Page 53 - Read Online

Page 2 of 19 Masiero et al. Mini-invasive Surg 2022;6:4 https://dx.doi.org/10.20517/2574-1225.2021.104

represents one of the most common VHD conditions. Men and women demonstrate dissimilar baseline
[1]
characteristics, morphological and clinical presentation, and outcomes . Different from valve surgery,
where patients were predominantly male, both sexes have been well represented in percutaneous treatment
[2]
of AS . Furthermore, women appeared to derive greater benefit compared to men with transfemoral aortic
valve implantation (TAVI) compared to surgical treatment. This review focuses on sex-specific differences
in the clinical management of degenerative AS, highlighting sex-specific technical considerations in the
percutaneous treatment of the disease, taking into account the latest technological innovations. In
particular, epidemiology, pathophysiology, diagnostic issues, treatment options, and clinical outcomes in
the female AS population are reported. Moreover, we evaluate whether a sex-based TAVI management,
from device selection to procedural tricks, might have an impact on clinical outcomes.

SEX-SPECIFIC CONSIDERATION IN THE DIAGNOSIS AND TREATMENT OF AS
Epidemiology of AS
AS is the most prevalent valvular heart disease requiring intervention, surgery or transcatheter, in Europe
[3,4]
and North America . The prevalence of AS is 4% by echocardiography, with equal frequency in men and
women and a mortality rate of over 50% at two years in symptomatic AS patients unless promptly treated. It
occurs primarily as a consequence of degenerative calcific disease, so its prevalence is rising rapidly due to
the aging population; it has been estimated that approximately 12% (Europe) and 4% (North America) of
the elderly patients (> 75 years) have symptomatic severe AS . Conversely, among the most frequent
[5]
congenital anomalies, bicuspid aortic valve (BAV) is 3-4 times more prevalent in men as compared to
women and is associated with earlier accelerated degeneration of the valve apparatus that tends to be more
severe than in tricuspid aortic valve . Although the evidence on the distribution of BAV phenotypes
[4,5]
between sexes is not consistent, observational series showed higher prevalence of stenotic dysfunction in
female patients compared to men more frequently affected by aortic regurgitation . As rigorous evidence is
[4]
still lacking in the percutaneous treatment of BAV, we focus our discussion on tricuspid aortic valve
stenosis.

Pathophysiology of degenerative AS
It is now recognized that degenerative age-related valve mineralization is a dynamic process with lipid
accumulation, chronic inflammation, and active valve leaflet calcification. It involves proinflammatory
monocytes and activated endothelial cells that stimulate macrophage accumulation, proteolytic enzymes
release, and the differentiation of myofibroblasts and smooth muscle cells into osteoblasts with resultant
osteogenic activity. However, little is known about the role of sex in the etiology and progression of the
disease.

To date, sex differences in the valves and the ventricular response to the pressure and volume overload due
to valvular disease have not been completely elucidated [Figure 1]. A lower collagen I-II and matrix
metalloproteinase 2 gene expression has been found in women vs. men in the interstitial cells of myocardial
biopsy specimens performed at the time of surgery; adjunctively, on a molecular level, decreased
extracellular fibrosis has been linked to the protective effect of estrogen in the female population. Therefore,
women display different patterns of hypertrophy and remodeling, with a different extent of ventricular
fibrosis and morphology of aortic valve disorder . As a matter of fact, differently from males, women
[2]
showed more frequent concentric left ventricular (LV) hypertrophy, smaller LV cavities, and greater relative
wall thicknesses facing the increased afterload of worsening AS. However, women more often experience
reversal of hypertrophy shortly after aortic valve replacement . Moreover, studies comparing the extent of
[6]
aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in men and
women with comparable degrees of AS revealed a lower AVC load, even after adjustment for body surface
[6]
area and echocardiographic parameters . Likewise, female sex was correlated to lower AVC progression