| 1. |
- Bang, Casper N., et al.
(författare)
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Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis : The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study
- 2012
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 690-696
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Tidskriftsartikel (refereegranskat)abstract
- Background 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). Methods 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. Results 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). Conclusions 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. (Am Heart J 2012;163:690-6.)
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| 2. |
- Greve, Anders M., et al.
(författare)
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Clinical implications of electrocardiographic left ventricular strain and hypertrophy in asymptomatic patients with aortic stenosis the simvastatin and ezetimibe in aortic stenosis study
- 2012
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Ingår i: Circulation. - Philadelphia : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 125:2, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- 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)] x 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.
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| 3. |
- Greve, Anders M., et al.
(författare)
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Differences in Cardiovascular Risk Profile Between Electrocardiographic Hypertrophy Versus Strain in Asymptomatic Patients With Aortic Stenosis (from SEAS Data)
- 2011
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 108:4, s. 541-547
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Tidskriftsartikel (refereegranskat)abstract
- 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 <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria (mean difference 0.12 m/s, p = 0.004). After similar adjustment, LV mass index was significantly greater in patients with electrocardiographic strain (mean difference 14.8 g/cm(2), p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria (mean differences 8.8 and 17.8 g/cm(2), respectively, p <0.001 for the 2 comparisons). In multiple comparisons patients with electrocardiographic strain had increased peak aortic jet velocity, blood glucose, and uric acid, whereas patients with LV hypertrophy by Sokolow-Lyon voltage criteria were younger and patients with LV hypertrophy by Cornell voltage duration criteria more often were women. In conclusion, electrocardiographic criteria for LV hypertrophy and strain are independently associated with peak aortic jet velocity and LV mass index. Moreover, clinical covariates differ significantly between patients with electrocardiographic strain and those with LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:541-547)
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| 4. |
- Greve, Anders M., et al.
(författare)
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Impact of QRS Duration and Morphology on the Risk of Sudden Cardiac Death in Asymptomatic Patients With Aortic Stenosis The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) Study
- 2012
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Ingår i: Journal of the American College of Cardiology. - New York : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:13, s. 1142-1149
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Tidskriftsartikel (refereegranskat)abstract
- 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 <85 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. 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 <85 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 duration <85 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). Conclusions QRS duration and morphology in asymptomatic patients with AS are independently associated with a poor prognosis, particularly the risk of SCD. (Simvastatin Ezetimibe in Aortic Stenosis [SEAS]; NCT00092677) (J Am Coll Cardiol 2012; 59: 1142-9) (C) 2012 by the American College of Cardiology Foundation
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| 5. |
- Greve, Anders M., et al.
(författare)
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Prognostic importance of atrial fibrillation in asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis study
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 166:1, s. 72-76
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Greve, Anders M., et al.
(författare)
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Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis : The SEAS study
- 2015
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 180, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- 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 4.3 years (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 10 min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min(-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 10 min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min(-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).
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| 7. |
- Greve, Anders M., et al.
(författare)
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Stroke in Patients With Aortic Stenosis The Simvastatin and Ezetimibe in Aortic Stenosis Study
- 2014
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 45:7, s. 1939-1946
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Tidskriftsartikel (refereegranskat)abstract
- 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<0.001). 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.
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