Fazal Khan MD, Brett Curran MD, Juan Crestanello MD, Phillip Rowse MD
Mayo Clinic Rochester
August 2024
Abbreviations & Definitions
MR – Mitral regurgitation
ERO – Effective regurgitant orifice
LA – Left atrium
LV – Left ventricle
LVESD – Left ventricular end-systolic diameter
MVr – Mitral valve repair
MVR – Mitral valve replacement
LVSD – Left ventricular systolic dysfunction
SAM – Systolic anterior motion
TEER – Transcatheter edge-to-edge repair
TMVR – Transcatheter mitral valve replacement
Indications and Guidelines for Management
Chronic mitral regurgitation (MR) is a relatively common valvular disorder that may occur because of a primary abnormality of the mitral valve apparatus (i.e., annulus, anterior/posterior leaflets, chordae tendinae, papillary muscles, and ventricular myocardium) or secondary to disease of the left ventricle (LV) or atria. This chapter will focus on primary MR.1 In the developed world, degenerative mitral valve disease is the most common etiology of chronic primary MR.2
Degenerative mitral valve disease includes two primary disorders: 1) myxomatous mitral valve disease and 2) fibroelastic deficiency. Myxomatous degeneration is primarily seen in older-aged patients and typically causes MR due to leaflet thickening/redundancy and/or elongation/rupture of the chordae (i.e., Barlow’s valve). Fibroelastic deficiency is primarily observed in younger populations. It may cause prolapse and MR due to a lack of connective tissue, leading to thinning and frailty of the leaflets or chordae.2,3 Mitral valve repair (MVr) is recommended over mitral valve replacement (MVR) for degenerative MR, with an expected operative mortality of <1% and a very low rate of reoperation due to the durability of repair.4
Early MVr for severe degenerative MR has been shown to improve clinical outcomes and restore comparable long-term survival of patients compared with age-matched individuals in the general population.1,5 Etiologies of acute MR are varied and include ischemic etiologies such as papillary muscle rupture after myocardial infarction, non-ischemic rupture of mitral chordae due to myxomatous valve disease or infective endocarditis, and blunt and/or iatrogenic trauma. Patients with an acute onset of severe MR may have significant hemodynamic abnormalities and require urgent/emergent surgical intervention.2,6,7
The recommended timing of MVr for treatment of severe primary MR focuses on early intervention before the development of significant left ventricular systolic dysfunction (LVSD). LVSD is defined as a left ventricular ejection fraction (LVEF) ≤60% or severe LV dilatation with an LVESD ≥40 mm. Serial echocardiograms are vital for tracking LV function and structural changes in patients with asymptomatic chronic severe MR, aiding in timely and informed management decisions.8,9 Patients with chronic severe primary MR who experience symptoms or have an LVEF <60% are recommended to have MVr to prevent heart failure and death.8,9
Table 1: Stages of chronic MR.11
| Stage | Definition | Valve Hemodynamics |
|---|---|---|
| A | At risk of MR | No MR jet or small central jet area that occupies <20% of the left atrium (LA) on Doppler (trace or mild MR) Small vena contracta <0.3 cm |
| B | Progressive MR | Central jet in 20–40% of LA or late systolic eccentric jet Vena contracta <0.7 cm Regurgitant volume <60 mL Regurgitant fraction <50% Effective regurgitant orifice (ERO) <0.40 cm2 Angiographic grade 1+ to 2+ |
| C | Asymptomatic severe MR | Central jet in >40% of LA or holosystolic eccentric jet Vena contracta ≥0.7 cm Regurgitant volume ≥60 mL Regurgitant fraction ≥50% ERO ≥0.40 cm2 Angiographic grade 3+ to 4+ |
| D | Symptomatic severe MR | Central jet in >40% of LA or holosystolic eccentric jet Vena contracta ≥0.7 cm Regurgitant volume ≥60 mL Regurgitant fraction ≥50% ERO ≥0.40 cm2 Angiographic grade 3+ to 4+ |
Table 2: Indications for interventions in degenerative MR.
| Surgery | Indications | Class | References |
|---|---|---|---|
| Acute primary MR | Urgent MVr, if possible, is indicated in the symptomatic patient with acute severe primary MR. Acute MR related to endocarditis: MVr is preferred over MVR. | 10-12 2, 6, 7 | |
| Chronic primary MR | In patients with Stage D MR, mitral valve surgery is recommended irrespective of LV systolic function. In patients with Stage C MR and LV systolic dysfunction (LVEF ≤60%, LVESD ≥40 mm), mitral valve surgery is recommended. In patients with severe MR for whom surgery is indicated, MVr is preferred over MVR. In patients with Stage C/D MR and LV systolic dysfunction in whom surgery is not an option or needs to be delayed, then medical treatment is reasonable. In patients with Stage C MR and normal LV systolic function, MVr is reasonable only in specialized valve centers. In patients with Stage D MR attributable to rheumatic disease, MVR is preferred. | I I I IIa IIa |
11, 15, 16 11, 17 11, 18, 19 11, 20, 21 11, 17, 22 11, 23, 24 |
| Percutaneous interventions | Transcatheter mitral valve replacement (TMVR) is an alternative to MVR/r in patients deemed inoperable and with suitable anatomy. In patients with Stage D MR and high or prohibitive surgical risk, transcatheter edge-to-edge repair (TEER) is reasonable if mitral valve anatomy is favorable and patient life expectancy is at least one year. | IIa | 2, 25, 26 11, 13, 14 |
Table 3: Classes of indications for surgery in primary MR.
| Indication | Criteria | Class of Indication | Level of Evidence |
|---|---|---|---|
| Symptoms | NYHA Class II or higher | I | A |
| Severity of MR | Severe with symptoms Vena contracta ≥0.7 cm Regurgitant volume ≥60 mL Regurgitant fraction ≥50% ERO ≥0.40 cm2 |
I | A |
| LV function and dimensions | LVEF <60% or LVESD >40 mm | I | A |
| Mitral valve anatomy | Repairable valve with correctable pathology | IIa | B |
Figure 1: Flow diagram of MR and treatment of choice modalities.
Supporting Evidence for Current Indications & Guidelines
Early MVr for severe degenerative MR has been shown to improve clinical outcomes and restore comparable long-term survival of patients compared with age-matched individuals in the general population.1,5 The evidence for current indications mentioned in this chapter is adopted from ACC/AHA Guidelines published in 2020 and 2024.8,9,11
Ongoing Trials/Recent Publications
To the best of our knowledge, the authors are not aware of any ongoing trials or publication on MR surgical indications but there are many ongoing trials and publications related to TEER and TMVR, such as the COAPT, MATTERHORN, APOLLO, SUMMIT, CLASP IID trials, and many more which is out of scope of this chapter. Further discussion may be found in the TEER/TMVR chapter.
Expert Commentary
Determining the ideal timing for mitral valve surgery is crucial to maximizing patient outcomes and minimizing the risk of complications. The onset of symptoms (dyspnea on exertion, orthopnea, or declining exercise tolerance) that result from severe chronic MR has been shown to worsen prognosis and remains an essential criterion in determining the indication for prompt MVr. In asymptomatic patients, MVr is optimally timed when the patient’s LV is approaching but has not yet reached parameters that indicate systolic dysfunction (LVEF ≤60% or LVESD ≥40 mm). This early approach to MVr aims to correct the MR before significant and irreversible LV remodeling has occurred. Early MVr also avoids intense surveillance and obviates the possibility that patients become lost to follow-up or delay intervention until advanced LV dysfunction ensues.
The benchmark standards for every cardiac surgeon who performs MVr include a low operative mortality rate (<1%) and a high likelihood of both a successful (>95%) and durable (95% freedom from reoperation) repair. The success of MVr is associated with increased surgical volume (>50 repairs/year) and surgeon expertise. The results of a minimally invasive approach (mini-thoracotomy or robotic-assisted) are similar to those of a full median sternotomy when performed by highly experienced surgeons. MVR should be reserved for situations where repair attempts have proven unsuccessful or in emergent situations such as acute ischemic MR, considering that a replaced mitral valve is preferable to a poor repair.
Indications for repair of SAM are greater than mild residual MR and/or increased LV outflow tract gradient. Repair techniques of SAM include upsizing the annuloplasty band, debulking the posterior leaflet with triangular or quadrangular resection, and neo-chordae to the posterior leaflet that will ventricularize the posterior leaflet, allowing the anterior leaflet room for a more posterior line of leaflet coaptation.
Long-term survival rates following successful/durable simple MVr are expected to be equivalent to those of the age-matched general population. Freedom from recurrent moderate or severe MR 15 to 20 years after surgery is expected to exceed 80%. These long-term outcomes surpass those associated with MVR, mainly when the procedure occurs at high-volume, specialized valve surgery centers. This is also true for elderly patients, underscoring the importance of durable repair techniques.
In summary, meticulous timing, expert surgical technique, and advanced procedural options are all critical factors in optimizing the management and outcomes of the mitral valve. Ongoing research and clinical experience will refine these approaches, ultimately enhancing patient care and surgical success.
Sources
1. Del Forno, B., et al., Mitral valve regurgitation: a disease with a wide spectrum of therapeutic options. Nat Rev Cardiol, 2020. 17(12): p. 807-827.
2. Harky, A., et al., Mitral valve diseases: Pathophysiology and interventions. Prog Cardiovasc Dis, 2021. 67: p. 98-104.
3. Enriquez-Sarano, M., C.W. Akins, and A. Vahanian, Mitral regurgitation. Lancet, 2009. 373(9672): p. 1382-94.
4. Castillo, J.G., et al., All anterior and bileaflet mitral valve prolapses are repairable in the modern era of reconstructive surgery. Eur J Cardiothorac Surg, 2014. 45(1): p. 139-45; discussion 145.
5. Watt, T.M.F., et al., Degenerative Mitral Valve Repair Restores Life Expectancy. Ann Thorac Surg, 2020. 109(3): p. 794-801.
6. Harky, A., et al., Mitral valve repair or replacement in native valve endocarditis? Systematic review and meta-analysis. J Card Surg, 2018. 33(7): p. 364-371.
7. He, K., et al., Valve replacement or repair in native mitral valve infective endocarditis-Which is better? A meta-analysis and systematic review. J Card Surg, 2022. 37(4): p. 1004-1015.
8. Jneid, H., et al., 2024 ACC/AHA Clinical Performance and Quality Measures for Adults With Valvular and Structural Heart Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Performance Measures. Circ Cardiovasc Qual Outcomes, 2024. 17(4): p. e000129.
9. Writing Committee, M., et al., 2024 ACC/AHA Clinical Performance and Quality Measures for Adults With Valvular and Structural Heart Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Performance Measures. J Am Coll Cardiol, 2024. 83(16): p. 1579-1613.
10. Leitman, M., et al., Assessment and Management of Acute Severe Mitral Regurgitation in the Intensive Care Unit. J Heart Valve Dis, 2017. 26(2): p. 161-168.
11. Otto, C.M., et al., 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021. 143(5): p. e35-e71.
12. Pillai, A.A., et al., Acute severe mitral regurgitation with cardiogenic shock following balloon mitral valvuloplasty: echocardiographic findings and outcomes following surgery. Cardiovasc Interv Ther, 2019. 34(3): p. 260-268.
13. Feldman, T., et al., Percutaneous repair or surgery for mitral regurgitation. N Engl J Med, 2011. 364(15): p. 1395-406.
14. Feldman, T., et al., Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II. J Am Coll Cardiol, 2015. 66(25): p. 2844-2854.
15. Gillinov, A.M., et al., Should patients with severe degenerative mitral regurgitation delay surgery until symptoms develop? Ann Thorac Surg, 2010. 90(2): p. 481-8.
16. Tribouilloy, C.M., et al., Impact of preoperative symptoms on survival after surgical correction of organic mitral regurgitation: rationale for optimizing surgical indications. Circulation, 1999. 99(3): p. 400-5.
17. Kang, D.H., et al., Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation. Circulation, 2009. 119(6): p. 797-804.
18. Lazam, S., et al., Twenty-Year Outcome After Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation: Analysis of a Large, Prospective, Multicenter, International Registry. Circulation, 2017. 135(5): p. 410-422.
19. Suri, R.M., et al., Effect of Recurrent Mitral Regurgitation Following Degenerative Mitral Valve Repair: Long-Term Analysis of Competing Outcomes. J Am Coll Cardiol, 2016. 67(5): p. 488-98.
20. Ahmed, M.I., et al., A randomized controlled phase IIb trial of beta(1)-receptor blockade for chronic degenerative mitral regurgitation. J Am Coll Cardiol, 2012. 60(9): p. 833-8.
21. Varadarajan, P., et al., Effect of Beta-blocker therapy on survival in patients with severe mitral regurgitation and normal left ventricular ejection fraction. Am J Cardiol, 2008. 102(5): p. 611-5.
22. Suri, R.M., et al., Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets. JAMA, 2013. 310(6): p. 609-16.
23. Chen, S.W., et al., Mitral valve repair versus replacement in patients with rheumatic heart disease. J Thorac Cardiovasc Surg, 2022. 164(1): p. 57-67 e11.
24. Waikittipong, S., Long-term outcomes of rheumatic mitral valve repair: Is it worthwhile to do it? Asian Cardiovasc Thorac Ann, 2021. 29(2): p. 91-97.
25. El Sabbagh, A., Y.N.V. Reddy, and R.A. Nishimura, Mitral Valve Regurgitation in the Contemporary Era: Insights Into Diagnosis, Management, and Future Directions. JACC Cardiovasc Imaging, 2018. 11(4): p. 628-643.
26. Winkel, M.G., F. Praz, and P. Wenaweser, Mitral and Tricuspid Transcatheter Interventions Current Indications and Future Directions. Front Cardiovasc Med, 2020. 7: p. 61.
