Effect of Functional Mitral Regurgitation on Outcome in Patients Receiving Cardiac Resynchronization Therapy for Heart Failure

Functional mitral regurgitation (FMR) is common in heart failure (HF), and negatively impacts prognosis. Cardiac resynchronization therapy (CRT) can improve FMR, but the long-term changes in and impact of FMR after CRT are still unclear. The present study investigated the prevalence, evolution and impact on mortality of FMR before and after CRT in patients with HF. A total of 1,313 patients (66 ± 11 years, 77% male, 59% ischemic heart disease) treated with CRT were evaluated. Patients were divided into 4 groups of FMR according to the evolution at 6 months after CRT: no or mild FMR at baseline which remained unchanged at 6 months (grade 0–1 FMR unchanged, n = 609 [51%]), no or mild FMR which worsened to moderate to severe (grade 0–1 FMR worsened, n = 66 [6%)]), moderate to severe FMR which improved to no or mild (grade 2–4 improved, n = 209 [18%]), and moderate to severe FMR which remained unchanged (grade 2–4 unchanged, n = 309 [26%]). Over a mean follow-up of 51 ± 38 months, 297 (25%) patients died. Those with baseline FMR grade 0–1 which remained unchanged at 6-month follow-up, as well as baseline FMR grade 2–4 which improved, had lower mortality rates than patients with 6-month FMR grade 2–4 regardless of baseline FMR grade (p <0.001). Baseline FMR grade 2–4 that remained unchanged at 6-month follow-up was associated with increased mortality, independent of the clinical and left ventricular volumetric responses to CRT (hazard ratio, 1.77; 95% confidence interval, 1.41–2.22, p <0.001). In conclusion, moderate to severe FMR at baseline which remains unchanged at 6 months after CRT implantation is strongly associated with long-term mortality in patients with HF. Functional mitral regurgitation (FMR) is common in heart failure (HF), and negatively impacts prognosis. Cardiac resynchronization therapy (CRT) can improve FMR, but the long-term changes in and impact of FMR after CRT are still unclear. The present study investigated the prevalence, evolution and impact on mortality of FMR before and after CRT in patients with HF. A total of 1,313 patients (66 ± 11 years, 77% male, 59% ischemic heart disease) treated with CRT were evaluated. Patients were divided into 4 groups of FMR according to the evolution at 6 months after CRT: no or mild FMR at baseline which remained unchanged at 6 months (grade 0–1 FMR unchanged, n = 609 [51%]), no or mild FMR which worsened to moderate to severe (grade 0–1 FMR worsened, n = 66 [6%)]), moderate to severe FMR which improved to no or mild (grade 2–4 improved, n = 209 [18%]), and moderate to severe FMR which remained unchanged (grade 2–4 unchanged, n = 309 [26%]). Over a mean follow-up of 51 ± 38 months, 297 (25%) patients died. Those with baseline FMR grade 0–1 which remained unchanged at 6-month follow-up, as well as baseline FMR grade 2–4 which improved, had lower mortality rates than patients with 6-month FMR grade 2–4 regardless of baseline FMR grade (p <0.001). Baseline FMR grade 2–4 that remained unchanged at 6-month follow-up was associated with increased mortality, independent of the clinical and left ventricular volumetric responses to CRT (hazard ratio, 1.77; 95% confidence interval, 1.41–2.22, p <0.001). In conclusion, moderate to severe FMR at baseline which remains unchanged at 6 months after CRT implantation is strongly associated with long-term mortality in patients with HF. Functional mitral regurgitation (FMR) is common in heart failure (HF), with a prevalence of approximately 50% in ischemic cardiomyopathy and 56%–65% in nonischemic cardiomyopathy.1Bursi F. Enriquez-Sarano M. Nkomo VV.T.T Jacobsen S.JJ. Weston S.AA. Meverden R.AA. Roger V.LL. Heart failure and death after myocardial infarction in the community: the emerging role of mitral regurgitation.Circulation. 2005; 111: 295-301Crossref PubMed Scopus (429) Google Scholar, 2Grigioni F. Enriquez-Sarano M. Zehr K.J.J Bailey K.R.R Tajik A.J.J Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment.Circulation. 2001; 103: 1759-1764Crossref PubMed Scopus (1199) Google Scholar, 3Agricola E. Stella S. Figini F. Piraino D. Oppizzi M. D'Amato R. Slavich M. Ancona M.B.B Margonato A. Non-ischemic dilated cardiopathy: prognostic value of functional mitral regurgitation.Int J Cardiol. 2011; 146: 426-428Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Moderate to severe FMR portends a poor prognosis, increasing HF hospitalizations and death.2Grigioni F. Enriquez-Sarano M. Zehr K.J.J Bailey K.R.R Tajik A.J.J Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment.Circulation. 2001; 103: 1759-1764Crossref PubMed Scopus (1199) Google Scholar, 4Rossi A. Dini F.L.L Faggiano P. Agricola E. Cicoira M. Frattini S. Simioniuc A. Gullace M. Ghio S. Enriquez-Sarano M. Temporelli P.L.L Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy.Heart. 2011; 97: 1675-1680Crossref PubMed Scopus (420) Google Scholar Cardiac resynchronization therapy (CRT) is a well-established HF therapy.5Brignole M. Auricchio A. Baron-Esquivias G. Bordachar P. Boriani G. Breithardt O.A.A Cleland J. Deharo J.C.C Delgado V. Elliott P.M.M Gorenek B. Israel C.W.W Leclercq C. Linde C. Mont L. Padeletti L. Sutton R. Vardas P.E.E Zamorano J.L. Achenbach S. Baumgartner H. Bax J.J. Bueno H. Dean V. Deaton C. Erol C. Fagard R. Ferrari R. Hasdai D. Hoes A.W.W Kirchhof P. Knuuti J. Kolh P. Lancellotti P. Linhart A. Nihoyannopoulos P. Piepoli M.F.F Ponikowski P. Sirnes P.A.A Tamargo J.L.L Tendera M. Torbicki A. Wijns W. Windecker S. Kirchhof P. Blomstrom-Lundqvist C. Badano L.P.P Aliyev F. Bansch D. Baumgartner H. Bsata W. Buser P. Charron P. Daubert J.C.C Dobreanu D. Faerestrand S. Hasdai D. Hoes A.W. Le Heuzey J.Y.Y Mavrakis H. McDonagh T. Merino JJJ.L.L. Nawar M.M.M Nielsen J.C.C Pieske B. Poposka L. Ruschitzka F. Tendera M. Van Gelder I.C.C Wilson C.M.M 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).Eur Heart J. 2013; 34: 2281-2329Crossref PubMed Scopus (1629) Google Scholar The prevalence of FMR after CRT treatment varies in studies.6Onishi T. Onishi T. Marek J.J. Ahmed M. Haberman S.C.C Oyenuga O. Adelstein E. Schwartzman D. Saba S. Gorcsan 3rd, J. Mechanistic features associated with improvement in mitral regurgitation after cardiac resynchronization therapy and their relation to long-term patient outcome.Circ Heart Fail. 2013; 6: 685-693Crossref PubMed Scopus (62) Google Scholar, 7Upadhyay G.A.A Chatterjee N.A.A Kandala J. Friedman D.J.J Park M.Y.Y Tabtabai S.R.R Hung J. Singh J.P.P Assessing mitral regurgitation in the prediction of clinical outcome after cardiac resynchronization therapy.Heart Rhythm. 2015; 12: 1201-1208Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 8Cipriani M. Lunati M. Landolina M. Proclemer A. Boriani G. Ricci R.P.P Rordorf R. Matassini M.V.V Padeletti L. Iacopino S. Molon G. Perego G.B.B Gasparini M. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy.Eur J Heart Fail. 2016; 18: 1060-1068Crossref PubMed Scopus (25) Google Scholar FMR may diminish, remain stable, or worsen after CRT, which may impact prognosis after CRT. No randomized study has investigated the prevalence, evolution, and impact on mortality of FMR before and after CRT in patients with HF. We analyzed the prevalence of FMR in a large cohort of HF patients who underwent CRT. Moreover, the relation between the change in FMR after 6 months of CRT, and the clinical and echocardiographic response to CRT was evaluated. Finally, the changes in FMR after CRT were related to long-term outcome during extended follow-up. HF patients who underwent quantitative assessment of MR severity at the echocardiographic core laboratory of the Leiden University Medical Center and subsequent CRT implantation according to contemporary guidelines were included in this retrospective evaluation.5Brignole M. Auricchio A. Baron-Esquivias G. Bordachar P. Boriani G. Breithardt O.A.A Cleland J. Deharo J.C.C Delgado V. Elliott P.M.M Gorenek B. Israel C.W.W Leclercq C. Linde C. Mont L. Padeletti L. Sutton R. Vardas P.E.E Zamorano J.L. Achenbach S. Baumgartner H. Bax J.J. Bueno H. Dean V. Deaton C. Erol C. Fagard R. Ferrari R. Hasdai D. Hoes A.W.W Kirchhof P. Knuuti J. Kolh P. Lancellotti P. Linhart A. Nihoyannopoulos P. Piepoli M.F.F Ponikowski P. Sirnes P.A.A Tamargo J.L.L Tendera M. Torbicki A. Wijns W. Windecker S. Kirchhof P. Blomstrom-Lundqvist C. Badano L.P.P Aliyev F. Bansch D. Baumgartner H. Bsata W. Buser P. Charron P. Daubert J.C.C Dobreanu D. Faerestrand S. Hasdai D. Hoes A.W. Le Heuzey J.Y.Y Mavrakis H. McDonagh T. Merino JJJ.L.L. Nawar M.M.M Nielsen J.C.C Pieske B. Poposka L. Ruschitzka F. Tendera M. Van Gelder I.C.C Wilson C.M.M 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).Eur Heart J. 2013; 34: 2281-2329Crossref PubMed Scopus (1629) Google Scholar Patients who underwent mitral valve surgery (replacement or repair) before or after CRT implantation (n = 110) and those with primary MR were excluded. Demographic, clinical, laboratory, electrocardiographic, and echocardiographic parameters were analyzed. Patients with previous infarction or revascularization, as well as significant coronary artery disease on invasive angiography were considered to have ischemic cardiomyopathy, whereas the remainder were considered nonischemic. Clinical evaluation included assessment of New York Heart Association (NYHA) class, quality of life (QoL, using the Minnesota Living with Heart Failure Questionnaire)9Rector T.S.S Kubo S.H.H Cohn J.N. Validity of the Minnesota Living with Heart Failure questionnaire as a measure of therapeutic response to enalapril or placebo.Am J Cardiol. 1993; 71: 1106-1107Abstract Full Text PDF PubMed Scopus (401) Google Scholar and a 6-minute walk test (6MWT) if able.10Guyatt G.H.H Sullivan M.J. Thompson P.J. Fallen E.L. Pugsley S.O. Taylor D.W. Berman L.B. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure.CMAJ. 1985; 132: 919-923PubMed Google Scholar Clinical and echocardiographic assessments were routinely repeated at 6 months after CRT implantation. Thereafter, patients were scheduled for regular outpatient visits. Two-dimensional transthoracic echocardiography was performed in all patients using a commercially available echocardiographic system (VIVID 7 or E9, General Electric before CRT implantation and after 6 were with or and as and Doppler to the were and for analysis General Electric ventricular and and left ventricular were the and using the Badano V. J. A. L. E. T. Lancellotti P. D. L. W. for cardiac echocardiography in the Society of and the European Association of Heart J 2015; PubMed Scopus Google Scholar The severity of FMR was according to using a and and was on a no or mild = moderate = moderate to severe = and severe = P. C. A. T. Badano L. Zamorano J.L. for the echocardiographic assessment of regurgitation: the European Association of Heart J 2013; PubMed Scopus Google Scholar and ventricular were in a as and CRT performed during follow-up at the of the Bax J.J. M.J. Clinical echocardiographic parameters to response to cardiac resynchronization J Cardiol. 97: Full Text Full Text PDF PubMed Scopus Google Scholar in FMR were at 6-month follow-up. Patients were divided in 4 patients with no or mild FMR (grade at baseline which remained unchanged at 6 patients with no or mild FMR (grade at baseline which worsened to moderate to severe MR at 6 months (grade patients with moderate to severe FMR (grade at baseline which improved to no or mild (grade at 6 and patients with moderate to severe FMR (grade at baseline which remained unchanged at 6 FMR changes were related to 6-month response to CRT. A clinical response to CRT was as improvement in at 6-month follow-up, whereas a echocardiographic response was as in at 6-month Bax J.J. M.J. Clinical echocardiographic parameters to response to cardiac resynchronization J Cardiol. 97: Full Text Full Text PDF PubMed Scopus Google Scholar were in the Cardiology Leiden University Medical The and analyzed. The the and the for patient that the were for patient In the present all were for clinical and on were and the are as and and as and were with analysis of using for and were with the and as The rates for FMR were with the and with the The follow-up at 6 months after CRT change in FMR grade was and FMR groups Independent of mortality were with the with the into the baseline grade 0–1 FMR unchanged, baseline grade 2–4 FMR improved, baseline grade 0–1 FMR worsened, baseline grade 2–4 FMR unchanged, ischemic of at 6 months, clinical and were performed with for New were and a p value was considered A total of 1,313 patients 66 ± 11 years, 77% with HF and baseline echocardiography who were treated with CRT were included in the The of HF was ischemic in 59% of the mean was ± and the mean ± No or mild FMR was in whereas had moderate to severe 6-month follow-up patients for the study of The severity of FMR before and after CRT implantation is in patients had no or mild FMR at patients had moderate or severe the patients with grade 0–1 FMR at the MR grade remained unchanged at 6-month follow-up in 609 whereas the MR grade to grade 2–4 FMR in 66 the patients with grade 2–4 FMR at the MR grade improved to grade 0–1 in 209 and remained unchanged in 309 at 6-month follow-up. Baseline of the patients according to the change in FMR are in changes in clinical and echocardiographic parameters are in Patients with grade 2–4 FMR at baseline which improved or remained unchanged at 6 months after CRT, had and lower at Patients with grade 2–4 FMR at baseline which remained unchanged had severe and had failure at according to FMR evolution grade FMR unchanged (n = grade FMR worsened (n = grade FMR improved (n = grade FMR unchanged (n = ± ± ± baseline or mild FMR unchanged at 6 ± baseline or mild FMR unchanged at 6 are mean ± = = FMR = functional mitral p baseline or mild FMR unchanged at 6 in a new in clinical and echocardiographic according to FMR evolution grade FMR unchanged (n = grade FMR worsened (n = grade FMR improved (n = grade FMR unchanged baseline FMR unchanged at 6 baseline FMR worsened at 6 baseline moderate to severe FMR improved at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± ± ± ± baseline FMR unchanged at 6 baseline FMR worsened at 6 baseline moderate to severe FMR improved at 6 ± baseline FMR unchanged at 6 baseline FMR worsened at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± ± ± baseline FMR unchanged at 6 ± baseline FMR unchanged at 6 baseline FMR worsened at 6 baseline moderate to severe FMR improved at 6 ± baseline moderate to severe FMR improved at 6 ± ± ± ± baseline FMR unchanged at 6 ± baseline FMR unchanged at 6 baseline FMR worsened at 6 ± baseline FMR worsened at 6 ± baseline FMR unchanged at 6 baseline FMR worsened at 6 ± baseline FMR unchanged at 6 baseline FMR worsened at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± ± baseline FMR unchanged at 6 ± ± baseline FMR unchanged at 6 baseline FMR worsened at 6 ± baseline FMR unchanged at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± baseline FMR unchanged at 6 ± baseline FMR unchanged at 6 ± ± baseline FMR unchanged at 6 baseline FMR worsened at 6 ± baseline FMR unchanged at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± ± ± ± ± baseline FMR unchanged at 6 baseline moderate to severe FMR improved at 6 ± ± ± ± ± ± baseline FMR unchanged at 6 ± ± baseline FMR unchanged at 6 are mean ± FMR = functional mitral = left = left ventricular = left ventricular = left ventricular 6 = walk = New York Heart Association = quality of p baseline FMR unchanged at 6 p baseline FMR worsened at 6 p baseline moderate to severe FMR improved at 6 in a new are mean ± = = FMR = functional mitral are mean ± FMR = functional mitral = left = left ventricular = left ventricular = left ventricular 6 = walk = New York Heart Association = quality of in functional HF at 6 follow-up for FMR are in was improvement in functional HF all the FMR the clinical response improvement in baseline to 6 was lower in patients with grade 0–1 FMR at baseline which worsened at follow-up with the groups for those with grade 0–1 FMR at baseline which remained unchanged, in patients with grade 2–4 FMR which improved and in patients with grade 2–4 FMR which remained unchanged = in at 6 follow-up for FMR are in was in patients with grade 2–4 FMR at baseline which improved and in those with grade 0–1 FMR at baseline which remained unchanged at 6-month follow-up with patients with grade 2–4 FMR at baseline which remained unchanged and patients with grade 0–1 FMR at baseline which worsened (p was in patients with grade 0–1 FMR at baseline which remained unchanged and grade 2–4 FMR at baseline which improved at 6-month follow-up and with those with grade 0–1 FMR at baseline which worsened and grade FMR at baseline which remained unchanged and p in left according to of evolution of functional mitral regurgitation in baseline to months after cardiac resynchronization therapy (CRT) are according to of evolution of of the a mean follow-up of 51 ± 38 months, 297 (25%) patients died. according to FMR responses 6 months, a and of the 609 patients with grade 0–1 FMR at baseline which remained unchanged at 6 months after CRT, at and months of follow-up, rates were in the of 209 patients with grade 2–4 FMR which improved at 6 months of follow-up. In the of 66 patients with grade 0–1 FMR at baseline which worsened, mortality Finally, the of 309 patients with baseline grade 2–4 FMR which improve after CRT the mortality rates p analysis baseline grade 2–4 FMR which remained unchanged at 6 months after CRT was associated with increased of mortality (hazard ratio, 1.77; 95% confidence interval, 1.41–2.22, p whereas the groups were of mortality and grade FMR grade FMR grade FMR grade FMR of heart at 6 months of at 6 months after cardiac resynchronization clinical = confidence = FMR = functional mitral = = left ventricular of at 6 months after cardiac resynchronization in a new = confidence = FMR = functional mitral = = left ventricular In this a prevalence of moderate or severe FMR was present at baseline in HF of CRT. The FMR grade improved to no or mild FMR after 6 months of CRT in a of In in those with no or mild FMR at a moderate to severe FMR after CRT. Patients in baseline FMR to moderate to severe FMR and those with moderate to severe baseline FMR in CRT improve FMR, had a long-term prognosis with patients who no or mild FMR after 6 months of CRT with mortality was independent of changes and clinical CRT The prevalence of FMR in patients with HF has in previous A. Dini F.L.L Faggiano P. Agricola E. Cicoira M. Frattini S. Simioniuc A. Gullace M. Ghio S. Enriquez-Sarano M. Temporelli P.L.L Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy.Heart. 2011; 97: 1675-1680Crossref PubMed Scopus (420) Google Scholar, 8Cipriani M. Lunati M. Landolina M. Proclemer A. Boriani G. Ricci R.P.P Rordorf R. Matassini M.V.V Padeletti L. Iacopino S. Molon G. Perego G.B.B Gasparini M. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy.Eur J Heart Fail. 2016; 18: 1060-1068Crossref PubMed Scopus (25) Google of and severity of mitral regurgitation to patients with left ventricular and heart J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar In the present study of a of the prevalence of moderate or severe FMR at baseline was to the of A. Dini F.L.L Faggiano P. Agricola E. Cicoira M. Frattini S. Simioniuc A. Gullace M. Ghio S. Enriquez-Sarano M. Temporelli P.L.L Independent prognostic value of functional mitral regurgitation in patients with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-ischaemic dilated cardiomyopathy.Heart. 2011; 97: 1675-1680Crossref PubMed Scopus (420) Google Scholar severe and M. Lunati M. Landolina M. Proclemer A. Boriani G. Ricci R.P.P Rordorf R. Matassini M.V.V Padeletti L. Iacopino S. Molon G. Perego G.B.B Gasparini M. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy.Eur J Heart Fail. 2016; 18: 1060-1068Crossref PubMed Scopus (25) Google Scholar have to FMR during and P. P. A. C. M. of cardiac resynchronization therapy on functional mitral regurgitation in heart J Cardiol. Full Text Full Text PDF PubMed Scopus Google Scholar, S. Leclercq C. T. S. C. Linde C. S. L. M. C. Daubert of pacing in patients with heart failure and J 2001; PubMed Scopus Google Scholar, E. M. M. J. F. C. P. J. Cardiac resynchronization in chronic heart J PubMed Scopus Google Scholar, Daubert E. D. L. L. The of cardiac resynchronization on and mortality in heart J 2005; PubMed Scopus Google Scholar, H. R. Schwartzman D. Gorcsan 3rd, J. A for in mitral regurgitation after cardiac resynchronization therapy: Cardiol. PubMed Scopus Google Scholar, Sutton T. E. M. J. of cardiac resynchronization therapy on left ventricular and in chronic heart PubMed Scopus Google Scholar CRT of FMR the and and is and mitral valve to FMR on mitral is and mitral in improved H. R. Schwartzman D. Gorcsan 3rd, J. A for in mitral regurgitation after cardiac resynchronization therapy: Cardiol. PubMed Scopus Google S. E. for functional mitral regurgitation: in PubMed Scopus Google Scholar, E. A. C. of cardiac resynchronization therapy on functional mitral regurgitation in heart Cardiol. PubMed Scopus Google Scholar, R. G. M. F. A. G. Padeletti L. of cardiac resynchronization therapy on the functional mitral regurgitation in heart J PubMed Scopus Google Scholar In the present patients with no or mild FMR at baseline which remained unchanged at 6-month follow-up and patients with moderate to severe FMR at baseline which improved at 6 months after CRT the that CRT the of functional improvement and in CRT with no or mild FMR at baseline which worsened at 6 months with whereas the was in those with moderate to severe FMR at baseline which remained that improvement and changes after CRT are in than changes in is the changes in FMR grade after CRT impact the long-term prognosis of HF In the Cardiac in Heart Failure FMR grade at months follow-up was independent of J. Ghio S. F. A. M. L. the long-term of cardiac resynchronization therapy on mortality baseline and the response a the in Heart Cardiol. PubMed Scopus Google Scholar In a study D. S. C. of mitral regurgitation on and outcome in patients cardiac resynchronization PubMed Scopus Google Scholar at 6 months the of and the of FMR were associated with D. S. C. of mitral regurgitation on and outcome in patients cardiac resynchronization PubMed Scopus Google Scholar the that at after CRT FMR worsened grade in of patients and remained significant but unchanged baseline in M. Lunati M. Landolina M. Proclemer A. Boriani G. Ricci R.P.P Rordorf R. Matassini M.V.V Padeletti L. Iacopino S. Molon G. Perego G.B.B Gasparini M. Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy.Eur J Heart Fail. 2016; 18: 1060-1068Crossref PubMed Scopus (25) Google Scholar The of improvement in FMR at follow-up after CRT was associated with increased study the that FMR response to CRT during the 6 months is of long-term and new to this Moderate to severe FMR at which remained unchanged at 6 months after CRT was associated with mortality in HF remained significant after for to impact on HF mortality, the response to CRT. FMR and volumetric response to CRT are the that a in FMR was independent of after for that the FMR is a of the volumetric response of the but to long-term The of the present study are as the for HF patients in FMR or after CRT. for patients with moderate to severe FMR after CRT are and may considered for mitral valve The of the on and in the in Cardiac study of 51 patients with moderate to severe FMR after A. W. S. F. R. J. S. C. J. O. of mitral regurgitation in to cardiac resynchronization therapy and Cardiol. 2011; PubMed Scopus Google Scholar the of the HF patients to therapy and patients to therapy and in of mortality and for D. G. B. G. T. C. F. D. M. or treatment for mitral J of PubMed Scopus Google Scholar The for of the for Heart Failure Patients with Functional MR on the of mitral valve in this was a FMR severity may that or which may Patients who before 6 months, underwent mitral valve or and those follow-up echocardiography at 6 months were therapy CRT is the of for HF patients with H. V. Bax J.J. M. C. P.J. B. Lancellotti P. E. D. R. J. P. A. T. O. Windecker S. Zamorano J.L. Guidelines for the of heart the Task Force for the of heart disease of the European Society of Cardiology and the European Association for surgery Heart J. PubMed Scopus Google Scholar and the of the present study are of may Finally, the study to the of FMR after CRT in HF was to FMR grade 0–1 at baseline to 2–4 at 6 months is independent of mortality, as this in 66 In conclusion, in the study of HF patients treated with CRT, moderate to severe FMR at which remained unchanged at 6 months, was strongly associated with increased mortality independent of and the clinical response to CRT. The of Heart Leiden University Medical Center has and is a for and has in The have to who to this have included as