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Beyond late gadolinium enhancement: the key role of diffuse myocardial fibrosis in severe aortic stenosis - an Equilibrium Contrast CMR study

Background

In severe aortic stenosis (AS), hemodynamics and conventional indices do not fully explain symptoms, prognosis or treatment response. We hypothesize that diffuse myocardial fibrosis (DMF) is a key missing factor in AS. This can now be accurately measured non-invasively using equilibrium contrast CMR (EQ-CMR) [1] involving a primed gadolinium infusion, T1 measurement pre- and post-infusion, and direct measure of blood volume of distribution (1-hematocrit). The derived myocardial volume of distribution (Vd(m)) correlates strongly with histological diffuse myocardial fibrosisin AS and this calibration can convert Vd(m) to DMF%. Cell volume can be calculated as 1-DMF%*LV mass.

Methods

63 severe AS patients with planned valve replacement underwent baseline and follow up EQ-CMR. Twenty normal controls were included. Baseline and follow-up assessment included NYHA, ECG, echocardiography (for diastolic function and valve area/velocities), BNP and six minute walk test (6MWT). Follow up was at 6-months (2 declined, 4 late deaths, 13 pacemakers, 11 outstanding, leaving 33). EQ-CMR results were expressed as Vd(m)/DMF% (continuous variable or severity tertiles), or cell volume.

Results

Baseline

AS patients had more fibrosis than controls (Vd(m):0.27±0.04 vs 0.24±0.04; DMF:17% vs 11%, p = 0.003) with a wide range (Vd(m):0.20-0.39; DMF:4-42%). Breathless patients had more DMF (NYHA class III/IV vs I/II: Vd(m):0.32±0.03 vs 0.26±0.04; DMF:15% vs 27%, p<0.001). DMF correlated with 6MWT (inversely, figure 1, r2=0.22, p=0.001) and aortic valve area (r2=0.21, p=0.001). DMF only correlated with EF in patients with LV impairment (n=15, r2=0.47, p=0.01). Severe DMF patients had worse diastolic function (p=0.029). In a multivariate analysis of all parameters classically associated with 6MWT distance, the only independent predictor was DMF (p=0.04). On univariate analysis there was a weak correlation with BNP and age.

Figure 1
figure1

Relationship of DMF with 6MWT and NYHA class.

Follow up

Overall, patients improved at follow-up (6MWT, EF, BNP, LV mass, LV volumes). However, only patients with severe fibrosis improved their exercise capacity (p=0.03). LVH regression (202g vs 183g, p=0.002) was shown to be cellular (161g vs. 142g, p<0.001) rather than fibrosis (36g vs 34g p=0.572) resolution, figure 2.

Figure 2
figure2

LVH regression redefined by EQ-CMR.

Conclusion

In this first clinical EQ-CMR study of severe AS, DMF is higher when there is LV impairment, diastolic dysfunction and more severe stenosis. DMF is the single best predictor of pre-op exercise capacity and post-op improvement. EQ-CMR shows that at 6-month post valve replacement LVH regression is predominantly reduced cell rather than fibrosis volume. EQ-CMR for the non-invasive measurement of DMF appears to be a significant cardiological advance.

References

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    Circulation. 2010, 122: 138-144. 10.1161/CIRCULATIONAHA.109.930636.

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Correspondence to Andrew S Flett.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Flett, A.S., Sado, D.M., Quarta, G. et al. Beyond late gadolinium enhancement: the key role of diffuse myocardial fibrosis in severe aortic stenosis - an Equilibrium Contrast CMR study. J Cardiovasc Magn Reson 13, O39 (2011). https://doi.org/10.1186/1532-429X-13-S1-O39

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Keywords

  • Valve Replacement
  • Aortic Stenosis
  • Diastolic Function
  • Late Gadolinium Enhancement
  • Severe Aortic Stenosis