RESUMO
Autophagy is an abnormal protein degradation and recycling process that is impaired in various neurological diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease. Spermidine is a natural polyamine found in various plant- and meat-based diets that can induce autophagy, and is decreased in various neurodegenerative diseases. It acts on epigenetic enzymes like E1A-binding protein p300, HAT enzymes like Iki3p and Sas3p, and α-tubulin acetyltransferase 1 that modulate autophagy. Histone modifications like acetylation, phosphorylation, and methylation could influence autophagy. Autophagy is epigenetically regulated in various neurodegenerative disorders with many epigenetic enzymes and miRNAs. Polyamine regulation plays an essential role in the disease pathogenesis of AD and PD. Therefore, in this review, we discuss various enzymes and miRNAs involved in the epigenetic regulation of autophagy in neurodegenerative disorders and the role of spermidine as an autophagy enhancer. The alterations in spermidine-mediated regulation of Beclin-1, LC3-II, and p62 genes in AD and other PD-associated enzymes could impact the process of autophagy in these neurodegenerative diseases. With the ever-growing data and such promising effects of spermidine in autophagy, we feel it could be a promising target in this area and worth further detailed studies.
Assuntos
Autofagia , Epigênese Genética , Doenças Neurodegenerativas , Espermidina , Espermidina/farmacologia , Espermidina/metabolismo , Humanos , Autofagia/efeitos dos fármacos , Autofagia/genética , Epigênese Genética/efeitos dos fármacos , Animais , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
The COVID-19 pandemic has thrown up innumerable challenges throughout the world, especially evident in the healthcare system. In emergency medicine, there is a new urgency around the clinical and ethical dilemmas clinicians face as they make decisions that impact upon the lives of their patients. Emergency clinicians are accustomed to upholding duty of care and acting in the best interests of patients. Clinical judgements are made every day about a patient's capacity to make their own decisions and act with free will. It is foreseeable that a duty of care owed to a patient may be in conflict with the responsibility to the health and safety of a community. What is particularly fraught for clinicians is the lack of clarity around this potential duty of care to the community, and navigating the potential conflict with duty of care to the patient. How much danger does the community need to be in, and how definable, imminent and specific does that risk need to be? An attempt to protect the community may well constitute either a breach of confidentiality or a breach of duty of care. This paper will explore the complex issues of respect for autonomy and the principle of non-maleficence, in the setting of COVID-19 and public health orders and illustrate the uncomfortable uncertainty that exists surrounding care of some of the most vulnerable patients in the community when their actions are contrary to public health recommendations.
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COVID-19 , Medicina de Emergência , Atenção à Saúde , Humanos , Pandemias , Saúde PúblicaRESUMO
"Why are neurotypicals so pig-ignorant about autism?" an autistic person wrote on the Curtin Autism Research Group's on-line portal as a response to a call for research questions. Co-produced with an autistic researcher, knowledge about and attitudes towards autism were analysed from 1,054 completed surveys, representing the Australian neurotypical adult population. The majority, 81.5% of participants had a high level of knowledge and 81.3% of participants had a strong positive attitude towards autism. Neither age, nor education level had an impact on attitudes. However, attitudes were influenced by knowledge about 'Societal Views and Ideas'; 'What it Could be Like to Have Autism'; and the demographic variables 'Knowing and having spent time around someone with autism'; and gender (women having more positive attitudes than men). Thus, targeted interventions, geared more towards men than women, to increase knowledge about autism could further improve attitudes and increase acceptance of the autistic community.
Assuntos
Transtorno Autístico/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preconceito/psicologia , Preconceito/estatística & dados numéricos , Distância Psicológica , Estigma Social , Inquéritos e Questionários , Adulto JovemAssuntos
Arritmias Cardíacas , Miosinas Cardíacas/genética , Átrios do Coração , Cadeias Pesadas de Miosina/genética , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/genética , Fibrose , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Humanos , Masculino , Mutação/genéticaRESUMO
With the advent of highly active antiretroviral therapy (HAART) survival rates among patients infected by HIV have increased. However, even though survival has increased HIV-associated neurocognitive disorders (HAND) still persist, suggesting that HAART-drugs may play a role in the neurocognitive impairment observed in HIV-infected patients. Given previous data demonstrating that astrocyte senescence plays a role in neurocognitive disorders such as Alzheimer's disease (AD), we examined the role of HAART on markers of senescence in primary cultures of human astrocytes (HAs). Our results indicate HAART treatment induces cell cycle arrest, senescence-associated beta-galactosidase, and the cell cycle inhibitor p21. Highly active antiretroviral therapy treatment is also associated with the induction of reactive oxygen species and upregulation of mitochondrial oxygen consumption. These changes in mitochondria correlate with increased glycolysis in HAART drug treated astrocytes. Taken together these results indicate that HAART drugs induce the senescence program in HAs, which is associated with oxidative and metabolic changes that could play a role in the development of HAND.
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A shortcut review was carried out to establish whether the presence of systemic inflammatory response criteria in emergency department patients with pancreatitis is predictive of the risk of death. Eight papers presented the best evidence to answer the clinical question. The review concludes that the presence of SIRS in emergency department patients with pancreatitis is associated with a higher risk of mortality.
Assuntos
Pancreatite/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Humanos , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Índice de Gravidade de Doença , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/mortalidadeRESUMO
A shortcut review was carried out to establish whether serum procalcitonin levels can be used to identify serious bacterial infection in ED patients with undifferentiated SIRS. 14 papers presented the best evidence to answer the clinical question. The review concludes that raised procalcitonin levels are associated with bacteraemia; however, there are no clinical management studies addressing this question in ED patients with SIRS.
Assuntos
Bacteriemia/diagnóstico , Calcitonina/análise , Síndrome de Resposta Inflamatória Sistêmica/complicações , Bacteriemia/etiologia , Bacteriemia/fisiopatologia , Calcitonina/sangue , Serviço Hospitalar de Emergência , HumanosRESUMO
Despite strong association between erectile dysfunction (ED) and cardiovascular disease (CVD), there is a paucity of clear clinical guidelines detailing when and how to evaluate for ED in patients with known CVD, or vice versa. This systematic review discuss the role of cardiologists and urologists in the characterization of risk and management of CVD in the setting of ED, as well as contrasting the current evaluation of CVD and ED from the standpoint of published consensus statements. A comprehensive literature review utilizing MEDLINE®, the Cochrane Library® Central Search, and the Web of Science was performed to identify all published peer-reviewed articles in the English language describing ED and CVD across various disciplines. There is strong consensus that men with ED should be considered at high risk of CVD. Available risk assessment tools should be used to stratify the coronary risk score in each patient. The 2012 Princeton III Consensus Conference expanded on existing cardiovascular recommendations, proposing an approach to the evaluation and management of cardiovascular risk in men with ED and no known CVD. This systematic review highlights the similarities and differences of the existing clinical guidelines and recommendations regarding assessment and management of ED and CVD, as well as the pathophysiological linkage between ED and CVD, which may permit physicians, including urologists, to perform opportunistic screening and initiate secondary prophylaxis with regard to cardiovascular risk factors, particularly in young, nondiabetic men with ED.
Assuntos
Doenças Cardiovasculares , Disfunção Erétil , Guias como Assunto , Humanos , Masculino , Medição de RiscoRESUMO
OBJECTIVES: The aim of this study was to determine whether early gadolinium enhancement (EGE) by cardiac magnetic resonance (CMR) in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. BACKGROUND: It remains controversial whether only the irreversibly injured myocardium enhances when CMR is performed in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction because it correlates well with T2-weighted imaging of the AAR, but this still requires pathological validation. METHODS: Eleven dogs underwent 2 h of coronary artery occlusion and 48 h of reperfusion before imaging at 1.5-T. EGE imaging was performed 3 min after contrast administration with coverage of the entire left ventricle. Late gadolinium enhancement imaging was performed between 10 and 15 min after contrast injection. AAR was defined as myocardium with blood flow <2 SD from remote myocardium determined by microspheres during occlusion. The size of infarction was determined with triphenyltetrazolium chloride. RESULTS: There was no significant difference in the size of enhancement by EGE compared with the size of AAR by microspheres (44.1 ± 15.8% vs. 42.7 ± 9.2%; p = 0.61), with good correlation (r = 0.88; p < 0.001) and good agreement by Bland-Altman analysis (mean bias 1.4 ± 17.4%). There was no difference in the size of enhancement by EGE compared with enhancement on native T1 and T2 maps. The size of EGE was significantly greater than the infarct by triphenyltetrazolium chloride (44.1 ± 15.8% vs. 20.7 ± 14.4%; p < 0.001) and late gadolinium enhancement (44.1 ± 15.8% vs. 23.5 ± 12.7%; p < 0.001). CONCLUSIONS: At 3 min post-contrast, EGE correlated well with the AAR by microspheres and CMR and was greater than infarct size. Thus, EGE enhances both reversibly and irreversibly injured myocardium.
Assuntos
Meios de Contraste/administração & dosagem , Circulação Coronária , Gadolínio DTPA/administração & dosagem , Infarto do Miocárdio/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Miocárdio/patologia , Animais , Velocidade do Fluxo Sanguíneo , Modelos Animais de Doenças , Cães , Corantes Fluorescentes/administração & dosagem , Imageamento por Ressonância Magnética , Microesferas , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Fatores de Tempo , Sobrevivência de TecidosRESUMO
BACKGROUND: We aimed to assess whether chronic obstructive pulmonary disease (COPD) is associated with expansion of the myocardial extracellular volume (ECV) using T1 measurements. METHODS: Adult COPD patients Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2 or higher and free of known cardiovascular disease were recruited. All study patients underwent measures of pulmonary function, 6-minute walk test, serum measures of inflammation, overnight polysomnography, and a contrast cardiac magnetic resonance study. RESULTS: Eight patients with COPD were compared with 8 healthy control subjects. The mean predicted forced expiratory volume at 1 second of COPD subjects was 68%. Compared with control subjects, patients had normal left ventricular (LV) and right ventricular size, mass, and function. However, compared with control subjects, the LV remodelling index (median, 0.87; interquartile range [IQR], 0.71-1.14; vs median, 0.62; IQR, 0.60-0.77; P » 0.03) and active left atrial emptying fraction was increased (median, 46; IQR, 41-49; vs median, 38; IQR, 33-43; P » 0.005), and passive left atrial emptying fraction was reduced (median, 24; IQR, 20-30; vs median, 44; IQR, 31-51; P » 0.007). The ECV was increased in patients with COPD (median, 0.32; IQR, 0.05; vs median, 0.27; IQR, 0.05; P = 0.001). The ECV showed a strong positive association with LV remodelling (r = 0.72; P = 0.04) and an inverse association with the 6-minute walk duration (r = -0.79; P = 0.02) and passive left atrial emptying fraction (r = -0.68; P = 0.003). CONCLUSIONS: Expansion of the ECV, suggestive of diffuse myocardial fibrosis, is present in COPD and is associated with LV remodelling, and reduced left atrial function and exercise capacity.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular/fisiologia , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Teste de Esforço , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos RetrospectivosRESUMO
AIMS: Knowledge of adverse events associated with regadenoson perfusion cardiac magnetic resonance (CMR) and patient tolerability has implications for patient safety and staff training. We sought to assess the safety and tolerability of regadenoson stress CMR. MATERIALS AND METHODS: A group of 728 consecutive patients (median age 58, 44% female) and 25 normal volunteers (median age 21, 24% female) were recruited from August 2009 to March 2012 using a prospective, cross-sectional study design. Subjects were stressed using fixed-dose regadenoson and imaged using a 1.5T MRI scanner. Symptoms and adverse events including death, myocardial infarction (MI), ventricular tachycardia (VT)/ventricular fibrillation (VF), hospitalization, arrhythmias, and haemodynamic stability were assessed. RESULTS: There were no occurrences of death, MI, VT/VF, high-grade atrioventricular block, or stress-induced atrial fibrillation. Notable adverse events included one case of bronchospasm and one case of heart failure exacerbation resulting in hospitalization. The most common symptoms in patients were dyspnoea (30%, n = 217), chest discomfort (27%, n = 200), and headache (15%, n = 111). There was minimal change between baseline and peak systolic and diastolic blood pressure in both patients and volunteers (P > 0.05). A blunted heart rate response to regadenoson was noted in patients with body mass index (BMI) ≥ 30 kg/m(2) (P < 0.001), and diabetes (P = 0.001). CONCLUSIONS: Regadenoson CMR is well tolerated and can be performed safely with few adverse events.
Assuntos
Meios de Contraste , Tolerância a Medicamentos , Imagem Cinética por Ressonância Magnética/métodos , Segurança do Paciente , Purinas , Pirazóis , Adulto , Idoso , Análise de Variância , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Meios de Contraste/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Imagem Cinética por Ressonância Magnética/efeitos adversos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/efeitos adversos , Imagem de Perfusão do Miocárdio/métodos , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Curva ROC , Medição de Risco , Estatísticas não Paramétricas , Adulto JovemRESUMO
Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study was to determine concordance and accuracy of vasodilator stress CMR and coronary CTA in the same subjects. We studied 151 consecutive subjects referred to detect or exclude suspected obstructive coronary artery disease (CAD) in patients without known disease or recurrent stenosis or ischemia in patients with previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner. CTA was performed on a 320-detector row system. Subjects were followed for cardiovascular events and downstream diagnostic testing. Subjects averaged 56 ± 12 years (60% male), and 62 % had intermediate pre-test probability for obstructive CAD. Follow-up averaged 450 ± 115 days and was 100% complete. CMR and CTA agreed in 92% of cases (κ 0.81, p < 0.001). The event-free survival was 97 % for non-ischemic and 39% for ischemic CMR (p < 0.0001). The event-free survival was 99% for non-obstructive and 36% for obstructive CTA (p < 0.0001). Using a reference standard including quantitative invasive angiography or major cardiovascular events, CMR and CTA had respective sensitivities of 93 and 98 %; specificities of 96 and 96%; positive predictive values of 91 and 91%; negative predictive values of 97 and 99%; and accuracies of 95 and 97%. Non-ischemic vasodilator stress CMR or non-obstructive coronary CTA were highly concordant and each confer an excellent prognosis. CMR and CTA are both accurate for assessment of obstructive CAD in a predominantly intermediate risk population.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores , Imagem de Perfusão do Miocárdio/métodos , Vasodilatadores/uso terapêutico , Adulto , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). METHODS: Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 µg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 µg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3-4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. RESULTS: Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 µl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 µl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = 0.07) and between adenosine and dipyridamole (2.12 ± 0.27 vs. 1.77 ± 0.33, p = 0.01). CONCLUSIONS: Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy and are superior to dipyridamole.
Assuntos
Adenosina , Circulação Coronária/efeitos dos fármacos , Dipiridamol , Imageamento por Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodos , Purinas , Pirazóis , Vasodilatação/efeitos dos fármacos , Vasodilatadores , Adenosina/administração & dosagem , Dipiridamol/administração & dosagem , Feminino , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Parenterais , Masculino , Valor Preditivo dos Testes , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Vasodilatadores/administração & dosagem , Adulto JovemRESUMO
INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Heme Oxigenase (Desciclizante)/biossíntese , Pulmão/enzimologia , Doenças Metabólicas/enzimologia , Propranolol/administração & dosagem , Sepse/enzimologia , Animais , Esquema de Medicação , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Pulmão/efeitos dos fármacos , Masculino , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/mortalidade , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Sepse/mortalidade , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
BACKGROUND: We aim to deliver large appliances into the left ventricle through the right ventricle and across the interventricular septum. This transthoracic access route exploits immediate recoil of the septum, and lower transmyocardial pressure gradient across the right versus left ventricular free wall. The route may enhance safety and allow subxiphoid rather than intercostal traversal. METHODS: The entire procedure was performed under real-time CMR guidance. An "active" CMR needle crossed the chest, right ventricular free wall, and then the interventricular septum to deliver a guidewire then used to deliver an 18Fr introducer. Afterwards, the right ventricular free wall was closed with a nitinol occluder. Immediate closure and late healing of the unrepaired septum and free wall were assessed by oximetry, angiography, CMR, and necropsy up to four weeks afterwards. RESULTS: The procedure was successful in 9 of 11 pigs. One failed because of refractory ventricular fibrillation upon needle entry, and the other because of inadequate guidewire support. In all ten attempts, the right ventricular free wall was closed without hemopericardium. There was neither immediate nor late shunt on oximetry, X-ray angiography, or CMR. The interventricular septal tract fibrosed completely. Transventricular trajectories planned on human CT scans suggest comparable intracavitary working space and less acute entry angles than a conventional atrial transseptal approach. CONCLUSION: Large closed-chest access ports can be introduced across the right ventricular free wall and interventricular septum into the left ventricle. The septum recoils immediately and heals completely without repair. A nitinol occluder immediately seals the right ventricular wall. The entry angle is more favorable to introduce, for example, prosthetic mitral valves than a conventional atrial transseptal approach.
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Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/métodos , Ventrículos do Coração/patologia , Imagem por Ressonância Magnética Intervencionista , Dispositivo para Oclusão Septal , Septo Interventricular/patologia , Idoso , Ligas , Animais , Cateteres Cardíacos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Estudos de Viabilidade , Feminino , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Animais , Desenho de Prótese , Punções , Suínos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Função Ventricular , Septo Interventricular/diagnóstico por imagem , Septo Interventricular/fisiopatologia , CicatrizaçãoRESUMO
BACKGROUND: Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI. METHODS: Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis. RESULTS: Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI's; LGE had two false positive MI's including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001). CONCLUSION: While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI's than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.
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Meios de Contraste , Gadolínio DTPA , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico , Imagem de Perfusão do Miocárdio/métodos , Miocárdio/patologia , Adulto , Idoso , Circulação Coronária , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeAssuntos
Átrios do Coração , Hematoma/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Miocárdio/patologia , Angiografia Coronária , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Hematoma/complicações , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicaçõesRESUMO
BACKGROUND: Disturbances in the myocardial extracellular volume fraction (ECV), such as diffuse or focal myocardial fibrosis or edema, are hallmarks of heart disease. Diffuse ECV changes are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE), or pre- or post-contrast T1-mapping alone. ECV measurement circumvents factors that confound T1-weighted images or T1-maps, and has been shown to correlate well with diffuse myocardial fibrosis. The goal of this study was to develop and evaluate an automated method for producing a pixel-wise map of ECV that would be adequately robust for clinical work flow. METHODS: ECV maps were automatically generated from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. The algorithm incorporates correction of respiratory motion that occurs due to insufficient breath-holding and due to misregistration between breath-holds, as well as automated identification of the blood pool. Images were visually scored on a 5-point scale from non-diagnostic (1) to excellent (5). RESULTS: The quality score of ECV maps was 4.23 ± 0.83 (m ± SD), scored for n=600 maps from 338 patients with 83% either excellent or good. Co-registration of the pre-and post-contrast images improved the image quality for ECV maps in 81% of the cases. ECV of normal myocardium was 25.4 ± 2.5% (m ± SD) using motion correction and co-registration values and was 31.5 ± 8.7% without motion correction and co-registration. CONCLUSIONS: Fully automated motion correction and co-registration of breath-holds significantly improve the quality of ECV maps, thus making the generation of ECV-maps feasible for clinical work flow.
Assuntos
Algoritmos , Cardiomiopatias/patologia , Aumento da Imagem/métodos , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Idoso , Feminino , Fibrose , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Diffuse myocardial fibrosis, and to a lesser extent global myocardial edema, are important processes in heart disease which are difficult to assess or quantify with cardiovascular magnetic resonance (CMR) using conventional late gadolinium enhancement (LGE) or T1-mapping. Measurement of the myocardial extracellular volume fraction (ECV) circumvents factors that confound T1-weighted images or T1-maps. We hypothesized that quantitative assessment of myocardial ECV would be clinically useful for detecting both focal and diffuse myocardial abnormalities in a variety of common and uncommon heart diseases. METHODS: A total of 156 subjects were imaged including 62 with normal findings, 33 patients with chronic myocardial infarction (MI), 33 with hypertrophic cardiomyopathy (HCM), 15 with non-ischemic dilated cardiomyopathy (DCM), 7 with acute myocarditis, 4 with cardiac amyloidosis, and 2 with systemic capillary leak syndrome (SCLS). Motion corrected ECV maps were generated automatically from T1-maps acquired pre- and post-contrast calibrated by blood hematocrit. Abnormally-elevated ECV was defined as >2SD from the mean ECV in individuals with normal findings. In HCM the size of regions of LGE was quantified as the region >2 SD from remote. RESULTS: Mean ECV of 62 normal individuals was 25.4 ± 2.5% (m ± SD), normal range 20.4%-30.4%. Mean ECV within the core of chronic myocardial infarctions (without MVO) (N=33) measured 68.5 ± 8.6% (p<0.001 vs normal). In HCM, the extent of abnormally elevated ECV correlated to the extent of LGE (r=0.72, p<0.001) but had a systematically greater extent by ECV (mean difference 19 ± 7% of slice). Abnormally elevated ECV was identified in 4 of 16 patients with non-ischemic DCM (38.1 ± 1.9% (p<0.001 vs normal) and LGE in the same slice appeared "normal" in 2 of these 4 patients. Mean ECV values in other disease entities ranged 32-60% for cardiac amyloidosis (N=4), 40-41% for systemic capillary leak syndrome (N=2), and 39-56% within abnormal regions affected by myocarditis (N=7). CONCLUSIONS: ECV mapping appears promising to complement LGE imaging in cases of more homogenously diffuse disease. The ability to display ECV maps in units that are physiologically intuitive and may be interpreted on an absolute scale offers the potential for detection of diffuse disease and measurement of the extent and severity of abnormal regions.