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Clinical Trial
. 2015 Dec 2;10(12):e0143761.
doi: 10.1371/journal.pone.0143761. eCollection 2015.

Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

Adam Csordas  1 , Fabian Nietlispach  1 , Philipp Schuetz  2 , Andreas Huber  2 , Beat Müller  2 , Francesco Maisano  3 , Maurizio Taramasso  3 , Igal Moarof  2 , Slayman Obeid  1 , Barbara E Stähli  1 , Martin Cahenzly  1 , Ronald K Binder  1 , Christoph Liebetrau  4 , Helge Möllmann  4 , Won-Keun Kim  4 , Christian Hamm  4 , Thomas F Lüscher  1
Affiliations
Clinical Trial

Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

Adam Csordas et al. PLoS One. .

Abstract

Background: Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR). Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population.

Objectives: We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population.

Methods: We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality.

Results: During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0-26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8-5.6, P = 0.13). The Harrell's C-statistic was 0.58 (95% CI 0.45-0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71-0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1-31.3), P <0.01) and improved the model's net reclassification index (0.89, 95% CI (0.28-1.59). These results were confirmed in the independent validation cohort.

Conclusions: Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis.

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Conflict of interest statement

Competing Interests: TFL has received educational or research grants to the institution from AstraZeneca, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic and St. Jude Medical and honoraria from AstraZeneca, Boston Scientific and St. Jude Medical. BM and PS received support from B⋅ R⋅ A⋅ H⋅ M⋅ S AG (now Thermo Fisher Scientific Biomarkers) to attend meetings and fulfill speaking engagements. BM and PS received support from bioMerieux to attend meetings and fulfill speaking engagements and received research grants from both firms, and BM has served as a consultant to both companies. RKB serves as consultant to Edwards Lifesciences and proctor to Botson Scientific and received a research grant from Edwards Lifesciences. FN serves as a consultant to Edwards Lifesciences, Medtronic, St. Jude Medical and DirectFlow. FM serves as a consultant to Medtronic and St. Jude Medical and receives royalties form Edwards Lifesciences. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Mortality rates of patients receiving TAVR, grouped by upper quartile of MR-proADM and EuroSCORE II.
(A) Hazard rates. (B) Cumulative hazard rates. (C) Cumulative survival probabilities. (D) Hazard ratio (ES II = EuroSCORE II).
Fig 2
Fig 2. Longitudinal trajectories of MR-proADM and CRP at post-interventional day 1–3 following TAVR.
(A) Median and interquartile range of biomarkers in patients after TAVR according to postoperative mortality. (B) Individual trajectories of MR-proADM and CRP with LOWESS smoothing following TAVR.
Fig 3
Fig 3. Predictiveness curves for the two risk models investigated (EuroSCORE II and EuroSCORE II+MR-proADM).
Open circles display observed proportions of death within risk deciles. Left: model based on EuroSCORE II; right: model based on both EuroSCORE II and MR-proADM (both upper quartile) (ES II = EuroSCORE II).
Fig 4
Fig 4. Overlay of Kaplan-Meier curves and RP mean survival curves in the two prognostic groups (upper and lower quartiles of RP-model predicted risk).
(A) Model for MR-proADM + EuroSCORE II. (B) Model for EuroSCORE II.
Fig 5
Fig 5. Validation of the RP-derived PI.
Solid lines: Kaplan-Meier survival curves in two prognostic groups (upper and lower quartiles of predicted risk) in the validation cohort. Dashed lines: RP mean survival functions in the same prognostic groups of the validation cohort by the model fit to the derivation cohort.
Fig 6
Fig 6. Clinical model enhancement by addition of MR-proADM.
Risk assessment plot for the reference (EuroSCORE II, dashed lines) and biomarker-enhanced (solid line) model for 1-year mortality; 1-specificity versus calculated risk for those with the event and sensitivity versus calculated risk for those without events are shown.
See this image and copyright information in PMC

References

    1. Adams DH, Popma JJ, Reardon MJ. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014;371(10):967–8. 10.1056/NEJMc1408396 . - DOI - PubMed
    1. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597–607. 10.1056/NEJMoa1008232 . - DOI - PubMed
    1. Linke A, Wenaweser P, Gerckens U, Tamburino C, Bosmans J, Bleiziffer S, et al. Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study. Eur Heart J. 2014;35(38):2672–84. 10.1093/eurheartj/ehu162 . - DOI - PubMed
    1. Arnold SV, Reynolds MR, Lei Y, Magnuson EA, Kirtane AJ, Kodali SK, et al. Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (Placement of Aortic Transcatheter Valve) trial. Circulation. 2014;129(25):2682–90. 10.1161/CIRCULATIONAHA.113.007477 - DOI - PMC - PubMed
    1. Duncan A, Ludman P, Banya W, Cunningham D, Marlee D, Davies S, et al. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis: the U.K. Transcatheter Aortic Valve Implantation Registry. JACC Cardiovasc Interv. 2015;8(5):645–53. 10.1016/j.jcin.2015.01.009 . - DOI - PubMed

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