Functional mitral regurgitation (FMR) is a condition that often affects patients with heart failure, particularly those with reduced left ventricular ejection fraction (HFrEF). The pathophysiology of FMR is complex, primarily involving left ventricular remodeling and dysfunction. This remodeling leads to distortion of the mitral valve apparatus, resulting in valve incompetence. This vicious cycle ultimately exacerbates the severity of heart failure and is associated with increased morbidity and mortality.
The management of FMR in patients with heart failure remains a topic of significant interest, focusing on optimising medical therapy and using advanced therapies such as cardiac resynchronisation therapy (CRT). Numerous clinical trials have highlighted the importance of addressing FMR in patients with heart failure to improve clinical outcomes.
In this case presentation, I will discuss a patient with severe symptomatic heart failure and functional mitral regurgitation who demonstrated significant improvement following the optimisation of medical therapy and the insertion of a cardiac resynchronisation therapy device. This case exemplifies the importance of a comprehensive and multidisciplinary approach to the management of heart failure, emphasising the role of advanced therapies in improving FMR and overall patient outcomes.
A 53-year-old male patient with severe dyspnea was referred for cardiac evaluation. The patient, a refugee from the Middle East, reported an absence of chest pain but acknowledged recurrent episodes of syncope before migration, with onset in his 30s. Over the preceding three months, he had multiple emergency department admissions due to acute episodes of pulmonary edema.
Upon assessment, he was classified as New York Heart Association (NYHA) functional class III. Physical examination identified peripheral pitting edema and crepitations on auscultation at the lung bases. His blood pressure measured 98/60 mmHg, and he was comfortable at rest.
ECG showed sinus rhythm at a rate of 95 bpm, left bundle branch block (LBBB), and a prolonged QRS duration of 177 ms. Furthermore, echocardiogram displayed severe left ventricular dysfunction and dilation accompanied by moderate to severe functional mitral valve regurgitation, as shown below:
4-chamber view: Severe LV impairment
PLAX-view: severe LV dilatation and impairment
3-chamber view: severe LV impairment
4-chamber view: moderate-severe FMR
2-chamber view: moderate to severe FMR
Progress, after Guideline-Directed Optimal Medical Therapy (GDOMT) and Cardiac Resynchronization Therapy (CRT)
The patient was initiated on Guideline Directed Medical Therapy (GDMT) for his heart failure, including Sacubitril/valsartan, Nebivolol, and Spironolactone. However, the treatment course was complicated by several hospital presentations due to severe hypotension and syncope episodes. A coronary angiogram revealed normal coronary arteries and a cardiac MRI failed to elucidate the etiology of his dilated cardiomyopathy.
A cardiac resynchronization therapy-defibrillator (CRT-D) device was implanted, as the patient remained symptomatic despite six months of maximum tolerated medical therapy. Two months post-implantation, he was admitted to the hospital following three shocks from the CRT-D device. Device interrogation determined the shocks were “inappropriate” and resulted from rapidly conducted atrial fibrillation (AF) episodes. Consequently, he was initiated on Amiodarone and Apixaban, the Nebivolol dosage was increased despite mild dizziness and low blood pressure, and appropriate defibrillator adjustments were made.
Two years following therapy initiation and intensive life-style modifications, the patient exhibited a marked improvement in exercise tolerance and remained entirely asymptomatic, classified as NYHA class I, with no subsequent hospitalizations. The most recent echocardiographic findings and ECG are presented below:
4-chamber view: improvement in LV function
3-chamber view: post CRT and medical therapy
2-chamber view: Near complete resolution of FMR
4-chamber post CRT: improvement in FMR
PLAX view: post OMT and CRT
Side-by-side echocardiogram comparison of before treatment and after improvement of Mitral Regurgitation
LV size before therapy
4-chamber Moderate-severe MR before therapy
2-chamber Moderate-severe MR before therapy
LV size after optimal medical therapy and CRT insertion
4-chamber after medical therapy and CRT
2-chamber after medical therapy and CRT
FMR frequently arises as a secondary consequence of heart failure, particularly when it involves left ventricular dysfunction. In the setting of heart failure, left ventricular dilation can compromise the coaptation of mitral valve leaflets, resulting in mitral regurgitation. This additional volume overload can exacerbate the underlying heart failure and further deteriorate cardiac function. Conversely, effective management and treatment of heart failure can result in improved left ventricular function and geometry, which, in turn, can lead to a reduction in FMR.
In light of these observations, therapeutic interventions targeting either FMR or heart failure can yield reciprocal benefits for the other condition. However, The evidence for directly improving heart failure by fixing functional mitral regurgitation (FMR) is subtle. While some studies have demonstrated that interventions targeting FMR can lead to symptomatic relief, the impact on long-term outcomes and improvements in cardiac function has been less clear.
For example, the COAPT trial showed that transcatheter mitral valve repair using the MitraClip device in patients with heart failure and significant secondary mitral regurgitation resulted in reduced hospitalizations for heart failure and improved survival compared to medical therapy alone. However, this trial primarily demonstrated improvements in symptoms and hospitalization rates rather than direct improvements in cardiac function.
On the other hand, the MITRA-FR trial found no significant difference in outcomes between the intervention group and the medical therapy group in terms of a composite endpoint of death and unplanned hospitalization for heart failure.
The discrepancy between these trials highlights the complexity of FMR and heart failure interactions and the importance of patient selection in determining the potential benefits of FMR interventions.
While fixing FMR can lead to symptomatic relief and improved quality of life in some patients with heart failure, it is not guaranteed to improve cardiac function or long-term outcomes in all cases directly. It is crucial to carefully evaluate each patient’s clinical characteristics, the severity of FMR, and the underlying cause of heart failure when considering therapeutic interventions targeting FMR. In many situations, like the case mentioned earlier, the primary focus should be treating heart failure instead of concentrating on secondary mitral regurgitation. In most instances, secondary mitral regurgitation will improve as left ventricular function and size respond to therapy over time.
References and further reading
- Stone, G. W. (2018). Transcatheter mitral-valve repair in patients with heart failure. New England Journal of Medicine, 379(24), 2307-2318.
- Obadia, J. F. (2018). Percutaneous repair or medical treatment for secondary mitral regurgitation. New England Journal of Medicine, 379(24), 2297-2306.
- Grayburn, P. A. (2018). Proportionate and disproportionate functional mitral regurgitation. JACC: Cardiovascular Imaging, 12(2), 353-362.
- Nishimura, R. A. (2017). 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease. Circulation, 135(25), e1159-e1195.
- Asgar, A. W. (2015). Secondary mitral regurgitation in heart failure. Journal of the American College of Cardiology, 65(12), 1231-1248.
- Goliasch, G. (2018). Refining the prognostic impact of functional mitral regurgitation in chronic heart failure. European Heart Journal, 39(1), 39-46.
- Deferm, S. (2019). Atrial functional mitral regurgitation: JACC review topic of the week. Journal of the American College of Cardiology, 73(20), 2465-2476.