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

Eur Heart J. 2016 Feb 21;37(8):713-23. doi: 10.1093/eurheartj/ehv525. Epub 2015 Oct 21.


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 (Vmax) 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, Vmax, 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.

Trial registration: ClinicalTrials.gov NCT00338676 NCT00647088.

Keywords: Aortic stenosis; Cardiovascular magnetic resonance imaging; Electrocardiogram strain; High-sensitivity troponin I concentrations; Midwall myocardial fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve Stenosis / mortality
  • Aortic Valve Stenosis / pathology*
  • Female
  • Fibrosis
  • Humans
  • Magnetic Resonance Angiography
  • Male
  • Myocardium / pathology*
  • Prognosis
  • Risk Assessment / methods
  • Survival Analysis

Associated data

  • ClinicalTrials.gov/NCT00338676
  • ClinicalTrials.gov/NCT00647088