α). In-stream microbial metabolism of labile DOM fractions largely contributed to autochthonous DOM and partial pressure CO2 increase in the headwater stream. Our findings indicate that quality and quantity of DOM in headwater streams play a crucial role in downstream carbon cycle. Furthermore, the evidence combined from PARAFAC components, pCO2 and spectral slope clearly highlights the importance of microbial metabolism of carbon in lotic systems, especially during a dry season with increased residence time.
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Materia Orgánica Disuelta , Ecosistema , Asia , Hidrología , NutrientesRESUMEN
Background: New-onset atrial fibrillation (NOAF) is a common complication during acute myocardial infarction (AMI) and sometimes can be completely asymptomatic, but the clinical implications of these asymptomatic episodes require further characterization. The objective of this study was to investigate the short- and long-term prognostic impact of post-MI NOAF based on the presence of AF-related symptoms. Methods: The New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai (NOAFCAMI-SH) registry was a retrospective cohort including participants with AMI without a documented history of AF. Patients with NOAF were divided into two groups according to the AF-related symptoms. The primary endpoint was all-cause mortality. Results: Of 2,399 patients included, 278 (11.6%) developed NOAF of whom 145 (6.0%) with asymptomatic episodes and 133 (5.5%) with symptomatic ones. During hospitalization, 148 patients died [106, 10, and 32 in the sinus rhythm (SR), asymptomatic, and symptomatic NOAF groups, respectively]. After multivariable adjustment, only symptomatic NOAF was associated with in-hospital mortality [odds ratio (OR): 2.32, 95% confidence interval (CI): 1.36-3.94] compared with SR. Over a median follow-up of 2.7 years, all-cause mortality was 3.2, 12.4, and 11.8% per year in the SR, asymptomatic, and symptomatic NOAF groups, respectively. After adjustment for confounders, it was the asymptomatic NOAF [hazard ratio (HR): 1.61, 95% CI: 1.09-2.37) rather than the symptomatic one (HR: 1.37, 95% CI: 0.88-2.12) that was significantly related to mortality. Similar results were also observed for cardiovascular mortality [HRs and 95% CI were 1.71 (1.10-2.67) and 1.25 (0.74-2.11) for asymptomatic and symptomatic NOAF, respectively]. Both asymptomatic and symptomatic NOAF episodes were associated with heart failure, whereas only those with symptomatic NOAF were at heightened risk of ischemic stroke. Our exploratory analysis further identified patients with asymptomatic high-burden NOAF as the highest-risk population (mortality: 19.6% per year). Conclusion: Among patients with AMI, symptomatic NOAF is related to in-hospital mortality and asymptomatic NOAF is associated with poor long-term survival. Registration: URL: https://clinicaltrials.gov/; Unique identifier: NCT03533543.
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PURPOSE: LAAO has been an alternative therapy to oral anticoagulants (OACs) for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF) with elevated CHA2DS2-Vasc score, but the long-term outcomes of LAAO and its impacts on cardiac electrical and mechanical remodeling remain to be learned. We aimed to describe the impact of left atrial appendage occlusion (LAAO) on atrial remodeling and cardiovascular outcomes within 5-year follow-up. PATIENTS AND METHODS: A total of 107 patients with nonvalvular atrial fibrillation (NVAF) undergoing LAAO in the Shanghai Tenth People's Hospital between January 2014 and July 2017 were included. All participants were followed for ECG, transthoracic echocardiography (TTE), and clinical outcomes (including cardiovascular death, heart failure, ischemic stroke/systemic embolism, and pericardial effusion) at 6 and 12 months, and thereafter every 12 months after LAAO discharge until 5 years. RESULTS: After LAAO, the left atrial diameter significantly increased at 6 months (48.6 ± 6.7 vs 46.5 ± 7.0 mm); heart rate decreased immediately after the procedure (78.5 ± 14.7 vs 85.3 ± 21.7 bpm) when compared with the pre-procedure level. The QTc interval prolongated to the highest value of 460.7 ± 46.8 ms at 6 months (pre-procedure level of 433.7±49.0 ms). All these changes return to the pre-procedure level within the follow-up. For clinical outcomes, 51 patients suffered the composite of cardiovascular death (n=4, 3.7%), heart failure (n=25, 23.4%), ischemic stroke/systemic embolism (n=22, 20.6%), and pericardial effusion (n=26, 26.2%). CONCLUSION: LAAO did not change ECG or TTE characteristics and nonprocedure-related pericardial effusion is common during long-term follow-up. Further studies are warranted to investigate the optimal time frame of anticoagulation in patients undergoing LAAO.
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Apéndice Atrial/cirugía , Fibrilación Atrial/cirugía , Remodelación Atrial/fisiología , Procedimientos Quirúrgicos Cardíacos/métodos , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/epidemiología , China , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/prevención & control , Resultado del TratamientoRESUMEN
The pathogenesis of acute myocardial infarction (AMI) is associated with cardiomyocyte necrosis and apoptosis. Numerous studies have determined the regulatory effects of Phosphatase and tensin homolog (PTEN) cell proliferation and apoptosis in other cell types. However, the potential role of PTEN in cardiomyocyte is unclear. In this study, we used H9c2 cells cultured under serum deprivation to simulate the apoptosis process of myocardial infarction. Small interference RNA (siRNA) of PTEN was used to knock down the expression of PTEN. Cell viability was determined by CCK-8. Cell proliferation was examined by Edu staining, and the protein expression was analyzed by Western blot. We also evaluated the generation of ROS, the degree of DNA damage, and cell apoptosis using immunofluorescence assay. As a result, we observed that serum deprivation in H9c2 cells increased PTEN expression. Functionally, the PTEN knockdown experiment using siRNA inhibited serum deprivation-induced cell apoptosis, ROS production, and DNA damage, whereas increased cell proliferation. All these effects could be reversed by phosphatidylinositol 3-kinase (PI3K) inhibitor, which indicated the PI3K/protein kinase B (AKT) might be the critical component of the PTEN effects during serum deficiency. In conclusion, our study indicated the role of the PTEN/PI3K/AKT pathway in serum deprivation-induced cytotoxicity in H9c2 cells.
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Técnicas de Cultivo de Célula , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Suero , Animales , Apoptosis , Línea Celular , Supervivencia Celular , Daño del ADN , Miocitos Cardíacos/metabolismo , Fosfohidrolasa PTEN/genética , Ratas , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
AIMS: We aimed to investigate the prognostic impact of the burden of new-onset atrial fibrillation (NOAF) on long-term cardiovascular outcomes in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective analysis consecutively included patients without a documented atrial fibrillation (AF) history who admitted for AMI at Shanghai Tenth People's Hospital between February 2014 and March 2018. Atrial fibrillation burden was measured as the percentage of time spent in AF, and its optimal cut-off value of 10.87% was identified by X-tile software. Of 2399 patients (mean age: 65.8 years, 76.6% of men), 278 (11.6%) developed NOAF during hospitalization. During a median follow-up of 2.7 years, the incidence of all-cause death was 3.19, 9.00, and 17.41 per 100 person-years in the sinus rhythm (SR), low-burden (AF burden ≤ 10.87%), and high-burden (AF burden > 10.87%) groups, respectively. After adjustment for confounders, it was the high-burden NOAF [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.28-2.95] rather than the low-burden one (HR: 1.47, 95% CI: 0.97-2.21) that was significantly associated with increased mortality compared with SR. Concordant results were obtained in our propensity score-matched analyses [2.55 (1.57-4.16) and 1.32 (0.85-2.05) for high- and low-burden NOAF, respectively). In addition, post-myocardial infarction NOAF was associated with an increased risk of heart failure irrespective of its burden. Only those high-burden individuals were at heightened risk of ischaemic stroke. The restricted cubic spline curves illustrated a dose-response relationship of NOAF burden with outcomes. CONCLUSION: In patients with NOAF complicating AMI, high AF burden was strongly associated with long-term outcomes.
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Fibrilación Atrial , Isquemia Encefálica , Infarto del Miocardio , Accidente Cerebrovascular , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , China/epidemiología , Humanos , Masculino , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Sistema de Registros , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.
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Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Animales , Apoptosis/genética , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Citometría de Flujo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
AIMS: New-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on heart failure (HF) is still not well characterized. We aimed to investigate the relationship between NOAF complicating AMI and HF hospitalization. METHODS AND RESULTS: Adult AMI patients identified in the New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in Shanghai registry who, discharged alive, had complete echocardiography and follow-up data from February 2014 to March 2018 were included. Patients were divided according to the presence of NOAF. The outcome measures were HF hospitalization and death during the observational period (until 10 April 2019). Cox proportional hazard models were performed in the whole population and propensity score-matched (PSM) cohort to assess the adjusted hazard ratio (HR) and 95% confidence interval (CI). Overall, 2075 patients (mean age: 65.2 ± 12.3 years, 77.3% were men) with AMI were analysed, of whom 228 (11.0%) developed NOAF. Advanced age, admission HF (Killip II-IV), impaired renal function, decreased left ventricular ejection fraction, increased heart rate, and left atrial enlargement were independent predictors of NOAF. Over a median observational period of 2.7 years, the annual incidence rates of HF hospitalization were 18.4% and 2.8% for patients with NOAF and sinus rhythm, respectively. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (HR: 3.14, 95% CI: 2.30-4.28, P < 0.001). Similar results were obtained when accounting for the competing risk of all-cause death (subdistribution HR: 3.06, 95% CI: 2.18-4.30, P < 0.001) or from the PSM cohort (HR: 2.82, 95% CI: 1.99-4.00, P < 0.001). Patients with persistent NOAF (HR: 5.81, 95% CI: 3.59-9.41) were at significantly higher risk of HF hospitalization when compared with those with transient one (HR: 2.61, 95% CI: 1.84-3.70, P interaction = 0.008). Although post-MI NOAF was significantly related to cardiovascular death (annual incidence rates for NOAF and sinus rhythm were 9.4% and 2.3%, respectively; HR: 1.97, 95% CI: 1.36-2.85, P < 0.001), such an association was attenuated when HF hospitalization (modelled as a time-varying covariate) and antithrombotic treatment were adjusted (HR: 1.37, 95% CI: 0.92-2.02, P = 0.121). CONCLUSIONS: In patients with AMI, NOAF is strongly associated with an increased long-term risk of HF hospitalization. Our findings suggest that strengthened secondary prevention of HF should be considered in this high-risk population.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Infarto del Miocardio , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , China/epidemiología , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) is reported to improve myocardial reperfusion. However, the long-term prognostic implication of TA remains unclear. We aimed to investigate the influence of adjunctive TA on long-term outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing PPCI. All STEMI patients from China that included in the TOTAL trial who were ≥18 years old and referred for PPCI within the 12 hours after symptom onset between January 2011 and November 2012 were retrospectively analyzed. Patients were divided into 2 groups based on the use of TA or not. The primary efficacy outcomes were 5-year major adverse cardiac events, a composite of cardiovascular death, recurrent MI, cardiogenic shock, or heart failure hospitalization. The primary safety outcome was a 5-year stroke. A total of 563 patients were included. The incidence rate of major adverse cardiac events at 5 years in the TA group was similar to that in the PCI group (hazard ratio [HR] 0.70; 95% confidence interval [CI] 0.42 to 1.17). In addition, TA was significantly associated with a nearly sevenfold increased risk of stroke at 5 years compared with PCI alone (HR 7.32, 95% CI 1.33 to 40.31). Our propensity scoring match analyses suggested that patients with an occluded lesion might benefit from the TA (HR 0.24, 95% CI 0.08 to 0.70). In conclusion, TA is not associated with improved outcomes in patients with STEMI but may have an adverse impact on stroke. Patients with an occluded infarct-related artery could benefit from the TA.
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Trombosis Coronaria/cirugía , Intervención Coronaria Percutánea , Complicaciones Posoperatorias/etiología , Infarto del Miocardio con Elevación del ST/cirugía , Accidente Cerebrovascular/etiología , Trombectomía/métodos , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The mineralization of dissolved organic matter (DOM) can partially explain riverine carbon dioxide (CO2) emissions to the atmosphere. However, little is known about how the DOM origin and composition drive CO2 partial pressures (pCO2). Here, we reveal links between aquatic pCO2, DOM optical parameters (a254, a350 and S275-295 and S350-400) and nutrients in a subtropical river in China's Dry-hot Valley Region. Biodegradation preferentially decomposed low molecular weight (LMW) DOMs, increasing high molecular weight (HMW) DOMs along the main stem. pCO2 was positively correlated with aromatic and lignin compounds, but negatively correlated with DOM molecular weight. Aquatic respiration of DOMs largely explained the pCO2 levels in the drought period, while terrestrial inputs were a pCO2 source in the initial-wet period. Our results illustrate how both DOM concentrations and speciation can explain pCO2 distribution and sources in rivers.
RESUMEN
AIM: To investigate the association between plasma S100A1 level and ST-segment elevation myocardial infarction (STEMI) and potential significance of S100A1 in post-infarction cardiac function. METHODS: We examined the plasma S100A1 level in 207 STEMI patients (STEMI group) and 217 clinically healthy subjects for routine physical examination without a history of coronary artery disease (Control group). Baseline characteristics and concentrations of relevant biomarkers were compared. The relationship between S100A1 and other plasma biomarkers was detected using correlation analysis. The predictive role of S100A1 on occurrence of STEMI was then assessed using multivariate ordinal regression model analysis after adjusting for other covariates. RESULTS: The plasma S100A1 level was found to be significantly higher (P<0.001) in STEMI group (3197.7±1576.0 pg/mL) than in Control (1423.5±1315.5 pg/mL) group. Furthermore, the correlation analysis demonstrated plasma S100A1 level was significantly associated correlated with hypersensitive cardiac troponin T (hs-cTnT) (r = 0.32; P < 0.001), creatine kinase MB (CK-MB) (r = 0.42, P < 0.001), left ventricular eject fraction (LVEF) (r = -0.12, P = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.61; P < 0.001) and hypersensitive C reactive protein (hs-CRP) (r = 0.38; P < 0.001). Moreover, the enrolled subjects who with a S100A1 concentration ≤ 1965.9 pg/mL presented significantly better cardiac function than the rest population. Multivariate Logistic regression analysis revealed that S100A1 was an independent predictor for STEMI patients (OR: 0.671, 95% CI 0.500-0.891, P<0.001). In addition, higher S100A1 concentration (> 1965.9 pg/mL) significantly increased the risk of STEMI as compared with the lower level (OR: 6.925; 95% CI: 4.15-11.375; P<0.001). CONCLUSION: These results indicated that the elevated plasma S100A1 level is an important predictor of STEMI in combination with several biomarkers and also potentially reflects the cardiac function following the acute coronary ischemia.
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Proteínas S100/sangre , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/fisiopatología , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/fisiopatología , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Forma MB de la Creatina-Quinasa/sangre , Ecocardiografía Doppler , Femenino , Pruebas de Función Cardíaca , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Troponina T/sangreRESUMEN
The aim of the study was to investigate the correlation between levels of 25-hydroxyvitamin D3, vitamin B12 and C and endothelial function of patients with coronary heart disease (CHD). Forty patients with CHD diagnosed in Shanghai Tenth People's Hospital from May 2016 to April 2017 were selected as the observation group. A total of 45 healthy individuals were selected as the control group. The participants included 54 males and 31 females. General information was collected. Peripheral serum biochemical indicators, levels of 25-hydroxyvitamin D3, vitamin B12 and C, homocysteine (Hcy), nitric oxide (NO) and endothelial NOS (eNOS) were measured. Arterial lesions detected by coronary angiography were recorded and indexes of observation and control group were compared for the correlation analysis. A proportion of hypertensive patients and their body mass index (BMI) were significantly higher in the observation than in the control group (P<0.05). Levels of 25-hydroxyvitamin D3, vitamin B12 and C in peripheral blood of observation were significantly lower than those of the control group (P<0.05). Compared with the control group, incidence of single-branch lesion and non-lesion rate were significantly lower, but incidence of double- and triple-branch lesions were significantly higher in observation than in control group (P<0.05). In addition, the level of Hcy in the observation group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in control group (P<0.05. The correlation analysis revealed that 25-hydroxyvitamin D3 (r=0.792, P<0.01), vitamin B12 (r=0.635, P<0.01) and vitamin C (r=0.703, P<0.01) were negatively correlated with serum NO level. Thus, hypertension, BMI, 25-hydroxyvitamin D3, vitamin B12 and C have independent predictive value for coronary endothelial dysfunction (P<0.05). In conclusion, serum levels of 25-hydroxyvitamin D3, vitamin B12 and C are closely related to vascular endothelial dysfunction in patients with CHD and affect the severity of vascular endothelial dysfunction in patients with CHD.