Circulation: Cardiovascular Imaging

ORIGINAL ARTICLE
Prognostic Value of Cardiac Magnetic Resonance–
Derived Right Ventricular Remodeling Parameters
in Pulmonary Hypertension
A Systematic Review and Meta-Analysis

See Editorial by Ostenfeld and Kjellström Yang Dong, MD*

Zhicheng Pan, PhD*
BACKGROUND: Cardiac right ventricular remodeling plays a substantial Dongfei Wang, PhD
role in pathogenesis, progression, and prognosis of pulmonary Jialan Lv, PhD
hypertension. Cardiac magnetic resonance is considered an excellent Juan Fang, BMSci
Rui Xu, BMSci
tool for evaluation of right ventricle. However, value of right ventricular
Jie Ding, PhD
remodeling parameters derived from cardiac magnetic resonance in Xiao Cui, MD
predicting adverse events is controversial. Xudong Xie, MD
Xingxiang Wang, MD
METHODS: The Pubmed (MEDLINE), Embase, Cochrane Library, Web of
Yucheng Chen, MD
Science, China National Knowledge Infrastructure platform (CNKI), China Xiaogang Guo , MD
Science and Technology Journal Database (VIP), and Wanfang databases were
Downloaded from http://ahajournals.org by on November 26, 2021

systematically searched until November 2019. Studies reporting hazard ratios

(HRs) for all-cause death and composite end point of pulmonary hypertension
were included. Univariate HRs were extracted from the included studies to
calculate pooled HRs of each right ventricular remodeling parameter.
RESULTS: Eight studies with 1120 patients examining all-cause death
(female: 44%–92%, age: 40–67 years old, follow-up time: 27–48
months) and 10 studies with 604 patients examining composite end
point (female: 60%–83%, age: 29–57 years old, follow-up time:
10–68 months) met the criteria. Right ventricular ejection fraction was
the only parameter which could predict both all-cause death (pooled
HR=0.95; P=0.014) and composite end point (pooled HR=0.95; P<0.001),
although right ventricular end-diastolic volume index (pooled HR=1.01;
P<0.001), right ventricular end-systolic volume index (pooled HR=1.01,
P=0.045), and right ventricular mass index (pooled HR=1.03, P=0.032)
only predicted composite outcome. Similar results were observed when
we conducted the meta-analysis among patients with World Health
Organization type I of pulmonary hypertension.
CONCLUSIONS: Cardiac magnetic resonance–derived right ventricular *Drs Dong and Pan contributed equally
to this article.
remodeling parameters have independent prognostic value for all-cause
Key Words:  hypertension, pulmonary
death and composite end point of patients with pulmonary hypertension. ◼ meta-analysis ◼ prognosis
Right ventricular ejection fraction was the strongest prognostic factor ◼ ventricular remodeling
among all the right ventricular remodeling parameters. Right ventricular © 2020 American Heart Association, Inc.
mass index, right ventricular end-diastolic volume index, and right https://www.ahajournals.org/journal/
ventricular end-systolic volume index also demonstrated prognostic value. circimaging

Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568 July 2020 1

 Dong et al; Prognostic Value of CMR-RV Parameters in PH
Clinical Perspective
Although there were many studies reporting
prognostic value of right ventricular remodeling
parameters derived from cardiac magnetic reso-
nance in patients with pulmonary hypertension,
various types of parameters existed and the results
were controversial. In this study, we systematically
reviewed studies regarding right ventricular remod-
eling parameters of prognostic value derived from
cardiac magnetic resonance, summarized various
types of right ventricular remodeling parameters,
and further conducted a meta-analysis of pooled
hazard ratio for these parameters in predicting
adverse events of patients with pulmonary hyper-
tension. This study could help in summarizing
the prognostic value of existing right ventricular
remodeling parameters and point out a future
research direction for the prognosis of patients
with pulmonary hypertension.
P
ulmonary hypertension (PH) is a pulmonary vas-
cular disease defined as a mean pulmonary ar-
tery pressure ≥25 mm Hg by right heart catheter-
ization at rest.1 Right ventricular remodeling (RVre),
including chamber enlargement, wall thickening,
myocardial fibrosis, and ejection decline, plays a sub-
Downloaded from http://ahajournals.org by on November 26, 2021
stantial role in pathogenesis, progression, and prog-
nosis of PH.2 Echocardiography has routinely been
used to evaluate right ventricle (RV) status because of
its low cost and convenience in operation.1 However,
because of irregular structure of RV and enlarged RV,
echocardiography could not reveal complete structure
of RV in PH. Besides, the poor reproducibility of echo-
cardiography cannot be ignored.3 Subsequently, car-
diac magnetic resonance (CMR) emerged as a robust
tool for evaluation of RV status.4,5 CMR can assess
structure, functions, and tissue characteristics of the
RV in PH with good reproducibility and was consid-
ered the gold standard for evaluation of RV volume
and systolic function.1,4,5 Nevertheless, the value of
RVre parameters derived from CMR in predicting ad-
verse events seems to be controversial. Presently, con-
clusions of studies concerning CMR’s prognostic value
range from no significant value to excellent prognostic
value.6–29 The reasons for the controversy could be at-
tributed to differences in the etiologies of PH, races of
participants, sample size, or measurement methods in
each study.
The purpose of this systematic review and meta-
analysis was to overview studies regarding prognostic
value of CMR-derived RVre parameters and further
explore pooled hazard ratio (HR) for these parameters
in predicting adverse events in PH.
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
METHODS
Literature Search Strategy
The authors declare that all supporting data are available within
the article and its Data Supplement. PH was defined following
the European Society of Cardiology and European Respiratory
Society guideline in 2015.1 Studies including prognosis of
PH ranging from World Health Organization (WHO) type I to
type V who underwent CMR at baseline were included in this
meta-analysis. RVre parameters included indices describing
RV deformation, volume, function, and tissue characteristics.
The Pubmed (MEDLINE), Embase, Cochrane Library, Web of
Science, China National Knowledge Infrastructure platform
(CNKI), China Science and Technology Journal Database (VIP),
and Wanfang databases were systematically searched for arti-
cles published under the guidance of the Preferred Reporting
Items for Systematic Reviews and Meta-Analysis statement
2015. before November 11, 2019. A search strategy (Table
I in the Data Supplement) was used with adaptation to each
database. Additionally, we manually checked for missing eli-
gible studies from each study’s references.
Study Selection
Articles were included based on following criteria: studies
including patients with PH who had undergone CMR exami-
nations; observation studies including cohort studies, case
control studies, or comparative studies; studies using Cox-
regression and publishing univariate HRs in their results. A lit-
erature selection flow diagram is presented in Figure 1. After
removing duplicates, assessment was based on title, abstract,
and full text. Articles were excluded by following criteria:
animal or in vitro experiments; age under 18 years; without
noninvasive PH remodeling parameters; cross-sectional stud-
ies; reviews, case reports, comments, or conference abstracts;
outcomes after surgery or endarterectomy and performing
HRs in a cohort including both PH and non-PH patients. The
selection was carried out by 2 independent authors. A meta-
analysis was performed on RVre parameters described in 3 or
more articles. Two end points, all-cause death and composite
end point (comprising a combination of all-cause death, car-
diopulmonary death, rehospitalization, lung transplantation,
and clinical worsening), were separately evaluated.
Data Extraction
Two authors independently extracted data from the selected
literature. Univariate HR (ratio between probability of adverse
event after and before per 1 unit increase of RV remodeling
parameters of patients with PH) and 95% CI of RVre parame-
ters were extracted from selected publications. Demographic
data and values of RVre parameters were also extracted.
Study Quality Assessment
For assessment of study quality, study design, loss to follow-
up, description of CMR protocol, measurement of CMR find-
ings, definition and measurement of outcomes, description of
statistical analysis, treatment of continuous predictors, multi-
variable adjustment, and multivariable analysis were assessed
as appropriate, following formerly defined criteria for prog-
nostic studies.30
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 Dong et al; Prognostic Value of CMR-RV Parameters in PH
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Statistical Analysis
Statistical analysis was performed using Stata 13.0
(StataCorp LP, College Station, TX) with package pr0012
from http://www.stata-journal.com/software/sj4-2. HR and
95% CI were transformed into logHR and SE by a formula
used previously: SE=[ln (upper boundary (95% CI))−ln (lower
boundary (95% CI))]/(2×1.96).31 A random-effect (Inverse
Variance heterogeneity) model using the DerSimonian-Laird
method was used to perform meta-analysis. Heterogeneity
among selected publications was assessed using Q-test
based on a χ2 test. I2>50% was defined as high hetero-
geneity. Galbraith plot was used to determine the source
of high heterogeneity on RVre parameters described in 5
or more articles. The sensitivity analysis was performed by
recalculating pooled HRs after excluding each article once.
Publication bias was assessed by Egger test in which RVre
parameters described in 5 or more articles were used. If
publication bias existed, nonparametric trim and fill method
was used to recalculate pooled HR. P value < 0.05 was con-
sidered statistically significant.
RESULTS
Search Results
After systematic literature search and cross-checking of
references, 698 studies were included. A total of 222
studies were removed as duplications and 412 stud-
ies were removed after assessing titles and abstracts.
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
Figure 1. Flow chart of study selection.
CMR indicates cardiac magnetic resonance; HR,
hazard ratio; PH, pulmonary hypertension; and
RV, right ventricle.
Through full-text assessments, 18 studies were finally
included (Figure 1). It is worth noting that RVre param-
eters of Saunders et al8 and Igata et al9 were normalized
before calculating univariate HRs. It means that RVre
parameters were transformed for normalized distribu-
tion before calculating HRs in these 2 studies.
Eight studies with 1120 patients examining end
point of all-cause death were included. Most of the
patients were female (ranging from 44% to 92%).
Mean age of these studies ranged from 40 to 67
years old. Patients with WHO type I PH constituted
the majority (ranging from 34.4% to 100%). Follow-
up time varied from 27 to 48 months. Additionally, 10
studies with 604 patients examining composite end
point were included, comprising 14 patients under-
gone lung transplantation. Most of the patients were
female (ranging from 60% to 83%). Mean age of
these studies ranged from 29 to 57 years old. Patients
with WHO type I PH constituted the majority (ranging
from 48% to 100%). Follow-up time varied from 10
to 68 months (Table 1 and 2).
Methodological Evaluation
Methods of image acquisition and post-analysis varied
across the studies. There were 2 studies using 3.0-T scan-
ners with slice thickness ranging from 5.0 to 10.0 mm. All
studies segmented RV on short axis, except for one study
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 Dong et al; Prognostic Value of CMR-RV Parameters in PH

Table 1.  Demographic Data From Included Publications

Slice Segmenting Age WHO NYHA III–IV

Author Field Strength, T Thickness, mm Method Sample Size (Mean±SD) Female (%) Classification* (%)
All-cause death
 Saunders et al8 1.5 5.1 Short axis PH: 408 59±15 65 I: 54.7% nr
Control: 24 II: 9.6%
III: 10.0%
IV: 22.5%
V: 3.2%
 Igata et al 9
3.0 nr Nr PH: 53 58±16 79 I: 58.4% nr
Control: 42 III: 22.6%
IV: 9.4%
V: 9.4%
 Dawes et al 10
1.5 8.0 Short axis PH: 256 67 (52–75) 44 I: 34.4% 82
Control: 256 II: 16.8%
III: 5.9%
IV: 41.4%
V: 1.5%
 Swift et al12 1.5 8.0 Short axis PH: 576 57±16 54 I: 100% 90.5
Control: NA
 Jensen et al19 1.5 7.0 Short axis PH: 48 Control: NA 40±14 80 I: 100% 17
 Corona- 3.0 6.0 Short axis PH: 49 57±12 92 I: 100% 43
Villalobos et al20
Control: 18
 Swift et al21 1.5 8.0 Short axis PH: 162 61±15 59 I: 50% 77.8
Control: 32 II: 12%
III: 11%
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IV: 27%
 Swift et al22 1.5 8.0 Short axis PH: 80 59±17 60 I: 100% 82.5
Control: NA
 Van Wolferen 1.5 6.0 Short axis PH: 64 Control: NA 43±13 73 I: 100% 89
et al29
Composite end point
 Bredfelt et al11 1.5 8.0 Short axis PH: 75 Control: NA 57±19 71 I: 88% nr
IV: 12%
 Li et al13 1.5 8.0 Short axis PH: 41 Control: NA 29±9 71 I: 100% 48
 Badagliacca 1.5 nr 4-chamber PH: 74 Control: NA 55±13 60 I: 100% 54
et al16 stacks
 Sato et al17 1.5 10.0 Axial slices PH: 68 Control: NA 55 (40–69) 77 I: 48% 60.3
III: 16%
IV: 31%
V: 5%
 Knight et al18 1.5 nr Short axis PH: 40 50 (45–5 75 I: 80% 62.5
Control: 20 9) IV: 20%
 Jacobs et al23 1.5 5.0 Short axis PH: 101 Control: NA 48±16 74 I: 100% 67.3
 Kang et al25 1.5 10.0 Short-axis PH: 30 Control: NA 45±13 74 I: 100% 53
 Yamada et al 26
1.5 10.0 Short axis PH: 41 Control: NA 39±14 71 I: 100% 51
 Freed et al27 1.5 10.0 Short axis PH: 58 Control: NA 53±14 74 I: 76% Nr
II: 14%
III: 1.7%
IV: 3.4%
V: 5.2%
(Continued )

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 Dong et al; Prognostic Value of CMR-RV Parameters in PH

Table 1. Continued

Slice Segmenting Age WHO NYHA III–IV

Author Field Strength, T Thickness, mm Method Sample Size (Mean±SD) Female (%) Classification* (%)
 van de 1.5 5.0 Short axis PH: 76 Control: NA 50±14 83 I: 100% 52
Veerdonk et al28
NA indicates not applicable; nr, not reported; NYHA, New York Heart Association; PH, pulmonary hypertension; and WHO, World Health Organization.
*WHO classification was consistent with the 2015 European Society of Cardiology/European Respiratory Society Guidelines for the diagnosis and treatment of
pulmonary hypertension.

Table 2.  Demographic Data From Included Publications

Follow-Up Period Correlation Between CMR-RV

PH-Specific Medication During (mo, mean±SD or Parameters and Clinical Prognostic
Author Follow-Up median [IQR]) Events n (%) Markers
All-cause death
 Saunders et al8 Prostanoid: 25%, others not reported 27±8 59 (15) RV insertion point T1 and mean RAP:
r=0.160, P=0.011; RV insertion point T1 and
mean PAP: r=0.165, P=0.011; RV insertion
point T1 and SvO2: r=−0.152, P=0.022
 Igata et al9 PGI2 28.3%, PDE5-I 39.6%, ERA Mean 44, SD not reported Nr N
39.6%, and soluble guanylate cyclase
stimulators 1.9%
 Dawes et al10 nr 48 (24–68) 93 (36) Global RV FD and mPAP r=0.42, P=0.001;
Global RV FD and PVR: r=0.30, P=0.001;
RV MAFD and mPAP: r=0.46, P=0.001;
RV MAFD and PVR: r=0.29, P=0.001; RV
MBFD and mPAP: r=0.27, P=0.001; RV
MBFD and PVR: r=0.2, P=0.001
 Swift et al12 nr 42 (17–142) 221 (38) N
 Jensen et al19 nr Nr 12 (25) N
 Corona-Villalobos PGI2 2.0%; CCB 4.0%; ERA 10.2%; 30±19 21 (43) N
et al20 PDEi 22.4%
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 Swift et al21 nr 36 (12–48) 39 (24) N

 Swift et al22 nr 32±14 23 (29) N
 Van Wolferen et al 29
Intravenous PGI2 47%; ERA 39%; 32±16 19 (30) N
PDE5-I 6%; CCB 8%
Composite end point
 Bredfelt et al11 ERA 41%; PDE5-I 23%; Median 28 36 (48) N
PGI2 4/5%;CCB 36%
 Li et al13 PAH-targeted therapy:82.9% 28 (21–41) 13 (32) N
 Badagliacca et al 16
CCB 8%; ERA 42%; PDE5-I 32%; 18 (2–33) 31 (42) N
intravenous PGI2 34%;
Treprostinil s.c. 14%
 Sato et al17 PGI2 26.5%, ERA 29.4%, PDE5-I 24 (9–34) 16 (24) N
22.1%; intravenous PGI2 6%
 Knight et al18 PDE5-I 70%; ERA 55%; intravenous 20 (12–28) 9 (27) N
PGI2 3%; Treatment naive 20%;
Oral PGI2 3%; inhaled PGI2 3%;
tyrosine-kinase inhibitor 5%
 Jacobs et al23 PGI2 25.7%; ERA 42.6%; 68 (30–97) 31 (30) N
PDE5-I 12.9%; CCB 9.9%
 Kang et al25 ERA 63%; PDE5-I 37%; 17±7 7 (23) RVOTACC and RHC-derived RV dP/dtmax:
PGI2 20%; CCB 50% r2=0.76, P=0.003
 Yamada et al26 Intravenous PGI2 34%; 45±26 4 (10) N
ERA 54%; PDE5-I 88%; CCB 22%
 Freed et al27 PGI2 31%; other PH medications 31% 10±6 19 (33) N
 van de Veerdonk et al28 CCB 1%; ERA 34%; PDE5-I 13%; 59 (30–74) 32 (42) Changes in PVR and changes in RVEF:
PGI2 11% r=0.330; P=0.005
CCB indicates calcium channel blockers 4.0%; CMR-RV, cardiac magnetic resonance–derived right ventricular; ERA, endothelin receptor antagonist; FD, fractal
dimension; IQR, interquartile range; MAFD, maximum apical fractal dimension; MBFD, maximum basal fractal dimension; mPAP, mean pulmonary aterial pressure;
nr, not reported; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PDE5-I, phosphodiesterase type 5 inhibitor; PDEi, phosphodiesterase
inhibitor; PGI2, prostacyclin; PH, pulmonary hypertension; PVR, pulmonary vessel resistance; RAP, right arterial pressure; RHC, right heart catheterization; RV, right
ventricle; RVEF, right ventricular ejection fraction; RVOTACC, right ventricle outflow tract acceleration; and SvO2, mixed venous oxygen saturation.

Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568 July 2020 5

 Dong et al; Prognostic Value of CMR-RV Parameters in PH

Table 3.  Methodological Evaluation of the Quality of the Studies

Description Treatment
Description Measurement Definition and of of Multivariable
Study Loss to of CMR of CMR Measurement Statistical Continuous Multivariable Analysis
Author Year design Follow-Up Protocol Findings of Outcomes Analysis Predictors Adjustment Appropriate
Saunders 2018 1 NR 1 1 1 1 1 0 NA
et al8
Igata et al9 2018 1 1 0 0 1 1 1 0 NA
Dawes et 2018 0 1 1 1 1 1 1 2 0
al10
Bredfelt et 2018 0 1 1 1 1 1 1 1 1
al11
Swift et al12 2017 0 1 1 1 1 1 1 2 1
Li et al3 2017 1 1 1 1 1 1 1 1 0
Badagliacca 2016 1 1 0 1 1 1 1 1 0
et al16
Sato et al17 2015 1 NR 1 1 1 1 1 1 0
Knight et 2015 1 1 0 1 1 1 1 1 0
al18
Jensen et 2015 1 1 0 1 1 1 1 1 0
al19
Corona- 2015 1 1 1 1 1 1 1 0 NA
Villalobos
et al20
Swift et al21 2014 0 1 1 1 1 1 1 2 0
Swift et al 22
2014 0 1 1 1 1 1 1 2 0
Jacobs et 2014 0 1 1 1 1 1 1 1 1
al23
Kang et al25 2014 1 NR 1 1 1 1 1 2 0
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Yamada et 2012 0 1 1 1 1 1 1 1 0
al26
Freed et al27 2012 1 1 1 1 1 1 1 1 0
van de 2011 1 1 1 1 1 1 1 2 0
Veerdonk
et al28
Van 2007 1 1 1 1 1 1 1 1 0
Wolferen
et al29
Study design (1, prospective; 0, retrospective); loss to follow up (1,<5%; 0, >5%); description of CMR protocol (1, well defined; 0, moderately
defined); measurement of CMR findings (1, well defined and measured appropriately; 0, moderately defined or moderately measured); definition and
measurement of outcomes (1, well defined; 0, moderately defined); description of statistical analysis (1, well defined and measured appropriately; 0,
moderately defined or moderately measured); treatment of continuous predictors (1, all kept continuous; 0, all categorized/dichotomized); multivariable
adjustment (2, yes, at least for age and sex; 1, multivariate adjustment for other factors; 0, no multivariate analysis performed or not described);
multivariable analysis appropriate (1 ≥10 events per predictor used; 0, <10 events per predictor used). CMR indicates cardiac magnetic resonance; NA,
not applicable; and NR, not reported.

which segmented RV into 4 chambers16 and another doing
so on axial axis17 (Table 1 and 2).
Quality of these studies was described in Table 3. Seven
studies were retrospective although the rest were prospec-
tive. Three studies did not report the number of patients
who lost following up.
Prognostic Value of RVre Parameters
Derived From CMR
Thirty-six RVre parameters were evaluated (Table II in
the Data Supplement). However, only 5 parameters
measuring all-cause death and 5 parameters measuring
composite end point were found in 3 or more studies
and could be evaluated. Pooled HRs were demonstrat-
ed in Figure 2. Right ventricular ejection fraction (RVEF)
was the only parameter predicting both all-cause death
(pooled HR=0.95; P=0.014) and composite end point
(pooled HR=0.95; P<0.001), although right ventricular
end-diastolic volume index (RVEDVI; pooled HR=1.01;
P<0.001), right ventricular end-systolic volume index
(RVESVI; pooled HR=1.01; P=0.045), and right ventric-
ular mass index (RVMI; pooled HR=1.03, P=0.032) only
predicted composite outcome.

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 Dong et al; Prognostic Value of CMR-RV Parameters in PH
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Figure 2. Prognostic value of right ventricular remodeling parameters of all the patients with pulmonary hypertension.
RVEDVI indicates right ventricular end-diastolic volume index; RVESVI, right ventricular end-systolic volume index; RVSVI, right ventricular stroke volume index;
RVEF, right ventricular ejection fraction; RVMI, right ventricular mass index; and VMI, ventricular mass index.

Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568 July 2020 7

 Dong et al; Prognostic Value of CMR-RV Parameters in PH
If we restricted the included subjects into patients
with WHO type I PH only, there were 4 studies depict-
ing only 2 parameters evaluating all-cause death and
6 studies depicting 3 parameters evaluating com-
posite end point (Figure  3). RVEF was still the only
parameter predicting both all-cause death (pooled
HR=0.98; P=0.015) and composite end point (pooled
HR=0.94; P<0.001). Nevertheless, when the subjects
of congenital PAH were excluded from this subgroup,
we found that RVEF could not predict all-cause death
(pooled HR=0.98; P=0.100) although only 3 studies
were included (Figure I in the Data Supplement).
Heterogeneity Test and Sensitivity
Analysis
We found that RVEDVI, RVESVI, RVEF, and RVMI evalu-
ating all-cause death manifested high heterogeneity
(I2>50%; Figure 2). Regarding the subgroup analysis of
patients with WHO type I PH, we found that RVEDVI
evaluating all-cause death still manifested high het-
erogeneity (I2>50%; Figure  3). We tried to analyze
the source of heterogeneity using Galbraith plot (Fig-
ure II in the Data Supplement). As not all the selected
articles had detailed subgroup information, no other
subgroup analysis was performed in this study. We per-
formed sensitivity analysis by recalculating pooled HRs
after excluding each article once, and the exclusion did
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not influence the results of the analysis, except for the
results measuring RVEDVI and RVESVI’s prediction abil-
ity for all-cause death were unstable after removing 2
articles by Swift et al21,22 separately (Figure III in the Data
Supplement ).
Publication Bias
Publication bias was evaluated in Table III in the Data
Supplement. RVEDVI and RVESVI measuring all-cause
death and RVEF measuring both all-cause death and
composite end point showed significant publication
bias. We performed nonparametric trim and fill meth-
od, and this did not influence general conclusion.
DISCUSSION
In this systematic review and meta-analysis, 18 different
studies containing 1724 patients were evaluated. We
found that RVEF was a parameter predicting both all-
cause death and composite end point, although RVED-
VI, RVESVI, and RVMI could predict composite outcome
among 36 RV remodeling parameters.
RVEF is one of the most commonly used parameters to
evaluate RV systolic function. It stands for 3-dimensional
movement on both short-axis and long-axis directions
compared with tricuspid annular plane systolic excursion
only on long-axis .4,20 Besides CMR, 3-dimension echocar-
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
diography and radionuclide angiography can also mea-
sure RVEF. However, insufficient spatial resolution restricts
their daily application.32,33 CMR-derived RVEF is con-
sidered the gold standard for its high spatial resolution
and reproducibility.1 This meta-analysis demonstrated
that CMR-derived RVEF was a robust index for evaluat-
ing prognosis of patients with PH. Notably, the predic-
tion ability of RVEF of all-cause death in the subgroup
of patients with noncongenital PAH was not proved in
this study for deficient publication, more studies about
this group should be conducted in the future. For that,
the difference of hemodynamics between congenital
and noncongenital PAH might influence RVre. Recently,
right ventricular-pulmonary arterial coupling emerged as
a new method to evaluate RV function and its interaction
with the pulmonary artery.34 Right ventricular-pulmonary
arterial coupling could be measured not only invasively
but also noninvasively by CMR alone.35,36 Additionally, this
parameter has been associated with prognosis of patients
with PH.37 Right ventricular-pulmonary arterial coupling is
a more advanced and objective index of RV systolic func-
tion, as RV and pulmonary artery are generally viewed as
a whole unit.34 However, RVEF seems not to be replaced
by right ventricular-pulmonary arterial coupling at once
for its easy availability and robust prognostic value.
Patients with PH have chronic RV afterload overload,
which stimulates and produces right ventricular hypertro-
phy (RVH). RVH can compensate for increased RV after-
load and maintain cardiac output. However, although
some patients develop benign remodeling of concentric
RVH and preserved RVEF, other patients develop malig-
nant remodeling of increased RV diastolic pressure, an
enlarged RV chamber, and myocardial fibrosis (Figure 4).
Malignant remodeling finally leads to right heart failure.34
In this meta-analysis, RVMI and ventricular mass index did
not predict the prognosis of PH in all-cause death. This
result is consistent with the meta-analysis of Baggen et
al.38 However, we found that RVMI representing for RVH
was related to composite end point. The prediction abil-
ity of RVMI revealed that although RVH was mechanically
a benign sign of right ventricle’s effort to compensate
for the increasing afterload, reverse events could also
be triggered at this time. This might be ascribed to more
demanding of blood supply for hypertrophy RV and the
following increasing burden of heart.39 Increasing RVMI
can also reflect an enlarged and maladapted RV. This
meta-analysis also demonstrated that RVEDVI and RVESVI
did not predict all-cause death of patients with PH. But
in sensitivity analysis, these 2 results were unstable. We
tried to discriminate these 2 literatures with the others
and found nothing special in study design, sample size,
or other aspects. We also found sensitivity analysis about
the meta-analysis of other RVre parameters demonstrated
stable. We thought that more studies should be conduct-
ed before we redo meta-analysis again to explore the abil-
ity of RVEDVI and RVESVI in predicting all-cause death.
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Figure 3. Prognostic value of right ventricular remodeling parameters for patients with type I pulmonary hypertension based on the World Health
Organization classification.
RVEDVI indicates right ventricular end-diastolic volume index; RVESVI, right ventricular end-systolic volume index; and RVEF, right ventricular ejection fraction.

Besides, ratio of RV mass and RV volume, namely, right
ventricular mass/volume ratio (RV M/V ratio), take both RV
hypertrophy and RV dilation into account. Badagliacca et
al16 found that the RV M/V ratio was also a good predictor
of the clinical worsening of patients with PH.
CMR-derived RVre parameters demonstrated prog-
nostic value during the follow up process of PH. Some
parameters such as RVEDVI, RVESVI, and RVEF should be
promoted to a more important position in routine evalu-
ation compared with current guideline.1 With emergence
of new technologies such as compressed sensing, CMR
image acquisition time would be drastically shortened so
that CMR evaluation could be more easily available.40,41
Besides conventional RVre parameters above, other
CMR-derived parameters reveal more information, like
right ventricle-pulmonary arterial coupling and RV M/V.
In addition, multiple parametric evaluations of RV pre-
dicting adverse events in PH are also underway.42 Prog-
nostic value of such parameters could be researched in
further studies.
This meta-analysis has some limitations. First, it cov-
ered diverse WHO PH subgroups and patients used dif-

Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568 July 2020 9

 Dong et al; Prognostic Value of CMR-RV Parameters in PH
Figure 4. Different types of cardiac magnetic resonance imaging of
right ventricle in pulmonary hypertension patients.
A, no obvious right ventricular dilation or hypertrophy; B, obvious right ven-
tricular hypertrophy; C, obvious right ventricular dilation.
Downloaded from http://ahajournals.org by on November 26, 2021
ferent drug therapies. The heterogeneity of patients in
both etiology and therapeutic regimen would influence
credibility of the results. However, the major part of
patients included was WHO type I patients. More stud-
ies about other patients with WHO type PH are needed
to explore RVre parameters prognostic prediction abil-
ity in these patients with PH. Second, high heteroge-
neity existed in pooled HRs of RVEDVI, RVESVI, RVEF,
and RVMI evaluating all-cause death in patients with
PH. Because of the obvious heterogeneity of the pub-
lications summary results included in this study, sub-
group analysis should be further adopted, and patients
should be stratified according to their sex, age, image
acquisition, and other confounding factors. Further-
more, corresponding HR values of each group should
be calculated. However, some of selected publications
did not contain detailed subgroup information. Thus,
subgroup analysis could not be performed in this study
except for WHO classification. Therefore, we used the
results of the random-effect model. Third, the power
of Egger’s test was insufficient since the number of
studies included was less than ten. This might have led
to the underestimation of nonsignificant HRs. Fourth,
only univariate HRs were calculated for large variability
among studies. Therefore, results of this study need to
be interpreted carefully. Fifth, sensitivity analysis of the
2 results that RVEDVI and RVESVI did not predict all-
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
cause death of patients with PH were unstable. More
studies should be conducted for RVEDVI and RVESVI’s
value in predicting all-cause death. Finally, as data were
incomplete in some studies, we could not calculate
exact cutoff value of each parameter that significantly
influenced HR.
CONCLUSIONS
CMR-derived RVre parameters have independent
prognostic value for all-cause death and composite
end point. RVEF was the strongest prognostic factor
of patients with PH among all the RVre parameters,
which were derived using CMR. Right ventricular
hypertrophy and dilation measured by RVMI, RVEDVI,
and RVESVI of patients with PH also demonstrated
prognostic value.
ARTICLE INFORMATION
Received March 16, 2020; accepted May 22, 2020.
The Data Supplement is available at https://www.ahajournals.org/doi/
suppl/10.1161/CIRCIMAGING.120.010568.
Correspondence
Xiaogang Guo, MD, Department of Cardiology, The First Affiliated Hospital
of Zhejiang University School of Medicine, No.79 Qing Chun Rd, Hangzhou
310006, China. Email gxg22222@zju.edu.cn
Affiliations
Department of Cardiology, The First Affiliated Hospital of Zhejiang University
School of Medicine (Y.D., Z.P., D.W., J.L., J.F., R.X., J.D., X.C., X.X., X.W., X.G.).
Department of Cardiology, West China Hospital, Sichuan University (Y.C.).
Sources of Funding
This study was supported by grant from the National Natural Science Founda-
tion, People’s Republic of China (No. 81470370).
Disclosures
None.
REFERENCES
1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau
G, Peacock A, Vonk Noordegraaf A, Beghetti M, et al. 2015 ESC/ERS
Guidelines for the diagnosis and treatment of pulmonary hypertension:
the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hy-
pertension of the European Society of Cardiology (ESC) and the European
Respiratory Society (ERS): endorsed by: Association for European Paedi-
atric and Congenital Cardiology (AEPC), International Society for Heart
and Lung Transplantation (ISHLT). Eur Respir J. 2015;46:903–975. doi:
10.1183/13993003.01032-2015
2. Ryan JJ, Archer SL. The right ventricle in pulmonary arterial hypertension:
disorders of metabolism, angiogenesis and adrenergic signaling in right ven-
tricular failure. Circ Res. 2014;115:176–188. doi: 10.1161/CIRCRESAHA.
113.301129
3. Bossone E, D’Andrea A, D’Alto M, Citro R, Argiento P, Ferrara F, Cittadini
A, Rubenfire M, Naeije R. Echocardiography in pulmonary arterial hyper-
tension: from diagnosis to prognosis. J Am Soc Echocardiogr. 2013;26:1–
14. doi: 10.1016/j.echo.2012.10.009
July 2020 10
 Dong et al; Prognostic Value of CMR-RV Parameters in PH
4. Peacock AJ, Vonk Noordegraaf A. Cardiac magnetic resonance imaging in
pulmonary arterial hypertension. Eur Respir Rev. 2013;22:526–534. doi:
10.1183/09059180.00006313
5. Alassas K, Mergo P, Ibrahim el-S, Burger C, Safford R, Parikh P, Shapiro
B. Cardiac MRI as a diagnostic tool in pulmonary hypertension. Future
Cardiol. 2014;10:117–130. doi: 10.2217/fca.13.97
6. Ren W, Zhang Z, Yang F, Yang Z-w, Li D. Prognosis value of cardiac
magnetic resonance cardiac function index in patients with pulmo-
nary hypertension. Acad J Sec Mil Med Univ. 2019;40:262–269. doi:
10.16781/j.0258-879x.2019.03.0262
7. Padervinskienė L, Krivickienė A, Hoppenot D, Miliauskas S, Basevičius A,
Nedzelskienė I, Jankauskas A, Šimkus P, Ereminienė E. Prognostic value
of left ventricular function and mechanics in pulmonary hypertension: a
pilot cardiovascular magnetic resonance feature tracking study. Medicina.
2019;55.pii:E73. doi: 10.3390/medicina55030073
8. Saunders LC, Johns CS, Stewart NJ, Oram CJE, Capener DA, Puntmann
VO, Elliot CA, Condliffe RC, Kiely DG, Graves MJ, et al. Diagnostic and
prognostic significance of cardiovascular magnetic resonance native myo-
cardial T1 mapping in patients with pulmonary hypertension. J Cardiovasc
Magn Reson. 2018;20:78. doi: 10.1186/s12968-018-0501-8
9. Igata S, Tahara N, Sugiyama Y, Bekki M, Kumanomido J, Tahara A, Hon-
da A, Maeda S, Nashiki K, Nakamura T, et al. Utility of the amplitude
of RV1+SV5/6 in assessment of pulmonary hypertension. PLoS One.
2018;13:e0206856. doi: 10.1371/journal.pone.0206856
10. Dawes TJW, Cai J, Quinlan M, de Marvao A, Ostrowski PJ, Tokarczuk PF,
Watson GMJ, Wharton J, Howard LSGE, Gibbs JSR, et al. Fractal analy-
sis of right ventricular trabeculae in pulmonary hypertension. Radiology.
2018;288:386–395. doi: 10.1148/radiol.2018172821
11. Bredfelt A, Rådegran G, Hesselstrand R, Arheden H, Ostenfeld E. Increased
right atrial volume measured with cardiac magnetic resonance is associ-
ated with worse clinical outcome in patients with pre-capillary pulmonary
hypertension. ESC Heart Fail. 2018;5:864–875. doi: 10.1002/ehf2.12304
12. Swift AJ, Capener D, Johns C, Hamilton N, Rothman A, Elliot C, Condliffe
R, Charalampopoulos A, Rajaram S, Lawrie A, et al. Magnetic resonance
imaging in the prognostic evaluation of patients with pulmonary arte-
rial hypertension. Am J Respir Crit Care Med. 2017;196:228–239. doi:
10.1164/rccm.201611-2365OC
13. Li W, Yang T, Zhang Y, Gu Q, Liu ZH, Ni XH, Luo Q, Xiong CM, He JG.
Downloaded from http://ahajournals.org by on November 26, 2021
Prognostic value of right ventricular ejection/filling parameters in IPAH us-
ing cardiac magnetic resonance: a prospective pilot study. Respirology.
2017;22:172–178. doi: 10.1111/resp.12861
14. Menezes de Siqueira ME, Pozo E, Fernandes VR, Sengupta PP, Modesto
K, Gupta SS, Barbeito-Caamano C, Narula J, Fuster V, Caixeta A, et al.
Characterization and clinical significance of right ventricular mechan-
ics in pulmonary hypertension evaluated with cardiovascular magnetic
resonance feature tracking. J Cardiovasc Magn Reson. 2016;18:39. doi:
10.1186/s12968-016-0258-x
15. Brewis MJ, Bellofiore A, Vanderpool RR, Chesler NC, Johnson MK, Naeije
R, Peacock AJ. Imaging right ventricular function to predict outcome in
pulmonary arterial hypertension. Int J Cardiol. 2016;218:206–211. doi:
10.1016/j.ijcard.2016.05.015
16. Badagliacca R, Poscia R, Pezzuto B, Papa S, Pesce F, Manzi G, Giannet-
ta E, Raineri C, Schina M, Sciomer S, et al. Right ventricular concen-
tric hypertrophy and clinical worsening in idiopathic pulmonary arte-
rial hypertension. J Heart Lung Transplant. 2016;35:1321–1329. doi:
10.1016/j.healun.2016.04.006
17. Sato T, Tsujino I, Ohira H, Oyama-Manabe N, Ito YM, Yamada A, Ikeda
D, Watanabe T, Nishimura M. Right atrial volume and reservoir function
are novel independent predictors of clinical worsening in patients with
pulmonary hypertension. J Heart Lung Transplant. 2015;34:414–423.doi:
10.1016/j.healun.2015.01.984
18. Knight DS, Steeden JA, Moledina S, Jones A, Coghlan JG, Muthurangu V.
Left ventricular diastolic dysfunction in pulmonary hypertension predicts
functional capacity and clinical worsening: a tissue phase mapping study. J
Cardiovasc Magn Reson. 2015;17:116. doi: 10.1186/s12968-015-0220-3
19. Jensen AS, Broberg CS, Rydman R, Diller G-P, Li W, Dimopoulos K, Wort
SJ, Pennell DJ, Gatzoulis MA, Babu-Narayan SV. Impaired right, left, or
biventricular function and resting oxygen saturation are associated with
mortality in eisenmenger syndrome a clinical and cardiovascular mag-
netic resonance study. Circ Cardiovasc Imaging. 2015;8:e003596. doi:
10.1161/circimaging.115.003596s
20. Corona-Villalobos CP, Kamel IR, Rastegar N, Damico R, Kolb TM, Boyce
DM, Sager A-ES, Skrok J, Shehata ML, Vogel-Claussen J, et al. Bidimen-
sional measurements of right ventricular function for prediction of survival
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
in patients with pulmonary hypertension: comparison of reproducibility
and time of analysis with volumetric cardiac magnetic resonance imaging
analysis. Pulm Circ. 2015;5:527–537. doi: 10.1086/682229
21. Swift AJ, Rajaram S, Capener D, Elliot C, Condliffe R, Wild JM, Kiely
DG. LGE patterns in pulmonary hypertension do not impact over-
all mortality. JACC Cardiovasc Imaging. 2014;7:1209–1217. doi:
10.1016/j.jcmg.2014.08.014
22. Swift AJ, Rajaram S, Campbell MJ, Hurdman J, Thomas S, Capener D, El-
liot C, Condliffe R, Wild JM, Kiely DG. Prognostic value of cardiovascular
magnetic resonance imaging measurements corrected for age and sex
in idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging.
2014;7:100–106. doi: 10.1161/CIRCIMAGING.113.000338
23. Jacobs W, van de Veerdonk MC, Trip P, de Man F, Heymans MW, Marcus JT,
Kawut SM, Bogaard HJ, Boonstra A, Vonk Noordegraaf A. The right ven-
tricle explains sex differences in survival in idiopathic pulmonary arterial
hypertension. Chest. 2014;145:1230–1236. doi: 10.1378/chest.13-1291
24. Cho IJ, Oh J, Chang HJ, Park J, Kang KW, Kim YJ, Choi BW, Shin S, Shim
CY, Hong GR, et al. Tricuspid regurgitation duration correlates with car-
diovascular magnetic resonance-derived right ventricular ejection fraction
and predict prognosis in patients with pulmonary arterial hypertension.
Eur Heart J Cardiovasc Imaging. 2014;15:18–23. doi: 10.1093/ehjci/jet094
25. Kang KW, Chang HJ, Yoo YP, Yoon HS, Kim YJ, Choi BW, Shim CY, Ha J,
Chung N. Cardiac magnetic resonance-derived right ventricular outflow
tract systolic flow acceleration: a novel index of right ventricular function
and prognosis in patients with pulmonary arterial hypertension. Int J Car-
diovasc Imaging. 2013;29:1759–1767. doi: 10.1007/s10554-013-0262-2
26. Yamada Y, Okuda S, Kataoka M, Tanimoto A, Tamura Y, Abe T, Okamura
T, Fukuda K, Satoh T, Kuribayashi S. Prognostic value of cardiac magnetic
resonance imaging for idiopathic pulmonary arterial hypertension before
initiating intravenous prostacyclin therapy. Circ J. 2012;76:1737–1743.
doi: 10.1253/circj.cj-11-1237
27. Freed BH, Gomberg-Maitland M, Chandra S, Mor-Avi V, Rich S, Archer
SL, Jamison EB Jr, Lang RM, Patel AR. Late gadolinium enhancement car-
diovascular magnetic resonance predicts clinical worsening in patients
with pulmonary hypertension. J Cardiovasc Magn Reson. 2012;14:11.
doi: 10.1186/1532-429X-14-11
28. van de Veerdonk MC, Kind T, Marcus JT, Mauritz G-J, Heymans MW, Bo-
gaard H-J, Boonstra A, Marques KMJ, Westerhof N, Vonk-Noordegraaf A.
Progressive right ventricular dysfunction in patients with pulmonary arteri-
al hypertension responding to therapy. J Am Coll Cardiol. 2011;58:2511–
2519. doi: 10.1016/j.jacc.2011.06.068
29. Van Wolferen SA, Marcus JT, Boonstra A, Marques KMJ, Bronzwaer
JGF, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A. Prognostic
value of right ventricular mass, volume, and function in idiopathic pul-
monary arterial hypertension. Eur Heart J. 2007;28:1250–1257. doi:
10.1093/eurheartj/ehl477
30. Hayden JA, Côté P, Bombardier C. Evaluation of the quality of prognosis
studies in systematic reviews. Ann Intern Med. 2006;144:427–437. doi:
10.7326/0003-4819-144-6-200603210-00010
31. Hulshof HG, Eijsvogels TMH, Kleinnibbelink G, van Dijk AP, George KP,
Oxborough DL, Thijssen DHJ. Prognostic value of right ventricular longitu-
dinal strain in patients with pulmonary hypertension: a systematic review
and meta-analysis. Eur Heart J Cardiovasc Imaging. 2019;20:475–484.
doi: 10.1093/ehjci/jey120
32. Amano H, Abe S, Hirose S, Waku R, Masuyama T, Sakuma M, Toyoda S,
Taguchi I, Inoue T, Tei C. Comparison of echocardiographic parameters to
assess right ventricular function in pulmonary hypertension. Heart Vessels.
2017;32:1214–1219. doi: 10.1007/s00380-017-0991-6
33. Courand PY, Pina Jomir G, Khouatra C, Scheiber C, Turquier S, Glérant JC,
Mastroianni B, Gentil B, Blanchet-Legens AS, Dib A, et al. Prognostic value
of right ventricular ejection fraction in pulmonary arterial hypertension.
Eur Respir J. 2015;45:139–149. doi: 10.1183/09031936.00158014
34. Vonk Noordegraaf A, Westerhof BE, Westerhof N. The relationship be-
tween the right ventricle and its load in pulmonary hypertension. J Am
Coll Cardiol. 2017;69:236–243. doi: 10.1016/j.jacc.2016.10.047
35. Nochioka K, Querejeta Roca G, Claggett B, Biering-Sørensen T, Matsushita
K, Hung CL, Solomon SD, Kitzman D, Shah AM. Right ventricular func-
tion, right ventricular-pulmonary artery coupling, and heart failure risk in
4 US communities: the atherosclerosis risk in communities (ARIC) study.
JAMA Cardiol. 2018;3:939–948. doi: 10.1001/jamacardio.2018.2454
36. Kubba S, Davila CD, Forfia PR. Methods for evaluating right ventricu-
lar function and ventricular-arterial coupling. Prog Cardiovasc Dis.
2016;59:42–51. doi: 10.1016/j.pcad.2016.06.001
July 2020 11
 Dong et al; Prognostic Value of CMR-RV Parameters in PH
37. Vanderpool RR, Pinsky MR, Naeije R, Deible C, Kosaraju V, Bunner C, Ma-
thier MA, Lacomis J, Champion HC, Simon MA. RV-pulmonary arterial
coupling predicts outcome in patients referred for pulmonary hyperten-
sion. Heart. 2015;101:37–43. doi: 10.1136/heartjnl-2014-306142
38. Baggen VJ, Leiner T, Post MC, van Dijk AP, Roos-Hesselink JW, Boersma
E, Habets J, Sieswerda GT. Cardiac magnetic resonance findings predict-
ing mortality in patients with pulmonary arterial hypertension: a sys-
tematic review and meta-analysis. Eur Radiol. 2016;26:3771–3780. doi:
10.1007/s00330-016-4217-6
39. Sano H, Tanaka H, Motoji Y, Fukuda Y, Mochizuki Y, Hatani Y, Matsu-
zoe H, Hatazawa K, Shimoura H, Ooka J, et al. Right ventricular relative
wall thickness as a predictor of outcomes and of right ventricular reverse
Downloaded from http://ahajournals.org by on November 26, 2021
Circ Cardiovasc Imaging. 2020;13:e010568. DOI: 10.1161/CIRCIMAGING.120.010568
remodeling for patients with pulmonary hypertension. Int J Cardiovasc
Imaging. 2017;33:313–321. doi: 10.1007/s10554-016-1004-z
40. Salerno M, Sharif B, Arheden H, Kumar A, Axel L, Li D, Neubauer S.
Recent advances in cardiovascular magnetic resonance: techniques
and applications. Circ Cardiovasc Imaging. 2017;10:e003951. doi:
10.1161/CIRCIMAGING.116.003951
41. Tolouee A, Alirezaie J, Babyn P. Compressed sensing reconstruction of
cardiac cine MRI using golden angle spiral trajectories. J Magn Reson.
2015;260:10–19. doi: 10.1016/j.jmr.2015.09.003
42. Sitbon O, Benza RL, Badesch DB, Barst RJ, Elliott CG, Gressin V, Lemarié
JC, Miller DP, Muros-Le Rouzic E, Simonneau G, et al. Validation of two
predictive models for survival in pulmonary arterial hypertension. Eur
Respir J. 2015;46:152–164. doi: 10.1183/09031936.00004414
July 2020 12