RESUMEN
Chronic coronary artery stenosis can lead to regional myocardial dysfunction in the absence of myocardial infarction by repetitive stunning, hibernation or both. The molecular mechanisms underlying repetitive stunning-associated myocardial dysfunction are not clear. We used non-targeted metabolomics to elucidate responses to chronically stunned myocardium in a canine model with and without ß-adrenergic blockade treatment. After development of left ventricular systolic dysfunction induced by ameroid constrictors on the coronary arteries, animals were randomized to 3 months of placebo, metoprolol or carvedilol. We compared these two ß-blockers with their different ß-adrenergic selectivities on myocardial function, perfusion and metabolic pathways involved in tissue undergoing chronic stunning. Control animals underwent sham surgery. Dysfunction in stunned myocardium was associated with reduced fatty acid oxidation and enhanced ketogenic amino acid metabolism, together with alterations in mitochondrial membrane phospholipid composition. These changes were consistent with impaired mitochondrial function and were linked to reduced nitric oxide and peroxisome proliferator-activated receptor signalling, resulting in a decline in adenosine monophosphate-activated protein kinase. Mitochondrial changes were ameliorated by carvedilol more than metoprolol, and improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. In summary, repetitive myocardial stunning commonly seen in chronic multivessel coronary artery disease is associated with adverse metabolic remodelling linked to mitochondrial dysfunction and specific signalling pathways. These changes are reversed by ß-blockers, with the non-selective inhibitor having a more favourable impact. This is the first investigation to demonstrate that ß-blockade-associated improvement of ventricular function in chronic myocardial stunning is associated with restoration of mitochondrial function. KEY POINTS: The mechanisms responsible for the metabolic changes associated with repetitive myocardial stunning seen in chronic multivessel coronary artery disease have not been fully investigated. In a canine model of repetitive myocardial stunning, we showed that carvedilol, a non-selective ß-receptor blocker, ameliorated adverse metabolic remodelling compared to metoprolol, a selective ß1-receptor blocker, by improving nitric oxide synthase and adenosine monophosphate protein kinase function, enhancing calcium/calmodulin-dependent protein kinase, probably increasing hydrogen sulphide, and suppressing cyclic-adenosine monophosphate signalling. Mitochondrial fatty acid oxidation alterations were ameliorated by carvedilol to a larger extent than metoprolol; this improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. Both ß-blockers improved the cardiac energy imbalance by reducing metabolites in ketogenic amino acid and nucleotide metabolism. These results elucidated why metabolic remodelling with carvedilol is preferable to metoprolol when treating chronic ischaemic left ventricular systolic dysfunction caused by repetitive myocardial stunning.
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Antagonistas de Receptores Adrenérgicos beta 1 , Estenosis Coronaria , Metabolómica , Metoprolol , Aturdimiento Miocárdico , Animales , Aturdimiento Miocárdico/tratamiento farmacológico , Aturdimiento Miocárdico/metabolismo , Aturdimiento Miocárdico/etiología , Perros , Metoprolol/farmacología , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/metabolismo , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Carvedilol/farmacología , Masculino , Propanolaminas/farmacología , Carbazoles/farmacología , Miocardio/metabolismo , Miocardio/patología , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismoRESUMEN
Purpose: The performance of the Low-Profile Visualized Intraluminal Support (LVIS) stentdeployed following balloon angioplasty is unknown in treating intracranial atherosclerotic stenosis, and this study was to investigate the safety and efficacy of the LVIS stent in treatingintracranial atherosclerotic stenosis in the middle cerebral artery M1 segment.Methods: Thirty-five patients were enrolled with 35 atherosclerotic stenoses at the M1 segment. The stenosis was about 75% in 16 patients, 80% in 15, and 90% in the rest four. The LVISstent was used to treat these patients. Results: The success rate of stenting was 97.1%. The stenting procedure was failed in onepatient because of intraprocedural dissection of the stenotic (75%) segment, resulting in a 30-day periprocedural complication rate of 2.9% (1/35). Before stenting, the stenosis rate ranged75%90% (mean 78.9% ± 4.7%), and after stenting, the diameter of the stented segment wassignificantly (P < 0.0001) increased to 1.53.4 mm (mean 2.1 ± 0.32 mm) ranging 68.2%100%(mean 94.0% ± 5.8%) of the normal arterial diameter, with the residual stenosis ranging 031.8%(median 4.8%, IQR 2.4%7.3%). Follow-up was performed at 620 months (mean 8.5) afterstenting. One patient (2.9%) had occlusion of the stented M1 segment with no symptoms, andtwo patients (5.7%) had slight asymptomatic instent stenosis (40%) at the M1 segment, with theinstent restenosis and occlusion rate of 8.6% (3/35). Conclusion: The braided LVIS stent can be safely applied for treatment of intracranialatherosclerotic stenosis in the middle cerebral artery with good safety and efficacy immediatelyafter stenting and at follow-up.(AU)
Objetivo: Nos propusimos analizar la seguridad y efectividad de la colocación de un stentlow-profile visualized intraluminal support (LVIS TM ) tras angioplastia con balón en pacientescon estenosis ateroscleróticas intracraneales en el segmento M1 de la arteria cerebral media(ACM). Métodos: Incluimos 35 pacientes con estenosis ateroscleróticas en el segmento M1 de la ACM;la estenosis era del 75% en 16 pacientes, del 80% en 15 y del 90% en los 4 restantes. En todoslos casos el tratamiento se basó en la colocación de un stent LVIS TM . Resultados: El stent se implantó con éxito en el 97,1% de los casos; en un paciente, el procedimiento no se pudo llevar a cabo a causa de una disección del segmento estenótico (estenosisdel 75%) durante la operación, lo que supone una tasa de complicaciones perioperatorias a los30 días del 2,9%. Antes de la colocación del stent, el grado de estenosis oscilaba entre el 75 yel 90% (media [DS]: 78,9% [4,7%]). Tras el procedimiento, el diámetro del segmento en el quese había colocado el stent aumentó de forma significativa (P < 0,0001) hasta los 1,5-3,4 mm(media: 2,1 mm [0,32]), logrando un 68,2-100% (media: 94,0% [5,8%]) del diámetro normal dela arteria, y una estenosis residual del 0 al 31,8% (mediana: 4,8%; p25-p75, 2,4-7,3%). Se realizóun seguimiento de entre 6 y 20 meses (media: 8,5) tras el procedimiento. Un paciente (2,9%)presentó una oclusión asintomática del segmento M1 intervenido, y 2 pacientes (5,7%) presentaron estenosis intrastent asintomáticas leves (40%) en M1, por lo que la tasa de reestenosisintrastent y oclusión fue del 8,6%. Conclusión: El stent LVIS TM es un tratamiento seguro y efectivo para las estenosis ateroscleróticas intracraneales en la ACM.(AU)
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Humanos , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/terapia , Stents , Angioplastia de Balón , Neurología , Enfermedades del Sistema NerviosoRESUMEN
INTRODUCTION: Patients with left carotid artery atherosclerotic stenosis have an increased ischemic stroke risk. Left carotid stenosis, the most common cause of the transient ischemic attack, is related to a higher risk of acute stroke. Left carotid artery stenosis is also associated with cerebral artery infarction. The significant coronary stenosis promotes ST-segment elevation myocardial infarctions. The severe coronary stenosis plays an important role in development and progression of myocardial infarction. However, the dynamic changes of circulating oxidative stress and inflammatory markers in the carotid stenosis combined with coronary artery stenosis are not clear, and it also remains unknown whether mark of oxidative stress and inflammation are potential therapeutic targets for carotid stenosis combined with coronary artery stenosis. AIM: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients. METHODS: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients. RESULTS: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients. CONCLUSION: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.
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Estenosis Carotídea , Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Humanos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estenosis Carotídea/complicaciones , Estenosis Carotídea/tratamiento farmacológico , Proteína C-Reactiva/análisis , Constricción Patológica , Factor de Necrosis Tumoral alfa/metabolismo , Factores de Riesgo , Biomarcadores/metabolismo , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Estenosis Coronaria/tratamiento farmacológicoRESUMEN
BACKGROUND: Sodium-glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids' plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. METHODS: In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. RESULTS: At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149-2.176]), macrophage grade (1.188, [CI 95%: 1.073-1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180-0.651]) were independent predictors of MACEs at 1 year of follow-up. CONCLUSIONS: SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids' deposit, and FCT in Mv-NOCS patients with T2DM.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Diabetes Mellitus Tipo 2 , Isquemia Miocárdica , Intervención Coronaria Percutánea , Placa Aterosclerótica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Enfermedad de la Arteria Coronaria/terapia , Placa Aterosclerótica/patología , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Intervención Coronaria Percutánea/métodos , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/patología , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/tratamiento farmacológico , Fibrosis , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Lípidos , Inflamación/patología , Tomografía de Coherencia Óptica/métodosRESUMEN
AIMS: Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE. METHODS AND RESULTS: A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054). CONCLUSION: Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía por Tomografía Computarizada , Reserva del Flujo Fraccional Miocárdico/fisiología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Angiografía Coronaria/métodos , Vasos Coronarios/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Valor Predictivo de las Pruebas , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: We sought to investigate the differences in coronary plaque morphology on coronary computed tomography angiography (CCTA) and medical therapy between acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD). We also explored the relationship between plaque morphology on CCTA at the initial phase and lesion morphology in the acute phase of ACS. METHODS: In 5967 patients who underwent invasive coronary angiography, 58 ACS and 91 SIHD patients who had prior CCTA imaging of the culprit lesion and denied ischemic heart disease at CCTA scanning were enrolled. RESULTS: Although the prevalence of positive remodeling was not different (P = 0.27), low-attenuation plaques (LAP) on prior CCTA were significantly higher in ACS than in SIHD (52% vs. 24%, P < 0.01). The frequency of coronary stenosis grading did not differ between the two groups (P = 0.14). In ACS patients, the frequencies of plaque rupture and lipid-rich plaque assessed by optical coherence tomography (OCT) were significantly higher in LAP than in non-LAP (73% vs. 23%, P < 0.01; 82% and 23%, P < 0.01). Multivariate regression analysis revealed that statin use and LAP on prior CCTA were predictors of future ACS events (P < 0.01, and P < 0.05, respectively). CONCLUSIONS: LAP on CCTA, not positive arterial remodeling, and lack of statin therapy were associated with ACS development. In addition, LAP more frequently led to the development of the plaque rupture type of ACS compared with non-LAP. Lipid-lowering therapy with statins might be useful to prevent plaque rupture in patients with LAP regardless of coronary stenosis.
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Síndrome Coronario Agudo , Estenosis Coronaria , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/epidemiología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/epidemiología , LípidosRESUMEN
La tomografía de coherencia óptica (OCT) es una técnica de imagen endovascular con elevada resolución espacial que permite evaluar las diferentes estructuras que componen la pared de las arterias coronarias, caracterizar morfológicamente la placa aterosclerótica y establecer el mecanismo fisiopatológico subyacente en los síndromes coronarios agudos (SCA). Se presenta el caso clínico de un paciente con infarto agudo de miocardio, donde la OCT evidenció que la reducción de la luz arterial estaba determinada principalmente por la presencia de trombo, a la vez que demostró una disrupción endotelial (ruptura de placa) como mecanismo fisiopatológico subyacente. Se adoptó una estrategia invasivo-conservadora, donde finalmente no se implantó stent. La información surgida de la OCT en este caso particular fue fundamental en la toma de decisiones.
Optical coherence tomography (OCT) is an endovascular imaging technique with high spatial resolution. It allows to evaluate the different structures that compose coronary arteries' wall, morphologically characterize atherosclerotic plaques and establish the underlying pathophysiological mechanism in acute coronary syndromes (ACS). The case of a patient with acute myocardial infarction is presented, in which OCT showed that the reduction of arterial lumen was determined mainly by the presence of thrombus, while also demonstrated endothelial disruption (plaque rupture) as the underlying pathophysiological mechanism. An invasive-conservative strategy was adopted and finally stent was not implanted. The information that emerged from the OCT in this particular case was fundamental in decision-making.
A tomografia de coerência óptica (OCT) é uma técnica de imagem endovascular com alta resolução espacial que permite a avaliação das diferentes estruturas que compõem a parede das artérias coronárias, a caracterização morfológica da placa aterosclerótica e o estabelecimento do mecanismo fisiopatológico subjacente de síndrome coronariana aguda (SCA). Apresentamos o caso clínico de um paciente com enfarte agudo do miocárdio, onde a OCT mostrou que a redução do lúmen arterial foi determinada principalmente pela presença de trombo, ao mesmo tempo que demonstrou uma ruptura endotelial (ruptura da placa) como causa fisiopatológica subjacente. Adotou-se uma estratégia invasiva-conservadora, onde finalmente o stent não foi implantado. As informações obtidas da OCT neste caso específico foram fundamentais na tomada de decisão.
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Humanos , Masculino , Persona de Mediana Edad , Trombosis Coronaria/diagnóstico por imagen , Tomografía de Coherencia Óptica , Infarto del Miocardio/diagnóstico por imagen , Trombosis Coronaria/tratamiento farmacológico , Cineangiografía , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/diagnóstico por imagen , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/terapiaRESUMEN
BACKGROUND: Previously, in the ESCAPE study, a randomized controlled trial, we found that 12 months of cilostazol administration significantly decreased coronary artery stenosis and the noncalcified plaque component compared with aspirin. The goal of the current study was to evaluate the effect of cilostazol treatment on cardiovascular events up to 7 years after the end of the original study. METHODS: After the end of the ESCAPE study with patients with type 2 diabetes mellitus (T2DM) and mild to moderate coronary artery stenosis, we decided to extend the ESCAPE study to investigate the long-term effect of cilostazol and aspirin, named the ESCAPE-extension study. The study participants had been investigated for cardiovascular events for up to 7 years, bringing the total follow-up time to a median of 5.2 years (interquartile range 3.6-6.7 years). Adverse events were also investigated. RESULTS: Among 100 participants from the original study, 88 were included in this extension study. Cilostazol treatment reduced the incidence of cardiovascular events in the patients with T2DM when compared with aspirin for a 5.2-year median follow-up (hazard ratio 0.24; 95% CI, 0.07-0.83). The cardiovascular benefit of cilostazol therapy was maintained along with age, sex, systolic blood pressure, low-density lipoprotein cholesterol, and coronary artery calcium score. No serious adverse events in the cilostazol group were noted in the follow-up period. CONCLUSIONS: In this ESCAPE-extension study, cilostazol treatment proved its efficacy in reducing cardiovascular events compared with aspirin in diabetic patients with subclinical coronary artery disease, suggesting the beneficial role of cilostazol in the primary prevention of cardiovascular disease.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Diabetes Mellitus Tipo 2 , Aspirina/efectos adversos , Aspirina/uso terapéutico , Cilostazol/uso terapéutico , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/prevención & control , Estenosis Coronaria/inducido químicamente , Estenosis Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study. METHODS: Patients 7-28 days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint. RESULTS: Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12 weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200 mg, 50 mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths. CONCLUSIONS: In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. CLINICALTRIALS: gov identifier: NCT03317002.
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Inhibidores de Proteína Activante de 5-Lipoxigenasa , Infarto del Miocardio , Inhibidores de Proteína Activante de 5-Lipoxigenasa/efectos adversos , Estenosis Coronaria/tratamiento farmacológico , Humanos , Infarto del Miocardio/tratamiento farmacológico , Pirazoles , Método Simple Ciego , Resultado del TratamientoRESUMEN
BACKGROUND: Administration of intracoronary (IC) adenosine allows an easily feasible, inexpensive, and more rapid alternative method for fractional flow reserve (FFR). It is common practice in many centers worldwide. Nicardipine is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not established. The purpose of present study was to compare the efficacy and safety of IC nicardipine and adenosine for assessing FFR. METHODS: One hundred and fifty-nine patients with a total of 193 vessels undergoing clinically indicated FFR assessment of intermediate coronary stenoses were included. For the initial assessment of FFR, hyperemia was induced by an IC adenosine. After a washout period of 3 min, FFR was reassessed using 200 µg of IC nicardipine. RESULTS: Hyperemic efficacy among two different stimuli was compared. The mean FFR with IC adenosine was 0.83 ± 0.09 and that with an IC nicardipine was 0.84 ± 0.09. The median FFR with an IC adenosine was 0.83 (0.78-0.91) and that with an IC nicardipine was 0.85 (0.79-0.91) (p-value 0.246). Both FFR values showed an excellent correlation (R2 = 0.982, p < 0.001). Nicardipine produced fewer changes in heart rate, less chest pain and less flushing than adenosine. Transient atrioventricular block occurred in 29 patients with IC adenosine and none with IC nicardipine. CONCLUSIONS: IC bolus injection of nicardipine could be introduced as a safe and practical alternative method of inducing hyperemia during FFR measurements. Compared to IC adenosine, IC nicardipine has a similar hyperemic efficacy and excellent side-effect profile.
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Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Hiperemia , Adenosina , Cateterismo Cardíaco , Angiografía Coronaria/métodos , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/tratamiento farmacológico , Vasos Coronarios , Reserva del Flujo Fraccional Miocárdico/fisiología , Humanos , Hiperemia/inducido químicamente , Nicardipino/efectos adversos , Índice de Severidad de la Enfermedad , VasodilatadoresRESUMEN
BACKGROUND: Stable angina pectoris in patients with coronary heart disease is a clinical syndrome of rapid transient ischemia and hypoxia of myocardium due to the increase of myocardial load on the basis of fixed severe coronary artery stenosis. In recent years, the incidence rate of this disease has been rising steadily, which seriously threatens human life and health. When the disease occurs, its complementary and alternative therapy can relieve chest pain, improve cardiac function, and reduce adverse events. However, in retrospect of all the studies, we lack systematic analysis of the efficacy and safety of various complementary and alternative therapies. The curative effects were ranked. On the basis of these findings, we conducted a study of complementary and alternative therapy in patients with coronary heart disease, and proposed a network meta-analysis (NMA) protocol to explore the efficacy of different complementary and alternative therapies. METHODS: We will comprehensively search the Chinese and English databases from the creation date to January 15, 2022. The randomized controlled trials of the supplementary and alternative treatment of stable angina pediatrics in patients with coronary heart disease and the relevant literature of the ongoing trials will be published. The 2 researchers will conduct literature screening and data extraction independently, using Cochrane system evaluator manual 5 3. The recommended bias risk assessment tool was used to evaluate the quality of the included study, Q-test was used and combined with heterogeneity analysis, and the analysis sensitivity was observed. The Review Manager 5.4 software provided by Cochrane Collaboration Network is used to statistically analyze the included literature, and the obtained results are made into forest map and funnel map for data analysis and processing. It is suggested that the evaluation will be used to formulate and evaluate the level, so as to classify the quality of NMA evidence. RESULTS: Through analysis, we will get the efficacy and safety ranking of different complementary and alternative therapies in the treatment of stable angina pediatrics in patients with coronary heart disease, so as to provide further reference for the selection of clinical treatment methods. CONCLUSION: The complementary and alternative treatment of stable angina peptis in patients with coronary heart disease has a positive effect on improving its symptoms. This study can provide evidence support for clinicians and patients. INPLASY REGISTRATION NUMBER: INPLASY202210066.
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Angina Estable , Terapias Complementarias , Estenosis Coronaria , Medicamentos Herbarios Chinos , Niño , Humanos , Angina Estable/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Metaanálisis como Asunto , Metaanálisis en Red , Revisiones Sistemáticas como AsuntoRESUMEN
ABSTRACT: The initiation of therapy for atherosclerotic cardiovascular disease (ASVCD) is currently guided by cohort-based risk scores. Coronary computed tomographic angiography (CCTA) offers more personalised risk assessments to optimise therapy allocation. This study investigates the utility of CCTA determined coronary stenosis (both obstructive and non-obstructive plaque) to guide allocation of lipid lowering therapy. A retrospective analysis of 450 patients with CCTA performed for the assessment of chest pain at a single centre was conducted. Baseline characteristics, investigations, treatments and clinical outcomes were recorded. The allocation of lipid lowering therapy was evaluated with three models, cohort-based risk score (pooled cohort equation), a previously validated CCTA based clinical risk score (pooled cohort equation and CCTA findings) and CCTA alone (without clinical characteristics). The reclassification analysis included 266 patients. Compared to the cohort-based risk score, CCTA based clinical risk score in total reassigned 23% of patients. CCTA alone compared to the CCTA based clinical risk score correctly reassigned 23% and incorrectly reassigned 10%. When comparing the performance of CCTA alone against the cohort-based risk score, both the additive NRI of 25.8 (95% CI 4.12-37.56) and absolute NRI of 13.2 (95% CI 5.88-19.77) was significant. Revascularisation was required in 3% with a low cohort-based risk, but no patients with low risk as per CCTA alone or CCTA based clinical risk score required revascularisation The use of a CCTA based clinical risk score or CCTA alone compared to cohort-based risk scores can improve the allocation of lipid lowering therapy.
Asunto(s)
Angiografía por Tomografía Computarizada/métodos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Fractional flow reserve (FFR) is considered the standard for assessment of the physiological significance of coronary artery stenosis. Intracoronary papaverine (PAP) is the most potent vasodilator used for the achievement of maximal hyperemia. However, its use can provoke ventricular tachycardia (VT) due to excessive QT prolongation. We evaluated the clinical efficacy and safety of the administration of PAP after nicorandil (NIC), a potassium channel opener that prevents VT, for optimal FFR measurement.A total of 127 patients with 178 stenoses were enrolled. The FFR values were measured using NIC (NIC-FFR) and PAP (PAP-FFR). We administered PAP following NIC (NIC-PAP). Changes in the FFR and electrogram parameters (baseline versus NIC versus PAP) were assessed and the incidence of arrhythmias after PAP was evaluated. In addition, we analyzed another 41 patients with 51 stenoses by assessing the FFR using PAP before NIC (PAP-NIC). After propensity score matching, the electrogram parameters between 2 groups were compared.The mean PAP-FFR was significantly lower than the mean NIC-FFR (0.82 ± 0.11 versus 0.81 ± 0.11, P < 0.05). The mean baseline-QTc, NIC-QTc, and PAP-QTc values were 425 ± 37 ms1/2, 424 ± 41 ms1/2, and 483 ± 54 ms1/2, respectively. VT occurred in only 1 patient (0.6%). Although PAP induced QTc prolongation (P < 0.05), the PAP-QTc duration was significantly shorter in NIC-PAP compared to PAP-NIC (P < 0.05).The administration of PAP with NIC may induce sufficient hyperemia and prevent fatal arrhythmia through reductions in the PAP-induced QTc prolongation during FFR measurement.
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Arritmias Cardíacas/epidemiología , Estenosis Coronaria/tratamiento farmacológico , Reserva del Flujo Fraccional Miocárdico/efectos de los fármacos , Nicorandil/farmacología , Papaverina/farmacología , Taquicardia Ventricular/prevención & control , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Estudios de Casos y Controles , Angiografía Coronaria/métodos , Angiografía Coronaria/estadística & datos numéricos , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/fisiopatología , Quimioterapia Combinada , Electrocardiografía/métodos , Femenino , Reserva del Flujo Fraccional Miocárdico/fisiología , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Humanos , Hiperemia/inducido químicamente , Hiperemia/fisiopatología , Incidencia , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Nicorandil/administración & dosificación , Nicorandil/uso terapéutico , Papaverina/administración & dosificación , Papaverina/efectos adversos , Papaverina/uso terapéutico , Estudios Retrospectivos , Seguridad , Taquicardia Ventricular/inducido químicamente , Taquicardia Ventricular/fisiopatología , Resultado del Tratamiento , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología , Vasodilatadores/uso terapéuticoRESUMEN
It remains inconclusive whether the additional low-density lipoprotein cholesterol (LDL-C) lowering effects of ezetimibe added to statin on coronary atherosclerosis and clinical outcomes are similar to those of statin monotherapy in the setting of comparable LDL-C reduction. We aimed to determine whether there were distinguishable differences in their effects on coronary atherosclerosis with intermediate stenosis between the combination of moderate-intensity statin plus ezetimibe and high-intensity statin monotherapy. Forty-one patients with stable angina undergoing percutaneous coronary intervention were randomized to receive either atorvastatin 10 mg plus ezetimibe 10 mg (ATO10/EZE10) or atorvastatin 40 mg alone (ATO40). The intermediate lesions were evaluated using a near-infrared spectroscopy-intravascular ultrasonography at baseline and after 12 months in 37 patients. The primary endpoint was percent atheroma volume (PAV). Mean LDL-C levels were significantly reduced by 40% and 38% from baseline in the ATO10/EZE10 group (n = 18, from 107 mg/dL to 61 mg/dL) and ATO40 group (n = 19, from 101 mg/dL to 58 mg/dL), respectively, without between-group difference. The absolute change of PAV was -2.9% in the ATO10/EZE10 group and -3.2% in the ATO40 group. The mean difference (95% confidence interval) for the absolute change in PAV between the 2 groups was 0.5% (-2.4% to 2.8%), which did not exceed the pre-defined non-inferiority margin of 5%. There was no significant reduction in lipid core burden index in both groups. In conclusion, the combination of atorvastatin 10 mg and ezetimibe 10 mg showed comparable LDL-C lowering and regression of coronary atherosclerosis in the intermediate lesions, compared with atorvastatin 40 mg alone.
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Anticolesterolemiantes/uso terapéutico , Atorvastatina/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Ezetimiba/uso terapéutico , Placa Aterosclerótica/tratamiento farmacológico , Anciano , LDL-Colesterol , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Espectroscopía Infrarroja Corta , Ultrasonografía IntervencionalRESUMEN
Coronary artery (CA) stenosis is a detrimental and often life-threatening sequela in Kawasaki disease (KD) patients with coronary artery aneurysm (CAA). Therapeutic strategies for these patients have not yet been established. All-trans-retinoic acid (atRA) is a modulator of smooth muscle cell functions. The purpose of this study was to investigate the effect of atRA on CA stenosis in a mouse model of KD. Lactobacillus casei cell wall extract (LCWE) was intraperitoneally injected into 5-week-old male C57BL/6 J mice to induce CA stenosis. Two weeks later, the mice were orally administered atRA (30 mg/kg) 5 days per week for 14 weeks (LCWE + atRA group, n = 7). Mice in the untreated group (LCWE group, n = 6) received corn oil alone. Control mice were injected with phosphate-buffered saline (PBS, n = 5). Treatment with atRA significantly suppressed CA inflammation (19.3 ± 2.8 vs 4.4 ± 2.8, p < 0.0001) and reduced the incidence of CA stenosis (100% vs 18.5%, p < 0.05). In addition, atRA suppressed the migration of human coronary artery smooth muscle cells (HCASMCs) induced by platelet-derived growth factor subunit B homodimer (PDGF-BB). In conclusion, atRA dramatically alleviated CA stenosis by suppressing SMC migration. Therefore, it is expected to have clinical applications preventing CA stenosis in KD patients with CAA.
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Aneurisma/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Tretinoina/farmacología , Aneurisma/inducido químicamente , Aneurisma/patología , Animales , Movimiento Celular/efectos de los fármacos , Pared Celular/química , Estenosis Coronaria/inducido químicamente , Estenosis Coronaria/patología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Modelos Animales de Enfermedad , Humanos , Lacticaseibacillus casei/química , Lipopolisacáridos/química , Lipopolisacáridos/toxicidad , Ratones , Síndrome Mucocutáneo Linfonodular/inducido químicamente , Síndrome Mucocutáneo Linfonodular/patología , Miocitos del Músculo Liso/efectos de los fármacosAsunto(s)
Estenosis Coronaria/tratamiento farmacológico , Reserva del Flujo Fraccional Miocárdico/efectos de los fármacos , Hiperemia/inducido químicamente , Papaverina/administración & dosificación , Resistencia Vascular/efectos de los fármacos , Anciano , Estenosis Coronaria/fisiopatología , Vasos Coronarios , Femenino , Humanos , Hiperemia/fisiopatología , Inyecciones Intraarteriales , Masculino , Persona de Mediana Edad , Vasodilatadores/administración & dosificaciónRESUMEN
BACKGROUND: The difference of chronic neointimal conditions of biodegradable polymer-coated and durable polymer-coated drug-eluting stent have not been well investigated. OBJECTIVE: We aimed to compare the angioscopic findings among SYNERGY biodegradable polymer-coated everolimus-eluting stent (BP-EES), ULTIMASTER biodegradable polymer-coated sirolimus-eluting stent (BP-SES), and XIENCE Alpine durable polymer-coated everolimus-eluting stent (DP-EES) 8 months after stent implantation. METHODS: Patients who underwent implantation of BP-EES (n = 30), BP-SES (n = 26), or DP-EES (n = 21) in Osaka Rosai Hospital from December 2015 to April 2017 were retrospectively enrolled. Coronary angioscopic evaluation including dominant grade of neointimal coverage (NIC) over the stent, maximum yellow plaque grade, and existence of red thrombi were performed 8 months after stent implantation. The incidence of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, and target vessel revascularization were assessed 1 year after coronary angioscopic evaluation among the three groups. RESULTS: The patient and lesion characteristics were similar among the three groups. Dominant grade of NIC and maximum yellow plaque grade were not significantly different among BP-EES, BP-SES, and DP-EES groups [mean ± SD, 1.50 ± 0.73, 1.58 ± 0.64, and 1.33 ± 0.48 (P = 0.38) and 0.83 ± 0.59, 0.81 ± 0.75, and 0.95 ± 0.38 (P = 0.68), respectively]. The existence of red thrombi was similar among the three groups [20, 12, and 19% (P = 0.67)]. There was no significant difference in the MACE 1 year after coronary angioscopic evaluation among the three groups [0, 8, and 0% (P = 0.13)]. CONCLUSIONS: Coronary angioscopic findings revealed that BP-EES, BP-SES, and DP-EES produced similar favorable NIC 8 months after stent implantation.
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Angiografía Coronaria , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Everolimus/administración & dosificación , Inmunosupresores/administración & dosificación , Stents , Anciano , Materiales Biocompatibles Revestidos , Stents Liberadores de Fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polímeros , Estudios RetrospectivosRESUMEN
BACKGROUND: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild. OBJECTIVES: This study sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques. METHODS: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically nonobstructive stenosis not intended for PCI but with IVUS plaque burden of ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) versus GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (nonpowered) safety endpoint was randomized target lesion failure (cardiac death, target vessel-related MI, or clinically driven target lesion revascularization) at 24 months. The secondary (nonpowered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (cardiac death, MI, unstable angina, or progressive angina) at latest follow-up. RESULTS: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by near-infrared spectroscopy-IVUS, the median plaque burden was 73.7%, the median MLA was 2.9 mm2, and the median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and the median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9 ± 2.6 mm2 compared with 3.0 ± 1.0 mm2 in GDMT alone-treated lesions (least square means difference: 3.9 mm2; 95% confidence interval: 3.3 to 4.5; p < 0.0001). Target lesion failure at 24 months occurred in similar rates of BVS-treated and GDMT alone-treated patients (4.3% vs. 4.5%; p = 0.96). Randomized lesion-related major adverse cardiac events occurred in 4.3% of BVS-treated patients versus 10.7% of GDMT alone-treated patients (odds ratio: 0.38; 95% confidence interval: 0.11 to 1.28; p = 0.12). CONCLUSIONS: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA, and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial. (PROSPECT ABSORB [Providing Regional Observations to Study Predictors of Events in the Coronary Tree II Combined with a Randomized, Controlled, Intervention Trial]; NCT02171065).
Asunto(s)
Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/estadística & datos numéricos , Placa Aterosclerótica/cirugía , Implantes Absorbibles , Anciano , Implantación de Prótesis Vascular , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/cirugía , Terapia Antiplaquetaria Doble , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/tratamiento farmacológico , Stents , Ultrasonografía IntervencionalRESUMEN
The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.
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Anastomosis Quirúrgica/efectos adversos , Esófago/cirugía , Dilatación Gástrica/etiología , Infarto de la Pared Inferior del Miocardio/etiología , Estómago/cirugía , Enfermedad Aguda , Anciano , Benzamidas/uso terapéutico , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/etiología , Electrocardiografía , Esofagectomía/métodos , Esófago/diagnóstico por imagen , Dilatación Gástrica/diagnóstico por imagen , Dilatación Gástrica/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Gastroparesia/diagnóstico por imagen , Gastroparesia/tratamiento farmacológico , Gastroparesia/etiología , Humanos , Infarto de la Pared Inferior del Miocardio/diagnóstico , Masculino , Morfolinas/uso terapéutico , Estómago/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Cavidad Torácica/diagnóstico por imagenRESUMEN
Abstract The universal definition of myocardial infarction (MI) provides five subtypes of acute myocardial infarction (AMI). We present an interesting case of a type 2 myocardial infarction caused by the dilation of the left thoracic stomach.