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1.
Kidney Int ; 103(6): 1180-1192, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36868377

RESUMEN

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events.


Asunto(s)
Hematínicos , Insuficiencia Renal Crónica , Adulto , Humanos , Calidad de Vida , Hemoglobinas/análisis , Barbitúricos/efectos adversos , Hematínicos/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico
2.
J Stroke Cerebrovasc Dis ; 32(2): 106891, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36473399

RESUMEN

OBJECTIVES: We aimed to summarize the known risk of vasculopathy (stroke, myocardial infarction [MI], and transient ischemic attack [TIA]) after herpes zoster (HZ) and the impact of antiviral treatment and vaccination against HZ on the risk of vasculopathy. MATERIALS AND METHODS: A narrative literature review was conducted in PubMed to identify evidence published in the past 15 years that was relevant to the scope of this article. RESULTS: Ten studies reported that HZ was associated with an increased risk of stroke and one UK study reported no association. Four studies reported that HZ was associated with an increased risk of MI, and four reported that HZ was associated with an increased risk of TIA. Two studies reported that antiviral treatment was associated with a reduced risk of stroke and an additional two studies reported no association between antiviral treatment and the risk of stroke. In addition, two studies reported that vaccination against HZ using the live zoster vaccine (ZVL) was associated with a reduced risk of stroke, and an additional two studies reported that the risk of stroke or MI after HZ was similar between ZVL vaccinated and unvaccinated individuals. CONCLUSIONS: HZ is associated with an increased risk of stroke, MI, or TIA (strongest association is between HZ and stroke). Further studies are needed to determine whether antiviral treatment or ZVL vaccination influence the risk of HZ-associated vasculopathy. In addition, the effect of the recombinant zoster vaccine on the risk of HZ-associated vasculopathy should be studied.


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Ataque Isquémico Transitorio , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Vacuna contra el Herpes Zóster/efectos adversos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/etiología , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Herpes Zóster/prevención & control , Herpesvirus Humano 3 , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Vacunación/efectos adversos , Infarto del Miocardio/inducido químicamente , Antivirales/efectos adversos
3.
Eur Radiol ; 26(5): 1493-502, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26253256

RESUMEN

OBJECTIVES: We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system. METHODS: Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (n = 168). Bland-Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated. RESULTS: Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (r = 0.95; p < 0.0001) and agreement (mean difference -10.4 [95% limits of agreement -258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups k = 0.88 and MESA centiles k = 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third. CONCLUSION: CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability. KEY POINTS: • Coronary calcium scores can be reliably determined on contrast-enhanced cardiac CT • This score can accurately risk stratify patients • Elimination of a dedicated calcium scan reduces patient radiation by a third.


Asunto(s)
Enfermedad Coronaria/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Anciano , Angiografía Coronaria/métodos , Vasos Coronarios/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Masculino , Tomografía Computarizada Multidetector/métodos , Variaciones Dependientes del Observador , Dosis de Radiación , Reproducibilidad de los Resultados
4.
J Cardiovasc Magn Reson ; 16: 5, 2014 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-24400841

RESUMEN

BACKGROUND: Restenosis of the carotid artery is common following carotid endarterectomy, but analysis of lesion composition has mostly been based on histological study of explanted restenotic lesions. This study investigated the ability of 3T cardiovascular magnetic resonance (CMR) to determine the components of recurrent carotid artery disease and examined whether these differed from primary atherosclerotic plaque. METHODS: 50 patients underwent 3T CMR of both carotid arteries using a standard multicontrast protocol: time-of-flight (TOF), T1-weighted (T1W), T2-weighted (T2W), and PD-weighted (PDW) Turbo-Spin-Echo (TSE) sequences. 25 patients had previously undergone carotid endarterectomy (mean time since surgery 1580 days, range 45-6560 days), and 25 with primary asymptomatic atherosclerotic plaques served as controls. Two experienced reviewers analysed the multicontrast CMR images according to the presence or absence of major plaque features and assigned an overall classification type. RESULTS: In patients with recurrent carotid disease following endarterectomy, the mean degree of restenosis was 51% (range 30-90%). Three distinct types of restenosis were identified: 5 patients (20%) showed CMR characteristics of fibro-atheromatous tissue, 11 patients (44%) had plaque features consistent with possible myointimal (fibromuscular) hyperplasia, and 6 patients (24%) had recurrent plaque suggestive of further lipid accumulation. Three patients (12%) showed evidence of post-surgical dissection of the carotid intima. Compared to primary atherosclerotic plaques, restenotic plaques were more likely to contain fibro-atheromatous tissue (p = 0.05) and smooth muscle (p < 0.01), and less likely to contain lipid (p < 0.01). Composition did not differ significantly between patients with early and late restenosis. CONCLUSIONS: As defined by CMR, restenotic lesions of the carotid artery fall into three distinct types and differ in composition from primary atherosclerotic plaques. If validated by subsequent histological studies, these findings could suggest a role for CMR in detecting high-risk (i.e. lipid-rich) restenotic lesions.


Asunto(s)
Arteria Carótida Común/patología , Arteria Carótida Común/cirugía , Estenosis Carotídea/patología , Estenosis Carotídea/cirugía , Endarterectomía Carotidea/efectos adversos , Imagen por Resonancia Magnética , Anciano , Arteria Carótida Común/química , Estenosis Carotídea/metabolismo , Medios de Contraste , Femenino , Fibrosis , Humanos , Lípidos/análisis , Masculino , Variaciones Dependientes del Observador , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Recurrencia , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
5.
Circulation ; 125(11): 1356-66, 2012 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-22315282

RESUMEN

BACKGROUND: The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) plays a pivotal role in maintaining endothelial function in experimental vascular disease models and in humans. Augmentation of endogenous BH4 levels by oral BH4 treatment has been proposed as a potential therapeutic strategy in vascular disease states. We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease. METHODS AND RESULTS: Forty-nine patients with coronary artery disease were randomized to receive low-dose (400 mg/d) or high-dose (700 mg/d) BH4 or placebo for 2 to 6 weeks before coronary artery bypass surgery. Vascular function was quantified by magnetic resonance imaging before and after treatment, along with plasma BH4 levels. Vascular superoxide, endothelial function, and BH4 levels were determined in segments of saphenous vein and internal mammary artery. Oral BH4 treatment significantly augmented BH4 levels in plasma and in saphenous vein (but not internal mammary artery) but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks endothelial nitric oxide synthase cofactor activity. There was no effect of BH4 treatment on vascular function or superoxide production. Supplementation of human vessels and blood with BH4 ex vivo revealed rapid oxidation of BH4 to BH2 with predominant BH2 uptake by vascular tissue. CONCLUSIONS: Oral BH4 treatment augments total biopterin levels in patients with established coronary artery disease but has no net effect on vascular redox state or endothelial function owing to systemic and vascular oxidation of BH4. Alternative strategies are required to target BH4-dependent endothelial function in established vascular disease states.


Asunto(s)
Biopterinas/análogos & derivados , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Administración Oral , Anciano , Biopterinas/administración & dosificación , Biopterinas/sangre , Método Doble Ciego , Femenino , Humanos , Masculino , Oxidación-Reducción/efectos de los fármacos , Resultado del Tratamiento
6.
J Cardiovasc Magn Reson ; 15: 69, 2013 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-23953780

RESUMEN

BACKGROUND: Atherosclerotic plaques in carotid arteries can be characterized in-vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been thoroughly validated with histology. However, the non-quantitative nature of multicontrast CMR and the need for extensive post-acquisition interpretation limit the widespread clinical application of in-vivo CMR plaque characterization. Quantitative T2 mapping is a promising alternative since it can provide absolute physical measurements of plaque components that can be standardized among different CMR systems and widely adopted in multi-centre studies. The purpose of this study was to investigate the use of in-vivo T2 mapping for atherosclerotic plaque characterization by performing American Heart Association (AHA) plaque type classification, segmenting carotid T2 maps and measuring in-vivo T2 values of plaque components. METHODS: The carotid arteries of 15 atherosclerotic patients (11 males, 71 ± 10 years) were imaged at 3 T using the conventional multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps of carotid arteries were generated by mono-exponential fitting to the series of images acquired by Multi-SE using nonlinear least-squares regression. Two reviewers independently classified carotid plaque types following the CMR-modified AHA scheme, one using multicontrast CMR and the other using T2 maps and time-of-flight (TOF) angiography. A semi-automated method based on Bayes classifiers segmented the T2 maps of carotid arteries into 4 classes: calcification, lipid-rich necrotic core (LRNC), fibrous tissue and recent IPH. Mean ± SD of the T2 values of voxels classified as LRNC, fibrous tissue and recent IPH were calculated. RESULTS: In 37 images of carotid arteries from 15 patients, AHA plaque type classified by multicontrast CMR and by T2 maps (+ TOF) showed good agreement (76% of matching classifications and Cohen's κ = 0.68). The T2 maps of 14 normal arteries were used to measure T2 of tunica intima and media (T2 = 54 ± 13 ms). From 11865 voxels in the T2 maps of 15 arteries with advanced atherosclerosis, 2394 voxels were classified by the segmentation algorithm as LRNC (T2 = 37 ± 5 ms) and 7511 voxels as fibrous tissue (T2 = 56 ± 9 ms); 192 voxels were identified as calcification and one recent IPH (236 voxels, T2 = 107 ± 25 ms) was detected on T2 maps and confirmed by multicontrast CMR. CONCLUSIONS: This carotid CMR study shows the potential of in-vivo T2 mapping for atherosclerotic plaque characterization. Agreement between AHA plaque types classified by T2 maps (+TOF) and by conventional multicontrast CMR was good, and T2 measured in-vivo in LRNC, fibrous tissue and recent IPH demonstrated the ability to discriminate plaque components on T2 maps.


Asunto(s)
Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/diagnóstico , Interpretación de Imagen Asistida por Computador/métodos , Angiografía por Resonancia Magnética , Placa Aterosclerótica , Anciano , Anciano de 80 o más Años , Automatización de Laboratorios , Enfermedades de las Arterias Carótidas/clasificación , Enfermedades de las Arterias Carótidas/patología , Femenino , Fibrosis , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Necrosis , Dinámicas no Lineales , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
7.
Clin Pharmacol Drug Dev ; 11(5): 562-575, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35355447

RESUMEN

Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor in development for treatment of anemia of chronic kidney disease. We evaluated the role of hepatic impairment on daprodustat pharmacokinetics, pharmacodynamics, and tolerability. Participants with mild (Child-Pugh Class A, score 5-6) and moderate (Child-Pugh Class B, score 7-9) hepatic impairment and matched healthy controls were administered single 6-mg doses of daprodustat. Exposure parameters were determined for daprodustat and its six metabolites. Comparisons resulted in 1.5- and 2.0-fold higher daprodustat Cmax and area under the curve (AUC) exposures in participants with mild and moderate hepatic impairment, respectively, versus controls; Cmax in mild hepatic impairment was comparable to controls. Similarly, aligned with parent drug, unbound daprodustat Cmax and AUC exposures increased 1.6- to 2.3-fold in hepatic-impaired participants versus controls, and metabolite exposures were 1.2- to 2.0-fold higher in participants with hepatic impairment. Erythropoeitin (EPO) baseline-corrected AUC exposures were between 0.3-fold lower and 2.2-fold higher in matched controls versus hepatic-impaired participants. No serious or study drug-related adverse events were reported. Daprodustat exposure was increased in participants with moderate and mild hepatic impairment compared with matched controls; however, no meaningful differences in EPO were observed and no new safety concerns were identified (ClinicalTrials.gov: NCT03223337).


Asunto(s)
Hepatopatías , Inhibidores de Prolil-Hidroxilasa , Barbitúricos , Femenino , Glicina/efectos adversos , Glicina/análogos & derivados , Glicina/farmacocinética , Humanos , Hepatopatías/metabolismo , Masculino , Inhibidores de Prolil-Hidroxilasa/efectos adversos , Inhibidores de Prolil-Hidroxilasa/farmacocinética
8.
J Magn Reson Imaging ; 33(5): 1136-43, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21509872

RESUMEN

PURPOSE: To test whether the k-space acquisition strategy used by fast-spin-echo (FSE) is a major source of blurring in carotid wall and plaque imaging, and investigate an alternative acquisition approach. MATERIALS AND METHODS: The effect of echo train length (ETL) and T(2) on the amount of blurring was studied in FSE simulations of vessel images. Edge sharpness was measured in black-blood T(1) W and proton density-weighted (PDW) carotid images acquired from 5 normal volunteers and 19 asymptomatic patients using both FSE and multiple-spin-echo (Multi-SE) sequences at 3 Tesla (T). Plaque images were classified and divided in group α (tissues' average T(2) ∼ 40-70 ms) and group ß (plaque components with shorter T(2) ). RESULTS: Simulations predicted 26.9% reduction of vessel edge sharpness from Multi-SE to FSE images (ETL = 9, T(2) = 60 ms). This agreed with in vivo measurements in normal volunteers (27.4%) and in patient group α (26.2%), while in group ß the loss was higher (31.6%). CONCLUSION: FSE significantly reduced vessel edge sharpness along the phase-encoding direction in T(1) W and PDW images. Blurring was stronger in the presence of plaque components with short T(2) times. This study shows a limitation of FSE and the potential of Multi-SE to improve the quality of carotid imaging.


Asunto(s)
Aterosclerosis/patología , Procesamiento de Imagen Asistido por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Arterias Carótidas/patología , Simulación por Computador , Femenino , Análisis de Fourier , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Protones
9.
Clin Pharmacol Drug Dev ; 10(12): 1419-1431, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34713596

RESUMEN

Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease. This phase 1, nonrandomized, 2-period, crossover study in 6 healthy men characterized the absorption, distribution, and excretion of daprodustat when administered as oral and intravenous (IV) doses of unlabeled and radiolabeled daprodustat ([14 C]-GSK1278863). Tolerability and pharmacokinetic properties of daprodustat, and its 6 metabolites in the systemic circulation, were also evaluated. The mean recovery of radiolabeled daprodustat was ≈95% by day 5, with the majority in feces and minor renal elimination, indicating that daprodustat and metabolites are primarily eliminated via hepatobiliary and fecal routes. Approximately 40% of total circulating radioactivity in plasma following both IV and oral administration was daprodustat; thus, 60% was attributed to metabolites. It was estimated that ≈80% of daprodustat was absorbed across the gastrointestinal tract, and ≈18% cleared by hepatic extraction. Pharmacokinetics were essentially dose proportional, with moderate (≈66%) oral tablet bioavailability. Following IV administration, daprodustat plasma clearance (19.3 L/h) and volume of distribution (14.6 L) were low, suggesting low tissue distribution outside systemic circulation with likely low penetration into tissues. Daprodustat was generally well tolerated, with no deaths or serious or significant adverse events reported.


Asunto(s)
Barbitúricos , Glicina , Disponibilidad Biológica , Estudios Cruzados , Glicina/análogos & derivados , Humanos , Masculino
10.
Circ Genom Precis Med ; 13(4): e002804, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32605384

RESUMEN

BACKGROUND: Left ventricular ejection fraction (EF) is an indicator of cardiac function, usually assessed in individuals with heart failure and other cardiac conditions. Although family studies indicate that EF has an important genetic component with heritability estimates up to 0.61, to date only 6 EF-associated loci have been reported. METHODS: Here, we conducted a genome-wide association study (GWAS) of EF in 26 638 adults from the Genetic Epidemiology Research on Adult Health and Aging and the UK Biobank cohorts. RESULTS: A meta-analysis combining results from Genetic Epidemiology Research on Adult Health and Aging and UK Biobank identified a novel locus: TMEM40 on chromosome 3p25 (rs11719526; ß=0.47 and P=3.10×10-8) that replicated in Biobank Japan and confirmed recent findings implicating the BAG3 locus on chromosome 10q26 in EF variation, with the strongest association observed for rs17617337 (ß=-0.83 and P=8.24×10-17). Although the minor allele frequencies of TMEM40 rs11719526 were generally common (between 0.13 and 0.44) in different ethnic groups, BAG3 rs17617337 was rare (minor allele frequencies<0.05) in Asian and African ancestry populations. These associations were slightly attenuated, after considering antecedent cardiac conditions (ie, heart failure/cardiomyopathy, hypertension, myocardial infarction, atrial fibrillation, valvular disease, and revascularization procedures). This suggests that the effects of the lead variants at TMEM40 or BAG3 on EF are largely independent of these conditions. CONCLUSIONS: In this large and multiethnic study, we identified 2 loci, TMEM40 and BAG3, associated with EF at a genome-wide significance level. Identifying and understanding the genetic determinants of EF is important to better understand the pathophysiology of this strong correlate of cardiac outcomes and to help target the development of future therapies.


Asunto(s)
Estudio de Asociación del Genoma Completo , Función Ventricular Izquierda/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , Proteínas Reguladoras de la Apoptosis/genética , Pueblo Asiatico/genética , Población Negra/genética , Femenino , Frecuencia de los Genes , Sitios Genéticos , Variación Genética , Insuficiencia Cardíaca/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Carácter Cuantitativo Heredable , Población Blanca/genética
14.
BMJ Open Qual ; 7(3): e000074, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30057949

RESUMEN

BACKGROUND: The use of the WHO safe surgery checklist has been shown to reduce morbidity and mortality from surgical procedures. However, whether a WHO-style safe procedure checklist can improve safety in the cardiac catheterisation laboratory (CCL) has not previously been investigated. OBJECTIVES: The authors sought to design and implement a safe procedure checklist suitable for all CCL procedures, and to assess its impact over the course of 1 year. METHODS: In the first 3 months, weekly PDSA cycles (Plan-Do-Study-Act) were used to optimise the design of the checklist through testing and staff feedback, and team briefing sessions were introduced before each procedure list. The impact of the checklist and team briefs was assessed by analysing in-house procedural data subsequently submitted to national audit databases. Staff and patient questionnaires were performed throughout the year. RESULTS: Introduction of the checklist was associated with a significant reduction of 3 min in average turnaround time (95% CI 25 s to 6 min, p=0.027). Similarly, an initial reduction in patient radiation exposure was recorded (dose area product reduction of 641.5 cGy/cm2; 95% CI 255.9 to 1027.1, p=0.002). The rate of reported complications from all procedures fell significantly from 2.0% in 2012/2013 (95% CI 1.6% to 2.4%) to 0.8% in 2013/2014 (95% CI 0.6% to 1.1%, p≤0.001). Staff climate questionnaires showed that technicians and radiographers gave more positive responses at the end of the study period compared with the beginning (p=0.001). CONCLUSIONS: The use of a team brief and WHO-derived safe procedure checklist in the CCL was associated with decreased radiation exposure, fewer procedural complications, faster turnarounds and improved staff experience.

15.
Artículo en Inglés | MEDLINE | ID: mdl-27418610

RESUMEN

BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported. METHODS AND RESULTS: A total of 190 patients underwent 1.5 Tesla CMR before transcatheter aortic valve implantation. Steady-state free precession sequences were used for aortic valve planimetry and to assess ventricular volumes and mass. Semiautomated image analysis was performed by 2 specialist reviewers blinded to patient treatment. Patient follow-up was obtained from the Office of National Statistics mortality database. The median age was 81.0 (interquartile range, 74.9-85.5) years; 50.0% were women. Impaired RV function (RV ejection fraction ≤50%) was present in 45 (23.7%) patients. Patients with RV dysfunction had poorer left ventricular ejection fractions (42% versus 69%), higher indexed left ventricular end-systolic volumes (96 versus 40 mL), and greater indexed left ventricular mass (101 versus 85 g/m(2); P<0.01 for all) than those with normal RV function. Median follow-up was 850 days; 21 of 45 (46.7%) patients with RV dysfunction died, compared with 43 of 145 (29.7%) patients with normal RV function (P=0.035). After adjustment for significant baseline variables, both RV ejection fraction ≤50% (hazard ratio, 2.12; P=0.017) and indexed aortic valve area (hazard ratio, 4.16; P=0.025) were independently associated with survival. CONCLUSIONS: RV function, measured on preprocedural CMR, is an independent predictor of mortality after transcatheter aortic valve implantation. CMR assessment of RV function may be important in the risk stratification of patients undergoing transcatheter aortic valve implantation.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Reemplazo de la Válvula Aórtica Transcatéter , Disfunción Ventricular Derecha/epidemiología , Función Ventricular Derecha , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/mortalidad , Ecocardiografía , Femenino , Humanos , Estimación de Kaplan-Meier , Londres/epidemiología , Imagen por Resonancia Magnética , Masculino , Valor Predictivo de las Pruebas , Prevalencia , Modelos de Riesgos Proporcionales , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Sístole , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del Tratamiento , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/mortalidad , Disfunción Ventricular Derecha/fisiopatología
16.
Eur J Heart Fail ; 18(6): 703-12, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26990920

RESUMEN

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. METHODS AND RESULTS: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2 ) on exercise, BNP, E/e', LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e' (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema. CONCLUSION: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation.


Asunto(s)
Desnervación , Insuficiencia Cardíaca/cirugía , Arteria Renal/inervación , Simpatectomía , Anciano , Anciano de 80 o más Años , Ecocardiografía , Tolerancia al Ejercicio , Femenino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Masculino , Péptido Natriurético Encefálico/sangre , Tamaño de los Órganos , Consumo de Oxígeno , Volumen Sistólico
17.
Int J Cardiol ; 104(2): 230-2, 2005 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-16168820

RESUMEN

Cannabis smoking is on the increase both in the United Kingdom and in the United States. For over three decades it has been known that cannabis has pathophysiological effects on the cardiovascular system, and previously an association with an increased risk of myocardial infarction has been reported. However, it is not yet known whether cannabis contributes directly to coronary artery disease. We describe two distinct cases; in the first cannabis use precipitated a malignant arrhythmia in a patient with critical ischaemia from longstanding coronary artery disease. In the second, a young patient presented with an acute myocardial infarction that had started whilst smoking marijuana; subsequently diffuse coronary artery disease was found at angiography despite the patient's low risk factor status. Patients who are known cannabis smokers and who have cardiovascular disease should be warned that it is likely to aggravate coronary ischaemia, and may even trigger myocardial infarction.


Asunto(s)
Cannabis/efectos adversos , Fitoterapia/efectos adversos , Adulto , Arritmias Cardíacas/inducido químicamente , Sistema Cardiovascular/efectos de los fármacos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/inducido químicamente , Preparaciones de Plantas/efectos adversos
18.
Hosp Med ; 66(4): 215-20, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15889869

RESUMEN

This article focuses on the key studies relevant to the clinical application of stem-cell research in cardiovascular disease. The authors also discuss current and future directions in clinical cardiovascular stem-cell research, including the potential problems and pitfalls that must be addressed to ensure the safety, as well as the efficacy, of treatment regimens in this rapidly evolving therapeutic field.


Asunto(s)
Enfermedades Cardiovasculares/terapia , Trasplante de Células Madre/tendencias , Diferenciación Celular , Ensayos Clínicos como Asunto , Predicción , Humanos , Selección de Paciente , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/métodos , Células Madre/citología
19.
J Invasive Cardiol ; 27(1): E1-4, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25589704

RESUMEN

The development of a large hematoma impairing visualization of the distal true lumen is a recognized complication of antegrade recanalization of chronic total occlusions, often forcing the operator to abort the procedure or switch to a retrograde approach. We describe a novel technique utilizing an over-the-wire balloon inflated in the proximal occluded vessel to block inflow and allow aspiration of the blood from the subintimal space. This decompressed the true lumen, restored distal visualization, and allowed successful reentry using a dedicated technology. Utilization of this novel technique may rescue antegrade recanalization attempts complicated by large subintimal hematomas.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Oclusión Coronaria/cirugía , Descompresión Quirúrgica , Hematoma , Hemostasis Quirúrgica , Complicaciones Intraoperatorias/cirugía , Complicaciones Posoperatorias/cirugía , Anciano , Angioplastia Coronaria con Balón/métodos , Puente de Arteria Coronaria/efectos adversos , Oclusión Coronaria/diagnóstico , Oclusión Coronaria/etiología , Oclusión Coronaria/fisiopatología , Descompresión Quirúrgica/instrumentación , Descompresión Quirúrgica/métodos , Hematoma/etiología , Hematoma/cirugía , Hemostasis Quirúrgica/instrumentación , Hemostasis Quirúrgica/métodos , Humanos , Masculino , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Resultado del Tratamiento
20.
EuroIntervention ; 11(3): 325-35, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24930135

RESUMEN

AIMS: Challenging coronary anatomies including chronic total occlusions (CTO), extreme vessel tortuosity, diseased bypass grafts, and anomalous coronary arteries pose difficulties in coronary interventions. The GuideLiner is a monorail catheter originally developed to facilitate delivery of stents to target lesions in tortuous vessels. We conducted a study on the feasibility and safety of utilising this catheter in a wider array of complex coronary interventions. METHODS AND RESULTS: Consecutive patients undergoing coronary or peripheral interventions where a GuideLiner was used were recruited into this study. Patient demographics, lesion and vessel characteristics, procedural details and outcomes were prospectively entered into our database and analysed. From September 2009 to October 2011, 54 consecutive patients underwent coronary intervention in our institution using a GuideLiner; 21 out of 54 coronary applications were motivated by the need to increase support to cross CTOs, predominantly of the RCA. Anomalous or angulated take-off of the treatment vessels (31%), previously deployed proximal stents (15%), heavy proximal calcification (9%) and tortuosity (7%) accounted for the remaining reasons. One patient had successful renal denervation with the aid of a GuideLiner catheter. Procedural success was 98% in our series with no device-related periprocedural complications such as ostial dissection or myocardial necrosis. CONCLUSIONS: The use of a GuideLiner facilitates the approach to complex coronary interventions including chronic total occlusion and saphenous vein graft intervention by providing greater back-up support and easier engagement of coronary ostia.


Asunto(s)
Angioplastia Coronaria con Balón , Catéteres Cardíacos , Enfermedad de la Arteria Coronaria/cirugía , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón/métodos , Cateterismo Cardíaco/métodos , Angiografía Coronaria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents , Resultado del Tratamiento
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