Sandbox: Pulmonary Valve regurgitation

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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]

Synonyms and related terms: Pulmonary Insufficiency, Pulmonary Incompetence, Pulmonary Valve Regurgitation, Pulmonary Regurgitation, Pulmonary Valve Incompetence.

Overview

Isolated pulmonary valve reguritation is a rare disease, it is usually associated with other congenital heart disease. PR usually occurs in patients who have underwent corrective surgery for tetralogy of Fallot or pulmonary valve stenosis. Mild PR is identified in 40 to 70% of patients with normal pulmonary valve and is clinically insignificant. Chronic severe PR usally presents with exercise intolerance and features of right heart failure with progression of the disease. If left untreated patients develop RV failure, arrythmias and sudden cardiac death. Echocardiography is the initial imaging modality to detect and quantify the severity of PR. CMR is the gold standard to study the morphology of the pulmonary valve, RVOT and the RV systolic function. Chronic significant PR is treated with pulmonary valve replacement. Timing of the surgery is an important prognostic factor determining the prognosis.

Historical Perspective

  • The pulmonary valve and its function of allowing blood to the lungs for nourishment was first described by Hippocrates.[1]
  • Erasistratus, mentioned the involvement of the pulmonary valve in the unidirectional flow.
  • Galen described the membranes of the valves and named them as "semilunar".
  • Mondino de Luzzi designed the sketch of the pulmonary valves in the anatomical position for the first time.
  • Realdo Colombo described the pulmonary circulation for the first time.

Epidemiology and Demographics

  • The prevalence of mild pulmonary regurgutation is present in 40% to 78% of patients with normal pulmonary valve anatomy.[2][3]
  • In patients born with congenital heart disease, 20% of patients have associated abnormalities of the pulmonary valve or the right ventricular outlet obstruction.

Classification

Based on the pulmonary Valve Morphology
Pulmonary Regurgitation is classified into primary and secondary types based on the involvement of the pulmonary Valve.

  • Primary Pulmonary Regurgitation:The pulmonary valve morphology is affected. Isolated PR is very rare and is most commonly associated with other congenital heart diseases.
  • Secondary or Functional Pulmonary Regurgitation: The pulmonary valve function is normal. Conditions such as pulmonary hypertension and PA aneurym cause dilation of the valve annulus leading to regurgitation.

Based on the Severity
Pulmonary regurgitation is classified into three categories based on the severity of the regurgitant jet demonstrated on the 2D echo.

Natural History, Prognosis, Complications

Natural History

  • Mild PR is a very common finding on 2D echo.
  • Majority of patients with mild PR are asymptomatic and have a beningn 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.
  • Patients with acute worsening of PR should be evaluated for associated conditions such as pulmonary hypertension which increase the pressure gradient.

Prognosis

  • Symptomatic patients are treated with pulmonary valve replacement and have a good prognosis.

Complications

  • Progressive right ventricular dilation increases the risk of ventricular arrhythmias and sudden cardiac death. Patients with tetralogy of Fallot are at increased risk of developing these complications compared to patients with isolated PR.

Pathophysiology

  • Patients with PR develop chronic right ventricular overload resulting in right ventricular remodelling and progressive decline in function.[4]
  • Progressive dilation of the right ventricle results in functional tricuspid regurgitation and increases the risk of developing arrhythmias.
  • 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.
  • In patients with increased pulmonary artery pressure from dysfunction of LV or residual pulmonary artery stenosis increases the severity of PR.
  • The severity of regurgitant jet is dependent on:[4]
    • Size of the regurgitant orifice
    • Afterload of the RV
    • RV diastolic complaince
    • Duration of RV diastole According to 2014, ACC/AHA valvular heart disease guidelines the stages of severe pulmonary regurgitation are described as follows:
Stage Definition Pulmonary Valve

Anatomy

Valve Hemodynamics Hemodynamic Consequences Symptoms
C,D Severe PR
  • Distorted or absent leaflets
  • Annular dilation
  • Color jet fills RVOT
  • CW jet density and contour: dense laminar flow with steep deceleration slope; may terminate abruptly
  • Paradoxical septal motion (volume overload pattern)
  • RV enlargement
None or variable and dependent on cause of PR and RV function

Causes

The most common causes of pulmonary regurgitation are following repair of tetralogy of Fallot and pulmonary stenosis. Other common causes include as follows:[5][6][7][8]

Congenital

Causes

Acquired

Causes

Chronic PR Acute PR
  • Quadricuspid or Bicuspid valves
  • Hypoplasia of the valves
  • Prolapse of the pulmonary valve
  • Infective endocarditis
  • Following transannular patching for tetralogy of Fallot
  • Post repair of pulmonary valve stenosis
  • Rheumatic heart disease
  • Carinoid Syndrome
  • Myxomatous Degeneration of the pulmonary valve.
  • Following transannular patching for tetralogy of Fallot
  • Following balloon or surgical valvulotomy or valvuloplasty for pulmonary stenosis
  • Absent pulmonary valve syndrome
  • Isolated congenital PR
  • Peripheral pulmonary artery stenosis
  • Pulmonary hypertension
  • Right ventricular outlet aneurysm
  • Neonatal Ebstein’s anomaly
  • Following balloon dilation of critical pulmonary stenosis
  • Perforation of valvar pulmonary atresia

Diagnosis

History and Symptoms

Clinical presentation of pulmonary regurgitation varies on the severity of the regurgitation and the right ventricular function.

Physical Examination

The physical examination findings in significant pulmonary regurgitation include:

Neck

  • Increased JVP
  • Prominent "a wave" may be present
  • Prominent "v wave" may be present in presence of tricuspid regurgitation
  • A palpable impulse (lift or heave) is usually present at the left lower sternal border because of right ventricular dilation.

Auscultation

  • Pulmonic regurgitation is associated with wide splitting of S2.
  • P2 is accentuated because of presence of pulmonary regurgitation. In case of, absence of pulmonic valves (congenital or secondary to surgical resection), P2 is inaudible.
  • A right-sided S3 may be audible and may also be accentuated with inspiration.
  • Likewise, a right-sided S4 may also be audible and accentuated with inspiration.
  • Murmur of residual pulmonic regurgitation after Tetralogy of Fallot repair:
    • It is a low-pitched and soft murmur.
    • Best heard along the second or third intercostal spaces adjacent to the left sternal border.
    • It is accentuated by squatting and inspiration.
    • It is made softer by Valsalva maneuvers or expiration.
  • Murmur of pulmonic regurgitation associated with Pulmonic hypertension:
    • When the pulmonary artery systolic pressure exceeds 60 mm Hg, dilatation of the pulmonary artery ring may then result in Graham-Steell's murmur.
    • It is a high-pitched, "blowing", early diastolic decrescendo murmur like that of aortic regurgitation.
    • Best heard along the left parasternal region.
    • It is accentuated by inspiration.

Echocardiography

It is the initial imaging diagnostic test to study the pulmonary valve, RVOT anatomy, to identify the presence and quantify the severity of PR. The findings include:[9]

  • In adults, visualization of the pulmonary valve is obtained from the parasternal short-axis view at the level of the aortic valve or from a subcostal approach.[10][11]
  • Pulmonary valve morphology anomalies such as bicuspid or quadricuspid valves, hypoplasia, dysplasia, absence of pulmonary valve and motion abnormalities can be detected.[12]
  • PR is diagnosed my demonstrating a diastolic jet in the RV outflow tract towards the RV.

Colour Flow Doppler

The findings suggestive of significant PR include: [13][14][15][16][17]

  • A narrow small central and spindle shaped regurgitant jet is seen in mild PR.
  • In severe PR a wide diastolic jet at the origin which occupies 65% of the the RVOT width is seen on colour doppler imaging. The duration of the jet increases with increasing severity of PR.
  • In severe PR, a rapid equalization of diastolic pressures between the pulmonary artery and RV occurs, resulting in a short-lived regurgitant jet which can mislead in diagnosis of the severity of PR.
  • In patients with chronic significant PR, dilation of the RV can be demonstrated. In patients with physiologic PR and acute PR RV dimensions are normal.

Vena Contracta Width

It is a more accurate method to assess the severity of PR, but it lacks validation studies.

Flow convergence method

It can be assessed in few patients but lacks validation studies.[18][19]

Pulsed Doppler

It is useful to assess the forward and regurgitant flows at the pulmonary annulus and the pulmonary artery, which can be used to calculate the regurgitant volume and regurgitant fraction.[20]

Spectral Doppler

The density of the CW signal provides a qualitative measure of regurgitation. [21]

  • Pressure half-time (PHT) of less than 100 ms has a high sensitivity and specificity for identifying hemodynamically significant PR in congenital heart disease.[19]
  • PR Index: It is a ratio expressed between the duration of PR and total diastole which is measured from the end of forward pulmonary flow to the beginning of the next forward pulmonary flow curve. It has shown to have equal sensitivity to determine the severity of PR when compared to CMR.[22]
  • Myocardial performance index Tei index determined by tissue doppler imaging is a sensitive indicator of RV function in patients with chronic PR.[23]

Exercise Echocardiography

It is used to unmask latent RV dysfunction and is a helpful investigation to assess the RV function in patients who have underwent an intervention for significant PR.

Determination of severity of PR based on the findings on echocardiography:

Parameters Mild Moderate Severe
Pulmonic valve morphology Normal Normal or abnormal Abnormal
Colour flow PR jet width Small, usually 10 mm in length with a narrow origin Intermediate
  • Large, with a wide origin
  • Can be brief in duration due to the equalization right ventricular and pulmonary diastolic pressures
Continous wave signal of PR jet Faint/slow deceleration Dense/variable Dense/steep deceleration, early termination of diastolic flow
Pulmonic vs. Aortic flow by pulse wave Normal or slightly increased Intermediate Greatly increased

EKG

  • EKG findings in chronic PR are non specific.
  • In patients with tetralogy of Fallot increased QRS duration with widened QRS complex reflects the severity of PR and right ventricular dilation predisposing the patients to develop malignant arrythmias. [24]
  • In patients with RV volume overload and isolated PR, QRS prolongation with rSr morphology can be seen in right precordial leads.
  • RBB is common in majority of patients who have tetralogy of Fallot repair with right ventriculotomy.

Chest X-Ray

Chest X-Ray in chronic PR the following findings can be demonstrated:

  • Cardiomegaly when there is dilation of the RV
  • Pulmonary artery dilation

Cardiac MRI

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 regurgitant fraction of PR by using sequences called “velocity- encoded phase-contrast images”.[25]
  • CMR is useful for evaluating pulmonary regurgitant fraction, RV end-diastolic and end- systolic volumes, and RV ejection fraction
  • CMR is the diagnostic modality preffered to determine the requirement of reintervention in patients with repaired tetralogy of Fallot and to assess the ventricular function and dimensions.

Cardiac Catheterization

Echo and CMR the investigations of choice in patients to detect and diagnose the severity of PR. Cardiac Catheterization is not a recommended for diagnosis of PR. In patients with poor echocardiographic windows and with pacemakers, CMR cannot be used, catheterization in such patients is a good alternative.

Treatment

Medical Therapy

  • There are no specific medical measures for management of PR.
  • Diuretics are recommended in patients with RV dysfunction for maintenance of fluid balance.
  • In patients with repaired tetralogy of Fallot, ACE inhibitors or beta-blockers are used to reverse the neuroharmonal activation and improve the symptoms.

Surgical Therapy

Indications for Surgery

Indications for Pulmonary Valve Replacement include:

  • Symptomatic patients with arrythmias or NYHA class higher than II
  • 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 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 pulmonic regurgitation in a patient with another cardiac lesion that requires operative intervention

Timing Of Surgery

  • 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.[26]
  • 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.

Surgical Options

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.[27]

Surgical Valve Implantation

  • 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.[28]
  • Bioprosthetic valves are usually preffered over mechanical valve prosthesis and have a longevity of around 15years.[29][30]
  • Mechanical valves are preffered in patients who are at high risk of reoperation such as patients with RV dysfunction.
  • Stenosis of the conduit is the major limitation and 25% of patients have to undergo a repeat intervention.
Transcatheter Pulmonary Valve Replacement
  • The Melody transcatheter pulmonary valve(Medtronic) is approved by FDA in 2010.[31]
  • The current transcatheter valves are designed to treat conduit and bioprosthetic valve failure only.[32][33][34][35][32]
  • They are not useful to treat patients who had a RVOT reconstruction by transannular patching.
Complications
  • 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.[36][37]
  • Device instability and dislodgement
  • Coronary compression due to stent placement
  • Pulmonary Artery obstruction

Outcomes

  • Patients with percutaneous pulmonary valve replacement have good outcome and are free of reintervention at 1year.
  • Patients 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. [29][38]

Follow Up

  • All the patients should undergo a baseline transthoracic echocardiogram after PVR.[39][40]
  • Anticoagulation is recommended in patients with mechanical valves and aspirin for patients with bioprosthetic valves.[30]
  • Oral anticoagulation in patients with bioprosthetic valves is recommended only when other indications such as atrial arrhythmia or prior thromoembolic event are present.
  • All patients are adviced for a lifelong follow up to assess the valve and systolic function.

Prevention

There are no primary preventive measures but all the patients with mechanical valve prosthesis are recommended for infective endocarditis prophylaxis.[41]

Recommendations

ACC / AHA Guidelines - Recommendations for Surgery for Adults With Previous Repair of Tetralogy of Fallot(DO NOT EDIT)

According to 2008 ACC/AHA guidelines, ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease[42]

Class I
"1. Pulmonary valve replacement is indicated for severe pulmonary regurgitation and symptoms or decreased exercise tolerance.(Level of Evidence: B) "
Class IIa
"1. Pulmonary valve replacement is reasonable in adults with previous tetralogy of Fallot, severe pulmonary regurgitation, and any of the following:

Recommendations for Percutaneous Pulmonary Valve Replacement

According to 2011, Indications for Cardiac Catheterization and Intervention in Pediatric Cardiac Disease, A Scientific Statement From the American Heart Association.[43]

Class IIa
"1.It is reasonable to consider percutaneous pulmonary valve replacement in a patient with an RV-to–pulmonary artery conduit with associated moderate to severe pulmonary regurgitation or stenosis provided the patient meets inclusion/exclusion criteria for the available valve .(Level of Evidence: A) "

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