29 results on '"Townend, Jonathan N"'
Search Results
2. Mineralocorticoid Receptor Antagonism in Heart Failure and Chronic Kidney Disease: Short-Term Pain for Long-Term Gain.
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Ferro, Charles J. and Townend, Jonathan N.
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CHRONIC kidney failure , *MINERALOCORTICOID receptors , *HEART failure , *ACUTE kidney failure - Abstract
[Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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3. Coronary artery bypass surgery as treatment for ischemic heart failure: the predictive value of viability assessment with quantitative positron emission tomography for symptomatic and functional outcome
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Pagano, Domenico, Townend, Jonathan N., Littler, William A., Horton, Richard, Camici, Paolo G., and Bonser, Robert S.
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Cardiac patients -- Drug therapy ,Heart failure -- Drug therapy ,Ischemia -- Drug therapy ,Surgery ,PET imaging ,Coronary artery bypass ,Health - Abstract
Byline: Domenico Pagano, Jonathan N. Townend, William A. Littler, Richard Horton, Paolo G. Camici, Robert S. Bonser Abstract: Objectives: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class [greater than or equal to] III) with and without angina. Methods: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [.sup.18F]-2-fluoro-2-deoxy-d-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. Results: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% [+ or -] 7% to 32% [+ or -] 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 [+ or -] 4 to 22 [+ or -] 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 [+ or -] 4 to 19 [+ or -] 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. Conclusions: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization. (J Thorac Cardiovasc Surg 1998;115:791-9 Article History: Received 11 July 1997; Revised 13 October 1997; Revised 3 November 1997; Accepted 6 November 1997 Article Note: (footnote) [star] From the Cardiothoracic Surgical Unita and University Department of Cardiovascular Medicine,c Queen Elizabeth Hospital, Birmingham, and MRC Cyclotron Unit and Royal Postgraduate Medical School,b Hammersmith Hospital, London, United Kingdom., [star][star] D. Pagano was supported by a Sheldon Clinical Research Fellowship of the West Midlands Health Authority, UK., a Address for reprints: Robert S. Bonser, MRCP, FRCS, Consultant Cardiothoracic Surgeon, Cardiothoracic Surgical Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom., aa 12/1/87532
- Published
- 1998
4. Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study.
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Hayer, Manvir K., Radhakrishnan, Ashwin, Price, Anna M., Liu, Boyang, Baig, Shanat, Weston, Christopher J., Biasiolli, Luca, Ferro, Charles J., Townend, Jonathan N., Steeds, Richard P., and Edwards, Nicola C.
- Abstract
A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T 1 mapping (biomarker of diffuse fibrosis), T 2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro–B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. Native myocardial T 1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/eʹ, N-terminal pro–B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO 2 Peak, %VO 2 VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T 1 time (p < 0.001). Native myocardial T 1 time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO 2 Peak (p < 0.001). Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862) [ABSTRACT FROM AUTHOR]
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- 2020
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5. Effect of quinapril on blood pressure and heart rate in congestive heart failure
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Townend, Jonathan N., West, John N., Davies, Michael K., and Littler, William A.
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Congestive heart failure -- Drug therapy ,Blood pressure ,Heart beat ,Health ,Quinapril (Medication) -- Evaluation - Abstract
The effect of quinapril on blood pressure (BP), heart rate (HR) and their variabilities in 12 patients with severe congestive heart failure (New York Heart Association class ill and IV) was assessed using ambulatory electrocardiographic and intraarterial monitoring. Mean = standard deviation daytime BP was 122/75 = 20/15 mm Hg at baseline and 113/70 = 13/16 mm Hg after 16 weeks of therapy with quinapril (p >0.05 for systolic and diastolic BP); mean nighttime BP was 114/69 = 19/14 mm Hg at baseline and 107/69 = 15/14 mm Hg with quinapril (p >0.05 for systolic and diastolic BP). Mean daytime HR was unchanged but nighttime HR was reduced from 77 = 11 to 71 = 10 beats/min, p = 0.02. HR variability difference between the 75th and 25th percentiles of the frequency distribution of RR intervals) increased from 91 = 34 to 134 = 47 ms, p = 0.008. The variability of successive differences between RR intervals also increased significantly (75th to 25th percetile = 17 = 4 ms at baseline and 31 = 26 ms with quinapril, p = 0.02). Long-term quinapril caused clinically unimportant decreases in BP in patients with severe congestive heart failure. An increase in vagal activity caused by the reduction in circulating angiotensin 11 may account for the effect of converting enzyme inhibition on HR and its variability. (Am J Cardiol 1992;69:1587-1590)
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- 1992
6. Vitamin E supplementation
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Fryer, Michael J, Boaz, Mona, Smetana, Shmuel, Green, Manfred S, Iuliano, Luigi, Micheletta, Fausta, Violi, Francesco, Fogarty, Andrew, Anastasios Gazis, Wheeler, David C, Townend, Jonathan N, Kendall, Martin J, and Nuttall, Sarah L
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Vitamin E -- Health aspects ,Heart attack -- Risk factors ,Antioxidants -- Dosage and administration - Published
- 2001
7. Dialysis Following Transcatheter Aortic Valve Replacement: Risk Factors and Outcomes: An Analysis From the UK TAVI (Transcatheter Aortic Valve Implantation) Registry.
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Ferro, Charles J., Law, Jonathan P., Doshi, Sagar N., de Belder, Mark, Moat, Neil, Mamas, Mamas, Hildick-Smith, David, Ludman, Peter, and Townend, Jonathan N.
- Abstract
Objectives This study sought to determine the risk factors for post-transcatheter aortic valve replacement (TAVR) dialysis and to determine the impact of pre-TAVR or post-TAVR dialysis on mortality. Background TAVR is now established as an alternative treatment to surgical aortic valve replacement. Data examining the impact of dialysis on outcomes after TAVR are lacking. Methods The UK TAVI (Transcatheter Aortic Valve Implantation) Registry was established to report outcomes on all TAVR procedures performed within the United Kingdom (2007 to 2014). Data were collected prospectively on 6,464 patients with a median follow-up of 625 days. Results The proportion of patients on dialysis before TAVR has remained constant at 1.8%. After TAVR, the proportion of patients newly needing dialysis after TAVR has fallen from 6.1% (2007 to 2008) to 2.3% (2013 to 2014). The risk of new dialysis requirement after TAVR was independently associated with lower baseline renal function, year of procedure, impaired left ventricular function, diabetes, use of an Edwards valve, a nontransfemoral approach, need for open surgery, and moderate-to-severe aortic regurgitation after the procedure. Requirement for new dialysis after TAVR was associated with higher mortality at 30 days (hazard ratio: 6.44; 95% confidence interval: 4.87 to 8.53) and at 4 years (hazard ratio: 3.54; 95% confidence interval: 2.99 to 4.19; p < 0.001 for all) compared with patients without dialysis requirement. Conclusions The proportion of patients needing dialysis after TAVR has decreased over time. Post-TAVR dialysis is associated with increased mortality. Factors identified with dialysis requirement after TAVR require further investigation. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Defining the Natural History of Uremic Cardiomyopathy in Chronic Kidney Disease: The Role of Cardiovascular Magnetic Resonance.
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Edwards, Nicola C., Moody, William E., Chue, Colin D., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard P.
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Chronic kidney disease (CKD) is an under-recognized, highly prevalent cardiovascular (CV) risk factor affecting 1 in 7 adults. Large epidemiological studies have clearly established a graded association between the severity of CKD and CV event rates. Although patients with end-stage renal disease who are undergoing dialysis are at greatest CV risk, the disease process is evident in the early stages of CKD with glomerular filtration rates as high as 75 ml/min/1.73 m². Indeed, these patients are at least 6 times more likely to die of CV disease than to reach end-stage CKD. Thus, the major impact of CKD on the population and the healthcare budget is not that of providing renal replacement therapy but the cost of death and disability from premature CV disease. Although end-stage CKD is characterized by a clustering of conventional atherosclerotic risk factors, it has little association with CV event rates. This is reflected in disproportionate levels of sudden cardiac death, heart failure, and stroke, rather than myocardial infarction. Thus it appears that nonatherosclerotic processes, including left ventricular hypertrophy and fibrosis, account for most of the excess CV risk. Over the past decade, the use of cardiac magnetic resonance in CKD has brought about an improved understanding of the adverse CV changes collectively known as uremic cardiomyopathy. The unique ability of cardiac magnetic resonance to provide a comprehensive noninvasive examination of cardiac structure and function, arterial function, myocardial tissue characterization (T
1 mapping and inversion recovery imaging), and myocardial metabolic function (spectroscopy) is ideally suited to characterize the phenotype of CV disease in CKD and to provide insight into the mechanisms leading to uremic cardiomyopathy. Concerns relating to an association between gadolinium contrast agents and nephrogenic systemic fibrosis in dialysis recipients have led to the use of lower doses and lower-risk gadolinium agents that appear to minimize this risk. [ABSTRACT FROM AUTHOR]- Published
- 2014
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9. Prediction of ESRD and Death Among People With CKD: The Chronic Renal Impairment in Birmingham (CRIB) Prospective Cohort Study.
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Landray, Martin J., Emberson, Jonathan R., Blackwell, Lisa, Dasgupta, Tanaji, Zakeri, Rosita, Morgan, Matthew D., Ferro, Charlie J., Vickery, Susan, Ayrton, Puja, Nair, Devaki, Dalton, R. Neil, Lamb, Edmund J., Baigent, Colin, Townend, Jonathan N., and Wheeler, David C.
- Abstract
Background: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). Study Design: Prospective cohort study with validation in a separate cohort. Setting & Participants: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). Factors: 44 baseline characteristics (including 30 blood and urine assays). Outcomes: ESRD and all-cause mortality. Results: In the CR IB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CIl, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. Limitations: Other important factors may have been missed because of limited study power. Conclusions: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results. [ABSTRACT FROM AUTHOR]
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- 2010
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10. Validation of the conductance catheter method for measurement of ventricular volumes under varying conditions relevant to cardiac surgery.
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Al-Khalidi, Abdul-Hakam, Townend, Jonathan N., Al-Khalidi, A H, Townend, J N, Bonser, R S, and Coote, J H
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CATHETERIZATION , *CARDIAC surgery , *BIOLOGICAL models , *CARDIAC catheterization , *CARDIOVASCULAR system physiology , *COMPARATIVE studies , *HEART ventricles , *HEART beat , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *VISCOSITY , *PRODUCT design , *EVALUATION research ,RESEARCH evaluation - Abstract
The development of the conductance catheter method has enabled continuous measurement of intraventricular volume in vivo, thus making assessment of pump performance of the heart in vivo possible using pressure-volume analysis. However, this method has not been validated under conditions where pump rate, conductance, viscosity, and temperature of the fluid in the heart chamber is changed as happens in cardiac surgery. To validate the method, pressure-volume data were measured by conductance catheter in a physical model of the human left ventricle. The volume, salinity, viscosity, and temperature of the fluid inside the model were rigorously controlled. The measured pressure-volume data were compared with the actual values to assess the accuracy and dependence of the conductance-measured volumes on salinity, viscosity, temperature, and pump rate. Conductance-measured volumes were not significantly different over a range of heart rates extending from 60 to 100 beats/min, and they were not significantly different over a salinity range of 0.2 to 2 normal saline, a viscosity range of 2.7 to 3.5 centipoise, or over a temperature range of 20 degrees C to 39 degrees C. The percentage errors between actual stroke volumes and conductance-derived volumes were of the order of 10% on average. Our data shows that for a broad range of conditions normally encountered during cardiac surgery, there is no dependence of conductance-measured volume on heart rate, viscosity, temperature, or salinity, provided the correct value of fluid resistivity is used. [ABSTRACT FROM AUTHOR]
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- 1998
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11. Granuloma formation around a retained perclose S suture presenting 12 months after implantation.
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Doshi, Sagar N., Smith, Simon, and Townend, Jonathan N.
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INFLAMMATION ,HEMOSTASIS ,HEMORRHAGE ,CATHETERIZATION ,FEMORAL artery ,GRANULOMA ,SURGICAL hemostasis ,INTRAVENOUS catheterization ,OPERATIVE surgery ,SUTURING - Abstract
Suture-mediated closure devices have become commonplace in interventional and diagnostic femoral catheterization procedures. Although they reduce the time to hemostasis, ambulation, and hospital discharge, they are associated with a greater potential for serious infection compared with manual compression, often with delayed presentation. Scrupulous aseptic procedure and careful technique are vital in reducing complications. Herein a case of sterile granuloma formation around an untrimmed Perclose S suture is reported, which presented 12 months after use of a suture-mediated closure device. [ABSTRACT FROM AUTHOR]
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- 2004
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12. Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.
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Wang, Kang-Ling, Balmforth, Craig, Meah, Mohammed N., Daghem, Marwa, Moss, Alastair J., Tzolos, Evangelos, Kwiecinski, Jacek, Molek-Dziadosz, Patrycja, Craig, Neil, Bularga, Anda, Adamson, Philip D., Dawson, Dana K., Arumugam, Parthiban, Sabharwal, Nikant K., Greenwood, John P., Townend, Jonathan N., Calvert, Patrick A., Rudd, James H.F., Verjans, Johan W., and Berman, Daniel S.
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MYOCARDIAL infarction , *ATHEROSCLEROTIC plaque , *POSITRON emission tomography , *CORONARY artery disease , *CORONARY arteries - Abstract
Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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13. Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors.
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Price, Anna M., Edwards, Nicola C., Hayer, Manvir K., Moody, William E., Steeds, Richard P., Ferro, Charles J., and Townend, Jonathan N.
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Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the “pure” effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance. [ABSTRACT FROM AUTHOR]
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- 2018
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14. The EARNEST Study: Interarm blood pressure differences should also be recorded.
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Moody, William E., Ferro, Charles J., and Townend, Jonathan N.
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- 2014
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15. The importance of selecting controls in kidney donor outcome studies.
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Moody, William E and Townend, Jonathan N
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ORGAN donors , *KIDNEY transplantation , *HEALTH - Abstract
A letter to the editor is presented in response to the article which discusses the importance of selecting kidney donors for examining effects of kidney donation on long term health outcomes.
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- 2014
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16. Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: Rationale and design of the EARNEST study.
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Moody, William E., Tomlinson, Laurie A., Ferro, Charles J., Steeds, Richard P., Mark, Patrick B., Zehnder, Daniel, Tomson, Charles R., Cockcroft, John R., Wilkinson, Ian B., and Townend, Jonathan N.
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Background: There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group. Hypotheses: The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure. Methods: This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease. Conclusions: These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program (NCT01769924). [Copyright &y& Elsevier]
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- 2014
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17. The EARNEST study: interarm blood pressure differences should also be recorded.
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Moody, William E, Ferro, Charles J, Townend, Jonathan N, and EARNEST Study Investigators
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- 2008
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18. The OPTIMMAL trial: losartan or captopril after acute myocardial infarction.
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Chowdhary, Saqib and Townend, Jonathan N
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- 2002
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19. Coronary flow velocity reserve and inflammatory markers in living kidney donors.
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Radhakrishnan, Ashwin, Price, Anna M., Pickup, Luke C., Law, Jonathan P., McGee, Kirsty C., Fabritz, Larissa, Senior, Roxy, Steeds, Richard P., Ferro, Charles J., and Townend, Jonathan N.
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FLOW velocity , *CARDIOVASCULAR diseases risk factors , *KIDNEYS , *GLOMERULAR filtration rate , *CHRONIC kidney failure - Abstract
Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. 25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. Doppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. This is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population. • Coronary flow velocity reserve is reduced in living kidney donors compared to controls. • Markers of inflammation are elevated in living kidney donors. • Inflammation may cause coronary microvascular dysfunction in living kidney donors. • Living kidney donors need aggressive cardiovascular risk factor management. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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20. Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study.
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Hayer, Manvir K., Radhakrishnan, Ashwin, Price, Anna M., Baig, Shanat, Liu, Boyang, Ferro, Charles J., Captur, Gabriella, Townend, Jonathan N., Moon, James C., Edwards, Nicola C., and Steeds, Richard P.
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KIDNEY transplantation , *HEART transplantation , *CARDIAC magnetic resonance imaging , *MAGNETIC resonance , *CHRONIC kidney failure - Abstract
Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD. • ECV is elevated in ESKD suggesting the elevated myocardial T1 times observed are indicative of diffuse interstitial fibrosis. • The contribution of myocardial oedema towards elevated T1 times and ECV cannot be excluded in ESKD. • Native T1 times is a stable and reproducible biomarker of fibrosis. [ABSTRACT FROM AUTHOR]
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- 2019
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21. Double-stenting of an ostial left main-stem lesion for elastic recoil
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Ratib, Karim, Doshi, Sagar N., and Townend, Jonathan N.
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- 2005
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22. Prognostic Utility of Calcium Scoring as an Adjunct to Stress Myocardial Perfusion Scintigraphy in End-Stage Renal Disease.
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Moody, William E, Lin, Erica L S, Stoodley, Matthew, McNulty, David, Thomson, Louise E, Berman, Daniel S, Edwards, Nicola C, Holloway, Benjamin, Ferro, Charles J, Townend, Jonathan N, Steeds, Richard P, and Birmingham Cardio-Renal Group
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CHRONIC kidney failure , *CORONARY disease , *DIAGNOSTIC imaging , *HEART function tests , *KIDNEY transplantation , *MYOCARDIAL infarction , *PROGNOSIS , *RESEARCH funding , *RISK assessment , *SINGLE-photon emission computed tomography , *PREDICTIVE tests , *PROPORTIONAL hazards models , *SEVERITY of illness index , *CALCINOSIS , *DIAGNOSIS ,CHRONIC kidney failure complications - Abstract
Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score ≥4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to-severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change = 2.52, p = 0.112). In conclusion, a perfusion defect on SPECT is an independent predictor of adverse outcome in potential renal transplant candidates regardless of the CACS. The use of CACS as an adjunct to SPECT perfusion data does not provide incremental prognostic utility for the prediction of mortality and nonfatal myocardial infarction in end-stage renal disease. [ABSTRACT FROM AUTHOR]
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- 2016
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23. Diffuse Interstitial Fibrosis and Myocardial Dysfunction in Early Chronic Kidney Disease.
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Edwards, Nicola C., Moody, William E., Mengshi Yuan, Hayer, Manvir K., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard P.
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KIDNEY diseases , *HEART fibrosis , *RIGHT ventricular hypertrophy , *CARDIOVASCULAR diseases risk factors , *GLOMERULAR filtration rate , *CARDIOMYOPATHIES , *GADOLINIUM - Abstract
Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57 ± 10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50 ± 22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986 ± 37 ms) and ECV (0.28 ± 0.04) compared with controls (955 ± 30 ms, 0.25 ± 0.03) and subjects who are hypertensive (956 ± 31 ms, 0.25 ± 0.02, p <0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r = -0.22, p <0.05, and r = -0.43, p <0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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24. Effects of age and chronic kidney disease on regional aortic distensibility: A cardiovascular magnetic resonance study.
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Chue, Colin D., Edwards, Nicola C., Ferro, Charles J., Townend, Jonathan N., and Steeds, Richard P.
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CARDIOVASCULAR disease diagnosis , *KIDNEY diseases , *CARDIAC magnetic resonance imaging , *HEALTH outcome assessment , *RANDOMIZED controlled trials - Abstract
Abstract: Background: Chronic kidney disease (CKD) is associated with increased arterial stiffness, an independent predictor of adverse cardiovascular outcome. Effects of CKD on regional aortic stiffness are unknown. This study aimed to determine the effects of CKD and ageing on regional thoracic aortic distensibility using cardiac magnetic resonance (CMR) imaging. Methods: This was a cross-sectional case control study comparing patients with stage II–IV non-diabetic CKD recruited from a university hospital with healthy controls. Aortic distensibility was measured in triplicate using CMR (1.5T) at ascending, proximal descending and distal descending thoracic aortic levels and calculated using previously validated formulae. Results: 189 patients and 40 controls were recruited. Distensibility was reduced at all three thoracic aortic levels in CKD patients compared to controls (2.8 vs. 4.1×10−3 mmHg−1; P <0.0005 for ascending aorta). The cohort was divided into tertiles of age and glomerular filtration rate (GFR); distensibility decreased with increasing age (P <0.0005) and decreasing GFR (P <0.02). In univariate analyses age (r=−0.688, P <0.0005), systolic blood pressure (r=−0.183, P =0.006) and GFR (r=0.172, P =0.009) all correlated with ascending aortic distensibility. In a multivariate regression model age and GFR were independent predictors of aortic distensibility at all three levels with 50% of the variation in ascending aortic distensibility explained (P <0.0005). Conclusions: Patients with early stage chronic kidney disease have reduced distensibility along the entire length of the thoracic aorta. This worsens with ageing and as kidney function declines, emphasizing the importance of early treatment whilst kidney function is still relatively preserved. [Copyright &y& Elsevier]
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- 2013
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25. Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?
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Moody, William E., Edwards, Nicola C., Madhani, Melanie, Chue, Colin D., Steeds, Richard P., Ferro, Charles J., and Townend, Jonathan N.
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CARDIOVASCULAR diseases , *ENDOTHELIUM , *KIDNEY diseases , *GLOMERULAR filtration rate , *HYPERTENSION , *DIABETES , *DISEASE progression , *PATHOLOGICAL physiology - Abstract
Abstract: Chronic kidney disease (CKD) is strongly associated with cardiovascular disease (CVD); a graded inverse relationship between estimated glomerular filtration rate (eGFR) and cardiovascular event rates has emerged from large-scale observational studies. Chronic kidney disease is also associated with endothelial dysfunction (ED) although the precise relationship with GFR and the “threshold” at which ED begins are contentious. Abnormal endothelial function is certainly present in late-stage CKD but data in early-stage CKD appear confounded by disease states such as diabetes and hypertension which themselves promote ED. Thus, the direct effect of a reduction in GFR on endothelial function and, therefore, cardiovascular (CV) risk is far from completely established. In human studies, the precise duration of kidney impairment is seldom known and the onset of CVD often insidious, making it difficult to determine exactly when CVD first appears in the context of CKD. Kidney donors provide a near-ideal experimental model of CKD; subjects undergo an acute change from normal to modestly impaired renal function at the time of nephrectomy and lack the confounding co-morbidity that has made observational studies of CKD patients so challenging to interpret. By examining changes in endothelial function in living kidney donors before and after nephrectomy, useful insight might be gained into the pathophysiology of CVD in CKD and help determine whether targeting ED or the renal disease itself has the potential to reduce CV risk. [Copyright &y& Elsevier]
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- 2012
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26. Effect of Spironolactone on Left Ventricular Systolic and Diastolic Function in Patients With Early Stage Chronic Kidney Disease
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Edwards, Nicola C., Ferro, Charles J., Kirkwood, Helen, Chue, Colin D., Young, Alistair A., Stewart, Paul M., Steeds, Richard P., and Townend, Jonathan N.
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SPIRONOLACTONE , *LEFT heart ventricle , *KIDNEY diseases , *CARDIOVASCULAR diseases risk factors , *ALDOSTERONE , *MINERALOCORTICOIDS , *ANGIOTENSINS , *BIOMARKERS , *INFLAMMATION - Abstract
Patients with early chronic kidney disease (CKD) have an increased risk for cardiovascular disease. Aldosterone levels are elevated and might impair ventricular function through adverse myocardial and vascular proinflammatory and fibrotic effects. In the Chronic Renal Impairment in Birmingham II (CRIB II) study, it was hypothesized that mineralocorticoid receptor blockade with spironolactone in addition to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers would improve left ventricular (LV) function and markers of inflammation, ventricular stretch, and collagen turnover in early CKD. A total of 112 patients with early CKD were randomized to spironolactone 25 mg/day or placebo for 40 weeks. Ventricular function was assessed by echocardiography and cardiac magnetic resonance imaging tagging. High-sensitivity C-reactive protein, N-terminal–pro-B-type natriuretic peptide, and aminoterminal propeptide of type III procollagen were measured. Spironolactone improved LV long-axis systolic function (Sm 8.2 ± 1.4 vs 7.7 ± 1.3 cm/s, p <0.05), torsion (7.77 ± 1.61° vs 6.77 ± 1.48°, p <0.05), and myocardial deformation (strain rate −1.14 ± 0.24 vs −1.09 ± 0.20 s−1, p <0.05) compared to placebo, without a change in the ejection fraction. Markers of LV relaxation (E/e′ ratio 7.2 ± 2.3 vs 8.5 ± 2.3, p <0.05) and suction (M-mode propagation velocity 56 ± 12 vs 50 ± 12 cm/s, p <0.05) were also improved. Spironolactone reduced N-terminal–pro-B-type natriuretic peptide (24.8 pmol/L [range 0.4 to 122.4] vs 39.4 pmol/L [range 10.8 to 102.4], p <0.01) and attenuated an increase in aminoterminal propeptide of type III procollagen observed with placebo. In conclusion, spironolactone improves markers of regional LV systolic and diastolic function in early CKD. [Copyright &y& Elsevier]
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- 2010
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27. Effect of Spironolactone on Left Ventricular Mass and Aortic Stiffness in Early-Stage Chronic Kidney Disease: A Randomized Controlled Trial
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Edwards, Nicola C., Steeds, Richard P., Stewart, Paul M., Ferro, Charles J., and Townend, Jonathan N.
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SPIRONOLACTONE , *PHARMACODYNAMICS , *LEFT heart ventricle , *AORTIC valve diseases , *CHRONIC kidney failure , *HEART diseases , *THERAPEUTICS , *RANDOMIZED controlled trials , *ACE inhibitors - Abstract
Objectives: We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD). Background: Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system. Methods: After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment. Results: Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (−14 ± 13 g vs. +3 ± 11 g, p < 0.01), pulse wave velocity (−0.8 ± 1.0 m/s vs. −0.1 ± 0.9 m/s, p < 0.01), augmentation index (−5.2 ± 6.1% vs. −1.4 ± 5.9%, p < 0.05), and aortic distensibility (0.69 ± 0.86 × 10−3 mm Hg vs. 0.04 ± 1.04 × 10−3 mm Hg, p < 0.01). Conclusions: The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720) [Copyright &y& Elsevier]
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- 2009
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28. Acute aldosterone antagonism improves cardiac vagal control in humans
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Fletcher, Janine, Buch, Ashesh N., Routledge, Helen C., Chowdhary, Saqib, Coote, John H., and Townend, Jonathan N.
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ALDOSTERONE , *CARDIAC arrest , *MINERALOCORTICOIDS , *DISEASE complications - Abstract
: ObjectivesWe have examined the acute effects (<45 min) of aldosterone antagonism on heart rate variability and baroreflex sensitivity, markers of cardiac vagal control, in 13 healthy subjects.: BackgroundEvidence for the beneficial effects of aldosterone antagonists comes from studies showing increased survival rates following their addition to standard heart failure therapy. Many mechanisms have been suggested for this action, including effects upon the autonomic nervous system.: MethodsHeart rate variability and baroreflex sensitivity were examined 30 min following the administration of potassium canrenoate (intravenous) (aldosterone antagonist) or saline (control).: ResultsActive treatment reduced resting heart rate (−6 ± 1 beats/min [mean ± standard error mean]) compared to control (0 ± 1 beat/min) (p < 0.001) and increased measures of high frequency (HF) heart rate variability. Root mean square of successive RR interval differences increased by 21 ± 5 ms versus −6 ± 5 ms control (p < 0.001); HF power increased by 1,369 ± 674 ms2with aldosterone antagonism compared to −255 ± 431 ms2 following saline infusion (p < 0.01). Baroreflex sensitivity (alpha-HF) was increased after active treatment (+4 ± 2 ms/mm Hg vs. 0 ± 1 ms/mm Hg control [p < 0.05]). No changes in plasma potassium levels were observed.: ConclusionsThese results provide evidence that aldosterone antagonists acutely improve cardiac vagal control, irrespective of any diuretic effects, and may in part explain their beneficial effects in treatment of heart failure. [Copyright &y& Elsevier]
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- 2004
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29. IMPACT OF RENAL FUNCTION ON SURVIVAL AFTER TRANS-CATHETER AORTIC VALVE IMPLANTATION: AN ANALYSIS OF THE UNITED KINGDOM REGISTRY.
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Chue, Colin Dominic, Ferro, Charles J., de Belder, Mark A., Moat, Neil E., Wendler, Olaf, Trivedi, Uday, Ludman, Peter F., and Townend, Jonathan N.
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KIDNEY physiology , *CARDIAC catheterization , *AORTIC valve diseases , *HEART valve prosthesis implantation - Published
- 2015
- Full Text
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