Sex Differences in the Etiology of Surgical Mitral Valve Disease

Surgical mitral valve disease is an entity that has evolved over the past 30 years.¹ With increasing rates of early coronary revascularization and a decreasing prevalence of rheumatic fever, the etiology of surgical disease in developed countries has shifted from rheumatic and ischemic in origin to one predominated by degenerative disease. This shift in etiology has been paralleled by an evolution in surgical technique. Mitral valve repair has allowed surgeons to reconstruct a degenerative valve without the use of a mechanical or biological prosthesis. In comparison with male patients, female patients undergo higher rates of mitral valve replacement than repair.^2,3 This difference has been theorized to be a factor to account for worse outcomes following mitral valve surgery in women. Attempts to explain this disparity in procedure choice have been linked to sex differences in the type of valve lesions.⁴ Mitral valve repair has the greatest success in cases of degenerative mitral regurgitation with posterior leaflet prolapse, and women have been shown to have less posterior prolapse than men.^4,5 In addition, women have a higher incidence of mitral stenosis as an indication for operation, thereby typically necessitating replacement.⁵ Prior studies have not accounted for sex differences in the etiology of surgical mitral valve disease and whether they have changed in the modern era.

The aim of this research was to assess sex differences in the etiology of surgical mitral valve disease and whether those differences have persisted over time. A retrospective analysis was performed of consecutive patients undergoing primary mitral valve surgery, either replacement or repair, at our institution from 1993 to 2016. Patients were identified from the Cardiovascular Information Registry, which represents a subset of the national Society of Thoracic Surgeons database. The Cardiovascular Information Registry collects information on all patients undergoing cardiothoracic surgery at our institution. Permission for use of data from this registry was granted by our institution’s Institutional Review Board, and informed consent was not required. We included patients who had undergone concomitant coronary artery bypass grafting or another valve procedure at the time of their mitral intervention. Patients who had previously undergone cardiac surgery were excluded. Coding of mitral valve disease etiology had been prospectively adjudicated at the time of surgery based on standards using a combination of clinical information, surgical impression of the valve, echocardiographic parameters, and surgical pathology. The information regarding etiology is available through our Cardiovascular Information Registry database. Terms applied for the etiology of valve disease were based on the Society of Thoracic Surgeons Database Collection Form. The prevalence of valve etiology was first stratified by sex with differences in categorical data compared by using χ² testing. The subjects were then divided into 5-year intervals, and differences in etiology were further stratified by time with temporal trends analyzed using the Cochran-Armitage test.

Our study cohort included 23 806 unique patients, 40.8% women (n=9713). For our overall cohort, the majority of patients presented with degenerative disease (58%). The next most prevalent etiologies of disease were ischemic (11.7%) and rheumatic (11.9%). The remaining 8 etiologies made up 18% of the population, each representing ≤6% of the cohort.

In analyzing sex-specific differences among the 3 most prevalent disease types, women had a markedly higher rates of rheumatic valve disease than men. Men presented with more degenerative and ischemic valve disease. All these differences were highly statistically significant (P<0.001). When our analysis was stratified by year, there were significant differences in the rates of these 3 causes of valve disease—degenerative, ischemic, and rheumatic—over time. We observed 2 distinct trends in this group. There was a significant increase in the percentage of degenerative valve disease (46.8%–63.4%, P<0.001) and a reduction in the prevalence of ischemic (14.1%–5.7%, P<0.001) and rheumatic disease (19.9%–8.3%, P<0.001). In evaluating disease prevalence over time by sex, despite the rates of rheumatic and ischemic valve disease declining overall, women maintained a significantly higher prevalence of rheumatic involvement than men (P<0.001) and a significantly lower prevalence of ischemic diseases (P<0.01) throughout the years studied. Although degenerative valve disease increased overall, women consistently had lower rates than men (P<0.001) (Figure). Our study highlights the differences in the etiology of surgical mitral valve disease between female and male patients. The most striking finding is a disproportionate amount of rheumatic mitral valve disease in women. The time analysis clarifies that, although there is a temporal shift in the etiology of surgical mitral valve disease for all patients, differences between the sexes persist even in the modern era of cardiac surgery. This variance in etiology is an important signal to be noted for surgical mitral valve disease. In identifying sex differences in the etiology of mitral valve disease, we have identified another avenue that potentially links patient to sex differences in procedure selection and outcomes.