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]