1. Natural History of Tricuspid Regurgitation: Primary vs Secondary
JoAnn Lindenfeld, MD
Professor of Medicine
Director , Heart Failures and Transplantation
Vanderbilt Heart and Vascular Institute

2. JoAnn Lindenfeld, MD I have relevant financial relationships
I have relevant financial relationships
< Consultant:
Relypsa, Resmed, Abbott, St. Jude, VWave, CVRx,
Novartis,
<Grants:
Novartis, Astra Zeneca, NIH, AHA

3. Natural History of Tricuspid Regurgitation(TR)
Is TR associated with poorer survival?
Is the poorer survival associated due to the TR or the associated comorbidities or both?
Primary TR
Secondary TR
Not a minor problem—affects 1.6 million people in the US

4. Causes of Primary and Secondary Tricuspid Regurgitation
Primary causes (25%)
     Rheumatic
Myxomatous
    Ebstein anomaly
    Endomyocardial fibrosis
    Endocarditis
    Carcinoid disease
   Traumatic (blunt chest injury, laceration)
Iatrogenic (pacemaker/defibrillator lead, RV biopsy)
Secondary (Functional) causes (75%)
  Left heart disease (LV dysfunction or valve disease) resulting in pulmonary
hypertension
Any cause of pulmonary hypertension (chronic lung disease, pulmonary
thromboembolism, left to right shunt)
Any cause of RV dysfunction (myocardial disease, RV ischemia/infarction)
Rogers JH, Bolling SF Circulation. 2009;119:

5. Causes of Primary and Secondary Tricuspid Regurgitation
Primary causes (25%) (5%?)
     Rheumatic
Myxomatous
    Ebstein anomaly
    Endomyocardial fibrosis
    Endocarditis
    Carcinoid disease
   Traumatic (blunt chest injury, laceration)
Iatrogenic (pacemaker/defibrillator lead, RV biopsy)
Secondary (Functional) causes (75%) (95%)
  Left heart disease (LV dysfunction or valve disease) resulting in pulmonary
hypertension
Any cause of pulmonary hypertension (chronic lung disease, pulmonary
thromboembolism, left to right shunt)
Any cause of RV dysfunction (myocardial disease, RV ischemia/infarction)
But these primary causes are rarely isolated TR
Rogers JH, Bolling SF Circulation. 2009;119:

6. The More Severe the TR the Worse the Survival
5223 consecutive VA patients with echo and degree of TR reported
Subgroups based on
Normal or High(> 40 mm Hg) Pulmonary Artery
Systolic Pressure(PASP)
Normal (≥ 50%) or reduced LVEF
Echocardiographic TR based on regurgitant jet/right atrial area
(mild < 19%, moderate 20-40%, severe > 41%)
No mention of mitral valve disease
Nath J, et al. JACC 2004;43:405-9

7. The More Severe the TR the Worse the Survival
No TR
(n = 600)
Mild TR
(n = 3,804)
Moderate TR
(n = 620)
Severe TR (n = 199)
p Value
Age (yrs)
62.2 ± 12.8
66.0 ± 12.6
71.9 ± 11.7
71.9 ± 12.4
<
LVEF (%)
57.3 ± 9.1
55.4 ± 11.6
47.1 ± 15.6
40.4 ± 17.2
RV dilation 8%
11%
35%
66%
RV dysfunction 3%
30%
61%
Dilated IVC 6%
44%
76%
Data are presented as the mean value ± SD or percentage of patients.
Nath J, et al. JACC 2004;43:405-9

8. The More Severe the TR the Worse the Survival
PASP ≥ 40 mm Hg
LVEF < 50%
LVEF ≥ 50%
PASP < 40 mm Hg
Nath J et al. JACC 2004; 43:405-9

9. TR is a Predictor of Survival but…..
Nath J et al. JACC 2004; 43:405-9

10. Toplinsky Y et al. JACC: Cardiovascular Imaging, 2014:7:1186-94

11. Baseline Characteristics of Patients With Isolated TR
All Isolated Functional TR (N = 353)
Trivial Isolated Functional TR (n = 211)
Mild to Severe Isolated Functional TR (n = 142)
p Value
Age, yrs
70 ± 14
71 ± 14
0.26
Atrial fibrillation
157 (44)
95 (45)
62 (44)
0.80
Male
115 (33)
71 (34)
44 (31)
0.60
Systolic blood pressure, mm Hg
129 ± 20
130 ± 19
128 ± 20
0.36
Hemoglobin, g/l
13.3 ± 1.6
13.4 ± 1.7
13.1 ± 1.6
0.07
Creatinine, mg/dl
1.13 ± 0.5
1.12 ± 0.3
1.14 ± 0.7
0.68
Bilirubin, mg/dl
0.71 ± 0.4
0.75 ± 0.5
0.68 ± 0.3
0.20
Ejection fraction, %
63 ± 6
64 ± 6
0.12
Age/comorbidity index
4.7 ± 3.0
4.7 ± 2.8
4.7 ± 3.2
Toplinsky Y et al. JACC: Cardiovascular Imaging, 2014:7:

12. Baseline Characteristics of Patients With Isolated TR
Isolated Tricuspid Regurgitation Severity
Severe (n = 68)
Trivial (n = 211)
Mild-Moderate (n = 74)
p Value
 Effective regurgitant orifice, mm2
27 ± 8∗
68 ± 37∗†
<0.0001‡
 Regurgitant volume, ml/beat
23.7 ± 7.9∗
51.4 ± 18.0∗†
 Jet area, cm2
<1
6.6 ± 3.5∗
10.4 ± 4.9∗†
 Tricuspid regurgitant peak velocity, m/s
2.5 ± 0.3
2.7 ± 0.3∗
2.6 ± 0.3∗
<0.0001
 Estimated right atrial pressure, mm Hg
6.0 ± 2.1
8.9 ± 4.0∗
11.9 ± 5.6∗†
 Right ventricular systolic pressure, mm Hg
30.7 ± 6.0
39.3 ± 6.9∗
40.0 ± 6.8∗
 Cardiac index, l/min/m2
2.9 ± 0.7
2.8 ± 0.7
2.6 ± 0.5∗
0.002
 E/A ratio
1.04 ± 0.5
1.06 ± 0.5
1.1 ± 0.5
0.9
 E/e′
11.8 ± 0.3
11.7 ± 4.3
11.6 ± 4.1
 RV enlargement moderate or severe, % 2
19∗
40∗†
 RV end-diastolic area indexed, cm2/m2
11.9 ± 2.5
13.9 ± 3.3
17.0 ± 0.5∗†
Toplinsky Y et al. JACC: Cardiovascular Imaging, 2014:7:

13. Prognosis is Much Worse with Severe Compared to Mild-Moderate Isolated TR
Mortality
Cardiac Death and HF
Also the same for atrial fibrillation or symptomatic vs asymptomatic
Toplinsky Y et al. JACC: Cardiovascular Imaging, 2014:7:

14. RV Dysfunction but not TR Is Associated with poor Outcomes Late After Left Heart Valve Procedures
Only age, LA size, RV systolic function, diabetes, CABG were associated with survival
Kammerlander AA et al. JACC 2014;

15. Impact of preoperative moderate/severe tricuspid regurgitation on patients undergoing TAVR replacement
TR was a risk factor for mortality after adjustment only if LVEF was >40%
Kaplan‐Meier curves showing cumulative all‐cause and cardiac death rates through 2 years after TAVR. Comparison of the cumulative all cause death (A) and cardiac death (B) rates through 2 years in patients with none/mild periprocedural tricuspid regurgitation (TR) compared with patients with moderate/severe periprocedural TR. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER.
n = 518
Barbanti M et al. Cath and CV Int 2015;85:677-84

16. Natural History of Tricuspid Regurgitation
Is TR associated with poorer survival? YES
Is the poorer survival associated due to the TR or the associated comorbidities or both?
Primary due to TR
In secondary ???
When is it too late for RV to reverse remodel?
When is it too late for the TV annulus to reverse remodel?
Why doesn’t the tricuspid valve enlarge? Or does it in some?