Continuing Education Activity

Pulmonary regurgitation, characterized by blood flow from the pulmonary artery back into the right ventricle during diastole, presents various underlying causes like pulmonary hypertension, congenital heart defects (eg, tetralogy of Fallot), iatrogenic influences, or conditions like carcinoid syndrome or rheumatic heart disease. While asymptomatic severe cases might not require therapy, valve replacement becomes crucial for symptomatic or progressive cases, focusing on alleviating symptoms and restoring normal hemodynamics. The choice between percutaneous or surgical approaches is determined by individual patient factors, anatomy, and risk considerations, with post-replacement lifelong monitoring, especially in those with prosthetic valves, being essential to ensure optimal outcomes and prevent complications like thrombosis or endocarditis.

Clinicians participating in a pulmonary regurgitation course can expect a comprehensive understanding of the condition's underlying causes, diagnostic approaches, and management strategies. They will gain insights into various etiologies, including pulmonary hypertension, congenital heart defects, and iatrogenic influences, allowing for more precise diagnosis and tailored treatment plans. The course covers guidelines for patient follow-ups, echocardiographic assessments, and indications for intervention, guiding clinicians in decision-making regarding valve replacement and the choice between percutaneous or surgical approaches. Additionally, emphasis is placed on lifelong post-replacement monitoring to prevent complications and ensure optimal patient outcomes.

Objectives:

• Determine the common etiologies that lead to the development of pulmonary regurgitation.

•  Assess the typical presentation of a patient with symptoms of pulmonary regurgitation.

• Identify the indications for surgical pulmonary valve replacement in patients with pulmonary regurgitation.

• Communicate the importance of collaboration among the interprofessional team to ensure the appropriate identification and selection of candidates for pulmonary valve replacement and enhance postoperative recovery.

Introduction

The pulmonary valve is a vital component of the cardiovascular system, serving as a thin tricuspid structure. This valve prevents backward flow into the right ventricle after propelling blood into the low-pressure pulmonary circulation.[1] Pulmonary regurgitation occurs when blood flows from the pulmonary artery back into the right ventricle during diastole. Physiologic pulmonary regurgitation, characterized as a trace, is commonly found in nearly all individuals, especially those advanced in age.[1]

Specific pathological conditions may result in excessive and clinically significant regurgitation, negatively impacting proper ventricle function. This regurgitation can manifest as clinical symptoms of right-sided volume overload and heart failure.[2] Pulmonary regurgitation is not typically the primary pathological process but rather a secondary finding associated with an underlying condition such as pulmonary hypertension or dilated cardiomyopathy. These underlying processes play a significant role in the development of pulmonary regurgitation.[2]

Understanding the intricate workings of the pulmonary valve and the factors contributing to pulmonary regurgitation is crucial for comprehensive patient care. By elucidating the mechanisms involved in the pathogenesis of pulmonary regurgitation, healthcare professionals can enhance their ability to diagnose, manage, and treat patients with this condition, ultimately improving patient outcomes and quality of life.

Etiology

Pulmonary hypertension and congenital heart defects, particularly tetralogy of Fallot, are the leading causes of a dysfunctional pulmonary valve resulting in regurgitation. Less frequently observed causes of pulmonary regurgitation encompass infective endocarditis, carcinoid syndrome, and rheumatic fever.[3]

Pulmonary Hypertension

Primary pulmonary hypertension primarily contributes to pulmonary regurgitation in adults, arising from various causative factors. Secondary or functional pulmonary regurgitation develops in individuals with a structurally normal pulmonary valve but who exhibit severe pulmonary arterial hypertension and dilation of the pulmonary artery.[4][3]

Tetralogy of Fallot

Tetralogy of Fallot, characterized by obstruction of right ventricle outflow, ventricular septal defect, right ventricle hypertrophy, and an overriding aorta, represents the most prevalent form of cyanotic congenital heart disease globally. This condition is estimated to affect around 2700 infants annually in the United States alone.[5] After surgical repair of tetralogy of Fallot, most patients often have significant residual pulmonary regurgitation.[4]

Iatrogenic Significant Pulmonary Regurgitation

This regurgitation frequently arises as a consequence of surgical valvotomy/valvectomy or balloon pulmonary valvuloplasty performed to address right ventricle outflow tract obstruction as part of the management of conotruncal abnormalities.[6][7][8][9]

Rheumatic Heart Disease

Rheumatic disease rarely affects the pulmonary valve, and when it does, there is a consistent association with rheumatic involvement of other cardiac valves.[10]

Carcinoid Heart Disease

In patients with liver metastasis from carcinoid disease, carcinoid heart disease can impact the heart in up to 60% of cases, often presenting as a valvular disease. Among a group of 74 patients with carcinoid syndrome who had carcinoid heart disease demonstrated by echocardiography, the pulmonary valve was affected in 88% of individuals.[11] Doppler evaluation of the pulmonary valve in 47 patients showed that 53% had pulmonary stenosis, while 81% exhibited pulmonary regurgitation.[11]

Medications

Significant pulmonary regurgitation can occur as a result of medications that affect serotoninergic pathways, such as methysergide, pergolide, and fenfluramine.[12]

Epidemiology

Researchers believe that 2 distinct demographic patterns characterize the prevalence of pulmonary regurgitation. First, this condition tends to be more prevalent in young patients who have undergone surgical repair for congenital pulmonary stenosis or right ventricle outflow tract obstruction. Secondly, patients diagnosed with pulmonary arterial hypertension commonly exhibit pulmonary regurgitation.[13] Due to the diverse range of underlying causes contributing to pulmonary regurgitation, accurately determining this condition's exact prevalence poses a challenge.[3] Nevertheless, recognizing these demographic trends and understanding the multifactorial nature of this condition can significantly contribute to proper diagnosis, management, and patient care.[14]

Pathophysiology

Pulmonary regurgitation results in a volume overload of the right ventricle, leading to enlargement, impaired function, and functional tricuspid valve regurgitation. The enlargement of the chambers also increases the risk of atrial and ventricular arrhythmias, as well as potential morbidity and mortality if left untreated.[5][15][16][17] Initially, pulmonary regurgitation is typically well-tolerated, and patients often remain asymptomatic for an extended period.[18] However, over time, the right ventricle undergoes dilation in response to the increased volume load while attempting to sustain cardiac output. The progressive dilation of the right ventricle eventually leads to impaired right ventricle function.[19][20][21][22] 

As functioning further deteriorates, cardiac output diminishes, necessitating increased heart rate and oxygen extraction to maintain sufficient tissue oxygenation. At this stage, the individual experiences poor tolerance to any increase in oxygen demand, such as during physical exercise.[19]

History and Physical

Most patients with pulmonary regurgitation are asymptomatic. Those who 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.[23] Patients may present with a progressive decrease in exercise tolerance.[24][25] Severe pulmonary regurgitation may present with signs and symptoms of right heart failure such as pedal edema, congestive hepatomegaly, and rarely, raised jugular vein distention. Patients may present with lightheadedness or palpitation with the onset of ventricular or atrial arrhythmias.[26] Pulmonary regurgitation secondary to pulmonary hypertension may show symptoms of the underlying condition such as left heart disease, chronic lung conditions such as chronic obstructive pulmonary disease or obstructive sleep apnea, or primary pulmonary arterial hypertension.[23] 

Cardiac examination findings are typically within normal limits in individuals with physiological pulmonary regurgitation. Some individuals with a lean physique may detect a faint early diastolic murmur in cases of mild pulmonary regurgitation. As pulmonary regurgitation increases significance, a systolic ejection murmur may be audible at the left upper sternal border due to increased right ventricle stroke volume. A third heart sound may be present, while a fourth one is uncommon. Mildly accentuated right ventricle impulse is generally observed in patients with severe pulmonary regurgitation; however, the jugular venous pressure is usually normal. A prominent jugular venous "a" wave may indicate pulmonary artery hypertension, while a prominent "v" wave is in patients with severe tricuspid valve regurgitation.[27]

The characteristic murmur associated with pulmonary regurgitation and pulmonary hypertension, known as the Graham-Steell murmur, is high-pitched and "blowing" in quality. This murmur begins with an accentuated second heart sound (P2 component). The duration of the murmur varies, and in cases where there is a pan-diastolic gradient between the pulmonary artery and right ventricle diastolic pressure, the murmur may occupy the entire diastolic phase. The intensity of the murmur may increase during inspiration. The characteristics of the pulmonary regurgitation murmur differ in patients without pulmonary hypertension, such as those who have undergone tetralogy of Fallot repair, resection of the pulmonary valve, right-sided endocarditis, idiopathic pulmonary artery dilation, or isolated absence of pulmonary valve. When the pulmonary artery diastolic pressure is normal or low, and the regurgitant flow rate reduces, the regurgitant murmur typically has a lower to medium pitch. This murmur may be brief, occurring early in diastole because of the early equalization of the pulmonary artery and right ventricle diastolic pressures. In patients with normal pulmonary pressures, the murmur of pulmonary regurgitation may not be audible. In certain congenital conditions, such as an absent pulmonary valve, the P2 component of the second heart sound is not heard—leading to a silent interval between A2 and the onset of the regurgitant murmur. These patients may also exhibit a loud to-and-fro murmur.[27]

Evaluation

An early diastolic murmur, the incidental finding of RV enlargement, or a history of surgical interventions, such as valvotomy or balloon pulmonary valvuloplasty for right ventricular outflow tract obstruction, should prompt suspicion of pulmonary regurgitation. Additionally, patients who have undergone surgical repair for tetralogy of Fallot commonly exhibit severe pulmonary regurgitation due to patch enlargement of the right ventricle outflow tract. In evaluating suspected valve disease, all patients should undergo an echocardiogram (ECG), which confirms the diagnosis and provides valuable insights into the underlying mechanism and severity of the valve disease. ECGs also assess pulmonary regurgitation's hemodynamic effects and evaluate associated conditions such as pulmonary artery hypertension or tricuspid valve regurgitation. Consider cardiovascular magnetic resonance (CMR) imaging for patients with moderate or greater pulmonary regurgitation, if available. CMR allows for a quantitative assessment of pulmonary regurgitation and the evaluation of right ventricle size and function—factors that can impact the timing of intervention. Computed tomography (CT) is generally unnecessary for diagnosing and evaluating pulmonary regurgitation. However, a CT may be beneficial in cases where ECG views are suboptimal and CMR is not feasible. Exercise testing is typically not required but may be helpful for patients who experience exertional symptoms disproportionate to the observed degree of valve disease and right ventricle dysfunction. Cardiac catheterization is generally unnecessary but may be beneficial in selected patients to evaluate pulmonary arterial hypertension. In summary, a comprehensive diagnostic approach for pulmonary regurgitation involves echocardiography as the initial modality of choice, with consideration for CMR imaging, CT scans, exercise testing, or cardiac catheterization in specific clinical scenarios.

Electrocardiogram: While an ECG is unnecessary for diagnosing pulmonary regurgitation, this testing assesses potentially associated conditions, including arrhythmias and indications of right ventricle hypertrophy and congenital heart disease. Typically, the ECG reveals sinus rhythm, although arrhythmias can develop, as mentioned earlier. Patients who have undergone repaired tetralogy of Fallot with longstanding severe pulmonary regurgitation often exhibit right bundle branch block with QRS prolongation. Right axis deviation and criteria for right ventricle hypertrophy may be evident in patients with concomitant right ventricle outflow tract obstruction or pulmonary arterial hypertension.[26] Obtaining an ECG aids in identifying these additional findings, contributing to the comprehensive evaluation of patients with pulmonary regurgitation.

Chest Radiography: Though not necessary for pulmonary regurgitation diagnosis, a chest radiograph is often conducted in dyspneic patients to assess potential pulmonary and cardiac causes. In individuals with severe pulmonary regurgitation, a notable radiographic finding is the enlargement of the right ventricle. Reduced retrosternal airspace on a lateral chest radiograph indicates this enlargement.[28] Additionally, on the posteroanterior image, superior displacement of the heart's apex causes the left heart border elevation. While the main pulmonary trunk may appear prominent, pulmonary vascularity usually remains normal. The right atrium may also show enlargement in patients with associated tricuspid regurgitation.[29] Patients who have undergone previous surgical interventions will exhibit radiographic features indicative of prior sternotomy/thoracotomy and valve prosthesis. Obtaining a chest radiograph aids in identifying these distinct radiographic manifestations, assisting in the comprehensive evaluation of patients with pulmonary regurgitation who present with dyspnea.

Echocardiography: Two-dimensional and Doppler echocardiography plays a crucial role in identifying the underlying mechanism of pulmonary regurgitation, such as flail or dysplastic cusps, restricted cusp mobility (typically observed in carcinoid heart disease), or mal-coaptation of pulmonary valve/functional pulmonary regurgitation secondary to idiopathic pulmonary artery dilatation or pulmonary arterial hypertension.[30][4][31][32][31] In cases of infective endocarditis affecting the pulmonary valve, visualizing vegetation on transthoracic and transesophageal echocardiography may pose challenges. However, these imaging modalities complement each other in providing a comprehensive assessment.[33] Parasternal short and long-axis windows are recommended for evaluating the anatomy of the pulmonary valve and assessing Doppler hemodynamics. Additional views, such as apical and subcostal, can complement the assessment of pulmonary valve anatomy and hemodynamics.[34] Both color and spectral Doppler echocardiography play a valuable role in quantifying the severity of pulmonary regurgitation.[35]

The width and duration of the regurgitant jet determine the severity of pulmonary regurgitation. In cases of mild pulmonary regurgitation, the regurgitant jet appears narrow. For moderate pulmonary regurgitation, the jet widens but remains less than 50 percent of the width of the pulmonary valve annulus. In severe pulmonary regurgitation, the color jet fills the RV outflow tract, exceeding 50 percent of the dimension of the pulmonary valve annulus. Pulmonary regurgitation typically manifests as a holo-diastolic jet, although in severe cases, early- to mid-diastolic equalization of the pulmonary artery and RV pressures leads to the cessation of the jet.[34][36] Severe pulmonary regurgitation can sometimes be underestimated by color flow Doppler echocardiography due to the laminar signal and the early diastolic termination of the jet. In evaluating pulmonary regurgitation severity, several ancillary echocardiographic parameters play a crucial role. These include vena contracta width, pulsed-wave Doppler flow measurement in the pulmonary arteries, and assessment of the density and contour of the continuous wave Doppler signal.[36]

The continuous wave Doppler signal for mild pulmonary regurgitation appears light with a slow deceleration rate. In cases of moderate pulmonary regurgitation, the continuous wave Doppler signal density is moderate, and the deceleration rate varies. A dense continuous wave Doppler signal, steep deceleration, and early termination of diastolic flow characterize severe pulmonary regurgitation.[37] Two-dimensional Doppler echocardiography enables the qualitative assessment of right ventricle enlargement, systolic dysfunction, and the sequelae associated with severe pulmonary regurgitation.[36] Transesophageal echocardiography, due to the anterior position of the pulmonary valve, rarely provides additional information regarding the severity of pulmonary regurgitation beyond that obtained from transthoracic echocardiography. Three-dimensional echocardiography has shown promise for the assessment of pulmonary regurgitation in select patients. A comprehensive echocardiographic evaluation should include determining left ventricular function, a prognostic factor for long-term survival. Additionally, associated anomalies such as branch pulmonary artery stenosis, tricuspid regurgitation, and intracardiac shunts should be assessed.[36]

Cardiac Magnetic Resonance Imaging: Cardiac magnetic resonance (CMR) imaging is the preferred modality for evaluating right ventricle enlargement and dysfunction, which bear significant consequences in the presence of longstanding moderate to severe pulmonary regurgitation.[37] CMR imaging offers the advantage of providing a quantitative assessment of pulmonary regurgitation severity, including calculating regurgitant volume and monitoring disease progression over time due to the absence of ionizing radiation, making this a safe option for serial evaluations.[16][35][38][39] Importantly, assessing pulmonary regurgitation severity, RV size, and function using CMR does not require administering exogenous contrast agents.

Computed Tomography: Computed tomography (CT) can assess the effects of pulmonary regurgitation on right heart dimensions and function. However, CT is usually reserved for non-serial evaluations unless there is a contraindication to cardiovascular magnetic resonance (CMR), like the presence of a non-MR-compatible implanted cardiac pacemaker or device. Serial CT imaging raises concerns regarding exposure to ionizing radiation and using iodinated contrast agents. Nonetheless, in specific scenarios, CT may offer valuable insights before the intervention, aiding in the determination of whether percutaneous intervention is feasible.[40][41][40] Additionally, CT may benefit surgical planning and assessing coronary anatomy and atherosclerosis before reoperation.[42][43][44]

Exercise stress test: Cardiopulmonary exercise testing offers valuable prognostic information and can aid in determining the optimal timing for pulmonary valve replacement in individuals experiencing exertional symptoms disproportionate to the severity of the disease and the extent of right ventricle dysfunction.[19][45] Further, exercise testing plays a crucial role in screening for exercise-induced arrhythmias and may provide insights for risk stratification in terms of sudden death.[46]

Cardiac Catheterization: Non-invasive modalities are generally effective in assessing pulmonary regurgitation's mechanism, severity, and hemodynamic burden. As a result, cardiac catheterization plays a limited role in diagnosing pulmonary regurgitation patients. Clinicians primarily utilize this modality to assess pulmonary vascular resistance in individuals with pulmonary arterial hypertension and to preoperatively evaluate coronary arteries, particularly in patients under consideration for percutaneous pulmonary valve replacement. In certain cases, preoperative invasive hemodynamic assessment can assist in risk stratification for patients with pulmonary regurgitation and associated conditions like severe tricuspid regurgitation, constrictive pericarditis, and right ventricle diastolic dysfunction. Hemodynamic findings in severe pulmonary regurgitation may include low pulmonary artery end-diastolic pressure, resulting in wide pulse pressure, elevated right ventricle end-diastolic pressure, and, in some instances, the pulmonary artery pressure tracing may resemble the right ventricle pressure tracing.[47] A pulmonary artery angiogram is not routinely performed to assess the severity of pulmonary regurgitation in contemporary clinical practice.

Treatment / Management

Patients diagnosed with moderate or severe pulmonary regurgitation should undergo annual follow-up assessments to monitor for any clinical changes. This follow-up should involve a thorough evaluation, including a comprehensive medical history, physical examination, and echocardiography. Conduct an earlier assessment to determine the optimal timing for pulmonary valve replacement if patients develop symptoms, and perform periodic cardiac magnetic resonance imaging (CMR) to complement the evaluation.

The general recommendation for adults who have undergone surgical repair for tetralogy of Fallot is to have regular follow-up appointments with a cardiologist specializing in adult congenital heart disease. This recommendation aligns with the guidelines provided by the American College of Cardiology and the American Heart Association.[37] Regular follow-up visits ensure appropriate monitoring and management of the condition per established clinical guidelines. Patients who have undergone percutaneous or surgical valvotomy should have long-term follow-up consisting of clinical examinations and echocardiography. This follow-up aims to assess various parameters, including the severity of pulmonary regurgitation, right ventricle size and function, pulmonary artery pressures, and tricuspid regurgitation. The frequency of follow-up visits should be tailored based on the severity of the disease, at least once every 5 years.[37] These evaluations enable the monitoring of disease progression, identification of any changes in cardiac function, and determination of the need for further intervention or treatment adjustments as necessary.

Patients who have asymptomatic severe pulmonary regurgitation and normal right ventricle function do not require any medical therapy.[37] However, in cases of secondary pulmonary regurgitation, treatment should be focused on addressing the underlying cause, such as carcinoid disease or pulmonary arterial hypertension. Consider medical therapy in patients who experience right heart failure accompanied by severe right ventricle dysfunction and are not suitable candidates for percutaneous or surgical interventions. Although their use is not proven to offer a survival benefit, angiotensin-converting enzyme inhibitors, diuretics, and digoxin may be utilized in such cases.[37] Endocarditis prophylaxis is generally unnecessary for native pulmonary regurgitation unless there is a documented history of prior endocarditis. 

Indications for Intervention

Percutaneous or surgical pulmonary valve replacement is indicated in the following settings:

• For symptomatic patients with moderate to severe pulmonary regurgitation, pulmonary valve replacement is recommended.[37]
• For asymptomatic patients with moderate to severe pulmonary regurgitation when any two of the following 4 criteria are present, pulmonary valve replacement is recommended:[48][49][50][51]
  • Progressive right or left ventricular systolic dysfunction.
  • Progressive right ventricle dilation (right ventricle end-systolic volume index [RVESVI] ≥ 80 mL/m2, right ventricle end-diastolic volume index [RVEDVI] ≥ 160 mL/m2, or RVEDV ≥ 2x LV end-diastolic volume).
  • RV systolic pressure ≥ two-thirds the systemic pressure.
  • Progressive reduction in exertional tolerance (noted on an exercise stress test or 6-minute walk test).

• In patients who are asymptomatic with moderate to severe pulmonary regurgitation and progressive tricuspid regurgitation (> moderate severity), pulmonary valve replacement can be considered.

Recommend simultaneous tricuspid annuloplasty for patients with moderate or more severe tricuspid valve regurgitation accompanied by tricuspid annular dilation. However, right ventricle remodeling after percutaneous pulmonary valve replacement can lead to improvement in secondary tricuspid valve regurgitation,[52][53][52] thereby avoiding repeat sternotomy. However, when the tricuspid valve is structurally abnormal due to factors such as iatrogenic injury resulting in a flail leaflet or leaflet perforation or previous endocarditis, consideration should be given to surgical tricuspid valve replacement.[54] This decision should be made based on careful evaluation and assessment of the specific circumstances and individual patient characteristics. Pulmonary valve replacement aims to alleviate the excessive volume burden on the right ventricle and prevent the development of irreversible ventricular dysfunction. Addressing the underlying pathology and restoring proper pulmonary valve function aims to restore normal hemodynamics and relieve the strain on the right ventricle, ultimately preserving long-term function.

In patients undergoing pulmonary valve replacement, clinicians commonly prefer bioprosthetic valves over mechanical valve prostheses because of their durability, lasting approximately 10 to 15 years post-implantation.[55][56][57] However, a mechanical valve prosthesis may be deemed appropriate for individuals at a high risk of requiring reoperation or who already have a mechanical valve prosthesis in situ (and consequently necessitate anticoagulation).[58][59] The decision regarding valve prosthesis should be made carefully, considering the individual patient's circumstances and risk factors.

Surgical vs Percutaneous Approach

The decision to approach pulmonary valve replacement must be on the basis of the individual patient's specific circumstances and risk factors.[60] Percutaneous pulmonary valve replacement (PPVR)is the preferred approach for treating pulmonary valve regurgitation in the contemporary era.[61][56][60][62][56] PPVR is associated with similar short- and mid-term mortality and shorter length of stay compared to surgical pulmonary valve replacement.[63][64][65][66][67] The introduction of novel self-expanding valve prostheses specifically designed to address complex anatomies of the native right ventricle outflow tract has dramatically expanded the eligibility for percutaneous pulmonary valve implantation in patients with severe pulmonary valve regurgitation.[68][61][69][70] This innovative approach now allows more patients to benefit from this procedure. The newer self-expanding valve system offers several advantages. First, this valve reduces the number of sternotomies patients must undergo throughout their lifetime. Secondly, the self-expanding valve system frame establishes an appropriate landing zone for future valve-in-valve implantations, enabling the implantation of up to 4 additional valves.[71][72] This feature may provide long-lasting benefits for some patients, potentially eliminating the need for further sternotomies in their lifetime.

Consider surgical pulmonary valve replacement in the following circumstances:[60]

• When the anatomy of the right ventricular outflow tract (RVOT) or pulmonary artery is unsuitable for percutaneous pulmonary valve replacement (PPVR). 
•  When there is a risk of coronary artery compression with PPVR. 
• When a small bioprosthesis or valved conduit is present, it could result in a high residual gradient (> 20 mmHg) after PPVR. Surgical pulmonary valve replacement may be necessary to ensure adequate antegrade blood flow and improve RV diastolic function.
• When the patient has other indications to undergo cardiac surgery.
• In the presence of active endocarditis. 
• When severe pulmonary artery aneurysm/dissection is present. (Surgical intervention may be required to address the aneurysm or dissection and replace the pulmonary valve as part of the treatment plan.)
• In cases of recurrent ventricular arrhythmias with a low success rate for percutaneous radiofrequency ablation necessitating a surgical ablation as an alternative treatment option.

Careful assessment of each patient's condition and determination of the most appropriate course of treatment based on the specific circumstances and considerations involved are essential steps for the medical team. Following pulmonary valve replacement, conducting an initial transthoracic echocardiogram to establish baseline valve hemodynamics is essential, which will serve as a reference for future assessments.

For patients with a mechanical valve prosthesis, meticulous anticoagulation management is necessary.[57][59][73] Temporary oral anticoagulation is recommended for 3 to 6 months after pulmonary valve replacement with a bioprosthesis, considering the observed cases of bioprosthetic valve thrombosis. Suggest daily aspirin administration for the lifespan of the prosthesis in patients with bioprosthetic pulmonary valves.[54] Patients with bioprosthetic pulmonary valves are recommended for long-term oral anticoagulation only when other indications, such as atrial arrhythmia, prior thromboembolic events, or signs of premature prosthesis dysfunction raising concerns about bioprosthetic valve thrombosis, are present.[74][75]

All patients with a prosthetic pulmonary valve require lifelong follow-up to assess the function of the valve and ventricle.[76][77] Early postoperative echocardiographic imaging ("fingerprint") to evaluate bioprosthetic valve function, followed by another assessment within the first 12 to 18 months after implantation to monitor for any changes associated with bioprosthetic valve thrombosis, is recommended.[54] Routine annual echocardiography is generally not required until 5 years after isolated pulmonary valve implantation unless there is a change in the patient's clinical presentation. Due to the increased risk of infective endocarditis associated with a prosthetic heart valve, antimicrobial prophylaxis for bacterial endocarditis is recommended by standard guidelines.[54]

Differential Diagnosis

Echocardiography is valuable for distinguishing pulmonary regurgitation from other causes of diastolic murmurs and right heart failure. When assessing a murmur consistent with pulmonary regurgitation, consider the differential diagnosis, including aortic regurgitation, which presents with a similar decrescendo diastolic murmur starting in early diastole. However, the pulmonary regurgitation murmur can be distinguished by its intensification during inspiration and its specific location (best heard over the left second and third interspaces, compared to aortic regurgitation, which is heard over the left sternal border or right second interspace). Although rare, stenosis of the left anterior descending coronary artery can also produce a diastolic murmur resembling pulmonary regurgitation. Mid- or late-diastolic murmurs associated with conditions like mitral or tricuspid stenosis are less likely to be confused with the pulmonary regurgitation murmur due to differences in timing, quality, and associated sounds.[78][79][80][81]

When encountering severe RV enlargement and dysfunction, consider other potential diagnoses such as primary right heart myopathy (eg, arrhythmogenic right ventricle cardiomyopathy), left-to-right shunt leading to right ventricle volume overload, tricuspid regurgitation, and the advanced stage of pulmonary hypertension. In a patient with pulmonary regurgitation who is symptomatic with signs of heart failure, a comprehensive cardiovascular evaluation, including a detailed medical history, thorough physical examination, and echocardiography, is necessary to determine the underlying cause of symptoms. If a patient with pulmonary regurgitation and preserved right ventricle function presents with symptomatic right heart failure, investigate alternative diagnoses such as restrictive physiology or constrictive pericarditis.[54][82][37]

Prognosis

Untreated severe pulmonary regurgitation leads to the enlargement of the right ventricle, systolic dysfunction, atrial/ventricular arrhythmias, and ultimately death.[5][15][16][17][22][83]. Pulmonary valve replacement, whether performed percutaneously or surgically, is an excellent treatment strategy with a periprocedural mortality rate of less than 1 percent when conducted by an experienced physician with favorable long-term outcomes.[84][38][57] The timing of intervention is a critical determinant of long-term patient morbidity and survival.

Preoperative right ventricle volume and function assessment using cardiovascular magnetic resonance (CMR) is prognostic. A preoperative right ventricle end-diastolic volume index of less than 160 mL/m and an end-systolic volume index of less than 80 mL/m are associated with normalizing ventricular dimensions within the first year following surgery. Similarly, a preoperative right ventricle end-systolic volume index less than 80 mL/m is strongly correlated with mid-to-late-term right ventricle normalization (mean follow-up of 6.3 years; an interquartile range of 4.9-9.5 years), characterized by an ejection fraction greater than 48% and a right ventricular end-diastolic volume <108 mL/m. Conversely, a right ventricular end-systolic volume <95 mL/m is associated with an increased risk of suboptimal hemodynamic outcomes and adverse clinical events.[38][48][85][86][87][88][89] Importantly, structural valve failure and infective endocarditis are significant long-term complications that may arise after pulmonary valve replacement. Therefore, meticulous follow-up is necessary to monitor these potential complications.[90][91][57][38]

Deterrence and Patient Education

There are no recommendations against regular physical activity in mild or moderate pulmonary regurgitation. Patients who are symptomatic 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 tetralogy of Fallot repair.

Enhancing Healthcare Team Outcomes

The establishment of a successful team-based program relies on the active involvement of dedicated congenital heart surgeons, cardiologists, and other specialists proficient in heart failure, imaging techniques (such as echocardiography, cross-sectional imaging, and advanced imaging modalities as needed), diagnostic and therapeutic cardiac catheterization, and electrophysiology. Before and after interventional or surgical procedures, comprehensive patient care should encompass risk assessment for sudden cardiac death, continuous cardiac rhythm monitoring, and appropriate medical interventions.

Many congenital heart conditions necessitate multiple interventions throughout a patient's lifetime. Considering the long-term implications of these interventions is crucial, as evidence suggests that survival rates decline significantly after the fifth sternotomy.[92] To mitigate the need for repeated sternotomies, an ideal therapeutic strategy involves a programmatic approach that integrates periodic percutaneous interventions whenever feasible, aiming to prevent sternotomy throughout the patient's lifespan. Ideally, these deliberations are conducted within regularly scheduled, multidisciplinary conferences, allowing all team members to collectively review the patient's workup and contribute their insights and opinions. This collaborative effort facilitates reaching a consensus on the optimal plan of action going forward.