Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction
Introduction
Mitral annular calcification (MAC) occurs secondary to dystrophic calcification of the mitral annulus and has been shown to be an independent predictor of cardiovascular events, including atrial fibrillation (AF),1,2 myocardial infarction,3 and cardiovascular death.3,4 MAC-related mitral valve (MV) dysfunction is caused by the encroachment of annular calcium onto the valve leaflets, resulting in restricted annular dynamics and decreased leaflet mobility and can lead to mitral stenosis and often, concomitant mitral regurgitation (MR). The transmitral gradient represents an integrative measure of the hemodynamic impact of MAC-related MV dysfunction and offers independent prognostic information,5,6 with markedly increased mortality at higher gradients. MAC is traditionally viewed as a female-predominant disease, and it is increasingly recognized that MAC-related MV dysfunction is more common among women.7,8 However, gender differences in the prevalence and natural history of MAC-related MV dysfunction and in the prognostic implications of the transmitral gradient remain poorly understood. An improved understanding of such differences may allow A more precise risk assessment and stratification, which in turn has important implications for patient selection for the expanding array of therapeutic options in this population.9 This study aimed to define the important differences in clinical characteristics, echocardiographic phenotypes, and clinical outcomes between women and men with MAC and MV dysfunction. We hypothesized that although MAC and MV dysfunction are more prevalent in women, the outcomes would be similarly affected by the presence of hemodynamically significant MAC across both genders.
Section snippets
Methods
All patients with MAC and a documented transmitral gradient on echocardiography performed for any clinical indication between 2001 and 2019 were included from a large institutional echocardiography database (Massachusetts General Hospital, Boston, Massachusetts). For patients with multiple echocardiograms, the earliest examination was included. After the exclusions for rheumatic and congenital mitral stenosis, previous surgical intervention, and missing clinical follow-up, the starting sample
Results
The study population consisted of 3,524 patients (average age 78 ± 11 years), with more women than men meeting the inclusion criteria of extensive MAC and MV dysfunction (MV gradient ≥3 mm Hg; Figure 2). Compared with men, women in the sample were older (79.3 ± 10.4 vs 75.5 ± 10.9 years, p <0.001) and had lower rates of common cardiovascular co-morbidities, including hyperlipidemia, diabetes mellitus, renal disease (stage ≥III CKD), coronary artery disease, and AF (Table 1). The rates of
Discussion
We present here data defining the gender differences in clinical characteristics, echocardiographic findings, and outcomes among patients with MAC-related MV dysfunction. The key findings are as follows. First, more women than men have extensive MAC with associated MV dysfunction, and although older, these women have lower rates of cardiovascular co-morbidities, such as coronary artery disease, AF, diabetes mellitus, and CKD. Next, important echocardiographic differences were observed among
Disclosures
The authors have no conflicts of interest to declare.
References (33)
- et al.
Mitral annular calcification predicts cardiovascular morbidity and mortality in middle-aged patients with atrial fibrillation: the Belgrade atrial fibrillation Study
Chest
(2011) - et al.
Impact of mitral annular calcification on cardiovascular events in a multiethnic community: the Northern Manhattan Study
JACC Cardiovasc Imaging
(2008) - et al.
Mitral valve dysfunction in patients with annular calcification: JACC review topic of the week
J Am Coll Cardiol
(2022) - et al.
Increased prevalence of mitral stenosis in women
J Am Soc Echocardiogr
(2006) - et al.
Frequency of mitral valve dysfunction from mitral anular calcium as detected by Doppler echocardiography
Am J Cardiol
(1985) - et al.
1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification
J Am Coll Cardiol
(2018) - et al.
Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the American Society of Echocardiography developed in collaboration with the Society for Cardiovascular Magnetic Resonance
J Am Soc Echocardiogr
(2017) - et al.
Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
J Am Soc Echocardiogr
(2015) - et al.
Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA)
Atherosclerosis
(2010) - et al.
Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study)
Am J Cardiol
(2006)
Risk factors associated with the incidence and progression of mitral annulus calcification: the multi-ethnic study of atherosclerosis
Am Heart J
Survival in patients with degenerative mitral stenosis: results from a large retrospective cohort study
J Am Soc Echocardiogr
Associations of long-term and early adult atherosclerosis risk factors with aortic and mitral valve calcium
J Am Coll Cardiol
Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study
J Am Coll Cardiol
Association of triglyceride-related genetic variants with mitral annular calcification
J Am Coll Cardiol
Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation
J Am Coll Cardiol
Cited by (1)
Considerations & challenges of mitral valve repair in females: Diagnosis, pathology, and intervention
2024, Current Opinion in Cardiology
This study was supported, in part, by a grant of the National Institutes of Health (Bethesda, Maryland) grant R01 HL141917 (Drs. Levine and Hung). Dr. Churchill is supported by the National Institutes of Health 1K23HL159262-01A1.
- 1
Drs. Churchill and Yucel contributed equally to this work as first authors.