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BACKGROUND: Aspirin and unfractionated heparin are often used during endovascular stroke treatment to improve reperfusion and outcomes. However, the effects and risks of anti-thrombotics for this indication are unknown. We therefore aimed to assess the safety and efficacy of intravenous aspirin, unfractionated heparin, both, or neither started during endovascular treatment in patients with ischaemic stroke. METHODS: We did an open-label, multicentre, randomised controlled trial with a 2 × 3 factorial design in 15 centres in the Netherlands. We enrolled adult patients (ie, ≥18 years) with ischaemic stroke due to an intracranial large-vessel occlusion in the anterior circulation in whom endovascular treatment could be initiated within 6 h of symptom onset. Eligible patients had a score of 2 or more on the National Institutes of Health Stroke Scale, and a CT or MRI ruling out intracranial haemorrhage. Randomisation was done using a web-based procedure with permuted blocks and stratified by centre. Patients were randomly assigned (1:1) to receive either periprocedural intravenous aspirin (300 mg bolus) or no aspirin, and randomly assigned (1:1:1) to receive moderate-dose unfractionated heparin (5000 IU bolus followed by 1250 IU/h for 6 h), low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h), or no unfractionated heparin. The primary outcome was the score on the modified Rankin Scale at 90 days. Symptomatic intracranial haemorrhage was the main safety outcome. Analyses were based on intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. This trial is registered with the International Standard Randomised Controlled Trial Number, ISRCTN76741621. FINDINGS: Between Jan 22, 2018, and Jan 27, 2021, we randomly assigned 663 patients; of whom, 628 (95%) provided deferred consent or died before consent could be asked and were included in the modified intention-to-treat population. On Feb 4, 2021, after unblinding and analysis of the data, the trial steering committee permanently stopped patient recruitment and the trial was stopped for safety concerns. The risk of symptomatic intracranial haemorrhage was higher in patients allocated to receive aspirin than in those not receiving aspirin (43 [14%] of 310 vs 23 [7%] of 318; adjusted OR 1·95 [95% CI 1·13-3·35]) as well as in patients allocated to receive unfractionated heparin than in those not receiving unfractionated heparin (44 [13%] of 332 vs 22 [7%] of 296; 1·98 [1·14-3·46]). Both aspirin (adjusted common OR 0·91 [95% CI 0·69-1·21]) and unfractionated heparin (0·81 [0·61-1·08]) led to a non-significant shift towards worse modified Rankin Scale scores. INTERPRETATION: Periprocedural intravenous aspirin and unfractionated heparin during endovascular stroke treatment are both associated with an increased risk of symptomatic intracranial haemorrhage without evidence for a beneficial effect on functional outcome. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.
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Isquemia Encefálica , Accidente Cerebrovascular , Adulto , Aspirina/uso terapéutico , Isquemia Encefálica/terapia , Heparina/efectos adversos , Humanos , Imagen por Resonancia Magnética , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. METHODS: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). RESULTS: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P<0.001 and 236 versus 270 minutes; P<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. CONCLUSIONS: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Procedimientos Endovasculares/métodos , Humanos , Estudios Longitudinales , Sistema de Registros , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment. METHODS: We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery. RESULTS: Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function. CONCLUSIONS: Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology.
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Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Fallo Renal Crónico , MicroARNs , Anciano , Angiopoyetina 2/genética , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/genética , Cognición , Disfunción Cognitiva/genética , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/genética , Imagen por Resonancia Magnética/métodos , MicroARNs/genética , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT). METHODS: The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD (eGFR ≤20 ml/min/1.73 m2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed. RESULTS: The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all p-values < 0.003). A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed. CONCLUSION: Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.
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Encéfalo/diagnóstico por imagen , Cognición , Disfunción Cognitiva , Función Ejecutiva , Fallo Renal Crónico , Desempeño Psicomotor , Anciano , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Demencia Vascular/diagnóstico , Femenino , Evaluación Geriátrica/métodos , Humanos , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/psicología , Imagen por Resonancia Magnética/métodos , Masculino , Países Bajos/epidemiología , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
PURPOSE: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. MATERIALS AND METHODS: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. RESULTS: Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). CONCLUSION: A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study.
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Tejido Adiposo/patología , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Ejercicio Físico/fisiología , Imagen por Resonancia Magnética/métodos , Femenino , Pruebas de Función Cardíaca , Humanos , Grasa Intraabdominal/patología , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Resistencia Física/fisiología , Estudios Prospectivos , Factores de Riesgo , Triglicéridos/análisisRESUMEN
Background: Ménière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought to be associated with MD, although controversy exists about whether this finding is specific to MD. Recent literature has revealed that two distinct ES pathologies, developmental hypoplasia and epithelial degeneration, can be distinguished in MD using the angular trajectory of the vestibular aqueduct (ATVA) or ED-ES system as a radiographic surrogate marker. It has been suggested that these two subtypes are associated with distinct phenotypical features. However, the clinical differences between the ATVA subtypes require further validation. Research objective: The objective of this study is to investigate whether (1) non-visualization of the ED-ES system is a discriminative radiological feature for MD in a cohort of vertigo-associated pathologies (VAPs) and whether (2) different angular trajectories of the ED-ES system in MD are associated with distinguishable clinical features. Setting: The study was conducted in the Vertigo Referral Center (Haga Teaching Hospital, The Hague, the Netherlands). Methods: We retrospectively assessed 301 patients (187 definite MD and 114 other VAPs) that underwent 4h-delayed 3D FLAIR MRI. We evaluated (1) the visibility of the ED-ES system between MD and other VAP patients and (2) measured the angular trajectory of the ED-ES system. MD patients were stratified based on the angular measurements into αexit ≤ 120° (MD-120), αexit 120°-140° (MD-intermediate), or αexit ≥ 140° (MD-140). Correlations between ATVA subgroups and clinical parameters were evaluated. Results: Non-visualization of the ED-ES system was more common in definite MD patients compared with other VAPs (P < 0.001). Among definite MD patients, the MD-140 subtype demonstrated a longer history of vertigo (P = 0.006), a higher prevalence of bilateral clinical disease (P = 0.005), and a trend toward a male preponderance (p = 0.053). No significant differences were found between ATVA subgroups regarding the presence or severity of auditory symptoms, or the frequency of vertigo attacks. Conclusion: Non-visualization of the ED-ES system is significantly associated with MD. Among MD patients with a visible ED-ES system, we demonstrated that the MD-140 subtype is associated with a longer disease duration, a higher prevalence of bilateral MD, and a trend toward a male preponderance.
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BACKGROUND: Head and neck paragangliomas are tumors associated with the parasympathetic nerve system and typically show an indolent growth pattern. Therefore a conservative management strategy is considered in selected cases. METHODS AND RESULTS: We present a case of a female patient who presented in 2003 with bilateral carotid body tumors and a tympanic tumor, associated with a mutation in the succinate dehydrogenase -sub-unit-D (SDHD). She was operated on the right carotid body tumor and the tympanic tumor. Thereafter the follow-up was performed with MR examinations at 2-year intervals. After an initial stable phase, over the last 3 years a spontaneous near-total regression of the contralateral carotid body tumor was observed, with only subtle rest-abnormalities visible in 2011. CONCLUSIONS: The present case underlines the indolent growth pattern of head and neck paragangliomas and for the first time describes a rare manifestation of spontaneous regression of a carotid body tumor. The literature was reviewed to discuss this phenomenon.
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Tumor del Cuerpo Carotídeo/genética , Mutación , Regresión Neoplásica Espontánea , Succinato Deshidrogenasa/genética , Adulto , Tumor del Cuerpo Carotídeo/patología , Tumor del Cuerpo Carotídeo/cirugía , Femenino , HumanosRESUMEN
BACKGROUND AND OBJECTIVES: In patients with ischemic stroke undergoing endovascular treatment (EVT), time to treatment and collateral status are important prognostic factors and may be correlated. We aimed to assess the relation between time to CT angiography (CTA) and a quantitatively determined collateral score and to assess whether the collateral score modified the relation between time to recanalization and functional outcome. METHODS: We analyzed data from patients with acute ischemic stroke included in the Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke Registry between 2014 and 2017, who had a carotid terminus or M1 occlusion and were treated with EVT within 6.5 hours of symptom onset. A quantitative collateral score (qCS) was determined from baseline CTA using a validated automated image analysis algorithm. We also determined a 4-point visual collateral score (vCS). Multivariable regression models were used to assess the relations between time to imaging and the qCS and between the time to recanalization and functional outcome (90-day modified Rankin Scale score). An interaction term (time to recanalization × qCS) was entered in the latter model to test whether the qCS modifies this relation. Sensitivity analyses were performed using the vCS. RESULTS: We analyzed 1,813 patients. The median time from symptom onset to CTA was 91 minutes (interquartile range [IQR] 65-150 minutes), and the median qCS was 49% (IQR 25%-78%). Longer time to CTA was not associated with the log-transformed qCS (adjusted ß per 30 minutes, 0.002, 95% CI -0.006 to 0.011). Both a higher qCS (adjusted common odds ratio [acOR] per 10% increase: 1.06, 95% CI 1.03-1.09) and shorter time to recanalization (acOR per 30 minutes: 1.17, 95% CI 1.13-1.22) were independently associated with a shift toward better functional outcome. The qCS did not modify the relation between time to recanalization and functional outcome (p for interaction: 0.28). Results from sensitivity analyses using the vCS were similar. DISCUSSION: In the first 6.5 hours of ischemic stroke caused by carotid terminus or M1 occlusion, the collateral status is unaffected by time to imaging, and the benefit of a shorter time to recanalization is independent of baseline collateral status.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Angiografía Cerebral/métodos , Circulación Colateral , Angiografía por Tomografía Computarizada/métodos , Procedimientos Endovasculares/métodos , Humanos , Oportunidad Relativa , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Resultado del TratamientoRESUMEN
A complication of ventriculoperitoneal (VP) shunting is overdrainage or overshunting of cerebrospinal fluid, which can cause formation of hygroma but in rare cases also cervical myelopathy at a later stage. In this article, we describe a very late complication of VP shunting. We present a 75-year-old man, previously given a VP shunt at the age of 46, who developed a progressive gait disturbance and ataxia of the limbs after 27 years. MRI showed a cervical stenosis and myelopathy as a result of venous engorgement due to chronic overshunting of the VP shunt. Revision of the VP shunt resulted in complete resolution of his neurological symptoms and the cervical myelopathy. Cervical myelopathy due to chronic overshunting is a rare and potentially very late complication of a VP shunt. Our case underlines the importance of awareness of this complication while proper treatment can reverse the associated symptoms fully.
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INTRODUCTION: Outcomes of surgery for Ménière's disease (MD) remain discordant. Recently, a new surgical procedure in which the endolymphatic duct is clipped was proposed. To date, only one prospective trial assessing this technique was published, yielding promising results. This protocol describes a prospective, double-blinded, randomised controlled trial that will be carried out to assess the effectiveness of this surgical intervention. METHODS: Eighty-four patients with intractable MD will be recruited from 13 hospitals in the Netherlands. Intraoperatively, randomisation will determine whether endolymphatic duct blockage (EDB) or endolymphatic sac decompression (ESD) will be performed. Randomisation will be 1:1 stratified for gender and duration of MD (recent-onset versus mature MD). All participants receive vestibular rehabilitation after surgery. Patients are followed up during 1 year after surgery. Follow-up visits will take place at 1 week, 3 months, 6 months and 12 months after surgery. The main study endpoint is proportion of patients who are free of vertigo spells at 12 months postoperatively. Secondary parameters include cumulative number of vertigo bouts, co-intervention, tinnitus, hearing, quality of life, cost effectiveness and a budget impact analysis. Total duration of the study is 4 years. ANALYSIS: The primary analysis will follow the intention-to-treat principle. For the primary outcome, a χ2 test will be performed. Secondary outcomes will be analysed using a linear mixed model (EDB versus decompression group) at the different time measurement point. ETHICS AND DISSEMINATION: This study was reviewed and approved by a board of specialists before funding was obtained, as well as by the Medical Research Ethics Committee Leiden-The Hague-Delft and the boards of all participating centres. Results of this study will be published in international peer-reviewed scientific journals and will be presented on (inter)national scientific conferences and meetings. TRIAL REGISTRATION NUMBERS: NL9095 and ISRCTN12074571; Pre-Results.
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Saco Endolinfático , Enfermedad de Meniere , Descompresión , Conducto Endolinfático , Saco Endolinfático/cirugía , Humanos , Enfermedad de Meniere/cirugía , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Research Objective: To investigate the correlation between clinical features and MRI-confirmed endolymphatic hydrops (EH) and blood-labyrinth barrier (BLB) impairment. Study Design: Retrospective cross-sectional study. Setting: Vertigo referral center (Haga Teaching Hospital, The Hague, the Netherlands). Methods: We retrospectively analyzed all patients that underwent 4 h-delayed Gd-enhanced 3D FLAIR MRI at our institution from February 2017 to March 2019. Perilymphatic enhancement and the degree of cochlear and vestibular hydrops were assessed. The signal intensity ratio (SIR) was calculated by region of interest analysis. Correlations between MRI findings and clinical features were evaluated. Results: Two hundred and fifteen patients with MRI-proven endolymphatic hydrops (EH) were included (179 unilateral, 36 bilateral) with a mean age of 55.9 yrs and median disease duration of 4.3 yrs. Hydrops grade is significantly correlated with disease duration (P < 0.001), the severity of low- and high-frequency hearing loss (both P < 0.001), and the incidence of drop attacks (P = 0.001). Visually increased perilymphatic enhancement was present in 157 (87.7%) subjects with unilateral EH. SIR increases in correlation with hydrops grade (P < 0.001), but is not significantly correlated with the low or high Fletcher index (P = 0.344 and P = 0.178 respectively). No significant differences were found between the degree of EH or BLB impairment and vertigo, tinnitus or aural fullness. Conclusion: The degree of EH positively correlates with disease duration, hearing loss and the incidence of drop attacks. The BLB is impaired in association with EH grade, but without clear contribution to the severity of audiovestibular symptoms.
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A 4-year-old girl presented with an alteration of consciousness and absence of speech after a short period of vomiting, diarrhoea and fever. MRI of the brain revealed a focal lesion in the splenium of the corpus callosum. Rotavirus was detected in the faeces. We concluded that the rotavirus infection had caused mild encephalopathy with a reversible splenial lesion.
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Encefalopatías/diagnóstico , Cuerpo Calloso , Infecciones por Rotavirus , Rotavirus/aislamiento & purificación , Trastornos del Habla/diagnóstico , Inconsciencia/diagnóstico , Encefalopatías/fisiopatología , Encefalopatías/virología , Preescolar , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Diagnóstico Diferencial , Heces/virología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Infecciones por Rotavirus/complicaciones , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/fisiopatología , Trastornos del Habla/etiología , Inconsciencia/etiologíaRESUMEN
The Dutch prospective multicenter cohort study COPE (Cognitive decline in Older Patients with End stage renal disease) aimed to investigate the association of cardiovascular structure and function with cerebrovascular changes and cognitive function in 85 older patients with chronic kidney disease stage 4 and 5, awaiting either dialysis or conservative care. MRI was performed measuring aortic stiffness (pulse wave velocity [PWV]) and cardiac systolic function (ejection fraction and cardiac index). Outcomes were MRI-derived cerebrovascular changes (microbleeds, lacunes and white matter hyperintensities) and cognitive function (memory, executive function and psychomotor speed). Mean age was 76 years and 66% were male. No statistically significant associations were observed between cardiovascular parameters and cerebrovascular changes. Cognitive function was worse in patients with high compared to low PWV in all three cognitive domains. Although there were clinically relevant associations of high PWV with poor cognition in all domains, after adjustment for age, sex and education only the Trail Making Test A remained statistically significant (p=0.030). In conclusion, this study suggests that a higher PWV might be associated with lower cognitive function, suggesting that arterial stiffness may be an underlying mechanism of development of cognitive impairment in older patients with ESRD. Larger studies should replicate and extend these findings.
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Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/etiología , Fallo Renal Crónico/complicaciones , Factores de Edad , Anciano , Sistema Cardiovascular/patología , Sistema Cardiovascular/fisiopatología , Toma de Decisiones Clínicas , Cognición , Árboles de Decisión , Manejo de la Enfermedad , Femenino , Pruebas de Función Cardíaca , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
AIMS: In animal models of obesity and diabetes mellitus, myocardial TG accumulation is associated with decreased myocardial function. In the physiologically ageing heart, myocardial triglyceride (TG) accumulation may also occur due to reduced myocardial fatty acid oxidation. The role of myocardial TG in the ageing human heart is unknown. Therefore, the purpose of our study was to evaluate the effects of ageing on myocardial TG content, and to determine the association between myocardial TG content and heart function. METHODS AND RESULTS: 1H-magnetic resonance spectroscopy and magnetic resonance imaging of the heart were performed in 43 healthy male subjects. Mean age (range) of the subjects was 44 (20-66) years. Body mass index (BMI), blood pressure, and biochemical markers were determined. Age correlated significantly to myocardial TG content (r = 0.57, P < 0.05) independently of BMI. Furthermore, myocardial TG content correlated negatively with left ventricular diastolic function (represented by E/A ratio, r = -0.68, P < 0.05). Multivariable analysis indicated myocardial TG content as independent predictor (P < 0.05) of the age related decrease in diastolic heart function. CONCLUSION: Myocardial TG content increases in the physiologically ageing male heart and is associated with the age-related decline in diastolic function, independent of BMI, blood pressure, and biochemical blood markers.
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Envejecimiento/fisiología , Diástole/fisiología , Corazón/fisiología , Triglicéridos/análisis , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Biomarcadores/análisis , Presión Sanguínea/fisiología , Índice de Masa Corporal , Métodos Epidemiológicos , Humanos , Angiografía por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Miocardio/químicaRESUMEN
CONTEXT: In animal experiments, high plasma concentrations of free fatty acids (FFAs) are associated with increased triglyceride (TG) stores in liver and heart, and impaired cardiac function. In humans caloric restriction increases plasma FFA levels. OBJECTIVE: Our objective was to assess the effects of progressive caloric restriction on myocardial and hepatic TG content and myocardial function. DESIGN: This was a prospective intervention study. PARTICIPANTS: This study included 10 lean healthy men. INTERVENTIONS: Three-day partial (471 kcal/d) and complete starvation was performed. OUTCOME MEASURES: Plasma levels of FFA, myocardial and hepatic TG content, and myocardial function were calculated. RESULTS: Plasma FFA increased from 0.6 +/- 0.4 mmol/liter to 1.2 +/- 0.4 and to 1.9 +/- 0.7 mmol/liter, after partial and complete starvation, respectively (P < 0.001). Myocardial TG content increased from 0.35 +/- 0.14% to 0.59 +/- 0.27%, and 1.26 +/- 0.49%, respectively (P < 0.01). The ratio between the early diastole and atrial contraction decreased from 2.2 +/- 0.4 to 2.1 +/- 0.4 (P = 0.7) and 1.8 +/- 0.4, respectively (P < 0.01), and diastolic early deceleration from 3.4 +/- 0.7 ml/sec(2) x 10(-3) to 2.9 +/- 0.5 and 2.8 +/- 0.9 ml/sec(2) x 10(-3), respectively (P < 0.05). Hepatic TG content decreased after partial starvation (from 2.23 +/- 2.24% to 1.43 +/- 1.33%; P < 0.05) but did not change upon complete starvation. CONCLUSIONS: Progressive caloric restriction induces a dose-dependent increase in myocardial TG content and a dose-dependent decrease in diastolic function in lean healthy men. Hepatic TG content showed a differential response to progressive caloric restriction, indicating that redistribution of endogenous TG stores is tissue specific.
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Restricción Calórica , Miocardio/metabolismo , Triglicéridos/metabolismo , Adulto , Glucemia/metabolismo , Presión Sanguínea/fisiología , Colesterol/sangre , Colesterol/metabolismo , Estudios de Cohortes , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Insulina/sangre , Insulina/metabolismo , Hígado/metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Estudios Prospectivos , Inanición/sangre , Inanición/metabolismoRESUMEN
CONTEXT: An association has been suggested between elevated plasma nonesterified fatty acid (NEFA) levels, myocardial triglyceride (TG) accumulation, and myocardial function. OBJECTIVE: Our objective was to investigate the effects of an elevation of plasma NEFA by a high-fat, high-energy (HFHE) diet on hepatic and myocardial TG accumulation, and on myocardial function. DESIGN: There were 15 healthy males (mean +/- sd age: 25.0 +/- 6.6 yr) subjected to a 3-d HFHE diet consisting of their regular diet, supplemented with 800 ml cream (280 g fat) every day. METHODS: (1)H-magnetic resonance spectroscopy was performed for assessing hepatic and myocardial TGs. Furthermore, left ventricular function was assessed using magnetic resonance imaging. RESULTS: The HFHE diet increased hepatic TGs compared with baseline (from 2.01 +/- 1.79 to 4.26 +/- 2.78%; P = 0.001) in parallel to plasma TGs and NEFA. Myocardial TGs did not change (0.38 +/- 0.18 vs. 0.40 +/- 0.12%; P = 0.7). The HFHE diet did not change myocardial systolic function. Diastolic function, assessed by dividing the maximum flow across the mitral valve of the early diastolic filling phase by the maximum flow of the atrial contraction (E/A ratio), decreased compared with baseline (from 2.11 +/- 0.39 to 1.89 +/- 0.33; P = 0.031). This difference was no longer significant after adjustment for heart rate (P = 0.12). CONCLUSIONS: Short-term HFHE diet in healthy males results in major increases in plasma TG and NEFA concentrations and hepatic TGs, whereas it does not influence myocardial TGs or myocardial function. These observations indicate differential, tissue-specific partitioning of TGs and/or fatty acids among nonadipose organs during HFHE diet.
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Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Hígado/metabolismo , Miocardio/metabolismo , Triglicéridos/metabolismo , Adulto , Ácidos Grasos no Esterificados/metabolismo , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Triglicéridos/análisis , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Older patients with end stage renal disease (ESRD) are at increased risk for cognitive decline, but detailed studies of the magnitude of cognitive decline on dialysis or comprehensive conservative management (CCM) are lacking and the underlying pathophysiological mechanisms have poorly been studied. OBJECTIVES: To describe the rationale and design of the COPE study. Study objectives are as follows. Firstly, to examine the severity of cognitive impairment in older patients reaching ESRD before dialysis and the rate of decline after dialysis or CCM initiation. Secondly, to study the association of blood biomarkers for microvascular damage and MRI derived measurements of small vessel disease with the rate of cognitive decline. Thirdly, to examine to what extent cardiac function is related to brain structure and perfusion in patients reaching ESRD. Finally, to study the association of cognitive and functional capacity with quality of life in pre-dialysis patients, as well as after dialysis or CCM initiation. STUDY DESIGN AND METHODS: The COPE study is a prospective, multicenter cohort study in the Netherlands, including prevalent and incident pre-dialysis patients ≥65 years old with eGFR ≤20 ml/min/1.73 m2, awaiting either dialysis or CCM initiation. At baseline extensive data is collected including a comprehensive geriatric assessment and laboratory tests. Brain and cardiac MRI for analysis of structural and functional abnormalities are performed at baseline and repeated following therapy change. All other measurements are repeated annually during four years of follow up, including an extra evaluation six months after initiation of dialysis. CONCLUSIONS: Knowledge of the magnitude of cognitive decline and its underlying pathophysiological mechanism, as well as its impact on functionality and quality of life can eventually help to postulate an algorithm for well balanced decision making in treatment strategies in older patients reaching ESRD. CLINICAL TRIAL REGISTRATION: The COPE study is registered on www.ccmo.nl (number: NL46389.058.13).
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Disfunción Cognitiva/epidemiología , Fallo Renal Crónico/complicaciones , Diálisis Renal/métodos , Biomarcadores , Cognición , Toma de Decisiones , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/terapia , Países Bajos , Prevalencia , Estudios Prospectivos , Calidad de VidaRESUMEN
Acute chest pain (ACP) is one of the most common presenting symptoms at the emergency department. The differential diagnosis is vast. To exclude life-threatening causes, radiologists encounter an increasing amount of thoracic computed tomography (CT) examinations including CT angiography of the heart and great vessels. The dual- and triple-rule CT examinations are currently implemented in clinical practice. We retrospectively identified chest CT examinations in the setting of acute chest pain in our hospitals and collected a variety of common and uncommon cases. In this pictorial essay, we present the most educative cases from patients who presented with acute chest pain in the emergency department of our hospitals and for whom a thoracic CT was ordered. When aortic emergencies, acute coronary syndrome, and pulmonary embolism are excluded, these cases may help the radiologist to suggest alternative diagnoses in the diagnostic challenge of acute chest pain. Teaching Points ⢠The number of chest CT examinations for ACP is increasing.⢠Chest CT examinations may help suggesting alternative diagnosis in ACP.⢠Radiologists should be aware of the differential diagnosis of ACP.