Tricuspid regurgitation

Etiology

Mild tricuspid regurgitation (TR) is a common finding frequently detected by echocardiography in normal subjects (85-90%).

It is mostly asymptomatic, not easily audible on physical examination and considered benign. Moderate and severe TR is associated with poor prognosis.

TR etiology may be divided into 2 groups: 

1) Functional or secondary TR is the most common cause of TR and is characterized by impaired valve coaptation secondary to annular dilatation and to right ventricular pressure and/or volume overload in the presence of structurally normal leaflets.

Pressure overload is most often caused by:

• pulmonary hypertension secondary to left-sided heart disease
• cor pulmonale 
• primary pulmonary hypertension
• ventricular volume overload related to atrial septal defects
• intrinsic disease of right ventricle (R)V – ischaemic origin or cardiomyopathy

2) Primary or organic TR with structurally altered valve leaflets.

Possible causes:

• infective endocarditis – especially in iv drug users
• rheumatic heart disease (commissural fusion, shortening and retraction of leaflets and of the chordae tendineae)
• iatrogenic valve damage – cardiac surgery, biopsies, catheter placement
• myxomatous disease
• carcinoid syndrome (lack of commissural fusion, thickened valve with markedly restricted motion during cardiac cycle)
• endomyocardial fibrosis 
• Ebstein’s anomaly or congenital defects

Pathophysiology

• TR induces right ventricular and atrial dilatation, both of which tend to increase annular dilatation, which is the key finding in functional TR. 
• With progression, the atrial compliance is lowered and the increased atrial pressure is transmitted to the systemic veins.
• Severe TR can also induce ventricular interdependence and reduction in both right-sided stroke volume and left ventricular (LV) preload.

Image 1 Possible causes of functional TR

Badano LP, Muraru D, Enriquez-Sarano M. Assessment of functional tricuspid regurgitation, EHJ, Volume 34, Issue 25, 1 July 2013, Pages 1875–1885.

Functional classification of TR is usually assessed using the Carpentier’s classification of TR:

Type 1 – Normal leaflet motion

• predominantly caused by annular dilation, rarely by leaflet perforation secondary to infective endocarditis or an iatrogenic complication

Type 2 – Tricuspid valve prolapse

• Prolapse of one or more leaflets
• MV leaflets exhibiting disproportionate excursion into the right atrium

Type 3 - Restricted Leaflet motion

• there is a decreased excursion of one or both leaflets
• consequence of rheumatic disease, toxic valvulopathy, significant calcification

Symptoms

Even severe TR may be well tolerated for a long period of time. It is most often discovered during an echocardiographic examination for another cause.

Most of the symptoms are associated with the associated right-sided heart failure and are load dependent.

• dyspnoea and fatigue
• right-sided congestion – oedema, ascites
• hepatomegaly, hepatojugular reflux, jugular vein expansion, holosystolic murmur
• dyspepsia, anorexia, weight loss – later stages 
• ECG – AF and incomplete RBBB are frequent

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Echocardiography of tricuspid regurgitation

Echocardiography is the primary imaging method for diagnosis and evaluation of the tricuspid regurgitation severity.

Image 2 Parameters measured with transthoracic echocardiography

Vahanian A, Beyersdorf F, Praz F, et al. ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2021 Aug 28:ehab395. doi: 10.1093/eurheartj/ehab395. Epub ahead of print. PMID: 34453165.

1) Tricuspid valve morphology

The tricuspid valve complex is similar to the mitral valve but has greater variability. It consists of the 3 leaflets, annulus, chordae tendineae, RV and papillary muscles. The tricuspid valve is located between the RA and the RV and is placed in a slightly more apical position than the mitral valve.

The tricuspid valve is best visualised using the:

• PLAX of RV inflow
• PSAX at the level of the aortic valve
• apical 4 chamber view
• subcostal views
• TOE – 4 chamber view at 0 degree in the basal transesophageal and esogastric junction

Secondary TR morphology can be evaluated by these parameters:

Systolic tenting area = the area between the tricuspid annulus and the tricuspid leaflets body. Area >1cm2 is associated with severe TR.

Coaptation distance = the distance between the tricuspid annular plane and the point of coaptation measured in mid-systole apical 4 chamber view

Image 3 Effect of the tenting area on ERO

Bigi R, Cortigiani L, Bovenzi F, Fiorentini C. Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications. Cardiovasc Ultrasound. 2009 Dec 14;7:57.

The annulus is not planar, but has a saddle shaped elliptical pattern.

Normal annulus diameter is 28+5 mm in the A4C, significant dilatation starts at 21 mm/m2 (>35 mm) in diastole.

It is rarely possible to visualize all three leaflets at once by 2D echo.

Real-time 3D TTE is capable of showing the whole valve in PSAX view and helps understand the morphology and underlying pathophysiology of TR.

‍TOE is used to view vegetations secondary to endocarditis, venous catheter and pacemaker lead infections and traumatic ruptures.

Image 4 The anatomy of tricuspid valve

Taramasso M, Pozzoli A, Basso C, et al. Compare and contrast tricuspid and mitral valve anatomy: interventional perspectives for transcatheter tricuspid valve therapies. EuroIntervention. 2018 Mar 20;13(16):1889-1898.

‍Video 1 Non-coaptation of leaflets leading to massive tricuspid regurgitation, A4C view  

Image 5  A4C zoomed view on the right heart and TR valve - Measurement of the gap between leaflets of the tricuspid valve reaching 13 mm, note also the significantly enlarged right atrium (area 32.00 cm2)

‍Video 2  3D image of the non-coaptactive tricuspid valve - 3D imaging of the tricuspid valve enables us to better visualize the anatomy, size and geometry of the valve. It is an indispensable part of TR echocardiography assessment before surgical or transcatheter interventional procedures. It puts the relationship between TV apparatus and surrounding cardiac structures into perspective. Below, you can see the regurgitant orifice area that the non-coaptive leaflets create at the centre.

Image 6  Dilated TV annulus (measured at the insertion points of TV leaflets) - 41 mm - leading to tricuspid regurgitation (A4C view)

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2) Colour flow Doppler (CFD) jet

Colour flow Doppler is a good method for detecting the presence of regurgitation, but it should not be used on its own to quantify the severity of TR.

The algorithm is similar to the assessment of mitral regurgitation, but the parameters are less developed. 

CFD gives us information on the presence, size and location of the jet. We can identify the origin of the jet, its width & length and flow convergence into regurgitant orifice. Every jet looks different and there may be more than one jet present.

There are 3 important regions of the regurgitant jet:

1. Colour Jet Area – expansion of the jet within the RA
2. Vena Contracta – narrowest part of the jet in the regurgitant orifice
3. Flow Convergence on the ventricular surface of the leaflets (PISA)

a) Colour jet area

The basic principle is that greater TR severity results in a larger jet within the RA.

The jet should be viewed in all views where it’s visible.

A large eccentric jet adhering, swirling, and reaching the posterior wall of the RA is in favour of severe TR.

b) Vena contracta (VC)

Vena contracta is the narrowest part of the regurgitant jet as it passes through the regurgitant orifice area.

‍Width of the vena contracta corresponds to the diameter of the regurgitant orifice and is a good semi-quantitative parameter of the severity of TR.

Measurement is usually performed in the A4C view with the same adjustment as for MR and should be averaged over two to three beats. 

Ultrasound beam should be perpendicular to flow and the narrowest part immediately superior to the regurgitant orifice is measured.

Severity of regurgitation estimated from VC diameter:

• ≥7 mm defines severe TR
• <6 mm suggests mild to moderate TR, but lower values are difficult to interpret.

Image 7 Vena contracta measurement in severe TR (10 mm), A4C view adjusted to right heart

c) Flow convergence

Flow convergence is a phenomenon seen when liquid flows from a large chamber through a smaller orifice at a fixed rate. Flow velocity gradually increases and is greatest as it converges on the narrowest region of the flow. (More on this method in Mitral Regurgitation).

This method assumes that the orifice is circular, but that is not the case in most of the secondary TR.

Often all parts of the jet are not visible and the jets are eccentric. This leads to great underestimation of the TR severity. 

How is it measured?

The PISA measurement is usually taken in the A4C view, but PSAX or PLAX may be used. Lower the imaging depth and the Nyquist limit to 15-40 cm/s. PISA radius is measured at mid-systole using the first aliasing hemisphere. 

Next EROA (effective regurgitant orifice area – basically the size of the “hole”) is estimated by dividing the instantaneous volume flow through the PISA by the regurgitant velocity, that can be measured by performing a CW Doppler through the TR jet.

An EROA ≥40 mm2 or a regurgitant volume (RVol) of ≥45 mL indicates severe TR.

Video 3 - Severe excentric TR visualised by Colour flow Doppler, A4C view 

Video 4  Massive tricuspid regurgitation, A4C view

Video 5  Severe tricuspid regurgitation, PSAX view at the level of aortic valve - an eccentric regurgitant jet directed against the interatrial septum. 

Video 6  Tricuspid regurgitation, large central regurgitant jet in modified PLAX view

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3) Pulsed wave Doppler - Anterograde velocity of tricuspid inflow

Pulsed wave (PW) Doppler is capable of analyzing waves reflected from a specific location. Thanks to that we can measure volumes of blood flowing in specific parts of the heart by placement of the Doppler line.

How is it measured?

This Doppler tracing is best measured in apical 4 window (A4C) with the Doppler line parallel to the direction of the flow at the tricuspid leaflet tips. 

Similar to MR, the severity of TR will affect the early tricuspid diastolic filling (E velocity). The tricuspid E-wave velocity increases with the severity of TR. 

A dominant E wave with a peak E velocity >1 m/s suggests severe TR.

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4) Continuous wave Doppler of TR jet

CW Doppler enables us to measure velocities across the tricuspid valve orifice.

Tricuspid regurgitation jet velocity reflects the pressure gradient between the RV and the right atrium throughout the systole.

‍To obtain an adequate signal use an RV-optimized apical four-chamber view and colour Doppler to locate the vena contracta.

a) Wave density on CW Doppler

The density of the CW Doppler signal is proportional to the number of blood cells (=volume of blood) within the sampling area.

‍The denser the signal, the more severe TR usually is. A faint CW Doppler signal is then suggestive of mild TR.

b) Waveform shape on CW Doppler

Waveform shape also aids in identifying the severity of TR.

• truncated/notched wave with triangular contour and an early peak velocity (blunt) – indicates elevated RA pressure or a great regurgitant pressure wave due to severe TR
• respiratory variation – decreased TR velocity with inspiration suggests an elevated RA pressure

The velocity of the TR jet does not provide specific information about the TR severity. As the TR progresses, the pressure difference between RV and RA almost equalises and even massive TR can have a low jet velocity (~2 m/s). Conversely, a mild TR can be associated with high-velocity jet when pulmonary hypertension is present!

Image 8 CW Doppler measurement of moderate/severe TR, A4C view - observe the dense signal and blunt triangular shape of the CW signal (peak velocity 2,43 m/s)

Image 9 CW Doppler measurement of severe TR jet, PSAX view - dense signal and triangular shape of the CW spectral shape. Peak velocity 3,48 m/s.

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5) Hepatic vein flow

PW Doppler evaluation of the hepatic venous flow pattern is another tool for grading TR (sensitivity 80%).

With increasing severity of TR the pressure in RA rises and propagates back into the venous system, resulting in a vena cava inferior dilatation (>2,1cm) and a systolic flow reversal in hepatic veins.

How is it measured?

Use a subcostal view and place the sample volume within a hepatic vein. This way the hepatic veins appear parallel to the Doppler line. The hepatic flow is highly influenced by respiration, making it difficult to capture as the sample volume moves out of the vein lumen, and should therefore be averaged across 3 beats.

In normal conditions, the flow pattern consists of anterograde systolic wave (S), antegrade diastolic wave (D) and a retrograde A-wave caused by atrial contraction with a rather low velocity (0.5 - 0.8 m/sec).

In the presence of severe TR a systolic flow reversal occurs, and the S wave appears above the line. 

‍Video 7  Dilated Inferior vena cava due to massive TR (non-collapsible with respiration)

Video 8 Dilated Inferior vena cava and Hepatic Veins with Colour Doppler - turbulent and reverse flow in the veins is visualized

Image 10 PW Doppler of Hepatic Vein Flow - systolic flow reversal is seen with positive S waves present

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6) RV function and dimensions

TR leads to RV dilation and dysfunction, RA enlargement and further tricuspid annular dilatation and tethering. It is therefore important to always assess the RV dimensions and function. 

With increasing diastolic pressure in the RV, the ventricle may be D shaped on PSAX views as the septum bulges towards the LV. This ventricular interdependence might reduce LV volume, causing restricted LV filling and increased LV diastolic and PAP pressure.

Image 11 Four examples of various degrees of TR

Lancellotti P, Tribouilloy C, Hagendorff A, et al. Scientific Document Committee of the European Association of Cardiovascular Imaging. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2013 Jul;14(7):611-44.

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Intervention

Management of TR is based on the cause of TR, the presence and extent of symptoms and signs of heart failure, the severity of TR, and the presence and extent of associated abnormalities, including pulmonary hypertension, tricuspid annular dilation, and other valve disease. 

1) Medical therapy

Is limited and generally symptomatic. Diuretics are usually used to reduce congestion. The underlying cause of functional TR needs to be identified and treated, if possible. If there is coexistent severe pulmonary hypertension, drugs reducing pulmonary artery pressure or pulmonary vascular resistance may be used.

2) Surgical treatment

Should be performed before the right ventricle gains irreversible dysfunction.

Patients with TR are typically older and suffer from multiple co-morbidities, making open-heart surgery a high-risk procedure.

The indication is usually discussed at the time of surgical correction of left-sided valvular lesions, as it does not increase operative risk and provides improvement of functional status and reverse remodelling of RV.

In severe primary tricuspid regurgitation, surgery is recommended even in asymptomatic patients with signs of progressive RV dilatation or decline in RV function. 

In functional/secondary TR, valve repair is preferable to valve replacement, as it is generally believed that the long-term results of tricuspid annuloplasty are better than those obtained after valve replacement, whether by mechanical or bioprosthetic implants. 

The most used method in patients with suitable anatomy, preserved right ventricular function and acceptable surgical risk is ring annuloplasty, preferably with prosthetic rings.

Nowadays, it consists of implantation of an undersized ring (rigid, semi-rigid, flexible) or a flexible band in a goal of reducing the annular dilation (Image 12).

Tornos Mas P, Rodríguez-Palomares JF, Antunes MJ. Secondary tricuspid valve regurgitation: a forgotten entity. Heart. 2015 Nov;101(22):1840-8.

Complete valve replacement should be considered when the TV leaflets are significantly damaged and the annulus is severely dilated.

TVR has a very high operative mortality (7 – 40%) and 10-year survival rates of 37 – 58%.

‍Valve replacement is usually performed alongside left-heart valve surgery.

Image 13 Indications for surgical treatment of tricuspid regurgitation

Vahanian A, Beyersdorf F, Praz F, et al. ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2021 Aug 28:ehab395. doi: 10.1093/eurheartj/ehab395. Epub ahead of print. PMID: 34453165.

3) Transcatheter treatment options

As of now, we have different groups of devices divided by the mechanism of action into annuloplasty devices, coaptation devices and heterotopic caval valve implantation.  

Image 14 Tricuspid valve treatment options

Asmarats L, Puri R, Latib A, Navia JL, Rodés-Cabau J. Transcatheter Tricuspid Valve Interventions: Landscape, Challenges, and Future Directions. J Am Coll Cardiol. 2018 Jun 26;71(25):2935-2956.

The TriClip technique is the most common technique applied for percutaneous TR treatment. It is based on the same principle as the MitraClip used on MV (Image 15).

A successful TriClip implantation was associated with reduced mortality and less readmission for heart failure.

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The procedure is at this time indicated for patients that have significant tricuspid regurgitation (4/4) or moderate TR with annulus dilatation >40mm (3/4) on TTE/TOE.

Suitable patient group

• patients with high operative risk - older patients with significant comorbidities (CKD, COPD,..)
• NYHA classification III-IV, dependent on diuretics
• readmissions for right-sided heart failure

Suitable echocardiography findings

• secondary TR without structural leaflet lesions, coaptation defect (ideally <4 mm)
• good TTE and TOE visibility for navigation during intervention
• preserved or partial leaflet mobility, mild annular dilatation
• normal RV function

Contraindications

• Significant pulmonary hypertension (sPAP >60 mmHg on TTE)
• Fixated severe precapillary pulmonary hypertension (on right-sided catheterization)
• Moderate to severe mitral regurgitation (>3/4)
• Previous intervention on TV (surgery or percutaneous)
• Active infectious endocarditis, rheumatic heart disease
• Unfavourable ICD/CS electrode position - the clip cannot be placed
• Pregnancy

Video 9 Release of the TriClip device, position check under skiascopy.

‍Video 10 TriClip in situ (A4C)

‍Image 16 Management of TR

Vahanian A, Beyersdorf F, Praz F, et al. ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2021 Aug 28:ehab395. doi: 10.1093/eurheartj/ehab395. Epub ahead of print. PMID: 34453165.

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References

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