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CLINICAL RESEARCH
Right ventricular dysfunction in patients
with idiopathic dilated cardiomyopathy:
Prognostic value and predictive factors
Dysfonction ventriculaire droite chez les patients avec cardiomyopathie
dilatée idiopathique : valeur pronostique et facteurs prédictifs
Clement Venner a, Christine Selton-Suty a,
Olivier Huttin a, Marie-Line Erpelding b,
Etienne Aliot a, Yves Juillière a,∗
a
Department of Cardiology, institut lorrain du cœur et des vaisseaux,
University Hospital of Nancy, Vandœuvre-lès-Nancy, France
b
Department of Clinical Epidemiology and Evaluation, S2R Centre, ESPRI,
University Hospital of Nancy, Nancy, France
Received 4 June 2015; received in revised form 3 August 2015; accepted 14 October 2015
KEYWORDS
Right ventricular
dysfunction;
Dilated
cardiomyopathy;
Propensity analysis;
Heart failure
Summary
Background. — Right ventricular (RV) dysfunction is an important predictor of impaired prognosis in idiopathic dilated cardiomyopathy.
Aims. — To determine the prognostic role of RV dysfunction, independent of left ventricular
(LV) dysfunction.
Methods. — A total of 136 consecutive patients (73% men; mean age 59.0 ± 13.2 years) with
idiopathic dilated cardiomyopathy (LV ejection fraction ≤ 45%) were enrolled retrospectively.
Thirty-four patients (25%, group 1) presented with RV dysfunction, defined as tricuspid annular
plane systolic excursion (TAPSE) ≤ 15 mm; 102 patients (group 2) had preserved RV function.
Abbreviations: CI, confidence interval; DCM, dilated cardiomyopathy; DT, deceleration time; FAC, fractional area change; HF, heart
failure; HR, hazard ratio; LV, left ventricular; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; MACE, major
adverse cardiac events; MRI, magnetic resonance imaging; OR, odds ratio; RV, right ventricular; RVEF, right ventricular ejection fraction;
sPAP, systolic pulmonary artery pressure; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation; TVI, time-velocity
integral.
∗ Corresponding author at: Department of Cardiology, institut lorrain du cœur et des vaisseaux, CHU Nancy—Brabois, rue du Morvan, 54511
Vandœuvre-lès-Nancy, France.
E-mail address: [email protected] (Y. Juillière).
http://dx.doi.org/10.1016/j.acvd.2015.10.006
1875-2136/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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ACVD-880; No. of Pages 11
ARTICLE IN PRESS
2
C. Venner et al.
Results. — Mean LV ejection fraction was 27.5 ± 8.7%. Mean TAPSE was 18.6 ± 5.4 mm
(15—21.8 mm). Multivariable predictors of RV dysfunction were LV outflow tract time-velocity
integral (odds ratio 0.8, 95% confidence interval [CI] 0.7—0.9; P = 0.003) and E-wave deceleration time ≤ 145 ms (odds ratio 4.1, 95% CI 1.3—12.8; P = 0.017). Major adverse cardiac event-free
survival rates at 1 and 2 years were 64% and 55%, respectively, in group 1 and 87% and 79%,
respectively, in group 2 (P = 0.002). Both by multivariable analysis and after stratification using
a propensity score, RV dysfunction emerged as an independent predictor for major adverse
cardiac events (hazard ratio 3.2, 95% CI 1.3—7.6; P = 0.009), along with right atrium area and
age.
Conclusion. — In idiopathic dilated cardiomyopathy, RV dysfunction with TAPSE ≤ 15 mm offers
additional prognostic information, independent of the extent of LV dysfunction.
© 2015 Elsevier Masson SAS. All rights reserved.
MOTS CLÉS
Dysfonction
ventriculaire droite ;
Cardiomyopathie
dilatée ;
Analyse de
propensité ;
Insuffisance
cardiaque
Résumé
But. — La dysfonction ventriculaire droite (VD) est un facteur prédictif important de l’altération
du pronostic dans la cardiomyopathie dilatée (CMD) idiopathique. Le but était de déterminer le
rôle pronostique de la dysfonction VD indépendamment du niveau de dysfonction ventriculaire
gauche (VG).
Méthodes. — Au total, 136 patients consécutifs (73 % d’hommes, âge moyen : 59,0 ± 13,2 ans)
avec CMD idiopathique (FEVG ≤ 45 %) étaient inclus rétrospectivement. Trente-quatre patients
(25 %, groupe 1) présentaient une dysfonction VD définie par une excursion systolique du plan
de l’anneau tricuspide (TAPSE) ≤ 15 mm et 102 (groupe 2) avaient une fonction VD préservée.
Résultats. — La FEVG moyenne était de 27,5 ± 8,7 %. Le TAPSE moyen était de 18,6 ± 5,4 mm
(15—21,8 mm). Les facteurs prédictifs de la dysfonction VD en analyse multivariée étaient
l’intégrale temps-vélocité (TVI) de la chambre de chasse du VG (OR 0,8 [95 % IC, 0,7—0,9],
p = 0,003) et le temps de décélération de l’onde E ≤ 145 ms (OR 4,1 [95 % IC, 1,3—12,8],
p = 0,017). La survie sans événements cardiaques majeurs (MACE) à 1 et 2 ans était respectivement de 64 % et 55 % dans le groupe 1 et de 87 % et 79 % dans le groupe 2 (p = 0,002).
Après analyse multivariée et stratification en utilisant un score de propensité, la dysfonction
VD apparaissait comme un facteur prédictif indépendant des MACE (HR 3,2 [95 % IC, 1,3—7,6],
p = 0,009), en plus de la surface de l’oreillette droite et de l’âge.
Conclusion. — Dans la CMD idiopathique, la dysfonction VD définie par un TAPSE ≤ 15 mm offre
une information pronostique additionnelle indépendante du niveau de dysfonction VG.
© 2015 Elsevier Masson SAS. Tous droits réservés.
Background
Idiopathic dilated cardiomyopathy (DCM) is the second most
frequent cause of heart failure (HF). Despite recent changes
in diagnosis and treatment of HF, prediction of prognosis
remains uncertain from one patient to another [1—3].
The effect of left ventricular (LV) function on outcome in
HF has been well documented [2—5]. Furthermore, the new
variables of myocardial deformation obtained by two- and
three-dimensional speckle tracking give additional prognostic information [6,7].
Right ventricular (RV) performance is connected to LV
dysfunction in multiple ways (shared fibres and septal
wall, biventricular cardiomyopathic process, increased LV
filling pressures, ventricular interdependence and inextensible pericardial space) [8,9]. Evaluation of RV performance
remains challenging in routine practice and, as a result,
RV function has long been neglected [8—10]. Progress in
echocardiography has helped to redefine the importance of
RV evaluation for further risk stratification [11,12].
The prevalence of RV dysfunction in DCM varies from 34
to 65% [13,14]. Several studies have demonstrated the additional prognostic value of RV dysfunction in HF and, most
particularly, in idiopathic DCM [15—18]. Propensity analyses
are rarely used in clinical studies; they are mostly used in
pharmacological and epidemiological studies, to counter the
effect of potential confounding bias caused by the indication for treatment. The use of a propensity analysis in this
context could provide further information about the prognostic role of RV dysfunction, independent of the level of LV
dysfunction, and also about the factors associated with RV
function [19,20]. Such an analysis has not been performed
in primary DCM.
The aim of our study was to establish the prevalence
of RV dysfunction in a consecutive series of patients with
idiopathic DCM, based on tricuspid annular plane systolic
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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RV dysfunction in idiopathic dilated cardiomyopathy
excursion (TAPSE), and to identify its determinants and
incremental prognostic effect for a given range of LV dysfunction, using a propensity analysis.
Methods
Study population
Between 1st January 2010 and 1st January 2012, we retrospectively selected 790 patients who had been referred
to our institution, and for whom the primary or associated
PMSI (Programme Médicalisé des Systèmes d’Information)
diagnosis was DCM. In order to isolate idiopathic DCM, this
database was crossed with hospitalization records, clinical
and echocardiographic data. Exclusion criteria were defined
to precisely distinguish idiopathic DCM from all other causes
of LV dysfunction or dilatation, and required a systematic
review of coronary angiograms. Ischaemic substrate was
defined as any stenosis ≥ 50% in either of the main coronary arteries or in one of their main side branches. Data
from patients with insufficient echocardiography or examination performed in an unstable clinical state were not
retained for analysis (n = 92). When the initial cause of hospitalization was acute HF, the echocardiography assessment at
discharge was retained. Data from 136 patients presenting
with idiopathic DCM were available for analysis.
Follow-up
Follow-up was censored on 1st January 2014, and consisted
of a telephone interview with the patient’s general physician. For all patients, we recorded data on the presence
and date of occurrence of all major adverse cardiac events
(MACE), defined as a composite criterion, including death
from cardiac cause (sudden cardiac death, ventricular
tachycardia, acute HF), heart transplantation and cardiacrelated hospitalizations.
The delay from the first hospitalization between January
2010 and January 2012 to the first event was retained for
survival analysis.
Echocardiographic assessment
Transthoracic echocardiograms were recorded on various
generations of Vivid systems (GE Vingmed Ultrasound,
Horten, Norway), and analyses were performed off-line on
an EchoPAC workstation (GE Healthcare, Milwaukee, MI,
USA).
Measurements were made according to guidelines
[21,22]. LV ejection fraction (LVEF) was measured according
to Simpson’s method. DCM was defined as LVEF ≤ 45% and left
ventricular end-diastolic diameter ≥ 55 mm. Global peak
systolic longitudinal strain was assessed by two-dimensional
speckle imaging in the apical four-chamber view. Diastolic
function analysis was based on mitral-pulsed Doppler inflow
and tissue-Doppler imaging at the lateral mitral annulus. A
restrictive pattern was defined as E-wave deceleration time
(DT) < 145 ms — the median value and in concordance with
previous studies [23,24]. Left and right atrial areas were
measured from the apical four-chamber view.
3
TAPSE was measured by M-mode, after two-dimensional
echocardiography guidance at the lateral tricuspid annulus,
as the maximal systolic excursion. Tissue Doppler imaging
at the tricuspid annular free wall allowed the assessment
of S-wave velocity. Fractional area change (FAC) in the right
ventricle was obtained according to image quality. Systolic
pulmonary artery pressure was calculated from tricuspid
regurgitation (TR) flow added to right atrial pressure estimated from the inferior vena cava. Right and left atrial areas
were measured at end-ventricular systole in a four-chamber
view.
Cardiac magnetic resonance imaging
assessment
Thirty-seven patients (27.2%) underwent cardiac magnetic
resonance imaging (MRI), performed using a 1.5-Tesla MRI
scanner (Signa HDxt; GE Healthcare, Milwaukee, WI, USA)
connected to an eight-element cardiac phased-array surface
coil. Cine images were obtained with a steady-state free
precession sequence in base-to-apex contiguous short-axis
slices for volume and mass quantification.
Statistical analysis
All continuous variables are described as means ± standard
deviations; all categorical variables are described with absolute and relative frequencies.
Intra- and interobserver variabilities of measure were
assessed using a Bland-Altman diagram for TAPSE. A receiver
operating characteristic curve was built to define an appropriate threshold for TAPSE, based on gold-standard cardiac
MRI-derived RV ejection fraction (RVEF). The area under
the curve of the model was 0.63, and the most pertinent
value was 15.4 mm (Se 0.86; 1—Sp 0.44). RV dysfunction
was defined by TAPSE ≤ 15 mm, and patients were divided
into two groups according to the presence (group 1) or
absence (group 2) of RV dysfunction. Comparisons according to the presence or absence of RV dysfunction and the
occurrence of MACE were realized with Student’s t test
for continuous variables and the Chi2 test for discrete
variables.
Bivariate and multivariable logistic regressions were used
to identify determinants of RV dysfunction. In the multivariable model, LVEF, LV end-diastolic diameter and age
were forced, and a stepwise variable selection method,
with a P value < 0.1 to enter the stepwise selection and a
P value < 0.05 to remain in the final model, was applied.
Results are expressed as odds ratios (ORs) with 95% confidence intervals (CIs).
To assess the prognostic effect of RV dysfunction on the
occurrence of MACE, several analyses were used. Survival
curves according to the presence or absence of RV dysfunction were generated by the Kaplan-Meier method, and
were compared using log-rank tests. Next, bivariate and
multivariable Cox regression analyses were used to assess
predictors of MACE, particularly including RV dysfunction as
a dependent variable.
Finally, to take into account the likely imbalance in the
baseline characteristics of patients with or without RV dysfunction and, more specifically, to address the effect of
the extent of LV dysfunction on RV dysfunction, we used
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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ACVD-880; No. of Pages 11
ARTICLE IN PRESS
4
C. Venner et al.
a propensity analysis [20]. Propensity scores of RV dysfunction were calculated for each patient, including variables
predictive of RV dysfunction obtained by multivariable logistic regression and variables supposed to influence both the
presence of RV dysfunction and patient outcome (LVEF,
LV end-diastolic diameter and age). A Cox multivariable
regression stratified by quintiles of propensity scores was
performed to predict the occurrence of MACE. Results are
expressed as hazard ratios (HRs) with 95% CIs.
For all tests, P < 0.05 was considered significant. All statistical analyses were performed using SAS software, version
9.3 (SAS Institute, Cary, NC, USA). Variables with more than
half non-missing values and with correlation with other
co-variables < 0.6 were selected for all bivariate analyses.
Significant variables in the bivariate analyses were candidates for all multivariable analyses.
Results
Baseline characteristics
Patient characteristics are listed in Table 1. The cause
of initial hospitalization was acute HF for 39 patients
(28.7%); the others (71.3%) were considered to be in a
stable haemodynamic state at inclusion, and most were hospitalized for device implantation, coronary angiography or
cardiac rehabilitation. The median duration of disease at
inclusion was 2.1 years, with no significant intergroup difference (1.5 years vs 2.6 years for groups 1 and 2, respectively;
U test P = 0.66).
Mean TAPSE was 18.6 ± 5.4 mm, and the reproducibility
of measures was as follows: mean bias −0.15 mm, limit of
concordance (−2.2; 1.8) for intraobserver variability; and
mean bias −0.19 mm, limit of concordance (−2.8; 2.4) for
interobserver variability.
Five patients (3.7%) had TAPSE > 30 mm. The mean
disease duration for these patients was 8.0 ± 7.8 years;
mean B-type natriuretic peptide concentration was
185.8 ± 81.6 pg/mL; mean systolic pulmonary artery pressure (sPAP) was 26.0 ± 17.0 mmHg; and only one had grade
2 TR. None of these patients had been enrolled at the
time of an acute HF hospitalization, and all received an
angiotensin-converting enzyme inhibitor > 50% maximal
dose. These high values of TAPSE were not responsible
for an outlier effect, according to Tukey’s method for the
detection of outlier values.
Patient characteristics according to RV
dysfunction and its predictors
Differences between groups of patients are listed in Table 1.
All echocardiographic and cardiac MRI variables of RV function (S-wave, FAC, right atrial size and RVEF) and LV function
(LVEF, four-chamber longitudinal peak systolic strain, LV outflow tract [LVOT] time-velocity integral [TVI] and E-wave DT)
were statistically more significantly altered in group 1 than
in group 2.
By multivariable analysis, E-wave DT ≤ 145 ms (OR 4.1,
95% CI 1.3—12.8; P = 0.017) and LVOT TVI (OR 0.8, 95% CI
0.7—0.9; P = 0.003) were the only factors associated with RV
dysfunction (Table 2).
Figure 1. Kaplan-Meier survival curves of major adverse cardiac events according to tricuspid annular plane systolic excursion
(TAPSE) ≤ or > 15 mm.
Association between RV dysfunction and MACE
None of the patients were lost to follow-up over a mean
of 2.7 ± 1.1 years (371 patient-years). Twenty-four patients
(17.6%) died in our cohort: 10 in group 1 (30%) and 14 in
group 2 (14%). The cause of death was cardiac-related for
20 patients (eight in group 1; 12 in group 2); the four other
deaths were the result of cancer or septic shock. Fortynine patients (36%) presented MACE, consisting of 20 cardiac
deaths (14.7%), 16 episodes of acute HF (11.8%), two heart
transplantations (1.5%) and 24 cardiac-related hospitalizations (17.6%). Overall, MACE were recorded in 18/34 (53%)
patients in group 1 and 31/102 (30%) in group (P = 0.02). The
mean time of occurrence of MACE after initial hospitalization was 1.3 ± 1.0 years.
MACE-free survival rates at 1, 2 and 3 years were 64%,
55% and 42% in group 1 compared with 87%, 79% and 68%
in group 2, respectively (P = 0.002), as shown in Fig. 1. In
a bivariate Cox regression, MACE were associated with age,
systolic blood pressure, RV dysfunction, left and right atrial
area ≥ 20 cm2 , sPAP and haemoglobin value. By multivariable analysis, only RV dysfunction (HR 2.4, 95% CI 1.3—4.3;
P = 0.006), right atrial area ≥ 20 cm2 (HR 2.2, 95% CI 1.1—4.1;
P = 0.019) and age (HR 1.03, 95% CI 1.0—1.1; P = 0.041) were
associated with an increased risk of MACE (Table 3).
After stratification by quintiles of propensity scores, RV
dysfunction (HR 3.2, 95% CI 1.3—7.6; P = 0.009), age and right
atrial area ≥ 20 cm2 remained the only factors associated
with the occurrence of MACE (Table 3).
Outcome regarding RV dysfunction and sPAP
A higher rate of MACE was observed in patients with RV
dysfunction and sPAP > 40 mmHg (Fig. 2). Patients with RV
dysfunction had a worse outcome than patients with preserved RV function. Patients with sPAP > 40 mmHg had a
worse outcome than patients with sPAP < 40 mmHg. Patients
with RV dysfunction and sPAP < 40 mmHg had an intermediate
outcome. sPAP was associated with MACE only in the bivariate Cox regression (HR 1.03, 95% CI 1—1.05; P = 0.019), but
not in the multivariable model (Table 3).
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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RV dysfunction in idiopathic dilated cardiomyopathy
Table 1
5
Patient characteristics according to right ventricular dysfunction.
All patients
Group 1 (TAPSE ≤ 15 mm)
Group 2 (TAPSE > 15 mm)
P
59.01 ± 13.24
100 (73.5)
82 (60.2)
58.50 ± 14.40
29 (85.3)
28 (82.4)
59.18 ± 12.89
71 (69.6)
54 (54.5)
0.80
0.07
0.0004a
0.20
Baseline features
Age (years)
Men
Prior acute HF
NYHA functional status
I—II
III
IV
Systolic blood pressure (mmHg)
Sinus rhythm
BNP (pg/mL)
Peak VO2 (L/min/m2 )
VE/VCO2 (%)
Therapy
ACEi
> 50% maximal dose
Beta-blockers
> 50% maximal dose
Aldosterone antagonists
Diuretics
> 80 mg/day furosemide
ICD
CRT
78 (57.3)
48 (35.3)
10 (7.4)
118.81 ± 21.55
115 (84.6)
751.18 ± 912.60
21.38 ± 6.49
35.52 ± 7.01
7 (47.1)
13 (38.2)
5 (14.7)
111.83 ± 16.80
24 (70.6)
1020.93 ± 999.55
23.34 ± 6.20
34.72 ± 5.45
33 (60.8)
35 (34.3)
5 (4.9)
121.53 ± 22.66
91 (89.2)
627.36 ± 849.92
20.69 ± 6.5
35.84 ± 7.57
0.036a
0.009a
0.06
0.14
0.57
120 (88.2)
101 (74.3)
123 (90.4)
68 (50.0)
50 (36.8)
108 (79.4)
46 (33.8)
58 (42.6)
42 (30.9)
29 (85.3)
21 (72.4)
32 (94.1)
12 (38.7)
16 (47.1)
31 (91.2)
17 (54.8)
11 (32.4)
8 (23.5)
91
80
91
56
34
77
29
47
34
0.54
0.046a
0.40
0.016a
0.15
0.05a
0.11
0.16
0.28
Echocardiography: LV
LVEDD (mm)
LVEF (%)
Four-chamber LVEF (%)
Four-chamber LPS (%)
LVOT TVI (cm/s)
E-wave DT (ms)
LA surface (cm2 )
MR > grade 2
65.83 ± 9.21
27.51 ± 8.71
26.42 ± 9.29
—8.00 ± 3.98
16.02 ± 5.64
154.94 ± 59.70
25.32 ± 6.95
45 (33.0)
64.68 ± 8.46
24.24 ± 7.93
22.96 ± 8.43
—5.62 ± 2.54
12.28 ± 4.30
119.89 ± 34.42
28.60 ± 7.82
15 (44.1)
66.22 ± 9.46
28.60 ± 8.73
27.58 ± 9.31
—8.73 ± 4.07
17.31 ± 5.48
166.15 ± 61.81
24.24 ± 6.32
30 (29.4)
0.40
0.014a
0.012a
< 0.001a
< 0.001a
< 0.001a
0.002a
0.12
Echocardiography: RV
TAPSE (mm)
RA surface (cm2 )
TR > grade 2
sPAP (mmHg)
S-wave (cm/s)
FAC
18.6 ± 5.4
20.84 ± 9.71
17 (12.5)
36.94 ± 12.21
9.71 ± 2.87
0.40 ± 0.14
11.9 ± 2.1
26.85 ± 13.64
8 (23.5)
38.83 ± 10.64
7.76 ± 1.73
0.30 ± 0.12
20.8 ± 4.2
18.82 ± 6.98
9 (8.9)
36.29 ± 12.70
10.39 ± 2.89
0.43 ± 0.13
< 0.001a
0.13
0.34
< 0.001a
0.001a
Cardiac MRI
LVEF (%)
RVEF (%)
28.34 ± 11.20
42.99 ± 17.52
24.82 ± 13.24
32.55 ± 17.67
29.59 ± 10.34
47.41 ± 15.77
0.23
0.016
(89.2)
(87.9)
(89.2)
(63.6)
(33.3)
(75.5)
(38.2)
(46.1)
(33.3)
a
Data are expressed as mean ± standard deviation or number (%). ACEi: angiotensin-converting enzyme inhibitor; BMI: body mass index;
BNP: brain natriuretic peptide; CRT: cardiac resynchronization therapy; DT: deceleration time; FAC: fractional area change; HF: heart
failure; ICD: internal cardiac defibrillator; LA: left atrial; LPS: longitudinal peak systolic strain; LV: left ventricle; LVEDD: left ventricular
end-diastolic diameter; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction; LVOT: left ventricular
outflow tract; MR: mitral regurgitation; MRI: magnetic resonance imaging; NYHA: New York Heart Association; RA: right atrial; RV:
right ventricle; RVEDV: right ventricular end-diastolic volume; RVEF: right ventricular ejection fraction; sPAP: systolic pulmonary artery
pressure; TAPSE: tricuspid annular plane systolic excursion; TR: tricuspid regurgitation; TVI: time-velocity integral; VCO2 : carbon
dioxide consumption; VE: pulmonary ventilation; VO2 : oxygen consumption.
a P ≤ 0.05.
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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C. Venner et al.
Table 2
Factors associated with tricuspid annular plane systolic excursion ≤ 15 mm.
N
TAPSE ≤ 15 mm
Bivariate regression
n
%
OR
95% CI
P
OR
95% CI
P
Multivariable regression
Age
136
34
25
1
0.97—1.03
0.80
1.02
0.99—1.06
0.23
LVEDD
134
34
25.4
0.98
0.94—1.03
0.40
0.95
0.90—1.01
0.11
Four-chamber
LVEF
136
34
25
0.95
0.90—0.99
0.0112
0.98
0.91—1.04
0.49
Heart rate
136
34
25
1.04
1.01—1.07
0.0015
0.84
0.74—0.94
0.0031
Systolic blood
pressure
< 100 mmHg
100—120 mmHg
120—140 mmHg
≥ 140 mmHg
Missing
14
40
27
26
29
5
15
5
5
4
35.7
37.5
18.5
19.2
13.8
1
1.08
0.41
0.43
0.29
CRP > 5 mg/L
No
Yes
Missing
58
53
25
10
18
6
17.2
34
24
1
2.47
1.52
GOT > 30 IU/L
No
Yes
Missing
61
32
43
14
13
7
23
40.6
16.3
1
2.3
0.65
Four-chamber
peak systolic
longitudinal
strain
< 10%
≥ 10%
Missing
Aortic TVI
0.13
0.13
1.02—6.00
0.48—4.75
0.06
0.91—5.79
0.24—1.78
0.0003
75
35
26
25
1
8
33.3
2.86
30.8
1
0.06
0.89
0.01—0.45
0.34—2.32
133
34
25.6
0.81
0.73—0.89
< 0.0001
< 0.0001
E-wave
deceleration
time
≤ 145 ms
> 145 ms
65
67
26
6
40
8.96
6.78
1
E/A
<1
1—2
>2
Missing
57
24
28
27
6
4
11
13
10.5
16.7
39.3
48.1
1
1.7
5.5
7.89
LA area
< 20 cm2
≥ 20 cm2
Missing
31
94
11
4
27
3
12.9
28.7
27.3
1
2.72
2.53
RA area
< 20 cm2
≥ 20 cm2
Missing
72
51
13
11
20
3
15.3
39.2
23.1
1
3.58
1.66
ECG sinus rhythm
0.30—3.83
0.09—1.77
0.10—1.85
0.06—1.32
2.56—17.96
0.0165
4.06
1
1.29—12.79
0.0004
0.43—6.67
1.77—17.13
2.54—24.52
0.18
0.87—8.51
0.47—13.75
0.0109
1.52—8.40
0.39—7.03
0.0214
CI: confidence interval; CRP: C-reactive protein; ECG: electrocardiogram; GOT: glutamic oxaloacetic transaminase: LA: left atrial;
LVEDD: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; OR: odds ratio; RA: right atrial; TAPSE: tricuspid
annular plane systolic excursion; TVI: time-velocity integral.
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
49/136
39/136
48/136
45/136
123/136
49/136
39/136
63.20
111.56
13.34
27.12
20.84
17.29
40.41
±
±
±
±
±
±
±
13.44
17.41
1.44
7.68
9.71
5.38
14.32
Bivariate Cox analysis
Multivariable Cox analysis
Multivariable regression
stratified on propensity scores
OR
95% CI
P
OR
95% CI
P
OR
95% CI
P
1.04
0.97
0.80
1.05
2.59
0.93
1.03
1.01—1.06
0.96—0.99
0.67—0.97
1.01—1.10
1.41—4.77
0.88—0.99
1.00—1.05
0.0053
0.0025
0.0194
0.0098
0.0022
0.0146
0.0190
1.027
1.001—1.053
0.0406
1.028
1.001—1.056
0.0402
0.851
0.700—1.036
0.11
0.826
0.670—1.071
0.07
2.153
2.350
1.133—4.089
1.273—4.339
0.0191
0.0063
2.241
3.170
1.103—4.553
1.327—7.570
0.0256
0.0094
ARTICLE IN PRESS
Age
Systolic BP
Haemoglobin
LA area ≥ 20 cm2
RA area ≥ 20 cm2
RV dysfunction
sPAP
Mean ± SD
+Model
n
ACVD-880; No. of Pages 11
Factors associated with the occurrence of a major adverse cardiac event.
RV dysfunction in idiopathic dilated cardiomyopathy
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
Table 3
7
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ARTICLE IN PRESS
8
C. Venner et al.
Figure 2. Kaplan-Meier survival curves of major adverse cardiac
events according to the level of right ventricular function and systolic pulmonary artery pressure (sPAP). TAPSE: tricuspid annular
plane systolic excursion.
Discussion
By defining RV function based on a threshold of TAPSE of
15 mm in DCM patients, our study showed that among various clinical, biological and echocardiographic variables,
only E-wave DT and LVOT TVI were significant predictors
of RV dysfunction. Furthermore, for the same extent of LV
dysfunction by both standard and propensity analyses, RV
dysfunction was confirmed to be a factor associated with
the occurrence of MACE in patients with DCM, along with
right atrial area ≥ 20 cm2 and age.
TAPSE and determinants of RV dysfunction
TAPSE is probably the most described variable in the
echocardiographic evaluation of RV systolic function.
Although it may appear reductive to assess RV global function through the displacement of the tricuspid annulus, it is
not complete nonsense, as longitudinal shortening of the RV
is the main component of RV ejection — the inward motion
of RV free wall and the traction by the septum being less
contributive [10].
TAPSE was used in our study to define RV dysfunction,
as it is the most described variable, but is also the most
routinely and easily performed measurement available in
practice. In the guidelines, cardiac MRI is recommended as
a gold-standard technique to assess biventricular function,
but lack of availability remains a limitation [25]. To identify
an optimal cut-off value for TAPSE, we used a receiver operating characteristic curve analysis based on an MRI-derived
RVEF < 45%. The value we obtained is in concordance with
previously published studies analysing adverse outcomes in
HF and, particularly, in primary DCM [26,27].
We selected a large panel of clinical, biological, functional and echocardiographic variables suspected to be
associated with RV function. In the multivariable analysis, only E-wave DT and aortic TVI remained significantly
associated. A decrease in E-wave DT to < 140 ms reflects an
increase in left atrial pressure, with a tendency towards
a restrictive filling pattern; previous studies have already
emphasized this threshold and the importance of diastolic
dysfunction on RV function in HF patients [23,24]. Ghio et al.
reported the importance of raised filling pressure, with a
four-fold increased risk of an event when associated with
reduced TAPSE values < 14 mm compared with patients with
preserved TAPSE and a non-restrictive filling pattern [23].
The intrinsic evaluation of RV performance remains a
challenge with echocardiography. Most of the variables are
load dependent and actually depict ventricular function in
light of the ventriculoarterial interaction at the time of
examination, for a given haemodynamic state.
The same limitations apply to tissue Doppler imaging
S-wave and FAC, despite their superior value in RV performance assessment compared with TAPSE [12,28]. A recent
study emphasized RV free-wall two-dimensional strain and
a value < —17% to predict reduced RVEF with high diagnostic
accuracy in a comparative assessment along with TAPSE, Swave and FAC [29]. Nevertheless, the performance of this
technique in the specific context of idiopathic DCM may
raise measurement difficulties (subendocardial definition,
RV spherical remodelling), and further studies need to be
specifically considered.
Ventricular elastance, measured as the ratio of endsystolic arterial pressure (simplified as mean PAP) over
end-systolic RV volume, could provide load-independent
information about RV intrinsic performance, but requires
invasive haemodynamic assessment, as direct evaluation of
end-systolic volume remains unachievable with conventional
echocardiography.
TAPSE values should therefore be interpreted taking into
consideration the estimated sPAP value. In the case of normal or moderately elevated values of sPAP (< 40 mmHg),
alteration of TAPSE (< 15 mm) probably reflects intrinsic RV
dysfunction. In the case of elevated sPAP (≥ 40 mmHg), it
seems tendentious to speculate whether the reduction in
TAPSE is caused by intrinsic RV dysfunction or is merely the
consequence of chronic afterload elevation. In our population, patients with RV dysfunction and elevated sPAP had the
poorer prognosis, and patients with preserved RV function
had a better outcome regardless of sPAP. These results support those published by Ghio et al., where patients with RV
dysfunction and elevated sPAP had a worse survival rate than
patients with normal RV function and normal sPAP, and there
was an intermediate prognosis for patients with isolated RV
dysfunction or elevated sPAP [23].
Determinants of adverse outcome and the role
of propensity analysis
Our population consisted of consecutive patients enrolled
retrospectively, which may in fact have been responsible
for a certain degree of heterogeneity, most specifically
regarding patients recruited after an acute HF event.
Despite this consideration, 71.3% of patients were recruited
in a stable haemodynamic state. At the time of inclusion, 88% of patients received an angiotensin-converting
enzyme inhibitor (74% had an optimal dose > 50% maximal
dose), 90% received a beta-blocker (50% had an optimal
dose > 50% maximal dose) and 37% received an aldosterone
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
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ACVD-880; No. of Pages 11
ARTICLE IN PRESS
RV dysfunction in idiopathic dilated cardiomyopathy
antagonist. Overall, 34% of patients had a daily dose of
furosemide > 80 mg/day. These results are concordant with
larger HF registries, such as the French ODIN cohort [30].
We identified age, right atrial area ≥ 20 cm2 and the presence of RV dysfunction as factors associated with an adverse
outcome, defined by an increased occurrence of MACE. Sallach et al. had already emphasized the role of right atrial
volume index as an independent predictive factor for mortality in HF patients after adjustment for age, LV systolic and
diastolic functions, and RV systolic function [31]. The measurement of right atrial volume index is not recommended in
recent guidelines, because of the limited data available and
the lack of normal values [21]; it may confer more robust
and accurate determination of right atrial size over right
atrial area, but it is not validated for daily practice.
The additional prognostic role of RV function in reducedEF HF has been known since the initial works on
thermodilution and isotopic RVEF [15,32,33]. Nevertheless,
analysis of the right ventricle often remains neglected compared with that of the left ventricle, because it is difficult
to analyse with routine imaging techniques, and probably
also because of its retrosternal position and the relative
load dependency of standard variables of RV function, as
already discussed. However, many variables of RV function and morphology have been shown to be predictors of
adverse outcome in patients with HF [13,32,34—36]. In the
presence of reduced-EF HF, RV involvement is a distinctive
feature of idiopathic DCM, as opposed to other aetiologies of
HF, independent of PAP values and LV dysfunction [14,25].
Distinguishing primary DCM from other aetiologies of DCM
(predominantly ischaemic cardiomyopathy) was necessary
when attempting to directly assess the prognostic effect of
RV dysfunction, and more specifically TAPSE. The substrate
of RV dysfunction differs between ischaemic and idiopathic
DCM; in idiopathic DCM, it mostly reflects a biventricular
involvement or the upstream consequence of raised LV filling
pressures or raised pulmonary pressures. The pathogenesis
of RV dysfunction is more likely heterogeneous in the case
of ischaemic cardiomyopathy, depending on the infarct size
and the location and duration of the disease. The effect
of the ischaemic substrate on TAPSE in previously published
studies was reported as either neutral or responsible for a
slight drop in values [14,23,37,38]. To avoid further bias we
chose to exclude all patients with signs of evolutive or previous myocardial ischaemia. Furthermore, the importance of
RV dysfunction in idiopathic DCM had been less specifically
addressed.
Propensity analyses are generally used in observational
studies to assess the effect of one therapy on outcome, in
order to eliminate bias caused by confounding factors linked
to the indication for this therapy or when the number of confounding variables is high [20]. Propensity analysis is worthy
of interest in this context, as it is validated when studying rare outcomes in patients with multiple risk factors.
Furthermore, statistical results obtained are less biased,
more robust and more precise than a regression approach
based on logistic regression [19]. In our case, propensity
analysis allowed us to discern the direct effect of RV dysfunction on outcome, independent of factors associated
with RV dysfunction (E-wave DT, LVOT TVI) and the extent
of LV dysfunction (based on LVEF and LV end-diastolic diameter). Hence we were able to obtain a better estimation
9
of the direct RV dysfunction effect. The use of propensity
analysis with Cox regression stratified by quintiles of propensity scores showed that RV dysfunction, along with age and
right atrial area, was a significant prognostic factor for MACE
among patients with DCM, independent of the level of LV
systolic and diastolic function.
Stratification on quintiles of propensity score is a technique that is particularly validated when the effect of the
therapy may reasonably vary according to the strength of
the indication for its use or, in our case, when the effect
of RV dysfunction on outcome is believed to vary according
to the range of level of LV dysfunction. Another statistical method could have been used, which involves matching
patients according to their age, LVEF and LV end-diastolic
diameter, and according to factors influencing the level of
RV dysfunction (LVOT TVI and E-wave DT), but this would
have limited the data sample and hampered the statistical
analysis.
Study limitations
This was a small, retrospective study; the patients included
depict the population of a tertiary centre specializing in
the diagnosis and therapeutic management of patients with
HF. Notwithstanding this consideration, and the fact that
most of our patients were in a stable haemodynamic state
at inclusion, it may have resulted in an inclusion bias, and
may not provide a clear representation of French patients
with HF overall, but our inclusion criteria matched those of
previously published studies in HF.
A standardized echocardiography protocol for the evaluation of DCM was not available for all patients, and some
RV function variables could not be included in the multivariable analysis because of missing data (S-wave, RV free
wall strain and FAC), which will have lowered the power of
the statistical analysis, despite their prognostic influence in
other studies.
Choice of and justification for TAPSE in the assessment of
RV function has been addressed specifically in the Discussion
section.
Conclusion
The simple measurement of TAPSE should probably be performed systematically in an echocardiographic examination,
as it conveys important prognostic information in the case of
idiopathic DCM. RV dysfunction, defined by TAPSE ≤ 15 mm,
was mostly related to restrictive LV diastolic filling pattern
(E-wave DT ≤ 145 ms). Through a propensity analysis, the
presence of RV dysfunction provided incremental prognostic
information, independent of the level of LV dysfunction.
Disclosure of interest
The authors declare that they have no competing interest.
References
[1] Elliott P, Andersson B, Arbustini E, et al. Classification of the
cardiomyopathies: a position statement from the European
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
+Model
ACVD-880; No. of Pages 11
ARTICLE IN PRESS
10
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
C. Venner et al.
Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2008;29:270—6.
Grzybowski J, Bilinska ZT, Ruzyllo W, et al. Determinants of
prognosis in nonischemic dilated cardiomyopathy. J Card Fail
1996;2:77—85.
Juilliere Y, Danchin N, Briancon S, et al. Dilated cardiomyopathy: long-term follow-up and predictors of survival. Int J
Cardiol 1988;21:269—77.
Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ. Systolic
and diastolic dysfunction in patients with clinical diagnosis of
dilated cardiomyopathy. Relation to symptoms and prognosis.
Circulation 1994;90:2772—9.
Solomon SD, Anavekar N, Skali H, et al. Influence of ejection
fraction on cardiovascular outcomes in a broad spectrum of
heart failure patients. Circulation 2005;112:3738—44.
Mignot A, Donal E, Zaroui A, et al. Global longitudinal strain
as a major predictor of cardiac events in patients with
depressed left ventricular function: a multicenter study. J Am
Soc Echocardiogr 2010;23:1019—24.
Nahum J, Bensaid A, Dussault C, et al. Impact of longitudinal myocardial deformation on the prognosis of chronic heart
failure patients. Circ Cardiovasc Imaging 2010;3:249—56.
Champion HC, Michelakis ED, Hassoun PM. Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary
circulation unit: state of the art and clinical and research implications. Circulation 2009;120:992—1007.
Voelkel NF, Quaife RA, Leinwand LA, et al. Right ventricular function and failure: report of a National Heart, Lung,
and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006;114:
1883—91.
Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical
importance, and management of right ventricular failure. Circulation 2008;117:1717—31.
Wahl A, Praz F, Schwerzmann M, et al. Assessment of right
ventricular systolic function: comparison between cardiac
magnetic resonance derived ejection fraction and pulsed-wave
tissue Doppler imaging of the tricuspid annulus. Int J Cardiol
2011;151:58—62.
Wang J, Prakasa K, Bomma C, et al. Comparison of novel
echocardiographic parameters of right ventricular function
with ejection fraction by cardiac magnetic resonance. J Am
Soc Echocardiogr 2007;20:1058—64.
Gulati A, Ismail TF, Jabbour A, et al. The prevalence
and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation
2013;128:1623—33.
La Vecchia L, Zanolla L, Varotto L, et al. Reduced right ventricular ejection fraction as a marker for idiopathic dilated
cardiomyopathy compared with ischemic left ventricular dysfunction. Am Heart J 2001;142:181—9.
Juilliere Y, Barbier G, Feldmann L, Grentzinger A, Danchin
N, Cherrier F. Additional predictive value of both left and
right ventricular ejection fractions on long-term survival
in idiopathic dilated cardiomyopathy. Eur Heart J 1997;18:
276—80.
Meluzin J, Spinarova L, Hude P, et al. Combined right ventricular systolic and diastolic dysfunction represents a strong
determinant of poor prognosis in patients with symptomatic
heart failure. Int J Cardiol 2005;105:164—73.
Meyer P, Filippatos GS, Ahmed MI, et al. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart
failure. Circulation 2010;121:252—8.
Sun JP, James KB, Yang XS, et al. Comparison of mortality rates
and progression of left ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy and dilated versus nondilated right ventricular cavities. Am J Cardiol 1997;80:1583—7.
[19] Glynn RJ, Schneeweiss S, Sturmer T. Indications for propensity
scores and review of their use in pharmacoepidemiology. Basic
Clin Pharmacol Toxicol 2006;98:253—9.
[20] Heinze G, Juni P. An overview of the objectives and
the approaches to propensity score analyses. Eur Heart J
2011;32:1704—8.
[21] Lang RM, Bierig M, Devereux RB, et al. Recommendations for
chamber quantification: a report from the American Society of
Echocardiography’s Guidelines and Standards Committee and
the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography,
a branch of the European Society of Cardiology. J Am Soc
Echocardiogr 2005;18:1440—63.
[22] Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report
from the American Society of Echocardiography endorsed by
the European Association of Echocardiography, a registered
branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr
2010;23:685—713 [quiz 86—8].
[23] Ghio S, Temporelli PL, Klersy C, et al. Prognostic relevance of
a non-invasive evaluation of right ventricular function and pulmonary artery pressure in patients with chronic heart failure.
Eur J Heart Fail 2013;15:408—14.
[24] Meta-analysis Research Group in Echocardiography Heart Failure Collaborators, Doughty RN, Klein AL, et al. Independence
of restrictive filling pattern and LV ejection fraction with mortality in heart failure: an individual patient meta-analysis. Eur
J Heart Fail 2008;10:786—92.
[25] McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines
for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of
Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart
Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14:
803—69.
[26] Damy T, Kallvikbacka-Bennett A, Goode K, et al. Prevalence
of, associations with, and prognostic value of tricuspid annular
plane systolic excursion (TAPSE) among out-patients referred
for the evaluation of heart failure. J Card Fail 2012;18:
216—25.
[27] Ghio S, Recusani F, Klersy C, et al. Prognostic usefulness
of the tricuspid annular plane systolic excursion in patients
with congestive heart failure secondary to idiopathic or
ischemic dilated cardiomyopathy. Am J Cardiol 2000;85:
837—42.
[28] Pavlicek M, Wahl A, Rutz T, et al. Right ventricular systolic function assessment: rank of echocardiographic methods
vs. cardiac magnetic resonance imaging. Eur J Echocardiogr
2011;12:871—80.
[29] Focardi M, Cameli M, Carbone SF, et al. Traditional and innovative echocardiographic parameters for the analysis of right
ventricular performance in comparison with cardiac magnetic resonance. Eur Heart J Cardiovasc Imaging 2015;16:
47—52.
[30] Juilliere Y, Suty-Selton C, Riant E, et al. Prescription of cardiovascular drugs in the French ODIN cohort of heart failure
patients according to age and type of chronic heart failure.
Arch Cardiovasc Dis 2014;107:21—32.
[31] Sallach JA, Tang WH, Borowski AG, et al. Right atrial volume
index in chronic systolic heart failure and prognosis. JACC Cardiovasc Imaging 2009;2:527—34.
[32] de Groote P, Millaire A, Foucher-Hossein C, et al. Right ventricular ejection fraction is an independent predictor of survival
in patients with moderate heart failure. J Am Coll Cardiol
1998;32:948—54.
[33] Gavazzi A, Berzuini C, Campana C, et al. Value of right ventricular ejection fraction in predicting short-term prognosis of
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006
+Model
ACVD-880; No. of Pages 11
ARTICLE IN PRESS
RV dysfunction in idiopathic dilated cardiomyopathy
patients with severe chronic heart failure. J Heart Lung Transplant 1997;16:774—85.
[34] Bursi F, McNallan SM, Redfield MM, et al. Pulmonary pressures
and death in heart failure: a community study. J Am Coll Cardiol
2012;59:222—31.
[35] Damy T, Viallet C, Lairez O, et al. Comparison of four right
ventricular systolic echocardiographic parameters to predict
adverse outcomes in chronic heart failure. Eur J Heart Fail
2009;11:818—24.
[36] de Groote P, Fertin M, Goeminne C, et al. Right ventricular systolic function for risk stratification in patients with
stable left ventricular systolic dysfunction: comparison of
11
radionuclide angiography to echoDoppler parameters. Eur
Heart J 2012;33:2672—9.
[37] Juilliere Y, Buffet P, Marie PY, Berder V, Danchin N, Cherrier F.
Comparison of right ventricular systolic function in idiopathic
dilated cardiomyopathy and healed anterior wall myocardial
infarction associated with atherosclerotic coronary artery disease. Am J Cardiol 1994;73:588—90.
[38] Kjaergaard J, Iversen KK, Akkan D, et al. Predictors of right
ventricular function as measured by tricuspid annular plane
systolic excursion in heart failure. Cardiovasc Ultrasound
2009;7:51.
Please cite this article in press as: Venner C, et al. Right ventricular dysfunction in patients with
idiopathic dilated cardiomyopathy: Prognostic value and predictive factors. Arch Cardiovasc Dis (2016),
http://dx.doi.org/10.1016/j.acvd.2015.10.006