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"Ray, Simon"
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Uncovering the treatable burden of severe aortic stenosis in the UK
ObjectiveTo estimate the population prevalence and treatable burden of severe aortic stenosis (AS) in the UK.MethodsWe adapted a contemporary model of the population profile of symptomatic and asymptomatic severe AS in Europe and North America to estimate the number of people aged ≥55 years in the UK who might benefit from surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI).ResultsWith a point prevalence of 1.48%, we estimate that 291 448 men and women aged ≥55 years in the UK had severe AS in 2019. Of these, 68.3% (199 059, 95% CI 1 77 201 to 221 355 people) would have been symptomatic and, therefore, more readily treated according to their surgical risk profile; the remaining 31.7% of cases (92 389, 95% CI 70 093 to 144 247) being asymptomatic. Based on historical patterns of intervention, 58.4% (116 251, 95% CI 106 895 to 1 25 606) of the 199 059 symptomatic cases would qualify for SAVR, with 7208 (95% CI 7091 to 7234) being assessed as being in a high, preoperative surgical risk category. Among the remaining 41.6% (82 809, 95% CI 73 453 to 92 164) of cases potentially unsuitable for SAVR, an estimated 61.7% (51 093, 95% CI 34 780 to 67 655) might be suitable for TAVI. We estimate that 172 859 out of 291 448 prevalent cases of severe AS (59.3%) will subsequently die within 5 years without proactive management.ConclusionsThese data suggest a high burden of severe AS in the UK requiring surgical or transcatheter intervention that challenges the ongoing capacity of the National Health Service to meet the needs of those affected.
Journal Article
Japan : top sights, authentic experiences
\"Lonely Planet Best of Japan is your passport to the most relevant, up-to-date advice on what to see and skip, and what hidden discoveries await you. See traditional geisha in Kyoto, hike up Mt Fuji, or shop around the clock in Tokyo; all with your trusted travel companion.\"--Publisher.
Book
The infective endocarditis team: recommendations from an international working group
The estimated incidence is 3-10 episodes each year per 100 000 population. 1 In industrially developed countries, IE increasingly occurs in older adults with intracardiac devices (pacemakers and implantable defibrillators), replacement heart valves and medical interventions such as haemodialysis. 2-4 Younger age groups are also affected, particularly intravenous drug users and those with adult congenital heart disease. 5 Staphylococci are now the most common causative organisms in international series and streptococci the second most common. 6 Resistance to antimicrobial agents, particularly vancomycin, is increasing. 1 7 Patients with IE remain in hospital for a median of 4-6 weeks 8 9 and approximately a half require inpatient cardiac surgery. 1 10 11 The inhospital mortality rate is about 20% 8 12 but varies widely according to age, comorbidity, heart failure, the presence of prosthetic material and the organism. 13 For example, in prosthetic valve IE with associated renal failure, the reported mortality may be 40%-50% 14 15 and with severe heart failure as high as 64%. [...]it may be difficult or impractical to set up comprehensive specialist IE care in small hospitals since the incidence of IE is low. [...]there must be strong links between referring hospitals and the specialist IE team at the cardiothoracic centre.
Journal Article
Japan
Lonely Planet Japan is your passport to the most relevant, up-to-date advice on what to see and skip, and what hidden discoveries await you. Explore a bamboo grove in Arashiyama, marvel at Shinto and Buddhist architecture in Kyoto, or relax in the hot springs of Noboribetsu Onsen; all with your trusted travel companion.
Book
Copper chelation in patients with hypertrophic cardiomyopathy
BackgroundDisturbances of copper (Cu) homeostasis can lead to hypertrophic cardiac phenotypes (eg, Wilson’s disease). We previously identified abnormal Cu homeostasis in patients with hypertrophic cardiomyopathy (HCM) and, therefore, hypothesised that Cu2+–selective chelation with trientine dihydrochloride may slow or reverse disease progression in HCM. The aim of this study was, therefore to explore the clinical efficacy, safety and tolerability of trientine in HCM.MethodsIn this medicines and healthcare products regulatory agency (MHRA) registered open-label pilot study, we treated 20 HCM patients with trientine for 6 months. Patients underwent a comprehensive assessment schedule including separate cardiac magnetic resonance imaging (CMR) and CMR 31P-spectroscopy at baseline and end of therapy. Predefined end points included changes in left ventricular mass (LVM), markers of LV fibrosis, markers of LV performance and myocardial energetics. Ten matched patients with HCM were studied as controls.ResultsTrientine treatment was safe and tolerated. Trientine caused a substantial increase in urinary copper excretion (0.42±0.2 vs 2.02±1.0, p=0.001) without affecting serum copper concentrations. Treatment was associated with significant improvements in total atrial strain and global longitudinal LV strain using both Echo and CMR. LVM decreased significantly in the treatment arm compared with the control group (−4.2 g v 1.8 g, p=0.03). A strong trend towards an absolute decrease in LVM was observed in the treatment group (p=0.06). These changes were associated with a significant change in total myocardial volume driven by a significant reduction in extracellular matrix (ECM) volume (43.83±18.42 mL vs 41.49±16.89 mL, p=0.04) as opposed to pure cellular mass reduction and occurred against a background of significant ECM volume increase in the control group (44.59±16.50 mL vs 47.48±19.30 mL, p=0.02). A non-significant 10% increase in myocardial phosphocreatine/adenosine triphosphate (PCr/ATP) ratio with trientine therapy (1.27±0.44 vs 1.4±0.39) was noted.ConclusionsCu2+–selective chelation with trientine in a controlled environment is safe and a potential future therapeutic target. A phase 2b trial is now underway.
Journal Article
استعادة التوازن : استراتيجية للشرق الأوسط برسم الرئيس الجديد
لا شك في أن الرئيس الرابع والأربعين للولايات المتحدة الأميركية سيجد في انتظاره سلسلة من التحديات الحاسمة، المعقدة والمتشابكة في الشرق الأوسط، التي تتطلب إيلاءها اهتماما عاجلا. ذلك أن النموذج الذي اعتمده جورج بدليو بوش القائم على تغيير أنظمة الحكم ونشر الديمقراطية بالقوة لم يعد يتلاءم والظروف المتغيرة التي ستواجه الإدارة الجديدة على الأرجح الحاجة ماسة إذن لأفكار جديدة، وتحليلات غير حزبية، وتوصيات حصيفة. والكتاب الذي بين أيديكم يفي بتلك الحاجة على أفضل وجه. في اتسعادة التوازن، تتضافر جهود الخبراء والمختصين بشؤون الشرق الأوسط من مجلس العلاقات الخارجية ومركز صبان لسياسة الشرق الأوسط بمعهد بروكنغز، لتطرح استراتيجية أميركية جديدة لمنظمة حيوية لكن متفجرة كالشرق الأوسط فبناء على أبحاث ميدانية معنقة، قام هؤلاء الخبراء ببلورة مجموعة من التوصيات السياسية برسم الرئيس الأميركي الجديد وقد قامت بفحصها وتمحيصها ونقدها هيئة من المختصين من كلا الحزبين يتمتعون بخبرة سياسية واسعة ومعرفة غنية بالمنطقة، هذا التمرين في تخطيط السياسات الذي استغرق سنة كاملة هو الأول من نوعه على الإطلاق، الذي يوحد جهود وقدرات العاملين في هاتين المؤسستين المحترمتين بالسياسة الخارجية لتنصب على درس وتحليل واحدة من أخطر وأهم مناطق العالم. وكل فصل من هذا الكتاب يستضيف اثنين أو أكثر من الباحثين في مجلس العلاقات الخارجية ومعهد بروكنغز لمعاينة واستعراض التحديات التي ستواجه الرئيس المقبل.
Book
Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study
Background
Serial surveillance endomyocardial biopsies are performed in patients who have recently undergone heart transplantation in order to detect acute cardiac allograft rejection (ACAR) before symptoms occur, however the biopsy process is associated with a number of limitations. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterize graft recovery following transplantation.
Methods
All patients receiving a heart transplant at a single UK centre over a period of 25 months were approached within one month of transplantation. Multiparametric CMR was prospectively performed on the same day as biopsy on four separate occasions (6 weeks, 10 weeks, 15 weeks and 20 weeks post-transplant). CMR included assessment of global and regional ventricular function, myocardial tissue characterization (T1 mapping, T2 mapping, extracellular volume, LGE) and pixel-wise absolute myocardial blood flow quantification. CMR parameters were compared with biopsy findings. As is standard, grade 2R or higher ACAR was considered significant.
Results
88 CMR-matched biopsies were performed in 22 patients. Eight (9%) biopsies in 5 patients demonstrated significant ACAR. Significant ACAR was associated with a reduction in circumferential strain (−12.7 ± 2.5% vs. -13.7 ± 3.6%, p = 0.047) but there was considerable overlap between groups. Whilst trends were observed between ACAR and proposed CMR markers of oedema, particularly after adjusting for primary graft dysfunction, differences were not significant. Significant improvements were seen in markers of graft structure and contractility, oedema and microvascular function over the period studied, although few parameters normalised.
Conclusions
This study provides novel insight into the myocardial injury associated with transplantation, and its recovery, however multiparametric CMR was not able to accurately detect ACAR during the early phase post-transplantation.
Journal Article
Incidence of Cancer and Mortality in Patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Trial
The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.
Journal Article