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CONTROVERSIES IN HEART FAILURE Should Moderate or Greater Mitral Regurgitation Be Repaired in All Patients With LVEF <30%? Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 Surgery, Mitral Regurgitation, and Heart Failure The Valves Are All Repairable But the Patients Are Not Edwin C. McGee, Jr, MD D espite advances in medical and surgical therapy, heart failure continues to be a formidable problem. More than 5 million individuals are affected by heart failure in the United States, and it is estimated that 550 000 new cases are diagnosed annually (www.americanheart.org). Advances have been made with medical therapy and cardiac resynchronization, but despite such measures, outcomes remain poor in individuals with advanced heart failure.1 Cardiac transplantation, the ultimate therapy for end-stage heart failure, is plagued by the limited supply of donor hearts and the need for lifelong immunosuppression. It remains, and will always be, a therapy that benefits, at best, only a few thousand individuals each year. Ventricular assist devices are improving but are still limited by problems such as infection and thromboembolism. Although several promising ventricular assist devices are in trial or recently approved, they are only available for those with the most advanced heart failure.2,3 For all intents and purposes the field of mechanical assistance remains, if not in its infancy, in its childhood. Many patients once thought to need transplant can benefit from conventional surgery like bypass and valve repair. Mahon et al4 from the Cleveland Clinic demonstrated equivalent intermediate survival for transplant and conventional surgery in a group of patients initially referred for transplant. We have learned from the ventricular reconstruction literature that many patients with advanced cardiomyopathy can have excellent long-term survival after conventional surgery.5–7 Surgeons who frequently deal with ischemic cardiomyopathy now no longer focus on left ventricular function, but rather the degree of hibernating myocardium that can be revascularized.8 Modern surgical heart failure specialists look for targets of opportunity which, when corrected, will help their patients’ compromised ventricles function more efficiently and potentially reverse remodel. Many heart failure patients can benefit from conventional surgical repairs but it is naïve to think that all patients with cardiomyopathy will benefit from standard surgeries like coronary bypass and valve repair. The critical issue is discerning those patients that will benefit from those that will not. In other words, when is enough, enough? Surgeons tend to be ego driven and appreciate sports analogies. We love to make first downs and put points on the board. We love it when our patients do well and manifest dramatic improvements. However, our “interceptions” do not lead to turnovers but rather patient morbidity and sometimes death. A key to successful conventional heart failure surgery The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part II of a 2-part article. Part I appears on page 281. From the Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, and Department of Surgery, Northwestern University’s Feinberg School of Medicine, Chicago, Ill. Correspondence to Edwin C. McGee, Jr, MD, Heart Transplantation and Mechanical Assistance, Cardiac Surgery, 201 East Huron St, Suite 11-140, Chicago, IL 60611. E-mail [email protected] (Circ Heart Fail. 2008;1:285-289.) © 2008 American Heart Association, Inc. Circ Heart Fail is available at http://circheartfailure.ahajournals.org 285 DOI: 10.1161/CIRCHEARTFAILURE.108.800185 286 Circ Heart Fail November 2008 Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 is being able to discriminate the patients that will improve from those that will not benefit or be potentially harmed from a surgical procedure. It is critical to recognize that in some patients it is often wise to “punt,” to therapies such as transplant or ventricular assist device (VAD), as opposed to trying a risky “Hail Mary” type conventional procedure. One size does not fit all. With these concepts in mind, how do we address the heart failure patient with significant (3⫹/4⫹) functional mitral regurgitation (MR)? MR is certainly an appealing target for surgical intervention, as significant functional MR is present in 49% of patients with heart failure.9 Functional MR is caused either by annular dilatation (Carpentier type I) or posterior leaflet restriction (Carpentier type IIIB).10) The former pathology is found in dilated cardiomyopathy; the latter is the hallmark of chronic ischemic MR. Both of these forms of cardiomyopathy account for most cases of heart failure in the developed world and are the leading diagnoses of patients on our cardiac transplant waiting lists.11 In functional MR, the leaflets are normal. Mitral repair in these patients is easily accomplished by ring annuloplasty and is straight forward. The question that begs is, “why not apply it to all heart failure patients” with significant MR? If we can fix their valves and alleviate MR, should not we do it before resorting to other “drastic” therapies? Does not unrepaired MR drive ventricular remodeling and thus fuel the heart failure epidemic? Should not all of these individuals undergo mitral valve repair (MVR) to give their ventricles a shot at reverse remodeling? Without question, any heart failure patient for whom mitral repair is being considered for functional MR should be optimally medically managed with -blockers and angiotensin-converting enzyme inhibitors. Optimal medical management is the cornerstone of modern heart failure therapy. In addition to providing a survival benefit, pharmacological therapy may reduce the severity of functional MR.12 Furthermore, cardiac resynchronization therapy can decrease MR in select patients.12 However, in many patients severe functional MR persists or recurs despite the above measures. Repair is an attractive option in these patients but must be considered before end organ dysfunction becomes irreversible or right ventricular function becomes impaired, as such conditions increase the risk of operative intervention and impact on long-term outcomes.13–15 Advanced cardiac failure impacts greatly on end organ function. Reversible end organ dysfunction can be improved by improving cardiac output by the short-term use of inotropes. Irreversible renal failure or hepatic failure does not respond to improved cardiac output and conventional surgical procedures in such patients are bound to fail. Indeed, our group rarely offers conventional surgery to inotrope dependent heart failure patients unless they have obstructive valvular pathology or are thought to have a great deal of hibernating myocardium.16 We generally feel that patients with MR whose ventricles are so compromised as to require inotropes to maintain end organ perfusion are best managed by transplant or mechanical assistance as destination therapy. What about the patients we can help? Is it safe to repair mitral valves in heart failure patients? The answer to this question is an emphatic “yes.” It was once thought that all patients with ventricular dysfunction and MR would suffer if their mitral valves were made competent as they would lose their pop-off valve.17 The “pop-off” theory has been disproved. Bolling18 was the first to demonstrate that MVR could be safely performed in patients even with the most compromised ventricles. In landmark studies from the University of Michigan, 140 patients (New York Heart Association class III/IV) with a mean ejection fraction of 26% underwent a downsized mitral annuloplasty with an operative mortality of 5%.18 Reverse ventricular remodeling, as evidenced by a decreased left ventricular end-diastolic diameter and improvement in ventricular ejection fraction, New York Heart Association class, and sphericity index were also demonstrated.19 Bishay et al20 at the Cleveland Clinic demonstrated an operative mortality of 2.3% in 44 patients with severe MR and severe left ventricular dysfunction, and also demonstrated reverse ventricular remodeling. The Acorn trial looked at outcomes of heart failure patients treated with and without the Acorn cardiac support device.21 Those patients with significant MR (N⫽193) underwent mitral surgery alone or mitral surgery plus placement of the Acorn cardiac support device.22 Again an impressively low operative mortality of 1.3% was demonstrated in the MVR stratum, along with concrete evidence of reverse remodeling, and improved quality of life.23 However, it is important to understand that the Acorn trial was not designed as a head-to-head comparison of MVR and medical therapy. It is also important to realize that in all of these studies the very low operative mortality rate is in part attributed to the fact that some of the patients required bale out with mechanical assistance and/or transplant. For example, the MVR stratum (control arm) of the Acorn trial with its impressively low operative mortality had 8 patients that needed support with a VAD and 16 ultimately required transplant.23 These studies clearly show that select patients with severe left ventricular dysfunction and severe MR can safely undergo ring annuloplasty and that their ventricles improve and that quality of life improves. However, none of these studies demonstrate an improvement in survival. In fact, a propensity matched retrospective study by Wu et al24 from the University of Michigan, showed no improvement in survival for the patients that underwent annuloplasty when compared with optimal medical management (Figure 1). The authors conclude that a randomized trial is needed to better ascertain outcomes for patients with ventricular dysfunction undergoing MVR.24 Prospective randomized trials are difficult to conduct in surgical populations. Is there anything we can do short of a head-to-head comparison of optimal medical therapy versus mitral repair for severe functional MR, that can be undertaken? Can we delve deeper into the current literature to see McGee Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 Figure 1. Event-free survival for non–mitral valve annuloplasty group (solid line) and mitral valve annuloplasty group (dotted line).24 if we can elucidate which patients derive long-term benefit from repair and which patients stay the same or worsen? Ischemic mitral regurgitation (IMR) results from tethering of the posterior mitral leaflet.10 It is truly a vexing problem. Patients with IMR have been treated with revascularization alone or revascularization plus mitral annuloplasty. The repair is technically straight forward but many groups have become nihilistic about the benefits of adding mitral annuloplasty for IMR given the high prevalence of recurrent MR and the lack of demonstrable survival benefit. A series of 585 patients with IMR that underwent mitral annuloplasty at the Cleveland Clinic demonstrated 30% rate of recurrent significant MR (3⫹/4⫹) at 1-year follow-up25 (Figure 2). A series of 390 patients also from the Cleveland Clinic compared the long-term functional status and survival in patients with IMR treated with coronary bypass alone and bypass plus mitral annuloplasty. Despite improved rates of early MR in the group receiving annuloplasty,26 no difference either in terms of 5-year functional status or survival was demonstrated26 (Figure 3). How do we explain this lack of benefit? Recurrent functional MR is often explained away as being the result of a “ventricular problem.” Valvular regurgitation in these patients is secondary to annular dilatation or leaflet tethering and is not caused by leaflet pathology per say. When these patients do poorly their bad ventricles and the lack of effective therapy for said bad ventricle is given as the response. Certainly for some patients that is the case but then why do some patients with functional MR manifest a benefit from alleviating their MR. We are faced with the question of whether the lack of benefit purely is the result of recurrence or is the recurrence of significant MR a marker for a ventricle that has passed the point of no return. In terms of the issue of recurrent MR, are we doing all that we can do to prevent recurrence? Are some methods of ring Functional Mitral Regurgitation in Heart Failure 287 Figure 2. Recurrent ischemic MR and the effect of annuloplasty type on return of 3⫹ or 4⫹ MR. The number of echocardiograms available at various time points is indicated, with the number of patients in parentheses. Symbols represent crude estimates of grouped raw data. Carpentier indicates CarpentierEdwards classic annuloplasty ring; Cosgrove, CosgroveEdwards annuloplasty system; Peri-Guard, bovine pericardial annuloplasty.25 annuloplasty more prone to recurrence than others? It was long thought that only the posterior annulus dilates. The intertrigonal or anterior annulus was thought to be fixed. Recent human cadaveric studies have shown that proportional dilatation occurs about the entire annulus and that the intertrigonal distance is not fixed.27 Miller’s28 group at Stanford has demonstrated intertrigonal dilation in an ovine model of chronic IMR and recommend that IMR is best managed by fixation of the intertrigonal and septal lateral dimension with a complete annuloplasty ring.29 Spoor et al30 from the University of Michigan, in a study looking at risks of recurrent MR in patients with functional MR and heart failure, identified the use of flexible rings as a risk factor for recurrent MR. Although ring type was not identified as a risk for recurrent MR in the Cleveland series, most patients in that series received partial, flexible rings.25 I think it is fair to argue that at least some of the high recurrence rate in this study was due to an annuloplasty technique that many feel is not adequate by today’s standards; conversely, many patients in this series were likely past the point of no return in terms of their ventricular pathology. At any rate, it is not fair or accurate to blame the high recurrence rate in this series completely on the underlying pathology. A recent study by Braun et al31 from the Netherlands may shed some light on when patients pass the point of no return. One hundred consecutive patients with IMR underwent coronary revascularization plus mitral annuloplasty with downsized complete rings.31 Only 1 of 75 patients available for late follow-up had ⬎2⫹ MR,31 which is clearly an improvement over the 20% rate of significant (3⫹/4⫹) recurrent MR in the Cleveland Clinic series.25 In an earlier report from the group in Leiden, a preoperative left ventricular end-diastolic diameter ⬍65 mm was predicative of reverse ventricular remod- 288 Circ Heart Fail November 2008 Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 Figure 3. Survival after coronary artery bypass grafting either alone or with concomitant mitral valve annuloplasty for functional ischemic MR.26 eling.32 In this most recent series, patients with an left ventricular end-diastolic diameter ⬍65 mm had a 5-year survival of 80% compared with a 49% 5-year survival in patients with a preoperative left ventricular end-diastolic diameter of ⬎65 mm.31 A study from Roshanali et al33 identified an interpapillary muscle distance of ⬎20 mm as a risk factor for recurrent IMR after repair. Calafiore et al34 identified tent height, defined as the distance between the mitral annulus and point of leaflet coaptation, ⬎10 mm as a risk factor for failure after annuloplasty for IMR. All of these measurements are surrogates for large, end stage ventricles. Patients with any of these parameters should certainly undergo conventional surgery such as mitral repair with caution. It is important to realize that many heart failure patients with functional MR will benefit from repair. It is equally important to realize that not all heart failure patients will manifest improvement after repair of functional MR. We have ample evidence that repair can be accomplished in sick patients with advanced heart failure with low morbidity and mortality, but patients with severely remodeled ventricles, right ventricular dysfunction, and end organ failure have likely missed their therapeutic window. Despite evidence of reverse ventricular remodeling and improved ventricular function, retrospective studies have failed to demonstrate a survival benefit for heart failure patients undergoing MVR, in part because such studies are no doubt comparing apples and oranges. Some patients are salvageable whereas others are McGee past the point of no return. A prospective randomized study is needed to address the issue. Until such a study occurs, certainly not all patients with an ejection fraction ⬍30% and significant functional MR should undergo repair. As clinicians we need to focus on markers that identify patients that have passed their window of opportunity. Certainly, questionable cases should be undertaken in centers that have experience in managing heart failure patients and that can offer advanced techniques as salvage therapy. As surgeons we have a great deal to offer heart failure patients but one size does not fit all and sometimes a punt is better than a Hail Mary. Functional Mitral Regurgitation in Heart Failure 14. 15. 16. 17. 18. Disclosures Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 None. 19. 20. References 1. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, Long JW, Ascheim DD, Tierney AR, Levitan RG, Watson JT, Meier P, Ronan NS, Shapiro PA, Lazar RM, Miller LW, Gupta L, Frazier OH, Desvigne-Nickens P, Oz MC, Poirier VL. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med. 2001;345:1435–1443. 2. Esmore DS, Kaye D, Salamonsen R, Buckland M, Begg JR, Negri J, Ayre P, Woodard J, Rosenfeldt FL. Initial clinical experience with the VentrAssist left ventricular assist device: the pilot trial. J Heart Lung Transplant. 2008; 27:479–485. 3. Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, Conte JV, Naka Y, Mancini D, Delgado RM, MacGillivray TE, Farrar DJ, Frazier OH. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885– 896. 4. Mahon NG, O’Neill JO, Young JB, Bennett R, Hoercher K, Banbury MK, Navia JL, Smedira NG, McCarthy PM, Starling RC. Contemporary outcomes of outpatients referred for cardiac transplantation evaluation to a tertiary heart failure center: impact of surgical alternatives. J Card Fail. 2004;10:273–278. 5. Athanasuleas CL, Buckberg GD, Stanley AW, Siler W, Dor V, Di Donato M, Menicanti L, Almeida de Oliveira S, Beyersdorf F, Kron IL, Suma H, Kouchoukos NT, Moore W, McCarthy PM, Oz MC, Fontan F, Scott ML, Accola KA. Surgical ventricular restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. J Am Coll Cardiol. 2004;44:1439 –1445. 6. O’Neill JO, Starling RC, McCarthy PM, Albert NM, Lytle BW, Navia J, Young JB, Smedira N. The impact of left ventricular reconstruction on survival in patients with ischemic cardiomyopathy. Eur J Cardiothorac Surg. 2006;30:753–759. 7. Mickleborough LL, Maruyama H, Liu P, Mohamed S. Results of left ventricular aneurysmectomy with a tailored scar excision and primary closure technique. J Thorac Cardiovasc Surg. 1994;107:690 – 698. 8. 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Surgery, Mitral Regurgitation, and Heart Failure: The Valves Are All Repairable But the Patients Are Not Edwin C. McGee, Jr Downloaded from http://circheartfailure.ahajournals.org/ by guest on May 12, 2017 Circ Heart Fail. 2008;1:285-289 doi: 10.1161/CIRCHEARTFAILURE.108.800185 Circulation: Heart Failure is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2008 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-3289. Online ISSN: 1941-3297 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circheartfailure.ahajournals.org/content/1/4/285 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation: Heart Failure can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. 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