Impact of Transcatheter Edge-to-Edge Mitral Valve Repair on Atrial Functional Mitral Regurgitation from the GIOTTO Registry

•Atrial functional mitral regurgitation (FMR) treated with transcatheter edge-to-edge repair was associated with similar procedural success rate but better clinical outcomes compared with ventricular FMR.•Accurate phenotyping of patients with FMR should be routinely achieved in clinical practice.•Further prospective, large investigations are needed to assess the role of the different types of devices (e.g., leaflets or annular approach) on early and late outcomes of patients with atrial FMR who refused or are at a high risk for cardiac surgery. Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478 days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio HR 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p 1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes. Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478 days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio HR 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p 1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes. Mitral valve (MV) regurgitation is the most common valvular disease and the second most frequent indication for heart valve intervention in the Western world after aortic stenosis.1Virani SS Alonso A Aparicio HJ Benjamin EJ Bittencourt MS Callaway CW Carson AP Chamberlain AM Cheng S Delling FN Elkind MSV Evenson KR Ferguson JF Gupta DK Khan SS Kissela BM Knutson KL Lee CD Lewis TT Liu J Loop MS Lutsey PL Ma J Mackey J Martin SS Matchar DB Mussolino ME Navaneethan SD Perak AM Roth GA Samad Z Satou GM Schroeder EB Shah SH Shay CM Stokes A VanWagner LB Wang NY Tsao CW American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke Statistics-2021 update: a report from the American Heart Association.Circulation. 2021; 143: e254-e743Crossref PubMed Scopus (3184) Google Scholar, 2El Sabbagh A Reddy YNV Nishimura RA Mitral valve regurgitation in the contemporary era: insights into diagnosis, management, and future directions.JACC Cardiovasc Imaging. 2018; 11: 628-643Crossref PubMed Scopus (127) Google Scholar, 3Vahanian A Beyersdorf F Praz F Milojevic M Baldus S Bauersachs J Capodanno D Conradi L De Bonis M De Paulis R Delgado V Freemantle N Gilard M Haugaa KH Jeppsson A Jüni P Pierard L Prendergast BD Sádaba JR Tribouilloy C Wojakowski W ESC/EACTS Scientific Document Group2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43: 561-632Crossref PubMed Scopus (1758) Google Scholar Functional mitral regurgitation (FMR) is because of an imbalance between leaflets tethering and closure forces leading to poor coaptation without intrinsic structural valve changes.2El Sabbagh A Reddy YNV Nishimura RA Mitral valve regurgitation in the contemporary era: insights into diagnosis, management, and future directions.JACC Cardiovasc Imaging. 2018; 11: 628-643Crossref PubMed Scopus (127) Google Scholar,4Zoghbi WA Levine RA Flachskampf F Grayburn P Gillam L Leipsic J Thomas JD Kwong RY P Atrial functional mitral a Cardiovasc Imaging. 2022; PubMed Scopus Google Scholar The of FMR nonischemic and ischemic leading to left ventricular and FMR a of FMR has the atrial FMR because of left atrial in with an of the mitral leaflets but with and S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google N S M of atrial functional mitral insights into and Cardiovasc Imaging. PubMed Scopus Google Scholar has that aFMR is associated with compared with and without mitral V M JR J P M and of mitral regurgitation in the clinical and Heart J. PubMed Scopus Google N S S C J C M and functional of mitral Cardiovasc Imaging. 2021; PubMed Scopus Google Scholar of peculiar a different and have different outcomes compared with ventricular N S M of atrial functional mitral insights into and Cardiovasc Imaging. PubMed Scopus Google M Transcatheter edge-to-edge repair for atrial functional mitral or Cardiovasc 2022; PubMed Scopus Google Scholar The guidelines this A Beyersdorf F Praz F Milojevic M Baldus S Bauersachs J Capodanno D Conradi L De Bonis M De Paulis R Delgado V Freemantle N Gilard M Haugaa KH Jeppsson A Jüni P Pierard L Prendergast BD Sádaba JR Tribouilloy C Wojakowski W ESC/EACTS Scientific Document Group2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43: 561-632Crossref PubMed Scopus (1758) Google Scholar on the role of transcatheter edge-to-edge repair in patients with aFMR are with of aFMR, different and no between ischemic and nonischemic SH M S L N M M S S after transcatheter edge-to-edge mitral valve repair according to mitral regurgitation etiology and cardiac Cardiovasc 2022; PubMed Scopus Google Scholar, N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google Scholar, A C J N N S M Transcatheter edge-to-edge repair for atrial mitral Cardiovasc 2022; PubMed Scopus Google Scholar, F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google Scholar, Reddy YNV R Sabbagh A Nishimura RA M M Atrial mitral and outcomes of transcatheter mitral valve edge-to-edge Cardiovasc 2022; PubMed Scopus Google Scholar, A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google Scholar, P L M N Praz F D D M C M S M M C M A R C M Baldus S N C S S P M J Transcatheter mitral valve repair in patients with atrial functional mitral Cardiovasc Imaging. 2022; PubMed Scopus Google Scholar, P V N M P J P C and of edge-to-edge mitral valve repair in atrial ventricular functional mitral J 2021; PubMed Scopus Google Scholar to the clinical impact of with the MitraClip for patients with aFMR compared with the other FMR ischemic FMR and nonischemic the prospective of Transcatheter treatment of mitral valve regurgitation The GIOTTO study is a multicenter, prospective registry enrolling patients with symptomatic and MR who with the MitraClip in between and 2020. The and and and of the MitraClip have F L AP C S De F M P A P A C De F C F M C M C and of transcatheter mitral valve repair with results from the of Of Transcatheter of Mitral Valve PubMed Scopus Google Scholar, F A C M P A M De F M C R De F A C L C of registry Of Transcatheter treatment of mitral valve of valve disease and mitral regurgitation after MitraClip J Heart 2021; PubMed Scopus Google Scholar, A F P P AP A De F M M C F F M L F C and outcomes of MitraClip in from patients in the GIOTTO J 2021; PubMed Scopus Google Scholar patients who were for MitraClip according to the guidelines and the heart and were of the device were from to MitraClip and this patients with The for = and or MR = were The FMR types were on aFMR, iFMR, and niFMR on the of cardiac and the clinical as the of ischemic heart disease or were by at in with the Association of S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google V M JR J P M and of mitral regurgitation in the clinical and Heart J. PubMed Scopus Google V J A L Flachskampf P D L W for cardiac by in an from the American of and the Association of PubMed Scopus Google Scholar with patients with aFMR the ejection fraction for and for or left for and for women, and or or of atrial fibrillation S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google V M JR J P M and of mitral regurgitation in the clinical and Heart J. PubMed Scopus Google V J A L Flachskampf P D L W for cardiac by in an from the American of and the Association of PubMed Scopus Google Scholar A report was for were by of or clinical at and was and the and was at to up to and The study with the of and was by the at patients in the study were for according to the of V De Bonis M C P D R J P A S Scientific Document ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 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The of FMR in with ejection fraction has a less etiology of with the ischemic and nonischemic causes of patients with aFMR have an atrial or mitral annular and and with and Sabbagh A Reddy YNV Nishimura RA Mitral valve regurgitation in the contemporary era: insights into diagnosis, management, and future directions.JACC Cardiovasc Imaging. 2018; 11: 628-643Crossref PubMed Scopus (127) Google S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google M Transcatheter edge-to-edge repair for atrial functional mitral or Cardiovasc 2022; PubMed Scopus Google R Lee S KR J Levine RA Mitral valve to annular insights into the of atrial functional mitral Cardiovasc Imaging. PubMed Scopus Google N A M S M A M in patients with atrial with the of mitral Cardiovasc Imaging. PubMed Scopus Google Scholar The guidelines and no on the management of aFMR are available Sabbagh A Reddy YNV Nishimura RA Mitral valve regurgitation in the contemporary era: insights into diagnosis, management, and future directions.JACC Cardiovasc Imaging. 2018; 11: 628-643Crossref PubMed Scopus (127) Google A Beyersdorf F Praz F Milojevic M Baldus S Bauersachs J Capodanno D Conradi L De Bonis M De Paulis R Delgado V Freemantle N Gilard M Haugaa KH Jeppsson A Jüni P Pierard L Prendergast BD Sádaba JR Tribouilloy C Wojakowski W ESC/EACTS Scientific Document Group2021 ESC/EACTS guidelines for the management of valvular heart disease.Eur Heart J. 2022; 43: 561-632Crossref PubMed Scopus (1758) Google S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google N S M of atrial functional mitral insights into and Cardiovasc Imaging. PubMed Scopus Google M Transcatheter edge-to-edge repair for atrial functional mitral or Cardiovasc 2022; PubMed Scopus Google Scholar the of patients with FMR with atrial etiology is in the of of the disease were A S A J A C P A C of mitral valve Cardiovasc PubMed Google Scholar that the of and is SS Alonso A Aparicio HJ Benjamin EJ Bittencourt MS Callaway CW Carson AP Chamberlain AM Cheng S Delling FN Elkind MSV Evenson KR Ferguson JF Gupta DK Khan SS Kissela BM Knutson KL Lee CD Lewis TT Liu J Loop MS Lutsey PL Ma J Mackey J Martin SS Matchar DB Mussolino ME Navaneethan SD Perak AM Roth GA Samad Z Satou GM Schroeder EB Shah SH Shay CM Stokes A VanWagner LB Wang NY Tsao CW American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke Statistics-2021 update: a report from the American Heart Association.Circulation. 2021; 143: e254-e743Crossref PubMed Scopus (3184) Google Scholar is that MR aFMR aFMR has in at to with or for in of and up to of a V M JR J P M and of mitral regurgitation in the clinical and Heart J. PubMed Scopus Google A L of atrial functional mitral regurgitation to atrial with PubMed Scopus Google N M S M C J C M treatment and of mitral regurgitation the of heart 2021; PubMed Scopus Google Scholar aFMR was in 6% of patients with FMR treated with the in other the rate of patients aFMR treated with has higher to difference is by the in (e.g., patients with and the between aFMR with patients with a of leaflets annular and the of (e.g., and SH M S L N M M S S after transcatheter edge-to-edge mitral valve repair according to mitral regurgitation etiology and cardiac Cardiovasc 2022; PubMed Scopus Google N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google Scholar, Reddy YNV R Sabbagh A Nishimura RA M M Atrial mitral and outcomes of transcatheter mitral valve edge-to-edge Cardiovasc 2022; PubMed Scopus Google Scholar, A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google J M M F S of edge-to-edge repair in patients with atrial functional mitral J. 2021; PubMed Scopus Google Scholar to clinical and with SH M S L N M M S S after transcatheter edge-to-edge mitral valve repair according to mitral regurgitation etiology and cardiac Cardiovasc 2022; PubMed Scopus Google Scholar, N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google Scholar, A C J N N S M Transcatheter edge-to-edge repair for atrial mitral Cardiovasc 2022; PubMed Scopus Google Reddy YNV R Sabbagh A Nishimura RA M M Atrial mitral and outcomes of transcatheter mitral valve edge-to-edge Cardiovasc 2022; PubMed Scopus Google P L M N Praz F D D M C M S M M C M A R C M Baldus S N C S S P M J Transcatheter mitral valve repair in patients with atrial functional mitral Cardiovasc Imaging. 2022; PubMed Scopus Google Scholar aFMR were less and had a lower risk and better and smaller than patients with other causes of and with and of in up to of the between aFMR and treatment outcomes is the available aFMR to be with better outcomes compared with other FMR treated J R R P atrial functional mitral clinical and management and Cardiovasc Imaging. 2021; PubMed Scopus Google Scholar, S M N A M and predictors of cardiac in treated patients with atrial functional mitral J PubMed Scopus Google Scholar, in transcatheter edge-to-edge insights into atrial functional mitral 2021; PubMed Scopus Google Scholar, C A Nishimura M M J S C of atrial and ventricular functional mitral 2021; Scopus Google Scholar outcomes have after A L of atrial functional mitral regurgitation to atrial with PubMed Scopus Google AM S M Mitral regurgitation associated with mitral annular in patients with atrial an PubMed Scopus Google A Nishimura S Mitral valve repair for atrial functional mitral regurgitation in patients with atrial Cardiovasc PubMed Scopus Google Scholar on aFMR treated with have a of MitraClip on MR and and early outcomes similar to patients with N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google Scholar, A C J N N S M Transcatheter edge-to-edge repair for atrial mitral Cardiovasc 2022; PubMed Scopus Google Scholar, F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google Scholar the rates at follow-up and the of a between different types of FMR (e.g., ischemic the that is available on this the procedural results and MR the clinical on at a follow-up and with other FMR N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google Reddy YNV R Sabbagh A Nishimura RA M M Atrial mitral and outcomes of transcatheter mitral valve edge-to-edge Cardiovasc 2022; PubMed Scopus Google P L M N Praz F D D M C M S M M C M A R C M Baldus S N C S S P M J Transcatheter mitral valve repair in patients with atrial functional mitral Cardiovasc Imaging. 2022; PubMed Scopus Google F L C A S D C C M P A M R A C AP F in patients with high after mitral valve transcatheter edge-to-edge repair for mitral J 2022; PubMed Scopus Google Scholar The peculiar clinical risk of patients with aFMR and at the compared with in MR and functional was S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google Scholar other as in a the different and in the ventricular causes of FMR be to the of the patients with aFMR in the ischemic nonischemic M J M F AP A D F D F C A C C R C mitral repair for functional and mitral a and Heart 2022; PubMed Scopus Google Scholar in to aFMR and of FMR postprocedural MR ≤1+ was a of late in is in with on the role of procedural after should be in of and are needed to the with and A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google F L AP C S De F M P A P A C De F C F M C M C and of transcatheter mitral valve repair with results from the of Of Transcatheter of Mitral Valve PubMed Scopus Google M M A L C P A M De F L C R De F A C L S C F M of procedural after transcatheter edge-to-edge mitral valve repair in mitral Cardiovasc 2022; PubMed Scopus Google R S M A A S of mitral regurgitation mitral to risk of heart failure after MitraClip J PubMed Google Scholar study has this is an of a multicenter, prospective registry on with the of study and the of with of aFMR is on a that is in prospective S D F Thomas JD Atrial functional mitral of the PubMed Scopus Google V M JR J P M and of mitral regurgitation in the clinical and Heart J. PubMed Scopus Google N A S F S outcomes with transcatheter edge-to-edge repair in atrial functional MR from the Cardiovasc 2022; PubMed Scopus Google F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google V J A L Flachskampf P D L W for cardiac by in an from the American of and the Association of PubMed Scopus Google Scholar the of aFMR treated by was smaller than in other the of and of on this compared with other F R D C L M A RA L JR C D J F V J P P D A R F and outcomes of transcatheter mitral valve repair in atrial functional mitral J 2021; PubMed Scopus Google A L C A M De F M R M A M L A C F Transcatheter edge-to-edge mitral valve repair in atrial functional mitral insights from the J 2022; PubMed Scopus Google Scholar the of this study be to the MitraClip and different The results of this GIOTTO subanalysis that aFMR is the prevalent of FMR but associated with better clinical outcomes after than patients with Postprocedural MR >1+, peripheral vasculopathy, and non-aFMR were independent predictors of worse outcomes after with the from The have no to for the of the with