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1.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203369

RESUMO

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder affecting one in 500 of the general population. Atrial fibrillation (AF) is the most common arrhythmia in patients with HCM. We sought to characterize the atrial electrophysiological and structural substrate in young and aging Gly203Ser cardiac troponin-I transgenic (HCM) mice. At 30 weeks and 50 weeks of age (n = 6 per strain each group), the left atrium was excised and placed on a multi-electrode array (MEA) for electrophysiological study; subsequent histological analyses and plasma samples were analyzed for biomarkers of extracellular matrix remodeling and cell adhesion and inflammation. Wild-type mice of matched ages were included as controls. Young HCM mice demonstrated significantly shortened atrial action potential duration (APD), increased conduction heterogeneity index (CHI), increased myocyte size, and increased interstitial fibrosis without changes in effective refractory periods (ERP), conduction velocity (CV), inflammatory infiltrates, or circulating markers of extracellular matrix remodeling and inflammation. Aging HCM mice demonstrated aggravated changes in atria electrophysiology and structural remodeling as well as increased circulating matrix metalloproteinases (MMP)-2, MMP-3, and VCAM-1 levels. This model of HCM demonstrates an underlying atrial substrate that progresses with age and may in part be responsible for the greater propensity for AF in HCM.


Assuntos
Fibrilação Atrial/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Átrios do Coração/metabolismo , Troponina I/metabolismo , Potenciais de Ação/fisiologia , Animais , Fibrilação Atrial/genética , Remodelamento Atrial/genética , Remodelamento Atrial/fisiologia , Pressão Sanguínea/fisiologia , Eletrofisiologia Cardíaca , Cardiomiopatia Hipertrófica/genética , Modelos Animais de Doenças , Eletrofisiologia , Feminino , Átrios do Coração/patologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Mutação , Troponina I/genética
2.
Medicine (Baltimore) ; 100(19): e25780, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106611

RESUMO

RATIONALE: Hepatocellular with tumor thrombi extending into 3 hepatic veins (HVs) and right atrium presents as a real clinical challenge. We report the first documented case of surgical resection of an advanced hepatocellular carcinoma (HCC) with extensive invasion to distal stomach, atrium and hepatic vasculatures. PATIENT CONCERNS: We present a case of 48-years old man with abdominal mass accompanying shortness of breath after activities. DIAGNOSES: Preoperative examination revealed giant HCC with tumor thrombi extending into portal vein, HVs, inferior vena cava, and atrium. INTERVENTIONS: Distal stomach involvement was confirmed at surgery and, distal gastrectomy, atrial reconstruction and ante-situm liver resection and autotransplantation under cardio-pulmonary bypass were performed. OUTCOMES: The operation time was 490 minutes, extracorporeal circulation time 124 minutes, and anhepatic time 40 minutes. Postoperative follow-up revealed normal hepatic and cardiac function with no sign of recurrence. LESSONS: This case illustrates that the extensive invasion of HCC to major vasculature and adjacent organs may not necessarily preclude the liver autotransplantation with multi-visceral resection as the treatment option of extremely advanced HCC patients.


Assuntos
Carcinoma Hepatocelular/secundário , Gastrectomia/métodos , Átrios do Coração/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Transplante de Fígado/métodos , Trombose/etiologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Átrios do Coração/patologia , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Cardiopatias/cirurgia , Veias Hepáticas/patologia , Veias Hepáticas/cirurgia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Veia Porta/patologia , Veia Porta/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/secundário , Neoplasias Gástricas/cirurgia , Trombose/diagnóstico , Trombose/cirurgia , Transplante Autólogo
3.
Radiol Med ; 126(9): 1159-1169, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34132927

RESUMO

BACKGROUND: Quantification of left atrial late gadolinium enhancement is a powerful clinical and research tool. Fibrosis burden has been shown to predict the success of pulmonary vein isolation, post-ablation reoccurrence, and major adverse cardiovascular events such as stroke. OVERVIEW: The standardized cardiovascular magnetic resonance imaging protocols 2020 update describes the key components of the examination. This review is a more in-depth guide, geared toward building left atrial late gadolinium enhancement imaging from the ground up. The standard protocol consists of the following: localization, pulmonary vein magnetic resonance angiography, cardiac cines, left ventricular, and atrial late gadolinium enhancement. We also review typical segmentation and post-processing techniques, as well as discuss pitfalls, limitations, and potential future innovations in this area. CONCLUSIONS: With sufficient experience and optimized protocols, left atrial late gadolinium enhancement imaging is a strong addition to the cardiac magnetic resonance imaging repertoire.


Assuntos
Meios de Contraste , Gadolínio , Átrios do Coração/diagnóstico por imagem , Aumento da Imagem , Imageamento por Ressonância Magnética/métodos , Fibrilação Atrial/etiologia , Fibrose/complicações , Fibrose/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Processamento de Imagem Assistida por Computador , Angiografia por Ressonância Magnética/métodos
4.
J Cardiothorac Surg ; 16(1): 151, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051789

RESUMO

BACKGROUND: Papillary fibroelastomas are rare but benign cardiac tumour that are often found on cardiac valvular surfaces. Their clinical manifestations ranging from clinically asymptomatic to substantial complications that are usually secondary to systemic embolism. Multiple theories have been proposed to explain the pathophysiology of its formation. CASE PRESENTATION: We reported a rare case of large papillary fibroelastoma in the right atrium of a young gentleman which was complicated with pulmonary embolism. Transthoracic echocardiography identified a large pedunculated mass measuring 3.4cmX3.4cmX2cm in right atrium with stalk attached to interatrial septum. The intracardiac mass was resected surgically, which revealed papillary fibroelastoma in histology examination. CONCLUSION: Differential diagnosis of intracardiac masses requires clinical information, laboratory tests and imaging modalities including echocardiography. Incidentally discovered papillary fibroelastomas are treated on the basis of their sizes, site, mobility and potential embolic complications. Due to the embolic risk inherent to intraacardiac masses, surgical resection represents an effective curative protocol in treating both symptomatic and asymptomatic right sided and left sided papillary fibroelastomas, with excellent long term postoperative prognosis.


Assuntos
Fibroelastoma Papilar Cardíaco/diagnóstico , Dispneia/etiologia , Embolia Pulmonar/etiologia , Adulto , Fibroelastoma Papilar Cardíaco/complicações , Fibroelastoma Papilar Cardíaco/patologia , Fibroelastoma Papilar Cardíaco/cirurgia , Cateteres de Demora , Cateteres Venosos Centrais , Nefropatias Diabéticas/complicações , Diagnóstico Diferencial , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Masculino , Diálise Renal
5.
Life Sci ; 278: 119595, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33974931

RESUMO

AIMS: EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play? MATERIALS AND METHODS: We generated an EphA4 knockout (KO) rat line with red fluorescent marker protein encoded by the mCherry cassette inserted downstream of the EphA4 promoter as a reporter. Using this system, we observed high expression of EphA4 in the heart atria and in the brain. KEY FINDINGS: EphaA4 KO rats (EphA4-/-) developed obvious atrial hypertrophy with an increased atria-to-heart weight ratio and atrial cardiomyocyte cross-sectional area at six months of age. EphA4-/- rats had reduced atrial end diastolic volume (EDV), atrial ejection fraction (EF) and left ventricular EF. They also exhibited increased amplitude of QRS complexes and QT intervals, with invisible p waves. RNA sequencing revealed that EphA4 KO altered the transcription of multiple genes involved in regulation of transcription and translation, ion binding, metabolism and cell adhesion. Deletion of EphA4 reduced IGF1 mRNA and protein expression, which is involved in cardiac remodeling. SIGNIFICANCE: Our data demonstrated that EphA4 was highly expressed in the atria and its deletion caused atrial dysfunction. Our findings also suggested that the EphA4 KO rat could be a potential model for studies on atrial remodeling.


Assuntos
Cardiomegalia/genética , Deleção de Genes , Átrios do Coração/patologia , Receptor EphA4/genética , Animais , Remodelamento Atrial , Cardiomegalia/patologia , Feminino , Átrios do Coração/metabolismo , Masculino , Ratos , Transcriptoma , Regulação para Cima
6.
Int Heart J ; 62(3): 616-626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054002

RESUMO

Atrial fibrillation (AF) is a relatively common complication of hypertension. Chronic hypertension induces cardiac HDAC6 catalytic activity. However, whether HDAC6 activation contributes to hypertension-induced AF is still uncertain. We examined whether chronic cardiac HDAC6 activation-induced atrial remodeling, leading to AF induction.The HDAC6 constitutively active transgenic (TG) (HDAC6 active TG) mouse overexpressing the active HDAC6 protein, specifically in cardiomyocytes, was created to examine the effects of chronic HDAC6 activation on atrial electrical and structural remodeling and AF induction in HDAC6 active TG and non-transgenic (NTG) mice. Left atrial burst pacing (S1S1 = 30 msec) for 15-30 sec significantly increased the frequency of sustained AF in HDAC6 active-TG mice compared with NTG mice. Left steady-state atrial pacing (S1S1 = 80 msec) decreased the atrial conduction velocity in isolated HDAC6 active TG compared with NTG mouse atria. The atrial size was similar between HDAC6 active TG and NTG mice. In contrast, atrial interstitial fibrosis increased in HDAC6 active TG compared with that of NTG mouse atria. While protein expression levels of both CX40 and CX43 were similar between HDAC6 active TG and NTG mouse atria, a heterogeneous distribution of CX40 and CX43 occurred in HDAC6 active-TG mouse atria but not in NTG mouse atria. Gene expression of interleukin 6 increased in HDAC6 active TG compared with NTG mouse atria.Chronic cardiac HDAC6 activation induced atrial electrical and structural remodeling, and sustained AF. Hypertension-induced cardiac HDAC6 catalytic activity may play important roles in the development of AF.


Assuntos
Fibrilação Atrial/fisiopatologia , Conexinas/metabolismo , Átrios do Coração/fisiopatologia , Desacetilase 6 de Histona/farmacologia , Interleucina-6/metabolismo , Animais , Fibrilação Atrial/etiologia , Fibrilação Atrial/metabolismo , Remodelamento Atrial , Estimulação Cardíaca Artificial/métodos , Estudos de Casos e Controles , Feminino , Fibrose , Átrios do Coração/patologia , Desacetilase 6 de Histona/metabolismo , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Interleucina-6/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Animais , Miócitos Cardíacos/metabolismo
7.
Medicine (Baltimore) ; 100(20): e25903, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011057

RESUMO

BACKGROUND: Some new trials have reported the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation. Limited by small number of studies and insufficient outcomes, previous meta-analyses also failed to draw a consistent conclusion on this topic. We thus conducted a new meta-analysis to systematically analyze the effect of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation. METHODS: Two independent investigators followed The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct the present meta-analysis. From the inception to June 2021, the EMBASE, PubMed, Web of Science, and Cochrane Library electronic databases were searched using the key phrases "atrial fibrillation," "chronic kidney disease," "catheter ablation," "renal failure," "renal function," "renal insufficiency," "end-stage renal disease," and "dialysis" for all relevant English-language trials. Observational or randomized controlled trial focusing on assessing the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation was included. P < .05 was set as the significance level. RESULTS: Our hypothesis was that chronic kidney disease is associated with increased atrial fibrosis and a higher risk of arrhythmia recurrence and that restoration of normal rhythm through catheter ablation is associated with improved kidney function. REGISTRATION NUMBER: 10.17605/OSF.IO/3WJAE.


Assuntos
Fibrilação Atrial/epidemiologia , Ablação por Cateter/estatística & dados numéricos , Átrios do Coração/patologia , Insuficiência Renal Crônica/epidemiologia , Fibrilação Atrial/patologia , Fibrilação Atrial/cirurgia , Causalidade , Fibrose , Taxa de Filtração Glomerular/fisiologia , Átrios do Coração/cirurgia , Humanos , Metanálise como Assunto , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Revisões Sistemáticas como Assunto , Resultado do Tratamento
8.
Res Vet Sci ; 136: 484-494, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33848803

RESUMO

Feline hypertrophic cardiomyopathy (HCM) is characterized by macrophage-driven myocardial remodeling processes in a pro-inflammatory environment. To further investigate the mechanisms behind these processes, the myocardial transcription of cytokines and remodeling enzymes was comparatively assessed in cats with HCM and cats without cardiac diseases. Sixty-seven cats were included, 17 cats with HCM (including 5 with atrial thrombus; AT), and 50 cats without cardiac diseases. The latter comprised 10 control cats (no cardiac or relevant systemic disease), 34 cats with diseases suspected to be associated with a systemic inflammatory state of which 18 suffered from feline infectious peritonitis (FIP), and 6 cats with multicentric lymphoma. Samples from atria, ventricular free walls and interventricular septum were examined using quantitative reverse transcriptase PCR. The overall highest myocardial marker transcriptions were observed in cats with multicentric lymphoma, FIP and HCM, followed by diseases likely associated with a systemic inflammatory state, and control cats. Inflammatory marker transcription predominated in the myocardium of cats with systemic inflammatory diseases, whereas in HCM the transcription of remodeling enzymes prevailed. Sex significantly influenced the myocardial transcription of several remodeling enzymes. These results suggest a versatile myocardial response depending on the disease and illustrates the relevance of sex for the cardiac response to cardiac and systemic disease in cats. A systemic inflammatory state appears to elicit an inflammatory phenotype in the myocardium, whereas in HCM, the myocardium mediates its own remodeling. In HCM, the identified markers might be involved in the ongoing remodeling processes causing structural and functional changes.


Assuntos
Remodelamento Atrial , Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/metabolismo , Citocinas/metabolismo , Miocárdio/metabolismo , Remodelação Ventricular , Animais , Remodelamento Atrial/genética , Biomarcadores/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Doenças do Gato/patologia , Gatos , Citocinas/genética , Peritonite Infecciosa Felina/metabolismo , Feminino , Átrios do Coração/patologia , Ventrículos do Coração/metabolismo , Inflamação/metabolismo , Inflamação/veterinária , Macrófagos/fisiologia , Masculino , Fenótipo , Transcrição Genética , Remodelação Ventricular/genética
9.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806765

RESUMO

By promoting atrial structural remodeling, atrial hypoxia contributes to the development of the atrial fibrillation substrate. Our study aimed to investigate the modulatory effect of hypoxia on profibrotic activity in cultured HL-1 cardiomyocytes and explore the possible signaling transduction mechanisms of profibrotic activity in vitro. Hypoxia (1% O2) significantly and time-dependently increased the expression of hypoxia-inducible factor (HIF)-1α and fibrotic marker proteins collagen I and III (COL1A and COL3A), transforming growth factor (TGF)-ß1 and α-smooth muscle actin (SMA). Western blot or immunohistochemistry analysis showed that hypoxia-induced increase in COL1A and COL3A was significantly attenuated by the addition of SP600125 (a specific c-Jun N-terminal kinase [JNK] inhibitor) or expression of dominant-negative JNK before hypoxia treatment. The inhibition of hypoxia-activated phosphorylation of JNK signal components (JNK, MKK4, nuclear c-Jun and ATF-2) by pre-treatment with SP600125 could suppress hypoxia-stimulated HIF-1α upregulation and fibrotic marker proteins expression. Hypoxia significantly increased reactive oxygen species (ROS) production in cultured HL-1 atrial cells. Pre-treatment with N-acetylcysteine significantly abrogated the expression of nuclear HIF-1α, JNK transduction components and fibrotic marker proteins. Taken together, these findings indicated that the hypoxia-induced atrial profibrotic response occurs mainly via the ROS/JNK pathway, its downstream upregulation of HIF-1α and c-Jun/ATF2 phosphorylation and nuclear translocation to up-regulate the expression of fibrosis-related proteins (COL1A, COL3A, TGF-ß1 and α-SMA). Our result suggests that suppression of ROS/JNK signaling pathway is a critical mechanism for developing a novel therapeutic strategy against atrial fibrillation.


Assuntos
Átrios do Coração/metabolismo , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Biomarcadores , Linhagem Celular , Fibrose , Expressão Gênica , Átrios do Coração/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Modelos Biológicos
11.
J Cardiovasc Electrophysiol ; 32(4): 1147-1160, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33682258

RESUMO

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia in clinical practice. However, current therapeutic interventions for atrial fibrillation have limited clinical efficacy as a consequence of major knowledge gaps in the mechanisms sustaining atrial fibrillation. From a mechanistic perspective, there is increasing evidence that atrial fibrosis plays a central role in the maintenance and perpetuation of atrial fibrillation. Electrophysiologically, atrial fibrosis results in alterations in conduction velocity, cellular refractoriness, and produces conduction block promoting meandering, unstable wavelets and micro-reentrant circuits. Clinically, atrial fibrosis has also linked to poor clinical outcomes including AF-related thromboembolic complications and arrhythmia recurrences post catheter ablation. In this article, we review the pathophysiology behind the formation of fibrosis as AF progresses, the role of fibrosis in arrhythmogenesis, surrogate markers for detection of fibrosis using cardiac magnetic resonance imaging, echocardiography and electroanatomic mapping, along with their respective limitations. We then proceed to review the current evidence behind therapeutic interventions targeting atrial fibrosis, including drugs and substrate-based catheter ablation therapies followed by the potential future use of electro phenotyping for AF characterization to overcome the limitations of contemporary substrate-based methodologies.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/patologia , Fibrilação Atrial/terapia , Fibrose , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Resultado do Tratamento
12.
Europace ; 23(23 Suppl 2): i169-i177, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33751082

RESUMO

AIMS: The aim of this study is to design a computer model of the left atrium for investigating fibre-orientation-dependent microstructure such as stringy fibrosis. METHODS AND RESULTS: We developed an approach for automatic construction of bilayer interconnected cable models from left atrial geometry and epi- and endocardial fibre orientation. The model consisted of two layers (epi- and endocardium) of longitudinal and transverse cables intertwined-like fabric threads, with a spatial discretization of 100 µm. Model validation was performed by comparison with cubic volumetric models in normal conditions. Then, diffuse (n = 2904), stringy (n = 3600), and mixed fibrosis patterns (n = 6840) were randomly generated by uncoupling longitudinal and transverse connections in the interconnected cable model. Fibrosis density was varied from 0% to 40% and mean stringy obstacle length from 0.1 to 2 mm. Total activation time, apparent anisotropy ratio, and local activation time jitter were computed during normal rhythm in each pattern. Non-linear regression formulas were identified for expressing measured propagation parameters as a function of fibrosis density and obstacle length (stringy and mixed patterns). Longer obstacles (even below tissue space constant) were independently associated with prolonged activation times, increased anisotropy, and local fluctuations in activation times. This effect was increased by endo-epicardial dissociation and mitigated when fibrosis was limited to the epicardium. CONCLUSION: Interconnected cable models enable the study of microstructure in organ-size models despite limitations in the description of transmural structures.


Assuntos
Endocárdio , Átrios do Coração , Simulação por Computador , Fibrose , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Pericárdio
13.
Medicine (Baltimore) ; 100(10): e24033, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725817

RESUMO

INTRODUCTION: One of the purposes of echocardiography is to determine the nature of a space-occupying lesion. The conventional transthoracic echocardiogram (TTE) is the preferred method for the diagnosis of cardiac space-occupying lesions as it can reveal the baseline information. For patients with poor conditions, however, TTE cannot clearly display the boundary, it has a limited role in determining the nature of the lesions. PATIENT CONCERNS: A 47-year-old woman presented with intermittent fever for 7 days and chest distress/shortness of breath for 5 days. DIAGNOSIS: In our current case, we inferred the nature of space-occupying lesions in the left atrium more accurately using transesophageal echocardiography (TEE) than TTE, which may offer diagnostic evidence for surgical treatment. INTERVENTIONS: The patient underwent surgical resection of the left atrial tumor and reconstruction of the left atrial wall. However, the patient's posterior lobe of the mitral valve was infiltrated by tumor, which was difficult to completely remove. OUTCOMES: Echocardiography was performed 3 months after surgery and the tumor recurred in the posterior lobe of the mitral valve. Although almost all tumors have been removed by surgery, the average survival time is often less than 1 year, as it is difficult to completely remove and easy to relapse with poor prognosis. CONCLUSION: Transesophageal echocardiography (TEE) plays a relatively more important role in the determination and differential diagnosis of cardiac space-occupying lesions.


Assuntos
Ecocardiografia Transesofagiana , Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Sarcoma/diagnóstico , Procedimentos Cirúrgicos Cardíacos , Diagnóstico Diferencial , Feminino , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Pessoa de Meia-Idade , Sarcoma/patologia , Sarcoma/cirurgia , Tomografia Computadorizada por Raios X
14.
Curr Urol Rep ; 22(4): 23, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33554309

RESUMO

PURPOSE OF REVIEW: To review the evidence regarding the current trends in surgical management of renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombosis. Recent published series have shown the role of minimally invasive surgery in IVC thrombectomy. This review article evaluates the present RCC with venous extent literature to assess the role of open and minimally invasive surgery in this scenario. RECENT FINDINGS: Robotic urological surgery has shown to have known benefits in radical prostatectomy, partial nephrectomy, and pyeloplasty. Recent published series showed feasibility of robotic IVC thrombectomy even for level IV cases. With growing number of robot-assisted and laparoscopic surgeries worldwide, there is a current tendency to treat this complex and challenging pathology with a minimally invasive approach, without compromising oncological outcomes.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Trombectomia/métodos , Veia Cava Inferior/cirurgia , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/patologia , Embolização Terapêutica , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Laparoscopia , Invasividade Neoplásica , Artéria Renal , Veias Renais/patologia , Veias Renais/cirurgia , Procedimentos Cirúrgicos Robóticos , Veia Cava Inferior/patologia , Trombose Venosa/patologia , Trombose Venosa/cirurgia
15.
BMC Neurol ; 21(1): 67, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573621

RESUMO

BACKGROUND: Systemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development. METHODS: This retrospective study identified 103 arteriosclerotic CSVD (aCSVD) patients (CSVD burdenlow 0 ~ 1, n = 61 and CSVD burdenhigh 2 ~ 4, n = 42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n = 81), structural magnetic resonance imaging and arterial spin labelling (ASL). Total CSVD burden was graded according to the ordinal "small vessel disease" rating score (0-4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh. RESULTS: Right atrial diameter (B coefficient, - 0.289; 95% CI, - 0.578 to - 0.001; P = 0.049) and left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P = 0.012) were independently associated with deep regional CBF in aCSVD patients. Binary logistic regression analysis demonstrated decreased deep regional CBF (OR 0.894; 95% CI 0.811-0.985; P = 0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve integrating clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve = 84.25, 95% CI 74.86-93.65%, P < 0.0001). CONCLUSION: The interrelationship of "cardiac -deep regional CBF-neuroimaging burden" reinforces the importance and prognostic significance of echocardiographic and cerebral hemodynamic assessment in CSVD early-warning.


Assuntos
Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Volume Sistólico/fisiologia , Idoso , Doenças de Pequenos Vasos Cerebrais/etiologia , Doenças de Pequenos Vasos Cerebrais/patologia , Feminino , Átrios do Coração/patologia , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Estudos Retrospectivos , Fatores de Risco , Função Ventricular Esquerda
16.
Circ Heart Fail ; 14(1): e006979, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33464950

RESUMO

BACKGROUND: Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation of cardiac MiVEC to pressure overload in mice and patients with aortic stenosis (AS). METHODS: In Tie2-Gfp mice subjected to transverse aortic constriction or sham surgery, we performed RNA sequencing of isolated cardiac Gfp+-MiVEC and validated the signature in freshly isolated MiVEC from left ventricle outflow tract and right atrium of patients with AS. We next compared their angiogenic and metabolic profiles and finally correlated molecular and pathological signatures with clinical phenotypes of 42 patients with AS (50% women). RESULTS: In mice, transverse aortic constriction induced progressive systolic dysfunction, fibrosis, and reduced microvascular density. After 10 weeks, 25 genes predominantly involved in matrix-regulation were >2-fold upregulated in isolated MiVEC. Increased transcript levels of Cartilage Intermediate Layer Protein (Cilp), Thrombospondin-4, Adamtsl-2, and Collagen1a1 were confirmed by quantitative reverse transcription polymerase chain reaction and recapitulated in left ventricle outflow tract-derived MiVEC of AS (P<0.05 versus right atrium-MiVEC). Fatty acid oxidation increased >2-fold in left ventricle outflow tract-MiVEC, proline content by 130% (median, IQR, 58%-474%; P=0.008) and procollagen secretion by 85% (mean [95% CI, 16%-154%]; P<0.05 versus right atrium-MiVEC for all). The altered transcriptome in left ventricle outflow tract-MiVEC was associated with impaired 2-dimensional-vascular network formation and 3-dimensional-spheroid sprouting (P<0.05 versus right atrium-MiVEC), profibrotic ultrastructural changes, and impaired diastolic left ventricle function, capillary density and functional status, especially in female AS. CONCLUSIONS: Pressure overload induces major transcriptional and metabolic adaptations in cardiac MiVEC resulting in excess interstitial fibrosis and impaired angiogenesis. Molecular rewiring of MiVEC is worse in women, compromises functional status, and identifies novel targets for intervention.


Assuntos
Estenose da Valva Aórtica/genética , Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Átrios do Coração/metabolismo , Ventrículos do Coração/metabolismo , Microvasos/metabolismo , Proteínas ADAMTS/genética , Idoso , Animais , Aorta , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/cirurgia , Colágeno Tipo I/genética , Constrição Patológica , Vasos Coronários/patologia , Modelos Animais de Doenças , Células Endoteliais/patologia , Proteínas da Matriz Extracelular/genética , Ácidos Graxos/metabolismo , Feminino , Perfilação da Expressão Gênica , Átrios do Coração/patologia , Implante de Prótese de Valva Cardíaca , Ventrículos do Coração/patologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Densidade Microvascular , Microvasos/patologia , Pró-Colágeno/metabolismo , Prolina/metabolismo , Pirofosfatases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Trombospondinas/genética
17.
Int J Mol Sci ; 22(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33514068

RESUMO

Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action po-tential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmaco-logical effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax), and decreased AP duration (APD), conduction velocity (CV), and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that disopyramide may be more effective against Pitx2-induced AF than propafenone and quinidine by prolonging WL.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Animais , Antiarrítmicos/química , Antiarrítmicos/farmacologia , Arritmias Cardíacas/genética , Arritmias Cardíacas/patologia , Fibrilação Atrial/genética , Fibrilação Atrial/patologia , Simulação por Computador , Disopiramida/química , Disopiramida/farmacologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/patologia , Humanos , Camundongos , Propafenona/química , Propafenona/uso terapêutico , Quinidina/química , Quinidina/farmacologia
18.
Int J Mol Med ; 47(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33448312

RESUMO

Atrial fibrillation (AF) is one of the most common tachyarrhythmias observed in the clinic and is characterized by structural and electrical remodelling. Atrial fibrosis, an emblem of atrial structural remodelling, is a complex multifactorial and patient­specific process involved in the occurrence and maintenance of AF. Whilst there is already considerable knowledge regarding the association between AF and fibrosis, this process is extremely complex, involving intricate neurohumoral and cellular and molecular interactions, and it is not limited to the atrium. Current technological advances have made the non­invasive evaluation of fibrosis in the atria and ventricles possible, facilitating the selection of patient­specific ablation strategies and upstream treatment regimens. An improved understanding of the mechanisms and roles of fibrosis in the context of AF is of great clinical significance for the development of treatment strategies targeting the fibrous region. In the present review, a focus was placed on the atrial fibrosis underlying AF, outlining its role in the occurrence and perpetuation of AF, by reviewing recent evaluations and potential treatment strategies targeting areas of fibrosis, with the aim of providing a novel perspective on the management and prevention of AF.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Ventrículos do Coração , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Fibrose , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos
19.
Mol Med Rep ; 23(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495806

RESUMO

Cardiac fibrosis is a common pathophysiological condition involved in numerous types of cardiovascular disease. The renin­angiotensin system, particularly angiotensin II (AngII), serves an important role in cardiac fibrosis and remodeling. Furthermore, p21­activated kinase 1 (PAK1) is a highly conserved serine/threonine protein kinase, which is abundantly expressed in all regions of the heart. However, the role of PAK1 in AngII­mediated activation of cardiac fibroblasts remains unknown. Therefore, the present study aimed to investigate the role of PAK1 in cardiac fibroblasts and its underlying mechanisms. Human cardiac fibroblasts (HCFs) were cultured and treated with PAK1 inhibitor IPA­3 or transduced with PAK1 short hairpin (sh)RNA by lentiviral particles to silence PAK1 expression levels. Subsequently, the cell proliferation and migration abilities of the HCFs were determined. Western blot analysis was used to detect the phosphorylation status of Janus kinase (JNK) and c­Jun. A Cell Counting Kit­8 assay showed that PAK1 inhibition following treatment of HCFs with 5 µM IPA­3 or PAK1­shRNA, significantly attenuated AngII­induced proliferation of fibroblasts. In addition, wound healing and Transwell migration assays demonstrated that inhibition of PAK1 significantly inhibited AngII­induced cell migration. Finally, decreased PAK1 expression levels downregulated AngII­mediated upregulation of α­smooth muscle actin (α­SMA), collagen I, phosphorylated (p)­JNK and p­c­Jun, a downstream molecule of JNK signaling. These findings indicate that PAK1 contributes to AngII­induced proliferation, migration and transdifferentiation of HCFs via the JNK/c­Jun pathway.


Assuntos
Angiotensina II/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/metabolismo , MAP Quinase Quinase 4/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases Ativadas por p21/metabolismo , Fibroblastos/patologia , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Humanos
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