Mitral Regurgitation in HF: Optimizing Outcomes

This transcript has been edited for clarity.
Hi. My name is Dharam Kumbhani. I’m an interventional cardiologist and structural interventionalist at UT Southwestern in Dallas. I am the section chief and the cardiac catheterization lab director here. I’m delighted to talk to you today about mitral regurgitation (MR) in heart failure. 
As we know, the mitral valve is a very complex structure. We also know that, broadly speaking, MR can be classified as primary — something that involves typically the leaflets or the chordae — or secondary, which is typically an issue with the atria, the ventricles, or the annulus. It is estimated that about 65%, or two thirds, of MR is secondary and the rest is primary. 
Clinical recognition of MR is typically assessed with auscultation as well as physical signs, such as volume overload. I want to emphasize that particularly for secondary MR in low-flow states, the murmur may actually be quite underwhelming. It’s not the loud, blowing, holosystolic murmur that we would be used to hearing in primary MR cases, so very careful assessment for that is important. I think when there is a suspicion of this condition in patients, augmentation with other imaging modalities and sometimes biomarker evaluations, such as brain-type natriuretic peptides, is also very helpful. 
The most important diagnostic test, of course, is transthoracic echocardiography (TTE) , which involves doing a detailed assessment of the mitral valve — determining any calcification on the leaflets, the size, volumes on the atrial side as well as the ventricular side, left ventricular (LV) function, pulmonary artery pressure (if possible), and right ventricular function, and then also other possible conditions, such as tricuspid regurgitation. I think doing a thorough assessment is extremely important to understanding how one would approach treatment of this condition. 
The other component is understanding the definition of severe secondary MR. The 2020 American College of Cardiology/American Heart Association (ACC/AHA) valvular heart disease guidelines define it on the basis of an effective regurgitant orifice area ≥ 0.4 cm2 and a regurgitant volume ≥ 60 mL. I think this distinction is also important to really being able to understand whether the patient has moderate secondary MR or severe secondary MR. 
When there is a question or suspicion of severe MR, and to fully understand the true etiology of the MR, transesophageal echocardiography (TEE) and cardiac MRI can be very helpful to understand the hemodynamics and the anatomy of the patient’s condition in great detail. Indeed, in the most recent iteration of the ACC/AHA valvular heart disease guidelines, it is a Class 1 indication to use TTE to establish the severity of the MR initially, and then, if needed — especially when an intervention is being contemplated — getting TEE also has a Class 1 recommendation. 
How does one think through the management of patients with MR? As I said, understanding the problem or the etiology is the first step. For secondary MR, also called “functional MR,” the first line of treatment is guideline-directed medical therapy (GDMT) for agents that work in heart failure. Particularly when the MR is related to heart failure with reduced ejection fraction, the drug classes that we know work really well, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, the guidelines recommend that treatment of LV dysfunction that is typically driving the MR is usually the first step. I think that is very important, and it is important to have these drugs implemented at the highest possible dose. 
The efficacy of these agents is not instantaneous. There is a time lag before the LV function improves and when we might see improvements in the degree of MR. Typically, there is a 3- to 6-month period before which we really start seeing an effect. Of course, these patients have to be augmented with diuretics frequently — typically using loop diuretics that help with decongestion and help from a systemic standpoint. 
The other thing that I want to point out is the ACC/AHA valvular heart disease guidelines also emphasize the importance of having a cardiologist who has particular expertise in the management of patients with heart failure and LV systolic dysfunction as a primary member of the valve team, to help to optimize the use of GDMT. 
Another aspect of optimization, other than guideline-directed medical therapy, is considering cardiac resynchronization therapy (CRT) for patients with impaired LV function and for those who have a left bundle-branch block with a QRS ≥ 150 msec. It is estimated that approximately 20% of patients with heart failure with reduced ejection fraction would meet the criteria for CRT, and about half of them will improve the degree of MR with CRT alone. I think it’s very important to look through other variables that may be helpful in reducing the degree of MR [such as untreated severe aortic regurgitation or atrial arrhythmias].
When you start thinking about functional MR, if you’re now contemplating a valve intervention, then the first step would be to get a detailed and comprehensive TEE, which can outline what the pathology is and help you to understand what the options are for the various therapies. 
There are two options, broadly speaking. One is surgery, and the other is a transcatheter intervention — transcatheter edge-to-edge repair (TEER). Surgery has been assessed before in clinical trials, and it was found that chordal-sparing mitral valve replacement actually did better from a long-term standpoint in terms of reducing the degree of residual or recurrent MR [and readmissions of heart failure]. This is not a therapeutic option for most patients, and indeed, in the guidelines, it is currently a Class 2b indication, meaning it can be considered in selected situations. 
On the other hand, what has been really encouraging is the role of mitral TEER (M-TEER) in reducing the annular size by approximating the leaflets. That has been shown in clinical trials to be very helpful for patients with functional MR. Again, the patients that have been studied have all had LV functional MR — so a low ejection fraction. 
There are three studies of which you should be aware. The first study is MITRA-FR. This was a study done in France, and there were about [300] patients with ventricular functional MR that were randomized to receiving TEER with the MitraClip or GDMT only. The researchers did not find any difference in heart failure hospitalizations or mortality in patients with M-TEER. 
On the other hand, the COAPT trial was really important. This was a larger trial, of 614 patients who had to be optimized on GDMT before they could be randomized to either M-TEER along with GDMT or continuing GDMT alone. There was a dramatic improvement in the primary endpoint with reductions both in heart failure hospitalizations and all-cause mortality. 
The benefits started early and appeared to be sustained over the 24-month duration of follow-up. There were also significant improvements in patient-related outcomes as well as markers of LV remodeling. On the basis of the results of the COAPT trial, the device was approved for use in the US and has certainly become a very important therapeutic option of how these patients are treated. 
Recently, the RESHAPE-HF2 trial was presented and published, and that also noted that, similar to COAPT, there was an improvement–a lower rate of heart failure hospitalization among patients with ventricular functional MR. On the basis of these trials, the guidelines currently have afforded a Class 2a recommendation for M-TEER in patients who have ventricular functional MR that has been treated optimally with GDMT and still have symptomatic moderate-to-severe or severe MR. 
Also, earlier this year, we saw the results of the MATTERHORN trial, which compared surgery vs M-TEER. At 1 year, they did not see any difference or any improvements with surgery compared with M-TEER. Based on these results, at least up to the shorter follow-up period, the way the guidelines ranked it, with a Class 2a recommendation for M-TEER and a Class 2b recommendation for surgery, still appeared to make sense. 
To summarize, MR is a very complex disease. Multiple components are involved in the condition, and multiple members of the heart team or the multidisciplinary team are really important in being able to successfully manage and treat patients with this problem. 
The first-line approach, as I said, should be GDMT. CRT should be considered when indicated, and when symptoms persist beyond using GDMT for a period of time, M-TEER can be considered. The outcomes with this technology have been very promising. 
Thank you so much for your attention.