Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis.

Objective: Sex-specific low flow was recently defined as stroke volume index (SVi) ≤40 ml/m² in men and ≤32 ml/m² in women. We tested the prognostic association of these cut-offs in patients with aortic stenosis (AS) with concordantly and discordantly graded AS (CGASEL and DGASEL) based on pressure recovery adjusted aortic valve area (energy loss, EL).

Methods: Data from 1351 patients with asymptomatic AS, peak jet velocity <4m/s and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used.

Gender Differences in Cardiac Organ Damage in Arterial Hypertension: Assessing the Role of Drug Nonadherence.

Introduction: Cardiac organ damage like left ventricular (LV) hypertrophy and left atrial (LA) enlargement is more prevalent in women than men with hypertension, but the mechanisms underlying this gender difference remain unclear.

Methods: We tested the association of drug nonadherence with the presence of LV hypertrophy and LA enlargement by echocardiography in 186 women and 337 men with uncontrolled hypertension defined as daytime systolic blood pressure (BP) ≥ 135mmHg despite the prescription of at least two antihypertensive drugs. Drug adherence was assessed by measurements of serum drug concentrations interpreted by an experienced pharmacologist.

Development and validation of the ASGARD risk score for safe monitoring in asymptomatic nonsevere aortic stenosis.

Aims: Current guidelines recommend serial echocardiography at minimum 1-2 year intervals for monitoring patients with nonsevere aortic valve stenosis (AS), which is costly and often clinically inconsequential.We aimed to develop and test whether the biomarker-based ASGARD risk score (Aortic Valve Stenosis Guarded by Amplified Risk Determination) can guide the timing of echocardiograms in asymptomatic patients with nonsevere AS.

Methods: The development cohort comprised 1,093 of 1,589 (69%) asymptomatic patients with mild-to-moderate AS who remained event-free one year after inclusion into the SEAS trial.

Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial.

Background: High-sensitivity Troponin T (hsTnT), a biomarker of cardiomyocyte overload and injury, relates to aortic valve replacement (AVR) and mortality in severe aortic stenosis (AS). However, its prognostic value remains unknown in asymptomatic patients with AS. We aimed to investigate if an hsTnT level >14 pg/mL (above upper limit of normal 99th percentile) is associated with echocardiographic AS-severity, subsequent AVR, ischaemic coronary events (ICE), and mortality in asymptomatic patients with non-severe AS.

Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial.

Importance: Recent studies have questioned the presumed low-risk status of patients with asymptomatic nonsevere aortic stenosis (AS). Whether annual N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements are useful for risk assessment is unknown.

Objective: To assess the association of annual NT-proBNP measurements with clinical outcomes in patients with nonsevere AS.

Sudden cardiac death in asymptomatic patients with aortic stenosis.

Objective: We 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).

Methods: Of the 1873 patients included in SEAS, 1849 (99%) with mild to moderate AS (jet velocity 2.5-4.

Higher left ventricular mass-wall stress-heart rate product and outcome in aortic valve stenosis.

Objective: Whether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown.

Methods: Data from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used.

Antihypertensive Treatment With β-Blockade in Patients With Asymptomatic Aortic Stenosis and Association With Cardiovascular Events.

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.

Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

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.

Relation of Left Ventricular Mass to Prognosis in Initially Asymptomatic Mild to Moderate Aortic Valve Stenosis.

Background: The prognostic importance of left ventricular (LV) mass in nonsevere asymptomatic aortic stenosis has not been documented in a large prospective study.

Methods And Results: Cox regression analysis was used to assess the impact of echocardiographic LV mass on rate of major cardiovascular events in 1656 patients (mean age, 67 years; 39.6% women) with mild-to-moderate asymptomatic aortic stenosis participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study.

High sensitivity C reactive protein as a prognostic marker in patients with mild to moderate aortic valve stenosis during lipid-lowering treatment: an SEAS substudy.

Aims: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS).

Methods And Results: In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.

Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: the SEAS study.

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.

Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF.

Objective: To evaluate the usefulness of velocity ratio (VR) in patients with low gradient severe aortic stenosis (LGSAS) and preserved EF.

Background: LGSAS despite preserved EF represents a clinically challenging entity. Reliance on mean pressure gradient (MPG) may underestimate stenosis severity as has been reported in the context of paradoxical low flow, LGSAS.

Usefulness of the electrocardiogram in predicting cardiovascular mortality in asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis Study).

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.

Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis.

Background: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS.

Methods: All patients (n=1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included.

Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.

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.

Indexing aortic valve area by body surface area increases the prevalence of severe aortic stenosis.

Background: To account for differences in body size in patients with aortic stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2 for AVA and <0.

Left atrial size and function as predictors of new-onset of atrial fibrillation in patients with asymptomatic aortic stenosis: the simvastatin and ezetimibe in aortic stenosis study.

Background: 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).

Methods: Data were obtained in asymptomatic patients with mild-to-moderate AS (2.

Left atrial systolic force and outcome in asymptomatic mild to moderate aortic stenosis.

Background And Aims: In patients with chronic pressure overload due to hypertension or aortic valve stenosis (AS), higher left atrial systolic force (LASF) is associated with a high-risk cardiovascular (CV) phenotype. We tested LASF as prognostic marker in patients with AS.

Methods: We used baseline and outcome data from 1,566 patients recruited in the Simvastatin and Ezetimibe in AS (SEAS) study evaluating the effect of placebo-controlled simvastatin and ezetimibe treatment on CV events.

Hypertension in aortic stenosis: implications for left ventricular structure and cardiovascular events.

The impact of hypertension on left ventricular structure and outcome during progression of aortic valve stenosis has not been reported from a large prospective study. Data from 1616 patients with asymptomatic aortic stenosis randomized to placebo-controlled treatment with combined simvastatin and ezetimibe in the Simvastatin Ezetimibe in Aortic Stenosis Study were used. The primary study end point included combined cardiovascular death, aortic valve events, and ischemic cardiovascular events.