RESUMEN
Small GTPases cycle between an inactive GDP-bound and an active GTP-bound state to control various cellular events, such as cell proliferation, cytoskeleton organization, and membrane trafficking. Clarifying the guanine nucleotide-bound states of small GTPases is vital for understanding the regulation of small GTPase functions and the subsequent cellular responses. Although several methods have been developed to analyze small GTPase activities, our knowledge of the activities for many small GTPases is limited, partly because of the lack of versatile methods to estimate small GTPase activity without unique probes and specialized equipment. In the present study, we developed a versatile and straightforward HPLC-based assay to analyze the activation status of small GTPases by directly quantifying the amounts of guanine nucleotides bound to them. This assay was validated by analyzing the RAS-subfamily GTPases, including HRAS, which showed that the ratios of GTP-bound forms were comparable with those obtained in previous studies. Furthermore, we applied this assay to the investigation of psychiatric disorder-associated mutations of RHEB (RHEB/P37L and RHEB/S68P), revealing that both mutations cause an increase in the ratio of the GTP-bound form in cells. Mechanistically, loss of sensitivity to TSC2 (a GTPase-activating protein for RHEB) for RHEB/P37L, as well as both decreased sensitivity to TSC2 and accelerated guanine-nucleotide exchange for RHEB/S68P, is involved in the increase of their GTP-bound forms, respectively. In summary, the HPLC-based assay developed in this study provides a valuable tool for analyzing small GTPases for which the activities and regulatory mechanisms are less well understood.
Asunto(s)
Trastornos Mentales , Mutación Missense , Proteína Homóloga de Ras Enriquecida en el Cerebro , Sustitución de Aminoácidos , Cromatografía Líquida de Alta Presión , Activación Enzimática/genética , Células HEK293 , Células HeLa , Humanos , Trastornos Mentales/enzimología , Trastornos Mentales/genética , Proteína Homóloga de Ras Enriquecida en el Cerebro/genética , Proteína Homóloga de Ras Enriquecida en el Cerebro/metabolismoRESUMEN
Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1 month, and 1 year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1 year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1 year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.
Asunto(s)
Síndrome Coronario Agudo , Aterosclerosis , Placa Aterosclerótica , Síndrome Coronario Agudo/complicaciones , Angiografía Coronaria/métodos , Humanos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/tratamiento farmacológico , Tirofibán/uso terapéutico , Tomografía de Coherencia Óptica/métodosRESUMEN
Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p < 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively.
Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patología , Vasos Coronarios/patología , Proteína C-Reactiva/análisis , Protrombina/metabolismo , Creatinina , Interleucina-6 , Ultrasonografía Intervencional/métodos , Valor Predictivo de las Pruebas , Tomografía de Coherencia Óptica/métodos , Biomarcadores , Fibrinógeno/metabolismo , Homocisteína/metabolismo , Inflamación/patología , Ácidos y Sales Biliares/metabolismo , Angiografía CoronariaRESUMEN
OBJECTIVES: To compare the postprocedural optical coherence tomography (OCT) findings and in-hospital outcomes among the three subtypes of calcified plaques: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion. BACKGROUND: Recently, three subtypes of calcified culprit plaques were reported in patients with acute coronary syndrome (ACS). How these subtypes respond to stenting is unknown. METHODS: ACS patients with calcified plaque at the culprit lesion were selected from our database. OCT findings at baseline and after stent implantation were compared. RESULTS: In the final analysis, 87 cases were included. Preprocedural OCT showed eruptive calcified nodules in 19 (21.8%) cases, superficial calcific sheet in 63 (72.4%), and calcified protrusion in 5 (5.7%). Stent edge dissection (SED) and incomplete stent apposition (ISA) were frequently observed in the eruptive calcified nodules group compared to superficial calcific sheet or calcified protrusion (SED; 47.4% vs. 17.5% vs. 20.0%; p = .032, ISA; 94.7% vs. 58.7% vs. 0.0%; p < .001). The superficial calcific sheet group had the smallest minimal stent area (MSA) among the three groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 6.29 ± 2.41 vs. 4.72 ± 1.37 vs. 6.56 ± 1.13; p = .007). The superficial calcific sheet group had a higher rate of periprocedural myocardial infarction compared to the eruptive calcified nodules group (60.3% vs. 31.6%; p = .028). CONCLUSIONS: This study demonstrated eruptive calcified nodules are associated with higher incidence of SED and ISA, whereas superficial calcific sheets are associated with small MSA and higher periprocedural myocardial infarction.
Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Placa Aterosclerótica , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/etiología , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Humanos , Intervención Coronaria Percutánea/efectos adversos , Stents , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the non-culprit plaques (NCPs) characteristics in acute coronary syndrome (ACS) patients with calcified plaques (CP). BACKGROUND: Recently, a new in vivo classification of calcified culprit plaques in patients with ACS was proposed. Characteristics of NCPs in this group of patients are unknown. METHODS: A total of 692 NCPs from 492 ACS patients were retrospectively compared based on the culprit plaque phenotype: 71 from CP patients, 383 from plaque rupture (PR) patients, 238 from plaque erosion (PE) patients. RESULTS: NCPs of CP patients had greater maximal calcium thickness, wider calcium arc, longer calcium length, and greater calcium index, compared to PR or PE patients (CP vs. PR: all p < .001, CP vs. PE: all p < .001). Thin-cap fibroatheroma was less prevalent (p = .023), fibrous cap was thicker (p = .035), and mean lipid arc was narrower in CP than in PR (p < .001). CONCLUSIONS: In conclusion, NCPs of CP patients had greater calcium burden and less vulnerability. This information may help to better understand the underlying mechanisms of ACS and to develop strategy for tailored management.
Asunto(s)
Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/etiología , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
OBJECTIVES: This study aimed to investigate the vascular response of lesions with a layered phenotype. BACKGROUND: Recent studies have shown that layered plaques at culprit lesions detected by optical coherence tomography (OCT) have greater plaque burden and more inflammatory features than non-layered plaques. METHODS: This is a retrospective observational study. A total of 193 target lesions from 193 patients [100 patients with acute coronary syndromes (ACS) and 93 with stable angina pectoris (SAP)] who had undergone OCT imaging of the culprit lesion both before and after stenting were included. Layered plaques were identified by OCT as plaques with layers of different optical density. Patients were divided into two groups based on the presence or absence of a layered phenotype at the culprit lesion, and pre- and post-procedure OCT findings were compared. RESULTS: Among 193 patients, 36 (36.0%) lesions in ACS patients and 56 (60.2%) lesions in SAP patients were found to have a layered phenotype at the culprit lesion. At baseline, percent area stenosis was greater in layered plaque than in non-layered plaque (p = .019). Following stent implantation, the stent expansion ratio and mean stent eccentricity index were significantly lower in layered plaques than in non-layered plaques (p = .041, p = .017, respectively), mainly derived from ACS patients. CONCLUSION: Following stent implantation, plaques with a layered phenotype had less stent expansion and more eccentric lumens. Aggressive balloon dilation may be required to obtain optimal stent outcomes in patients with a layered plaque phenotype at the culprit lesion.
Asunto(s)
Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Humanos , Stents , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.
Asunto(s)
Angina Estable/patología , Placa Aterosclerótica/patología , Anciano , Enfermedad de la Arteria Coronaria/patología , Estenosis Coronaria/patología , Trombosis Coronaria/patología , Vasos Coronarios/patología , Femenino , Humanos , Lípidos/análisis , Macrófagos/patología , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Calcificación Vascular/patologíaRESUMEN
As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite: 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.
Asunto(s)
Plaquetas/patología , Trombosis Coronaria/patología , Placa Aterosclerótica/patología , Adulto , Anciano , Constricción Patológica/metabolismo , Constricción Patológica/patología , Angiografía Coronaria , Trombosis Coronaria/complicaciones , Trombosis Coronaria/metabolismo , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/metabolismo , Plasma Rico en Plaquetas/metabolismoRESUMEN
Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.
Asunto(s)
Síndrome Coronario Agudo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Placa Aterosclerótica , Infarto del Miocardio con Elevación del ST , Trombosis , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Angiografía Coronaria , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Placa Aterosclerótica/diagnóstico por imagen , Inhibidores de Agregación Plaquetaria/uso terapéutico , Infarto del Miocardio con Elevación del ST/complicaciones , Tomografía de Coherencia ÓpticaRESUMEN
Previous studies have reported a circadian variation in the onset of ST-segment elevation myocardial infarction (STEMI). However, underlying mechanisms for the circadian variation have not been fully elucidated. We investigated the relationship between onset of STEMI and the underlying pathology using optical coherence tomography (OCT). Patients with a diagnosis of STEMI were selected from a multicenter OCT registry. Patients were divided into 4 groups based on the estimated time of onset (00:00-05:59, 06:00-11:59, 12:00-17:59, or 18:00-23:59). Underlying pathologies of MI (plaque rupture, plaque erosion, and calcified plaque) were compared among the 4 groups. Among 648 patients, plaque rupture was diagnosed in 386 patients (59.6%), plaque erosion in 197 patients (30.4%), and calcified plaque in 65 patients (10.0%). A marked circadian variation was detected in the incidence of plaque rupture with a peak at 09:00, whereas it was not evident in plaque erosion or calcified plaque. The probability of plaque rupture significantly increased in the periods of 06:00-11:59 [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.30-3.49, p = 0.002] and 12:00-17:59 (OR 2.10, 95% CI 1.23-3.58, p = 0.005), compared to the period of 00:00-05:59. This circadian pattern was observed only during weekdays (p = 0.010) and it was not evident during the weekend (p = 0.742). Plaque rupture occurred most frequently in the morning and this circadian variation was evident only during weekdays. Acute MI caused by plaque rupture may be related to catecholamine surge.
Asunto(s)
Placa Aterosclerótica/patología , Infarto del Miocardio con Elevación del ST/patología , Anciano , Ritmo Circadiano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Tomografía de Coherencia ÓpticaRESUMEN
Recent studies have shown that healed plaque at the culprit lesion detected by optical coherence tomography (OCT) is a sign of pan-vascular vulnerability and advanced atherosclerosis. However, the clinical significance of healed plaque is unknown. A total of 265 patients who had OCT imaging of a culprit vessel and 2-year clinical follow-up data were included. Patients were stratified based on the presence or absence of a layered plaque phenotype, defined as layers of different optical density by OCT at either culprit or non-culprit lesions. The association between layered plaque and major adverse cardiac events (MACE), defined as cardiac death, acute coronary syndromes (ACS), or revascularization, was studied. Among 265 patients, 96 (36.2%) had the layered plaque phenotype. Layered plaque was more frequently observed in stable angina pectoris patients than in ACS patients (57.8%vs. 25.1%, p < 0.001). The average clinical follow-up period was 672 ± 172 days. Cumulative MACE was significantly higher in patients with layered plaque (p = 0.041), which was primarily driven by the high revascularization rate at 2 years (p = 0.002). Multivariate regression analysis showed that presence of layered plaque and low-density lipoprotein cholesterol levels were independently associated with an increased risk of revascularization (p = 0.026, p = 0.008, respectively). Patients with healed plaque in the culprit vessel had a higher incidence of revascularization, as compared to those without healed plaque, at 2 years.
Asunto(s)
Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Vasos Coronarios , Infarto del Miocardio , Placa Aterosclerótica , Tomografía de Coherencia Óptica/métodos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/terapia , Angina Estable/diagnóstico , Angina Estable/fisiopatología , LDL-Colesterol/sangre , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Revascularización Miocárdica/métodos , Revascularización Miocárdica/estadística & datos numéricos , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Placa Aterosclerótica/fisiopatología , PronósticoRESUMEN
Healed coronary plaques, morphologically characterized by a layered pattern, are signatures of previous plaque disruption and healing. Recent optical coherence tomography (OCT) studies showed that layered plaque is associated with vascular vulnerability. However, factors associated with layered plaques have not been studied. The aim of this study was to investigate predictors for layered plaque at the culprit plaques and at non-culprit plaques. Patients with coronary artery disease who underwent pre-intervention OCT imaging of the culprit lesion were included. Layered plaques were defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components. Among 313 patients, layered plaque at the culprit lesion was observed in 18.8% of ST-segment elevation myocardial infarction patients, 36.3% of non-ST-segment elevation acute coronary syndrome patients, and 53.4% of stable angina pectoris (SAP) patients (p < 0.001). In the multivariable model, SAP, multivessel disease, type B2/C lesion, and diameter stenosis > 70% were independent predictors for layered plaque at the culprit lesion. In addition, 394 non-culprit plaques in 190 patients were assessed to explore predictors for layered plaques at non-culprit lesions. SAP, and thin-cap fibroatheroma and layered plaque at the culprit lesion were independent predictors for layered plaques at non-culprit lesions. In conclusion, clinical presentation of SAP was a strong predictor for layered plaque at both culprit plaques and non-culprit plaques. Development and biologic significance of layered plaques may be related to a balance between pan-vascular vulnerability and endogenous anti-thrombotic protective mechanism.
Asunto(s)
Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria/diagnóstico , Vasos Coronarios , Infarto del Miocardio , Placa Aterosclerótica , Tomografía de Coherencia Óptica/métodos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/fisiopatología , Angina Estable/diagnóstico , Angina Estable/fisiopatología , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Placa Aterosclerótica/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
Corticosteroids have been used for the treatment of a great variety of diseases. Therefore, the relationship between high doses of cortisol and infections has been widely known and prophylactic therapy has been established. Adrenocortical carcinoma is a rare malignancy with poor prognosis, so little is known about how to deal with the complications resulting from hormone excess such as Cushing's syndrome. Here we report a case of an 82-year-old woman who presented with a 1-day history of dyspnea and was finally diagnosed as disseminated cryptococcosis at autopsy. The patient had received a diagnosis of metastatic adrenocortical carcinoma and Cushing's syndrome three months earlier. The findings of this study indicate the relation between severe hypercortisolemia due to adrenocortical carcinoma and opportunistic infections. In the setting of adrenocortical carcinoma with Cushing's syndrome, clinicians should maintain a high index of suspicion for opportunistic infections including cryptococcosis, which are potentially treatable by early detection and prompt intervention.
Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Criptococosis , Síndrome de Cushing , Neoplasias de la Corteza Suprarrenal/complicaciones , Carcinoma Corticosuprarrenal/complicaciones , Carcinoma Corticosuprarrenal/diagnóstico , Anciano de 80 o más Años , Criptococosis/complicaciones , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Síndrome de Cushing/diagnóstico , Femenino , HumanosRESUMEN
OBJECTIVES: The aim of this study is to investigate the association between fractional flow reserve (FFR) values and change in coronary physiological indices after elective percutaneous coronary intervention (PCI). BACKGROUND: Decision making for revascularization when FFR is 0.75-0.80 is controversial. METHODS: A retrospective analysis was performed of 296 patients with stable angina pectoris who underwent physiological examinations before and after PCI. To investigate the differences of coronary flow improvement between territories with low-FFR (<0.75) and grey-zone FFR (0.75-0.80), serial changes in physiological indices including mean transit time (Tmn), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were compared between these two groups. RESULTS: Compared to low-FFR territories, grey-zone FFR territories showed significantly lower prevalence of Tmn shortening, CFR improvement, and decrease in IMR (Tmn shorting, 63.9% vs. 87.0%, P < .001; CFR improvement, 63.0% vs. 75.7%, P = .019; IMR decrease, 51.3% vs. 63.3%, P = .040) and lower extent of their absolute changes (Tmn shorting, 0.06 (-0.03 to 0.16) vs. 0.22 (0.07-0.45), P < .001; CFR improvement, 0.45 (-0.32 to 1.87) vs. 1.08 (0.02-2.44), P < .01; IMR decrease, 0.2 (-44.0 to 31.3) vs. 2.9 (-2.9 to 11.8), P = .022). Multivariate analysis showed that pre-PCI IMR predicted improved coronary flow profile in both groups, whereas pre-PCI FFR predicted increased coronary flow indices in low-FFR territories. CONCLUSIONS: Worsening of physiological indices after PCI was not uncommon in territories showing grey-zone FFR. Physiological assessment combining FFR and IMR may help identify patients who may benefit by PCI, particularly those in the grey zone.
Asunto(s)
Angina Estable/terapia , Cateterismo Cardíaco , Enfermedad de la Arteria Coronaria/terapia , Reserva del Flujo Fraccional Miocárdico , Microcirculación , Intervención Coronaria Percutánea , Resistencia Vascular , Anciano , Angina Estable/diagnóstico , Angina Estable/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Epicardial focal coronary artery stenosis, diffuse coronary disease, and microvascular resistance (MR) may limit coronary flow. The purpose of percutaneous coronary intervention (PCI) is to increase coronary flow by targeting epicardial lesions. After PCI, MR might change and affect coronary flow. We investigated whether PCI influences MR using the index of microcirculatory resistance (IMR) and if pre-PCI fractional flow reserve (FFR) or MR predicts the post-PCI change in hyperaemic coronary flow. METHODS AND RESULTS: This prospective study included 245 vessels from 229 patients with stable angina pectoris undergoing elective PCI. FFR and IMR were measured before and after PCI. Post-PCI increase in hyperaemic coronary flow was assessed using the change in thermodilution-derived transit time (pre-PCI Tmn - post-PCI Tmn ). IMR significantly decreased after PCI (median 1.9; interquartile range, -4.9 to 10.1) and was significantly associated with pre-PCI IMR (r = 0.70, P < 0.001). Increased coronary flow was significantly correlated with pre-PCI IMR (r = 0.62, P < 0.001) and pre-PCI FFR (r = 0.51, P < 0.001). In multivariate analysis, factors significantly associated with decreased post-PCI IMR were pre-PCI IMR (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.19; P < 0.001) and angiographic reference diameter (OR, 2.44; 95% CI; 1.09-5.48; P = 0.03). Factors significantly associated with increased coronary flow post-PCI were pre-PCI IMR (OR, 1.15; 95% CI, 1.08-1.23; P < 0.001) and pre-PCI FFR (OR, <0.001; 95% CI, 0.000-0.003; P < 0.001). CONCLUSION: PCI affected MR. Pre-PCI FFR and MR were independent predictors of post-PCI changes in hyperaemic coronary flow. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Angina Estable/terapia , Estenosis Coronaria/terapia , Vasos Coronarios/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Hiperemia/fisiopatología , Microcirculación , Intervención Coronaria Percutánea , Resistencia Vascular , Anciano , Angina Estable/diagnóstico , Angina Estable/fisiopatología , Cateterismo Cardíaco/instrumentación , Distribución de Chi-Cuadrado , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/fisiopatología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Termodilución , Transductores de Presión , Resultado del TratamientoRESUMEN
BACKGROUND: The effect of prior use of aspirin (ASA) on the onset of acute coronary syndrome (ACS) has not been clarified. This study used optical coherence tomography (OCT) to investigate the morphological features of culprit lesions of ACS in patients with prior ASA use.MethodsâandâResults:In total, 442 patients with their first ACS episode undergoing OCT for the culprit lesions were investigated. Clinical characteristics, OCT findings, and adverse events at 30 days were compared between patients with prior ASA use and ASA-naïve patients (non-ASA). 67 patients (15.2%) had received ASA at presentation. The ASA group was older, had higher frequency of dyslipidemia and hypertension, and lower renal function than the non-ASA group. Non-ST-elevation ACS was more prevalent in the ASA than in the non-ASA group (79.1 vs. 53.6%, P<0.001). Propensity score matching yielded 49 patients in both groups. OCT revealed less frequent thrombi in the ASA than in the non-ASA group in both the entire (37.3 vs. 75.2%, P<0.001) and score-matched cohorts (38.8 vs. 75.5%, P<0.001), whereas no significant difference was observed in plaque characteristics. Rate of adverse events did not differ between the ASA and the non-ASA groups in the matched cohort. CONCLUSIONS: With a first ACS presentation, patients with prior ASA use were more likely to present with non-ST-elevation ACS with less frequent intraluminal thrombi, but no significant difference in underlying plaque characteristics or clinical course.
Asunto(s)
Síndrome Coronario Agudo/patología , Aspirina/farmacología , Tomografía de Coherencia Óptica/métodos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/tratamiento farmacológico , Factores de Edad , Anciano , Estudios de Casos y Controles , Dislipidemias/etiología , Femenino , Humanos , Hipertensión/etiología , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Trombosis/etiologíaRESUMEN
BACKGROUND: The relationship between the features of morphologically unstable plaque and physiological lesion severity remains elusive. We aimed to investigate this relationship using optical coherence tomography (OCT)-derived high-risk plaque characteristics and fractional flow reserve (FFR) as the degree of anatomical and physiological stenosis severity.MethodsâandâResults:We investigated 286 de novo intermediate and severe coronary lesions in 248 patients who underwent OCT and FFR examinations. Lesions were divided into tertiles based on either FFR or quantitative coronary angiographic diameter stenosis (QCA-%DS). The OCT findings were compared among the tertiles of FFR and QCA-%DS. FFR and QCA tertiles were defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74≤FFR≤0.81), and FFR-T3 (FFR >0.81); and QCA-T1 (%DS ≥61%), QCA-T2 (51%≤%DS<61%), and QCA-T3 (%DS <51%). The prevalence of thin-cap fibroatheroma (TCFA) was significantly greater in FFR-T1 (20.0%) than in FFR-T2 and FFR-T3 (7.0%, P=0.03 and 7.7%, P=0.04, respectively), although no significant differences were observed among the QCA tertiles. CONCLUSIONS: Physiological severity of coronary stenosis evaluated by FFR correlated with plaque instability in terms of TCFA. Preferable clinical outcomes for lesions with negative FFR based on the existing clinical evidence might be attributable to less likelihood of TCFA.
Asunto(s)
Constricción Patológica/patología , Placa Aterosclerótica/patología , Anciano , Estenosis Coronaria , Femenino , Reserva del Flujo Fraccional Miocárdico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Índice de Severidad de la Enfermedad , Tomografía de Coherencia Óptica/métodosRESUMEN
Specific signatures of culprit lesions detected on multidetector computed tomography (MDCT) were identified as predictors of periprocedural myocardial injury (PMI) after percutaneous coronary intervention (PCI) in patients with stable angina; PMI has been shown to be associated with a worse prognosis. We investigated the association between preprocedural culprit lesion characteristics, assessed by MDCT, and PMI after PCI for chronic total occlusion (CTO). From three medical centers, 81 patients who underwent pre-PCI MDCT and CTO PCI, and systematic cardiac troponin (cTn) sampling before and after PCI, were included. Patients were divided into two groups according to the presence or absence of post-PCI cTn elevation. Patient characteristics, MDCT findings, and procedural variables were compared between the two groups. Procedure success was observed in 65 patients (80.2%) and was not associated with PMI. The incidence of PMI was higher in patients treated with the retrograde versus the antegrade approach. On MDCT, lesion length and the presence of the napkin-ring sign were significantly associated with PMI. Multivariate analysis revealed that the lesion length (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.01-1.08; P < 0.05), napkin-ring sign (OR: 5.41; 95% CI: 1.01-29.0; P < 0.05), and retrograde approach (OR: 4.78; 95% CI: 1.28-15.4; P < 0.05) were significant predictors of PMI. PMI is not uncommon in patients undergoing elective CTO PCI, regardless of procedure success or failure. Pre-PCI MDCT may help identify patients at high risk for PMI after CTO PCI.
Asunto(s)
Lesiones Cardíacas/etiología , Tomografía Computarizada Multidetector , Intervención Coronaria Percutánea/efectos adversos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Estudios RetrospectivosRESUMEN
This study investigates whether hyperemic microvascular resistance (MR) is influenced by elective percutaneous coronary intervention (PCI) by using the index of microcirculatory resistance (IMR). Seventy-one consecutive patients with stable angina pectoris undergoing elective PCI were prospectively studied. The IMR was measured before and after PCI and at the 10-mo follow-up. The IMR significantly decreased until follow-up; the pre-PCI, post-PCI, and follow-up IMRs had a median of 19.8 (interquartile range, 14.6-28.9), 16.2 (11.8-22.1), and 14.8 (11.8-18.7), respectively (P < 0.001). The pre-PCI IMR was significantly correlated with the change in IMR between pre- and post-PCI (r = 0.84, P < 0.001) and between pre-PCI and follow-up (r = 0.93, P < 0.001). Pre-PCI IMR values were significantly higher in territories with decreases in IMR than in those with increases in IMR [pre-PCI IMR: 25.4 (18.4-35.5) vs. 12.5 (9.4-16.8), P < 0.001]. At follow-up, IMR values in territories showing decreases in IMR were significantly lower than those with increases in IMR [IMR at follow-up: 13.9 (10.9-17.6) vs. 16.6 (14.0-21.4), P = 0.013]. The IMR decrease was significantly associated with a greater shortening of mean transit time, indicating increases in coronary flow (P < 0.001). The optimal cut-off values of pre-PCI IMR to predict a decrease in IMR after PCI and at follow-up were 16.8 and 17.0, respectively. In conclusion, elective PCI affected hyperemic MR and its change was associated with pre-PCI MR, resulting in showing a wide distribution. Overall hyperemic MR significantly decreased until follow-up. The modified hyperemic MR introduced by PCI may affect post-PCI coronary flow.
Asunto(s)
Angina Estable/cirugía , Circulación Coronaria/fisiología , Estenosis Coronaria/cirugía , Vasos Coronarios/fisiología , Microvasos/fisiología , Intervención Coronaria Percutánea , Resistencia Vascular/fisiología , Anciano , Angina Estable/fisiopatología , Estudios de Cohortes , Estenosis Coronaria/fisiopatología , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Hiperemia/fisiopatología , Modelos Logísticos , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Right phrenic nerve injury (PNI) is a major concern during superior vena cava (SVC) isolation due to the anatomical close proximity. The functional and histological severity of PNI parallels the degree of the reduction in the compound motor action potential (CMAP) amplitude. This study aimed to evaluate the feasibility of monitoring CMAPs during SVC isolation to anticipate PNI during atrial fibrillation (AF) ablation. METHODS: Thirty-nine paroxysmal AF patients were prospectively enrolled. Radiofrequency energy was delivered point-by-point for 30 seconds with 20 W until eliminating all SVC potentials after the pulmonary vein isolation. Right diaphragmatic CMAPs were obtained from modified surface electrodes by pacing from the right subclavian vein. Radiofrequency applications were applied without fluoroscopy under CMAP monitoring at sites with phrenic nerve capture by high output pacing. RESULTS: Electrical SVC isolation was successfully achieved with a mean of 9.4 ± 3.3 applications in all patients. In 3 (7.5%) patients, the SVC was isolated without radiofrequency delivery at phrenic nerve capture sites. Among a total of 346 applications in the remaining 36 patients, 71 (20.5%) were delivered while monitoring CMAPs. In 1 (1.4%) application, the RF application was interrupted due to a decrease in the CMAP amplitude. However, no PNI was detected on fluoroscopy, and the decreased amplitude recovered spontaneously. The remaining 70 (98.6%) applications exhibited no significant changes in the CMAP amplitude throughout the applications (from 1.01 ± 0.47 to 0.98 ± 0.45 mV, P = 0.383). CONCLUSIONS: Stable right diaphragmatic CMAPs could be obtained, and monitoring CMAPs might be useful for anticipating right PNI during SVC isolation.