Tricuspid Regurgitation

Etiology

In tricuspid regurgitation, lesions fall into 2 categories: primary, where intrinsic abnormalities in the tricuspid valvular apparatus are responsible, and secondary, where right atrial or ventricular dilatation causes tricuspid regurgitation. The most common cause of tricuspid regurgitation is secondary or functional regurgitation. Secondary disorders like tricuspid annular dilation and leaflet tethering in right ventricular pressure and volume overload are largely responsible for tricuspid regurgitation compared to primary disorders involving the valve apparatus.[6][7][8]

Secondary Tricuspid Regurgitation

Tricuspid regurgitation is most commonly secondary in adults, with probable normal anatomical leaflets and chords. Dilatation of the right atrium and the right ventricle, along with dilatation of the tricuspid annulus and tethering of the tricuspid valve leaflet, are some of the causes of secondary tricuspid regurgitation.[9] This may result from conditions affecting the right ventricle or may be due to an increase in right ventricle systolic pressure, often with pulmonary hypertension. The valves are anatomically normal, but because of the enlarged right ventricular cavity and dilatation of the annulus, the leaflets fail to coapt appropriately. Conditions affecting the right ventricle that eventually cause tricuspid regurgitation include cardiomyopathies and ischemic heart diseases involving the right ventricular myocardium and tricuspid papillary muscles.[10]

The conditions that induce pulmonary hypertension and secondary right ventricle dilatation include the following:

• Left-sided heart disease: Left ventricular dysfunction or left-sided valvular heart disease resulting in pulmonary hypertension
• Pulmonary hypertension: Cor pulmonale, pulmonary embolism, pulmonary hypertension of any cause left to right shunt
• Right atrial abnormalities: Atrial fibrillation [11]
• Stenosis of the pulmonic valve or pulmonary artery
• Hyperthyroidism

Primary Tricuspid Regurgitation

In adolescents and young adults, the cause of tricuspid regurgitation is usually congenital, but conditions that directly affect the tricuspid valvular apparatus are rare in adults.

Causes of primary TR include the following:

Acquired disease 

• Infective endocarditis: Intravenous drug use, neoplasms, alcoholism, extensive burns, infected indwelling catheters, and immune deficiency cause infection of the valve
  • An annular abscess is common.
• Iatrogenic: Direct valve injury from a permanent pacemaker or implantable cardioverter-defibrillator lead placement or removal or endomyocardial biopsy in cardiac transplant recipients. 
  • Its prevalence is increasing due to the widespread use of devices with right-sided leads, necessitating specialized interdisciplinary management that includes electrophysiologists skilled in device therapy and transvenous lead extraction. The condition may arise from mechanical interference of the lead with the tricuspid valve apparatus or pacing-induced right ventricular dysfunction.
• Traumatic: Chest wall or deceleration injury trauma
• Rheumatic valve disease: The most common cause of pure tricuspid regurgitation due to damage to the tricuspid leaflets.
  • The valves undergo fibrous thickening without commissural fusion, fused chordae, or calcific deposits.
• Carcinoid syndrome: Isolated tricuspid regurgitation (may occur)
  • The valve leaflets adhere to the right ventricular wall owing to the fibrous plaques on the valve leaflets and the endocardium. Thus, the tricuspid cusps do not coapt appropriately during systole—causing tricuspid regurgitation.[12] 
• Myxomatous degeneration associated with tricuspid valve prolapse
  • This occurs in as many as 40% of patients with mitral valve prolapse.
• Marantic endocarditis in systemic lupus erythematosus or rheumatoid arthritis
• Endomyocardial fibrosis
• Drug-induced disease
  • In some studies, there is an association between tricuspid regurgitation and the combined use of the anorectic drugs fenfluramine and phentermine. The dopamine agonist pergolide may induce tricuspid regurgitation.[13][14]

Congenital conditions 

• Ebstein anomaly: The most common form of congenital disease affecting the tricuspid valve. The tricuspid valve's posterior and septal leaflets are displaced apically in the right ventricle, resulting in its atrialization.
• Connective tissue disorder (eg, Marfan or Ehlers-Danlos Syndrome): Pure tricuspid regurgitation is seen and may be due to mildly dilated tricuspid annulus without floppy leaflets and floppy tricuspid valve leaflets.[15]
• Tricuspid valve tethering with ventricular septal aneurysm and perimembranous ventricular septal defect
• Tricuspid valve dysplasia
• Giant right atrium 

Epidemiology

Moderate to severe tricuspid regurgitation (TR) affects approximately 3% to 6% of the general population.[16] Still, its prevalence is significantly higher among patients with left-sided valve disorders, particularly those with heart failure (HF), encompassing both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), where it ranges from 10% to 23%.[17] In the context of heart failure, TR is linked to a higher risk of mortality and increased rates of HF-related hospitalizations.[18]

The negative impact on prognosis escalates with the severity of TR and persists regardless of right ventricular dysfunction, pulmonary hypertension, associated mitral regurgitation, left ventricular dysfunction, or atrial fibrillation.[19] Tricuspid regurgitation presents at different age groups depending on its etiology. An Ebstein anomaly may be diagnosed at birth and during early childhood. Rheumatic valvular disease is the most common form of tricuspid regurgitation in patients older than 15.

The prevalence of right heart failure (RHF) is substantial, but it varies greatly depending on the underlying causes, populations studied, and the criteria used for diagnosis. In many earlier studies, RHF has often been described as right ventricular dysfunction (RVD). Results from a meta-analysis of 11 studies involving patients with heart failure with reduced ejection fraction (HFrEF) revealed a broad range in the prevalence of RVD, from 19% to 77%, mainly due to varying definitions of RVD.[20]

Similarly, results from another meta-analysis involving 4835 patients with HFpEF found that the prevalence of RVD was 28% when defined by tricuspid annular plane systolic excursion (TAPSE) less than 16 mm, 18% when using right ventricular (RV) fractional area change (FAC) less than 35%, and 21% for RV S' less than 9.5 cm/s. Regardless of the criteria or cause, RVD has been consistently associated with an increased risk of both morbidity and mortality. The impact of RHF on survival is influenced by the clinical severity, with the most severe presentations—characterized by TAPSE  less than 17 mm, New York Heart Association class IV, peripheral edema, and the need for diuretic therapy—being linked to the lowest 5-year survival rates.[21]

Pathophysiology

Primary structural abnormalities of the tricuspid valvular apparatus or secondary abnormalities due to myocardial dysfunction or dilatation are responsible for the structural incompetence of the tricuspid valve.[22] The backflow of blood from the right ventricle into the right atrium during systole defines tricuspid regulation. In mild to moderate cases of tricuspid regurgitation, no significant hemodynamic consequences are noted due to the comparatively compliant nature of the right atrium. However, in severe cases, right ventricular volume overload develops, which eventually results in right-sided congestive heart failure presenting with peripheral edema, ascites, and hepatic congestion.

The tricuspid annulus is dynamic and changes with the change in loading conditions; factors affecting the degree of tricuspid regurgitation include right ventricular preload, afterload, and right ventricular systolic function.[2] During inspiration, the severity of tricuspid regurgitation increases. The right ventricle widens during inspiration, further enlarging the tricuspid valve annulus and increasing the effective regurgitant orifice area.[23]

Carpentier’s functional classification, based on leaflet mobility, can describe secondary TR effectively. Carpentier type I corresponds to normal leaflet motion with predominant tricuspid annulus dilation, which is common in atrial secondary TR. Carpentier type IIIb involves leaflet tethering with restricted systolic motion, typically seen in ventricular secondary TR. While the Carpentier classification was initially designed to guide mitral valve surgical repair or replacement, its application for TR is less established but practical for case discussion and presentation. However, the Carpentier classification may be used to discuss and present cases.

The Carpentier classification categorizes mitral valve regurgitation into 3 types based on the motion of the leaflets:

• Type I: Normal Leaflet Motion
  • Causes: Annular dilation, leaflet perforationJet Direction: Centrally directed regurgitation jet
• Type II: Excessive Leaflet Motion
  • Causes: Papillary muscle rupture, chordal rupture, redundant chordaeJet Direction: Eccentric jet, directed away from the involved leaflet
• Type III: Restricted Leaflet Motion
• IIIa: Restricted in Both Systole and Diastole
  • Causes: Rheumatic heart diseaseJet Direction: May be centrally or eccentrically directed
• IIIb: Restricted in Diastole
  • Causes: Papillary muscle dysfunction, left ventricular dilationJet Direction: May be centrally or eccentrically directed [24]

History and Physical

Symptoms

Patients present with clinical features of right-sided heart failure. These features may be painful hepatosplenomegaly, ascites, and peripheral edema. In severe cases, pulsations in the neck from the distended and pulsatile jugular veins are noted. Exercise intolerance may be seen. Clinical features of the underlying condition causing tricuspid regurgitation may be observed. For example, pulmonary hypertension may cause symptoms such as weakness, shortness of breath, and exercise intolerance; patients presenting with infective endocarditis, a common cause of tricuspid regurgitation, may present with febrile episodes.

Physical Examination

• Jugular venous distension with a prominent V wave reflects the elevation in right atrial pressure. An increase in venous return causes jugular venous distension, which is more prominent with inspiration (Kussmaul sign)
• S3 gallop is associated with an extremely dilated right ventricle
• Pansystolic murmur: high-pitched and loudest in the fourth intercostal space in the parasternal region. The intensity of the murmur increases during inspiration, exercise, and leg raising (due to an increase in venous return) and decreases in a standing position and during the Valsalva maneuver
• Ascites
• Cachexia and jaundice
• Atrial fibrillation
• Peripheral edema
• The right ventricular heave is due to a dilated right ventricle and S4 gallop, which increases with inspiration.

Evaluation

The primary modality used to diagnose and evaluate tricuspid regurgitation is Doppler echocardiography. This modality is used to precisely contemplate regurgitant blood flow and its flow velocity and accurately measure the systolic pressure in the right ventricle. See Video. Tricuspid Valve Doppler. Echocardiography modalities have various advantages and pitfalls (see Table 1). 

Echocardiographic Findings

• Tricuspid valve motion may be normal or abnormal. Characteristic primary valvular abnormalities include Ebstein anomaly, leaflet prolapse, flail leaflet, endocarditis, carcinoid heart disease, and rheumatic valve disease.
• A dilated right atrium and right ventricle in moderate to severe tricuspid regurgitation.
• The tricuspid annulus is often dilated.
• The paradoxical interventricular septal movement reflects the increased volume within the right ventricle (diastolic overload).
• Right ventricle function may be hyperdynamic, normal, or reduced, thus reflecting the underlying cause of tricuspid regurgitation and the degree of right ventricle compensation.
• There may be other abnormalities seen when tricuspid regurgitation is due to pulmonary hypertension secondary to a left-sided cardiac abnormality.
• The peak regurgitant flow velocity across the tricuspid valve is measured, which helps estimate the right ventricular and pulmonary arterial systolic pressure. The modified Bernoulli equation converts this to a pressure gradient, which is then added to estimate the right atrial pressure. Thus, the extent of pulmonary hypertension can be estimated.[25][26]
• Normal right ventricular systolic function is characterized by tricuspid annular plane systolic excursion >16 mm, fractional area change >35%, and right ventricle end-systolic area <20 cm². 
• Stages of tricuspid regurgitation are presented in Table 2.   
• Parameter/severity of tricuspid regurgitation is categorized as mild, moderate, or severe (see Table 3).

Table 1. Advantages and Pitfalls of Echocardiography Modalities

Table 2. Stages of Tricuspid Regurgitation 

Table 3. Grading Severity of Tricuspid Regurgitation Based on Echocardiography Findings

Additional Tests

Chest Radiography 

The following findings are noted:

• Marked cardiomegaly in severe tricuspid regurgitation
• Pleural effusions and ascites with diaphragmatic elevation
• Pulmonary arterial and venous hypertension are common

Serum chemistry: Abnormal liver function test and hyperbilirubinemia secondary to hepatic congestion may be noted.

Electrocardiography: Nonspecific ST and T waves in the right precordial leads reflecting right ventricular dysfunction seen. If pulmonary hypertension causes tricuspid regurgitation, the electrocardiogram may show right axis deviation, indicating right ventricle hypertrophy and tall R waves in V1 to V2. In severe pulmonary hypertension, right atrial hypertrophy and P pulmonale may also be present.

Cardiac catheterization: Elevated end-diastolic pressures in the right atrium and right ventricle are noted.

Cardiac CT scan and magnetic resonance (CMR) imaging can provide valuable information in defining tricuspid valve anatomy in various imaging planes; however, these imaging modalities have the limitation that flow cannot be separated from structural imaging, as can be done with color Doppler echocardiography. Both help determine the right ventricular size, function, and remodeling.

Treatment / Management

Treatment preference depends on the severity of tricuspid regurgitation, etiology, and the presence and extent of associated abnormalities, including pulmonary hypertension, heart failure, and other valve conditions.

Management of severe tricuspid regurgitation includes medical therapy, counseling regarding pregnancy and physical activity, consideration of tricuspid valve surgery, and evaluation and treatment of the underlying cause.

Medical Treatment

Control fluid overload adequately for patients with tricuspid regurgitation secondary to left-sided heart failure. Diuretics, particularly loop diuretics, are commonly recommended. Advise a restricted salt intake. Consider elevating the head of the bed to improve dyspnea. Additionally, treatment may include using digitalis, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and anticoagulants for optimal management in these cases. Atrial fibrillation, if present, can be controlled by starting the patients on antiarrhythmics.

The following medications are used:

• Diuretics (eg, furosemide)
• Antiarrhythmics
• Digoxin
• Angiotensin-converting enzyme inhibitors
• Anticoagulants

Tricuspid Valve Surgery

The necessity for tricuspid valve surgery hinges on whether surgery for left-sided (aortic or mitral) valve disease is warranted. In a comprehensive international survey focusing on patients with severe left-sided valvular heart disease (VHD) across Europe, several key findings emerged from the results:

• Moderate to severe tricuspid regurgitation (TR) was commonly observed in patients with severe mitral valve disease but was infrequent in those with aortic valve disease.• An escalation in TR severity was linked to a more severe clinical presentation and reduced overall survival at the 6-month mark.• The rate of performing concomitant tricuspid valve (TV) procedures during left-sided heart valve surgeries was high in mitral valve surgeries but notably lower in aortic valve surgeries.• There was strong alignment (88% overall) between the guideline-recommended class I indications for concomitant TV surgery in patients with severe TR and actual clinical practice, particularly for those undergoing mitral valve surgery (95%).• In the majority of cases (76% overall), patients with moderate TR also underwent concomitant TV surgery during left-sided valve procedures.[28](B3)

For patients undergoing left-sided valve surgery

• Tricuspid valve surgery is recommended in patients with severe tricuspid regurgitation, as observed in the 2014 American Heart Association/American College of Cardiology (AHA/ACC) and the 2012 European Society of Cardiology (ESC) valvular disease guidelines [3][29][30] 
(A1)

For patients undergoing left-sided valve surgery and who have mild, moderate, or severe tricuspid regurgitation, concomitant tricuspid valve repair is recommended in the following cases:

• Dilation of the tricuspid annulus (transthoracic echocardiogram indicating a diameter of greater than 40 mm or 21 mm/m² indexed for body surface area or intraoperative diameter greater than 70 mm).
• Previous history of right heart failure; this is a recommendation in the AHA/ACC valve guidelines,[31] and similar recommendations are indicated in the 2012 ESC guidelines.[32]
(A1)

Isolated Tricuspid Surgery

The medical community still needs to establish the optimal timing for isolated tricuspid valve surgery. In primary tricuspid regurgitation, surgical intervention is indicated when the patient is symptomatic despite medical therapy. In patients who are refractory to medical treatment but have severe tricuspid regurgitation, tricuspid valve surgery is suggested (weak recommendation). For patients exhibiting refractoriness to medical treatment yet facing severe tricuspid regurgitation, there is a weak recommendation for tricuspid valve surgery. The preferred timing is before the onset of significant right ventricular dysfunction to control or prevent symptoms, aligning with the 2014 AHA/ACC valvular guidelines.[31](A1)

Tricuspid valve surgery is strongly recommended in symptomatic and severe isolated tricuspid regurgitation without right ventricular dysfunction, as per the 2012 ESC valvular guidelines.[32] In asymptomatic or minimally symptomatic patients with severe tricuspid regurgitation, the role of tricuspid valve surgery is ambiguous.

The 2014 AHA/ACC valvular guidelines note this uncertainty and include a very weak recommendation for considering tricuspid valve surgery for asymptomatic or minimally symptomatic patients with severe primary tricuspid regurgitation and progressive moderate or more significant RV dilation and systolic dysfunction.[31] The ESC guidelines view surgery in this setting slightly more favorably and indicate considering surgery in patients with severe isolated tricuspid regurgitation with mild or no symptoms and progressive right ventricular dilation or deterioration of right ventricular function.[32](A1)

Treatment Based on the Etiology

There is a recommendation to excise the tricuspid valve without immediate replacement in endocarditis. The excision of the diseased valve wipes out the endocarditis while continuing antibiotic treatment. If right heart failure symptoms prove refractory to medical management and the infection is well controlled, surgeons can insert an artificial valve. Asymptomatic tricuspid regurgitation in Ebstein anomaly does not necessitate surgery. However, symptomatic patients may require treatment through tricuspid valve repair or replacement.

For patients with tricuspid stenosis and regurgitation due to carcinoid disease, valve replacement is a viable option if the symptoms are severe or right ventricular dysfunction is evident. The procedure can significantly improve the patient's condition and, possibly, survival rate. However, repairing complex deformities is not always reliable. Previous studies have suggested using mechanical prostheses instead of bioprostheses because of the latter's potential to fail early due to carcinoid plaque formation. Nevertheless, warfarin use presents a higher bleeding risk in patients with liver dysfunction. Bioprosthetic valves may be a better choice for old and young patients, especially women of childbearing age, as it eliminates the need for long-term anticoagulation.

Differential Diagnosis

Differential diagnosis of tricuspid regurgitation include the following:

• Ascites
• Cirrhosis
• Ebstein anomaly
• Eisenmenger syndrome
• Heart failure
• Marfan syndrome
• Cardiogenic shock
• Atrial fibrillation
• Dilated cardiomyopathy
• Biliary disease
• Cor pulmonale
• Mitral regurgitation
• Carcinoid tumor

Prognosis

The growing attention to TR often called the "forgotten valve," stems from consistent evidence in three key areas. First, numerous studies have demonstrated that higher grades of TR severity are independently associated with increased mortality.[33] Second, isolated surgical procedures for TR are rarely performed and carry an in-hospital mortality rate of approximately 8% to 10%.[34] Finally, the early success of transcatheter repair and replacement techniques has expanded access to treatments that are considered relatively low-risk.[35] The prognosis of tricuspid regurgitation is generally good. The presence of elevated pulmonary artery pressure and pulmonary hypertension predict an increased incidence of right ventricular dysfunction and the need for inotropic support post tricuspid valve surgery. 

Complications

Complications of Tricuspid Regurgitation

Increasing evidence suggests that severe TR significantly affects clinical outcomes across various cardiovascular conditions. The fact that many patients present late with advanced TR underscores the disease's underrecognition and the limitations of current guideline-directed medical therapies.

• Cardiac cirrhosis
• Ascites
• Thrombus formation and embolization

Complications of Operative Interventions

Due to the high in-hospital mortality rates linked to isolated tricuspid valve surgery, there is ongoing exploration of transcatheter alternatives to enhance survival and reduce hospitalizations related to heart failure.

• Heart block
• Thrombosis of the prosthetic valve
• Infection
• Arrhythmias