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Objective: In hypertension, indexes of midwall left ventricular (LV) function may identify patients at higher cardiovascular (CV) risk independent of normal LV ejection fraction (EF). We analyzed the association of baseline and new-onset LV midwall dysfunction with CV outcome in a large population of patients with asymptomatic aortic stenosis (AS). Methods: One thousand four hundred seventy-eight patients with asymptomatic AS and normal EF (≥50%) at baseline in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a median of 4.3 years. LV systolic function was assessed by biplane EF and midwall shortening (MWS, low if

One of the biggest controversies in valvular heart diseases is the best treatment strategy in asymptomatic patients with severe, organic mitral valve regurgitation (MR) and preserved left ventricul...

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (pCONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

The paper by Shareen Jaijee and colleagues1 in this edition of Heart puts figures onto what many cardiologists will recognise as an everyday reality of our specialty. It makes unwelcome but not unexpected reading. In the last 15 years, progress with regards to gender representation in UK cardiology practice2 and leadership appears to have stood still or at best run at a pedestrian pace. Female cardiologists are still in a minority, particularly in interventional specialities, in academic cardiology and as leaders and are substantially more likely to have been on the receiving end of inappropriate behaviour from professional colleagues. Disturbingly, a third of female cardiologists reported sexual harassment.1 UK women training in cardiology also report3 experiencing sexism particularly in the latter years of training (15%) when studying in tertiary centres where more interventional cardiology and research training is located and are more likely to change their preferred subspecialty choice away from intervention and electrophysiology.3 Non-cardiology trainee respondents to a survey mentioned witnessing and experiencing bullying and sexism by cardiologists and cardiology trainees as a reason not to choose a career in cardiology, with sexism more often reported by women.4 Negative attitudes and behaviours in UK cardiology therefore affect people at every stage and will likely need multiple actions to stamp out. One positive finding in this paper1 is that the great majority of cardiologists, both male and female, feel positive about their choice of specialty despite the obstacles and negative factors reported. This is …

Background Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. Objectives This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. Methods Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery–based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. Results Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p, Central Illustration

In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on clinicaltrials.gov: NCT00092677).

Background Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. Materials and methods We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. Results Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). Conclusion Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

Mitral regurgitation (MR) is the second most common form of valvular disease requiring surgery. Correct identification of surgical candidates and optimising the timing of surgery are key in management. For primary MR, this relies upon a balance between the peri-operative risks and rates of successful repair in patients undergoing early surgery when asymptomatic with the potential risk of irreversible left ventricular dysfunction if intervention is performed too late. For secondary MR, recognition that this is a highly dynamic condition where MR severity may change is key, although data on outcomes in determining whether concomitant valve intervention is performed with revascularisation has raised questions regarding timing of surgery. There has been substantial interest in the use of stress echocardiography to risk stratify patients in mitral regurgitation. This article reviews the role of stress echocardiography in both primary and secondary mitral regurgitation and discusses how this can help clinicians tackle the challenges of this prevalent condition.

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.Trial registration number: NCT00092677; Post-results.

Impaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT.We undertook (123)I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups.Global and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

There is increasing recognition of the need for collaboration between oncologists, acute physicians and specialists to improve the quality of care and outcomes of acutely unwell patients with cancer. At The Christie, a tertiary oncology hospital, a model has been developed to deliver acute medical and specialty support services. This delivers, among many things, a consultant-led acute medical ward round on weekdays. There has been a significant increase in the number of patients admitted to the oncology assessment unit (OAU) since its introduction, in part due to an increased number of direct discharges from the unit. Collaborative working between oncologists and acute physicians with a shared vision for high-quality care for patients has ensured that this change has been implemented smoothly. This has included development of patient flow models to optimise bed usage, so that a higher number of patients can access these specialist services.

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p = 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p ≥0.14). In conclusion, in a non–prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).

Mitral stenosis (MS) has become less common in developed countries following the declining incidence of rheumatic fever, but it remains a major health problem worldwide. Atrial fibrillation is a common accompaniment and may trigger the onset of pulmonary oedema. Medical treatment is aimed at control of atrial fibrillation and prevention of thromboembolism. Patients with symptoms and a valve area

Objective The aim of the current study was to identify predictors of paraprosthetic aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and examine its influence on short/medium-term mortality using the UK TAVI Registry. TAVI is an effective treatment for high-risk patients with severe symptomatic aortic stenosis (AS), but paraprosthetic AR has been associated with increased in-hospital and mid-term mortality. Methods Between January 2007 and December 2011, 2584 TAVI procedures were performed in the UK. Patients undergoing ‘valve-in-valve’ procedures, patients with aortic regurgitation as the primary pathology and with no recorded severity of AR were excluded from this analysis (n=144). In total, therefore, 2440 patients were included. Balloon-expandable and self-expanding devices were implanted in 52.7 and 47.2%, respectively, using either transfemoral (67.7%) or non-transfemoral, surgical access (32.3%). Results Postprocedural AR was observed in 68%, mild AR in 57% and moderate-severe in 10%. A large aortic annulus, high preprocedural transaortic gradient, and use of self-expanding valve were independent predictors of moderate-severe AR. Moderate-severe (but not mild) AR was associated with increased mortality, and this relationship appeared significant for the balloon-expandable but not the self-expanding device. Conclusions Our data suggest that a large aortic annulus, high preprocedural transaortic gradient, and use of the self-expanding valve predict moderate-severe AR after TAVI. Such a degree of AR is associated with a significantly worse outcome with the balloon-expandable, but not with the self-expanding valve. Further studies are needed to verify this and explore potential mechanisms.

To the Editor: In October 2013, autochthonous transmission of chikungunya was detected in the Caribbean area, which resulted in the current epidemic of chikungunya in the Western Hemisphere (1). The chikungunya virus strain that caused this epidemic belongs to the Asian lineage, not to the strain descending from the East/Central/South African (ECSA) lineage that spread in the Indian Ocean region after 2004. This ECSA lineage was reported mainly to cause long-lasting musculoskeletal and rheumatic disorders in chikungunya virus–infected patients (2–8). In 1984 in South Africa, Brighton and Simson reported post-chikungunya destructive polyarthritis (6). Twenty years later, the arthritogenic pathogenesis of viruses in the ECSA chikungunya virus lineage was confirmed after outbreaks in the Indian Ocean region (2–5,7,8). Because >870,000 suspected cases of chikungunya have occurred during the past 12 months in the Western Hemisphere (http://www.paho.org/hq/index.php?option=com_content&view=article&id=9436), it is crucial to know whether infection with the epidemic Asian strain will cause chronic inflammatory and potentially destructive rheumatism. We report post-chikungunya rheumatoid arthritis from Saint Martin, the epicenter of the current epidemic. A 70-year-old woman (artist–painter) in Saint Martin sought treatment in June 2014 for joint pains and disabilities persisting after chikungunya. Her medical history included high blood pressure, hypothyroidism, and 3 dengue infections. During October 2013, the patient had high-grade fever, intense fatigue, and a maculopapular troncular exanthema without lymphadenopathy. Five days later, she had distal polyarthritis (joint pain and swelling) in interphalangeal joints, wrists, and ankles without plantar involvement. Recent infection with chikungunya virus was confirmed (IgM and IgG against chikungunya virus was detected in 2 blood samples), and recent dengue was excluded according to the criteria of the National Reference Center on Arboviral Diseases (http://www.niaid.nih.gov/labsandresources/resources/dmid/wrceva/Pages/default.aspx). Despite initial brief improvement, the patient never totally recovered and subsequently chronic polyarthritis developed, which involved >10 joints, including interphalangeal joints, wrists, and knees. Nonsteroidal antiinflammatory drugs did not relieve the diffuse pain, stiffness, and swelling. She was given oral corticotherapy (20 mg/day) beginning in January 2014. She was referred to another hospital in France 5 months later because of treatment failure. She reported continuous pain in the left knee and wrists and multiple tenosynovitis on flexors and extensors of the fingers (Figure). She did not report any fever or axial, shoulder, or hip pain. Radiographs of the involved joints showed no abnormalities. Figure Swollen and stiff hands of a 70-year-old woman with post-chikungunya rheumatoid arthritis 10 months after acute infection with chikungunya virus, Saint Martin. The patient had mild inflammation (C-reactive protein level 13 mg/L, fibrinogen level 3.4 g/L) but no specific autoimmunity (results were negative for anticitrullinated peptide antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and antinuclear antibodies). Serologic results for viruses other than chikungunya virus were negative or indicated past vaccination. The patient’s condition met the 2010 American College of Rheumatology/European League against Rheumatism criteria for rheumatoid arthritis (https://www.rheumatology.org/practice/clinical/classification/ra/ra_2010.asp), and the only cause observed for this disease was acute chikungunya. For this corticosteroid-resistant, seronegative, and nondestructive post-chikungunya rheumatoid arthritis, methotrexate was prescribed at a weekly low dose after exclusion of contraindications, but the patient was not followed-up after she returned to Saint Martin. The reported case was caused by chikungunya virus infection during an epidemic in Saint Martin in October 2013. This unfavorable post-chikungunya outcome of chronic inflammatory rheumatism 8 months later indicates a probable course of post-chikungunya disorders in the Western Hemisphere, as has already been observed in Africa and Asia. Previous outbreaks in Reunion and India offer insights regarding patients’ post-chikungunya chronic status with long-lasting pain and disability, impaired quality of life, and extensive treatment (2,3,9). The spectrum of post-chikungunya rheumatic and musculoskeletal disorders includes multiple tendinitis and tenosynovitis, plantar fasciitis, mechanical disbalance in susceptible joints, tunnel syndromes, edematous polyarthralgia, rheumatoid arthritis, and psoriatic arthritis (2,4,5). Although the proportion of patients with chronic disease has decreased, post-chikungunya chronic inflammatory rheumatism, mostly rheumatoid arthritis, develops in ≈5% of these patients (8). These patients had a poor prognosis and were given disease-modifying anti-rheumatic drugs (DMARDs), despite the postinfectious origin of rheumatism (4,5). Patients with post-chikungunya rheumatoid arthritis should benefit from methotrexate, which is recommended for treatment of classic rheumatoid arthritis (10). In our experience, resistance to or dependence on corticosteroids beyond the third month after disease onset is highly evocative of post-chikungunya chronic inflammatory rheumatism. This finding requires early treatment with DMARDs to control the inflammatory process, prevent bone erosions, and prevent inevitable side effects of prolonged corticotherapy. To date, the efficacy of different DMARDs for treatment of post-chikungunya chronic inflammatory rheumatism has not been evaluated. Therefore, physicians should follow the international guidelines for treatment of classic rheumatoid arthritis and psoriatic polyarthritis, which recommend methotrexate as first-line treatment for patients fulfilling chronic inflammatory rheumatism criteria after 3 months of evolution. We found that the Asian strain of chikungunya virus has induced arthritic disorders in the Western Hemisphere. Thus, a possible increase in post-chikungunya rheumatoid arthritis should not be overlooked. Physicians and public health authorities should prepare a response to the patients’ post-chikungunya stage in the epidemic areas. Clinical vigilance is recommended to identify patients with unfavorable outcomes 3 months after disease onset and for those in whom post-chikungunya chronic inflammatory rheumatism develops and who require specific treatment. Detailed guidelines for diagnosis and treatment of these patients with chronic rheumatoid arthritis are needed.

Left atrial (LA) size and function change with chronically increased left ventricular (LV) filling pressures. It remains unclear whether these variations in LA parameters can predict new-onset atrial fibrillation (AF) in asymptomatic patients with aortic stenosis (AS).Data were obtained in asymptomatic patients with mild-to-moderate AS (2.5 ≤ transaortic Doppler velocity ≤ 4.0m/s), preserved LV ejection fraction (EF), no previous AF, and were enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. Peak-aortic velocity, LA(max) volumeLAmin volume were measured by echocardiography. LA conduit (LA(con)) volume was defined as LV stroke volume-LA stroke volume. LA function was expressed as LA-EF (LA(max)-LAmin volume/LA(max)).In the 1159 patients included, new-onset AF occurred in 71 patients (6.1%) within a mean follow-up of 4.2 ± 0.9 years. Mean age was 66 ± 9.7 years, aortic valve area index 0.6 ± 0.2 cm(2)/m(2), LV mass 99.2 ± 29.7 g/m(2), LA(max) volume 34.6 ± 12.0 mL/m(2), LAmin volume 17.9 ± 9.3 mL/m(2), LA-EF 50 ± 15% and LA(con) volume 45 ± 21 mL/m(2). Baseline LAmin volume predicted new-onset AF in Cox multivariable analysis (HR:2.3 [95%CI:1.3-4.4], P0.01), and added prognostic information on AF development beyond conventional risk factors (likelihood ratio, P0.01). In comparison of c-indexes LAmin volume was superior to all other LA measurements. Net reclassification index improved by 15.9% when adding LAmin volume to a model with classic risk factors for AF (P=0.01).LAmin volume independently predicted new-onset AF in patients with asymptomatic AS and was superior to LA-EF, LA(con) and LA(max) volumes and conventional risk factors.

Infective endocarditis (IE) is uncommon but important because it is difficult to manage and universally fatal unless appropriately treated. 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 weeks8 ,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%.15 The outcome can be improved by prompt diagnosis and antibiotic therapy and by early surgery when indicated.8 ,10 ,16 ,17 Despite this, the diagnosis may be delayed, mistakes may be made in the type, duration or dose of antibiotic18 or the antibiotic may be started before blood cultures are obtained.11 Patients are still frequently referred to a specialist only at an advanced stage with heart failure6 ,11 ,18–20 or may not receive surgery even when indicated.8 As expected, non-compliance with guidelines is associated with a worse outcome.20 A multidisciplinary team (MDT) approach is increasingly seen as best practice where decision …

Background— Extracellular matrix expansion is a key element of ventricular remodeling and a potential therapeutic target. Cardiovascular magnetic resonance (CMR) T 1 -mapping techniques are increasingly used to evaluate myocardial extracellular volume (ECV); however, the most widely applied methods are without histological validation. Our aim was to perform comprehensive validation of (1) dynamic-equilibrium CMR (DynEq-CMR), where ECV is quantified using hematocrit-adjusted myocardial and blood T 1 values measured before and after gadolinium bolus; and (2) isolated measurement of myocardial T 1 , used as an ECV surrogate. Methods and Results— Whole-heart histological validation was performed using 96 tissue samples, analyzed for picrosirius red collagen volume fraction, obtained from each of 16 segments of the explanted hearts of 6 patients undergoing heart transplantation who had prospectively undergone CMR before transplantation (median interval between CMR and transplantation, 29 days). DynEq-CMR–derived ECV was calculated from T 1 measurements made using a modified Look-Locker inversion recovery sequence before and 10 and 15 minutes post contrast. In addition, ECV was measured 2 to 20 minutes post contrast in 30 healthy volunteers. There was a strong linear relationship between DynEq-CMR–derived ECV and histological collagen volume fraction ( P r =0.745; P r 2 =0.555 and between-subject: r =0.945; P r 2 =0.893; for ECV calculated using 15-minute postcontrast T 1 ). Correlation was maintained throughout the entire heart. Isolated postcontrast T 1 measurement showed significant within-subject correlation with histological collagen volume fraction ( r =−0.741; P r 2 =0.550 for 15-minute postcontrast T 1 ), but between-subject correlations were not significant. DynEq-CMR–derived ECV varied significantly according to contrast dose, myocardial region, and sex. Conclusions— DynEq-CMR–derived ECV shows a good correlation with histological collagen volume fraction throughout the whole heart. Isolated postcontrast T 1 measurement is insufficient for ECV assessment.

Background— Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study. Methods and Results— The relation between baseline ELI and rate of aortic valve events and combined total mortality and hospitalization for heart failure resulting from the progression of AS was assessed by multivariate Cox regression and reclassification analysis in 1563 patients with initial asymptomatic AS in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. During 4.3 years follow-up, a total of 498 aortic valve events and 181 combined total mortalities and hospitalizations for heart failure caused by the progression of AS occurred. In Cox regression analyses, 1-cm 2 /m 2 lower baseline ELI predicted a 2-fold higher risk both for aortic valve events and for combined total mortality and hospitalization for heart failure independently of baseline peak aortic jet velocity or mean aortic gradient and independently of aortic root size (all P Conclusions— In asymptomatic AS patients without known atherosclerotic disease or diabetes mellitus, ELI provides independent and additional prognostic information to that derived from conventional measures of AS severity, suggesting that ELI should be measured in such patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

Background Patients with aortic stenosis ( AS ) often have concomitant hypertension. Antihypertensive treatment with a β‐blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS . Methods and Results We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity‐matched Cox regression and competing risk analyses were used to assess risk ratios for all‐cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow‐up of 4.3±0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all‐cause mortality (hazard ratio 0.5, 95% confidence interval 0.3‐0.7, P P P =0.004). This was confirmed in competing risk analyses (all P AS severity (all P >0.1). Conclusions In post hoc analyses Bbl therapy did not increase the risk of all‐cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS . A prospective study may be warranted to determine if Bbl therapy is in fact beneficial. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00092677.

Background— The relationship between procedural volume and prognosis after percutaneous coronary intervention (PCI) remains uncertain, with some studies finding in favor of an inverse association and some against. This UK study provides a contemporary reassessment in one of the few countries in the world with a nationally representative PCI registry. Methods and Results— A nationwide cohort study was performed using the national British Cardiovascular Intervention Society registry. All adult patients undergoing PCI in 93 English and Welsh NHS hospitals between 2007 and 2013 were analyzed using hierarchical modeling with adjustment for patient risk. Of 427 467 procedures (22.0% primary PCI) in 93 hospitals, 30-day mortality was 1.9% (4.8% primary PCI). 87.1% of centers undertook between 200 and 2000 procedures annually. Case mix varied with center volume. In centers with 200 to 399 PCI cases per year, a smaller proportion were PCI for ST-segment–elevation myocardial infarction (8.4%) than in centers with 1500 to 1999 PCI cases per year (24.2%), but proportionally more were for ST-segment–elevation myocardial infarction with cardiogenic shock (8.4% versus 4.3%). For the overall PCI cohort, after risk adjustment, there was no significant evidence of worse, or better, outcomes in lower volume centers from our own study, or in combination with results from other studies. For primary PCI, there was also no evidence for increased or decreased mortality in lower volume centers. Conclusions— After adjustment for differences in case mix and clinical presentation, this study supports the conclusion of no trend for increased mortality in lower volume centers for PCI in the UK healthcare system. Clinical Trial Registration— https://www.clinicaltrials.gov . Unique identifier: NCT02184949.

There is a growing expectation that information about the performance of clinical services and individual doctors is made publicly available. Patients have a legitimate interest in knowing the care they receive is of high quality, but there are some potential risks in public reporting of these data, not least that of risk-averse behaviour by clinicians concerned about loss of reputation and livelihood that potentially denies patients appropriate treatment. The development of reliable metrics to assess clinical performance is complex, evolving and often controversial. In the USA, the Society of Thoracic Surgeons and the American College of Cardiology (ACC) have published principles for public reporting of outcomes central to which is the use of high-quality, robust and validated clinical data.1 National registries such as the National Cardiovascular Data Registries (NCDR) in the USA and the National Institute for Cardiovascular Outcomes Research audits in the UK are fundamental to the quality of clinical data used for performance reporting as is the involvement and oversight of the respective professional societies who are best placed to define what good looks like. Approaches to publication differ. In the UK, National Health Service England has published individual consultant outcomes for 11 specialties including interventional cardiology and cardiac surgery.2 In the USA, the ACC and NCDR have launched a voluntary programme of public reporting of performance data by institution.3 Although in its infancy, it is gaining considerable professional and public support. For interventional cardiology and adult cardiac surgery in the UK, there are two levels of negative outlier on the basis of 3-year rolling analysis of national audit data: alert and alarm. An alert means that observed survival is 2 SD below the expected mean and an alarm that survival is 3 SD below the expected mean. Data review and validation is rigorous, but …

Background Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. Methods Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. Results The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. Conclusions In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality.

We examined pulmonary artery pressure (PAP) characteristics of CF adults, studied clinical correlates and long-term survival.Comprehensive clinical data were collected and Doppler echocardiography was used to estimate PAP in 109 stable CF adults and 50 healthy controls.CF patients had lower day and night-time oxygen status, elevated CRP and BNP, and elevated PAP (27.7(13.2, 62.8) mmHg patients v 17.9(11.3, 30.9) mmHg controls, p0.001). Even patients with mild pulmonary disease had raised PAP. PAP measurements strongly correlated with arterial partial pressure of oxygen (PaO(2), r=-0.673, p0.001), and FEV(1) percentage predicted (FEV(1)%, r=-0.642, p0.001) which were both independent predictors of PAP. At 10 year follow up PAP measurements were related to survival but FEV(1)% and PaO(2) were both stronger predictors of death.PAP is raised in CF adults and correlates with pulmonary disease severity. Unlike PaO(2) and FEV(1)%, it does not appear to be an independent prognostic marker.

Objectives The aim of the study was to examine the predictive value of QRS duration and morphology during watchful waiting in asymptomatic patients with aortic stenosis (AS). Background QRS duration and morphology are associated with poor prognosis in many different populations, but the predictive value, particularly of the risk of sudden cardiac death (SCD), in asymptomatic patients with AS has not been well studied. Methods Data were obtained in asymptomatic AS patients randomized to simvastatin/ezetimibe combination versus placebo in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. The impact of QRS duration, evaluated as a categorical variable of = 100 ms (excluding bundle branch block [BBB]) and QRS morphology in those with BBB, on cardiovascular morbidity and mortality was assessed by adjusting for clinical and echocardiographic covariates. Results QRS data were available in 1,542 patients who were followed for a mean of 4.3 +/- 0.8 years (6,631 patient-years of follow-up). There were 68 cardiovascular deaths (4.6%), including 27 SCDs (1.8%). QRS duration was = 100 ms in those without BBB in 144 (9.3%), and 102 (6.6%) in those with BBB. In multivariable analyses, those with QRS duration >= 100 ms had, compared with those with QRS duration

Background— The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described. Methods and Results— Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V 4 through V 6 ) and LVH, assessed by Sokolow-Lyon voltage criteria (R V5–6 +S V1 ≥35 mV) and Cornell voltage-duration criteria {[RaVL+S V3 +(6 mV in women)]×QRS duration ≥2440 mV · ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3±0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4–6.8; P =0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0–16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3–3.1; both P =0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3–4.9; P =0.008). Conclusions— ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

Background Prognostic information for asymptomatic patients with aortic stenosis (AS) from prospective studies is scarce and there is no risk score available to assess mortality. Objectives To develop an easily calculable score, from which clinicians could stratify patients into high and lower risk of mortality, using data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Method A search for significant prognostic factors (p < 0.01) among SEAS patients was made by a combined judgemental and statistical elimination procedure to derive a set of three factors (age, gender and smoking) that were forced into the model, and four additional factors captured by the data: left-ventricular mass index, bilirubin, heart rate and natural logarithm of C reactive protein. Calibration was done by comparing observed with calculated number of deaths by tenths of calculated risk using coefficients from the simvastatin + ezetimibe group on placebo group patients. Results Discrimination was good with ROC area of 0.76 for all patients. Estimated probabilities of death were categorised into thirds. An optimised split point of estimated 5-year risk was about 15% (close to the upper 14% tertile split point), with risk 4 times as high in the upper compared to the two lower thirds. The SEAS score performed better than another established high risk score developed for other purposes. Conclusion A new seven factor model for risk stratification of patients with mild to moderate asymptomatic AS identified a high risk group for total mortality with good discrimination properties. Trial registration number ClinicalTrials.gov, NCT 00092677.

To evaluate the incidence of intraoperative and early postoperative complications (up to 2 months after implant) of endocardial permanent pacemaker insertion in all patients undergoing their first implant at our Center, we prospectively evaluated all pacemaker implantation procedures performed from April 1992 to September 1993. A standard “audit” form was completed at implant, recording patient demographic data, medical history, details of pacemaker hardware used, and any acute complications. Follow-up information was also collected prospectively onto standard forms at the pacemaker outpatient clinic. The study was performed in a United Kingdom tertiary referral Cardiothoracic Center. Nine hundred and fifty consecutive patients underwent implantation of their first endocardial permanent pacemaker from April 1992 to September 1993. Implant and follow-up data to 2 months were available on 926 (97.5%) of these patients at analysis, 51.4% were male (median age 77 years; range 16–99). Dual chamber units were implanted in 53% of patients, single chamber atrial in 6%, and ventricular in 41%. At implant, 23% of patients had a temporary pacing leadin situ. Most (93%) implants were performed via the subclavian vein. Acute complications were rare: 9 patients developed pneumothorax requiring medical treatment and 10 patients developed an insignificant pneumothorax. Arterial puncture without sequelae was documented in 2.7% of attempts at subclavian vein cannulation. Complications requiring re-operation occurred in 3.5% of patients overall; lead displacement [n=14 patients (1.5%)] was the most common reason for re-operation. Atrial lead displacement [n=10 patients (1.85% of atrial leads)] was significantly more common than ventricular lead displacement [n=4 patients (0.46% of ventricular leads),p=0.02]. Pacemaker pocket infection led to reoperation in 9 patients (0.97%) and was significantly more common in patients with a temporary pacing lead at implant (2.35%) compared with those without (0.56%,p

A patent foramen ovale (PFO) is detectable in 20-25% of the population. Some, but not all, case control studies have found an increased incidence of PFO in patients with cryptogenic stroke. Prospective cohort studies have failed to convincingly demonstrate a link between PFO and first stroke, and evidence linking PFO to recurrent stroke is far from compelling. The rate of recurrent stroke in medically treated patients is low, but the development of devices for PFO closure has lead to enthusiasm in some quarters to pursue a strategy of device closure. Nonrandomized studies have suggested a lower risk of recurrent events with device closure but the data are heterogeneous, and potentially prone to bias. Device implantation is associated with a risk of major adverse events of between 1.5% and 2.3%, and there is a significant rate of failure to close shunts. The results of randomized trials of device closure are keenly awaited. Migraine with aura has been linked with PFO. A recent metanalysis suggested an association, but the one prospective population study did not. The well-publicized and controversial MIST Trial is the only randomized trial of device closure in migraineurs yet published, and failed to demonstrate a convincing benefit from device closure. Other conditions such as platypnea-orthodeoxia syndrome and prevention of decompression sickness in divers, may justify device closure. Evidence for a role of PFO in the etiology of cryptogenic stroke and migraine is contradictory. It is possible that some patients might benefit from PFO closure but there is scant evidence of sufficient quality to justify routine PFO closure in either group. It is essential that ongoing randomized trials of device closure are completed.

Mitral stenosis is nearly always a consequence of rheumatic heart disease. It is characterised by a narrowed valve orifice that obstructs flow from left atrium to left ventricle causing a rise in left atrial pressure and left atrial enlargement. Longstanding elevation of left atrial pressures may cause secondary pulmonary hypertension. Breathlessness is the most common symptom. Atrial fibrillation is common. Patients in atrial fibrillation require tight control of heart rate and should be anticoagulated. Patients with moderate or severe symptoms should be offered balloon mitral valvuloplasty if the anatomy is suitable or valve replacement if it is not. Mitral regurgitation may be due to a number of different aetiologies of which degenerative valve disease is the most common. Asymptomatic patients with good left ventricular function can be followed with regular echocardiography but should be considered for surgery at the first sign of symptoms or impaired left ventricular function. Valve repair is superior to replacement in most degenerative valves. Other aetiologies include ischaemic and rheumatic disease. Acute ischaemic regurgitation due to papillary muscle rupture is a surgical emergency. Chronic ischaemic regurgitation is more common and results from distortion of the mechanism of mitral valve closure. Moderate or severe ischaemic regurgitation should be corrected in patients undergoing coronary bypass surgery. Severe symptomatic ischaemic regurgitation may require surgery in its own right. Many ischaemic valves can be repaired. Most incompetent rheumatic valves require replacement.

Objectives The aim of this analysis was to assess the diagnostic importance of pressure recovery in evaluation of aortic stenosis (AS) severity. Background Although pressure recovery has previously been demonstrated to be particularly important in assessment of AS severity in groups of patients with moderate AS or small aortic roots, it has never been evaluated in a large clinical patient cohort. Methods Data from 1,563 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study was used. Inner aortic diameter was measured at annulus, sinus, sinotubular junction, and supracoronary level. Aortic valve area index (AVAI) was calculated by continuity equation and pressure recovery and pressure recovery adjusted AVAI (energy loss index [ELI]), by validated equations. Primarily, sinotubular junction diameter was used to calculate pressure recovery and ELI, but pressure recovery and ELI calculated at different aortic root levels were compared. Severe AS was identified as AVAI and ELI ≤0.6 cm 2 /m 2 . Patients were grouped into tertiles of peak transaortic velocity. Results Pressure recovery increased with increasing peak transaortic velocity. Overestimation of AS severity by unadjusted AVAI was largest in the lowest tertile and if pressure recovery was assessed at the sinotubular junction. In multivariate analysis, a larger difference between AVAI and ELI was associated with lower peak transaortic velocity (beta = 0.35) independent of higher left ventricular ejection fraction (beta = –0.049), male sex (beta = –0.075), younger age (beta = 0.093), and smaller aortic sinus diameter (beta = 0.233) (multiple R 2 = 0.18, p < 0.001). Overall, 47.5% of patients classified as having severe AS by AVAI were reclassified to nonsevere AS when pressure recovery was taken into account. Conclusions For accurate assessment of AS severity, pressure recovery adjustment of AVA must be routinely performed. Estimation of pressure recovery at the sinotubular junction is suggested.

Valvular heart disease, particularly aortic stenosis and mitral regurgitation, accounts for a large proportion of cardiology practice, and their prevalence is predicted to increase. Management of the asymptomatic patient remains controversial. Biomarkers have been shown to have utility in the management of cardiovascular disease such as heart failure and acute coronary syndromes. In this state-of-the-art review, we examine the current evidence relating to natriuretic peptides as potential biomarkers in aortic stenosis and mitral regurgitation. The natriuretic peptides correlate with measures of disease severity and symptomatic status and also can be used to predict outcome. This review shows that natriuretic peptides have much promise as biomarkers in common valvular heart disease, but the impact of their measurement on clinical practice and outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality.

Asymptomatic aortic stenosis (AS) carries risk of heart failure and sudden death during watchful waiting. However, it remains unclear whether NT-proBNP, and its change from last year, in asymptomatic aortic valve stenosis (AS) predicts outcome. We evaluated 1577 asymptomatic AS patients from the

Aims Chronic primary mitral regurgitation (MR) results in enhanced filling of the left ventricle (LV) during early diastole. Filling is impaired with the onset of LV systolic dysfunction, due to increased myocardial stiffness and reduced restoring forces. We investigated echocardiographic parameters of early diastolic function in relation to LV systolic function. Methods and results Early diastolic transmitral flow and tissue Doppler velocities, propagation velocity of early filling (Vp), and early diastolic strain rates (SR-E) were measured in 30 patients with chronic degenerative MR and 30 age-matched controls. MR subjects were further subdivided into group 1 (14 subjects) if they had well compensated LV, and group 2 (16 subjects) if they had one or more of the following: functional limitation (> NYHA class I), LV end-systolic diameter ≥4.0 cm, and LV ejection fraction ≤60%. Group 1 had increased early diastolic transmitral flow and tissue velocities, Vp and SR-E, compared with controls. Vp and SR-E in group 2 (46.5 ± 9.92 cm/s and 1.44 ± 0.36 s−1, respectively) decreased significantly compared with group 1 (74.4 ± 19.9 cm/s and 1.96 ± 0.53 s−1, P ≤ 0.002). Onset and peak of early long-axis expansion and myocardial lengthening were significantly delayed in MR, and this delay was directly correlated with preload parameters. Conclusion In chronic MR, novel echocardiographic measurements of early diastolic function exhibit a biphasic pattern depending on the state of LV systolic function, and may prove useful in the timing of surgery.

Aims To study global and regional left atrial (LA) mechanics in chronic primary mitral regurgitation (MR) with echocardiography. Methods and results LA volumes during reservoir, conduit, and contractile phases were measured in 27 MR patients and 25 controls. LA ejection fraction (EF) and ejection force were calculated. Reservoir (SR-R), conduit (SR-C), and contractile phase (SR-A) strain rates, and reservoir phase strain were obtained. LA volumes were higher in MR in all phases. In MR, ejection force was increased (21.5 vs. 12.3 kdynes, P = 0.001); reservoir phase strain (32.91 ± 14.26%), SR-R (2.65 ± 0.87), SR-C (−2.02 ± 0.58), and SR-A (−2.55 ± 1.31 s−1) were increased (23.14 ± 7.96%, 1.62 ± 0.53, −1.29 ± 0.59, −1.98 ± 0.65 s−1, in controls, respectively, P ≤ 0.004). Regional deformation correlated with corresponding volumetric parameters. Despite enhanced SR-A in MR, LA EF was unchanged (31.34 vs. 29.23%, P = ns), and LA contractile tissue velocity ( A ′) was reduced (−5.39 ± 1.95 vs. −6.91 ± 1.80 cm/s, P = 0.006). The LA contractile contribution to left ventricular filling was significantly reduced in MR. Conclusion LA deformation is increased in all phases in MR. Unchanged LA EF and reduced A ′ may reflect the reduced contractile contribution to left ventricular filling.

Low-Flow Aortic Stenosis in Asymptomatic Patients: Valvular–Arterial Impedance and Systolic Function From the SEAS SubstudyDana Cramariuc, Giovanni Cioffi, Ashild E. Rieck, Richard B. Devereux, Eva...

Torsion is essential for normal systolic and diastolic function of the left ventricle (LV), and is known to be abnormal in animal models of mitral regurgitation (MR). There are no comparable data in humans.To study LV torsion in humans with chronic primary MR using speckle-tracking echocardiography.Rotation and rotation rate were measured from two-dimensional (2D) greyscale LV base and apex short-axis images by speckle-tracking echocardiography in 38 patients and 30 controls. Using custom software, plots of torsion against time were constructed by deducting base rotation from apex rotation. Loops of torsion against LV radial/longitudinal displacement and volume were automatically plotted.Peak systolic torsion, systolic torsional velocity and untwisting velocity were similar in the two groups. In controls, untwisting started 23 ms before aortic valve closure but was delayed in MR to 15 ms after aortic valve closure, p0.001. In normal subjects there was rapid untwisting during isovolumic relaxation, with minimal expansion of the LV radial and longitudinal axes. In MR, early untwisting rate was decreased, with less untwisting for a given volume increase. Extensive LV remodelling and worsening MR were associated with progressive reductions in systolic torsion and untwisting velocity, and progressive delay in the onset of untwisting.Chronic MR results in significant delay and slowing of LV untwisting, such that early untwisting is coupled with chamber expansion. Correlations between disease severity and torsional parameters suggest a potential role of these variables in assessing early signs of ventricular dysfunction.

AIMS Migraine with aura and patent foramen ovale (PFO) are associated. The Percutaneous Closure of PFO in Migraine with Aura (PRIMA) trial is a multicentre, randomized trial to investigate the effect of percutaneous PFO closure in patients refractory to medical treatment. METHODS Migraine with aura patients and PFO who were unresponsive to preventive medications were randomized to PFO closure or medical treatment. Both groups were given acetylsalicylic acid 75-100 mg/day for 6 months and clopidogrel 75 mg/day for 3 months. The primary endpoint was reduction in monthly migraine days during months 9-12 after randomization compared with a 3-month baseline phase before randomization. The committee reviewing the headache diaries were blinded to treatment assignment. RESULTS One hundred and seven patients were randomly allocated to treatment with an Amplatzer PFO Occluder (N = 53) or control with medical management (N = 54). The trial was terminated prematurely because of slow enrolment. Eighty-three patients (40 occluder, 43 control) completed 12-month follow-up. Mean migraine days at baseline were 8 (±4.7 SD) in the closure group and 8.3 (±2.4) in controls. The primary endpoint was negative with -2.9 days after PFO closure vs. -1.7 days in control group (P = 0.17). Patent foramen ovale closure caused five adverse events without permanent sequelae. CONCLUSION In patients with refractory migraine with aura and PFO, PFO closure did not reduce overall monthly migraine days.

Background and aims: Mitral valve prolapse (MVP) is common and highly variable in its severity, but the factors underlying this variability are unclear. In this study, we tested the hypothesis that polymorphic variations in Matrix Metalloproteinase (MMP) genes might be predictors of left ventricular (LV) remodelling and severity of regurgitation in MVP. Methods and results: 70 MVP patients and 75 normal subjects were studied. We performed comprehensive echocardiography and analyzed promoter polymorphisms in the MMP-1 and MMP-3 genes. The MMP-3 -1612 5A/6A polymorphism showed strong associations with indices of mitral regurgitation and LV remodelling: Patients with 5A/5A allele had more pronounced remodelling and more severe mitral regurgitation than patients with the 6A/6A or 5A/6A alleles. We then cloned and sequenced 2 kb fragments of MMP-3 promoter from patients with 5A/5A and 6A/6A genotypes and found 4 different sets of promoter haplotypes. Promoter analysis showed that higher promoter activity was related to a more severe phenotype and that the haplotype variants had a more dominant role in determining the activity. Conclusions: Our data identifies the MMP-3 promoter haplotype as a novel marker of an adverse disease course in MVP, suggesting the presence of genetic determinants for the severity of MVP.

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in the risk-benefit ratio of statin treatment.

Objectives: To define best practice standards for mitral valve repair surgery. Design: Development of standards for process and outcome by consensus. Setting: Multidisciplinary panel of surgeons, anaesthetists, and cardiologists with interests and expertise in caring for patients with severe mitral regurgitation. Main outcome measures: Standards for best practice were defined including the full spectrum of multidisciplinary aspects of care. Results: 19 criteria for best practice were defined including recommendations on surgical training, intraoperative transoesophageal echocardiography, surgery for atrial fibrillation, audit, and cardiology and imaging issues. Conclusions: Standards for best practice in mitral valve repair were defined by multidisciplinary consensus. This study gives centres undertaking mitral valve repair an opportunity to benchmark their care against agreed standards that are challenging but achievable. Working towards these standards should act as a stimulus towards improvements in care.

The burden of valvular heart disease (VHD) is rising rapidly as life expectancy increases. The prevalence in the USA alone is 13% in those aged over 75 years,1 while the global prevalence of rheumatic heart disease is estimated at 15.6–19.6 million.2 Despite this, the treatment of VHD still lacks an adequate research base. None of the 64 recommendations in the 2012 European Society of Cardiology (ESC) VHD guidelines3 had Level A evidence and only 14% had Level B evidence. This compares with 28% at Level A and 42% at Level B among the 270 recommendations in the 2010 ESC myocardial revascularisation guidelines.4 Therefore, there is an urgent need to stimulate the investigation. In this article, we identify deficits in our knowledge which may be amenable to research and make a call for national and international collaborative efforts to address this evidence gap. The prevalence of VHD in industrialised countries has been extrapolated from studies predominantly conducted in the USA,1 while the prevalence of rheumatic disease in sub-Saharan Africa is extrapolated from studies in North Africa. True figures need to be established nationally, while for rare causes of VHD (eg, carcinoid or antiphospholipid syndrome), this might be better done using international registries with standardised protocols. Serial echocardiography within these projects will improve our understanding of the contemporary natural history of VHD, which was previously determined in small cohorts of patients and generally with fewer comorbidities compared with the present. The genetics and developmental biology of VHD are poorly understood. Collation of genetic analyses from established bio-banks and twin studies may identify new determinants of disease or its progression. Such techniques may also provide clues towards the development of treatments for challenging conditions such as endomyocardial fibrosis. Lipid-lowering therapy has not been successful in modifying the progression …

Background: Atrial en-face reconstructions are commonly used to assess mitral valve morphology in three dimensional (3D) echocardiography but may miss important abnormalities. Objective: To present a systematic method for the analysis of the regurgitant mitral valve using a combination of en-face and longitudinal views for better anatomical evaluation. Methods: Detailed 3D assessment was done on 58 patients undergoing mitral valve repair. En-face and longitudinal views were compared for detection and location of primary pathology. The quality of acquisitions under general anaesthesia and sedation was also compared. Results: Recognition of valve structure was significantly better with longitudinal reconstruction for both mitral leaflets but not for the commissures. Accurate identification of pathology was possible in 95% cases, compared with 50% for en-face reconstruction (p < 0.001). There was no significant difference between imaging under sedation and anaesthesia. Conclusion: En-face reconstructions alone are inadequate. Additional longitudinal reconstructions are necessary to ensure full inspection of valve morphology.

AIMS: Transoesophageal echocardiography (TOE) plays a vital role in the assessment of mitral valve morphology. However, the accuracy of TOE may be limited by inadequate recognition of all segments. We aimed to evaluate the role of three-dimensional (3D) echocardiography in this respect. METHODS AND RESULTS: Seventy-five patients were studied prior to mitral valve repair surgery. A scoring protocol was devised for recognition of the eight Carpentier segments (0=inadequate for analysis, 1=adequate, 2=good). Using surgical findings as the gold standard, TOE and 3D were compared for adequate recognition scores and accurate detection of functional morphology. Adequate recognition was more frequently obtained with 3D imaging (97% of segments by 3D c.f. 90% by TOE; p = 0.000). The major difference was seen at the commissures (adequate scores in 143/150 commissures by 3D c.f. 90/150 by TOE; p = 0.000). 3D matched more closely to surgical findings, achieving exact functional description in 92% of segments vs 79% segments with TOE (p = 0.000). This incremental value of 3D was seen in both commissures and the anterior leaflet but not in the posterior leaflet. CONCLUSIONS: In this study 3D was superior not only for complete recognition of the mitral valve but also for the accurate localisation and identification of pathology.

Medalists represent a unique group of survivors of over 50 years of type 1 diabetes (T1D) (1,2). A subgroup of Medalists, escapers , remains free of micro- and macrovascular complications. To date, there are no published studies on cardiac structure and function in these subjects. We have undertaken a comprehensive multiparametric cardiac MRI study (3,4) to quantify myocardial structure, function, deformation, perfusion, and fibrosis in a cohort of 13 subjects with extreme-duration T1D and 14 healthy control subjects (Table 1). View this table: Table 1 Clinical characteristics and cardiac MRI data The T1D group had a mean duration of diabetes of 47.4 ± 5.1 years (median 48.0 years). Eight participants had a history of retinopathy and 12 were receiving statin and ACE inhibitor therapy. The mean HbA1c over the previous 16 years was 8.3 ± …