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BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.
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Endocardite Bacteriana , Endocardite , Idoso , Feminino , Humanos , Idoso de 80 Anos ou mais , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/terapia , Endocardite/diagnóstico por imagem , Endocardite/terapia , Ecocardiografia , ComorbidadeRESUMO
Objectives: To compare the outcomes after transcatheter aortic valve replacement (TAVR) through a transfemoral (TF) and transcarotid (TC) access at our institution. Methods: From January 2014 to January 2020, 62 TC-TAVR and 449 TF-TAVR were performed using 2 prosthesis devices (Edwards SAPIEN 3, n = 369; Medtronic Evolut R, n = 142). Propensity score matching was used to adjust for imbalance in the baseline characteristics of the study groups. Results: Propensity score matching provided 62 matched pairs with comparable operative risk (mean European System for Cardiac Operative Risk Evaluation II, TC-TAVR 7.6% vs TF-TAVR 6.6%, P = .17). Thirty-day mortality (4.8% vs 3.2%, P = 1.00) and 2-year mortality (11.3% vs 12.9%, P = .64) after TC-TAVR were comparable with TF-TAVR. Strokes were numerically more frequent after TC-TAVR compared with TF-TAVR (3.2% vs 0%, P = .23), but the difference did not reach statistical significance. TF-TAVR was associated with a significantly greater risk of permanent pacemaker implantation (29.0% vs 12.9%, P = .04) compared with TC-TAVR. Other complications were not frequent and were similarly distributed between the matched groups. Conclusions: TC access for TAVR was associated with satisfactory results compared to the femoral access. TC-TAVR could be considered a valid and safe alternative to TF-TAVR when femoral access is contraindicated.
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BACKGROUND: The Cobra PzF coronary stent is cobalt chromium with flat thin struts, nano-coated with Polyzene-F that enhance rapid reendothelialization and reduce the risk of stent thrombosis and restenosis. It is designed to overcome shortfalls of BMS and DES in patients requiring short DAPT duration. AIMS: To report procedural and 1-year clinical outcomes following Cobra PzF stent implantation in routine practice PCI. METHODS: e-Cobra registry is a multicenter prospective study to evaluate Cobra PzF stent in routine practice in patients deemed appropriate for short DAPT after PCI. The primary endpoint was MACE rate at 12 months (Cardiac death, MI, TLR). The secondary endpoint was definite stent thrombosis at 12 months. RESULTS: Among 940 patients (72% men, 72.8 ± 13.4 years) with multiple co-morbidities, 47% had acute coronary syndromes, and 62% were defined as high bleeding risk. A total of 1,229 lesions were treated with 1,314 stents. 36% of patients had lesion type B2 or C classification. Angiographic success was achieved in all cases. One-year follow-up was available for 97% of patients. The primary endpoint occurred in 9.0% of patients, including cardiac death 3.7%, MI 4.8%, and TLR 4.3%. Definite stent thrombosis occurred in six out of 915 (0.7%). CONCLUSION: The Cobra PzF stent was safe and effective in routine practice patients and seems feasible in situations when short DAPT or Mono Antiplatelet Therapy (MAPT) is needed. One-year follow-up was associated with satisfactory clinical outcomes and validate previously reported data.
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Intervenção Coronária Percutânea , Stents , Idoso , Idoso de 80 Anos ou mais , Materiais Revestidos Biocompatíveis , Angiografia Coronária , Reestenose Coronária/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Estudos Prospectivos , Desenho de Prótese , Stents/efeitos adversos , Trombose/etiologia , Resultado do TratamentoRESUMO
Early infarct-related artery (IRA) patency is associated with better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). Using the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 registry, we investigated factors related to IRA patency (thrombolysis in myocardial infarction [TIMI] 2/3 flow) at the start of procedure in patients admitted for primary percutaneous coronary intervention. FAST-MI 2010 is a nationwide French registry including 4,169 patients with acute MI. Of 1,452 patients with STEMI with primary percutaneous coronary intervention, 466 (32%) had TIMI 2/3 flow of IRA before the procedure. Mean age (62 ± 14 years in both groups), Global Registry of Acute Coronary Event score (141 ± 31 vs 142 ± 34), and time from onset to angiography (472 ± 499 vs 451 ± 479 minutes) did not differ according to IRA patency (TIMI 2/3 vs TIMI 0/1). Using multivariate logistic regression analysis, IRA patency was more frequently found in patients having called earlier (time from onset to electrocardiogram [ECG] <120 minutes; odds ratio [OR] 1.49; 95% confidence interval [CI] 1.17 to 1.89), or receiving rapid-onset of action (prasugrel or glycoprotein IIb-IIIa) antiplatelet therapy in the prehospital setting (OR 1.59, 95% CI 1.14 to 2.21). Increasing time from diagnostic ECG to angiography was also associated with IRA patency (>90 minutes; OR 1.37, 95% CI 1.08 to 1.75). In conclusion, preprocedural IRA patency is observed in one third of patients with STEMI, it is more frequently found in patients having received fast-acting antiplatelet therapy before angiography, and in patients having called early. Higher IRA patency with increasing time delays from qualifying ECG to angiography suggests an additional role of spontaneous or medication-mediated fibrinolysis.
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Angiografia Coronária/métodos , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Eletrocardiografia , Infarto do Miocárdio/diagnóstico , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Cuidados Pré-Operatórios/métodos , Vasos Coronários/fisiopatologia , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Estudos Prospectivos , Fatores de Risco , Grau de Desobstrução VascularRESUMO
AIMS: To assess the impact of the composition in L- and D- of lactic acid stereo copolymers without drug elution on the in situ behaviour of prototype stents in terms of biomechanics and biocompatibility. METHODS AND RESULTS: PLA50, 75, and 92 stereo-copolymer stents (L/D lactic acid ratio from 1 to 11.5) were processed using the injection moulding facilities of Arterial Remodeling Technologies (Noisy le Roi, France). The resulting 3 mm outer diameter tubes having a diameter at the desired nominal size were laser-cut and crimped on regular angioplasty balloons and chemically sterilised prior to implantation in iliac rabbit arteries. Acute recoil was higher in PLA50 and PLA75 stent-treated arteries than in those with PLA92 stents (17.4 ± 11.4 vs. 13.5 ± 7.6 vs. 4.1 ± 3.8 %, respectively, p=0.001). At one month, in-stent area was higher in PLA92 than in PLA50 and PLA75 stented arteries (5.9 ± 0.6 vs. 1.6 ± 1.6 vs. 2.6 ± 3.2 mm², respectively, p<0.001). Re-endothelialisation was complete, and inflammation was mild around the struts, similar among the three stents. Late lumen loss and neointimal area were low and similar in PLA92 stent-treated arteries one and six months after angioplasty (0.2 ± 0.2 vs. 0.3 ± 0.2 mm, p=0.60; 0.5 ± 0.5 vs. 0.5 ± 0.8 mm², p=0.72, respectively). At six months, inflammation decreased compared to one-month follow-up (1.4 ± 0.5 vs. 0.6 ± 0.5, p=0.006). CONCLUSIONS: A stereo-copolymer composition strongly influences biomechanical properties of PLA bioresorbable stents in agreement with what has been known for a long time from other applications, but not biocompatibility. PLA92 stents appeared as presenting acceptable acute deployment and 6-month favourable outcome in the rabbit model despite the absence of drugs.
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Angioplastia , Artéria Ilíaca , Ácido Láctico/administração & dosagem , Polímeros/administração & dosagem , Stents , Animais , Fenômenos Biomecânicos , Seguimentos , Masculino , Poliésteres , CoelhosRESUMO
BACKGROUND: Human Herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis in immunocompromised or immunocompetent patients. However the physiopathological mechanisms of HHV-6 related acute myocarditis and the involvement of subsequent HHV-6 reactivation phases in the development of chronic cardiomyopathies remain to be assessed. OBJECTIVES: To describe a case of fatal HHV-6 chronic myocarditis in an immunocompetent adult. STUDY DESIGN: Case report and detailed histological and viral diagnoses by combination of histology/immunohistochemistry and polymerase chain reaction techniques on cardiac tissues. RESULTS: Histopathological analysis of ventricular tissues showed large interstitial and scarring fibrotic areas with a moderate mononuclear cell infiltrate compatible with histological aspect of chronic myocarditis. Detection of both HHV-6 by real-time PCR and viral glycoproteins in mononuclear and endothelial cells by immunohistochemistry evidenced an ongoing cardiac HHV-6 replication with viral late protein synthesis activity. CONCLUSIONS: This case report indicates that HHV-6 can establish a chronic active myocarditis leading to heart failure in immunocompetent subjects.
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Herpesvirus Humano 6/genética , Miocardite/virologia , Infecções por Roseolovirus/virologia , Biópsia , Linhagem Celular Tumoral , Doença Crônica , Evolução Fatal , Feminino , Humanos , Imunocompetência , Pessoa de Meia-Idade , Miocardite/patologia , Miocárdio/patologia , Infecções por Roseolovirus/patologiaRESUMO
The diagnosis of acute myocarditis is complex and challenging. The use of the Dallas criteria in the diagnosis of myocarditis is associated with poor sensitivity and specificity because of the sampling error related to the often focal distribution of the specific histological lesions in cardiac tissue and the variability in pathological interpretation. To improve histological diagnosis, additional virological evaluation of cardiac tissues is required, with immunohistochemical and polymerase chain reaction (PCR) techniques allowing identification and quantification of viral infection markers. The diagnostic gold standard is endomyocardial biopsy (EMB) with the histological Dallas criteria, in association with new immunohistochemical and PCR analyses of cardiac tissues. Using real-time PCR and reverse transcription PCR assays, parvovirus B19, Coxsackie B virus, human herpesvirus 6 (HHV-6) type B and adenovirus have been detected in 37, 33, 11 and 8% of EMB, respectively, from young adults (aged<35 years) with histologically proven acute myocarditis. Viral co-infections have also been found in 12% of acute myocarditis cases, generally parvovirus B19 plus HHV-6. Moreover, herpesviruses such as the Epstein-Barr virus or cytomegalovirus can also be associated with myocarditis after heart transplantation. During the clinical course of myocarditis, the immunohistochemical detection of enterovirus, adenovirus or parvovirus B19 capsid proteins or herpesvirus late proteins is necessary to differentiate a viral cardiac infection with replication activities from a persistent or latent cardiac infection. These new viral diagnostic approaches can lead to better identification of the aetiology of myocarditis and may therefore enable the development and evaluation of specific aetiology-directed treatment strategies.
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Miocardite/virologia , Doença Aguda , Adulto , Antivirais/uso terapêutico , Autoanticorpos/sangue , Biópsia , Fármacos Cardiovasculares/uso terapêutico , Diagnóstico por Imagem , Progressão da Doença , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Técnicas de Diagnóstico Molecular , Miocardite/diagnóstico , Miocardite/tratamento farmacológico , Miocardite/imunologia , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
Matrix metalloproteinases (MMP) play a deleterious role in numerous vascular diseases. In contrast, gingival matrix remodelling is adequately regulated by the gingival fibroblast (GF). Here, we aimed to evaluate the GF activity on MMP-7 expression and secretion in coculture with aorta rings. We evaluated MMP-7 transcription and secretion in rabbit aorta rings cultured or not with gingival fibroblasts in collagen gels. GF induced an increase of TIMP-1 transcription and secretion, followed, similarly to other MMPs, by the formation of TIMP-1/MMP-7 complexes. There was also a decrease of MMP-7 mRNA by RT-PCR in aorta rings cocultured with gingival fibroblasts. Interestingly, in contrast with other MMPs (which were not influenced at a transcription level), GF stimulated the release of TGF-beta1, which in turn inhibited the transcription and synthesis of MMP-7, as shown by neutralizing MMP-7 inhibition due to gingival fibroblast by overexpressing decorin (a TGF beta 1 inhibitor) or by silencing TGF beta 1 using siRNA. We showed that healing properties of the GF could be transposed to another organ, i.e., ex vivo aneurism model, implicating a down-regulation of MMP-7.
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Aorta/enzimologia , Fibroblastos/enzimologia , Gengiva/citologia , Inibidores de Metaloproteinases de Matriz , Adenoviridae/genética , Animais , Aorta/citologia , Técnicas de Cocultura , Decorina , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/citologia , Humanos , Metaloproteinase 7 da Matriz/metabolismo , Proteoglicanas/metabolismo , RNA Interferente Pequeno/metabolismo , Coelhos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Transcrição Gênica , Transfecção , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismoRESUMO
AIMS: In-stent restenosis is related to neointimal hyperplasia. Heating reduces neointimal hyperplasia but promotes constrictive remodeling after balloon angioplasty. We aimed to assess the ability of local heating in inhibiting restenosis and in-stent neointimal hyperplasia and its potential side effects on arterial thrombosis. METHODS AND RESULTS: Atherosclerotic-like lesions were induced in iliac rabbit arteries. One month later, both iliac rabbit arteries were stented. In each animal, one artery was randomized to local heating at four temperatures (50, 60, 80, and 100 degrees C). The contra lateral artery was used as control. Angiographic and histomorphometric analysis were performed 42 days after angioplasty. Immunohistochemistry was performed 3, 15, and 42 days after angioplasty. Angiographic significant reduction of in-stent restenosis after moderate heating (50 degrees C) was related to in-stent neointimal hyperplasia trend to be lower after moderate local heating when compared with controls. In contrast, in-stent thrombosis was similar to controls. Higher temperatures (i.e. 80 and 100 degrees C) also reduced in-stent neointimal hyperplasia but were most frequently associated with severe in-stent thrombosis. Local heating was associated with decreased cell proliferation, collagen density, and increased smooth muscle cell apoptosis and heat shock protein expression. CONCLUSION: Moderate heating represents a promising approach to prevent in-stent restenosis via the limitation of the proliferative response without thrombosis induction.
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Aterosclerose/terapia , Oclusão de Enxerto Vascular/prevenção & controle , Temperatura Alta/uso terapêutico , Artéria Ilíaca/patologia , Stents , Túnica Íntima/patologia , Angioplastia com Balão , Animais , Apoptose/fisiologia , Proliferação de Células , Constrição Patológica/prevenção & controle , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP70/metabolismo , Hiperplasia/prevenção & controle , Miócitos de Músculo Liso/citologia , Coelhos , Distribuição Aleatória , Prevenção Secundária , Resultado do TratamentoRESUMO
AIMS: Although underestimated by interventional cardiologists for a long time, radiation exposure of operators and patients is currently a major concern. The objective of the present operator-blinded registry was to compare related-peripheral arterial route radiation exposure of operators. METHODS AND RESULTS: During 420 consecutive coronary angiograms (CAs) and percutaneous coronary interventions (PCIs), four interventional cardiologists were blindly screened. Radiation exposures were assessed using electronic personal dosimeters. Protection of operator was ensured using a lead apron, low leaded flaps, and leaded glass. Radiation exposure of operators was significantly higher using the radial route when compared with the femoral route for both CAs and CAs followed by ad hoc PCIs: 29.0 [1.0-195.0] microSv vs. 13.0 [1.0-164.0] microSv; P < 0.0001 and 69.5 [4.0-531.0] microSv vs. 41.0 [2.0-360.0] microSv; P = 0.018, respectively. Similarly, radiation exposure of patients was significantly higher using the radial route when compared with the femoral route for both CAs and CAs followed by ad hoc PCIs. Moreover, procedural durations and fluoroscopy times were significantly higher throughout the radial route. CONCLUSIONS: Although the radial route decreases peripheral arterial complication rates, increased radiation exposure of operators despite extensive use of specific protection devices is currently a growing problem for the interventional cardiologist health. Radial route indication should be promptly reconsidered in the light of the present findings.
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Angiografia Coronária/instrumentação , Exposição Ocupacional , Proteção Radiológica/instrumentação , Radiografia Intervencionista/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Segurança de Equipamentos , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial/diagnóstico por imagem , Doses de Radiação , Radiometria/métodosRESUMO
OBJECTIVE: Embryo-like gingival healing properties are attributed to the gingival fibroblast (GF) and could be used as a model for other types of healing dysfunctions. Abdominal aortic aneurysm (AAA) formation is associated with elastin degradation and increase in matrix metalloproteinase (MMP)-9 activity. We aimed to validate the concept of using GF healing properties in arteries. METHODS AND RESULTS: We evaluated MMP-9 and its tissue inhibitor (TIMP-1) in rabbit aortic rings cultured in collagen gels with or without GFs and observed throughout 21 days. We also performed cocultures of human smooth muscle cells (hSMCs) with either gingival, dermal, or adventitial fibroblasts, and alone (control). In control arteries, elastic fibers became spontaneously sparse. In presence of GFs, elastic fibers were preserved. There was a dramatically reduced protein level of MMP-9 in coculture of aorta and GFs, in contrast with control aorta. MMP-9 expression was unaffected by GFs. MMP-9 inhibition was related to increased TIMP-1 secretion, TIMP-1 forming a complex with MMP-9. Cell cocultures of hSMC with GFs showed similar results. Dermal and adventitial fibroblasts did not affect MMP-9. CONCLUSIONS: Elastic fiber degradation was specifically preserved by GFs via reduction of MMP-9 protein level by increasing TIMP-1 synthesis. Vascular transfer of gingival fibroblasts could be a promising approach to treat AAA.
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Aorta/metabolismo , Elastina/metabolismo , Fibroblastos/fisiologia , Gengiva/citologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Animais , Aneurisma da Aorta Abdominal/terapia , Células Cultivadas , Técnicas de Cocultura/métodos , Humanos , Metaloproteinase 9 da Matriz/metabolismo , CoelhosRESUMO
OBJECTIVE: To compare bleeding complications and results of percutaneous coronary intervention (PCI) between patients treated by radial and femoral approaches for acute myocardial infarction (AMI,) and using abciximab and 5 French guiding-catheters. PATIENTS: 114 consecutive patients with AMI were prospectively randomised. Exclusion criteria were a history of coronary artery bypass graft, cardiogenic shock, atrioventricular block, and contraindication to abciximab or a negative Allen test. Local haemostasis was achieved by manual compression. RESULTS: Baseline characteristics were similar between the two groups. Peripheral arterial complication rates and delays to patient ambulation were significantly lower in the radial group than in the femoral group, whereas in-hospital stay was similar between the two groups. A cross over was more often necessary in the radial group than in the femoral group. Coronary angiography duration and fluoroscopy time were significantly longer in the radial group than in the femoral group, whereas PCI duration was similar in both groups. CONCLUSIONS: The FARMI trial showed that the radial route lowered peripheral arterial complication rates and allowed earlier ambulation, despite no significant benefit on the duration of hospitalisation.
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Angioplastia Coronária com Balão/métodos , Anticorpos Monoclonais/uso terapêutico , Anticoagulantes/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Abciximab , Angioplastia Coronária com Balão/efeitos adversos , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: During percutaneous coronary intervention, the technique of stent implantation (both direct and complementary stenting) is guided using both clinical and angiographic features. We assessed potential relationships between procedural parameters and angioplasty-induced variations in inflammatory parameters in patients treated by these two different techniques. METHODS: A total of 85 consecutive patients due to undergo stent implantation were prospectively enrolled. Inflammation was assessed in terms of C-reactive protein, fibrinogen, erythrocyte sedimentation rate and leukocyte count in samples taken before and 24 h after angioplasty. Patients were classified based on whether they underwent complementary (n=47) or direct stenting (n=38). RESULTS: Inflammation after complementary stenting was related to the duration of inflation (r=0.59; p<0.001), whereas inflammation after direct stenting was related to the inflation pressure (r=0.61; p=0.007), as assessed by C-reactive protein variation. None of the other parameters influenced the inflammatory response. CONCLUSIONS: The inflammatory response after stent implantation depends on the mode of stenting. We therefore hypothesize that the inflammatory response after stenting might be related to the histological composition of the atherosclerotic plaques involved.
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Angioplastia Coronária com Balão , Inflamação/fisiopatologia , Stents , Proteína C-Reativa/análise , HumanosRESUMO
Cardiac papillary fibroelastomas are rare benign tumors of the heart with potential for life-threatening complications. The incidence of multiple lesions is less than 10% of all reported cases. Preoperative transesophageal echocardiography is important for detecting all cardiac sites involving this tumor, because excision of all such tumors must be performed to prevent serious complications. Here, the first ever case is reported of multiple infected papillary fibroelastoma of the mitral valve, aortic valve and left ventricular outflow tract with massive mitral insufficiency in a patient with hypertrophic cardiomyopathy.
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Cardiomiopatia Hipertrófica/complicações , Endocardite Bacteriana/complicações , Fibroma/complicações , Neoplasias Cardíacas/complicações , Infecções Estafilocócicas/complicações , Adulto , Cardiomiopatia Hipertrófica/diagnóstico , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Fibroma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Humanos , Masculino , Infecções Estafilocócicas/diagnósticoAssuntos
Angioplastia/efeitos adversos , Aterosclerose/cirurgia , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/patologia , Homocisteína/sangue , Miocárdio/patologia , Biomarcadores/sangue , Feminino , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. METHODS: We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. FINDINGS: Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9.9% (range -20 to 0.3) relative to baseline (p=0.011) whereas in the treated group it improved by 6.6% (-5.7 to 50.8; comparison between groups p=0.002). INTERPRETATION: These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.
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Embrião de Mamíferos/citologia , Infarto do Miocárdio/terapia , Miocárdio/citologia , Transplante de Células-Tronco , Animais , Diferenciação Celular , Divisão Celular , Linhagem da Célula , Sobrevivência de Enxerto , Camundongos , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Ovinos , Volume SistólicoRESUMO
Constrictive remodeling after arterial injury is related to collagen accumulation. Cross-linking has been shown to induce a scar process in cutaneous wound healing and is increased after arterial injury. We therefore evaluated the effect of cross-linking inhibition on qualitative and quantitative changes in collagen, elastin, and arterial remodeling after balloon injury in the atherosclerotic rabbit model. Atherosclerotic-like lesions were induced in femoral arteries of 28 New Zealand White rabbits by a combination of air desiccation and a high-cholesterol diet. After 1 mo, balloon angioplasty was performed in both femoral arteries. Fourteen rabbits were fed beta-aminopropionitrile (beta-APN, 100 mg/kg) and compared with 14 untreated animals. The remodeling index, i.e., the ratio of external elastic lamina at the lesion site to external elastic lamina at the reference site, was determined 4 wk after angioplasty for both groups. Pyridinoline was significantly decreased in arteries from beta-APN-treated animals compared with controls, confirming inhibition of collagen cross-linking: 0.30 (SD 0.03) and 0.52 (SD 0.02) mmol/mol hydroxyproline, respectively (P = 0.002). Scanning and transmission electron microscopy showed a profound disorganization of collagen fibers in arteries from beta-APN-treated animals. The remodeling index was significantly higher in beta-APN-treated than in control animals [1.1 (SD 0.3) vs. 0.8 (SD 0.3), P = 0.03], indicating favorable remodeling. Restenosis decreased by 33% in beta-APN-treated animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was significantly lower in beta-APN-treated animals than in controls: 23.0% (SD 3.8) vs. 29.4% (SD 4.0) (P = 0.004). These findings suggest that collagen and elastin cross-linking plays a role in the healing process via constrictive remodeling and restenosis after balloon injury in the atherosclerotic rabbit model.
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Artérias/metabolismo , Artérias/patologia , Colágeno/metabolismo , Elastina/metabolismo , Aminopropionitrilo/farmacologia , Angiografia , Animais , Artérias/lesões , Aterosclerose/metabolismo , Aterosclerose/patologia , Cateterismo , Colágeno/química , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Elastina/química , Inibidores Enzimáticos/farmacologia , Matriz Extracelular/metabolismo , Artéria Femoral/lesões , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Microscopia Eletrônica de Transmissão , Proteína-Lisina 6-Oxidase/antagonistas & inibidores , Proteína-Lisina 6-Oxidase/farmacologia , CoelhosRESUMO
BACKGROUND: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. METHODS: O(2)(-) and H(2)O(2 )production was quantified in cultured cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. RESULTS: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27 vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9 +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05), lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control arteries. CONCLUSIONS: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.
Assuntos
Adenoviridae/genética , Angioplastia com Balão , Arteriosclerose/terapia , Catalase/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Artéria Ilíaca , Superóxido Dismutase/genética , Animais , Aorta/metabolismo , Células Cultivadas , Colágeno/antagonistas & inibidores , Endotélio Vascular/fisiopatologia , Humanos , Artéria Ilíaca/metabolismo , Artéria Ilíaca/fisiopatologia , Inflamação/prevenção & controle , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo , Coelhos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Prevenção SecundáriaRESUMO
AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.
Assuntos
Mioblastos Esqueléticos/transplante , Infarto do Miocárdio/terapia , Animais , Cateterismo Cardíaco/métodos , Infarto do Miocárdio/fisiopatologia , Recuperação de Função Fisiológica , Ovinos , Função Ventricular Esquerda/fisiologiaRESUMO
Direct stenting (DS) is accepted as reducing procedural cost and duration and 5 Fr guiding catheters as lowering peripheral vascular complications. We aimed to evaluate the feasibility and safety of both strategies. We retrospectively studied 150 consecutive patients treated with DS strategy using a 5 Fr femoral approach. A need for 6 Fr devices or balloon predilatation defined 5 Fr DS failure. Procedural success was defined as good angiographic result (residual stenosis < 30% and TIMI flow 3) without ischemic complications. A total of 161 out of 174 lesions were elected as suitable for DS. The success rate of 5 Fr DS was 87.6% (141/161 lesions). The procedural success rate was 92% (138/150 patients). The angiographic success rate was 96.3% (155/161 lesions). Other complications were six non-Q-wave MI and one repeat angioplasty for acute in-stent thrombosis. Only one major peripheral vascular complication occurred. Direct stenting through 5 Fr guiding catheters in selected lesions is safe and effective with a low incidence of peripheral arterial complications.