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

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 (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.

© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1

Nomogram for aortic stenosis clinical score. The risk probability can be also calculated using a nomogram. For example, a 50-year-old female patient with peak aortic jet velocity of 4.0 m/s, high-sensitivity cardiac troponin concentration of 30 ng/L and electrocardiogram strain pattern would have a risk probability of 78% (high risk).

Figure 2

Aortic stenosis-related events stratified according to the risk of midwall myocardial fibrosis in the internal outcome cohort (A) and external outcome cohort (B).

Figure 3

Cardiovascular (A) and all-cause mortality (B) in the internal outcome cohort.

Figure 4

Incremental prognostic value of the clinical score. In the clinical score, high-sensitivity cardiac troponin I concentrations and electrocardiographic strain pattern provided incremental prognostic value over and above peak aortic jet velocity, age, and sex (A). While patients at low risk had very favourable prognosis, high-risk patients had very high event rate, regardless of sex (B and C) or median age (D andE).

Figure 5

Improvement in risk stratification using the clinical score in patients with moderate and severe aortic stenosis. Compared with the natural history of patients with moderate/severe aortic stenosis (green dotted line), the clinical risk score demonstrated significant improvement in identifying patients at low and high risk for adverse events. Furthermore, patients at intermediate risk had an event rate very similar to that prior to risk stratification. This supported the incremental role of the clinical score over the traditional assessment of aortic stenosis severity.