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1.
Br J Radiol ; 94(1117): 20200894, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33053316

RESUMO

Incidental coronary and cardiac calcification are frequent findings on non-gated thoracic CT. We recommend that the heart is reviewed on all CT scans where it is visualised. Coronary artery calcification is a marker of coronary artery disease and it is associated with an adverse prognosis on dedicated cardiac imaging and on non-gated thoracic CT performed for non-cardiac indications, both with and without contrast. We recommend that coronary artery calcification is reported on all non-gated thoracic CT using a simple patient-based score (none, mild, moderate, severe). Furthermore, we recommend that reports include recommendations for subsequent management, namely the assessment of modifiable cardiovascular risk factors and, if the patient has chest pain, assessment as per standard guidelines. In most cases, this will not necessitate additional investigations. Incidental aortic valve calcification may also be identified on non-gated thoracic CT and should be reported, along with ancillary findings such as aortic root dilation. Calcification may occur in other parts of the heart including mitral valve/annulus, pericardium and myocardium, but in many cases these are an incidental finding without clinical significance.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Calcinose/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Achados Incidentais , Tomografia Computadorizada por Raios X/métodos , Calcificação Vascular/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Consenso , Coração , Humanos , Sociedades Médicas , Reino Unido
3.
Int Heart J ; 61(6): 1294-1297, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33191339

RESUMO

Porcelain aorta, defined as extensive calcification of the ascending aorta or aortic arch, is a reported risk factor for embolic stroke during cardiac surgery. However, the time course of the progression of aortic calcification leading to porcelain aorta has not been elucidated. We herein describe a 70-year-old woman who was followed up for systemic lupus erythematosus and antiphospholipid syndrome for approximately 20 years. A routine computed tomography scan revealed progression of ascending aortic calcification to porcelain aorta. The calcification was absent during the preceding 12 years, partial 6 years later, and total after another 3 years. Computed tomography also demonstrated aortic and mitral valve calcification in the development of porcelain aorta. During the 3 years prior to the last admission, annual echocardiography examinations showed progression of calcific aortic stenosis with symptoms. The patient was admitted to our institution for aortic valve replacement. Considering the high risk of perioperative stroke associated with porcelain aorta, transcatheter aortic valve implantation was performed. Postoperative transthoracic echocardiography revealed improvement of the aortic stenosis with no symptoms. The present case revealed aortic calcific progression to porcelain aorta during an approximately 10-year period with deterioration of aortic stenosis within a short time. The aortic and valvular calcification could be attributed to the inflammatory process of systemic lupus erythematosus and antiphospholipid syndrome. The presence of aortic and mitral annular calcification in the serial imaging can provide information on aortic and valvular atherosclerotic progression, which may be modifiable by early steroid-lowering therapy.


Assuntos
Síndrome Antifosfolipídica/complicações , Doenças da Aorta/complicações , Estenose da Valva Aórtica/complicações , Valva Aórtica/patologia , Calcinose/complicações , Lúpus Eritematoso Sistêmico/complicações , Calcificação Vascular/complicações , Corticosteroides/uso terapêutico , Idoso , Síndrome Antifosfolipídica/tratamento farmacológico , Aorta/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Progressão da Doença , Ecocardiografia , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Substituição da Valva Aórtica Transcateter , Calcificação Vascular/diagnóstico por imagem
4.
PLoS One ; 15(11): e0238407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237915

RESUMO

Calcific aortic valve disease (CAVD) is a deadly disease that is rising in prevalence due to population aging. While the disease is complex and poorly understood, one well-documented driver of valvulopathy is serotonin agonism. Both serotonin overexpression, as seen with carcinoid tumors and drug-related agonism, such as with Fenfluramine use, are linked with various diseases of the valves. Thus, the objective of this study was to determine if genetic ablation or pharmacological antagonism of the 5-HT2B serotonin receptor (gene: Htr2b) could improve the hemodynamic and histological progression of calcific aortic valve disease. Htr2b mutant mice were crossed with Notch1+/- mice, an established small animal model of CAVD, to determine if genetic ablation affects CAVD progression. To assess the effect of pharmacological inhibition on CAVD progression, Notch1+/- mice were treated with the 5-HT2B receptor antagonist SB204741. Mice were analyzed using echocardiography, histology, immunofluorescence, and real-time quantitative polymerase chain reaction. Htr2b mutant mice showed lower aortic valve peak velocity and mean pressure gradient-classical hemodynamic indicators of aortic valve stenosis-without concurrent left ventricle change. 5-HT2B receptor antagonism, however, did not affect hemodynamic progression. Leaflet thickness, collagen density, and CAVD-associated transcriptional markers were not significantly different in any group. This study reveals that genetic ablation of Htr2b attenuates hemodynamic development of CAVD in the Notch1+/- mice, but pharmacological antagonism may require high doses or long-term treatment to slow progression.


Assuntos
Valva Aórtica/patologia , Colesterol/metabolismo , Hemodinâmica/genética , Receptor Notch1/genética , Receptor 5-HT2B de Serotonina/genética , Animais , Estenose da Valva Aórtica/genética , Estenose da Valva Aórtica/patologia , Calcinose/genética , Calcinose/patologia , Dieta , Modelos Animais de Doenças , Progressão da Doença , Ecocardiografia/métodos , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Hemodinâmica/fisiologia , Hipercolesterolemia/genética , Hipercolesterolemia/patologia , Hiperlipidemias/genética , Hiperlipidemias/patologia , Camundongos
5.
PLoS One ; 15(10): e0240532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057457

RESUMO

BACKGROUND: The ability of heart valve cells to respond to their mechanical environment represents a key mechanism by which the integrity and function of valve cusps is maintained. A number of different mechanotransduction pathways have been implicated in the response of valve cells to mechanical stimulation. In this study, we explore the expression pattern of several mechanosensitive ion channels (MSC) and their potential to mediate mechanosensitive responses of human valve interstitial cells (VIC). METHODS: MSC presence and function were probed using the patch clamp technique. Protein abundance of key MSC was evaluated by Western blotting in isolated fibroblastic VIC (VICFB) and in VIC differentiated towards myofibroblastic (VICMB) or osteoblastic (VICOB) phenotypes. Expression was compared in non-calcified and calcified human aortic valves. MSC contributions to stretch-induced collagen gene expression and to VIC migration were assessed by pharmacological inhibition of specific channels. RESULTS: Two MSC types were recorded in VICFB: potassium selective and cation non-selective channels. In keeping with functional data, the presence of both TREK-1 and Kir6.1 (potassium selective), as well as TRPM4, TRPV4 and TRPC6 (cationic non-selective) channels was confirmed in VIC at the protein level. Differentiation of VICFB into VICMB or VICOB phenotypes was associated with a lower expression of TREK-1 and Kir6.1, and a higher expression of TRPV4 and TRPC6. Differences in MSC expression were also seen in non-calcified vs calcified aortic valves where TREK-1, TRPM4 and TRPV4 expression were higher in calcified compared to control tissues. Cyclic stretch-induced expression of COL I mRNA in cultured VICFB was blocked by RN-9893, a selective inhibitor of TRPV4 channels while having no effect on the stretch-induced expression of COL III. VICFB migration was blocked with the non-specific MSC blocker streptomycin and by GSK417651A an inhibitor of TRPC6/3. CONCLUSION: Aortic VIC express a range of MSC that play a role in functional responses of these cells to mechanical stimulation. MSC expression levels differ in calcified and non-calcified valves in ways that are in part compatible with the change in expression seen between VIC phenotypes. These changes in MSC expression, and associated alterations in the ability of VIC to respond to their mechanical environment, may form novel targets for intervention during aortic valvulopathies.


Assuntos
Estenose da Valva Aórtica/patologia , Valva Aórtica/patologia , Calcinose/patologia , Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Miofibroblastos/metabolismo , Osteoblastos/metabolismo , Valva Aórtica/citologia , Estenose da Valva Aórtica/tratamento farmacológico , Calcinose/tratamento farmacológico , Diferenciação Celular , Células Cultivadas , Humanos , Canais Iônicos/antagonistas & inibidores , Mecanotransdução Celular/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Cultura Primária de Células , Estreptomicina/farmacologia , Estreptomicina/uso terapêutico
6.
Arterioscler Thromb Vasc Biol ; 40(12): 2910-2921, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33086873

RESUMO

OBJECTIVE: Leaflet thickening, fibrosis, and hardening are early pathological features of calcific aortic valve disease (CAVD). An inadequate understanding of the resident aortic valve cells involved in the pathological process may compromise the development of therapeutic strategies. We aim to construct a pattern of the human aortic valve cell atlas in healthy and CAVD clinical specimens, providing insight into the cellular origins of CAVD and the complex cytopathological differentiation process. Approach and Results: We used unbiased single-cell RNA sequencing for the high-throughput evaluation of cell heterogeneity in 34 632 cells isolated from 6 different human aortic valve leaflets. Cellular experiments, in situ localization, and bulk sequencing were performed to verify the differences between normal, healthy valves and those with CAVD. By comparing healthy and CAVD specimens, we identified 14 cell subtypes, including 3 heterogeneous subpopulations of resident valve interstitial cells, 3 types of immune-derived cells, 2 types of valve endothelial cells, and 6 novel valve-derived stromal cells found particularly in CAVD leaflets. Combining additional verification experiments with single-cell transcriptome profiling provided evidence of endothelial to mesenchymal transition involved in lesion thickening of the aortic valve leaflet. CONCLUSIONS: Our findings deconstructed the aortic valve cell atlas and suggested novel functional interactions among resident cell subpopulations. Our findings may provide insight into future targeted therapies to prevent CAVD.


Assuntos
Valva Aórtica/metabolismo , Calcinose/genética , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal , Redes Reguladoras de Genes , Doenças das Valvas Cardíacas/genética , Transcriptoma , Valva Aórtica/patologia , Calcinose/metabolismo , Calcinose/patologia , Estudos de Casos e Controles , Comunicação Celular , Células Cultivadas , Análise por Conglomerados , Células Endoteliais/patologia , Feminino , Fibrose , Perfilação da Expressão Gênica , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , RNA-Seq , Análise de Célula Única
7.
Asian Cardiovasc Thorac Ann ; 28(7): 381-383, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33023307
8.
Arch Cardiovasc Dis ; 113(11): 674-678, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868256

RESUMO

BACKGROUND: Donor heart shortage has extended the waiting time and increased the mortality of patients on the transplant waiting list. Widening old standard donor criteria has successfully increased the number of heart transplantations, but for many years, a valve disease in a donor heart has been considered a primary contraindication for organ donation. AIMS: To analyse the results of aortic and mitral valvular surgery in marginal donor hearts with valvulopathy before orthotopic heart transplantation. METHODS: Between January 2012 and November 2015, we performed 53 heart transplantations in our department. In four donors, echocardiography performed at the time of organ procurement showed a valvular disease: three had moderate-to-severe mitral regurgitation; and one had moderately severe aortic valve stenosis. RESULTS: The mean bench mitral repair and aortic replacement time, aortic cross-clamp time and total ischaemic time were: 18 (range 7-25) minutes, 78.7 (range 57-98) minutes and 184 (range 89-255) minutes, respectively. Intraoperative transoesophageal echocardiography showed good mitral repair or aortic prosthetic valve function, and good right and left ventricular function. One patient died of infectious pneumonia after 1 month. The mean duration of follow-up for the patients discharged home was 75±13 months, and all have returned to an active unrestricted lifestyle. CONCLUSIONS: Our limited series demonstrates that conventional valvular procedures performed on otherwise healthy donor hearts with mitral and aortic valve pathology can efficaciously expand the donor pool for orthotopic cardiac transplantation and decrease the mortality rate on the waiting list.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/patologia , Valva Aórtica/transplante , Calcinose/cirurgia , Seleção do Doador , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/transplante , Doadores de Tecidos/provisão & distribução , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Estudos de Viabilidade , Feminino , Sobrevivência de Enxerto , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Anuloplastia da Valva Mitral/efeitos adversos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-32910562

RESUMO

The Ross procedure is now a well established treatment for aortic valve pathology in young adult patients. However, there are several technical aspects of this operation that are still under debate. One of them is the necessity for reconstruction of the right ventricular outflow tract. Cryopreserved or decellularized pulmonary homografts are the gold standard but, in some cases, and especially in urgent patients, their availability cannot be guaranteed. Stentless xenografts (such as the Medtronic Freestyle Aortic Root) can be inappropriate for some patients with large right outflow tracts, because it can be difficult to suture them without tension. The use of bio conduits handmade using straight Dacron grafts and stented xenografts can be helpful as a third choice.  In this video tutorial we demonstrate our technique for right ventricular outflow tract reconstruction in a young adult patient. We believe that our technique should be included in the armamentarium of every Ross surgeon for use in adult patients. However, long-term outcomes for these stented xenografts in the right outflow position should be carefully evaluated in the future.


Assuntos
Valva Aórtica , Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Polietilenotereftalatos/uso terapêutico , Obstrução do Fluxo Ventricular Externo/cirurgia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Materiais Biocompatíveis/uso terapêutico , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico
10.
Am J Cardiol ; 134: 108-115, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933756

RESUMO

Aim is to report on the results of an optimized balloon filling algorithm and suggest a refinement of the implantation approach to maximize safety. Appropriate sizing of balloon expandable valves during transcatheter aortic valve implantation is crucial. Study comprised 370 consecutive patients receiving SAPIEN 3 valve between 2015 and 2018. Valve expansion/recoil measurement in the inflow area, annular area, and outflow area was performed previously and postimplantation. Nominal balloon filling resulted in underexpansion-23 mm (20.96 mm), 26 mm (23.88 mm), and 29 mm (27.56 mm) SAPIEN 3 valves at the annular level. Increased balloon filling by 2 cc resulted in a gradual increase in valve diameter reaching 97.35% (23 mm), 96.50% (26 mm), and 96.11% (29 mm) of the nominal valve diameter. Final diameters were usually higher in the valvular inflow and outflow tracts. The 29 mm valve did not reach its nominal diameter with 2 cc overfilling and in none of inflow area (95.48%), annular area (96.11%), or outflow area (96.86%). Device success (by VARC II) was 96.2%. No root or septal rupture, device migration, mitral valve injury, coronary obstruction, or dissection occurred. Rate of new permanent pacemaker implantation was 8.3%. Paravalvular leakage was none or trace in most patients. Mean valve gradient was 10.77 mm Hg postprocedure. 1.9% of the patients had a maximum gradient of >40 mm Hg, 2.2% >20 mm Hg. In conclusion, an optimized balloon filling algorithm resulted in appropriate valve gradients, low levels of paravalvular leakage, low rates of permanent pacemaker implantation and no annular rupture.


Assuntos
Algoritmos , Estenose da Valva Aórtica/cirurgia , Doença do Sistema de Condução Cardíaco/epidemiologia , Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/epidemiologia , Substituição da Valva Aórtica Transcateter/métodos , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/epidemiologia , Doença do Sistema de Condução Cardíaco/terapia , Feminino , Humanos , Masculino , Tamanho do Órgão , Complicações Pós-Operatórias/diagnóstico por imagem , Pressão , Ajuste de Prótese
11.
Arterioscler Thromb Vasc Biol ; 40(11): e296-e308, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32938214

RESUMO

OBJECTIVE: Resident valvular interstitial cells (VICs) activate to myofibroblasts during aortic valve stenosis progression, which further promotes fibrosis or even differentiate into osteoblast-like cells that can lead to calcification of valve tissue. Inflammation is a hallmark of aortic valve stenosis, so we aimed to determine proinflammatory cytokines secreted from M1 macrophages that give rise to a transient VIC phenotype that leads to calcification of valve tissue. Approach and Results: We designed hydrogel biomaterials as valve extracellular matrix mimics enabling the culture of VICs in either their quiescent fibroblast or activated myofibroblast phenotype in response to the local matrix stiffness. When VIC fibroblasts and myofibroblasts were treated with conditioned media from THP-1-derived M1 macrophages, we observed robust reduction of αSMA (alpha smooth muscle actin) expression, reduced stress fiber formation, and increased proliferation, suggesting a potent antifibrotic effect. We further identified TNF (tumor necrosis factor)-α and IL (interleukin)-1ß as 2 cytokines in M1 media that cause the observed antifibrotic effect. After 7 days of culture in M1 conditioned media, VICs began differentiating into osteoblast-like cells, as measured by increased expression of RUNX2 (runt-related transcription factor 2) and osteopontin. We also identified and validated IL-6 as a critical mediator of the observed pro-osteogenic effect. CONCLUSIONS: Proinflammatory cytokines in M1 conditioned media inhibit myofibroblast activation in VICs (eg, TNF-α and IL-1ß) and promote their osteogenic differentiation (eg, IL-6). Together, our work suggests inflammatory M1 macrophages may drive a myofibroblast-to-osteogenic intermediate VIC phenotype, which may mediate the switch from fibrosis to calcification during aortic valve stenosis progression.


Assuntos
Estenose da Valva Aórtica/metabolismo , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Calcinose/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Miofibroblastos/metabolismo , Osteoblastos/metabolismo , Osteogênese , Comunicação Parácrina , Animais , Estenose da Valva Aórtica/patologia , Calcinose/patologia , Proliferação de Células , Matriz Extracelular/metabolismo , Fibrose , Humanos , Masculino , Miofibroblastos/patologia , Osteoblastos/patologia , Fenótipo , Via Secretória , Transdução de Sinais , Sus scrofa , Células THP-1
12.
Am J Physiol Heart Circ Physiol ; 319(5): H1123-H1141, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32986963

RESUMO

Calcific aortic valve disease (CAVD) is characterized by valvular fibrosis and calcification and driven by differentiating valvular interstitial cells (VICs). Expression data from patient biopsies suggest that transforming growth factor (TGF)-ß1 is implicated in CAVD pathogenesis. However, CAVD models using isolated VICs failed to deliver clear evidence on the role of TGF-ß1. Thus, employing cultures of aortic valve leaflets, we investigated effects of TGF-ß1 in a tissue-based three-dimensional (3-D) CAVD model. We found that TGF-ß1 induced phosphorylation of Mothers against decapentaplegic homolog (SMAD) 3 and expression of SMAD7, indicating effective downstream signal transduction in valvular tissue. Thus, TGF-ß1 increased VIC contents of rough endoplasmic reticulum, Golgi, and secretory vesicles as well as tissue levels of RNA and protein. In addition, TGF-ß1 raised expression of proliferation marker cyclin D1, attenuated VIC apoptosis, and upregulated VIC density. Moreover, TGF-ß1 intensified myofibroblastic VIC differentiation as evidenced by increased α-smooth muscle actin and collagen type I along with diminished vimentin expression. In contrast, TGF-ß1 attenuated phosphorylation of SMAD1/5/8 and upregulation of ß-catenin while inhibiting osteoblastic VIC differentiation as revealed by downregulation of osteocalcin expression, alkaline phosphatase activity, and extracellular matrix incorporation of hydroxyapatite. Collectively, these effects resulted in blocking of valvular tissue calcification and associated disintegration of collagen fibers. Instead, TGF-ß1 induced development of fibrosis. Overall, in a tissue-based 3-D CAVD model, TGF-ß1 intensifies expressional and proliferative activation along with myofibroblastic differentiation of VICs, thus triggering dominant fibrosis. Simultaneously, by inhibiting SMAD1/5/8 activation and canonical Wnt/ß-catenin signaling, TGF-ß1 attenuates osteoblastic VIC differentiation, thus blocking valvular tissue calcification. These findings question a general phase-independent CAVD-promoting role of TGF-ß1.NEW & NOTEWORTHY Employing aortic valve leaflets as a tissue-based three-dimensional disease model, our study investigates the role of transforming growth factor (TGF)-ß1 in calcific aortic valve disease pathogenesis. We find that, by activating Mothers against decapentaplegic homolog 3, TGF-ß1 intensifies expressional and proliferative activation along with myofibroblastic differentiation of valvular interstitial cells, thus triggering dominant fibrosis. Simultaneously, by inhibiting activation of Mothers against decapentaplegic homolog 1/5/8 and canonical Wnt/ß-catenin signaling, TGF-ß1 attenuates apoptosis and osteoblastic differentiation of valvular interstitial cells, thus blocking valvular tissue calcification. These findings question a general phase-independent calcific aortic valve disease-promoting role of TGF-ß1.


Assuntos
Estenose da Valva Aórtica/metabolismo , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Calcinose/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Actinas/metabolismo , Animais , Valva Aórtica/ultraestrutura , Estenose da Valva Aórtica/patologia , Apoptose , Calcinose/patologia , Cálcio/metabolismo , Células Cultivadas , Ciclina D1/genética , Ciclina D1/metabolismo , Fibrose , Ovinos , Proteína Smad7/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
14.
Pan Afr Med J ; 36: 118, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821329

RESUMO

The purpose is to study the short- and medium-term morbidity and mortality linked to the implantation of an aortic prosthesis during cardiac surgery. This is a longitudinal, retrospective and descriptive study which takes place over a period from January 2017 to March 2020 (38 months) at the level of the thoracic and cardiovascular surgery clinic of the university Hospital Center of Fann in Dakar. All patients who underwent aortic valve replacement during this period were included in the study. A number of the series was 25 patients with a sex ratio of 2.66. The average age of the patients was 29.5 years (8-51 years). In the patients' history, 19 patients (76%) had a notion of recurrent angina. Exercise dyspnea was the most common functional symptomatology present in 24 patients (96%). In the series, there were 22 cases (88%) of aortic insufficiency of various grades (2 to 4) with 7 cases (28%) associated with mitral insufficiency. We had 3 cases (12%) of aortic stenosis. All patients received surgical management under cardiopulmonary bypass. The average duration of cardiopulmonary bypass was 132 minutes ± 41.21 (53-226 minutes). The average duration of aortic clamping was 101 minutes ± 31.87 (53-164 minutes). The surgical procedures consisted in replacing the aortic valve with a biological prosthesis in one patient (4%) and a mechanical prosthesis in 24 patients (96%). The average length of hospital stay in intensive care was 5 days ± 4.03 (2-20 days). The average length of hospital stay was 20.76 days ± 13.19 (9 to 64 days). The average duration of follow-up was 8.2 months ± 4.57 (1 week - 32 months). During the follow-up, only one patient (4%) had developed infectious endocarditis on prosthesis and only one patient (4%) had a complication related to anticoagulant therapy (antivitamin K) such as gingivorrhagia and melena. We had recorded a single case of death at 6 months, a late mortality of 4%. Aortic valve replacement surgery, by median sternotomy gives satisfactory short- and medium-term results with negligible morbidity and negligible operative mortality.


Assuntos
Valva Aórtica/cirurgia , Ponte Cardiopulmonar , Implante de Prótese de Valva Cardíaca/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Valva Aórtica/patologia , Insuficiência da Valva Aórtica/epidemiologia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/cirurgia , Criança , Feminino , Seguimentos , Humanos , Tempo de Internação , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Senegal , Esternotomia/métodos , Adulto Jovem
15.
Pediatr Cardiol ; 41(8): 1645-1650, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32851436

RESUMO

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Since heritability is suspected, actual guidelines recommend to perform an echocardiographic assessment for first-degree relatives (FDR) of patient with BAV. This study aimed to assess the effectiveness and the feasibility of the current guidelines for the screening of FDR of patient with BAV in a pediatric cardiology daily practice. Consecutive patients with BAV and their FDR were prospectively included from January 2015 to March 2018 at Centre Hospitalier Universitaire de Laval, Quebec City (Canada). Data were retrospectively collected and analyzed. A total of 713 FDR of 213 consecutives index cases [median age: 11 (6-20) years] were studied. Up to 32 (6.6%) FDR had a BAV and 26 (5.4%) had an aortic valve dysfunction. A total of 14 (2.9%) FDR had an ascending aorta dilatation according to Z-score including 6 (1.2%) patients with an ascending aorta ≥ 45 mm. No statistically significant differences regarding BAV, aortic valve dysfunction and ascending aorta dilatation prevalence were identified between generations. Screening was done in 482 (67.6%), prescribed but not done in 134 (19%), not prescribed in 92 (13%) and declined in 5 (1%) FDR. The prevalence of BAV in FDR was similar to prospective adult studies and supports actual guidelines in pediatric cardiology practice. Ascending aorta dilatation was rare in our young population. Exhaustiveness and additional burden to implement current guidelines remain a challenge in daily practice.


Assuntos
/diagnóstico , Programas de Rastreamento/métodos , Pediatria/normas , Guias de Prática Clínica como Assunto , Adolescente , Aorta/diagnóstico por imagem , Aorta/patologia , Doenças da Aorta/diagnóstico , Doenças da Aorta/epidemiologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Canadá , Cardiologia/normas , Criança , Ecocardiografia , Família , Estudos de Viabilidade , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Adulto Jovem
16.
Eur J Endocrinol ; 183(4): 463-470, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32822316

RESUMO

Objective: Turner syndrome (TS) is a rare disorder affecting 1/2500 female newborn. Aortic dilatation (AD) and aortic dissection represent a major concern in TS. The aims of our study were to describe the aortic root growth, potential aortic dilatation (AD) risk factors and cardiovascular outcomes in a cohort of patients with TS. Methods: Among 204 adult patients included, 197 were studied using a standardized 1.5 Tesla MRI protocol. AD was defined as an aortic diameter ≥20 mm/m2 at the Valsalva sinuses and/or at the ascending aorta, when indexed to body surface area. Results: At baseline, AD was present in 81/197 (41.1%) and 32/197 (16.2%) of patients, at the levels of Valsalva and ascending aorta, respectively. The aortic Valsalva diameter was larger in patients treated for thyroiditis (P < 0.001). Potential risk factors of AD were aging (P < 0.001) and the presence of bicuspid aortic valve (BAV) (P = 0.002). The hazard ratio (HR) of AD occurrence in the presence of BAV was 2.2 (95% CI: 1.33-3.71). After a median follow-up period of 5.1 years (n = 143), AD was present in 58/143 (40.6%) and 25/143 (17.5%) of patients at the levels of Valsalva and ascending aorta, respectively. The median aortic growth of the Valsalva sinuses remained stable. At the ascending aorta, it increased by 0.14 ± 0.61 mm/year. Only one aortic-related death was observed. Conclusion: AD is common in adult patients with TS. However, our results are rather reassuring, as the median aortic diameters remained stable after 5.1 years and few aortic events were observed.


Assuntos
Doenças da Aorta/epidemiologia , Síndrome de Turner/epidemiologia , Adulto , Aorta/diagnóstico por imagem , Aorta/patologia , Doenças da Aorta/complicações , Doenças da Aorta/diagnóstico , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Estudos de Coortes , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico , Dilatação Patológica/epidemiologia , Progressão da Doença , Feminino , França/epidemiologia , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/patologia , Humanos , Masculino , Prevalência , Síndrome de Turner/complicações , Adulto Jovem
17.
Medicine (Baltimore) ; 99(29): e21286, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702920

RESUMO

Calcific aortic valve disease (CAVD) is highly prevalent in our aging world and has no effective pharmaceutical treatment. Intense efforts have been made but the underlying molecular mechanisms of CAVD are still unclear.This study was designed to identify the critical genes and pathways in CAVD by bioinformatics analysis. Microarray datasets of GSE12644, GSE51472, and GSE83453 were obtained from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and functional and pathway enrichment analysis was performed. Subsequently, the protein-protein interaction network (PPI) was constructed with Search Tool for the Retrieval of Interacting Genes and was visualized with Cytoscape to identify the most significant module. Hub genes were identified by Cytoscape plugin cytoHubba.A total of 179 DEGs, including 101 upregulated genes and 78 downregulated genes, were identified. The enriched functions and pathways of the DEGs include inflammatory and immune response, chemotaxis, extracellular matrix (ECM) organization, complement and coagulation cascades, ECM receptor interaction, and focal adhesion. The most significant module in the PPI network was analyzed and genes among it were mainly enriched in chemotaxis, locomotory behavior, immune response, chemokine signaling pathway, and extracellular space. In addition, DEGs, with degrees ≥ 10 and the top 10 highest Maximal Chique Centrality (MCC) score, were identified as hub genes. CCR1, MMP9, VCAM1, and ITGAX, which were of the highest degree or MCC score, were manually reviewed.The DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis of CAVD and might serve as candidate therapeutic targets for CAVD.


Assuntos
Estenose da Valva Aórtica/genética , Valva Aórtica/patologia , Calcinose/genética , Genes/genética , Predisposição Genética para Doença/genética , Estenose da Valva Aórtica/etiologia , Calcinose/etiologia , Estudos de Casos e Controles , Biologia Computacional , Genes/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos
18.
Prog Cardiovasc Dis ; 63(4): 475-481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32640281

RESUMO

Patients with a bicuspid aortic valve (BAV) frequently develop aneurysms of the aortic root and tubular ascending aorta. Aneurysms of the aortic arch, in the absence of concomitant aortopathies, are much less common. According to the 2018 American Association of Thoracic Surgery consensus guidelines on BAV-related aortopathy, prophylactic surgical aortic repair / replacement is recommended starting at a maximum aortic diameter of 50 mm in patients with risk factors. Concomitant aortic surgery is also recommended at an aortic diameter of 45 mm in those patients with other indications for cardiac surgery (most commonly aortic valve procedures). The ultimate goal of prophylactic aortic surgery is the prevention of aortic catastrophes, e.g. aortic rupture or acute aortic dissection, which are associated with high morbidity and mortality. The surgical technique used - in elective and emergency cases - depends on the involvement and nature of the aortic valve disease, as well as the extent of aortic aneurysm formation. The current review focusses on the surgical management of the aortic root, tubular ascending aorta, and proximal aortic arch in BAV patients. Despite the abovementioned recommendations, many BAV patients develop acute aortic syndromes below the recommended aortic diameter thresholds. Further research is therefore required in order to identify high-risk BAV subgroups that would benefit from earlier surgical repair.


Assuntos
Aneurisma Aórtico/cirurgia , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/cirurgia , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/etiologia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Implante de Prótese Vascular , Anuloplastia da Valva Cardíaca , Doenças das Valvas Cardíacas/patologia , Humanos , Técnicas de Sutura
19.
Life Sci ; 257: 118086, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679147

RESUMO

AIMS: To investigate the role of PP2A in calcified aortic valve disease (CAVD). MATERIALS AND METHODS: The expressions of PP2A subunits were detected by real-time polymerase chain reaction (RT-PCR) and western blot in aortic valves from patients with CAVD and normal controls, the activities of PP2A were analyzed by commercial assay kit at the same time. Aortic valve calcification of mice was evaluated through histological and echocardiographic analysis. ApoE-/- mice and ApoE-/- mice injected intraperitoneally with PP2A inhibitor LB100 were fed a high-cholesterol diet for 24 weeks. Immunofluorescent staining was used to locate the cell-type in which PP2A activity was decreased, the PP2A activity of valvular interstitial cells (VICs) treated with osteogenic induction medium was assessed by western blot and commercial assay kit. After changing the activity of VICs through pharmacologic and genetic intervention, the osteoblast differentiation and mineralization were assessed by western blot and Alizarin Red staining. Finally, the mechanism was clarified by using several specific inhibitors. KEY FINDINGS: PP2A activity was decreased both in calcified aortic valves and human VICs under osteogenic induction. The PP2A inhibitor LB100 aggravated the aortic valve calcification of mice. Furthermore, PPP2CA overexpression inhibited osteogenic differentiation of VICs, whereas PPP2CA knockdown promoted the process. Further study revealed that the ERK/p38 MAPKs signaling pathways mediated the osteogenic differentiation of VICs induced by PP2A inactivation. SIGNIFICANCE: This study demonstrated that PP2A plays an important role in CAVD pathophysiology, PP2A activation may provide a novel strategy for the pharmacological treatment of CAVD.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Valva Aórtica/patologia , Apolipoproteínas E/genética , Calcinose/fisiopatologia , Osteogênese/genética , Proteína Fosfatase 2/genética , Animais , Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/genética , Calcinose/genética , Diferenciação Celular/genética , Técnicas de Silenciamento de Genes , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Piperazinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Am J Cardiol ; 128: 151-158, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650909

RESUMO

Normal-flow low-gradient severe aortic stenosis (NF-LG-SAS), defined by an aortic valve area (AVA) <1 cm², mean pressure gradient (MPG) <40 mm Hg and indexed stroke volume ≥35 ml/m², is the most prevalent form of low-gradient aortic stenosis (AS) with preserved ejection fraction (PEF). However, the true severity of AS in these patients is controversial. The aim of this Doppler echocardiographic study was to investigate changes over time in the hemodynamic severity of patients with NF-LG-SAS with PEF. We retrospectively identified 96 patients who had 2 Doppler echocardiographic examinations without an intervening event. After a median follow-up of 25 (interquartile range 15 to 52) months, progression was observed, with increased transaortic MPG (from 28 [25 to 33] to 39 [34 to 50] mm Hg; p<0.001), peak aortic jet velocity (from 3.46 [3.20 to 3.64] to 4.01 [3.70 to 4.39] m/s; p<0.001), and decreased AVA (from 0.87 [0.82 to 0.94] to 0.72 [0.62 to 0.81] cm²; p<0.001). Median annual rates of progression were 4.3 (1.7 to 8.1) mm Hg/year, 0.25 (0.08 to 0.44) m/s/year, and -0.05 (-0.10 to -0.02) cm²/year, respectively. There was no significant change in left ventricular ejection fraction over time (p = 0.74). At follow-up, 46 patients (48%) acquired the features of classical high-gradient severe AS (MPG ≥40 mm Hg). This study shows that most patients with NF-LG-SAS with PEF exhibit significant hemodynamic progression of AS severity without EF impairment. These findings suggest that NF-LG-SAS with PEF is an "intermediate" stage between moderate AS and classical high-gradient severe AS requiring close monitoring.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Velocidade do Fluxo Sanguíneo , Progressão da Doença , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Tamanho do Órgão , Pressão , Estudos Retrospectivos , Índice de Gravidade de Doença
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