Left ventricular myocardial work in degenerative mitral regurgitation and its impact on outcome

Abstract Introduction Few studies have evaluated the utility of quantifying myocardial work (MW) in degenerative mitral regurgitation (DMR). Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction but is influenced by loading conditions. Myocardial work quantification, which combines strain data with non-invasive estimation of left ventricular pressure, enables pressure-strain loop analysis, which has been shown to correlate with myocardial oxygen consumption. Objective We aimed to investigate MW alterations in a large population of patients with DMR. Method Patients with varying degrees of DMR (from none to severe) were prospectively enrolled and underwent comprehensive transthoracic echocardiography. Global left ventricular (LV) longitudinal strain (GLS) was assessed, and myocardial work was measured retrospectively (EchoPAC 203, GE Healthcare). Patients were categorized into two groups based on DMR severity at baseline (grade 0-2, n=331; grade 3-4, n=394). Major cardiovascular events were recorded and considered censored at the time of mitral valve intervention. Results 725 patients (≥16 years, 55±16 years, 69% male) were included. Patients with grade 3-4 DMR were older (61±14 vs 48±17 years, P<0.0001), more frequently male (73 vs 43%, P<0.0001), had more cardiovascular risk factors, were more symptomatic, and had higher levels of NT-pro-BNP (495±972 vs 196±366, P<0.0001). Heart rate (71±12 vs 68±12, P=0.003) and systolic BP (135±18 vs 129±18, P<0.0001) were slightly higher. Left ventricular and atrial remodeling were worse, PASP was higher (39±15 vs 27±7 mmHg, P<0.0001), LV ejection fraction (69±7 vs 66±7%, P<0.0001) and GLS (21.5±3.0 vs 20.7±2.4, P=0.0001) were higher, but the forward stroke volume index (P<0.0001) was lower. Regarding MW, patients with grade 3-4 DMR had an increase in global work index (GWI, 2291±485 vs 2023±401, P<0.0001), global constructive work (GCW, 2626±526 vs 2533±477, P<0. 0001), global positive work (GPW, 2522±497 vs 2357±437, P<0. 0001), but a decrease in global wasted work (120±65 vs 124±88, P<0.0001) and global negative work (233±114 vs 330±132, P<0.0001). During follow-up (5.3±3.3 years), 117 events were recorded before intervention : 11 cardiovascular deaths, 67 heart failure events, 31 new cases of AF, and 8 strokes. Mitral valve intervention was performed in 318 (81%) patients with DMR grade 3-4, but in only 13 (4%) of patients with grade 0-2. In univariable Cox model analysis, GLS was a significant predictor of events (P=0.006), whereas MW parameters were strong predictors of outcome (GWI, P<0.0001; GCW, P<0.0001; GPW, P<0.0001). A GCW ≥ 2532 emerged as a reliable predictor of adverse events before intervention. Conclusion MW analysis in DMR highlights unique pathophysiological features and appears to be a promising tool for outcome prediction. Integrating MW assessment into the clinical evaluation of DMR may help guide therapeutic management and follow-up.Univariate analysis in all cohort  Univariate/multivariate analysis MR 3-4