| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Hadziselimovic, Edina, et al.
(författare)
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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
- 2022
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 7:4, s. 435-444
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Tidskriftsartikel (refereegranskat)abstract
- 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. Design, Setting, and Participants: Analysis of annual NT-proBNP concentrations in the multicenter, double-blind Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) randomized clinical trial was performed. SEAS was conducted from January 6, 2003, to April 1, 2008. Blood samples were analyzed in 2016, and data analysis was performed from February 10 to October 10, 2021. SEAS included 1873 patients with asymptomatic AS not requiring statin therapy with transaortic maximal flow velocity from 2.5 to 4.0 m/s and preserved ejection fraction. This substudy included 1644 patients (87.8%) with available blood samples at baseline and year 1. Exposures: Increased age- and sex-adjusted NT-proBNP concentrations at year 1 and a 1.5-fold or greater relative NT-proBNP concentration change from baseline to year 1. Moderate AS was defined as baseline maximal flow velocity greater than or equal to 3.0 m/s. Main Outcomes and Measures: Aortic valve events (AVEs), which are a composite of aortic valve replacement, cardiovascular death, or incident heart failure due to AS progression, were noted. Landmark analyses from year 1 examined the association of NT-proBNP concentrations with outcomes. Results: Among 1644 patients, 996 were men (60.6%); mean (SD) age was 67.5 (9.7) years. Adjusted NT-proBNP concentrations were within the reference range (normal) in 1228 of 1594 patients (77.0%) with NT-proBNP values available at baseline and in 1164 of 1644 patients (70.8%) at year 1. During the next 2 years of follow-up, the AVE rates per 100 patient-years for normal vs increased adjusted NT-proBNP levels at year 1 were 1.39 (95% CI, 0.86-2.23) vs 7.05 (95% CI, 4.60-10.81) for patients with mild AS (P <.01), and 10.38 (95% CI, 8.56-12.59) vs 26.20 (95% CI, 22.03-31.15) for those with moderate AS (P <.01). Corresponding all-cause mortality rates were 1.05 (95% CI, 0.61-1.81) vs 4.17 (95% CI, 2.42-7.19) for patients with mild AS (P <.01), and 1.60 (95% CI, 0.99-2.57) vs 4.78 (95% CI, 3.32-6.87) for those with moderate AS (P <.01). In multivariable Cox proportional hazards regression models, the combination of a 1-year increased adjusted NT-proBNP level and 1.5-fold or greater NT-proBNP level change from baseline was associated with the highest AVE rates in both patients with mild AS (hazard ratio, 8.12; 95% CI, 3.53-18.66; P <.001) and those with moderate AS (hazard ratio, 4.05; 95% CI, 2.84-5.77; P <.001). Conclusions and Relevance: The findings of this study suggest that normal NT-proBNP concentrations at 1-year follow-up are associated with low AVE and all-cause mortality rates in patients with asymptomatic nonsevere AS. Conversely, an increased 1-year NT-proBNP level combined with a 50% or greater increase from baseline may be associated with high AVE rates. Trial Registration: ClinicalTrials.gov Identifier: NCT00092677.
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| 6. |
- Nielsen, Olav W., et al.
(författare)
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Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS)
- 2016
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 134:6, s. 455-468
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP >= 160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP < 120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP >= 90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure < 50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP >= 160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P= 0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus.
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