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Objective: This study assessed the patterns and clinical significance of potential drug-drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018-2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann-Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to 'aspirin + captopril' combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information.
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This prospective study aimed to investigate the ability of cardiac autonomic nervous system (CANS) activity assessment to predict appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease (CAD) during long-term follow-up period. We enrolled patients with CAD and ICD implantation indications that included both secondary and primary prevention of sudden cardiac death. Before ICD implantation CANS was assessed by using heart rate variability (HRV), myocardium scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG) and erythrocyte membranes ß-adrenoreactivity (EMA). The study's primary endpoint was the documentation of appropriate ICD therapy. Of 45 (100.0%) patients, 15 (33.3%) had appropriate ICD therapy during 36 months follow-up period. Patients with appropriate ICD therapy were likely to have a higher summed 123I-MIBG score delayed (p < 0.001) and lower 123I-MIBG washout rate (p = 0.008) indicators. These parameters were independently associated with endpoint in univariable and multivariable logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.933 (95% confidence interval 0.817-0.986; sensitivity 100.00%; specificity 93.33%). Combined CANS activity assessment is useful in prediction of appropriate ICD therapy in patients with CAD during long-term follow-up period after device implantation.
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BACKGROUND: The left bundle branch block, nonischemic heart failure (HF) and female gender are the most powerful predictors of a super response to cardiac resynchronization therapy (CRT). It is important to identify super responders who can derive most benefits from CRT. We aimed to establish a predicting model that could be used for prognosis of a super response to CRT in short-term period. METHODS: Patients with QRS ≥ 130 ms, New York Heart Association (NYHA) II-III class of HF, left ventricle ejection fraction (LVEF) ≤ 35% and indications for CRT were included in the study. Before and 6 month after CRT the electrocardiography, echocardiography and cardiac scintigraphy were performed. The study's primary endpoint was the NYHA class improvement ≥ 1 and left ventricle end systolic volume decrease > 30% or LVEF improvement > 15% after 6 month CRT. Based on collected data, we developed a predictive model regarding a super response to CRT. RESULTS: Of 49 (100.0%) patients, 32 (65.3%) had a super response to CRT. Patients with a super response were likelier to have a lower cardiac index (p = 0.007), higher rates of interventricular delay (IVD) (p = 0.003), phase standard deviation of left ventricle anterior wall (PSD LVAW) (p = 0.009) and ∆QRS (p = 0.02). Only IVD and PSD LVAW were independently associated with a super response to CRT in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.812 (sensitivity 90.62%; specificity 70.59%). CONCLUSION: Our predictive model is able to distinguish patients with a super response to CRT.
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Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the ß2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.
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Adaptação Fisiológica , Temperatura Baixa , Humanos , Animais , Sistema Cardiovascular/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The purpose of this study was to test the hypothesis that melatonin-containing food (FMT) consumption is associated with a better sleep schedule and cognitive and psychoemotional state in older adults. A cross-sectional study of 557 (79% females) older adults living in the community with a mean age of 68.9 ± 7.7, ranging from 50 to 90 years, was conducted. The study, conducted in May and September 2023 using a face-to-face interview, collected personal data and assessed FMT intake during the day (FMTday) and for dinner (FMTdinner), life satisfaction, positive and negative affect, depression severity, cognitive functions, and sleep characteristics. Multiple regression and logistic regression analysis, adjusted for co-factors, were used to assess the association between the studied indicators. Multiple regression analysis showed that older adults with higher FMT consumption are more satisfied with life (FMTdinner: ß = 0.107; ∆R2 = 0.011; p = 0.020), have a lower level of depression (FMTday: ß = -0.124; ∆R2 = 0.015; p = 0.003), and higher scores in positive affect (FMTday: ß = 0.169; ∆R2 = 0.016; p = 0.007; FMTdinner: ß = 0.136; ∆R2 = 0.019; p = 0.003). Logistic regression analysis showed that older adults with higher FMT consumption are less likely to have depression (FMTday: OR, 0.614; 95% CI, 0.436-0.864; p = 0.005; FMTdinner: OR, 0.671; 95% CI, 0.476-0.945; p = 0.023), and they perform better on logical thinking tests (FMTday: OR, 2.066; 95% CI, 1.131-2.204; p = 0.013; FMTdinner: OR, 1.887; 95% CI, 1.183-2.138; p = 0.033). A greater life satisfaction as well as a decrease in the cognitive impairment and psychoemotional state of older adults is associated with a higher consumption of melatonin-containing foods.
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Melatonina , Feminino , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Cognição , Satisfação Pessoal , RefeiçõesRESUMO
BACKGROUND: The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Angiotensin 1-7 has some promise in this regard. OBJECTIVE: The objective of this article is analysis of published data on the cardioprotective properties of angiotensin 1-7. METHODS: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. RESULTS: Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart. Angiotensin 1-7 can prevent not only ischemic but also reperfusion cardiac injury. The activation of the Mas receptor plays a key role in these effects of angiotensin 1-7. Angiotensin 1-7 alleviates Ca2+ overload of cardiomyocytes and reactive oxygen species production in ischemia/reperfusion (I/R) of the myocardium. It is possible that both effects are involved in angiotensin 1-7-triggered cardiac tolerance to I/R. Furthermore, angiotensin 1-7 inhibits apoptosis of cardiomyocytes and stimulates autophagy of cells. There is also indirect evidence suggesting that angiotensin 1-7 inhibits ferroptosis in cardiomyocytes. Moreover, angiotensin 1-7 possesses anti-inflammatory properties, possibly achieved through NF-kB activity inhibition. Phosphoinositide 3-kinase, Akt, and NO synthase are involved in the infarct-reducing effect of angiotensin 1-7. However, the specific end-effector of the cardioprotective impact of angiotensin 1-7 remains unknown. CONCLUSION: The molecular nature of the end-effector of the infarct-limiting effect of angiotensin 1-7 has not been elucidated. Perhaps, this end-effector is the sarcolemmal KATP channel or the mitochondrial KATP channel.
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Angiotensina I , Traumatismo por Reperfusão Miocárdica , Fragmentos de Peptídeos , Transdução de Sinais , Angiotensina I/farmacologia , Fragmentos de Peptídeos/farmacologia , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Transdução de Sinais/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Apoptose/efeitos dos fármacosRESUMO
Adolescents are an at-risk group for circadian misalignment. The contribution of sleep-wake rhythm instability to the psychoemotional, cognitive, and weight disorders of adolescents has been studied in sufficient detail. At the same time, there is insufficient information about the association between chrononutrition indices and the well-being of adolescents. The aim of this study is to investigate the relationship between chrononutrition indices and academic achievement, psychoemotional state, and anthropometric indicators in adolescents. The study involved 12,759 students in grades 6-11 of secondary schools, aged 14.2 ± 1.7 years old; 57.2% of whom were girls. Participants provided personal data, frequency and time of meals during the day and at night, on weekdays and weekends, and completed the Zung Self-Rating Depression Scale and the Yale Food Addiction Scale. There is a U-shaped association between eating mid-phase (EPFc), eating jetlag (EJL), and eating window (EW) with GPA, ZSDSI, and FA. At the same time, the frequency of night eating (NE) is linearly associated with the studied parameters. NE is the strongest predictor of ZSDSI (ß = 0.24), FA (ß = 0.04), and GPA (ß = -0.22). EPFc, EJL, and EW practically do not differ in the strength of their association with the studied indicators. ZSDSI is most closely associated with the chrononutrition indices. There is a weak negative association between BMI and EW (ß = -0.03) and NE (ß = -0.04). Thus, circadian eating disorders are more often observed in adolescents with poor academic performance, high levels of depression, and food addiction.
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Desempenho Acadêmico , Sono , Feminino , Humanos , Adolescente , Criança , Masculino , Estudos Transversais , Escolaridade , Estudantes/psicologia , Ritmo Circadiano , Inquéritos e QuestionáriosRESUMO
Food is an important source of melatonin (MT), which belongs to a group known as chronobiotics, a class of substances that affect the circadian system. Currently, no studies have been conducted on how the consumption of foods containing MT (FMT) is associated with indicators characterizing the human circadian system. In this study, we tested the hypothesis that FMT consumption is associated with chronotype and social jetlag. A total of 1277 schoolchildren and university students aged M (SD) 19.9 (4.1) years (range: 16-25 years; girls: 72.8%) participated in a cross-sectional study. Each participant completed an online questionnaire with their personal data (sex, age, height, weight, waist circumference, and academic performance) and a sequence of tests to assess their sleep-wake rhythm (the Munich Chronotype Questionnaire), sleep quality (the Pittsburgh Sleep Quality Index), and depression level (the Zung Self-Rating Depression Scale). Study participants also completed a modified food frequency questionnaire that only included foods containing MT (FMT). They were asked how many foods containing MT (FMT) they had eaten for dinner, constituting their daily serving, in the past month. The consumption of foods containing MT (FMT) during the day (FMTday) and at dinner (FMTdinner) was assessed using this test. Multiple regression analyses were performed to assess the association between the studied indicators. We found that higher FMTday values were associated with early chronotype (ß = -0.09) and less social jetlag (ß = -0.07), better sleep quality (ß = -0.06) and lower levels of depression (ß = -0.11), as well as central adiposity (ß = -0.08). Higher FMTdinner values were associated with a lower risk of central adiposity (ß = -0.08). In conclusion, the data obtained confirm the hypothesis that the consumption of foods containing MT (FMT) is associated with chronotype and social jetlag in adolescents and young adults.
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The study aimed to assess clinical pharmacology patterns of prescribed and taken medications in older cardiovascular patients using electronic health records (EHRs) (n = 704) (2019-2022). Medscape Drug Interaction Checker was used to identify pairwise drug-drug interactions (DDIs). Prevalence rates of DDIs were 73.5% and 68.5% among taken and prescribed drugs, respectively. However, the total number of DDIs was significantly higher among the prescribed medications (p < 0.05). Serious DDIs comprised 16% and 7% of all DDIs among the prescribed and taken medications, respectively (p < 0.05). Median numbers of DDIs between the prescribed vs. taken medications were Me = 2, IQR 0-7 vs. Me = 3, IQR 0-7 per record, respectively. Prevalence of polypharmacy was significantly higher among the prescribed medications compared with that among the taken drugs (p < 0.05). Women were taking significantly more drugs and had higher prevalence of polypharmacy and DDIs (p < 0.05). No sex-related differences were observed in the list of prescribed medications. ICD code U07.1 (COVID-19, virus identified) was associated with the highest median DDI number per record. Further research is warranted to improve EHR structure, implement patient engagement in reporting adverse drug reactions, and provide genetic profiling of patients to avoid potentially serious DDIs.
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The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon, also known as microvascular obstruction (MVO). However, studies performed in the isolated perfused hearts subjected to ischemia/reperfusion (I/R) do not suggest the involvement of microembolization and microthrombi in this phenomenon. The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction. Consequently, the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi, platelets, and neutrophils. Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries. However, reperfusion triggers more pronounced damage, possibly mediated by pyroptosis. MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling. Therefore, pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles. Ischemic conditioning protocols have been shown to prevent MVO, with L-type Ca 2+ channel blockers appearing the most effective in treating MVO.
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Approximately 13% of the Russian population suffers from chronic kidney disease (CKD). Such a high prevalence of the disease, as well as the complexity and high cost of renal replacement therapy, explain the need for developing and implementing new approaches to treat patients at the pre-dialysis stages. The data collected in recent decades highlight the importance of gut microbiota in the progression of CKD. This review provides information about the microbiota composition in healthy individuals and patients with CKD and discusses the mechanisms of interaction in the intestine-kidney system. The article also presents the specifics of the violation of gut microbiota (GM) and correction thereof in CKD.
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BACKGROUND: The use of percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%-7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP-sensitive K+ (KATP ) channel openers (KCOs) can be classified as such drugs. RESULTS: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no-reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol-enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no-reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. CONCLUSION: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP ) and sarcolemmal KATP (sarcKATP ) channels, triggered free radicals' production, and kinase activation.
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Traumatismo por Reperfusão Miocárdica , Fenômeno de não Refluxo , Intervenção Coronária Percutânea , Humanos , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Apoptose , Reperfusão , Trifosfato de Adenosina , Canais KATPRESUMO
BACKGROUND: Cardiac resynchronization therapy (CRT) improves the outcome in patients with heart failure (HF). However, approximately 30% of patients are nonresponsive to CRT. The aim of this study was to determine the role of the left ventricular (LV) mechanical dyssynchrony (MD) and scar burden as predictors of CRT response. METHODS: In this study, we included 56 patients with HF and the left bundle-branch block with QRS duration ≥ 150 ms who underwent CRT-D implantation. In addition to a full examination, myocardial perfusion imaging and gated blood-pool single-photon emission computed tomography were performed. Patients were grouped based on the response to CRT assessed via echocardiography (decrease in LV end-systolic volume ≥15% or/and improvement in the LV ejection fraction ≥5%). RESULTS: In total, 45 patients (80.3%) were responders and 11 (19.7%) were nonresponders to CRT. In multivariate logistic regression, LV anterior-wall standard deviation (adjusted odds ratio (OR) 1.5275; 95% confidence interval (CI) 1.1472-2.0340; p = 0.0037), summed rest score (OR 0.7299; 95% CI 0.5627-0.9469; p = 0.0178), and HF nonischemic etiology (OR 20.1425; 95% CI 1.2719-318.9961; p = 0.0331) were the independent predictors of CRT response. CONCLUSION: Scar burden and MD assessed using cardiac scintigraphy are associated with response to CRT.
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In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is 5-6%. Consequently, it is necessary to develop fundamentally novel drugs capable of reducing mortality in patients with acute myocardial infarction. Apelins could be the prototype for such drugs. Chronic administration of apelins mitigates adverse myocardial remodeling in animals with myocardial infarction or pressure overload. The cardioprotective effect of apelins is accompanied by blockage of the MPT pore, GSK-3ß, and the activation of PI3-kinase, Akt, ERK1/2, NO-synthase, superoxide dismutase, glutathione peroxidase, matrix metalloproteinase, the epidermal growth factor receptor, Src kinase, the mitoKATP channel, guanylyl cyclase, phospholipase C, protein kinase C, the Na+/H+ exchanger, and the Na+/Ca2+ exchanger. The cardioprotective effect of apelins is associated with the inhibition of apoptosis and ferroptosis. Apelins stimulate the autophagy of cardiomyocytes. Synthetic apelin analogues are prospective compounds for the development of novel cardioprotective drugs.
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The aim of the study was to evaluate the inflammatory changes in the myocardium, based on endomyocardial biopsy (EMB) data in patients undergoing radiofrequency ablation (RFA) for idiopathic atrial fibrillation (AF). A total of 67 patients with idiopathic AF were enrolled in the study. Patients underwent the intracardiac examination, RFA of AF, and EMB with histological and immunohistochemical studies. The catheter-treatment effectiveness, and occurrence of early and late recurrences of atrial tachyarrhythmias, were assessed depending on the identified histological changes. Nine patients (13.4%) did not have any histological changes in the myocardium according to EMB. Fibrotic changes were detected in 26 cases (38.8%). Inflammatory changes according to the Dallas criteria were observed in 32 patients (47.8%). The follow-up period for patients averaged 19.3 ± 3.7 months. The effectiveness rates of primary RFA were 88.9% in patients with the intact myocardium, 46.2% in patients with fibrotic changes of varying severity, and 34.4% in patients with the presence of criteria for myocarditis. No early recurrence of arrhythmias was observed in patients with unchanged myocardia. The presence of inflammatory and fibrotic changes in the myocardium increased the rates of early and late arrhythmia recurrences and accordingly halved the effectiveness RFA of AF.
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The search for novel drugs for the treatment of acute myocardial infarction and reperfusion injury of the heart is an urgent aim of modern pharmacology. Opioid peptides could be such potential drugs in this area. However, the molecular mechanism of the infarct-limiting effect of opioids in reperfusion remains unexplored. The objective of this research was to study the signaling mechanisms of the cardioprotective effect of deltorphin II in reperfusion. Rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). The ratio of infarct size/area at risk was determined. This study indicated that the cardioprotective effect of deltorphin II in reperfusion is mediated via the activation of peripheral δ2 opioid receptor (OR), which is most likely localized in cardiomyocytes. We studied the role of guanylyl cyclase, protein kinase Cδ (PKCδ), phosphatidylinositol-3-kinase (PI3-kinase), extracellular signal-regulated kinase-1/2 (ERK1/2-kinase), ATP-sensitive K+-channels (KATP channels), mitochondrial permeability transition pore (MPTP), NO synthase (NOS), protein kinase A (PKA), Janus 2 kinase, AMP-activated protein kinase (AMPK), the large conductance calcium-activated potassium channel (BKCa-channel), reactive oxygen species (ROS) in the cardioprotective effect of deltorphin II. The infarct-reducing effect of deltorphin II appeared to be mediated via the activation of PKCδ, PI3-kinase, ERK1/2-kinase, sarcolemmal KATP channel opening, and MPTP closing.
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Ischemia/reperfusion (I/R) of the heart leads to increased autophagic flux. Preconditioning stimulates autophagic flux by AMPK and PI3-kinase activation and mTOR inhibition. The cardioprotective effect of postconditioning is associated with activation of autophagy and increased activity of NO-synthase and AMPK. Oxidative stress stimulates autophagy in the heart during I/R. Superoxide radicals generated by NADPH-oxidase acts as a trigger for autophagy, possibly due to AMPK activation. There is reason to believe that AMPK, GSK-3ß, PINK1, JNK, hexokinase II, MEK, PKCα, and ERK kinases stimulate autophagy, while mTOR, PKCδ, Akt, and PI3-kinase can inhibit autophagy in the heart during I/R. However, there is evidence that PI3-kinase could stimulate autophagy in ischemic preconditioning of the heart. It was found that transcription factors FoxO1, FoxO3, NF-κB, HIF-1α, TFEB, and Nrf-2 enhance autophagy in the heart in I/R. Transcriptional factors STAT1, STAT3, and p53 inhibit autophagy in I/R. MicroRNAs could stimulate and inhibit autophagy in the heart in I/R. Long noncoding RNAs regulate the viability and autophagy of cardiomyocytes in hypoxia/reoxygenation (H/R). Nitric oxide (NO) donors and endogenous NO could activate autophagy of cardiomyocytes. Activation of heme oxygenase-1 promotes cardiomyocyte tolerance to H/R and enhances autophagy. Hydrogen sulfide increases cardiac tolerance to I/R and inhibits apoptosis and autophagy via mTOR and PI3-kinase activation.
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Traumatismo por Reperfusão Miocárdica , Transdução de Sinais , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Glicogênio Sintase Quinase 3 beta , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Miócitos Cardíacos/metabolismo , Isquemia , Reperfusão , Autofagia , Fosfatidilinositol 3-QuinasesRESUMO
BACKGROUND: Impaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF. METHODS AND RESULTS: The study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum 123I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response. CONCLUSION: CRT response can be predicted by cardiac 123I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , 3-Iodobenzilguanidina , Resultado do Tratamento , Disfunção Ventricular Esquerda/terapia , Insuficiência Cardíaca/terapiaRESUMO
We study 6000 author-publication observations to investigate predictors of early career success in six fields of economics. Concentrating on top researchers enables us to control for the effects of ability and effort, and focusing on the start of their careers minimizes distortions from reputation feedback. Our results reveal that the most important predictor for early career success is the ranking of an author's PhD granting institution, followed by his first placement. Our insights suggest that a counterfactual decrease in the Alma mater of a high ability author, who graduated from a top 10 university, by as little as 10 to 20 ranks, reduces his probability of getting a top 5 publication significantly by 13 percentage points. Lowering the ranking of his Alma mater by another 80 ranks decreases his chances of getting a top publication by a factor of three. Our findings suggest that the economics publication market values Alma mater signals, discounting newcomers graduating from- or working at lower ranked departments.
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Instalações de Saúde , Oligoquetos , Humanos , Animais , Probabilidade , Resolução de Problemas , PesquisadoresRESUMO
Acute myocardial infarction (AMI) is one of the main reasons of cardiovascular disease-related death. The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate in AMI. Adverse cardiac remodeling is a serious problem in cardiology. An increase in the effectiveness of AMI treatment and prevention of adverse cardiac remodeling is difficult to achieve without understanding the mechanisms of reperfusion cardiac injury and cardiac remodeling. Inhibition of pyroptosis prevents the development of postinfarction and pressure overload-induced cardiac remodeling, and mitigates cardiomyopathy induced by diabetes and metabolic syndrome. Therefore, it is reasonable to hypothesize that the pyroptosis inhibitors may find a role in clinical practice for treatment of AMI and prevention of cardiac remodeling, diabetes and metabolic syndrome-triggered cardiomyopathy. It was demonstrated that pyroptosis interacts closely with apoptosis and autophagy. Pyroptosis could be inhibited by nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 inhibitors, caspase-1 inhibitors, microRNA, angiotensin-converting enzyme inhibitors, angiotensin â ¡ receptor blockers, and traditional Chinese herbal medicines.