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1.
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
2.
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
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.

5.
Arterioscler Thromb Vasc Biol ; 41(7): 2201-2214, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34039022
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.
EuroIntervention ; 17(8): e688-e698, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33896763

RESUMO

BACKGROUND: In peripheral artery disease, two different types of calcification are frequently observed, i.e., medial and intimal calcification. AIMS: The aim of this study was to determine the ability of intravascular ultrasound (IVUS) imaging and optical frequency domain imaging (OFDI) to detect medial and intimal calcification in human peripheral arteries. METHODS: We performed ex vivo intravascular imaging of cadaveric human peripheral arteries with calcifications. IVUS and OFDI images were co-registered with histology. A total of 12 legs from nine patients were examined, and 438 cross-sectional images were co-registered with histology. RESULTS: OFDI could detect 183 of 231 intimal calcifications by histology, whereas IVUS could detect 194 (OFDI: sensitivity 79%, specificity 86%, area under the curve [AUC] 0.83; IVUS: sensitivity 84%, specificity 85%, AUC 0.85). Of 245 medial calcifications by histology, 160 and 164 were detected by OFDI and IVUS, respectively (OFDI: sensitivity 65%, specificity 85%, AUC 0.75; IVUS: sensitivity 67%, specificity 80%, AUC 0.74). Medial calcification with overlying intimal calcification (overlapped calcification) and an unclear border between intima and media were the main reasons for misdiagnosis. Without those 89 overlapped calcifications, sensitivity in both OFDI and IVUS was improved (OFDI: sensitivity 81%, specificity 85%, AUC 0.83; IVUS: sensitivity 88%, specificity 80%, AUC 0.84). CONCLUSIONS: There are limitations in detecting medial calcification in overlapped intimal calcification and with an unclear border between intima and media by both IVUS and OFDI. It is important to distinguish medial calcification from intimal calcification before proceeding with endovascular therapy since different approaches will be required.


Assuntos
Doença da Artéria Coronariana , Doença Arterial Periférica , Espessura Intima-Media Carotídea , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Tomografia de Coerência Óptica , Ultrassonografia de Intervenção
8.
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
9.
J Vasc Interv Radiol ; 32(6): 792-801.e5, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677117

RESUMO

PURPOSE: To compare the long-term vascular healing responses of healthy swine iliofemoral arteries treated with a polymer-free paclitaxel-eluting stent (Z-PES, Zilver PTX) or a fluoropolymer-based paclitaxel-eluting stent (FP-PES, Eluvia). MATERIALS AND METHODS: Bilateral iliofemoral arteries in 20 swine were treated with a Z-PES (n = 16) or a FP-PES (n = 24) and were examined histologically at 1, 3, 6, and 12 months. RESULTS: Morphometric analysis revealed larger external and internal elastic lamina, stent expansion, and lumen area in the FP-PES than in the Z-PES at all timepoints. Luminal narrowing was similar in the 2 groups at 1 month; however, greater stenosis was observed in the Z-PES group at 3 months, with significant regression thereafter, resulting in equivalent stenosis at 6 and 12 months. Greater drug effect and less complete vessel healing were found in the FP-PES group at all timepoints, including greater numbers of malapposed struts with excessive fibrin deposition at 1 and 3 months, than in the Z-PES group. Three of 12 FP-PESs from the 6- and 12-month cohorts also showed circumferential medial disruption with peri-strut inflammation, whereas no abnormal findings were observed in contralateral Z-PESs. CONCLUSIONS: Prolonged paclitaxel release with the presence of a permanent polymer may contribute to the differential vascular responses seen for the Z-PES and FP-PES groups, including medial layer disruption and aneurysmal vessel degeneration that was sometimes observed in the FP-PES group. These distinct features should be confirmed by pathology and in vivo imaging of human superficial femoral arteries to determine their clinical significance.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Stents Farmacológicos , Procedimentos Endovasculares/instrumentação , Artéria Femoral/efeitos dos fármacos , Paclitaxel/administração & dosagem , Polímeros , Animais , Fármacos Cardiovasculares/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/patologia , Neointima , Paclitaxel/efeitos adversos , Desenho de Prótese , Suínos , Porco Miniatura , Fatores de Tempo , Remodelação Vascular/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
10.
JACC Cardiovasc Interv ; 14(3): 304-315, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33541541

RESUMO

OBJECTIVES: The aim of this study was to understand the anatomy of periarterial nerve distribution in human accessory renal arteries (ARAs). BACKGROUND: Renal denervation is a promising technique for blood pressure control. Despite the high prevalence of ARAs, the anatomic distribution of periarterial nerves around ARAs remains unknown. METHODS: Kidneys with surrounding tissues were collected from human autopsy subjects, and histological evaluation was performed using morphometric software. An ARA was defined as an artery arising from the aorta above or below the dominant renal artery (DRA) or an artery that bifurcated within 20 mm of the takeoff of the DRA from the aorta. The DRA was defined as an artery that perfused >50% of the kidney. RESULTS: A total of 7,287 nerves from 14 ARAs and 9 DRAs were evaluated. The number of nerves was smaller in the ARA than DRA (median: 30 [interquartile range: 17.5 to 48.5] vs. 49 [interquartile range: 36 to 76]; p < 0.0001). In both ARAs and DRAs, the distance from the arterial lumen to nerve was shortest in the distal, followed by the middle and proximal segments. On the basis of the post-mortem angiography, ARAs were divided into large (≥3 mm diameter) and small (<3 mm) groups. The number of nerves was greatest in the DRA, followed by the large and small ARA groups (53 [41 to 97], 38 [25 to 53], and 24.5 [10.5 to 36.3], respectively; p = 0.001). CONCLUSIONS: ARAs showed a smaller number of nerves than DRAs, but these results were dependent on the size of the ARA. Ablation, especially in large ARAs, may allow more complete denervation with the potential to further reduce blood pressure.


Assuntos
Obstrução da Artéria Renal , Artéria Renal , Sistema Nervoso Simpático , Humanos , Rim , Simpatectomia , Resultado do Tratamento
11.
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
12.
Cardiovasc Revasc Med ; 24: 1-10, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32928693

RESUMO

AIMS: The advantage of biodegradable-polymer drug-eluting stents (BP-DES) versus durable-polymer (DP) DES remains uncertain. We compared neointimal formation and endothelial barrier function of new BP sirolimus-eluting stents (BP-SES, BuMA Supreme®) to other contemporary BP-DES, DP-DES, and bare metal stents (BMS). METHODS AND RESULTS: Light microscopic assessment in swine coronary arteries showed comparable neointimal formation between BP-SES and DP everolimus-eluting stent (DP-EES). The performance of BP-SES was compared with DP-EES (Xience Xpedition®), BP-EES (Synergy®), and BMS (Multi-Link Vision®) at 45- and 90-days in rabbit ilio-femoral arteries using Evans blue dye (EBD) followed by immunostaining for endothelial barrier proteins (p120/vascular endothelial-cadherin [VE-cad]) to evaluate endothelial barrier function and scanning electron microscopy (SEM) to determine strut tissue coverage. BMS followed by BP-SES and BP-EES exhibited smaller EBD positive areas versus that of DP-EES at 45- and 90-days. p120/VE-cad immunostaining and SEM-determined strut coverage was greater at 45- and 90-days for BMS followed by all DESs. Regardless of stent type, the lack of p120/VE-cad co-localization showed greater leukocyte and platelet aggregation. CONCLUSION: Three types of DES showed different endothelial healing pattern regardless their equivalent suppression of neointimal formation.

13.
EuroIntervention ; 17(3): 248-256, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32149708

RESUMO

BACKGROUND: The relative thrombogenicity and albumin adsorption and retention of different durable polymers used in coronary stents has not been tested. AIMS: This study sought to compare the thromboresistance and albumin binding capacity of different durable polymer drug-eluting stents (DES) using dedicated preclinical and in vitro models. METHODS: In an ex vivo swine arteriovenous shunt model, a fluoropolymer everolimus-eluting stent (FP-EES) (n=14) was compared with two durable polymer DES, the BioLinx polymer-coated zotarolimus-eluting stent (BL-ZES) (n=9) and a CarboSil elastomer polymer-coated ridaforolimus-eluting stent (EP-RES) (n=6), and bare metal stents (BMS) (n=10). Stents underwent immunostaining using a cocktail of antiplatelet antibodies and a marker for inflammation and were then evaluated by confocal microscopy (CM). Albumin retention was assessed using a flow loop model with labelled human serum albumin (FP-EES [n=8], BL-ZES [n=4], EP-RES [n=4], and BMS [n=7]), and scanned by CM. RESULTS: The area of platelet adherence (normalised to total stent surface area) was lower in the order FP-EES (9.8%), BL-ZES (32.7%), EP-RES (87.6%) and BMS (202.0%), and inflammatory cell density was least for FP-EES

Assuntos
Stents Farmacológicos , Intervenção Coronária Percutânea , Adsorção , Albuminas , Animais , Everolimo , Intervenção Coronária Percutânea/efeitos adversos , Polímeros , Desenho de Prótese , Stents , Suínos , Resultado do Tratamento
14.
Int J Cardiol ; 327: 52-57, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33242506

RESUMO

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) is a suitable strategy after stent implantation especially in patients at high risk for bleeding. The thromboresistant characteristics and the healing profile permanent polymer stents such as the Resolute Onyx- drug-eluting stent (DES) has never been tested against the current approved stents for short-term DAPT, the polymer free (PF) biolimus-eluting stent (PF-BES) and bare metal stents (BMS) in dedicated preclinical models. METHODS: An ex-vivo porcine arteriovenous shunt and in-vivo flow loop model were used to evaluate thromboresistance. The healing profile was assessed in the rabbit model at 28 days by confocal microscopy (CM), scanning electron microscopy (SEM) and histology. Onyx-DES was separately compared with Onyx-BMS in first experiment and PF-BES in second experiment. RESULTS: In an ex-vivo shunt model, CM and SEM showed significantly less platelet adhesion for Onyx-DES relative to Onyx-BMS and PF-BES. In a flow loop model using human blood, platelet adhesion was also significantly less in Onyx-DES as compared to PF-BES and Onyx-BMS. In the healing study, Onyx-BMS showed significantly greater healing profile relative to Onyx-DES as expected, whereas Onyx-DES showed equivalent endothelial coverage by SEM and significantly less Evan's blue uptake and comparable colocalization of p120 and vascular endothelial-cadherin when compared with PF-BES. CONCLUSIONS: Onyx-DES showed qualities of thomboresistance and healing which appear to be compatible with short-term DAPT. Thromboresistance was superior to PF-BES and healing was equivalent to PF-BES in this pre-clinical study. Onyx-DES might provide advantages when considering short-term DAPT especially in patients at high risk of bleeding.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Animais , Terapia Antiplaquetária Dupla , Humanos , Polímeros , Desenho de Prótese , Coelhos , Stents , Suínos , Resultado do Tratamento
15.
Atherosclerosis ; 306: 85-95, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32654790

RESUMO

Atherosclerotic lesion progression is associated with intimal calcification. The earliest lesion that shows calcification is pathologic intimal thickening in which calcifications appear as microcalcifications that vary in size from <0.5 to 15 µm. The calcifications become larger as plaques progress, becoming punctate (>15 µm to 1 mm in diameter), fragmented (>1 mm), and eventually sheet-like calcification (>3 mm). When stratified by plaque type, maximum calcifications are observed in fibrocalcific plaques, followed by healed plaque ruptures. Lesions of acute thrombi, i.e., plaque rupture and erosions, which are the most frequent causes of acute coronary syndromes, show much less calcification than stable fibrocalcific plaques. Conversely, a calcified nodule, the least common lesion of acute thrombosis, occurs in highly calcified lesions. Pro-inflammatory cytokines observed in unstable plaques may provoke an early phase of osteogenic differentiation of smooth muscle cells (SMCs), a release of calcifying extracellular matrix vesicles, and/or induce apoptosis of macrophages and SMCs, which also calcify. Recent pathologic and imaging based studies indicate that lesions with dense calcifications are more likely to be stable plaques (fibrocalcific plaques), while micro, punctate, or fragmented calcifications are associated with either early stage plaques or unstable lesions (plaque rupture or erosion). Clinical non-invasive computed tomography (CT) studies show that the greater the calcium score, the higher the likelihood of patients developing future acute coronary events. This appears contradictory with the findings from pathologic autopsy studies. However, CT analysis of calcium subtypes is limited by resolution and blooming artifacts. Thus, areas of heavy calcification may not be the cause of future events as pathologic studies suggest. Rather, calcium may be an overall marker for the extent of disease. These types of discrepancies can perhaps be resolved by invasive or non-invasive high resolution imaging studies carried out at intervals in patients who present with acute coronary syndromes versus stable angina patients. Coronary calcium burden is greater in stable plaques than unstable plaques and there is a negative correlation between necrotic core area and area of calcification. Recent clinical studies have demonstrated that statins can reduce plaque burden by demonstrating a reduction in percent and total atheroma volume. However, calcification volume increases. In summary, pathologic studies show that sheet calcification is highly prevalent in stable plaques, while microcalcifications, punctate, and fragmented calcifications are more frequent in unstable lesions. Both pathologic and detailed analysis of imaging studies in living patients can resolve some of the controversies in our understanding of coronary calcification.


Assuntos
Aterosclerose , Calcinose , Cálcio , Doença da Artéria Coronariana , Placa Aterosclerótica , Calcinose/diagnóstico por imagem , Cálcio/metabolismo , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Osteogênese
16.
Future Med Chem ; 12(12): 1181-1195, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32431177

RESUMO

Mammalian target of rapamycin (mTOR) inhibitors have been applied to vascular coronary devices to avoid neointimal growth and have become the predominant pharmacological agents used to prevent restenosis. mTOR inhibitors can affect not only proliferating vascular smooth muscle cells but also endothelial cells and therefore can result in delayed healing of the vessel including endothelialization. Emerging evidence suggests accelerated atherosclerosis due to the downstream negative effects on endothelial barrier functional recovery. The development of neoatherosclerosis within the neointima of drug-eluting stents can result in late thrombotic events. This type of problematic healing response may open the way for specific mTOR kinase inhibitors, such as ATP-competitive mTOR inhibitors. These inhibitors demonstrate a better healing profile than traditional limus-based drug-eluting stent and their clinical efficacy remains unknown.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Aterosclerose/tratamento farmacológico , Humanos , Inibidores de Proteínas Quinases/química , Serina-Treonina Quinases TOR/metabolismo
17.
Circ Cardiovasc Interv ; 13(5): e008869, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32338525

RESUMO

BACKGROUND: Struts have been considered as covered when tissue overlying the struts is >0 µm by optical coherence tomography (OCT). However, there is no confirmatory study to validate this definition by histology which is the gold standard. The aim of the present study was to assess the appropriate cutoff value of neointimal thickness of stent strut coverage by OCT with histology confirmation. METHODS: We performed ex vivo OCT imaging of human coronary arteries with stents at autopsy. A total of 46 stents in 39 vessels from 25 patients were examined in this study, and a total of 165 cross-sectional images were co-registered with histology to determine the optimal cutoff value for strut coverage by OCT which was defined as luminal endothelial cells with 2 abluminal layers of smooth muscles cells and matrix. Considering the resolution of OCT is 10 to 20 µm, the cutoff values were assessed at ≥20, ≥40, and ≥60 µm. RESULTS: A total of 2235 struts were reviewed by histology, 1216 were considered as well-matched struts which were analyzed in this study. By histology, 160 struts were identified as uncovered, while 1056 struts were covered. The OCT assessment without consideration of neointimal thickness yielded a poor specificity of 37.5% and sensitivity 100%. Of 3 cutoff values, the cutoff value of ≥40 µm yielded the best sensitivity (99.3%), specificity (91.0%), positive predictive value (98.6%), and negative predictive value (95.6%) as compared with ≥20 and ≥60 µm. CONCLUSIONS: Neointimal thickness ≥40 µm by OCT yielded the most accurate cutoff value to identify stent strut coverage validated by histology.


Assuntos
Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Intervenção Coronária Percutânea/instrumentação , Stents , Tomografia de Coerência Óptica , Idoso , Autopsia , Vasos Coronários/patologia , Células Endoteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neointima , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Reepitelização , Sistema de Registros , Resultado do Tratamento
18.
Front Immunol ; 11: 397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292401

RESUMO

The Triggering Receptor Expressed on Myeloid cells-like 4 (TREML4) is a member of the TREM receptor family, known modulators of inflammatory responses. We have previously found that TREML4 expression positively correlates with human coronary arterial calcification (CAC). However, the role of TREML4 in the pathogenesis of cardiovascular disease remains incompletely defined. Since macrophages play a key role in inflammatory conditions, we investigated if activated macrophages selectively expressed TREML4 and found that carriage of either one of the eQTL SNP's previously associated with increased TREML4 expression conferred higher expression in human inflammatory macrophages (M1) compared to alternatively activated macrophages (M2). Furthermore, we found that TREML4 expression in human M1 dysregulated several inflammatory pathways related to leukocyte activation, apoptosis and extracellular matrix degradation. Similarly, murine M1 expressed substantial levels of Treml4, as did oxLDL treated macrophages. Transcriptome analysis confirmed that murine Treml4 controls the expression of genes related to inflammation and lipid regulation pathways, suggesting a possible role in atherosclerosis. Analysis of Apoe-/-/Treml4-/- mice showed reduced plaque burden and lesion complexity as indicated by decreased stage scores, macrophage content and collagen deposition. Finally, transcriptome analysis of oxLDL-loaded murine macrophages showed that Treml4 represses a specific set of genes related to carbohydrate, ion and amino acid membrane transport. Metabolomic analysis confirmed that Treml4 deficiency may promote a beneficial relationship between iron homeostasis and glucose metabolism. Together, our results suggest that Treml4 plays a role in the development of cardiovascular disease, as indicated by Treml4-dependent dysregulation of macrophage inflammatory pathways, macrophage metabolism and promotion of vulnerability features in advanced lesions.


Assuntos
Aterosclerose/patologia , Doenças Cardiovasculares/patologia , Macrófagos/metabolismo , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Animais , Apolipoproteínas E/deficiência , Aterosclerose/imunologia , Aterosclerose/metabolismo , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/metabolismo , Regulação da Expressão Gênica/imunologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Macrófagos/imunologia
19.
EuroIntervention ; 16(5): 395-403, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32310132

RESUMO

AIMS: The aim of this study was to determine the ability of optical frequency domain imaging (OFDI)/optical coherence tomography (OCT) imaging systems to visualise the presence of cholesterol crystals (CCR) in human atherosclerotic coronary arteries. METHODS AND RESULTS: We performed ex vivo imaging of human coronary arteries by OFDI/OCT. A total of 559 cross-sectional images from 45 autopsy cases were co-registered with histology; 117 histologic sections showed presence of necrotic core with cholesterol clefts (CC). We modified a previously used OFDI/OCT definition for identification of CCRs which we now define as a linear and discrete high-intensity signal (bright area) within the plaque with sharp borders between it and adjacent low-/intermediate-intensity tissue. Additionally, the high-intensity signal is not a spot but a well-defined area distinguishing it from macrophages which lack sharp borders. OFDI/OCT imaging identified the presence of CCR in 30 of the 117 histologic sections. The sensitivity and specificity of OFDI/OCT for detection of CCR was 25.6% and 100.0%, respectively. By multivariate analysis, significant predictors to visualise CCR by OCT/OFDI were 1) an overlying fibrous plaque, and 2) the presence of stacked CC, defined as CC arranged one on top of another with >3 layers of CC. The prevalence of complicated plaques (i.e., plaque haemorrhage and late necrotic core) was significantly higher in detectable CCR by OFDI/OCT as compared to undetectable CCR. CONCLUSIONS: The presence of stacked CCs is required to detect CCR by OFDI/OCT. Detection of CCR by OCT/OFDI may help us to identify the late stages of atherosclerotic coronary plaque progression and improve risk stratification.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Colesterol , Vasos Coronários/diagnóstico por imagem , Estudos Transversais , Humanos , Tomografia de Coerência Óptica
20.
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
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