Elsevier

JACC: Cardiovascular Imaging

Volume 14, Issue 12, December 2021, Pages 2288-2300
JACC: Cardiovascular Imaging

Original Research
Principal Morphomic and Functional Components of Secondary Mitral Regurgitation

https://doi.org/10.1016/j.jcmg.2021.05.020Get rights and content
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Abstract

Objectives

The aim of this work was to identify the key morphological and functional features in secondary mitral regurgitation (sMR) and their prognostic impact on outcome.

Background

Secondary sMR in patients with heart failure and reduced ejection fraction 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.

Methods

Morphomic and functional network profiling were performed on a cohort of patients with stable heart failure optimized on guideline-based medical therapy. Principal component (PC) analysis and subsequent cluster analysis were used to condense the morphomic and functional data first into PCs with varimax rotation (PCVmax) and second into homogeneous clusters. Clusters and PCs were tested for their correlations with clinical outcomes.

Results

Morphomic and functional data from 383 patients were profiled and subsequently condensed into PCs. PCVmax 1 describes high loadings of left atrial morphological information, and PCVmax 2 describes high loadings of left ventricular (LV) topology. Based on these components, 4 homogeneous clusters were derived. sMR was most prominent in clusters 3 and 4, with the morphological difference being left ventricular size (median end-diastolic volume 188 mL [interquartile range: 160 mL-224 mL] vs 315 mL [264 mL-408 mL]; P < 0.001). Clusters were associated with mortality (P < 0.001), but sMR remained independently associated with mortality after adjusting for the clusters (adjusted 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 component. 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. Unsupervised clustering supports the association of sMR with mortality predominantly driven by the small LV cavity phenotype, as previously suggested by a conceptional framework and termed disproportionate sMR.

Key Words

atrial functional mitral regurgitation
heart failure with reduced ejection fraction
secondary mitral regurgitation

Abbreviations and Acronyms

EROA
effective regurgitant orifice area
HFrEF
heart failure with reduced ejection fraction
LA
left atrial
LV
left ventricular
MV
mitral valve
PCVmax
principal components after varimax rotation
PISA
proximal isovelocity surface area
RA
right atrial
RegVol
regurgitant volume
RegFrac
regurgitant fraction
sMR
secondary mitral regurgitation
TR
tricuspid regurgitation
VCW
vena contracta width

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs Bartko and Heitzinger contributed equally to this work and are joint first authors.