RESUMO
BACKGROUND: Transcatheter aortic valve replacement is an established treatment option for patients with severe symptomatic aortic stenosis and is most commonly performed through the transfemoral access route. Percutaneous access site closure can be achieved using dedicated plug-based or suture-based vascular closure device (VCD) strategies, but randomized comparative studies are scarce. METHODS: The CHOICE-CLOSURE trial (Randomized Comparison of Catheter-based Strategies for Interventional Access Site Closure during Transfemoral Transcatheter Aortic Valve Implantation) is an investigator-initiated, multicenter study, in which patients undergoing transfemoral transcatheter aortic valve replacement were randomly assigned to vascular access site closure using either a pure plug-based technique (MANTA, Teleflex) with no additional VCDs or a primary suture-based technique (ProGlide, Abbott Vascular) potentially complemented by a small plug. The primary end point consisted of access site- or access-related major and minor vascular complications during index hospitalization, defined according to the Valve Academic Research Consortium-2 criteria. Secondary end points included the rate of access site- or access-related bleeding, VCD failure, and time to hemostasis. RESULTS: A total of 516 patients were included and randomly assigned. The mean age of the study population was 80.5±6.1 years, 55.4% were male, 7.6% of patients had peripheral vascular disease, and the mean Society of Thoracic Surgeons score was 4.1±2.9%. The primary end point occurred in 19.4% (50/258) of the pure plug-based group and 12.0% (31/258) of the primary suture-based group (relative risk, 1.61 [95% CI, 1.07-2.44], P=0.029). Access site- or access-related bleeding occurred in 11.6% versus 7.4% (relative risk, 1.58 [95%CI: 0.91-2.73], P=0.133) and device failure in 4.7% versus 5.4% (relative risk, 0.86, [95% CI, 0.40-1.82], P=0.841) in the respective groups. Time to hemostasis was significantly shorter in the pure plug-based group (80 [32-180] versus 240 [174-316] seconds, P<0.001). CONCLUSIONS: Among patients treated with transfemoral transcatheter aortic valve replacement, a pure plug-based vascular closure technique using the MANTA VCD is associated with a higher rate of access site- or access-related vascular complications but a shorter time to hemostasis compared with a primary suture-based technique using the ProGlide VCD. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04459208.
Assuntos
Estenose da Valva Aórtica/cirurgia , Doenças Vasculares Periféricas/cirurgia , Substituição da Valva Aórtica Transcateter , Dispositivos de Oclusão Vascular , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Artéria Femoral/cirurgia , Hemorragia/etiologia , Hemostasia/fisiologia , Humanos , Masculino , Suturas/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Dispositivos de Oclusão Vascular/efeitos adversosRESUMO
BACKGROUND: Previous studies have reported slightly higher stroke rates in Takotsubo Syndrome compared to acute myocardial infarction. Our goal was to evaluate the temporal course of stroke rates and left ventricular recovery in patients with Takotsubo Syndrome. METHODS: We retrospectively examined the clinical and imaging data of 72 patients with Takotsubo Syndrome. The data collected came from January 2005 to March 2017. Left ventricular performance was evaluated by cardiovascular magnetic resonance imaging (MRI) in all patients during the acute phase of Takotsubo Syndrome and in a follow-up scan 2 months later. Acute stroke and major adverse clinical events, such as myocardial infarction or recurrence of Takotsubo Syndrome and death, were also determined for each patient at 30 days and 12 months after initial presentation. RESULTS: The MRI scans performed during the acute phase of Takotsubo Syndrome demonstrated apical ballooning with anterior wall motion dysfunction in 65 (90%) patients. Imaging performed 2 months later demonstrated resolution of this in 97% of those patients. Median left ventricular ejection fraction also significantly increased between both scans (49.5% vs. 64.0%, P < 0.001). We observed 9 (12%) events in the study population within 12 months of the initial diagnosis of Takotsubo Syndrome. Stroke had an event rate of 2.8% after 30 days and 4.2% after 12 months. CONCLUSIONS: Apical ballooning was found in the majority of our Takotsubo Syndrome patients on the MRI scans performed at presentation. This finding was subsequently associated with higher than expected stroke rates within 30 days of diagnosis and with rapid recovery of left ventricular function within 2 months of diagnosis. This suggests that rapid improvement in left ventricular morphology and function may facilitate the formation of cardiac emboli and consequently increase stroke rates in Takotsubo Syndrome. Although no guidelines currently exist for the treatment of Takotsubo Syndrome, these results may point to a potential role for temporary oral anticoagulation in high-risk patients. Future studies should examine if stroke rates after Takotsubo Syndrome have been underestimated.
Assuntos
Anticoagulantes/administração & dosagem , Volume Sistólico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/tratamento farmacológico , Função Ventricular Esquerda , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Proteção , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans. METHODS AND RESULTS: A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<0.0005) and PES (18.7%; P<0.0005). CoCr-EES showed a lower inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%; SES=35%; PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%; SES=40%; PES=19%; P=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%). CONCLUSIONS: CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.
Assuntos
Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Stents Farmacológicos , Imunossupressores/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Autopsia , Materiais Biocompatíveis , Ligas de Cromo , Doença da Artéria Coronariana/terapia , Reestenose Coronária/epidemiologia , Reestenose Coronária/patologia , Trombose Coronária/epidemiologia , Trombose Coronária/patologia , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neointima/patologia , Paclitaxel/administração & dosagem , Prevalência , Sistema de Registros , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/análogos & derivadosRESUMO
The mitral clipping technique is emerging as a promising new treatment option for severe mitral regurgitation. The device was designed and assessed in intermediate risk populations, which is in contrast to the real world, where most patients are deemed to be at very high risk for open heart surgery. The cardiac anatomy of these patients often challenges the freedom grades of the current mitral clip device. In this case presentation, we describe a novel technique overcoming extreme atrial dilation in a patient with severe mitral regurgitation despite previous implantation of two mitral clips. Based on a low/anterior trans-septal puncture, this procedure relied on a counter clock-wise 90° turn of the steerable sheath and alignment of the clip delivery system to the mitral valve, thereby gaining additional longitudinal freedom. This resulted in the successful implantation of two additional clips with achievement of a mild to moderate mitral regurgitation without relevant gradient and dramatic and sustained clinical improvement of the patient.
Assuntos
Cateterismo Cardíaco/métodos , Cardiomegalia/etiologia , Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Mitral/terapia , Valva Mitral , Idoso , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Cardiomegalia/diagnóstico , Cardiomegalia/fisiopatologia , Dilatação Patológica , Ecocardiografia Transesofagiana , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/fisiopatologia , Desenho de Prótese , Punções , Radiografia Intervencionista , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Background: The location and severity of vascular calcification may influence closure device success in transfemoral transcatheter aortic valve implantation. The aim of this study was to analyze effects of vascular access-site calcification on vascular and bleeding outcomes post-transcatheter aortic valve implantation. Methods: The Randomized Comparison of CatHeter-based Strategies fOr Interventional ACcess SitE CLOSURE during Transfemoral Transcatheter Aortic Valve Implantation (CHOICE-CLOSURE) trial assigned 516 patients to access site closure using a pure plug-based technique (MANTA, Teleflex) or a primary suture-based technique (ProGlide, Abbott Vascular). The principal finding of the overall study was that access-site or access-related complications were more common after the plug-based strategy compared to percutaneous closure with a suture-based strategy. In this predefined subgroup analysis, the overall cohort was split into patients with and without anterior calcification at the access site and divided by degree of calcification severity using the classification system developed in the MANTA vs. suture-based vascular closure after transcatHeter aortic valve replacement (MASH) trial. Differences in bleeding and vascular complications were compared. The primary endpoint consisted of access-site- or access-related major and minor vascular complications. Results: There were more access-site-related major and minor vascular complications for patients with anterior wall vascular calcification and MASH severe calcification. No significant interaction with choice of closure technique in terms of access-site-related major and minor vascular complications was observed (odds ratio 1.70, 95% CI 0.77-3.78, p = 0.19 for the primary endpoint in plug- vs. suture-based strategy in patients with anterior calcification, odds ratio 1.78, 95% CI 0.56-5.65, p = 0.33 for primary endpoint in plug- vs. suture-based strategy with MASH severe calcification, pint = 0.97 for anterior calcification, pint = 0.95 for MASH severe calcification). Conclusions: The total number of vascular complications was found to be greater in the presence of anterior and MASH severe calcification. Overall, the presence of anterior or severe calcification does not significantly modify the efficacy of the suture-based strategy compared to the plug-based strategy.
RESUMO
PURPOSE: To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. MATERIALS AND METHODS: All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. RESULTS: Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P<.0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, P<.0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P<.0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (κ=0.87 and 0.85, respectively) and was good for intravascular US (κ=0.66). CONCLUSION: Systematic and standardized comparison between invasive and noninvasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Tomografia de Coerência Óptica/métodos , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia de Intervenção/métodos , Cadáver , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaAssuntos
Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Migração de Corpo Estranho/diagnóstico por imagem , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico por imagem , Stents/efeitos adversos , Angiografia Coronária , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
OPINION STATEMENT: Vulnerable carotid plaques at risk for rupture/ulceration do not always correlate with the severity of stenosis at bifurcation sites. Therefore, information on plaque morphology and composition is essential for identifying patients at high risk for acute major cerebrovascular events. Traditional imaging modalities, including angiography and ultrasound, are slowly being replaced by CT imaging, as this technology is readily available in most hospitals and provides high-resolution capabilities at relatively low cost. Improvements in MRI, particularly high-resolution gadolinium-enhanced MRI, currently make this modality the most informative technology, as it allows easy identification of lesion morphometry, calcification, and hemorrhage. Further, multimodal imaging of carotid artery plaques using fluorodeoxyglucose positron emission tomography/CT is slowly growing out of its infancy and is providing valuable information on the inflammatory component of the plaque, a critical indicator of lesion instability. These recent advancements in imaging technologies will no doubt dictate early treatment options for symptomatic and asymptomatic patients with noncritical carotid stenosis in the near future. Ultimately, however, the identification of important molecular surrogates in early lesion progression may eventually predict late-term risk and likely will provide the ideal strategy for reducing the morbidity and mortality of stroke.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Aterosclerose/genética , Hipolipoproteinemias/genética , Lipoproteínas HDL/genética , Mutação/genética , Transportador 1 de Cassete de Ligação de ATP , Dispneia/etiologia , Feminino , Heterozigoto , Humanos , Lipoproteínas HDL/sangue , Pessoa de Meia-IdadeRESUMO
AIMS: Transradial access (TRA) has become a standard approach for cardiac catheterization. However, an obstacle to TRA is the risk of radial artery occlusion (RAO) after radial access in about 5%-10% of patients. We analyzed the safety and efficacy of getting vascular access after RAO by percutaneous transluminal angioplasty in cases of chronic radial occlusion. METHODS AND RESULTS: Chronic RAO was confirmed by Allen test and color Doppler in 8 patients. TRA was achieved by puncture in the distal tabatiere (anatomical snuffbox) using Seldinger's technique followed by insertion of a 5 Fr radial introducer sheath. Angiogram was obtained before percutaneous transluminal angioplasty with a 2.0 mm coronary balloon to reopen the artery. Puncture of the occluded radial artery, percutaneous transluminal angioplasty, and subsequent coronary catheterization and PCI were successful in all 8 patients. One complication was a dissection of the radial artery without further adverse events. No hemorrhage or compartment syndrome occurred. CONCLUSIONS: With increased application of TRA, the incidence of RAO is also rising. Some patients with RAO require repeat cardiac catheterization. Given the risk of damaging the contralateral radial artery in subsequent procedures, using the same access site is desirable. We demonstrate that it is feasible to get access to an occluded radial artery by percutaneous transluminal angioplasty.
Assuntos
Angioplastia Coronária com Balão/métodos , Arteriopatias Oclusivas/diagnóstico , Cateterismo Periférico/métodos , Doença da Artéria Coronariana/complicações , Artéria Radial , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Cateterismo Cardíaco/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , UltrassonografiaRESUMO
Despite prompt revascularization, some patients with acute myocardial infarction (AMI) develop myocardial scars, which can be visualized by late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). Our goal was to identify angiographic findings that were predictive for scar development in patients after reperfused AMI.We examined 136 patients after first ST-elevated myocardial infarction by CMR after a median of 4 days (range: 2-7). Patients with manifestation of LGE were matched to patients without LGE by means of age and gender. Clinical follow-up with a combined primary endpoint including myocardial reinfarction, congestive heart failure, stroke, death and development of left ventricular thrombus was reported after 24 months.Patients with manifestation of LGE had a significant longer time of symptom-to-intervention, a higher prevalence of anterior AMI, and more proximal culprit lesions. Furthermore, left ventricular ejection fraction was significantly decreased, and peak values of infarct markers were significantly higher in these patients. Preinterventional thrombolysis in myocardial infarction-0-flow was significantly more frequent in patients with LGE manifestation. The presence of 3-vessel disease (odds ratio 53.99, 95% confidence interval 8.22-354.63, Pâ<.001), a proximal culprit lesion, and high creatine kinase myocardial band (CK-MB) values were identified as independent predictors of LGE. Follow-up demonstrated a higher incidence of clinical events in the group with LGE, with the most common cause of heart failure (38.2% vs 7.4%, Pâ<.001).The extent of angiographic findings in AMI plays a major role in the manifestation of LGE. The presence of a multivessel disease, a proximal culprit lesion, and high values of CK-MB are strong independent predictors for LGE manifestation.
Assuntos
Meios de Contraste , Angiografia Coronária , Gadolínio , Angiografia por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Medical devices such as implant delivery systems are commonly used during minimally invasive procedures in the cardiovascular system. These devices often have lubricious polymer coatings to reduce friction between the device and blood vessels but coatings may separate and potentially cause serious injuries to patients. METHODS: Lubricious coated eSheaths for transcatheter heart valve implantation were assessed for luminal integrity at the proximal, medial and distal part. We assessed the number, depths and area of luminal trails using environmental scanning electron microscope (ESEM), white light interferometry (WLI) and optical profilometry using area scale fractal complexity (asfc) as surface parameters. A total of 15 eSheaths were retrieved and analyzed after successful femoral transcatheter Sapien 3 implantation in patients (23 mm valve- 14F eSheath, 26 mm valve- 14F eSheath and 29 mm valve- 16F eSheath, n = 5 for each group). Unused eSheaths (14F and 16F) served as controls (n = 5 for each group). RESULTS: ESEM revealed significantly greater number of trails after TAVR passage with the 23 mm, 26 mm and 29 mm valves compared to unused control 14F and 16F eSheaths (13.9 ± 3.1, 14.2 ± 2.3, 15.8 ± 1.7 vs. 0.08 ± 0.1 and 1.0 ± 0.5 [n]; p ≤ 0.0001 for all comparisons). Similarly, WLI showed minor, but significantly greater areas of luminal defects after 23 mm, 26 mm and 29 mm valve implantation vs. 14F and 16F unused controls (7.5 ± 0.9, 10.3 ± 1.1, 10.4 ± 1.4 vs. 4.1 ± 0.4 and 2.2 ± 0.4 [µm2], p = 0.0081). Likewise, the 3D-surface-measurement showed comparable results after implantation of the 23 mm, 26 mm and 29 mm valves vs. 14F and 16F unused control eSheaths (79.5 ± 6.3, 105.9 ± 5.3, 98.8 ± 4.8 vs. 5.1 ± 2.8 and 5.6 ± 0.5 [asfc] p = 0.0001). CONCLUSION: Measurable defects of the luminal layer occur during balloon expandable TAVR using 14F and 16F eSheaths though this is likely clinically insignificant. Further clinical investigations including a prospective assessment of minor peripheral embolization are needed to fully address the impact of this luminal defects.
Assuntos
Substituição da Valva Aórtica Transcateter , Equipamentos e Provisões , HumanosRESUMO
BACKGROUND: Enteroviridae such as coxsackievirus B3 (CVB3) are important infectious agents involved in viral heart disease, hepatitis, and pancreatitis, but no specific antiviral therapy is available. METHODS AND RESULTS: The aim of the present study was to evaluate the impact of RNA interference on viral replication, cytopathogenicity, and survival. Small interfering RNA (siRNA) molecules were designed against the viral 2A region (siRNA-2A), which is considered to be highly conserved and essential for both virus maturation and host cytopathogenicity. siRNA-2A exhibited a significant protective effect on cell viability mediated by marked inhibition of CVB3 gene expression and viral replication. In highly susceptible type I interferon receptor-knockout mice, siRNA-2A led to significant reduction of viral tissue titers, attenuated tissue damage, and prolonged survival. Repeated siRNA-2A transfection was associated with a further improvement of survival. Various control siRNA molecules had no protective effect in vitro or in vivo. CONCLUSIONS: RNA interference directed against the 2A protease encoding genomic region effectively confers intracellular immunity toward CVB3-mediated cell injury and improves survival, suggesting a potential role for RNA interference for future treatment options targeting enteroviral diseases.
Assuntos
Infecções por Coxsackievirus/tratamento farmacológico , Interferência de RNA , RNA Interferente Pequeno/farmacologia , Proteínas Virais/antagonistas & inibidores , Animais , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/genética , Sistemas de Liberação de Medicamentos , Enterovirus/enzimologia , Enterovirus/patogenicidade , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Receptores de Interferon/deficiência , Taxa de Sobrevida , Transfecção , Resultado do Tratamento , Proteínas Virais/genética , Virulência , Replicação Viral/efeitos dos fármacosAssuntos
Artérias Carótidas/cirurgia , Estenose das Carótidas/cirurgia , Stents/efeitos adversos , Acidente Vascular Cerebral/etiologia , Idoso , Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Oclusão Coronária/patologia , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/patologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Microtomografia por Raio-X/métodos , Autopsia , Oclusão Coronária/diagnóstico por imagem , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , StentsRESUMO
In-stent restenosis is a hyperproliferative disease which can be successfully treated by drug-eluting stents releasing compounds that exhibit cell-cycle inhibitory properties to inhibit coronary smooth muscle cell (CASMC) proliferation and migration, resembling the key pathomechanisms of in-stent restenosis. Cyclin-dependent kinases (CDK) are key regulators of the eukaryotic cell cycle. CDK activity may be blocked by novel compounds such as flavopiridol. Therefore, CDK inhibitors are attractive drugs to be used for the local prevention of in-stent restenosis. In this study, we demonstrate that flavopiridol leads to potent inhibition of CASMC proliferation and migration. Molecular effects on cell-cycle regulatory mechanisms and distribution were evaluated by post-transcriptional assessment of distinct cyclins and cyclin-dependent kinase inhibitor (CKI) levels and flow cytometry. Cellular necrosis and apoptosis was assessed in CASMC and coronary endothelial cells. Flavopiridol induced a potent antiproliferative effect by cell-cycle inhibition in G1 and G2/M and led to increased protein levels of CKIs p21cip1 and p27kip1 as well as p53 in CASMC. Hyperphosphorylation of retinoblastoma protein was abrogated and mitogen-mediated smooth muscle cell migration significantly reduced. No accelerated cytotoxicity or increased apoptosis was detectable. Flavopiridol-coated stents, implanted in rat carotid arteries, led to significant decrease of neointima formation. As proof of principle, our results demonstrate that stents eluting CDK inhibitors such as flavopiridol effectively inhibit neointima formation. Therefore, this new class of therapeutics may be suitable for further clinical investigations on drug-eluting stents to prevent in-stent restenosis.
Assuntos
Vasos Coronários/citologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Piperidinas/farmacologia , Stents , Animais , Apoptose/efeitos dos fármacos , Lesões das Artérias Carótidas/tratamento farmacológico , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/patologia , Cateterismo/efeitos adversos , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas/citologia , Células Cultivadas/efeitos dos fármacos , Ciclina A/biossíntese , Ciclina A/genética , Ciclina D , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/biossíntese , Ciclinas/genética , Implantes de Medicamento , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Flavonoides/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Genes p53/efeitos dos fármacos , Humanos , Modelos Animais , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Piperidinas/administração & dosagem , Ratos , Proteína Supressora de Tumor p53/biossíntese , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genética , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologiaRESUMO
AIMS: Transcatheter mitral valve repair has become a promising alternative treatment option for severe symptomatic mitral regurgitation in patients at high risk for open heart surgery with heart-lung bypass. METHODS AND RESULTS: We describe the first successful procedure of mitral clipping through a right lateral mini-thoracotomy via the right upper pulmonary vein in a patient with an agenesis of the inferior vena cava. The set-up of the MitraClip system on a separate table located at 70¡ on the right side of the patient and the fixation of the steerable sheath at the entry into the thorax with constant posterior pressure enabled clip implantation using the usual manoeuvres with marked reduction of the mitral insufficiency. CONCLUSIONS: The access through the right upper pulmonary vein using the usual right mini-thoracotomy enabled a successful mitral clipping even in the absence or occlusion of the inferior vena cava.
Assuntos
Anuloplastia da Valva Mitral/métodos , Insuficiência da Valva Mitral/cirurgia , Veias Pulmonares , Veia Cava Inferior/anormalidades , Idoso , Cateterismo Cardíaco/métodos , Humanos , Masculino , Toracotomia/métodosRESUMO
Innovative catheter systems with lower-profile sheaths and a dynamic expansion mechanism (DEM) were recently introduced for transcatheter aortic valve replacement (TAVR). However, the labeling of 14 F and 16 F eSheaths denote the inner nominal diameter. Exact changes of the clinically relevant outer diameters during usage are not available. eSheaths were measured every 30 mm using a digital caliper. Unused 14 F and 16 F eSheaths served as controls. Maximum eSheath diameters were measured after insertion of the Edwards Commander Delivery System (ECDS) into 14 F and 16 F eSheaths.Finally, eSheaths were retrieved and measured after TAVR. Outer diameters of control 14 F eSheaths were 5.8 mm and 6.50 mm for the 16 F eSheath. Introduction of the 23 mm and 26 mm ECDS into 14 F eSheaths showed a maximum diameter of 7.65 mm and 7.64 mm (P = NS). Introduction of the 29 mm ECDS into the 16 F eSheath showed the greatest diameter of 8.18 mm (P = 0.03). After TAVR, diameters of the 14 F eSheaths were 7.14 mm (23 mm valve) and 7.26 mm (26 mm valve) (P = NS), while 16 F eSheaths were 8.10 mm (29 mm valve) (P ≤ 0.03). Nominal 14 F and 16 F eSheaths showed a significant increase of the outer diameter during advancement of the ECDS and after TAVR implantation.