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1.
Int J Mol Sci ; 22(6)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808720

RESUMO

Using a murine model of chronic ischemic cardiomyopathy caused by an old myocardial infarction (MI), we have previously found that three doses of 1 × 106 c-kit positive cardiac cells (CPCs) are more effective than a single dose of 1 × 106 cells. The goal of this study was to determine whether the beneficial effects of three doses of CPCs (1 × 106 cells each) can be fully replicated by a single combined dose of 3 × 106 CPCs. Mice underwent a 60-min coronary occlusion; after 90 days of reperfusion, they received three echo-guided intraventricular infusions at 5-week intervals: (1) vehicle × 3; (2) one combined dose of CPCs (3 × 106) and vehicle × 2; or (3) three doses of CPCs (1 × 106 each). In the combined-dose group, left ventricular ejection fraction (LVEF) improved after the 1st CPC infusion, but not after the 2nd and 3rd (vehicle) infusions. In contrast, in the multiple-dose group, LVEF increased after each CPC infusion; at the final echo, LVEF averaged 35.2 ± 0.6% (p < 0.001 vs. the vehicle group, 27.3 ± 0.2%). At the end of the study, the total cumulative change in EF from pretreatment values was numerically greater in the multiple-dose group (6.6 ± 0.6%) than in the combined-dose group (4.8 ± 0.8%), although the difference was not statistically significant (p = 0.08). Hemodynamic studies showed that several parameters of LV function in the multiple-dose group were numerically greater than in the combined-dose group (p = 0.08 for the difference in LVEF). Compared with vehicle, cardiomyocyte cross-sectional area was reduced only in the multiple-dose group (-32.7%, 182.6 ± 15.1 µm2 vs. 271.5 ± 27.2 µm2, p < 0.05, in the risk region and -28.5%, 148.5 ± 12.1 µm2 vs. 207.6 ± 20.5 µm2, p < 0.05, in the noninfarcted region). LV weight/body weight ratio and LV weight/tibia length ratios were significantly reduced in both cell treated groups vs. the vehicle group, indicating the attenuation of LV hypertrophy; however, the lung weight/body weight ratio was significantly reduced only in the multiple-dose group, suggesting decreased pulmonary congestion. Taken together, these results indicate that in mice with chronic ischemic cardiomyopathy, the beneficial effects of three doses of CPCs on LV function and hypertrophy cannot be fully replicated with a single dose, notwithstanding the fact that the total number of cells delivered with one or three doses is the same. Thus, it is the multiplicity of doses, and not the total number of cells, that accounts for the superiority of the repeated-dose paradigm. This study supports the idea that the efficacy of cell therapy in heart failure can be augmented by repeated administrations.


Assuntos
Cardiomiopatias/etiologia , Dosagem de Genes , Isquemia Miocárdica/complicações , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Animais , Biomarcadores , Biópsia , Pesos e Medidas Corporais , Cardiomiopatias/diagnóstico , Cardiomiopatias/metabolismo , Cardiomiopatias/terapia , Células Cultivadas , Modelos Animais de Doenças , Ecocardiografia , Fibrose , Testes de Função Cardíaca , Hemodinâmica , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Camundongos , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Isquemia Miocárdica/etiologia , Proteínas Proto-Oncogênicas c-kit/metabolismo
2.
Nat Commun ; 12(1): 869, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558521

RESUMO

The beating heart possesses the intrinsic ability to adapt cardiac output to changes in mechanical load. The century-old Frank-Starling law and Anrep effect have documented that stretching the heart during diastolic filling increases its contractile force. However, the molecular mechanotransduction mechanism and its impact on cardiac health and disease remain elusive. Here we show that the mechanically activated Piezo1 channel converts mechanical stretch of cardiomyocytes into Ca2+ and reactive oxygen species (ROS) signaling, which critically determines the mechanical activity of the heart. Either cardiac-specific knockout or overexpression of Piezo1 in mice results in defective Ca2+ and ROS signaling and the development of cardiomyopathy, demonstrating a homeostatic role of Piezo1. Piezo1 is pathologically upregulated in both mouse and human diseased hearts via an autonomic response of cardiomyocytes. Thus, Piezo1 serves as a key cardiac mechanotransducer for initiating mechano-chemo transduction and consequently maintaining normal heart function, and might represent a novel therapeutic target for treating human heart diseases.


Assuntos
Canais Iônicos/metabolismo , Mecanotransdução Celular , Miocárdio/metabolismo , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Cálcio/metabolismo , Sinalização do Cálcio , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Deleção de Genes , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Homeostase , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Especificidade de Órgãos , Pirazinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tiadiazóis/metabolismo , Regulação para Cima
3.
Medicine (Baltimore) ; 100(5): e23188, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592818

RESUMO

ABSTRACT: To explore the short-term effect of high-dose spironolactone (80 mg/d) on chronic congestive heart failure (CHF).The general clinical data of 211 patients with CHF from February 2016 to August 2019 were collected and analyzed. Patients were divided into Low-dose group (taking 40 mg/d spironolactone) and High-dose group (taking 80 mg/d spironolactone) according to the patient's previous dose of spironolactone. The changes of B-type brain natriuretic peptide (BNP), NT-pro BNP (N terminal pro B type natriuretic peptide), echocardiography, 6-minute walking test (6MWT), and comprehensive cardiac function assessment data were collected for analysis.Compared with before treatment, the blood potassium of the two groups increased significantly (P < .05), but the blood potassium did not exceed the normal range. Compared with before treatment, BNP, NT-pro BNP, LVEDD, LVEDV and NYHA grading were significantly decreased (P < .05), LVEF and 6-MWT were significantly increased (P < .05). Compared with the Low-dose group, the high-dose group BNP (117.49 ±â€Š50.32 vs 195.76 ±â€Š64.62, P < .05), NT-pro BNP (312.47 ±â€Š86.28 vs 578.47 ±â€Š76.73, P < .05), LVEDD (45.57 ±â€Š5.69 vs 51.96 ±â€Š5.41, P <.05), LVEDV (141.63 ±â€Š51.14 vs 189.85 ±â€Š62.49, P < .05) and NYHA grading (1.29 ±â€Š0.41 vs 1.57 ±â€Š0.49, P < .05) were significantly reduced, but, 6-MWT (386.57 ±â€Š69.72 vs 341.73 ±â€Š78.62, P < .05), LVEF (41.62 ±â€Š2.76 vs 36.02 ±â€Š2.18, P < .05) and total effective rate (92.68% vs 81.39%, P < .05) increased significantly.Compared with 40 mg spironolactone, 80 mg spironolactone can rapidly reduce BNP and NT-pro BNP concentration, enhance exercise tolerance, improve clinical signs and cardiac function classification, and has better efficacy.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Espironolactona/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Potássio/sangue , Estudos Retrospectivos , Espironolactona/administração & dosagem , Teste de Caminhada
4.
Anticancer Res ; 41(1): 369-378, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419833

RESUMO

BACKGROUND/AIM: We investigated the prognostic impact of hemoglobin (Hb) levels in tumour patients receiving routine cardiological surveillance during anticancer treatment. The aim of the study was to identify independent predictors of all-cause mortality in a cardio-oncological collective. PATIENTS AND METHODS: A total of 551 patients (273 males, 278 females) were enrolled in the Mannheim Registry for Cardiooncology and were included in the present analysis. Median follow-up was 41 months (95% CI=40-43). RESULTS: Patients were grouped according to a pretherapeutic Hb-threshold (determined by ROC analysis) into cohorts with Hb<11.4 g/dl (n=232, 42.1%) and Hb >11.4 g/dl (n=319, 57.9%). Patients with lower Hb levels were older at the time of first diagnosis (63.8±14.4 vs. 59.9±15.4 years, p=0.003) and were more likely to have advanced tumour stages (92 (39.7%) vs. 83 (26.0%), p=0.0007). There were no differences regarding cardiovascular comorbidities such as hypertension or diabetes, while chronic kidney disease was more common in patients with lower Hb. Anticoagulants were used more often in patients with lower Hb (88 (37.9%) vs. 84 (26.3%), p=0.01). Left ventricular ejection fraction (LVEF) was lower in patients with Hb <11.4 g/dl (51.9±11.0% vs. 55.1±9.7%, p=0.003). Correlation analysis revealed a significant correlation of Hb levels and LVEF (R2=0.07, p<0.0001). During follow-up, a total of 140 patients (25.4%) were deceased, with significantly more deaths occurring in the group of patients with low Hb values [108 (46.6%) vs. 32 (10.0%), p<0.0001]. In multivariable analysis, Hb was identified as independent predictor for mortality (OR=5.3, CI=0.41-0.89, p<0.0001). CONCLUSION: Low Hb levels were identified as an independent predictor of mortality in patients with cancer. There was a significant correlation of Hb and LVEF, suggesting that low Hb values are not solely due to anaemia, but rather reflect the severity of cancer.


Assuntos
Anemia/sangue , Índices de Eritrócitos , Hemoglobinas , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/etiologia , Biomarcadores , Causas de Morte , Comorbidade , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Prognóstico , Curva ROC , Sistema de Registros
5.
Anticancer Res ; 41(1): 409-415, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419838

RESUMO

BACKGROUND/AIM: We aimed to evaluate the correlation between stroke volume variation (SVV) and intraoperative blood loss (IBL) in hepatocellular carcinoma (HCC) resection and examine the perioperative utility of SVV-based management. PATIENTS AND METHODS: Ninety-five patients who underwent partial or sub-segmental hepatectomy for HCC between 2013 and 2019 at the University of Yamanashi Hospital were retrospectively analyzed. A correlation analysis between IBL and SVV was performed, and then all cases were divided into three groups: high, middle, and low-SVV groups. Perioperative short-term outcomes based on SVV groups were analyzed. RESULTS: There was a weak but significant negative correlation between SVV and IBL (ρ=-0.372, p<0.001). Comparative analysis revealed that low-SVV was associated with a high incidence of postoperative complications and blood transfusion (p=0.018 and 0.037, respectively), and high-SVV was not related with postoperative complications. CONCLUSION: SVV-based management is a significant and feasible strategy to achieve safe and exact surgical resection of HCC.


Assuntos
Perda Sanguínea Cirúrgica , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Monitorização Intraoperatória , Volume Sistólico , Idoso , Biomarcadores , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Carcinoma Hepatocelular/diagnóstico , Feminino , Testes de Função Cardíaca , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias , Estudos Retrospectivos
6.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450984

RESUMO

Trauma remains a leading global cause of mortality, particularly in the young population. In the United States, approximately 30,000 patients with blunt cardiac trauma were recorded annually. Cardiac damage is a predictor for poor outcome after multiple trauma, with a poor prognosis and prolonged in-hospitalization. Systemic elevation of cardiac troponins was correlated with survival, injury severity score, and catecholamine consumption of patients after multiple trauma. The clinical features of the so-called "commotio cordis" are dysrhythmias, including ventricular fibrillation and sudden cardiac arrest as well as wall motion disorders. In trauma patients with inappropriate hypotension and inadequate response to fluid resuscitation, cardiac injury should be considered. Therefore, a combination of echocardiography (ECG) measurements, echocardiography, and systemic appearance of cardiomyocyte damage markers such as troponin appears to be an appropriate diagnostic approach to detect cardiac dysfunction after trauma. However, the mechanisms of post-traumatic cardiac dysfunction are still actively being investigated. This review aims to discuss cardiac damage following trauma, focusing on mechanisms of post-traumatic cardiac dysfunction associated with inflammation and complement activation. Herein, a causal relationship of cardiac dysfunction to traumatic brain injury, blunt chest trauma, multiple trauma, burn injury, psychosocial stress, fracture, and hemorrhagic shock are illustrated and therapeutic options are discussed.


Assuntos
Suscetibilidade a Doenças , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Disfunção Ventricular/etiologia , Disfunção Ventricular/fisiopatologia , Ferimentos e Lesões/complicações , Animais , Biomarcadores , Ativação do Complemento , Gerenciamento Clínico , Metabolismo Energético , Cardiopatias/diagnóstico , Cardiopatias/metabolismo , Testes de Função Cardíaca , Humanos , Índice de Gravidade de Doença , Disfunção Ventricular/diagnóstico , Disfunção Ventricular/metabolismo
7.
Int J Mol Sci ; 22(3)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33503985

RESUMO

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are antihyperglycemic agents with cardioprotective properties against diabetic cardiomyopathy (DCM). However, the distinctive mechanisms underlying GLP-1RAs and SGLT2is in DCM are not fully elucidated. The purpose of this study was to investigate the impacts of GLP1RAs and/or SGLT2is on myocardial energy metabolism, cardiac function, and apoptosis signaling in DCM. Biochemistry and echocardiograms were studied before and after treatment with empagliflozin (10 mg/kg/day, oral gavage), and/or liraglutide (200 µg/kg every 12 h, subcutaneously) for 4 weeks in male Wistar rats with streptozotocin (65 mg/kg intraperitoneally)-induced diabetes. Cardiac fibrosis, apoptosis, and protein expression of metabolic and inflammatory signaling molecules were evaluated by histopathology and Western blotting in ventricular cardiomyocytes of different groups. Empagliflozin and liraglutide normalized myocardial dysfunction in diabetic rats. Upregulation of phosphorylated-acetyl coenzyme A carboxylase, carnitine palmitoyltransferase 1ß, cluster of differentiation 36, and peroxisome proliferator-activated receptor-gamma coactivator, and downregulation of glucose transporter 4, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α2 to adenosine monophosphate-activated protein kinase α2, and the ratio of phosphorylated protein kinase B to protein kinase B in diabetic cardiomyocytes were restored by treatment with empagliflozin or liraglutide. Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3, interleukin-1ß, tumor necrosis factor-α, and cleaved caspase-1 were significantly downregulated in empagliflozin-treated and liraglutide-treated diabetic rats. Both empagliflozin-treated and liraglutide-treated diabetic rats exhibited attenuated myocardial fibrosis and apoptosis. Empagliflozin modulated fatty acid and glucose metabolism, while liraglutide regulated inflammation and apoptosis in DCM. The better effects of combined treatment with GLP-1RAs and SGLT2is may lead to a potential strategy targeting DCM.


Assuntos
Compostos Benzidrílicos/farmacologia , Cardiomiopatias Diabéticas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glucosídeos/farmacologia , Liraglutida/farmacologia , Miocárdio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Citocinas/biossíntese , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Modelos Animais de Doenças , Ecocardiografia , Ácidos Graxos/metabolismo , Fibrose , Glucose/metabolismo , Testes de Função Cardíaca , Hipoglicemiantes/farmacologia , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Ratos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
8.
Am J Physiol Heart Circ Physiol ; 320(4): H1337-H1347, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33513086

RESUMO

Although atrial fibrillation (AF) is the most common cardiac arrhythmia, its early identification, diagnosis, and treatment is still challenging. Due to its heterogeneous mechanisms and risk factors, targeting an individualized treatment of AF demands a large amount of patient data to identify specific patterns. Artificial intelligence (AI) algorithms are particularly well suited for treating high-dimensional data, predicting outcomes, and eventually, optimizing strategies for patient management. The analysis of large patient samples combining different sources of information such as blood biomarkers, electrical signals, and medical images opens a new paradigm for improving diagnostic algorithms. In this review, we summarize suitable AI techniques for this purpose. In particular, we describe potential applications for understanding the structural and functional bases of the disease, as well as for improving early noninvasive diagnosis, developing more efficient therapies, and predicting long-term clinical outcomes of patients with AF.


Assuntos
Inteligência Artificial , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Diagnóstico por Computador , Testes de Função Cardíaca , Terapia Assistida por Computador , Potenciais de Ação , Fibrilação Atrial/fisiopatologia , Tomada de Decisão Clínica , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Reconhecimento Automatizado de Padrão , Valor Preditivo dos Testes
9.
Int J Mol Sci ; 22(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445410

RESUMO

Dilated cardiomyopathy (DCM) is the leading indication for heart transplantation. TTN gene truncating mutations account for about 25% of familial DCM cases and for 18% of sporadic DCM cases. The clinical relevance of specific variants in TTN has been difficult to determine because of the sheer size of the protein for which TTN encodes, as well as existing extensive genetic variation. Clinicians should communicate novel clinically-relevant variants and genotype-phenotype associations, so that animal studies evaluating the molecular mechanisms are always conducted with a focus on clinical significance. In the present study, we report for the first time the novel truncating heterozygous variant NM_001256850.1:c.72777_72783del (p.Phe24259Leufs*51) in the TTN gene and its association with DCM in a family with sudden death. This variant occurs in the A-band region of the sarcomere, in a known mutational hotspot of the gene. Truncating titin variants that occur in this region are the most common cause of DCM and have been rarely reported in asymptomatic individuals, differently from other pathogenic TTN gene variants. Further studies are warranted to better understand this particular clinically-relevant variant.


Assuntos
Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/genética , Conectina/genética , Morte Súbita Cardíaca/etiologia , Mutação da Fase de Leitura , Biomarcadores , Cardiomiopatia Dilatada/diagnóstico , Análise Mutacional de DNA , Diagnóstico por Imagem , Eletrocardiografia , Feminino , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade
10.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450865

RESUMO

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI; however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11b+F4/80+CD206low cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.


Assuntos
Elastase de Leucócito/deficiência , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Neutrófilos/enzimologia , Animais , Apoptose/genética , Biomarcadores , Biópsia , Modelos Animais de Doenças , Testes de Função Cardíaca , Insulinas/metabolismo , Elastase de Leucócito/metabolismo , Camundongos , Camundongos Knockout , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Remodelação Ventricular/genética
11.
Eur J Endocrinol ; 184(2): 289-298, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33513126

RESUMO

Background: Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods: From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results: In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (ß = -12.43, P < 0.001), end-systolic volume (ß = -7.12, P < 0.001), stroke volume (ß = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (ß = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions: Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.


Assuntos
Insulina/sangue , Pulmão/patologia , Função Ventricular Direita/fisiologia , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Feminino , Alemanha , Testes de Função Cardíaca , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Fatores de Risco
12.
N Engl J Med ; 384(4): 345-352, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33503343

RESUMO

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).


Assuntos
Parada Cardíaca , Coração/fisiologia , Pulso Arterial , Suspensão de Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Extubação , Pressão Sanguínea/fisiologia , Morte , Eletrocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Cuidados para Prolongar a Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
13.
High Blood Press Cardiovasc Prev ; 28(1): 69-78, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33369723

RESUMO

The HEART score is used to effectively risk stratify undifferentiated chest pain patients in the Emergency Department (ED). It is unclear whether such risk stratification can be applied among ED high utilizers. We aim to determine the efficacy and safety of using the HEART score to predict 30-day short-term major adverse cardiac events (MACE) in ED high utilizers. We conducted a retrospective, observational study in which ED high utilizers were defined as patients who had four or more ED visits within the past 12 months. ED high utilizers presenting at the study ED with chest pain were enrolled. Patients in which the HEART score was utilized were placed in the HEART group and patients with no HEART scores documented were placed to the usual care group. Hospital admissions and cardiac stress tests performed during the index hospitalizations, and 30-day MACE rates were analyzed and compared between the HEART and usual care groups. From January 1, 2017 to December 31, 2019, a total of 8,315 patient visits from ED high utilizers were enrolled. In the HEART group, 49% of ED visits were admitted with 20% receiving stress tests. A 30-day MACE outcome occurred among 1.4% of visits. In the usual care group, 44% of ED visits were admitted, with only 9% receiving index stress tests and a 1.5% of 30-day MACE occurrence (p=0.727). The study showed that similar short-term MACE outcomes occurred between patients using HEART scores and usual care to risk stratify chest pain among ED high utilizers.


Assuntos
Angina Pectoris/diagnóstico , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Indicadores Básicos de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Angina Pectoris/etiologia , Angina Pectoris/terapia , Registros Eletrônicos de Saúde , Feminino , Testes de Função Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
15.
Sci Rep ; 10(1): 22257, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33335236

RESUMO

We aimed to clarify clinical implications of intrarenal hemodynamics assessed by intrarenal Doppler ultrasonography (IRD) and their prognostic impacts in heart failure (HF). We performed a prospective observational study, and examined IRD and measured interlobar renal artery velocity time integral (VTI) and intrarenal venous flow (IRVF) patterns (monophasic or non-monophasic pattern) to assess intrarenal hypoperfusion and congestion in HF patients (n = 341). Seven patients were excluded in VTI analysis due to unclear imaging. The patients were divided into groups based on (A) VTI: high VTI (VTI ≥ 14.0 cm, n = 231) or low VTI (VTI < 14.0 cm, n = 103); and (B) IRVF patterns: monophasic (n = 36) or non-monophasic (n = 305). We compared post-discharge cardiac event rate between the groups, and right-heart catheterization was performed in 166 patients. Cardiac index was lower in low VTI than in high VTI (P = 0.04), and right atrial pressure was higher in monophasic than in non-monophasic (P = 0.03). In the Kaplan-Meier analysis, cardiac event rate was higher in low VTI and monophasic groups (P < 0.01, respectively). In the Cox proportional hazard analysis, the combination of low VTI and a monophasic IRVF pattern was a predictor of cardiac events (P < 0.01). IRD imaging might be associated with cardiac output and right atrial pressure, and prognosis.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Rim/fisiopatologia , Prognóstico , Idoso , Biomarcadores/metabolismo , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Hemodinâmica , Humanos , Estimativa de Kaplan-Meier , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ultrassonografia Doppler
16.
S Afr Med J ; 110(6): 491-496, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32880560

RESUMO

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has undergone rapid expansion internationally over the past 15 years. In view of resource constraints in developing countries, a major challenge in applying this technology lies in identifying patients most likely to benefit. The development of a risk prediction model for TAVI has proved elusive, with a reported area under the curve (AUC) of 0.6 - 0.65. The available models were developed in a First-World setting and may not be applicable to South Africa (SA). OBJECTIVES: To evaluate novel indicators and to develop a TAVI risk prediction model unique to the SA context. The current work represents the important initial steps of derivation cohort risk model development and internal validation. METHODS: Seven-year experience with 244 successive TAVI implants in three centres in Western Cape Province, SA, was used to derive risk parameters. All outcomes are reported in accordance with the Valve Academic Research Consortium definitions. Multiple preprocedural variables were assessed for their impact on 1-year survival using univariate and multivariate models. RESULTS: Factors found not to correlate with 1-year survival included age, renal function and aortic valve gradients. The commonly used surgical risk prediction models (Society of Thoracic Surgeons score and EuroSCORE) showed no correlation with outcomes. Factors found to correlate best with 1-year survival on multivariate analysis were preprocedural body mass index (BMI) (favouring higher BMI), preprocedural left ventricular end-diastolic dimension (LVED) and ejection fraction (EF) (favouring smaller LVED and higher EF), absence of atrial fibrillation, and three novel parameters: independent living, ability to drive a car, and independent food acquisition/cooking. Discriminant analysis of these factors yielded an AUC of 0.8 (95% confidence interval 0.7 - 0.9) to predict 1-year survival, with resubstitution sensitivities and specificities of 72% and 71%, respectively. CONCLUSIONS: Apart from existing predictors, we identified three novel risk predictors (independent living, ability to drive a car, and independent food acquisition/cooking) for 1-year survival in TAVI candidates. These novel parameters performed well in this early evaluation, with an AUC for predicting 1-year survival higher than the AUCs for many of the internationally derived parameters. The parameters are inexpensive and easy to obtain at the initial patient visit. If validated prospectively in external cohorts, they may be applicable to other resource-constrained environments.


Assuntos
Substituição da Valva Aórtica Transcateter/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Testes de Função Cardíaca , Humanos , Vida Independente , Testes de Função Renal , Masculino , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , África do Sul/epidemiologia , Taxa de Sobrevida
19.
Life Sci ; 256: 117920, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32522571

RESUMO

AIM: We investigated the effects of high-intensity interval and continuous short-term exercise on body composition and cardiac function after myocardial ischemia-reperfusion injury (IRI) in obese rats. METHODS: Rats fed with a standard chow diet (SC) or high-fat diet (HFD) for 20 weeks underwent systolic blood pressure (SBP), glycemia and dual-energy X-ray absorptiometry analyses. Then, animals fed with HFD were subdivided into three groups: sedentary (HFD-SED); moderate-intensity continuous training (HFD-MICT); and high-intensity interval training (HFD-HIIT). Exercised groups underwent four isocaloric aerobic exercise sessions, in which HFD-MICT maintained the intensity continuously and HFD-HIIT alternated it. After exercise sessions, all groups underwent global IRI and myocardial infarct size (IS) was determined histologically. Fat and muscle mass were weighted, and protein levels involved in muscle metabolism were assessed in skeletal muscle. RESULTS: HFD-fed versus SC-fed rats reduced lean body mass by 31% (P < 0.001), while SBP, glycemia and body fat percentage were increased by 10% (P = 0.04), 30% (P = 0.006) and 54% (P < 0.001); respectively. HFD-induced muscle atrophy was restored in exercised groups, as only HFD-SED presented lower gastrocnemius (32%; P = 0.001) and quadriceps mass (62%; P < 0.001) than SC. PGC1-α expression was 2.7-fold higher in HFD-HIIT versus HFD-SED (P = 0.04), whereas HFD-HIIT and HFD-MICT exhibited 1.7-fold increase in p-mTORSer2481 levels compared to HFD-SED (P = 0.04). Although no difference was detected among groups for IS (P = 0.30), only HFD-HIIT preserved left-ventricle developed pressure after IRI (+0.7 mmHg; P = 0.9). SIGNIFICANCE: Short-term exercise, continuous or HIIT, restored HFD-induced muscle atrophy and increased mTOR expression, but only HIIT maintained myocardial contractility following IRI in obese animals.


Assuntos
Composição Corporal/fisiologia , Miocárdio/metabolismo , Animais , Glicemia/metabolismo , Pressão Sanguínea , Dieta Hiperlipídica , Regulação da Expressão Gênica , Testes de Função Cardíaca , Treinamento Intervalado de Alta Intensidade , Humanos , Estudos Longitudinais , Masculino , Modelos Animais , Músculo Esquelético/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/etiologia , Obesidade/etiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal , Ratos , Ratos Wistar , Sarcopenia/etiologia
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