Functional Mitral Regurgitation Outcome and Grading in HFrEF

Dec 08, 2021
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Authors:
Benfari G, Antoine C, Essayagh B, et al.
Citation:
Functional Mitral Regurgitation Outcome and Grading in Heart Failure With Reduced Ejection Fraction. JACC Cardiovasc Imaging 2021;14:2303-2315.
Summary By:
Sarah Kohnstamm, MD, FACC

Quick Takes

  • This study evaluated the link between functional mitral regurgitation (FMR) as quantified by effective regurgitation orifice area (EROA) and excess mortality in patients with HFpEF.
  • Excess mortality in FMR already starts at a low EROA of 0.1 cm2. Subsequent EROA increments are associated with a steep increase in excess mortality, with a 1-year mortality of 28.5% at an EROA of 0.3 cm2, which is lower than the current US guideline-based threshold of 0.4 cm2 for severe MR.
  • An expanded EROA-based FMR grading system should be considered to align current guidelines and recommendations.

Study Questions:

What is the link between functional mitral regurgitation (FMR), as quantified by effective regurgitant orifice area (EROA), and excess mortality? And how does this compare to mortality seen in degenerative mitral regurgitation (DMR)?

Methods:

The study population was patients aged >50 years diagnosed with heart failure with reduced ejection fraction (HFrEF) (EF <50%), stage B-C, who underwent comprehensive echocardiography—including routine-practice FMR quantification—from 2003–2011. The FMR cohort was compared to a simultaneous cohort of DMR.

FMR cohort (n = 6,381), exclusion criteria:

  • Organic mitral valve disease (prolapse, flail-leaflet, ≥ trivial rheumatic or degenerative mitral valve thickening/calcification)
  • ≥ Moderate aortic stenosis/regurgitation
  • ≥ Moderate mitral stenosis
  • Organic tricuspid valve disease
  • Pericardial, hypertrophic, infiltrative, congenital disease
  • Prior valve surgery
  • History of cancer

DMR cohort (n = 2,416): Patients with isolated mitral valve prolapse with otherwise similar inclusion and exclusion criteria.

Outcomes: All-cause mortality at 1 year, long-term mortality. Dates of death were retrieved using Accurint records.

Results:

FMR cohort (n = 6,381):

  • Age 70 ± 11 years, 31% women, EF 36 ± 10%.
  • Only 2,556 (40%) had FMR.
  • For patients under medical management, 1-year mortality was high (15.6%).
  • EROA was 0.09 ± 0.13 cm2, markedly skewed to the left (i.e., 49% in 0.01-0.19, 31% in 0.20-0.29, 12% in 0.30-0.39, and only 8% in ≥0.40).
  • EROA was the strongest independent predictor of mortality under medical management.
  • 1-year mortality increased from 15.4% with EROA 0.01-0.19 cm2 to 21.4% for 0.20-0.39 cm2, and 39.7% in those >0.40 cm2 (adjusted odds ratio, 1.57; 95% confidence interval, 1.19-2.97; p = 0.001).

For the DMR cohort (n = 2,416), EROA was more evenly distributed (27% in 0.01-0.19, 21% in 0.20-0.29, 14% in 0.30-0.39, and 38% in ≥0.40). Moreover, the increase in mortality with increasing 0.10 cm2 EROA increments was less steep in the DMR cohort than the FMR cohort (p < 0.0001).

Conclusions:

  1. FMR was found frequently in this large cohort of HFrEF patients.
  2. EROA values in the FMR cohort skewed markedly towards low values in FMR, but was highly predictive of survival, independent of all echocardiographic variables.
  3. EROA in FMR patients differed significantly from EROA in a parallel cohort of DMR patients, both in its distribution and in the impact of 0.10 cm2 increments on mortality.
  4. For example, 1-year mortality was 28.5% in FMR patients with EROA of >0.3 cm2, a cutoff lower than the current US guideline-based threshold of 0.40 cm2 for severe mitral regurgitation.

Perspective:

FMR (also referred to as “secondary” MR) is characterized by structurally normal leaflets and underlying left ventricular dilation and/or dysfunction. FMR is considered a fundamentally distinct clinical entity from DMR. Despite lower regurgitant volumes, FMR has been linked to higher mortality and morbidity. Likewise, surgical mitral interventions have not consistently led to improvement in FMR outcomes. Finally, there have been discordant guidelines regarding the classification of MR severity, with European guidelines using distinct EROA cutoffs for FMR versus DMR patients, while American College of Cardiology/American Heart Association guidelines have identical EROA thresholds for each group.

The current study screened a large cohort of HFrEF patients for FMR and stratified outcomes by EROA, demonstrating sharp increases in 1-year and long-term mortality with increasing 0.1 cm2 increments. Furthermore, they compared the FMR cohort to a similar-sized DMR cohort and found not only a markedly different EROA distribution, but less excess mortality at higher 0.1 cm2 increments. These findings strongly suggest the need for routine reporting of EROA and argue for unification of discordant guidelines via an expanded FMR grading scale.

Of note, FMR is a dynamic process and EROA and regurgitant volumes can change dramatically based on patient volume status, blood pressure, heart rate, etc. While the authors indicate that EROA measurements “could be measured in routine practice,” obtaining accurate and reproducible EROAs on serial echocardiograms may prove challenging in a real-world setting.

Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Mitral Regurgitation

Keywords: Aortic Valve Stenosis, Cardiac Surgical Procedures, Diagnostic Imaging, Dilatation, Echocardiography, Heart Failure, Heart Valve Diseases, Mitral Valve Insufficiency, Mitral Valve Prolapse, Mitral Valve Stenosis, Stroke Volume, Ventricular Dysfunction


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