clinical carDiology: original article
Diastolic dysfunction without abnormalities in left
atrial and left ventricular geometry does not affect
quality of life in elderly women
Alfried Germing MD1, Michael Gotzmann MD1, Tamara Schikowski PhD2,
Andrea Vierkötter PhD2, Ulrich Ranft PhD2, Andreas Mügge MD1
A Germing, M Gotzmann, t schikowski, A Vierkötter, U Ranft,
A Mügge. diastolic dysfunction without abnormalities in left atrial
and left ventricular geometry does not affect quality of life in elderly
women. exp Clin Cardiol 2011;16(2):37-39.
BACkGRoUnd/AiMs: Advanced age and female sex are associated with
increased myocardial stiffness, even in the absence of cardiovascular disease.
Left ventricular (LV) hypertrophy and left atrial (LA) enlargement are typi-
cal findings in patients with LV diastolic dysfunction (DD). Because DD has
been described in asymptomatic subjects, its clinical impact remains contro-
versial. It has previously been hypothesized that mild DD has no clinical
impact when natriuretic peptide levels are normal. The present study aimed
to determine the impact of LA volume and LV mass on DD in elderly
women.
Methods And ResUlts: A cross-sectional survey was used to
investigate a cohort of 311 randomly selected, nonhospitalized elderly
E chocardiography is a robust and validated method to assess dia-
stolic left ventricular (LV) function. Diastolic dysfunction (DD)
according to the LV filling pattern defined by echocardiography is usu-
ally divided into mild, moderate and severe categories (1). The preva-
lence of any degree of DD markedly increases with age, particularly in
women (2-6). The prevalence of mild DD has been reported to be
high. Whereas higher degrees of DD are clearly associated with a poor
prognosis (2,7,8) and elevated levels of natriuretic peptides (9,10), the
relevance of mild DD remains unclear, particularly in elderly patients.
As previously reported (8), mild DD could reflect pathological LV
changes with an increase in all-cause mortality. By contrast, a recent
large study (11) did not provide evidence of higher mortality in patients
with heart failure, preserved systolic function and mild DD. However,
recent publications (12,13) describe changes in LV filling patterns as an
age-dependent physiological process.
Left atrial size appears to be a powerful indicator of abnormal LV
relaxation (14,15). Concentric LV hypertrophy is frequently found in
DD (15). When mild DD occurs as a physiological process in advanced
age, it should not be associated with significant changes in left atrial
and LV geometry. Therefore, left atrial and LV morphology may be
features that distinguish between pathological and physiological pro-
cesses of DD in elderly women.
The present study analyzed neurohormonal stimulation, quality of
life, and parameters of left atrial and LV geometry in unselected, non-
hospitalized women older than 70 years of age in relation to diastolic
function. We hypothesized that study participants with mild DD have
normal left atrial and LV geometry. These findings would further sup-
port the hypothesis that mild DD is a normal physiological LV filling
pattern in elderly women.
Methods
The Study on the influence of Air pollution on Lung function,
Inflammation and Aging (SALIA) (16) cohort comprised 4874 women.
The cohort was previously described in detail. A supplementary survey
1Medizinische Klinik II, Kardiologie und Angiologie, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Bochum; 2Institut für
Umweltmedizinische Forschung (IUF) an der Heinrich Heine-Universität Düsseldorf gGmbH, Düsseldorf, Germany
Correspondence: Dr Alfried Germing, Medizinische Klinik II, Kardiologie und Angiologie Berufsgenossenschaftliches Universitatsklinikum Bergmannsheil
GmbH, Burkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. Telephone 49-0234-302-6050, fax 49-0234-302-6084, e-mail alfried.germing@rub.de
Received for publication December 12, 2010. Accepted March 3, 2011
Exp Clin Cardiol Vol 16 No 2 2011
women (mean [± SD] age 74.3±2.9 years). Examination comprised quality
of life, measurement of brain natriuretic peptide (BNP) levels and echocar-
diography. The prevalences of different degrees of DD were as follows: mild
47.9% (n=149), moderate 36.7% (n=114) and severe 4.8% (n=15).
Compared with normal diastolic function, moderate and severe DD were
associated with higher BNP levels (P=0.038 and P<0.001, respectively)
and elevated indexes of LA volume (LAVI) (P=0.007 and P<0.001, respec-
tively) and LV mass (LVMI) (P=0.074 and P=0.017, respectively).
Participants with normal diastolic function and mild DD had no signifi-
cant differences in quality of life, BNP levels, LAVI or LVMI.
ConClUsion: Mild DD is common in elderly women and is not associ-
ated with increased BNP levels or poor quality of life. Compared with
individuals with moderate and severe DD, LAVI and LVMI are normal in
patients with mild DD.
key Words: Diastolic dysfunction; Elderly women; Left atrial volume; Left
ventricular mass
was conducted with 403 randomly selected women from April 2007 to
November 2008. A cross-sectional cardiovascular study was realized in
334 of 403 participants. Twenty-three patients were excluded due to
previous valvular heart surgery and insufficient image quality in the
echocardiographic examination. A total of 311 participants formed the
final study cohort. The examination consisted of medical history,
physical examination, measurement of brain natriuretic peptide (BNP)
levels and echocardiography. The Minnesota Living with Heart Failure
questionnaire (17) was used to assess quality life.
Plasma BNP levels were measured on the same day of echocardiog-
raphy. The blood samples were collected in EDTA-containing tubes.
After prompt centrifugation, BNP levels were measured using a
chemoluminescent immunoassay kit (Biosite Triage, USA).
Transthoracic echocardiography was performed according to the
guidelines of the American Society of Echocardiography (18) using a
digital ultrasound scanner (Vivid 7, General Electrics, Norway). Data
from three cardiac cycles (five cycles in the presence of atrial fibrilla-
tion) were analyzed. An experienced cardiologist, blinded to the par-
ticipants’ clinical data, performed the ultrasound examination. LV
diameter, posterior wall and septal thickness, and left atrial diameter
were measured by M-mode from the parasternal views. Left atrial vol-
ume was measured by manual tracing of end-systolic endocardial bor-
ders using the apical four-chamber view. LV myocardial mass was
calculated according to the Devereux formula. The Quinones formula
was used for measurement of LV ejection fraction. Values were aver-
aged for each patient. Peak velocities of early (E) and late (A) diastolic
filling and deceleration time (DT) were derived from the transmitral
Doppler profile. Doppler tissue imaging was taken from the lateral
mitral annulus, and revealed early (E′) and late (A′) diastolic peak
velocities, from which the mitral E/E′ ratio was subsequently calcu-
lated. Inter- and intraobserver correlation for echocardiographic meas-
urement variables reached 0.92 and 0.96, respectively.
According to recent guidelines (1), normal diastolic function was
considered as a lateral E/E′ ratio of less than 10. DD was graded as mild
©2011 Pulsus Group Inc. All rights reserved 37
Germing et al

Table 1 The mean LV ejection fraction was 67.8±6.9%. Only 12 partici-

baseline and echocardiographic characteristics pants (3.9%) demonstrated an LV ejection fraction of 55% or less. The
Normal prevalence of DD in the study cohort was high (89.4%): 149 partici-
diastolic Diastolic dysfunction pants (47.9%) had mild DD, 114 participants (36.7%) had moderate
function Mild Moderate Severe DD and 15 participants (4.8%) had severe DD. Only 33 participants
(n=33) (n=149) (n=114) (n=15) (10.6%) had normal diastolic function. The E/E′ ratio was signifi-
BNP, pg/mL 60.4±34.3 52.4±34.7 80.4±79.5 309±415 cantly elevated in patients with DD of any severity. Participants with
P=0.235* P=0.038† P<0.001‡ normal diastolic function and mild DD did not show differences in
Quality of life 7.8±6.5 7.9±8.6 9.2±8 12.6±7.6 indexes of left atrial volume (LAVI) (20±6.5 mL/m2 and 20.6±6.8 mL/m2,
P=0.935* P=0.294† P=0.029‡
respectively) and indexes of LV mass (LVMI) (115±26 g/m2 and
117±30 g/m2, respectively). In patients with moderate or severe DD,
LAVI, mL/m² 20±6.5 20.6±6.8 24±8.7 38.2±17.4
LAVI (24±8.7 mL/m2 and 38.2±17.4 mL/m2, respectively) and LVMI
P=0.703* P=0.007† P<0.001‡
(125±26 g/m2 and 140±43 g/m2, respectively) were significantly ele-
LVMI, g/m² 115±26 117±30 125±26 140±43
vated. The echocardiographic characteristics of the study participants
P=0.718* P=0.074† P=0.017‡ are presented in Table 1.
LVEF, % 68.6±6.9 67.9±7.1 68.3±6.3 62.8±9.2 The levels of BNP were higher in participants with moderate or
P=0.588* P=0.824† P=0.041‡ severe DD than in participants with normal diastolic function.
LVEDD, mm 45.2±4.3 45±4.8 45.8±4.3 46.3±7.5 However, BNP levels were identical in participants with mild DD and
P=0.790* P=0.533† P=0.537† subjects with normal diastolic function.
LVESD, mm 26.2±4.7 26.5±4.7 27±4.7 30.3±7.2
P=0.801* P=0.437* P=0.033* disCUssion
E/A ratio 0.9±0.14 0.63±0.07 1.03±0.33 7.2±3.9 According to recent guidelines (1), our study used specific echocardio-
P<0.001* P=0.029† P<0.001‡ graphic parameters to evaluate diastolic function, and analyzed the
DT, ms 206±38 249±68 216±54 163±49 data to precisely differentiate between normal and pathological dia-
P<0.001* P=0.372† P=0.002‡ stolic function, as well as grading the severity of DD. Increased age and
E/E´ ratio 8.1±2.1 11±3.9 13.9±3.2 23.8±11.3
female sex were important determinants of DD (4-8,14). A prevalence
of LV DD of any severity was previously reported to be 66.6% in
P<0.001* P<0.001† P<0.001‡
women older than 75 years of age (7). Our data and other reports
Data presented as mean ± SD. *P value for mild diastolic dysfunction versus
(2,13) are consistent with these observations. The prevalence of LV
normal diastolic dysfunction; †P value for moderate diastolic dysfunction versus
DD of any severity in elderly women was high, with the majority dem-
normal diastolic dysfunction; ‡P value for severe diastolic dysfunction versus
onstrating mild DD.
normal diastolic dysfunction. BNP Brain natriuretic peptide; DT Deceleration
Echocardiographical studies (12,13) suggest that transmitral LV
time; E´ Peak early diastolic mitral annular velocity; E/A Peak early and late
inflow patterns underly an age-dependent process, and mild DD may
diastolic filling velocity; LAVI Left atrial volume index; LVEF Left ventricular
represent a normal and physiological alteration in increased age.
ejection fraction; LVMI Left ventricular mass index; LVEDD Left ventricular end-
However, assessment of left atrial and LV geometry provides additional
diastolic diameter; LVESD Left ventricular end-systolic diameter
information on diastolic function. LV hypertrophy usually leads to
increased relaxation time, which reduces early diastolic filling.
Increased LVMI and relative wall thickness were previously found to
to severe according to the following categories: mild DD was defined as be associated with Doppler parameters of DD (19). Different geomet-
a lateral E/E′ ratio of greater than 10, an E/A ratio of less than 0.8 and a ric patterns reflecting an LV remodelling process have been reported
DT of greater than 200 ms; moderate DD was characterized by a lat- (19-21). In addition, left atrial assessment is clinically important
eral E/E′ ratio of greater than 10, an E/A ratio of between 0.8 and 1.5, because there is a significant relationship between left atrial remodel-
and DT of between 160 ms and 200 ms; and severe DD was defined ling and echocardiographic indexes of diastolic function (22).
as a lateral E/E’ ratio of greater than 10, an E/A ratio of greater than Observational studies (14) have shown that a LAVI of greater than
2 and DT of less than 160 ms. 34 mL/m2 is an independent predictor of health, heart failure, atrial
Numerical values were expressed as mean ± SD. Continuous vari- fibrillation and ischemic stroke, and is a reliable predictor of exercise
ables were compared between groups using an unpaired t test (for nor- capacity in patients with isolated DD (23). Progressive increases in left
mally distributed variables) or Mann-Whitney U test (for non-normally atrial size is directly correlated with age, LV mass and DD (24). As
distributed variables). c2 analysis was used to compare categorical vari- recently reported (20), increasing LV wall thickness is a typical finding
ables. All reported probability values were two-tailed, and P<0.05 was in women of advanced age. Therefore, enlargement of the left atrium
considered to be statistically significant. Analyses were performed with and an increase in LV wall thickness reflect a chronic remodelling pat-
SPSS version 17.0 (IBM Corporation, USA). tern associated with pathophysiological processes.
In our study, individuals with normal diastolic function and mild
ResUlts DD demonstrated similar geometric parameters of LAVI and LVMI. In
The mean age of the 311 participants was 74.3±2.9 years (range 69.1 to contrast, individuals with moderate or severe DD showed elevated
79.1 years). Cardiovascular risk factors were common in the study LAVI and increased LVMI versus participants with mild DD. The
cohort: hypertension (n=221 [71.4%]), hypercholesterolemia (n=164 association of LAVI with diastolic function grade is consistent with
[52.7%]), current or previous smoking (n=56 [18%]), diabetes (n=34 the literature (25,26).
[10.9%]) and obesity (n=81 [26%]). The clinical characteristics of DD is characterized by elevated LV filling pressure and impaired
patients with normal diastolic function and mild or moderate DD were relaxation. These pathophysiological changes lead to neurohormonal
similar; however, the prevalence of hypertension was higher in partici- activation, reflected by an elevation in BNP levels (10,27,28). In
pants with severe DD. Participants with severe DD more often had a patients with suspected heart failure and normal ejection fraction, LAVI
history of myocardial infarction, hospitalization due to heart failure, is a powerful independent predictor of LV DD as predicted by serum
stroke and atrial fibrillation. Although patients with normal diastolic natriuretic peptide levels (29,30). Concordantly, in our study cohort of
function and mild DD had identical scores in quality of life measure- elderly women, participants with mild DD and normal diastolic function
ments, the presence of severe DD was significantly associated with did not differ in BNP levels. However, BNP levels were increased signifi-
poor quality of life (P=0.029). cantly in individuals who demonstrated more severe DD, suggesting that

38 Exp Clin Cardiol Vol 16 No 2 2011


BNP measurements effectively distinguish among severities of DD.
These findings corroborate previous reports (10).
In our study cohort, participants with normal diastolic function
and mild DD were effectively distinguished from individuals with
moderate or severe DD. Individuals with normal diastolic function and
mild DD did not differ in BNP levels, left atrial volume or LV mass.
Our hypothesis that mild DD in women older than 70 years of age has
no clinical impact is further supported by findings from the quality of
life questionnaire. Whereas participants with normal diastolic func-
tion and mild DD had identical quality of life scores, severe DD was
significantly linked to poorer quality of life. The geometric parameters
LAVl and LVMI must be considered when evaluating the clinical rel-
evance of LV DD in elderly women.
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