Philipp E. Bartko, Gregor Heitzinger, Georg Spinka, Noemi Pavo, Suriya Prausmüller, Stefan Kastl, Henrike Arfsten, Timothy C. Tan, Catherine Gebhard, Julia Mascherbauer, Christian Hengstenberg; Guido Strunk, Martin Hülsmann, Georg Goliasch

Background: Secondary mitral regurgitation in patients with heart failure and reduced ejection fraction (sMR) typically results from distortion of the underlying cardiac architecture. The morphological components which may account for the clinical impact of sMR have not been systematically assessed or correlated with clinical outcomes.
Objectives: To identify the key morphologic and functional features in sMR and their prognostic impact on outcome.

Methods: Morphomic and functional network profiling was performed on a cohort of stable heart failure patients optimized on guideline based medical therapy. Principal component analysis with varimax-rotation and subsequent cluster analysis was then used to condense the morphomic and functional data fist into principal components (factors) and second into homogenous clusters. Clusters and principal components (factors) are tested for their correlations with clinical outcomes.

Results: Morphomic and functional data from 383 patients were profiled and subsequently condensed into principal components (factors). Factor 1 describes high loadings of left atrial morphological information, factor 2 high loadings of left ventricular topology. Based on these factors, four homogenous clusters were derived. sMR was most prominent in cluster 3 and 4 with the morphological difference being left ventricular size (end diastolic volume 188ml (160-224) versus 315ml (264-408), P<0.001). Clusters were associated with mortality (P<0.001), however, sMR remained independently associated with mortality after adjusting for the clusters (adj.HR 1.42, 95% CI 1.14–1.77; P<0.01). The detrimental association of sMR with mortality was mainly driven by cluster 3 (HR 2.18, 95% CI 1.32-3.60; P=0.002), the “small LV cavity” phenotype.

Conclusions: These results challenge the current perceptions that sMR in heart failure with reduced ejection fraction results exclusively from global or local LV remodeling and are suggestive of a potential role of the left atrial. The association of sMR with mortality cannot be purely attributed to cardiac morphology alone, supporting other complementary key aspects of mitral valve closure consistent with the force balance theory. The association of sMR with mortality entirely driven by the small LV cavity phenotype refines the prognostic impact of sMR at the interface of anatomic variability.