Pulmonic regurgitation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2], Aravind Kuchkuntla, M.B.B.S[3], Javaria Anwer M.D.[4]

Pulmonic regurgitation (PR) is a condition where the pulmonary valve is not strong enough to prevent backflow into the right ventricle. Nearly all individuals have physiologic (trace-to-mild) pulmonic regurgitation and the incidence increases with advancing age. Hence, there is a backward flow of blood from the pulmonary artery, through the pulmonary valve, and into the right ventricle of the heart during diastole.

PVR may be classified according to the pulmonary valve morphology and severity of the disease. However, in a small percentage of patients, it is a normal finding. PVR may share overlapping symptoms with certain other conditions such as aortic regurgitation, tricuspid re gurgitation, left to right shunting, right ventricular cardiomyopathy, pulmonary hypertension, infective endocarditis, carcinoid heart disease, syphilis and Marfan syndrome.

The main pathophysiologic mechanism for pulmonary regurgitation includes the backflow of blood into the right ventricle resulting in ventricular overload and ventricular remodeling. Complications that may result from pulmonary regurgitation include progressive right ventricular dilatation, heart failure, tricuspid regurgitation, ventricular arrhythmias, and sudden cardiac death.

The diagnosis of pulmonic regugitation may include detailed history, and physical examination. Certain diagnostic tests such as echocardiography and cardiac MRI may help confirm the diagnosis. The mainstay of treatment for PR may include medical therapy for mild to moderate cases and pulmonary valve replacement in severe cases. Medical therapy may include use of diuretics and ACE inhibitors in patients with right ventricular dysfunction.

Lifelong follow up may be required among patients with PR to monitor pulmonary valve morphology and to assess right ventricular function.

Pulmonic regurgitation murmur was first described as Graham-Steell murmur by Dr. Graham Steel in 1888. Before that The pulmonary valve and its function of allowing blood to the lungs for nourishment was first described by Hippocrates. Ibn Nafis then described the pulmonary circulation. Mondino drew a sketch of the pulmonic valve. In 1888 an early blowing diastolic murmur due to pulmonary hypertension was described by Graham-steel, known as Graham-steel murmur. Techniques were then developed to diagnose pulmonary valve regurgitation via the dye method and cardiac catheterization.

Pulmonary valve regurgitation (PR) may be classified according to etiology of the regurgitant flow, severity of the disease and chronicity. Based on the etiology of the regurgitant flow, PR may be classified into primary and secondary/ functional types. The severity of the disease may classify into mild, moderate, and severe disease. New York Heart Association’s (NYHA) functional classification helps to gauge the severity of the heart failure which is a complication of PR. The severity of PR can be assessed by utilizing the American Heart Association and American College of Cardiology (AHA/ACC) staging of valvular heart disease (VHD).

Pulmonary valve is located at the junction of the right ventricular outflow tract and pulmonary artery. Three equal-sized, semilunar cusps or leaflets make up the pulmonary valve. Pulmonary valve opens during right ventricular systole and closes during right ventricular diastole. Pulmonary regurgitation (PR) may be caused by an acquired alteration in the valvular morphology, idiopathic dilatation of the pulmonary artery (IDPA), pulmonic valve ring dilatation, congenital absence or malformation of the valve, and increasing regurgitation causing right ventricular volume overload. The pathophysiologic mechanism of pulmonic regurgitation includes right ventricular overload resulting in the right ventricular remodeling and progressive decline in function. The rate of decline in right ventricular systolic function is affected by associated conditions such as peripheral pulmonary artery stenosis and pulmonary hypertension which further increase the severity of pulmonary regurgitation. Among patients with severe PR, the gene expression pattern of GRK2 and β2-adrenoceptor (molecular markers of cardiac dysfunction) has been reported to be altered. Isolated PR is uncommon and is usually demonstrated with other valvular abnormalities or in certain conditions. Conditions associated include TOF, rheumatic heart disease and syphilis. On gross pathology vegetative lesions on the pulmonic valve leaflets may be observed among patients with acquired alteration in the valvular leaflet morphology.

A small percentage of pulmonic regurgitation is normal and occasionally can be heard in thin subjects. The most common causes of PR are following repair of tetralogy of Fallot and pulmonary stenosis.

Pulmonic regurgitation (PR) must be differentiated from other diseases that cause blowing decrescendo murmur such as aortic regurgitation. The diseases which may present with overlapping symptoms as pulmonic regurgitation may include aortic regurgitation, tricuspid regurgitation, left to right shunting, right ventricular cardiomyopathy, pulmonary hypertension, infective endocarditis, carcinoid heart disease, syphilis and marfan syndrome.

The prevalence of mild PR among patients with normal anatomy of the pulmonary valve is 40% to 78%. Among patients born with congenital heart disease, 20% of patients have associated abnormalities of the pulmonary valve or the right ventricular outlet obstruction. The incidence and prevalence of PR increases with age. 24% of the deaths due to valvular heart disease are attributed to tricuspid valve and pulmonic valve abnormalities combined. There is one study supporting the increased prevalence of PR among women. In developing countries Pulmonary hypertension (PAH) is primarily due to rheumatic heart disease (RHD) which is rare in developed countries. PAH is a major cause of secondary PR.

MOst potent risk factors for the development of pulmonic regurgitation may include pulmonary hypertension, surgical repair of teratology of Fallot, and congenital heart diseases. Less common but important risk factors include endocarditis, left sided heart disease, previous Ross procedure, collagen vascular disease, and malignancies involving the main pulmonary artery.

There are no specific screening recommendations for patients with pulmonary regurgitation (PR). However, patients on an increased risk of developing PR secondary to conditions such as repair of Tetralogy of Fallot (TOF), pulmonary atresia or truncus arteriosus may be evaluated by routine echocardiography, ECG or MRI to assess right ventricular size and status of pulmonary valve. A study recommends considering ADAMTS19 genetic testing among all patients with multiple semilunar valve abnormalities. The key diagnostic tests that may be used for screening of PAH (a major risk factor for PR) may include doppler transthoracic echocardiography, DLCO, BNP, NT-pro-BNP, serum urate levels, and ECG.

The majority of patients with mild pulmonary regurgitation (PR) are asymptomatic and have a benign course, not progressing to chronic PR. Patients tolerate severe chronic PR for a long period of time and begin to develop symptoms when the right ventricle function begins to decline. Chronic severe PR leads to progressive dilation and systolic dysfunction of the right ventricle resulting in symptoms. The severity of PR after TOF repair can increase over time and patients may develop symptoms from an early age. Complications that may result from PR include progressive right ventricular dilatation, heart failure, tricuspid regurgitation, ventricular arrhythmias, and sudden cardiac death. The prognosis of pulmonic regurgitation depends on the severity of the condition, etiology, and associated complications. Symptomatic patients are treated with pulmonary valve replacement (PVR) and have a good prognosis.

The diagnosis of pulmonic regurgitation may include detailed history, physical examination and diagnostic tests such as EKG, echocardiography, chest x ray and cardiac MRI.

The history and clinical presentation of pulmonary regurgitation (PR) vary with the cause of the regurgitation and right ventricular dysfunction. The patient may present with a history related to the primary cause of PR. Isolated pulmonary regurgitation is usually asymptomatic. However, patients with chronic PR may present with symptoms of heart failure such as dyspnea on exertion, fatigue, ankle edema, hemoptysis, nocturnal cough and palpitations. Smoking or intravenous drug use (recreational) history are important to assess the cause fo PR.

Physical examination findings of pulmonary regurgitation (PR) includes a well-appearing patient. On neck exam, increased JVP, prominent “a” wave, “v” wave in the neck may be observed. Precordial (cardiac) exam may reveal a palpable apical impulse (lift or heave) is usually present at the left lower sternal border because of right ventricular dilation. On auscultation, it may be associated with wide splitting of S2 with right sided S3 accentuated with respiration. Murmur of pulmonic regurgitation may vary depending on the underlying cause. Pedal edema and hepatomegaly demonstrate right heart failure.

EKG findings among patients wit chronic Pulmonic regurgitation (PR) may be non-specific. Ventricular tachycardia is demonstrated on EKG among patients with PR and RV dilatation. Patients may develop atrial flutter/fibrillation after years of PR development. Among patients with tetralogy of Fallot (TOF), increased QRS duration with widened QRS complex reflects the severity of PR and right ventricular dilation predisposes the patients to develop malignant arrythmias.

Chest x ray may not be required for the diagnosis of pulmonic regurgitation (PR). However, lateral and PA view of chest radiograph may help determining the right ventricular enlargement. Right atrial enlargement may also be seen among patients with concomitant tricuspid regurgitation. On plain chest Xray PR may be characterized by right ventricular enlargement, prominent pulmonary trunk, features of tricuspid regurgitation (TR), and of congestive heart failure (CHF).

Echocardiography is the initial test that may be used to assess pulmonary valve morphology, RVOT anatomy, and to identify the presence and quantify the severity of pulmonary regurgitation (PR). Different modes of echocardiography may be used to improve the accuracy of findings and assess the severity of the disease which include doppler|color flow doppler, continuous wave doppler, pulsed doppler, spectral doppler and exercise echocardiography. The severity of PR can be assessed by observing color pulmonic valve morphology, flow PR jet size and density, and regurgitant Fraction (RF) via doppler echocardiography.

Cardiac magnetic resonance(CMR) is a gold standard for assessment of morphology of the pulmonary valve, for quantification of the severity of the regurgitation and the RV systolic function. CMR is useful in quantification of the regurgitant volume and the regurgitant fraction of PR by using sequences called “velocity- encoded phase-contrast images”. CMR is useful for evaluating pulmonary regurgitant fraction, RV end-diastolic and end-systolic volume and RV ejection fraction. CMR is the diagnostic modality preferred to determine the requirement of re-intervention among patients with repaired tetralogy of Fallot and to assess the ventricular function and dimensions.

Pulmonary angiography may play a role among patients with TOF repair having pulmonary regurgitation.

Treatment of pulmonic regurgitation may include medical therapy, surgical therapy and regular follow up.

Treatment of pulmonic regurgitation may be divided into medical and surgical treatment. Medical management of pulmonic regurgitation may include use of diuretics in patients with RV dysfunction. ACE inhibitors and beta blockers may be used to reverse neurohormonal activation and improve symptoms. Antibiotic prophylaxis may be indicated in certain conditions such as patients with cyanotic heart disease, prosthetic heart valves, rheumatic heart disease, and patients previously having sustained bacterial endocarditis. Among patients with carcinoid heart disease subcutaneously administered octreotide in 2–4 divided doses (50–1500 μg/day) provides symptomatic and biochemical benefit.

Surgical management of pulmonic regurgitation may include pulmonary valve replacement (PVR). The major indications for PVR may include symptomatic patients with arrythmias or NYHA class higher than II, an ejection fraction of less than 40% when assessed with CMR, patients with progressive right ventricular regurgitation(right ventricular end- diastolic volume ≥160 mL/m2 or end-systolic volume ≥82 mL/m2 on CMR), moderate to severe tricuspid valve regurgitation, resulting from annular dilatation, patients at risk of developing arrythmias and with prolonged QRS duration.(total QRS duration ≥180 msec, or QRS duration increase >3.5 msec per year and severe pulmonic regurgitation among patients with another cardiac lesion that requires operative intervention. Timing of pulmonary valve replacement is not well defined. However timely intervention is advised before the onset of RV dysfunction. Pulmonary valve replacement (PVR) by surgical and percutaneous approach is the definitive treatment for the management of chronic PR and has proven to improve RV function, New York Heart Association Functional Class status, quality of life, and reduce risk for development of RV tachyarrhythmias and sudden cardiac death. Among patients with arrhythmias, intraoperative electrophysiological mapping with cryoablation during pulmonary valve replacement has demonstrated promising results.

Follow up of the patients with pulmonic regurgitation requires regular echocardiographic monitoring after PVR. Oral anticoagulation among patients with bioprosthetic valves is recommended only when other indications such as atrial arrhythmia or prior thromboembolic event are present. Upon surveillance among patients with PR monitoring right ventricular dilatation and its sequelae holds more significance than the regurgitation itself.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

Pulmonic regurgitation murmur was first described as Graham-Steell murmur by Dr. Graham Steel in 1888. Before that The pulmonary valve and its function of allowing blood to the lungs for nourishment was first described by Hippocrates. Ibn Nafis then described the pulmonary circulation. Mondino drew a sketch of the pulmonic valve. In 1888 an early blowing diastolic murmur due to pulmonary hypertension was described by Graham-steel, known as Graham-steel murmur. Techniques were then developed to diagnose pulmonary valve regurgitation via the dye method and cardiac catheterization.

• The concept that the cusps of pulmonary valve have the texture different than the ventricles was first described by the father of medicine, Hippocrates (460-377 B.C). The scientist first described that the function of the pulmonary valve is to avoid backflow of blood to the ventricles, ensuring one-way flow through the heart.^[1]
• Pulmonary circulation was first described by Ibn Nafis (1210-1288 AD). The book was forgotten until 1924 when the manuscript No.62243 titled Commentary on the anatomy of the Canon of Avicenna was found in Germany.^[2]
• The first ever sketch design of the pulmonary valves in their anatomical position was published in a 1541 publication Anatomia Mundini, Ad Vetustis. It was the work of Mondino de Luzzi (1270 A.D -1326 A.D) an Italian physician, anatomist, and professor of surgery in Bologna. He is also known as the Restorer of anatomy. His work also includes describing the course of pulmonary artery (vena arterialis) and pulmonary vein (arteria venalis).^[3][4]

• Pulmonic regurgitation murmur was first described by Dr. Graham Steel in 1888. Graham-Steell murmur (named after himself) was described in his two publications in Manchester Medical Chronicle. He attributed an early blowing diastolic murmur over and below the pulmonic area to the longstanding pressure in the pulmonary artery, independet of any disease or deformity of the valves. The murmur due to pulmonary hypertension has since been named after the person himself, Graham Steel murmur.^[5][6]
• The term “semilunar” was first used by Galen in 1968 while describing the membranes of the valves in his book De Usu Partium, Volume 1.^[4]

• It was long thought that pulmonic regurg can not be diagnosed during the life-time of a patient. In 1956, Ralph F. Morton and Thomas N Stern presented a case of isolated nonsurgical pulmonic regurgitation during the life, suggested by the physical exam, phonocardiography, and fluoroscopy. It was definitively diagnosed by cardiac catheterization.^[7]
• Due to the transient, soft nature of the murmur and and resemblance with aortic regurgitation, the need to illustrate the regurgitation by another method arose. In 1958, Wanzer et al. first described the use of Evans blue dye to diagnose the pulmonic valve regurgitation.^[8] In 1959, Collins et al. used cardiogreen dye and radioactive krypton (Kr85) to demonstrate the regurg.^[9]
• In 1952, Charles A. Hufnagel implanted the first artificial heart valve (caged ball valve, mitral valve) among 10 patients. The implant was a long-term success.^[10]
• In 2000, Bonhoeffer et al. reported a first bovine (sheep) transcatheter pulmonic valve repair (tPVR). Abovine jugular venous valve was sewn inside a platinum-iridium stent and then hand-crimped onto a balloon catheter. The device insertion via internal jugular approach was a success with subsequent explantation of the stents.^[11]
• In 2000, two months following the initial trial among sheep, again Bonhoeffer et al. reported the first ever successful percutaneous replacement of pulmonary valve in the RV to PA prosthetic conduit via right femoral vein. The recipient 12-year-old male patient with pulmonary atresia and VSD had valve dysfunction post implant at the age of 4 years.^[12]

No significant impact of PR discovery and treatment on cultural history has been reported. There were no outbreaks associated with PR reported in history.

• Shaun White is an American professional snowboarder. The three-time Olympic champion suffered from TOF and has undergone three separate repair surgeries during hs childhood.^[13][14]
• Jennie Garth, a Hollywood actress mentioned having a heart condition saying: “I have a leaky valve. She also said “I can feel a little weird fluttering.”^[15][16] Some literature mentions the actress having mitral regurgitation but it is not clear whether the valvular insufficiency involves pulmonic or mitral valves.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

Pulmonary valve regurgitation (PR) may be classified according to etiology of the regurgitant flow, severity of the disease and chronicity. Based on the etiology of the regurgitant flow, PR may be classified into primary and secondary/ functional types. The severity of the disease may classify into mild, moderate and severe disease. New York Heart Association’s (NYHA) functional classification helps to gauge the severity of the heart failure which is a complication of PR. The severity of PR can be assessed by utilizing the American Heart Association and American College of Cardiology (AHA/ACC) staging of valvular heart disease (VHD).

Pulmonary regurgitation (PR) may be classified into subtypes based on the etiology of the regurgitant flow, severity of the disease and chronicity.^[1]

Pulmonary regurgitation (PR) may be classified into two subtypes based on either intrinsic or extrinsic factors involved in the development of the disease:

• Primary pulmonary regurgitation^[2]: The valvular pathology is the cause of PR. Isolated PR is very rare and is most commonly associated with other congenital heart diseases.
• Secondary or functional pulmonary regurgitation^[3][4][5]: The pulmonary valve function is normal. Conditions such as pulmonary hypertension and pulmonary artery aneurysm cause dilation of the valve annulus resulting in regurgitation. Secondary PR is more common than primary PR.

Pulmonary valve regurgitation may be classified into three categories based on the severity of the regurgitant flow:^[6][7]

Pulmonic regurgitation (PR) may be classified into two subtypes based on the chronicity of the disease. Chronic diseases are broadly defined as conditions that last 1 year or more.^[8]

• Acute PR^[9]:
  • Severe acute PR may occur due to infective endocarditis and blunt chest trauma with direct injury to heart structures specially among patients with abnormal dilation of pulmonary arteries.
  • Acute PR due to endocarditis may be low or high-pressure type. A low-pressure PR may progress to high-pressure PR.
• Chronic PR:
  • Chronic low-pressure PR^[9]:
    1. Congenital causes include pulmonic valve abnormalities and idiopathic dilatation of the pulmonary artery (IDPA).
    2. Acquired cause include post pulmonary valve stenosis repair or TOF repair, tertiary syphilis, chronic endocarditis, rheumatic heart disease, carcinoid heart disease, and Marfan’s syndrome.
  • Chronic high-pressure PR: Causes include primary and secondary pulmonary hypertension.

• According to the 2018 ACHD guidelines, moderate or greater pulmonary valve regurgitation lies under moderate complexity according to ACHD (adult congenital heart disease) anatomic and physiological classification.^[10]
• Pulmonic regurgitation may lead to right and eventually left heart failure. New York Heart Association’s (NYHA) functional classification helps to guage the severity of the heart failure via physical disability of the patient. To read more about the NYHA classification click here.

The staging described is based on 2014 According to the American Heart Association and American College of Cardiology (AHA/ACC) valvular heart disease 2014 guidelines.

Staging is based on the progression of the disease. Although the staging has not been specified for PR, it is a useful tool to access the disease course.

• Stage A (at risk) : Patient has developed risk factors for VHD. Asymptomatic patient. Development of pulmonary hypertension (PAH) as a risk for PR is an example.
• Stage B (progressive): Patient has developed mild-moderate VHD. Asymptomatic patient.
• Stage C (asymptomatic severe): Patient has developed severe VHD. Asymptomatic patient but exercise test can confirm symptom status.
• Stage D (symptomatic severe): Patient has developed severe VHD. Symptomatic patient such as heart failure symptoms.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

Pulmonary valve is located at the junction of the right ventricular outflow tract and pulmonary artery. Three equal-sized, semilunar cusps or leaflets make up the pulmonary valve. Pulmonary valve opens during right ventricular systole and closes during right ventricular diastole. Pulmonary regurgitation (PR) may be caused by an acquired alteration in the valvular morphology, idiopathic dilatation of the pulmonary artery (IDPA), pulmonic valve ring dilatation, congenital absence or malformation of the valve, and increasing regurgitation causing right ventricular volume overload. The pathophysiologic mechanism of pulmonic regurgitation includes right ventricular overload resulting in the right ventricular remodeling and progressive decline in function. The rate of decline in right ventricular systolic function is affected by associated conditions such as peripheral pulmonary artery stenosis and pulmonary hypertension which further increase the severity of pulmonary regurgitation. Among patients with severe PR, the gene expression pattern of GRK2 and β2-adrenoceptor (molecular markers of cardiac dysfunction) has been reported to be altered. Isolated PR is uncommon and is usually demonstrated with other valvular abnormalities or in certain conditions. Conditions associated include TOF, rheumatic heart disease and syphilis. On gross pathology vegetative lesions on the pulmonic valve leaflets may be observed among patients with acquired alteration in the valvular leaflet morphology.

• Location: Pulmonary valve is located at the junction of the right ventricular outflow tract and pulmonary artery. Pulmonic valve lies anterior and superior to the aortic valve at third intercostal space level. Infundibulum of the right ventricle separates it from tricuspid valve.^[1]

• Structure: Three equal sized, semilunar cusps or leaflets make up the pulmonary valve. Based on the corresponding aortic valve, the cusps are named right, left and anterior.^{[2] [2]}
• The three cusps are joined by commissures and the cusps are thinner when compared to the aortic valve, due to a low pressure in the right ventricle.^[2]
• Histologically, the pulmonary valve consists of stratified extracellular matrix compartments. The layers constitute fibrosa, spongiosa and ventricularis.^[3]
• The diameter of pulmonic valve is demonstrated to be closely related to the body size. For adult men (>17 years age) mean pulmonary valve diameter is 26.2 +/- 2.3 mm and 23.9 +/- 2.2 mm for adult women.^[4]
• Physiology: The right ventricle delivers the received blood entirely to the pulmonary circulation every beat, maintaining optimum pressure.^[5] Pulmonary valve opens during right ventricular systole allowing the deoxygenated blood to be delivered to the lungs. ^[2] During the right ventricular diastole the pulmonary valves close completely to prevent regurgitation (back flow) of the blood into the right ventricle.^[2]
• The closure of the pulmonic valve contributes to the P2 component of the second heart sound (S2).

The pathogenesis of pulmonic regurgitation involves the following mechanisms:^[6][7]

• The diastolic pressure difference between main pulmonary artery (MPA and right ventricle (RV) is usually very small and steers the pulmonic regurgitation. The right ventricular stiffness due to right ventricular hypertrophy (such as in Tetralogy of Fallot and fibrosis) increases the ventricular diastolic pressure. Increased ventricular diastolic pressure decreases the gradient causing regurgitation. A slight increase in the intrathoracic pressure (such as among ventilated patients) can accentuate PR considerably.^[8]
• Along with diastolic pressure difference between right ventricle and pulmonary artery, the degree/ severity/ volume of regurgitant jet is dependent on:^[9][10]
  • Size/ area of the regurgitant orifice
  • Afterload of the right ventricle/ capacitance of pulmonary arteries
  • Right ventricle diastolic compliance
  • Duration of right ventricular diastole
• Torricelli principle sums up some of the factors influencing regurgitant volume:^[10]

PR volume = regurgitant orifice area · constant · diastolic time · mean diastolic pressure difference between the MPA and RV.(P2−P1)0.5.

• The most common cause of PR is post repair of TOF to relieve right ventricle outflow tract (RVOT) obstruction. The valvular lesion is thought to be due to the disruption of pulmonary valve‘s morphological integrity. In a TOF patient even after the RVOT obstruction relief, the right ventricle (RV) is hypertrophied and pulmonary arteries are usually hypoplastic, both demonstrating low compliance. Among children, tachycardia leads to shorter duration diastoles.

Regurgitation is avoided despite large regurgitation orifice due to Torricelli principle. Progressively, an increased size and capacitance of central pulmonary ateries and right ventricular dilatation occurs due to increased RV stroke volume. The changes described progress with age accompanied by a longer duration of diastole and decreased heart rate. This progressively leads to an increase in the degree of PR.

• The development of pulmonic regurgitation due to tophus valvular vegetations has been reported in a case. The patient reported had long-standing cyanotic congenital heart disease and developed hyperuricemia secondary to polycythemia. The possible mechanism of development of the vegetations involved hemodynamic valvular trauma in the setting of sustained hyperuricemia and subsequent dystrophic calcification at primary tophus lesion.

• The exact pathogenesis of dilatation of the pulmonary artery is not fully understood. The demonstration of the disease among pediatric population signals the congenital nature of the etiology. Main pulmonary artery and the origin of its right and left main pulmonary arteries are majorly affected. It is thought that pulmonary artery dilatation is mediated by the unequal division of truncus arteriosus communis. Other proposed mechanisms include maldevelopment of the whole pulmonary tree and the association of hypoplastic aorta with dilated.

A study utilized pulsed doppler echocardiography and cineangiography to identify the significance of pulmonic valve ring dimensions in the development of PR. It reported the ratio of sagittal to the transverse diameter of the pulmonic valve ring to be greater among patients with PR. In patients with PAH the study also demonstrated greater dilatation of the sagittal diameter of the pulmonic valve ring than pulmonary sinus diameter. In the light of the results, the etiology of PR was attributed to the distortion of pulmonic valve ring.

• Absent pulmonary valve syndrome (APVS) is rare and involves developmental abnormality and dysplasia or absolute absence of pulmonary valve cusps. A variable degree of dilatation/aneurysm of the main pulmonary artery always accompanies the disorder.
• It is thought that the development of pulmonary artery aneurysm is mediated by either the congenital weakness or cystic medial degeneration of the pulmonary artery walls. An association between cystic medial degeneration and increased hemodynamic forces then leads to aneurysm formation. Pulmonary artery aneurysms have been associated with structural cardiac and vascular abnormalities, vasculitis, and infection (such as syphilis).
• The pathogenesis of Fallot type (APVS) involves either agenesis of ductus arteriosus or post pulmonary stenotic dilatation due to increased stroke volume.
• Quuadricuspid pulmonary valve is rare but may cause PR. Thick valvular leaflets with decreased mobility without complete closure during diastole may lead to the development of PR.^[19]

• Patients with pulmonic regurgitation (PR) develop chronic right ventricular overload resulting in right ventricular remodeling and progressive decline in function. The rate of decline in right ventricular systolic function is also affected by associated conditions such as peripheral pulmonary artery stenosis and pulmonary hypertension which accentuates PR. Among patients with increased pulmonary artery pressure from dysfunction of left ventricle or residual pulmonary artery stenosis the severity of PR is increased. Progressive dilation of the right ventricle results in functional tricuspid regurgitation and increases the risk of developing arrhythmias.

• ADAMTS19 has been identified as a novel causative gene for autosomal recessive cardiac valve disease. ADAMTS is a disintegrin and metalloproteinase with thrombospondin motifs protein family. All patients demonstrated anomalies of the aortic and/or pulmonary heart valves, such as thickening of valve leaflets, stenosis and insufficiency.^[20][21]
• Among patients with severe pulmonary regurgitation (PR), the gene expression pattern of GRK2 and β2-adrenoceptor ( molecular markers of cardiac dysfunction) has been reported to be altered. The lymphocyte expression of described adrenoceptors and kinases demonstrates neurohumoral changes in heart failure.^[22]
• 25% cases of absent pulmonary valve syndrome (APVS) are associated with chromosomal anomalies such as Trisomy 21, Trisomy 13, chromosome 6 and 7 deletions.^[23]
• 22q11 micro-deletion has been shown to be associated with 25% cases of APVS.^[24]

Isolated PR is uncommon and is usually demonstrated with other valvular abnormalities or in certain conditions. The most important conditions/diseases associated with PR include:

• TOF: Surgical repair of pulmonic stenosis associated with TOF may lead to PR. Post TOF repair, PR is a common complication.
• Marfan syndrome: Dilatation of pulmonary artery root is one of the established diagnostic criteria of Marfan syndrome.^[25] Although other valvular regurgitations are common in Marfan syndrome, pulmonic regurgitation is also possible.
• Rheumatic heart disease: The disease is uncommon among developed countries but developing countries still share the burden of the disease.^[26][27]
• Syphilis: Although a rare cause, pulmonary artery dilatation and PAH may be caused by tertiary syphilis. Given the prognostic implications and available treatments, early detection of PAH.^[28] Being a sexually transmitted disease (STD), it is important to screen the patient for other STDs.

• On gross pathology vegetative lesions on the pulmonic valve leaflets may be observed among patients with acquired alteration in the valvular leaflet morphology.^[11]

• On polarized light microscopy of the material taken from the pulmonic valve, negatively birefringent crystals may be observed in acquired alteration in the valvular leaflet morphology.^[11]

• http://www.uwhealth.org/page.asp?contentid=11094
• http://www.cvphysiology.com/Heart%20Disease/HD005.htm

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2] Aravind Kuchkuntla, M.B.B.S[3], Aysha Anwar, M.B.B.S[4], Javaria Anwer M.D.[5]

Pulmonic regurgitation may be normal (physiologic) and occasionally a murmur can be heard among thin subjects. Life-threatening cause of PR include chest trauma. The most common causes of pulmonary regurgitation are following the repair of tetralogy of Fallot and pulmonary stenosis. PR is also common among patients with pulmonary hypertension (PAH). Rheumatic heart disease is also an uncommon cause and is more commonly observed in developing countries. The primary causes of PR include an intrinsic pathology in the pulmonic valve and secondary causes include extrinsic causes. The causes of pulmonic regurgitation may also be reckoned on the basis of the organ systems involved.

• Life-threatening causes of PR include chest trauma.

• Secondary PR is more common than primary PR.^[1]
• Pulmonic regurgitation (PR) is most common after TOF or pulmonary stenosis repair .^[2][3]
• PR is also common among patients with pulmonary hypertension (PAH).^[4]

• Carcinoid heart disease, infective endocarditis, tertiary syphilis, and connective tissue disorders are uncommon causes of PR.^[4]
• Rheumatic heart disease is also an uncommon cause and is more commonly observed in developing countries.
• Idiopathic dilatation of pulmonary artery is a rare cause of PR.^[5][6]
• Pulmonary artery aneurysm is not a common cause of PR but the aneurysm itself is most commonly caused by congenital defects and secondly tertiary syphilis. Atherosclerotic, degenerative, and traumatic causes are also included.^[7][8]
• Takayasu arteritis is a rare cause of PAH and may cause PR.^[9]

• PR may be physiologic or pathologic. Pathologic causes may be divided among primary and secondary. Isolated PR is very rare and is most commonly associated with other congenital heart diseases.^[10] The following flow chart demonstrates the causes of PR based upon the etiology.
  

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3]

Pulmonic regurgitation (PR) must be differentiated from other diseases that cause blowing decrescendo murmur such as aortic regurgitation. The diseases which may present with overlapping symptoms as pulmonic regurgitation may include aortic regurgitation, tricuspid regurgitation, left to right shunting, right ventricular cardiomyopathy, pulmonary hypertension, infective endocarditis, carcinoid heart disease, syphilis and marfan syndrome.

Pulmonic regurgitation (PR) must be differentiated from other diseases that cause blowing decrescendo murmur such as aortic regurgitation. The diseases which may present with overlapping symptoms as pulmonic regurgitation may include the following:

• Pulmonary hypertension
• Infective endocarditis
• Rheumatic heart disease
• Congenital abnormalities: tetralogy of Fallot, ventricular septal defect, valvular pulmonic stenosis
• Carcinoid heart disease (the majority of patients with metastatic disease will have both pulmonic stenosis and pulmonic regurgitation)
• Marfan syndrome
• Syphilis infection
• Trauma from withdrawing a Swan-Ganz catheter with the balloon inflated
• Following valvuloplasty of pulmonary stenosis
• Absence of the pulmonic valve
• Fenestrations in or redundant leaflets of the pulmonic valve

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

The prevalence of mild PR among patients with normal anatomy of the pulmonary valve is 40% to 78%. Among patients born with congenital heart disease, 20% of patients have associated abnormalities of the pulmonary valve or the right ventricular outlet obstruction. The incidence and prevalence of PR increases with age. 24% of the deaths due to valvular heart disease are attributed to tricuspid valve and pulmonic valve abnormalities combined. There is one study supporting the increased prevalence of PR among women. In developing countries Pulmonary hypertension (PAH) is primarily due to rheumatic heart disease (RHD) which is rare in developed countries. PAH is a major cause of secondary PR.

• The prevalence of valvular heart disease in U.S. population is estimated to be 2.5%. About 13% of U.S population born before 1943 have valvular heart disease.^[1]
• The prevalence of mild PR among patients with normal anatomy of the pulmonary valve is 40% to 78%.^[2][3][4][5]
• In 1987, the prevalence of PR among patients with structurally normal hearts was estimated to be 5% in Boston area population, USA.^[2]
• In 1990, the prevalence of PR among normal patients (21 – 82 years) was estimated to be 31%.^[5]
• In 1992, the prevalence of PR among children (birth- 14 years) with structurally normal hearts was estimated to be 21.9% in Jerusalem, Israel population. Pulmonic regurgitation was the most common of all valvular regurgitations detected among children.^[6]
• In 1993, the prevalence of rheumatic fever in the developing countries was estimated to be 18.6/1000.^[7] Rheumatic fever is still a significant cause of PR in developing countries.
• There is a 50% chance of cardiac involvement in carcinoid syndrome.^[8] A large US case series on carcinoid syndrome reported that 81% of individuals demonstrated PR. ^[9]

• Among patients born with congenital heart disease, 20% of patients have associated abnormalities of the pulmonary valve or the right ventricular outlet obstruction.^[2]
• Rheumatic heart disease (RHD), a rare cause of PR in developed countries but developing world still shares the burden of the disease.
  • In 1989, the incidence rate of rheumatic fever in developing countries was estimated to be 100 per 100,000 young individuals.^[10]
  • In 1993, the incidence rate of rheumatic fever in the developing countries was estimated to be 206/100,000.^[7]
  • In 2013, 120 deaths were attributed to RHD in a referral cardiac center of northern India (Patna).^[11]
• Among patients with mechanical heart valves, the incidence of major thromboembolic events has been estimated to be approximately:
  • In the absence of antithrombotic therapy, 4 per 100 patient-years.^[12]
  • In the absence of systemic anticoagulation, 23 per 100 patient-years.^[13]

• In 2017, CDC reported that 24% of deaths due to valvular heart disease were attributed to tricuspid valve and pulmonic valve abnormalities combined.^[1]

• The prevalence of pulmonary regurgitation (PR) is estimated to have two demographic peaks. The first peak is among young patients with repaired congenital pulmonary stenosis. The second peak is among patients with pulmonary arterial hypertension (PAH).^[14] The multitude of causes makes the determination of exact prevalence of PR difficult.^[15]
• In the U.S population, the prevalence of valvular heart disease is higher among older adults.^[1]
• In 1989, a meta‐analysis reported that 29% of the patients with isolated congenital PR develop symptoms within 40 years. The risk of development of symptoms demonstrated an increase with age, particularly after 40 years.^[16]
• In 1990, the incidence of mild degree valvular regurgitation in normal subjects was estimated to increase with age.^[5]
• In 2017, the incidence of PR among Tibetans (one of the highest cities in the world) was speculated to increase with age.^[17]
• Carcinoid symptoms typically appear at a mean age of 55–60 years and usually takes 2 years before symptoms due to valvular disease develop.^[8]

• There is no racial or ethnic predilection for pulmonary regurgitation.

• In 2017, Pulmonic regurgitation (PR) was speculated to be more prevalent among Tibetan women.^[17]

• Among developed countries such as the United States, Pulmonary hypertension (PAH) is primarily due to left heart disease. Other conditions that cause PAH include sickle cell disease; pulmonary embolus, and chronic obstructive pulmonary disease (COPD).^[18] PAH is a major cause of secondary PR.
• Rheumatic heart disease (RHD) is not a common cause of PAH or PR among developed countries. Due to the early detection and development of treatment strategies RHD is rare among developed countries.^[19][20]

• Among developing countries Pulmonary hypertension (PAH) is primarily due to rheumatic heart disease (RHD), schistosomiasis, congenital heart disease, hemolytic diseases. PAH is a major cause of secondary PR. The burden of PAH is greater among developing than developed countries.^[19][21]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2], Javaria Anwer M.D.[3]

Most potent risk factors for the development of pulmonic regurgitation may include pulmonary hypertension, surgical repair of teratology of Fallot, and congenital heart diseases. Less common but important risk factors include endocarditis, left sided heart disease, previous Ross procedure, collagen vascular disease, and malignancies involving the main pulmonary artery.

• The most potent risk factors for the development of pulmonic regurgitation (PR) include^{[1][2][3][4][5]}:
  • Pulmonary hypertension (most common risk factor)
  • Surgical repair of tetralogy of Fallot (most common risk factor), pulmonary stenosis or pulmonary atresia
  • Congenital heart diseases (such as Eisenmenger’s syndrome)

• Less common but important risk factors for the development of pulmonic regurgitation (PR) include^{[4][6][7][8][9][10]}:
  • Previous Ross procedure
  • Endocarditis (more common among IV drug users)
  • Left-sided heart disease
  • Chronic kidney disease (CKD): Although an established risk factor for other valvular regurgitation, CKD is strongly associated with PAH)
  • Collagen vascular disease/ Myxomatous degeneration of the pulmonary valve
  • Malignancies that involve main pulmonary artery
  • Rheumatic fever (more common among developing countries)
  • Chest trauma (cause of acute severe PR)
  • Tertiary syphilis
  • Marfan’s syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2], Javaria Anwer M.D.[3]

There are no specific screening recommendations for patients with pulmonary regurgitation (PR). However, patients on an increased risk of developing PR secondary to conditions such as repair of Tetralogy of Fallot (TOF), pulmonary atresia or truncus arteriosus may be evaluated by routine echocardiography, ECG or MRI to assess right ventricular size and status of pulmonary valve. A study recommends considering ADAMTS19 genetic testing among all patients with multiple semilunar valve abnormalities. The key diagnostic tests that may be used for screening of PAH (a major risk factor for PR) may include doppler transthoracic echocardiography, DLCO, BNP, NT-pro-BNP, serum urate levels, and ECG.

• There are no specific screening tests for the detection of pulmonary regurgitation (PR). However, patients on an increased risk of developing PR secondary to other conditions may benefit from regular screening.

• Conditions such as repair of Tetralogy of Fallot (TOF), pulmonary atresia or truncus arteriosus may be evaluated by routine echocardiography, ECG or MRI to assess right ventricular size and status of pulmonary valve. The technique helps early detection of pulmonary valve abnormality among cases where it is highly suspected.^[1]
• According to ACC/AHA 2008 Guidelines for the Management of Adults With CHD, patients with repaired TOF should have^[2]:
  • At least an annual follow-up with adult CHD expert.
  • Echocardiographic and/or MRIs performed by staff with expertise in adult CHD
  • Screened for heritable causes of their condition (eg, 22q11 deletion)

A study recommends considering ADAMTS19 genetic testing among all patients with multiple semilunar valve abnormalities (specifically in the presence of subaortic membrane) to facilitate the estimation of heart valve diseae related phenotype frequency.^[3] The recommendation is based on the identification of ADAMTS19 as a novel causative gene for autosomal recessive heart valve disease including aortic and pulmonic valve insufficiency.^[4]

• PR is common among patients with pulmonary hypertension (PAH).^[5] Screening methods have been developed for PAH and may help lower the burden of the disease provided early detection and intervention of PR develops.
• According to the 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension (PAH) the key diagnostic tests that may be used for screening of PAH include^[6][7]:
  • Doppler transthoracic echocardiography (TTE) possesses the highest level of evidence as a recommended screening test for suspected PAH.
  • Pulmonary function tests particularly, DLCO of <60% may be used as a screening method for individuals at high risk of PAH. 75% of patients (majorly tobacco smokers or older individuals) with idiopathic PAH have a reduced DLCO. It is important to note that a normal DLCO does not exclude PAH diagnosis.^[8][9]
  • Blood biomarkers such as BNP, NT-pro-BNP, and serum urate levels are recommended to be included in PAH screening and elevated levels have been reported to be predictive of PAH. PAH accentuates myocardial wall stress resulting in the release of the hormones tested.^[10]
  • ECG is a component of PAH screening algorithm. The screening technique has been unsuccessful in identifying early-stage PAH but right axis deviation on ECG has been reported to help discriminate patients with and without PAH. The technique has helped improve the disease detection.

• APVS is a rare cause of PR but with poor prognosis. The defect may appear in children with no family history of genetic disorders, born to healthy mothers. It has been diagnosed via ultrasonography due to its suggesting features such as^[11][12][13]:
  1. Pulmonary artery aneurysm/ dilatation (with or without involving its branches)
  2. Massive PR
  3. PS
  4. VSD
  5. Overriding aorta (some of the features described may be due to accompanying TOF)
  6. Reversed end-diastolic flow (REDF) in the umbilical artery at 10-14 weeks of gestation has been reported to be associated with APVS. Although at 10-14 weeks, REDF is a rare finding. If present, it is associated with major fetal cardiac anomalies specially Fallot type APVS.
• Among the cases reported (APVS together with TOF), early detection helped early intervention (fetuses were aborted after parents’ consent among two of a few cases reported).^[12]
• Therefore, it is suggested that early fetal echocardiography screening should be performed for every fetus to confidently diagnose this rare anomaly in time. It is also important to consider the possibility of associated chromosomal abnormalities.^[13]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: , Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

The majority of patients with mild pulmonary regurgitation (PR) are asymptomatic and have a benign course, not progressing to chronic PR. Patients tolerate severe chronic PR for a long period of time and begin to develop symptoms when the right ventricle function begins to decline. Chronic severe PR leads to progressive dilation and systolic dysfunction of the right ventricle resulting in symptoms. The severity of PR after TOF repair can increase over time and patients may develop symptoms from an early age. Complications that may result from PR include progressive right ventricular dilatation, heart failure, tricuspid regurgitation, ventricular arrhythmias, and sudden cardiac death. The prognosis of pulmonic regurgitation depends on the severity of the condition, etiology, and associated complications. Symptomatic patients are treated with pulmonary valve replacement (PVR) and have a good prognosis.

• Mild PR^[1]:
  • The majority of patients with mild PR are asymptomatic and have a benign course, not progressing to chronic PR.
  • Mild PR is a common finding on 2D echo.
• Acute worsening of PR:
  • Patients with acute worsening of PR should be evaluated for associated conditions such as pulmonary hypertension which increase the pressure gradient.
• Chronic PR^[2]:
  • Patients tolerate severe chronic PR for a long period of time and begin to develop symptoms when the right ventricular systolic function begins to decline or marked dilatation occur. In a symptomatic patient RV dysfunction has usually become irreversible.
  • Chronic severe PR leads to progressive dilation and systolic dysfunction of the RV(right ventricle) resulting in symptoms.
• Isolated congenital PR^[3]:
  • Among patients with isolated congenital PR, it is uncommon to develop symptoms before 30 years of age.
  • After the age of 40 years, the development of symptoms such as right heart failure or even SCD demonstrates an increased risk.
• Post TOF repair^[4][5]:
  • Among patients with TOF repair, symptoms may develop at an early age. Thie finding is partly attributed to the effect of associated lesions on myocardial function. Post complete TOF repair, impaired exercise capacity is directly related to the degree of residual PR.
  • The severity of PR after TOF repair can increase over time. The data is supported by experimental^[6][7] and clinical^[8] evidence.
• Idiopathic Dilatation of Pulmonary Artery (IDPA)^[9][10]:
  • The condition is usually asymptomatic but may demonstrate symptoms in case of development of complications. The duration of illness has been demonstrated to be more than 20 years among 10% patients.
  • Dilated pulmonary arteries may lead to the compression of left main coronary artery.

• Common complications of pulmonary regurgitation (PR) include:^{[11][12][13][14][15][5]}
  1. Progressive right ventricular(RV) dilatation
  2. RV dysfunction
  3. Heart failure (HF): Exercise intolerance is one of the features of HF. To read about the degree of HF and its manifestations according to NYHA classification click here.
  4. Tricuspid regurgitation
  5. Ventricular arrhythmias (such as ventricular tachycardia)
  6. Hepatic congestion may develop secondary to right heart failure. Hepatic dysfunction may ensue thromboembolic events.
  7. Sudden cardiac death:
  • Among patients with repaired TOF, pulmonic regurgitation is a major hemodynamic lesion associated with ventricular tachycardia and sudden cardiac death.
  • Sudden cardiac death among patients with IDPA is due to the compression of left main coronary artery.^[9][16]

• The prognosis of pulmonic regurgitation depends on the severity of the condition, etiology and associated complications.^[17]
• Mild to moderate PR is not associated with shortened survival.^[17]
• The prognosis of symptomatic patients of PR is good after pulmonary valve replacement.^[18] Surgical Pulmonic Valve Repair (PVR) improves right ventricular filling and increases left ventricular stroke volume.^[19] Ten year overall and event-free survival after PVR is 98% and 70%, respectively.^[20]
• Among patients with pulmonary hypertension (PAH), the severity and duration of PAH determines the ultimate prognosis.
• The prognosis of PR due to congenital absence of pulmonic valve is poor and may limit patient‘s life expectancy in the absence of valve replacement. Absent pulmonary valve (APVS) is associated with severe regurgitation and complications secondary to respiratory distress.^[21]
• Higher pre-operative RV end-systolic volume index (ESVI) is the only independent risk factor for suboptimal outcomes post pulmonary valve replacement.^[20]
• QRS duration of ⩾180 ms on resting EKG has been demonstrated to be a strong predictor of ventricular arrhythmias and sudden death among patients post TOF repair.^[22]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2], Aysha Anwar, M.B.B.S[3], Javaria Anwer M.D.[4]

Treatment of pulmonic regurgitation (PR) may be divided into medical and surgical treatment. Medical management of PR may include use of diuretics among patients with RV dysfunction. ACE inhibitors and beta blockers may be used to reverse neurohormonal activation and improve symptoms. Antibiotic prophylaxis may be indicated in certain conditions such as patients with cyanotic heart disease, prosthetic heart valves, rheumatic heart disease, and previously sustained bacterial endocarditis. Surgical management of PR may include pulmonary valve replacement (PVR). The major indications for PVR may include symptomatic patients with arrythmias or NYHA class higher than II, an ejection fraction of less than 40% when assessed with CMR, patients with progressive right ventricular regurgitation(right ventricular end-diastolic volume ≥160 mL/m2 or end-systolic volume ≥82 mL/m2 on CMR), moderate to severe tricuspid valve regurgitation, resulting from annular dilatation, patients at risk of developing arrythmias and with prolonged QRS duration (total QRS duration ≥180 msec, or QRS duration increase >3.5 msec per year and severe PR among patients with another cardiac lesion that requires operative intervention. Timing of pulmonary valve replacement is not well defined. However timely intervention is advised before the onset of RV dysfunction. Among patients with arrhythmias, intraoperative electrophysiological mapping with cryoablation during pulmonary valve replacement has demonstrated promising results.

Treatment of pulmonic regurgitation (PR) may be divided into medical and surgical treatment:

• There are no specific medical measures for the management of PR.
• Diuretics are recommended in patients with RV dysfunction or PAH for maintenance of fluid balance.^[1]
• Among patients with repaired tetralogy of fallot, ACE inhibitors or beta-blockers are used to reverse the neuroharmonal activation and improve the symptoms.^[2][3]

The American Heart Association Recommendations on Prevention of Bacterial Endocarditis indicate that antibiotic prophylaxis is not necessary for pulmonic regurgitation in those patients with otherwise structurally normal pulmonic valves, particularly if there is no diastolic murmur. It should be noted, though, that those patients with the following conditions may warrant antibiotic prophylaxis:^[4]

1. Complex cyanotic heart disease
2. Prosthetic heart valves
3. Patients with congenital heart disease and PR
4. Acquired PR as the result of rheumatic heart disease
5. Patients with complex cyanotic heart disease
6. In patients who have previously sustained bacterial endocarditis

• Among patients with severe acute PR due to the large duct (such as in neonatal Ebstein’s anomaly or post balloon dilation of pulmonary stenosis or perforation of valvar pulmonary atresia)^[5][6]:
  • If TR accompanies the situation, a circular shunt may occur leading to poor systemic blood flow. The treatment involves stopping the prostaglandins and urgent duct ligation among unstable patients.
  • If tricuspid valve is competent, increasing ventilation, oxygen, and nitric oxide to cause pulmonary vasodilatation can reduce PR.

• General measures for the treatment of heart failure include^[7]:
  • Diet: Salt and water restriction
  • Monitoring: Weight and fluid balance monitoring
  • Mobility: Mobility and compression stockings help prevent the development of deep venous thrombosis and leg edema.
  • Right heart failure: A combination of loop diuretics and digoxin (may help with right ventricular contractility). Often, loop diuretics alone are enough to achieve sufficient fluid loss, but if additional diuresis is required, the judicious coadministration of a Thiazide diuretic may be administered with loop diuretics to achieve optimal fluid balance.
• To read more about the medical therapy utilized in heart failure, click here.

Subcutaneously administered octreotide in 2–4 divided doses (50–1500 μg/day) provides symptomatic and biochemical benefit. Octreotide (somatostatin analog) binds to somatostatin receptors, and reduces the vasoactive peptides that provoke carcinoid syndrome. Concomitant monitoring of BSL and blood glucose levels is required. Lanreotide (BIM23014, angiopeptin and somatuline) is a newer somatostatin analog, has an advantage of less frequent administrations, and can be used as an alternative to octreotide.

Pulmonary valve replacement (PVR) is one of the most common procedures performed among adults with congenital heart disease, due to different diseases causing regurgitation or stenosis. Patients may undergo reoperations during their lifetime.^[9]

Indications for pulmonary valve replacement (PVR) include:^{[10][11][6][9]}

• Symptomatic patients with arrythmias or NYHA class higher than II.
• Ejection fraction of less than 40% when assessed with cardiac MRI. Both right and left ventricular dysfunction serve as an indication.
• Patients with progressive right ventricular dysfunction (right ventricular end-diastolic volume ≥160 mL/m2 or end-systolic volume ≥82 mL/m2 on CMR).
• Moderate to severe tricuspid regurgitation, resulting from annular dilation.
• Patients at risk of developing arrythmias and with prolonged QRS duration.(total QRS duration ≥180 msec, or QRS duration increase >3.5 msec per year).
• Severe PR in a patient with another cardiac lesion (such as RVOT aneurysm) that requires operative intervention.
• According to ACC/AHA guidelines, PVR is reasonable among adults with the previous TOF, severe PR, and any of the following:
  • Moderate to severe RV dysfunction/ enlargement
  • Development of symptomatic or sustained artial and/or ventricular arrhythmias
  • Moderate to severe TR

• Timing of pulmonary valve replacement is not well defined as in aortic and mitral regurgitation. However timely intervention is advised before the onset of RV dysfunction.^[12]
• Pulmonary valve should be replaced before RV end-diastolic volume-index (EDVI) exceeds 163 mL/m2 or RV end-systolic volume index (ESVI) exceeds 80 mL/m2. RV ESVI is the major factor to be considered.^[13]
• Delayed intervention has shown to have poor outcomes and higher rate of re-intervention.
• The prime goals of pulmonary valve replacement include improved functional class and quality of life, maintenance of right (and left) ventricular function, risk modification of arrhythmia and sudden cardiac death.^[14]

• Bioprosthetic valves:
  • Usually preferred over mechanical valve prosthesis and have a longevity of around 15years.^{[15][16][17][18]}
  • Bioprosthesis utilizes biological tissue that are usually harvested from the [[pericardium}pericardial sac]] of either cows or horses.^[19]
  • Do not require anticoagulation.^[20]
  • Indications^[21]: Informed patient‘s desire or if there are contraindications/high risk to anticoagulation.
• Mechanical valves:
  • Preferred among patients at high risk of reoperation such as patients with RV dysfunction.^[22]
  • Some of the examples include bileaflet (Carbomedics), titing disc (Medtronic-Hall), and the cage.^[23]
  • Require long-term anticoagulation.^[24]
  • Indications^[25]: Age <65-70 years and long life expectancy, informed patient‘s desire, another heart valve contains a mechanical implant, patient is on anticoagulation already or there are no contraindications to anticoagulation. Patients requiring a redo surgery are high-risk.

• Pulmonary valve replacement (PVR) by surgical and percutaneous approach is the definitive treatment for the management of chronic PR and has proven to improve RV function, New York Heart Association Functional Class status, quality of life, and reduce risk for development of RV tachyarrhythmias and sudden cardiac death.^[26]
• Surgical repair may combine pulmonary valve insertion with correction of the associated defects such as reduction of aneurysmal RVOT or intraoperative cryoablation.^[6]
• The indications for both surgical or transcatheter pulmonary valve replacement are similar.
• In the case of free PR with severe discrepancy (>35%) between right and left pulmonary blood flow, patients should undergo balloon dilation, with/without an endoluminal stent implantation.^[9]

• Various valved conduits are placed to replace the pulmonic valve which include homografts from cadavers, valved conduits, and the contegra bovine jugular vein graft or a bioprosthetic valve implanted directly in the RV outflow tract.^[27]
• Stenosis of the conduit is the major limitation and 25% of patients have to undergo a repeat intervention.

• The Melody transcatheter pulmonary valve (Medtronic) was approved by FDA in 2010.^[28]
• The current transcatheter valves are designed to treat conduit and bioprosthetic valve failure only.^{[29][30][31][32]}
• For transcatheter valve replacement eligibility, the morphology of RVOT (determined viaCT or MRI) serves as the major criterion. a determination that may easily be made at CT or MRI.^[9]
• Contraindications:
  • Patients with an aneurysmal appearance of RVOT do not qualify for transcatheter pulmonary valve implantation.^[9]
  • They are not useful to treat patients who had a RVOT reconstruction by transannular patching.

• Common complications of pulmonary regurgitation (PR) treatment include:
  • Complications post pulmonic valve replacement (PVR) are^[15]:
    1. Prosthetic valve failure (PVR or interventional catheter procedure is required to be redone).
    2. Prosthetic valve dysfunction (death due to prosthetic valve dysfunction is very rare).
    3. Atrial fibrillation and atrial flutter are rare complications.
    4. Stent fracture: It leads to an increase in RV outflow tract gradient and RV pressure and its incidence is around 21% in 1 series that used the Melody valve and was the major reason for a repeat intervention.^[33][34]
    5. Device instability and dislodgement^[35]
    6. Coronary compression due to stent placement^[36]
    7. Pulmonary artery obstruction.
  • Complications post transcatheter pulmonic valve implantation (TPVI) are:
    1. Infective endocarditis is not an uncommon complication. A few patients (such as of streptococcal infection) may be managed medically and surgical or percutaneous reintervention may be required for others.^[37]

• Patients with percutaneous pulmonary valve replacement have good outcome and are free of reintervention at 1 year.^[38]
• Patients with CMR derived pre operative right ventricular end diastolic volume index of less than 160ml/m² and end systolic volume index of less than 80ml/m² showed better outcomes. ^[15][39][40]

• An invasive electrophysiological study to ablate atrial flutter, and map (if not ablate) ventricular tachycardia is recommended among patients with documented atrial flutter or ventricular tachycardia.^[6]
• Before a patient reaches end­stage heart failure, resynchronization therapy is the suggested treatment for dilated right ventricles with the RBBB.^[6]
• Among patients with arrhythmias, intraoperative electrophysiological mapping with cryoablation during pulmonary valve replacement has demonstrated promising results. Complete resolution of pre‐existing arrhythmias has been reported.^[41]