Prognostic Value of a Simple Echocardiographic Parameter

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


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


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


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


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


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.

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