Functional mitral regurgitation (FMR) is a complication of ischemic or dilated cardiomyopathy, occurring secondary to left ventricular (LV) geometrical distortion from tenting, inferobasilar migration, apical displacement, annular dilation and posterior leaflet restriction, and/or regional LV wall dysfunction. MR leads to a vicious cycle of LV volume overload, increased geometric distortion and progressive MR. FMR complicating congestive heart failure predicts a poor survival. Mitral surgery, to treat FMR has been undertaken with an acceptably low operative mortality. However, the exact MR surgery (repair or replacement) for which patient and what benefit, remains controversial.

Congestive heart failure is one of the world’s leading causes of morbidity and mortality. As our population ages, the number of patients suffering from end-stage heart failure will continue to rise. In the United States alone, there are nearly 7 million patients suffering from heart failure. In 2012, heart failure “therapy” cost the United States over $50 billion. This total includes health care services, medications, and lost productivity. Yet of the 700,000 new congestive heart failure (CHF) patients diagnosed each year, less than 3000 are offered transplantation due to limitations of age, comorbid conditions and donor availability. Even fewer are presently served with a mechanical assist device. One of the most common (up to 50% of patients) and serious problems in cardiomyopathy is the development of functional or secondary mitral regurgitation. Functional mitral regurgitation (FMR), nonorganic mitral valve (MV) disease, may eventually affect almost all heart failure patients as a preterminal or terminal event.¹ FMR is not caused by intrinsic disease of the valve, but by left ventricular (LV) remodeling, dilation, and dysfunction leading to geometric reconfiguration of the mitroventricular apparatus, including papillary muscle displacement and annular dilation. MV leaflets become tethered, with failure of anterior-posterior leaflet coaptation, resulting in symmetric or asymmetric regurgitation.^2,3 The progressive dilatation of the left ventricle initially gives rise to FMR that begets further ventricular dilatation and more FMR. FMR is associated with poor quality of life and a reduction in long-term survival. Mitral surgery, while not addressing the underlying ventricular pathology, hopefully could interrupt this cycle of ventricular deterioration through the restoration of mitral competency.

It has been well documented that even small amounts of FMR are harmful in CHF patients. Grigioni et al⁴ showed that when FMR regurgitant volume was >30 ml the 5-year survival was <35% compared to 44% for a regurgitant volumes of 1 to 29 ml and 61% for CHF patients with no MR. Bursi⁵ also examined the role of FMR and its impact in CHF. CHF patients (469) were followed for mortality according to severity of their FMR. Their 5-year survival was 83% in patients with no/1+ FMR, 64% in 2+, 58% in 3+, and 46% in 4 + (p < .0001). The association between FMR and Major Adverse Cardiac and Cerebrovascular Events (MACCE) was strong and independent in this propensity matched analysis. A further study⁶ denoted that among 303 patients post MI, ischemic MR was present in 194 (64%), and was a significant independent predictor of long-term mortality (relative risk, RR [95% confidence interval, CI] = 1.88, p = .003).¹ Additionally, in a study from the Duke Cardiovascular Databank,⁷ 3-4+ FMR was present in 30% of 2057 HF patients with an left ventricular ejection fraction (LVEF) < 40%, and was an independent predictor of 5-year mortality (adjusted hazard ratio [95% CI] = 1.23).² Lastly, the Mayo Clinic⁸ looked at the prognostic implications of FMR in patients with advanced systolic CHF in a heart failure clinic. Of 558 NYHA III-IV patients, those with at least moderate MR had a 5-year survival of only 27%. These studies demonstrate that FMR is not just a sign of advanced CHF, but an independent determinant of CHF death. That FMR is bad for CHF patients is supported by many other studies that show that the severity of MR impacts quality of life, as well as survival. Furthermore, there is a strong association between the presence of ischemic FMR severity and heart failure hospitalizations. However, while the presence of FMR predicts a poor prognosis in patients with left ventricular dysfunction and heart failure, unfortunately, “proof” that correction of FMR improves prognosis remains elusive.

Historically, the surgical approach to FMR was nonvalve sparing MV replacement, at a time when little was understood of the interdependence of ventricular function and the annular-papillary muscle continuity. Consequently, patients with low EF who underwent MV replacement with removal of the subvalvular apparatus had prohibitively high mortality rates. As explanation the erroneous concept of a beneficial “pop-off” effect of FMR was conceived. This idea erroneously proposed that mitral incompetence provided low-pressure relief during systolic ejection for the failing ventricle, and that removal of this effect through mitral replacement was responsible for the perioperative deterioration of ventricular function. Consequently, MV replacement in patients with heart failure and FMR was discouraged.

A firm understanding of the anatomy of the MV is fundamental to the surgical management of FMR. The MV apparatus consists of the annulus, leaflets, chordae tendineae, and papillary muscles as well as the entire left ventricle. These structures form a “closure cylinder” with the papillary musculature directly aligned beneath the annulus. Most importantly, the maintenance of chordal, annular, and subvalvular continuity is essential for the preservation of mitral geometric relationships, as well as ventricular twist mechanics and systolic power. MR in heart failure is not primarily related to the valve but to ventricular pathology. The degree of LV distortion reflects the degree of MR. As the ventricle fails, progressive dilatation of the LV results in outward papillary muscle migration, alteration of the closure cylinder, and thus loss of the zone of coaptation (Fig. 37-1).

The end result of progressive FMR and global ventricular remodeling is similar regardless of the etiology of cardiomyopathy. The primary lesion in ischemic FMR is leaflet tethering, which results from ventricular remodeling associated with an ischemic insult. Posterior-lateral and apical displacement of the papillary muscles, which correlates with a measurable “tethering distance,” leads to apical tenting and restriction of the free margin of the leaflets and poor leaflet coaptation. Tethering of secondary chordae can lead to a “seagull” deformation of the anterior leaflet. Although both papillary muscles may be displaced, the posterior papillary muscle usually predominates, which leads to tethering of the “P3” leaflet segment.^9,10 This is seen in posterior infarction related to the posterior descending artery distribution and the mitral regurgitation jet is usually eccentric and posteriorly directed along the P3 area which is restricted (Fig. 37-2). In contrast, left anterior descending infarction leads to more global remodeling involving both papillary muscles, and more diffuse leaflet tethering with large central jets of mitral regurgitation. Although annular dilatation and ventricular remodeling accompanies all MR, it is usually an associated finding, as opposed to a primary causal lesion in ischemic mitral regurgitation. The degree of annular dilatation is much less in ischemic mitral regurgitation than in degenerative mitral regurgitation, which is one of the reasons that “downsizing” of the mitral ring annuloplasty may best address leaflet tethering in ischemic MV regurgitation. Conversely, FMR associated with dilated cardiomyopathies tends to have more symmetric distortion with more annular dilation than asymmetric ischemic FMR.^11,12 Because of this difference in geometric distortion, as well as patient comorbidity profiles, it may be that dilated and ischemic FMR patients should be thought of and treated in somewhat different manners.

Despite the underlying pathology, the goals of therapy for FMR patients are to improve symptoms and quality of life, reduce heart failure hospitalization, and, hopefully to improve survival. The therapies shown to be most effective for FMR are those directed at the underlying LV dysfunction, most importantly guideline-directed medical therapy (GDMT) for HF.^1,13-15 Cardiac resynchronization (with or without a defibrillator) if indications are met (wide QRS > 150 ms) should also be considered when appropriate.^16,17 Finally of course, coronary revascularization should be performed in patients with ischemia and myocardial viability. While all patients with FMR should receive GDMT for management of CAD, LV dysfunction and heart failure, unfortunately morbidity and mortality of patients with CHF and secondary FMR remains high. A recent study showed that among 404 FMR patients treated with GDMT, 4-year cardiac mortality occurred in 43 and 45% with moderate and severe MR, respectively, compared to only 6% with mild MR (p = .003).¹³ Furthermore, moderate or severe FMR was also shown to be a high independent predictor of new onset HF in patients with ischemic LV dysfunction (RR = 3.2, p = .0001). The role of surgical MV repair or replacement is to potentially interrupt the vicious cycle of LV volume overload causing LV dilatation leading to secondary MR, which further increases LV volume overload and dilatation further increasing MR.

The present AHA/ACC Valve Guidelines (2014) and the ESC/EACTS Guidelines^18,19 have separate guidelines for functional or secondary ischemic mitral regurgitation (FMR). As noted, these guidelines state that treating ischemia with coronary artery bypass grafting or percutaneous methods should be primarily undertaken for FMR. Additionally, all FMR patients should have guideline GDMT, with consideration for CRT, if they have a QRS greater than 150 ms. However, if the patients remain symptomatic with severe mitral regurgitation or stage D disease, they may be considered for “MV surgery” as a 2B indication. Yet, from the surgeon’s perspective, while it is recommended that surgical correction of FMR should be considered exactly how to successfully correct FMR remains unclear. Currently, the most common technique to restore valve competence is placing an undersized or restrictive annuloplasty ring to reduce mitral annulus size and increase leaflet coaptation. Unfortunately, ischemic FMR may persist or recur after restrictive MV annuloplasty. Persistent or recurrent FMR in post op patients is understandably associated with unabated ventricular dilatation, an escalation of CHF symptomatology and possible reduction in long-term survival.

Surgical mitral annuloplasty improves symptoms in patients with CHF and it has been shown that mitral repair is feasible with a low mortality. Several authors have demonstrated 30-day mortality rates as low as 1 to 5% for mitral repair for MR in CHF. Recently, Geidel reported that the late results of restrictive annuloplasty in patients with FMR and advanced cardiomyopathy demonstrated a 3% 30-day mortality and 91% 12 months survival with little postoperative recurrence of significant MR. Similarly, data from Germany in transplant candidates, showed a 7% operative mortality and no difference in survival after MV repair versus transplant indicating that high risk MV surgery in patients with cardiomyopathy and FMR may offer a mid-term alternative treatment for patients with drug refractory heart failure and FMR.^20-22 Perhaps, the most compelling data for the safety and efficacy of MV repair for FMR comes from the MV surgery alone arm of the prospective Acorn trial (CorCap Cardiac Support Device, a prospective, randomized, multicenter trial). The Acorn trial showed a 98% 30-day survival rate, 2% repeat reoperation, and 85% 24 months survival and significant improvements in quality of life, exercise performance, and NYHA class. Furthermore, in the MV surgery arm, improvement in LV volumes, mass, and shape was sustained out to 5 years with little recurrence of significant MR.²³

However, the “achilles heel” of MV repair in may series of FMR is persistent, residual or recurrent MR.^24-27 It was learned that the intertrigonal distance is not stable in FMR, with dilatation occurring along, not only the insertion of the posterior leaflet, but also in the anterior portion. This intertrigonal portion dilates and although once considered to be a “measurable” standard by which to size annuloplasty rings, it is now known from a landmark paper of Hueb that this is not the case.²⁸ Therefore, previous methods of FMR sizing were incorrect and “undersizing” rings has become the standard for these functional MR patients. This may partly explain the operation “failing” and recurrence of mitral regurgitation in functional MR patients when using too large “classic-sized” rings or when using a partial or flexible rings.

However, despite undersizing rings, there is significant disparity in reccurence rates among FMR series. The lack of a mortality benefit may be partially explained by the absence of a durable repair. When McGee and Gillinov²⁴ showed no mortality benefit in FMR after mitral repair, they also noticed the rate of recurrent significant MR to be 30 to 40% at 1 year. Others have shown even higher rates of return of FMR, up to 80%.²⁹ This has led to an attempt to identify surgical predictors of recurrent MR and for improved surgical techniques that result in a more permanent repair.³⁰ In order to observe a survival benefit in these patients after mitral repair, FMR must be fixed permanently, as residual and recurrent MR may obscure or obliterate any possible survival benefit.

Many of the mechanisms of recurrent functional MR have been elucidated and include annular level and subvalvar components. Major predictors of recurrent FMR include LV size greater than 65 mm, a coaptation depth of greater than 1 cm below the annular plane and angulation of the MV apparatus, all of which indicate degree of LV distortion. In patients with a posterior leaflet angle > 45° (high posterolateral restriction) undergoing restrictive annuloplasty for ischemic MR, preoperative echo was shown to accurately predict persistence of MR and 3-year survival. Also studies show that the angle between the tip of the anterior leaflet and the annular plane is a predictor of MR recurrence. An anterior leaflet angle greater than 25 to 40° was a predictor of MR recurrence. Many have also shown LV function or degree of MR as determinants of recurrent MR while others point out the importance of both LV sphericity and tethering depth as predictors.^31-33

One of the most important LV predictor of recurrent MR may be left ventricular end diastolic dimension (LVEDD) > 65 mm. In patients with preoperative LVEDD of 65 mm or less, restrictive mitral annuloplasty with revascularization provided a mortality benefit for ischemic mitral regurgitation and heart failure; however, when LVEDD exceeded 65 mm, outcome was poor and a different approach to CHF should be considered. Perhaps, the most important mechanistic predictor of recurrent FMR is an increased anterior-posterior or septal-lateral mitral annular diameter. This is the most significant determinant of FMR as leaflet coaptation and therefore mitral competency, is dependent upon the diameter of the MV annulus. The MV is thought to have roughly twice the amount of coaptive surface as needed. This redundancy allows for LV volume changes and explains why obligatory FMR occurs when the LVEDD approaches 65 mm. Furthermore, this may explain why FMR is evanescent. Studies of FMR reveal that decreasing filling and systemic vascular resistance lead to reduction in dynamic FMR. This is attributed to a reduction in the mitral orifice area relating to decreased LV volume and annular distension.³⁴

This complex relationship between mitral annular area and leaflet coaptation may explain why an undersized “valvular” repair may help a “ventricular” problem. Three-dimensional magnetic resonance imaging and echo studies showed that the mitral annulus flattens and significantly increases its AP diameter. This CHF-related change has been shown not only in animal models, but in humans as well. Kongsaerepong et al³⁵ found that the strongest predictor of recurrent FMR following mitral repair was a residual large AP diameter, that is, a “too large” ring. Lastly, Spoor demonstrated that the use of flexible rings (which flex and allow the largest AP diameter) as opposed to a rigid complete ring was associated with a five times higher recurrent mitral regurgitation rate. Presently numerous rigid, complete FMR specific rings with stable AP dimension reduction are available.¹⁰

Interestingly, acute remodeling of the base of the heart with complete rigid, undersized rings may also play a beneficial role in FMR hearts. These disease-specific rings may reestablish an ellipsoid shape to the LV, as evidenced by the acute decreased sphericity index and LV volumes. Restoration of LV geometry is of paramount importance in CHF patients. This has been demonstrated by the Restore—MV trial. In that trial ischemic FMR patients, requiring coronary artery bypass graft (CABG) did better with a direct LV reshaping device (Coapsys), than with CABG with the addition of an undersized mitral ring, even though they had slightly more residual MR. This study pointed out the differential effects of MR and the LV.³⁶ In summary, patients with predictors of failure should be considered poor candidates for FMR repair, and alternatives should be contemplated. Unfortunately, progression of ventricular disease may have the worst predictive outcome for these patients. This is not amenable by mitral repair and one must be aware that fundamentally FMR is a ventricular disease.