The optimal timing of tricuspid valve surgery for asymptomatic or minimally symptomatic patients with severe primary TR has not been established. Extrapolation from limited experi- ences reported for patients with stable carcinoid heart disease and patients with a flail tricuspid leaflet, as well as application of the manage- ment principles adopted for patients with severe MR, suggest that serial assessments of RV size and function might trigger consideration of cor- rective surgery in selected patients with severe primary TR when a pattern of continued deterio- ration can be established and the surgical risk is In otherwise healthy patients without other comorbidities, such as patients with severe TR attributable to trauma, the surgical risk associated with tricuspid valve operation is low (<1% to 2% operative mortality Figure 10. Tricuspid regurgitation. Colors correspond to Table 2. GDMT indicates guideline-directed management and therapy; HF, heart failure; PAP, pulmonary artery pressure; PH, pulmonary hypertension; RV, right ventricular; TR, tricuspid regurgitation; and TV, tricuspid valve. CLINICAL STATEMENTS AND GUIDELINES rate) in the absence of RV dysfunction or pulmo- nary hypertension. 6. Isolated tricuspid valve surgery for severe TR his- torically has been performed relatively late in the natural history of the disease, when patients have become symptomatic with signs of right-sided HF. Unadjusted mortality rates for isolated tricuspid valve surgery have therefore exceeded those reported for isolated aortic or mitral valve surgery, and this trend has been even more pronounced for reoperative tri- cuspid surgery late after left-sided valve surgery.1,2,39 This high reoperative mortality rate is likely related to the advanced nature of RV failure encountered at the time of the second procedure, residual pulmo- nary hypertension, LV dysfunction, and other valve abnormalities.


Unadjusted mortality rates for isolated tricuspid valve surgery have therefore exceeded those reported for isolated aortic or mitral valve surgery, and this trend has been even more pronounced for reoperative tri- cuspid surgery late after left-sided valve surgery.1,2,39 This high reoperative mortality rate is likely related to the advanced nature of RV failure encountered at the time of the second procedure, residual pulmo- nary hypertension, LV dysfunction, and other valve abnormalities. The hazards imposed by reoperation have influenced decision-making for initial repair of functional TR at the time of left-sided valve surgery in an attempt to prevent the development of severe TR later after the left-sided valve surgery. However, if there is no significant pulmonary hypertension or severe RV systolic dysfunction, operation for severe symptomatic isolated TR years after surgery for left- sided disease may improve symptoms of right-sided HF, if done before the onset of severe RV dysfunc- tion or end-organ damage with either hepatic or 9. PULMONIC VALVE DISEASE See guidelines for the management of adults with con- genital heart disease.1 10. MIXED VALVE DISEASE 10.1. Diagnosis of Mixed VHD Recommendations for Diagnosis and Follow-Up of Patients With Mixed Valve Disease COR LOE Recommendations For patients with mixed valve disease, TTE is recommended to assess the etiology, severity, and pathophysiological impact. In patients with ambiguous symptoms that are suspected to be attributable to mixed mitral valve disease, further assessment of filling pressure by using biomarkers or invasive hemodynamic measurements at rest or with exercise is reasonable. Synopsis Mixed valve disease is either 1) stenosis and regurgita- tion of a single valve or 2) stenosis or regurgitation of 2 separate valves.


Synopsis Mixed valve disease is either 1) stenosis and regurgita- tion of a single valve or 2) stenosis or regurgitation of 2 separate valves. Mixed valve disease presents a special diagnostic challenge to the clinician in assessing the im- pact of the lesions on cardiac remodeling, ventricular function, and timing of intervention.1 5 For many pa- tients with mixed valve disease, there is a predominant valve lesion (ie, stenosis versus regurgitation; mitral versus aortic), and symptoms and pathophysiology re- semble those of a pure dominant lesion. When pres- sure overload predominates, there is usually concentric hypertrophy, whereas volume overloads cause chamber dilation and eccentric hypertrophy; management should follow the guidelines for the predominant lesion. How- ever, in other cases, patients present with a more bal- anced picture, with the mixed pathophysiology making patient management difficult. It may be that neither lesion by itself reaches Stage C as described in previ- ous sections for pure lesions, yet the lesions may be, in combination, severe enough to impact outcome. Mixed valve disease was primarily attributable to rheumatic disease in the past, but it is now more frequently seen with degenerative disease or after prior chest radiation.5 Decision-making for patients with mixed valve disease is frequently complex and may require referral to or con- sultation with a Comprehensive Valve Center. Recommendation-Specific Supportive Text 1. The complex nature of mixed valve disease requires a comprehensive imaging approach that involves assessing each lesion separately and then collectively judging how the lesions affect the patient s overall presentation. TTE is the standard modality for measuring jet velocities, valve areas, regurgitant flow, and regurgitant orifice areas. TTE establishes the baseline for pathoanatomy and pathophysiology from which comparison is made as the lesions progress over time.


TTE establishes the baseline for pathoanatomy and pathophysiology from which comparison is made as the lesions progress over time. Doppler hemodynamics have been validated for patients with single-valve disease but have not necessarily been studied in patients with multivalve disease. Limitations exist for assessment of calculations, such as those for valve areas, because of differen- tial flows with multivalve disease.2 5 2. The complex nature of mixed valve disease makes it necessary to consider all available data to reach a final management decision. Although natural history data for many types of mixed valve disease are lacking, it is reasonable to assume that the onset of symptoms is a neg- ative prognostic occurrence, as it is for all other valve lesions. The difficulty may lie in attribut- ing such symptoms to the mixed valve disease at hand, especially if TTE demonstrates moder- ate but not severe mixed disease. Elevated BNP and elevated filling pressures at catheterization, either at rest or with exercise, support that car- diac disease is the cause of the patient s symp- toms and may help to further quantify lesion severity. CLINICAL STATEMENTS AND GUIDELINES 10.2. Timing of Intervention for Mixed VHD 10.2.1. Intervention for Mixed AS and AR Recommendations for Timing of Intervention for Mixed AS and AR Referenced studies that support the recommendations are summarized in Online Data Supplement 33.


Intervention for Mixed AS and AR Recommendations for Timing of Intervention for Mixed AS and AR Referenced studies that support the recommendations are summarized in Online Data Supplement 33. COR LOE Recommendations In symptomatic patients with combined AS and AR and a peak transvalvular jet velocity of at least 4.0 m/s or a mean transvalvular gradient of at least 40 mmHg, AVR is In asymptomatic patients with combined AS and AR who have a jet velocity of 4.0 m/s with an LVEF <50%, SAVR is recommended.1,2 Synopsis The indications for AVR in patients with combined AS and AR and a peak transvalvular jet velocity of 4.0 m/s are the same as for patients with severe isolated AS. Recommendation-Specific Supportive Text 1. Currently, isolated moderate AS or moderate AR is placed in Stage B, progressive disease for which no therapeutic action is indicated. However, some patients with moderate mixed disease develop symptoms that stem from their valve disease. Formerly, the argument was raised that if there were no AR, the aortic jet velocity and gradient would be correspondingly lower and would not meet the definitions for severe AS, and obvi- ously there would be only moderate AR by defi- nition. Therefore, no action was recommended. However, recent data suggest that the natural his- tory of moderate mixed disease behaves similarly to that of pure severe AS1,2 and that moderate mixed disease has a mortality risk similar to that of pure severe AS. Thus, valve replacement is war- ranted for the symptomatic patient if the patient s data fulfill any of the criteria for severe AS. The decision about whether to proceed with TAVI ver- sus SAVR is discussed in Section 3.2.4.2. 2.


The decision about whether to proceed with TAVI ver- sus SAVR is discussed in Section 3.2.4.2. 2. For patients with mixed moderate AS/AR who have developed LV dysfunction, as evidenced by an LVEF of <50%, and who have no other reason for LV dysfunction, valve disease is presumed to be the cause. In such patients, SAVR is indicated.1,2 10.2.2. Intervention for Mixed AS and MR Patients with combined AS and MR present a dif- ficult and complex decision-making process. There are many potential different scenarios and nuances involved to arrive at the optimal approach for an in- dividual patient, which needs to be made by an MDT with shared decision-making with the patient. Over- all, patients with severe AS and severe primary MR are best treated with SAVR and mitral valve surgery unless the surgical risk is high or prohibitive. If there is a high or prohibitive surgical risk, a staged procedure, with TAVI followed by mitral TEER, can be effective. If there is severe AS and severe secondary MR, either SAVR and mitral valve surgery or a staged approach with TAVI followed by mitral TEER are options. Be- cause there are limited data to support COR, the writ- ing committee has created a table that provides the reader with a perspective on possible interventions in these complex patients (Table 21). Evaluating the short- and long-term outcomes of these approaches will be important. These proposed procedures are based on the following: Many patients with AS also have significant MR that is attributable to either organic (primary) causes or LV remodeling (secondary MR). AVR for AS reduces LV pressure, thereby reducing the pressure gradi- ent that propels volume across the incompetent mitral valve.


AVR for AS reduces LV pressure, thereby reducing the pressure gradi- ent that propels volume across the incompetent mitral valve. Although it is reasonable to expect that AVR would reduce MR by reducing LV systolic pressure, this fails to occur in many cases. Not sur- prisingly, primary MR is more likely to persist after AVR than is secondary MR because AVR does not correct intrinsic mitral valve disease.1 5 Therefore, in patients with both AS and MR who are at a low or intermediate surgical risk, it is reasonable to address both valves with surgery. This is particularly true if the mitral valve can be repaired.1 For patients with both AS and severe primary MR in whom the mitral valve cannot be repaired, a deci- sion about treatment of the MR will need to be made by the MDT, taking into consideration mul- tiple factors, including the additive risk of a mitral valve replacement. Mitral TEER at a later date may be an option but is likely to have a suboptimal result if the valve cannot be surgically repaired. Thus, double valve replacement with both AVR and mitral valve replacement would be an option if they can be performed at an acceptable level of risk, given that the outcome of the MR after AVR is uncertain. Patients with severe AS who are at high to prohibi- tive surgical risk are best served by TAVI.


Patients with severe AS who are at high to prohibi- tive surgical risk are best served by TAVI. As noted previously, primary MR may not improve after If symptoms persist after TAVI and if there is suitable anatomy, percutaneous mitral repair can be performed, which can reduce MR and improve For patients with AS who have secondary MR, the fate of MR after SAVR or TAVI is uncertain.2 5,7 10 Although secondary MR is more likely to improve after AVR than is MR attributable to primary mitral valve disease, secondary MR does not improve or may even worsen after AVR in many cases.7 10 The mechanism by which reduction in LV pressure after CLINICAL STATEMENTS AND GUIDELINES AVR does not reduce secondary MR is unknown. With SAVR, the mitral valve can be inspected and addressed, unlike with TAVI, where the mitral valve is left untreated. An alternative approach to patients with AS and secondary MR is to perform TAVI first, and if symptoms remain with persistent severe MR, mitral TEER can be performed if there is suitable anatomy.6 The transcatheter approach would be preferred if the patient is at high to pro- hibitive surgical risk. 10.2.3. Intervention for Mixed MS and MR Mixed MS and MR often occurs in patients with rheu- matic valve disease. Occasionally, mixed MS/MR can oc- cur in patients with severe mitral annular calcification. Asymptomatic mixed disease may be benign because MS protects the LV from the severe volume overload of pure MR. However, if symptoms attributable to mixed mitral disease occur, they are likely because of increased LA pressure from combined increased LA inflow from MR and obstruction to outflow from the LA.


However, if symptoms attributable to mixed mitral disease occur, they are likely because of increased LA pressure from combined increased LA inflow from MR and obstruction to outflow from the LA. An en- larged LA, a high transmitral gradient, or direct mea- surement of a high LA or pulmonary artery wedge pres- sure suggest a valvular basis for the patient s symptoms. In such cases, mitral valve replacement may be neces- sary if therapy with diuretics do not relieve symptoms, but it should be performed only in patients who have severe limiting symptoms 10.2.4. Intervention for Mixed MS and AR Combined MS and AR usually result from rheumatic heart disease. When they occur concomitantly, MS is usually the more severe lesion. However, because MS limits LV filling, it may reduce the stroke volume pre- sented to the aortic valve, in turn reducing the apparent severity of AR.1,2 Furthermore, MS reduces the LV cav- ity size for any degree of AR, causing further potential underestimation of AR severity. In this regard, contrast aortography visualizes AR flow, instead of the echo- cardiographic visualization of AR velocity of flow, and may be helpful, as is precise assessment of AR regur- gitant fraction. In patients who have continued severe symptoms not responsive to diuretics, intervention with valve surgery should be pursued. If mitral anatomy is favorable, options are PMBC to treat the MS, followed by AVR or SAVR and open mitral commissurotomy. In this way, the increased mortality risk of double valve replacement is avoided.3 10.2.5. Intervention for Mixed MS and AS Almost always the product of rheumatic heart disease, the combination of MS and AS can be very confusing to the clinician.


Intervention for Mixed MS and AS Almost always the product of rheumatic heart disease, the combination of MS and AS can be very confusing to the clinician. When either lesion is severe, it may limit cardiac output, resulting in reduced flow to the other valve, which reduces transvalvular gradient, leading to underestimation of lesion severity. Echocardiography and invasive hemodynamics are usually necessary to fully assess the severity of each lesion and to decide on appropriate intervention. 11. PROSTHETIC VALVES 11.1. Evaluation and Selection of Prosthetic Valves 11.1.1. Diagnosis and Follow-Up of Prosthetic Valves Recommendations for Diagnosis and Follow-Up of Prosthetic Valves Referenced studies that support the recommendations are summarized in Online Data Supplement 34. COR LOE Recommendations In patients with a surgical or transcatheter prosthetic valve and in patients who have had valve repair, an initial postprocedural TTE study is recommended for evaluation of valve hemodynamics and ventricular function.1 4 In patients with a prosthetic valve or prior valve repair and a change in clinical symptoms or signs suggesting valve dysfunction, repeat TTE is recommended. In patients with a prosthetic valve replacement or prior valve repair and clinical symptoms or signs that suggest prosthetic valve dysfunction, additional imaging with TEE, gated cardiac CT, or fluoroscopy is recommended, even if TTE does not show valve dysfunction. In patients with a bioprosthetic surgical valve, TTE at 5 and 10 years and then annually after implantation is reasonable, even in the absence of a change in clinical status. In patients with a bioprosthetic TAVI, TTE annually is reasonable. Table 21.


In patients with a bioprosthetic TAVI, TTE annually is reasonable. Table 21. AS/MR Mixed Valve Disease Severe AS Severe MR Surgical Risk Procedure SAVR candidate Primary MR Repairable valve Low intermediate SAVR Surgical mitral valve repair SAVR candidate Primary MR Valve not repairable Low intermediate SAVR Surgical mitral valve replacement TAVI candidate Primary Repairable valve High prohibitive TAVI Mitral TEER* SAVR candidate TAVI candidate Secondary MR Low intermediate SAVR Surgical mitral valve repair/mitral valve replacement or TAVI Mitral TEER* TAVI candidate Secondary MR High prohibitive TAVI Mitral TEER* *Consider TEER as a later staged procedure if symptoms and severe MR persist after treatment of the AS. AS indicates aortic stenosis; MR, mitral regurgitation; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation; and TEER, transcatheter edge-to-edge repair. CLINICAL STATEMENTS AND GUIDELINES Synopsis The clinical course of patients with prosthetic heart valves or repaired native valves is influenced by several factors, including ventricular function, AF, pulmonary hypertension, and CAD, as well as by the development of valve-related complications. The interval between routine follow-up visits depends on the patient s valve type, the presence of residual heart disease, and other clinical factors. Attention to optimal dental care and en- docarditis prophylaxis and any needed anticoagulation is a requisite component of care. TTE is the primary imaging modality for postopera- tive assessment of prosthetic valve or repaired native valve function. In the absence of early complications, the index study is performed during hospitalization or within the first several weeks thereafter, depending on individual patient circumstances and the type of valve procedure. Additional imaging, such as TEE, cardiac CT, or fluoroscopy, may be required when valve dysfunc- tion is suspected and in the context of the clinical pre- sentation.


Additional imaging, such as TEE, cardiac CT, or fluoroscopy, may be required when valve dysfunc- tion is suspected and in the context of the clinical pre- sentation. A schedule for surveillance TTE studies has become an established feature of long-term follow-up, although the frequency of routine studies that are per- formed in the absence of clinical change will vary as a function of valve type. Recommendation-Specific Supportive Text 1. TTE after valve implantation or repair provides an assessment of the procedural results and serves as a baseline against which comparison can be made for any change. TTE provides accurate mea- surements of transvalvular velocities and pressure gradients, as well as detection and quantitation of transvalvular and paravalvular leak.1 4 Normal transvalvular velocities and gradients vary across different types and sizes of prosthetic valves but are also affected by patient-specific factors, including body size and cardiac output. The postoperative study, recorded when the patient is asymptomatic and in a stable hemodynamic state, provides Doppler flow data for a specific valve in an individual patient. In addition, TTE pro- vides assessment of other valve disease(s), pulmo- nary artery pressure, atrial size, LV and RV size and function, and pericardial disease. 2. Bioprosthetic or repaired native valve dysfunc- tion typically presents with the insidious onset of HF symptoms or a change in the ausculta- tory findings. More abrupt and severe symptoms may occur with infective endocarditis or rupture of a valve cusp. Patients with mechanical valve dysfunction may present with HF, shock, throm- boembolic events, hemolysis, or a change in auscultatory findings. Presentation may often be acute or subacute because of thrombus forma- tion and more abrupt impairment of leaflet open- ing or closure. Attention should be directed to the trend in recent INR determinations.


Attention should be directed to the trend in recent INR determinations. Prosthesis patient mismatch and functional stenosis of a repaired native valve are also to be considered in the evaluation of patients with HF symptoms. Repeat noninvasive assessment begins with trans- thoracic echocardiography, comparison with the index postoperative study when available, and the use of other modalities as dictated by the clinical context and preliminary findings. 3. TTE is the preferred approach for initial assessment of suspected prosthetic valve dysfunction because it allows for measurement of transvalvular velocity, gradient, and valve area. TTE also allows quantita- tion of LV volumes and LVEF, an estimate of pulmo- nary artery systolic pressure, and evaluation of right heart function. However, the LA side of a prosthetic mitral valve is obscured by acoustic shadowing from the TTE approach, resulting in reduced sensi- tivity for detection of prosthetic MR and prosthetic mitral valve thrombus, pannus, or vegetation. TEE provides superior imaging of the LA side of the mitral prosthesis and is accurate for diagnosis of prosthetic mitral valve dysfunction.5,6 Both TTE and TEE are also needed for patients with prosthetic aortic valves in whom the posterior aspect of the valve is shadowed on the TTE approach and the anterior aspect of the valve is shadowed on the TEE has superior sensitivity for the detection of vegetations and abscess formation in patients with suspected prosthetic valve (or annu- loplasty ring) endocarditis. With mechanical valve obstruction, fluoroscopy or CT imaging can also be helpful for detection of reduced motion caused by pannus ingrowth or thrombus. 4.


With mechanical valve obstruction, fluoroscopy or CT imaging can also be helpful for detection of reduced motion caused by pannus ingrowth or thrombus. 4. Studies based on TTE follow-up estimate that approximately 30% of patients with a surgical aortic valve bioprosthesis develop evidence of valve dysfunction over the 10 years after implan- tation (defined as an increase in mean gradient of 10 mmHg or a worsening of transprosthetic regurgitation from mild to moderate or from moderate to severe).9 The incidence of clinically important structural valve deterioration increases markedly more than 10 years after surgery, such that routine annual TTE studies thereafter are rea- Risk factors associated with acceler- ated (<5 years) valve deterioration include young age (<60 years) at implantation, smoking, diabe- tes mellitus, chronic kidney disease, initial mean gradient 15 mmHg, and valve type.9,12 The selec- tive adoption of an earlier, annual TTE screening program may be considered for at-risk patients on an individual basis, as up to 13% of patients CLINICAL STATEMENTS AND GUIDELINES with a surgical aortic valve develop hemodynamic valve dysfunction at a median of 6.7 to 9.9 years Patients typically remain asymptomatic until valve dysfunction is severe enough to result in adverse hemodynamic conse- quences or AF. Depending on the valve type and mechanism of regurgitation, some patients with asymptomatic, significant prosthetic valve regur- gitation may require reintervention. For example, if prosthetic regurgitation is attributable to a bio- prosthetic leaflet tear, more severe acute regur- gitation may occur suddenly and cause clinical decompensation. With prosthetic valve stenosis, TTE diagnosis while the patient is asymptomatic alerts the clinician to the need for more frequent follow-up.


With prosthetic valve stenosis, TTE diagnosis while the patient is asymptomatic alerts the clinician to the need for more frequent follow-up. A standardized definition and grading system for structural valve deterioration for sur- gical and transcatheter aortic valves have been In patients with mechanical valve prostheses, routine annual TTE evaluation is not needed if the postoperative baseline study is nor- mal and no clinical change is apparent. Many of these patients require TTE studies for other indi- cations, however, such as for the assessment of LV function, pulmonary artery pressure, or other cardiac or valve disease. 5. Durability data for bioprosthetic TAVI valves are less robust than the data for surgically implanted bioprosthetic valves. To date, the intermediate- term durability of TAVI valves has compared favorably with that of SAVR valves, as reported in randomized trials and registries.14 21 For the most part, these data reflect observations made in older patients and may not be applicable to younger populations (eg, <70 years). TAVI-based protocols typically include routine TTE before dis- charge and at 30 days and 1 year, in part because of reporting requirements. In the absence of clini- cal change, routine annual TTE studies are reason- able as experience continues to accumulate. 11.1.2. Selection of Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve Recommendations for Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve Referenced studies that support the recommendations are summarized in Online Data Supplement 35. COR LOE Recommendations For patients who require heart valve replacement, the choice of prosthetic valve should be based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indications for and risks of anticoagulant therapy and the potential need for and risks associated with valve reintervention.


COR LOE Recommendations For patients who require heart valve replacement, the choice of prosthetic valve should be based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indications for and risks of anticoagulant therapy and the potential need for and risks associated with valve reintervention. 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 <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.)


(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 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.


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.


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.


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.


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.


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.


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.


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.


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).


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 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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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%.


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.


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.


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.


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.


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.


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.


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.


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.


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.