Learning From Controversy: Management of Severe Ischemic Mitral Regurgitation at the Time of CABG
2019; Elsevier BV; Volume: 108; Issue: 2 Linguagem: Inglês
10.1016/j.athoracsur.2019.05.004
ISSN1552-6259
Autores Tópico(s)Cardiac pacing and defibrillation studies
ResumoIschemic mitral regurgitation (IMR) is a consequence of regional wall motion abnormalities induced by myocardial ischemia or infarction.1Grigioni F. Detaint D. Avierinos J.F. Scott C. Tajik J. Enriquez-Sarano M. Contribution of ischemic mitral regurgitation to congestive heart failure after myocardial infarction.J Am Coll Cardiol. 2005; 45: 260-267Crossref PubMed Scopus (177) Google Scholar Adverse left ventricular (LV) remodeling develops in approximately 50% of patients after a myocardial infarction.2Bursi F. Enriquez-Sarano M. Nkomo V.T. et al.Heart failure and death after myocardial infarction in the community: the emerging role of mitral regurgitation.Circulation. 2005; 111: 295-301Crossref PubMed Scopus (386) Google Scholar, 3Perez de Isla L. Zamorano J. Quezada M. et al.Functional mitral regurgitation after a first non-ST-segment elevation acute coronary syndrome: contribution to congestive heart failure.Eur Heart J. 2007; 28: 2866-2872Crossref PubMed Scopus (28) Google Scholar The presence of any degree of IMR identifies patients with LV dysfunction who have a higher mortality risk than those without IMR.2Bursi F. Enriquez-Sarano M. Nkomo V.T. et al.Heart failure and death after myocardial infarction in the community: the emerging role of mitral regurgitation.Circulation. 2005; 111: 295-301Crossref PubMed Scopus (386) Google Scholar This fact alone remains the primary driver for recommending a mitral valve (MV) procedure in patients with severe IMR. For related article, see page 536 For related article, see page 536 The appropriate surgical management of severe IMR at the time of coronary artery bypass grafting (CABG) is in evolution. Some experts advocate chordal-sparing MV replacement, whereas others support restrictive mitral annuloplasty (RA) repair.4Acker M.A. Parides M.K. Perrault L.P. et al.Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.N Engl J Med. 2014; 370: 23-32Crossref PubMed Scopus (544) Google Scholar, 5Goldstein D. Moskowitz A.J. Geijins A.C. et al.Two year outcomes of surgical treatment in severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (446) Google Scholar, 6Nappi F. Lusini M. Spadaccio C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation: a randomized trial.J Am Coll Cardiol. 2016; 24: 2334-2346Crossref Scopus (98) Google Scholar, 7Gillinov A.M. Wierup P.N. Blackstone E.H. et al.Is repair preferable to replacement for ischemic mitral regurgitation?.J Thorac Cardiovasc Surg. 2001; 122: 1125-1141Abstract Full Text Full Text PDF PubMed Scopus (454) Google Scholar, 8Reece T.B. Tribble C.G. Ellman P.I. et al.Mitral repair is superior to replacement when associated with coronary artery disease.Ann Surg. 2004; 239: 671-675Crossref PubMed Scopus (70) Google Scholar, 9Al-Radi O.O. Austin P.C. Tu J.V. David T.E. Yau T.M. Mitral repair versus replacement for ischemic mitral regurgitation.Ann Thorac Surg. 2005; 79: 1260-1267Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 10Vassileva C.M. Boley T. Markwell S. Hazelrigg S. Meta-analysis of short-term and long-term survival following repair versus replacement for ischemic mitral regurgitation.Eur J Cardiothorac Surg. 2011; 39: 295-303Crossref PubMed Scopus (124) Google Scholar RA is generally associated with lower operative morbidity and mortality, as well as with the presumed benefits of preserving the subvalvular apparatus to maintain LV systolic function. However, 1-year mitral regurgitation (MR) recurrence rates as high as 30% to 40% with RA in IMR have been reported. MV replacement, although more effective and durable in addressing IMR, is associated with greater operative risk and greater long-term risks of thromboembolism, valve deterioration, and endocarditis.7Gillinov A.M. Wierup P.N. Blackstone E.H. et al.Is repair preferable to replacement for ischemic mitral regurgitation?.J Thorac Cardiovasc Surg. 2001; 122: 1125-1141Abstract Full Text Full Text PDF PubMed Scopus (454) Google Scholar, 8Reece T.B. Tribble C.G. Ellman P.I. et al.Mitral repair is superior to replacement when associated with coronary artery disease.Ann Surg. 2004; 239: 671-675Crossref PubMed Scopus (70) Google Scholar, 9Al-Radi O.O. Austin P.C. Tu J.V. David T.E. Yau T.M. Mitral repair versus replacement for ischemic mitral regurgitation.Ann Thorac Surg. 2005; 79: 1260-1267Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar, 10Vassileva C.M. Boley T. Markwell S. Hazelrigg S. Meta-analysis of short-term and long-term survival following repair versus replacement for ischemic mitral regurgitation.Eur J Cardiothorac Surg. 2011; 39: 295-303Crossref PubMed Scopus (124) Google Scholar The National Heart, Lung and Blood Institute–sponsored Cardiothoracic Surgical Trials Network (CTSN) sought to address this controversy by comparing chordal-sparing MV replacement with RA in 251 patients with severe IMR.4Acker M.A. Parides M.K. Perrault L.P. et al.Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.N Engl J Med. 2014; 370: 23-32Crossref PubMed Scopus (544) Google Scholar, 5Goldstein D. Moskowitz A.J. Geijins A.C. et al.Two year outcomes of surgical treatment in severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (446) Google Scholar Chordal-sparing MV replacement resulted in a significant reduction over RA in the prevalence of MR at 1 year (2.3% vs 32.6%) and 2 years (3.8% vs 58.8%). There was no difference between the 2 groups in the degree of LV reverse remodeling, New York Heart Association functional class, LV ejection fraction, survival, or major adverse cardiac and cerebrovascular events at 1 and 2 years. Although the rates of serious adverse events and overall hospital readmissions were comparable, patients undergoing repair had more frequent serious adverse events related to heart failure and cardiovascular readmissions at 2 years. Collectively, these data support the use of MV replacement in the setting of severe IMR. Critics of the CTSN trial believe that the high prevalence of MR with RA was related to surgical deficiencies in the conduct of the CTSN trial, including the finding that only 75% of patients received concomitant CABG surgery (eliminating the possibility of improved regional wall motion in 25% of patients) and undersizing of the mitral annulus with RA was insufficient (limiting the ability of the leaflets to form an improved zone of coaptation to reduce tenting height and tenting area).6Nappi F. Lusini M. Spadaccio C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation: a randomized trial.J Am Coll Cardiol. 2016; 24: 2334-2346Crossref Scopus (98) Google Scholar In the Papillary Muscle Approximation Randomized Trial, Nappi and colleagues6Nappi F. Lusini M. Spadaccio C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation: a randomized trial.J Am Coll Cardiol. 2016; 24: 2334-2346Crossref Scopus (98) Google Scholar achieved a 2-year prevalence of MR with RA of 13.2%, which they claimed was the result of more effective annular reduction as seen by a greater mean difference between annular size and ring size compared with the CTSN trial. Herein lies the controversy because in recent years, respected surgeons have strongly advocated for overcorrection RA (“the tighter, the better”). However, an overcorrection strategy is beginning to show signs of unraveling as we grow in our understanding that (1) RA does not reliably prevent persistence or recurrence of moderate to severe IMR; (2) overcorrected RA does lead to mitral stenosis, and (3) excessive restriction using severely undersized annuloplasty rings is associated with exacerbating leaflet tethering.4Acker M.A. Parides M.K. Perrault L.P. et al.Mitral-valve repair versus replacement for severe ischemic mitral regurgitation.N Engl J Med. 2014; 370: 23-32Crossref PubMed Scopus (544) Google Scholar, 5Goldstein D. Moskowitz A.J. Geijins A.C. et al.Two year outcomes of surgical treatment in severe ischemic mitral regurgitation.N Engl J Med. 2016; 374: 344-353Crossref PubMed Scopus (446) Google Scholar, 11Capoulade R. Zeng X. Overbey J.R. et al.Impact of left ventricular to mitral valve ring mismatch on recurrent ischemic mitral regurgitation after ring annuloplasty.Circulation. 2016; 134: 1247-1256Crossref PubMed Scopus (41) Google Scholar This last point deserves further explanation. A post hoc analysis by the CTSN investigators highlights the importance of understanding the impact of RA on the spatial relationship between the left ventricle and the mitral annulus.11Capoulade R. Zeng X. Overbey J.R. et al.Impact of left ventricular to mitral valve ring mismatch on recurrent ischemic mitral regurgitation after ring annuloplasty.Circulation. 2016; 134: 1247-1256Crossref PubMed Scopus (41) Google Scholar RA has the potential to disrupt this ischemia-induced abnormal geometric spatial relationship further by exacerbating tethering of the posterior leaflet, especially if the ischemic papillary muscles remain laterally and apically displaced relative to the mitral annulus. Because the anterior leaflet is attached to the fibrous trigones, it is the posterior leaflet that is primarily affected by RA, and the mitral annular area is decreased by reducing the anterior-posterior dimension. If the posterior-inferior-lateral wall of the left ventricle remains displaced, there will be an increase in the geometric mismatch between the left ventricle and the mitral annulus and an exacerbation of posterior leaflet tethering with overcorrection RA. With this in mind, the CTSN investigators evaluated the ratio of LV end-systolic dimension (LVESD) to prosthetic annuloplasty ring size and its ability to predict the risk of persistent or recurrent MR after RA.11Capoulade R. Zeng X. Overbey J.R. et al.Impact of left ventricular to mitral valve ring mismatch on recurrent ischemic mitral regurgitation after ring annuloplasty.Circulation. 2016; 134: 1247-1256Crossref PubMed Scopus (41) Google Scholar The CTSN investigators identified that a ratio of LVESD to ring size of 2 or greater was associated with an increased risk of persistent or recurrent MR. Increased tethering between the papillary muscle and the leaflet edge may be produced by overcorrection of the annular dimension. Thus, RA is a necessary, but insufficient procedure in the treatment of severe IMR. Surgeons can readily assess this issue in the preoperative evaluation and plan accordingly in the operating room. However, will this be enough to ensure the elimination of MR in the operating room and provide a durable result with RA alone? A logical adjuvant to appropriate-sized annular correction with RA is to reduce the LVESD. Theoretically, this would have a result opposite to that of annular overcorrection by bringing the papillary muscle closer to the mitral leaflet edge, thereby reducing tethering forces. It is well recognized that reanimating ischemic muscle through coronary revascularization and improved regional wall motion will reduce LVESD. Given that one cannot reliably predict preoperatively the degree of regional wall motion improvement achievable with revascularization alone (and the likelihood of reducing LVESD and IMR), one may wish to consider additional ventricular surgical procedures that have been advocated as a complement to an appropriately sized RA. Papillary muscle approximation (PMA) has been advocated and studied by Nappi and colleagues in patients with severe IMR as an adjuvant ventricular procedure to reduce LVESD and thus posterior leaflet tethering.6Nappi F. Lusini M. Spadaccio C. et al.Papillary muscle approximation versus restrictive annuloplasty alone for severe ischemic mitral regurgitation: a randomized trial.J Am Coll Cardiol. 2016; 24: 2334-2346Crossref Scopus (98) Google Scholar In this issue of The Annals of Thoracic Surgery, Nappi and colleagues12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar evaluated preoperative echocardiograms in the population of patients who underwent CABG and in combination with RA and PMA in the Papillary Muscle Approximation Randomized Trial. Nappi and colleagues12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar sought to determine whether any baseline echocardiographic parameter served as a marker for MR recurrence. Of the 48 patients who underwent CABG with RA and PMA, 37 survived to 5 years and constituted the study population available for matched clinical and echocardiographic evaluation. At baseline, 21 patients had moderate to severe MR, and 16 had severe MR. Of the 37 patients, 31 left the operating room with no MR or trace MR, and 6 had mild MR. By 5 years, 27 (73%) had no MR or trace MR, 9 (24.3%) had moderate MR, 1 (2.7%) had moderate to severe MR, and no patients had severe MR. Therefore, at 5 years, a very durable reduction in MR severity was achieved with RA plus PMA, and no patients had severe MR. Nappi and colleagues12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar do not comment on the clinical condition of these 10 patients with moderate MR and whether they had more frequent heart failure events or hospitalizations. However, moderate MR is generally well tolerated with guideline medical therapy. These excellent results surpass those of other published reports of late MR prevalence in severe IMR treated by RA alone. In addition, the results surpass the other arm of the Papillary Muscle Approximation Randomized Trial. In that arm, at 5 years, 34 of 48 surviving patients who underwent CABG and RA alone experienced a 55.9% prevalence of moderate or greater MR, despite having a prevalence of 15% at 2 years (38 patients). Despite time delayed in achieving a significant level of MR severity, the data are consistent with the data from the CTSN trial and other published reports demonstrating a significant prevalence of late MR with RA alone. Consistent with the reduction in MR prevalence, patients who underwent CABG in combination with RA and PMA experienced a significant improvement over baseline in LV ejection fraction, reverse LV remodeling, MV tenting height, MV tenting area, and interpapillary muscle distance. These improvements were further magnified when the 27 patients with no MR or trace MR were compared with the 10 patients with moderate or greater MR. Predictive statistical modeling identified preoperative factors associated with persistent or recurrent MR after revascularization in combination with RA and PMA: (1) MV tenting area larger than 3.1 cm2, (2) LV end-diastolic dimension (LVEDD) greater than 64 mm, and (3) LVESD greater than 54 mm. These findings make intuitive sense because these markers are all consistent with very large ischemic remodeled ventricles, which are less likely to recover sufficient regional and global function and thus to undergo reverse remodeling after CABG. Our current understanding of the surgical techniques for performing an RA and a PMA procedure provides little insight into how we could adjust these procedures in the operating room to deal with the severely dilated and remodeled left ventricle. Although the surgeon may be driven to overcorrect the RA in such a circumstance (to achieve an adequate intraoperative result), it is precisely in these situations that MV replacement should be the recommended option. Considering the dilated remodeled ventricle and those factors associated with late recurrence outlined by Nappi and coauthors12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar prompt one to ask why these investigators limited the correction by PMA to only a 25% reduction in the end-diastolic interpapillary muscle distance. Is it possible that a more aggressive reduction to 50% or even the elimination of any distance between the papillary muscles would result in a more effective reduction in LVESD and less recurrent MR? This is certainly a question worth addressing in an animal model of IMR. Finally, there is ample evidence to pursue an appropriate reparative strategy for patients with severe IMR that includes both an annular and a ventricular procedure. The CTSN trial provided an intriguing example. Those 74 patients in the CTSN trial with severe IMR who did not experience persistent or recurrent MR after RA had a dramatically smaller left ventricle at 2-year follow-up compared with those patients with recurrent MR after RA alone (43 ± 26 mL/m2 vs 63 ± 27 mL/m2) and, surprisingly, when compared with those patients who underwent MV replacement (61 ± 39 mL/m2). We must pursue a better understanding of how to achieve this clinical goal of LV reverse remodeling through continued rigorous evaluation of mitral annular and LV geometric relationships in ischemic heart disease. In summary, the choice MV procedure to perform in severe ischemic MR has been an evolving discussion with advocates for both an MV replacement and an MV reparative procedure. The data provided by Nappi and colleagues12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar add significantly to our understanding and have practical therapeutic relevance. Surgical decision making in patients with severe IMR is enhanced by preoperative identification of those patients most likely to have an improvement in regional wall motion and global LV function after CABG. Preoperative evaluation of myocardial viability, echocardiographic assessment of regional and global LV systolic function, and echocardiographic assessment of MV tethering parameters can help in the planning of which MV procedure to perform. Cardiac magnetic resonance imaging with gadolinium hyperenhancement is an appropriate tool when findings on echocardiographic or radionuclide imaging are equivocal or in patients suspected to have LV scar. Individual treatment decisions require balancing the risks of adverse perioperative events for each therapy against the predicted benefits of a lower incidence of postoperative MR, better reverse remodeling, and improved clinical outcomes. Geometric parameters that favor an MV replacement over an MV reparative procedure have been further clarified by Nappi and colleagues,12Nappi F. Lusini M. Singh S.S.A. Santana O. Chello M. Mihos C.G. Risk of ischemic mitral regurgitation recurrence after combined valvular and subvalvular repair.Ann Thorac Surg. 2019; 108: 536-543Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar and they include patients with large ventricles (LVESD >55 mm and LVEDD >65 mm), MV tenting area larger than 3 cm2, and factors previously known such as documented scar or basal aneurysm or dyskinesia in the inferior-posterior-lateral left ventricle and poor coronary targets in the circumflex or right coronary distributions because of the reduced likelihood that revascularization will provide significant enhancement of LV contractility and LV reverse remodeling. Recognition of the likelihood of a durable repair after CABG plus RA and PMA in patients presenting with a nondilated LV, low MV tenting area, and good coronary targets should influence surgeons to favor MV reparative therapy over MV replacement. Restrictive annuloplasty and papillary muscle approximation combined with CABG is an appropriate option in patients with severe IMR. Risk of Ischemic Mitral Regurgitation Recurrence After Combined Valvular and Subvalvular RepairThe Annals of Thoracic SurgeryVol. 108Issue 2PreviewMitral valve repair (MVr) combined with papillary muscle approximation (PMA) may improve repair durability in severe ischemic mitral regurgitation (MR), when compared with MVr alone. We sought to identify preoperative transthoracic echocardiographic markers associated with MR recurrence after MVr with PMA. Full-Text PDF Pathophysiologic Mechanisms of Subvalvular Repair and Its Clinical ImplicationsThe Annals of Thoracic SurgeryVol. 110Issue 1PreviewThe observations by Dr Michler,1 as well as by our group, should provide food for thought and potentially lead to revisiting the randomized clinical trials published on the subject that require another type of surgical comparison: a “complete mitral repair” (ie, involving both the valvular apparatus and subvalvular)2 vs chordal-sparing mitral replacement3 and the Mitraclip (Abbott Vascular, Santa Clara, CA) procedure.4,5 Full-Text PDF
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