Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.872
Filtrar
1.
BMC Cardiovasc Disord ; 20(1): 521, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308143

RESUMO

BACKGROUND: Calcific aortic valve disease (CAVD) pathophysiology is a complex, multistage process, usually diagnosed at advanced stages after significant anatomical and hemodynamic changes in the valve. Early detection of disease progression is thus pivotal in the development of prevention and mitigation strategies. In this study, we developed a diet-based, non-genetically modified mouse model for early CAVD progression, and explored the utility of two-photon excited fluorescence (TPEF) microscopy for early detection of CAVD progression. TPEF imaging provides label-free, non-invasive, quantitative metrics with the potential to correlate with multiple stages of CAVD pathophysiology including calcium deposition, collagen remodeling and osteogenic differentiation. METHODS: Twenty-week old C57BL/6J mice were fed either a control or pro-calcific diet for 16 weeks and monitored via echocardiography, histology, immunohistochemistry, and quantitative polarized light imaging. Additionally, TPEF imaging was used to quantify tissue autofluorescence (A) at 755 nm, 810 nm and 860 nm excitation, to calculate TPEF 755-860 ratio (A860/525/(A755/460 + A860/525)) and TPEF Collagen-Calcium ratio (A810/525/(A810/460 + A810/525)) in the murine valves. In a separate experiment, animals were fed the above diets till 28 weeks to assess for later-stage calcification. RESULTS: Pro-calcific mice showed evidence of lipid deposition at 4 weeks and calcification at 16 weeks at the valve commissures. The valves of pro-calcific mice also showed positive expression for markers of osteogenic differentiation, myofibroblast activation, proliferation, inflammatory cytokines and collagen remodeling. Pro-calcific mice exhibited lower TPEF autofluorescence ratios, at locations coincident with calcification, that correlated with increased collagen disorganization and positive expression of osteogenic markers. Additionally, locations with lower TPEF autofluorescence ratios at 4 and 16 weeks exhibited increased calcification at later 28-week timepoints. CONCLUSIONS: This study suggests the potential of TPEF autofluorescence metrics to serve as a label-free tool for early detection and monitoring of CAVD pathophysiology.


Assuntos
Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Calcinose/patologia , Microscopia de Fluorescência por Excitação Multifotônica , Animais , Valva Aórtica/metabolismo , Estenose da Valva Aórtica/metabolismo , Biomarcadores/metabolismo , Calcinose/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Diagnóstico Precoce , Masculino , Camundongos Endogâmicos C57BL , Valor Preditivo dos Testes , Fatores de Tempo
2.
J UOEH ; 42(3): 291-295, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879194

RESUMO

We report a case of a 77-year-old male who had been diagnosed with normal-flow high-pressure gradient severe aortic stenosis (AS) two years previously. In accordance with his wishes, it was decided not to perform surgery. He visited our hospital with anorexia and weight loss and was diagnosed with gastric cancer. Echocardiography showed a change to paradoxical low-flow low-pressure gradient severe AS (PLFLPG AS). A decrease in stroke volume is typically associated with a smaller LV size, but the reason for a smaller LV size in PLFLPG AS remains unclear. In this case, the change to PLFLPG AS was thought to be due to a decrease in whole body oxygen consumption, and this may help to understand the pathology.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Baixo Débito Cardíaco , Progressão da Doença , Ecocardiografia , Ventrículos do Coração/patologia , Humanos , Masculino , Consumo de Oxigênio , Índice de Gravidade de Doença , Neoplasias Gástricas/complicações , Volume Sistólico
3.
Prog Cardiovasc Dis ; 63(4): 496-502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526213

RESUMO

Calcific aortic valve stenosis (AS) is the most common form of acquired valvular heart disease needing intervention and our understanding of this disease has evolved from one of degenerative calcification to that of an active process driven by the interplay of genetic factors and chronic inflammation modulated by risk factors such as smoking, hypertension and elevated cholesterol. Lipoprotein(a) [Lp (a)] is a cholesterol rich particle secreted by the liver which functions as the major lipoprotein carrier of phosphocholine-containing oxidized phospholipids. Lp(a) levels are largely genetically determined by polymorphisms in the LPA gene. While there is an extensive body of evidence linking Lp(a) to atherosclerotic cardiovascular disease, emerging evidence now suggests a similar association of Lp(a) to calcific AS. In this article, we performed a systematic review of all published literature to assess the association between Lp(a) and calcific aortic valve (AV) disease. In addition, we review the potential mechanisms by which Lp(a) influences the progression of valve disease. Our review identified a total of 21 studies, varying from case-control studies, prospective or retrospective observational cohort studies to Mendelian randomized studies that assessed the association between Lp(a) and calcific AS. All but one of the above studies demonstrated significant association between elevated Lp(a) and calcific AS. We conclude that there is convincing evidence supporting a causal association between elevated Lp(a) and calcific AS. In addition, elevated Lp(a) predicts a faster hemodynamic progression of AS, and increased risk of AV replacement, especially in younger patients. Further research into the clinical utility of Lp(a) as a marker for predicting the incidence, progression, and outcomes of sclerodegenerative AV disease is needed.


Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/epidemiologia , Valva Aórtica/patologia , Calcinose/sangue , Calcinose/epidemiologia , Lipoproteína(a)/sangue , Estenose da Valva Aórtica/patologia , Calcinose/patologia , Humanos
4.
J Cardiovasc Magn Reson ; 22(1): 46, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32564773

RESUMO

BACKGROUND: Myocardial fibrosis is a major determinant of outcome in aortic stenosis (AS). Novel fast real-time (RT) cardiovascular magnetic resonance (CMR) mapping techniques allow comprehensive quantification of fibrosis but have not yet been compared against standard techniques and histology. METHODS: Patients with severe AS underwent CMR before (n = 110) and left ventricular (LV) endomyocardial biopsy (n = 46) at transcatheter aortic valve replacement (TAVR). Midventricular short axis (SAX) native, post-contrast T1 and extracellular volume fraction (ECV) maps were generated using commercially available modified Look-Locker Inversion recovery (MOLLI) (native: 5(3)3, post-contrast: 4(1)3(1)2) and RT single-shot inversion recovery Fast Low-Angle Shot (FLASH) with radial undersampling. Focal late gadolinium enhancement was excluded from T1 and ECV regions of interest. ECV and LV mass were used to calculate LV matrix volumes. Variability and agreements were assessed between RT, MOLLI and histology using intraclass correlation coefficients, coefficients of variation and Bland Altman analyses. RESULTS: RT and MOLLI derived ECV were similar for midventricular SAX slice coverage (26.2 vs. 26.5, p = 0.073) and septal region of interest (26.2 vs. 26.5, p = 0.216). MOLLI native T1 time was in median 20 ms longer compared to RT (p < 0.001). Agreement between RT and MOLLI was best for ECV (ICC > 0.91), excellent for post-contrast T1 times (ICC > 0.81) and good for native T1 times (ICC > 0.62). Diffuse collagen volume fraction by biopsies was in median 7.8%. ECV (RT r = 0.345, p = 0.039; MOLLI r = 0.40, p = 0.010) and LV matrix volumes (RT r = 0.45, p = 0.005; MOLLI r = 0.43, p = 0.007) were the only parameters associated with histology. CONCLUSIONS: RT mapping offers fast and sufficient ECV and LV matrix volume calculation in AS patients. ECV and LV matrix volume represent robust and universally comparable parameters with associations to histologically assessed fibrosis and may emerge as potential targets for clinical decision making.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Biópsia , Feminino , Fibrose , Humanos , Masculino , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Substituição da Valva Aórtica Transcateter , Remodelação Ventricular
5.
Vascul Pharmacol ; 130: 106679, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387621

RESUMO

BACKGROUND: Treatment with non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) or rivaroxaban (a direct inhibitor of factor [F] Xa) attenuates atherosclerotic plaque progression in hypercholesterolemic mice. PURPOSE: To evaluate the effect of NOACs application on the expression of coagulation proteins in loco within stenotic aortic valves and in valve interstitial cells (VICs) from patients with severe aortic stenosis (AS). METHODS: Primary cultures of VICs obtained from 90 patients undergoing aortic valve replacement were stimulated with TNF-α (50 ng/mL) and pre-treated with rivaroxaban (1 and 10 ng/mL) or dabigatran (25 and 250 ng/mL). The expression of coagulation proteins was analyzed by immunofluorescence. Cytokine levels were measured by ELISA. RESULTS: FX, FXa, FVII, thrombin and PAR1/2 were present in loco within human aortic stenotic valves. Cultured VICs exhibited constant expression of FX, TF, PAR1/2. Exposure of VICs to TNF-α caused the upregulated expression of TF, PAR1/2 and induced expression of thrombin, FVII and FXa. FX was expressed by 80% of VICs, regardless of stimulation. Cultured VICs were able to synthesize metalloproteinases 1-3, IL-6, IL-32, IL-34, osteopontin and osteocalcin, the levels of which increased under TNF-α stimulation. NOACs added to culture inhibited coagulation factor and PAR1/2 expression. Moreover, NOACs down-regulated VIC-derived proteins responsible for valve calcification and extracellular matrix remodeling. CONCLUSIONS: NOACs at therapeutic concentrations may inhibit the effects of FXa and thrombin at in vitro level. It might be speculated that long-term treatment with rivaroxaban or dabigatran could attenuate the progression of AS in humans.


Assuntos
Antitrombinas/farmacologia , Estenose da Valva Aórtica/tratamento farmacológico , Valva Aórtica/efeitos dos fármacos , Fatores de Coagulação Sanguínea/metabolismo , Dabigatrana/farmacologia , Inibidores do Fator Xa/farmacologia , Mediadores da Inflamação/metabolismo , Rivaroxabana/farmacologia , Idoso , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Fatores de Coagulação Sanguínea/genética , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transdução de Sinais
6.
BMC Med Genet ; 21(1): 93, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375772

RESUMO

BACKGROUND: Pathogenic SLC6A1 variants have been reported in patients with myoclonic-atonic epilepsy (MAE). NOTCH1, encoding a member of the Notch family of proteins, is known to be associated with aortic valve disease. The PRIMPOL variant has only been identified in Chinese patients with high myopia. Exome sequencing analysis now allows the simultaneous detection of multiple genetic etiologies for patients with complicated clinical features. However, the presence of three Mendelian disorders in one patient supported by their respective pathogenic variants and clinical phenotypes is very rare. CASE PRESENTATION: Here, we report a 4-year-old Chinese boy who presented with MAE, delayed language, borderline intellectual disability (ID), mildly impaired social skills and attention deficit hyperactivity disorder (ADHD). He also had mild aortic valve stenosis and high myopia. Using whole-exome sequencing (WES), we identified three variants: (1) SLC6A1, NM_003042.4: c.881-883del (p.Phe294del), (2) NOTCH1, NM_017617.5:c.1100-2A > G and (3) PRIMPOL, NM_152683.4:c.265 T > G (p.Tyr89Asp). Parental Sanger sequencing confirmed that SLC6A1 and NOTCH1 variants were de novo, whereas the PRIMPOL variant was inherited from the father who also had high myopia. Furthermore, the PRIMPOL variant was absent from the genomes of the paternal grandparents, and thus was also a de novo event in the family. All three variants are classified as pathogenic. CONCLUSION: The SLC6A1 variant could explain the features of MAE, delayed language, borderline ID, impaired social skills and ADHD in this patient, whereas the features of aortic valve stenosis and high myopia of the patient may be explained by variants in NOTCH1 and PRIMPOL, respectively. This case demonstrated the utility of exome sequencing in uncovering the multiple pathogenic variants in a patient with complicated phenotypes due to the blending of three Mendelian disorders.


Assuntos
Epilepsias Mioclônicas/genética , Epilepsia Generalizada/genética , Predisposição Genética para Doença , Miopia/genética , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , Pré-Escolar , DNA Primase/genética , DNA Polimerase Dirigida por DNA/genética , Epilepsias Mioclônicas/patologia , Epilepsia Generalizada/patologia , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Testes Genéticos , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Enzimas Multifuncionais/genética , Mutação/genética , Miopia/patologia , Receptor Notch1/genética , Sequenciamento Completo do Exoma
7.
Ann Thorac Surg ; 110(4): 1364-1371, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32454012

RESUMO

BACKGROUND: Aortic valve neocuspidization (AVNeo) (Ozaki procedure) has excellent midterm results in adults. Outcomes in patients with a small native aortic annulus are unknown. We report early outcomes in young patients with small native aortic valve annuli. METHODS: Retrospective data of patients undergoing AVNeo between 2015 and 2019 were reviewed. Patients with native aortic annulus less than 21 mm undergoing 3-leaflet AVNeo were included. RESULTS: A total of 51 patients were identified (median age 7.9 years; median weight 21 kg), and 80% patients were less than or equal to 12 years age. Preoperative indication was aortic regurgitation (AR) (n = 23), aortic stenosis (AS) (n = 22), or mixed AS and AR (n = 6). Baseline anatomy was quadricuspid (n = 1), tricuspid (n = 23), bicuspid (n = 15), or unicuspid (n = 12) valve. Preoperative peak gradient for AS and mixed AS and AR patients was 55.36 mm Hg. Median native annulus diameter was 17 mm; sinus and annular enlargements were required in 22 patients and 9 patients, respectively. Median intensive care unit and hospital length of stay were 2.0 days and 7.2 days, respectively. There were no reinterventions, and there was 1 hospital mortality unrelated to aortic valve. At discharge, 94% of patients had less than or equal to mild AR, and the median peak gradient was 18 mm Hg. At mean follow-up of 11.9 months, 80% and 82% of patients had less than moderate AR and AS, respectively. Three patients required surgical reintervention. In annular enlargement patients, mean annulus Z score remained greater than 0 at follow-up. CONCLUSIONS: The Ozaki procedure has acceptable short-term results in young patients with small aortic annuli. A larger aortic annulus can be achieved with surgical annular enlargement. Long-term follow-up is necessary to determine late valve function and potential continued annular growth.


Assuntos
Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/cirurgia , Anuloplastia da Valva Cardíaca/métodos , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Tempo de Internação , Masculino , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Arterioscler Thromb Vasc Biol ; 40(6): e153-e165, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295422

RESUMO

OBJECTIVE: Macrophages have been described in calcific aortic valve disease, but it is unclear if they promote or counteract calcification. We aimed to determine how macrophages are involved in calcification using the Notch1+/- model of calcific aortic valve disease. Approach and Results: Macrophages in wild-type and Notch1+/- murine aortic valves were characterized by flow cytometry. Macrophages in Notch1+/- aortic valves had increased expression of MHCII (major histocompatibility complex II). We then used bone marrow transplants to test if differences in Notch1+/- macrophages drive disease. Notch1+/- mice had increased valve thickness, macrophage infiltration, and proinflammatory macrophage maturation regardless of transplanted bone marrow genotype. In vitro approaches confirm that Notch1+/- aortic valve cells promote macrophage invasion as quantified by migration index and proinflammatory phenotypes as quantified by Ly6C and CCR2 positivity independent of macrophage genotype. Finally, we found that macrophage interaction with aortic valve cells promotes osteogenic, but not dystrophic, calcification and decreases abundance of the STAT3ß isoform. CONCLUSIONS: This study reveals that Notch1+/- aortic valve disease involves increased macrophage recruitment and maturation driven by altered aortic valve cell secretion, and that increased macrophage recruitment promotes osteogenic calcification and alters STAT3 splicing. Further investigation of STAT3 and macrophage-driven inflammation as therapeutic targets in calcific aortic valve disease is warranted.


Assuntos
Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Calcinose/patologia , Macrófagos/fisiologia , Fator de Transcrição STAT3/fisiologia , Animais , Valva Aórtica/imunologia , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/imunologia , Estenose da Valva Aórtica/fisiopatologia , Transplante de Medula Óssea , Calcinose/imunologia , Calcinose/fisiopatologia , Movimento Celular , Óxidos S-Cíclicos/farmacologia , Modelos Animais de Doenças , Expressão Gênica , Genótipo , Humanos , Inflamação/patologia , Macrófagos/química , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteogênese , Receptor Notch1/análise , Receptor Notch1/genética , Receptor Notch1/fisiologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética
9.
Prog Cardiovasc Dis ; 63(3): 219-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277995

RESUMO

Elevated circulating concentrations of lipoprotein(a) [Lp(a)] is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e. > 50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).


Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Artérias/metabolismo , Aterosclerose/sangue , Calcinose/sangue , Lipoproteína(a)/sangue , Placa Aterosclerótica , Animais , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Artérias/patologia , Aterosclerose/epidemiologia , Aterosclerose/patologia , Aterosclerose/terapia , Biomarcadores/sangue , Calcinose/epidemiologia , Calcinose/patologia , Calcinose/terapia , Humanos , Lipoproteína(a)/química , Prognóstico , Fatores de Risco , Regulação para Cima
10.
Arterioscler Thromb Vasc Biol ; 40(5): 1370-1382, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32188274

RESUMO

OBJECTIVE: Aortic valve (AV) calcification plays an important role in the progression of aortic stenosis (AS). MMP-10 (matrix metalloproteinase-10 or stromelysin-2) is involved in vascular calcification in atherosclerosis. We hypothesize that MMP-10 may play a pathophysiological role in calcific AS. Approach and Results: Blood samples (n=112 AS and n=349 controls) and AVs (n=88) from patients undergoing valve replacement were analyzed. Circulating MMP-10 was higher in patients with AS compared with controls (P<0.001) and correlated with TNFα (tumor necrosis factor α; rS=0.451; P<0.0001). MMP-10 was detected by immunochemistry in AVs from patients with AS colocalized with aortic valve interstitial cells markers α-SMA (α-smooth muscle actin) and vimentin and with calcification markers Runx2 (Runt-related transcription factor 2) and SRY (sex-determining region Y)-box 9. MMP-10 expression in AVs was further confirmed by RT-qPCR and western blot. Ex vivo, MMP-10 was elevated in the conditioned media of AVs from patients with AS and associated with interleukin-1ß (rS=0.5045, P<0.001) and BMP (bone morphogenetic protein)-2 (rS=0.5003, P<0.01). In vitro, recombinant human MMP-10 induced the overexpression of inflammatory, fibrotic, and osteogenic markers (interleukin-1ß, α-SMA, vimentin, collagen, BMP-4, Sox9, OPN [osteopontin], BMP-9, and Smad 1/5/8; P<0.05) and cell mineralization in aortic valve interstitial cells isolated from human AVs, in a mechanism involving Akt (protein kinase B) phosphorylation. These effects were prevented by TIMP-1 (tissue inhibitor of metalloproteinases type 1), a physiological MMP inhibitor, or specifically by an anti-MMP-10 antibody. CONCLUSIONS: MMP-10, which is overexpressed in aortic valve from patients with AS, seems to play a central role in calcification in AS through Akt phosphorylation. MMP-10 could be a new therapeutic target for delaying the progression of aortic valve calcification in AS.


Assuntos
Estenose da Valva Aórtica/enzimologia , Valva Aórtica/enzimologia , Valva Aórtica/patologia , Calcinose/enzimologia , Metaloproteinase 10 da Matriz/metabolismo , Osteogênese , Adulto , Idoso , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , Calcinose/genética , Calcinose/patologia , Estudos de Casos e Controles , Células Cultivadas , Feminino , Fibrose , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 10 da Matriz/genética , Pessoa de Meia-Idade , Osteogênese/genética , Fosforilação , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
11.
PLoS One ; 15(3): e0230002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160250

RESUMO

INTRODUCTION: Severe aortic stenosis (AS) is the most common valvular heart disease in the western world. Various factors are related to severe AS prognosis, including chronic kidney disease. The aim of this study was to evaluate the prognostic value of urea level in patients with severe AS. METHODS: We prospectively enrolled 142 patients (79.1±9.4 years, 88 women) with severe AS (mean valve area 0.67± 0.17 cm2). Clinical assessment, blood tests and echocardiography were performed at enrollment and follow up. The patient population was divided into low and high urea level groups, according to the median urea level at enrollment (72 patients, mean urea 35.5±6.2 mg/dL and 70 patients, mean urea 61.1±17.8 mg/dL, respectively). Hundred and twelve patients (79%) underwent aortic valve intervention. The primary endpoint was all-cause and cardiovascular mortality. OUTCOMES: During follow-up of 37±19.5 months, 56 (37.1%) patients died, 39 due to cardiovascular causes. In univariate analysis, age, urea level, creatinine, New York Heart Association (NYHA) class and aortic valve intervention were associated with all-cause mortality. However, in multivariate analysis only aortic valve intervention and blood urea were independent predictors of all-cause mortality (HR 0.494; 95% CI 0.226-0.918, P = 0.026 and HR 1.015; 95% CI 1.003-1.029, P = 0.046 respectively). Urea level, NYHA class and age were also significant predictors of cardiovascular mortality. Whereas, in multivariate analysis, only urea level predicted cardiovascular mortality in these patients (HR 1.017; CI 1.003-1.031 P = 0.019). CONCLUSIONS: Blood urea, a generally readily available and routinely determined marker of renal function, is an independent prognostic factor in patients with severe AS.


Assuntos
Estenose da Valva Aórtica/patologia , Doenças Cardiovasculares/mortalidade , Ureia/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Estenose da Valva Aórtica/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Intervalo Livre de Doença , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
Arterioscler Thromb Vasc Biol ; 40(4): 885-900, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32160774

RESUMO

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.


Assuntos
Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/fisiopatologia , Animais , Estenose da Valva Aórtica/patologia , Comunicação Celular , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Humanos , Inflamação/fisiopatologia , Lipoproteínas/metabolismo , Miofibroblastos/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia , RNA não Traduzido/metabolismo , Calcificação Vascular/fisiopatologia
13.
J Card Surg ; 35(5): 1125-1128, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32163624

RESUMO

BACKGROUND: We present the case of a patient with severe quadricuspid aortic valve (QAV) stenosis who underwent treatment with transcatheter aortic valve implantation (TAVI). CASE SUMMARY: An 87-year-old woman was referred to our department with severe aortic stenosis. Computed tomography angiography revealed a QAV with four separate equal-sized leaflets, similar in appearance to a four-leaf clover. The patient underwent successful implantation of a 23 mm Edwards Sapien 3 transcatheter valve via left transfemoral access. The valve positioning across the aortic annulus was fluoroscopically challenging due to difficulty visualizing all four cusps in only one two-dimensional view and to the position of the left main coronary artery, which was very low. The immediate result of the TAVI was good, with no aortic regurgitation and no coronary damage. Follow-up to 6 months was free of event. CONCLUSION: This case demonstrates that QAV stenosis can be treated using TAVI with good clinical outcomes.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/anormalidades , Valva Aórtica/cirurgia , Substituição da Valva Aórtica Transcateter/métodos , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Angiografia por Tomografia Computadorizada , Feminino , Fluoroscopia , Seguimentos , Humanos , Resultado do Tratamento
14.
Mol Biol Rep ; 47(3): 1809-1820, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32002794

RESUMO

Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.


Assuntos
Calcinose/genética , Polimorfismo de Nucleotídeo Único , alfa-2-Glicoproteína-HS/genética , alfa-2-Glicoproteína-HS/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Calcinose/metabolismo , Calcinose/patologia , Estudos de Casos e Controles , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Calcificação Vascular/genética , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
15.
Am J Med ; 133(9): 1095-1100.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32081657

RESUMO

BACKGROUND: Patients with aortic stenosis are nearly twice as likely to have a diagnosis of gout compared with individuals without aortic valve disease. METHODS: This retrospective study evaluated consecutive adults age ≥65 years with aortic stenosis between December 2012 and November 2016 who underwent at least 2 transthoracic echocardiograms (TTEs) separated by at least 1 year. Severe aortic stenosis was defined as any combination of an aortic valve peak velocity ≥4.0 m/sec, mean gradient ≥40 mm Hg, aortic valve area ≤1 cm2, or decrease in left ventricular ejection fraction as a result of aortic stenosis. RESULTS: Of the 699 study patients, gout was present in 73 patients (10%) and not found in 626 patients (90%). Median follow-up was 903 days [552-1302] for patients with gout and 915 days [601-1303] for patients without gout (P = 0.60). The presence of severe aortic stenosis on follow-up transthoracic echocardiogram was more frequent in patients with gout compared to those without gout (74% vs 54%, P = 0.001; hazard ratio [HR] 1.45 [1.09-1.93]), even among the 502 patients without severe aortic stenosis at baseline (63% vs 39%, P = 0.003; hazard ratio 1.43 [1.07-1.91]). Gout remained associated with the development of severe aortic stenosis after multivariable adjustment (adjusted hazard ratio [aHR] 1.46 [1.03-2.08], P = 0.03). The annualized reduction in aortic valve area was numerically greater in the group with gout compared with the group without gout (-0.10 cm2/y [-0.18, -0.03] vs -0.08 cm2/y [-0.16, -0.01], P = 0.09); annualized change in peak velocity and mean gradient did not differ between groups. CONCLUSIONS: Progression to severe aortic stenosis was more frequent in patients with gout compared with those without gout, supporting the hypothesis that gout is a risk factor for aortic stenosis.


Assuntos
Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/patologia , Gota/complicações , Gota/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
16.
Korean J Radiol ; 21(3): 268-279, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32090519

RESUMO

OBJECTIVE: To determine the most valuable cardiac magnetic resonance feature tracking (CMR-FT) parameters for evaluating aortic stenosis (AS) and determine whether they can predict the prognosis in asymptomatic AS patients with preserved ejection fraction (pEF). MATERIALS AND METHODS: A prospective cohort of 123 moderate to severe AS patients (60 males, 68.6 ± 9.2 years) and 32 control subjects (14 males, 67.9 ± 4.4 years) underwent echocardiography and 3T CMR imaging from 2011-2015. CMR cine images were analyzed using CMR-FT to assess the left ventricular radial, circumferential, and longitudinal peak strain (PS) in 2- and 3-dimensions. The primary endpoints were clinical cardiac events (CCEs), including cardiac death, heart failure, and AS-associated symptom development. For statistical analysis, logistic regression and log-rank tests were used. RESULTS: Global PSs differed between AS patients and controls and between severe and moderate AS patients (p < 0.05). Two-dimensional (2D) global radial and longitudinal PSs changed gradually with the severity of AS groups (p < 0.001). Twenty-two of 67 asymptomatic AS patients with pEF experienced CCEs during the follow-up (median: 31.1 months). 2D global longitudinal PS (GLPS) was the single risk factor for CCE (p = 0.017). The relative risk for CCE was 3.9 (p = 0.016, 95% confidence interval: 1.2-11.9) based on 2D GLPS with a cutoff of -17.9% according to receiver operating characteristic curve analysis. Survival analysis demonstrated that asymptomatic AS patients with pEF having impaired 2D GLPS experienced worse event-free survival than the others (p = 0.041). CONCLUSION: 2D global longitudinal and radial PSs may reflect cardiac dysfunction according to the degree of AS. 2D GLPS might be a prognostic predictor of CCEs in asymptomatic AS patients with pEF.


Assuntos
Estenose da Valva Aórtica/patologia , Ventrículos do Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética/métodos , Idoso , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/fisiopatologia , Área Sob a Curva , Doenças Assintomáticas , Estudos de Casos e Controles , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Curva ROC , Fatores de Risco , Volume Sistólico
17.
Semin Thorac Cardiovasc Surg ; 32(3): 531-538, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060012

RESUMO

Palliation of patients with hypoplastic left heart syndrome remains challenging. Although coronary ischemia can be catastrophic, the prevalence and pathologies of anomalies of the coronary arteries remains unknown. We reviewed 119 specimens with the features of hypoplastic left heart syndrome, focusing our attention on the aortic root and the coronary arteries. We found 36 (30%) specimens with the combination of mitral and aortic atresia, 26 (22%) with mitral and aortic stenosis, and 57 (48%) with mitral stenosis combined with aortic atresia. In 29 specimens (24%), the coronary arteries were not located in the center of any sinuses, while in 24 specimens (21%) at least 1 coronary artery was located very proximal to a raphe or commissure, with potential for obstruction. The specimens with combined stenosis were more likely to have eccentric positions of the coronary arteries (11 specimens, 42%), compared to the 3 specimens with combined atresia (9%, P = 0.009). The specimens with combined stenosis were also more likely to have positioning at risk for obstruction (9 specimens, 35%), compared to those with combined atresia (3 specimens, 9%, P = 0.05). Coronary arterial fistulous communications were found in 11 specimens (9%), significantly more frequently in specimens with mitral stenosis and aortic atresia (9 specimens, 16%, P = 0.041). The origins of the coronary arteries in patients with hypoplastic left heart syndrome place them at potential risk for ischemia, with fistulous communications being a particular risk in those with mitral stenosis combined with aortic atresia.


Assuntos
Anormalidades Múltiplas , Anomalias dos Vasos Coronários/patologia , Vasos Coronários/patologia , Síndrome do Coração Esquerdo Hipoplásico/patologia , Fístula Vascular/patologia , Valva Aórtica/anormalidades , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/patologia , Chicago , Anomalias dos Vasos Coronários/complicações , Florida , Humanos , Síndrome do Coração Esquerdo Hipoplásico/complicações , Valva Mitral/anormalidades , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/patologia , Isquemia Miocárdica/etiologia , Fístula Vascular/complicações
18.
Eur Radiol ; 30(1): 640-651, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407030

RESUMO

OBJECTIVES: The aim of this study was to investigate the prevalence and prognostic value of late gadolinium enhancement (LGE), as assessed by cardiovascular magnetic resonance (CMR) imaging, in patients with aortic stenosis. METHODS AND RESULTS: A systematic search of PubMed and EMBASE was performed, and observational cohort studies that analysed the prevalence of LGE and its relation to clinical outcomes in patients with aortic stenosis were included. Odds ratios were used to measure an effect of the presence of LGE on both all-cause and cardiovascular mortality. Nineteen studies were retrieved, accounting for 2032 patients (mean age 69.8 years, mean follow-up 2.8 years). We found that LGE is highly prevalent in aortic stenosis, affecting half of all patients (49.6%), with a non-infarct pattern being the most frequent type (63.6%). The estimated extent of focal fibrosis, expressed in % of LV mass, was equal to 3.83 (95% CI [2.14, 5.52], p < 0.0001). The meta-analysis showed that the presence of LGE was associated with increased all-cause (pooled OR [95% CI] = 3.26 [1.72, 6.18], p = 0.0003) and cardiovascular mortality (pooled OR [95% CI] = 2.89 [1.90, 4.38], p < 0.0001). CONCLUSIONS: LGE by CMR is highly prevalent in aortic stenosis patients and exhibits a substantial value in all-cause and cardiovascular mortality prediction. These results suggest a potential role of LGE in aortic stenosis patient risk stratification. KEY POINTS: • Up to the half of aortic stenosis patients are affected by myocardial focal fibrosis. • Sixty-four percent of focal fibrosis detected by LGE-CMR is non-infarct type. • The presence of focal fibrosis triples all-cause and cardiovascular mortality.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Idoso , Aorta/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Prevalência , Prognóstico
19.
JACC Cardiovasc Imaging ; 13(2 Pt 2): 589-600, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31326472

RESUMO

OBJECTIVES: The present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress-strain relationships. BACKGROUND: Separating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS). METHODS: A total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress-strain relationships were constructed using control subjects' data and fitted to linear regression. End-systolic stress-strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery. RESULTS: GCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress-strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress-strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress-strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001). CONCLUSIONS: Myocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress-strain indexes allow identification of patients with increased myocardial fibrosis and predict the extent of functional recovery after aortic valve replacement.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Miocárdio/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/cirurgia , Biópsia , Estudos de Casos e Controles , Ecocardiografia Doppler , Feminino , Fibrose , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA