Integrative characterization of asymptomatic vs. symptomatic patients with moderate-severe primary mitral regurgitation

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by NHLBI and Specialized Centers of Clinically Oriented Research grant in cardiac dysfunction, by Department of Veteran Affairs for Merit Review and NIH Grant P01. Background Optimal timing for surgery in primary mitral regurgitation (PMR) is a subject of debate. Purpose Use a combination of imaging, circulating biomarkers and histology to define the transition from asymptomatic (asx) to symptomatic (sx) stage in moderate-severe PMR. Methods 57 controls, 82 sx and 47 asx patients with moderate to severe PMR underwent cardiac MR(CMR), plasma BNP, levels of xanthine oxidase (XO) activity, and circulating markers of collagen (Col) synthesis (propeptide of procollagen type I, PICP) and degradation (Col type I fibers, ICTP). Results A progressive worsening in the severity of adverse LV remodeling was noted based on CMR indices listed in Table 1. The 3D mid-wall LV endocardial curvature to wall thickness was lower in normal and similar in asx and sx patients.Plasma BNP was progressively higher in normal vs. asx vs sx (Figure 1A). The levels of XO activity were higher in sx vs. asx (Figure 1B,1C). Levels of PICP were similar among the three; levels of ICTP were significantly higher in the sx vs the asx (Figure 1D,1E). LV biopsies revealed large areas of patchy replacement fibrosis and areas devoid of interstitial Col (Figure 1F). From the subgroup of 56 patients who underwent CMR 6 months after surgery, 27% had LVEF < 50%. The preoperative LVEF, LVESV, LVESD and LA emptying fraction were predictors of postoperative drop in LVEF. Conclusion Increased COl breakdown coupled with markers of oxidative stress and CMR-based LV remodeling characterize the transition from asx to sx PMR. Longitudinal studies are needed to define cutoff"s for patient selection and optimal timing for MV surgery. CMR indices in normal, asx and sx PMR. Normal (57) Moderate/Severe MR Asymptomatic (56) Pre-Surgery MR Symptomatic (81) P-value Age 48 (34, 55) 54 (46, 62) * 57 (50, 67) * <0.0001 Female/Male 30(53%)/27(47%) 35(63%)/21(38%) 25(31%)/56(69%) LVEF (%) 64 (61, 67) 62 (59, 66) 63 (59, 67) 0.3482 LV EDV (mL/m2) 71 (61, 76) 89 (73, 103) * 100 (83, 123) *# <0.0001 LV ESV (mL/m2) 24 (21, 29) 32 (26, 38) * 36 (28, 47) * <0.0001 LVSV (mL/m2) 43 (37, 50) 54 (43, 66) * 60 (54, 77) *# <0.0001 LVED Mass/Volume 0.7 (0.6, 0.8) 0.6 (0.5, 0.7) * 0.6 (0.6, 0.7) * 0.0012 LVED Mass/Vol x SI 1.29 (1.05, 1.50) 0.97 (0.77, 1.15) * 0.94 (0.77, 1.14) * <0.0001 Regurgitant Volume (mL) ― 38 (26, 54) 57 (38, 83) # 0.001 Regurgitant Fraction (%) ― 39 (28, 50) 46 (36, 56) # 0.042 Table 1 shows the CMR indices of LV remodeling in normal, asymptomatic and symptomatic patients with moderate-severe PMR. p-values *vs. Normal; # vs. Asymptomatic. Kruskal-Wallis test or unpaired t-test Abstract Figure 1.