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1.
Artigo em Inglês | MEDLINE | ID: mdl-38387435

RESUMO

AIMS: To evaluate the diagnosis and imaging of patients with mitral regurgitation and the management in routine clinical practice across Europe, the EACVI Scientific Initiatives Committee performed a survey across European centres. In particular, the routine use of echocardiography, advanced imaging modalities, heart valve clinics and heart valve teams was explored. METHODS AND RESULTS: A total of 61 responders, mainly tertiary centres or university hospitals, from 26 different countries responded to the survey, which consisted of 22 questions. For most questions related to echocardiography and advanced imaging, the answers were relatively homogeneous and demonstrated good adherence to current recommendations. In particular, the centres used a multiparametric echocardiographic approach, and selected the effective regurgitant orifice and vena contracta width as their preferred assessments. Two-dimensional (2D) measurements are still the most widely used parameters to assess left ventricular structure, however the majority use three-dimensional (3D) trans-oesophageal echocardiography (TOE) to evaluate valve morphology in severe MR. The majority of centres reported the onsite availability and clinical use of ergometric stress echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance imaging (CMR). Heart valve clinics and heart valve teams were also widely prevalent. CONCLUSION: Consistent with current guidelines echocardiography (TTE and TOE) remains the first line and central imaging modality for the assessment of mitral regurgitation although the complementary use of 3D TOE, CT and CMR appears to be growing. Heart valve clinics and heart valve teams are now widely prevalent.

2.
Eur Heart J Cardiovasc Imaging ; 24(8): 1120-1128, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37131301

RESUMO

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.


Assuntos
Estenose da Valva Aórtica , Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Ecocardiografia , Valva Aórtica/diagnóstico por imagem , Função Ventricular Esquerda , Volume Sistólico , Índice de Gravidade de Doença , Resultado do Tratamento , Estudos Retrospectivos
3.
Kardiol Pol ; 81(4): 338-349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36871309

RESUMO

Cardiovascular disease (CVD) is the leading cause of death worldwide affecting both sexes equally. However, in comparison to men, in women, it often is underrecognized and undertreated in both primary and secondary prevention settings. It is clear, that in the healthy population, there are profound differences both anatomically and biochemically between women and men, and this may impact how both groups present when they become ill. Moreover, some diseases affect more frequently women than men such as myocardial ischemia or infarction without obstructive coronary disease, Takotsubo syndrome, some atrial arrhythmias, or heart failure with preserved ejection fraction. Therefore, diagnostic and therapeutic strategies that have been established largely on the basis of clinical studies with a predominantly male population must be adapted before being applied to women. There is a paucity of data regarding cardiovascular disease in women. It is inadequate to only perform a subgroup analysis evaluating a specific treatment or invasive technique when women constitute fifty percent of the population. In this regard, this may affect the time of clinical diagnosis and severity assessments of some valvulopathies. In this review, we will focus on the differences in the diagnosis, management, and outcomes for women with the most frequent cardiovascular pathologies including coronary artery disease, arrhythmia, heart failure, and valvopathies. In addition, we will describe diseases that exclusively affect women that are related to pregnancy, and some of them are life-threatening. Although the lack of research on women plays a role in the poorer outcomes in women, especially in ischemic heart disease, some techniques such as transcatheter aortic valve implantation and transcatheter edge-to-edge therapy seem to have better outcomes in women.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Masculino , Feminino , Fatores de Risco
4.
Front Immunol ; 13: 974826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420265

RESUMO

Systemic lupus erythematosus (SLE) patients display an increased risk of cardiovascular disease (CVD). With the improved clinical management of other classical severe manifestation of the disease, CVD is becoming one of the most relevant complications of SLE, and it is an important factor causing morbidity and mortality. Several immune constituents have been shown to be involved in the pathogenesis of atherosclerosis and endothelial damage in SLE patients, including specific circulating cell populations, autoantibodies, and inflammatory mediators. In this review, we summarize the presentation of CVD in SLE and the role of the autoimmune responses present in SLE patients in the induction of atherogenesis, endothelial impairment and cardiac disease. Additionally, we discuss the utility of these immune mediators as early CVD biomarkers and targets for clinical intervention in SLE patients.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Cardiopatias , Lúpus Eritematoso Sistêmico , Humanos , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Biomarcadores , Aterosclerose/etiologia
6.
Am J Trop Med Hyg ; 103(4): 1480-1486, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700660

RESUMO

Chagas disease is an emerging infectious disease in Europe and other non-endemic areas, mainly owing to migration from endemic areas. We aimed at investigating the value of advanced echocardiography (ECHO) and cardiac magnetic resonance (CMR) in patients newly diagnosed with Chagas disease to compare findings with those of electrocardiogram (ECG) and conventional ECHO and thus detecting cardiac abnormalities. We included consecutive patients with newly diagnosed Chagas disease and registered cardiac test results (ECG, ECHO, and CMR). We divided ECHO parameters into three tiers: 1) left ventricular ejection fraction, regional wall motion abnormality, and left ventricular diastolic dimension (ECHO-1); 2) other common ECHO parameters (ECHO-2); and 3) global longitudinal strain (GLS) (ECHO-3). Cardiac magnetic resonance included global and segmental biventricular function, the presence of myocardial fibrosis, and edema. The study comprised 100 patients from South America. The mean age was 43.9 ± 0.9 years, and 66% were women. Mean time living in Spain was 9.7 ± 0.5 years. The ECG revealed ≥ 2 abnormal findings in 47% of patients. ECHO-1 was abnormal in 22% of patients, ECHO-2 in 52%, and GLS in 16%. Cardiac magnetic resonance was abnormal in 50% of cases, and in 3% of these, ECHO was normal. When ECG and conventional ECHO were taken together, abnormalities were detected in 83% of patients. This value increased to 86% and 92% for GLS and CMR, respectively. These findings suggest that ECG and conventional ECHO should be used routinely as standard cardiac tests for newly diagnosed cases of Chagas disease. The value of advanced ECHO techniques and CMR is low.


Assuntos
Cardiomiopatia Chagásica/diagnóstico , Doença de Chagas/patologia , Coração/fisiopatologia , Doenças Transmissíveis Emergentes , Ecocardiografia/métodos , Eletrocardiografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , América do Sul , Espanha , Função Ventricular Esquerda
7.
Echocardiography ; 37(6): 850-857, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32433805

RESUMO

OBJECTIVE: Morphological and functional right ventricular (RV) changes during normal pregnancy remain poorly characterized. Similar to left ventricle, RV load and function are expected to change, and establishing reference values for RV during a healthy pregnancy is critical for the evaluation of pregnancy-related heart disease. The aim of the study was to describe RV adaptation in a prospective cohort. METHODS: Serial echocardiographic examinations were performed in second trimester (24 ± 2 weeks), third (32 ± 2 week) trimester, and postpartum (>3 months after delivery). Nulliparous women were evaluated as control group. RV linear dimensions, areas, and function were assessed and compared. RESULTS: Forty-three pregnant women were evaluated and compared with nineteen nulliparous women as control. Function parameters decreased along gestation. RV fractional area fell from second to third trimester (52.01 ± 0.92 vs 48.73 ± 0.97, P < .05), as well as tricuspid annular plane systolic excursion (2.62 ± 0.05 vs 2.41 ± 0.05, P < .05); however, RV longitudinal strain (L) decreased earlier, showing main changes from second trimester (26.17 ± 0.86 vs 22.71 ± 0.57, P < .003, control vs second trimester). S'-wave velocity followed a different pattern without changes during pregnancy. RV diameters significantly increased during pregnancy: basal (3.65 ± 0.06 vs 3.90 ± 0.06, P < .05), mid- (2.70 ± 0.06 vs 3.00 ± 0.07, P < .05), longitudinal (6.90 ± 0.09 vs 7.32 ± 0.11, P < .05), and right ventricle outflow tract proximal diameter (3.20 ± 0.06 vs 3.44 ± 0.06, P < .05). RV areas also suffered early variation during pregnancy. In postpartum evaluation, all these changes were reversed. CONCLUSION: During pregnancy, RV experiments important variations. RV size increases, and its function decreases. Changes in LS were earlier compared with other function measures.


Assuntos
Ventrículos do Coração , Função Ventricular Direita , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Gravidez , Estudos Prospectivos , Valores de Referência
8.
Cell Rep ; 29(4): 1041-1054.e5, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31644901

RESUMO

During heart regeneration in the zebrafish, fibrotic tissue is replaced by newly formed cardiomyocytes derived from preexisting ones. It is unclear whether the heart is composed of several cardiomyocyte populations bearing different capacity to replace lost myocardium. Here, using sox10 genetic fate mapping, we identify a subset of preexistent cardiomyocytes in the adult zebrafish heart with a distinct gene expression profile that expanded after cryoinjury. Genetic ablation of sox10+ cardiomyocytes impairs cardiac regeneration, revealing that these cells play a role in heart regeneration.


Assuntos
Miócitos Cardíacos/metabolismo , Regeneração , Fatores de Transcrição SOXE/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Coração/fisiologia , Miócitos Cardíacos/fisiologia , Fatores de Transcrição SOXE/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
9.
Rev. esp. cardiol. (Ed. impr.) ; 72(5): 392-397, mayo 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-188386

RESUMO

Introducción y objetivos: Los tratamientos actuales de la estenosis aórtica (EAo) grave incluyen el implante percutáneo de válvula aórtica (TAVI) y la cirugía de sustitución valvular aórtica (SVAo). El objetivo es describir la evolución de los pacientes con EAo grave tras la indicación de intervención, las variables que influyen en su pronóstico y los determinantes de un tiempo de espera superior a 2 meses. Métodos: Subanálisis del registro IDEAS (Influencia del Diagnóstico de Estenosis Aórtica Severa) en los pacientes a los que se indicó intervención. Resultados: De 726 pacientes con EAo grave diagnosticada en enero de 2014, se indicó intervención a 300 que son el foco del presente estudio. La media de edad era 74,0 +/- 9,7 años. Se intervino a 258 pacientes (86,0%): 59 con TAVI y 199 con SVAo. Al año, 42 (14,0%) continuaban sin intervención, ya sea por seguir en espera (34) o haber fallecido (8). La mitad de los pacientes que murieron antes del procedimiento fallecieron en los primeros 100 días. El tiempo hasta la intervención fue 2,9 +/- 1,6 meses para el TAVI y 3,5 +/- 0,2 meses para la SVAo (p = 0,03). Los predictores de mortalidad independientes fueron el sexo masculino (HR = 2,6; IC95%, 1,1-6,0), la insuficiencia mitral moderada-grave (HR = 2,6; IC95%, 1,5-4,5), la movilidad reducida (HR = 4,6; IC95%, 1,7-12,6) y la falta de intervención (HR = 2,3; IC95%, 1,02-5,03). Conclusiones: Los pacientes con EAo grave en espera de intervención tienen alto riesgo de mortalidad. Hay indicadores clínicos asociados con peor pronóstico que podrían indicar la necesidad de una intervención precoz


Introduction and objectives: Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months. Methods: Subanalysis of the IDEAS (Influence of the Severe Aortic Stenosis Diagnosis) registry in patients indicated for TAVI or SAVR. Results: Of 726 patients with severe AS diagnosed in January 2014, the decision to perform an intervention was made in 300, who were included in the present study. The mean age was 74.0 +/- 9.7 years. A total of 258 (86.0%) underwent an intervention: 59 TAVI and 199 SAVR. At the end of the year, 42 patients (14.0%) with an indication for an intervention did not receive it, either because they remained on the waiting list (34 patients) or died while waiting for the procedure (8 patients). Of the patients who died while on the waiting list, half did so in the first 100 days. The mean waiting time was 2.9 +/- 1.6 for TAVI and 3.5 +/- 0.2 months for SAVR (P = .03). The independent predictors of mortality were male sex (HR, 2.6; 95%CI, 1.1-6.0), moderate-severe mitral regurgitation (HR, 2.6; 95%CI, 1.5-4.5), reduced mobility (HR, 4.6; 95%CI, 1.7-12.6), and non intervention (HR, 2.3; 95%CI, 1.02-5.03). Conclusions: Patients with severe aortic stenosis a waiting therapeutic procedures have a high mortality risk. Some clinical indicators predict a worse prognosis and suggest the need for early intervention


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Implante de Prótese de Valva Cardíaca/métodos , Resultado do Tratamento , Progressão da Doença , Listas de Espera , Indicadores de Morbimortalidade , Doença Catastrófica , Estudos Prospectivos , Índice de Gravidade de Doença
10.
Aging Cell ; 18(3): e12936, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30884114

RESUMO

Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. We investigated the mechanisms underlying vessel stiffness in LmnaG609G/G609G mice with ubiquitous progerin expression, and tested the effect of treatment with nitrites. We also bred LmnaLCS/LCS Tie2Cre+/tg and LmnaLCS/LCS SM22αCre+/tg mice, which express progerin specifically in endothelial cells (ECs) and in vascular smooth muscle cells (VSMCs), respectively, to determine the specific contribution of each cell type to vascular pathology. We found vessel stiffness and inward remodeling in arteries of LmnaG609G/G609G and LmnaLCS/LCS SM22αCre+/tg , but not in those from LmnaLCS/LCS Tie2Cre+/tg mice. Structural alterations in aortas of progeroid mice were associated with decreased smooth muscle tissue content, increased collagen deposition, and decreased transverse waving of elastin layers in the media. Functional studies identified collagen (unlike elastin and the cytoskeleton) as an underlying cause of aortic stiffness in progeroid mice. Consistent with this, we found increased deposition of collagens III, IV, V, and XII in the media of progeroid aortas. Vessel stiffness and inward remodeling in progeroid mice were prevented by adding sodium nitrite in drinking water. In conclusion, LmnaG609G/G609G arteries exhibit stiffness and inward remodeling, mainly due to progerin-induced damage to VSMCs, which causes increased deposition of medial collagen and a secondary alteration in elastin structure. Treatment with nitrites prevents vascular stiffness in progeria.


Assuntos
Modelos Animais de Doenças , Músculo Liso Vascular/efeitos dos fármacos , Progéria/tratamento farmacológico , Progéria/genética , Nitrito de Sódio/farmacologia , Nitrito de Sódio/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Animais , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Progéria/patologia , Nitrito de Sódio/administração & dosagem
11.
Rev Esp Cardiol (Engl Ed) ; 72(5): 392-397, 2019 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29997054

RESUMO

INTRODUCTION AND OBJECTIVES: Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months. METHODS: Subanalysis of the IDEAS (Influence of the Severe Aortic Stenosis Diagnosis) registry in patients indicated for TAVI or SAVR. RESULTS: Of 726 patients with severe AS diagnosed in January 2014, the decision to perform an intervention was made in 300, who were included in the present study. The mean age was 74.0 ± 9.7 years. A total of 258 (86.0%) underwent an intervention: 59 TAVI and 199 SAVR. At the end of the year, 42 patients (14.0%) with an indication for an intervention did not receive it, either because they remained on the waiting list (34 patients) or died while waiting for the procedure (8 patients). Of the patients who died while on the waiting list, half did so in the first 100 days. The mean waiting time was 2.9 ± 1.6 for TAVI and 3.5 ± 0.2 months for SAVR (P = .03). The independent predictors of mortality were male sex (HR, 2.6; 95%CI, 1.1-6.0), moderate-severe mitral regurgitation (HR, 2.6; 95%CI, 1.5-4.5), reduced mobility (HR, 4.6; 95%CI, 1.7-12.6), and nonintervention (HR, 2.3; 95%CI, 1.02-5.03). CONCLUSIONS: Patients with severe aortic stenosis awaiting therapeutic procedures have a high mortality risk. Some clinical indicators predict a worse prognosis and suggest the need for early intervention.


Assuntos
Estenose da Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Tomada de Decisão Clínica , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/mortalidade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Análise de Sobrevida , Substituição da Valva Aórtica Transcateter/mortalidade , Listas de Espera
12.
Nat Commun ; 9(1): 428, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382818

RESUMO

During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a+ cells, with a small contribution from tbx5a- SHF progenitors. Notably, ablation of ventricular tbx5a+-derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration.


Assuntos
Ventrículos do Coração/citologia , Miocárdio/citologia , Miócitos Cardíacos/citologia , Regeneração/genética , Proteínas com Domínio T/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Diferenciação Celular , Linhagem da Célula/genética , Rastreamento de Células , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Ventrículos do Coração/crescimento & desenvolvimento , Ventrículos do Coração/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Organogênese/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteínas com Domínio T/deficiência , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
13.
Proc Natl Acad Sci U S A ; 113(46): E7250-E7259, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27799555

RESUMO

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24-/- mouse model of HGPS. Challenge of Zmpste24-/- mice with the ß-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery. Patch-clamping in Zmpste24-/- cardiomyocytes revealed prolonged calcium-transient duration and reduced sarcoplasmic reticulum calcium loading and release, consistent with the absence of isoproterenol-induced ventricular arrhythmia. Zmpste24-/- progeroid mice also developed severe fibrosis-unrelated bradycardia and PQ interval and QRS complex prolongation. These conduction defects were accompanied by overt mislocalization of the gap junction protein connexin43 (Cx43). Remarkably, Cx43 mislocalization was also evident in autopsied left ventricle tissue from HGPS patients, suggesting intercellular connectivity alterations at late stages of the disease. The similarities between HGPS patients and progeroid mice reported here strongly suggest that defective cardiac repolarization and cardiomyocyte connectivity are important abnormalities in the HGPS pathogenesis that increase the risk of arrhythmia and premature death.


Assuntos
Arritmias Cardíacas/fisiopatologia , Doença do Sistema de Condução Cardíaco/fisiopatologia , Progéria/fisiopatologia , Adolescente , Adulto , Animais , Arritmias Cardíacas/metabolismo , Cálcio/fisiologia , Doença do Sistema de Condução Cardíaco/metabolismo , Criança , Pré-Escolar , Conexina 43/metabolismo , Conexina 43/fisiologia , Feminino , Coração/fisiologia , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Metaloendopeptidases/genética , Metaloendopeptidases/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Lâmina Nuclear/fisiologia , Progéria/metabolismo , Retículo Sarcoplasmático/fisiologia , Adulto Jovem
14.
Am J Cardiol ; 118(2): 244-50, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27239021

RESUMO

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies.


Assuntos
Estenose da Valva Aórtica/terapia , Tratamento Conservador , Sistema de Registros , Taxa de Sobrevida , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/fisiopatologia , Doenças Assintomáticas , Tomada de Decisão Clínica , Comorbidade , Ecocardiografia , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Razão de Chances , Prognóstico , Índice de Gravidade de Doença , Espanha , Volume Sistólico , Centros de Atenção Terciária , Resultado do Tratamento
17.
Cell Rep ; 12(10): 1691-703, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26321646

RESUMO

After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.


Assuntos
Coração/fisiologia , Regeneração , Telomerase/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Proliferação de Células , Expressão Gênica , Técnicas de Inativação de Genes , Miocárdio/enzimologia , Miócitos Cardíacos/fisiologia , Técnicas de Cultura de Tecidos , Peixe-Zebra
18.
J Hypertens ; 33(4): 843-50; discussion 850, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25915889

RESUMO

OBJECTIVE: The Notch pathway has been linked to pulmonary hypertension, but its role in systemic hypertension and, in particular in left ventricular hypertrophy (LVH), remains poorly understood. The main objective of this work was to analyse the effect of inhibiting the Notch pathway on the establishment and maintenance of angiotensin II (Ang-II)-induced arterial hypertension and LVH in adult mice with inducible genetic deletion of γ-secretase, and to test preclinically the therapeutic efficacy of γ-secretase inhibitors (GSIs). BASIC METHODS: We analysed Ang-II responses in primary cultures of vascular smooth muscle cells obtained from a novel mouse model with inducible genetic deletion of the γ-secretase complex, and the effects of GSI treatment on a mouse cardiac cell line. We also investigated Ang-II-induced hypertension and LVH in our novel mouse strain lacking the γ-secretase complex and in GSI-treated wild-type mice. Moreover, we analysed vascular tissue from hypertensive patients with and without LVH. MAIN RESULTS: Vascular smooth muscle cells activate the Notch pathway in response to Ang-II both 'in vitro' and 'in vivo'. Genetic deletion of γ-secretase in adult mice prevented Ang-II-induced hypertension and LVH without causing major adverse effects. Treatment with GSI reduced Ang-II-induced hypertrophy of a cardiac cell line 'in vitro' and LVH in wild-type mice challenged with Ang-II. We also report elevated expression of the Notch target HES5 in vascular tissue from hypertensive patients with LVH compared with those without LVH. CONCLUSION: The Notch pathway is activated in the vasculature of mice with hypertension and LVH, and its inhibition via inducible genetic γ-secretase deletion protects against both conditions. Preliminary observations in hypertensive patients with LVH support the translational potential of these findings. Moreover, GSI treatment protects wild-type mice from Ang-II-induced LVH without affecting blood pressure. Our results unveil the potential use of GSIs in the treatment of hypertensive patients with LVH.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Cardiomegalia/prevenção & controle , Dibenzazepinas/uso terapêutico , Hipertensão/prevenção & controle , Hipertrofia Ventricular Esquerda/prevenção & controle , Angiotensina II , Animais , Pressão Sanguínea/efeitos dos fármacos , Células Cultivadas , Dibenzazepinas/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Hipertensão/induzido quimicamente , Masculino , Camundongos , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
PLoS One ; 9(12): e115604, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25532015

RESUMO

AIMS: While zebrafish embryos are amenable to in vivo imaging, allowing the study of morphogenetic processes during development, intravital imaging of adults is hampered by their small size and loss of transparency. The use of adult zebrafish as a vertebrate model of cardiac disease and regeneration is increasing at high speed. It is therefore of great importance to establish appropriate and robust methods to measure cardiac function parameters. METHODS AND RESULTS: Here we describe the use of 2D-echocardiography to study the fractional volume shortening and segmental wall motion of the ventricle. Our data show that 2D-echocardiography can be used to evaluate cardiac injury and also to study recovery of cardiac function. Interestingly, our results show that while global systolic function recovered following cardiac cryoinjury, ventricular wall motion was only partially restored. CONCLUSION: Cryoinjury leads to long-lasting impairment of cardiac contraction, partially mimicking the consequences of myocardial infarction in humans. Functional assessment of heart regeneration by echocardiography allows a deeper understanding of the mechanisms of cardiac regeneration and has the advantage of being easily transferable to other cardiovascular zebrafish disease models.


Assuntos
Temperatura Baixa/efeitos adversos , Ecocardiografia/métodos , Ventrículos do Coração/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Regeneração/fisiologia , Disfunção Ventricular/diagnóstico , Disfunção Ventricular/prevenção & controle , Animais , Infarto do Miocárdio/etiologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Disfunção Ventricular/etiologia , Peixe-Zebra/crescimento & desenvolvimento
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