Clinical Research in Cardiology

, Volume 108, Issue 3, pp 264–272 | Cite as

Predictors of mortality in ischaemic versus non-ischaemic functional mitral regurgitation after successful transcatheter mitral valve repair using MitraClip: results from two high-volume centres

  • Mitsunobu Kitamura
  • Hidehiro Kaneko
  • Michael Schlüter
  • Dimitry Schewel
  • Tobias Schmidt
  • Hannes Alessandrini
  • Felix Kreidel
  • Michael Neuss
  • Christian Butter
  • Karl-Heinz Kuck
  • Christian FrerkerEmail author
Original Paper



Transcatheter edge-to-edge mitral valve repair using the MitraClip has been widely performed in surgical high-risk patients with reduced left ventricular systolic function and severe functional mitral regurgitation (FMR). Ischaemic heart disease is the leading aetiology of heart disease worldwide. We aimed to assess the clinical implications of ischaemic aetiology in patients with severe FMR who underwent MitraClip implantation.

Methods and results

From two high-volume centres in Germany, we retrospectively compared the clinical outcomes and clinical predictors of all-cause mortality after MitraClip implantation in patients with ischaemic (I-FMR) and non-ischaemic FMR (NI-FMR). In the overall FMR cohort (n = 575), there were 336 (58%) patients with I-FMR and 239 (42%) with NI-FMR. There was no significant difference in survival between the two groups (log-rank p = 0.78). In a multivariable Cox regression analysis of all-cause mortality, different predictors were observed for either group. In I-FMR patients, decreasing tricuspid annular systolic excursion [adjusted hazard ratio (HRadj) 1.06, 95% confidence interval (95% CI) 1.01–1.14 /1 mm, p = 0.028] and increasing logistic EuroSCORE (HRadj 1.02, 95% CI 1.00–1.03, p = 0.037) were independent predictors, whereas in NI-FMR patients, NT-pro BNP (HRadj 1.05, 95% CI 1.02–1.08, p = 0.001) and age (HRadj 1.06, 95% CI 1.01–1.11, p = 0.013) were independently predictive of mortality.


Despite the similar survival between ischaemic and non-ischaemic FMR, different predictors of all-cause mortality were demonstrated. Further clinical studies are mandated to focus on each FMR subgroup with stratification by ischaemic origin.


Transcatheter edge-to-edge mitral valve repair MitraClip Functional mitral regurgitation Ischaemic functional mitral regurgitation Non-ischaemic functional mitral regurgitation 



Coronary artery bypass grafting


Coronary artery disease


Estimated glomerular filtration rate


Functional mitral regurgitation


Heart failure


Interquartile range


Left ventricle/ventricular


logistic EuroSCORE


Mitral regurgitation


N-terminal pro-brain natriuretic peptide


New York Heart Association


Right ventricle/ventricular


Tricuspid annular plane systolic excursion




Compliance with ethical standards

Conflict of interest

Dr. Kuck has received research funding from Abbott Vascular. Dr. Frerker, Dr. Butter, and Dr. Neuss have received lecture honoraria and travel grants from Abbott Laboratories, Abbott Park (Illinois, USA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Ethical approval

All patients provided written informed consent and the study protocol conformed to the ethical guidelines of the 1964 Declaration of Helsinki and its later amendments.


  1. 1.
    Feldman T, Wasserman HS, Herrmann HC, Gray W, Block PC, Whitlow P, St Goar F, Rodriguez L, Silvestry F, Schwartz A, Sanborn TA, Condado JA, Foster E (2005) Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol 46:2134–2140CrossRefGoogle Scholar
  2. 2.
    Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, Whitlow PL, Gray W, Low R, Herrmann HC, Lim S, Foster E, Glower D (2009) Everest Investigators. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) cohort. J Am Coll Cardiol 54:686–694CrossRefGoogle Scholar
  3. 3.
    Maisano F, Franzen O, Baldus S, Schäfer U, Hausleiter J, Butter C, Ussia GP, Sievert H, Richardt G, Widder JD, Moccetti T, Schillinger W (2013) Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol 62:1052–1061CrossRefGoogle Scholar
  4. 4.
    Baldus S, Schillinger W, Franzen O, Bekeredjian R, Sievert H, Schofer J, Kuck KH, Konorza T, Mollmann H, Hehrlein C, Ouarrak T, Senges J, Meinertz T, German Transcatheter Mitral Valve Interventions (TRAMI) investigators (2012) MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail 14:1050–1055CrossRefGoogle Scholar
  5. 5.
    Rossi A, Dini FL, Faggiano P, Agricola E, Cicoira M, Frattini S, Simioniuc A, Gullace M, Ghio S, Enriquez-Sarano M, Temporelli PL (2011) 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 97:1675–1680CrossRefGoogle Scholar
  6. 6.
    Taramasso M, Maisano F, Latib A, Denti P, Buzzatti N, Cioni M, La Canna G, Colombo A, Alfieri O (2014) Clinical outcomes of MitraClip for the treatment of functional mitral regurgitation. EuroIntervention 10:746–752CrossRefGoogle Scholar
  7. 7.
    Kaneko H, Suzuki S, Uejima T, Kano H, Matsuno S, Takai H, Oikawa Y, Yajima J, Aizawa T, Yamashita T (2014) Functional mitral regurgitation and left ventricular systolic dysfunction in the recent era of cardiovascular clinical practice, an observational cohort study. Hypertens Res 37:1082–1087CrossRefGoogle Scholar
  8. 8.
    Kaneko H, Neuss M, Weissenborn J, Butter C (2016) Prognostic significance of right ventricular dysfunction in patients with functional mitral regurgitation undergoing MitraClip. Am J Cardiol 118:1717–1722CrossRefGoogle Scholar
  9. 9.
    Kajimoto K, Sato N, Takano T, investigators of the Acute Decompensated Heart Failure Syndromes (ATTEND) registry (2016) Functional mitral regurgitation at discharge and outcomes in patients hospitalized for acute decompensated heart failure with a preserved or reduced ejection fraction. Eur J Heart Fail 18:1051–1059CrossRefGoogle Scholar
  10. 10.
    Pighi M, Estevez-Loureiro R, Maisano F, Ussia GP, Dall’Ara G, Franzen O, Laroche C, Settergren M, Winter R, Nickenig G, Gilard M, Di Mario C, Transcatheter Valve Treatment (TCVT) Sentinel Registry Investigators of the EURObservational Research Programme (EORP) of the European Society of Cardiology (2017) Immediate and 12-month outcomes of ischemic versus nonischemic functional mitral regurgitation in patients treated with Mitraclip (from the 2011 to 2012 pilot sentinel registry of percutaneous edge-to-edge mitral valve repair of the European Society of Cardiology). Am J Cardiol 119:630–637CrossRefGoogle Scholar
  11. 11.
    Michler RE, Smith PK, Parides MK, Ailawadi G, Thourani V, Moskowitz AJ, Acker MA, Hung JW, Chang HL, Perrault LP, Gillinov AM, Argenziano M, Bagiella E, Overbey JR, Moquete EG, Gupta LN, Miller MA, Taddei-Peters WC, Jeffries N, Weisel RD, Rose EA, Gammie JS, DeRose JJ Jr, Puskas JD, Dagenais F, Burks SG, El-Hamamsy I, Milano CA, Atluri P, Voisine P, O’Gara PT, Gelijns AC, for the CTSN (2016) Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med 374:1932–1941CrossRefGoogle Scholar
  12. 12.
    Feldman T, Mehta A, Guerrero M, Levisay JP, Salinger MH (2016) MitraClip therapy for mitral regurgitation: secondary mitral regurgitation. Interv Cardiol Clin 5:83–91Google Scholar
  13. 13.
    Schäfer U, Maisano F, Butter C, Franzen O, Baldus S, Hausleiter J, Ussia GP, Sievert H, Geist V, Widder JD, Moccetti T, Schillinger W (2016) Impact of preprocedural left ventricular ejection fraction on 1-year outcomes after MitraClip implantation (from the ACCESS-EU phase I, a prospective, multicenter, nonrandomized postapproval study of the MitraClip therapy in Europe). Am J Cardiol 118:873–880CrossRefGoogle Scholar
  14. 14.
    Capodanno D, Adamo M, Barbanti M, Giannini C, Laudisa ML, Cannata S, Curello S, Imme S, Maffeo D, Bedogni F, Petronio AS, Ettori F, Tamburino C, Grasso C, Grasp-It Investigators (2015) Predictors of clinical outcomes after edge-to-edge percutaneous mitral valve repair. Am Heart J 170:187–195CrossRefGoogle Scholar
  15. 15.
    Matsumoto T, Nakamura M, Yeow WL, Hussaini A, Ram V, Makar M, Gurudevan SV, Trento A, Siegel RJ, Kar S (2014) Impact of pulmonary hypertension on outcomes in patients with functional mitral regurgitation undergoing percutaneous edge-to-edge repair. Am J Cardiol 114:1735–1739CrossRefGoogle Scholar
  16. 16.
    Ellis SG, Whitlow PL, Raymond RE, Schneider JP (2002) Impact of mitral regurgitation on long-term survival after percutaneous coronary intervention. Am J Cardiol 89:315–318CrossRefGoogle Scholar
  17. 17.
    Deja MA, Grayburn PA, Sun B, Rao V, She L, Krejca M, Jain AR, Leng Chua Y, Daly R, Senni M, Mokrzycki K, Menicanti L, Oh JK, Michler R, Wrobel K, Lamy A, Velazquez EJ, Lee KL, Jones RH (2012) Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial. Circulation 125:2639–2648CrossRefGoogle Scholar
  18. 18.
    Mirabel M, Iung B, Baron G, Messika-Zeitoun D, Detaint D, Vanoverschelde JL, Butchart EG, Ravaud P, Vahanian A (2007) What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J 28:1358–1365CrossRefGoogle Scholar
  19. 19.
    Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ (2017) Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the american society of echocardiography developed in collaboration with the society for cardiovascular magnetic resonance. J Am Soc Echocardiogr 30:303–371CrossRefGoogle Scholar
  20. 20.
    Di Donato M, Dabic P, Castelvecchio S, Santambrogio C, Brankovic J, Collarini L, Joussef T, Frigiola A, Buckberg G, Menicanti L, Group R (2006) Left ventricular geometry in normal and post-anterior myocardial infarction patients: sphericity index and ‘new’ conicity index comparisons. Eur J Cardiothorac Surg 29(Suppl 1):S225–S230CrossRefGoogle Scholar
  21. 21.
    Nagasaki M, Nishimura S, Ohtaki E, Kasegawa H, Matsumura T, Nagayama M, Koyanagi T, Tohbaru T, Misu K, Asano R, Sumiyoshi T, Hosoda S (2006) The echocardiographic determinants of functional mitral regurgitation differ in ischemic and non-ischemic cardiomyopathy. Int J Cardiol 108:171–176CrossRefGoogle Scholar
  22. 22.
    Juliani PS, Das-Neves-Pereira JC, Monteiro R, Correia AT, Moreira LFP, Jatene FB (2018) Left ventricular chamber geometry in cardiomyopathies: insights from a computerized anatomical study. ESC Heart Fail 5:355–364CrossRefGoogle Scholar
  23. 23.
    Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV, Massaro JM, Mauri L (2011) Everest II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 364:1395–1406CrossRefGoogle Scholar
  24. 24.
    Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Munoz DR, Rosenhek R, Sjogren J, Tornos Mas P, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL, ESC Scientific Document Group (2017) 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 38:2739–2791CrossRefGoogle Scholar
  25. 25.
    Neuss M, Schau T, Schoepp M, Seifert M, Holschermann F, Meyhofer J, Butter C (2013) Patient selection criteria and midterm clinical outcome for MitraClip therapy in patients with severe mitral regurgitation and severe congestive heart failure. Eur J Heart Fail 15:786–795CrossRefGoogle Scholar
  26. 26.
    Godino C, Salerno A, Cera M, Agricola E, Fragasso G, Rosa I, Oppizzi M, Monello A, Scotti A, Magni V, Montorfano M, Cappelletti A, Margonato A, Colombo A (2016) Impact and evolution of right ventricular dysfunction after successful MitraClip implantation in patients with functional mitral regurgitation. Int J Cardiol Heart Vasc 11:90–98Google Scholar
  27. 27.
    Giannini C, Fiorelli F, Colombo A, De Carlo M, Weisz SH, Agricola E, Godino C, Castriota F, Golino P, Petronio AS (2016) Right ventricular evaluation to improve survival outcome in patients with severe functional mitral regurgitation and advanced heart failure undergoing MitraClip therapy. Int J Cardiol 223:574–580CrossRefGoogle Scholar
  28. 28.
    Park SJ, Park JH, Lee HS, Kim MS, Park YK, Park Y, Kim YJ, Lee JH, Choi SW, Jeong JO, Kwon IS, Seong IW (2015) Impaired RV global longitudinal strain is associated with poor long-term clinical outcomes in patients with acute inferior STEMI. JACC Cardiovasc Imaging 8:161–169CrossRefGoogle Scholar
  29. 29.
    Mentias A, Raza MQ, Barakat AF, Hill E, Youssef D, Krishnaswamy A, Desai MY, Griffin B, Ellis S, Menon V, Tuzcu EM, Kapadia SR (2017) Prognostic significance of ischemic mitral regurgitation on outcomes in acute ST-elevation myocardial infarction managed by primary percutaneous coronary intervention. Am J Cardiol 119:20–26CrossRefGoogle Scholar
  30. 30.
    Bouma W, Willemsen HM, Lexis CP, Prakken NH, Lipsic E, van Veldhuisen DJ, Mariani MA, van der Harst P, van der Horst IC (2016) Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction. Clin Res Cardiol 105:981–991CrossRefGoogle Scholar
  31. 31.
    Giannini C, Petronio AS, De Carlo M, Guarracino F, Conte L, Fiorelli F, Pieroni A, Di Bello V (2014) Integrated reverse left and right ventricular remodelling after MitraClip implantation in functional mitral regurgitation: an echocardiographic study. Eur Heart J Cardiovasc Imaging 15:95–103CrossRefGoogle Scholar
  32. 32.
    Schwencke C, Bijuklic K, Ouarrak T, Lubos E, Schillinger W, Plicht B, Eggebrecht H, Baldus S, Schymik G, Boekstegers P, Hoffmann R, Senges J, Schofer J (2017) Impact of cardiac comorbidities on early and 1-year outcome after percutaneous mitral valve interventions: data from the German transcatheter mitral valve interventions (TRAMI) registry. Clin Res Cardiol 106:249–258CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Mitsunobu Kitamura
    • 1
  • Hidehiro Kaneko
    • 2
  • Michael Schlüter
    • 3
  • Dimitry Schewel
    • 1
  • Tobias Schmidt
    • 1
  • Hannes Alessandrini
    • 1
  • Felix Kreidel
    • 1
  • Michael Neuss
    • 2
  • Christian Butter
    • 2
  • Karl-Heinz Kuck
    • 1
  • Christian Frerker
    • 1
    Email author
  1. 1.Department of CardiologyAsklepios Klinik St. GeorgHamburgGermany
  2. 2.Heart Center Brandenburg in Bernau/Berlin & Medical School Brandenburg (MHB)BernauGermany
  3. 3.Asklepios ProresearchHamburgGermany

Personalised recommendations