Most patients with pulmonary regurgitation are asymptomatic. Those that are symptomatic may present initially with symptoms of exertional dyspnea as a result of reduced cardiac output stemming from the volume overload to the right heart.[9] Patients may present with a progressive decrease in exercise tolerance.[10][11][11] Severe PR may present with signs and symptoms of right heart failure such as pedal edema, congestive hepatomegaly, and rarely, raised JVD. Patients may present with the complications that result from RV dilation, particularly symptomatic ventricular arrhythmia.[12]

In clinical presentations where an underlying pathology is determined as the root cause for pulmonary regurgitation, symptoms of the underlying disease are prominent. Pulmonary regurgitation secondary to pulmonary hypertension may show symptoms of the underlying condition such as left heart disease, chronic lung conditions such as COPD or OSA, or primary pulmonary arterial hypertension.[9] 

Auscultation in pulmonary regurgitation would reveal a diastolic decrescendo murmur heard in the 2nd and 3rd left intercostal spaces. Also appreciated is an S3, indicating volume overload. Being a right-sided murmur, the intensity of the murmur would increase during inspiration (owing to the increased preload) and would reduce during the Valsalva maneuver.[9] Since the reversal of flow begins in diastole and occurs due to increased pressure gradient between the 2 compartments, the murmur is diastolic and decrescendo in character. 

It is worth mentioning the changes in auscultatory findings in patients with or without pulmonary arterial hypertension. As a large gradient exists between the pulmonary artery and right ventricle due to elevated pulmonary artery pressures the murmur of PR is diastolic, heard throughout diastole (whereas it is short-lived in cases without pulmonary hypertension), decrescendo, associated with loud P2 and heard in the 2nd and 3rd left intercostal spaces and increases with inspiration.[13]

An echocardiogram is the investigation of choice for pulmonary regurgitation as it determines the severity, cause, mechanism, and determines progression to ventricular remodeling and heart failure.[14] It is more imperative to identify ventricular dilation during follow up rather than the severity of pulmonary regurgitation independently. The severity of pulmonary regurgitation can be determined by the area occupied by the regurgitant jet. A regurgitant jet larger than 50% of the pulmonary valve annulus is indicative of severe PR.[14] Other investigations that can be used are an electrocardiogram (EKG) and a chest x-ray. Although not diagnostic, they can be instrumental in diagnosing complications. An EKG can prove to be useful in patients who present with arrhythmias brought on by the right ventricular dilation secondary to the volume overload. A chest X-ray would reveal right ventricular dilation identified in a lateral chest x-ray as reduced retrosternal space. 

Cardiac MRI can be used in moderate and severe PR and has been found to be as useful in noninvasive Doppler echocardiography. It can be used to quantify the regurgitant jet and can be used for monitoring the progression of the disease.[15]

Exercise stress EKG is used in order to assess the risks associated with progressive RV dilation. It is particularly useful in detecting ventricular arrhythmias and in assessing the risk of sudden cardiac death and cardiovascular morbidity.[16]

Monitoring: The most common cause of pulmonary regurgitation encountered is iatrogenic following tetralogy of Fallot repair. According to the AHA/ACC guidelines for adults with adult congenital heart disease, patients must be followed up with history, clinical examination, and echocardiogram annually.[17] Any change in symptoms, particularly a decrease in exercise tolerance, dyspnea, chest pain, or new murmurs, must be investigated.

Recommended treatment modalities as per the AHA/ACA guidelines are based on the severity of symptoms and the progression of PR, as evidenced by the echocardiogram. In asymptomatic patients with PR, treatment is not recommended unless 2/4 of the following criteria are met. Criteria include mild or moderate RV or LV systolic dysfunction, severe RV dilation (right ventricular end-diastolic volume >160ml/m2), right ventricular systolic pressure (RVSP) due to right ventricular outflow tract (RVOT) >2/3 of systemic pressure or progressively reduced exercise tolerance.[17]

All symptomatic patients with PR should be treated with surgical methods.[18][19] The preferred methods of treatment are primarily surgical pulmonary valve replacement with a bioprosthesis valve or a mechanical valve. A bioprosthesis valve is preferred due to the durability of the prosthesis, low risk of valve failure, and limited period of anticoagulation as compared to mechanical valves. Percutaneous pulmonary valve replacement is a rapidly developing field in interventional cardiology. The areas that need to be addressed in this field include modifying factors that reduce its eligibility due to variations in the anatomy of the RV outflow tract.[20][21] Tricuspid regurgitation occurs as a part of the sequelae of complications that follow pulmonary regurgitation and therefore need to be addressed as well. In patients with tricuspid regurgitation, tricuspid annuloplasty may be performed. Additionally, large akinetic RVOT segments may be encountered, which need to be resected as well as they can further worsen prognosis.[8] 

Medical therapy is only recommended if the cause of pulmonary regurgitation is secondary to a primary medical condition such as pulmonary arterial hypertension or carcinoid disease. Medical therapy in the form of medications targeting heart failure such as diuretics, ACE inhibitors, and beta-blockers is only recommended in patients that are symptomatic with severe PR and are poor surgical candidates owing to age or comorbidities.

The differential diagnosis following history and physical examination would explore the causes of diastolic murmurs heard along the left sternal border. A murmur in this location could either be related to aortic regurgitation or pulmonary regurgitation. These can be differentiated using maneuvers. Being a right-sided murmur, the pulmonary regurgitation diastolic decrescendo murmur would increase in intensity on inspiration due to the negative intrathoracic pressure generated and would reduce in intensity if the patient performs the Valsalva maneuver. These distinguishing characteristics can be used if an asymptomatic patient presents with a murmur. However, if the presenting symptom is related to the complications that can arise as a result of pulmonary regurgitation, the differential diagnosis would cover the causes of right heart failure as well. It is essential to explore the causes of the same, which include chronic pulmonary emboli, constrictive pericarditis, infective endocarditis, and restrictive cardiomyopathy.

There continues to be debate over the need and timing of surgical pulmonary valve replacement in cases of repaired tetralogy of Fallot. In the absence of pulmonary valve repair, patients with pulmonary regurgitation will develop RV dilation, RV systolic dysfunction, left ventricular dysfunction, arrhythmias, and sudden cardiac death. It has been found that the risk of arrhythmias is greater in cases where biventricular dysfunction has set in.[9]

Favorable outcomes following repair include a reduction in RV volume, improvement in RV systolic function noticed during the first postoperative year, improved exercise tolerance, reduction in risk of arrhythmias, improvement in New York Heart Association (NYHA) class for patients initially graded NYHA class I and II.[22] It has been found that early PV repair can be instrumental in preventing irreversible RV remodeling from setting in. The rate of freedom from reoperation in the 10 years following surgery was found to be favorable.[23] PV repair, coupled with intraoperative cryoablation has been found to be effective in the treatment and prevention of preexisting arrhythmias, including atrial flutter/fibrillation and monomorphic ventricular tachycardia.

Untreated pulmonary regurgitation can result in ventricular arrhythmias, right heart failure, congestive hepatomegaly, anasarca, left ventricular systolic dysfunction, and sudden cardiac death. Causes of death in patients with pulmonary regurgitation include sudden cardiac death from ventricular arrhythmias and heart failure from progressive ventricular dysfunction.[24] Regular follow up, and early surgical intervention could beneficially reduce the onset of these complications.[25] 

Complications following a pulmonary valve replacement is also a point of contention. Increased frequency of repeat surgical intervention and prosthetic valve failure are complications that follow. Following surgical pulmonary valve replacement with a mechanical valve, anticoagulation and prophylaxis against bacterial endocarditis are advised.[26]

In mild or moderate PR, there are no recommendations against regular physical activity. Symptomatic patients with pulmonary regurgitation may present with a progressive decrease in exercise tolerance, and clinicians must be alerted to the importance of such symptoms in conjunction with a history of Tetrology of Fallot repair.

Pulmonary regurgitation is a disease entity that can present years after a surgical tetralogy of Fallot repair. Primary care providers play a pivotal role in the follow up of such patients. Paying close attention to the history and physical examination can lead to detecting pulmonary regurgitation earlier on in the course of the disease before irreversible biventricular remodeling sets in. Alerting a cardiologist to symptoms of decreased exercise tolerance can be beneficial in determining the optimal timing for a pulmonary valve replacement. At this stage, pharmacists, nurses, and other health care providers contribute to the interprofessional collaborative efforts.