The mildly symptomatic patient with low EF, moderate/severe mitral regurgitation and QRS 140 ms Cecilia Linde Karolinska University Hospital Stockholm
Presenter Disclosure Information Cecilia Linde, MD, PhD The following relationships exist related to this presentation: Consulting Fees, Medtronic and St. Jude Research Grants, Medtronic and the Sweden Heart and Lung Foundation
Importance of mitral regurgitation in heart failure Functional mitral regurgitation Consequence of LV systolic dysfunction Or a direct result of dyssynchrony Valvular mitral regurgitation Also responsible for HF progression Mod/sev MR aggravates symptoms and is linked to adverse outcome
Mitral regurgitation Absent/Minimal = 0 Mild = 1 Moderate = 2 Mod/sev = 3 Severe = 4
The case NYHA I/II, MR, low LVEF, QRS 140 ms Drug refractory Mild Symptoms NYHA II HF low LVEF + Electrical dyssynchrony QRS 140 ms + Mitral regurg 2-4 + CRT + 60% Guidelines offer no recommendation for Mitral regurgitation Will this patient improve?
Mitral regurgitation in RCT of CRT in patients NYHA III/IV
Mustic Study Mod/severe MR in NYHA III HF pts in RCTs for CRT MUSTIC Baseline: NYHA III, LVEF 22%, QRS 172 ms, MR 8.1+4.1 cm 2 Mod/Severe MR common and significantly reduced by CRT (12 months) It was an on/off phenomenon and came back in inactive crossover phase Duncan et al Eur Heart J 2003
ms cm2 % mm mm Mustic Study 90 80 70 60 50 40 20 15 10 5 0 MR jet area BASELINE MUSTIC 1-year Follow-up NYHA III QRS > 150 ms, LVEDD> 60 mm LVEDD BASELINE 8.1+4.1 cm 2 M12 p <0.01 M12 LVEF (radionuclides) 35 25 15 p <0.01 + 5% BASELINE - 1.9 + 4-1 cm 2 M12 p <0.01 80 70 60 50 40 600 500 400 300 200 LVESD BASELINE DFT BASELINE M12 M12 p <0.01 (Linde et al JACC 2002;40:111) p <0.01
Mean difference in mitral regurgitation index (u) 0 MR index index (u) over time in the CARE-HF study NYHA III/IV LVEF 25%, QRS 160 ms, MR index 0.21 % MR index= Area of jet/ area of LA in systole Ghio S et al. Eur J Heart Fail 2009;11:480-488 3 months 9 months 18 months 29 months -2-4 -6-8 P<0.0001 P=0.0001 P=0.004 P=0.015 CRT significantly reduced MR index already at discharge with maintained effect of 4 U p= 0.015 over time
Mitral regurgitation in RCT of CRT in patients with mild heart failure NYHA II/I
REVERSE and MADIT-CRTCRT in NYHA II/I Reduction in heart failure related hospitalizations REVERSE: Time to first heart failure hospitalization in the first 12 months (secondary end point) MADIT-CRT: Kaplan-Meier estimate of heart-failure free survival probability (part of primary end point) 2.4 years - 53 % relative risk reduction - 41 % relative risk reduction C. Linde et al., JACC 2008; 52: 1834-43 Moss, AJ, et al., NEJM 2009 361;1329)
Powered Secondary End Point: LVESVi over 24 months 110 LVESVi (ml/m 2 ) 100 90 80 96,6 93,9 92,5 76,8 CRT OFF 91,6 CRT ON 88,8 94,5 P<0.0001 70 73,6 69,2 69,7 60 0 6 12 18 24 Months Since Randomization Progressive P-value reverse compares remodeling 24-month by changes. CRT evolved over 18 months in REVERSE Daubert et al JACC 2009;54:1837
Moderate/severe MR in REVERSE LVEF 26%, QRS 154 ms, MR 15 % (jet in LA) = mild MR was found in minority of pts, was mild and was not significantly affected by CRT (12 months) St John Sutton M et al Circulation 2009;120:1858
Mod/sev MR in in MADIT-CRT LVEF 24.6%, QRS 159 ms, MR 0.22-0.24 cm Solomon et al Cir 2010;122:985 Most often mild MR P=0.02 In MADIT CRT MR was mild and most often did not change by CRT MR improvement > 1 point more often in CRT vs control p=0.02 Mitral jet width (m=88) significantly reduced in CRT p<0.0003
Observational studies
Verhaert D et al Circ Cardiovasc Imaging 2012;5:21 Estimated time course of MR severity in CRT treated pts N=266, NYHA II-IV LVEF 25%, QRS 162 ms MR measured as Vena contracta (VC) witdh Decrease in MR was immediate day 3 and was maintained at same magnitude over follow up of 3.6 years
Time course of reverse remodeling LVESVi MR measured as Vena contracta (VC) witdh Early Long term Longer term reduction in MR is correlated to decrease in LVESVi Verhaert D et al Circ Cardiovasc Imaging 2012;5:21
Event-free survival in pt +/- mod/sev residual MR after 6 months CRT In 266 pts most in NYHA III, 40% had MR > 2 at baseline Pts with less mod/severe residual MR after 6 months of CRT had better survival Verhaert D et al Circ Cardiovasc Imaging 2012;5:21
Di Biase L et al Europace 2011;13:829 Impact of CRT on severity of MR 794 pt treated with CRT from 4 registries Mitral regurgitation present in 86% Mod/severe MR grade 3-4 in 35% Improvements of MR > 1 after 12 months in 46% In those with mod/severe MR grade 3-4 63% p< 0.01 improved (Improvement = NYHA > 1 and LVEF > 5%)
Baseline and 3 months MR severity in 794 pt treated with CRT from 4 registries followed for 12 months Di Biase L et al Europace 2011;13:829 More advanced MR at baseline and reduction in MR after 3 months were predictors of response (NYHA > 1 and LVEF > 5%)
Conclusions Mitral regurgitation in NYHA III/IV CRT candidates Moderate severe mitral regurgitation is present in 35% of CRT candidates pts more symptomatic and more dilated ventricles CRT reduces MR, reverses remodeling and improves symptoms and prognosis in these pts
Conclusions Mitral regurgitation in NYHA I/II CRT candidates Mitral regurgitation is found in 15% of CRT candidates mild NYHA I/II and is mostly mild as evidenced from RCT (REVERSE, MADIT-CRT) Most commonly MR is unaffected by CRT But in MADIT-CRT MR was somewhat reduced by CRT but evidence is less clear
Conclusions Mitral regurgitation in NYHA III/IV CRT candidates Reduction of mitral regurgitation is immediate and linked to reverse remodeling MR at baseline in some studies predicts response to CRT but Early reduction of MR is a predictor of response to CRT And linked to better survival
The case NYHA I/II, mod/sev MR, low LVEF QRS 140 ms Drug refractory Mild Symptoms NYHA II HF LVEF low + Electrical dyssynchrony QRS 140 ms QRS > 120 ms + Mitral regurg 2-4 + CRT + 60% Guidelines offer no recommendation for Mitral regurgitation This pt is rare but will probably improve