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The right atrium and tricuspid annulus are cardinal structures in tricuspid regurgitation with or without pulmonary hypertension
The Right Atrium and Tricuspid Annulus are Cardinal Structures in Tricuspid Regurgitation with or without Pulmonary Hypertension Naohiko Nemoto, Jonathan G. Schwartz, John R. Lesser, Wesley D. Pedersen, Paul Sorajja, Ross Garberich, Erin M. Spinner, Robert S. Schwartz PII: DOI: Reference:
S0167-5273(16)33521-5 doi:10.1016/j.ijcard.2016.11.075 IJCA 23937
To appear in:
International Journal of Cardiology
Received date: Accepted date:
17 July 2016 5 November 2016
Please cite this article as: Nemoto Naohiko, Schwartz Jonathan G., Lesser John R., Pedersen Wesley D., Sorajja Paul, Garberich Ross, Spinner Erin M., Schwartz Robert S., The Right Atrium and Tricuspid Annulus are Cardinal Structures in Tricuspid Regurgitation with or without Pulmonary Hypertension, International Journal of Cardiology (2016), doi:10.1016/j.ijcard.2016.11.075
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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The Right Atrium and Tricuspid Annulus are Cardinal Structures in Tricuspid Regurgitation with or without Pulmonary Hypertension
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Naohiko Nemoto, #Jonathan G. Schwartz, John R. Lesser, Wesley D. Pedersen, Paul Sorajja, Ross Garberich, *Erin M. Spinner, Robert S. Schwartz
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Minneapolis Heart Institute and Foundation, Minneapolis, MN, #Stanford University Medical Center, Stanford CA, and *Edwards Lifesciences, Irvine CA
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Short Title: Tricuspid Regurgitation and Right Heart Structure
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Corresponding Author: Robert S. Schwartz MD, FACC, FAHA, FSCCT Minneapolis Heart Institute 920 E 28th Street Minneapolis MN,55076 Tel: 612 863 3698 Email: [email protected]
Conflicts of Interest: Dr Spinner is a full-time employee of Edwards LifeSciences No other conflicts of interest Funding for this Project: Minneapolis Heart Institute Foundation
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Abbreviations Used:
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Tricuspid Valve Regurgitation Right Atrium Right Atrial Volume Index Tricuspid Annulus Area Right Ventricle
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PH Pulmonary Hypertension PASP Pulmonary Artery Systolic Pressure
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TR RA RAi TAA RV
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Abstract
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Background
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Right heart structural abnormalities occur in both tricuspid regurgitation (TR) and pulmonary hypertension (PH). They may occur independently or
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together, but their joint effects on cardiac structure are incompletely described.
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This study examined the interactions of TR severity and PH on right heart structural changes.
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Methods
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The study evaluated 455 patients undergoing both echocardiography
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and CT angiography (CTA). Cases were divided into 3 groups by TR severity: trace (n=217), mild (n=174), and significant (moderate or severe, n=64). Each
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TR level was subdivided into two groups by PH absent or present. Cardiac structural measurements included tricuspid annulus area (TAA), right atrial (RA) and right ventricular volume (RV) indexed to body surface area.
Results Analysis by TR and PH showed that indexed RA Volume and TAA were very sensitive to TR severity.
RA volume was most affected by pulmonary
hypertension when TR was trace or mild, while PH had less effect on TAA. In
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significant TR, neither RA volume nor TAA were changed by PH. Indexed RV
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volume was insensitive to trace and mild TR, and PH similarly had little effect.
Conclusions
mild TR.
PH impacts RA volume but only in trace and
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severity, trace through significant.
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RA volume and tricuspid annulus area enlarge in proportion to TR
RA volume best reflects TR impact on right heart structure, both with Right atrial volume and tricuspid annulus area are the cardinal
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and without PH.
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indices of TR-induced right heart structural disease at all severities.
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Ultramini Abstract
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Right heart structural effects of TR and PH were examined in this study.
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Patients were evaluated by echo and CTA, and grouped by TR severity as trace, mild, and significant, and were subdivided by PH absence/presence.
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Analysis by TR severity and PH showed that Indexed RA volume is the
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parameter most sensitive to TR severity, and PH causes incremental RA volume increases in trace/mild TR. Indexed tricuspid annulus area (TAA) similarly
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increases with TR severity, but was unaffected by PH at any TR severity. RV
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volume is insensitive to TR severity and PH.
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Indexed right atrial volume and tricuspid annulus area are cardinal indices for TR-induced right heart structural disease and increase proportionally to TR RA volume is more sensitive to PH than is tricuspid annular area.
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severity.
TR
severity may be more accurately assessed by increased RA volume and annulus area.
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Perspective Statement
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The right atrium (RA) and tricuspid annulus (TA) are the cardinal cardiac They each enlarge
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structures affected by tricuspid regurgitation (TR).
with TR severity. The right ventricle exhibits minimal change across TR Pulmonary hypertension (PH) enhances TR-mediated RA and
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severity.
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RV size in significant TR.
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TA dilation, but only in trace and mild TR. PH has no effect on RA, TA, or
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Central Message
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Right atrial volume and Tricuspid Annulus Area are the most sensitive to
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TR severity, and are also sensitive to pulmonary hypertension.
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Introduction
TR induces maladaptive structural heart changes including
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and mortality (1).
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Functional tricuspid regurgitation (TR) has important effects on morbidity
right heart enlargement, tricuspid annulus circularization and area enlargement TR may occur in conjunction with normal pulmonary pressure, but left
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(2-5).
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heart valve disease (LVD) often causes pulmonary hypertension (PH) that increases TR severity (6).
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The quantitative effects of TR and PH on right heart structure remain
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incompletely defined, in part because TR creates volume overload while PH
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causes pressure overload, both of which may independently contribute to structural changes. This study sought to clarify the relationships between TR, PH,
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and their impact on cardiac structural changes.
Methods Patients were identified from the Minneapolis Heart Institute Advanced Imaging database with both 3DCT and echocardiography studies.
Clinical data
were collected from the electronic medical record, and patients were grouped according to echo-defined TR and the presence or absence of PH, Figure 1. Patients underwent comprehensive 2D-echocardiography.
Tricuspid
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leaflet anatomy and hepatic venous flow patterns were assessed using the
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parasternal RV inflow, parasternal short-axis, apical 4-chamber, and subcostal
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views.
TR severity was graded as trace, mild, or significant (moderate or
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severe), based on the 1) TR jet size by color flow imaging, 2) the relative size of
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the regurgitant jet (relative to the RA area), and 3) the hepatic venous flow pattern (hepatic venous systolic flow reversal by pulsed wave Doppler
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echocardiography, including the presence of severe TR), as recommended by
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the guidelines of the American Society of Echocardiography (7).
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Cardiac CT imaging was performed per standard clinical protocol and 3-D image analysis used standard workstation tools (VITREA, Vital
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Images/Toshiba).
The tricuspid annulus major and minor diameters, annulus
area, and RA, and RV long axes and areas were measured using 4-chamber and orthogonal 2-chamber views (Figure 2) and as previously described (8). RA and RV volumes were calculated at mid-diastole using Simpson’s method, and volumes were indexed to body surface area (BSA), also previously described (8). Pulmonary artery systolic pressure (PASP) was estimated as the sum of the peak TR velocity derived systolic pressure gradient (measured by
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continuous-wave Doppler echocardiography) and estimated RA pressure. RA
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pressure was approximated according the size of the inferior vena cava and the
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changes in its size during respiration (9). Patients in whom the PASP could not be estimated by echocardiography (ie, patients without TR) were not included in A value of 5 mmHg was assigned to a small vena cava
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this study (n=167).
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collapsing >50% in diameter during quiet inspiration, 20mm Hg assigned to very dilated vena cava without respiratory variation in size, and 10 to 15 mm Hg Pulmonary hypertension was defined as
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assigned to intermediate findings.
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estimated PASP > 40mm Hg or more.
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Hemodynamic status of all patients was stable during CTA and echocardiography examinations. The time period between CTA and
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echocardiography was less than one month.
Results Patient characteristics by group are shown in Table 1.
Significant
differences were found in age, gender, hypertension, COPD, CKD, CHF, left valve disease, AF, EF and PASP.
Table 2a shows that PH prevalence
increased significantly with TR severity. Table 2b shows quantitative structural right heart changes across TR
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severity and pulmonary hypertension status. These are summarized as follows.
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RA Volume Index (iRA)
iRA progressively increased across all TR severity through trace, mild,
In significant TR, PH had no effect on iRA.
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mild.
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and significant with incremental enlargement with PH only when TR was trace or
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Tricuspid Annulus Area Index (iTAA)
At each TR grade, PH had no incremental effect on iTAA.
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significant.
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iTAA index increased progressively with TR from trace, mild, and
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Tricuspid Annulus Circularization The normally ellipsoidal tricuspid annulus had no associated shape
change (circularization) with TR grades trace or mild. The annulus circularized when TR became significant.
RV Volume Index (iRV) iRV increased progressively with TR severity at all levels. At each level, PH had no significant incremental RV volume effect.
RV volume increase was
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most pronounced as TR progressed from mild to significant. As with the RA, RV
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volume was more sensitive to volume overload (TR grade) than pressure
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overload (PA pressure).
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Discussion
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Tricuspid regurgitation is widely prevalent, with more than 14% of the US population having mild or greater TR. TR has strong prognostic impact, and
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successful tricuspid valve repair improves long term results (10) (11).
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Pulmonary hypertension is a factor in TR severity, though the literature is
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incomplete regarding the strength of interaction.
One study addressed this
question using an ex-vivo heart chamber model, and found high transvalvular
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pressure caused annular dilation increased and worsened TR . In this model high transvalvular pressure increased leaflet coaptation area and decreased valve tenting area, thus reducing rather than increasing TR severity (12). This study found a strong association between TR severity and PH, though causality cannot be inferred. These findings from the model data were found in this study’s clinical data. We recently reported that mild, early TR is associated with right atrial enlargement and tricuspid annular dilation (8). These findings prompted
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additional study of right heart structural changes across higher TR grades and
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the effects of pulmonary hypertension. TR creates chamber volume overload
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through regurgitant volume (13), while pulmonary hypertension constitutes pressure overload (14-16). These two factors often interact, since regurgitant This
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volume increases with larger trans-tricuspid valve pressure gradients.
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study thus examined right heart structural change associated with TR of all severity, both with and without PH.
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Results showed that Indexed RA volume and tricuspid annulus area both
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enlarge incrementally across trace, mild and significant TR.
PH incrementally
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increased the RA volume in both trace and mild TR, but in cases of significant TR, both TAA and iRA are unaffected by PH presence/absence.
As previously
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shown, RV volume increases only in late significant TR, and is also minimally sensitive to pulmonary hypertension. This study also suggests that PH alone does not produce significant TR. The data show that normal structural anatomy (normalized annulus area, RA and RV volumes) in the setting of significant TR are all unaffected by PH presence/absence. Significant TR may thus require RA, RV and TAA enlargement, consistent with previous results (17). Taken together these results suggest that the RA and tricuspid annulus
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dilate at low pressure (likely from TR derived volume overload), and increased
RA dilation in trace or mild TR should
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chamber walls and greater compliance.
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by PH derived pressure overload. This is plausible based on thin right heart
thus be taken seriously, as it suggests regurgitant volume, even at lower
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pulmonary pressure, is enough to initiate structural heart disease and is
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associated with higher long term mortality in patients with PH (18-21). While the tricuspid annulus area also increases with TR severity, it is
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less sensitive to PH. Mechanisms for these differential responses to PH between
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as the RA expands.
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the RA and tricuspid annulus are uncertain but may result from annular tethering
This study extends prior findings that RA enlargement is an early change It shows that both RA volume and tricuspid annulus area are
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in mild TR.
cardinal indices of structural heart disease across a broad range of TR severity, with and without PH.
Their measurement should be strongly considered for
determining structural heart effects in TR, and may find use in guiding the timing of therapeutic intervention.
Limitations The study has several limitations.
It was retrospective and from a
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single center, and the number of patients in each TR group was relatively
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Selection bias was potentially present in that all subjects underwent
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small.
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CT and 2D echocardiography for clinical reasons, and non-TR patients were excluded in this study, because PA pressure was measured
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echocardiographically, requiring TR for measurement techniques.
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Legends
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Patient distribution and groups according to echocardiographically
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Figure 1
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defined tricuspid valve regurgitation (none/trace, mild and
Methods for RA, RV, and Tricuspid Annulus Area Measurement
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The long axes of the RA and RV were measured from the 4-chamber
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view (A) and a plane orthogonal to this 4-chamber view (B). RA and RV
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areas were measured by manual tracing from these views. RA and RV
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volumes were calculated using Simpson’s method. RA: right atrium,
RV:right ventricle
The tricuspid annulus plane (C) was measured in a plane defined by the
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Figure 2
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moderate/severe).
tricuspid leaflets’ most basal attachments. Measurements of area (D), major and minor diameters are shown (E). TAA:tricuspid annulus area. Figure Adapted from (8)
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PH(+)
Significant TR
Significant TR
(n=22)
(n=42)
65.6
68.8
(59.5, 71.7)ac
(64.4, 73.2)bc
1.95
1.89
1.86
(1.93, 2.04)
(1.89, 2.02)
(1.78, 2.01)
(1.78, 1.95)
10 (33.3)
53 (52.0)
31 (43.1)
8 (36.4)
17 (40.5)
0.05
96 (51.3)
13 (43.3)
43 (42.2)
37 (51.4)
9 (40.9)
21 (50.0)
0.65
HT, N (%)
124 (66.3)
18 (60.0)
53 (52.0)
57 (79.2)
11 (50.0)
29 (69.1)
0.0053
DM, N (%)
36 (19.3)
7 (23.3)
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Table 1 Patient Characteristics
17 (16.7)
13 (18.1)
3 (13.6)
6 (14.3)
0.9217
6 (3.2)
1 (3.3)
7 (6.9)
3 (4.2)
3 (13.6)
3 (7.1)
0.2406
COPD, N (%)
12 (6.4)
2 (6.7)
1 (1.0)
13 (18.1)
1 (4.6)
7 (16.7)
0.0003
CKD, N (%)
12 (6.4)
3 (10.0)
8 (7.8)
2 (2.8)
0 (0.0)
10 (23.8)
0.0045
CHF, N (%)
18 (9.6)
3 (10.0)
13 (12.8)
16 (22.2)
6 (27.3)
14 (33.3)
0.0010
Left valve
25 (187)
11 (36.7)
29 (28.4)
31 (43.1)
10 (45.5)
26 (61.9)
<0.0001
31 (16.6)
10 (33.3)
29 (28.4)
26 (36.1)
11 (50.0)
18 (42.9)
0.0001
59
57
58
57
48
52
<0.0001
mean (95% CI)
(57.7, 61.2)a
(52, 61)ab
(56, 60)a
(43, 53)c
(49, 56)bc
PASP
31±5a
47±7b
33±4a
35±4a
55±15c
PH(-)
PH(+)
Trace TR
Trace TR
Mild TR
Mild TR
(n=187)
(n=30)
(n=102)
(n=72)
Age, mean
61.9
66.3
62.7
(95% CI)
(59.8, 64.0)a
(61.1, 71.5)ab
(59.9, 65.5)a
BSA, mean
2.00
1.98
1.98
(95% CI)
(1.96, 2.04)
(1.89, 2.08)
Gender (male)
106 (56.7)
IHD, N (%)
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N (%)
EF (%)
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disease, N (%) AFib, N (%)
(66.0, 72.8)b
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Cardiomyopathy
69.4
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N (%)
PH(-)
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PH(+)
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PH(-)
(54,60) ab 47±8b
P-value
0.002
0.06
<0.0001
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Table 2a
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Relationship between TR severity and PH Trace TR
Mild TR
Significant TR
PH(-)
187 (86.2)
102 (58.6)
22 (34.4)
PH(+)
30 (13.8)
72 (41.4)
42 (65.6)
P value
<0.001
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Table 2b
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N (%)
n-TAA*
PH(+)
PH(-)
PH(+)
PH(-)
PH(+)
Trace TR
Trace TR
Mild TR
Mild TR
Significant TR
Significant TR
(n=187)
(n=30)
(n=102)
(n=72)
(n=22)
(n=42)
667
685
724
924
873
(647, 688)
a
Minor/Major
0.78
TAD (cm)
(0.76, 0.79)
RA index*
44 (42, 46)
a
RV index*
58 (56, 60)
a
LA index*
45 (43, 47)
a
55 (53, 57)
a
726
ab
abc
b
63 (57, 69)
b
0.78 ac
(847, 1007)
c
0.84 a
c
0.84 bc
<0.001 c
(0.79, 0.88)
(0.81, 0.87)
bc
49 (46, 52)b
56 (52, 61)c
78 (68, 89)d
72 (65, 79)
d
<0.001
ab
58 (55, 61)ab
63 (59, 67)b
84 (76, 94)c
79 (73, 86)c
<0.001
bc
50 (47, 53)b
57 (53, 62)c
59 (52, 68)c
58 (53, 64)c
<0.001
ab
57 (54, 61)ac
61 (57, 66)bc
67 (59, 76)b
68 (63, 75)b
<0.001
Mean adjusted for age and gender, *geometric means (95% CI)
abcd
(820, 930)
<0.001
(0.75, 0.81)
51 (45, 57)
60 (54, 67)
(690, 760)
P value
(0.77, 0.82)
51 (50, 57)
#
(698, 756) 0.79
(0.76, 0.84)
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LV index*
(636, 738) 0.81
a
D
(95% CI)
PH(-)
TE
#
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Mean
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Structural Heart Enlargement by TR and PH
cells with same superscripts within row do not differ,
p>0.05
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References Nath J, Foster E, Heidenreich PA. Impact of tricuspid regurgitation on long-term
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1. 2.
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survival. J Am Coll Cardiol 2004;43:405-9.
Sagie A, Schwammenthal E, Padial LR, Vazquez de Prada JA, Weyman AE, Levine
SC R
RA. Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol 1994;24:446-53. 3.
Sugimoto T, Okada M, Ozaki N, Hatakeyama T, Kawahira T. Long-term evaluation of treatment for functional tricuspid regurgitation with regurgitant volume:
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characteristic differences based on primary cardiac lesion. J Thorac Cardiovasc Surg 1999;117:463-71. 4.
Fukuda S, Gillinov AM, Song JM et al. Echocardiographic insights into atrial and journal 2006;152:1208-14.
5.
MA
ventricular mechanisms of functional tricuspid regurgitation. American heart Kim HK, Kim YJ, Park JS et al. Determinants of the severity of functional tricuspid Braunwald NS, Ross J, Morrow AG. Conservative management of tricuspid
TE
6.
D
regurgitation. Am J Cardiol 2006;98:236-42. regurgitation in patients undergoing mitral valve replacement. Circulation 7.
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1967;35:I63-9.
Zoghbi WA, Enriquez-Sarano M, Foster E et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802. Nemoto N, Lesser JR, Pedersen WR et al. Pathogenic structural heart changes in
AC
8.
early tricuspid regurgitation. J Thorac Cardiovasc Surg 2015. 9.
Nagueh SF, Kopelen HA, Zoghbi WA. Relation of mean right atrial pressure to echocardiographic and Doppler parameters of right atrial and right ventricular function. Circulation 1996;93:1160-9.
10.
Rogers JH, Bolling SF. Surgical approach to functional tricuspid regurgitation: should we be more aggressive? Curr Opin Cardiol 2014;29:133-9.
11.
Teman NR, Huffman LC, Krajacic M, Pagani FD, Haft JW, Bolling SF. "Prophylactic" tricuspid repair for functional tricuspid regurgitation. Ann Thorac Surg 2014;97:1520-4.
12.
Casa LD, Dolensky JR, Spinner EM, Veledar E, Lerakis S, Yoganathan AP. Impact of pulmonary hypertension on tricuspid valve function. Annals of biomedical engineering 2013;41:709-24.
13.
Rodriguez L, Anconina J, Flachskampf FA, Weyman AE, Levine RA, Thomas JD. Impact of finite orifice size on proximal flow convergence. Implications for Doppler
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quantification of valvular regurgitation. Circ Res 1992;70:923-30. 14.
Hill MR, Simon MA, Valdez-Jasso D, Zhang W, Champion HC, Sacks MS. Structural
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and mechanical adaptations of right ventricle free wall myocardium to pressure 15.
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overload. Annals of biomedical engineering 2014;42:2451-65.
Louie EK, Lin SS, Reynertson SI, Brundage BH, Levitsky S, Rich S. Pressure and
SC R
volume loading of the right ventricle have opposite effects on left ventricular ejection fraction. Circulation 1995;92:819-24. 16.
Rogers JH, Bolling SF. The tricuspid valve: current perspective and evolving management of tricuspid regurgitation. Circulation 2009;119:2718-25. Mutlak D, Aronson D, Lessick J, Reisner SA, Dabbah S, Agmon Y. Functional
NU
17.
tricuspid regurgitation in patients with pulmonary hypertension: is pulmonary artery
pressure
the
only
18.
of
regurgitation
severity?
Chest
MA
2009;135:115-21.
determinant
Sandoval J, Bauerle O, Palomar A et al. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 1994;89:1733-44. Cioffi G, de Simone G, Mureddu G, Tarantini L, Stefenelli C. Right atrial size and
D
19.
TE
function in patients with pulmonary hypertension associated with disorders of respiratory system or hypoxemia. Eur J Echocardiogr 2007;8:322-31. Raymond RJ, Hinderliter AL, Willis PW et al. Echocardiographic predictors of
CE P
20.
adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002;39:1214-9.
Willens HJ, Fertel DP, Qin J, Labrador E, Lowery MH. Effects of age and pulmonary arterial hypertension on the different phases of right atrial function. Int J
AC
21.
Cardiovasc Imaging 2008;24:703-10.
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Figure 1
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Figure 2
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Highlights for Review
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It is well known that right heart structural abnormalities occur in tricuspid regurgitation and pulmonary hypertension, and they may occur independently or
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together. What is unknown is the relative impact of each on cardiac structure.
This study examined the interactions of TR severity and PH on right heart
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structural changes.
but less so to pulmonary hypertension.
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TR severity,
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We found that RA Volume and the Tricuspid annulus area were very sensitive to In significant TR, neither
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RA volume nor TAA are substantially affected by PH.
RA volume and tricuspid annulus area are thus the most sensitive structures to TR, enlarge in proportion to TR severity.
By contrast, pulmonary hypertension
impacts RA volume less, and tehn in trace and mild TR. RA volume best reflects TR impact on right heart structure, both with and without PH. Right atrial volume and tricuspid annulus area are the cardinal indices of TR-induced right heart structural disease at all severities.
S0167-5273(16)33521-5 doi:10.1016/j.ijcard.2016.11.075 IJCA 23937
To appear in:
International Journal of Cardiology
Received date: Accepted date:
17 July 2016 5 November 2016
Please cite this article as: Nemoto Naohiko, Schwartz Jonathan G., Lesser John R., Pedersen Wesley D., Sorajja Paul, Garberich Ross, Spinner Erin M., Schwartz Robert S., The Right Atrium and Tricuspid Annulus are Cardinal Structures in Tricuspid Regurgitation with or without Pulmonary Hypertension, International Journal of Cardiology (2016), doi:10.1016/j.ijcard.2016.11.075
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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The Right Atrium and Tricuspid Annulus are Cardinal Structures in Tricuspid Regurgitation with or without Pulmonary Hypertension
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Naohiko Nemoto, #Jonathan G. Schwartz, John R. Lesser, Wesley D. Pedersen, Paul Sorajja, Ross Garberich, *Erin M. Spinner, Robert S. Schwartz
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Minneapolis Heart Institute and Foundation, Minneapolis, MN, #Stanford University Medical Center, Stanford CA, and *Edwards Lifesciences, Irvine CA
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Short Title: Tricuspid Regurgitation and Right Heart Structure
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Corresponding Author: Robert S. Schwartz MD, FACC, FAHA, FSCCT Minneapolis Heart Institute 920 E 28th Street Minneapolis MN,55076 Tel: 612 863 3698 Email: [email protected]
Conflicts of Interest: Dr Spinner is a full-time employee of Edwards LifeSciences No other conflicts of interest Funding for this Project: Minneapolis Heart Institute Foundation
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Abbreviations Used:
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Tricuspid Valve Regurgitation Right Atrium Right Atrial Volume Index Tricuspid Annulus Area Right Ventricle
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PH Pulmonary Hypertension PASP Pulmonary Artery Systolic Pressure
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TR RA RAi TAA RV
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Abstract
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Background
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Right heart structural abnormalities occur in both tricuspid regurgitation (TR) and pulmonary hypertension (PH). They may occur independently or
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together, but their joint effects on cardiac structure are incompletely described.
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This study examined the interactions of TR severity and PH on right heart structural changes.
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Methods
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The study evaluated 455 patients undergoing both echocardiography
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and CT angiography (CTA). Cases were divided into 3 groups by TR severity: trace (n=217), mild (n=174), and significant (moderate or severe, n=64). Each
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TR level was subdivided into two groups by PH absent or present. Cardiac structural measurements included tricuspid annulus area (TAA), right atrial (RA) and right ventricular volume (RV) indexed to body surface area.
Results Analysis by TR and PH showed that indexed RA Volume and TAA were very sensitive to TR severity.
RA volume was most affected by pulmonary
hypertension when TR was trace or mild, while PH had less effect on TAA. In
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significant TR, neither RA volume nor TAA were changed by PH. Indexed RV
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volume was insensitive to trace and mild TR, and PH similarly had little effect.
Conclusions
mild TR.
PH impacts RA volume but only in trace and
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severity, trace through significant.
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RA volume and tricuspid annulus area enlarge in proportion to TR
RA volume best reflects TR impact on right heart structure, both with Right atrial volume and tricuspid annulus area are the cardinal
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and without PH.
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indices of TR-induced right heart structural disease at all severities.
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Ultramini Abstract
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Right heart structural effects of TR and PH were examined in this study.
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Patients were evaluated by echo and CTA, and grouped by TR severity as trace, mild, and significant, and were subdivided by PH absence/presence.
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Analysis by TR severity and PH showed that Indexed RA volume is the
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parameter most sensitive to TR severity, and PH causes incremental RA volume increases in trace/mild TR. Indexed tricuspid annulus area (TAA) similarly
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increases with TR severity, but was unaffected by PH at any TR severity. RV
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volume is insensitive to TR severity and PH.
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Indexed right atrial volume and tricuspid annulus area are cardinal indices for TR-induced right heart structural disease and increase proportionally to TR RA volume is more sensitive to PH than is tricuspid annular area.
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severity.
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severity may be more accurately assessed by increased RA volume and annulus area.
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Perspective Statement
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The right atrium (RA) and tricuspid annulus (TA) are the cardinal cardiac They each enlarge
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structures affected by tricuspid regurgitation (TR).
with TR severity. The right ventricle exhibits minimal change across TR Pulmonary hypertension (PH) enhances TR-mediated RA and
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severity.
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RV size in significant TR.
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TA dilation, but only in trace and mild TR. PH has no effect on RA, TA, or
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Central Message
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Right atrial volume and Tricuspid Annulus Area are the most sensitive to
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TR severity, and are also sensitive to pulmonary hypertension.
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Introduction
TR induces maladaptive structural heart changes including
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and mortality (1).
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Functional tricuspid regurgitation (TR) has important effects on morbidity
right heart enlargement, tricuspid annulus circularization and area enlargement TR may occur in conjunction with normal pulmonary pressure, but left
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(2-5).
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heart valve disease (LVD) often causes pulmonary hypertension (PH) that increases TR severity (6).
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The quantitative effects of TR and PH on right heart structure remain
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incompletely defined, in part because TR creates volume overload while PH
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causes pressure overload, both of which may independently contribute to structural changes. This study sought to clarify the relationships between TR, PH,
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and their impact on cardiac structural changes.
Methods Patients were identified from the Minneapolis Heart Institute Advanced Imaging database with both 3DCT and echocardiography studies.
Clinical data
were collected from the electronic medical record, and patients were grouped according to echo-defined TR and the presence or absence of PH, Figure 1. Patients underwent comprehensive 2D-echocardiography.
Tricuspid
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leaflet anatomy and hepatic venous flow patterns were assessed using the
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parasternal RV inflow, parasternal short-axis, apical 4-chamber, and subcostal
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views.
TR severity was graded as trace, mild, or significant (moderate or
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severe), based on the 1) TR jet size by color flow imaging, 2) the relative size of
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the regurgitant jet (relative to the RA area), and 3) the hepatic venous flow pattern (hepatic venous systolic flow reversal by pulsed wave Doppler
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echocardiography, including the presence of severe TR), as recommended by
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the guidelines of the American Society of Echocardiography (7).
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Cardiac CT imaging was performed per standard clinical protocol and 3-D image analysis used standard workstation tools (VITREA, Vital
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Images/Toshiba).
The tricuspid annulus major and minor diameters, annulus
area, and RA, and RV long axes and areas were measured using 4-chamber and orthogonal 2-chamber views (Figure 2) and as previously described (8). RA and RV volumes were calculated at mid-diastole using Simpson’s method, and volumes were indexed to body surface area (BSA), also previously described (8). Pulmonary artery systolic pressure (PASP) was estimated as the sum of the peak TR velocity derived systolic pressure gradient (measured by
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continuous-wave Doppler echocardiography) and estimated RA pressure. RA
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pressure was approximated according the size of the inferior vena cava and the
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changes in its size during respiration (9). Patients in whom the PASP could not be estimated by echocardiography (ie, patients without TR) were not included in A value of 5 mmHg was assigned to a small vena cava
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this study (n=167).
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collapsing >50% in diameter during quiet inspiration, 20mm Hg assigned to very dilated vena cava without respiratory variation in size, and 10 to 15 mm Hg Pulmonary hypertension was defined as
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assigned to intermediate findings.
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estimated PASP > 40mm Hg or more.
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Hemodynamic status of all patients was stable during CTA and echocardiography examinations. The time period between CTA and
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echocardiography was less than one month.
Results Patient characteristics by group are shown in Table 1.
Significant
differences were found in age, gender, hypertension, COPD, CKD, CHF, left valve disease, AF, EF and PASP.
Table 2a shows that PH prevalence
increased significantly with TR severity. Table 2b shows quantitative structural right heart changes across TR
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severity and pulmonary hypertension status. These are summarized as follows.
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RA Volume Index (iRA)
iRA progressively increased across all TR severity through trace, mild,
In significant TR, PH had no effect on iRA.
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mild.
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and significant with incremental enlargement with PH only when TR was trace or
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Tricuspid Annulus Area Index (iTAA)
At each TR grade, PH had no incremental effect on iTAA.
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significant.
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iTAA index increased progressively with TR from trace, mild, and
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Tricuspid Annulus Circularization The normally ellipsoidal tricuspid annulus had no associated shape
change (circularization) with TR grades trace or mild. The annulus circularized when TR became significant.
RV Volume Index (iRV) iRV increased progressively with TR severity at all levels. At each level, PH had no significant incremental RV volume effect.
RV volume increase was
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most pronounced as TR progressed from mild to significant. As with the RA, RV
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volume was more sensitive to volume overload (TR grade) than pressure
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overload (PA pressure).
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Discussion
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Tricuspid regurgitation is widely prevalent, with more than 14% of the US population having mild or greater TR. TR has strong prognostic impact, and
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successful tricuspid valve repair improves long term results (10) (11).
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Pulmonary hypertension is a factor in TR severity, though the literature is
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incomplete regarding the strength of interaction.
One study addressed this
question using an ex-vivo heart chamber model, and found high transvalvular
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pressure caused annular dilation increased and worsened TR . In this model high transvalvular pressure increased leaflet coaptation area and decreased valve tenting area, thus reducing rather than increasing TR severity (12). This study found a strong association between TR severity and PH, though causality cannot be inferred. These findings from the model data were found in this study’s clinical data. We recently reported that mild, early TR is associated with right atrial enlargement and tricuspid annular dilation (8). These findings prompted
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additional study of right heart structural changes across higher TR grades and
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the effects of pulmonary hypertension. TR creates chamber volume overload
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through regurgitant volume (13), while pulmonary hypertension constitutes pressure overload (14-16). These two factors often interact, since regurgitant This
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volume increases with larger trans-tricuspid valve pressure gradients.
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study thus examined right heart structural change associated with TR of all severity, both with and without PH.
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Results showed that Indexed RA volume and tricuspid annulus area both
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enlarge incrementally across trace, mild and significant TR.
PH incrementally
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increased the RA volume in both trace and mild TR, but in cases of significant TR, both TAA and iRA are unaffected by PH presence/absence.
As previously
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shown, RV volume increases only in late significant TR, and is also minimally sensitive to pulmonary hypertension. This study also suggests that PH alone does not produce significant TR. The data show that normal structural anatomy (normalized annulus area, RA and RV volumes) in the setting of significant TR are all unaffected by PH presence/absence. Significant TR may thus require RA, RV and TAA enlargement, consistent with previous results (17). Taken together these results suggest that the RA and tricuspid annulus
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dilate at low pressure (likely from TR derived volume overload), and increased
RA dilation in trace or mild TR should
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chamber walls and greater compliance.
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by PH derived pressure overload. This is plausible based on thin right heart
thus be taken seriously, as it suggests regurgitant volume, even at lower
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pulmonary pressure, is enough to initiate structural heart disease and is
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associated with higher long term mortality in patients with PH (18-21). While the tricuspid annulus area also increases with TR severity, it is
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less sensitive to PH. Mechanisms for these differential responses to PH between
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as the RA expands.
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the RA and tricuspid annulus are uncertain but may result from annular tethering
This study extends prior findings that RA enlargement is an early change It shows that both RA volume and tricuspid annulus area are
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in mild TR.
cardinal indices of structural heart disease across a broad range of TR severity, with and without PH.
Their measurement should be strongly considered for
determining structural heart effects in TR, and may find use in guiding the timing of therapeutic intervention.
Limitations The study has several limitations.
It was retrospective and from a
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single center, and the number of patients in each TR group was relatively
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Selection bias was potentially present in that all subjects underwent
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small.
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CT and 2D echocardiography for clinical reasons, and non-TR patients were excluded in this study, because PA pressure was measured
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echocardiographically, requiring TR for measurement techniques.
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Legends
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Patient distribution and groups according to echocardiographically
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Figure 1
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defined tricuspid valve regurgitation (none/trace, mild and
Methods for RA, RV, and Tricuspid Annulus Area Measurement
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The long axes of the RA and RV were measured from the 4-chamber
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view (A) and a plane orthogonal to this 4-chamber view (B). RA and RV
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areas were measured by manual tracing from these views. RA and RV
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volumes were calculated using Simpson’s method. RA: right atrium,
RV:right ventricle
The tricuspid annulus plane (C) was measured in a plane defined by the
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Figure 2
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moderate/severe).
tricuspid leaflets’ most basal attachments. Measurements of area (D), major and minor diameters are shown (E). TAA:tricuspid annulus area. Figure Adapted from (8)
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PH(+)
Significant TR
Significant TR
(n=22)
(n=42)
65.6
68.8
(59.5, 71.7)ac
(64.4, 73.2)bc
1.95
1.89
1.86
(1.93, 2.04)
(1.89, 2.02)
(1.78, 2.01)
(1.78, 1.95)
10 (33.3)
53 (52.0)
31 (43.1)
8 (36.4)
17 (40.5)
0.05
96 (51.3)
13 (43.3)
43 (42.2)
37 (51.4)
9 (40.9)
21 (50.0)
0.65
HT, N (%)
124 (66.3)
18 (60.0)
53 (52.0)
57 (79.2)
11 (50.0)
29 (69.1)
0.0053
DM, N (%)
36 (19.3)
7 (23.3)
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Table 1 Patient Characteristics
17 (16.7)
13 (18.1)
3 (13.6)
6 (14.3)
0.9217
6 (3.2)
1 (3.3)
7 (6.9)
3 (4.2)
3 (13.6)
3 (7.1)
0.2406
COPD, N (%)
12 (6.4)
2 (6.7)
1 (1.0)
13 (18.1)
1 (4.6)
7 (16.7)
0.0003
CKD, N (%)
12 (6.4)
3 (10.0)
8 (7.8)
2 (2.8)
0 (0.0)
10 (23.8)
0.0045
CHF, N (%)
18 (9.6)
3 (10.0)
13 (12.8)
16 (22.2)
6 (27.3)
14 (33.3)
0.0010
Left valve
25 (187)
11 (36.7)
29 (28.4)
31 (43.1)
10 (45.5)
26 (61.9)
<0.0001
31 (16.6)
10 (33.3)
29 (28.4)
26 (36.1)
11 (50.0)
18 (42.9)
0.0001
59
57
58
57
48
52
<0.0001
mean (95% CI)
(57.7, 61.2)a
(52, 61)ab
(56, 60)a
(43, 53)c
(49, 56)bc
PASP
31±5a
47±7b
33±4a
35±4a
55±15c
PH(-)
PH(+)
Trace TR
Trace TR
Mild TR
Mild TR
(n=187)
(n=30)
(n=102)
(n=72)
Age, mean
61.9
66.3
62.7
(95% CI)
(59.8, 64.0)a
(61.1, 71.5)ab
(59.9, 65.5)a
BSA, mean
2.00
1.98
1.98
(95% CI)
(1.96, 2.04)
(1.89, 2.08)
Gender (male)
106 (56.7)
IHD, N (%)
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N (%)
EF (%)
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disease, N (%) AFib, N (%)
(66.0, 72.8)b
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Cardiomyopathy
69.4
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N (%)
PH(-)
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PH(+)
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PH(-)
(54,60) ab 47±8b
P-value
0.002
0.06
<0.0001
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Table 2a
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Relationship between TR severity and PH Trace TR
Mild TR
Significant TR
PH(-)
187 (86.2)
102 (58.6)
22 (34.4)
PH(+)
30 (13.8)
72 (41.4)
42 (65.6)
P value
<0.001
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Table 2b
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N (%)
n-TAA*
PH(+)
PH(-)
PH(+)
PH(-)
PH(+)
Trace TR
Trace TR
Mild TR
Mild TR
Significant TR
Significant TR
(n=187)
(n=30)
(n=102)
(n=72)
(n=22)
(n=42)
667
685
724
924
873
(647, 688)
a
Minor/Major
0.78
TAD (cm)
(0.76, 0.79)
RA index*
44 (42, 46)
a
RV index*
58 (56, 60)
a
LA index*
45 (43, 47)
a
55 (53, 57)
a
726
ab
abc
b
63 (57, 69)
b
0.78 ac
(847, 1007)
c
0.84 a
c
0.84 bc
<0.001 c
(0.79, 0.88)
(0.81, 0.87)
bc
49 (46, 52)b
56 (52, 61)c
78 (68, 89)d
72 (65, 79)
d
<0.001
ab
58 (55, 61)ab
63 (59, 67)b
84 (76, 94)c
79 (73, 86)c
<0.001
bc
50 (47, 53)b
57 (53, 62)c
59 (52, 68)c
58 (53, 64)c
<0.001
ab
57 (54, 61)ac
61 (57, 66)bc
67 (59, 76)b
68 (63, 75)b
<0.001
Mean adjusted for age and gender, *geometric means (95% CI)
abcd
(820, 930)
<0.001
(0.75, 0.81)
51 (45, 57)
60 (54, 67)
(690, 760)
P value
(0.77, 0.82)
51 (50, 57)
#
(698, 756) 0.79
(0.76, 0.84)
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LV index*
(636, 738) 0.81
a
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(95% CI)
PH(-)
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#
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Mean
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Structural Heart Enlargement by TR and PH
cells with same superscripts within row do not differ,
p>0.05
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References Nath J, Foster E, Heidenreich PA. Impact of tricuspid regurgitation on long-term
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1. 2.
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survival. J Am Coll Cardiol 2004;43:405-9.
Sagie A, Schwammenthal E, Padial LR, Vazquez de Prada JA, Weyman AE, Levine
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RA. Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients. J Am Coll Cardiol 1994;24:446-53. 3.
Sugimoto T, Okada M, Ozaki N, Hatakeyama T, Kawahira T. Long-term evaluation of treatment for functional tricuspid regurgitation with regurgitant volume:
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characteristic differences based on primary cardiac lesion. J Thorac Cardiovasc Surg 1999;117:463-71. 4.
Fukuda S, Gillinov AM, Song JM et al. Echocardiographic insights into atrial and journal 2006;152:1208-14.
5.
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ventricular mechanisms of functional tricuspid regurgitation. American heart Kim HK, Kim YJ, Park JS et al. Determinants of the severity of functional tricuspid Braunwald NS, Ross J, Morrow AG. Conservative management of tricuspid
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6.
D
regurgitation. Am J Cardiol 2006;98:236-42. regurgitation in patients undergoing mitral valve replacement. Circulation 7.
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1967;35:I63-9.
Zoghbi WA, Enriquez-Sarano M, Foster E et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802. Nemoto N, Lesser JR, Pedersen WR et al. Pathogenic structural heart changes in
AC
8.
early tricuspid regurgitation. J Thorac Cardiovasc Surg 2015. 9.
Nagueh SF, Kopelen HA, Zoghbi WA. Relation of mean right atrial pressure to echocardiographic and Doppler parameters of right atrial and right ventricular function. Circulation 1996;93:1160-9.
10.
Rogers JH, Bolling SF. Surgical approach to functional tricuspid regurgitation: should we be more aggressive? Curr Opin Cardiol 2014;29:133-9.
11.
Teman NR, Huffman LC, Krajacic M, Pagani FD, Haft JW, Bolling SF. "Prophylactic" tricuspid repair for functional tricuspid regurgitation. Ann Thorac Surg 2014;97:1520-4.
12.
Casa LD, Dolensky JR, Spinner EM, Veledar E, Lerakis S, Yoganathan AP. Impact of pulmonary hypertension on tricuspid valve function. Annals of biomedical engineering 2013;41:709-24.
13.
Rodriguez L, Anconina J, Flachskampf FA, Weyman AE, Levine RA, Thomas JD. Impact of finite orifice size on proximal flow convergence. Implications for Doppler
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quantification of valvular regurgitation. Circ Res 1992;70:923-30. 14.
Hill MR, Simon MA, Valdez-Jasso D, Zhang W, Champion HC, Sacks MS. Structural
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and mechanical adaptations of right ventricle free wall myocardium to pressure 15.
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overload. Annals of biomedical engineering 2014;42:2451-65.
Louie EK, Lin SS, Reynertson SI, Brundage BH, Levitsky S, Rich S. Pressure and
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volume loading of the right ventricle have opposite effects on left ventricular ejection fraction. Circulation 1995;92:819-24. 16.
Rogers JH, Bolling SF. The tricuspid valve: current perspective and evolving management of tricuspid regurgitation. Circulation 2009;119:2718-25. Mutlak D, Aronson D, Lessick J, Reisner SA, Dabbah S, Agmon Y. Functional
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17.
tricuspid regurgitation in patients with pulmonary hypertension: is pulmonary artery
pressure
the
only
18.
of
regurgitation
severity?
Chest
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2009;135:115-21.
determinant
Sandoval J, Bauerle O, Palomar A et al. Survival in primary pulmonary hypertension. Validation of a prognostic equation. Circulation 1994;89:1733-44. Cioffi G, de Simone G, Mureddu G, Tarantini L, Stefenelli C. Right atrial size and
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19.
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function in patients with pulmonary hypertension associated with disorders of respiratory system or hypoxemia. Eur J Echocardiogr 2007;8:322-31. Raymond RJ, Hinderliter AL, Willis PW et al. Echocardiographic predictors of
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20.
adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002;39:1214-9.
Willens HJ, Fertel DP, Qin J, Labrador E, Lowery MH. Effects of age and pulmonary arterial hypertension on the different phases of right atrial function. Int J
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21.
Cardiovasc Imaging 2008;24:703-10.
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Figure 1
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Figure 2
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Highlights for Review
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It is well known that right heart structural abnormalities occur in tricuspid regurgitation and pulmonary hypertension, and they may occur independently or
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together. What is unknown is the relative impact of each on cardiac structure.
This study examined the interactions of TR severity and PH on right heart
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structural changes.
but less so to pulmonary hypertension.
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TR severity,
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We found that RA Volume and the Tricuspid annulus area were very sensitive to In significant TR, neither
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RA volume nor TAA are substantially affected by PH.
RA volume and tricuspid annulus area are thus the most sensitive structures to TR, enlarge in proportion to TR severity.
By contrast, pulmonary hypertension
impacts RA volume less, and tehn in trace and mild TR. RA volume best reflects TR impact on right heart structure, both with and without PH. Right atrial volume and tricuspid annulus area are the cardinal indices of TR-induced right heart structural disease at all severities.