Management and prognosis of surgical aortic and mitral prosthetic valve regurgitation

INTRODUCTION — Prosthetic valve dysfunction encompasses prosthetic valve obstruction (stenosis) and prosthetic valve regurgitation. Regurgitation associated with prosthetic heart valves includes regurgitation through the valve (transvalvular) as well as paravalvular regurgitation (also known as paravalvular leak [PVL]). Symptomatic severe prosthetic valve regurgitation is an uncommon complication of surgical valve replacement. However, it is associated with poor outcomes with both conservative management and surgical treatment.

This topic will discuss the prognosis and management of prosthetic valve regurgitation. Clinical manifestations and diagnosis of surgical prosthetic valve regurgitation as well as diagnosis and management of transcatheter heart valve regurgitation are discussed separately. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation" and "Transcatheter aortic valve implantation: Complications".)

MANAGEMENT

Approach to management — The approach to management of prosthetic valve regurgitation includes monitoring asymptomatic patients, medical therapy for the cause of regurgitation (when treatable) and medical management of the sequelae of regurgitation, and evaluation of patients with severe prosthetic regurgitation for valve intervention (surgical or transcatheter), starting with determination of surgical risk.

Diagnosis and evaluation of prosthetic valve regurgitation is discussed separately. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation".)

●Asymptomatic patients with prosthetic valve regurgitation should be monitored, with frequency of monitoring based upon the severity of regurgitation and associated clinical findings. (See 'Monitoring' below.)

●Medical therapy includes treatment of the cause of regurgitation (when treatable) and medical management of the consequences of regurgitation (heart failure [HF] and hemolysis). Patients with any magnitude of prosthetic valve regurgitation with a treatable cause (eg, endocarditis, thrombus) should receive appropriate treatment and follow-up. Many patients with a treatable cause have symptoms related to the cause, but some (eg with thrombus) may be asymptomatic.

●Patients with severe prosthetic regurgitation should be evaluated for intervention (surgical or transcatheter), starting with evaluation of surgical risk. (See "Estimating the risk of valvular procedures".)

•Patients with severe prosthetic regurgitation with symptoms (HF or intractable hemolysis) should undergo valve intervention (surgery or transcatheter procedure). The choice of valve intervention depends upon the type of valve, the patient’s estimated surgical risk, and the feasibility of transcatheter intervention. (See 'Indications' below.)

•For operable asymptomatic patients with severe bioprosthetic regurgitation with criteria for valve replacement, we suggest surgical prosthetic valve replacement given the risk of acute decompensation with further valve deterioration. Transcatheter valve-in-valve (TViV) procedures have shown similar success rates and entail less procedural risk, but the available evidence comparing both procedures is still scarce and mainly focused on non-operable patients. (See 'Indications' below.)

Monitoring — Echocardiography is the method of choice to evaluate and monitor prosthetic valve function. A complete echocardiography examination should include 2D imaging of the prosthesis, evaluation of the leaflet mobility and morphology, gradients measuring, estimation of the regurgitation severity, a full comprehensive chamber evaluation including both function and dimensions, and calculation of pulmonary artery systolic pressure.

Following prosthetic valve implantation, at least one baseline echocardiogram is indicated, generally at the first postoperative follow-up visit. (See "Overview of the management of patients with prosthetic heart valves", section on 'Serial follow-up'.)

The frequency of monitoring in asymptomatic patients depends upon the severity of the regurgitation as well as associated findings [1,2]:

●Patients with trivial or mild prosthetic valve regurgitation with normal valve appearance and function should receive routine follow-up. Routine monitoring after prosthetic valve implantation is discussed separately. (See "Overview of the management of patients with prosthetic heart valves", section on 'Serial follow-up'.)

●For patients with moderate aortic or mitral regurgitation, we suggest repeat echocardiography every one to two years.

●For patients with severe aortic or mitral regurgitation, we suggest repeat echocardiography every six months.

In addition, echocardiography should be performed if any new symptoms occur after valve replacement or if complications are suspected. Further diagnostic evaluation of patients with prosthetic valve regurgitation is discussed separately. (See "Clinical manifestations and diagnosis of surgical aortic and mitral prosthetic valve regurgitation", section on 'Approach to diagnosis and evaluation'.)

Medical therapy — Medical therapy for patients with prosthetic valve regurgitation includes treatment of the cause of regurgitation and treatment of the consequences of regurgitation (ie, medical treatment of HF and hemolysis).

Treatment of cause of regurgitation — In a minority of cases, prosthetic valve regurgitation is caused by a treatable disease process, which should be promptly treated. When prosthetic valve regurgitation is due to mechanical or biologic prosthetic valve thrombosis, treatment of valve thrombosis usually corrects the regurgitation. (See "Bioprosthetic valve thrombosis, thromboembolism, and obstruction: Management".)

When prosthetic valve regurgitation is caused by infective endocarditis, an appropriate antibiotic regimen should be started as soon as possible to treat the infection. However, the prosthetic valve regurgitation does not generally resolve and may progress while the patient is receiving appropriate antibiotics. Surgical consultation is recommended to evaluate and monitor for the presence of an indication for surgical intervention. (See "Antimicrobial therapy of prosthetic valve endocarditis" and "Surgery for prosthetic valve endocarditis".)

Treatment of consequences of regurgitation — The role of medical therapy to treat symptomatic HF in patients with prosthetic valve regurgitation is generally limited to temporary stabilization in patients awaiting redo valve surgery or percutaneous intervention and palliative care for patients who are not candidates for surgical or percutaneous intervention [1]. The objective of medical treatment is to relieve congestion and reduce afterload, which is achieved with the use of diuretics and angiotensin converting enzyme (ACE) inhibitors. If systolic ventricular dysfunction appears, standard therapy for HF with reduced ejection fraction should be administered. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)

Supportive medical therapy is indicated in patients with hemolysis. If clinically significant hemolysis is present, iron and folate supplementation is indicated to correct deficiencies in these nutrients. Erythropoietin injection or programmed blood transfusions may be required to treat symptomatic anemia. If hemolysis is intractable, surgical or transcatheter therapy (ie, device closure for paravalvular leak [PVL]; transcatheter aortic valve replacement [TAVR] for transvalvular regurgitation, although the last rarely causes hemolysis) is indicated as discussed below. (See 'Indications' below and "Diagnostic approach to anemia in adults", section on 'Hemolysis'.)

Intervention

Indications — Indications for valve intervention for prosthetic valve regurgitation are similar to those for native valve regurgitation. The following recommendations for valve intervention for prosthetic valve regurgitation are in general agreement with recommendations in the 2020 American College of Cardiology/American Heart Association and 2021 European Society of Cardiology valve guidelines [1,2]:

●For symptomatic patients (HF or intractable hemolysis) with severe prosthetic regurgitation:

•For patients with mechanical transvalvular regurgitation:

-For patients with HF or intractable hemolysis due to severe mechanical prosthetic transvalvular regurgitation, we recommend surgical replacement of the valve prosthesis (redo prosthetic valve replacement).

•For patients with bioprosthetic transvalvular regurgitation:

-With low to intermediate risk – For patients with HF or intractable hemolysis due to severe bioprosthetic transvalvular regurgitation with low to intermediate surgical risk (ie, Society of Thoracic Surgeons [STS] operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical replacement of the valve prosthesis. (See 'On surgical treatment' below.)

-With high or greater risk – For patients with HF or intractable hemolysis due to severe bioprosthetic aortic regurgitation who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (ie, STS operative risk score >8 percent or at a >15 percent risk of mortality at 30 days), we suggest a transcatheter valve-in-valve (VIV) procedure at a center with expertise in this procedure. (See 'On transcatheter valve-in-valve implantation' below.)

A VIV procedure is an option for a failed bioprosthetic valve but not for a failed mechanical valve.

•For patients with paravalvular regurgitation (with a mechanical or bioprosthetic valve):

-For patients with HF or intractable hemolysis due to severe paravalvular regurgitation with low to intermediate surgical risk (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical repair of the leak or replacement of the valve prosthesis. (See 'For symptomatic patients' below.)

-For patients with HF or intractable hemolysis due to severe paravalvular regurgitation who have high surgical risk (ie, STS operative risk score >8 percent or at a >15 percent risk of mortality at 30 days) and anatomic features suitable for catheter-based therapy as assessed by a heart valve team, we suggest percutaneous repair at a center with expertise in this procedure. (See 'On transcatheter closure of paravalvular leaks' below.)

●For asymptomatic patients with severe bioprosthetic regurgitation who are deemed operable (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical prosthetic valve replacement rather than continued conservative therapy. (See 'For asymptomatic patients' below.)

Evidence — Indications for intervention for severe prosthetic regurgitation are based upon observational data suggesting improvement in outcomes compared with medical therapy alone.

On surgical treatment

For symptomatic patients — Limited data are available on treatment options for symptomatic prosthetic (transvalvular or paravalvular) regurgitation. Data are lacking on the natural history of symptomatic prosthetic transvalvular regurgitation and the effect of treatment. However, indirect data are available from observational studies of patients with symptomatic severe native valve disease showing high mortality risk for patients treated medically, lack of efficacy of medical therapy, and association between surgical treatment and improved symptoms and reduced mortality rates. As an example, an observational study found a mortality rate of 6 percent per year in patients with severe native aortic regurgitation (AR) with class II symptoms and a mortality rate of nearly 24.6 percent per year for patients with severe native AR with class III or IV symptoms treated medically (without surgery) [3]. Among patients with severe AR, aortic valve surgery was associated with reduced cardiovascular mortality. (See "Natural history and management of chronic aortic regurgitation in adults".)

Similarly, observational data in patients with symptomatic chronic primary mitral regurgitation (MR) suggest that chronic severe MR has an annual mortality rate of approximately 6 percent per year (higher among patients with severe symptoms) and early mitral valve surgery is associated with reduced mortality. (See "Chronic primary mitral regurgitation: Indications for intervention".)

Limited data are available on the effect of surgical treatment on PVL. In an observational study of 96 patients with mitral PVL with mean follow-up of five years, the mortality rate at follow-up was 12 percent among patients treated with valve reoperation compared with 26 percent for patients treated conservatively [4]. In addition, there were significant improvements in mean hematocrit levels and New York Heart Association (NYHA) class III/IV symptoms after surgery.

However, surgical management of prosthetic regurgitation is limited by the high risk of the procedure, with survival varying from 40 to 50 percent at 10 years and operative mortality rates around 5 to 10 percent [5-7]. As an example, in an observational study of 155 patients undergoing redo aortic valve surgery, operative mortality was 4.5 percent [8]. In a series of 282 patients undergoing reoperation for mitral bioprosthetic failure, an operative mortality rate of 7.4 percent was observed [9]. The operative mortality following redo prosthetic valve replacement is generally higher than that for primary valve replacement (eg, 4.6 versus 2.2 percent) [7]. However, some studies have found that a nonurgent redo procedure in patients with NYHA functional class I/II symptoms and absence of active endocarditis has the same surgical risk as a first valve surgery [10].

It is not clearly known whether surgical risks and outcomes differ with PVLs versus transvalvular regurgitation, but observational data suggest that PVLs results tend to be worse, with less complete surgical correction [5,11]. As an example, in a series of 122 patients with symptomatic mitral or aortic PVL who underwent surgery, PVL repair was feasible in 65 percent and prosthetic valve replacement was required in 35 percent [5]. Mortality at 30 days was 10.7 percent. Two patients (1.6 percent) with residual severe mitral PVL were treated successfully with redo surgery before discharge and one additional patient underwent redo surgery during follow-up (median of seven years). Actuarial survival was 39 percent at 12 years.

For asymptomatic patients — For operable patients with asymptomatic severe prosthetic regurgitation, redo surgery is suggested since such patients are likely to require surgical intervention soon, and the risk of surgical intervention is considerably lower when the patient is asymptomatic than after severe symptoms of HF develop [7,10]. Acute bioprosthetic valve failure with acute aortic regurgitation or acute mitral regurgitation is a cause of acute HF and cardiogenic shock [12,13]. However, the risk of acute decompensation in patients with asymptomatic severe prosthetic regurgitation is unknown.

On transcatheter valve-in-valve implantation — A transcatheter VIV procedure involves catheter-based valve implantation inside an already implanted failed (stenotic, regurgitant, or both) bioprosthetic valve. This approach is an alternative to replacement of a degenerated surgically-implanted valve in patients who are at high risk for open surgical therapy (ie, Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM] ≥8 percent or a ≥15 percent risk of mortality at 30 days).

VIV implantation has also been used to salvage suboptimal initial TAVR and clinically significant early paravalvular aortic regurgitation [14,15]. (See "Transcatheter aortic valve implantation: Complications".)

Aortic valve-in-valve procedure — Outcomes with aortic VIV procedure were reported for 459 multinational registry patients (mean age 77.6 years; 56 percent men) with a failed bioprosthetic surgical aortic valve (stenosis in 39.4 percent, regurgitation in 30.3 percent, and combined in 30.3 percent) undergoing VIV implantation between 2007 and May 2013 [16]. The median STS-PROM was 9.8 percent. Both balloon-expandable (53.6 percent) and self-expandable (46.4 percent) valves were implanted.

●At 30-day follow-up:

•The mortality rate was 7.6 percent. The mortality rate was highest in patients with stenosis (10.5 versus 4.3 percent in the regurgitation group and 7.2 percent in those with combined stenosis and regurgitation).

•The balloon- and self-expandable valve groups were similar in terms of mortality and stroke rate. Major/life-threatening bleeding and acute kidney injury events were more frequent in the balloon-expandable device group. Permanent pacemaker implantation was more frequent in the self-expandable device group.

•At least moderate aortic regurgitation was noted in 5.4 percent and was more common in the regurgitation group (9.4 versus 2.8 percent in the stenosis group and 5 percent in the combined group) and in the self-expandable device group (8.9 versus 2.4 percent in the balloon-expandable device group).

•Post-procedural residual aortic stenosis (lower mean orifice area and higher mean gradient) was greater in the stenosis group (mean orifice area 1.39 cm² and mean gradient 18.5 mmHg) compared with the regurgitation (1.56 cm² and 12 mmHg) and combined stenosis and regurgitation (1.56 cm² and 16.1 mmHg) groups.

●At one-year follow-up:

•Overall one-year Kaplan-Meier survival rate was 83.2 percent. Surviving patients had good functional status (NYHA class I/II).

•Survival rates were similar with balloon- and self-expandable devices.

•Factors associated with mortality within one year included having baseline stenosis and a small (label size ≤21 mm) surgical bioprosthesis.

The PARTNER 2 Valve-in-Valve Registry reported relatively low mortality and complication rates, improved hemodynamics, and excellent functional and quality-of-life outcomes at one year after aortic VIV [17,18].

Several systematic reviews have compared outcomes of percutaneous VIV procedures against SAVR. A meta-analysis of almost 500 patients found similar rates of all-cause early- and midterm mortality with VIV and SAVR [19]. In contrast, another meta-analysis studying data on a total of 342 patients found that redo SAVR was associated with lower all-cause mortality and superior hemodynamic results at mean follow-up of 18 months [20].

Mitral valve-in-valve procedure — Limited data suggest that transcatheter mitral valve-in-valve can also be performed safely in selected patients with results comparable to those with surgical therapy. An observational study compared 40 patients who underwent minimally invasive mitral valve replacement surgery with 21 patients who underwent a transapical mitral VIV procedure. The two-year survival rates were 86 versus 87 percent in patients undergoing redo mitral valve replacement compared with those undergoing VIV implantation without significant differences in safety end points [21].

On transcatheter closure of paravalvular leaks — Transcatheter closure has developed as a less invasive solution to treat PVLs. A variety of devices are used off label to close PVLs since there are no devices specifically designed and approved for this purpose, and procedures are often long and technically demanding. General anesthesia is also required, with proper anticoagulation, especially if transseptal puncture is performed. Percutaneous closure is often assisted by fluoroscopy in combination with transesophageal echocardiography, and sometimes intracardiac echocardiography is also required to locate anterior PVLs. Also, computed tomography transesophageal echocardiography fusion images can provide intraprocedural guidance [22].

Percutaneous closure of PVL can be approached from various options: transapical, transaortic, or transseptal. Most aortic PVLs can be successfully handled from retrograde transaortic approach, while mitral PVLs are technically more challenging, with the transapical approach providing the most versatile access.

A systematic review and meta-analysis included 12 studies with a total of 362 patients with mechanical or bioprosthetic valves who underwent transcatheter reduction of PVL [23]; the three largest studies contributed more than half of the patients [22,24,25].

●Technical success (defined as successful delivery of the device) occurred in 82.3 percent of mitral procedures and 86.9 percent of aortic procedures. Procedural success (defined as delivery of the device without interference with the prosthetic valve and resulting in immediate reduction in regurgitation by at least one grade) occurred in 73.7 percent mitral procedures and 84.1 percent aortic procedures.

●Overall mortality was 22.7 percent during variable periods of follow-up (mean follow-up ranged from 1 to 42 months). Cardiac death was reported in 5.7 percent after a successful procedure and in 12 percent after a failed procedure.

●A combined end point of improvement in NYHA functional class or hemolytic anemia was achieved in 71 percent of patients following a successful procedure and in 28.4 percent of patients after a failed procedure.

●The need for subsequent surgical reintervention was reduced after successful transcatheter reduction compared with a failed procedure (6.8 versus 31.8 percent).

In two of the largest included studies (with a combined total of 158 patients), at six months the survival rate was 91 percent, at 12 months it was 89.2 percent, at 18 months it was 86.5 percent, and three-year survival was 64.5 percent [22,24]. Major adverse cardiac events at 30 days occurred in 8.7 percent.

Limited data are available to directly compare outcomes with surgical and transcatheter PVL closure. Early data suggest noninferiority of PVL percutaneous closure versus surgical correction and superiority to conservative management. A single-center observational study included 122 patients who underwent surgical treatment for PVL (surgical repair or redo surgical prosthetic valve replacement if repair was judged unfeasible by the surgeon) and 17 patients who underwent transcatheter closure (via a surgical transapical approach) described a higher in-hospital mortality rate for surgical patients (9.3 versus 0 percent) and surgical treatment was a borderline significant risk factor for in-hospital mortality (odds ratio: 8, 95% CI 1.8 to 13; p = 0.05) [26]. All patients had less than moderate residual regurgitation after the procedure.

PROGNOSIS

Transvalvular prosthetic regurgitation — The prognosis of prosthetic regurgitation depends upon the severity of regurgitation as well as the pathologic process involved. Transvalvular regurgitation is almost exclusively due to bioprosthetic valve degeneration but can very rarely occur with a mechanical valve with a stuck leaflet.

Isolated mild transvalvular regurgitation has no prognostic impact in the absence of a pathologic process such as thrombosis or infectious endocarditis. Moderate transvalvular bioprosthetic regurgitation generally results from a degenerative or nonstructural pathologic process affecting the prosthetic valve, and although it may have no prognostic impact if valve function remains stable, the disease process quite often progresses to a fully degenerated valve with severe regurgitation.

The following are risk factors for a rapid bioprosthetic valve degenerative process [27]:

●Younger age at implantation

●Mitral position

●Older generation of bioprosthesis

●Chronic kidney disease

●Hyperparathyroidism

●Hypertension

●Left ventricular hypertrophy

●Left ventricular dysfunction

Also, some studies suggest that atherosclerotic risk factors play an important role in aortic bioprosthetic degeneration [28].

Severe transvalvular regurgitation has a poor outcome if uncorrected [29]. Long-term follow-up is required to assess prosthetic valve outcomes since valve-related complications including prosthetic valve regurgitation occur and evolve over variable time intervals following valve implantation.

Paravalvular prosthetic regurgitation — Prognosis in patients with paravalvular prosthetic regurgitation depends upon its cause (eg, much worse prognosis with endocarditis) and severity. Mild paravalvular leaks (PVLs) are considered benign in the absence of significant hemolysis [30]. In contrast, elevated mortality rates have been reported in patients with moderate PVLs in some studies, worse in the case of mitral compared with aortic PVLs [31]. In addition, hemolysis associated with PVL has been associated with worse short-term outcomes, even if significant anemia was not present at the time of the PVL diagnosis [32]. Patients with severe PVL have poor short-term prognosis, with high mortality rates and high risk of PVL after surgical treatment [11]. A worse prognosis has been described with mitral PVLs compared with aortic PVLs. In a study that included 54 patients with mild to moderate PVL, end points were cardiac death, all-cause mortality, repeat surgery, and urgent admission for heart failure. The eight-year event-free survival rate of 70±12 percent for aortic PVLs, compared with 16±8 percent for mitral ones [31].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

SUMMARY AND RECOMMENDATIONS

●Severe prosthetic mitral or aortic transvalvular or paravalvular regurgitation is associated with poor prognosis. (See 'Prognosis' above.)

●The approach to management of prosthetic valve regurgitation includes monitoring asymptomatic patients, medical therapy for the cause of regurgitation (when treatable) and medical management of the sequelae of regurgitation (heart failure [HF] and hemolysis), and evaluation of patients with severe prosthetic regurgitation for valve intervention (surgical or transcatheter), starting with determination of surgical risk. (See 'Approach to management' above.)

●The following are indications for valve intervention in patients with severe prosthetic regurgitation:

•For mechanical transvalvular regurgitation – For patients with HF or intractable hemolysis due to severe mechanical prosthetic transvalvular regurgitation, we suggest surgical replacement of the valve prosthesis (Grade 2C). (See 'For symptomatic patients' above.)

•For bioprosthetic transvalvular regurgitation:

-With low to intermediate risk – For patients with HF or intractable hemolysis due to severe bioprosthetic transvalvular regurgitation with low to intermediate surgical risk (ie, Society of Thoracic Surgeons [STS] operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical replacement of the valve prosthesis (Grade 2C). (See 'For symptomatic patients' above.)

-With high or greater risk – For patients with HF or intractable hemolysis due to severe bioprosthetic aortic regurgitation with who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (ie, STS operative risk score >8 percent or at a >15 percent risk of mortality at 30 days), we suggest a transcatheter valve-in-valve procedure at a center with expertise in this procedure (Grade 2C). (See 'On transcatheter valve-in-valve implantation' above.)

A valve-in-valve procedure is an option for a failed bioprosthetic valve but not for a failed mechanical valve.

•For paravalvular regurgitation:

-With low to intermediate risk – For patients with HF or intractable hemolysis due to severe paravalvular regurgitation (with a mechanical or bioprosthetic valve) with low to intermediate surgical risk (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical repair of the leak or replacement of the valve prosthesis (Grade 2C). (See 'For symptomatic patients' above.)

-With high risk – For patients with HF or intractable hemolysis due to severe paravalvular regurgitation (with a mechanical or bioprosthetic valve) and who have high surgical risk (ie, STS operative risk score >8 percent or at a >15 percent risk of mortality at 30 days), and anatomic features suitable for catheter-based therapy as assessed by a heart valve team, we suggest percutaneous repair at a center with expertise in this procedure (Grade 2C). (See 'On transcatheter closure of paravalvular leaks' above.)

•For asymptomatic patients with severe bioprosthetic regurgitation who are deemed operable (ie, STS operative risk score ≤8 percent or a ≤15 percent risk of mortality at 30 days), we suggest surgical prosthetic valve replacement rather than continued conservative therapy (Grade 2C). (See 'For asymptomatic patients' above.)

●Indications for intervention for severe prosthetic regurgitation are based upon observational data suggesting improvement in outcomes with intervention compared with medical therapy alone. (See 'Evidence' above.)