For patients of any age requiring valve replacement for whom anticoagulant therapy is contraindicated, cannot be managed appropriately, or is not desired, a bioprosthetic valve is recommended. For patients <50 years of age who do not have a contraindication to anticoagulation and require AVR, it is reasonable to choose a mechanical aortic prosthesis over a For patients 50 to 65 years of age who require AVR and who do not have a contraindication to anticoagulation, it is reasonable to individualize the choice of either a mechanical or bioprosthetic AVR, with consideration of individual patient factors and after informed In patients >65 years of age who require AVR, it is reasonable to choose a bioprosthesis over a mechanical valve.1 For patients <65 years of age who have an indication for mitral valve replacement, do not have a contraindication to anticoagulation, and are unable to undergo mitral valve repair, it is reasonable to choose a mechanical mitral prosthesis over a bioprosthetic valve.1,7,10,11 7. For patients 65 years of age who require mitral valve replacement and are unable to undergo mitral valve repair, it is reasonable to choose a bioprosthesis over a mechanical In patients <50 years of age who prefer a bioprosthetic AVR and have appropriate anatomy, replacement of the aortic valve by a pulmonic autograft (the Ross procedure) may be considered at a Comprehensive Valve Synopsis Shared decision-making about the choice of prosthetic valve type is influenced by several factors, including pa- tient age, values, and preferences; expected bioprosthetic valve durability, avoidance of patient prosthesis mis- match, and the potential need for and timing of reinter- vention; and the risks associated with long-term VKA an- ticoagulation after a mechanical valve replacement. (See also Section 3.2.4 regarding valve choice in patients with AS.) Despite the significantly higher rate of bioprosthetic structural valve deterioration observed in younger versus many younger patients choose to avoid a mechanical prosthesis because they are unwilling to consider long-term VKA therapy because of the incon- venience of monitoring, dietary restrictions, medication interactions, and the need to restrict participation in some types of athletic activity. A mechanical valve might be a prudent choice for patients for whom a second surgical procedure would be very high risk (eg, those with prior radiation exposure). The availability of TAVI has changed Recommendations for Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES the dynamics of the discussion of the trade-offs between mechanical and bioprosthetic valves in younger patients Recommendation-Specific Supportive Text 1. The choice of valve prosthesis in each patient is based on consideration of several factors, includ- ing valve durability, expected hemodynamics for valve type and size, surgical or interventional risk, the potential need for long-term anticoagulation, and patient values and preferences. The trade-off between the risk of reintervention for biopros- thetic valve deterioration and the risk of long- term anticoagulation should be discussed. Some patients prefer to avoid repeat surgery and are willing to accept the risks and inconvenience of lifelong anticoagulant therapy. Other patients are unwilling to consider long-term anticoagulation because of the inconvenience of monitoring, the attendant dietary and medication interactions, and the need to restrict participation in some types of physical activity. The incidence of struc- tural deterioration of a bioprosthesis is greater in younger patients, but the risk of bleeding from anticoagulation is higher in older patients. In patients with shortened longevity or multiple comorbidities, a bioprosthesis might be more appropriate. In women who desire subsequent pregnancy, the issue of anticoagulation during pregnancy is an additional consideration (see pregnancy-related issues in Section 13.5).20,21 2. Anticoagulant therapy with VKA is necessary in all patients with a mechanical valve to prevent valve thrombosis and thromboembolic events. If anti- coagulation is contraindicated or if the patient refuses VKA therapy, an alternative valve choice is appropriate. Newer anticoagulant agents have not been shown to be safe or effective in patients with mechanical heart valves. 3. Patients <50 years of age at the time of AVR incur a higher and earlier risk of bioprosthetic Overall, the predicted 15-year risk of needing reoperation because of structural deterioration is 22% for patients 50 years of age, 30% for patients 40 years of age, and 50% for patients 20 years of age, although it is recognized that all bioprostheses are not alike in terms of durability.11 Anticoagulation with a VKA can be accomplished with acceptable risk in most patients <50 years of age, particularly in compliant patients with appropriate monitoring of INR levels. Thus, the balance between valve durability and risk of bleeding and thromboembolic events favors the choice of a mechanical valve in patients <50 years of age, unless anticoagulation is not desired, cannot be monitored, or is contraindicated. 4. Uncertainty and debate continue about which type of AVR is appropriate for patients 50 to 65 years of age. Newer surgical bioprosthetic valves may show greater freedom from struc- tural deterioration, specifically in the older indi- vidual, although a high late mortality rate in these studies may preclude recognition of valve dys- The risks of bleeding and throm- boembolism with mechanical prostheses are low, especially in compliant patients with appropriate INR monitoring. Several studies have shown a sur- vival advantage with a mechanical prosthesis in this age group. Alternatively, large retrospective observational studies have shown similar long- term survival rates in patients 50 to 69 years of age undergoing mechanical versus bioprosthetic In general, patients with mechanical valves experience a higher risk of bleeding because of anticoagulation, whereas individuals who receive bioprosthetic valves expe- rience a higher rate of reoperation attributable to structural deterioration of the prosthesis, as well as perhaps a decrease in survival rate.6,25 27 Several other factors should be considered in the choice of type of valve prosthesis (see Section 11.1). Ultimately, the choice of mechanical versus Table 22. Selected Factors That May Impact Shared Decision-Making for the Choice of Prosthetic Valve Favor Mechanical Prosthesis Favor Bioprosthesis Age <50 y Increased incidence of structural deterioration with bioprosthesis 50% for age 20 y) Lower risk of anticoagulation complications Age >65 y Low incidence of structural for age >70 y) Higher risk of anticoagulation complications Patient preference (avoid risk of reintervention) Patient preference (avoid risk and inconvenience of anticoagulation) Low risk of long-term anticoagulation High risk of long-term anticoagulation Compliant patient with either home monitoring or close access to INR monitoring Limited access to medical care or inability to regulate VKA Other indication for long-term anticoagulation (eg, AF) Access to surgical centers with low reoperation mortality rate High-risk reintervention (eg, porcelain aorta, prior radiation therapy) Access to transcatheter ViV replacement Small aortic root size for AVR (may preclude ViV procedure in future) TAVI valves have larger effective orifice areas for smaller valve sizes (avoid patient prosthesis mismatch) AF indicates atrial fibrillation; AVR, aortic valve replacement; INR, international normalized ratio; TAVI, transcatheter aortic valve implantation; ViV, valve-in-valve; and VKA, vitamin K antagonist. CLINICAL STATEMENTS AND GUIDELINES bioprosthetic valve replacement for all patients, but especially for those between 50 and 65 years of age, should be made in a shared decision-mak- ing process that must account for the trade-offs between durability (and the need for reinterven- tion), bleeding, and thromboembolism.1 5. In patients >65 years of age at the time of bio- prosthetic AVR, the likelihood of primary struc- tural deterioration at 15 to 20 years is only about In addition, older patients are at higher risk of bleeding complications related to VKA ther- apy and more often require interruption of VKA therapy for noncardiac surgical and interventional procedures. It is reasonable to use a bioprosthetic valve in patients >65 years of age to avoid the risks of anticoagulation because the durability of the valve exceeds the expected years of life. 6. In general, patients with mechanical valve replace- ment experience a higher risk of bleeding because of anticoagulation, whereas individuals who receive a bioprosthetic valve replacement incur a higher risk of repeat intervention attributable to structural valve deterioration. In patients <65 years of age, observational data suggest better long-term outcomes with a mechanical mitral valve replace- ment, even when the risks and inconvenience of long-term VKA anticoagulation are considered. In a propensity-matched analysis from New York s Statewide Planning and Research Cooperative System (SPARCS), although there was no survival difference for patients 50 to 69 years of age under- going mechanical versus bioprosthetic mitral valve the rates of reoperation were lower (HR: 0.59) with a mechanical valve, though stroke risk (HR: 1.62) was higher. In the 2017 report from the California Office of Statewide Health Planning for patients who underwent mitral-valve replacement and were 40 to 69 years of age, receipt of a biological prosthesis was associ- ated with a mortality rate significantly higher than that seen with receipt of a mechanical prosthesis.1 The choice of a mechanical mitral valve in patients <65 years of age who are good candidates for anticoagulation should account for these observa- tional, nonrandomized data and abide by the prin- ciples of shared decision-making.1,7,10 7. Hazards associated with anticoagulation increase with age, and rates of structural valve deterioration decline significantly. In patients >65 years of age, the ratio of valve durability to life expectancy supports the use of a bio- prosthetic mitral valve replacement, which allows avoidance of the risks of long-term VKA anticoagulation in these older patients. In 1 Figure 11. Prosthetic valves: choice of biopros- thetic versus mechanical valve type. Colors correspond to Table 2. *Approximate ages, based on US Actuarial Life Expectancy tables, are provided for guidance. The balance between expected patient longevity and valve durability var- ies continuously across the age range, with more durable valves preferred for patients with a longer life expectancy. Bioprosthetic valve durability is finite (with shorter durability for younger patients), whereas mechanical valves are very durable but require lifelong anticoagulation. Long-term (20-y) data on outcomes with surgical bioprosthetic valves are available; robust data on transcatheter bioprosthetic valves extend to only 5 y, leading to uncertainty about longer-term outcomes. The deci- sion about valve type should be individualized on the basis of patient-specific factors that might af- fect expected longevity. See Section 3.2.4.2 for a discussion of the choice of TAVI versus SAVR. AVR indicates aortic valve replacement; CVC, Compre- hensive Valve Center; VKA, vitamin K antagonist; SAVR, surgical aortic valve replacement; and TAVI, transcatheter aortic valve implantation. CLINICAL STATEMENTS AND GUIDELINES observational study, the expected durability of a bioprosthetic mitral valve replacement was 11.4 years in patients <60 years of age, 16.6 years in those 60 to 70 years of age, and 19.4 years in those >70 years of age.11 In the 2017 report from the California Office of Statewide Health Planning and Development,1 overall survival rates were similar for patients 70 to 79 years of age who underwent mechanical versus biopros- thetic mitral valve replacement, and bleeding risk was lower with a bioprosthetic valve.1 8. Replacement of the aortic valve with a pulmo- nary autograft (the Ross procedure) is a complex operation involving replacement of the aortic valve by the patient s own pulmonic valve, along with placement of a pulmonic valve homograft. The Ross procedure allows the patient to avoid a prosthetic heart valve and the risks of antico- agulation, and it provides excellent valve hemody- namics. However, both the pulmonic homograft in the pulmonic position and the pulmonary autograft (the neoaortic valve) are at risk of valve degeneration. The failure of the Ross procedure is most often attributable to regurgitation of the neoaortic valve in the second decade after the operation. In addition, at least half of pulmonic homograft valves require reintervention within 10 to 20 years. Calcification of the homograft and adhesions between the homograft and neoaorta may increase the difficulty of reoperation. The Ross procedure typically is reserved for younger patients with appropriate anatomy and tissue characteristics in whom anticoagulation is either contraindicated or undesirable, and it is per- formed only at Comprehensive Valve Centers by surgeons experienced in this procedure.12 14,32 11.2. Antithrombotic Therapy Recommendations for Antithrombotic Therapy for Prosthetic Valves Referenced studies that support the recommendations are summarized in Online Data Supplement 36. COR LOE Recommendations In patients with a mechanical prosthetic valve, anticoagulation with a VKA is For patients with a mechanical bileaflet or current-generation single-tilting disk AVR and no risk factors for thromboembolism, anticoagulation with a VKA to achieve an INR For patients with a mechanical AVR and additional risk factors for thromboembolism (eg, AF, previous thromboembolism, LV dysfunction, hypercoagulable state) or an older-generation prosthesis (eg, ball-in-cage), anticoagulation with a VKA is indicated to achieve an INR of 3.0.9,10 For patients with a mechanical mitral valve replacement, anticoagulation with a VKA is indicated to achieve an INR of 3.0.9,11 For patients with a bioprosthetic TAVI, aspirin 75 to 100 mg daily is reasonable in the absence of other indications for oral For all patients with a bioprosthetic SAVR or mitral valve replacement, aspirin 75 to 100 mg daily is reasonable in the absence of other indications for oral anticoagulants.9,15 18 For patients with a bioprosthetic SAVR or mitral valve replacement who are at low risk of bleeding, anticoagulation with a VKA to achieve an INR of 2.5 is reasonable for at least 3 months and for as long as 6 months after surgical replacement.15,19 25 For patients with a mechanical SAVR or mitral valve replacement who are managed with a VKA and have an indication for antiplatelet therapy, addition of aspirin 75 to 100 mg daily may be considered when the risk of bleeding is low.26 For patients with a mechanical On-X AVR and no thromboembolic risk factors, use of a VKA targeted to a lower INR (1.5 2.0) may be reasonable starting 3 months after surgery, with continuation of aspirin 75 to 100 mg For patients with a bioprosthetic TAVI who are at low risk of bleeding, dual- antiplatelet therapy with aspirin 75 to 100 mg and clopidogrel 75 mg may be reasonable for 3 to 6 months after valve For patients with a bioprosthetic TAVI who are at low risk of bleeding, anticoagulation with a VKA to achieve an INR of 2.5 may be reasonable for at least 3 months after valve 3: Harm B-R For patients with bioprosthetic TAVI, treatment with low-dose rivaroxaban (10 mg daily) plus aspirin (75 100 mg) is contraindicated in the absence of other indications for oral anticoagulants.30 3: Harm B-R For patients with a mechanical valve prosthesis, anticoagulation with the direct thrombin inhibitor, dabigatran, is 3: Harm C-EO For patients with a mechanical valve prosthesis, the use of anti-Xa direct oral anticoagulants has not been assessed and is Synopsis Antithrombotic therapy after prosthetic valve implanta- tion is provided to prevent valve/leaflet thrombosis and reduce the incidence of thromboembolic complications. The use of any strategy must be balanced against the risk of bleeding. VKAs remain the cornerstone of therapy Recommendations for Antithrombotic Therapy for Prosthetic Valves (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES for patients with mechanical valve prostheses. Oral anti- thrombin and anti-Xa agents are not approved for use in these patients. The addition of mono- or dual-antiplatelet therapy to VKA treatment for other indications (eg, acute coronary syndrome or percutaneous coronary interven- tion [PCI]) must be done with caution. The evidence base for the optimal antithrombotic strategy across subgroups of patients who have received a bioprosthetic valve is not robust. Practice patterns around the use of antiplatelet and anticoagulant medications in these patients vary as a function of method of implantation (surgical versus transcatheter), the presence of any independent indica- tion for anticoagulation (eg, AF, venous thromboembolic disease), and local/institutional care pathways (Figure 12). Recommendation-Specific Supportive Text 1. All patients with mechanical valves require life- long anticoagulant therapy with a VKA.1 5 In addi- tion to the thrombogenicity of the intravascular prosthetic material, mechanical valves impose abnormal flow conditions, with zones of low flow within their components, as well as areas of high-shear stress, which can cause platelet activa- tion that leads to valve thrombosis and embolic events. Therapy with an oral VKA at an INR goal appropriate for the comorbidity of the patient and the type and position of the mechanical valve prosthesis is required to decrease the incidence of thromboembolism and associated morbid- ity. Data show that anticoagulation with a VKA is protective against valve thrombosis (OR: 0.11; 95% CI: 0.07 0.2) and thromboembolic events (OR: 0.21; 95% CI: 0.16 0.27). It is preferable to specify a single INR target for each patient and to recognize that the acceptable range includes 0.5 INR units on each side of this target. A spe- cific target is preferable because it reduces the likelihood of patients having INR values consis- tently near the upper or lower boundary of the range. Fluctuations in INR are associated with an increased incidence of complications in patients with prosthetic heart valves.19,38 2. The rate of thromboembolism in patients with a bileaflet mechanical AVR treated with a VKA is estimated to be 0.53% per patient-year over the INR range of 2.0 to 4.5. In a large retrospective study, adverse events increased if the INR was >4.0 in patients with a mechanical AVR. In patients with a current-generation mechanical AVR with- out other risk factors for thromboembolism, in the group treated to an INR of 2.0 to 3.0, the risk of thromboembolic events was similar to, but the risk of bleeding lower than, those of the group treated to an INR of 3.0 to 4.5 (P<0.01).7 In a ran- domized trial comparing moderate-intensity (INR 2.0 3.0) with high-intensity (INR 3.0 to 4.5) oral anticoagulation in patients with a single mechani- cal valve replacement, there was no difference in embolic events but a reduction in bleeding with the moderate-intensity group.8 In a study com- paring an INR target of 1.5 to 2.5 with a target of 2.0 to 3.0 in patients with current-generation mechanical aortic prosthetic valves and no other thromboembolic risk factors, the lower INR target range was noninferior, but the quality of the evi- dence was low.6 For current-generation mechani- cal valve prostheses in the aortic position, an INR of 2.5 (range, 2.0 3.0) provides a reasonable bal- ance between the risks of thromboembolism and 3. In patients with an aortic mechanical prosthesis who are at higher risk of thromboembolic com- plications, the INR should be maintained at 3.0 (range, 2.5 3.5). Risk factors include AF, previous thromboembolism, hypercoagulable state, and older-generation prosthesis (eg, ball-in-cage).10 Severe LV dysfunction may also increase throm- 4. The incidence of thromboembolism is higher with mitral than with aortic mechanical valves, and it is lower in mitral mechanical valve patients with a higher rather than a lower INR. In the GELIA (German Experience with Low Intensity Anticoagulation) study of patients with a mechanical mitral prosthesis, a lower INR range (2.0 3.5) was associated with a lower survival rate than that seen with a higher target INR Patient compliance may be challenging with higher INR goals. In one study, patients with a target INR between 2.0 and 3.5 were within that range 74.5% of the time. In contrast, patients with a target INR of 3.0 to 4.5 were within range only 44.5% of the time. An INR target of 3.0 (range, 2.5 3.5) provides a rea- sonable balance between the risks of under- or over-anticoagulation in patients with a mechani- cal mitral valve.9 5. Prior recommendations about the use of anti- platelet therapy after TAVI were derived from the protocols used in the pivotal randomized stud- ies showing the safety and effectiveness of this technology. These protocols were in turn adopted from studies of patients undergoing PCI. The small and underpowered ARTE trial (Aspirin Versus Aspirin plus Clopidogrel Following Transcatheter Aortic Valve Implantation) suggested that single- agent therapy, compared with dual-agent ther- apy, tended to reduce the risk of major adverse events (death, myocardial infarction, stroke, tran- sient ischemic attack, and major or life-threaten- ing bleeding) after TAVI. Whereas there were no CLINICAL STATEMENTS AND GUIDELINES differences between the groups with respect to death, stroke, or myocardial infarction, dual ther- apy was associated with a significantly increased risk of major or life-threatening bleeding.12 A systematic review and meta-analysis comprising approximately 2500 patients suggested that sin- gle-agent therapy is associated with fewer 30-day deaths and less major bleeding than is seen with There are several ongoing trials on this subject.39 6. The risk of thromboembolism is approximately 0.7% per year in patients with biological valves in sinus rhythm; Figure 13 is derived from several studies in which most patients were not undergo- ing therapy with VKA. Among patients with bio- prosthetic valves, those with a mitral prosthesis have higher rates of thromboembolism than do those with an aortic prosthesis (2.4% per patient- year versus 1.9% per patient-year).15 In studies of patients with bioprosthetic aortic valves who were in sinus rhythm and had no other indi- cations for anticoagulation, the incidence of thromboembolic events, bleeding, and death was similar in those who received aspirin or aspirin- like antiplatelet agents only and in those who There are no studies examin- ing the long-term effects of antiplatelet agents in patients with bioprosthetic mitral valve repair or mitral valve repair; the beneficial effects seen with bioprosthetic aortic valves may apply to mitral valves, as well.9,18 7. Many patients who undergo surgical implantation of a bioprosthetic mitral or aortic valve will not require lifelong anticoagulation in the absence of an independent indication, such as AF. However, there is an increased risk of ischemic stroke early after operation, particularly in the first 90 to 180 days after either bioprosthetic AVR or mitral valve Anticoagulation early after valve implantation is intended to decrease the risk of thromboembolism until the prosthetic valve is fully endothelialized. The potential ben- efit of anticoagulation therapy must be weighed against the risk of bleeding. In a nonrandomized Figure 12. Antithrombotic therapy for prosthetic valves. Colors correspond to Table 2. *Thromboembolic risk factors include an older-generation valve, AF, previous thromboembolism, hypercoagulable state, and LV sys- tolic dysfunction. For a mechanical On-X AVR and no thromboembolic risk factors, a goal INR of 1.5 2.0 plus aspirin 75 100 mg daily may be reasonable starting 3 months after surgery. ASA indicates aspirin; AVR, aortic valve replacement; INR, international normalized ratio; MVR, mitral valve replacement; VKA, vitamin K antagonist; Rx, medication; and TAVI, transcatheter aortic valve implantation. CLINICAL STATEMENTS AND GUIDELINES study, patients with a bioprosthetic mitral valve replacement who received anticoagulation had a lower rate of thromboembolism than that of those who did not receive therapy with VKA.15 Even with routine anticoagulation early after mitral valve surgery, the incidence of ischemic stroke within the first 30 postoperative days was higher after replacement with a biological pros- thesis than after mitral valve repair (1.5% 0.4%) or replacement with a mechanical prosthesis.21 Small studies have not established a convincing net benefit of anticoagulation after implantation of a bioprosthetic AVR24,25 ; however, a large obser- vational Danish registry demonstrated a lower risk of stroke and death with VKA, which extended up to 6 months, without a significantly increased Concern has been raised about the incidence of subclinical bioprosthetic valve leaflet thrombosis after surgical valve replace- In addition, the PARTNER 2 (Placement of Aortic Transcatheter Valves) investigators reported that the use of anticoagulation after bioprosthetic AVR in intermediate or higher sur- gical risk patients was safe and associated with a significant reduction in 6-month stroke rates.23 Ninety-five percent of the anticoagulated patients in this registry were discharged on warfarin in preference to a direct oral anticoagulant. 8. The prior recommendation to add low-dose aspi- rin to therapeutic VKA therapy for a mechanical valve prosthesis was based on studies performed decades ago that included many patients with older-generation prostheses who also had addi- tional thromboembolic and vascular risk factors. A 2013 Cochrane Systematic Review showed that compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events and the total mortality rate but at the cost of an increased and offsetting risk of major bleeding.26 The authors pointed out that the quality of the included tri- als tended to be low, possibly reflecting the era when most trials were conducted. An individu- alized approach that takes the risk of bleeding into account is required. 9. In patients without risk factors who receive a mechanical On-X aortic heart valve (On-X Life Technologies Inc., Austin, Texas), targeting the INR to a lower goal (1.5 2.0) in conjunction with aspirin 81 mg daily may be a strategy for long-term management. Warfarin dosing is tar- geted to an INR of 2.5 (range, 2.0 3.0) for the first 3 months after surgery, during which low- dose aspirin is also used.27 This recommenda- tion is based on a single RCT27 of lower- versus standard-intensity VKA therapy (with low-dose aspirin) in patients undergoing On-X AVR. The lower-intensity INR group experienced signifi- cantly less major and minor bleeding, whereas the rates of stroke, transient ischemic attack, total neurological events, and all-cause mortal- ity were similar between the 2 groups. A sub- sequent publication from these investigators showed harm with a strategy of dual-antiplate- let therapy versus low-intensity anticoagulation plus low-dose aspirin.28 The routine use of dual-antiplatelet therapy for 6 months after TAVI, which has been the default strategy since the introduction of this technol- ogy into clinical use, has been not been rigor- ously assessed (see previous discussion). There are several ongoing trials evaluating antithrom- botic strategies after TAVI. A small, single-center RCT of patients receiving a self-expanding TAVI device showed no difference in a composite endpoint of major adverse cardiac and cerebro- vascular events or life-threatening bleeding with aspirin plus clopidogrel versus aspirin alone at Compared with single- agent therapy, dual-antiplatelet therapy may be associated with a higher risk of bleeding and no significant difference in rates of valve leaflet thrombosis, thromboembolism, or valve perfor- Other procedural and patient factors may impact the decision to use dual-antiplatelet therapy. The selective use of VKA therapy might be consid- ered after TAVI in patients at low bleeding risk on an individual basis. The PARTNER 2 investigators reported that the use of an anticoagulant (95% warfarin) after TAVI in intermediate or higher surgical risk patients was associated with a lower incidence of an increase in mean gradient >10 mmHg over the first year after implantation.23 This Doppler finding may reflect the development of leaflet thrombosis, for which a change in the frequency of follow-up examinations or treatment could be considered. VKAs may be more effective than direct oral anticoagulants for reduction of death, myocardial infarction, and cerebrovascular events in patients undergoing TAVI with an indi- cation for anticoagulation.33 The selective short- term use of VKAs after ViV TAVI is predicated on the observation that valve thrombosis may be more frequent in this patient population.32 The GALILEO (Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy after Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes) trial assessed a strategy of low-dose rivaroxaban (10 mg daily) plus low-dose aspirin (75 100 mg daily) versus an antiplatelet strategy CLINICAL STATEMENTS AND GUIDELINES of low-dose aspirin plus clopidogrel (75 mg daily). The study was terminated prematurely by the Data and Safety Monitoring Board because of safety concerns. The rivaroxaban strategy was associated with a higher risk of death or thrombo- embolic complications and a higher risk of bleed- ing than those seen with the antiplatelet-based Dabigatran was compared with warfarin in the RE-ALIGN (Randomized, Phase II Study to Evaluate the Safety and Pharmacokinetics of Oral Dabigatran Etexilate in Patients after Heart Valve Replacement) trial. It was stopped prematurely for excessive thrombotic and bleeding complications in the dabigatran arm.4,5 The safety and efficacy of conventional-dose oral anti-Xa agents in patients with a mechanical valve prosthesis have not been evaluated.33 36 11.3. Bridging Therapy Recommendations for Bridging Therapy During Interruption of Oral Anticoagulation in Patients With Prosthetic Heart Valves COR LOE Recommendations For patients with mechanical heart valves who are undergoing minor procedures (eg, dental extractions or cataract removal) where bleeding is easily controlled, continuation of VKA anticoagulation with a therapeutic INR is recommended. For patients with a bileaflet mechanical AVR and no other risk factors for thromboembolism who are undergoing invasive procedures, temporary interruption of VKA anticoagulation, without bridging agents while the INR is subtherapeutic, is recommended. For patients with a mechanical valve prosthesis receiving VKA therapy who require immediate/ emergency noncardiac surgery or an invasive procedure, administration of 4-factor prothrombin complex concentrate (or its activated form) is reasonable. Figure 13. Management of embolic events and valve thrombosis. Colors correspond to Table 2. 3D indicates 3-dimensional; 4D, 4-dimensional; AVR, aortic valve replacement; CT, computed tomography; INR, international nor- malized ratio; MVR, mitral valve replacement; Rx, medication; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; and VKA, vitamin K antagonist. CLINICAL STATEMENTS AND GUIDELINES For patients with bioprosthetic heart valves or annuloplasty rings who are receiving anticoagulation for AF, it is reasonable to consider the need for bridging anticoagulant therapy around the time of invasive procedures on the basis of the CHA2 -VASc score weighed against the risk of bleeding. For patients who are undergoing invasive procedures and have 1) a mechanical AVR and any thromboembolic risk factor, 2) an older-generation mechanical AVR, or 3) a mechanical mitral valve replacement, bridging anticoagulation therapy during the preoperative time interval when the INR is subtherapeutic is reasonable on an individualized basis, with the risks of bleeding weighed against the benefits of thromboembolism prevention. Synopsis The management of patients with prosthetic heart valves or repaired native valves in whom interrup- tion of anticoagulant therapy is needed for diagnostic or surgical procedures should take into account the type and location of the valve, the type of proce- dure, thromboembolic risk factors, the length of time over which oral anticoagulation will be withheld, and bleeding risk. Bridging therapy with either intra- venous unfractionated heparin (UFH) or low-molec- ular-weight heparin (LMWH) has evolved empirically to reduce thromboembolic events during temporary interruption of oral anticoagulation in higher-risk pa- tients, such as those with a mechanical mitral valve replacement or AVR and additional risk factors for Recommendation-Specific Supportive Text 1. Antithrombotic therapy should not be stopped for procedures in which bleeding is unlikely or would be inconsequential if it occurred (eg, surgery on the skin, dental cleaning, or simple treatment for dental caries). Eye surgery, particularly for cata- racts or glaucoma, is usually associated with very little bleeding and thus is frequently performed without alteration of anticoagulation with a VKA. 2. In patients with a bileaflet mechanical AVR and no other risk factors, the risk of thromboembo- lism after stopping anticoagulation with a VKA is small if the drug is withheld for only a few days. In these low-risk patients, the inconvenience and expense of bridging anticoagulation can be avoided. When it is necessary to interrupt VKA therapy, the agent is stopped 2 to 4 days before the procedure and restarted as soon as bleeding risk allows, typically 24 hours after surgery.2,3 3. In patients with mechanical valves on long-term VKA therapy who require emergency surgery or invasive procedures, anticoagulation can be reversed by administration of intravenous pro- thrombin complex concentrate. It replaces the coagulation factors that are decreased by VKAs and contains all coagulant factors, including II, VII, IX, and X, in inactivated form. Onset of effect is within 5 to 15 minutes, and duration of effect persists for 12 to 24 hours. With fresh frozen plasma, onset of effect is longer (1 4 hours), and duration of effect is shorter (<6 hours), depending on the dose given. The effect of prothrombin complex concentrate can be prolonged with vitamin K, if indicated.4 4. Although the large phase III trials comparing NOACs with warfarin excluded patients with moderate to severe rheumatic MS or mechani- cal heart valves, some did include patients with other VHD and bioprosthetic valve replacement Many patients who develop an indica- tion for anticoagulation late after bioprosthetic heart valve replacement or native valve repair are treated safely with direct oral anticoagulants, as predicated on their CHA2 -VASc score and the predicted risks of bleeding. Considerations about the need for bridging therapy in these individu- als can follow the same strategy applied to other subsets of patients who have AF without mod- erate to severe rheumatic MS or a mechanical prosthesis. 5. When interruption of oral VKA therapy is deemed necessary, the agent is usually stopped 3 to 4 days before the procedure and is restarted postopera- tively as soon as bleeding risk allows. Bridging anticoagulation with intravenous UFH or subcuta- neous LMWH is started when the INR falls below the therapeutic threshold (ie, 2.0 or 2.5, depend- ing on the clinical context), usually 36 to 48 hours before surgery, and is stopped 4 to 6 hours (for intravenous UFH) or 12 hours (for subcutaneous LMWH) before the procedure. There are no ran- domized comparative-effectiveness trials evaluat- ing a strategy of bridging versus no bridging in adequate numbers of patients with prosthetic heart valves who need temporary interruption of oral anticoagulant therapy, although such studies are ongoing. The evidence cited to support bridg- ing therapy derives from cohort studies with poor or no comparator groups.1,6 14 In patient groups other than those with mechanical heart valves, increasing concerns have surfaced that bridging therapy exposes patients to higher bleeding risks without reducing the risk of thromboembolism.15 Accordingly, decisions about bridging should be individualized and should account for the trade- offs between thrombosis and bleeding. Recommendations for Bridging Therapy During Interruption of Oral Anticoagulation in Patients With Prosthetic Heart Valves (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES 11.4. Excessive Anticoagulation and Serious Bleeding With Prosthetic Valves Recommendations for Management of Excessive Anticoagulation and Serious Bleeding in Patients With Prosthetic Valves Referenced studies that support the recommendations are summarized in Online Data Supplement 37. COR LOE Recommendations For patients with mechanical valves and uncontrollable bleeding who require immediate reversal of anticoagulation, administration of 4-factor prothrombin complex (or its activated form) is reasonable. For patients with mechanical valves and uncontrollable bleeding who have received 4-factor prothrombin concentrate complex, adjunctive use of intravenous vitamin K is reasonable if resumption of VKA therapy is not anticipated for 7 days. For patients with bioprosthetic valves or annuloplasty rings who are receiving a direct oral anticoagulant and who require immediate reversal of anticoagulation because of uncontrollable bleeding, treatment with idarucizumab (for dabigatran) or andexanet alfa (for anti-Xa agents) is reasonable.1 5 For patients with a mechanical prosthetic valve and supratherapeutic INR (>5.0) who are not actively bleeding, the benefit of individualized treatment with oral vitamin K, in addition to temporary withdrawal of the VKA, is uncertain. Synopsis Excessive VKA anticoagulation greatly increases the risk of hemorrhage. However, a rapid decrease in INR to a subtherapeutic level may increase the risk of thrombo- Nevertheless, for patients who require im- mediate reversal of VKA anticoagulation because of severe or life-threatening bleeding or the need for an emergency procedure, reversal is indicated.7 Preference is placed on the use of rapid-acting and reliable agents, such as prothrombin complex concentrate or its acti- vated form. Addition of vitamin K can be considered on an individual basis.8 13 Specific antidotes are available to reverse the effects of dabigatran (idarucizumab) and the oral anti-Xa (andexanet alfa) anticoagulants. Recommendation-Specific Supportive Text 1. Four-factor prothrombin complex concentrate includes factors II, VII, IX, and X. Onset of effect is within 5 to 15 minutes, and duration of effect is 12 to 24 hours. It is a more specific and reliable reversal agent than fresh frozen plasma.8 2. Vitamin K is a cofactor for hepatic production of factors II, VII, IX, and X. Onset of effect depends on the route of administration (intravenous versus oral), and the dose given should be predicated on the presence of active bleeding, the maintenance dose of the VKA, the magnitude of INR elevation, and the desired range into which to reduce the INR.7,9 11 A 10-mg intravenous dose is recommended for life- threatening bleeding when there is no concern for restarting the VKA within the next week. 3. Idarucizumab (two, 2.5-mg bolus infusions no more than 15 minutes apart) is indicated to reverse the effect of dabigatran when clinically indicated.1,5 Andexanet alfa (bolus and 2-hour infusion, with the dose dependent on the timing of exposure and the individual agent) is used to reverse the effect of the oral anti-Xa agents. Experience with these agents Prothrombin complex concen- trate (or its activated form) has also been used with direct oral anticoagulant related bleeding. 4. A systematic review of the effectiveness and safety of administering vitamin K to patients receiving VKA therapy with an INR between 4.5 and 10.0 and without bleeding indicated a nonsignificant increased risk of mortality and thromboembolism with vitamin K administration, with only moderate certainty of the evidence. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR, with very low certainty of the evidence. The findings suggested that patients on VKA therapy who have an INR between 4.5 and 10.0 and are not bleeding are not likely to benefit from routine vitamin K administration in addition to temporary VKA cessation.13 11.5. Thromboembolic Events With Prosthetic Valves Recommendations for Management of Thromboembolic Events With Prosthetic Valves COR LOE Recommendations In patients with a mechanical AVR who experience a stroke or systemic embolic event while in therapeutic range on VKA anticoagulation, it is reasonable to increase the INR goal from 2.5 (range, 2.0 3.0) to 3.0 (range, 2.5 3.5) or to add daily low-dose aspirin (75 100 mg), with assessment of bleeding risk. In patients with a mechanical mitral valve replacement who experience a stroke or systemic embolic event while in therapeutic range on VKA anticoagulation, it is reasonable to increase the INR goal from 3.0 (range, 2.5 3.5) to 4.0 (range, 3.5 4.0) or to add daily low-dose aspirin (75 100 mg), with assessment of bleeding risk. In patients with a bioprosthetic surgical or transcatheter aortic valve or bioprosthetic mitral valve who experience a stroke or systemic embolic event while on antiplatelet therapy, VKA anticoagulation, instead of antiplatelet therapy may be considered after assessment of bleeding risk.1,2 Synopsis For patients with a mechanical valve who suffer an embolic event, it is important to assess the adequacy CLINICAL STATEMENTS AND GUIDELINES of VKA anticoagulation, document time spent in the therapeutic range, exclude IE, screen for new-onset AF, and consider whether an underlying hypercoagulable state might be a contributing factor. Thromboembolism in bioprosthetic heart valve recipients should similarly raise suspicion of IE or new-onset AF in the right clini- cal setting. Leaflet thrombosis occurs more frequently with bioprosthetic transcatheter aortic valves than with bioprosthetic surgical aortic valves.1 4 Intensification of antithrombotic therapy should always account for indi- vidual patient bleeding risk (Figure 13). Recommendation-Specific Supportive Text 1. There are no comparative-effectiveness trials from which to assess the relative utility of higher-inten- sity VKA therapy versus standard VKA therapy plus low-dose aspirin in mechanical valve recipi- ents who have experienced stroke or systemic embolism while in target INR range. Excluding the common clinical occurrence of extended time in a subtherapeutic INR range is the first priority. Assessment of medication adherence, intercur- rent illness, new or recently adjusted medications, dietary changes, and alcohol intake is critical. Whether to intensify VKA therapy or add low- dose aspirin is a patient-specific, shared decision- making proposition that must weigh several factors, including bleeding risk. 2. The approach to management of the patient with a systemic embolic event and a mechani- cal mitral prosthesis includes review of INR levels to ensure the patient is in the target INR range most of the time. INR levels may have been sub- therapeutic because of suboptimal medication adherence, intercurrent illness, new or recently adjusted medications, dietary changes, or alcohol intake. Whether to intensify VKA therapy or add low-dose aspirin is a patient-specific, shared deci- sion-making proposition that must weigh several factors, including bleeding risk. 3. In those patients with a bioprosthetic valve who have a stroke or embolic event, further imaging with TEE or 3D CT scanning may show leaflet thrombosis, which should respond to anticoagu- lation with either a VKA or a NOAC.1,2 The effec- tiveness of anticoagulation in aortic and mitral bioprosthetic valve recipients in whom leaflet thrombosis cannot be established as the cause of thromboembolism is uncertain, and patients should undergo a full neurological evaluation to rule out other causes of the neurological event. Shared decision-making that accounts for bleed- ing risk is a central feature of management. 11.6. Acute Mechanical Valve Thrombosis 11.6.1. Diagnosis of Acute Mechanical Valve Thrombosis Recommendation for Diagnosis of Acute Mechanical Valve Thrombosis Referenced studies that support the recommendation are summarized in Online Data Supplement 38. COR LOE Recommendation In patients with suspected mechanical prosthetic valve thrombosis, urgent evaluation with TTE, TEE, fluoroscopy, and/ or multidetector CT imaging is indicated to assess valve function, leaflet motion, and the presence and extent of thrombus.1 7 Synopsis Mechanical valve thrombosis is typically a subacute to acute event resulting in rapid valve dysfunction because of abnormal or absent motion of the valve leaflets, which often is associated with inadequate VKA anticoagulation. However, recurrent valve thrombosis can be associated with pannus ingrowth in the chronic setting. Mechanical valve thrombosis can present with rapid onset of symp- toms or acute pulmonary edema. Physical examination may demonstrate a stenotic murmur and muffled closing clicks, and further urgent diagnostic evaluation is required. The annual rate of prosthetic valve thrombosis with me- chanical valves ranges from 0.1% to 5.7%. Higher rates of mechanical valve thrombosis are seen for some specific valve types, within the first 3 months after valve implanta- tion and, for mechanical valves implanted in the mitral or tricuspid position compared with the aortic position.8 Recommendation-Specific Supportive Text 1. Mechanical prosthetic valve thrombosis is diag- nosed by an abnormally elevated velocity or gra- dient across the prosthesis, with either limited leaflet motion or attached mobile densities con- sistent with thrombus, or both. Prosthetic valve obstruction is usually defined as a mean trans- valvular gradient increase >50% (or an increase >10 mmHg across an aortic prosthesis) compared with baseline, after exclusion of other causes, such as a high-output state. When mechani- cal valve thrombosis is suspected, imaging and Doppler data from TTE provide information on valve function, estimated pulmonary pressures, and LV size and systolic function.9 Leaflet motion should be visualized with CT or TEE (particularly for a mitral prosthesis) or fluoroscopy (for an aor- Prolonged periods of obser- vation under fluoroscopy or TEE may be required to diagnose intermittent obstruction. The pres- ence and quantification of thrombus and pannus should be evaluated by either TEE or CT.6,7,10 12 CLINICAL STATEMENTS AND GUIDELINES Recommendation for Intervention for Mechanical Prosthetic Valve Thrombosis Referenced studies that support the recommendation are summarized in Online Data Supplement 38. COR LOE Recommendation For patients with a thrombosed left-sided mechanical prosthetic heart valve who present with symptoms of valve obstruction, urgent initial treatment with either slow-infusion, low- dose fibrinolytic therapy or emergency surgery Synopsis Patients presenting with a thrombosed mechanical valve require urgent therapy. The 2 options of low- dose, continuous-infusion thrombolytic therapy or emergency surgery are both effective, with the decision to proceed with either one based on multiple clinical factors and local experience and expertise. Recommendation-Specific Supportive Text 1. The decision between surgery and systemic fibrinolysis for symptomatic left-sided mechani- cal valve thrombosis should be individualized (Table 23) after review by the heart valve team, while engaging the patient in a process of shared decision-making and accounting for local experi- ence and expertise. The overall 30-day mortality rate with surgery is 10% to 15%, with a lower mortality rate of <5% in patients with NYHA class I or II symptoms.2,3,7 Recent studies using an echocardiogram-guided, slow-infusion, low-dose fibrinolytic protocol have shown hemodynamic success rates >90%, with embolic event rates <2% and major bleeding rates <2%.13 Systemic fibrinolysis is therefore an acceptable alternative to reoperation in patients at high or prohibitive surgical risk and in patients who have a small thrombus burden, mild HF symptoms (NYHA class I or II), and low bleeding risk. Absence of surgi- cal expertise should be considered in the clinical decision-making process as a factor that favors thrombolytics, whereas recurrent valve thrombo- sis favors a surgical approach (Table 23). 11.7. Bioprosthetic Valve Thrombosis 11.7.1. Diagnosis of Bioprosthetic Valve Thrombosis Recommendation for Diagnosis of Bioprosthetic Valve Thrombosis COR LOE Recommendation In patients with suspected bioprosthetic valve thrombosis, 3D TEE or 4D CT imaging can be useful to rule out leaflet thrombosis.1 5 Synopsis Bioprosthetic valve thrombosis is most common in the first 3 months after implantation but also has been de- scribed in patients years (typically 1 or 2) after valve im- plantation, with the longest interval being 6.5 years.6 Bioprosthetic valves are less thrombogenic than their mechanical counterparts. However, the diagnosis of subclinical bioprosthetic valve thrombosis has increased with use of CT imaging and as a function of the in- creased numbers of implanted bioprosthetic valves, in- Recommendation-Specific Supportive Text 1. Bioprosthetic valve thrombosis appears to be more common with transcatheter than with surgical bioprosthetic valves. Leaflet thrombosis often is suspected on the basis of an increased transvalvular velocity on routine echocardio- graphic monitoring and can be confirmed by the finding of hypoattenuation of the valve leaflets on CMR imaging. When there is clinical evidence of stenosis, 3D TEE or 4D CT imaging may be useful to detect a layer of valve throm- bus, which may respond to treatment with oral anticoagulation. 11.7.2. Medical Therapy Recommendation for Medical Therapy Referenced studies that support the recommendation are summarized in Online Data Supplement 39. COR LOE Recommendation In patients with suspected or confirmed bioprosthetic valve thrombosis who are hemodynamically stable and have no contraindications to anticoagulation, initial treatment with a VKA is reasonable.1 6 Synopsis Patients with an obstructed bioprosthesis may have a thin layer of thrombus causing reduced leaflet motion. VKA treatment may result in resolution of the thrombus and improvement in valve function. Recommendation-Specific Supportive Text 1. Multiple small nonrandomized studies support the use of VKAs to treat patients with clinical and subclinical bioprosthetic valve thrombosis after both SAVR and TAVI.1,3,4,6,7 VKA anticoagulation can result in a significant reduction of transvalvu- lar gradient, improved leaflet motion, and clinical CLINICAL STATEMENTS AND GUIDELINES 11.8. Prosthetic Valve Stenosis 11.8.1. Diagnosis of Prosthetic Valve Stenosis Recommendations for Diagnosis of Prosthetic Valve Stenosis Referenced studies that support the recommendations are summarized in Online Data Supplement 40. COR LOE Recommendations In patients with suspected mechanical or bioprosthetic valve stenosis, TTE and TEE are recommended to diagnosis the cause and severity of valve obstruction, assess ventricular function, and estimate pulmonary artery In patients with mechanical valve stenosis, fluoroscopy or cine-CT is recommended to assess motion of the mechanical valve leaflets. In patients with bioprosthetic valve stenosis, 3D TEE or 4D CT imaging can be useful to rule out leaflet thrombosis.3 7 Synopsis Prosthetic valve stenosis can occur with both mechani- cal and bioprosthetic valves. Echocardiographic defi- nitions of stenosis severity have been provided by the American Society of Echocardiography.1 Obstruction of a mechanical valve may be caused by thrombus for- mation that leads to abnormal leaflet mobility, pannus ingrowth, or a combination of the two.8 Bioprosthetic valve stenosis may be caused by structural valve dete- rioration, with leaflet degeneration by thickening, cal- cification, or tear as the end stage of a slowly progres- sive process resulting in abnormal leaflet motion, or it may be attributable to other structural causes, includ- ing stent creep. Bioprosthetic valve stenosis may also be attributable to nonstructural causes, such as endocardi- tis, leaflet thrombus, or pannus. The progressive stages are defined by the Valve Academic Research Consor- Recommendation-Specific Supportive Text 1. TTE and TEE assessment can appropriately detect and quantify prosthetic valve stenosis.1 TTE within 3 months after valve implantation is useful to provide baseline data on valve hemodynamics and ventricular function. In some patients, the orifice area of the implanted prosthesis may be inadequate to meet the cardiac output demands of the patient, even when the prosthetic valve itself is functioning normally. This circumstance, termed patient prosthesis mismatch, is associ- ated with a high transvalvular gradient, per- sistent LV hypertrophy, and an increased rate of cardiac events after valve replacement.10,11 Diagnosis in the setting of bileaflet mechanical valves is complicated by nonlaminar patterns of blood flow, for which significant pressure recovery may be present; thus, a high velocity in the central narrow slit-like orifice may not cor- relate with prosthetic valve stenosis or patient prosthesis mismatch. Prosthetic valve stenosis is distinguished from patient prosthesis mismatch by comparison with the early postoperative base- line study and by visualization of the appearance and motion of the valve leaflets. Prosthetic valve stenosis is characterized by a clinical course of progressive increase in transvalvular velocity and pressure gradient in conjunction with abnormal thickened/calcified leaflets (for bioprosthetic valves) or evidence of pannus formation (with mechanical valves). 2. The motion of the leaflets of a mechanical valve is best evaluated radiographically with fluoros- copy or cine-CT imaging because strong reflec- tions from the mechanical valve obscure motion on echocardiographic imaging in most patients, particularly as assessed on images from the trans- thoracic approach. With fluoroscopic imaging, the angle of imaging must be adjusted to dem- onstrate leaflet motion from a side view, permit- ting measurement of the angles of opening and closure that can be compared with expected values for that valve type. Cine-CT images are obtained at a high frame rate focused on the prosthetic valve in a 3D acquisition. Compared with fluoroscopy, cine-CT 3D images are less operator dependent for measuring opening and closing angles. In addition, cine-CT allows detection of pannus or thrombus on or adjacent Table 23. Systemic Fibrinolysis Versus Surgery for Prosthetic Valve Thrombosis Favor Surgery Favor Fibrinolysis Readily available surgical expertise No surgical expertise available Low surgical risk High surgical risk Contraindication to fibrinolysis No contraindication to fibrinolysis Recurrent valve thrombosis First-time episode of valve thrombosis NYHA class IV NYHA class I, II, or III ) Small clot ( 0.8 cm2 ) LA thrombus No LA thrombus Concomitant CAD in need of revascularization No or mild CAD Other valve disease No other valve disease Possible pannus Thrombus visualized Patient choice Patient choice CAD indicates coronary artery disease; and NYHA, New York Heart Association. Adapted from several references.2,5,7,13,14 CLINICAL STATEMENTS AND GUIDELINES to the valve, which is not possible with fluoros- copy. When excessive gradients are present with normal leaflet motion and no thrombus, either patient prosthesis mismatch or pannus forma- tion is present (or both). 3. Stenosis of a bioprosthesis may occur because of progressive structural valve degeneration or pan- nus formation. However, stenosis can also occur because of a thin layer of thrombus on the valve cusps, which is reversible with oral anticoagula- tion therapy. Bioprosthetic valves are less throm- bogenic than their mechanical counterparts. However, the diagnosis of subclinical bioprosthetic valve thrombosis has increased with the use of CT imaging and as a function of the increased num- bers of implanted bioprosthetic valves, including When there is clinical evidence of biopros- thetic valve stenosis, 3D TEE or 4D CT imaging may be useful to detect a layer of valve thrombus as the cause of the obstruction. 11.8.2. Intervention for Prosthetic Valve Stenosis Recommendations for Intervention for Prosthetic Valve Stenosis Referenced studies that support the recommendations are summarized in Online Data Supplement 40. COR LOE Recommendations In patients with symptomatic severe stenosis of a bioprosthetic or mechanical prosthetic valve, repeat surgical intervention is indicated unless surgical risk is high or prohibitive.1 3 For severely symptomatic patients with bioprosthetic aortic valve stenosis and high or prohibitive surgical risk, a transcatheter ViV procedure is reasonable when performed at a Comprehensive Valve Center.4,5 For patients with significant bioprosthetic valve stenosis attributable to suspected or documented valve thrombosis, oral anticoagulation with a VKA is reasonable.6 13 Synopsis Cumulative survival rates are higher with reoperative AVR than with transcatheter ViV treatment for prosthetic valve stenosis, and a surgical approach is associated with a re- duced incidence of patient prosthesis mismatch, reduced incidence of paravalvular leak, and lower aortic valve gra- The VIVID (Valve-In-Valve International Data) reg- istry examined outcomes with ViV treatment of 459 pa- tients, of whom 40% had isolated stenosis and 30% had Within 1 month after the ViV procedure, 7.6% of patients died and 1.7% had a major stroke. Of the survivors, 93% experienced good functional status (NYHA class I or II), with an overall 1-year survival rate of Some systematic reviews comparing outcomes of transcatheter ViV with those of repeat SAVR suggest that hemodynamic outcomes are similar, but stroke and bleeding risks are lower with ViV.15 There is a subset of patients with bioprosthetic valve stenosis attributable to thrombus on the leaflets who may respond to oral anti- coagulation with a VKA (Figure 14).6 13 Recommendation-Specific Supportive Text 1. Reoperative surgery for prosthetic valve stenosis is associated with acceptable mortality and morbid- ity rates in the current era, but the risks are typi- cally higher than those estimated at the time of initial surgery because of older patient age, clini- cal status at the time of intervention, and reop- The decision to proceed with surgical versus transcatheter intervention is based on available expertise, individual patient and valve characteristics, and shared decision-making. 2. Catheter-based therapy with transcatheter ViV has emerged as an acceptable alternative to reopera- tive surgery for the treatment of high and prohib- itive surgical risk patients with bioprosthetic AS.4,5 Although coronary artery obstruction is more com- mon with aortic ViV procedures than with TAVI for native AS, rates of paravalvular leak and permanent pacemaker implantation are lower with aortic ViV procedures than with TAVI for native AS. Annulus rupture has not been reported. Transcatheter ViV also has been successfully performed for failed surgi- cal bioprostheses in the mitral, pulmonic, and tricus- pid positions, although LV outflow obstruction may occur after mitral ViV implantation. 3. A subset of patients presents with stenosis of a bioprosthetic valve attributable to leaflet throm- bosis that results in decreased mobility of the leaf- lets. Leaflet thrombosis can occur from 1 month to years after implantation. If the patient is stable and has no contraindication to long-term anti- coagulation, a trial of oral anticoagulation with VKA may result in resolution of the thrombus and improvement in hemodynamics.6 13 However, these patients are at increased risk of recurrent thrombosis (if the anticoagulation is stopped) and early structural deterioration, and thus they require close follow-up.17 11.9. Prosthetic Valve Regurgitation Regurgitation in a mechanical prosthetic valve may be transvalvular, caused by impaired motion of the valve disk secondary to pannus, thrombus, or vegetation in- terfering with complete closure of the valve occluders, or paravalvular, caused by suture line disruption related to technical error at implantation, suture failure, annu- lar disruption, or endocarditis. Patients with severe mi- tral annular calcification are particularly vulnerable to developing late paravalvular leak. Regurgitation in bio- prosthetic valves may be paravalvular but more often is CLINICAL STATEMENTS AND GUIDELINES transvalvular, caused by leaflet immobility secondary to calcification or leaflet perforation or flail associated with areas of focal calcification.1 Echocardiographic defini- tions of prosthetic valve regurgitation severity have been published by the American Society of Echocardiography.2 11.9.1. Diagnosis of Prosthetic Valve Regurgitation Recommendations for Diagnosis of Prosthetic Valve Regurgitation Referenced studies that support the recommendations are summarized in Online Data Supplement 41. COR LOE Recommendations In patients with suspected mechanical or bioprosthetic valve regurgitation, TTE and TEE are recommended to determine the cause and severity of the leak, assess ventricular function, and estimate pulmonary artery systolic pressure.1 4 In patients undergoing a transcatheter procedure for paravalvular prosthetic regurgitation, 3D TEE is recommended for Synopsis The clinical presentation of prosthetic valve regur- gitation varies depending on its severity, hemody- namic effects, and etiology. In asymptomatic pa- tients, prosthetic valve regurgitation may be found incidentally on routine clinical or imaging follow-up. A change in auscultatory findings (eg, change in prosthetic valve sounds or a new murmur) should prompt suspicion of prosthetic valve dysfunction. Symptomatic patients with prosthetic valve regurgi- tation present with unexplained or new-onset HF or significant hemolysis with or without anemia. TTE is inadequate for evaluation of prosthetic mitral valves; TEE is needed when prosthetic MR is a concern. A critical step in evaluation of the patient with pros- thetic valve regurgitation is to distinguish transval- vular from paravalvular leak, which also requires TEE in addition to TTE. Figure 14. Management of prosthetic valve stenosis and regurgitation. Colors correspond to Table 2. 3D indicates 3-dimensional; 4D, 4-dimensional; CT, computed tomography; CVC, Comprehensive Valve Center; HF, heart failure; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography/echocardiogram; and ViV, valve-in-valve. *See Figure 13 if valve thrombosis is suspected. CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. Echocardiography is the primary imaging modality to assess the location and quantify the severity of pros- thetic valve regurgitation, often requiring both TTE and TEE approaches.1,3 Although TTE provides supe- rior assessment of transvalvular gradients, chamber sizes, and function, TEE is better suited to identify the cause and location of regurgitation and is essential for prosthetic mitral valve because of acoustic shadow- ing on TTE. Even with prosthetic aortic valves, acous- tic shadowing may affect detection of a paravalvular leak by either TTE or TEE, with TTE being suboptimal to assess posterior paravalvular leak and TEE subop- timal to assess anterior defects.3 The Valve Academic Research Consortium (VARC) has suggested an approach for assessment of paravalvular leak severity and constructed a 5-class grading scheme.7 2. 3D echocardiography plays a significant role in determining the precise location and size of the paravalvular leak in patients undergoing interven- tion. For a successful transcatheter paravalvular leak closure, adequate paravalvular leak assess- ment includes 1) precise location of the defect(s), 2) precise dimensions, 3) orientation of the defect in relation to the sewing ring and prosthetic valve occluders or leaflets, and 4) location and orienta- tion of the subvalvular structures. Real-time 3D TEE allows optimal visualization of the defects and direct guidance for catheter movement and positioning of the implanted device(s) during the transcatheter 3D TEE also allows assessment of residual regurgitation after device placement. Limitations of 3D TEE include artifacts of ultrasound imaging (eg, dropout, acoustic shadowing, rever- beration artifacts) and reduced temporal and spatial Transcatheter closure using intracardiac echocardiography guidance is possible and allevi- ates the need for conscious sedation or anesthesia but allows only 2D and color Doppler imaging.9 11.9.2. Medical Therapy Medical therapy for prosthetic valve regurgitation is ap- propriate in asymptomatic patients or when the cause of regurgitation is valve thrombosis (see Sections 11.6 and 11.8) or prosthetic valve endocarditis (see Section 12.3), although further intervention may ultimately be needed in many of these patients. Some patients tolerate asymp- tomatic prosthetic valve regurgitation for many years, sim- ilar to patients with native valve regurgitation. However, there may be patients who develop rapid progression of the severity of bioprosthetic valve regurgitation because of leaflet degeneration. In patients with hemolytic ane- mia attributable to paravalvular regurgitation, medical management with folic acid and iron supplementation or periodic transfusion may be possible when the anemia is not severe, with intervention reserved for patients with symptomatic intractable anemia (see Section 11.8.3). Recommendations for Intervention Referenced studies that support the recommendations are summarized in Online Data Supplement 41. 