Update on mitral regurgitation: Which treatment is best for which disease entity?

The concept of dysproportional mitral regurgitation makes it now possible to optimise therapy through meaningful patient characterisation.

Heart failure with reduced ejection fraction (HFrEF) in functional mitral regurgitation very common

Severe mitral regurgitation is associated with progressive left ventricular dysfunction and congestive heart failure. Drug treatment of patients alleviates symptoms but has no effect on disease progression. The path towards optimal patient care has not been easy over the past decades. A key factor was that traditional approaches to characterising secondary or functional mitral regurgitation had largely ignored the importance of the left ventricle.

"30-50% of patients with severe heart failure have high-grade mitral regurgitation", explained Prof. Rottbauer. Adding that the prognosis of HFrEF patients depends to a large extent on the severity of mitral valve regurgitation. To support these statements, he presented important key figures on functional mitral regurgitation to the DGK 2023 auditorium. According to a clinical study from 2004, there was a correlation between haemodynamically significant mitral regurgitation and advanced heart failure (EF ≤ 35%).

The severity of mitral regurgitation correlated with the severity of systolic dysfunction, diastolic dysfunction, ventricular dilatation, atrial dilatation, and pulmonary hypertension. The presence of haemodynamically significant mitral regurgitation was associated with increased mortality.1,2 A 2011 study confirmed these data, and also showed that with increasing severity of mitral regurgitation (LVEF < 25%), the risk of mortality also increased.1,3 By presenting these study results, Prof. Rottbauer conveyed to the audience that functional mitral regurgitation can occur very frequently in heart failure with reduced ejection fraction (HFrEF) and can be associated with increased mortality.1

New AHA guidelines for the treatment of heart failure and mitral valve regurgitation are in agreement

The current American Heart Association (AHA) guideline on heart failure dates from 2022 and replaces two older guidelines from 2013 and 2017, providing patient-centred recommendations for clinicians on the prevention, diagnosis and treatment of patients with heart failure. This guideline is the first time that cardiology guidelines for the treatment of different clinical pictures correspond with each other. Thus, this new guideline also takes a position on the treatment of heart failure in mitral valve regurgitation:

The same recommendation is made in the AHA guideline on the treatment of valvular heart disease.1,5

MitraClip® versus mitral valve reconstruction: EVEREST II

Various procedures are available for interventional mitral valve repair: The MitraClip® and mitral valve repair. In the EVEREST II study, the MitraClip® system was investigated with mitral valve surgery for the treatment of mitral regurgitation. The included patients suffered from chronic mitral regurgitation (grade 3+ or 4+; symptomatic patients: LVEF ≥ 25%, LVESD of ≤ 55 mm; asymptomatic patients with at least one of the following conditions: LVEF of 25 to 60%, LVESD of 40 to 55 mm, new atrial fibrillation, pulmonary hypertension). The advantage of the MitraClip® system over mitral valve surgery was greater safety with similar improvements in clinical outcomes. In terms of reduction of mitral regurgitation, mitral valve surgery performed better.

However, an intention-to-treat analysis of EVEREST II showed similar results in terms of mortality and mitral regurgitation. An important difference between the two methods was the rate of surgery for mitral valve dysfunction. This was 20% in the MitraClip® group (compared to 2.2% in the mitral valve surgery group).1,6 Rottenbauer emphasised in his presentation that reoperation of this 20% of patients was a sustainable treatment success when the MitraClip® procedure was successfully performed. An important limitation of EVEREST II was patient selection. Patients with both degenerative and functional mitral regurgitation were included. Degenerative mitral regurgitation is definitely a domain of cardiac surgery. This is not the case with functional mitral regurgitation, said Prof. Rottenbauer.1

Controversial results on the use of the MitraClip® in functional mitral regurgitation: MITRA-FR verus COAPT

The MITRA-FR trial compared drug treatment with the addition of the MitraClip® procedure in patients with chronic heart failure, reduced left ventricular ejection fraction and severe secondary mitral valve regurgitation. There was no significant difference in mortality and hospitalisation rates. In this study, the use of the MitraClip® procedure did not improve the prognosis of patients.1,7 The COAPT study provided the opposite results. The annualised hospitalisation rate due to heart failure was 35.8% per patient year in the MitraClip® group and 67.9% per patient year in the control group. The MitraClip® group also performed better in terms of death from any cause (within 24 months) (29.1% versus 46.1%). Both results were significant.1,8

Where does this incredible difference between the MITRA-FR and COAPT studies come from?

A closer look at the two studies reveals important differences in patient selection: The COAPT trial excluded patients with a markedly dilated left ventricle and/or severe right heart disease.1 The MITRA-FR trial enrolled patients whose mitral regurgitation correlated with the degree of left ventricular dilatation. In contrast, patients in the COAPT trial had disproportionate mitral regurgitation [effective regurgitation orifice area (EROA) was ≈ 30% higher and left ventricular volume was ≈30% smaller]. The patients in the COAPT trial benefited from the MitraClip®. In addition to the decrease in hospitalisation and mortality rates, a significant decrease in left ventricular end-diastolic volume was observed.1,9

The concept of dysproportional mitral regurgitation

From this observation, the concept of dysproportional mitral regurgitation has emerged. According to this concept, characterising mitral regurgitation as proportional or disproportionate to left ventricular end-diastolic volume (LVEDV) is critical for selecting optimal treatment for patients with chronic heart failure and systolic dysfunction.1,9

  1. Rottenbauer, Wolfgang, Univ.-Prof. Dr. med., Lecture: Valve vitiation in heart failure: Always treat? Only interventional? Heart failure update (Original German title: Klappenvitien bei Herzinsuffizienz: Immer behandeln? Nur noch interventionell? Update Herzinsuffizienz), Session Chair: Prof. Dr. Birgit Aßmus; Prof. Dr. Norbert Frey, 89. Annual Conference of the German Society for Cardiology [Deutschen Gesellschaft für Kardiologie (DGK)], 08:35 Uhr, 13 April 2023.
  2. Patel JB. et al. (2004). Mitral regurgitation in patients with advanced systolic heart failure. J Card Fail. 2004 Aug;10(4):285-91. 
  3. Pecini R. et al. (2011). The relationship between mitral regurgitation and ejection fraction as predictors for the prognosis of patients with heart failure. Eur J Heart Fail. 2011 Oct;13(10):1121-5.
  4. Heidenreich PA. et al. (2022). 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.
  5. Otto CM. et al. (2021). 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation Vol.143, No.5.
  6. Feldman T. et al. (2011). Percutaneous Repair or Surgery for Mitral Regurgitation. N Engl J Med 2011; 364:1395-1406.
  7. Obadia JF. et al. (2018). Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med. 2018 Dec 13;379(24):2297-2306. 
  8. Stone GW. et al. (2018). Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med. 2018 Dec 13;379(24):2307-2318.
  9. Grayburn PA. et al. (2019). Proportionate and Disproportionate Functional Mitral Regurgitation: A New Conceptual Framework That Reconciles the Results of the MITRA-FR and COAPT Trials. JACC Cardiovasc Imaging. 2019 Feb;12(2):353-362.