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BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.
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Amônia , Eletrocardiografia , Ventrículos do Coração , Infarto do Miocárdio , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Feminino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Imagem de Perfusão do Miocárdio/métodos , Ventrículos do Coração/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Compostos Radiofarmacêuticos , Técnicas de Imagem de Sincronização Cardíaca , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Reprodutibilidade dos TestesRESUMO
The high mortality rate among patients with acute myocardial infarction (AMI) is one of the main problems of modern cardiology. It is quite obvious that there is an urgent need to create more effective drugs for the treatment of AMI than those currently used in the clinic. Such drugs could be enzyme-resistant peptide analogs of glucagon-like peptide-1 (GLP-1). GLP-1 receptor (GLP1R) agonists can prevent ischemia/reperfusion (I/R) cardiac injury. In addition, chronic administration of GLP1R agonists can alleviate the development of adverse cardiac remodeling in myocardial infarction, hypertension, and diabetes mellitus. GLP1R agonists can protect the heart against oxidative stress and reduce proinflammatory cytokine (IL-1ß, TNF-α, IL-6, and MCP-1) expression in the myocardium. GLP1R stimulation inhibits apoptosis, necroptosis, pyroptosis, and ferroptosis of cardiomyocytes. The activation of the GLP1R augments autophagy and mitophagy in the myocardium. GLP1R agonists downregulate reactive species generation through the activation of Epac and the GLP1R/PI3K/Akt/survivin pathway. The GLP1R, kinases (PKCε, PKA, Akt, AMPK, PI3K, ERK1/2, mTOR, GSK-3ß, PKG, MEK1/2, and MKK3), enzymes (HO-1 and eNOS), transcription factors (STAT3, CREB, Nrf2, and FoxO3), KATP channel opening, and MPT pore closing are involved in the cardioprotective effect of GLP1R agonists.
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Cardiotônicos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Transdução de Sinais , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
OBJECTIVE: To evaluate whether index of microcirculatory resistance (IMR) is associated with left ventricular (LV) remodeling in acute anterior ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: This was a single-center retrospective cohort study. The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled. After PPCI, IMR was measured immediately by using pressure/temperature guidewire. The success rate of IMR measurement was 100%. Also we collected some related clinical data from the medical records and laboratory results. Infarct size [assessed as creatine kinase (CK) peak], echocardiography at baseline and 1 year follow-up were assessed. LV adverse remodeling (LVAR) was defined as ≥20% increase in LV end-diastolic volume (LVEDV). RESULTS: A total of forty-three patients were enrolled, with an average age of (58.7±12.4) years.The patients were divided into two groups as IMR ≤25 and IMR>25 by normal values recommended by previous literature. Compared with IMR ≤25 group, IMR>25 group had a higher percentage of initial thrombolysis in myocardial infraction (TIMI) grade 0 (95.7% vs. 65.0%, P=0.029), higher serum CK peak value [4 090 (383, 15 833)vs. 1 580 (396, 5 583), P=0.004]. The IMR>25 group suffered higher rates of ventricular aneurysm (30.4% vs. 5.0%, P=0.021). There was no difference in LVEDV [(111.0±18.8) mL vs. (115.0±23.6) mL, P=0.503] between the two groups 1 day after MI, but after 1 year, LVEDV in IMR>25 group was significantly higher than in IMR≤25 group [(141.5±33.7) mL vs. (115.9±27.9) mL, P=0.018]. The incidence of LVAR was more significant in IMR>25 group (47.4% vs. 11.8%, P=0.024). Binary Logistics regression showed that IMR [B=0.079, exp(B) (95%CI)=1.082 (1.018ï¼1.149), P=0.011] and serum triglyceride level [B=1.610, exp(B) (95%CI)=5.005 (1.380ï¼18.152), P=0.014] were the predictors of LVAR 1 year after MI. IMR had a good predictive value for LVAR 1 year after MI [area under the curve (AUC)=0.749, P=0.019], IMR>29 was a good cutoff value with sensitivity 81.8% and specificity 68.0%. CONCLUSION: Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvascular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Estudos Retrospectivos , Microcirculação , Remodelação Ventricular , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
BACKGROUND: A couple of cardiac magnetic resonance (CMR) attributes strongly predict adverse remodeling after ST-segment elevation myocardial infarction (STEMI); however, the value of incorporating high-risk CMR attributes, particularly, in patients with non-reduced ejection fraction, remains undetermined. This study sought to evaluate the independent and incremental predictive value of a multiparametric CMR approach for adverse remodeling after STEMI across left ventricular ejection fraction (LVEF) categories. METHODS: A total of 157 patients with STEMI undergoing primary percutaneous coronary intervention were prospectively enrolled. Adverse remodeling was defined as ≥20% enlargement in left ventricular end-diastolic volume from index admission to 3 months of follow-up. RESULTS: Adverse remodeling occurred in 23.6% of patients. After adjustment for clinical risk factors, a stroke volume index <29.6 mL/m2, a global longitudinal strain >-7.5%, an infarct size >39.2%, a microvascular obstruction >4.9%, and a myocardial salvage index <36.4 were independently associated with adverse remodeling. The incidence of adverse remodeling increased with the increasing number of high-risk CMR attributes, regardless of LVEF (LVEF ≤ 40%: P = 0.026; 40% < LVEF < 50%: P = 0.001; LVEF ≥ 50%: P < 0.001). The presence of ≥4 high-risk attributes was an independent predictor of LV adverse remodeling (70.0% vs. 16.8%, adjusted OR 9.68, 95 CI% 3.25-28.87, P < 0.001). Furthermore, the number of high-risk CMR attributes had an incremental predictive value over reduced LVEF and baseline clinical risk factors (AUC: 0.81 vs. 0.68; P = 0.002). CONCLUSIONS: High-risk CMR attributes showed a significant association with adverse remodeling after STEMI across LVEF categories. This imaging-based model provided incremental value for adverse remodeling over traditional clinical factors and LVEF.
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BACKGROUND: Under the adverse remodeling of the right ventricle and interventricular septum in pulmonary arterial hypertension (PAH) the left ventricle (LV) dynamics is impaired. Despite the benefits of combined aerobic and resistance physical trainings to individuals with PAH, its impact on the LV is not fully understood. OBJECTIVE: To test whether moderate-intensity combined physical training performed during the development of PAH induced by MCT in rats is beneficial to the LV's structure and function. METHODS: Male Wistar rats were divided into two groups: Sedentary Hypertensive Survival (SHS, n = 7); and Exercise Hypertensive Survival (EHS, n = 7) to test survival. To investigate the effects of combined physical training, another group of rats were divided into three groups: Sedentary Control (SC, n = 7); Sedentary Hypertensive (SH, n = 7); and Exercise Hypertensive (EH, n = 7). PAH was induced through an intraperitoneal injection of MCT (60 mg/kg). Echocardiographic evaluations were conducted on the 22nd day after MCT administration. Animals in the EHS and EH groups participated in a combined physical training program, alternating aerobic (treadmill running: 50 min, 60% maximum running speed) and resistance (ladder climbing: 15 climbs with 1 min interval, 60% maximum carrying load) exercises, one session/day, 5 days/week for approximately 4 weeks. RESULTS: The physical training increased survival and tolerance to aerobic (i.e., maximum running speed) and resistance (i.e., maximum carrying load) exertions and prevented reductions in ejection fraction and fractional shortening. In addition, the physical training mitigated oxidative stress (i.e., CAT, SOD and MDA) and inhibited adverse LV remodeling (i.e., Collagen, extracellular matrix, and cell dimensions). Moreover, the physical training preserved the amplitude and velocity of contraction and hindered the reductions in the amplitude and velocity of the intracellular Ca2+ transient in LV single myocytes. CONCLUSION: Moderate-intensity combined physical training performed during the development of MCT-induced PAH in rats protects their LV from damages to its structure and function and hence increases their tolerance to physical exertion and prolongs their survival.
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RATIONALE AND OBJECTIVES: To develop a radiomics model based on cardiac computed tomography (CT) for predicting left ventricular adverse remodeling (LVAR) in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: Patients with severe AS who underwent TAVR from January 2019 to December 2022 were recruited. The cohort was divided into adverse remodeling group and non-adverse remodeling group based on LVAR occurrence, and further randomly divided into a training set and a validation set at an 8:2 ratio. Left ventricular radiomics features were extracted from cardiac CT. The least absolute shrinkage and selection operator regression was utilized to select the most relevant radiomics features and clinical features. The radiomics features were used to construct the Radscore, which was then combined with the selected clinical features to build a nomogram. The predictive performance of the models was evaluated using the area under the curve (AUC), while the clinical value of the models was assessed using calibration curves and decision curve analysis. RESULTS: A total of 273 patients were finally enrolled, including 71 with adverse remodeling and 202 with non-adverse remodeling. 12 radiomics features and five clinical features were extracted to construct the radiomics model, clinical model, and nomogram, respectively. The radiomics model outperformed the clinical model (training AUC: 0.799 vs. 0.760; validation AUC: 0.766 vs. 0.755). The nomogram showed highest accuracy (training AUC: 0.859, validation AUC: 0.837) and was deemed most clinically valuable by decision curve analysis. CONCLUSION: The cardiac CT-based radiomics features could predict LVAR after TAVR in patients with severe AS.
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Activation of the CXCL12/CXCR4/ACKR3 axis is known to aid myocardial repair through ischemia-triggered hypoxia-inducible factor-1α (HIF-1α). To enhance the upregulation of HIF-1α, we administered roxadustat, a novel prolyl hydroxylase inhibitor (PHI) clinically approved by the European Medicines Agency 2021 for the treatment of renal anemia, with the purpose of improving LV function and attenuating ischemic cardiomyopathy. METHODS: We evaluated roxadustat's impact on HIF-1 stimulation, cardiac remodeling, and function after MI. Therefore, we analyzed nuclear HIF-1 expression, the mRNA and protein expression of key HIF-1 target genes (RT-PCR, Western blot), inflammatory cell infiltration (immunohistochemistry), and apoptosis (TUNEL staining) 7 days after MI. Additionally, we performed echocardiography in male and female C57BL/6 mice 28 days post-MI. RESULTS: We found a substantial increase in nuclear HIF-1, associated with an upregulation of HIF-1α target genes like CXCL12/CXCR4/ACKR3 at the mRNA and protein levels. Roxadustat increased the proportion of myocardial reparative M2 CD206+ cells, suggesting beneficial alterations in immune cell migration and a trend towards reduced apoptosis. Echocardiography showed that roxadustat treatment significantly preserved ejection fraction and attenuated subsequent ventricular dilatation, thereby reducing adverse remodeling. CONCLUSIONS: Our findings suggest that roxadustat is a promising clinically approved treatment option to preserve myocardial function by attenuating adverse remodeling.
Assuntos
Glicina , Subunidade alfa do Fator 1 Induzível por Hipóxia , Isoquinolinas , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Remodelação Ventricular , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Camundongos , Remodelação Ventricular/efeitos dos fármacos , Glicina/análogos & derivados , Glicina/farmacologia , Glicina/uso terapêutico , Masculino , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isoquinolinas/farmacologia , Isoquinolinas/uso terapêutico , Apoptose/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Quimiocina CXCL12/genética , Miocárdio/patologia , Miocárdio/metabolismoRESUMO
Background: Intramyocardial hemorrhage (IMH) occurs after ST-elevation myocardial infarction (STEMI) and has been documented using cardiac magnetic resonance imaging. The prevalence and prognostic significance of IMH are not well described, and the small sample size has limited prior studies. Methods: We performed a comprehensive literature search of multiple databases to identify studies that compared outcomes in STEMI patients with or without IMH. The outcomes studied were major adverse cardiovascular events (MACE), infarct size, thrombolysis in myocardial infarction (TIMI) flow after percutaneous coronary intervention (PCI), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and mortality. Odds ratios (ORs) and standardized mean differences with corresponding 95% CIs were calculated using a random effects model. Results: Eighteen studies, including 2824 patients who experienced STEMI (1078 with IMH and 1746 without IMH), were included. The average prevalence of IMH was 39%. There is a significant association between IMH and subsequent MACE (OR, 2.63; 95% CI, 1.79-3.86; P < .00001), as well as IMH and TIMI grade <3 after PCI (OR, 1.75; 95% CI, 1.14-2.68; P = .05). We also found a significant association between IMH and the use of glycoprotein IIb/IIIa inhibitors (OR, 2.34; 95% CI, 1.42-3.85; P = .0008). IMH has a positive association with infarct size (standardized mean difference, 2.19; 95% CI, 1.53-2.86; P < .00001) and LVEDV (standardized mean difference, 0.7; 95% CI, 0.41-0.99; P < .00001) and a negative association with LVEF (standardized mean difference, -0.89; 95% CI, -1.15 to -0.63; P = .01). Predictors of IMH include male sex, smoking, and left anterior descending infarct. Conclusions: Intramyocardial hemorrhage is prevalent in approximately 40% of patients who experience STEMI. IMH is a significant predictor of MACE and is associated with larger infarct size, higher LVEDV, and lower LVEF after STEMI.