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BACKGROUND: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. METHODS AND RESULTS: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin-ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. CONCLUSIONS: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.
Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Placa Aterosclerótica , Tomografia de Coerência Óptica , Humanos , Masculino , Placa Aterosclerótica/diagnóstico por imagem , Feminino , Angiografia por Tomografia Computadorizada/métodos , Tomografia de Coerência Óptica/métodos , Idoso , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Estudos Retrospectivos , Valor Preditivo dos Testes , Diabetes Mellitus/epidemiologia , Calcificação Vascular/diagnóstico por imagem , Remodelação Vascular , FibroseRESUMO
BACKGROUND: Recently, it was reported that noncalcified plaque (NCP) volume was an independent predictor for cardiac events. Pericoronary adipose tissue (PCAT) attenuation is a marker of vascular inflammation and has been associated with increased cardiac mortality. The aim of this study was to evaluate the relationships between NCP volume, plaque vulnerability, and PCAT attenuation. METHODS: Patients who underwent preintervention coronary computed tomography angiography and optical coherence tomography were enrolled. Plaque volume was measured by computed tomography angiography, plaque vulnerability by optical coherence tomography, and the level of coronary inflammation by PCAT attenuation. The plaques were divided into 2 groups of high or low NCP volume based on the median NCP volume. RESULTS: Among 704 plaques in 454 patients, the group with high NCP volume had a higher prevalence of lipid-rich plaque (87.2% versus 75.9%; P<0.001), thin-cap fibroatheroma (38.1% versus 20.7%; P<0.001), macrophage (77.8% versus 63.4%; P<0.001), microvessel (58.2% versus 42.9%; P<0.001), and cholesterol crystal (42.0% versus 26.7%; P<0.001) than the group with low NCP plaque volume. The group with high NCP volume also had higher PCAT attenuation than the group with low NCP volume (-69.6±10.0 versus -73.5±10.6 Hounsfield unit; P<0.001). In multivariable analysis, NCP volume was significantly associated with thin-cap fibroatheroma and high PCAT attenuation. In the analysis of the combination of PCAT attenuation and NCP volume, the prevalence of thin-cap fibroatheroma was the highest in the high PCAT attenuation and high NCP volume group and the lowest in the low PCAT attenuation and low NCP volume group. CONCLUSIONS: Higher NCP volume was associated with higher plaque vulnerability and vascular inflammation. The combination of PCAT attenuation and NCP volume may help identify plaque vulnerability noninvasively. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.
Assuntos
Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodos , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos , Inflamação/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Tecido AdiposoRESUMO
BACKGROUND: High cardiovascular mortality has been reported in young patients with diabetes. However, the underlying pathology in different age groups of patients with diabetes has not been studied. METHODS AND RESULTS: The aim of this study was to investigate the plaque characteristics and underlying pathology of acute coronary syndrome in different age groups of patients with or without diabetes in a large cohort. Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging were included. Culprit plaque was classified as plaque rupture, plaque erosion, or calcified plaque and stratified into 5 age groups. Plaque characteristics including features of vulnerability were examined by optical coherence tomography. Among 1394 patients, 482 (34.6%) had diabetes. Patients with diabetes, compared with patients without diabetes, had a higher prevalence of lipid-rich plaque (71.2% versus 64.8%, P=0.016), macrophage (72.0% versus 62.6%, P<0.001), and cholesterol crystal (27.6% versus 19.7%, P<0.001). Both diabetes and nondiabetes groups showed a decreasing trend in plaque erosion with age (patients with diabetes, P=0.020; patients without diabetes, P<0.001). Patients without diabetes showed an increasing trend with age in plaque rupture (P=0.004) and lipid-rich plaque (P=0.018), whereas patients with diabetes had a high prevalence of these vulnerable features at an early age that remained high across age groups. CONCLUSIONS: Patients without diabetes showed an increasing trend with age in plaque rupture and lipid-rich plaque, whereas patients with diabetes had a high prevalence of these vulnerable features at an early age. These results suggest that atherosclerotic vascular changes with increased vulnerability start at a younger age in patients with diabetes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04523194, NCT03479723. URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041692.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Diabetes Mellitus , Placa Aterosclerótica , Humanos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/patologia , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Lipídeos , Placa Aterosclerótica/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodosRESUMO
Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.
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Doenças Cardiovasculares , Hematínicos , Insuficiência Renal Crônica , Adulto , Humanos , Hematínicos/uso terapêutico , Diálise Renal , Eritropoese , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Darbepoetina alfa/uso terapêuticoRESUMO
Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.
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Aterosclerose , Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Placa Aterosclerótica , Aterosclerose/patologia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Humanos , Infarto do Miocárdio/complicações , Placa Aterosclerótica/patologia , Stents , Tomografia de Coerência Óptica/métodosRESUMO
AIMS: The aim of the present study was to consider whether the ultrastructural features of cardiomyocytes in dilated cardiomyopathy can be used to guide genetic testing. METHODS AND RESULTS: Endomyocardial biopsy and whole-exome sequencing were performed in 32 consecutive sporadic dilated cardiomyopathy patients [51.0 (40.0-64.0) years, 75% men] in initial phases of decompensated heart failure. The predicted pathogenicity of ultrarare (minor allele frequency ≤0.0005), non-synonymous variants was determined using the American College of Medical Genetics guidelines. Focusing on 75 cardiomyopathy-susceptibility and 41 arrhythmia-susceptibility genes, we identified 404 gene variants, of which 15 were considered pathogenic or likely pathogenic in 14 patients (44% of 32). There were five sarcomeric gene variants (29% of 17 variants) found in five patients (16% of 32), involving a variant of MYBPC3 and four variants of TTN. A patient with an MYBPC3 variant showed disorganized sarcomeres, three patients with TTN variants located in the region encoding the A-band domain showed sparse sarcomeres, and a patient with a TTN variant in encoding the I-band domain showed disrupted sarcomeres. The distribution of diffuse myofilament lysis depended on the causal genes; three patients with the same TMEM43 variant had diffuse myofilament lysis near nuclei (P = 0.011), while two patients with different DSP variants had lysis in the peripheral areas of cardiomyocytes (P = 0.033). CONCLUSIONS: Derangement patterns of myofilament and subcellular distribution of myofilament lysis might implicate causal genes. Large-scale studies are required to confirm whether these ultrastructural findings are related to the causative genes.
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Cardiomiopatia Dilatada , Insuficiência Cardíaca , Miocárdio , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Proteínas de Transporte/genética , Conectina/genética , Desmoplaquinas/genética , Feminino , Testes Genéticos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/ultraestrutura , Miofibrilas/patologia , Sarcômeros/genética , Sarcômeros/patologiaRESUMO
Pathological studies have suggested that features of vulnerable atherosclerotic plaques likely to progress and lead to acute cardiovascular events have specific characteristics. Given the progress of intravascular coronary imaging technology, some large prospective studies have detected features of vulnerable atherosclerotic plaques using these imaging modalities. However, the rate of cardiovascular events, such as acute coronary syndrome, has been found to be considerably reduced in the limited follow-up period available in the statin era. Additionally, not all disrupted plaques lead to thrombus formation with clinical presentation. If sub-occlusive or occlusive thrombus formation does not occur, a thrombus on a disrupted plaque will organize without any symptoms, forming a "healed plaque". Although vulnerable plaque detection using intracoronary imaging is focused on "thin-cap fibroatheroma" leading to plaque rupture, superficial plaque erosion is increasingly recognized; however, the underlying mechanism of thrombus formation on eroded plaques is not well understood. One of intravascular imaging, optical coherence tomography (OCT) has the highest image resolution and has enabled detailed characterization of the plaque in vivo. Here, we reviewed the status and limitations of intravascular imaging in terms of detecting vulnerable plaque through mainly OCT studies. We suggested that vulnerable plaque should be reconsidered in terms of eroded plaque and healed plaque and that both plaque and circulating blood should be assessed in greater detail accordingly.
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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.
Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Angiografia Coronária , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/diagnóstico por imagem , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Tomografia de Coerência ÓpticaRESUMO
BACKGROUND: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN. METHODS: Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed. RESULTS: The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 µg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). CONCLUSIONS: Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.
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Anemia/tratamento farmacológico , Darbepoetina alfa/uso terapêutico , Insuficiência Renal Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise RenalRESUMO
BACKGROUND: Although heart failure (HF) with preserved ejection fraction (HFpEF) is more common in postmenopausal women than in men, the effect of sex hormones on cardiac diastolic function remains unclear. We examined the effect of gonadectomy with or without the angiotensin receptor blocker olmesartan (Olm) in an isoproterenol (ISO) -induced mouse model of left ventricular hypertrophy (LVH) and cardiac diastolic dysfunction. METHODS: ISO or ISO with Olm were administered for 28 days in sham-operated male and female, castrated (CAS), and ovariectomized (OVX) mice. LV ejection fraction (EF) and E/A ratio were analyzed by echocardiography, and the LV and lung weight corrected by tibial length were used as indices of LVH and lung congestion, respectively. RESULTS: On echocardiography, systolic function did not differ between the four groups. LV/tibial length (TL) and Lung/TL significantly increased in all groups. The LV/TL ratio was lower in castrated-ISO vs. Male-Sham-ISO but did not differ between Female-Sham-ISO and OVX-ISO. However, the Lung/TL ratio of OVX-ISO was greater than that of Female-Sham-ISO. Olm prevented LV hypertrophy in all groups. The decrease in E/A and increase in lung weight were improved by Olm in Male-Sham and OVX-ISO but not in the other groups. CONCLUSION: These sex differences suggest that sex hormones play a pivotal role in modulating cardiac hypertrophy and diastolic dysfunction induced by chronic ß-adrenoceptor stimulation, and thus affect the therapeutic potential of angiotensin receptor blockade.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Cardiomegalia/etiologia , Cardiomegalia/prevenção & controle , Castração/efeitos adversos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Imidazóis/uso terapêutico , Isoproterenol/efeitos adversos , Tetrazóis/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Animais , Cardiomegalia/diagnóstico , Cardiomegalia/fisiopatologia , Diástole , Modelos Animais de Doenças , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Humanos , Imidazóis/farmacologia , Masculino , Camundongos Endogâmicos , Volume Sistólico , Tetrazóis/farmacologiaRESUMO
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.
Assuntos
Plaquetas/patologia , Trombose Coronária/patologia , Placa Aterosclerótica/patologia , Adulto , Idoso , Constrição Patológica/metabolismo , Constrição Patológica/patologia , Angiografia Coronária , Trombose Coronária/complicações , Trombose Coronária/metabolismo , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/metabolismo , Plasma Rico em Plaquetas/metabolismoRESUMO
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.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Placa Aterosclerótica , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/terapia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Humanos , Stents , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
ß3-Adrenergic receptor expression is enhanced in the failing heart, but its functional effects are unclear. We tested the hypothesis that a ß3-agonist improves left ventricular (LV) performance in heart failure. We examined the chronic effects of a ß3-agonist in the angiotensin II (Ang II)-induced cardiomyopathy mouse model. C57BL/6J mice were treated with Ang II alone or Ang II + BRL 37344 (ß3-agonist, BRL) for 4 weeks. Systolic blood pressure in conscious mice was significantly elevated in Ang II and Ang II + BRL mice compared with control mice. Heart rate was not different among the three groups. Systolic performance parameters that were measured by echocardiography and an LV catheter were similar among the groups. LV end-diastolic pressure and end-diastolic pressure-volume relationships were higher in Ang II mice compared with control mice. However, the increase in these parameters was prevented in Ang II + BRL mice, which suggested improvement in myocardial stiffness by BRL. Pathologic analysis showed that LV hypertrophy was induced in Ang II mice and failed to be prevented by BRL. However, increased collagen I/III synthesis, cardiac fibrosis, and lung congestion observed in Ang II mice were inhibited by BRL treatment. The cardioprotective benefits of BRL were associated with downregulation of transforming growth factor-ß1 expression and phosphorylated-Smad2/3. Chronic infusion of a ß3-agonist has a beneficial effect on LV diastolic function independent of blood pressure in the Ang II-induced cardiomyopathy mouse model. SIGNIFICANCE STATEMENT: Chronic infusion of a ß3-adrenergic receptor agonist attenuates cardiac fibrosis and improves diastolic dysfunction independently of blood pressure in an angiotensin II-induced hypertensive mouse model. This drug might be an effective treatment of heart failure with preserved ejection fraction.
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Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Angiotensina II/farmacologia , Cardiomiopatias/fisiopatologia , Diástole/efeitos dos fármacos , Receptores Adrenérgicos beta 3/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Modelos Animais de Doenças , Ecocardiografia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
Statin therapy reduces low-density lipoprotein cholesterol (LDL-C), inflammation, and atherosclerotic cardiovascular disease. We investigated the association between LDL-C and statin therapy on the prevalence of plaque rupture (PR). Patients with acute coronary syndromes who underwent optical coherence tomography imaging of the culprit lesion were divided into 4 groups based on LDL-C level and statin use (Group 1: LDL-C ≤ 100 without statin; Group 2; LDL-C ≤ 100 with statin; Group 3: LDL-C > 100 with statin; Group 4: LDL-C > 100 without statin), and the prevalence of PR was compared between the groups. Among 896 patients, PR was diagnosed in 444 (49.6%) patients. The prevalence of PR was significantly different among the 4 groups (p = 0.007): it was highest in the high LDL-C without statin group and lowest in the low LDL-C without statin group (53.9% and 39.2%, respectively). Compared with the high LDL-C without statin group, the low LDL-C without statin and low LDL-C with statin groups had a significantly lower prevalence of PR (p = 0.001, p = 0.040, respectively), and the low LDL-C with statin group had a significantly higher prevalence of calcification (p = 0.037). The patients with naturally low LDL-C have the lowest risk of PR. The patients with low LDL-C achieved by statin therapy had a higher prevalence of calcification. When LDL-C level is elevated, early and aggressive treatment with statin may help to prevent PR by stabilizing plaques through calcification.
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Síndrome Coronariana Aguda/diagnóstico por imagem , LDL-Colesterol/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Placa Aterosclerótica/diagnóstico por imagem , Síndrome Coronariana Aguda/sangue , Idoso , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Modelos Logísticos , Macrófagos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Ruptura Espontânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Tomografia de Coerência Óptica , Calcificação Vascular/diagnóstico por imagemRESUMO
Background Seasonal variations in acute coronary syndromes (ACS) have been reported, with incidence and mortality peaking in the winter. However, the underlying pathophysiology for these variations remain speculative. Methods and Results Patients with ACS who underwent optical coherence tomography were recruited from 6 countries. The prevalence of the 3 most common pathologies (plaque rupture, plaque erosion, and calcified plaque) were compared between the 4 seasons. In 1113 patients with ACS (885 male; mean age, 65.8±11.6 years), the rates of plaque rupture, plaque erosion, and calcified plaque were 50%, 39%, and 11% in spring; 44%, 43%, and 13% in summer; 49%, 39%, and 12% in autumn; and 57%, 30%, and 13% in winter (P=0.039). After adjusting for age, sex, and other coronary risk factors, winter was significantly associated with increased risk of plaque rupture (odds ratio [OR], 1.652; 95% CI, 1.157-2.359; P=0.006) and decreased risk of plaque erosion (OR, 0.623; 95% CI, 0.429-0.905; P=0.013), compared with summer as a reference. Among patients with rupture, the prevalence of hypertension was significantly higher in winter (P=0.010), whereas no significant difference was observed in the other 2 groups. Conclusions Seasonal variations in the incidence of ACS reflect differences in the underlying pathobiology. The proportion of plaque rupture is highest in winter, whereas that of plaque erosion is highest in summer. A different approach may be needed for the prevention and treatment of ACS depending on the season of its occurrence. Registration URL: https://www.cliniâcaltrâials.gov. Unique identifier: NCT03479723.
Assuntos
Síndrome Coronariana Aguda/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Estações do Ano , Calcificação Vascular/epidemiologia , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Europa (Continente)/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Prevalência , Sistema de Registros , Ruptura Espontânea , Fatores de Tempo , Tomografia de Coerência Óptica , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico por imagemRESUMO
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.
Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Vasos Coronários , Infarto do Miocárdio , Placa Aterosclerótica , Tomografia de Coerência Óptica/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/terapia , Angina Estável/diagnóstico , Angina Estável/fisiopatologia , LDL-Colesterol/sangue , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Revascularização Miocárdica/métodos , Revascularização Miocárdica/estatística & dados numéricos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Placa Aterosclerótica/fisiopatologia , PrognósticoRESUMO
AIMS: This study aims to determine the implications associated with long-term prognosis of heart failure (HF) in patients with dilated cardiomyopathy (DCM) presenting initially as decompensated HF. We stratified the phase of DCM patients without late gadolinium enhancement (LGE) based on ultrastructural changes in cardiomyocytes. METHODS AND RESULTS: Left ventricular (LV) endomyocardial biopsy was performed in 55 consecutive DCM patients with initial decompensated HF. Ultrastructural changes in cardiomyocytes detected by electron microscopy were compared with data including LGE with cardiac magnetic resonance and HF recurrence. Of the 55 DCM patients, 24 (44%) showed LGE, and 26 (47%) showed recurrence decompensated HF, while 23 patients (42%) showed autophagic vacuoles in cardiomyocytes by electron microscopy. Multivariate analysis identified atrial fibrillation [hazard ratio (HR), 3.40; 95% confidence interval (CI), 1.45-7.98], haemoglobin level (HR, 0.82; 95% CI, 0.68-0.99), beta-blocker use (HR, 0.18; 95% CI, 0.05-0.74), and autophagic vacuoles (HR, 0.25; 95% CI, 0.09-0.65) as predictors of HF recurrence in the total patient population. In patients without LGE, only autophagic vacuoles were independent predictors of readmission because of HF (HR, 0.29; 95% CI, 0.09-0.90). In patients with LGE, atrial fibrillation (HR, 19.10; 95% CI, 2.97-123.09), and mid-linear LGE (HR, 12.96; 95% CI, 2.02-82.94) were independent predictors of readmission because of HF. CONCLUSIONS: In DCM patients with LGE, characterised by progression of LV remodelling, the LGE pattern was a predictor of HF recurrence, whereas in patients without LGE, absence of autophagic vacuoles was a predictor of HF recurrence.