Pulmonary Regurgitation

Overview

Anatomy

Pulmonary or pulmonic valve:

• Semilunar valve between the right ventricle (RV) and pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy (PA)
• Consists of 3 cusps: anterior, left, and right
• Opens during systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle as the RV pressure exceeds the pulmonary trunk Pulmonary Trunk Truncus Arteriosus pressure
• Closes during diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle as the RV pressure drops ( S2 S2 Heart Sounds), preventing retrograde flow Retrograde flow Veins: Histology from the pulmonary trunk Pulmonary Trunk Truncus Arteriosus

Epidemiology and Etiology

Definition

• Abnormal backflow of blood through the pulmonic valve into the RV during ventricular diastole Ventricular diastole Cardiac Cycle
• Trace or mild (physiologic) pulmonic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (PR) found commonly in normal individuals

Epidemiology and Etiology

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: moderate to severe pulmonary regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) affects approximately 0.11% of adults (compared to 0.67% for tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)).
• Median age at diagnosis: 77 years
• Gender Gender Gender Dysphoria distribution: Nearly equal between males and females
• Moderate PR:
  • 77% due to pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
• Severe PR:
  • 52% congenital or iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome (e.g., post-surgical treatment or pulmonary balloon valvotomy Balloon valvotomy Percutaneous procedure to separate and stretch the valve leaflets to increase the valve opening. Tricuspid Stenosis for pulmonary stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) in children)
  • 39% due to pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
• Other causes:
  • Carcinoid: Often presents with mixed pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy disease (both PR and pulmonary stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)).
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
  • Marfan syndrome Marfan syndrome Marfan syndrome is a genetic condition with autosomal dominant inheritance. Marfan syndrome affects the elasticity of connective tissues throughout the body, most notably in the cardiovascular, ocular, and musculoskeletal systems. Marfan Syndrome: associated with dilation of the pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy ring
• Congenital PR (isolated) is rare.

Pathophysiology and Clinical Presentation

Pathophysiology

• PR stems from the following abnormalities:
  • Abnormalities in valve morphology
  • Dilation of the pulmonic valve ring
  • Congenitally absent or malformed valve
• With PR, the backflow causes increased preload Preload Cardiac Mechanics and afterload Afterload Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics.
• RV overload → RV enlargement to compensate for the increased volume → RV dysfunction (tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (TR) may follow)
• RV dysfunction eventually leads to ↓ cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics → ↑ heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology to maintain tissue oxygenation → symptoms of exercise intolerance due to increased oxygen demand.
• Complications: RV failure, thromboembolic events, hepatic congestion, arrhythmias

Symptoms

• Commonly asymptomatic during mild to moderate disease
• Severe PR:
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, palpitations Palpitations Ebstein’s Anomaly, syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
  • With associated TR and RV failure: hepatic congestion, ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema

Signs

• Increased jugular venous pressure Jugular Venous Pressure Portal Hypertension (JVP)
• Graham-Steell murmur:
  • Hallmark of PR
  • High-pitched, decrescendo diastolic murmur heard best at the 2nd left intercostal space at the sternal border (from ↑ RV stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle)
  • Increases with inspiration Inspiration Ventilation: Mechanics of Breathing
  • Diminishes with Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse
  • Split S2 S2 Heart Sounds with loud P2, and an RV lift (from RV enlargement)

Diagnosis and Management

Diagnosis

• Transthoracic echocardiogram Transthoracic echocardiogram Endocarditis ( TTE TTE Imaging of the Heart and Great Vessels) with Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography):
  • Assessment of pulmonic valve morphology and function
  • Detects severity of PR, which is determined by jet width and duration
  • Severe PR: The regurgitant jet fills the RV outflow tract (> 50% pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy annulus width).
  • Also shows RV enlargement, systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy
• Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG)):
  • Right ventricular hypertrophy Right Ventricular Hypertrophy Tetralogy of Fallot 
  • Right axis deviation 
  • Right atrial (RA) enlargement (P pulmonale)
  • Arrhythmias from RV dilation
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • Prominent PA
  • RA and RV enlargement
• Exercise testing:
  • Can detect exercise-induced arrhythmias
  • Evaluates exertional symptoms to help decide need for valve replacement

• Cardiac magnetic resonance Cardiac magnetic resonance Aortic Regurgitation imaging:
  • Helps assess RV size and function 
  • Evaluates severity of PR by quantifying the regurgitant jet
• Cardiac catheterization Cardiac Catheterization Procedures in which placement of cardiac catheters is performed for therapeutic or diagnostic procedures. Cardiac Surgery:
  • Not necessary for diagnosis
  • Used in evaluating pulmonary vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing and preoperative coronary artery Coronary Artery Truncus Arteriosus disease assessment

Management

• Monitoring:
  • Annual examination and echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA)
  • Those with repaired tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot or who have undergone balloon valvotomy Balloon valvotomy Percutaneous procedure to separate and stretch the valve leaflets to increase the valve opening. Tricuspid Stenosis need at least a yearly cardiology check-up.
• Medical therapy:
  • Associated heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, angiotensin converting enzyme inhibitors Angiotensin converting enzyme inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis prophylaxis Prophylaxis Cephalosporins: with history of infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
• Surgical pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy replacement:
  • Symptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Mild or moderate RV or left ventricular systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy
  • Severe RV dilation
  • RV systolic pressure due to RV outflow tract > ⅔ of systemic pressure
  • Progressively reduced exercise tolerance Tolerance Pharmacokinetics and Pharmacodynamics
• Transcatheter Pulmonary Valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy Replacement (TPVR):
  • Minimally invasive option for severe PR with suitable anatomy (e.g., prior surgical conduits)
  • Common in repaired tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot or post-surgical PR to avoid open surgery
  • Indicated for symptomatic PR, RV dysfunction, or severe RV dilation (assessed by MRI/CT)
• Anticoagulation Anticoagulation Pulmonary Hypertension Drugs:
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with mechanical valve prosthesis
  • Temporary (3–6 months) for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with bioprosthetic valves

Clinical Relevance

• Tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot (TOF): cyanotic congenital heart disease characterized by the tetrad of RVH, an overriding aorta Overriding Aorta Tetralogy of Fallot, pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS), and a ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot. Surgically corrected TOF is a common cause of subsequent pulmonary regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD).
• Ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot: a common heart defect that allows passage of blood from the high-pressure left ventricle to the lower-pressure right ventricle. Ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot produces a holosystolic murmur Holosystolic Murmur Tricuspid Valve Atresia (TVA) in the left 3rd and 4th interspaces along the sternum Sternum A long, narrow, and flat bone commonly known as breastbone occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck. Chest Wall: Anatomy. Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension can occur, resulting in high-pressure pulmonary valve Pulmonary valve A valve situated at the entrance to the pulmonary trunk from the right ventricle. Heart: Anatomy regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). 
• Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension: a heterogeneous condition of high blood pressure in the pulmonary vasculature that could be idiopathic Idiopathic Dermatomyositis (without underlying lung or cardiac disease) or from secondary causes. Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension may lead to PR and right heart abnormalities.
• Carcinoid syndrome Carcinoid syndrome A symptom complex associated with carcinoid tumor and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. Symptoms are caused by tumor secretion of serotonin, prostaglandins, and other biologically active substances. Cardiac manifestations constitute carcinoid heart disease. Carcinoid Tumors and Syndrome: small, slow-growing neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma. The tumors are associated with unregulated vasoactive hormone production, inducing development of fibrous Fibrous Fibrocystic Change endocardial plaques and leading to pulmonic and tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy abnormalities.
• Rheumatic fever Rheumatic fever Acute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever: a late complication of untreated streptococcal pharyngeal infection characterized by valvular abnormalities, most commonly of the left heart. While rare, the pulmonic valve can be affected concurrently with the mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy.