prognostic value of a simple echocardiographic parameter
TRANSCRIPT
CLINICAL STUDY
Prognostic Value of a Simple Echocardiographic Parameter, theRight Ventricular Systolic to Diastolic Duration Ratio, in Patients
with Advanced Heart Failure with Non-IschemicDilated Cardiomyopathy
Boqing Xu,1 MD, Takayuki Kawata,2 MD, Masao Daimon,1 MD, Koichi Kimura,2 MD,
Tomoko Nakao,1 MD, Seitetz C. Lee,2 MD, Megumi Hirokawa,2 MD, Aya Yoshinaga,3 MD,
Masafumi Watanabe,2 MD, Yutaka Yatomi,1 MD and Issei Komuro,2 MD
SummaryThe prognostic value of the right ventricular (RV) systolic to diastolic duration ratio (S/D ratio) in patients
with advanced heart failure is not clear.
We enrolled 45 patients with DCM (40 ± 13 years, 33 male) who were admitted to our hospital for evalu-
ation or treatment of heart failure. The RV systolic and diastolic durations were measured using continuous
Doppler imaging of tricuspid regurgitation, and the RV S/D ratio was calculated. Cardiac events were defined as
cardiac death or left ventricular assist device implantation within the first year. Twenty-eight cardiac events oc-
curred. The RV S/D ratio was significantly higher in the event group than in the event-free group (1.8 ± 0.8
versus 1.2 ± 0.5, P = 0.008). Univariate analysis showed that the RV S/D ratio, plasma brain natriuretic peptide
concentration, left atrial volume index, and mitral deceleration time were associated with these events. Receiver
operating characteristic curve analysis revealed that the optimal RV S/D cutoff value to predict events was 1.2
(sensitivity 79%, specificity 65%, area under the curve 0.745). Kaplan-Meier analysis indicated a significantly
higher event rate in patients with an RV S/D ratio > 1.2 (log-rank test, P = 0.003). The addition of an RV S/D
ratio > 1.2 improved the prognostic utility of a model that included conventional variables (P = 0.014).
In patients with advanced heart failure with DCM, the RV S/D ratio was higher in patients with events
than in those without events. The addition of the RV S/D ratio to conventional parameters may provide better
prognostic information.
(Int Heart J 2018; 59: 968-975)
Key words: Prognosis, Tricuspid regurgitation, Right ventricular function
There is increasing appreciation of the potential im-
pact of right ventricular (RV) function on out-
come, even in patients with left-sided heart fail-
ure. However, assessing the RV function is difficult be-
cause of its complex anatomy and wall motion. Although
the RV ejection fraction can be derived from several im-
aging modalities, such as scintigraphy, magnetic reso-
nance, computed tomography, or 3D echocardiography,
these are relatively expensive, have limited availability,
and can require off-line calculations that are time consum-
ing. Simple parameters that are easy to obtain and have
high reproducibility are needed in daily practice.
In pediatric cardiomyopathy, previous reports have
shown that the ratio between the duration of systole and
diastole (S/D ratio), a fundamental characteristic of car-
diac action, is an index of global left ventricular (LV) and
RV function.1-3) The value of the RV S/D ratio in children
with pulmonary arterial hypertension is also temporally
associated with worse RV function, hemodynamics, exer-
cise capability, clinical status, and survival.4) The higher
the RV S/D ratio in children with pulmonary arterial hy-
pertension, the higher the risk of an adverse outcome.4)
However, the role of the RV S/D ratio for predicting prog-
nosis in patients with advanced heart failure is not clear.
We hypothesized that the RV S/D ratio would be abnor-
mally elevated in patients with advanced heart failure with
dilated cardiomyopathy (DCM) who had a worse progno-
sis.
From the 1Department of Clinical Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 2Department of Cardiovascular
Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan and 3Department of Cardiovascular Medicine, Nippon Medical School,
Tokyo, Japan.
This work was partially supported by a Grant-in-Aid for Scientific Research C (15K01326) from the Japan Society for the Promotion of Science (Takayuki
Kawata).
Address for correspondence: Takayuki Kawata, MD, Department of Cardiovascular Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku,
Tokyo, 113-8655 Japan. E-mail: [email protected]
Received for publication August 16, 2017. Revised and accepted December 6, 2017.
Released in advance online on J-STAGE July 18, 2018.
doi: 10.1536/ihj.17-475
All rights reserved by the International Heart Journal Association.
968
Int Heart J
September 2018 969UTILITY OF RV SYSTOLIC TO DIASTOLIC DURATION RATIO
Figure 1. A: A 2-D echocardiogram and continuous Doppler images of TR of a 56-year-old male patient who had a cardiac
event (left ventricular assist device implantation) and an RV S/D ratio of 3.68. B: The same recordings of a 36-year-old male
patient who did not have a cardiac event and an RV S/D ratio of 0.97. S indicates systolic duration; and D, diastolic duration.
Methods
Patients and protocol: We retrospectively analyzed 55
Stage C/D, New York Heart Association Class III/IV pa-
tients with DCM, who were admitted to our institution for
evaluation of heart transplantation or management of heart
failure. The diagnosis of DCM was established as LV dys-
function in the absence of coronary artery disease docu-
mented by coronary angiography, and the absence of spe-
cific heart muscle disease or active myocarditis on endo-
myocardial biopsy. Patients with mechanical circulatory
support or on ventilators at admission were excluded. The
echocardiography findings after admission were reviewed,
and patients with atrial fibrillation, LV ejection fraction �35%, lack of tricuspid regurgitation (TR), or inadequate
image quality to assess TR duration were also excluded.
Medical records were reviewed to obtain the following in-
formation: vital status; medical treatment; laboratory data
including hemoglobin, sodium, plasma brain natriuretic
peptide (BNP) concentration, and estimated glomerular fil-
tration rate at the time of echocardiography since they
have been reported as prognostic predictors or factors as-
sociated with outcomes in heart failure;5-7) and outcome
data. The date of echocardiography was considered as the
entry time-point of observation. Primary outcomes were
defined as the implantation of a LV assist device or car-
diac death within the first year. The attending physician
determined the timing of device implantation based on
whether the patient developed cardiogenic shock, had pro-
gressive decline of end-organ function, or was considered
inotrope-dependent despite optimal medical therapy. Our
data collection protocol was approved by the institutional
review board of the University of Tokyo Hospital.
Echocardiography: Our echocardiography laboratory is
maintained according to the guidelines of the Japanese
Society of Echocardiography.8) In all subjects, cardiac
chamber quantification by 2D echocardiography was per-
formed according to guidelines.9) LV diameters were
measured using 2D echocardiography according to the
recommended criteria. The thickness of the interventricu-
lar septum and that of the LV posterior wall were meas-
ured at end-diastole. The LV mass was calculated using
diastolic measurements of LV diameter and wall thickness
on 2D echocardiography according to the cube formula.9)
LV end-diastolic and end-systolic volumes were deter-
mined from the apical views using the biplane disc sum-
mation method. The LV ejection fraction was calculated
by the following equation: 100 × (end-diastolic volume -
end-systolic volume)/end-diastolic volume. The left atrial
(LA) volume was measured using the biplane method of
disks. Each parameter was indexed for body surface area,
when appropriate. To assess conventional diastolic pa-
rameters, mitral inflow velocities were determined by
pulsed Doppler imaging.10) The peak early (E) and late
(A) diastolic velocities, the E-wave deceleration time from
the peak of the early diastolic wave to the baseline, and
the E/A ratio were assessed from the mitral inflow veloc-
ity pattern. The mitral annular motion velocity was re-
corded at both the lateral and medial mitral annulus in the
apical 4-chamber view by pulsed tissue Doppler. The peak
early diastolic velocity (e’) of the annulus was measured
and the ratio of the peak early diastolic transmitral flow
velocity to the annular velocity (E/e’) was calculated. Be-
cause quantitative assessments of mitral regurgitation were
not performed in all patients, qualitative assessments
(mild, moderate, or severe) by an expert sonographer and
the physician were conducted. TR severity was graded ac-
cording to the guidelines.11)
Evaluation of conventional RV function parameters:Based on the guidelines,9) tricuspid annular plane systolic
excursion (TAPSE), tissue Doppler-derived systolic tricus-
pid annulus motion velocity (S’), and RV fractional area
change (FAC) were used to assess the conventional RV
systolic function. TAPSE was measured on the M-mode
tracing obtained from the RV-focused apical 4-chamber
view, with the M-mode cursor aligned along the lateral
site of the tricuspid annulus. Pulsed Doppler tissue imag-
ing at the lateral site of the tricuspid annulus was acquired
from the RV-focused apical 4-chamber view to measure
peak systolic, early diastolic, and late diastolic annular ve-
locities. These measurements were obtained at the end of
expiration to minimize translational motion. Angle-
dependent parameters, including TAPSE and S’, were ob-
tained using the optimal angle of incidence available. The
FAC was calculated from the RV-focused apical 4-
chamber view using the following formula: 100 × (RV
Int Heart J
September 2018970 Xu, ET AL
Table I. Patient Characteristics
Event (n = 28) Event free (n = 17) P
Age (years) 38 ± 14 42 ± 10 0.27
Gender (Male/Female) 23/5 10/7 0.09
BMI (kg/m2) 20.6 ± 3.2 22.5 ± 5.2 0.13
BSA (m2) 1.69 ± 0.15 1.66 ± 0.24 0.58
SBP (mmHg) 86 ± 6 91 ± 11 0.03
DBP (mmHg) 55 ± 8 57 ± 10 0.53
HR (bpm) 86 ± 18 82 ± 21 0.52
Serum BNP (pg/mL) 969.0 ± 660.0 571.8 ± 444.7 0.03
Hb (g/dL) 13.0 ± 2.1 13.7 ± 2.0 0.32
Na (mEq/L) 138 ± 4 135 ± 4 0.063
eGFR (mL/minute/1.73m2) 74 ± 41 68 ± 22 0.543
Device
ICD or CRTD 10 (36%) 4 (24%) 0.39
Medical treatment
Beta blocker 25 (89.3%) 17 (100%) 0.16
ACE inhibitor 20 (71.4%) 10 (58.8%) 0.38
ARB 6 (21.4%) 4 (23.5%) 0.87
MRB 21 (75.0%) 13 (76.5%) 0.91
Diuretics 24 (85.7%) 15 (88.2%) 0.81
Tolvaptan 8 (28.6%) 4 (23.5%) 0.71
Vitamin K antagonist 16 (57.1%) 11 (64.7%) 0.62
Amiodarone 14 (50.0%) 6 (35.3%) 0.34
PDE III inhibitor 11 (39.3%) 5 (29.4%) 0.50
Digitalis 2 (7.1%) 3 (17.6%) 0.28
BMI indicates body mass index; BSA, body surface area; SBP, systolic blood pres-
sure; DBP, diastolic blood pressure; HR, heart rate; Hb, hemoglobin; BNP, brain na-
triuretic peptide; eGFR, estimated glomerular filtration rate; ICD, implantable cardio-
verter defibrillator; CRTD, cardiac resynchronization therapy defibrillator; ACE,
angiotensin-converting enzyme; ARB, angiotensin receptor blocker; MRB, mineralo-
corticoid receptor blocker; and PDE III, phosphodiesterase III.
Table II. Echocardiographic Data
Event (n = 28) Event free (n = 17) P
LVEDVI (mL/m2) 176 ± 68 151 ± 40 0.17
LVESVI (mL/m2) 148 ± 63 122 ± 37 0.14
LVEF (%) 17 ± 5.4 19 ± 5.6 0.18
LVMI (g/m2) 200 ± 76 170 ± 58 0.16
E/A ratio 2.7 ± 0.8 2.1 ± 1.2 0.06
DT (mseconds) 115 ± 31 145 ± 59 0.048
E/e’ medial 19.3 ± 10.7 20.5 ± 11.1 0.75
LAVI (mL/m2) 71 ± 22 57 ± 16 0.026
RV FAC (%) 21 ± 10 28 ± 8 0.022
RV S’ (cm/second) 7.4 ± 3.2 8.0 ± 2.0 0.43
TAPSE (mm) 13.6 ± 3.8 15.1 ± 4.5 0.23
RV MPI 0.62 ± 0.08 0.59 ± 0.06 0.132
≥ moderate MR 16 (57.1%) 3 (17.6%) 0.04
≥ moderate TR 5 (17.9%) 3 (17.6%) 0.99
TRPG (mmHg) 35 ± 11 28 ± 9 0.032
RV S/D duration ratio 1.8 ± 0.8 1.2 ± 0.5 0.008
Maximal IVC (mm) 20.8 ± 4.3 18.3 ± 4.4 0.059
LVEDVI indicates left ventricular end diastolic volume index; LVESVI, left
ventricular end systolic volume index; LVEF, left ventricular ejection frac-
tion; LVMI, left ventricular mass index; DT, deceleration time; LAVI, left
atrial volume index; RV, right ventricular; FAC, fractional area change;
TAPSE, tricuspid annular plane systolic excursion; MPI, myocardial perfor-
mance index; MR, mitral regurgitation; TR, tricuspid regurgitation; TRPG,
tricuspid regurgitation pressure gradient; S/D, systolic/diastolic; and IVC, in-
ferior vena cava.
Int Heart J
September 2018 971UTILITY OF RV SYSTOLIC TO DIASTOLIC DURATION RATIO
Figure 2. The mean RV S/D ratio in patients with a cardiac event
was 1.8 ± 0.8, which is higher than in those without a cardiac event
(1.2 ± 0.5, P = 0.008).
Figure 3. Association between the RV S/D ratio and the pressure gradient of tricuspid regur-
gitation.
end-diastolic area - RV end-systolic area) / RV end-
diastolic area. Moreover, the tissue Doppler myocardial
performance index (MPI) was measured from pulsed Dop-
pler tissue imaging at the lateral site of the tricuspid annu-
lus.
Measurement of the RV S/D ratio: Based on an enve-
lope of TR as assessed by continuous Doppler imaging,
the durations of RV systole and diastole were measured,
and the RV S/D ratio was calculated (Figure 1). Accord-
ing to previous reports,1-4) the duration of RV systole was
measured from the onset to the end of the Doppler TR en-
velope. The duration of RV diastole was measured from
the end of the Doppler TR envelope to the onset of the
next TR envelope. The RV S/D ratio in our study was ob-
tained from simple measurements of TR duration rather
than an analysis of the cardiac cycle.
Statistical analysis: All data were expressed as the mean
± SD for continuous variables and as percentages for cate-
gorical variables. All statistical analyses were conducted
utilizing SPSS 17.0 software (SPSS Inc., Chicago, IL,
USA). A Student’s t-test was used to assess differences
between the mean values of continuous variables. Cate-
gorical variables were compared with the Fisher’s exact
test. Pearson’s linear correlation analysis was used to de-
termine the correlations between the RV S/D ratio and
other echocardiographic parameters. The optimal cutoff
value of the S/D ratio was determined by receiver operat-
ing characteristic curve analysis. The cumulative event-
free rates were obtained using the Kaplan-Meier method,
and the difference between survival curves was tested by
the log-rank test. The association of selected variables
with the one-year outcome was evaluated using a univari-
ate Cox proportional hazards model. Moreover, Cox pro-
portional hazards models were compared to find the in-
crease in the prognostic benefit of adding the RV S/D ra-
tio as an input variable along with clinical and routine
echocardiographic variables. A statistically significant in-
crease in the global log-likelihood chi-square of the model
was interpreted as indicating an incremental prognostic
value. To determine the reproducibility of the RV S/D ra-
tio, a total of 10 randomly selected examinations were
analyzed twice by one investigator at a 1-week interval, as
well as by a second investigator. Intra- and interobserver
variabilities were expressed as intraclass correlation coeffi-
cients. A probability value of < 0.05 was considered sig-
nificant.
Int Heart J
September 2018972 Xu, ET AL
Figure 4. Associations between the RV S/D ratio and conventional RV parameters. Only the FAC was significantly associated
with the RV S/D ratio.
Results
Five patients were excluded because of the lack of
TR, and two more were excluded due to inadequate image
quality of the TR envelope. Three patients with atrial fib-
rillation were also excluded. Therefore, 45 patients with
DCM were included in the present study. During the first
year, there were 28 cardiac events (4 cardiac deaths and
24 LV assist device implantations).
Patients’ characteristics and echocardiographic data:Patients’ general characteristics are summarized in Table I.
The patients were divided into an event group (n = 28)
and an event-free group (n = 17). There were no signifi-
cant differences in any of the characteristics between the
two groups, except that systolic blood pressure was lower
and serum BNP concentration was higher in the event
group. The results of echocardiography are summarized in
Table II. Compared with event-free patients, patients with
a one-year event had a larger LA volume index, a shorter
mitral deceleration time, more frequent significant mitral
regurgitation, a higher TR pressure gradient, and an ele-
vated RV S/D duration ratio (1.8 ± 0.8 versus 1.2 ± 0.5, P= 0.008, Figure 2).
Associations between the RV S/D ratio and echocar-diographic parameters: Since RV function strongly de-
pends on RV afterload, we confirmed an association be-
tween the RV S/D ratio and the TR pressure gradient as
well as conventional RV parameters. The RV S/D ratio
tended to correlate with the TR pressure gradient in the
present study, but this association was not significant (Fig-
ure 3). As for the conventional RV parameters (Figure 4),
there was an inverse correlation between the RV S/D ratio
and FAC, whereas there were no significant associations
between the RV S/D ratio and TAPSE, and S’ and tissue
Doppler MPI.
Factors associated with one-year outcome: Table III
shows the results of univariate Cox proportional hazards
analysis to find the factors associated with one-year
events. As shown in the table, serum BNP concentration,
LA volume index, mitral deceleration time, FAC, and RV
S/D duration ratio were factors associated with the out-
comes in the present study. Receiver operating characteris-
tic curve analysis revealed that the optimal cutoff value of
RV S/D to predict events was 1.2 (sensitivity, 79%; speci-
ficity, 65%; area under the curve, 0.745; Figure 5).
Kaplan-Meier analysis indicated that the event rate was
significantly higher in patients with an RV S/D ratio > 1.2
(Figure 5).
Incremental value of the RV S/D ratio: The incremental
value of the RV S/D ratio is shown in Figure 6. From Ta-
ble III, we selected serum BNP concentration and LA vol-
ume index as conventional variables to include in a Cox
proportional hazards model. Mitral deceleration time was
not obtained in several patients because of mitral inflow
Int Heart J
September 2018 973UTILITY OF RV SYSTOLIC TO DIASTOLIC DURATION RATIO
Figure 5. Receiver operating characteristic curve analysis indicated that the optimal cutoff value of the RV S/D ra-
tio to predict outcome was 1.2. The sensitivity was 97%, the specificity was 65%, and the area under the curve was
0.745 (left). Kaplan-Meier analysis revealed that the cardiac event rate was significantly higher in patients with an RV
S/D ratio > 1.2 (right).
Table III. Univariate Cox Proportional Hazards Analysis
Variables HR (95% CI) P
Etiological variables
Age (years) 0.976 (0.948 to 1.006) 0.117
Gender (male) 0.500 (0.190 to 1.320) 0.162
BMI (kg/m2) 0.936 (0.856 to 1.024) 0.148
BSA (m2) 1.452 (0.225 to 9.394) 0.695
Serum BNP (pg/mL) 1.001 (1.000 to 1.001) 0.023
Hb (g/dL) 1.533 (0.943 to 2.493) 0.085
Na (mEq/L) 1.171 (0.988 to 1.388) 0.069
eGFR (mL/minute/1.73m2) 0.930 (0.861 to 1.004) 0.064
SBP (mmHg) 0.957 (0.913 to 1.004) 0.073
DBP (mmHg) 0.688 (0.950 to 1.035) 0.688
HR (bpm) 1.010 (0.991 to 1.029) 0.295
Echocardiographic variables
LVEDVI (mL/m2) 1.002 (0.997 to 1.007) 0.458
LVESVI (mL/m2) 1.002 (0.997 to 1.008) 0.400
LVEF (%) 0.956 (0.893 to 1.023) 0.192
LVMI (g/m2) 1.002 (0.997 to 1.007) 0.380
E/A ratio 1.409 (0.913 to 2.174) 0.121
DT (mseconds) 0.986 (0.973 to 1.000) 0.048
E/e’ medial 0.985 (0.943 to 1.029) 0.494
LAVI (ml/m2) 1.019 (1.000 to 1.039) 0.049
RV FAC (%) 1.182 (1.021 to 1.367) 0.025
RV S’ (cm/second) 0.906 (0.628 to 1.307) 0.598
TAPSE (mm) 0.952 (0.724 to 1.253) 0.728
RV MPI 1.050 (0.999 to 1.103) 0.053
≥ moderate MR 0.379 (0.034 to 4.265) 0.432
≥ moderate TR 2.107 (0.191 to 23.304) 0.543
TRPG (mmHg) 1.036 (0.998 to 1.075) 0.063
RV S/D duration ratio 1.865 (1.203 to 2.893) 0.005
Maximal IVC (mm) 1.079 (0.990 to 1.176) 0.082
Abbreviations as in n Tables I and II.
fusion; therefore, we excluded mitral deceleration time
from this analysis. The addition of an RV S/D ratio > 1.2
to the conventional variables significantly improved the
prognostic utility of the Cox model (P = 0.014). When the
FAC was used in the model, the chi-square value was
smaller than when the RV S/D ratio was used.
Intra- and interobserver variability: The reproducibility
of the RV S/D ratio was excellent. The intraclass correla-
tion coefficients of the intra- and interobserver measure-
ments were 0.99 and 0.96, respectively.
Discussion
The major finding of this study was that the RV S/D
ratio was associated with outcomes in univariate analysis
in patients with advanced heart failure with DCM. In ad-
dition, an RV S/D ratio > 1.2 was significantly associated
with an increased one-year cardiac event rate. Further-
more, an RV S/D ratio > 1.2 also provided a significant
incremental prognostic value over clinical and routine
echocardiographic parameters.
Since the concept of “peculiar RV function” has not
yet been fully elucidated, assessments of the RV function
remain difficult, although recent advances in imaging mo-
dalities make it possible to assess RV morphology. There-
fore, we focused on the cardiac phase, a basic component
of cardiac function. Although the pre-ejection time, ejec-
tion time, and isovolumic relaxation time have been com-
monly used to assess cardiac function, the systolic and
diastolic durations have not been routinely measured, al-
though these are fundamental components of the cardiac
cycle and are readily available. Despite the fact that this is
a classical method, the advantage of the S/D ratio is that
it is very simple and easy to measure, and it does not re-
quire assessments of RV morphology, volume, or contrac-
tion and expansion, which are still difficult to assess cor-
rectly by imaging modalities. Moreover, the RV S/D ratio
can be measured even by portable echo machines, and
off-line analysis is unnecessary.
For the conventional parameters of RV function, only
the FAC was associated with the one-year outcome in the
present study. In fact, receiver operating characteristic
curve analysis revealed that the optimal cutoff value of
FAC to predict events was 22.3% (sensitivity, 61%; speci-
ficity, 76%; area under the curve, 0.716), and the area un-
der the curve was similar to that obtained with the RV S/
Int Heart J
September 2018974 Xu, ET AL
Figure 6. The incremental benefit of adding an RV S/D ratio > 1.2
on the association between conventional parameters (BNP and LAVI)
and one-year events. Model 1, based on clinical and routine echocar-
diographic parameters (BNP and LAVI), was significantly improved
by the addition of the RV S/D ratio > 1.2 (model 2). LAVI indicates
LA volume index; and BNP, brain natriuretic peptide.
D ratio. Although the FAC has been shown to be an index
of RV global systolic function and is recommended in the
current guidelines,9) it has several limitations. Measuring
the FAC requires complete, accurate, and high-quality RV
echocardiograms to ensure clear delineation of the RV en-
docardial border. Furthermore, it is difficult to delineate
the entire RV wall, especially in an enlarged RV. More-
over, it is apparent that minor variations in the 4-chamber
plane position with respect to the RV crescent shape may
result in variability of the RV size when linear measure-
ments are performed. Therefore, the RV FAC has only fair
interobserver reproducibility.9) Moreover, the FAC neglects
the contribution of the RV outflow tract to overall systolic
function. In contrast, the RV S/D ratio can be measured
without information on the complete RV endocardial bor-
der and wall motion, and measuring the RV S/D ratio was
simpler and more accurate than the FAC in selected sub-
jects in the present study. Indeed, the reproducibility of
the RV S/D ratio was excellent in this study. A previous
report has shown that a higher RV S/D ratio was associ-
ated with a worse RV FAC, worse hemodynamics as
measured by catheterization, a shorter 6-minute walk dis-
tance, and worse clinical outcomes in children with pul-
monary arterial hypertension.4) In this study, an inverse
correlation between the RV S/D ratio and the FAC was
observed, and this result agrees with a prior study. A
higher RV S/D ratio may reflect worse hemodynamics and
functional status as well as worse RV systolic dysfunction.
A previous report indicated that tissue Doppler MPI
and the RV S/D ratio may provide complementary infor-
mation on predicting RV dysfunction.12) However, tissue
Doppler MPI was not associated with outcomes in pa-
tients with advanced heart failure with DCM in the pre-
sent study. This may be because tissue Doppler MPI is
load dependent and unreliable when right atrial (RA) pres-
sure is elevated.9) Our patients had a relatively dilated in-
ferior vena cava, indicating an elevated RA pressure.
The systole constitutes about 50% of the cardiac cy-
cle in healthy adults.13) Ventricular failure is characterized
by a prolongation of the pre-ejection period due to a de-
creased rate of rise of intraventricular pressure and abbre-
viation of ejection time.13) In the present study, the dura-
tion of the systole was measured from the onset to the
end of the Doppler envelope of TR.1-4,12) Therefore, the
systolic duration included the isovolumic contraction
phase, ejection phase, and isovolumic relaxation phase,
which is simply the total time that RV pressure was
higher than RA pressure. In the cardiac cycle, the systolic
duration is relatively prolonged when there is RV systolic
and diastolic dysfunction (due to prolongation of both iso-
volumic phases); therefore, the RV S/D ratio rises in RV
dysfunction. We postulate that the RV S/D ratio is a use-
ful measurement, since it may reflect not only prolonga-
tion of isovolumic contraction and relaxation times (which
are part of the systolic duration as defined by the TR du-
ration), but also the shortening of the diastolic filling du-
ration. Therefore, in patients with advanced heart failure
due to DCM, the filling of the RV takes longer in prepa-
ration to open the pulmonary valve, but there is insuffi-
cient time for ejection and filling. Actually, our patients
with DCM had an increased RV S/D ratio even in the
event-free group compared with control groups in prior
reports.1,2) Moreover, our results show that the more pro-
longed the RV S/D ratio, the higher the risk of one-year
events. Although the utility of the RV S/D ratio has not
been reported in adolescent or adult patients, previous re-
ports have shown that the RV S/D ratio is increased in
children with pulmonary arterial hypertension, patients
with restrictive cardiomyopathy, and patients with DCM
compared with controls.1,2,4) This suggests that an in-
creased RV S/D ratio is probably a nonspecific index of
abnormal global cardiac performance.
An increased S/D ratio suggests that a compromised
systole function leads to impaired diastole function, owing
to a shortened diastole that is greater than the expected
rate-related decrease in diastole.14-17) The heart rate is a
major determinant of diastolic and systolic durations. The
duration of the systole is linearly related to the heart rate,
with an inverse relationship between the ejection time and
the heart rate.16) The diastole is longer at lower heart rates
because of a longer diastasis.14,15) In the present study,
there was a significant weak positive correlation (r =
0.455, P = 0.002) between the heart rate and the RV S/D
ratio, which was similar to those reported in previous
studies.1-4) However, there was no significant difference in
the heart rate between patients with or without events, in-
dicating that the severity of heart failure per se caused an
increase in the RV S/D ratio.
Limitations: There are several limitations of the present
study. First, since this study was retrospective, it is neces-
sary to validate our results in a prospective observational
study. Second, this study was conducted at a single center,
and consequently included a limited number of patients.
However, our hospital is one of the high-volume centers
that manages patients with advanced heart failure and per-
forms heart transplantation in Japan. A Doppler envelope
of trace TR might be difficult to visualize entirely; how-
ever, the onset and termination of the envelope is usually
visible, allowing measurements of the duration of TR.
Int Heart J
September 2018 975UTILITY OF RV SYSTOLIC TO DIASTOLIC DURATION RATIO
Furthermore, since patients with DCM often have TR that
is more than trace, an adequate Doppler envelope can be
recorded easily in most subjects. More than half of our
patients reached the primary endpoint during hospitaliza-
tion after their baseline echocardiographic examination,
and multiple full studies in the echocardiographic labora-
tory could not be performed. Since it is uncertain whether
the RV S/D ratio will change with the treatment of heart
failure, further investigation should provide new insights
into this issue. Although net reclassification improvement
and integrated discrimination improvement have been
commonly used to show the incremental value of a diag-
nostic parameter, these methods are very complex and dif-
ficult to use. Therefore, we used the global log-likelihood
chi-square of the model in this study. Finally, we only
analyzed patients with advanced heart failure with DCM,
and it is not clear if our results apply to patients with
other cardiac diseases. The RV S/D ratio in various car-
diac diseases should also be investigated in future studies.
Conclusion
In patients with advanced heart failure with DCM,
the RV S/D ratio was higher in those with events than in
those without events. The measurement of the RV S/D ra-
tio, in addition to conventional parameters, may provide
better prognostic information in these patients.
Disclosures
Conflicts of interest: The authors declare that there is no
relationship with any industry.
References
1. Friedberg MK, Silverman NH. Cardiac ventricular diastolic and
systolic duration in children with heart failure secondary to idi-
opathic dilated cardiomyopathy. Am J Cardiol 2006; 97: 101-5.
2. Friedberg MK, Silverman NH. The systolic to diastolic duration
ratio in children with heart failure secondary to restrictive cardi-
omyopathy. J Am Soc Echocardiogr 2006; 19: 1326-31.
3. Friedberg MK, Silverman NH. The systolic to diastolic duration
ratio in children with hypoplastic left heart syndrome: a novel
Doppler index of right ventricular function. J Am Soc Echocar-
diogr 2007; 20: 749-55.
4. Alkon J, Humpl T, Manlhiot C, McCrindle BW, Reyes JT,
Friedberg MK. Usefulness of the Right ventricular systolic to
diastolic duration ratio to predict functional capacity and sur-
vival in children with pulmonary arterial hypertension. Am J
Cardiol 2010; 106: 430-6.
5. Anand I, McMurray JJ, Whitmore J, et al. Anemia and its rela-
tionship to clinical outcome in heart failure. Circulation 2004;
110: 149-54.
6. Stanek B, Frey B, Hülsmann M, et al. Prognostic evaluation of
neurohumoral plasma levels before and during beta-blocker
therapy in advanced left ventricular dysfunction. J Am Coll Car-
diol 2001; 38: 436-42.
7. Imamura T, Kinugawa K. Prognostic impacts of hyponatremia,
renal dysfunction, and high-dose diuretics during a 10-year
study period in 4,087 Japanese heart failure patients. Int Heart J
2016; 57: 657-8.
8. Nakatani S, Akaishi M, Asanuma T, et al. Guidelines from the
Japanese Society of Echocardiography: Guidance for the man-
agement and maintenance of echocardiography equipment. J
Echocardiogr 2015; 13: 1-5.
9. Lang RM, Badano LP, Mor-Avi V, 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. Eur Heart
J Cardiovasc Imaging 2015; 16: 233-71.
10. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations
for the evaluation of left ventricular diastolic function by echo-
cardiography: An update from the American Society of Echo-
cardiography and the European Association of Cardiovascular
Imaging. Eur Heart J Cardiovasc Imaging 2016; 17: 1321-60.
11. Lancellotti P, Moura L, Pierard LA, et al. European Association
of Echocardiography recommendations for the assessment of
valvular regurgitation. Part 2: mitral and tricuspid regurgitation
(native valve disease). Eur J Echocardiogr 2010; 11: 307-32.
12. Patel DR, Cui W, Gambetta K, Roberson DA. A comparison of
Tei index versus systolic to diastolic ratio to detect left ventricu-
lar dysfunction in pediatric patients. J Am Soc Echocardiogr
2009; 22: 152-8.
13. Weissler AM, Harris WS, Schoenfeld CD. Systolic time intervals
in heart failure in man. Circulation 1968; 37: 149-59.
14. Chung CS, Karamanoglu M, Kovács SJ. Duration of diastole
and its phases as a function of heart rate during supine bicycle
exercise. Am J Physiol Heart Circ Physiol 2004; 287: H2003-8.
15. Spitaels S, Arbogast R, Fouron JC, Davignon A. The influence
of heart rate and age on the systolic and diastolic time intervals
in children. Circulation 1974; 49: 1107-15.
16. Boudoulas H, Geleris P, Lewis RP, Rittgers SE. Linear relation-
ship between electrical systole, mechanical systole, and heart
rate. Chest 1981; 80: 613-7.
17. Cokkinos DV, Heimonas ET, Demopoulos JN, Harralambakis A,
Tsartsalis G, Gardikas CD. Influence of heart rate increase on
uncorrected pre-ejection period/left ventricular ejection time
(PEP/LVET) ratio in normal individuals. Br Heart J 1976; 38:
683-8.