Burden, treatment use, and outcome of secondary mitral regurgitation across the spectrum of heart failure: observational cohort study

Abstract

Objectives: To define prevalence, long term outcome, and treatment standards of secondary mitral regurgitation (sMR) across the heart failure spectrum.

Design: Large scale cohort study.

Setting: Observational cohort study with data from the Viennese community healthcare provider network between 2010 and 2020, Austria.

Participants: 13 223 patients with sMR across all heart failure subtypes.

Main outcome measures: Association between sMR and mortality in patients assigned by guideline diagnostic criteria to one of three heart failure subtypes: reduced, mid-range, and preserved ejection fraction, was assessed.

Results: Severe sMR was diagnosed in 1317 patients (10%), correlated with increasing age (P<0.001), occurred across the entire spectrum of heart failure, and was most common in 656 (25%) of 2619 patients with reduced ejection fraction. Mortality of patients with severe sMR was higher than expected for people of the same age and sex in the same community (hazard ratio 7.53; 95% confidence interval 6.83 to 8.30, P<0.001). In comparison with patients with heart failure and no/mild sMR, mortality increased stepwise with a hazard ratio of 1.29 (95% confidence interval 1.20 to 1.38, P<0.001) for moderate and 1.82 (1.64 to 2.02, P<0.001) for severe sMR. The association between severe sMR and excess mortality was consistent after multivariate adjustment and across all heart failure subgroups (mid-range ejection fraction: hazard ratio 2.53 (95% confidence interval 2.00 to 3.19, P<0.001), reduced ejection fraction: 1.70 (1.43 to 2.03, P<0.001), and preserved ejection fraction: 1.52 (1.25 to 1.85, P<0.001)). Despite available state-of-the-art healthcare, high volume heart failure, and valve disease programmes, severe sMR was rarely treated by surgical valve repair (7%) or replacement (5%); low risk transcatheter repair (4%) was similarly seldom used.

Conclusion: Secondary mitral regurgitation is common overall, increasing with age and associated with excess mortality. The association with adverse outcome is significant across the entire heart failure spectrum but most pronounced in those with mid-range and reduced ejection fractions. Despite these poor outcomes, surgical valve repair or replacement are rarely performed; similarly, low risk transcatheter repair, specifically in the heart failure subsets with the highest expected benefit from treatment, is seldom used. The current data suggest an increasing demand for treatment, particularly in view of an expected increase in heart failure in an ageing population.

Fig 1

Prevalence of secondary mitral regurgitation in patients with heart failure stratified by age. (Upper panel) Prevalence of no/mild, moderate, and severe secondary mitral regurgitation according to age groups in heart failure. (Lower panel) Prevalence of secondary mitral regurgitation overall and according to heart failure type (preserved, mid-range, and reduced ejection fractions). The prevalence of severe secondary mitral regurgitation is most substantial among patients with reduced ejection fraction followed by mid-range and preserved ejection fractions. Heart failure subtypes: HFmrEF=mid-range ejection fraction; HFpEF=preserved ejection fraction; HFrEF=reduced ejection fraction. sMR=secondary mitral regurgitation

Fig 2

Kaplan-Meier survival analysis according to severity of secondary mitral regurgitation in patients with heart failure. Long term survival analysis comparing patients with heart failure with no/mild, moderate, or severe secondary mitral regurgitation (log rank P<0.001). The grey dashed line represents the expected survival of the general Austrian population of same age and sex. CI=confidence interval; HF=heart failure; sMR=secondary mitral regurgitation

Fig 3

Subgroup analysis of long term mortality for patients with heart failure and severe secondary mitral regurgitation. Univariable Cox regression analyses using the median values of the total study population as cut off points for continuous data. The P value for interaction refers to an interaction between severe secondary mitral regurgitation and the respective subgroup. Secondary mitral regurgitation outcome according to heart failure type. CI=confidence interval; LA=left atrium; LV=left ventricle; RV=right ventricle; RVF=right ventricular function

Fig 4

Kaplan-Meier survival analysis in patients with severe secondary mitral regurgitation across the spectrum of heart failure. Long term survival analysis of patients with heart failure and severe secondary mitral regurgitation compared with patients with heart failure and no/mild secondary mitral regurgitation as disease controls in those with preserved (log rank P<0.001), mid-range (log rank P<0.001), and reduced (log rank P<0.001) ejection fractions. The grey dashed line represents the expected survival of the general Austrian population of same age and sex. Heart failure subtypes: HFmrEF=mid-range ejection fraction; HFpEF=preserved ejection fraction; HFrEF=reduced ejection fraction. CI=confidence interval; LVEF=left ventricular ejection fraction; sMR=secondary mitral regurgitation