Stages of Secondary MR Stage Definition Valve Anatomy Valve Hemodynamics* Associated Cardiac Findings Symptoms A At risk of MR Normal valve leaflets, chords, and annulus in a patient with CAD or cardiomyopathy No MR jet or small central jet area <20% LA on Doppler Small vena contracta Normal or mildly dilated LV size with fixed (infarction) or inducible (ischemia) regional wall motion abnormalities Primary myocardial disease with LV dilation and systolic dysfunction Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy B Progressive MR Regional wall motion abnormalities with mild tethering of mitral leaflet Annular dilation with mild loss of central coaptation of the mitral leaflets Regurgitant volume Regurgitant fraction Regional wall motion abnormalities with reduced LV systolic function LV dilation and systolic dysfunction attributable to primary myocardial disease Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy C Asymptomatic severe MR Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet Annular dilation with severe loss of central coaptation of the mitral leaflets Regurgitant volume Regurgitant fraction Regional wall motion abnormalities with reduced LV systolic function LV dilation and systolic dysfunction attributable to primary myocardial disease Symptoms attributable to coronary ischemia or HF may be present that respond to revascularization and appropriate medical therapy D Symptomatic severe MR Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet Annular dilation with severe loss of central coaptation of the mitral leaflets Regurgitant volume Regurgitant fraction Regional wall motion abnormalities with reduced LV systolic function LV dilation and systolic dysfunction attributable to primary myocardial disease HF symptoms attributable to MR persist even after revascularization and optimization of medical therapy Decreased exercise tolerance Exertional dyspnea *Several valve hemodynamic criteria are provided for assessment of MR severity, but not all criteria for each category will be present in each patient. Categorization of MR severity as mild, moderate, or severe depends on data quality and integration of these parameters in conjunction with other clinical evidence. The measurement of the proximal isovelocity surface area by 2D TTE in patients with secondary MR underestimates the true ERO because of the crescentic shape of the proximal convergence. May be lower in low-flow states. 2D indicates 2-dimensional; CAD, coronary artery disease; ERO, effective regurgitant orifice; HF, heart failure; LA, left atrium; LV, left ventricular; MR, mitral regurgitation; and TTE, transthoracic echocardiogram. CLINICAL STATEMENTS AND GUIDELINES Recommendations for Intervention for Secondary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 31. COR LOE Recommendations In patients with chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) who have persistent symptoms (NYHA class II, III, or IV) while on optimal GDMT for HF (Stage D), TEER is reasonable in patients with appropriate anatomy as defined on TEE and with LVEF between 20% and 50%, LVESD 70 mm, and pulmonary artery systolic pressure In patients with severe secondary MR (Stages C and D), mitral valve surgery is reasonable when CABG is undertaken for the treatment of myocardial ischemia.9 15 In patients with chronic severe secondary MR from atrial annular dilation with preserved LV systolic function (LVEF 50%) who have severe persistent symptoms (NYHA class III or IV) despite therapy for HF and therapy for associated AF or other comorbidities (Stage D), mitral valve surgery may be considered.16 20 In patients with chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) who have persistent severe symptoms (NYHA class III or IV) while on optimal GDMT for HF (Stage D), mitral valve surgery may be In patients with CAD and chronic severe secondary MR related to LV systolic dysfunction (LVEF <50%) (Stage D) who are undergoing mitral valve surgery because of severe symptoms (NYHA class III or IV) that persist despite GDMT for HF, chordal-sparing mitral valve replacement may be reasonable to choose over downsized annuloplasty Synopsis Mitral TEER is indicated to improve symptoms and pro- long life in a select subset of patients with chronic se- vere secondary MR, LV systolic dysfunction, and persis- tent severe symptoms while on optimal GDMT. Surgery may improve symptoms in these patients, with mitral valve replacement preferred over repair. A subset of pa- tients with severe MR attributable to AF may benefit from mitral valve surgery and concomitant atrial maze procedure (Figure 9). Recommendation-Specific Supportive Text 1. The COAPT trial of transcatheter treatment of secondary MR demonstrated improvement in sur- vival, hospitalization, symptoms, and quality of life in patients with persistent symptoms despite optimization of GDMT who were randomized to TEER, as compared with those randomized to con- tinued GDMT. In contrast, MITRA-FR (Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) enrolled patients with greater degrees of LV enlargement and less severe MR (mean ERO area 0.31 cm2 ) and reported no benefit of TEER in reducing the composite endpoint of death or hospitalization as compared with medical therapy. In addition, the inclusion criterion in MITRA-FR of an LVESD up to 70 mm represents extreme dilation; in contrast, in the COAPT trial, the mean LVESD was smaller (52 9 mm), and even the LVEDD rarely exceeded 70 mm (mean 62 7 mm). Thus, the enrollment criteria in COAPT trial (LVEF between 20% and 50%, LVESD 70 mm, pulmonary artery systolic pressure 70 mmHg, and persistent symptoms [NYHA class II, III, or IV] while on optimal GDMT) are the current standard selection criteria for TEER for secondary MR. Observational studies have suggested that a greater reduction in MR sever- ity with TEER is associated with greater LV and LA reverse remodeling.1 8,48,49 The exact anatomy and mechanism of MR also needs to be taken into consideration when determining candidacy for transcatheter repair. 2. There is no proof that surgical correction of chronic secondary MR is effective in prolonging life, but observational studies and a substudy of the randomized STICH trial suggest that it is wise to address the mitral valve during CABG for severe CAD when secondary MR is severe. Although it may be hoped that the revascular- ization will recruit hibernating myocardium and reduce chronic secondary MR, this has not been demonstrated, and failing to correct chronic severe secondary MR may leave the patient with severe residual MR. The risks and benefits of additional surgical interventions should be weighed in patients with LV systolic dysfunc- For patients with secondary MR under- going operation for other valve disease, see Section 10.2 (Timing of Intervention for Mixed Valve Disease). 3. MR may develop in patients with preserved LV systolic function who have progressive LA dila- tion, leading to enlargement of the mitral annu- lus and malcoaptation of the leaflets.51,52 This may arise in conditions such as HF with preserved LVEF, restrictive cardiomyopathy, and nonobstruc- tive hypertrophic cardiomyopathy. These patients often have associated AF, which may contribute to the progression of LA and annular dilation, thus increasing the severity of MR,18,53 and suc- cessful ablation of AF may reduce or eliminate Isolated annular dilation accounts for <20% of patients referred for surgery of severe MR in the STS database, but it is also the etiology with CLINICAL STATEMENTS AND GUIDELINES the highest mitral valve repair rates (85%).16,17 The limited data addressing mitral valve repair in patients with annular dilation related to AF indi- cate low operative risk.18 20 4. There is limited evidence that mitral valve sur- gery improves survival in symptomatic patients with secondary MR. In addition, surgery may improve symptoms and quality of life in these patients whose symptoms persist despite GDMT. Small RCTs demonstrate that mitral valve surgery reduces chamber size and improves peak oxygen consumption in chronic severe secondary MR. Ischemic or dilated cardiomyopathy presents dif- ferent challenges for mitral repair. Regurgitation is caused by annular dilation, as well as by apical and lateral displacement of the papillary muscles. New techniques have facilitated mitral repair in this situation, but durability of the repair is dependent primarily on regression or progression of ventricular dilation. If the heart continues to dilate, long-term durability of the repair is moot; the survival of the patient is limited.9,12,21 43 5. In an RCT of mitral valve repair versus mitral valve replacement in patients with severe isch- emic MR, there was no difference between repair and mitral valve replacement in survival rate or LV remodeling at 2 years. However, the rate of recurrence of moderate or severe MR over 2 years was higher in the repair group than in the replacement group, leading to a higher incidence of HF and repeat hospitalization. The lack of apparent benefit of valve repair over valve replacement in secondary MR versus pri- mary MR, with less durable repairs in secondary MR, highlights that primary and secondary MR Figure 9. Secondary MR. Colors correspond to Table 2. *Chordal-sparing MV replacement may be reasonable to choose over downsized annuloplasty repair. AF indicates atrial fibrillation; CABG, coronary artery bypass graft; ERO, effective regurgitant orifice; GDMT, guideline-directed management and therapy; HF, heart failure; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; MR, mitral regurgitation; MV, mitral valve; PASP, pulmonary artery systolic pressure; RF, regurgitant fraction; RVol, regurgitant volume; and Rx, medication. CLINICAL STATEMENTS AND GUIDELINES 8. TRICUSPID VALVE DISEASE 8.1. Classification and Stages of TR Trace to mild degrees of TR of no physiological con- sequence are commonly detected on TTE in subjects with anatomically normal valves. However, significant or worsening TR is associated with poor long-term Primary disorders of the tricuspid appa- ratus that can lead to more significant degrees of TR include rheumatic disease, IE, congenital disease (Eb- stein s), myxomatous changes, and other problems af- fecting the tricuspid valve leaflets (blunt chest trauma, carcinoid, drugs, and radiation) (Table 19). A growing number of patients develop significant TR from iatro- genic etiologies (device leads and endomyocardial biop- Most cases of significant TR are secondary and related to tricuspid annular dilation and leaflet tether- ing in the setting of RV remodeling because of pressure or volume overload, as seen in patients with pulmo- nary hypertension (primary or secondary to left-sided heart disease) or dilated cardiomyopathies.11 13 In addi- tion, there appears to be a subgroup of patients with significant isolated TR attributable primarily to annular dilation, usually associated with AF in the absence of pulmonary hypertension or LV systolic dysfunction.2,14 18 Table 20 shows the stages of TR as defined for other valve lesions. Asymptomatic patients with severe TR (Stage C) present with an elevated central venous pres- sure and imaging evidence of significant TR. Symptomatic patients with severe TR (Stage D) have symptoms of fatigue, abdominal bloating, and periph- eral edema. End-organ damage, such as hepatic failure and renal failure, is an adverse consequence of Stage D TR that markedly affects survival.19 23 The severity of TR can be dynamic and dependent on changes in preload and pulmonary pressure. 8.2. Tricuspid Regurgitation 8.2.1. Diagnosis of TR Recommendations for Diagnosis of TR COR LOE Recommendations In patients with TR, TTE is indicated to evaluate the presence and severity of TR, determine the etiology, measure the sizes of the right- sided chambers and inferior vena cava, assess RV systolic function, estimate pulmonary artery systolic pressure, and characterize any associated left-sided heart disease.1,2 In patients with TR, invasive measurement of the cardiac index, right-sided diastolic pressures, pulmonary artery pressures, and pulmonary vascular resistance, as well as right ventriculography, can be useful when clinical and noninvasive data are discordant or Synopsis TTE can determine the etiology of TR and its effect on the RV. Cardiac catheterization is of clinical value if the information from TTE is inadequate or discordant with the clinical presentation.6 10 Recommendation-Specific Supportive Text 1. TTE can distinguish primary TR (abnormal valve leaflets) from secondary TR (normal valve leaf- lets), define any associated left-sided valvular or myocardial disease, and provide an estimate of pulmonary artery systolic pressure.11 15 Characterization of the severity of TR relies on an integrative assessment of multiple param- eters, as recommended by the American Society of Echocardiography and European Association but many limitations remain. In patients with TR undergoing left- sided valve surgery, an annular diastolic diameter ) indicates an increased risk of persistent or progressive TR after isolated mitral valve surgery.13 Pulmonary artery systolic pressure is estimated from maximal TR velocity. Assessment of RV systolic function is challenged by geometric and image acquisition constraints, as well as by variability in RV loading condi- Normal RV systolic function is defined by several parameters, including tricuspid annu- lar plane systolic excursion >16 mm, tricuspid valve systolic annular velocity >10.0 cm/s, and RV end-systolic area <20.0 cm2 or fractional area change >35%. Other imaging modalities, such as 3D TEE, magnetic resonance imaging, and CT scan, may provide more accurate information on the status of the RV. 2. When physical examination and TTE data on estimated pulmonary artery systolic pressure are either discordant or inadequate, invasive mea- surement of pulmonary artery pressures and pul- monary vascular resistance can be helpful to guide Table 19. Classification of TR Primary Secondary Rheumatic Infective endocarditis Iatrogenic (device leads, endomyocardial biopsy) Congenital (eg, Ebstein s, levo- transposition of the great arteries) Other (eg, trauma, carcinoid, drugs, irradiation) Pulmonary hypertension with RV remodeling (primary or secondary to left-sided heart disease) Dilated cardiomyopathy Annular dilation (associated with AF)* RV volume overload (shunts/high output) *Isolated TR is associated with AF and has LVEF >60%, pulmonary artery systolic pressure <50 mm Hg, and no left-sided valve disease, with normal- appearing tricuspid valve leaflets. AF indicates atrial fibrillation; LVEF, left ventricular ejection fraction; RV, right ventricular; and TR, tricuspid regurgitation. CLINICAL STATEMENTS AND GUIDELINES clinical decision-making in individual patients.3 5 A weak TR signal or the presence of severe TR may result in underestimation of pulmonary systolic pressure; direct invasive measurement can resolve this uncertainty. Data from invasive measurement are essential for patients in whom the cause of pulmonary hypertension is uncertain or when assessment of pulmonary vascular reactivity after vasodilator challenge is needed. Direct measure- ments of right atrial pressure may also be useful for clinical decision-making. Right ventriculogra- phy may further aid in the evaluation of the sever- ity of TR and the status of the RV. Thermodilution cardiac output measurements may be inaccurate with severe TR, and thus a Fick cardiac output should be measured to apply to the calculation of pulmonary resistance. 8.2.2. Medical Therapy Recommendations for Medical Therapy for TR COR LOE Recommendations In patients with signs and symptoms of right-sided HF attributable to severe TR (Stages C and D), diuretics can be useful. In patients with signs and symptoms of right-sided HF attributable to severe secondary TR (Stages C and D), therapies to treat the primary cause of HF (eg, pulmonary vasodilators to reduce elevated pulmonary artery pressures, GDMT for HF with reduced LVEF, or rhythm control of AF) can be Synopsis Diuretic therapy treats the systemic congestion in pa- tients with severe symptomatic TR. In patients with sec- ondary TR, treatment of the underlying primary cause may decrease the severity of the TR. Recommendation-Specific Supportive Text 1. Patients with severe TR usually present with signs or symptoms of right-sided HF, including periph- eral edema and ascites. Low-salt diet and support stockings may be helpful. Diuretics can be used to decrease volume overload in these patients. Loop diuretics are typically provided and may relieve systemic congestion, but their use can be limited by worsening low-flow syndrome. Aldosterone antagonists may be of additive benefit, especially in the setting of hepatic congestion, which may promote secondary hyperaldosteronism. 2. Medical therapies for management of severe TR (Stages C and D) are limited. Attention should be focused on the underlying etiologies in patients with secondary TR. Reduction of pul- monary artery pressures and pulmonary vascular resistance with specific pulmonary vasomodula- tors may be helpful to reduce RV afterload and secondary TR in selected patients with pulmo- GDMT is effective for sec- ondary TR attributable to HF with reduced LVEF. Restoration of normal sinus rhythm may be effective for secondary TR attributable to annu- lar dilation associated with AF.3,4 Table 20. Stages of TR Stage Definition Valve Hemodynamics Hemodynamic Consequences Clinical Symptoms and Presentation B Progressive TR Central jet <50% RA Vena contracta width <0.7 cm Regurgitant volume <45 mL None None C Asymptomatic severe TR Central jet 50% RA Vena contracta width 0.7 cm Regurgitant volume 45 mL Dense continuous wave signal with triangular shape Hepatic vein systolic flow reversal Dilated RV and RA Elevated RA with c-V wave Elevated venous pressure No symptoms D Symptomatic severe TR Central jet 50% RA Vena contracta width 0.7 cm Regurgitant volume 45 mL Dense continuous wave signal with triangular shape Hepatic vein systolic flow reversal Dilated RV and RA Elevated RA with c-V wave Elevated venous pressure Dyspnea on exertion, fatigue, ascites, edema c-V wave indicates systolic positive wave; ERO, effective regurgitant orifice; RA, right atrial; RV, right ventricular; and TR, tricuspid regurgitation. CLINICAL STATEMENTS AND GUIDELINES 8.2.3. Timing of Intervention Recommendations for Timing of Intervention Referenced studies that support the recommendations are summarized in Online Data Supplement 32. COR LOE Recommendations In patients with severe TR (Stages C and D) undergoing left-sided valve surgery, tricuspid valve surgery is recommended.1 8 In patients with progressive TR (Stage B) undergoing left-sided valve surgery, tricuspid valve surgery can be beneficial in the context of either 1) tricuspid annular dilation (tricuspid annulus end diastolic diameter >4.0 cm) or 2) prior signs and symptoms of right-sided HF.3 10 In patients with signs and symptoms of right-sided HF and severe primary TR (Stage D), isolated tricuspid valve surgery can be beneficial to reduce symptoms and recurrent In patients with signs and symptoms of right- sided HF and severe isolated secondary TR attributable to annular dilation (in the absence of pulmonary hypertension or left-sided disease) who are poorly responsive to medical therapy (Stage D), isolated tricuspid valve surgery can be beneficial to reduce symptoms and recurrent hospitalizations.11,12,15 19 In asymptomatic patients with severe primary TR (Stage C) and progressive RV dilation or systolic dysfunction, isolated tricuspid valve surgery may be considered.12,20 In patients with signs and symptoms of right- sided HF and severe TR (Stage D) who have undergone previous left-sided valve surgery, reoperation with isolated tricuspid valve surgery may be considered in the absence of severe pulmonary hypertension or severe RV Synopsis Treatment of secondary TR is targeted at pulmonary hypertension or myocardial disease. Surgical treatment is performed for selected patients with TR at the time of surgery for left-sided valve lesions to treat severe TR (Stages C and D) and to prevent later development of severe TR in patients with progressive TR (Stage B). Surgical intervention should be considered for selected patients with isolated TR (either primary TR or second- ary TR attributable to annular dilation in the absence of pulmonary hypertension or dilated cardiomyopathy). Intervention for severe isolated TR had a high reported operative mortality rate (up to 8% to 20%), but most of these interventions were performed after end-organ However, outcomes of patients with severe primary TR are poor with medical management. There is renewed interest in earlier surgery for patients with se- vere isolated TR before the onset of severe RV dysfunc- tion or end-organ damage.2,11,12,18,19,22 This interest is attributable to 1) an increasing number of patients pre- senting with right-sided HF from isolated TR,23 25 advanced surgical techniques, and 3) better selection processes, resulting in a lower operative risk with docu- mented improvement in symptoms (Figure 10).11,12,15 19 There is growing interest in the development of cath- eter-based therapies for these patients with severe iso- Recommendation-Specific Supportive Text 1. Severe TR of either a primary or secondary etiol- ogy may not improve predictably after treatment of the left-sided valve lesion and reduction of RV afterload; as such, severe TR should be addressed as part of the index procedure.1,2,28 31 Reoperation for severe, isolated TR after left-sided valve surgery is associated with a perioperative mortality rate of Tricuspid valve repair does not add appreciably to the risks of surgery.1,2,28 31 There has been a significant increase in the number of tricuspid valve repairs performed for this indica- tion over the past decade. Tricuspid valve repair is preferable to replacement, but replacement may be necessary if there is marked dilation of the annulus or intrinsic disease of the tricuspid leaf- Observational data have shown a lower operative risk with tricuspid valve repair than with replacement, but this may be related to patient selection, given that the latter would be inserted in patients with a severely dilated annulus and abnormal leaflets to prevent recurrent or residual regurgitation. The risks and benefits of tricuspid valve operation should be carefully considered in the presence of severe RV systolic dysfunction or irreversible pulmonary hypertension because of the possibility of RV failure after operation. 2. Left uncorrected at the time of left-sided valve surgery, mild or moderate degrees of second- ary TR may progress over time in approximately 25% of patients and result in reduced long-term functional outcome and survival.32 Risk factors for persistence or progression of TR include tricuspid annulus dilation (>40 mm diameter or 21 mm/m2 diameter indexed to body surface area on pre- operative TTE measured at end diastole; >70 mm diameter on direct intraoperative measure- ment of the intercomissural distance), degree of RV dysfunction or remodeling, leaflet tether- ing height, pulmonary artery hypertension, AF, and intra-annular RV pacemaker or implantable Several observational studies and one prospective RCT have demonstrated the benefit of tricuspid repair at the time of mitral valve surgery for progres- sive TR (Stage B) with tricuspid annulus dilation on echocardiographic and functional parameters, although data on outcomes such as survival and major adverse events are lacking.3 10,33 35 Because CLINICAL STATEMENTS AND GUIDELINES the severity of TR may be dynamic, dependent on the preload and pulmonary pressures, a past his- tory of signs or symptoms of right-sided HF indi- cates the propensity to develop more severe TR and should be considered an indication for con- comitant tricuspid valve repair. 3. In patients with symptomatic severe primary TR, reduction or elimination of the regurgitant vol- ume load by tricuspid valve surgery can allevi- ate systemic venous and hepatic congestion and decrease reliance on diuretics.11,12,20 Patients with severe congestive hepatopathy may also benefit from surgery to prevent irreversible cirrhosis of the liver. Quality and duration of long-term survival are related to residual RV function. In patients with severe symptomatic primary TR from either device leads or endomyocardial biopsy, TR develops rap- idly, and surgery can be done before the onset of Correction of symptomatic severe primary TR (Stage D) in patients without left-sided valve disease would preferentially be per- formed before the onset of significant RV dysfunc- tion or end-organ damage. Randomized studies of early intervention are lacking, and the benefit might be limited by the risk of intervention, subop- timal reduction in TR severity, or suboptimal dura- bility of currently available approaches to tricuspid valve repair and replacement. 4. There is now recognition that TR can develop in association with AF and annular dilation (a form of Notably, AF-related TR appears to represent a fundamentally different pathophysiol- ogy from other forms of secondary TR, with greater basal dilation and annular enlargement, as com- pared with the RV elongation with leaflet tethering seen in patients who have secondary TR caused by pulmonary hypertension or myocardial disease.24 These patients with AF-related TR have rapid pro- gression of TR severity and right-sided chamber dila- tion. In appropriately selected symptomatic patients with AF-related severe TR, quality of life and symp- toms can be improved by surgical intervention for TR. In patients undergoing intervention, overall outcomes are better in those without severe RV dysfunction or end-organ damage. Newer surgical techniques and a better selection process resulted in an acceptable operative mortality rate (<4% to 5%) for isolated TR in selected patients.2,11,12,15 19,22,38 5. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. For patients of any age requiring valve replacement for whom anticoagulant therapy is contraindicated, cannot be managed appropriately, or is not desired, a bioprosthetic valve is recommended. For patients <50 years of age who do not have a contraindication to anticoagulation and require AVR, it is reasonable to choose a mechanical aortic prosthesis over a For patients 50 to 65 years of age who require AVR and who do not have a contraindication to anticoagulation, it is reasonable to individualize the choice of either a mechanical or bioprosthetic AVR, with consideration of individual patient factors and after informed In patients >65 years of age who require AVR, it is reasonable to choose a bioprosthesis over a mechanical valve.1 For patients <65 years of age who have an indication for mitral valve replacement, do not have a contraindication to anticoagulation, and are unable to undergo mitral valve repair, it is reasonable to choose a mechanical mitral prosthesis over a bioprosthetic valve.1,7,10,11 7. For patients 65 years of age who require mitral valve replacement and are unable to undergo mitral valve repair, it is reasonable to choose a bioprosthesis over a mechanical In patients <50 years of age who prefer a bioprosthetic AVR and have appropriate anatomy, replacement of the aortic valve by a pulmonic autograft (the Ross procedure) may be considered at a Comprehensive Valve Synopsis Shared decision-making about the choice of prosthetic valve type is influenced by several factors, including pa- tient age, values, and preferences; expected bioprosthetic valve durability, avoidance of patient prosthesis mis- match, and the potential need for and timing of reinter- vention; and the risks associated with long-term VKA an- ticoagulation after a mechanical valve replacement. (See also Section 3.2.4 regarding valve choice in patients with AS.) Despite the significantly higher rate of bioprosthetic structural valve deterioration observed in younger versus many younger patients choose to avoid a mechanical prosthesis because they are unwilling to consider long-term VKA therapy because of the incon- venience of monitoring, dietary restrictions, medication interactions, and the need to restrict participation in some types of athletic activity. A mechanical valve might be a prudent choice for patients for whom a second surgical procedure would be very high risk (eg, those with prior radiation exposure). The availability of TAVI has changed Recommendations for Prosthetic Valve Type: Bioprosthetic Versus Mechanical Valve (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES the dynamics of the discussion of the trade-offs between mechanical and bioprosthetic valves in younger patients Recommendation-Specific Supportive Text 1. The choice of valve prosthesis in each patient is based on consideration of several factors, includ- ing valve durability, expected hemodynamics for valve type and size, surgical or interventional risk, the potential need for long-term anticoagulation, and patient values and preferences. The trade-off between the risk of reintervention for biopros- thetic valve deterioration and the risk of long- term anticoagulation should be discussed. Some patients prefer to avoid repeat surgery and are willing to accept the risks and inconvenience of lifelong anticoagulant therapy. Other patients are unwilling to consider long-term anticoagulation because of the inconvenience of monitoring, the attendant dietary and medication interactions, and the need to restrict participation in some types of physical activity. The incidence of struc- tural deterioration of a bioprosthesis is greater in younger patients, but the risk of bleeding from anticoagulation is higher in older patients. In patients with shortened longevity or multiple comorbidities, a bioprosthesis might be more appropriate. In women who desire subsequent pregnancy, the issue of anticoagulation during pregnancy is an additional consideration (see pregnancy-related issues in Section 13.5).20,21 2. Anticoagulant therapy with VKA is necessary in all patients with a mechanical valve to prevent valve thrombosis and thromboembolic events. If anti- coagulation is contraindicated or if the patient refuses VKA therapy, an alternative valve choice is appropriate. Newer anticoagulant agents have not been shown to be safe or effective in patients with mechanical heart valves. 3. Patients <50 years of age at the time of AVR incur a higher and earlier risk of bioprosthetic Overall, the predicted 15-year risk of needing reoperation because of structural deterioration is 22% for patients 50 years of age, 30% for patients 40 years of age, and 50% for patients 20 years of age, although it is recognized that all bioprostheses are not alike in terms of durability.11 Anticoagulation with a VKA can be accomplished with acceptable risk in most patients <50 years of age, particularly in compliant patients with appropriate monitoring of INR levels. Thus, the balance between valve durability and risk of bleeding and thromboembolic events favors the choice of a mechanical valve in patients <50 years of age, unless anticoagulation is not desired, cannot be monitored, or is contraindicated. 4. Uncertainty and debate continue about which type of AVR is appropriate for patients 50 to 65 years of age. Newer surgical bioprosthetic valves may show greater freedom from struc- tural deterioration, specifically in the older indi- vidual, although a high late mortality rate in these studies may preclude recognition of valve dys- The risks of bleeding and throm- boembolism with mechanical prostheses are low, especially in compliant patients with appropriate INR monitoring. Several studies have shown a sur- vival advantage with a mechanical prosthesis in this age group. Alternatively, large retrospective observational studies have shown similar long- term survival rates in patients 50 to 69 years of age undergoing mechanical versus bioprosthetic In general, patients with mechanical valves experience a higher risk of bleeding because of anticoagulation, whereas individuals who receive bioprosthetic valves expe- rience a higher rate of reoperation attributable to structural deterioration of the prosthesis, as well as perhaps a decrease in survival rate.6,25 27 Several other factors should be considered in the choice of type of valve prosthesis (see Section 11.1). Ultimately, the choice of mechanical versus Table 22. Selected Factors That May Impact Shared Decision-Making for the Choice of Prosthetic Valve Favor Mechanical Prosthesis Favor Bioprosthesis Age <50 y Increased incidence of structural deterioration with bioprosthesis 50% for age 20 y) Lower risk of anticoagulation complications Age >65 y Low incidence of structural for age >70 y) Higher risk of anticoagulation complications Patient preference (avoid risk of reintervention) Patient preference (avoid risk and inconvenience of anticoagulation) Low risk of long-term anticoagulation High risk of long-term anticoagulation Compliant patient with either home monitoring or close access to INR monitoring Limited access to medical care or inability to regulate VKA Other indication for long-term anticoagulation (eg, AF) Access to surgical centers with low reoperation mortality rate High-risk reintervention (eg, porcelain aorta, prior radiation therapy) Access to transcatheter ViV replacement Small aortic root size for AVR (may preclude ViV procedure in future) TAVI valves have larger effective orifice areas for smaller valve sizes (avoid patient prosthesis mismatch) AF indicates atrial fibrillation; AVR, aortic valve replacement; INR, international normalized ratio; TAVI, transcatheter aortic valve implantation; ViV, valve-in-valve; and VKA, vitamin K antagonist. CLINICAL STATEMENTS AND GUIDELINES bioprosthetic valve replacement for all patients, but especially for those between 50 and 65 years of age, should be made in a shared decision-mak- ing process that must account for the trade-offs between durability (and the need for reinterven- tion), bleeding, and thromboembolism.1 5. In patients >65 years of age at the time of bio- prosthetic AVR, the likelihood of primary struc- tural deterioration at 15 to 20 years is only about In addition, older patients are at higher risk of bleeding complications related to VKA ther- apy and more often require interruption of VKA therapy for noncardiac surgical and interventional procedures. It is reasonable to use a bioprosthetic valve in patients >65 years of age to avoid the risks of anticoagulation because the durability of the valve exceeds the expected years of life. 6. In general, patients with mechanical valve replace- ment experience a higher risk of bleeding because of anticoagulation, whereas individuals who receive a bioprosthetic valve replacement incur a higher risk of repeat intervention attributable to structural valve deterioration. In patients <65 years of age, observational data suggest better long-term outcomes with a mechanical mitral valve replace- ment, even when the risks and inconvenience of long-term VKA anticoagulation are considered. In a propensity-matched analysis from New York s Statewide Planning and Research Cooperative System (SPARCS), although there was no survival difference for patients 50 to 69 years of age under- going mechanical versus bioprosthetic mitral valve the rates of reoperation were lower (HR: 0.59) with a mechanical valve, though stroke risk (HR: 1.62) was higher. In the 2017 report from the California Office of Statewide Health Planning for patients who underwent mitral-valve replacement and were 40 to 69 years of age, receipt of a biological prosthesis was associ- ated with a mortality rate significantly higher than that seen with receipt of a mechanical prosthesis.1 The choice of a mechanical mitral valve in patients <65 years of age who are good candidates for anticoagulation should account for these observa- tional, nonrandomized data and abide by the prin- ciples of shared decision-making.1,7,10 7. Hazards associated with anticoagulation increase with age, and rates of structural valve deterioration decline significantly. In patients >65 years of age, the ratio of valve durability to life expectancy supports the use of a bio- prosthetic mitral valve replacement, which allows avoidance of the risks of long-term VKA anticoagulation in these older patients. In 1 Figure 11. Prosthetic valves: choice of biopros- thetic versus mechanical valve type. Colors correspond to Table 2. *Approximate ages, based on US Actuarial Life Expectancy tables, are provided for guidance. The balance between expected patient longevity and valve durability var- ies continuously across the age range, with more durable valves preferred for patients with a longer life expectancy. Bioprosthetic valve durability is finite (with shorter durability for younger patients), whereas mechanical valves are very durable but require lifelong anticoagulation. Long-term (20-y) data on outcomes with surgical bioprosthetic valves are available; robust data on transcatheter bioprosthetic valves extend to only 5 y, leading to uncertainty about longer-term outcomes. The deci- sion about valve type should be individualized on the basis of patient-specific factors that might af- fect expected longevity. See Section 3.2.4.2 for a discussion of the choice of TAVI versus SAVR. AVR indicates aortic valve replacement; CVC, Compre- hensive Valve Center; VKA, vitamin K antagonist; SAVR, surgical aortic valve replacement; and TAVI, transcatheter aortic valve implantation. CLINICAL STATEMENTS AND GUIDELINES observational study, the expected durability of a bioprosthetic mitral valve replacement was 11.4 years in patients <60 years of age, 16.6 years in those 60 to 70 years of age, and 19.4 years in those >70 years of age.11 In the 2017 report from the California Office of Statewide Health Planning and Development,1 overall survival rates were similar for patients 70 to 79 years of age who underwent mechanical versus biopros- thetic mitral valve replacement, and bleeding risk was lower with a bioprosthetic valve.1 8. Replacement of the aortic valve with a pulmo- nary autograft (the Ross procedure) is a complex operation involving replacement of the aortic valve by the patient s own pulmonic valve, along with placement of a pulmonic valve homograft. The Ross procedure allows the patient to avoid a prosthetic heart valve and the risks of antico- agulation, and it provides excellent valve hemody- namics. However, both the pulmonic homograft in the pulmonic position and the pulmonary autograft (the neoaortic valve) are at risk of valve degeneration. The failure of the Ross procedure is most often attributable to regurgitation of the neoaortic valve in the second decade after the operation. In addition, at least half of pulmonic homograft valves require reintervention within 10 to 20 years. Calcification of the homograft and adhesions between the homograft and neoaorta may increase the difficulty of reoperation. The Ross procedure typically is reserved for younger patients with appropriate anatomy and tissue characteristics in whom anticoagulation is either contraindicated or undesirable, and it is per- formed only at Comprehensive Valve Centers by surgeons experienced in this procedure.12 14,32 11.2. Antithrombotic Therapy Recommendations for Antithrombotic Therapy for Prosthetic Valves Referenced studies that support the recommendations are summarized in Online Data Supplement 36. 