RESUMO
BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.
Assuntos
Doença da Artéria Coronariana , Vasos Coronários , Endotélio Vascular , Febuxostat/administração & dosagem , Xantina Oxidase , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Supressores da Gota/administração & dosagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Resultado do Tratamento , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismoRESUMO
PURPOSE OF REVIEW: This review will focus on our approach for the treatment of refractory in-stent restenosis. RECENT FINDINGS: The discovery of bare metal stents over three decades ago set a milestone in the evolution of percutaneous coronary intervention, which is currently the most widely performed procedure for the treatment of symptomatic coronary disease. However, the broad utilization of stents resulted in the new phenomenon of in-stent restenosis (ISR). Over the years, there has been an increase of the incidence of ISR despite continued improvement of drug-eluting stent (DES) technology. The mechanism of ISR is multifactorial, including biological, mechanical, patient, and operator-related factors. The most common factor is aggressive neointimal proliferation and neoatherosclerosis. ISR presentation is not benign, and treatment is challenging, especially in cases of DES-ISR. We review available therapy modalities for ISR, including medical therapy, scoring balloons, atheroablative therapies, repeat DES, vascular brachytherapy, drug-coated balloons, and coronary artery bypass grafting.
Assuntos
Doença da Artéria Coronariana/cirurgia , Reestenose Coronária , Vasos Coronários/patologia , Stents Farmacológicos , Intervenção Coronária Percutânea , Fármacos Cardiovasculares/uso terapêutico , Angiografia Coronária , Doença da Artéria Coronariana/patologia , Humanos , Intervenção Coronária Percutânea/métodos , Desenho de Prótese , Resultado do TratamentoRESUMO
BACKGROUND: Coronary endothelial function (CEF) in patients with coronary artery disease (CAD) varies among coronary segments in a given patient. Because both coronary vessel wall eccentricity and coronary endothelial dysfunction are predictors of adverse outcomes, we hypothesized that local coronary endothelial dysfunction is associated with local coronary artery eccentricity. METHODS: We used 3 T coronary CMR to measure CEF as changes in coronary cross-sectional area (CSA) and coronary blood flow (CBF) during isometric handgrip exercise (IHE), a known endothelial-dependent stressor, in 29 patients with known CAD and 16 healthy subjects. Black-blood MRI quantified mean coronary wall thickness (CWT) and coronary eccentricity index (EI) and CEF was determined in the same segments. RESULTS: IHE-induced changes in CSA and CBF in healthy subjects (10.6 ± 6.6% and 38.3 ± 29%, respectively) were greater than in CAD patients 1.3 ± 7.7% and 6.5 ± 19.6%, respectively, p < 0.001 vs. healthy for both measures), as expected. Mean CWT and EI in healthy subjects (1.1 ± 0.3 mm 1.9 ± 0.5, respectively) were less than those in CAD patients (1.6 ± 0.4 mm, p < 0.0001; and 2.6 ± 0.6, p = 0.006 vs. healthy). In CAD patients, we observed a significant inverse relationship between stress-induced %CSA change and both EI (r = -0.60, p = 0.0002), and CWT (r = -0.54, p = 0.001). Coronary EI was independently and significantly related to %CSA change with IHE even after controlling for mean CWT (adjusted r = -0.69, p = 0.0001). For every unit increase in EI, coronary CSA during IHE is expected to change by -6.7 ± 9.4% (95% confidence interval: -10.3 to -3.0, p = 0.001). CONCLUSION: There is a significant inverse and independent relationship between coronary endothelial macrovascular function and the degree of local coronary wall eccentricity in CAD patients. Thus anatomic and physiologic indicators of high-risk coronary vascular pathology are closely related. The noninvasive identification of coronary eccentricity and its relationship with underlying coronary endothelial function, a marker of vascular health, may be useful in identifying high-risk patients and culprit lesions.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Hemodinâmica , Imagem Cinética por Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Força da Mão , Humanos , Contração Isométrica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Remodelação VascularRESUMO
Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups (P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients (P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS.
Assuntos
Endotelina-1/fisiologia , Síndrome Metabólica/fisiopatologia , Obesidade Metabolicamente Benigna/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Adulto , Endotelina-1/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Antebraço/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato/farmacologia , Peptídeos Cíclicos/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/fisiologiaRESUMO
Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of N(G)-monomethyl-l-arginine (l-NMMA, 0.3 mg·kg(-1)·min(-1)), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ~8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. l-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 ± 2.5 (mean ± SE, placebo) vs. -0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P < 0.0001) and CBF (P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients.
Assuntos
Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiologia , Endotélio Vascular/fisiologia , Força da Mão , Óxido Nítrico/metabolismo , Vasoconstrição , Vasodilatação , Adulto , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico , Circulação Coronária , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Exercício Físico , Feminino , Testes de Função Cardíaca/métodos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , ômega-N-Metilarginina/farmacologiaRESUMO
Calcified and resistant narrowing of arteries poses significant difficulty in performing percutaneous coronary interventions (PCIs), as they increase the risk of subpar outcomes leading to worse clinical outcomes. Despite the existence of dedicated technologies and devices, including various balloons and atherectomy systems, they often do not ensure sufficient plaque modification and ideal vessel preparation for optimal stent deployment. Intravascular lithotripsy (IVL), a technology originally developed for urological procedures, has recently been used to safely and selectively disrupt calcified depositions in both peripheral and coronary arteries by sonic waves that seamlessly transfer to nearby tissue, enhancing vessel compliance with minimal impact on soft tissues. In the coronary arteries, the use of IVL plays a role in the process of "vessel preparation" before the placement of stents, which is crucial for restoring blood flow in patients with severe coronary artery disease (CAD), and is considered a minimally invasive technique, reducing the need for open heart surgeries and associated risks and complications. Studies have shown that IVL can lead to improved procedural success rates and favorable long-term outcomes for patients with severely calcified coronary artery disease. With the advent of IVL, the disruption of severe calcification of coronary artery and stenotic lesions before stent implantations can be performed. Despite promising data for treating calcified lesions, IVL is significantly underutilized in clinical practice, long-term clinical data and extensive research are needed to validate its further safety and efficacy. In this article, we reviewed the literature discussing the use of IVL in the coronary arteries as an approach for addressing intravascular atherosclerotic plaques, particularly focusing on heavily calcified plaques that are resistant to standard initial PCI, while also evaluating its safety in comparison to alternative methods.
RESUMO
d-Propranolol (d-Pro: 2-8 mg·(kg body mass)(-1)·day(-1)) protected against cardiac dysfunction and oxidative stress during 3-5 weeks of iron overload (2 mg Fe-dextran·(g body mass)(-1)·week(-1)) in Sprague-Dawley rats. At 3 weeks, hearts were perfused in working mode to obtain baseline function; red blood cell glutathione, plasma 8-isoprostane, neutrophil basal superoxide production, lysosomal-derived plasma N-acetyl-ß-galactosaminidase (NAGA) activity, ventricular iron content, and cardiac iron deposition were assessed. Hearts from the Fe-treated group of rats exhibited lower cardiac work (26%) and output (CO, 24%); end-diastolic pressure rose 1.8-fold. Further, glutathione levels increased 2-fold, isoprostane levels increased 2.5-fold, neutrophil superoxide increased 3-fold, NAGA increased 4-fold, ventricular Fe increased 4.9-fold; and substantial atrial and ventricular Fe-deposition occurred. d-Pro (8 mg) restored heart function to the control levels, protected against oxidative stress, and decreased cardiac Fe levels. After 5 weeks of Fe treatment, echocardiography revealed that the following were depressed: percent fractional shortening (%FS, 31% lower); left ventricular (LV) ejection fraction (LVEF, 17%), CO (25%); and aortic pressure maximum (P(max), 24%). Mitral valve E/A declined by 18%, indicating diastolic dysfunction. Cardiac CD11b+ infiltrates were elevated. Low d-Pro (2 mg) provided modest protection, whereas 4-8 mg greatly improved LVEF (54%-75%), %FS (51%-81%), CO (43%-78%), P(max) (56%-100%), and E/A >100%; 8 mg decreased cardiac inflammation. Since d-Pro is an antioxidant and reduces cardiac Fe uptake as well as inflammation, these properties may preserve cardiac function during Fe overload.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Cardiopatias/prevenção & controle , Sobrecarga de Ferro/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Propranolol/uso terapêutico , Acetilglucosaminidase/sangue , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/química , Animais , Débito Cardíaco/efeitos dos fármacos , Progressão da Doença , Relação Dose-Resposta a Droga , Ecocardiografia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa , Cardiopatias/sangue , Cardiopatias/etiologia , Cardiopatias/metabolismo , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Masculino , Miocárdio/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Perfusão , Propranolol/administração & dosagem , Propranolol/química , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Superóxido Dismutase/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: In a previous study we identified metallothionein (MT) as a candidate gene potentially influencing collaterogenesis. In this investigation, we determined the effect of MT on collaterogenesis and examined the mechanisms contributing to the effects we found. METHODS AND RESULTS: Collateral blood flow recovery was assessed using laser Doppler perfusion imaging, and angiogenesis was measured using a Matrigel plug assay. Smooth muscle cells were isolated from MT knockout (KO) mice for functional assays. Gene expression of matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, and Fat cadherin in smooth muscle cells was measured by real-time polymerase chain reaction, and protein levels of vascular endothelial growth factor and matrix metalloproteinase-9 were determined using enzyme-linked immunosorbent assay and Western blot. CD11b(+) macrophages were tested for invasiveness using a real-time impedance assay. Both flow recovery and angiogenesis were impaired in MT KO mice. Proliferation, migration, and invasion were decreased in MT KO smooth muscle cells, and matrix metalloproteinase-9, platelet-derived growth factor, and vascular endothelial growth factor expression were also decreased, whereas FAT-1 cadherin expression was elevated. MT KO CD11b(+) cells were more invasive than wild-type cells. CONCLUSIONS: MT plays an important role in collateral flow recovery and angiogenesis, an activity that appears to be mediated, in part, by the effects of MT on the functionality of 3 cell types essential for these processes: endothelial cells, smooth muscle cells, and macrophages.
Assuntos
Artérias/crescimento & desenvolvimento , Macrófagos/fisiologia , Metalotioneína/fisiologia , Músculo Liso Vascular/fisiologia , Neovascularização Fisiológica/fisiologia , Animais , Artérias/citologia , Movimento Celular/fisiologia , Proliferação de Células , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Membro Posterior/irrigação sanguínea , Macrófagos/citologia , Masculino , Metalotioneína/genética , Camundongos , Camundongos Knockout , Modelos Animais , Músculo Liso Vascular/citologia , Fluxo Sanguíneo Regional/fisiologiaRESUMO
It is estimated that each year in the United States >780,000 persons will experience an acute coronary syndrome. Approximately 70% of these will have non-ST-elevation myocardial infarction (NSTEMI). Optimal timing of angiography in NSTEMI is a matter of debate. The aim of this retrospective analysis was to evaluate whether and how the timing of percutaneous coronary intervention (PCI) affects the 1-year rate of major adverse cardiac events (MACE) in patients presenting with NSTEMI. Within our PCI database, we identified 1550 patients who underwent PCI for NSTEMI. We then divided the population into 3 groups based on door-to-balloon time (D2BT) (group 1â¯=â¯D2BT <90 minutes; group 2â¯=â¯D2BT >90 minutes <24 hours; group 3â¯=â¯D2BT >24 hours). Primary outcome was MACE, a composite of MI, death and target vessel revascularization (TVR), or TVR at 1 year. Baseline characteristics were heterogeneous among the 3 groups, with patients who underwent angiograms >24 hours from presentation being older with more cardiovascular co-morbidities. Patients with D2BT <90 minutes were more likely to present with cardiogenic shock and had higher troponin levels. In-hospital mortality was similar among the 3 groups, but 1-year MACE/TVR was significantly higher in groups 1 and 3, driven by worse mortality. In this large cohort of patients presenting with NSTEMI, patients who underwent PCI between 90 minutes to 24 hours from presentation had better 1-year outcomes but also had fewer co-morbidities and with significantly lower prevalence of cardiogenic shock and high troponin on presentation. Therefore, treatment selection bias makes causal inference concerning rapid revascularization and outcome unreliable. Randomized clinical trials are warranted to assess outcome of rapid revascularization in patients presenting with NSTEMI.
Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/métodos , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Tempo para o Tratamento , Idoso , Angiografia Coronária , District of Columbia/epidemiologia , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
Patients undergoing percutaneous coronary intervention (PCI) often have high-bleeding-risk (HBR) factors. Dual antiplatelet therapy (DAPT) further increases this risk of bleeding. We sought to compare clinical outcomes according to presence or absence of HBR factors in patients with elevated ischemic risk (DAPT score ≥ 2) undergoing PCI. We evaluated all patients undergoing PCI at MedStar Washington Hospital Center (January 2009 to July 2018) with DAPT score ≥2, which is associated with elevated risk of ischemic events. Patients were categorized as HBR group (HBR score ≥1) or low-bleeding-risk (LBR) group (HBR scoreâ¯=â¯0). Outcomes included major adverse cardiac events such as target vessel revascularization, stent thrombosis, death, and bleeding events at 30 days, 6 months, 1 year, and 2 years. The final cohort consisted of 7,499 patients: 3,949 patients had LBR features, and 3,550 patients had HBR features. The 2 groups were different at baseline, with HBR patients being older and having a higher prevalence of congestive heart failure and renal dysfunction than the LBR group. The mean DAPT score was 2.96±1.1 for the LBR group and 3.7±1.4 for the HBR group (p <0.001). During follow-up at 30 days, 6 months, and 1 and 2 years, the rates of target vessel revascularization and stent thrombosis were not significantly different between the 2 groups. Bleeding events and all-cause mortality were significantly more frequent in the HBR group than in the LBR group. In conclusion, patients undergoing PCI often have pre-existing risk factors that predispose them to ischemic and bleeding complications. Prolonged duration of DAPT to mitigate ischemic events could lead to a disproportionate increase in bleeding events, especially in HBR patients.
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/terapia , Hemorragia/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/epidemiologia , Idoso , Causas de Morte , Comorbidade , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia Gastrointestinal/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Prevalência , Insuficiência Renal/epidemiologia , Risco , Medição de Risco , StentsRESUMO
Hypomagnesemia continues to be a significant clinical disorder that is present in patients with diabetes mellitus, alcoholism, and treatment with magnesuric drugs (diuretics, cancer chemotherapy agents, etc.). To determine the role of magnesium in cardiovascular pathophysiology, we have used dietary restriction of this cation in animal models. This review highlights some key observations that helped formulate the hypothesis that release of substance P (SP) during experimental dietary Mg deficiency (MgD) may initiate a cascade of deleterious inflammatory, oxidative, and nitrosative events, which ultimately promote cardiomyopathy, in situ cardiac dysfunction, and myocardial intolerance to secondary stresses. SP acts primarily through neurokinin-1 receptors of inflammatory and endothelial cells, and may induce production of reactive oxygen and nitrogen species (superoxide anion, NO*, peroxynitrite, hydroxyl radical), leading to enhanced consumption of tissue antioxidants; stimulate release of inflammatory mediators; promote tissue adhesion molecule expression; and enhance inflammatory cell tissue infiltration and cardiovascular lesion formation. These SP-mediated events may predispose the heart to injury if faced with subsequent oxidative stressors (ischemia/reperfusion, certain drugs) or facilitate development of in situ cardiac dysfunction, especially with prolonged dietary Mg restriction. Significant protection against most of these MgD-mediated events has been observed with interventions that modulate neuronal SP release or its bioactivity, and with several antioxidants (vitamin E, probucol, epicaptopril, d-propranolol). In view of the clinical prevalence of hypomagnesemia, new treatments, beyond magnesium repletion, may be needed to diminish deleterious neurogenic and prooxidative components described in this article.
Assuntos
Cardiomiopatias , Deficiência de Magnésio/complicações , Inflamação Neurogênica , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Dieta , Endotoxemia/metabolismo , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Inflamação Neurogênica/etiologia , Inflamação Neurogênica/fisiopatologia , Neuropeptídeos/metabolismo , Estresse Oxidativo , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores da Neurocinina-1/metabolismoRESUMO
Despite on-going evolution and iteration of drug-eluting stent (DES) technology, the prevalence of in-stent restenosis (ISR) remains relatively unchanged, encompassing ≈10% of percutaneous coronary interventions. The mechanism of ISR is multifactorial, including biological, mechanical, patient, and operator-related factors. The main mechanical contributors are stent underexpansion or fracture, while biological factors include local inflammation leading to aggressive neointimal proliferation and late neoatherosclerosis. Intracoronary imaging is critical to identify the mechanism of ISR and tailor therapy accordingly. The presentation of DES-ISR is not benign and is challenging for optimal treatment. Among the proposed treatment modalities are scoring and high-pressure balloons, percutaneous coronary intervention with additional DES, atheroablative therapies by laser or mechanical atherectomy, drug-coated balloons, vascular brachytherapy, and surgical revascularization. We propose a new classification for ISR that differentiates among mechanical, biological, and mixed etiologies. Stratifying ISR by mechanism guides individualized treatment of DES-ISR to improve clinical outcomes. An algorithmic approach, guided by intracoronary imaging, for the treatment of DES-ISR, is recommended based on the specific cause of restenosis.
Assuntos
Doença da Artéria Coronariana/terapia , Reestenose Coronária/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/epidemiologia , Técnicas de Apoio para a Decisão , Humanos , Incidência , Seleção de Pacientes , Desenho de Prótese , Retratamento , Fatores de Risco , Resultado do TratamentoRESUMO
On June 12, 2018, the US Food and Drug Administration (FDA) convened a meeting of the Circulatory System Devices Panel to advise on the safety and effectiveness of the INCRAFT® AAA Stent Graft System for the treatment of abdominal aortic aneurysms (AAA) and to consider a premarket approval application sponsored by Cordis, Inc., for Unique identifier: NCT01664078 based on the results of the pivotal INSPIRATION trial (URL: https://clinicaltrials.gov/ct2/show/NCT01664078). The INCRAFT® AAA Stent Graft System is designed for endovascular repair of infrarenal AAAs with complex aortic anatomies. The stent-graft system utilizes nitinol stent and polyester graft technology in an ultra-low profile delivery system, with the goal of isolating the aneurysmal sac and preventing sac rupture. The multicenter, prospective, non-randomized investigation trial met its primary composite safety and effectiveness endpoints but also showed higher-than-anticipated rates of stent fracture and endoleaks. The committee discussion focused on how these events impact the long-term safety and effectiveness, as well as the benefit/risk profile, of the device. While the panel acknowledged the risk of the device, the panel's final vote supported that the benefits of the INCRAFT AAA Stent Graft System outweigh the risks and that a post-marketing study should be mandated. The FDA approved the device for use in complex access anatomies in December 2018.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Aprovação de Equipamentos , Procedimentos Endovasculares/instrumentação , Stents , United States Food and Drug Administration , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Endoleak/etiologia , Procedimentos Endovasculares/efeitos adversos , Medicina Baseada em Evidências , Humanos , Segurança do Paciente , Desenho de Prótese , Falha de Prótese , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND/PURPOSE: Women are underrepresented in cardiovascular clinical studies. Black women have a higher ischemic heart disease mortality risk than their white counterparts. However, there exist limited outcome data comparing black women and white women after percutaneous coronary intervention (PCI). The aim of this retrospective analysis was to evaluate for racial disparities in 1-year major adverse cardiovascular events (MACE) in women undergoing PCI. METHODS/MATERIALS: Within our PCI database, we identified 4776 female patients who underwent PCI between 2003 and 2016. Of those, 1916 were black and 2860 were white. Endpoints included MACE, death, myocardial infarction, target vessel revascularization (TVR) and stent thrombosis (ST) at 30â¯days and 1â¯year. A proportional Cox hazard model analysis was performed to assess outcomes after adjustment for confounding factors. RESULTS: Black women presented at a younger age and had a significantly higher prevalence of risk factors. Periprocedural and in-hospital outcomes were similar in the 2 groups. At 30â¯days and 1â¯year, the rates of myocardial infarction, TVR and ST were significantly higher in black women. After adjustment for baseline differences, only ST appears to be more likely to occur in black women than in white women. CONCLUSIONS: In this large cohort of women with coronary artery disease undergoing PCI, we observed racial disparities primarily in baseline characteristics indicative of need for interventions to achieve early diagnosis and better prevention in black women. Future directions should include efforts to identify and better characterize the factors underlying and contributing to cardiovascular outcomes in women after PCI. SUMMARY: In this real-world analysis from a large cohort of women with coronary artery disease undergoing percutaneous coronary intervention at a US tertiary-care center, racial disparities were observed, especially in baseline characteristics, indicating late presentation.
Assuntos
Negro ou Afro-Americano , Doença da Artéria Coronariana/terapia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Intervenção Coronária Percutânea , População Branca , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Fatores Raciais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND/PURPOSE: We aimed to assess the reported complications and event modes for the GuideLiner and Guidezilla extension catheters. METHODS/MATERIALS: The US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was queried for reported events. RESULTS: Of the 65 cases with reported GuideLiner-related issues, 15 (23%) involved the inability to pass equipment through or damage to percutaneous coronary intervention (PCI) devices in the GuideLiner catheter, 38 (58%) involved GuideLiner catheter fracture, 9 (14%) involved coronary artery dissection, 2 (3%) involved coronary artery perforation, and 1 (1.5%) involved thrombus formation in the catheter. Of the 408 cases with reported Guidezilla-related issues, 53 (13%) involved inability to pass or damaged PCI devices into the Guidezilla catheter, 117 (29%) involved inability to advance the Guidezilla catheter to the target lesion, 59 (14%) involved kinked Guidezilla catheter, mostly because of partial or complete catheter fracture upon further investigation, 164 (40%) involved a broken Guidezilla catheter, 10 (2.5%) involved coronary artery dissection, 2 (0.5%) involved coronary artery perforation, 1 (0.2%)involved aortic dissection, 1 (0.2%) involved thrombosis formation, and 1 (0.2%) involved no-reflow phenomenon. CONCLUSIONS: Findings from the MAUDE database highlight the complications and modes of events associated with the use of GuideLiner and Guidezilla extension catheters. SUMMARY: To assess the reported complications and event modes for the GuideLiner and Guidezilla extension catheters, the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was queried. There were more reports on Guidezilla-related events during the search period. The events for both extension catheters mainly involved the inability to pass equipment through or damage to percutaneous coronary intervention (PCI) devices in the extension catheter, extension catheter fracture, coronary artery dissection and perforation and, occasionally, the death of the patients.
Assuntos
Cateteres Cardíacos/efeitos adversos , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Vigilância de Produtos Comercializados , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Desenho de Equipamento , Falha de Equipamento , Humanos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos , United States Food and Drug AdministrationRESUMO
BACKGROUND/PURPOSE: Appropriate patient selection for mechanical circulatory support following percutaneous coronary intervention (PCI) remains a challenge. This study aims to evaluate the role of coronary perfusion pressure and other left ventricular hemodynamics to predict cardiovascular collapse following PCI. METHODS/MATERIALS: We retrospectively analyzed all patients who underwent PCI for acute coronary syndrome (ACS) from 2003 to 2016. Coronary perfusion pressure was calculated for each patient and defined as the difference in mean arterial pressure and left ventricular end diastolic pressure (LVEDP). Logistic regression analysis was performed to determine predictor of composite outcome of in-hospital mortality, myocardial infarction (MI), congestive heart failure (CHF), and cardiogenic shock. RESULTS: Nine hundred twenty-two patients were analyzed. Two-hundred twenty-eight (25%) presented with ST-elevation MI (STEMI) while 694 (75%) underwent PCI for unstable angina or non-Q-wave MI. The mean LVEDP was significantly higher in the STEMI patients (24⯱â¯9 vs. 19⯱â¯8â¯mmâ¯Hg, pâ¯<â¯0.05) and perfusion pressure significantly lower (68⯱â¯24 vs. 74⯱â¯18â¯mmâ¯Hg, pâ¯<â¯0.05). Eighty-seven (9.4%) reached the composite endpoint, and there was no difference between the STEMI and Not-STEMI groups. Neither LVEDP nor coronary perfusion pressure was a predictor of the composite outcome following multivariable logistic regression analysis for either STEMI or Not-STEMI patients. Increasing age, chronic renal insufficiency (CRI), CHF, and low left ventricular ejection fraction were predictors of the composite outcome for Not-STEMI patients, whereas only history of cerebrovascular accident and CRI were predictors for STEMI patients. CONCLUSIONS: In hemodynamically stable patients presenting with ACS, LVEDP and coronary perfusion pressure are not predictive of in-hospital cardiovascular collapse. SUMMARY: The authors retrospectively analyzed 922 patients from a single center who underwent percutaneous coronary intervention (PCI) for acute coronary syndromes to evaluate the role of coronary perfusion pressure and other left ventricular hemodynamics to predict cardiovascular collapse following PCI. They found that neither coronary perfusion pressure nor left ventricular end diastolic pressure was predictive of in-hospital cardiovascular collapse.
Assuntos
Síndrome Coronariana Aguda/terapia , Circulação Coronária , Hemodinâmica , Intervenção Coronária Percutânea/efeitos adversos , Choque/etiologia , Função Ventricular Esquerda , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Choque/mortalidade , Choque/fisiopatologia , Choque/terapia , Volume Sistólico , Resultado do Tratamento , Pressão VentricularRESUMO
Race has been identified as an independent risk factor for poor prognosis and an independent predictor of survival in coronary artery disease. Race-related dissimilarities have been identified in cardiovascular patients in terms of age of presentation, co-morbidities, socioeconomic status, and treatment approach as well as genetically driven race-related disparities in responsiveness to medications. Antiplatelet therapy represents a fundamental component of therapy in cardiovascular patients, especially in patients presenting with acute coronary syndromes. It has been argued that the different level of platelet reactivity and varying response to antiplatelet therapy among races may account in part for worse outcomes in certain populations. The purpose of this review is to describe genotypic and phenotypic race-related differences in platelet reactivity and responsiveness to cardiovascular treatment, focusing on antiplatelet therapy to highlight the need establish a more effective and targeted antithrombotic strategy.
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Grupos Raciais , Genótipo , Humanos , Fenótipo , Resultado do TratamentoRESUMO
BACKGROUND/PURPOSE: Right ventricular (RV) mechanical circulatory support remains an important adjunctive therapy for RV failure refractory to medical therapy. Impella RP (Abiomed, Danvers, MA) is approved for providing temporary RV support for patients with acute right heart failure or decompensation following left ventricular assist device implantation, myocardial infarction, heart transplant, or open-heart surgery. Robust data on the most commonly reported complications and failure modes for the Impella RP are lacking. We analyzed the post-marketing surveillance data from the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database to assess these endpoints. MATERIALS/METHODS: The MAUDE database was queried for the time period January 1, 2009, through December 31, 2018, for Impella devices by Searching for the following event types: "injury", "malfunction", "death", and "other". The search yielded 436 device reports. Impella RP medical device reports were screened, and 35 reports were included for the final analysis. RESULTS: In cases of reported complications, Impella RP was placed most commonly for right ventricular failure (RVF) developing in postcardiotomy patients (20%). The most commonly reported complications included bleeding (42.9%) and vascular complications (22.8%). The modes of failure included damage or fracture of the device elements (34.2%); thrombus, or clot in the system (17.1%); and device detachment (8.6%). CONCLUSIONS: Findings from the MAUDE database highlight the failure modes of the Impella RP device that should be addressed in order to improve the device performance and obtain improved clinical outcomes when utilized for RVF.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Vigilância de Produtos Comercializados , Falha de Prótese , Disfunção Ventricular Direita/terapia , Função Ventricular Direita , Bases de Dados Factuais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Desenho de Prótese , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologiaRESUMO
Percutaneous coronary intervention (PCI) has evolved dramatically, along with patient complexity. We studied trends in in-hospital mortality with changes in patient complexity over the last decade stratified by clinical presentation. The study population included all patients presenting to the cardiac catheterization lab between January 2009 and July 2018. Expected in-hospital mortality was calculated using the National Cardiovascular Data Registry CathPCI risk scoring system. Yearly mean in-hospital mortality rates (%) were plotted and smoothed by weighted least squares regression for each presentation: ST-elevation myocardial infarction (STEMI), non-ST-elevation acute coronary syndrome (NSTE-ACS), and stable ischemic coronary artery disease (SI CAD). The overall cohort included 13,732 patients who underwent PCI during the study period, of whom 2,142 were for STEMI, 2,836 for NSTE-ACS, and 8,754 for SI CAD. Indications for PCI have changed over time, with more PCIs being performed for NSTE-ACS and STEMI than for SI CAD. NSTE-ACS and STEMI patients had a steady decrease in in-hospital mortality over time compared with SI CAD patients. Overall observed mortality continues to decrease in NSTE-ACS patients, with reduction in the observed mortality rate within the STEMI population to below expected since 2013. Patient complexity has not changed significantly. These results may be attributed to improved patient selection coupled with optimal pharmacotherapy with more robust therapies during procedure and hospitalization.
Assuntos
Doença da Artéria Coronariana/cirurgia , Previsões , Intervenção Coronária Percutânea/mortalidade , Sistema de Registros , Idoso , Causas de Morte/tendências , Doença da Artéria Coronariana/mortalidade , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis (AS) and prior chest radiation is associated with poor outcomes in comparison with patients without prior radiation. Our objective was to compare clinical outcomes of patients with and without prior chest radiation undergoing transcatheter aortic valve replacement (TAVR) for symptomatic severe AS. METHODS/MATERIALS: Between January 2003 and January 2017, 1150 patients underwent TAVR at our institution. Of these, 44 had prior chest radiation. Baseline demographic and clinical characteristics, procedural details, and clinical outcomes were prospectively collected. RESULTS: Patients with prior chest radiation were younger, 76⯱â¯13â¯years, compared with those without prior chest radiation, 82⯱â¯8â¯years (pâ¯=â¯0.002). Median Society of Thoracic Surgeons score for chest radiation patients was 7⯱â¯4, compared to 8⯱â¯5 in those without prior radiation. Despite higher prevalence of complete heart block, there was no significant difference between the 2 groups with regard to the need for permanent pacemaker implantation. There was a trend toward longer length of intensive care unit stay in chest radiation patients, but there was no significant difference in 30-day or 1-year mortality. CONCLUSIONS: Thus, TAVR appears to be a safe treatment option in the short and medium term for patients with symptomatic severe AS and prior chest radiation.