Continuing Education Activity
Pulmonic regurgitation (PR) is most commonly seen secondary to various etiologies causing pulmonary hypertension. It also appears in post valvotomy patients. The clinical picture is dominated by primary lung disease in most cases, and with disease progression, exertional dyspnea fatigue, and lower extremity swelling may be reported. The classic murmur of PR-Graham Steell murmur is heard when systolic pulmonary pressure exceeds 55 mmHg. Commonly seen EKG findings include tall P waves indicating right atrial enlargement secondary to pulmonary hypertension. Doppler echocardiography is extremely accurate in detecting PR. The most crucial aspect of management is treating the primary condition. Valve replacement may be necessary at times. The prognosis of this condition depends on the severity of PR. This activity reviews the evaluation and management of pulmonic regurgitation (PR) and the importance of the interprofessional team.
- Outline the etiology and pathophysiology of pulmonic regurgitation.
- Describe the common presenting features and physical findings of pulmonary regurgitation.
- Review the investigation findings and management options available for pulmonic regurgitation.
- Describe interprofessional team strategies for enhancing healthcare team outcomes in treating patients with pulmonic regurgitation.
The pulmonary valve is located at the junction of the distal end of the right ventricular outflow tract and the pulmonary artery. It is comprised of three semilunar leaflets which are of equal dimensions. These leaflets are joined by three commissures, which are the attachments between the pulmonic wall and the leaflets. The pulmonic valve is not attached to papillary muscles, as we see with atrioventricular valves. The microscopic structure of the leaflets consists of five layers from ventricular end to arterial end are called: lamina ventricularis, lamina radialis, lamina spongiosa, lamina fibrosa, and lamina arterialis. The pulmonic valves help in delivering deoxygenated blood from the right ventricle to the lung vasculature during systole when they open completely. They close completely during diastole to prevent regurgitant flow. By far, the most common cause of pulmonic regurgitation (PR) is the dilation of the valve ring.
Secondary to Pulmonary Hypertension
Idiopathic Pulmonary arterial hypertension (PAH)
Associated with left heart disease
- Left heart failure
- Aortic and mitral valve disease.
Associated with lung disease
- Chronic obstructive lung disease
- Interstitial lung disease
- Obstructive sleep apnea
Associated with chronic thromboembolism of lungs
Other disorders of the pulmonary vasculature
- Sickle cell disease
Pulmonic valve disease
- Postvalvotomy (iatrogenic)
- Endocarditis 
- Post ROSS procedure (pulmonary autograft for aortic valve disease)
- Drugs like methysergide, pergolide, fenfluramine
- Pulmonary hypertension
- Idiopathic dilation
- Marfan syndrome
- Post-tetralogy of Fallot (TOF) repair
Pulmonary regurgitation has bimodal prevalence. The first peak appears in young individuals who underwent surgical repair of the valve for congenital heart diseases. This condition is also prevalent in the adult population with pulmonary hypertension due to various reasons. The exact prevalence is hard to predict as there is a multitude of causes for pulmonary hypertension, which in turn can lead to PR. No racial or ethnic predilection exists. The differing frequency of PR between woman and men corresponds to the specific etiology resulting in this condition.
The valve opening and closing are mainly due to the pressure changes across it. The normal anatomy of the pulmonary valve is such that they can open only in the direction of blood flow, which is from the ventricle to the pulmonary artery. Normal pulmonary artery pressure is 15 to 28 mmHg during systole and 5 to 16 mmHg during diastole. Right ventricular (RV) pressures range from 15 to 28 mmHg during systole and 0 to 8 mmHg during diastole. During systole, the ventricular pressure increases to higher than the pulmonary artery (PA) pressure resulting in the opening of the valve and causing the blood flow from the ventricle to the pulmonary artery. Towards the end of the systole and the beginning of diastole, after most of the blood from the ventricle empties into the pulmonary artery, the valves close because of higher pressure inside the pulmonary artery, which pushes the valve leaflets to a closed position preventing any leak into the ventricle. If the valve is defective or if the pressure in the pulmonary artery is very high, there could be a backward leak of blood from the pulmonary artery into the right ventricle, causing pulmonary regurgitation.
PR demonstrates an increase in both preload and afterload. The reverse pressure gradient from the pulmonary artery to the right ventricle (RV), which is the driver of the PR, progressively decreases throughout diastole and accounts for the decrescendo nature of the diastolic murmur. With pulmonary regurgitation, the end-diastolic volume of the right ventricle remains higher than normal. As the disease progresses, the right ventricular diastolic pressure and cavity size increase due to the backflow. The forward cardiac output (CO) remains preserved during the early stages of the disease, but may not increase in a normal fashion with exercise and declines over time. A reduced RV ejection fraction may be an early indicator of hemodynamic compromise. In advanced stages, there is a significant enlargement of the RV and right atrium (RA) with marked elevation of the jugular venous pressure. As the diastolic pressure in the right ventricle increases with the progression of the disease, the murmur becomes shorter in duration.
Drugs that act through serotonergic pathways like fenfluramine or dopaminergic pathways like pergolide, cabergoline act through 5HT2B receptors causing proliferation of valve endothelium, causing valvulopathy and PR similar to carcinoid disease.
History and Physical
The etiology of pulmonary regurgitation mainly determines the history. In PR secondary to pulmonary hypertension, the clinical picture is dominated by the primary lung disease or the high pulmonary vascular resistance rather than the volume load. Isolated PR causes RV volume overload and maybe tolerated for many years without difficulty unless it complicates. In most patients, clinical manifestations of the primary disease are severe and usually overshadow the PR, which often results only in incidental auscultatory findings. Patients with PR caused by infective endocarditis who develop septic pulmonary emboli and pulmonary hypertension often exhibit severe RV failure. With the disease progression, the patient may report fatigue, exertional dyspnea, abdominal fullness/bloating, and lower extremity swelling.
Post Ross procedure: Ross procedure is a pulmonary autograft placement in place of the diseased aortic valve, which is a common procedure in congenital aortic valve disease. Ross procedure is the only aortic valve intervention that has long term survival benefit. As per the recent American Journal of Cardiology consensus (2018), this procedure is also under consideration for selected young patients. In this procedure, a pulmonary autograft replaces the aortic valve, and a pulmonary autograft replaces the pulmonic valve. Aortic regurgitation is a known complication post-procedurally, which can occur anytime. Another major complication of this procedure is PR, which can occur after 10 to 15 years of the procedure.
Post-TOF repair: Despite major advances in the TOF repair in the past few decades, many patients experience several complications secondary to the post-surgical hemodynamic and electrophysiological abnormalities. Right bundle branch block, residual intra-cardiac shunts, tricuspid regurgitation, etc., cause pulmonary annular dilatation causing PR.
Jugular venous distension with large v waves (Lancisi sign) can be seen in patients with PR secondary to pulmonary hypertension if the right ventricular pressure is high enough to cause tricuspid insufficiency as well.
- The first heart sound (S) is normal.
- P2 is not audible in patients with congenital absence of the pulmonic valve; however, this sound becomes accentuated in patients with PR secondary to pulmonary hypertension. There may be a wide splitting of S2 caused by prolongation of RV ejection accompanying the augmented RV stroke volume.
- A systolic ejection click can be heard sometimes in the second left intercostal space, due to sudden expansion of the pulmonary artery by augmented RV stroke volume.
- An S3 and S4 originating from the right ventricle are often audible, most readily in the fourth intercostal space at the left parasternal area, and become augmented by inspiration.
- In the absence of pulmonary hypertension, the PR murmur is a diamond-shaped, diastolic low pitched murmur which commences as soon as the pulmonary artery and the right ventricular pressures diverge (approximately 0.04 seconds after P2). The auscultation of the peak intensity of this murmur is when the gradient between these pressures is maximal, and soon, it ends with equilibration of the pressures.
- The Graham Steell murmur: It is heard when systolic pulmonary artery pressure exceeds approximately 55 mm Hg, resulting in dilatation of the pulmonary annulus causing high-velocity regurgitant jet. It is a high pitched, blowing, decrescendo murmur beginning immediately after P2, most prominent in the left 2 to 4 intercostal spaces, increases in intensity with inspiration exhibits little change after amyl nitrite inhalation or vasopressor administration, is diminished during the Valsalva strain, and returns to baseline intensity almost immediately after release of the Valsalva strain.
Progression of PR:
As per 2014 AHA/ACC guidelines, all valvular heart diseases progress through four stages
- Stage A: Patients at risk for PR, who still have not developed it
- Stage B: Asymptomatic patients with mild or moderate PR
- Stage C: Asymptomatic patients with severe PR
- Stage D: Symptomatic patients with PR
Descriptions of the severity of PR appear in the section of the investigations below.
Commonly seen EKG findings in pulmonary regurgitation in the absence of pulmonary artery hypertension (PAH) are rSR configuration in the right precordial leads, which reflects RV diastolic overload. If it is secondary to PAH, then a P-pulmonale (tall p waves- indicating right atrial enlargement), increased r to s ratio in the right precordial leads along with right axis deviation can be seen. These findings are secondary to RV hypertrophy.
On a chest X-ray, both pulmonary artery and right ventricular enlargement are visible, but these signs are nonspecific. Fluoroscopy may demonstrate pronounced pulsation of the main pulmonary artery.
Right ventricular dilation, along with hypertrophy, appears in two-dimensional echocardiography in patients with pulmonary hypertension. Abnormal motion of the septum characteristic of volume overload of the right ventricle in diastole and/or septal flutter may be evident. The motion of the pulmonic valve may point to the cause of the PR. The absence of a waves and systolic notching of the posterior leaflet suggest pulmonary hypertension; large a waves indicate pulmonic stenosis. Doppler echocardiography is extremely accurate in detecting PR and in helping to estimate its severity.
- Mild PR - Normal right ventricular dimensions with thin (less than 10mm in length) regurgitant jet width by color doppler
- Moderate PR - Normal or dilated right ventricle with intermediate regurgitant jet width (less than 50% of pulmonic valve annulus)
- Severe PR- Dilated right ventricle (except in acute PR) with large regurgitant jet width (greater than 50% of pulmonic valve annulus)
In PR, opacification of the right ventricle is noticed following the injection of contrast into the pulmonary artery due to the regurgitant jet.
Cardiac magnetic resonance helps in assessing pulmonary artery dilation and severity of PR.
Treatment / Management
Treatment of the primary condition is the most crucial aspect of the management. For example, treating the lesion responsible for PAH, such as mitral valve regurgitation/stenosis, often improve PR.
Symptomatic patients who are not surgical candidates receive management with heart failure therapy, especially diuretics, ACE inhibitors, and digoxin.
Patients with iatrogenic PR caused by the surgical correction of tetralogy of Fallot (TOF) might benefit from a treatment specifically directed at the pulmonary valve. In such conditions, valve replacement may be necessary, preferably with a porcine bioprosthesis or a pulmonary allograft. With recent advances, transcatheter pulmonary valve replacement is being implemented with great success in native pulmonic valve disease and PR following surgical correction of congenital heart defects.
The following are the indications for surgery:
1. Severe symptomatic PR
2. Asymptomatic severe PR with two out of four of the following conditions
- Elevated right ventricular volume (end-diastolic vol. index more than 160 mL/m^2 or end-systolic volume index of 80 ml/m2)
- Elevated right ventricular pressure.
- Reduced exercise tolerance
- Mild to moderate systolic dysfunction of either right or left ventricle
A bioprosthetic valve is preferable to a mechanical valve as long term anticoagulation is not required and has better longevity (up to 15 years).
Percutaneous pulmonary valve implantation is indicated in patients with dysfunctional conduit in the right ventricular outflow tract with a regurgitant prosthetic valve. This procedure involves artificial valve placement through central venous access. The success rate of this procedure is about 94% to 98%. Procedural complication rates are between 3% to 6%, among which coronary artery compression is the most important one. Another advantage of this procedure is very less hospitalization time (4 to 5 days), and patients will be able to go back to their work immediately post-discharge. Infective endocarditis forms the most important delayed complication.
Pulmonary regurgitation can be seen in several underlying heart and lung conditions, as noted in the etiology. Identifying the underlying cause can be the most challenging aspect and also plays a critical role in the management of PR.
Clinically it is very important to distinguish the blowing decrescendo murmur of PR from a similar murmur noticed in aortic regurgitation. PR can sometimes coexist as one of the multivalvular lesions involving mitral and aortic valves. Such cases need further investigations with echocardiography to check the severity of each lesion.
Mild PR on echocardiography will not require a followup unless the patient becomes symptomatic or if the initial echocardiogram showed signs of early RV dysfunction. Moderate to severe PR needs regular follow up with history, physical exam, and echocardiography to assess the disease progression and the need for surgery.
As per adult congenital heart disease guidelines by AHA/ACC, patients who underwent TOF repair should have an annual check-up with a cardiologist with expertise in that area.
Prognosis depends on the severity of pulmonary regurgitation. Most patients with PR secondary to repair for tetralogy of Fallot do well, but there could be delayed mortality, which is related to right ventricular dysfunction. If PR is mild to moderate, there is no significant reduction in survival. However, with severe PR and persistently elevated RV volume may lead to RV failure and propensity for arrhythmias and increased risk of cardiac death.
In PR secondary to pulmonary hypertension, time of diagnosis, and duration of pulmonary hypertension play a significant role in the prognosis. Early diagnosis of pulmonary hypertension and the presence of a reversible cause for PAH carries a good prognosis.
RV enlargement leading to right-sided heart failure and sudden cardiac death are some of the major complications of severe PR. Other complications include hepatic congestion secondary to right heart failure, thromboembolic events, arrhythmias are not so uncommon with severe PR.
Complications post pulmonic valve replacement include valve failure and infective endocarditis.
Postoperative and Rehabilitation Care
Three to six months of anticoagulation for patients with bioprosthetic valves and life long anticoagulation for mechanical valves.
Baseline echo for valve hemodynamics followed by another 2D echocardiogram at one year to 18 months and then as needed if the patient develops symptoms.
Deterrence and Patient Education
Patients with mild to moderate PR do not need any restrictions for athletic activities. The literature does not mention any specific comments on the deterrence of this condition. No specific dietary restrictions are necessary unless there are heart failure symptoms, in which case a salt-restricted diet is beneficial.
Pearls and Other Issues
The American Heart Association (AHA) recommendations on infective endocarditis prevention do not support the necessity of using antibiotic prophylaxis in pulmonic regurgitation for otherwise structurally normal pulmonic valves, especially if there is no audible diastolic murmur. However, PR in congenital heart malformations, acquired valvular dysfunction as in rheumatic heart disease, complex cyanotic heart disease, prosthetic valves, and prior bacterial endocarditis comprise moderate- to high at-risk conditions that warrant antibiotic prophylaxis.
Infective endocarditis prophylaxis is not recommended in PR with a normal valve structure. Antibiotic prophylaxis is recommended in the following circumstances:
- PR with cyanotic heart disease
- A patient with a previous history of infective endocarditis
- Valvular dysfunction with rheumatic heart disease
- PR after repair of congenital heart diseases with residual defects
- Prosthetic valves
Enhancing Healthcare Team Outcomes
An interprofessional team is useful in the management of PR. It can include primary care providers, cardiologists, cardiology nurses, and pharmacists. PR may worsen with time, and hence patients (with moderate to severe disease) should be monitored at least with annual visits. Assessing the exercise capacity during each visit will help the clinician in estimating the need and timing for surgical repair. Primary care providers often are the first to diagnose the condition and refer to the cardiologist. Cardiology nurses monitor and educate patients and their families. The nurses arrange to follow up and report changes in status to the team. Pharmacists review medication choices, dosage, and potential interactions. They stress compliance and educate patients about possible side effects. These interprofessional collaborative efforts will lead to improved outcomes in patients with pulmonic regurgitation. [Level 5]