Dataset Information

Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement.

ABSTRACT:

Aims

Cardiac fibrosis is associated with left ventricular (LV) remodelling and contractile dysfunction in aortic stenosis (AS). The fibrotic process in this condition is still unclear. The aim of this study was to determine the role of both local and systemic inflammation as underlying mechanisms of LV fibrosis and contractile dysfunction. The diagnostic values of 2D-strain echocardiography and serum biomarkers in the evaluation of cardiac fibrosis in this condition were assessed through correlation analyses.

Methods and results

Patients with AS referred for surgical valve replacement were prospectively and consecutively included. They all had a comprehensive echocardiography including 2D strain. Blood samples were collected to measure cytokines and inflammatory biomarkers using Luminex bead-based assays. A per-surgical myocardial biopsy of the basal antero-septal segment (S1) was performed. Serial sections of each biopsy were stained with Sirius red. Digital image analysis was used to quantify fibrosis. Immunostainings using specific antibodies against macrophage, glycoprotein (gp) 130, and interleukin 6 (IL-6) were also performed. Patients were divided into tertiles reflecting the severity of fibrosis: mild, moderate, and severe load (TF1 to TF3). The mean age of the 58 included patients was 73 ± 11 years. Twenty-four (43%) were in New York Heart Association III-IV. Mean aortic valve area was 0.8 ± 0.2 cm² . Mean aortic stenosis peak velocity and mean gradient were respectively 4.5 ± 0.8 m/s and 54 ± 15 mmHg. The mean LV ejection fraction was 54 ± 12%, and the global LV longitudinal strain was -15 ± 4%. The mean S1 strain, corresponding to the biopsied region, was -10 ± 6% and was strongly correlated to fibrosis load (R = 0.83, P < 0.0001). TF3 was associated with higher mortality (P = 0.009), higher serum C-reactive protein and IL-6, and lower gp130 compared with the other tertiles (P < 0.05). IL-6 and gp130 were expressed in the heart and respectively in the plasma membrane of macrophages and in the cytoplasm of both macrophages and cardiomyocytes. During follow-up, three patients died and were all in the third fibrosis tertile.

Conclusions

We found a positive correlation between elevated inflammatory markers and degree of fibrosis load. These two parameters were associated with worse outcomes in patients with severe AS. Our results may be of interest especially in patients for whom a transcatheter aortic valve implantation is indicated and myocardial biopsy is not possible. Strategies aiming at preventing inflammation might be considered to decrease or limit the progression of cardiac fibrosis in patients followed for AS.

SUBMITTER: Galat A

PROVIDER: S-EPMC6676299 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement.

Galat Arnault A Guellich Aziz A Bodez Diane D Lipskaia Larissa L Moutereau Stéphane S Bergoend Eric E Hüe Sophie S Ternacle Julien J Mohty Dania D Monin Jean-Luc JL Derumeaux Geneviève G Radu Costin C Damy Thibaud T

ESC heart failure 20190521 4

<h4>Aims</h4>Cardiac fibrosis is associated with left ventricular (LV) remodelling and contractile dysfunction in aortic stenosis (AS). The fibrotic process in this condition is still unclear. The aim of this study was to determine the role of both local and systemic inflammation as underlying mechanisms of LV fibrosis and contractile dysfunction. The diagnostic values of 2D-strain echocardiography and serum biomarkers in the evaluation of cardiac fibrosis in this condition were assessed through ...[more]

PMID: 31115164

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Project description:ImportanceThe Centers for Medicare & Medicaid Services national coverage determination for transcatheter aortic valve replacement (TAVR) includes volume requirements for surgical aortic valve replacement (SAVR) for hospitals seeking to initiate or continue TAVR programs. Evidence regarding the association between SAVR volume and TAVR outcomes is limited.ObjectiveTo examine the association of hospital SAVR and combined SAVR and TAVR volumes with patient outcomes of TAVR procedures performed within 1 year, 2 years, and for the entire period after initiation of TAVR programs.Design, setting, and participantsThis observational cohort study included 60 538 TAVR procedures performed in 438 hospitals between October 1, 2011, and December 31, 2015, among Medicare beneficiaries.Main outcomes and measuresThe associations between SAVR volume, SAVR and TAVR volumes, and risks of death, death or stroke, and readmissions within 30 days were determined using a hierarchical logistic regression model adjusting for patient and hospital characteristics. The association between SAVR and SAVR and TAVR volumes and 1-year and 2-year mortality after TAVR procedures was determined using a multivariable proportional hazard model with a robust variance estimator. The associations for procedures performed within 1 year, 2 years, and for the entire period after initiation of TAVR programs were examined.ResultsAmong the 60 538 patients, 29 173 were women and 31 365 were men, with a mean (SD) age of 82.3 (8.0) years. Hospitals with high SAVR volume (mean annual volume, ≥97 per year) were more likely to adopt TAVR early and had a higher growth in TAVR volumes over time (median TAVR volume by hospitals with high SAVR volume and low SAVR volume: year 1, 32 vs 19; year 2, 48 vs 28; year 3, 82 vs 38; year 4, 118 vs 54; P < .001). In adjusted analysis, high hospital SAVR volume alone was not associated with better patient outcomes after TAVR. When hospital TAVR and SAVR volumes were jointly analyzed, patients treated in hospitals with high TAVR volume had lower 30-day mortality after TAVR (high TAVR and low SAVR vs low TAVR and low SAVR: odds ratio, 0.85; 95% CI, 0.72-0.99; high TAVR and high SAVR vs low TAVR and high SAVR: odds ratio, 0.81; 95% CI, 0.69-0.95), the effect of which was more pronounced when hospitals also had high SAVR volume. Patients treated in hospitals with high SAVR volume and high TAVR volume had the lowest 30-day mortality (vs hospitals with low SAVR volume and TAVR volume: odds ratio, 0.77; 95% CI, 0.66-0.89).Conclusions and relevanceHospitals with high SAVR volume are most likely to be fast adopters of TAVR. Hospital SAVR volume alone is not associated with better TAVR outcomes. Accumulating high volumes of TAVR is associated with lower mortality after TAVR, particularly when hospitals have high SAVR volumes. Hospitals with high caseloads of both SAVR and TAVR are likely to achieve the best outcomes.

Project description:ImportanceTranscatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce.ObjectiveTo compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS.Design, setting, and participantsThis retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts.ExposuresPrimary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization.Main outcomes and measuresThe primary outcomes were 30-day and 3-year survival.ResultsOverall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not.Conclusions and relevanceTranscatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.

Dataset Information

Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement.

Aims

Methods and results

Conclusions

Publications

Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement.

Similar Datasets

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