Secondary Mitral Regurgitation Common, Undertreated in HF

Secondary mitral regurgitation (sMR) is common in patients with heart failure (HF) and is associated with increased mortality, but it is undertreated, according to a new study.

Investigators analyzed data from more than 13,000 HF patients in an Austrian health network and found sMR to be common across the HF spectrum and correlated with increasing age. One-tenth of all HF patients and one-quarter of those with reduced ejection fraction (EF) were found to have severe sMR.

In patients with severe sMR, interventions such as surgical valve repair, valve replacement, and transcatheter valve repair were underused, with only 7%, 5%, and 4% of all patients, respectively, receiving these treatments.

Compared with patients with HF and no or only mild sMR, mortality in those with moderate or severe sMR was 29% and 82% higher, respectively.

“Secondary mitral regurgitation is not a benign condition and is associated with excess mortality,” Georg Goliasch, MD, PhD, and Philipp Bartko, MD, PhD, both leaders of the working group and both associate professors at the Medical University of Vienna, told theheart.org | Medscape Cardiology in an e-mail.

“Echocardiographic screening helps to identify secondary mitral regurgitation, [which is] ultimately a treatment target to improve patient outcome,” they said.

The study was published online June 30 in BMJ.

“Mandatory” Data

Most previous studies of mitral regurgitation have focused on primary mitral regurgitation, which is “less prevalent and has different disease specific and epidemiological characteristics, making interpretation of outcomes and treatment standards for sMR impossible,” the study authors write.

The investigators set out to describe the demographic characteristics of sMR across all HF subgroups, explore the association between sMR and mortality according to HF subtype, and look at current treatment of sMR in “state-of-the-art” healthcare facilities.

“Prevalence, outcome, and treatment utilization of secondary mitral regurgitation have not been studied among the entire HF spectrum before, although these data are mandatory for international comparison, monitoring of tailored treatment programs, and planning of public health policy,” Goliasch and Bartko said.

Using data from 2010 to 2020 in the Medical University of Vienna medical health records and echo database, the investigators identified 13,223 patients with HF (median age, 70 years; 66% male) who had undergone a transthoracic echocardiogram and had no evidence of organic primary mitral valve disease or significant primary disease of another valve.

The primary endpoint was all-cause mortality, with data drawn from the Austrian Death Registry.

In all, 56% of patients presented with preserved, 25% with mid-range, and 20% with reduced ejection fractions.

sMR was absent or mild in 30% of patients, moderate in 60%, and severe in 10%.

Stepwise Increase

Severe sMR was more common in women than in men (12% vs 9%) and in patients with reduced EF (25%), whereas the prevalence of moderate sMR rose with increasing age.

The more severe the sMR, the greater the increases in the left ventricular (LV) end-diastolic and left atrial (LA) diameters and the higher the N-terminal pro-brain natriuretic peptide (NT-proBNP) level.

Effect of sMR Severity on LV Diameter, LA Diameter, and NT-proBNP Level
sMR severity	LV Diameter, mm	LA Diameter, mm	NT-proBNP Level, ng/L
No/mild	46	56	633
Moderate	47	59	1400
Severe	53	65	3700

Over the total observation period, only a fraction of patients with moderate to severe sMR underwent surgical mitral valve repair (1.5%), mitral valve replacement (1.1%), or transcatheter mitral valve repair (0.8%).

Patients with HF and preserved EF had the fewest mitral valve interventions, followed by those with mid-range and reduced EFs (2.2%, 2.5%, and 3.1%, respectively).

During a median follow-up of 60 months, 33% of patients died.

At 4 years, 39% of HF patients with severe sMR and 25% of those with no/mild sMR had died, compared with an expected 2% fatal event rate for persons of the same age and sex in the community (P < .001). A similar pattern was observed at 8 years (55%, 37% and 14%, respectively; P <.001).

Compared with the expected survival for people of the same age and sex, excess mortality was seen in patients with moderate sMR (hazard ratio [HR], 5.08) and those with severe sMR (HR, 7.53; P < .001 for both).

When compared with HF patients with no/mild sMR, the risk for mortality climbed with increased sMR severity, with unadjusted hazard ratios of 1.29 for moderate regurgitation and 1.82 for severe regurgitation (P < .001 for both).

The results remained “virtually unchanged” after multivariable adjustment in a traditional clinical risk factor model and in a bootstrap adjusted model, the authors report.

The significant adverse impact of severe sMR in HF patients was consistent across all the examined subgroups, except for patients with severely reduced right ventricular function.

The excess mortality of severe sMR was most pronounced in patients with HF and mid-range EF (HR, 2.53) and reduced EF (HR, 1.70), followed by preserved EF (HR, 1.52; P <.001 for all).

“Mortality was high overall and in each HF subgroup,” an impact that was “previously established in patients with reduced EF, but not in mid-range and preserved EF in HF,” Goliasch and Bartko commented.

“Despite broad population healthcare coverage and all available state-of-the-art treatment options, surgical valve repair and replacement are rarely performed owing to the associated high risk features of patients with sMR,” the authors write. Less-invasive treatment is also rarely used; however, “transcatheter mitral valve repair should be considered across the entire spectrum of heart failure to keep up with the increasing demand for treatment.”

Multidisciplinary Approach

Commenting on the study for theheart.org | Medscape Cardiology, Gurusher Panjrath, MD, director of the heart failure and mechanical circulatory program at George Washington University Hospital, Washington, DC, said that its “biggest take-home message is to re-emphasize that clinicians need to be looking at and recognizing sMR in the HF population.”

Panjrath, who is the immediate-past chair of the American College of Cardiology’s Heart Failure and Transplant Section Leadership Council and was not involved with the study, said clinicians should “appreciate the association with outcomes and see it as an opportunity to enhance management and overcome therapeutic inertia.”

In patients who have moderate to severe sMR despite appropriate medical management, “consideration should be made for surgical or transcatheter mitral valve repair, as appropriate,” Panjrath said.

The lack of proof that surgical valve repair or replacement can improve survival in sMR “justifies a conservative surgical approach restricted to those for whom another cardiac procedure, such as bypass grafting, is vital,” the authors write.

They also note that there is a paucity of controlled data on the effect of sMR with transcatheter mitral repair in HF with mid-range and preserved EFs, but that the ongoing RESHAPE-HF2 trial of the MitraClip might clarify whether or not treatment benefit with an expanded EF spectrum up to 45% can be expected.

The study was supported by the Austrian Science Fund. Goliasch and Bartko report no relevant financial relationships. The other authors’ disclosures are listed in the paper. Panjrath reports no relevant financial relationships.

BMJ. Published online June 30, 2021. Full text

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