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1.
Europace ; 23(7): 1072-1083, 2021 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-33792661

RESUMO

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.


Assuntos
Cardiomiopatia Dilatada , Desfibriladores Implantáveis , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/terapia , Meios de Contraste , Feminino , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Volume Sistólico , Função Ventricular Esquerda
2.
Eur J Nutr ; 60(6): 3437-3447, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33635408

RESUMO

PURPOSE: Exercise plays an important role in preventing and treating postprandial dysmetabolism. We investigated the postprandial metabolic responses to a standard lunch when a session of aerobic exercise is performed in the early postprandial phase or divided between the pre- and postprandial period. METHODS: Nine healthy volunteers consumed a standardised mixed lunch and rested for the following 3 h (Con) or performed 40 min of cycling at 65% V̇O2max after lunch (CPPEx), or two 20-min sessions, one before (SplitEx1) and the other after lunch (SplitEx2), at the same intensity. RESULTS: At 1-h post-lunch, a significant reduction (P < 0.001) in glycaemia was observed for CPPEx (- 25 ± 10%) and SplitEx (- 34 ± 7%) compared to Con. Yet, a post-exercise rebound lessened the exercise effect on the glycaemic area under the curve (AUC) at 2 and 3 h. At 1 h, a significant reduction (P < 0.009) in plasma insulin (SplitEx - 53 ± 31%; CCPEx - 48 ± 20%) and C-peptide (SplitEx - 57 ± 20%; CCPEx - 47 ± 24%) was observed compared to Con. Glucose-dependent insulinotropic polypeptide (GIP) increased after the meal, without differences between conditions. Compared with SplitEx1, cortisol response was attenuated during SplitEx2 and CPPEx. At 3 hours, triglyceride AUC was significantly higher (P = 0.039) in SplitEx compared to Con (+ 19 ± 8%). CONCLUSION: Forty minutes of postprandial exercise or 20 min of pre- and postprandial exercise are both effective at attenuating the glycaemic and insulinaemic response to a mixed lunch, while a higher lipaemia was found in the pre- and postprandrial exercise condition.


Assuntos
Almoço , Período Pós-Prandial , Glicemia , Peptídeo C , Estudos Cross-Over , Exercício Físico , Humanos , Insulina , Masculino
4.
Eur J Appl Physiol ; 116(3): 573-82, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26712605

RESUMO

PURPOSE: Postprandial hyperglycemia and glycemic oscillations have been associated with increased oxidative stress. We sought to investigate the effect of two walking exercise protocols performed during lunchtime on glycemic control and oxidative stress in type 2 diabetic (T2D) patients. METHODS: Nine T2D patients participated in three randomized crossover trials; a control trial (Con), with participants having a standard lunch followed by their normal daily activities and two exercise trials (ContEx and Splitex). In ContEx, subjects performed 40 min of brisk walking 40 min after lunch, whereas in SplitEx the walking exercise was divided in two 20-min isoenergetic bouts, before and 40 min after meal. 24-h glycemic control was monitored by continuous glucose monitoring. 24-h urinary levels of 8-iso PGF2ɑ were measured as a marker of oxidative stress. RESULTS: SplitEx resulted in less time spent in moderate hyperglycemia after lunch vs ContEx (42.4 ± 38.7% vs 68.2 ± 32.7%, P = 0.04). ContEx reduced hyperglycemic time after breakfast consumed the morning after the exercise session (58.3 ± 29.6 Con vs 40.2 ± 33.4% ContEx, P = 0.02). Compared with Con, 24-h urinary isoprostanes were decreased both in ContEx (-68%, P = 0.02) and SplitEx (-63%, P = 0.04). CONCLUSIONS: Splitting an exercise session into two bouts, pre- and post-lunch, affects mainly the glycemic response to lunch, while a single-continuous isoenergetic session exerts its effect later in the 24-h period. Both exercise modalities effectively attenuate systemic oxidative stress with similar overall benefits.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício , Estresse Oxidativo , Caminhada , Idoso , Diabetes Mellitus Tipo 2/sangue , Humanos , Almoço , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial
5.
Nutrients ; 16(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38674861

RESUMO

The detrimental impacts of postprandial hyperglycemia on health are a critical concern, and exercise is recognized a pivotal tool in enhancing glycemic control after a meal. However, current exercise recommendations for managing postprandial glucose levels remain fairly broad and require deeper clarification. This review examines the existing literature aiming to offer a comprehensive guide for exercise prescription to optimize postprandial glycemic management. Specifically, it considers various exercise parameters (i.e., exercise timing, type, intensity, volume, pattern) for crafting exercise prescriptions. Findings predominantly indicate that moderate-intensity exercise initiated shortly after meals may substantially improve glucose response to a meal in healthy individuals and those with type 2 diabetes. Moreover, incorporating short activity breaks throughout the exercise session may provide additional benefits for reducing glucose response.


Assuntos
Diabetes Mellitus Tipo 2 , Exercício Físico , Controle Glicêmico , Período Pós-Prandial , Humanos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Controle Glicêmico/métodos , Hiperglicemia/prevenção & controle
6.
Circulation ; 126(25): 3000-7, 2012 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-23168414

RESUMO

BACKGROUND: It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. METHODS AND RESULTS: Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm(2) versus 4.2±2.1 mm(2); P=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P=0.01). CONCLUSIONS: CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.


Assuntos
Angiografia Coronária/métodos , Infarto do Miocárdio/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ultrassonografia de Intervenção
9.
Ann Nutr Metab ; 62(1): 14-25, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23208206

RESUMO

Atherosclerosis-related cardiovascular disease and diabetes mellitus are leading causes of mortality in the world and both disorders are closely related to the postprandial phenomena. Regular exercise is being strongly advocated as a precious tool in easing the global burden of chronic disease. Although exercise intensity, duration and frequency are well established in current guidelines for healthy and diabetic individuals, there is still no consensus on the optimal timing of exercise in relation to the last meal. The present paper reviews the existing literature on the 'when?' of aerobic exercise for metabolic control in healthy and diabetic individuals. Effective control of postprandial phenomena might prove to be a useful tool in the prevention of chronic disease. Exercise appears to influence glycemic and triglyceridemic responses differently depending on the meal composition and time lapse from meals. In healthy individuals, fasted-state exercise favors postprandial triglyceridemic control and the insulin sensitivity related to it. However, there is a lack of data on this matter in diabetic patients. On the other hand, when postprandial glycemia is of concern, aerobic exercise works better when performed after a meal, both in healthy and in diabetic patients.


Assuntos
Glicemia/metabolismo , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Período Pós-Prandial , Doença Crônica , Diabetes Mellitus Tipo 2/terapia , Índice Glicêmico , Humanos , Hiperlipidemias/metabolismo , Resistência à Insulina , Refeições , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Eur Heart J Cardiovasc Imaging ; 24(4): 472-482, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35792682

RESUMO

AIMS: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. CONCLUSION: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.


Assuntos
Cardiomiopatias , Desfibriladores Implantáveis , Insuficiência Cardíaca , Disfunção Ventricular Direita , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Prognóstico , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Desfibriladores Implantáveis/efeitos adversos , Fatores de Risco , Imagem Cinética por Ressonância Magnética/métodos , Cardiomiopatias/complicações , Espectroscopia de Ressonância Magnética/efeitos adversos , Função Ventricular Direita , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/terapia , Disfunção Ventricular Direita/etiologia
11.
JACC Cardiovasc Imaging ; 16(11): 1387-1400, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37227329

RESUMO

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.


Assuntos
Cardiomiopatias , Desfibriladores Implantáveis , Isquemia Miocárdica , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Desfibriladores Implantáveis/efeitos adversos , Meios de Contraste , Imagem Cinética por Ressonância Magnética , Valor Preditivo dos Testes , Gadolínio , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/terapia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/terapia , Cardiomiopatias/complicações , Espectroscopia de Ressonância Magnética/efeitos adversos , Sistema de Registros , Fatores de Risco
12.
Nat Chem Biol ; 6(4): 264-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20190762

RESUMO

We describe a new method for producing homogeneous eukaryotic N-glycoproteins. The method involves the engineering and functional transfer of the Campylobacter jejuni glycosylation machinery in Escherichia coli to express glycosylated proteins with the key GlcNAc-Asn linkage. The bacterial glycans were then trimmed and remodeled in vitro by enzymatic transglycosylation to fulfill a eukaryotic N-glycosylation. It provides a potentially general platform for producing eukaryotic N-glycoproteins.


Assuntos
Eucariotos/metabolismo , Engenharia Genética , Glicoproteínas/biossíntese , Glicosilação , Campylobacter jejuni/genética , Campylobacter jejuni/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Eucariotos/química , Glicoproteínas/química
13.
J Diet Suppl ; 19(4): 499-514, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33759678

RESUMO

Six months of supplementation with a multi-ingredient nutrition supplement was investigated in older adults with low skeletal muscle mass given the recently purported benefits of such approaches. Community-dwelling older adults (age, 74.9 ± 3.6 y; M/F, 18/19) participated in a double-blind, placebo-controlled, randomized trial involving daily consumption of either fruit juice placebo (PLA) or supplement (SUPP) in the form of a 200-mL carton of a juice-based emulsion of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) (3000 mg as 1500 mg docosahexaenoic acid and 1500 mg eicosapentaenoic acid), whey protein isolate (8 g), vitamin D3 (400 IU), and resveratrol (150 mg). Body composition, physical function, and circulating markers of metabolic health were assessed at baseline (PRE), and after 3 (MID) and 6 (POST) months of supplementation. Lean body mass (LBM) was unchanged in either group, but fat mass increased in SUPP by 1.41 (0.75, 2.07) kg at POST (+6.4%; p < .001; d = 0.20). Hand-grip strength was maintained in SUPP, but declined in PLA by 2.50 (0.81, 4.19) kg at POST (-6.8%; p = .002; d = 0.38). Short physical performance battery score was unchanged in PLA, but increased in SUPP by 1.13 (0.41, 1.84) above PRE at POST (p = .001; d = 0.47). Circulating markers of metabolic health were unchanged in response to the intervention in either PLA or SUPP. Long-term supplementation with an LC n-3 PUFA-rich multi-ingredient nutrition supplement demonstrates potential efficacy for improving physical function in older adults in the absence of exercise training and independent of a change in LBM.


Assuntos
Ácidos Graxos Ômega-3 , Força Muscular , Idoso , Composição Corporal , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/farmacologia , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Poliésteres/metabolismo , Poliésteres/farmacologia
14.
Blood ; 113(10): 2275-83, 2009 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-19005180

RESUMO

The antibody-mediated delivery of therapeutic agents to sites of angiogenesis is an attractive strategy for anticancer therapy, but is largely unexplored in hematologic malignancies. In the present study, we show that the extra domain B (EDB) of fibronectin, a marker of angiogenesis, is expressed in B-cell non-Hodgkin lymphoma (NHL) and that the human monoclonal anti-EDB antibody L19 can selectively localize to the lymphoma-associated subendothelial extracellular matrix. In vivo, the preferential accumulation of the antibody at the tumor site was confirmed by quantitative biodistribution analyses with radioiodinated antibody preparations. The fusion protein L19-IL2, which mediates the delivery of interleukin-2 (IL-2) to the neovasculature, displayed a superior antilymphoma activity compared with unconjugated IL-2 in localized and systemic xenograft models of NHL. When coadministered with rituximab, L19-IL2 induced complete remissions of established localized lymphomas and provided long-lasting protection from disseminated lymphoma. The combined use of rituximab and L19-IL2, which dramatically increases the infiltration of immune effector cells in lymphomas, may deserve clinical investigations, facilitated by the fact that L19-IL2 is currently being studied in phase II clinical trials in patients with solid tumors.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos/administração & dosagem , Antineoplásicos/administração & dosagem , Imunoterapia/métodos , Interleucina-2/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Animais , Anticorpos Monoclonais Murinos , Terapia Combinada , Fibronectinas/antagonistas & inibidores , Fibronectinas/imunologia , Imunofluorescência , Humanos , Imuno-Histoquímica , Camundongos , Rituximab , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Strength Cond Res ; 25(5): 1326-32, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21273913

RESUMO

The aim of this study was to examine the effect of aging and training status on ventilatory response during incremental cycling exercise. Eight young (24 ± 5 years) and 8 older (64 ± 3 years) competitive cyclists together with 8 young (27 ± 4 years) and 8 older (63 ± 2 years) untrained individuals underwent a continuous incremental cycling test to exhaustion to determine ventilatory threshold (VT), respiratory compensation point (RCP), and maximal oxygen uptake (VO2max). In addition, the isocapnic buffering (IB) phase was calculated together with the hypocapnic hyperventilation. Ventilatory threshold occurred at similar relative exercise intensities in all groups, whereas RCP was recorded at higher intensities in young and older cyclists compared to the untrained subjects. The IB phase, reported as the difference between VT and RCP and expressed either in absolute (ml·min⁻¹·kg⁻¹ VO2) or in relative terms, was greater (p < 0.01) in both young and older trained cyclists than in untrained subjects, who were also characterized by a lower exercise capacity. Isocapnic buffering was particularly small in the older untrained volunteers. Although young untrained and older trained subjects had a similar level of VO2max, older athletes exhibited a larger IB. In addition, a higher absolute but similar relative IB was observed in young vs. older cyclists, despite a higher VO2max in the former. In conclusion, the present study shows that aging is associated with a reduction of the IB phase recorded during an incremental exercise test. Moreover, endurance training induces adaptations that result in an enlargement of the IB phase independent of age. This information can be used for the characterization and monitoring of the physiological adaptations induced by endurance training.


Assuntos
Envelhecimento/fisiologia , Limiar Anaeróbio/fisiologia , Teste de Esforço/métodos , Resistência Física/fisiologia , Esforço Físico , Adaptação Fisiológica , Fatores Etários , Idoso , Análise de Variância , Estudos de Coortes , Tolerância ao Exercício/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Ventilação Pulmonar/fisiologia , Fatores de Risco , Adulto Jovem
16.
Diagnostics (Basel) ; 11(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34829434

RESUMO

BACKGROUND: Inflammation plays a key role in atrial fibrillation (AF). Epicardial adipose tissue around the atrial wall can influence atrial morpho-functional properties. The aim of this study was to assess whether an increased quantity and/or density of adipose tissue located around the left atrium (Fat-LA) are related to AF, independently from atrial size. METHODS: eighty patients who underwent AF ablation and 80 patients without history of AF were selected. The Fat-LA mass was quantified as tissue within -190 to -30 Hounsfield Units (HU) on cardiac computed tomography angiograms (CCTA), and the mean adipose tissue attenuation was assessed. RESULTS: Adipose tissue mass was higher in patients with AF (5.42 ± 2.94 mL) versus non-AF (4.16 ± 2.55 mL, p = 0.007), but relative fat quantity did not differ after adjusting for atrial size. Mean fat density was significantly higher in AF (-69.15 HU) versus non-AF (-76.82 HU, p < 0.0001) participants. In the logistic regression models, only the addition of mean Fat-LA attenuation led to a significant improvement of the model's chi-square (from 22.89 of the clinical model to 31.69 of the clinical and adipose tissue attenuation model, p < 0.01) and discrimination (AUC from 0.775 to 0.829). CONCLUSIONS: Fat-LA volume is significantly greater only in absolute terms in patients with AF, but this difference does not hold after adjusting for the larger LA of AF subjects. On the contrary, a higher Fat-LA density was associated with AF, independently from LA size, providing incremental value over other variables that are associated with AF.

17.
Radiology ; 256(1): 83-92, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20574086

RESUMO

PURPOSE: To evaluate the prognostic value of multidetector computed tomographic (CT) coronary angiography in a diabetic population known to have or suspected of having coronary artery disease (CAD) compared with that in nondiabetic individuals. MATERIALS AND METHODS: Institutional review board approval and patient informed consent were obtained. Three hundred thirteen patients with type 2 diabetes mellitus (DM) and 303 patients without DM underwent unenhanced 64-detector row CT, at which a calcium score was obtained, followed by CT angiography. Multidetector CT coronary angiograms were retrospectively classified as normal, showing nonobstructive CAD (50% luminal narrowing). During follow-up after CT angiography, major events (cardiac death, nonfatal myocardial infarction, and unstable angina requiring hospitalization) and total events (major events plus coronary revascularizations) were recorded for each patient. Cox proportional hazards analysis and Kaplan-Meier analysis were used to compare survival rates. RESULTS: In the group of 313 patients with DM, there were 213 men, and the mean age was 62 years +/- 11 (standard deviation). In the group of 303 patients without DM, there were 203 men, and the mean age was 63 years +/- 11. The mean number of diseased segments (5.6 vs 4.4, P = .001) and the rate of obstructive CAD (51% vs 37%, P < .001) were higher in patients with DM. Patients were followed up for a mean of 20 months +/- 5.4 (range, 6-44 months). At multivariate analysis, DM (P < .001) and evidence of obstructive CAD (P < .001) were independent predictors of outcome. Obstructive CAD remained a significant multivariate predictor for both patients with DM and patients without DM. In both patients with DM and patients without DM with absence of disease, the event rate was 0%. The event rate increased to 36% in patients without DM but with obstructive CAD and was highest (47%) in patients with DM and obstructive CAD. CONCLUSION: In both patients with DM and patients without DM, multidetector CT coronary angiography provides incremental prognostic information over baseline clinical variables, and the absence of atherosclerosis at CT coronary angiography is associated with an excellent prognosis. Multidetector CT coronary angiography might be a clinically useful tool for improving risk stratification in both patients with DM and patients without DM.


Assuntos
Angiografia Coronária/métodos , Doença das Coronárias/diagnóstico por imagem , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos
18.
Bioconjug Chem ; 21(2): 302-13, 2010 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-20073477

RESUMO

Synthesis of three new cationic thiol-reactive maleimide-porphyrin derivatives and their use in site-specific conjugation to monoclonal antibodies is reported. The selective reactivity toward thiols is demonstrated using competition experiments, where both thiols and amines are present. This selectivity was used to successfully achieve specific conjugation of two porphyrins to cysteine residues present in the antiangiogenic antibody L19, expressed in small immunoprotein (SIP) format. The effect of length and hydrophilicity of the linkage between porphyrin and maleimide was also investigated, and maximum photocytotoxicity was achieved with the longest and most hydrophilic chain. Immunoreactivity and in vitro photocytotoxicity for these well-characterized porphyrin-antibody conjugates are described.


Assuntos
Inibidores da Angiogênese/química , Anticorpos Monoclonais/química , Porfirinas/química , Aminas/química , Animais , Sítios de Ligação , Células CHO , Cricetinae , Cricetulus , Imunoconjugados/química , Imunoproteínas/química , Maleimidas/química , Oxirredução , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/síntese química , Solubilidade , Especificidade por Substrato , Compostos de Sulfidrila/química , Água/química
19.
Eur Radiol ; 20(4): 846-54, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19760230

RESUMO

OBJECTIVES: The aim of the study was to compare the coronary artery calcium score (CACS) and computed tomography coronary angiography (CTCA) for the assessment of non-obstructive/obstructive coronary artery disease (CAD) in high-risk asymptomatic subjects. METHODS: Two hundred and thirteen consecutive asymptomatic subjects (113 male; mean age 53.6 +/- 12.4 years) with more than one risk factor and an inconclusive or unfeasible non-invasive stress test result underwent CACS and CTCA in an outpatient setting. All patients underwent conventional coronary angiography (CAG). Data from CACS (threshold for positive image: Agatston score 1/100/1,000) and CTCA were compared with CAG regarding the degree of CAD (non-obstructive/obstructive; or=50% lumen reduction). RESULTS: The mean calcium score was 151 +/- 403 and the prevalence of obstructive CAD was 17% (8% one-vessel and 10% two-vessel disease). Per-patient sensitivity, specificity, positive and negative predictive values of CACS were: 97%, 75%, 45%, and 100%, respectively (Agatston >or=1); 73%, 90%, 60%, and 94%, respectively (Agatston >or=100); 30%, 98%, 79%, and 87%, respectively (Agatston >or=1,000). Per-patient values for CTCA were 100%, 98%, 97%, and 100%, respectively (p < 0.05). CTCA detected 65% prevalence of all CAD (48% non-obstructive), while CACS detected 37% prevalence of all CAD (21% non-obstructive) (p < 0.05). CONCLUSION: CACS proved inadequate for the detection of obstructive and non-obstructive CAD compared with CTCA. CTCA has a high diagnostic accuracy for the detection of non-obstructive and obstructive CAD in high-risk asymptomatic patients with inconclusive or unfeasible stress test results.


Assuntos
Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Angiografia Coronária/estatística & dados numéricos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Fatores de Risco , Adulto Jovem
20.
Eur Radiol ; 20(1): 81-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19657651

RESUMO

To evaluate the diagnostic accuracy of 64-slice CT coronary angiography (CT-CA) for the detection of significant coronary artery stenosis in patients with zero on the Agatston Calcium Score (CACS). We enrolled 279 consecutive patients (96 male, mean age 48 +/- 12 years) with suspected coronary artery disease. Patients were symptomatic (n = 208) or asymptomatic (n = 71), and underwent conventional coronary angiography (CAG). For CT-CA we administered an IV bolus of 100 ml of iodinated contrast material. CT-CA was compared to CAG using a threshold for significant stenosis of >or=50%. The prevalence of disease demonstrated at CAG was 15% (1.4% in asymptomatic). The population at CAG showed no or non-significant disease in 85% (238/279), single vessel disease in 9% (25/279), and multi-vessel disease in 6% (16/279). Sensitivity, specificity, and positive and negative predictive values of CT-CA vs. CAG on the patient level were 100%, 95%, 76%, and 100% in the overall population and 100%, 100%, 100%, and 100% in asymptomatic patients, respectively. CT-CA proves high diagnostic performance in patients with or without symptoms and with zero CACS. The prevalence of significant disease detected by CT-CA was not negligible in asymptomatic patients. The role of CT-CA in asymptomatic patients remains uncertain.


Assuntos
Calcinose/diagnóstico por imagem , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Calcinose/complicações , Estenose Coronária/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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