Echocardiographic predictors of left ventricular interstitial fibrosis in chronic primary mitral regurgitation with preserved ejection fraction: the underrecognized role of diastolic dysfunction

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Abstract Background Myocardial fibrosis is a well-known risk factor for morbidity and mortality in patients with chronic primary mitral regurgitation (MR). Extracellular volume (ECV), a marker of interstitial fibrosis assessed with cardiovascular magnetic resonance imaging (CMR), was correlated with echocardiographic markers of left ventricular (LV) systolic and diastolic dysfunction in a previous study cohort of patients with severe primary MR. In addition, diastolic dysfunction has recently been recognized as a distinct phenotype in patients with primary MR associated with similar prognosis compared to patients with systolic dysfunction. Purpose To investigate whether echocardiographic parameters of subclinical LV systolic function, diastolic dysfunction or MR severity are correlated with interstitial fibrosis in chronic primary MR patients with a preserved ejection fraction (EF). Methods Prospective inclusion of patients with chronic primary MR and a LVEF>50%. All patients underwent transthoracic echocardiography and CMR scan (1.5T). Echocardiographic assessment of LV systolic and diastolic function was performed, including global longitudinal strain (GLS). MR severity was assessed using a multi-integrative approach. Extracellular volume (ECV) was calculated from the native and post-contrast T1 times. Results A total of 50 patients with primary MR were included (58% males, age 56 ± 16 years old). CMR and transthoracic echocardiography were performed within 30 ± 65 days. MR severity was variable with 20% mild, 32% moderate, 12% moderate-severe and 36% severe MR. Mean LVEF and GLS were within normal range (59.1% ± 5.3% and –19.8% ± 2.9% respectively). Mean ECV was 27.8% ± 2.5%. ECV did not show a significant correlation with MR severity grade or markers of LV systolic function like LVEF (Rho=-0.121, p=0.42) or GLS (Rho=0.089, p=0.59). However, we did observe a statistically significant correlation between ECV and markers of LV diastolic dysfunction such as mean E/e’ (Rho=0.291, p=0.050) and deceleration time (Rho=-0.308, p=0.037). Even in patients with non-severe MR (grade 1 to 3), the correlation between ECV and E/e’ remained significant (Rho=0.438, p=0.017). In a multivariate regression analysis E/e’ and MR grade were associated with ECV, even after correction for age and gender (R squared 0.248, p=0.017 and p=0.044 respectively). Conclusion In patients with chronic primary MR and a preserved LVEF, the presence of interstitial fibrosis, measured as ECV, was associated with echocardiographic parameters of diastolic rather than systolic dysfunction, independent of MR severity. These findings suggest that diastolic dysfunction can be a subclinical marker of myocardial fibrosis (and subsequently adverse outcomes) in patients with primary MR. Correlation ECV and E/e'

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