By Michael H. Crawford, MD, Editor

SYNOPSIS: This retrospective review of the natural history of severe calcific mitral valve stenosis demonstrates such patients die often partly because of a high comorbidity burden and partly as a result of the valve stenosis.

SOURCE: Kato N, Padang R, Scott CG, et al. The natural history of severe calcific mitral stenosis. J Am Coll Cardiol 2020;75:3048-3057.

Increased longevity and the decline in rheumatic heart disease in developed countries has led to a rise in the prevalence of mitral annular calcification and (occasionally) calcific mitral stenosis (MS). Since little is known about the appropriate management of calcific MS, investigators from the Mayo Clinic sought to assess the clinical characteristics and predictors of mortality in such patients.

The authors collected adults with severe calcific MS from an echocardiographic database from 2003 to 2017. Severe calcific MS was defined as a valve area < 1.5cm2 by the continuity equation. Patients with significant disease of other valves or moderate or more mitral regurgitation were excluded. The primary endpoints were all-cause mortality and cardiovascular events. Severe calcific MS was discovered in 200 patients: mean age of 78 years, 82% were women, and the mean follow-up was 2.8 years. Symptoms thought to be caused by MS were present in 60%, with dyspnea the most common (49%). In a multivariable analysis, symptoms were associated with higher transmitral gradients, low stroke volume, chronic lung disease, and atrial fibrillation.

Of the 32 patients who received mitral valve interventions, surgical mitral valve replacement was performed in 31 and transcatheter replacement in one. Without intervention, all-cause mortality was 28% at one year, 48% at three years. Multivariable determinants of all-cause mortality without intervention were inactivity (hazard ratio [HR], 6.59), left ventricular ejection fraction < 50% (HR, 5.48), right ventricular systolic pressure > 50 mmHg, and transmitral gradient > 8 mmHg. The authors concluded that patients with severe calcific MS often had comorbidities that limited survival. Valve-specific independent predictors of mortality included right ventricular systolic pressure > 50 mmHg and transmitral gradient > 8 mmHg. Symptoms did not predict mortality.

COMMENTARY

Mitral annular calcification is a frequent finding in echocardiograms performed in elderly patients. Severe calcific MS is much less common. It took the Mayo Clinic 14 years to amass 200 cases. Nevertheless, this is a challenging entity to manage, as this paper illustrates. For starters, the pathophysiology is different from rheumatic MS in that the calcium starts in the annulus, then moves into the base of the leaflets. There is no leaflet thickening, chordal shortening, or commissural fusion. Thus, the restricting orifice is a tubular structure at the leaflet base rather than the dome shape of commissural fusion seen in rheumatic MS. Also, the patients are elderly and carry a high burden of comorbidities, which can cause symptoms and disability.

Deciding when the symptoms are because of MS is difficult. Trying to objectify them by exercise testing would be problematic in this age group. In this study, 60% of those with severe calcific MS exhibited symptoms thought to be caused by valve disease, but this was determined by chart review and could be inaccurate. In addition, the echocardiographic confirmation of calcific MS is complicated. The pressure half-time method tends to overestimate valve area because of the reduced net atrioventricular compliance caused by comorbidities, such as atrial fibrillation, and reduced left ventricular systolic and diastolic function. Thus, the continuity equation is the technique of choice, but it presents its own problems — mainly, the inaccuracy of estimating the reference flow at another valve site. Finally, the planimetry method is limited by difficulty in determining the limiting orifice in a heavily calcified valve structure.

Kato et al showed patients with severe calcific MS carried a high comorbidity burden with a Charlson Comorbidity Index average of 5 (> 4 considered high), and 7% of their patients were inactive. Also, morbidity was high at 28% in one year without intervention. Multivariable predictors of mortality were related to comorbidities (inactivity and low left ventricular ejection fraction) and the severity of MS (transmitral gradient and pulmonary artery systolic pressure), as would be expected. Interestingly, symptoms were not predictive of mortality, probably because they were not exclusively the result of MS. In this study, 23% of symptomatic patients underwent an intervention (surgical valve replacement in almost all). The data were not robust enough to determine if intervention improved survival. Surgery is challenging because of the calcified annulus, comorbidities, and age. Careful patient selection is key.

Currently, transcatheter mitral valve replacement has not been particularly successful, but is developing. Low ejection fraction, if not caused by infarction, may not be a contraindication to surgery. Severe MS can lead to low ejection fraction because of reduced left ventricular filling, which improves with relief of the mitral obstruction. In asymptomatic patients, watchful waiting makes sense since this study showed progression of calcific MS is much slower than that observed with rheumatic MS (0.05 vs. 0.2 cm2/year). This retrospective review of the Mayo Clinic experience with severe calcific MS adds to our knowledge of the natural history of this entity and will serve as a reference point for future interventional studies.