Tricuspid Stenosis

Etiology

Tricuspid stenosis is the narrowing of the tricuspid orifice that obstructs blood flow from the right atrium to the right ventricle. The right atrium hypertrophies and distends, and sequelae of right heart disease-induced heart failure develop but without right ventricular dysfunction. The right ventricle remains underfilled and small. The cause of tricuspid stenosis can be broadly classified into 3 categories: acquired, congenital, and iatrogenic.[2]

Acquired Tricuspid Stenosis

Rheumatic heart disease is the most common cause of acquired tricuspid stenosis. The condition almost always occurs in conjunction with mitral stenosis. In a series of 173 patients with rheumatic heart disease, 15 had tricuspid stenosis [3]

Large infected vegetations can cause relative stenosis.[4] Carcinoid syndrome can produce isolated tricuspid stenosis or, more commonly, mixed regurgitant and stenosed lesions.[5]

Systemic diseases that can cause tricuspid stenosis include systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APAS), known to cause nonbacterial thrombotic endocarditis. Hypereosinophilic syndrome and endomyocardial fibrosis can also give rise to tricuspid stenosis.[6]

Benign tumors like atrial myxomas can produce this valvular abnormality.[7] Among metastatic tumors, renal and ovarian tumors are known to metastasize and grow into the tricuspid orifice, causing stenosis.[8]

Congenital

Congenital tricuspid stenosis is very rare, arising from tricuspid deformities due to deformed leaflets and chordae and displacement of the entire valve apparatus. Tricuspid stenosis is usually found in conjunction with other cardiac abnormalities, such as:

• Small-volume right ventricular sinus cavity
• Pulmonary atresia or severe pulmonary valvar stenosis and no ventricular septal defect
• Absent right ventricle sinus and a double-inlet single left ventricle
• Ventricular septal defect without pulmonary valvar atresia or severe stenosis
• Rhabdomyoma of ventricular septum

Other less common causes of tricuspid stenosis include congenital abnormalities such as Ebstein anomaly and metabolic or enzymatic abnormalities such as Fabry and Whipple diseases.[9][10]

Iatrogenic

The presence of permanent pacing and fusion of implantable cardioverter defibrillator leads within subvalvular structures can cause tricuspid stenosis.[11][12] Tricuspid stenosis may also occur after overzealous tricuspid valve repair for tricuspid regurgitation, eg, bioprosthetic tricuspid valve stenosis (a serious and late complication of tricuspid valve replacement).[13] 

Valvular disease linked to anorectic medications, such as fenfluramine, phentermine, and methysergide, can also lead to tricuspid narrowing. Prolonged use of these drugs is connected to thickened, fibrotic, and hypomobile tricuspid leaflets, leading to varying levels of valve stenosis and regurgitation.[14][15][16] Methysergide has been associated with tricuspid stenosis since 1974.[17] Microdosing of certain psychedelic drugs can increase the risk of valvulopathy and tricuspid stenosis.[18]

Epidemiology

Tricuspid stenosis accounts for about 2.4% of all cases of organic tricuspid valve disease and is commonly seen in young women. This condition accounts for less than 1% of valvular heart diseases.[19][20] In a study of 13,289 patients with primary valvular disease, tricuspid stenosis was found in 0.3%, followed only by pulmonary stenosis in 0.04%. At least 90% of these patients had rheumatic heart disease.[21]

Pathophysiology

The primary result of tricuspid stenosis is right atrial pressure elevation and right-sided congestion. Tricuspid stenosis causes increased pressure between the right atrium and ventricle during diastole, amplified during inspiration and exercise, and reduced during expiration. Increasing severity of tricuspid stenosis leads to failure to augment cardiac output during exercise. Clinically, tricuspid stenosis results in signs and symptoms of systemic congestion.

The valves consist of an outer layer of valve endothelial cells (VECs) surrounding 3 layers of the extracellular matrix, each with a specialized function and interspersed with interstitial valve cells (VICs).[19] Genetic or acquired (eg, environmental) causes that disrupt the normal organization and composition of the extracellular matrix and communication between VECs and VICs alter valve mechanics and interfere with the valve leaflet function, culminating in valve damage.[22] Rheumatic tricuspid stenosis is characterized by diffuse fibrous thickening of the leaflets and fusion of 2 or 3 commissures. Leaflet thickening usually occurs without calcific deposits, and the anteroseptal commissure is most involved.

Tricuspid stenosis in carcinoid syndrome is caused by the deposition of fibrous plaques through vasoactive substance-mediated reactions, mainly serotonin. The deposition of endocardial plaques results in plaque distortion, leading to tricuspid stenosis and regurgitation. Methysergide and serotonin share common chemical properties. Methysergide, a synthetic ergot alkaloid, causes fibrotic thickening and structural deterioration of the tricuspid valve.[23] 

SLE can lead to tricuspid stenosis. This condition may result in the formation of immune deposits and fibrous plaques, along with the development of Libman-Sacks endocarditis. The fibrous reaction can cause valve thickening and commissural fusion, while Libman-Sacks endocarditis can lead to valve obstruction.[24] Incompletely developed leaflets, shortened or malformed chordae, a small annulus, or an abnormal number or size of papillary muscles may result in congenital tricuspid stenosis.[25]

Limited data exist on the natural history of isolated tricuspid stenosis, often associated with rheumatic mitral valve disease. Like mitral stenosis, acquired tricuspid stenosis results from a chronic, slowly progressive disease process characterized by a gradual increase in stenosis severity and a slow onset of symptoms. The underlying cause influences the mortality rate associated with tricuspid stenosis.

History and Physical

History

Patients with tricuspid stenosis may present with features of systemic congestion and reduced cardiac output, frequently with accompanying valvular heart disease such as mitral stenosis. Common symptoms include exertional dyspnea, fatigue, and exertional syncope.[26][27] Patients often experience general fatigue and weakness due to low cardiac output. These symptoms may be accompanied by a loss of appetite and a history of weight loss. The patient may also describe a feeling of fast neck pulsations. Right hypochondriac pain may be due to the stretching of the Glisson capsule by the congested liver. Carcinoid tumors, if present, may manifest with skin flushing, diarrhea, palpitations, and fatigue.

Clues to the possible etiology of the condition may be obtained from a thorough history. For example, patients may report signs and symptoms of a prior rheumatic fever episode. Infants may have the condition as a prenatal diagnosis. Chronic medical conditions, long-term use of certain medications, and prior surgical procedures may all be helpful during the clinical investigation.

Physical

The lungs are clear in patients with isolated tricuspid stenosis. Pulmonary edema often occurs due to a concomitant mitral valve pathology. The precordial examination may reveal an opening snap followed by a middiastolic rumble at the left 4th intercostal space with a shorter duration and softer intensity than a mitral stenosis murmur. The murmur and opening snap intensity increase with maneuvers that boost blood flow across the tricuspid valve, such as inspiration, leg raising, amyl nitrate inhalation, squatting, or exercise. The jugular venous pressure is elevated in tricuspid stenosis. Thus, the Kussmaul sign, or failure of jugular venous pressure to fall with inspiration, may also be seen. Signs of systemic congestion include leg edema, ascites, anasarca, and congestive hepatopathy. 

Evaluation

The diagnosis of tricuspid stenosis may be complicated by the subtlety of symptoms in some patients and overlapping presentations in others where it cooccurs with another cardiac pathology. Thus, diagnostic testing is usually critical to the comprehensive evaluation of this condition.

Laboratory Studies

Metabolic panels may reveal mildly elevated unconjugated bilirubin, alkaline phosphatase, or aminotransferases, usually related to hepatic congestion. Arterial blood gas analysis may show respiratory alkalosis with varying degrees of compensation in patients with persistent shortness of breath.[28]

However, the laboratory findings in most cases are nonspecific and potentially influenced by the underlying cause. For example, patients with SLE may manifest with pancytopenia and antinuclear antibody positivity. Individuals with carcinoid syndrome may have elevated blood levels of 5-hydroxyindoleacetic acid and N-terminal pro-b-type natriuretic peptide, which are sensitive and specific predictors of carcinoid heart disease.[29]

Chest Radiograph

Isolated tricuspid stenosis may manifest with right atrial enlargement and clear lung fields. When accompanying mitral stenosis, interstitial edema or straightening of the left heart border may be seen. 

Electrocardiogram 

An electrocardiogram may show P-pulmonale—tall and peaked P waves—as evidence of right atrial enlargement. Tall and peaked T waves are mainly observed in leads II, III, and aVF. At least 50% of patients develop atrial fibrillation. 

Jugular Venous Pulse Tracing

The jugular venous pressure is elevated with a prominent or giant A wave classically greater in height than usually perceived. The conspicuous A wave is due to contraction of the right atrium against a stenosed tricuspid valve in sinus rhythm.

If tricuspid regurgitation coexists or when the rhythm is not regular, as in atrial fibrillation and flutter, the A wave becomes undermined by a similarly elevated V wave. A slow y descent may also be seen due to delayed emptying of the right atrium into the right ventricle.[30] 

Transthoracic Echocardiogram 

A transthoracic echocardiogram (TTE) is performed to assess the valve area and gradients across the valve to determine the severity of tricuspid stenosis and guide management strategy (see Image. Tricuspid Stenosis on Transthoracic Echocardiography). TTE parameters help establish the severity of the disease.[31] These TTE parameters are:

• Thickening and distortion of the tricuspid valve, with or without calcification
• Commissural fusion with doming of the valve
• Valve area less than 1 cm² signifies severe tricuspid stenosis. This parameter is calculated by dividing 190 with pressure half-time. The normal area of the tricuspid valve is 4 cm².
• Transvalvular gradient across the tricuspid valve of more than 5 to 10 mm Hg at a heart rate of 70 beats per minute suggests severe stenosis. Gradients are affected by the patient's hemodynamic status.
• Significant tricuspid regurgitation that can potentially alter the management strategy. Surgical correction may be needed instead of percutaneous intervention.
• Pressure half-time of more than 190 msec
• Inflow-time velocity integral of more than 60 cm
• Right atrial enlargement
• Plethoric inferior vena cava

Cardiac Catheterization

Tricuspid stenosis manifests with a large right atrial A wave of 12 to 20 mm Hg and a mean diastolic gradient of 4 to 8 mm Hg across the tricuspid valve. The mean gradient across the tricuspid valve is more significant in tricuspid stenosis, as an end-diastolic gradient may be absent due to the lower filling pressures on the right side of the heart.[32] Elevated right atrial pressures with a slow fall in early diastole and a diastolic pressure gradient across the tricuspid valve are characteristic of tricuspid stenosis.

Treatment / Management

Little evidence exists regarding the management and outcomes of tricuspid stenosis. Treatment centers on addressing the underlying mechanical obstruction. Medical therapy has a limited role. 

Medical

Loop diuretics may help relieve systemic and hepatic congestion in patients with severe, symptomatic tricuspid stenosis.[33] Caution is advised, however, since diuretics may excessively decrease the preload in patients with a low output state. Not every tricuspid stenosis case requires invasive intervention. SLE and APAS treatment may reduce the “coating” over the valves and chordae and, subsequently, stenosis and regurgitation.[34] Fenfluramine or methysergide withdrawal has been associated with valve normalization.[35] However, advanced cases often warrant surgical therapy besides medical management.(A1)

Intervention

Percutaneous valvotomy can be performed for patients with unacceptable surgical risk and absence of tumor, thrombus, vegetation, and insignificant or mild tricuspid regurgitation. Surgical correction (repair or replacement) is suggested for patients with low-to-moderate surgical risk or significant regurgitation. Surgical correction is recommended for patients with coexisting valvular heart diseases, such as mitral stenosis.[36]

Surgical procedures used to treat tricuspid stenosis include valvotomy and valve replacement or repair. Valvotomy is performed using 1, 2, or 3 balloons. While some stenosis may persist, the change in valve area significantly reduces the transvalvular pressure gradient and right atrial pressure.[37] Valve area generally increases by 1 to 2 cm2.[38] Bioprosthetic valve stenosis can be treated with balloon valvotomy or valve-in-valve replacement.

Tricuspid valve surgery includes repair or replacement. Surgery is usually reserved for cases with concomitant mitral valve involvement. Repair should be attempted when reasonable. Sometimes, a simple open commissurotomy suffices. When repair is not an option, valve replacement may be performed with an open approach. No differences in long-term outcomes have been established between bioprosthetic and mechanical valves.[39] However, a mechanical valve is preferred over a bioprosthetic carcinoid syndrome to avoid rapid degeneration.(A1)

Tricuspid valve surgery is indicated for symptomatic severe tricuspid stenosis accompanied by tricuspid regurgitation (eg, rheumatic and carcinoid heart diseases), as percutaneous balloon tricuspid commissurotomy may worsen regurgitation. The operative mortality for isolated tricuspid stenosis is significant and increases if performed with other valvular surgery (10% and 16%, respectively).[40](B2)

Differential Diagnosis

Diseases that can delay right atrial emptying during diastole and mimic tricuspid stenosis include but are not limited to the following:

• Cardiac mass-occupying lesions or tumors
• Thrombotic events or emboli
• Atrial myxoma/rhabdomyoma
• Congenital membranes causing supravalvular obstruction
• Tricuspid atresia
• Endocarditis with large vegetation near or around the right ventricular outflow tract
• Endomyocardial fibrosis/Loeffler endocarditis

Conditions that impair right-sided heart filling and produce similar symptoms and physical findings to those with tricuspid stenosis include the following:

• Restrictive cardiomyopathy
• Pericarditis (effusive-constrictive vs constrictive) [41]

A good clinical evaluation and judicious use of diagnostic exams can help distinguish these conditions and determine the appropriate management approach.

Staging

Clinical symptoms, hemodynamic and echocardiographic assessment, and valve anatomy determine the stage of tricuspid stenosis. The staging is as follows:

• A: Patients at risk for the disease
• B: Progressive disease but mild-to-moderate and asymptomatic
• C: Severe but asymptomatic disease
• D: Severe and symptomatic disease [33]

Stages A and B are usually asymptomatic and do not warrant intervention. Adapted from the American Heart Association executive summary on valvular heart diseases and Nishimura et al, the staging of severe tricuspid stenosis (stages C & D) is elucidated in Table 1. (See Table 1. Staging of Severe Tricuspid Stenosis.)

Table 1. Staging of Severe Tricuspid Stenosis

Prognosis

The underlying cause and the degree of ventricular dysfunction primarily determine the prognosis for tricuspid stenosis. Most patients with isolated tricuspid stenosis who undergo intervention have a good prognosis.[20] However, substantial evidence on long-term outcomes is lacking due to the rarity of this condition.

Complications

The complications of tricuspid stenosis include atrial fibrillation, heart failure, liver failure, and infective endocarditis. Early treatment and continuous monitoring can minimize the risk of these complications.