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Isolated mitral valve prolapse is an independent predictor of aortic root size in a general population

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Mitral valve prolapse (MVP) is associated with aortic root (AoR) enlargement in patients with inherited connective tissue disorders. This report evaluated whether MVP is related to AoR dimension in a large population with otherwise normal echocardiographic parameters. We retrospectively analysed echocardiograms performed by a single echocardiographer between 2001 and 2007 for various clinical indications. Six hundred and twenty-seven subjects with isolated MVP were found and then matched by sex, age, and body mass index to 627 individuals without MVP. The whole sample included 454 men and 800 women with an average age of 37.9 +/- 0.3 years and a body mass index of 23.7 +/- 0.1 kg/m(2). MVP subjects had a higher AoR diameter (30.4 +/- 0.1 vs. 29.5 +/- 0.1 cm; P < 0.0001) compared with controls. Furthermore, multivariate analyses demonstrated an independent association between MVP and AoR size (P < 0.0001) in a model that included age, gender, body mass index, body surface area, blood pressure levels, and left ventricular mass index as confounding variables. Isolated MVP is an independent predictor of greater AoR size in a large population with otherwise normal echocardiographic parameters.
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Isolated mitral valve prolapse is an independent
predictor of aortic root size in a general
population
Jose
´R. Matos-Souza1, Mariana E. Fernandes-Santos1, Eduardo L. Hoehne2,
Kleber G. Franchini1, and Wilson Nadruz Jr1*
1
Department of Internal Medicine, School of Medicine, University of Campinas, Cidade Universita
´ria ‘Zeferino Vaz’, 13081-970 Campinas, SP, Brazil; and
2
Department of Preventive
Medicine, School of Medicine, University of Campinas, Brazil
Received 30 September 2009; accepted after revision 24 November 2009; online publish-ahead-of-print 17 December 2009
Aims Mitral valve prolapse (MVP) is associated with aortic root (AoR) enlargement in patients with inherited connective
tissue disorders. This report evaluated whether MVP is related to AoR dimension in a large population with other-
wise normal echocardiographic parameters.
Methods
and results
We retrospectively analysed echocardiograms performed by a single echocardiographer between 2001 and 2007 for
various clinical indications. Six hundred and twenty-seven subjects with isolated MVP were found and then matched
by sex, age, and body mass index to 627 individuals without MVP. The whole sample included 454 men and 800
women with an average age of 37.9 +0.3 years and a body mass index of 23.7 +0.1 kg/m
2
. MVP subjects had a
higher AoR diameter (30.4 +0.1 vs. 29.5 +0.1 cm; P,0.0001) compared with controls. Furthermore, multivariate
analyses demonstrated an independent association between MVP and AoR size (P,0.0001) in a model that included
age, gender, body mass index, body surface area, blood pressure levels, and left ventricular mass index as confounding
variables.
Conclusion Isolated MVP is an independent predictor of greater AoR size in a large population with otherwise normal echocar-
diographic parameters.
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Keywords Mitral valve prolapse Aortic root Echocardiography
Introduction
Mitral valve prolapse (MVP) is a common echocardiographic vari-
ation that may be detected in 2 4% of some populations.
1
Although MVP is most frequently a primary condition,
2,3
it has
been often associated with osteoarticular abnormalities, such
shallow chest and articular hypermobility, leading to the suggestion
that MVP might be actually a manifestation of collagen
modification.
1
In accordance with this assumption, MVP is also associated with
heritable disorders of connective tissue, such as Marfan and
EhlersDanlos syndromes.
4
Although subjects with such disorders
comprise ,12% of MVP cases,
4
they provide relevant
information regarding the potential phenotypic spectrum related
to MVP. In this context, several lines of evidence demonstrated
that aortic root (AoR) dilatation is usually seen along with MVP
in subjects with heritable disorders of connective tissue,
5–7
indicat-
ing that abnormalities in mitral valve and AoR structures may rep-
resent a phenotypic continuum. Nevertheless data available to date
have failed to detect significant changes in AoR diameter in sub-
jects with primary MVP.
6,8 – 11
It is noteworthy, however, that
these aforementioned studies included a small number of subjects,
which probably limited the statistical power of such analyses. Thus,
the aim of the present report was to evaluate whether the pres-
ence of MVP influences AoR dimension in a large sample of sub-
jects with normal AoR size and normal cardiac parameters.
Both authors contributed equally to this study.
*Corresponding author. Tel: þ55 19 3521 7836, Fax: þ55 19 3521 7836, Email: wilnj@fcm.unicamp.br
Published on behalf of the European Society of Cardiology. All rights reserved. &The Author 2009. For permissions please email: journals.permissions@oxford journals.org.
European Journal of Echocardiography (2010) 11, 302–305
doi:10.1093/ejechocard/jep219
by guest on November 29, 2016Downloaded from
Methods
Study population
We performed a retrospective analysis of echocardiogramsperformed by a
single echocardiographer (Dr Matos-Souza) between January 2001 and
March 2007 for various clinical indications at a single cardiology/echocardio-
graphy centre. Inclusion criteria were age over 18 years and normal left ven-
tricular and left atrial (LA) dimensions according to the A mericanSociety o f
Echocardiography.
12
Echocardiographic exclusion criteria were: (i) valvular
disease, except MVP or minimal mitral regurgitation; (ii) left ventricular
hypertrophy, defined as left ventricular mass index .110 g/m
2
for
women and .125 g/m
2
for men;
13
(iii) signs of left ventricular diastolic, sys-
tolic, or segmental dysfunction; (iv) signs of pulmonary hypertension; (v)
congenital heart disease; and (vi) AoR dilatation. The study was approved
by the Ethics Committee of the University of Campinas.
Six hundred and twenty-seven subjects with isolated MVP fulfilled the
inclusion criteria for the study. A similar number of individuals without
MVP matched by sex, age, and body size were then randomly selected
as controls from the database. Clinical evaluated variables were
extracted from patient records and included age, sex, height, weight,
and blood pressure levels. Body mass index was calculated as body
weight divided by height squared (kg/m
2
), while body surface area was
calculated according to the Dubois formula. Blood pressure was
measured using mercury sphygmomanometers with the subjects in
the sitting position before the echocardiographic examination.
Echocardiography
Echocardiography studies were performed on each subject at rest in
the left lateral decubitus position using a Vivid 3 apparatus (General
Electric) equipped with a 2.5 MHz transducer as previously
described.
14
AoR and LA diameters as well as left ventricular mass
were assessed according to the American Society of Echocardiography
recommendations.
12
AoR diameter was measured at the level of Val-
salva’s sinuses by M-mode tracings under two-dimensional control as
the maximal distance between the two leading edges of the anterior
and posterior AoR walls, while LA maximal diameter was measured
in the anteroposterior position. The reproducibility of measuring
AoR and LA diameters and left ventricular mass as well as diagnosing
MVP was determined in recordings obtained from 20 healthy subjects
(10 with MVP). Intraobserver left ventricular mass, LA diameter, and
AoR diameter variabilities were ,6, ,4, and ,3% respectively,
whereas interobserver variabilities of these parameters were ,10,
,7, and ,5% respectively. Intraobserver and interobserver corre-
lations for echocardiographic MVP diagnosis was .0.90.
The echocardiographic criterion for the diagnosis of MVP was based
on that reported by Freed et al.
15
Briefly, subjects were classified as
having MVP if displacement of mitral leaflets exceeded 2 mm. AoR
was considered normal when its diameter was equal to or smaller
than 36 mm in women and 39 mm in men. These cut-off points
were below the 98th percentile values in a group of 356 normotensive,
non-obese (body mass index between 20 and 25 kg/m
2
), apparently
normal adults (196 women and 160 men; mean age 56.0 +0.6
years) evaluated in the same unit for a cardiovascular check-up in
the previous 3 years.
16
The thickness of the mitral leaflets during dia-
stasis was measured from the leading to the trailing edge of the thickest
area of the midportion of the leaflet, excluding focal areas of thickness
and chordae.
15
Statistical analysis
Descriptive statistical results are given as the mean+standard error.
x
2
test and unpaired t-test were used to compare categorical and con-
tinuous variables, respectively. Univariate correlations between vari-
ables were assessed by Pearson’s or Spearman’s methods. Multiple
linear regression analysis with stepwise forward method was used to
assess the independent relationships between AoR and studied par-
ameters. A P-value of ,0.01 was considered significant.
Results
Clinical and echocardiographic features of the studied sample are
shown in Table 1. Although no differences in age, sex, anthropo-
metric measurements, blood pressure levels, and left ventricular
mass index were detected, subjects with MVP presented higher
AoR diameter, AoR/body surface area, as well as a lower LA diam-
eter in comparison to controls. Among subjects with MVP, 55%
(n¼345) presented mitral valve leaflets thickening 5 mm.
However, no differences in clinical and echocardiographic features
were detected between MVP individuals with thickened leaflets
...............................................................................................................................................................................
Table 1 Characteristics of studied subjects
Variable All (n51254) MVP (n5627) Controls (n5627) P
Age, years 37.9 +0.3 37.9 +0.5 37.9 +0.4 NS
Sex, male/female 454/800 227/400 227/400 NS
Height, cm 166.9 +0.3 167.5 +0.4 166.4 +0.5 NS
Weight, kg 66.2 +0.4 66.3 +0.5 66.2 +0.5 NS
Body mass index, kg/m
2
23.7 +0.1 23.6 +0.1 23.9 +0.1 NS
Body surface area, m
2
1.75 +0.01 1.76 +0.01 1.75 +0.01 NS
Systolic blood pressure, mmHg 125.0 +0.6 124.7 +0.7 125.3 +0.8 NS
Diastolic blood pressure, mmHg 79.8 +0.3 79.5 +0.4 80.1 +0.4 NS
Left atrium diameter, mm 31.8 +0.1 31.3 +0.1 32.2 +0.1 ,0.0001
AoR diameter, mm 30.0 +0.1 30.4 +0.1 29.5 +0.1 ,0.0001
AoR/body surface area, mm/m
2
17.06 +0.06 17.27 +0.08 16.86 +0.08 ,0.0001
Left ventricular mass index, g/m
2
89.1 +0.5 89.2 +0.6 89.1 +0.6 NS
AoR, aortic root; MVP, mitral valve prolapse. NS, non-significant. P-values are related to the comparison between MVP vs. controls.
Mitral prolapse and aortic root size 303
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and MVP subjects with valve leaflets thickening ,5 mm (data not
shown).
Univariate regression analyses were performed in order to
evaluate relationships between AoR diameter and clinical/echocar-
diographic variables (Table 2). AoR diameter exhibited a direct cor-
relation with MVP in the whole sample (r¼0.13; P,0.0001),
while age, male gender, height, weight, body mass index, body
surface area, blood pressure levels, and left ventricular mass
index displayed significant correlation coefficients with AoR diam-
eter in the whole sample as well as in both studied subgroups (r
0.200.60; all P,0.0001).
A stepwise regression model was constructed to evaluate the
independent contribution of different factors to AoR size
(Table 3). This model included age, gender, body mass index,
body surface area, systolic blood pressure, diastolic blood
pressure, left ventricular mass index, and the presence of MVP
as independent variables. Male gender and age were found to be
the foremost predictors of AoR diameter, while left ventricular
mass index and MVP contributed to explain its variance to a
lesser extent.
Discussion
MVP and enlarged AoR frequently coexist in patients with inher-
ited connective tissue disorders, indicating that these echocardio-
graphic alterations may represent a phenotypic continuum.
5–7
Previous studies have also investigated whether AoR diameter is
increased in individuals with primary MVP.
6,8 – 11
Nevertheless,
they failed to find significant differences in AoR diameter according
to the presence or not of MVP. Noticeably, these latter reports
enrolled a small number of subjects with isolated MVP, which
varied from 10 to 100 individuals per study. Such feature probably
limited the statistical power of the analysis. In the present report
we evaluated a much larger sample (627 subjects with isolated
MVP) and detected higher average AoR diameter and AoR/body
surface area compared with measurements obtained from a
similar number of individuals without MVP. In addition, results of
multivariate analysis revealed that MVP was an independent predic-
tor of greater AoR diameter in the whole sample. Overall, these
data support the notion that alterations in mitral valve and AoR
structure may indeed comprise a phenotypic continuum even in
individuals with isolated MVP. In accordance with this hypothesis,
previous studies have also described decreased elastic properties
in the aorta of subjects with MVP.
17,18
One potential limitation to the assumption that greater AoR size
is related to isolated MVP was that we did not know whether the
enrolled individuals had diagnoses of inherited connective tissue
disorders, since there were a variety of reasons for examination
referral. Thus, inclusion of subjects with such diseases in the
MVP group could have contributed to increase the average AoR
diameter in this population.
5–7
However, this hypothesis seems
less probable since primary MVP is much more prevalent than sec-
ondary MVP to established connective tissue disorders.
2,3,19
In this
context, it has been estimated that no more than 1 2% of patients
with MVP have an associated connective tissue disorder.
4
More-
over, the presence of MVP in adults with heritable disorders of
connective tissue is usually associated with AoR dilatation,
5 – 7,20
an echocardiographic feature excluded from our analysis.
It was noteworthy that MVP subjects presented a smaller LA
diameter in comparison to controls. However, we believe that
this finding might not a represent a real reduction in LA dimension.
LA diameter was measured in the anteroposterior position
according to echocardiographic guidelines.
12
Noticeably, this
evaluation may subestimate LA dimension since expansion of the
LA can be limited by the thoracic cavity between the sternum
and the spine. In this regard, increases in the AoR diameter are
known to compress the adjacent LA, leading to a reduction in
the anteroposterior diameter of this latter chamber.
21
Given that
the MVP and control groups had a similar body size, it is possible
that the higher AoR diameter in the MVP group was responsible
for the observed lower LA size in this population. This hypothesis
is further supported by our findings showing that the average
increase in AoR diameter in MVP was of 0.9 cm, which was
quite comparable to the average decrease in LA diameter in com-
parison to controls.
....................................................
...............................................................................
Table 2 Univariate correlations of aortic root
diameter
Variable AoR diameter (r)
All
(n51254)
MVP
(n5627)
Controls
(n5627)
Age 0.27 0.26 0.30
Male gender 0.49 0.46 0.53
Height 0.45 0.38 0.51
Weight 0.50 0.43 0.59
Body mass index 0.34 0.27 0.46
Body surface area 0.52 0.45 0.60
Systolic BP 0.21 0.21 0.20
Diastolic BP 0.22 0.22 0.21
LV mass index 0.33 0.30 0.36
MVP 0.13 –
AoR, aortic root; MVP, mitral valve prolapse; BP, blood pressure; LV, left
ventricular. All P-values were ,0.0001.
................................................................................
Table 3 Stepwise regression analysis
Step Variable R
2
change Fratio P
Aortic root size (dependent)
1 Male gender 0.241 395.9 ,0.0001
2 Age 0.087 161.9 ,0.0001
3 Body surface area 0.051 103.1 ,0.0001
4 Left ventricular mass
index
0.030 62.4 ,0.0001
5 Mitral valve prolapse 0.014 30.0 ,0.0001
Body mass index, systolic blood pressure and diastolic blood pressure did not
improve the model.
J.R. Matos-Souza et al.304
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Some potential limitations of the present study deserve further
comments. First, our data were extracted from databases, there-
fore, the examinations or the diagnoses could not be reviewed.
However, we reduced this bias by only including exams carried
out by a single echocardiographer. Moreover, intraobserver and
interobserver correlations were performed and revealed high
reproducibility in echocardiographic examinations. Second, we
had no access to clinical features such as prevalence of hyperten-
sion, smoking, and diabetes, which are acknowledged markers of
cardiovascular risk. Nevertheless, several reports have demon-
strated that these variables are not consistent determinants of
AoR size,
22 – 25
suggesting that the lack of clinical characterization
on these topics played no major influence in our results.
In conclusion, the present report demonstrated that MVP is an
independent determinant of the greater AoR size in a large popu-
lation with otherwise normal echocardiographic parameters. This
result supports the notion that alterations in the mitral valve and
AoR structures may represent a phenotypic continuum in subjects
with isolated MVP.
Conflict of interest: none declared.
Funding
This study was sponsored by grants from Fundac¸a˜o de Amparo a
`Pes-
quisa do Estado de Sa˜o Paulo (Proc. 05/56986-5) and Conselho Nacio-
nal de Desenvolvimento Cientı
´fico e Tecnolo
´gico (Proc. 304329/06-1
and 474206/07-6), Brazil.
References
1. Davies MJ, Moore BP, Braimbridge MV. The floppy mitral valve: study of incidence,
pathology and complications in surgical, necropsy and forensic material. Br Heart J
1978;40:468–81.
2. Boudoulas H, Kolibash AJ, Baker P, King BD, Wooley CF. Mitral valve prolapse
and the mitral valve prolapse syndrome: a diagnostic classification and pathogen-
esis of symptoms. Am Heart J 1989;118:796 818.
3. Devereux RB. Recent developments in the diagnosis and management of mitral
valve prolapse. Curr Opin Cardiol 1995;10:107 16.
4. Grau JB, Pirelli L, Yu P-J, Galloway AC, Ostrer H. The genetics of mitral valve pro-
lapse. Clin Genet 2007;72:288 –95.
5. Glesby MJ, Pyeritz RE. Association of mitral valve prolapse and systemic abnorm-
alities of connective tissue. A phenotypic continuum. JAMA 1989;262:523 8.
6. Roman MJ, Devereux RB, Kramer-Fox R, Spitzer MC. Comparison of cardiovas-
cular and skeletal features of primary mitral valve prolapse and Marfan syndrome.
Am J Cardiol 1989;63:317 21.
7. Yen JL, Lin SP, Chen MR, Niu DM. Clinical features of Ehlers– Danlos syndrome.
J Formos Med Assoc 2006;105:475 80.
8. Brown OR, DeMots H, Kloster FE, Roberts A, Menashe VD, Beals RK. Aortic root
dilatation and mitral valve prolapse in Marfan’s syndrome: an ECHOCARDIO-
graphic study. Circulation 1975;52:651– 7.
9. Haikal M, Alpert MA, Whiting RB, Kelly D. Increased left ventricular mass in idio-
pathic mitral valve prolapse. Chest 1982;82:329 33.
10. Yazici M, Ataoglu S, Makarc S, Sari I, Erbilen E, Albayrak S et al. The relationship
between echocardiographic features of mitral valve and elastic properties of
aortic wall and Beighton hypermobility score in patients with mitral valve pro-
lapse. Jpn Heart J 2004;45:447 –60.
11. Seliem MA, Duffy CE, Gidding SS, Berdusis K, Benson DW Jr. Echocardiographic
evaluation of the aortic root and mitral valve in children and adolescents with iso-
lated pectus excavatum: comparison with Marfan patients. Pediatr Cardiol 1992;13:
20– 3.
12. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Rec-
ommendations for chamber quantification. Recommendations for chamber
quantification. Eur J Echocardiogr 2006;7:79 108.
13. Marcus R, Krause L, Weder AB, Dominguez-Meja A, Schork NJ, Julius S. Sex-
specific determinants of increased left ventricular mass in the Tecumseh Blood
Pressure Study. Circulation 1994;90:928– 36.
14. Sales ML, Ferreira MC, Leme CA Jr, Velloso LA, Gallani MC, Colombo RC et al.
Non-effect of p22-phox -930A/G polymorphism on end-organ damage in Brazi-
lian hypertensive patients. J Hum Hypertens 2007;21:504 6.
15. Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL et al. Prevalence
and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1 7.
16. Cipolli JA, Souza FA, Ferreira-Sae MC, Pio-Magalha˜es JA, Figueiredo ES,
Vidotti VG et al. Sex-specific hemodynamic and non-hemodynamic determinants
of aortic root size in hypertensive subjects with left ventricular hypertrophy.
Hypertens Res 2009;32:956 61.
17. Boudoulas H, Wooley CF. Floppy mitral valve/mitral valve prolapse/mitral valvular
regurgitation: effects on the circulation. J Cardiol 2001;37:15 20.
18. Kardesoglu E, Ozmen N, Aparci M, Cebeci BS, Uz O, Dincturk M. Abnormal
elastic properties of the aorta in the mitral valve prolapse syndrome. Acta
Cardiol 2007;62:151 –5.
19. Duren DR, Becker AE, Dunning AJ. Long-term follow-up of idiopathic mitral valve
prolapse in 300 patients: a prospective study. J Am Coll Cardiol 1988;11:42 7.
20. Aburawi EH, O’Sullivan J. Relation of aortic root dilatation and age in Marfan’s
syndrome. Eur Heart J 2007;28:376 9.
21. Come PC, Fortuin NJ, White RI Jr, McKusick VA. Echocardiographic assessment
of cardiovascular abnormalities in the Marfan syndrome. Comparison with clinical
findings and with roentgenographic estimation of aortic root size. Am J Med 1983;
74:465–74.
22. Kim M, Roman MJ, Cavallini MC, Schwartz JE, Pickering TG, Devereux RB. Effect
of hypertension on aortic root size and prevalence of aortic regurgitation. Hyper-
tension 1996;28:47 –52.
23. Cuspidi C, Meani S, Fusi V, Valerio C, Sala C, Zanchetti A. Prevalence and corre-
lates of aortic root dilatation in patients with essential hypertension: relationship
with cardiac and extracardiac target organ damage. J Hypertens 2006;24:573 80.
24. Palmieri V, Bella JN, Arnett DK, Roman MJ, Oberman A, Kitzman DW et al. Aortic
root dilatation at sinuses of valsalva and aortic regurgitation in hypertensive and
normotensive subjects. The hypertension genetic epidemiology network study.
Hypertension 2001;37:1229 35.
25. Vasan RS, Larson MG, Levy D. Determinants of echocardiographic aortic root
size. The Framingham Heart Study. Circulation 1995;91:734 40.
Mitral prolapse and aortic root size 305
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... It has also been observed that isolated MVP, which is not associated with connective tissue disorders, was an independent predictor of aortic diameter increase. [15] In another study, it was determined that aortic distensibility was significantly reduced in patients with MVP compared with a control group. [16] The aim of the present study was to assess aortic distensibility in MVP patients using applanation tonometry as well as the conventional echocardiographic examination to compare the 2 methods and examine the relationship between conventional (echocardiographic) and current diagnostic methods (PWV). ...
... [23] The fact that isolated MVP, which is not associated with connective tissue disease, is an independent predictor of a larger aortic size was demonstrated in a study of 1254 patients, and it was noted that this result supported the view that mitral valve and aortic structural changes may represent phenotypic integration. [15] Similarly, in patients with isolated MVP, increased inflammatory processes and increased MMP activity are not just limited to mitral valves but may also cause similar pathologies in the aorta. It may be the cause of the reduction in aortic distensibility in patients with isolated MVP, as observed in our study. ...
Article
Objective: Mitral valve prolapse (MVP) is a heart valve anomaly that affects a considerable segment of the population. Studies of patients with isolated MVP have shown that aortic distensibility decreased as the aortic diameter increased. The aim of this study was to compare evaluations of aortic distensibility in MVP patients using both applanation tonometry and the conventional echocardiographic examination. Methods: A total of 36 consecutive patients with MVP (16 male and 20 female) and 23 healthy controls (11 male and 12 female) were included in this study. The difference in aortic diameter and distensibility was examined using echocardiography and pulse wave velocity (PWV) was measured with applanation tonometry. Results: According to the echocardiographic measurements, the aortic distensibility was lower in the MVP patients than in the control group (6.2±4.0 cm².dyn⁻¹.10⁻⁶ vs. 10.0±5.2 cm². dyn⁻¹.10⁻⁶; p=0.02). The PWV measured with applanation tonometry was significantly higher in the MVP patients than in the control group (9.0±2.4 m/s vs. 7.2±1.4 m/s; p=0.006). Conclusion: The results of this study showed that aortic distensibility was reduced in patients with isolated MVP compared with a healthy control group. There was a moderate negative correlation between the results of both methods.
... В связи с тем, что ПМК является независимым предиктором увеличенного размера аорты [9], сопоставили ее диаметр на уровне синусов Вальсальвы с учетом ПМК. Размер аорты в случаях ПМК соста-вил 2,5 (2,3-2,6) см, а в группе здоровых -2,4 (2,2-2,5) см (U=568,5; р=0,232). ...
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Aim. To assess the condition of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse (MVP). Material and methods. Totally, 91 patient studied with primary MVP at the age 21 (19-24) y. First grade mitral regurgitation was found in 45,1% and II — in 54,9% patients. MVP was solitary variant (6,6%) and comorbid with 1-3 minor anomalies of the heart (93,4%). Doppler-echocardiography was done on Vivid07 equipment (Israel). The grade of systemic involvement of connective tissue was 2 (1,5-4,0) points. Controls were 10 healthy persons, matched by age, sex, smoking, body mass index. By the immune enzyme method we checked plasmatic concentrations of L-, E-, Р-selectins, ICAM-1, VCAM-1, PECAM-1 (Bender MedSystems GmbH, Austria). Findings are presented as mediana (25-75 percentiles). Results. In MVP patients the levels of Е-selectin — 43,0 (33,7-54,8) ng/ mL, ICAM-1 — 669,9 (546,4-883,3) ng/mL and VCAM-1 — 925,0 (707,5-1215,0) ng/mL, were significantly higher, and the level of РЕСАМ-1 — 49,8 (40,4-63,2) ng/mL, in opposite, lower than in control group. L- and P-selectins levels in MVP group were measured as relevant to controls values (p>0,05). In regurgitation cases of II degree, the level of E-selectin and ICAM-1 were maximal (p<0,05). Values of VCAM-1 in MVP patients independently from degree of regurgitation were significantly higher than controls values. There was moderate direst relation of the quantity of minor heart anomalies and level of ICAM-1 (rs=+0,30, р<0,05). In MVP group with increased E-selectin significantly higher was aorta diameter at the level of Valsalva sinuses — 2,5 (2,3-2,7) cm, than in PMV without increased E-selectin level — 2,3 (2,2-2,5) cm (р<0,05). Conclusion. In patients with primary MVP there is an increase of circulating concentrations of E-selectin, ICAM-1, VCAM-1, that represents the level of adhesion, and witnesses about subclinical endothelial dysfunction. For screening evaluation of severity of adhesion disorders of endothelium in MVP it is important to take into account its hemodynamic significance, multiple minor heart anomalies and data on aorta diameter on the level of Valsalva sinuses. © 2016 Vserossiiskoe Obshchestvo Kardiologov. All Rights Reserved.
... Больший диаметр аорты у пациентов с миксоматозной болезнью Барлоу также может быть обусловлен более выраженными изменениями экстрацеллюлярного матрикса [33]. Известно, что миксоматозный ПМК является независимым предиктором ее большего размера в общей популяции с неизмененными в остальном эхокардиографическими показателями [34]. ...
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Aim. To assess systolic left ventricular (LV) function in patients with mitral valve prolapse (MVP) and different morphological MV disorders. Material and methods. The study included 233 patients (mean age 53,8±12,9 years), who underwent MV surgery due to MPV and severe mitral regurgitation (MR) at the V. A. Almazov Federal Centre of Heart, Blood, and Endocrinology in 2009- 2011. The resected MV segments underwent a pathomorphological examination; preoperative strain and strain rate were assessed with the speckle tracking method (EchoPAC’08). Results. Based on the pathomorphological data, Barlow’s disease was registered in 60 patients (25,8%), and fibroelastic deficiency in 173 patients (74,2%). The preintervention echocardiography did not demonstrate any significant difference between the two groups in terms of preoperative MR volume (70,5±9,6 ml vs. 71,6±8,5 ml, p=0,40), systolic LV function (ejection fraction 52,7±6,6% vs. 52,0±7,4%; p=0,53) and diastolic LV function (E/e’ 12,2±3,9 vs. 12,8±4,2; p=0,35). Despite no difference in ejection fraction, the Barlow’s disease group demonstrated a significant reduction in LV longitudinal systolic (-13,5±2,2% vs. -16,6±2,3%; p=0,008) and diastolic strain (1,14±0,20 s-1 vs. 1,34±0,18 s-1; p=0,04), as well as in strain rate (-0.89±0,15 s-1 vs. -1,14±0,15 s-1; p=0,002), compared to the fibroelastic deficiency group. Conclusion. Patients with Barlow’s disease, compared to patients with fibroelastic deficiency, have a lower preoperative LV systolic function, which might affect the postoperative long-term survival rates. The deteriorated LV function could be due to the damage of endocardial and intramyocardial extracellular matrix in Barlow’s disease.
... 21 In some inherited connective tissue disorders with extracellular matrix damage and involvement of the cardiovascular system (Marfan, Loeys-Dietz syndromes), the primary impairment of the left ventricular systolic function, which does not depend on aortic or mitral regurgitation, has also been reported. 15,22 We revealed in the Barlow's disease group larger aortic diameter and higher prevalence of aortic valve prolapse, which have been described in previous studies for patients with MVP 23,24 and also associated with damage of the extracellular matrix. 25,26 Of interest was our observation that the longitudinal systolic strain correlates with aortic root size in Barlow's disease group, which may result from the same defect in structure of the extracellular matrix. ...
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The aim of the study is to determine the impact of the underlying etiology (Barlow's disease or fibroelastic deficiency) on left ventricular function in patients with degenerative mitral valve disease and severe mitral regurgitation. We studied 233 patients (mean age: 53.8 ± 12.9) undergoing surgery for severe mitral regurgitation due to degenerative mitral valve disease at Almazov Federal Heart Centre between 2009 and 2011. Pathologic diagnoses for valvular tissue specimens were provided by an experienced pathologist. Preoperative strain and strain rate were determined using speckle tracking (Vivid 7 Dimension, EchoPAC'08). Barlow's disease was identified by the pathologist in 60 patients (25.8%), and fibroelastic deficiency in 173 patients (74.2%). There were no significant differences between groups in preoperative mitral regurgitation volume (70.5 ± 9.6 vs. 71.6 ± 8.5 ml, P = 0.40), and in global systolic (ejection fraction: 52.7 ± 6.6 vs. 52.0 ± 7.4%, P = 0.53) and diastolic (E/e': 12.2 ± 3.9 vs. 12.8 ± 4.2, P = 0.35) left ventricular function. Despite the lack of difference in ejection fraction and diastolic tissue Doppler parameters, in patients with Barlow's disease in comparison with fibroelastic deficiency a significant decrease of the left ventricular longitudinal systolic strain (-13.5 ± 2.2 vs. -15.6 ± 2.3%, P = 0.00001) and early diastolic strain rate (1.04 ± 0.20 vs. 1.14 ± 0.18 s, P = 0.0004) were detected. Patients with severe mitral regurgitation due to Barlow's disease have a lower preoperative left ventricular systolic function than those with fibroelastic deficiency, which may affect their postoperative prognosis.
... Although the presence of myocardial fibrosis in patients with mitral valve prolapse has been reported previously, further studies using magnetic resonance imaging or integrated backscatter assessment are needed. 30 However, these changes in deformations may be the first signs of future deterioration of the left ventricular systolic function by mitral valve prolapse progression. [16][17][18] Moreover, we found aortic root enlargement in young patients with prolapse. ...
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Background: In some inherited connective tissue diseases with involvement of the cardiovascular system, for example, Marfan syndrome, early impairment of left ventricular function, which have been described as Marfan-related cardiomyopathy has been reported. Our aim was to evaluate the left ventricular function in young adults with mitral valve prolapse without significant mitral regurgitation using two-dimensional strain imaging and to determine the possible role of the transforming growth factor-β pathway in its deterioration. Methods: We studied 78 young adults with mitral valve prolapse without mitral regurgitation in comparison with 80 sex-matched and age-matched healthy individuals. Longitudinal strain and strain rates were defined using spackle tracking. Concentrations of transforming growth factor-β₁ and β₂ in serum were determined by enzyme-linked immunosorbent assays. Results: In 29 patients, classic relapse was identified with a leaflet thickness of ≥ 5 mm; 49 patients had a non-classic mitral valve prolapse. Despite the similar global systolic function, a significant reduction in global strain was found in the classic group (-15.5 ± 2.9%) compared with the non-classic group (-18.7 ± 3.8; p = 0.0002) and the control group (-19.6 ± 3.4%; p < 0.0001). In young adults with non-classic prolapse, a reduction in longitudinal deformation was detected only in septal segments. Transforming growth factor-β₁ and β₂ serum levels were elevated in patients with classic prolapse as compared with the control group and the non-classic mitral valve prolapse group. Conclusions: These changes in the deformations may be the first signs of deterioration of the left ventricular function and the existence of primary cardiomyopathy in young adults with mitral valve prolapse, which may be caused by increased transforming growth factor-β signalling.
... Although the presence of myocardial fibrosis in patients with mitral valve prolapse has been reported previously, further studies using magnetic resonance imaging or integrated backscatter assessment are needed. 30 However, these changes in deformations may be the first signs of future deterioration of the left ventricular systolic function by mitral valve prolapse progression. [16][17][18] Moreover, we found aortic root enlargement in young patients with prolapse. ...
Article
Methods: The study group consisted of 43 patients (mean age=13.3±3.9) and 42 healthy children (mean age=12.9±3.4). Left ventricular end-diastolic, end-systolic, left atrial diameters, interventricular septum, and left ventricular posterior wall thickness were measured. Ejection and shortening fractions were calculated by M-mode. Measurements were adjusted to the body surface area. Mitral annulus, and systolic and diastolic diameters of the aortic annulus and aorta at each level were obtained; z-scores, aortic strain, distensibility, stiffness index were calculated. Carotid intima-media thickness and flow-mediated dilatation were studied. Patients were classified as classical/non-classical mitral valve prolapse and younger/older patients. Results: Left ventricular end-systolic, end-diastolic, and left atrial diameters (p=0.009, p=0.024, p=0.001) and aortic z-scores at annulus, sinus valsalva, and sinotubuler junction were larger (p=0.008, p=0.003, p=0.002, respectively) in the mitral valve prolapse group. Aortic strain and distensibility increased and stiffness decreased at the ascending aorta in the patient group (p=0.012, 0.020, p=0.019, respectively). Classical mitral valve prolapse had lower strain and distensibility and higher stiffness of the aorta at sinus valsalva level (p=0.010, 0.027, 0.004, respectively). Carotid intima-media thickness was thinner in the patient group, especially in the non-classical mitral valve prolapse group (p=0.037). Flow-mediated dilatation did not differ among the groups. Conclusion: Mitral valve prolapse is a systemic disease of the connective tissue causing enlarged cardiac chambers and increased elasticity of the aorta. Decreased carotid intima-media thickness in this group may indicate low atherosclerosis risk.
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Background: Mitral valve prolapse (MVP) is a valvular heart disease in which the two valve flaps of the mitral valve do not close equally, and part of the mitral valve slips backward loosely into the left atrium during systole. In general, MVP is associated with low body mass index (BMI), as confirmed by several studies. However, the reason for the higher prevalence of MVP in patients with low BMI remains unknown. Objectives: There is no reliable evidence on the role of genetics or pathophysiological factors in this correlation, and the hypothesis that the size of BMI may lead to MVP or vice versa has not yet been established. Materials and Methods: In this study, all the articles were evaluated in terms of the inclusion criteria. In total, we found 546 articles via PubMed and Google scholar, out of which 30 articles were mainly focusing on MVP, MVR as the major complication of MVP, and BMI, which were included in this systematic review. Results: Among these reviewed studies, patients with MVP had a lower BMI score compared to the subjects without MVP. The low and high BMI score were 28±5 kg/m and 31±6 kg/m, respectively. Conclusions: In the present study, we concluded that low BMI is directly associated with the occurrence of MVP.
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Aortic root (AoR) dilatation is more frequently observed in hypertensive individuals and is independently associated with left ventricular (LV) hypertrophy. Although the LV structure has sex-specific predictors, it remains unknown whether there are gender-related differences in the determinants of AoR size. We carried out a cross-sectional analysis of clinical, laboratory, anthropometric, funduscopic and echocardiographic features of 438 hypertensive patients with LV hypertrophy (266 women and 172 men). Women with enlarged AoR had higher cardiac output (P=0.0004), decreased peripheral vascular resistance (P=0.009), higher prevalence of mild aortic regurgitation (P=0.02) and increased waist circumference (P=0.04), whereas AoR-dilated men presented with a higher prevalence of concentric LV hypertrophy (P=0.0008) and mild aortic regurgitation (P=0.005) and increased log C-reactive protein levels (P=0.02), compared with sex-matched normal AoR subjects. In women, AoR dilatation associated with cardiac output, mild aortic regurgitation and waist circumference in a multivariate model including age, body surface area, height, homeostasis model assessment index, LV mass index, diastolic blood pressure, menopause status and use of antihypertensive medications as independent variables. Conversely, AoR dilatation associated with LV relative wall thickness, log C-reactive protein and mild aortic regurgitation without contributions from diastolic blood pressure, height, body surface area, LV mass index, peripheral vascular resistance and antihypertensive medications in men. Taken together, these results suggest that both volume overload and abdominal obesity are related to AoR dilatation in hypertensive women, whereas AoR enlargement is associated more with inflammatory and myocardial growth-related parameters in hypertensive men with LV hypertrophy.
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More than half of all patients evaluated in our clinic for the possible diagnosis of a heritable disorder of connective tissue could not be classified in the current nosology, yet they had considerable clinical evidence of a systemic defect of the extracellular matrix. As a group, these patients share many manifestations of the Marfan syndrome including long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse, and mild dilatation of the aortic root. Clinical clustering did not emerge when patients were stratified by mitral valve prolapse or aortic dilatation. The clinical phenotype of patients with mitral valve prolapse constitutes a continuum, from Marfan syndrome at one extreme to isolated mitral valve prolapse due to myxomatous proliferation of the valve leaflets. In the absence of biochemical or DNA markers, discerning whether a patient with mitral valve prolapse and mild aortic root dilatation (in the absence of ectopia lentis or a family history) has Marfan syndrome, or another heritable disorder of connective tissue, will continue to be a clinical challenge. Until subclassification based on refined clinical, genetic, and laboratory investigations is possible, the patients we describe are best seen as having an "overlap" heritable connective-tissue disorder. We suggest the acronym "MASS phenotype" to emphasize involvement of the mitral valve, aorta, skeleton, and skin. (JAMA. 1989;262:523-528)
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In the study of 1984 routine hospital necropsies the mitral valve was examined from the left atrium in the intact heart with a pressure head of water in the left ventricle. The valve was graded from grade O (normal) to grade 4: grade 1, expansion of a small part of one cusp only; grade 2, over one-third of the posterior cusp or one-half of the anterior cusp expanded, with intact chordae; grade 3, ruptured chordae; grade 4, chordal fusion to ventricular wall. The frequency of grade 2 to 4 floppy valves rose with age with an overall incidence of 3.9 per cent in men and 5.2 per cent in women. Grade 1 floppy valves have no clinical significance. Grade 2 floppy valves were found to be associated with auscultatory signs but often only contributed to cardiac failure or were coincidental findings. Grade 3 and 4 floppy valves were direct causes of death from bacterial endocarditis and/or severe mitral regurgitation. The surgical series of floppy valves showed that chordal rupture was the event which most commonly made operation necessary in middle age: in a minority this was caused by bacterial endocarditis. Dilatation of the annulus was an important contributory factor but can produce significant mitral regurgitation without chordal rupture, particularly in inherited connective tissue disorders such as the Marfan syndrome. Forensic necropsies confirm that sudden death occurs in patients with floppy valves. The majority have grade 3 or 4 floppy valves and presumably significant mitral regurgitation. A minority have minimal valve involvement and the mechanism of death is unexplained. The exact magnitude of the risk for any patient with a floppy valve of developing bacterial endocarditis, or chordal rupture leading to significant mitral regurgitation, or of dying suddenly, is not known but must be very low considering the frequency of the valve lesion. The essential pathology of the floppy mitral valve is weakening of the central fibrous core allowing cusp expansion and chordal elongation to occur. The weakness of the collagen is in part genetically determined, in part age related. Identical changes occur in the tricuspid valve, and in the aortic root, leading to aortic regurgitation. Similar pathological changes are well recognised in other mammals, particularly the aged dog.
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Echocardiographic and phonocardiographic findings in 35 patients with Marfan's Syndrome and ten patients without Marfan's or other clinically apparent connective tissue disorders but with angiographic and echocardiographic evidence of mitral prolapse are reported and compared. Echocardiography revealed aortic root dilatation and/or mitral valve prolapse in 97% of the patients with Marfan's Syndrome. Aortic root dilatation was found in 60% of this group (74% of males, 33% of females) while mitral valve prolapse was found in 91% (87% of males, 100% of females). The incidence of aortic dilatation and mitral prolapse in patients with Marfan's syndrome was essentially equal in children and adults of the same sex. None of the nine adults or one child with mitral prolapse but without evidence of Marfan's Syndrome or other clinically apparent connective tissue disorder had aortic root enlargement. Ausculatory examination and phnocardiography revealed abnormalities in 54% of the patients with Marfan's Syndrome. Aortic regurgitation was found in 23% of this group (35% of males, 0% of females) while mitral regurgitation and/or mitral clicks were found in 46% (39% of males, 58% of females). Aortic regurgitation was much more frequent in adult males with Marfan's Syndrome (7/14, 50%) than male children (1/9, 11%), while the incidence of abnormal mitral sounds was essentially the same in adults (33% of males, 60% of females) and children (43% of males, 57% of females) of the same sex with Marfan's Syndrome. Abnormal mitral sounds were more frequent in patients without Marfan's who had mitral prolapse (90%) than in those with Marfan's (46%). It appears that cardiac abnormalities are a consistent manifestation of Marfan's Syndrome and that ultrasound is a more sensitive indicator of these abnormalities in such patients than ausculation or phonocardiography.
Article
Pectus excavatum, mitral valve prolapse (MVP), and dilated aortic root occur frequently in patients with Marfan's syndrome (MS). Patients with isolated pectus excavatum (IPE) have a high prevalence of MVP, but it is not known whether aortic root dilatation is a risk in those patients. To test the hypothesis that IPE and MS represent a spectrum of connective tissue dystrophy with MV and aortic root involvement, two-dimensional (2D) echocardiography was used to measure the aortic root diameter and assess for MVP in IPE (n = 31), MS (n = 14), and normal (n = 16) gender- and age-matched patients. Aortic root was measured in parasternal long- and short-axis views, just above the aortic sinuses, at end systole, in six cardiac cycles, and averaged. Parasternal long-axis view was used to assess for MVP. Aortic root diameter in IPE patients was not different from that in normal subjects, 24 +/- 4 mm vs 22 +/- 4 mm (p = NS), respectively, both were significantly smaller than that in MS patients (30 +/- 5 mm; p less than 0.05). MVP was present in 17 of 31 (55%) IPE patients vs 12 of 14 (86%) MS patients (p = NS) and in only 1 of 16 (6%) normal subjects (p less than 0.05) vs both IPE and MS. We conclude that young patients with IPE represent an isolated form of connective tissue abnormality because of the presence of pectus excavatum and MVP, but this is different from the systemic involvement of MS because of the lack of other systemic findings, including aortic root dilatation and changes in body habitus.
Article
A clinical classification for patients with MVP is not well defined and the pathogenesis of symptoms in symptomatic patients with MVP remains poorly understood. To this end, 399 patients from our MVP (auscultation/echocardiographic-angiographic) population were analyzed. Symptoms were primarily or directly related to progressive valvular dysfunction in 86 patients (mean age 67). Following a long clinical course, 76 of these patients eventually had mitral valve surgery with pathologic confirmation of “floppy, myxomatous” mitral valves in all.Three hundred thirteen patients (mean age 30) with MVP and normal left ventricular function had symptoms (chest pain, palpitations, fatigue, exercise intolerance, dyspnea, syncope or presyncope, postural phenomena, neuropsychiatric symptoms) that could not be explained on the basis of valvular dysfunction alone. Studies in subsets of 65 of these patients showed: (1) increased urine catecholamine excretion and hypersensitivity to isoproterenol infusion; (2) abnormal plasma catecholamine response after volume expansion; (3) abnormal renin and aldosterone response after volume depletion; or (4) decreased exercise tolerance associated with decreased left ventricular volumes with upright exercise.Thus two groups of symptomatic patients with MVP were defined: (1) patients with MVP in whom symptoms were directly related to mitral valve dysfunction and complications (at present we refer to this group as MVP-anatomic) and (2) patients with MVP in whom symptoms were related primarily to neuroendocrine-autonomic dysfunction (at present we refer to this group as MVP-syndrome). This classification is clinically useful in the stratification of MVP patients in general and to separate MVP patients with symptoms related to or associated with autonomic dysfunction from patients whose symptoms are related primarily to progressive mitral valve dysfunction.
Article
More than half of all patients evaluated in our clinic for the possible diagnosis of a heritable disorder of connective tissue could not be classified in the current nosology, yet they had considerable clinical evidence of a systemic defect of the extracellular matrix. As a group, these patients share many manifestations of the Marfan syndrome including long limbs, deformity of the thoracic cage, striae atrophicae, mitral valve prolapse, and mild dilatation of the aortic root. Clinical clustering did not emerge when patients were stratified by mitral valve prolapse or aortic dilatation. The clinical phenotype of patients with mitral valve prolapse constitutes a continuum, from Marfan syndrome at one extreme to isolated mitral valve prolapse due to myxomatous proliferation of the valve leaflets. In the absence of biochemical or DNA markers, discerning whether a patient with mitral valve prolapse and mild aortic root dilatation (in the absence of ectopia lentis or a family history) has Marfan syndrome, or another heritable disorder of connective tissue, will continue to be a clinical challenge. Until subclassification based on refined clinical, genetic, and laboratory investigations is possible, the patients we describe are best seen as having an "overlap" heritable connective-tissue disorder. We suggest the acronym "MASS phenotype" to emphasize involvement of the mitral valve, aorta, skeleton, and skin.
Article
The association of primary mitral valve prolapse (MVP) with thoracic bony abnormalities has led to the suggestion that MVP may be a forme fruste of the Marfan syndrome. Echocardiographic, skeletal and anthropometric findings in 59 subjects with primary MVP and 59 age- and sex-matched patients with Marfan syndrome were compared with those in 59 control subjects. Subjects with mitral prolapse were similar to control subjects and differed (p less than 0.025 to p less than 0.001) from the patients with Marfan syndrome in aortic root dimensions, height, arm span, upper/lower segment ratio and prevalences of arachnodactyly, scoliosis and pectus carinatum. Subjects with mitral prolapse and patients with Marfan syndrome had similar body mass indexes and prevalences of pectus excavatum and straight back. All 3 groups were similar in arm span/height ratio. The 5 subjects with MVP and arachnodactyly had lower weights, smaller body surface areas and smaller aortic root dimensions, and were more likely to have scoliosis than subjects with MVP without arachnodactyly. Thus, primary MVP differs from the Marfan syndrome in all major skeletal and cardiovascular features.