Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis

ObjectivesThe goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis.BackgroundMyocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions.MethodsBetween January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service.ResultsA total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis.ConclusionsMidwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification. (The Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735

Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium†

To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health

170: Is the survival after aortic valve replacement gender related – follow up of 993 patients with aortic stenosis?

It has been shown during the past few years that woman's heart is different than man's. It is stressed, that women are on increased risk of aortic valve replacement (AVR) due to greater hypertrophy and worse its regression.ObjectiveThe aim of the study was to estimate whether the survive after AVR is gender related or there are any other parameters which have impact on follow up after surgery in aortic stenosis (AS).Methodology993 pts (408 women, age 65±10 yrs) after AVR due to AS were observed mean 7,5±4 yrs after surgery. Following parameters were taken into account: gender, age, significance of AS (transaortic gradient – MAG), left ventricle hypertrophy (mass index- LVMI), ejection fraction (EF) and presence of coronary artery stenosis (CAD) assessed before AVR.The results of Cox regression analysis are shown in the table. Additionally we analyzed the factors related with survival in men and women separately. They were comparable in both groups except the presence of CAD that had borderline impact only on 10 yrs survival in men.ConclusionThe survival after aortic valve replacement is much worse in men. The reason is unknown but it is not explained by the presence of the coronary artery disease.Table – ResultsFollow upDeathsParameters iOdds ratiop=3 yrs64 ptsAge1,06 (1,03–1,09)0,000113 womenMale gender3,7 (2,0–6,9)0,00151 menEF1,006 (1,001–1,0110,035 yrs100 ptsAge1,079 (1,04–1,09)0,0001Male gender3,0 (1,8–4,8)0,000123 womenEF1,007 (1,002–1,01)0,00477 menMAG0,98 (0,97–0,99)0,00017 yrs140 ptsAge1,06 (1,04–1,08)0,0001Male gender2,4 (1,6–1,08)0,000137 womenMAG0,99 (0,98–0,995)0,09103 menLVMI1,1 (1,0–1,005)0,000110 yrs199 ptsAge1,05 (1,035–1,07)0,09Male gender1,8 (1,4–2,6)0,000162 womenMAG0,99 (0,86–0,997)0,0001137 menCAD1,3 (0,96–1,8)0,08

Refined multiscale entropy : application to 24-h Holter recordings of heart period variability in healthy and aortic stenosis subjects

Multiscale entropy (MSE) was proposed to characterize complexity as a function of the time-scale factor tau. Despite its broad use, this technique suffers from two limitations: 1) the artificial MSE reduction due to the coarse graining procedure and 2) the introduction of spurious MSE oscillations due to the suboptimal procedure for the elimination of the fast temporal scales. We propose a refined MSE (RMSE), and we apply it to simulations and to 24-h Holter recordings of heart rate variability (HRV) obtained from healthy and aortic stenosis (AS) groups. The study showed that the refinement relevant to the elimination of the fast temporal scales was more helpful at short scales (spanning the range of short-term HRV oscillations), while that relevant to the procedure of coarse graining was more useful at large scales. In healthy subjects, during daytime, RMSE was smaller at short scales (i.e., tau = 1-2) and larger at longer scales (i.e., tau = 4-20) than during nighttime. In AS population, RMSE was smaller during daytime both at short and long time scales (i.e., tau = 1 -11) than during nighttime. RMSE was larger in healthy group than in AS population during both daytime (i.e., tau = 2 -9) and nighttime (i.e., tau = 2). RMSE overcomes two limitations of MSE and confirms the complementary information that can be derived by observing complexity as a function of the temporal scal

Multiscale sample entropy in heart rate variability of aortic stenosis patients

In the present document the multiscale entropy (MSE) methodology has been applied to analyze the complex behavior of the heart rate variability (HRV), in patients with aortic stenosis (AS). A set of healthy voluntaries have been used as a control group. MSE analysis calculates an entropy rate over different time scales to assess the complexity of time series, evaluating short-term and long-term correlations. Daytime and nighttime have been considered to study variations of the complexity inside the same group of population. A statistical analysis showed that entropy was significantly higher in healthy subjects than in AS subjects in all the scales during daytime, with exception at scale 1. During nighttime, entropy in healthy subjects was significantly higher than in AS subjects only in scales from 1 to 7. Multiscale entropy is helpful to characterize AS patients and distinguish them from healthy subjects

Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.

We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-β activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84 × 10(-5)), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload