Tricuspid regurgitation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2], Fatimo Biobaku M.B.B.S [3], Basir Gill, M.B.B.S, M.D.[4]

Tricuspid regurgitation (TR) occurs due to the failure of the heart’s tricuspid valve to close properly during systole. As a result, with each right ventricular contraction, there is retrograde blood flow from the right ventricle into the right atrium.

TR is increasingly recognized as a clinically important valvular disease rather than a benign or incidental finding. Moderate and severe TR are independently associated with increased morbidity and mortality, even after adjustment for left-sided heart disease and comorbid conditions. Symptoms of TR are often nonspecific and may be delayed, leading to underdiagnosis and late referral.

TR can be classified as primary or secondary. Primary (or organic) TR results from an organic lesion of the tricuspid valve itself, whereas secondary (or functional) TR is caused by left-sided heart disease and/or pulmonary hypertension without an intrinsic abnormality of the tricuspid valve.

The pathophysiology of TR depends on whether TR is primary or secondary. Primary TR results from an organic abnormality in one or more parts of the tricuspid valve, such as the leaflets, chordae tendineae, or papillary muscles. Secondary tricuspid regurgitation accounts for more than 80% of TR encountered in clinical practice. Secondary TR results from hemodynamic and structural changes in the right ventricle and tricuspid valve apparatus secondary to left-sided heart disease (especially in the setting of mitral valve pathology) and/or pulmonary hypertension. Tricuspid annular dilation is the most important factor in the pathophysiology of secondary TR. In addition, tethering of the leaflets and inadequate leaflet coaptation also contribute to secondary TR.

Most cases of tricuspid regurgitation are secondary (functional), primarily due to tricuspid annulus (TA) dilation and right ventricular enlargement and dysfunction. Such dilation leads to a derangement of the normal anatomy and mechanics of the tricuspid valve and the muscles governing its proper function, resulting in tricuspid valve incompetence. Common causes of right ventricular dilation include left-sided heart pathology, pulmonary hypertension, and right ventricular infarction

The blowing holosystolic murmur of tricuspid regurgitation must be distinguished from mitral regurgitation and a ventricular septal defect.

Moderate or severe TR affects approximately 1·6 million individuals in the USA. Secondary TR is more common than primary TR, accounting for more than 80% of clinically encountered TR.

TR is a common finding. Trace or mild degrees of tricuspid regurgitation of no clinical consequence can be seen in patients with normal tricuspid valve leaflets and annular dimensions. TR might not be recognized clinically until fairly late in its natural history. Patients with significant TR may remain asymptomatic, despite impaired right ventricular function. Approximately 30% to 50% of patients with severe MR have significant secondary TR. Significant degrees of TR has been noted with the onset of atrial fibrillation, especially in older patients above 75 years of age. Moderate and severe TR are associated with increased morbidity and mortality. The higher the severity of TR, the worse the prognosis.

The stage of TR can be estimated based on specific criteria for the valve anatomy, valve hemodynamics, associated cardiac findings, and symptoms. The stages of TR are:

• At the risk of TR
• Progressive TR
• Asymptomatic severe TR
• Symptomatic severe TR

The history of a patient with suspected or confirmed TR should include information about the possible etiologies of primary and secondary TR. TR occurs most commonly secondary to pulmonary hypertension and left heart failure; therefore, detailed information about these conditions should be obtained. The majority of TR cases are asymptomatic. Symptoms of TR include clinical manifestations related to right heart failure such as peripheral edema and abdominal distention. If left heart failure or pulmonary hypertension is the underlying etiology of TR, the patient might have symptoms related to these diseases.

On examination, the jugular venous pressure is usually elevated, and ‘cv’ waves can be seen. The liver may be enlarged and is often pulsatile (the latter finding being virtually diagnostic of tricuspid insufficiency). Peripheral edema is often found. In severe cases, there may be ascites and even cirrhosis (so-called cardiac cirrhosis). Tricuspid insufficiency may lead to the presence of a pansystolic heart murmur. Such a murmur is usually of low frequency and is best heard at the left sternal border. It tends to increase with inspiration. However, the murmur may be inaudible, reflecting the relatively low pressures on the right side of the heart. A third heart sound may also be present.

Transthoracic echocardiography (TTE) is the technique of choice for the evaluation of TR and it should be performed in a patient with suspected tricuspid regurgitation to confirm the diagnosis, determine the etiology, and establish the baseline severity. Echocardiography is also useful for the assessment of right ventricular function and diameter.

A chest X-ray is a useful test during the initial evaluation as well as during follow-up among adolescent and young adult patients with tricuspid regurgitation.

A electrocardiogram (ECG) might have no significant abnormalities. Findings suggestive of right atrial enlargement and hypertrophy might be present secondary to either pulmonary hypertension or to the hemodynamic consequences of TR itself. In the case of TR secondary to left heart disease, the ECG might demonstrate changes related to the underlying condition.

Cardiac stress testing might be useful in the evaluation of asymptomatic patients with evidence of severe tricuspid regurgitation. Cardiac stress testing might identify limitations in exercise, which can guide the consideration of surgery as a treatment modality.

Cardiac magnetic resonance (CMR) may be beneficial for the evaluation of the structure and function of the right atrium and right ventricle, as well as the severity of the tricuspid regurgitation when echocardiography findings are inconclusive, particularly before tricuspid valve surgery.

Cardiac catheterization is useful to evaluate tricuspid regurgitation when the results of the non-invasive testing are insufficient. Cardiac catheterization can be performed when there is discrepancy between the clinical findings and the results of non-invasive testing, in order to rule out cardiac etiologies of pulmonary hypertension as the cause of the patient’s symptoms. Right ventriculography and hemodynamic assessment by cardiac catheterization are used to assess the function of the right ventricle and estimate the severity of the valvular regurgitation.

The main therapy is treatment of the underlying cause. The aim of medical therapy among patients with TR is to treat right heart failure, left heart failure, and/or pulmonary hypertension in case they are present. Medical therapy with diuretics helps improve volume overload.

In most cases, surgery is not indicated. However, tricuspid valve repair at the time of left-sided valve surgery is now recommended in cases of severe TR irrespective of symptoms. It should be considered in mild/moderate secondary TR with significant dilation of the tricuspid annulus. Tricuspid valve surgery can also be beneficial for patients with severe primary TR that is unresponsive to medical therapy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2] Fatimo Biobaku M.B.B.S [3] Basir Gill, M.B.B.S, M.D.[4]

Tricuspid regurgitation (TR) can be broadly classified as primary or secondary. Primary (or organic) TR results from an organic lesion of the tricuspid valve itself, whereas secondary (or functional) TR is caused by left heart failure or pulmonary hypertension without an intrinsic abnormality of the tricuspid valve.

Mechanistically, TR can be classified as primary, secondary or cardiac implantable electronic device (CIED) related. Primary (or organic) TR results from an organic lesion of the tricuspid valve itself, whereas secondary (or functional) TR is caused by left-sided heart disease and/or pulmonary hypertension without an intrinsic abnormality of the tricuspid valve.^[1] Secondary (functional) TR can be further classified according to the predominant mechanism and cardiac remodeling pattern into atrial secondary TR and ventricular secondary TR.^[1] Atrial secondary TR is characterized by right atrial enlargement and tricuspid annular dilation with relatively preserved right ventricular size and function, whereas ventricular secondary TR is associated with right ventricular dilation, papillary muscle displacement, leaflet tethering, and often pulmonary hypertension.^[1] TR in the presence of a CIED lead is classified as either CIED associated TR or CIED related TR. CIED associated TR is not directly caused by the lead while the CIED related TR is directly caused by lead placement.^[1][2][3][4]

Abbreviations: CIED, cardiac implantable electronic device; TR, tricuspid regurgitation

Based on severity, TR is expanded over a 5-grade scale.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2] ; Fatimo Biobaku M.B.B.S [3] ; Vamsikrishna Gunnam M.B.B.S [4] ; Basir Gill, M.B.B.S, M.D.[5]

Tricuspid regurgitation (TR) results in a retrograde flow of blood into the right atrium due to the incompetent tricuspid valve. The pathophysiology of TR depends on whether TR is primary or secondary. Primary TR results from an organic abnormality in one or more parts of the tricuspid valve, such as the leaflets, chordae tendineae, or papillary muscles. Secondary TR commonly results from hemodynamic and structural changes in the right ventricle and tricuspid valve apparatus secondary to left-sided heart pathology and/or pulmonary hypertension. Tricuspid annular dilation is the most important factor in the pathophysiology of secondary TR. In addition, tethering of the leaflets and inadequate leaflet coaptation also contribute to secondary TR.

The tricuspid valve apparatus includes the following structures:^{[1][2][3][4][5][6][1]}

• Leaflets: Septal, anterior, and posterior
• Chordae tendineae
• Papillary muscles

• The pathogenesis of the tricuspid regurgitation involves backflow of blood into the right atrium during systole.^[7]
• When compared to other chambers in the heart right atrium is relatively and hemodynamically stable so there are no noticeable consequences with mild to moderate tricuspid regurgitation.
• But when the regurgitation is severe there is noticeable increase in the venous pressure and right atrial pressure which might result in right-sided heart failure.
• Symptoms of right-sided heart failure include:
  • Ascites
  • Liver failure
  • Shortness of breath
  • Fatigue
  • Edema in ankles, legs, feet and/or abdomen

• Right ventricular systolic dysfunction leads to decreased cardiac output due to continuous rise in right ventricular pressure.^[8]
• Impaired renal function ensues in the presence of increased central and renal venous pressure.^[9]

• Primary TR results from an organic abnormality in one or more parts of the tricuspid valve. ^{[5][10][11][12]}
• Conditions that might contribute to the primary distortion of the tricuspid valve include:^[13][14][15]
  • Rheumatic heart disease
  • Marantic endocarditis
  • Drug-induced tricuspid regurgitation by using drugs like fenfluramine, phentermine and pergolide^[16][17]
  • Ischemic heart disease in which the damages to right ventricle and papillary muscles rupture
  • By placing a permanent pacemaker
  • Implantable cardioverter-defibrillator lead placement
  • Endomyocardial biopsy in cardiac transplant recipients
  • Congenital etiologies like ebstein’s anomaly and marfan syndrome
  • Carcinoid syndrome
  • Iatrogenic etiologies
  • Infectious etiologies which include infective endocarditis.

• The most common cause of tricuspid regurgitation in adults is secondary / functional which can be defined as without anatomical anomalies and normal leaflet and chords structure.
• More than 80% of the cases of TR seen in clinical practice is secondary(functional) in nature and related to tricuspid annular dilatation and leaflet tethering in the setting of right ventricular remodeling caused by pressure or volume overload (or both), myocardial infarction, or trauma.^[6][18]
• In secondary TR, progressive tricuspid annular dilation and right ventricular remodeling lead to worsening leaflet malcoaptation. As regurgitation severity increases, volume overload of the right atrium and ventricle further accelerates chamber dilation, creating a self-perpetuating cycle of disease progression.^[19]
• Ventricular secondary TR is generally associated with more advanced right ventricular dysfunction and worse prognosis than atrial secondary TR.^[19]
• The underlying pathophysiology of secondary TR involves the following changes:^{[1][20][21][22][23]}

• Left heart failure and/or pulmonary hypertension causes dilation of the right ventricle and subsequent tricuspid annular dilation.
• The tricuspid annular dilatation leads to a disruption of the coordinated function of the papillary muscle, tricuspid leaflets and the tricuspid annulus, causing tethering of the leaflets.
• The conditions that might lead to pulmonary hypertension and right ventricular dilation include the following:
  • Left heart failure
  • Mitral stenosis / mitral regurgitation
  • Pulmonic valve stenosis
  • Pulmonary artery stenosis
  • Pulmonary disease
  • Shunt from left to right
  • Eisenmenger syndrome
  • Hyperthyroidism
• When secondary TR is present, it causes further progressive right ventricular remodeling which distorts normal leaflet coaptation.

• In summary, tricuspid annular dilation is the most important factor in the pathophysiology of secondary TR, though tethering of the leaflets and inadequate leaflet coaptation also contribute to secondary TR.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2] Fatimo Biobaku M.B.B.S [3]

Most cases of significant tricuspid regurgitation are due to tricuspid annular dilation and leaflet tethering secondary to right ventricular remodeling from volume and/or pressure overload. Such dilation leads to derangement of the normal anatomy and mechanics of the tricuspid valve and the muscles governing its proper function. The result is incompetence of the tricuspid valve. Common causes of right ventricular dilation include left heart failure, pulmonary hypertension, and right ventricular infarction.

Life-threatening causes of TR, which encompass conditions which may result in death or permanent disability within 24 hours if left untreated, include:^[1][2][3]

• Acute cardiac allograft rejection
• Acute coronary syndrome
• Blunt or penetrating chest trauma
• Infective endocarditis
• Myocardial rupture
• Papillary muscle rupture from ischemic heart disease
• Pulmonary embolism

Common causes of primary tricuspid regurgitation may include:^{[4][5][6][7][8]}

Congenital disease

• Ebstein’s anomaly
• Tricuspid valve dysplasia, hypoplasia, or cleft
• Double orifice tricuspid valve

Some genetic conditions may cause TR which includes the following:^[9][10]

• Trisomy 21
• Trisomy 18
• Trisomy 13
• Turner syndrome

Acquired disease

• Marantic endocarditis
• Rheumatic disease (with left-sided disease)
• Carcinoid syndrome
• Drug-induced tricuspid regurgitation by using drugs like fenfluramine, phentermine and pergolide^[11][12]
• Tricuspid valve prolapse
• Endomyocardial biopsy in cardiac transplant recipients
• Ischemic heart diseases
• Radiation
• Cardiac device (permanent pacemaker, implantable cardioverter-defibrillator) leads
• Trauma

1. Right ventricular endomyocardial biopsy
2. Blunt chest wall trauma^[13]

• Degenerated bioprosthesis

Common causes of secondary tricuspid regurgitation may include:^[4][14]

• Right ventricular and tricuspid annular dilatation

1. Left-sided valvular and/or myocardial disease
2. Pulmonary hypertension independent of left-sided cardiac pathology
3. Right ventricular infarction with remodeling

• Chronic right ventricular pacing (dyssynchrony)
• Atrial fibrillation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2] Basir Gill, M.B.B.S, M.D.[3]

The blowing holosystolic murmur of tricuspid regurgitation must be distinguished from the murmur of mitral regurgitation and a ventricular septal defect.

When diagnosing the mechanism of secondary TR, clinicians must differentiate between atrial and ventricular etiologies; atrial secondary TR occurs without significant right ventricular (RV) remodeling and is often seen in heart failure with preserved ejection fraction (HFpEF).^[1] CIED-related TR must be differentiated from other causes of secondary TR by determining if the lead is directly interfering with the valve apparatus through impingement, perforation, or avulsion.^[2]

Severe tricuspid regurgitation may mimic constrictive pericarditis or restrictive cardiomyopathy due to similar hemodynamic features, including elevated right-sided filling pressures and systemic venous congestion. Comprehensive imaging and, in selected cases, invasive hemodynamic assessment may be required for differentiation.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2] Fatimo Biobaku M.B.B.S [3] Basir Gill, M.B.B.S, M.D.[4]

Tricuspid regurgitation (TR) of mild degree is common in individuals with anatomically normal valves and it has no physiological consequence. Approximately 1.6 million individuals in the USA are estimated to have moderate or severe tricuspid regurgitation. Secondary TR is more common than primary TR, accounting for more than 80% of the TR seen in clinical practice. Clinically significant tricuspid regurgitation is more prevalent in older adults and is observed more frequently in women. Increasing TR severity is associated with a stepwise increase in mortality, and even mild TR has been linked to adverse long-term outcomes.

• The incidence of tricuspid regurgitation is approximately 0.9% in USA.^{[1][2][3][4][3][5]}
• The incidence of tricuspid regurgitation is approximately < 1% internationally.
• In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

• Secondary tricuspid regurgitation constitutes about 80% of significant TR.^[2][6]
• The prevalence of tricuspid regurgitation is approximately 1,600,000 in USA.
• Moderate or severe tricuspid regurgitation has been estimated to be present in up to 1·6 million individuals in the USA.^[3][4]
• The prevalence of TR is reported to be as high as 5.6% in women and 1.5% in men older than 70 years. The Framingham Heart Study, a prospective epidemiologic study, evaluated the prevalence and severity of TR and other valvular diseases by color Doppler examinations in 1,696 men and 1,893 women.^[7]
• The prevalence of TR (with a severity ranging from trace to ≥ moderate regurgitation) was 82% in men and 85.7% in women.
• When trace regurgitation is excluded, the prevalence of TR of a severity ≥ mild was 14.8% in men and 18.4% in women
• In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
• The prevalence of [disease/malignancy] is estimated to be [number] cases annually.

• Patients of all age groups may develop [disease name].
• The severity of tricuspid regurgitation increases with age.
• Tricuspid regurgitation associated with Ebstein anomaly can be diagnosed at birth or in early childhood.
• Tricuspid regurgitation associated with rheumatic fever can be diagnosed usually after 15 years of age.
• As the age increases the severity of TR also increases especially in people who are more than 70 years of age.
• [Disease name] commonly affects individuals younger than/older than [number of years] years of age.
• [Chronic disease name] is usually first diagnosed among [age group].
• [Acute disease name] commonly affects [age group]
• The prevalence of TR increases with age. Shown below are tables depicting the prevalence of TR by age and severity in men and women according to the results of the Framingham Heart Study.^[8]

• There is no racial predilection to tricuspid regurgitation.
• [Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

• [Disease name] affects men and women equally.
• Women are little more commonly affected by tricuspid regurgitation than males.
• The progression of tricuspid regurgitation from mild to moderate to severe also based upon the gender

. .. The study revealed that TR is the second most common valvular regurgitation in the general population, after mitral regurgitation. The prevalence of TR (with a severity ranging from trace to ≥ moderate regurgitation) was 82% in men and 85.7% in women. When trace regurgitation is excluded, the prevalence of TR of a severity ≥ mild was 14.8% in men and 18.4% in women. The elevated prevalence of trace regurgitation can be a normal finding related to an artifact or an anatomic characteristic of the closure of the tricuspid valve.^[8]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2], Fatimo Biobaku M.B.B.S [3], Basir Gill, M.B.B.S, M.D.[4]

Tricuspid regurgitation (TR) is a common finding. TR is mostly a trace or mild regurgitation and usually has no symptoms when pulmonary hypertension and heart failure are absent. However, moderate and severe TR is associated with increased morbidity and mortality. The more severe the TR, the worse the prognosis.

• TR is a common valvular abnormality usually presenting with no symptoms when pulmonary hypertension and heart failure are absent.^[1]
• When symptoms are present, they develop progressively. TR might not be recognised clinically until fairly late in its natural history.^[2]
• Patients with significant TR may remain asymptomatic, despite impaired right ventricular function.^[3]
• Significant degrees of TR have been noted with the onset of atrial fibrillation, especially in older patients above 75 years of age.^[2]
• TR can be present in isolation or associated with other medical conditions. TR commonly occurs among patients with mild/moderate mitral regurgitation (MR) or mitral stenosis.
• Approximately 30-50% of patients with severe MR have significant secondary TR.^[3][4][5]
• Severe TR with pulmonary hypertension/right ventricular dysfunction has a worse prognosis and frequently requires surgical intervention. Isolated mitral valve surgery for mitral valve abnormalities is associated with no improvement of TR in the majority of patients.^[6]
• It is also not uncommon to have residual TR following isolated left-sided valve surgery, especially when some preoperative risk factors are present.^[7]
• Tricuspid valve surgery at the time of left-sided valvulopathy decreases the rate of postoperative residual tricuspid regurgitation.^[8]

• Risk factors for residual TR following isolated left-sided valve surgery

• There is an increased risk of residual tricuspid regurgitation following isolated left-sided valve surgery if the following preoperative risk factors are present:^[7]
  • Older age
  • Female gender
  • Atrial fibrillation
  • Rheumatic etiology
  • Mitral valve surgery
  • Previous valve surgery
  • Long duration of left-sided valve disease before surgery
  • 2+/3+ preoperative TR
  • Enlarged left and right atria

• Complications of tricuspid regurgitation include:^[9][10][11]
  • Right heart failure
  • Atrial arrhythmia
  • Ventricular arrhythmia
  • Cirrhosis
  • Endocarditis
  • Weight loss
  • Anorexia

Tricuspid regurgitation often progresses insidiously, with symptoms developing late in the disease course. Severe TR managed conservatively is associated with high mortality, particularly in the presence of right ventricular dysfunction, hepatic congestion, or renal impairment. End-organ dysfunction related to chronic venous congestion, including cardiohepatic and cardiorenal syndromes, is a major determinant of prognosis.^[12] Recent clinical trials (TRILUMINATE and TRISCEND II) have shown that transcatheter interventions significantly improve quality of life and functional status compared to medical therapy alone, though 1-year mortality benefits have not yet been demonstrated.^[13][14]

• Increased morbidity and mortality is associated with moderate and severe TR.
• The higher the severity of the TR, the worse the prognosis.^[1][15][16] 5223 ambulatory patients in the US Veterans Health Administration system were followed up for 4 years, and increasing severity of tricuspid regurgitation was associated with worse survival ( independent of age, biventricular systolic function, right ventricular size, and inferior vena cava dilatation).^[17][18]
• Severe isolated TR is associated with a worse prognosis compared to the general population.^[19]
• The 5-year survival was 74% in 813 patients with moderate or severe, isolated tricuspid regurgitation who were medically managed and followed up at a center in South Korea.^[2][20]
• Ventricular secondary TR, resulting from RV dilation due to primary RV disease or pulmonary hypertension, carries a less favorable prognosis than atrial secondary TR.^[21]
• Tricuspid regurgitation has been independently associated with reduced long-term survival in patients with ischemic or idiopathic left ventricular systolic dysfunction, with or without clinical heart failure.^[2][22][23]
• Right ventricular dysfunction is associated with postoperative morbidity and mortality following tricuspid valve surgery.^[24]
• Residual TR following TV repair during concomitant left-sided valve surgery is associated with increased morbidity and mortality.^[25]

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