42. Functional Mitral Regurgitation- Clinical Scenarios

J Hunter Mehaffey, MD and Kenan W Yount, MD

Adapted from 1^st edition chapter “Ischemic Mitral Regurgitation” written by Kenan W. Yount, MD, MBA, and Gorav Ailawadi, MD

Concept

• Primary mitral regurgitation (MR) is caused by a primary leaflet abnormality. Usually this is the result of degenerative disease.
• By contrast, secondary MR (the focus of this chapter) occurs when structurally normal valve leaflets are unable to coapt completely, owing to a distortion of either (1) the annulus or (2) the subvalvular apparatus.

• Annular dilation as a result of dilated cardiomyopathy results in Type II MR, which is frequently referred to as “functional” mitral regurgitation.
• Subvalvular distortion (usually tethering of the posterior leaflet) can occur as a consequence of left ventricular (LV) remodeling as the result of ischemic heart disease (e.g., prior inferior myocardial infarction).
• Either mechanism is essentially a disease of the LV rather than the mitral valve itself.
• Patients who have LV dysfunction and secondary MR have a much worse prognosis than patients with either abnormality in isolation.
• It is controversial whether myocardial revascularization alone will be enough for some of these patients.
• It is controversial whether addressing the MR will be of value for some of these patients.

Chief complaint

“A 60 year-old female with a past medical history significant for hypertension, dyslipidemia, coronary artery  disease, and non ST-segment  elevation  myocardial  infarction treated medically 3 years  ago  presents  with  increasing  shortness of breath. She describes a history of fatigue and shortness of breath worsened by exertion. She denies recent anginal episodes.”

Differential

Acute coronary syndrome, HFrEF, structural valve disease, COPD

• Other diagnoses to consider: acute postinfarction ischemic MR (with or without papillary muscle rupture; see “Alternative Scenarios”); ischemic CAD with concomitant MR as a result of other etiologies (e.g., degenerative mitral valve disease, rheumatic disease, endocarditis).

Carpentier’s classification system – describes the mechanism of MR.

• Type I involves normal leaflet motion—MR results from LV enlargement and subsequent annular dilatation (e.g., functional MR).
• Type II involves leaflet prolapse (e.g., degenerative MR; acute papillary rupture after MI)
• Type III involves leaflet restriction and is further subdivided into IIIa (restriction during systole and diastole) and IIIb (restriction during systole alone). Rheumatic disease classically results in Type IIIa whereas chronic ischemic disease is Type IIIb.

Differential secondary MR

• Functional MR: Type I mechanism. Dilated cardiomyopathy producing global LV dilation resulting in annular enlargement. These patients may have severely depressed LV function (usually LVEF < 35%), hence the term “functional.”
• Ischemic MR: Type IIIb mechanism.Prior myocardial infarction or ischemic remodeling resulting in asymmetric ventricular remodeling, most often affecting the inferior and lateral LV wall. Although it can be seen with global LV remodeling, the distinguishing feature usually involves substantial disruption of the subvalvular apparatus, especially downward and lateral (i.e., apical) displacement of the posteromedial papillary muscle leading to leaflet tethering. Note that the term “ischemic” MR classically refers to a chronic condition rather than acute papillary rupture after an MI.
• These two entities lie along a clinical spectrum given the heterogeneity of ischemic heart disease. Although they cannot be completely separated, clarifying the mechanism will help determine surgical management because the degree of LV dysfunction, chamber remodeling, and valvular complex disruption differ with each.

History and physical

A focused history and physical should clarify any recent history of acute coronary syndrome (ACS) or angina. Most patients have symptoms of congestive heart failure (CHF) due to worsening LV function and moderate-to-severe MR in the setting of known or unknown prior MI. Consequently, it is necessary to obtain a history of prior cardiac interventions, prior imaging, and progression of current symptomatology. Comorbidities, such as diabetes, pulmonary disease, kidney disease, cerebrovascular disease, and peripheral arterial disease impact surgical outcomes. These patients tend to be high-risk with operative mortality approaching 5-10%.

Tests

• CXR may show pulmonary edema and an enlarged cardiac silhouette. Also assess for calcification of the aorta and arch which would warrant a CT.
• EKG may show changes of a prior inferior MI.
• Transthoracic echo (TTE) may show evidence of prior MI and LV dysfunction. Given the primary mechanism is leaflet tethering in ischemic MR, the regurgitant jet will be directed toward the restricted leaflet; annular dilatation, however, will cause the jet to appear central. Grade – 1 = mild, 2 = moderate, 3 = moderately severe, 4 = severe.
• Transesophageal echo (TEE) is the study of choice to clarify the mechanism of regurgitation. The grade of MR may be lower on TEE intraoperatively due to anesthesia and ventricular unloading. Rely on the estimated degree of regurgitation preoperatively by TTE but ensure that you have a TEE prior to any intervention to give the best anatomical detail and clarity.
• Coronary angiography may show significant multivessel CAD; look for an occluded vessel with inferior wall motion abnormality on the left ventriculogram. Clarify right versus left dominance (left dominance is more problematic if the circumflex were injured during mitral valve surgery).
• Viability testing may identify patients most likely to benefit from valve intervention. MR in the setting of inferior scar tissue or a tethered posterior leaflet is unlikely to improve with CABG alone while MR in the setting viable myocardium may improve with CABG alone.

Index scenario (additional information)

“Left heart catheterization revealed multivessel disease: there is left main disease (~ 70% stenosis) and proximal LAD stenosis; the RCA is occluded but the LAD target and OM targets appear acceptable. MRI shows good viability anteriorly but there is concern for non-viable scarred myocardium inferiorly. A more recent TTE shows LVEF to be estimated at 30-35% with pulmonary hypertension, severe mitral regurgitation, and inferior wall motion abnormality. TEE shows a restricted and tethered posterior mitral leaflet and confirms severe mitral regurgitation.”

Treatment/management

The benefit of surgical revascularization (CABG) is clear, provided the patient has suitable coronary targets affected by high-grade proximal lesions resulting in ischemic but viable myocardium.

This patient has severe MR and thus expert consensus still favors simultaneous correction of the severe MR at the time of CABG. The question of which surgical strategy has been the subject of substantial research.

Historically, mitral valve repair (MVr) with a reduction annuloplasty (slightly undersized, complete ring, e.g., 28-30 mm) was favored over mitral valve replacement (MVR) for secondary MR based on its relatively lower perioperative morbidity and mortality; the presumed benefits of preserving the subvalvular apparatus to help preserve LV function; and less need for re-intervention given the risk of bioprosthetic structural valve deterioration. Annular reduction for a Type I mechanism was thought to decrease wall stress and improve LV function. For patients with a Type IIIb mechanism, this approach proved insufficient due to the more localized pattern of geometric deformation, possibly explaining their higher rates of recurrent MR postoperatively. Subvalvular interventions to reposition the posterior papillary muscle toward the septal annulus have been employed and reported on retrospectively but have largely fallen out of favor. Most practitioners do not perform ancillary subvalvular interventions in the setting of IMR.

A large randomized trial conducted by the Cardiothoracic Surgical Trials Network (CTSN) dramatically changed clinical practice by comparing MVr vs. chordal sparing MVR at the time of CABG for severe MR. This trial showed no significant differences in LV remodeling, survival, or outcome at 1 or 2 years. Additionally, there was a significantly higher rate of recurrent MR in the MVr cohort, which thus predisposed MVr patients to recurrent heart failure, atrial fibrillation, repeat interventions, and repeat hospitalizations. Of note, is that at 2 years, mortality approached 20-25% in both groups, confirming the overall poor prognosis of this patient group regardless of surgical strategy. Thus, replacement for this patient population gives you the best chance of leaving the operating room with a single pump run and no MR.

Given these data, most surgeons now favor a chordal-sparing mitral valve replacement (MVR) at the time of CABG for severe MR. A bioprosthetic valve is logical given that most patients in whom replacement is favored in these settings will not experience valve degeneration in their lifetime.

One caveat is that in some situations (e.g., at the time of an apical incision such as an LVAD or Dor) some surgeons may instead employ a simple Alfieri suture for predominantly Type I mechanism secondary MR.

Operative steps

• Swan-Ganz catheter placement should be considered in these patients given their LV dysfunction and pulmonary hypertension.
• Intraoperative TEE is imperative to clarify the mechanism of MR and determine the quality of the repair, but it is not reliable in judging the severity of MR. Go by the preoperative grade.
• Median sternotomy is the classic approach for combined mitral valve-CABG.
• Bi-caval cannulation is routine. Some practitioners favor femoral cannulation for the IVC.
• Myocardial Protection: After the aorta is cross-clamped, antegrade cardioplegic arrest followed by intermittent retrograde cardioplegic infusion is wise for a diseased left ventricle. Practitioners are divided on whether to incorporate del Nido during coronary operations and thus try to avoid broaching that discussion on a board exam. Regardless of the order of the grafts, all distal anastomoses should be performed prior to mitral valve replacement to avoid excess manipulation of the heart after MVR, as that predisposes to AV groove dissociation. When RCA disease is present, consideration should be given to prioritizing that graft first to enable periodic antegrade delivery to the RV since it may be inadequately protected by retrograde alone.
• After completion of the distal CABG anastomoses, expose the mitral valve via left atriotomy. The left atrium is usually dilated enough in these patients to approach the valve from Waterston’s (or Sondergaard’s) groove rather than necessitating a trans-septal approach.  That said, some surgeons may prefer a right sided approach. 
• Everting pledgeted sutures through the annulus in a horizontal fashion. The anterior portion is usually approached last as it is the most difficult to expose. Closely spaced sutures (some practitioners overlap sutures) may prevent dehiscence. Size according to both inter-trigonal and anterior leaflet size using the manufacturers sizer. Sutures are then placed through the sewing ring and secured to the annulus with either hand-tie or Cor-knot.
• After valve replacement, close the left atriotomy. Some surgeons leave a temporary LA or LV vent in place prior to tying down the left atriotomy closure.
• Proceed with proximal anastomoses.

Potential questions/alternative scenarios

“The same patient presents but has more diffuse coronary disease with less obvious targets and a global dilated cardiomyopathy with an LVEF of 15%.”

Such a patient primarily has LV disease and should instead be considered for LVAD. If the decision is made to proceed instead with an LVAD, it is more controversial whether to address the mitral valve at the time of LVAD. Replacement of the valve would require arresting the heart and thus many practitioners instead favor an Alfieri suture via the LV apex after apical coring (if they choose to address the MR at all during the LVAD operation).

“A 70-year-old male presents with 2⁺ MR, and 3 vessel CAD each with > 70% stenosis. Would you perform a CABG or CABG MVR? He has a history of poorly controlled diabetes, COPD and ESRD.”

This patient has moderate IMR with multivessel CAD. Options include surgical revascularization alone versus concomitant mitral valve repair. Few surgeons would replace the mitral valve in the setting of only moderate MR. The CTSN trial looking specifically at moderate MR at the time of CABG found that concomitant MVr resulted in longer operative times, longer hospitalizations, higher rates of atrial fibrillation, and higher rates of stroke; however, it resulted in less MR at 1-2 years with but without any favorable effect on  LV reverse remodeling. Surgical correction thus introduces a higher perioperative risk in the setting of an already higher predicted operative mortality operation for only moderate. In a patient who has these many comorbidities one would certainly be justified in doing the most expeditious operation with least risk, which in this case is a CABG alone. Perhaps MitraClip would be an option down the road for that patient if the MR progresses.

For a healthier individual who can tolerate a ring annuloplasty or Alfieri suture, doing so may decrease the incidence of worsening MR in the future. In that scenario, a viability study may help guide the decision: irreversible disease from infarction would seemingly benefit more from a concomitant MV intervention. Judgement also comes into play with 2⁺ MR. As a rule of thumb, 3-4⁺ should get a replacement unless you have good reason to limit cardiopulmonary bypass time and the patient just barely makes 3⁺ MR.

“The patient experiences recurrent severe MR one year after the operation.”
The patient’s coronary anatomy should be re-evaluated, and any ischemic disease addressed. Repeat TEE is warranted to clarify the mechanism of the progressive MR.

If the mechanism is secondary: Strong consideration must be given to maximizing guideline-directed medical for heart failure (e.g., increasing beta-blockade, ACE/ARB). Consideration should also be given for Cardiac Resynchronization Therapy (CRT) if indicated (e.g., wide QRS in setting of low EF). The MIRACLE trial revealed that CRT not only induced reverse remodeling but also reduced the degree of IMR at 12 months, likely by correcting dyssynchrony between the posterior papillary muscle and the lateral LV wall. The degree of MR should then be reassessed once maximal heart failure therapy has been achieved.

If severe MR persists despite these interventions, the patient should be considered for a percutaneous mitral valve repair (such a patient is almost certain to be high or prohibitive risk for re-operation). Any decision to intervene warrants a detailed assessment of frailty and comorbidities that will potentially limit the patient’s lifespan and quality of life independent of their MR. In this scenario, a TEE could determine whether the patient has anatomy suitable for a MitraClip procedure.

The COAPT trial showed significantly lower rates of hospitalization for heart failure at 2 years and lower all-cause mortality at 2 years in patients undergoing MitraClip for secondary MR  The results are in contrast to the MITRA-FR trial conducted in Europe, but the criticism of MITRA-FR has been that it included substantial numbers of patients with less severe degrees of MR and patients in whom medical therapy may not have been maximized. Consequently, for patients who have heart failure symptoms truly refractory to maximal medical therapy with a high degree of mitral regurgitation and severe LV dysfunction not amenable to LVAD, MitraClip can certainly be considered.

If the mechanism is instead primary: Assuming the patient is symptomatic and a good operative candidate, he may be a candidate for re-operation. This sometimes is approached from a right thoracotomy if prior CABG has been performed and the bypass grafts are patent. However, such a patient’s comorbidities may render them high or prohibitive risk for re-operation, in which case, MitraClip can certainly be considered.

“A 68-year-old male presents with worsening chest pain that began acutely 2 days ago. He had some improvement initially and did not come into the hospital. He now presents with worsening chest pain and increasing shortness of breath. A coronary angio shows a 70% mid circumflex lesion and an 80% RCA lesion. He is left dominant with the circumflex giving off the PDA. His echo shows a ruptured posterior papillary muscle. He is on moderate doses of epinephrine and levophed with PAP of 50/20 and cardiac index of 2.0. His EF is estimated at 50%. His blood pressure is 80/40 mmHg. Physical exam reveals bilateral crackles and a new holosystolic murmur. His CXR shows acute pulmonary edema. How would you proceed.”

At least 25% of patients develop either a new mitral murmur or have TTE evidence of MR after an acute MI. Usually, these are transient alterations that ultimately resolve, but MR can be persistent in approximately 1-5% of patients as a result of papillary muscle ischemia. Papillary muscle rupture is increasingly rare with today’s focus on rapid revascularization after acute STEMI. Nevertheless, it still carries a mortality approaching 50-75% without surgical intervention and 20-25% with surgical intervention. Major contributors to mortality are advanced age, the duration of preoperative shock, the presence of other cardiovascular comorbidities, and operative delay. Postoperative morbidity can result from peripheral organ failure and stroke. Acute IMR occurs 2-7 days (mean 4 days) after MI. Patients present with acute dyspnea due to pulmonary edema and cardiogenic shock. A new holosystolic murmur with the above history could be seen in either an acute VSD or acute IMR. Unlike an acute VSD, MR is best heard at the apex rather than the left sternal border and does not have an associated thrill.

The posteromedial papillary muscle is more vulnerable because of its single blood supply (RCA for right dominant or circumflex for left dominant) compared to the dual blood supply of the anterolateral papillary muscle (LAD and circumflex). Papillary muscle rupture results in flail leaflet. Unlike acute VSD, acute IMR is more commonly associated with acute inferior STEMI.

• Tests: EKG may show signs of inferior MI whereas an acute VSD may show conduction abnormalities. A bedside TTE may demonstrate flail mitral leaflets and a mass attached to the chordae, representing the ruptured papillary muscle.
• Preoperative Stabilization: Acute MR can rapidly result in pulmonary edema and multisystem organ failure from reduced forward flow. Inotropes (e.g., milrinone), and vasodilators (e. g., nitroprusside, nitric oxide) can stabilize the patient’s hemodynamic status; by contrast, volume overload or increased afterload would worsen the patient’s MR. Intubation and mechanical ventilation may be required for respiratory failure. Diuretics may reduce pulmonary edema, but caution should be taken not to create prerenal azotemia. Mechanical support with an intra-aortic balloon pump (IABP) should be strongly considered. Some patients may need to be stabilized with ECMO if they have already progressed to severe end organ dysfunction and there is question over whether that is salvagable with an operation.
• Role of PCI/CABG: Pre-operative cardiac catheterization is often performed at the time of diagnosing the MI. This may occur a few days prior to the papillary rupture in which case a stent or angioplasty was likely performed or the cath may be done at the time of diagnosing the MR if the patient presented in a delayed fashion. If the patient’s coronary lesions have not already been addressed, then a CABG and MVR should be done. Otherwise proceed to an MVR alone unless there is suspicion for stent thrombosis (EKG with evolving infarct) in which case the cath should be redone.
• Operation: Papillary rupture is an emergent situation, and intervention should not be delayed unless the patient is prohibitive risk. Mitral valve repair for papillary muscle rupture is rarely possible. Re-implanting a ruptured papillary muscle into recently infarcted LV tissue can result in repair failure, prolonging bypass time in a patient who has already been in shock. Consequently, mitral valve replacement with chordal preservation if possible is preferred.
  
  

Pearls/pitfalls

• Carpentier Classification: Critical to understanding mitral regurgitation mechanism.
• Severe MR with symptomatic CAD: Combined CABG-mitral valve replacement.
• Moderate MR with symptomatic CAD: Combined CABG-mitral valve repair will decrease MR severity more than CABG alone, but it may have no effect on survival. Consequently, preoperative risk factors, viability, and symptoms should help guide the decision to add mitral valve repair to a CABG.
• Severe MR with Dilated Cardiomyopathy: Maximize medical therapy/consider percutaneous repair vs LVAD/transplant.
• Acute MR from papillary muscle rupture: Surgical emergency; few would find fault with valve replacement.

Suggested readings

• Carpentier Classification: Stone et al. Section on “Primary versus secondary MR” within “Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 1: Clinical Trial Design Principles.” J Am Coll Cardiol. 2015 Jul 21;66(3): pages 282-284 only.
• Severe MR with symptomatic CAD: Goldstein et al for CTSN. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med 2016; 374:344-353.
• Moderate MR with symptomatic CAD: Michler et al for CTSN. Two-Year Outcomes of Surgical Treatment of Moderate Ischemic Mitral Regurgitation. N Engl J Med 2014; 371:2178-2188
• Severe MR with Dilated Cardiomyopathy: Stone et al for COAPT. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 2018; 379:2307-2318.
• Acute MR from papillary muscle rupture: Carrott, Gardner, Kron. Section on “Acute Ischemic Mitral Regurgitation” within “Chapter 56: Surgery for Complications of Myocardial Infarction.” Mastery of Cardiothoracic Surgery 2014, 3^rd edition. pages 548-551 only.