Author + information
- Roy Beigel, MD and
- Robert J. Siegel, MD∗ ()
- ↵∗The Heart Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Room 5623, Los Angeles, California 90048-1804.
The 2012 guidelines for the management of valvular heart disease by the European Society of Cardiology (ESC) (1) recommend that for functional mitral regurgitation (MR), an effective regurgitant orifice area (EROA) of >20 mm2 should be considered severe; however, an EROA of >40 mm2 is used as the cutoff for degenerative MR.
Several nonrandomized studies have shown that cardiac mortality is increased in the presence of functional MR and reduced left ventricular (LV) ejection fraction (2). Patients with an EROA of ≥20 mm2 have a lower 5-year survival rate and a higher risk of congestive heart failure. This same association is present for lesser degrees of MR; with an EROA of 1 to 19 mm2, there is an increased 5-year mortality rate and a high risk of congestive heart failure. Current American College of Cardiology/American Heart Association (ACC/AHA) (3) and ESC guidelines (1) use a matrix of criteria for the diagnosis of severe MR, as shown in Table 1. No single criterion in isolation is sufficient to establish a diagnosis of severe MR. EROA can be calculated by the proximal isovelocity surface area (PISA) or by measuring the MR volume or regurgitant volume by assessing the LV volume and LV forward stroke volume. Most echocardiography laboratories do not use the latter volumetric technique because it is time-consuming and can be associated with significant errors due to unreliable endocardial edge detection. In addition, calculations of forward stroke volume may be inaccurate because they are generally based on the assumption that the LV outflow tract is circular, whereas, in fact, recent 3-dimensional echocardiography and computed tomography data have shown that it is generally oval.
Thus, most clinical laboratories rely on flow convergence assessment or the PISA method to assess the EROA. However, the use of the PISA to assess the EROA has also been shown to be highly problematic: Table 2 lists >10 substantial limitations to the PISA method. In addition to these limitations, reliance on a single method to assess MR severity in functional MR deviates from the wisdom of using multiple criteria to grade MR severity, which was supported by the initial ACC/AHA guideline committees and the American and the European echocardiography societies.
Unlike degenerative MR, especially in the setting of a flail leaflet where MR severity is relatively fixed, functional MR varies with the patients' hemodynamic status. Because functional MR severity may be highly variable, patients should be assessed while on optimal therapy (including revascularization and/or cardiac resynchronization therapy) before classifying them as severe.
The rationale for the ESC recommendations to lower the threshold for grading MR severity in the setting of functional MR is in part related to the adverse prognosis associated with MR in patients with LV dysfunction. However, associations do not always equal causation, therapeutic indications, or therapeutic benefit. CAST (Cardiac Arrhythmia Suppression Trial) serves as an example of why associated phenomena should not be used as targets for treatment. For years, “it was known” that ventricular ectopy in the setting of reduced LV function was associated with a worse prognosis as well as being associated with a higher incidence of sudden death. However, the CAST clearly showed that treating this associated variable (premature ventricular contractions) with antiarrhythmic agents increased all-cause mortality and also serves as an example of why associated phenomena should not be used as targets for treatment.
Multiple trials demonstrate that for functional MR (ischemic or nonischemic), surgery with revascularization or mitral valve repair or replacement does not improve the 5-year survival rate (4). The only therapies that are beneficial for functional MR are those that improve ventricular function such as beta-blockers and angiotensin-converting enzyme inhibitors. Until now, moderate MR has been defined by an EROA of 0.20 to 0.39 mm2. Patients with 3+ to 4+ MR who have moderate (2+) residual MR after placement of a MitraClip (Abbott Vascular, Abbott Park, Illinois) have reverse remodeling, a decrease in LV end-diastolic volume from 159 ml to 141 ml (p < 0.001), a trend toward a decrease in end-systolic volume from 82 ml to 77 ml (p = 0.07), and improvement in symptoms after 1 year (5). However, according to the recent ESC criteria, patients with moderate functional MR would be classified inappropriately as having severe MR and would be candidates for further intervention.
With the development of percutaneous techniques, there may be an inclination to treat less severe degrees of MR in an attempt to improve the status of patients with impaired LV function. However, this approach is likely to be problematic. It will be difficult to assess improvement or treatment success (a decrease in MR) if patients with an EROA of 20 to 30 mm2 are treated. Clinical follow-up and assessment of improvement will be complicated by the patients' underlying LV dysfunction. At present, if the criteria for MR severity are to be reduced in the setting of functional disease, an EROA threshold of 30 mm2 would be more amenable to determining whether the intervention reduced MR severity. With an EROA between 20 and 30 mm2, it will be difficult to discern whether the intervention actually decreased MR severity, and even more so if the EROA is 20 to 25 mm2. It is also important not to use a single variable but to maintain the matrix of echocardiographic Doppler parameters listed in Table 1, which have been the standard used to define MR severity.
Any degree of MR worsens patient prognosis; however, mitral valve surgery does not improve prognosis unless LV function is improved. MitraClip patients with a 2+ (moderate) MR result have an improvement in symptoms, functional capacity, and ventricular size. These findings suggest that moderate MR (EROA of >0.20 and <0.30 cm2) does not adversely affect either the left ventricle or patient prognosis and should not be classified as severe, despite the most recent ESC guideline/recommendations (1).
Please note: Dr. Beigel is a recipient of a fellowship grant from the Israel Heart Society. Dr. Siegel has reported that he has no relationships relevant to the contents of this paper to disclose.
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