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1.
Circulation ; 146(19): 1415-1424, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36148649

RESUMO

BACKGROUND: Morbidity from undiagnosed atrial fibrillation (AF) may be preventable with early detection. Many consumer wearables contain optical photoplethysmography (PPG) sensors to measure pulse rate. PPG-based software algorithms that detect irregular heart rhythms may identify undiagnosed AF in large populations using wearables, but minimizing false-positive detections is essential. METHODS: We performed a prospective remote clinical trial to examine a novel PPG-based algorithm for detecting undiagnosed AF from a range of wrist-worn devices. Adults aged ≥22 years in the United States without AF, using compatible wearable Fitbit devices and Android or iOS smartphones, were included. PPG data were analyzed using a novel algorithm that examines overlapping 5-minute pulse windows (tachograms). Eligible participants with an irregular heart rhythm detection (IHRD), defined as 11 consecutive irregular tachograms, were invited to schedule a telehealth visit and were mailed a 1-week ambulatory ECG patch monitor. The primary outcome was the positive predictive value of the first IHRD during ECG patch monitoring for concurrent AF. RESULTS: A total of 455 699 participants enrolled (median age 47 years, 71% female, 73% White) between May 6 and October 1, 2020. IHRDs occurred for 4728 (1%) participants, and 2070 (4%) participants aged ≥65 years during a median of 122 (interquartile range, 110-134) days at risk for an IHRD. Among 1057 participants with an IHRD notification and subsequent analyzable ECG patch monitor, AF was present in 340 (32.2%). Of the 225 participants with another IHRD during ECG patch monitoring, 221 had concurrent AF on the ECG and 4 did not, resulting in an IHRD positive predictive value of 98.2% (95% CI, 95.5%-99.5%). For participants aged ≥65 years, the IHRD positive predictive value was 97.0% (95% CI, 91.4%-99.4%). CONCLUSIONS: A novel PPG software algorithm for wearable Fitbit devices exhibited a high positive predictive value for concurrent AF and identified participants likely to have AF on subsequent ECG patch monitoring. Wearable devices may facilitate identifying individuals with undiagnosed AF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04380415.


Assuntos
Fibrilação Atrial , Dispositivos Eletrônicos Vestíveis , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Prospectivos , Fotopletismografia , Eletrocardiografia Ambulatorial , Eletrocardiografia/métodos
2.
Curr Cardiol Rep ; 25(12): 1883-1896, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38041726

RESUMO

PURPOSE OF REVIEW: To discuss physiologic and methodologic advances in the echocardiographic assessment of right heart (RH) function, including the emergence of artificial intelligence (AI) and point-of-care ultrasound. RECENT FINDINGS: Recent studies have highlighted the prognostic value of right ventricular (RV) longitudinal strain, RV end-systolic dimensions, and right atrial (RA) size and function in pulmonary hypertension and heart failure. While RA pressure is a central marker of right heart diastolic function, the recent emphasis on venous excess imaging (VExUS) has provided granularity to the systemic consequences of RH failure. Several methodological advances are also changing the landscape of RH imaging including post-processing 3D software to delineate the non-longitudinal (radial, anteroposterior, and circumferential) components of RV function, as well as AI segmentation- and non-segmentation-based quantification. Together with recent guidelines and advances in AI technology, the field is shifting from specific RV functional metrics to integrated RH disease-specific phenotypes. A modern echocardiographic evaluation of RH function should focus on the entire cardiopulmonary venous unit-from the venous to the pulmonary arterial system. Together, a multi-parametric approach, guided by physiology and AI algorithms, will help define novel integrated RH profiles for improved disease detection and monitoring.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Direita , Humanos , Inteligência Artificial , Ecocardiografia/métodos , Ventrículos do Coração , Insuficiência Cardíaca/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Função Ventricular Direita
3.
Circulation ; 143(8): 837-851, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33617315

RESUMO

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Congressos como Assunto , Doença das Coronárias/epidemiologia , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Complicações do Diabetes/epidemiologia , Humanos , Morbidade/tendências , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Urbanização
4.
Europace ; 24(9): 1372-1383, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-35640917

RESUMO

Digital technology is now an integral part of medicine. Tools for detecting, screening, diagnosis, and monitoring health-related parameters have improved patient care and enabled individuals to identify issues leading to better management of their own health. Wearable technologies have integrated sensors and can measure physical activity, heart rate and rhythm, and glucose and electrolytes. For individuals at risk, wearables or other devices may be useful for early detection of atrial fibrillation or sub-clinical states of cardiovascular disease, disease management of cardiovascular diseases such as hypertension and heart failure, and lifestyle modification. Health data are available from a multitude of sources, namely clinical, laboratory and imaging data, genetic profiles, wearables, implantable devices, patient-generated measurements, and social and environmental data. Artificial intelligence is needed to efficiently extract value from this constantly increasing volume and variety of data and to help in its interpretation. Indeed, it is not the acquisition of digital information, but rather the smart handling and analysis that is challenging. There are multiple stakeholder groups involved in the development and effective implementation of digital tools. While the needs of these groups may vary, they also have many commonalities, including the following: a desire for data privacy and security; the need for understandable, trustworthy, and transparent systems; standardized processes for regulatory and reimbursement assessments; and better ways of rapidly assessing value.


Assuntos
Cardiologia , Doenças Cardiovasculares , Insuficiência Cardíaca , Telemedicina , Dispositivos Eletrônicos Vestíveis , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Inteligência Artificial , Glucose , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos
5.
Circulation ; 141(9): e120-e138, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-31992057

RESUMO

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.


Assuntos
American Heart Association , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Saúde Global , Formulação de Políticas , Vigilância da População , Serviços Preventivos de Saúde/normas , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
6.
Adv Funct Mater ; 31(37)2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34733130

RESUMO

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects high-risk atherosclerotic plaques at early stages could prevent these sequelae. The abundance of immune cells in the arterial wall, especially inflammatory Ly-6Chi monocytes and foamy macrophages, is indicative of plaque inflammation, and may be associated with plaque vulnerability. Hence, we sought to develop a new method that specifically targets these immune cells to offer clinically-relevant diagnostic information about cardiovascular disease. We combine ultra-selective nanoparticle targeting of Ly-6Chi monocytes and foamy macrophages with clinically-viable photoacoustic imaging (PAI) in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high-dimensional single-cell flow cytometry (13-parameter) showed that our nanoparticles were almost-exclusively taken up by the Ly-6Chi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identified inflamed atherosclerotic plaques that display ~6-fold greater signal compared to controls (P<0.001) six hours after intravenous injection of ultra-selective carbon nanotubes, with in vivo corroboration via optical imaging. Our highly selective strategy may provide a targeted, non-invasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions.

7.
Bioinformatics ; 35(9): 1610-1612, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30304439

RESUMO

MOTIVATION: Radiologists have used algorithms for Computer-Aided Diagnosis (CAD) for decades. These algorithms use machine learning with engineered features, and there have been mixed findings on whether they improve radiologists' interpretations. Deep learning offers superior performance but requires more training data and has not been evaluated in joint algorithm-radiologist decision systems. RESULTS: We developed the Computer-Aided Note and Diagnosis Interface (CANDI) for collaboratively annotating radiographs and evaluating how algorithms alter human interpretation. The annotation app collects classification, segmentation, and image captioning training data, and the evaluation app randomizes the availability of CAD tools to facilitate clinical trials on radiologist enhancement. AVAILABILITY AND IMPLEMENTATION: Demonstrations and source code are hosted at (https://candi.nextgenhealthcare.org), and (https://github.com/mbadge/candi), respectively, under GPL-3 license. SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.


Assuntos
Algoritmos , Software , Aprendizado Profundo , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
8.
Circulation ; 137(18): e495-e522, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29618598

RESUMO

Physical inactivity is one of the most prevalent major health risk factors, with 8 in 10 US adults not meeting aerobic and muscle-strengthening guidelines, and is associated with a high burden of cardiovascular disease. Improving and maintaining recommended levels of physical activity leads to reductions in metabolic, hemodynamic, functional, body composition, and epigenetic risk factors for noncommunicable chronic diseases. Physical activity also has a significant role, in many cases comparable or superior to drug interventions, in the prevention and management of >40 conditions such as diabetes mellitus, cancer, cardiovascular disease, obesity, depression, Alzheimer disease, and arthritis. Whereas most of the modifiable cardiovascular disease risk factors included in the American Heart Association's My Life Check - Life's Simple 7 are evaluated routinely in clinical practice (glucose and lipid profiles, blood pressure, obesity, and smoking), physical activity is typically not assessed. The purpose of this statement is to provide a comprehensive review of the evidence on the feasibility, validity, and effectiveness of assessing and promoting physical activity in healthcare settings for adult patients. It also adds concrete recommendations for healthcare systems, clinical and community care providers, fitness professionals, the technology industry, and other stakeholders in order to catalyze increased adoption of physical activity assessment and promotion in healthcare settings and to contribute to meeting the American Heart Association's 2020 Impact Goals.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Exercício Físico , Promoção da Saúde , Estilo de Vida Saudável , Comportamento de Redução do Risco , American Heart Association , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Nível de Saúde , Humanos , Prognóstico , Fatores de Proteção , Fatores de Risco , Comportamento Sedentário , Estados Unidos/epidemiologia
9.
J Cardiovasc Magn Reson ; 21(1): 77, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842900

RESUMO

BACKGROUND: The diagnostic utility of cardiovascular magnetic resonance (CMR) is limited during the early stages of myocarditis. This study examined whether ferumoxytol-enhanced CMR (FE-CMR) could detect an earlier stage of acute myocarditis compared to gadolinium-enhanced CMR. METHODS: Lewis rats were induced to develop autoimmune myocarditis. CMR (3 T, GE Signa) was performed at the early- (day 14, n = 7) and the peak-phase (day 21, n = 8) of myocardial inflammation. FE-CMR was evaluated as % myocardial dephasing signal loss on gradient echo images at 6 and 24 h (6 h- & 24 h-FE-CMR) following the administration of ferumoxytol (300µmolFe/kg). Pre- and post-contrast T2* mapping was also performed. Early (EGE) and late (LGE) gadolinium enhancement was obtained after the administration of gadolinium-DTPA (0.5 mmol/kg) on day 14 and 21. Healthy rats were used as control (n = 6). RESULTS: Left ventricular ejection fraction (LVEF) was preserved at day 14 with inflammatory cells but no fibrosis seen on histology. EGE and LGE at day 14 both showed limited myocardial enhancement (EGE: 11.7 ± 15.5%; LGE: 8.7 ± 8.7%; both p = ns vs. controls). In contrast, 6 h-FE-CMR detected extensive myocardial signal loss (33.2 ± 15.0%, p = 0.02 vs. EGE and p < 0.01 vs. LGE). At day 21, LVEF became significantly decreased (47.4 ± 16.4% vs control: 66.2 ± 6.1%, p < 0.01) with now extensive myocardial involvement detected on EGE, LGE, and 6 h-FE-CMR (41.6 ± 18.2% of LV). T2* mapping also detected myocardial uptake of ferumoxytol both at day 14 (6 h R2* = 299 ± 112 s- 1vs control: 125 ± 26 s- 1, p < 0.01) and day 21 (564 ± 562 s- 1, p < 0.01 vs control). Notably, the myocardium at peak-phase myocarditis also showed significantly higher pre-contrast T2* (27 ± 5 ms vs control: 16 ± 1 ms, p < 0.001), and the extent of myocardial necrosis had a strong positive correlation with T2* (r = 0.86, p < 0.001). CONCLUSIONS: FE-CMR acquired at 6 h enhance detection of early stages of myocarditis before development of necrosis or fibrosis, which could potentially enable appropriate therapeutic intervention.


Assuntos
Meios de Contraste/administração & dosagem , Óxido Ferroso-Férrico/administração & dosagem , Gadolínio DTPA/administração & dosagem , Imageamento por Ressonância Magnética , Miocardite/diagnóstico por imagem , Doença Aguda , Animais , Modelos Animais de Doenças , Progressão da Doença , Diagnóstico Precoce , Fibrose , Masculino , Miocardite/patologia , Miocardite/fisiopatologia , Miocárdio/patologia , Necrose , Valor Preditivo dos Testes , Ratos Endogâmicos Lew , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda
10.
J Magn Reson Imaging ; 45(4): 1144-1153, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27689830

RESUMO

PURPOSE: To evaluate Arg-Gly-Asp (RGD)-conjugated human ferritin (HFn) iron oxide nanoparticles for in vivo magnetic resonance imaging (MRI) of vascular inflammation and angiogenesis in experimental carotid disease and abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: HFn was genetically engineered to express the RGD peptide and Fe3 O4 nanoparticles were chemically synthesized inside the engineered HFn (RGD-HFn). Macrophage-rich left carotid lesions were induced by ligation in FVB mice made hyperlipidemic and diabetic (n = 14), with the contralateral right carotid serving as control. Murine AAAs were created by continuous angiotensin II infusion in ApoE-deficient mice (n = 12), while control mice underwent saline infusion (n = 8). All mice were imaged before and after intravenous injection with either RGD-HFn-Fe3 O4 or HFn-Fe3 O4 using a gradient-echo sequence on a whole-body 3T clinical scanner, followed by histological analysis. The nanoparticle accumulation was assessed by the extent of T2*-induced carotid lumen reduction (% lumen loss) or aortic T2*-weighted signal intensity reduction (% SI [signal intensity] loss). RESULTS: RGD-HFn-Fe3 O4 was taken up more than HFn-Fe3 O4 in both the ligated left carotid arteries (% lumen loss; 69 ± 9% vs. 36 ± 7%, P = 0.01) and AAAs (% SI loss; 47 ± 6% vs. 20 ± 5%, P = 0.01). The AAA % SI loss correlated positively with AAA size (r = 0.89, P < 0.001). Histology confirmed the greater accumulation and colocalization of RGD-HFn-Fe3 O4 to both vascular macrophages and endothelial cells. CONCLUSION: RGD-HFn-Fe3 O4 enhances in vivo MRI by targeting both vascular inflammation and angiogenesis, and provides a promising translatable MRI approach to detect high-risk atherosclerotic and aneurysmal vascular diseases. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1144-1153.


Assuntos
Aneurisma da Aorta Abdominal/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Ferritinas/metabolismo , Inflamação/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Oligopeptídeos/metabolismo , Animais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/metabolismo , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/metabolismo , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/metabolismo , Modelos Animais de Doenças , Compostos Férricos/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Masculino , Camundongos , Nanopartículas , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologia
11.
Circ Res ; 116(7): e40-50, 2015 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-25654979

RESUMO

RATIONALE: The mechanism of functional restoration by stem cell therapy remains poorly understood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta-derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and precardiac properties. In this study, the restorative effects of 3 AMC-derived subpopulations were examined in a murine myocardial injury model: (1) unselected AMCs, (2) ckit(+)AMCs, and (3) AMC-derived induced pluripotent stem cells (MiPSCs). OBJECTIVE: To determine the differential restorative effects of the AMC-derived subpopulations in the murine myocardial injury model using multimodality imaging. METHODS AND RESULTS: SCID (severe combined immunodeficiency) mice underwent left anterior descending artery ligation and were divided into 4 treatment arms: (1) normal saline control (n=14), (2) unselected AMCs (n=10), (3) ckit(+)AMCs (n=13), and (4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular function, whereas bioluminescence imaging assessed stem cell engraftment during a 4-week period. Immunohistological labeling and reverse transcriptase polymerase chain reaction of the explanted myocardium were performed. The unselected AMC and ckit(+)AMC-treated mice demonstrated transient left ventricular functional improvement. However, the MiPSCs exhibited a significantly greater increase in left ventricular function compared with all the other groups during the entire 4-week period. Left ventricular functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSC-treated animals lacked any evidence of de novo cardiac differentiation. CONCLUSION: The functional restoration seen in MiPSCs was characterized by increased myocardial viability and sustained engraftment without de novo cardiac differentiation, indicating salvage of the injured myocardium.


Assuntos
Células-Tronco Pluripotentes Induzidas/transplante , Imageamento por Ressonância Magnética/métodos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Imagem Multimodal , Infarto do Miocárdio/terapia , Miocárdio/patologia , Animais , Separação Celular/métodos , Sobrevivência Celular , Estenose Coronária/complicações , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Genes Reporter , Sobrevivência de Enxerto , Xenoenxertos , Humanos , Ligadura , Medições Luminescentes , Masculino , Manganês , Células-Tronco Mesenquimais/química , Camundongos , Camundongos Mutantes , Camundongos SCID , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Placenta/citologia , Gravidez , Proteínas Proto-Oncogênicas c-kit/análise , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homeostase do Telômero , Função Ventricular Esquerda
13.
Stroke ; 47(4): 1101-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26941255

RESUMO

BACKGROUND AND PURPOSE: Atherosclerosis is a leading cause of mortality worldwide, contributing to both strokes and heart attacks. Macrophages are key players in atherogenesis, promoting vascular inflammation and arterial remodeling through cysteine cathepsin proteases. We used a cathepsin-targeted activity-based probe in human carotid plaque to assess its diagnostic potential and evaluate macrophage subtypes ex vivo. METHODS: Carotid plaque specimens surgically removed during endarterectomy from 62 patients (age range, 38% female, 28% symptomatic) were graded pathologically as either stable (Grade 1) or unstable (Grade 2 or 3). A cathepsin activity-based probe was used to quantify individual cathepsins in plaque tissue and macrophage subtypes. RESULTS: Cathepsin B and S activities were increased in unstable carotid plaques. They were quantified using the probe to biochemically investigate individual cathepsins (Cathepsin B and S: 0.97 and 0.90 for grade 3 versus 0.51 and 0.59 for grade 1; P=0.006 and P=0.03 arbitrary units (AU), respectively). Higher cathepsin activity was observed in carotid plaques from symptomatic patients (Cathepsin B and S: 0.65 and 0.77 for asymptomatic, 0.99 and 1.17 for symptomatic; P=0.008 and P=0.005 AU, respectively). Additionally, it was demonstrated that M2 macrophages from unstable plaques express cathepsin activity 5-fold higher than M2 macrophages from stable plaques (25.52 versus 5.22; P=0.008 AU). CONCLUSIONS: Targeting cathepsin activity in human carotid plaques may present a novel diagnostic tool for characterizing high-risk plaques. Novel cathepsin activity patterns within plaques and macrophage subpopulations suggest their involvement in the transition to active disease.


Assuntos
Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/metabolismo , Catepsinas/metabolismo , Macrófagos/metabolismo , Placa Aterosclerótica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Doenças das Artérias Carótidas/patologia , Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Placa Aterosclerótica/cirurgia
14.
Radiology ; 280(3): 826-36, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27332865

RESUMO

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Genes Reporter , Coração/diagnóstico por imagem , Transplante de Células-Tronco Mesenquimais , Imagem Molecular/métodos , Imagem Multimodal/métodos , Animais , Radioisótopos de Flúor , Guanina/análogos & derivados , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Suínos
15.
Radiology ; 280(3): 815-25, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27308957

RESUMO

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Genes Reporter , Transplante de Células-Tronco Mesenquimais/métodos , Imagem Molecular , Imagem Multimodal , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Animais , Feminino , Luciferases de Vaga-Lume/metabolismo , Medições Luminescentes , Camundongos , Camundongos Nus , Tomografia por Emissão de Pósitrons , Transfecção
16.
Cardiovasc Diabetol ; 15: 24, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26846539

RESUMO

BACKGROUND: A novel MRI technique, employing dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI), can evaluate the physiologically unstable peri-infarct region. Dual contrast MEMRI-DEMRI enables comprehensive evaluation of telmisartan to salvage the peri-infarct injury to elucidate the underlying mechanism of restoring the ischemic cardiomyopathy in the diabetic mouse model. METHODS AND RESULTS: Dual contrast MEMRI-DEMRI was performed on weeks 1, 2, and 4 following initiation of telmisartan treatment in 24 left anterior descendent artery ligated diabetic mice. The MRI images were analyzed for core infarct, peri-infarct, left ventricular end-diastolic, end-systolic volumes, and the left ventricular ejection fraction (LVEF). Transmission electron microscopy (TEM) and real-time PCR were used for ex vivo analysis of the myocardium. Telmisartan vs. control groups demonstrated significantly improved LVEF at weeks 1, 2, and 4, respectively (33 ± 7 %*** vs. 19 ± 5 %, 29 ± 3 %*** vs. 22 ± 4 %, and 31 ± 2 %*** vs 18 ± 6 %, ***p < 0.001). The control group demonstrated significant differences in the scar volume measured by MEMRI and DEMRI, demonstrating peri-infarct injury. Telmisartan group significantly salvaged the peri-infarct injury. The myocardial effects were validated by TEM, which confirmed the presence of the injured but viable cardiomyocyte morphology in the peri-infarct region and by flow cytometry of venous blood, which demonstrated significantly increased circulating endothelial progenitor cells (EPCs). CONCLUSION: The improved cardiac function in ischemic cardiomyopathy of diabetic mice by telmisartan is attributed to the attenuation of the peri-infarct injury by the angiogenic effects of EPCs to salvage the injured cardiomyocytes. Dual-contrast MEMRI-DEMRI technique tracked the therapeutic effects of telmisartan on the injured myocardium longitudinally.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Meios de Contraste/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Gadolínio DTPA/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Manganês/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fibrose , Citometria de Fluxo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica de Transmissão , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Volume Sistólico/efeitos dos fármacos , Telmisartan , Fatores de Tempo , Sobrevivência de Tecidos , Função Ventricular Esquerda/efeitos dos fármacos
17.
Circ J ; 80(6): 1269-77, 2016 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-27151335

RESUMO

Inflammation plays a significant role in a wide range of cardiovascular diseases (CVDs). The numerous implications of inflammation in all steps of CVDs, including initiation, progression and complications, have prompted the emergence of noninvasive imaging modalities as diagnostic, prognostic and monitoring tools. In this review, we first synthesize the existing evidence on the role of inflammation in vascular and cardiac diseases, in order to identify the main targets used in noninvasive imaging. We chose to focus on positron emission tomographic (PET) and magnetic resonance imaging (MRI) studies, which offer the greatest potential of translation and clinical application. We detail the main preclinical and clinical studies in the following CVDs: coronary and vascular atherosclerosis, abdominal aortic aneurysms, myocardial infarction, myocarditis, and acute heart transplant rejection. We highlight the potential complementary roles of these imaging modalities, which are currently being studied in the emerging technology of PET/MRI. Finally, we provide a perspective on innovations and future applications of noninvasive imaging of cardiovascular inflammation. (Circ J 2016; 80: 1269-1277).


Assuntos
Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/patologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Humanos , Miocardite/diagnóstico por imagem
19.
Magn Reson Med ; 73(5): 1764-74, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24806049

RESUMO

PURPOSE: To develop a self-gated alternating repetition time balanced steady-state free precession (ATR-SSFP) pulse sequence for fat-suppressed cardiac cine imaging. METHODS: Cardiac gating is computed retrospectively using acquired magnetic resonance self-gating data, enabling cine imaging without the need for electrocardiogram (ECG) gating. Modification of the slice-select rephasing gradients of an ATR-SSFP sequence enables the acquisition of a one-dimensional self-gating readout during the unused short repetition time (TR). Self-gating readouts are acquired during every TR of segmented, breath-held cardiac scans. A template-matching algorithm is designed to compute cardiac trigger points from the self-gating signals, and these trigger points are used for retrospective cine reconstruction. The proposed approach is compared with ECG-gated ATR-SSFP and balanced steady-state free precession in 10 volunteers and five patients. RESULTS: The difference of ECG and self-gating trigger times has a variability of 13 ± 11 ms (mean ± SD). Qualitative reviewer scoring and ranking indicate no statistically significant differences (P > 0.05) between self-gated and ECG-gated ATR-SSFP images. Quantitative blood-myocardial border sharpness is not significantly different among self-gated ATR-SSFP ( 0.61±0.15 mm -1), ECG-gated ATR-SSFP ( 0.61±0.15 mm -1), or conventional ECG-gated balanced steady-state free precession cine MRI ( 0.59±0.15 mm -1). CONCLUSION: The proposed self-gated ATR-SSFP sequence enables fat-suppressed cardiac cine imaging at 1.5 T without the need for ECG gating and without decreasing the imaging efficiency of ATR-SSFP.


Assuntos
Técnicas de Imagem de Sincronização Cardíaca , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Algoritmos , Feminino , Humanos , Masculino , Meglumina/análogos & derivados , Contração Miocárdica/fisiologia , Compostos Organometálicos , Valores de Referência , Sensibilidade e Especificidade
20.
Cardiovasc Digit Health J ; 5(2): 59-69, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38765618

RESUMO

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual's elevated 10-year ASCVD risk score based on retinal images and limited demographic data. Methods: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual's 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%. Results: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%. Conclusion: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.

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