Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Cancer Res ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642183

RESUMO

The relationship between cancer and autoimmunity is complex. However, the incidence of solid tumors such as melanoma has increased significantly among patients with previous or newly diagnosed systemic autoimmune disease (AID). At the same time, immune checkpoint blockade (ICB) therapy of cancer induces de novo autoinflammation and exacerbates underlying AID, even without evident anti-tumor responses. Recently, systemic lupus erythematosus (SLE) activity was found to drive myeloid-derived suppressor cell (MDSC) formation in patients, a known barrier to healthy immune surveillance and successful cancer immunotherapy. Crosstalk between MDSCs and macrophages generally drives immune suppressive activity in the tumor microenvironment. However, it remains unclear how peripheral pre-generated MDSC under chronic inflammatory conditions modulates global macrophage immune functions and the impact it could have on existing tumors and underlying lupus nephritis. Here we show that pathogenic expansion of SLE-generated MDSCs by melanoma drives global macrophage polarization and simultaneously impacts the severity of lupus nephritis and tumor progression in SLE-prone mice. Molecular and functional data showed that MDSCs interact with autoimmune macrophages and inhibit cell surface expression of CD40 and the production of IL-27. Moreover, low CD40/IL-27 signaling in tumors correlated with high TAM infiltration and ICB therapy resistance both in murine and human melanoma exhibiting active IFNγ signatures. These results suggest that preventing global macrophage reprogramming induced by MDSC-mediated inhibition of CD40/IL-27 signaling provides a precision melanoma immunotherapy strategy, supporting an original and advantageous approach to treat solid tumors within established autoimmune landscapes.

2.
Expert Rev Cardiovasc Ther ; 19(8): 725-737, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34263701

RESUMO

INTRODUCTION: Cerebrovascular events are one of the most serious consequences after transcatheter aortic valve replacement (TAVR). More than half of the cerebrovascular events following TAVR are due to procedure-related emboli. Embolic protection devices (EPDs) have the potential to decrease cerebrovascular events during TAVR procedure. However, randomized controlled trials (RCTs) have not conclusively determined if EPDs are effective, likely because of small number of patients enrolled. However, meta-analyses and propensity-matched analyses from large registries have shown efficacy and suggest the importance of EPDs in prevention of stroke during TAVR and perhaps other structural heart procedures. AREAS COVERED: This review will focus on clinical and histopathologic studies examining the efficacy, safety, and histopathologic device capture findings in the presence and absence of EPDs during TAVR procedures. EXPERT OPINION: Clinical studies have not conclusively determined the efficacy of EPDs. Current ongoing large-scale RCT (PROTECTED TAVR [NCT04149535]) has the potential to prove their efficacy. Histopathological evaluation of debris captured by EPDs contributes to our understanding of the mechanisms of TAVR procedure-related embolic events and suggests the importance of preventing cerebral embolization of debris released during this and other structural heart procedures.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Desenho de Prótese , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
3.
JAMA Cardiol ; 6(9): 1013-1022, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34076677

RESUMO

Importance: Unexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined. Objective: To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. Design, Setting, and Participants: This genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. Main Outcomes and Measures: The frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. Results: The median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. Conclusions and Relevance: In this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

4.
Int J Cardiol ; 338: 42-49, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174338

RESUMO

BACKGROUND: Recent clinical studies have suggested the feasibility of 1-month dual antiplatelet therapy (DAPT) for patients receiving drug-eluting stent (DES). Although our previous ex-vivo swine arteriovenous (AV) shunt studies under low dose heparin treatment suggested superior thromboresistance of fluoropolymer-coated everolimus-eluting stent (FP-EES) when compared to other polymer-based DESs, the relative thromboresistance of different DESs under single antiplatelet therapy (SAPT) has never been examined. This study aimed to evaluate platelet adhesion under SAPT in competitive DESs in the in vitro flow loop model and ex vivo swine AV shunt model. METHODS: The thrombogenicity of FP-EES, BioLinx polymer zotarolimus-eluting stent (BL-ZES), and biodegradable polymer everolimus-eluting stent (BP-EES) was assessed acutely using the swine AV shunt model under aspirin or clopidogrel SAPT. Stents were immunostained using antibodies against platelets and inflammatory markers and evaluated by confocal microscopy. Also, the adhesion of platelet and albumin on the three DESs was assessed by an in-vitro flow loop model using human platelets under aspirin SAPT and fluorescent albumin, respectively. RESULTS: In the shunt model, FP-EES showed significantly less platelet and inflammatory cell adhesion than BL-ZES and BP-EES. In the flow loop model, FP-EES showed significantly less platelet coverage and more albumin adsorption than BL-ZES and BP-EES. CONCLUSIONS: These results suggest FP-EES may have particular advantage for short-term DAPT compared to other DESs.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Implantes Absorvíveis , Animais , Stents Farmacológicos/efeitos adversos , Everolimo , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária , Desenho de Prótese , Stents , Suínos , Resultado do Tratamento
6.
Future Cardiol ; 17(6): 931-944, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33876697

RESUMO

Catheter-based renal denervation is a novel treatment approach for patients with hypertension and initial unblinded trials have shown promising results. The Paradise™ Ultrasound Renal Denervation System (ReCor Medical, CA, USA) is an ultrasound-based catheter with a distal balloon that acts as a coolant to protect the renal arterial wall. This device received CE-mark in 2012. Randomized, sham-controlled trials and postmarket studies have shown promising efficacy and safety results. Currently, three additional ongoing randomized, sham-controlled trials are underway in the USA, Europe, Japan and Korea, and the results will be pivotal in device approval in some of these countries. These studies with larger numbers of patients and longer duration of follow-up are needed to further confirm the safety and efficacy of this device.

7.
J Am Coll Cardiol ; 77(13): 1599-1611, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33795033

RESUMO

BACKGROUND: Calcified nodule (CN) has a unique plaque morphology, in which an area of nodular calcification causes disruption of the fibrous cap with overlying luminal thrombus. CN is reported to be the least frequent cause of acute coronary thrombosis, and the pathogenesis of CN has not been well studied. OBJECTIVES: The purpose of this study is to provide a comprehensive morphologic assessment of the CN in addition to providing an evolutionary perspective as to how CN causes acute coronary thrombosis in patients with acute coronary syndromes. METHODS: A total of 26 consecutive CN lesions from 25 subjects from our autopsy registry were evaluated. Detailed morphometric analysis was performed to understand the plaque characteristics of CN and nodular calcification. RESULTS: The mean age was 70 years, with a high prevalence of diabetes and chronic kidney disease. CNs were equally distributed between men and women, with 61.5% of CNs found in the right coronary artery (n = 16), mainly within its mid-portion (56%). All CNs demonstrated surface nonocclusive luminal thrombus, consisting of multiple nodular fragments of calcification, protruding and disrupting the overlying fibrous cap, with evidence of endothelial cell loss. The degree of circumferential sheet calcification was significantly less in the culprit section (89° [interquartile range: 54° to 177°]) than in the adjacent proximal (206° [interquartile range: 157° to 269°], p = 0.0034) and distal (240° [interquartile range: 178° to 333°], p = 0.0004) sections. Polarized picrosirius red staining showed the presence of necrotic core calcium at culprit sites of CNs, whereas collagen calcium was more prevalent at the proximal and distal regions of CNs. CONCLUSIONS: Our study suggests that fibrous cap disruption in CN with overlying thrombosis is initiated through the fragmentation of necrotic core calcifications, which is flanked-proximally and distally-by hard, collagen-rich calcification in coronary arteries, which are susceptible to mechanical stress.


Assuntos
Síndrome Coronariana Aguda/complicações , Trombose Coronária/etiologia , Vasos Coronários/patologia , Morte Súbita Cardíaca/etiologia , Calcificação Vascular/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Trombose Coronária/patologia , Vasos Coronários/diagnóstico por imagem , Morte Súbita Cardíaca/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia , Microtomografia por Raio-X
8.
Expert Rev Cardiovasc Ther ; 19(9): 801-816, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33470872

RESUMO

Introduction: In-stent restenosis (ISR) has been one of the biggest limitations to the success of percutaneous coronary intervention for the treatment of coronary artery disease (CAD). The introduction of drug-eluting stent (DES) was a revolution in the treatment of CAD because these devices drastically reduced ISR to very low levels (<5%). Subsequently, newer generation DES treatments have overcome the drawbacks of first-generation DES, i.e. delayed endothelialization, and late stent thrombosis. However, the issue of late ISR, including neoatherosclerosis after DES implantation especially in high-risk patients and complex lesions, still exists as a challenge to be overcome.Areas covered: We discuss the mechanisms of ISR development including neoatherosclerosis, past and current clinical status of ISR, and methods to predict and overcome this issue from pathological and clinical points of view.Expert opinion: The initial drawbacks of first-generation DES, such as delayed endothelial healing and subsequent risk of late stent thrombosis, have been improved upon by the current generation DES. To achieve better long-term clinical outcomes, further titration of drug-release and polymer degradation profile, strut thickness as well as material innovation are needed.


Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Angiografia Coronária , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Stents , Resultado do Tratamento
9.
Expert Rev Med Devices ; 17(3): 189-200, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32101062

RESUMO

Introduction: Coronary bifurcation lesions are involved in up to 20% of all percutaneous coronary interventions (PCI). However, bifurcation lesion intervention is associated with a high complication rate, and optimal treatment of coronary bifurcation is an ongoing debate.Areas covered: Both different stenting techniques and a variety of devices have been suggested for bifurcation treatment, including the use of conventional coronary stents, bioresorbable vascular scaffolds (BVS), drug-eluting balloons (DEB), and stents dedicated to bifurcations. This review will summarize different therapeutic approaches with their advantages and shortcomings, with special emphasis on histopathologic and physiologic effects of each treatment strategy.Expert opinion: Histopathology and clinical data have shown that a more simple treatment strategy is beneficial in bifurcation lesions, achieving superior results. Bifurcation interventions through balloon angioplasty or placement of stents can importantly alter the bifurcation's geometry and accordingly modify local flow conditions. Computational fluid dynamics (CFD) studies have shown that the outcome of bifurcation interventions is governed by local hemodynamic shear conditions. Minimizing detrimental flow conditions as much as possible should be the ultimate strategy to achieve long-term success of bifurcation interventions.


Assuntos
Stents/tendências , Aterosclerose/terapia , Humanos , Tecidos Suporte/química , Resultado do Tratamento
10.
JACC Cardiovasc Interv ; 13(4): 418-427, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32081234

RESUMO

OBJECTIVES: The objective of this study was to comprehensively evaluate the pathology of acute and chronic femoral stenting in symptomatic atherosclerotic patients and to understand the causes of stent failure (SF) using multimodality imaging including micro-computed tomography. BACKGROUND: Although the pathology of coronary stenting has been well studied, the pathology of lower extremity femoral stenting remains poorly understood. METHODS: Twelve stented femoral lesions removed at surgery (n = 10) and at autopsy (n = 2) were obtained from 10 patients (median age 74 years; interquartile range [IQR]: 66 to 82 years) with histories of peripheral artery disease (critical limb ischemia in 7) (7 men and 3 women). All specimens underwent radiography, micro-computed tomography, and histological assessment. RESULTS: The median duration of implantation was 150 days (IQR: 30 to 365 days), the median stent diameter was 5.90 mm (IQR: 5.44 to 7.16 mm), and the median stent length was 39.5 mm (IQR: 27 to 107.5 mm). Of the 12 stented lesions, 2 had drug-eluting stents, and 10 had bare-metal stents. SF was observed in 8 of 12 lesions. The major cause of SF was acute thrombosis (6 of 8), but causes varied (delayed healing, stent underexpansion, false lumen stenting, and fracture), and 2 had restenosis. Stent fractures were observed in 3 cases by micro-computed tomography. Both drug-eluting stents, implanted for >1 year, showed delayed healing with circumferential peristrut fibrin deposition and SF. CONCLUSIONS: This histological study is the first to examine the pathological cause of SF. Stent thrombosis was the major cause of SF. Delayed healing was a common feature of bare-metal stents implanted for <90 days, while all drug-eluting stents, despite implantation duration >1 year, showed delayed healing.


Assuntos
Procedimentos Endovasculares/instrumentação , Artéria Femoral , Isquemia/terapia , Imagem Multimodal , Doença Arterial Periférica/terapia , Falha de Prótese , Stents , Calcificação Vascular/terapia , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo , Procedimentos Endovasculares/efeitos adversos , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/patologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/patologia , Valor Preditivo dos Testes , Trombose/diagnóstico por imagem , Trombose/patologia , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/patologia , Cicatrização , Microtomografia por Raio-X
11.
Eur Heart J ; 41(6): 786-796, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31803916

RESUMO

AIMS: Vascular calcification is routinely encountered in percutaneous coronary intervention (PCI) and severe coronary calcification is a known predictor of in-stent restenosis and stent thrombosis. However, the histopathologic mechanisms behind such events have not been systematically described. METHODS AND RESULTS: From our registry of 1211 stents, a total of 134 newer-generation drug-eluting stents (DES) (Xience, Resolute-Integrity, PROMUS-Element, and Synergy) with duration of implant ≥30 days were histologically analysed. The extent of calcification of the stented lesions was evaluated radiographically and divided into severe (SC, n = 46) and non-severely calcified lesions (NC, n = 88). The percent-uncovered struts per section {SC vs. NC; median 2.4 [interquartile range (IQR) 0.0-19.0] % vs. 0.0 (IQR 0.0-4.6) %, P = 0.02} and the presence of severe medial tears (MTs) (59% vs. 44%, respectively, P = 0.03) were greater in SC than NC. In addition, SC had a higher prevalence of ≥3 consecutive struts lying directly in contact with surface calcified area (3SC) (52% vs. 8%, respectively, P < 0.0001). Multivariate analysis demonstrated that sections with duration of implantation ≤6 months [odds ratio (OR): 7.7, P < 0.0001], 3SC (OR: 6.5, P < 0.0001), strut malapposition (OR: 5.0, P < 0.0001), and lack of MTs (OR: 2.5, P = 0.0005) were independent predictors of uncovered struts. Prevalence of neoatherosclerosis was significantly lower in SC than that of NC (24% vs. 44%, P = 0.02). CONCLUSION: Severe calcification, especially surface calcified area is an independent predictor of uncovered struts and delayed healing after newer-generation DES implantation. These data expand of knowledge of the vascular responses of stenting of calcified arteries and suggests further understand of how best to deal with calcification in patients undergoing PCI.


Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Calcificação Vascular , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos/efeitos adversos , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Tomografia de Coerência Óptica , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem
12.
Nat Rev Cardiol ; 17(1): 37-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31346257

RESUMO

Implantation of drug-eluting stents (DES) is the dominant treatment strategy for patients with symptomatic coronary artery disease. However, the first-generation DES had substantial drawbacks, including delayed healing, local hypersensitivity reactions and neoatherosclerosis, which all led to a steady increase in major adverse cardiovascular events over time. Subsequently, newer-generation DES were introduced with thinner struts, different scaffold designs (to improve deliverability while maintaining radial strength), different durable and biodegradable polymers - and in some cases no polymer (to improve vascular biocompatibility) - and new antiproliferative drug types and doses. Currently, >30 different DES are commercially available in Europe, with fewer available in the USA but with many new entrants coming onto the US market in the next few years. Never before have cardiologists been faced with so many choices of stent, each with its own unique design. In this Review, we detail preclinical and pathology studies for each stent design, examining thromboresistance, speed of neointimal coverage and completeness of healing, including endothelialization. We conclude by discussing how these design characteristics might affect the potential for shortening the minimum duration of dual antiplatelet therapy needed after coronary intervention.


Assuntos
Doença da Artéria Coronariana/terapia , Vasos Coronários/patologia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Cicatrização , Animais , Proliferação de Células , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Vasos Coronários/diagnóstico por imagem , Humanos , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Desenho de Prótese , Fatores de Risco , Resultado do Tratamento
13.
J Vasc Surg Venous Lymphat Disord ; 8(2): 280-284, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31281102

RESUMO

VenaSeal (Medtronic, Minneapolis, Minn) is a cyanoacrylate polymer adhesive for the treatment of patients with chronic venous insufficiency. As an implanted device, questions remain about how long cyanoacrylate persists after closure. In this report, a 65-year-old man was examined 5.5 years after cyanoacrylate closure, and a segment of great saphenous vein was excised for histopathologic analysis. Findings were typical of a foreign body reaction. The vessel was occluded with collagenized mature fibrous tissue and polymer remnants, which were encapsulated by multinucleated giant cells. Focal areas of granulomatous inflammation were present in the vein wall extending to the adventitia.


Assuntos
Cianoacrilatos/administração & dosagem , Embolização Terapêutica , Reação a Corpo Estranho/patologia , Veia Safena/patologia , Varizes/terapia , Insuficiência Venosa/terapia , Idoso , Doença Crônica , Cianoacrilatos/efeitos adversos , Embolização Terapêutica/efeitos adversos , Reação a Corpo Estranho/etiologia , Humanos , Masculino , Veia Safena/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/patologia , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/patologia
16.
J Vasc Interv Radiol ; 30(1): 103-109, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30527654

RESUMO

PURPOSE: To investigate morphometric characteristics and differences in particulate embolization between 3 drug-coated balloons (DCBs). MATERIALS AND METHODS: Effects of 3 overlapping DCBs (IN.PACT, Ranger, and Stellarex) were assessed in 24 femoral arteries of 12 swine with 28-day follow-up. Histologic analysis of treated arterial wall site and downstream skeletal muscle and coronary band changes were assessed for evidence of emboli. Paclitaxel concentration for downstream skeletal muscle and coronary band and vessel diameters with downstream changes were also measured. RESULTS: Signs of drug effect, such as medial smooth muscle cell (SMC) loss in depth and circumference, were not significantly different for all 3 DCBs (IN.PACT vs Ranger vs Stellarex: SMC loss depth, 2.8 [interquartile range [IQR]: 2.1-3.6] vs 3.2 [IQR: 2.3-3.8] vs 3.5 [IQR: 2.6-3.8], P = .7; SMC loss circumference, 1.0 [IQR: 1.0-1.0] vs 1.3 [IQR: 1.0-1.8] vs 1.0 [IQR: 1.0-1.2], P = .08). Percentage of sections with vascular changes in downstream nontarget tissues from arteries was similar in all 3 DCBs (42.9% vs 25.0% vs 28.6%, P = .2). Downstream levels of paclitaxel concentration in skeletal muscle were significantly higher for IN.PACT (216.5 ng/g vs 91.5 ng/g vs 101.9 ng/g, P = .01). Median vessel diameters with evidence of downstream changes were smallest for IN.PACT compared with Ranger and Stellarex (57 µm vs 74 µm vs 64 µm). CONCLUSIONS: All 3 DCBs exhibited no significant difference in local target site drug effect based on histologic analysis. Downstream effects of paclitaxel and/or downstream emboli were highest for IN.PACT compared with Ranger and Stellarex, whereas vessel diameters with evidence of downstream changes were smaller for IN.PACT vs Ranger and Stellarex.


Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Vasos Coronários/efeitos dos fármacos , Artéria Femoral/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Paclitaxel/administração & dosagem , Dispositivos de Acesso Vascular , Angioplastia com Balão/efeitos adversos , Animais , Vasos Coronários/patologia , Desenho de Equipamento , Artéria Femoral/patologia , Modelos Animais , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Sus scrofa , Fatores de Tempo
17.
JACC Cardiovasc Imaging ; 12(8 Pt 1): 1501-1513, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30553660

RESUMO

OBJECTIVES: The aim of this study was to comprehensively evaluate the pathology of the lower extremity arteries across their entire length in subjects dying with abundant risk factors and to evaluate the clinical and imaging implications of the pathological characteristics. BACKGROUND: Lower extremity peripheral arterial disease is a major cause of cardiovascular morbidity, but a systematic characterization of the pathology has never been undertaken. METHODS: Twelve legs were obtained from 8 cadavers with histories of coronary risk factors (median age 82 years, 6 men); 8 of 12 legs were evaluated using computed tomography before the major peripheral arteries were dissected along their entire length. Dissected arteries were cut serially at 3 to 4 mm, and a total of 2,987 sections were examined. RESULTS: Luminal irregularities and stenosis were more commonly seen in computed tomography images of above-the-knee (AK) arteries. Atherosclerotic lesions were histologically confirmed and were more common in AK (95.7%) than below-the-knee (BK) (56.8%) arteries. Occluded vessels were observed at 18 sites, including 8 AK and 10 BK arteries. Pathologically, acute thrombus was observed in all 8 AK sites, of which 3 were associated with plaque rupture and 5 were related to calcified nodules. The 10 occluded BK arteries revealed chronic total occlusions, of which one-half were embolic in origin and one-half were associated with atherosclerotic lesions. Intimal (75.3%) and medial (86.2%) calcifications were commonly encountered. Proportionate to the neointimal atherosclerosis, intimal calcification was more severe in AK arteries; the severity of medial calcification was no different between AK and BK arteries. Calcification was significantly greater in arteries excised from subjects with compared with those without diabetes. CONCLUSIONS: Atherosclerosis occurs more commonly in AK arteries and luminal occlusion from acute thrombosis secondary to rupture or calcified nodules. BK occlusion was chronic in nature, and at least one-half of lesions were embolic in origin. Medial calcification was similarly common in AK and BK arteries but more prevalent in subjects with diabetes.


Assuntos
Artérias/patologia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/patologia , Trombose/patologia , Calcificação Vascular/patologia , Idoso , Idoso de 80 Anos ou mais , Artérias/diagnóstico por imagem , Cadáver , Angiografia por Tomografia Computadorizada , Dissecação , Feminino , Humanos , Masculino , Neointima , Doença Arterial Periférica/diagnóstico por imagem , Valor Preditivo dos Testes , Fatores de Risco , Trombose/diagnóstico por imagem , Calcificação Vascular/diagnóstico por imagem
18.
JACC Cardiovasc Interv ; 11(13): 1262-1273, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29976363

RESUMO

OBJECTIVES: This study investigated differences between transcatheter heart valve (THV) types and regarding debris captured by a cerebral embolic protection system (Claret Medical Sentinel, Santa Rosa, California). BACKGROUND: Differences of THV types and cerebral injury after transcatheter aortic valve replacement (TAVR) are not well understood. METHODS: A total of 246 patients pooled from 2 prospective studies (SENTINEL [Cerebral Protection in Transcatheter Aortic Valve Replacement] trial, N = 100; SENTINEL-H [Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement] trial, N = 146) were included in the analysis. Histopathologic assessment and histomorphometric analyses of debris were compared with THV types. Analyses were differentiated by particle size (≥150, ≥500, and ≥1,000 µm), particle count, total particle area, and maximum of largest dimension. Only commercially available THVs were included: 16% Evolut R (EvR), 15% Lotus, 59% SAPIEN 3 (S3), and 10% SAPIEN XT (XT). RESULTS: Particles were captured in 99% of patients. There was a significantly higher amount of debris related to the vascular bed (valve tissue, arterial wall, calcification) in EvR patients compared with S3 patients; 53% of all patients irrespective of valve type had at least 1 particle ≥1 mm. Larger particles (≥500 and ≥1,000 µm) were significantly more frequent in EvR than XT and S3 patients. Lotus patients with particles ≥1,000 µm were significantly more frequent than in S3 patients. Particle count, total particle area, and maximum of largest dimension were significantly higher in both Lotus and EvR patients compared with S3 and XT. CONCLUSIONS: Debris was captured in 99% of patients, of whom 53% had at least 1 particle of debris >1 mm. The number and size of particles captured during a procedure in which EvR or Lotus THV was used were higher and larger than with a Sapien THV. Regardless, embolic debris, including large particles, is universal across valve types and provides mechanistic support for the potential benefit of using cerebral embolic protection in all TAVR procedures.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Dispositivos de Proteção Embólica , Próteses Valvulares Cardíacas , Embolia Intracraniana/prevenção & controle , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Embolia Intracraniana/etiologia , Embolia Intracraniana/patologia , Masculino , Estudos Multicêntricos como Assunto , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
19.
J Am Heart Assoc ; 7(13)2018 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-29960991

RESUMO

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with the risk of cerebral embolism. The origin of periprocedural brain embolism in the setting of VT ablation is often unknown and strategies to avoid it are sparse. The aim of this study was to assess the safety and feasibility of an endovascular 2-filter-based cerebral protection system (CPS) in left ventricular VT ablation procedures in patients with ischemic heart disease. Furthermore, histopathological correlates of periprocedural embolization were investigated. METHODS AND RESULTS: In this pilot study, 11 patients with ischemic heart disease and sustained VT underwent left ventricular catheter ablation under CPS surveillance. The placement of the CPS was conducted before the ablation procedure via the right radial artery. The VT ablation procedure was performed via a combined transaortic and transseptal approach. All VTs were successfully ablated. Placement and retrieval of the CPS was successful and safe in all cases. No periprocedural complications related to the CPS were observed and no periprocedural transient ischemic attack or stroke occurred. Debris captured by the CPS was detected in all patients. Histology revealed that acute thrombus was the most common type of debris (91%), followed by arterial wall tissue (73%) and foreign material (55%). Less frequently found were myocardium (27%), calcification (9%), necrotic core (9%), and valve tissue (9%). CONCLUSIONS: Cerebral protection during VT ablation seems to be safe and feasible. Ablation procedures of VT are associated with embolization of embolic debris, which was found in every patient.


Assuntos
Ablação por Cateter/instrumentação , Dispositivos de Proteção Embólica , Embolia Intracraniana/prevenção & controle , Isquemia Miocárdica/complicações , Acidente Vascular Cerebral/prevenção & controle , Taquicardia Ventricular/cirurgia , Idoso , Ablação por Cateter/efeitos adversos , Circulação Cerebrovascular , Estudos de Viabilidade , Feminino , Humanos , Embolia Intracraniana/etiologia , Embolia Intracraniana/fisiopatologia , Masculino , Isquemia Miocárdica/fisiopatologia , Projetos Piloto , Desenho de Prótese , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Taquicardia Ventricular/complicações , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
20.
Cardiovasc Pathol ; 36: 15-19, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30005391

RESUMO

Generalized arterial calcification of infancy (GACI), or idiopathic infantile arterial calcification, is a rare autosomal-recessive disease recognized aAs an inherited disorder characterized by severe pathologic calcification of large- and medium-sized arteries accompanied by smooth muscle cell (SMC) hyperplasia leading to vascular obstruction [1]. The prognosis is extremely poor, with 85% of affected infants dying within the first 6 months of life. Loss-of-function mutations in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene is recognized as the main defect associated with GACI [1]. The underlying pathogenesis of osteogenic transition leading to calcification and severe stenosis in GACI, however, is poorly understood. Herein, we present a case of a GACI patient with cardiac complications who exhibited extensive vascular disease at autopsy.


Assuntos
Vasos Coronários/patologia , Calcificação Vascular/patologia , Autopsia , Biópsia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Evolução Fatal , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Músculo Liso Vascular/patologia , Mutação , Miocárdio/patologia , Neointima , Fenótipo , Diester Fosfórico Hidrolases/genética , Pirofosfatases/genética , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/enzimologia , Calcificação Vascular/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...