JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 75, NO.

24, 2020

ª 2020 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

EDITORIAL COMMENT

Calcific Mitral Stenosis

Echoes of Aging*

Shantanu P. Sengupta, MD, DNB,a Jagdish C. Mohan, MD, DMb

“The Anthropocene touches each one of us, not known; however, it constitutes <0.5% of the
unevenly, unexpectedly, and sometimes painfully.” echocardiographic database (6,7) and approximately
—Steve Mentz (1) 13.6% of all types of MS in the Euro Heart Survey (8).

C
Mitral annular calcification, on the other hand, is
alcific mitral valve stenosis (MS) is a disease
present in up to 42% of the free-living elderly adults
of the elderly, characterized by impaired
and correlates with worse cardiovascular, renal, and
left-atrial emptying due to reduced opening
metabolic status (9). Unlike post-inflammatory rheu-
of the mitral-valve orifice. Moderate to severe
matic MS, there is no thickening of the leaflets,
valvular heart disease affects the elderly with a fre-
chordal shortening, or commissural fusion in this
quency of 13.2% in those $75 years of age, without
phenotype (10). Its biological behavior and progres-
any gender predilection (2). Degenerative MS in the
sion have not been studied in great detail. Some
elderly is a complex clinical entity that has gained
calcification does occur in rheumatic MS, but it
importance in recent years. Increasing age with
essentially involves commissures, rough zone of the
concomitant cardiovascular and metabolic risk fac-
leaflets, and rarely the annulus. Isolated mitral
tors is associated with calcific noninflammatory
annular calcification with reduced orifice poses
degeneration of the fibrous skeleton of the heart.
unique diagnostic and therapeutic challenges (11).
Calcification of mitral annulus is common in the
Moreover, its natural history is ill defined. Trans-
elderly. When it extends and invades into the base
mitral diastolic pressure gradient is a valid and robust
of valve leaflets and results in reduced orifice of dias-
parameter of obstruction severity and prognosis but
tole flow with unrestricted leaflet tips and elevated
can vary significantly depending upon stroke volume
transmitral gradients, it is labeled the clinicoechocar-
and heart rate (12). Orifice shape is tubular in calcific
diographic entity of calcific MS.
MS, unlike in rheumatic MS, wherein it is dome-
The first reported case of mitral annular calcifica-
shaped because of commissural fusion (13). It is
tion was described more than 4,000 years ago in a
difficult to perform direct planimetry of the mitral
60-year-old Egyptian woman (3). Mitral annular
orifice by 2-dimensional (2D) echocardiography,
calcification causing inflow obstruction was initially
although color-coded real-time 3D echocardiography
suggested in a pathological study in 1962 (4). The first
has been shown to be more reliable in estimating
extensively documented case of calcific MS was re-
orifice area (13). Pressure half-time is not reliable and
ported by Ramirez and Flowers (5). The exact preva-
mostly overestimates effective orifice area because of
lence of the calcific MS in the general population is
reduced net left-atrioventricular compliance second-
ary to associated comorbidities (11,13). Reduced left-
*Editorials published in the Journal of the College of Cardiology reflect the sided atrioventricular compliance commonly present
views of the authors and do not necessarily represent the views of JACC
in calcific MS is also an underlying mechanism of
or the American College of Cardiology.
elevated pulmonary artery pressures that adversely
From the aSengupta Hospital and Research Institute, Nagpur, India; and
affect the prognosis (14). Continuity equation method
the bFortis Hospital, Shalimar Bagh, Delhi, India. Both authors have re-
ported that they have no relationships relevant to the contents of this remains the gold standard to estimate mitral valve
paper to disclose. area in calcific MS (11,13). Limited data exist on
The authors attest they are in compliance with human studies committees appropriate modes of therapy in symptomatic pa-
and animal welfare regulations of the authors’ institutions and Food and
tients, and this lack of data represents a major fron-
Drug Administration guidelines, including patient consent where appro-
priate. For more information, visit the JACC author instructions page. tier to be conquered (15).

ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2020.04.056

JACC VOL. 75, NO. 24, 2020 Sengupta and Mohan 3059
JUNE 23, 2020:3058–60 Calcific Mitral Stenosis

In this issue of the Journal, Kato et al. (16) have re-
ported natural history of severe calcific MS (mitral
valve area # 1.5 cm2 ) in a fairly large series of patients
from a retrospective database of 14 years. Most pa-
tients were elderly, with a female preponderance,
multiple comorbidities, and approximately 60% of 200
patients studied were truly symptomatic owing to
valve disease at baseline. The mean age of the studied
population was 78 years. Calcific severe MS represents
41% of all mitral stenosis in this series. Only 22% of
SEE PAGE 3048
symptomatic patients underwent mitral valve in-
terventions. Probability of 3-year event-free survival
was 34%, and total survival in conservatively managed
patients was 52%. This portends extremely high risk in
patients with severe calcific MS. Of note, symptomatic
status was not associated with mortality in follow-up.
The factors that were associated with high mortality
were absence of intervention, transmitral gradient
of $8 mm Hg, left-ventricular ejection fraction <50%,
right-ventricular systolic pressure $50 mm Hg, atrial
fibrillation, higher comorbid status, and inactivity.
Progression of calcific MS was slower than that re-
ported for post-inflammatory MS (17). Other studies
have reported progression in approximately 50% (18)
and more progression in younger patients, in female
patients, and those with diabetes mellitus (19,20).
Owing to its size and near completeness of follow-up,
this study represents an important landmark in the
natural history of degenerative MS. A much larger
database of calcific MS of all grades showed similar
clinical characteristics, comorbidities, and a 5-year
survival of 47%, which was worse in higher grades of
MS (21). There are several other studies focusing on
similar observations (19,22). Of late, a substantial body
of literature is accumulating with regard to valvar and
nonvalvar determinants of natural history of calcific
mitral stenosis; however, guidelines have yet to
emerge on line of management.
In the current study, Kato et al. (16) have not used
exercise tests to quantify symptom status of the
cohort assessed. The detection of symptoms or exer-
cise intolerance can be challenging in the elderly and
with comorbidities, as they are less likely to complain
of symptoms during usual daily activities. Admitting
to symptoms is dependent on literacy, personality,
mood, cognition, culture, and idiosyncrasy (23).
The management of severe calcific MS presents
enormous technical challenges. Surgical implantation
of a valve on top of the calcium ring can lead to sig-
nificant paravalvular regurgitation. Stitches around
the calcium bar can injure circumflex artery, coronary
sinus, or conduction system. Rarely, calcium ring in
the atrioventricular fibrofatty groove, if included
within a sheath, can be removed en bloc if the correct
plane is identified. A careful look at the calcium,
associated hemodynamics, and comorbidities will
decide whether transcatheter therapy will be in the
future for this group of patients. Symptomatic patients
with lower valve area, higher transmitral pressure
gradients, higher pulmonary-artery pressures, less
comorbidity, and lower calcium score will be more
suitable for this approach. Such patients, however, are
very few in clinical practice. In the multicentric regis-
try of transcatheter mitral valve replacement in 116
patients, 1-year mortality was 54%, although those
who survived for 30 days had good 1-year prognoses
(24). Tissue-engineered valves with regenerative, self-
repair capacities and novel degradable metal and
elastomeric scaffold-based tissue heart valve hold
good promise for management of calcific MS (25,26).
Hence, the findings presented in the current study are
important, add to our knowledge of knowing the life
history of severe calcific MS, and provide a road map
for future collaborative investigations among re-
searchers focusing on echoes of aging.
ADDRESS FOR CORRESPONDENCE: Dr. Shantanu P.
Sengupta, Sengupta Hospital and Research Institute,
Ravinagar, Nagpur, India. E-mail: senguptasp@gmail.com.

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KEY WORDS aging, calcific, mitral