Tricuspid Regurgitation

Etiology

The lesions in tricuspid regurgitation may be categorized as primary where the intrinsic abnormalities in the tricuspid valvular apparatus are responsible or secondary where the right ventricular dilatation causes tricuspid regurgitation. Secondary disorders like tricuspid annular dilation and/or leaflet tethering in the setting of right ventricular pressure and/or volume overload are largely responsible for tricuspid regurgitation as compared to primary disorders involving the valve apparatus. [5],[6],[7]

Secondary Tricuspid Regurgitation

In adults, tricuspid regurgitation is most commonly secondary with probable normal anatomical leaflets and chords. Dilatation of the right atrium, the right ventricle, along with dilatation of the tricuspid annulus[8], and tethering of the tricuspid valve leaflet are some of the causes of secondary tricuspid regurgitation. This may result due to 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.[9]

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

• Left-sided heart failure
• Mitral stenosis or regurgitation
• Primary pulmonary disease: Cor pulmonale, pulmonary embolism, pulmonary hypertension of any cause
• 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 in adults, conditions that directly affect the tricuspid valvular apparatus are rare.

Causes of primary TR include:

• Direct valve injury from a permanent pacemaker or implantable cardioverter-defibrillator lead placement or removal or endomyocardial biopsy in cardiac transplant recipients
• Chest wall or deceleration injury trauma
• Infective endocarditis: Intravenous drug use, neoplasms, alcoholism, extensive burns, infected indwelling catheters, and immune deficiency causes infection of the valve. An annular abscess is common.
• Ebstein anomaly is the most common form of congenital disease affecting the tricuspid valve: The posterior and the septal leaflets of the tricuspid valve are displaced apically in the right ventricle resulting in its atrialization.
• Rheumatic valve disease is the most common cause of pure tricuspid regurgitation due to damage of 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.[10]
• Myxomatous degeneration associated with tricuspid valve prolapse, which occurs in as many as 40% of patients with prolapse of the mitral valve
• Connective tissue disorder, for example, Marfan syndrome, Ehlers-Danlos: Pure tricuspid regurgitation is seen. It may be due to mildly dilated tricuspid annulus without floppy leaflets and floppy tricuspid valve leaflets.[11]
• Marantic endocarditis in systemic lupus erythematosus or rheumatoid arthritis
• 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. [12],[13]

Epidemiology

The incidence of tricuspid regurgitation in the United States is found to be 0.9%. No gender or racial differences in the incidences are noted.

Tricuspid regurgitation presents at different age groups depending on its etiology. 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 years.

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.[14] Tricuspid regurgitation is defined by the backflow of blood from the right ventricle into the right atrium during systole. In mild to moderate cases of tricuspid regurgitation, no major hemodynamic consequences are noted due to the comparatively compliant nature of the right atrium. However, in severe cases, right ventricular volume overload develops that eventually results in right-sided congestive heart failure presenting with peripheral edema, ascites, and hepatic congestion.

The severity of tricuspid regurgitation is increased during inspiration. The right ventricle widens during inspiration, which further enlarges the tricuspid valve annulus, hence increasing the effective regurgitant orifice area.[15]

History and Physical

Symptoms

Patients present with clinical features of right-sided heart failure. These may be painful hepatosplenomegaly, ascites, and peripheral edema. In severe cases, pulsations in the neck from the distended and pulsatile jugular veins is 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 or 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. Increase in venous return causes jugular venous distension, and it is more prominent with inspiration (Kussmaul’s sign).
• S3 gallop is associated with an extremely dilated RV.
• Pansystolic murmur: It is high pitched and loudest in the fourth intercostal space in the parasternal region. The intensity of the murmur increases during inspiration, exercise, leg raising (due to increase in venous return) and decreases in standing position and during Valsalva maneuver.
• Ascites
• Cachexia and jaundice
• Atrial fibrillation
• Peripheral edema
• Right ventricular heave due to dilated right ventricle and S4 gallop that increases with inspiration

Evaluation

The main modality used to diagnose and evaluate tricuspid regurgitation is Doppler echocardiography. It is used to precisely contemplate regurgitant blood flow and its flow velocity and accurately measure the systolic pressure in the right ventricle

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.
• The dilated right atrium and right ventricle in the presence of moderate to severe tricuspid regurgitation
• The tricuspid annulus is often dilated.
• The paradoxical interventricular septal movement that reflects the increased volume within the right ventricle (diastolic overload)
• Right ventricle function that may be hyperdynamic, normal, or reduced, thus reflecting the underlying cause of tricuspid regurgitation and the degree of RV compensation.
• Other abnormalities may be seen when the tricuspid regurgitation are due to pulmonary hypertension secondary to a left-sided cardiac abnormality.
• The peak regurgitant flow velocity across the tricuspid valve is measured which helps in estimating the right ventricular and pulmonary arterial systolic pressure. The modified Bernoulli equation is used to convert it to a pressure gradient following which the gradient is added to an estimate of the right atrial pressure. Thus the extent of pulmonary hypertension can be estimated. [16][17]

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 common

Serum Chemistry: Abnormal liver function test, 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 ECG may show right axis deviation indicating RV 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.

Treatment / Management

The preference of treatment depends on the severity of tricuspid regurgitation, etiology, and the presence and the 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

In patients with tricuspid regurgitation secondary to left-sided heart failure, adequate control of fluid overload is indicated. Diuretics are suggested in these cases. Loop diuretics are commonly used. Restricted intake of salt is indicated. The head of the bed should be elevated as it may improve dyspnea. Digitalis, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors and anticoagulants are indicated in these patients. Atrial fibrillation, if present, can be controlled by starting the patients on antiarrhythmics.

The following medications are used:

• Diuretics: Furosemide
• Antiarrhythmics
• Digoxin
• Angiotensin-converting enzyme inhibitors
• Anticoagulants

Tricuspid Valve Surgery

Indications for tricuspid valve surgery depend upon whether surgery for left-sided (aortic or mitral) valve disease is indicated

For patients undergoing left-sided valve surgery:

1. Tricuspid valve surgery is recommended in these patients with severe TR, 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 [18],[19],[20] 
2. Patients undergoing left-sided valve surgery and who have mild, moderate or severe TR, concomitant tricuspid valve repair is recommended in the following cases:
(A1)

• 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[21], and similar recommendations are indicated in the 2012 ESC guidelines[22]
(A1)

Isolated Tricuspid Surgery

The appropriate timing of isolated tricuspid valve surgery is not well established.

In patients who are refractory to medical treatment but have severe tricuspid regurgitation, tricuspid valve surgery is suggested (weak recommendation). It is preferred to perform it before the onset of significant right ventricular dysfunction to control or prevent symptoms, as recommended in the 2014 AHA/ACC valvular guidelines.[21](A1)

In symptomatic and severe isolated tricuspid regurgitation without right ventricular dysfunction, tricuspid valve surgery is strongly recommended as per the 2012 ESC valvular guidelines.[22]

In asymptomatic or minimally symptomatic patients with severe TR, the role of tricuspid valve surgery is ambiguous. The 2014 AHA/ACC valvular guidelines note this uncertainty and include a very weak recommendation that tricuspid valve surgery may be considered for asymptomatic or minimally symptomatic patients with severe primary tricuspid regurgitation and progressive moderate or greater RV dilation and/or systolic dysfunction.[21]. The ESC guidelines view surgery in this setting slightly more favorably and indicate that surgery should be considered in patients with severe isolated tricuspid regurgitation with mild or no symptoms and progressive right ventricular dilation or deterioration of right ventricular function.[22](A1)

Treatment Based on the Etiology

In tricuspid valve endocarditis, it is recommended to excise the tricuspid valve without immediate replacement. The excision of the diseased valve wipes out the endocarditis while the antibiotic treatment is continued. An artificial valve can be inserted if the right heart failure symptoms are refractory to medical management and the infection is well controlled.

In Ebstein anomaly, no surgery is needed in asymptomatic tricuspid regurgitation. However, symptomatic patients may need to be treated with the tricuspid valve repair or replacement.

Differential Diagnosis

The differential diagnosis of tricuspid regurgitation are as follows:

• 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

Prognosis of tricuspid regurgitation is generally good.

Complications

Complications include:

1. Cardiac cirrhosis
2. Ascites
3. Thrombus formation and embolization

Complications of operative interventions include:

1. Heart block
2. Thrombosis of the prosthetic valve
3. Infection
4. Arrhythmias