29
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Aims

          Midwall myocardial fibrosis on cardiovascular magnetic resonance (CMR) is a marker of early ventricular decompensation and adverse outcomes in aortic stenosis (AS). We aimed to develop and validate a novel clinical score using variables associated with midwall fibrosis.

          Methods and results

          One hundred forty-seven patients (peak aortic velocity ( V max) 3.9 [3.2,4.4] m/s) underwent CMR to determine midwall fibrosis (CMR cohort). Routine clinical variables that demonstrated significant association with midwall fibrosis were included in a multivariate logistic score. We validated the prognostic value of the score in two separate outcome cohorts of asymptomatic patients (internal: n = 127, follow-up 10.3 [5.7,11.2] years; external: n = 289, follow-up 2.6 [1.6,4.5] years). Primary outcome was a composite of AS-related events (cardiovascular death, heart failure, and new angina, dyspnoea, or syncope). The final score consisted of age, sex, V max, high-sensitivity troponin I concentration, and electrocardiographic strain pattern [ c-statistic 0.85 (95% confidence interval 0.78–0.91), P < 0.001; Hosmer–Lemeshow χ 2 = 7.33, P = 0.50]. Patients in the outcome cohorts were classified according to the sensitivity and specificity of this score (both at 98%): low risk (probability score <7%), intermediate risk (7–57%), and high risk (>57%). In the internal outcome cohort, AS-related event rates were >10-fold higher in high-risk patients compared with those at low risk (23.9 vs. 2.1 events/100 patient-years, respectively; log rank P < 0.001). Similar findings were observed in the external outcome cohort (31.6 vs. 4.6 events/100 patient-years, respectively; log rank P < 0.001).

          Conclusion

          We propose a clinical score that predicts adverse outcomes in asymptomatic AS patients and potentially identifies high-risk patients who may benefit from early valve replacement.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms.

          The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF. Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed. These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.

            Calcific aortic stenosis has many characteristics in common with atherosclerosis, including hypercholesterolemia. We hypothesized that intensive lipid-lowering therapy would halt the progression of calcific aortic stenosis or induce its regression. In this double-blind, placebo-controlled trial, patients with calcific aortic stenosis were randomly assigned to receive either 80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and calcification were assessed with the use of Doppler echocardiography and helical computed tomography, respectively. The primary end points were change in aortic-jet velocity and aortic-valve calcium score. Seventy-seven patients were assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and 0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second per year). Progression in valvular calcification was 22.3+/-21.0 percent per year in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent confidence interval, 0.947 to 1.050). Intensive lipid-lowering therapy does not halt the progression of calcific aortic stenosis or induce its regression. This study cannot exclude a small reduction in the rate of disease progression or a significant reduction in major clinical end points. Long-term, large-scale, randomized, controlled trials are needed to establish the role of statin therapy in patients with calcific aortic stenosis. Copyright 2005 Massachusetts Medical Society.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis

              Aims High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome. Methods and results Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm2) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity. Conclusions In patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.
                Bookmark

                Author and article information

                Journal
                Eur Heart J
                Eur. Heart J
                eurheartj
                ehj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                21 February 2016
                21 October 2015
                21 October 2015
                : 37
                : 8 , Focus Issue on Imaging
                : 713-723
                Affiliations
                [1 ]British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh , Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
                [2 ]National Heart Center Singapore , Singapore, Singapore
                [3 ]Cardiology Department, AP-HP, Bichat Hospital , Paris, France
                [4 ]Biochemistry Department, AP-HP, Tenon Hospital , Paris, France
                Author notes
                [* ]Corresponding author. Tel: +44 131 242 6515, Fax: +44 131 242 6379, Email: cchin03m@ 123456gmail.com
                Article
                ehv525
                10.1093/eurheartj/ehv525
                4761400
                26491110
                b647b7bd-ce2e-40d6-b800-dfd6da442c11
                © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 June 2015
                : 24 August 2015
                : 17 September 2015
                Funding
                Funded by: British Heart Foundation http://dx.doi.org/10.13039/501100000274
                Award ID: CH/09/002
                Award ID: FS/10/024
                Award ID: FS/10/26
                Award ID: FS/14/78/31020
                Funded by: Wellcome Trust Senior Investigator Award
                Award ID: WT103782AIA
                Funded by: National Research Foundation-Ministry of Health, Singapore
                Funded by: Wellcome Trust Clinical Research Facility
                Funded by: Clinical Research Imaging Centre
                Funded by: NHS Research Scotland through NHS Lothian
                Funded by: COFRASA
                Funded by: GENERAC
                Funded by: Assistance Publique–Hôpitaux de Paris
                Categories
                Clinical Research
                Valvular Heart Disease

                Cardiovascular Medicine
                aortic stenosis,midwall myocardial fibrosis,cardiovascular magnetic resonance imaging,high-sensitivity troponin i concentrations,electrocardiogram strain

                Comments

                Comment on this article