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ObjectiveWe retrospectively analysed outcome data from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study to assess the incidence and potential risk factors of sudden cardiac death (SCD) in this prospectively followed cohort of asymptomatic patients with aortic stenosis (AS).MethodsOf the 1873 patients included in SEAS, 1849 (99%) with mild to moderate AS (jet velocity 2.5–4.0 m/s at baseline) and available clinical, echocardiographic and follow-up data were analysed. Patients undergoing aortic valve replacement were censored at the time of operation.ResultsDuring an overall follow-up of 46.1±14.6 months, SCD occurred in 27 asymptomatic patients (1.5%) after a mean of 28.3±16.6 months. The annualised event rate was 0.39%/year. The last follow-up echocardiography prior to the event showed mild to moderate stenosis in 22 and severe stenosis (jet velocity >4 m/s) in 5 victims of SCD. The annualised event rate after the diagnosis of severe stenosis was 0.60%/year compared with 0.46%/year in patients who did not progress to severe stenosis (p=0.79). Patients with SCD were older (p=0.01), had a higher left ventricular mass index (LVMI, p=0.001) and had a lower body mass index (BMI, p=0.02) compared with patients surviving follow-up. Cox regression analysis identified age (HR 1.06, 95% CI 1.01 to 1.11 per year, p=0.02), increased LVMI (HR 1.20, 95% CI 1.10 to 1.32 per 10 g/m2, p2, p=0.01) as independent risk factors of SCD.ConclusionSCD in patients with asymptomatic mild to moderate AS is rare and strongly related to left ventricular hypertrophy but not stenosis severity.

Background Adjustment of cardiac dimensions by measures of body size appears intuitively convincing and in patients with aortic stenosis, aortic valve area (AVA) is commonly adjusted by body surface area (BSA). However, there is little evidence to support such an approach. Objective To identify the adequate measure of body size for the adjustment of aortic stenosis severity. Methods Parameters of aortic stenosis severity (jet velocity, mean pressure gradient (MPG) and AVA) and measures of body size (height, weight, BSA and body mass index (BMI)) were analysed in 2843 consecutive patients with aortic stenosis (jet velocity >= 2.5 m/s) and related to outcomes in a second cohort of 1525 patients from the Simvastatin/Ezetimibe in Aortic Stenosis (SEAS) study. Results Whereas jet velocity and MPG were independent of body size, AVA was significantly correlated with height, weight, BSA and BMI (Pearson correlation coefficient (r) 0.319, 0.281, 0.317 and 0.126, respectively, all p

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.

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.

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.

Bioprosthetic valve replacement is the treatment of choice in older patients with symptomatic severe aortic valve disease. Thrombosis of bioprosthetic valves has been considered a rare complication; however, in the presence of valvular obstruction, therapeutic consequences for the individual patient may be dramatic including repeat valve replacement or thrombolysis. We therefore evaluated oral anticoagulation with phenprocoumon as an alternative treatment for obstructive thrombosis of bioprosthetic valves. Six of 470 patients who had received a single stented bioprosthetic aortic valve from January 2007 through December 2008 at our hospital presented with obstructive bioprosthetic valve thrombosis within 14 months postoperatively. All 6 patients (1% of study population) had received a porcine valve (p = 0.1 vs pericardial), were hemodynamically stable, were in sinus rhythm, and were taking acetylsalicylic acid 100 mg/day. Echocardiography showed an increase in mean pressure gradient early postoperatively from 23.3 ± 4 to 57.0 ± 10 mm Hg (p0.001). Five patients were started on phenprocoumon and followed for 114 ± 54 days, when mean pressure gradient had returned to 23.5 ± 6 mm Hg. No adverse events were observed during that period. One patient presenting with dyspnea and fever underwent emergency repeat valve replacement for suspected endocarditis, with histology showing long-term thrombosis of the explanted valve. In conclusion, oral anticoagulation with phenprocoumon represents a safe and effective treatment in clinically stable patients with obstructive thrombosis of bioprosthetic aortic valves, thus obviating repeat valve surgery or thrombolysis.

Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow-Lyon voltage and Cornell voltage duration criteria; and strain by T-wave inversion and ST-segment depression. Degree of AS severity was evaluated by echocardiography as peak aortic jet velocity and LV mass was indexed by body surface area. After adjustment for age, gender, LV mass index, heart rate, systolic and diastolic blood pressures, blood glucose, digoxin, antiarrhythmic drugs, drugs acting on the renin angiotensin system, diuretics, beta blockers and calcium receptor blockers; peak aortic jet velocity was significantly greater in patients with electrocardiographic strain (mean difference 0.13 m/s, p

Background The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the Task Force aimed at developing recommendations for adult and paediatric cardiologists to acquire the additional qualification "Adults with Congenital Heart Disease" (ACDH). Methods The members of the interdisciplinary Task Force were selected on the basis of their special clinical, scientific and organisational expertise. The leading author submitted a draft version, which was revised by a sub-group of the interdisciplinary Task Force. It was subsequently agreed upon and re-circulated by all the members of the Task Force. The recommendations were then presented to the relevant committees of all participating associations and groups and approved following detailed discussion. Results A training programme for acquiring an additional qualification in the treatment of adults with congenital heart disease was created successfully. Conclusions The medical care of adults with congenital heart disease is a sub-speciality in the border area between adult cardiology and paediatric cardiology. ACHD cardiologists are to be specially trained experts with appropriate knowledge and special skills and experience in the diagnosis and therapy of congenital heart disease in adults. ACHD cardiologists should be able to recognise and treat problems that occur in adulthood in connection with congenital heart disease.

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.

Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks, and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s). A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC Web Site (http://www.escardio.org/guidelines/rules). Members of this Task Force were selected by the ESC to represent all physicians involved with the medical care of patients in this pathology. In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing and reviewing panels have provided disclosure statements of all relationships they may have which …

The present study tests the consistency of echocardiographic criteria for the grading of aortic valve stenosis.Current guidelines/recommendations define severe stenosis as an aortic valve area (AVA)1 cm2 (or0.6 cm2 adjusted for body surface area), mean pressure gradient (DeltaPm)40 mmHg, or peak flow velocity (Vmax)4 m/s. We tested the consistency of the three criteria for the grading of aortic valve stenosis in 3483 echocardiography studies performed in 2427 patients with normal left ventricular (LV) systolic function and a calculated AVA ofor =2 cm2. We calculated curve fits for the relationship between AVA and DeltaPm using the Gorlin equation and between AVA and Vmax based on the continuity equation for our study population. An AVA of 1.0 cm2 correlated to a DeltaPm of 21 mmHg and a Vmax of 3.3 m/s. Conversely, a DeltaPm of 40 mmHg corresponds to an AVA of 0.75 cm2 and a Vmax of 4.0 m/s to an AVA of 0.82 cm2. Consequently, severe stenosis was diagnosed in 69% of patients based on AVA, 45% on Vmax, and 40% on DeltaPm. Stroke volume was lower in inconsistently graded patients (65 +/- 11 mL vs. consistently graded: 70 +/- 14 mL, P0.001).The criteria for the grading of aortic stenosis are inconsistent in patients with normal systolic LV function. On the basis of AVA, a higher proportion of patients is classified as having severe aortic valve stenosis compared with mean pressure gradient and peak flow velocity. Discrepant grading in these patients may be partly due to reduced stroke volume.

BACKGROUND: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown.METHODS: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se.RESULTS: 1563 patients were followed for a mean of 4.3years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n=151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10min(-1) faster, 95% CI: 1.0-1.7, both p≤0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10min(-1) faster, 95% CI: 1.2-1.7, both p≤0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p≥0.06 for interaction).CONCLUSIONS: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).

To the Editor, We thank Dr San Roman and colleagues for their comment1 on our editorial.2 They suggest that all cases with endocarditis should be referred to a reference centre because the specialist expertise to monitor their progress may not be available at general hospitals. The typical length of intravenous antibiotic therapy for patients with endocarditis is 4–6 weeks, and beds in …

Hypertension and coronary heart disease are common in aortic stenosis (AS) and may impair prognosis for similar AS severity. Different changes in the electrocardiogram may be reflective of the separate impacts of AS, hypertension, and coronary heart disease, which could lead to enhanced risk stratification in AS. The aim of this study was therefore to examine if combining prognostically relevant electrocardiographic (ECG) findings improves prediction of cardiovascular mortality in asymptomatic AS. All patients with baseline electrocardiograms in the SEAS study were included. The primary end point was cardiovascular death. Backward elimination (p >0.01) identified heart rate, Q waves, and Cornell voltage-duration product as independently associated with cardiovascular death. Multivariate logistic and Cox regression models were used to evaluate if these 3 ECG variables improved prediction of cardiovascular death. In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow-up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate (hazard ratio [HR] 1.5 per 11.2 minute(-1) [1 SD], 95% confidence interval [CI] 1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 mm [1 SD], 95% CI 1.1 to 1.6), and Cornell voltage-duration product (HR 1.4 per 763 mm × ms [1 SD], 95% CI 1.2 to 1.7) remained independently associated with cardiovascular death. Combining the prognostic information contained in each of the 3 ECG variables improved integrated discrimination for prediction of cardiovascular death by 2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p ≤0.04) beyond other important risk factors. ECG findings add incremental predictive information for cardiovascular mortality in asymptomatic patients with AS.

ECG signs of myocardial abnormality provide independent prognostic information in asymptomatic aortic stenosis (AS). It is unknown if the sum of ECG abnormalities further improves discriminatory power for prediction of cardiovascular outcomes. Patients with complete 12-lead ECGs in the simvastatin/

We hypothesized that increased myocardial oxygen consumption (MOC) may be a predictor of heart failure (HF) in mild-to-moderate aortic stenosis (AS). MOC was available in 1,623 (87%) of 1,873 patients in the Simvastatin in Ezetimibe in Aortic Stenosis study with asymptomatic mild-to-moderate AS.

Background and Purpose— There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes. Methods— Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years and female sex (CHA 2 DS 2 -VASc) scores. Results— One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1–6.6), CHA 2 DS 2 -VASc score (HR 1.4 per unit; 95% CI, 1.1–1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1–1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4–7.2, all P ≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7–14.0; P Conclusions— In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA 2 DS 2 -VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

In pregnant women, anticoagulation is needed for women with mechanical valves, for women who are at increased risk of venous thrombembolism, those who have cardiomyopathies and severely impaired ejection fraction (EF), for high-risk patients with atrial fibrillation, those who have acute coronary syndromes and for some patients with congenital heart disease. The most frequently used drugs are Vitamin K antagonists, heparins, clopidogrel, and acetyl salicylic acid. They differ in the level of protection and risk they bear for the mother and her fetus and their precise use varies according to the specific indication. Both the indications and drugs have been discussed in the guidelines of the European Society of Cardiology on the management of cardiovascular diseases in pregnancy and were recently reviewed in European Heart Journal ((Regitz-Zagrosek et al. 2011) and Current Problems in Cardiology, in press). The present chapter is based on these publications.

Background: The frequency and prognostic importance of atrial fibrillation (AF) in asymptomatic mild-to-moderate aortic stenosis (AS) has not been well described. Methods: Clinical examination, electrocardiography and echocardiography were obtained in asymptomatic patients with mild-to-moderate AS and preserved left ventricular (LV) systolic function, randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. At inclusion, AF was categorized as episodic or longstanding. Rhythm change was assessed on annual in-study electrocardiograms. Impact of AF on cardiovascular morbidity and mortality was determined by adjusting for biomarkers, clinical- and echocardiographic covariates. Results: Mean follow-up was 4.3 +/- 0.8 years (6,721 patient-years of follow-up). At baseline, episodic AF was present in 87 patients (5.6%), longstanding AF in 55 (3.5%) and no AF in 1,421 (90.9%). Incidence of new-onset AF was 1.2%/year; highest in those with impaired LV function. In multivariable analysis, longstanding AF was compared to no AF at baseline, associated with a 4.1-fold higher risk of heart failure (CI 1.2 to 13.8, p = 0.02) and a 4.8-fold higher risk of non-hemorrhagic stroke (CI 1.7 to 13.6, p = 0.003). Conclusion: Rate of AF is moderate in asymptomatic AS. Longstanding but not episodic AF was, independently predictive of increased risk of heart failure and non-hemorrhagic stroke. New-onset AF was associated with cardiac decompensation. (c) 2011 Elsevier Ireland Ltd. All rights reserved.

Aims In aortic valve stenosis (AS), having a small aortic root may influence both the assessment of AS severity and the treatment strategy. The aim was to test the prognostic implications of having a small aortic root in AS within a large prospective study. Methods and results We used data from 4.3-year follow-up of 1560 patients with asymptomatic, initially mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study. A small aortic root was defined as inner aortic sinotubular junction diameter indexed for body height

Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS).Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1:1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events.During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P.001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P.001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03).Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis.

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).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.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 of85 ms versus 85 to 99 ms and ≥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.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 was85 ms in 900 patients (58.4%), 85 to 99 ms in 396 (25.7%), ≥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 duration85 ms, a 5-fold higher risk of SCD (95% confidence interval: 1.8 to 13.7, p = 0.002) and a 2.5-fold higher risk of cardiovascular death (95% confidence interval: 1.2 to 5.1, p = 0.01).QRS duration and morphology in asymptomatic patients with AS are independently associated with a poor prognosis, particularly the risk of SCD.

Response to Letters Regarding Article, "Outcome of Patients With Low-Gradient "Severe" Aortic Stenosis and Preserved Ejection Fraction"

Aims To report aortic root geometry by echocardiography in a large population of healthy, asymptomatic aortic stenosis (AS) patients in relation to current vendor-specified requirements for transcatheter aortic valve implantation (TAVI). Methods and results Baseline data in 1481 patients with asymptomatic AS (mean age 67 years, 39% women) in the Simvastatin Ezetimibe in AS study were used. The inner aortic diameter was measured at four levels: annulus, sinus of Valsalva, sinotubular junction and supracoronary, and sinus height as the annulo-junctional distance. Analyses were based on vendor-specified requirements for the aortic root geometry for current available prostheses, CoreValve and Edwards-Sapien. The ratio of sinus of Valsalva height to sinus width was 1:2. In multivariate linear regression analysis, larger sinus of Valsalva height was associated with older age, larger sinus of Valsalva diameter, lower ejection fraction and smaller supracoronary diameter (multiple R 2 = 0.19, P < 0.01). The required annulus diameter for implantation of CoreValve was met in 61.9%, and for the Edwards-Sapien prosthesis in 66.9%. Overall, annular dimension feasible for TAVI using any available prosthesis was found in 78.2% of patients and in 77.7% of patients also the required minimum sinus of Valsalva height was found. Comparing the group of patients who met TAVI requirements to those who did not, the latter included more women and patients with lower body height and weight and significantly smaller aortic root diameters (all P < 0.05). Conclusion Among AS patients in the SEAS study, 27% of women and 19% of men did not have aortic root geometry fulfilling current requirements for TAVI.

On echocardiography approximately one-third of patients with severe aortic valve stenosis based on aortic valve area (AVA1.0 cm(2)) demonstrate a non-severe mean pressure gradient (DeltaPm;or =40 mm Hg) despite apparently normal left ventricular function. It has been suggested that inconsistent echocardiographic grading may be due to 'paradoxical' low stroke volume. However, the correct echocardiographic assessment of stroke volume hinges on the often problematic measurement of the left ventricular outflow tract (LVOT) diameter.To investigate whether inconsistent grading and reduced stroke volume persist when the quantification of aortic valve stenosis is based on cardiac catheterisation which is independent of LVOT measurements.333 consecutive patients underwent cardiac catheterisation within 30 days after their index echocardiography showing an AVAor =2 cm(2) and shortening fractionor =30%. On invasive testing 85 patients (26%) demonstrated inconsistent (AVA1 cm(2) and DeltaPmor =40 mm Hg) and 153 (46%) consistent grading (AVA1 cm(2) and DeltaPm40 mm Hg) with the remainder (28%) presenting with a calculated AVAor =1 cm(2). Inconsistently graded patients were older (71 vs 67 years, p0.006) with no differences in sex or body surface area between groups. Stroke volume and stroke volume index were significantly lower in inconsistently graded patients (63+/-14 vs 73+/-18 ml and 35+/-7 vs 39+/-7 ml/m(2), respectively, both p0.001). However, 41/85 (48%) of inconsistently graded patients had a normal stroke volume index35 ml/m(2).In the framework of current guidelines inconsistent grading of aortic valve stenosis is common, extends to cardiac catheterisation and is only partially explained by low stroke volume despite apparently normal left ventricular systolic function.

In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, combined ezetimibe (10 mg) and simvastatin (40 mg) decreased low-density lipoprotein cholesterol levels by 50% and ischemic cardiovascular event (ICE) risk by 22% compared to placebo. A larger decrease in ICE risk might have been expected for the degree of lipid-lowering observed. This analysis investigated relations between changes in lipoprotein components (LCs), and ICE risk decrease in the SEAS trial in all patients, by severity of aortic stenosis (AS), and compared to results of other clinical trials. A total of 1,570 patients with baseline aortic jet velocity (JV) data, baseline and 1-year low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B, and no ICEs during the first year were included in the analysis. Relations between on-treatment measurements of 1-year LCs and time-to-ICE occurrence were assessed in all patients and in JV tertiles (2.8, 2.8 to 3.3, and3.3 m/s). Observed and predicted ICE risk decreases were compared by Cox model. Decreases in LCs after 1 year of ezetimibe plus simvastatin were associated with decreased ICE risk in all patients and in the 2 lower JV tertiles (p0.05 to0.001) but not in tertile 3. In JV tertiles 1 and 2, ICE risk decreased by 47% and 36%, respectively, was reasonably well predicted by all LCs, and was consistent with findings from meta-regression analyses in other populations. In conclusion, the degree of lipid lowering by ezetimibe plus simvastatin may predict the extent of ICE risk decrease in patients with mild AS, but ICE risk prediction in patients with more severe AS is confounded by AS-associated cardiovascular events and a shorter interval of exposure to lipid lowering.

Background: Downstream pressure recovery (PR) in the aorta affects transvalvular pressure gradient measurement and calculation of aortic valve area by continuity equation in patients with aortic stenosis (AS). Methods: To assess the clinical importance of PR on evaluation of severity of AS, echocardiographic data in 1562 patients with asymptomatic aortic stenosis (mean age 67 ± 10, 39% women, 51% hypertensive) recruited in the Simvastatin Ezitimibe in Aortic Stenosis (SEAS) study was used. The inner diameter of the ascending aorta was measured at annulus and at sinutubular junction. The aortic valve area (AVAI) was calculated from annular diameter and velocity time integrals from sub- and transaortic flow by Doppler. PR and PR corrected AVAI assessed as energy loss index (ELI) were calculated by previously published equations. Severe aortic stenosis was defined as AVAI 2 /m 2 and ELI 2 /m 2 , respectively. Patients were grouped into tertiles of peak transaortic Doppler velocity ( Results: In the total study population, PR ranged from 1.22–16.75 mmHg (mean 5.9±2.3), AVAI from 0.20 –1.85 cm 2 /m 2 (mean 0.67±0.22) and ELI from 0.22–5.94 cm 2 /m 2 (mean 0.89±0.45). PR increased significantly with severity of AS (Table 1 ). Both AVAI and ELI decreased with increasing peak transaortic velocity, and the overestimation of AS severity by using unadjusted AVA was largest in the lowest tertile (Table 1 ). Conclusion: Severity of AS is often overestimated in milder degrees of asymptomatic AS if correction for pressure recovery is not performed. Adjustment of AVA for the effect of energy loss should be performed routinely, and this may be especially important for accuracy of severity assessment in patients with relatively low transvalvular velocities. Table 1

Physical check-ups among athletes with valvular heart disease are of significant relevance. In athletes with mitral valve stenosis the extent of allowed physical activity is dependant on the size of the left atrium and the severity of the valve defect. Patients with mild-to-moderate mitral valve regurgitation can participate in all types of sport associated with low and moderate isometric stress and moderate dynamic stress. Patients under anticoagulation should not participate in any type of contact sport. Asymptomatic athletes with mild aortic valve stenosis can take part in all types of sport, as long as left ventricular function and size are normal, a normal response to exercise at the level performed during athletic activities is present and there are no arrhythmias. Asymptomatic athletes with moderate aortic valve stenosis should only take part in sports with low dynamic and static stress. Aortic valve regurgitation is often present due to connective tissue disease of a bicuspid valve. Athletes with mild aortic valve regurgitation, with normal end diastolic left ventricular size and systolic function can participate in all types of sport. A mitral valve prolapse is often associated with structural diseases of the myocardium and endocardium. In patients with mitral valve prolapse Holter-ECG monitoring should also be performed to detect significant arrhythmias. All athletes with known valvular heart disease, a previous history of infective endocarditis and valve surgery should receive endocarditis prophylaxis before dental, oral, respiratory, intestinal and genitourinary procedures associated with bacteraemia. Sport activities have to be avoided during active infection with fever.

Guidelines and Expert Consensus Documents aim to present management recommendations based on all of the relevant evidence on a particular subject in order to help physicians select the best possible management strategies for the individual patient suffering from a specific condition, taking into account the impact on outcome and also the risk–benefit ratio of a particular diagnostic or therapeutic procedure. Numerous studies have demonstrated that patient outcomes improve when guideline recommendations, based on the rigorous assessment of evidence-based research, are applied in clinical practice. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. The profusion of documents can put at stake the authority and credibility of guidelines, particularly if discrepancies appear between different documents on the same issue, as this can lead to confusion in the minds of physicians. In order to avoid these pitfalls, the ESC and other organizations have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. The ESC recommendations for guidelines production can be found on the ESC website.1 It is beyond the scope of this preamble to recall all but the basic rules. In brief, the ESC appoints experts in the field to carry out a comprehensive review of the literature, with a view to making a critical evaluation of the use of diagnostic and therapeutic procedures and assessing the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. Estimates of expected health outcomes are included, where data exist. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined in what follows. The Task Force members of the writing panels, …

Severe primary mitral regurgitation (MR) has a poor outcome if left uncorrected. Successful mitral valve repair has the unique potential to restore normal life expectancy and is superior to valve replacement. Despite this, mitral repair is performed relatively infrequently and many patients with potentially reparable valves have a replacement instead, subjecting them to unnecessary risk. Surgery in asymptomatic patients is a particularly difficult issue with some units advocating surgery irrespective of symptoms, based purely on the severity of regurgitation. This strategy cannot be widely adopted with the current patchy provision of high-quality valve repair surgery. Misplaced enthusiasm for early operation runs the risk of a failed repair and the hazards of a mechanical prosthesis. To ensure optimal treatment for patients with MR, cardiologists must be aware of the indications for valve repair and ensure that patients with potentially reparable valves are referred to surgeons with proven expertise, even if this means a shift from established practice. Surgical units need to promote subspecialization and rigorously audit their outcomes. There are currently no agreed standards for best practice in mitral valve repair and this is an area where professional societies may wish to take a role.

Observational data indicate a possible effect of statin therapy on reducing risk of lens opacities. 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease or other serious comorbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg

Autores/Miembros del Grupo de Trabajo: Vera Regitz-Zagrosek (Presidente) (Alemania) *, Carina Blomstrom Lundqvist (Suecia), Claudio Borghi (Italia), Renata Cifkova (Republica Checa), Rafael Ferreira (Portugal), Jean-Michel Foidart a (Belgica), J. Simon R. Gibbs (Reino Unido), Christa Gohlke-Baerwolf (Alemania), Bulent Gorenek (Turquia), Bernard Iung (Francia), Mike Kirby (Reino Unido), Angela H.E.M de Maas (Paises Bajos), Joao Morais (Portugal), Petros Nihoyannopoulos (Reino Unido), Petronella G. Pieper (Paises Bajos), Patrizia Presbitero (Italia), Jolien W. Roos-Hesselink (Paises Bajos), Maria Schaufelberger (Suecia), Ute Seeland (Alemania) y Lucia Torracca (Italia)

Responsabilidad: Las Guias de Practica Clinica recogen la opinion de la ESC y se han elaborado tras una consideracion minuciosa de las evidencias disponibles en el momento en que fueron escritas. Se anima a los profesionales de la sanidad a que las tengan en plena consideracion cuando ejerzan su juicio clinico. No obstante, las Guias de Practica Clinica no deben invalidar la responsabilidad individual de los profesionales de la salud a la hora de tomar decisiones adecuadas a las circunstancias individuales de cada paciente, consultando con el propio paciente y, cuando sea necesario y pertinente, con su tutor o representante legal. Tambien es responsabilidad del profesional de la salud verificar las normas y los reglamentos que se aplican a los farmacos o dispositivos en el momento de la prescripcion. El contenido de las Guias de Practica Clinica de la Sociedad Europea de Cardiologia (ESC) ha sido publicado para uso exclusivamente personal y educacional. No esta autorizado su uso comercial. No se autoriza la traduccion o reproduccion en ningun formato de las Guias de la ESC ni de ninguna de sus partes sin un permiso escrito de la ESC. El permiso puede obtenerse enviando una solicitud por escrito a Oxford University Press, la empresa editorial de European Heart Journal y representante autorizada de la ESC para gestionar estos permisos. © The European Society of Cardiology 2010. Reservados todos los derechos. Para la solicitud de permisos dirijase por correo electronico a: journals. permissions@oxfordjournals.org Los comentarios-anotaciones (*) incluidos en esta traduccion de la Guia han sido realizados por el Dr. Jose M. Oliver Ruiz (Madrid, Espana).

in men/women), RWT and midwall shortening were evaluated in 1728 patients (39% women, aged 67±10 years) with asymptomatic AS, re- cruited in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. RWT was defined as the ratio of either posterior wall thickness (RWTp, concentric geometry if ≥0.43), or the average of posterior and septal wall thickness (RWTm, concentric geometry if ≥0.45) to LV radius. Both variables were also normalized for age using previously published regression coefficients (RWTpa and RWTma, concentric geometry if ≥0.40 and 0.41, respectively). Results: Average peak transaortic velocity was 3.09±0.54 m/sec. Compared to RWTp and RWTm, use of RWTpa and RWTma reclassified LV geometry in 2.8% and 3.5% of patients (Table 1). Compared to RWTp, use of RWTm reclassified LV geometry in 11.2% of patients (183 from eccentric to concen- tric and 11 from concentric to eccentric geometry) (p