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1.
Future Cardiol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34521223

RESUMO

Major advances have been made in coronary artery stent technology over the last decades. Drug-eluting stents reduced in-stent restenosis and have shown better outcomes compared with bare metal stents, yet some limitations still exist to their use. Because they delay healing of the vessel wall, longer dual antiplatelet therapy is mandatory to mitigate against stent thrombosis and this limitation is most concerning in subjects at high risk for bleeding. The COBRA PzF nanocoated coronary stent has been associated with accelerated endothelialization relative to drug-eluting stents, reduced inflammation and thromboresistance in preclinical studies, suggesting more flexible dual antiplatelet therapy requirement with potential benefits especially in those at high bleeding risk. Here, we discuss the significance of COBRA PzF in light of recent experimental and clinical studies.

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
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
5.
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.

6.
Arterioscler Thromb Vasc Biol ; 41(7): 2201-2214, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34039022
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.
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
9.
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.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33863660

RESUMO

BACKGROUND: Cytokine storm-related hypercoagulation may be important in the pathogenesis of stent thrombosis in patients with SARS-CoV-2. Whether stent polymers behave differently under such conditions has never been explored. METHODS: Fluorinated polymer-nanocoated and uncoated COBRA stents (CeloNova), BioLinx-polymer-coated Resolute Onyx stents (Medtronic), and Synergy stents (Boston Scientific), which are abluminally coated with a bioabsorbable polymer, were exposed to human blood from healthy donors which was supplemented with 400 pg/mL IL-6 and 100 pg/mL TNF-α, similar to what is seen in cytokine storm caused by SARS-CoV-2. Platelet adhesion and neutrophil activation, assessed by immunofluorescence, were compared under cytokine storm and control conditions (untreated blood) (n = 4 experimental runs). RESULTS: Platelet adhesion values, defined as %platelet-covered area x staining intensity, were significantly lower in coated and uncoated COBRA and in Resolute Onyx than in Synergy under control conditions (1.28 × 107 ± 0.43 × 107 vs. 2.92 × 107 ± 0.49 × 107 vs. 3.57 × 107 ± 0.73 × 107 vs. 9.94 × 107 ± 0.99 × 107; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 107 ± 0.38 × 107) compared to all other devices (uncoated COBRA: 5.92 × 107 ± 0.96 × 107; Resolute Onyx: 7.27 × 107 ± 1.82 × 107; Synergy: 11.28 × 107 ± 1.08 × 107; p ≤ 0.0001). Although cytokine storm conditions significantly increased neutrophil activation in all stents, it was significantly less in coated and uncoated COBRA, and in Resolute Onyx than in Synergy. CONCLUSIONS: Blood-biomaterials interactions may determine the thrombogenic potential of stents. Under simulated cytokine storm conditions, fluoropolymer-coated stents showed the most favorable anti-thrombogenic and anti-inflammatory properties.

11.
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
12.
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
13.
Catheter Cardiovasc Interv ; 97(7): 1422-1429, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522027

RESUMO

BACKGROUND: Mechanical thrombectomy is increasingly being used as an alternative to pharmacologic therapies for the treatment of patients with acute deep venous thrombosis (DVT) and pulmonary embolism (PE) and allows direct histopathologic comparison of thrombi extracted from living patients. We performed histopathologic analysis to thrombi extracted from cases of DVT and PE to gain insights into their relative cellular compositions. METHODS: Thrombus retrieved using a catheter-based thrombectomy system (ClotTriever for lower extremity DVT and FlowTriever for PE) from the 17 patients (7 DVT cases and 10 PE cases) were histologically evaluated. Histological features were used to estimate their age and pathological characteristics. RESULTS: The thrombus in all cases were composed of fibrin, platelets, red blood cells, and acute inflammatory cells. The weights of thrombus obtained from DVT versus PE cases were heavier (DVT 7.2 g (g) (5.6-10.2) vs. PE 4.8 g (3.6-6.8), p = .01). Overall thrombus healing (i.e., thrombus composed of smooth muscle cells, endothelial cells, and proteoglycans) was different between DVT and PE cases. 6/7 (86%) with features of late stage healing were from DVT cases while only three of ten (30%) were from PE cases while PE contained more acute thrombi with 7/10 (70%) stage 2 as compared 1/7 (14%) for DVT (p = .0498). CONCLUSION: This study is the first to directly compare the histology of extracted thrombus in DVT versus PE cases from patients with clinical events. Overall PE cases demonstrated significantly earlier stage thrombus with a larger component of red blood cells.


Assuntos
Embolia Pulmonar , Trombose , Trombose Venosa , Células Endoteliais , Humanos , Embolia Pulmonar/diagnóstico por imagem , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem
14.
Int J Hematol ; 114(1): 141-145, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33638034

RESUMO

Congenital deficiency of protein C (PC) is a rare disease that causes thrombophilia during the neonatal and infantile periods. Despite anticoagulative treatments, purpura fulminans and major vessel thrombosis often occur. We report a 7-year-old girl with congenital PC deficiency who underwent deceased donor liver transplantation (LT) and experienced complications accompanied by initial poor graft function (IPGF). Before LT, she had cerebral and ophthalmic hemorrhage, and seven episodes of purpura fulminans. The operation was successfully performed; however, the liver graft developed IPGF. Hyperammonemia and coagulopathy required continuous hemodiafiltration and infusion of fresh frozen plasma. It took 22 days for PC activity to reach reference levels. The changes in clotting and anticlotting activities in the patient's plasma were revealed using clot waveform analysis and the HemosIL ThromboPath® assay. PC activity remained normal for 5 years after LT. Even when IPGF occurs, liver function including PC activity can remain normal for a long time after recovery from IPGF. LT can be a curative treatment for congenital PC deficiency.


Assuntos
Transplante de Fígado , Fígado/fisiopatologia , Deficiência de Proteína C/congênito , Deficiência de Proteína C/terapia , Coagulação Sanguínea , Criança , Feminino , Hemodiafiltração , Humanos , Deficiência de Proteína C/sangue , Deficiência de Proteína C/fisiopatologia , Transplantes/fisiopatologia
15.
Circulation ; 143(10): 1031-1042, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33480806

RESUMO

BACKGROUND: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain. METHODS: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. RESULTS: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm2 area of necrosis, whereas 11 of 14 (78.6%) showed evidence of focal (>20 necrotic myocytes with an area of ≥0.05 mm2 but <1 cm2) myocyte necrosis. Cardiac thrombi were present in 11 of 14 (78.6%) cases with necrosis, with 2 of 14 (14.2%) having epicardial coronary artery thrombi, whereas 9 of 14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19-infected patients presenting with ST-segment-elevation myocardial infarction. Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining compared with intramyocardial thromboemboli from COVID-19-negative subjects and with aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. CONCLUSIONS: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.


Assuntos
COVID-19/virologia , Trombose Coronária/etiologia , Infarto do Miocárdio , Miocárdio/patologia , Idoso , COVID-19/patologia , Trombose Coronária/patologia , Trombose Coronária/virologia , Vasos Coronários/patologia , Vasos Coronários/virologia , Feminino , Coração/virologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/virologia , SARS-CoV-2 , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/virologia
16.
Histochem Cell Biol ; 155(4): 503-512, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33398434

RESUMO

Hypertension leads to structural remodeling of cerebral blood vessels, which has been implicated in the pathophysiology of cerebrovascular diseases. The remodeling and progression of arteriolosclerosis under hypertension involve fibrosis along with the production of type I collagen around cerebral arterioles. However, the source and regulatory mechanisms of this collagen production remain elusive. In this study, we examined if perivascular macrophages (PVMs) are involved in collagen production around cerebral small vessels in hypertensive SHRSP/Izm rats. Immunoreactivity for type I collagen around cerebral small vessels in 12-week-old hypertensive rats tended to higher than those in 4-week-old hypertensive and 12-week-old control rats. In ultrastructural analyses using transmission electron microscopy, the substantial deposition of collagen fibers could be observed in the intercellular spaces around PVMs near the arterioles of rats with prolonged hypertension. In situ hybridization analyses revealed that cells positive for mRNA of Col1a1, which comprises type I collagen, were observed near cerebral small vessels. The Col1a1-positive cells around cerebral small vessels were colocalized with immunoreactivity for CD206, a marker for PVMs, but not with those for glial fibrillary acidic protein or desmin, markers for other perivascular cells such as astrocytes and vascular smooth muscle cells. These results demonstrated that enhanced production of type I collagen is observed around cerebral small vessels in rats with prolonged hypertension and Col1a1 is expressed by PVMs, and support the concept that PVMs are involved in collagen production and vascular fibrosis under hypertensive conditions.


Assuntos
Artérias Cerebrais/metabolismo , Colágeno Tipo I/biossíntese , Hipertensão/metabolismo , Macrófagos/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
17.
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
18.
J Am Coll Cardiol ; 77(3): 314-325, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33478655

RESUMO

To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors' experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection. Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy. Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart. It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis. Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19.


Assuntos
COVID-19 , Miocardite/virologia , Biópsia , COVID-19/patologia , Humanos , Miocardite/patologia , Miocárdio/patologia
19.
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.

20.
Eur J Vasc Endovasc Surg ; 61(1): 146-154, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33187923

RESUMO

OBJECTIVE: To co-register conventional computed tomography angiography (CTA), with ex vivo micro-computed tomography (microCT) and histology of popliteal atherosclerotic plaques. Improving the non-invasive imaging capabilities may be valuable to advance patient care with peripheral arterial obstructive disease towards lesion and individual based treatment. METHODS: In this prospective observational study, 12 popliteal arteries from 11 symptomatic patients who had undergone transfemoral amputations for chronic limb threatening ischaemia and who had pre-operative CTA, were analysed ex vivo by microCT and histology. A total of 353 histological cross sections were co-registered with microCT and CTA, and classified as: lipid rich (LP, n = 26), fibrous (FP, n = 80), or calcific (CP, n = 247) plaques. CTA and microCT plaque density was calculated in 791 regions of interest as Hounsfield units (HU). RESULTS: CTA and microCT could identify plaque components that were confirmed by histology such as fibrous tissue (FP), lipid pool/core (LP), and calcification (CP). MicroCT densities were 77.8 HU for FP (IQR 52.8, 129.5 HU), -28.4 HU for LP (IQR -87.1, 13.2 HU), and 3826.0 HU for CP (IQR 2989.0, 4501.0 HU). CTA densities of the three components of the plaque were: 78.0 HU for FP (IQR 59.5, 119.8 HU), 32.5 HU for LP (IQR 15.0, 42 HU), and 641.5 HU for CP (IQR 425.8, 1135 HU). The differences were statistically significant between the HU densitometric characteristics among the three groups (p < .0001) for both imaging modalities. Overall, microCT performed better diagnostically than conventional CTA for the three types of plaques: areas under the receiving operator characteristics curve were greater for microCT than CTA for FP (0.97 vs. 0.90), for LP (0.88 vs. 0.67), and for CP (0.97 vs. 0.90). CONCLUSION: CTA and microCT can be used to identify histological atherosclerotic plaque components, with better diagnostic performance for microCT. This study demonstrates the feasibility of using microCT to assess plaque morphology lesions in a manner that approaches histology thus becoming a useful tool for ex vivo assessment of atherosclerosis and towards lesion based treatment.


Assuntos
Angiografia por Tomografia Computadorizada , Isquemia/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Microtomografia por Raio-X , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Isquemia/patologia , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/patologia , Placa Aterosclerótica/patologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/patologia , Estudos Prospectivos , Microtomografia por Raio-X/métodos
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