Mitral valve surgery is an established therapy for rheumatic MS, with the preferred approach being commissurotomy (either closed, where the valve is opened blindly through the LA or LV, or open, which allows more extensive surgery under direct visual- ization) when anatomy is favorable.31 36 However, in the presence of severe valvular thickening and subvalvular fibrosis with leaflet tethering, mitral valve replacement may be the best option. In addi- tion to those who have suboptimal valve anatomy (or failed PMBC), patients with moderate or severe TR may also have a better outcome with a surgi- cal approach that includes tricuspid valve repair.37 Patients undergoing surgical commissurotomy at centers with a high level of expertise may have better long-term outcomes than those undergoing Because the natural history of rheumatic MS is one of slow progression over decades, sur- gery should be delayed until the patient has severe limiting symptoms (NYHA class III or IV), particu- larly if mitral valve repair is contemplated. asymptomatic will do well for years without inter- vention, an elevation of pulmonary artery pressure is an indication that there is progressive elevation of LA pressure affecting the pulmonary circulation. An elevated pulmonary pressure can be assessed by Doppler echocardiography. Although there may be a decrease in pulmonary pressure after relief of the rheumatic MS,38 some patients will have developed intrinsic pulmonary vascular disease, as evidenced by a poorer long-term survival rate in patients who have pulmonary hypertension before Figure 7. Intervention for MS. Colors correspond to Table 2. *Repair, commis- surotomy, or valve replacement. AF indicates atrial fibrillation; CVC, Comprehensive Valve Center; MR, mitral regurgitation; MS, mitral stenosis; MV, mitral valve; MVA, mitral valve area; NYHA, New York Heart Association; PASP, pulmonary artery systolic pressure; and PMBC, percutaneous mitral balloon commissurotomy. CLINICAL STATEMENTS AND GUIDELINES An elevated pulmonary arterial resistance before intervention is associated with RV dysfunction and TR after the procedure.40 42 Thus, PMBC may prevent the adverse consequences of irreversible pulmonary hypertension if it can be performed with a high success rate and low risk in patients who are developing pulmonary hyper- tension. Correction of the MR before irreversible changes occur can be curative. Thus, in chronic primary MR, MR is the disease. 4. The new onset of AF may be an indication for pro- ceeding with PMBC in the asymptomatic patient with a favorable valve morphology for several rea- sons. First, AF may be the equivalent of symptom onset, signifying that rheumatic MS is resulting in progressive LA damage. Second, AF increases the risk of thromboembolic events in patients with rheumatic MS. In addition, a shortened diastolic filling interval with AF and a rapid ventricular response further increase LV pressure. Finally, the presence of AF is associated with worse outcomes in patients with rheumatic MS and with subop- timal results after PMBC.43 In theory, lowering a high LA pressure after PMBC might be beneficial in restoring normal sinus rhythm. Although there is no randomized trial to prove the effectiveness of intervening early, there is a documented improve- ment in P-wave dispersion after PMBC, which may affect the ability to restore normal sinus rhythm.15 5. Some patients have symptoms from rheumatic MS even with a mitral valve area >1.5 cm2 and a resting mean transmitral gradient <10 mmHg. This may be related to the variability and reliability of measuring a mitral valve area by either planim- etering a short-axis image of the mitral valve or using a diastolic half-time for indirect calculation of the mitral valve area. There are also patients who have a relatively low gradient at rest who generate a much higher gradient with exercise, with symptoms developing from the higher LA pressure. Thus, in these patients in whom there is a discrepancy between the clinical symptoms and the resting hemodynamics, exercise testing with measurement of the mean transmitral gradient or the direct pulmonary artery wedge, or both, is Patients who increase their gradients to >15 mmHg with exercise have been shown to improve symptomatically after PMBC.16 6. Both anatomic valve morphology and the pres- ence of commissural calcification predict suc- cessful PMBC. However, in all such series, this predictive ability is not absolute, with 42% of patients with an anatomic valve Wilkins morphol- ogy score >822,23,31,32 having an optimal outcome (25% increase in mitral valve area to >1.5 cm2 ) and 38% of patients with commissural calcium having event-free survival at 1.8 years.18,19,22,23 Accordingly, severely symptomatic patients who are poor surgi- cal candidates may benefit from PMBC even with suboptimal valve anatomy.17 Patients who refuse surgery may also be offered PMBC after discussion about the potential complications associated with this procedure when it is performed in patients with suboptimal valve anatomy. 6.3. Nonrheumatic Calcific MS Recommendation for Nonrheumatic Calcific MS COR LOE Recommendation In severely symptomatic patients (NYHA class III or IV) with severe MS (mitral valve area 1.5 , Stage D) attributable to extensive mitral annular calcification, valve intervention may be considered only after discussion of the high procedural risk and the individual patient s preferences and values.1 3 Synopsis Although most MS in the world results from rheumatic heart disease, calcific MS is found with increasing fre- quency in the elderly population in high-income coun- Calcific MS is the result of calcification of the mitral annulus that extends into the leaflet bases, result- ing both in narrowing of the annulus and rigidity of the leaflets. In contrast to rheumatic MS, there is no commis- sural fusion, and the leaflet tips are usually unaffected. The progression of calcific MS is variable, ranging from an increase of <1.0 to up to 9 mmHg per year.9,11 The prognosis of this group of patients is poor, with a 5-year survival rate <50%, most likely because of advanced age and other comorbidities.4 Determination of the severity of stenosis is difficult because of extensive calcification, which prevents measurement of an accurate planime- tered area, and the significant abnormalities of LA and LV compliance, which cause a high gradient in the absence of severe obstruction.12 16 These patients are at high risk with any intervention because of the extensive calcifica- tion, as well as advanced age and multiple comorbidi- ties. Thus, in patients with calcific MS, the indications for any intervention differ from those for rheumatic MS, and intervention for calcific MS should be performed only in the highly symptomatic patient. Nonrheumatic MS can also be present after radiation therapy and after a mitral valve repair with a small annuloplasty ring. Recommendation-Specific Supportive Text 1. Indications for intervention in patients with cal- cific MS are different from those for rheumatic MS for the following reasons. First, because calci- fication involves the annulus and base of the leaf- lets without commissural fusion, there is no role CLINICAL STATEMENTS AND GUIDELINES for PMBC or surgical commissurotomy. Second, the presence of severe mitral annular calcification can be quite challenging for the surgeon because of technically difficult in securely attaching the prosthetic valve and placement of the prosthetic valve may result in narrowing of the orifice.17 22 Finally, patients with calcification are often elderly and debilitated, have multiple comorbidities, and are at high surgical risk.1 3 For these reasons, intervention should be delayed until symptoms are severely limiting and cannot be managed with diuresis and heart rate control. Catheter-based therapies for these high surgical risk patients are being developed and evaluated.23 7. MITRAL REGURGITATION 7.1. Acute MR Acute MR may be caused by disruption of different parts of the mitral valve apparatus. IE may cause leaflet perfo- ration or chordal rupture. Spontaneous chordal rupture may occur in patients with myxomatous mitral valve dis- ease. Rupture of the papillary muscle occurs in patients who have an acute ST-segment elevation myocardial infarction, usually associated with an inferior infarction. The acute volume overload on the LV and LA results in pulmonary congestion and low forward cardiac out- Diagnosis of the presence and etiology of acute MR, along with urgent intervention, may be lifesaving. 7.1.1. Diagnosis of Acute MR In patients with acute MR, TTE is the initial imaging mo- dality of choice to evaluate LV function, RV function, pulmonary artery pressure, and mechanism of MR. The patient with severe acute MR, which might occur from chordal rupture, usually experiences acute hemody- namic decompensation. The sudden volume overload increases LA and pulmonary venous pressures, leading to pulmonary congestion and hypoxia, whereas de- creased blood delivery to the tissues with a concomitant decrease in LV systolic pressure limits the pressure gradi- ent, driving MR to early systole. Thus, the murmur may be short and unimpressive, as may be the color jet of MR by TTE. In the presence of sudden acute and he- modynamic instability after myocardial infarction, with hyperdynamic LV function by TTE and no other cause for the deterioration, TEE can be especially helpful in detecting papillary muscle or chordal rupture or valvular vegetations and annular abscesses that may further ac- centuate the need for a more urgent surgical approach.1 7.1.2. Medical Therapy Vasodilator therapy improves hemodynamic compen- sation in acute MR. The premise for use of vasodila- tors in acute MR is a reduction in impedance of aortic flow, thereby preferentially guiding flow away from the LV-to-LA pathway, decreasing MR while simultaneously increasing forward output to the LV-to-aortic path- This is usually accomplished by infusion of an easily titratable agent, such as sodium nitroprusside or nicardipine. Use of vasodilators is often limited by sys- temic hypotension that is exacerbated when peripheral resistance is decreased. Intra-aortic balloon counterpul- sation can be helpful to treat acute severe MR. By low- ering systolic aortic pressure, intra-aortic balloon coun- terpulsation decreases LV afterload, increasing forward output while decreasing regurgitant volume. Simulta- neously, intra-aortic balloon counterpulsation increases diastolic and mean aortic pressures, thereby supporting the systemic circulation. The use of a percutaneous cir- culatory assist device may stabilize a patient with acute hemodynamic compromise before the procedure. Prompt mitral valve surgery, preferably mitral repair if possible, is lifesaving in the symptomatic patient with acute severe primary MR. The severity of acute primary MR is variable, and some patients with more moderate amounts of MR may develop compensation as LV dila- tion allows for lower filling pressure and increased for- ward cardiac output. However, most patients with acute severe MR require surgical correction for reestablishment of normal hemodynamics and for relief of symptoms.1 5 This is especially true for a complete papillary muscle rup- ture that causes very severe MR, which is poorly tolerated. 7.2. Chronic Primary MR 7.2.1. Stages of Chronic Primary MR In assessing the patient with chronic MR, it is important to distinguish between chronic primary (degenerative) MR and chronic secondary (functional) MR, as these 2 conditions have more differences than similarities. Pri- mary MR is a disease of the mitral valve apparatus, and secondary MR is a disease of the ventricle or atria. In chronic primary MR, the pathology of 1 of the com- ponents of the valve (leaflets, chordae tendineae, papil- lary muscles, annulus) causes valve incompetence, with systolic regurgitation of blood from the LV to the LA (Table 17). The most common cause of chronic primary MR in high-income countries is mitral valve prolapse, which has a wide spectrum of etiology and presenta- tion. Younger populations present with severe myxo- matous degeneration with gross redundancy of both anterior and posterior leaflets and the chordal appa- ratus (Barlow s valve). A subset of these patients will present with ventricular arrhythmias, mitral annular disjunction, and LV dilation. Alternatively, older popu- lations present with fibroelastic deficiency disease, in which lack of connective tissue leads to chordal rup- ture. The differentiation between these 2 etiologies may have implications for operative intervention. Other CLINICAL STATEMENTS AND GUIDELINES less common causes of chronic primary MR include IE, connective tissue disorders, rheumatic heart disease, cleft mitral valve, and radiation heart disease. If vol- ume overload of chronic primary MR is prolonged and severe, it causes myocardial damage, HF, and eventual death. Correction of the MR before irreversible changes occur can be curative. 7.2.2. Diagnosis and Follow-Up of Chronic Primary MR 7.2.2.1. Diagnostic Testing: Initial Diagnosis Recommendations for Diagnostic Testing: Initial Diagnosis of Chronic MR Referenced studies that support the recommendations are summarized in Online Data Supplement 25. COR LOE Recommendations In patients with known or suspected primary MR, TTE is indicated for baseline evaluation of LV size and function, RV function, LA size, pulmonary artery pressure, and the mechanism and severity of primary MR (Stages A to D).1 5 In patients with primary MR, when TTE provides insufficient or discordant information, TEE is indicated for evaluation of the severity of MR, mechanism of MR, and status of LV function (Stages B to D). In patients with primary MR, CMR is indicated to assess LV and RV volumes and function and may help with assessing MR severity when there is a discrepancy between the findings on clinical assessment and echocardiography.6 9 In patients with severe primary MR undergoing mitral intervention, intraoperative TEE is indicated to establish the anatomic basis for primary MR (Stages C and D) and to guide Synopsis TTE is the initial imaging modality for patients with primary MR to look at valve morphology, severity of the MR, and the status of the LV, with TEE, CMR, or cardiac catheterization performed when insufficient or discordant information is obtained from the TTE. A TEE should be used to guide mitral valve interventions. Recommendation-Specific Supportive Text 1. TTE images provide the diagnostic data needed for clinical decision-making in chronic primary The outcome of the patient with chronic primary MR is determined by lesion severity,5 the presence of LV dys- function, and whether valve pathology is cor- rectable by valve repair, which is superior to valve replacement when repair is possible. Usually only severe (not mild or moderate) MR leads to nega- Favorable loading conditions in MR increase LVEF but do not affect the extent of shortening. Thus, a normal LVEF in MR is approximately 70%. The onset of LV dysfunction is inferred when LVEF declines toward 60% or when the LV is unable to contract to a diameter <40 mm at end systole.16 18 Although chamber volumes may give more information about car- 2D volume accuracy is variable in clinical practice. Determination of MR severity is made by integrating all available data. These data include measurements of the effective ori- fice area, regurgitant volume, regurgitant frac- tion (obtained by using the proximal isovelocity surface area or quantitative Doppler flow mea- color jet area, vena contracta, continuous-wave Doppler intensity, and the trans- mitral jet velocity curve. In mitral valve prolapse, MR may be non-holosystolic (mid-late systole). Thus, careful attention in assessing its severity is needed as conventional color Doppler parameter may overestimate its severity on a single image frame. Volumetric measurements provide a better assessment in this situation.9 2. TEE provides excellent imaging of the mitral valve and should be performed when TTE images are inadequate to fulfill the goals of TTE noted pre- viously. TEE is especially useful in cases of MR attributable to IE because TEE can provide infor- mation about other potentially infected struc- tures. TEE may allow more precise quantitation of regurgitant severity and provide a better esti- mate of the likelihood of a successful surgical valve repair than does TTE. Three-dimensional TEE may be helpful in further visualizing the abnormal mitral valve anatomy, offering a sur- gical view of the valve. Mitral valve repair is preferable to valve replacement because of a lower operative mortality rate and avoidance of the complications inherent to prosthetic valves. Although the final decision about repair versus replacement is made in the operating room, TEE can help predict surgical strategy beforehand. Thus, if repair is likely, it might be performed ear- lier in the course of the disease than if replace- ment is necessary. 3. In most cases, TTE provides the data needed for adequate cardiac evaluation of the patient with MR. However, in cases where TTE image quality is poor, CMR may be of value in MR evaluation. CMR produces highly accurate data on LV volumes, RV volumes, and LVEF, as well as an assessment of regurgitant fraction for estimating MR severity.6 9 However, outcome data on large numbers of patients have been derived from echocardiogra- phy, and it is uncertain whether CMR data can be used interchangeably with echocardiographic data in predicting outcomes. CMR is less helpful in establishing mitral pathoanatomy. CLINICAL STATEMENTS AND GUIDELINES 4. Intraoperative TEE is the standard for imaging dur- ing MR surgery. Before the operative incision, TEE may give the surgeon a better understanding of the valve anatomy and type of repair that will likely be performed, although this decision is ultimately made when the valve is inspected visually.10,11 Three-dimensional TEE ( surgical view ) may be helpful in further visualizing the abnormal mitral valve anatomy. Because anesthesia lessens after- load, preload, and mitral valve closing force, deci- sions about severity of MR should be evaluated at the same loading conditions as occurred during the awake state. Intraoperative TEE is especially help- ful in gauging the adequacy of repair.11 Because even mild residual MR after repair increases the likelihood of later repair failure that would necessi- surgeons strive for near-perfect operative repair. Adequacy of repair is judged by TEE after physiological filling pressure and blood pressure have been established. If more than trivial MR is detected in the operating room after repair, repair revision usually ensues. TEE also helps to diagnose underfilling of the LV, which can lead to systolic anterior leaflet motion with outflow obstruction and unneeded repair. In those patients with primary severe MR who are at high surgical risk, TEE is helpful in determining the feasibility of transcatheter edge-to-edge repair.22,23 7.2.2.2. Diagnostic Testing: Changing Signs or Symptoms Recommendation for Diagnostic Testing: Changing Signs or Symptoms in Patients With Primary MR Referenced studies that support the recommendation are summarized in Online Data Supplement 26. COR LOE Recommendation In patients with primary MR (Stages B to D) and new-onset or changing symptoms, TTE is indicated to evaluate the mitral valve apparatus and LV function.1,2 Synopsis A repeat TTE provides clinically relevant information about patients who are being followed for primary MR who develop new-onset symptoms. Table 17. Stages of Chronic Primary MR Stage Definition Valve Anatomy Valve Hemodynamics* Hemodynamic Consequences Symptoms A At risk of MR Mild mitral valve prolapse with normal coaptation Mild valve thickening and leaflet restriction No MR jet or small central jet area <20% LA on Doppler Small vena contracta <0.3 cm None None B Progressive MR Moderate to severe mitral valve prolapse with normal coaptation Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE Central jet MR 20% 40% LA or late systolic eccentric jet MR Vena contracta <0.7 cm Regurgitant volume <60 mL Regurgitant fraction <50% Angiographic grade 1+ to 2+ Mild LA enlargement No LV enlargement Normal pulmonary pressure None C Asymptomatic severe MR Severe mitral valve prolapse with loss of coaptation or flail leaflet Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE Thickening of leaflets with radiation heart disease Central jet MR >40% LA or holosystolic eccentric jet MR Vena contracta 0.7 cm Regurgitant volume 60 mL Regurgitant fraction 50% Angiographic grade 3+ to 4+ Moderate or severe LA enlargement LV enlargement Pulmonary hypertension may be present at rest or with exercise LVESD <40 mm LVESD 40 mm None D Symptomatic severe MR Severe mitral valve prolapse with loss of coaptation or flail leaflet Rheumatic valve changes with leaflet restriction and loss of central coaptation Prior IE Thickening of leaflets with radiation heart disease Central jet MR >40% LA or holosystolic eccentric jet MR Vena contracta 0.7 cm Regurgitant volume 60 mL Regurgitant fraction 50% Angiographic grade 3+ to 4+ Moderate or severe LA enlargement LV enlargement Pulmonary hypertension present 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. ERO indicates effective regurgitant orifice; IE, infective endocarditis; LA, left atrium/atrial; LV, left ventricular; LVEF, left ventricular ejection fraction; LVESD; left ventricular end-systolic dimension; and MR, mitral regurgitation. CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. The onset of symptoms in severe MR (dyspnea on exertion, orthopnea, or declining exercise tolerance) is an indication for mitral intervention even if LV function is preserved.2 Symptoms are the culmina- tion of the pathophysiology of MR and may indicate changes in LV or LA compliance; increase in pulmo- nary artery pressure; decrease in RV function; or the coexistence of TR. Therefore, symptoms add patho- physiological data not readily available from imag- ing, if other confounding factors can be excluded. Furthermore, there is no evidence that treatment with diuretics or other therapies that might relieve symptoms changes the prognostic effect of symp- tom onset. Once symptoms have occurred and are caused by MR, mitral valve surgery will improve the natural history even if medication has led to improve- ment. Repeat TTE at the time of symptom onset is indicated to confirm that symptoms are likely attrib- utable to MR or its effect on the LV, which in turn supports surgical correction.1 The new onset of AF is also an indication for repeat TTE to look for changes in severity of MR and the status of the LV. 7.2.2.3. Diagnostic Testing: Routine Follow-Up Recommendations for Diagnostic Testing: Routine Follow-Up for Chronic Primary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 27. COR LOE Recommendations For asymptomatic patients with severe primary MR (Stages B and C1), TTE is indicated every 6 to 12 months for surveillance of LV function (estimated by LVEF, LVEDD, and LVESD) and assessment of pulmonary artery pressure.1 11 In asymptomatic patients with severe primary MR (Stages B and C1), use of serum biomarkers and novel measurements of LV function, such as global longitudinal strain, may be considered as an adjunct to guide timing of intervention.12 21 Synopsis Asymptomatic patients with severe primary MR require periodic TTE to determine optimal timing of interven- tion. Biomarkers and other measures of LV function, such as global longitudinal strain, may also be helpful to guide intervention. Recommendation-Specific Supportive Text 1. TTE provides valuable information for surveillance of LV function (estimated by LVEF and LVESD) and pulmonary artery pressure in asymptomatic patients with severe primary MR (Stage C1) if Chronic severe MR is tolerated poorly, reaching a trigger for surgery at an average rate of about 8% per This progression varies from patient to patient, and because prognosis worsens if cor- rection of MR is delayed beyond the onset of these triggers, referral to a Comprehensive Valve Center for early repair or careful surveillance is of value. Because echocardiographic measure- ments are variable, management decisions that rest on these measurements should be con- firmed by repeat sequential TTE. In patients with milder chronic primary MR (Stages A and B), TTE is indicated periodically to evaluate for changes in MR severity, depending on valve anatomy and other considerations, because regurgitation may worsen over time. Because this process may develop slowly, MR can become severe and even lead to LV dysfunction in the absence of symp- toms or clinical signs (Table 4).3,6 2. Symptom onset is a crucial demarcation point in the natural history of MR and also a trigger for intervention. Because symptoms develop gradu- ally, patients may fail to recognize or ignore symp- toms. Natriuretic peptide levels provide objective evidence in patients with chronic severe MR, with elevated levels indicating increased reliance on preload to maintain an adequate forward cardiac Thus, serum natriuretic peptide levels may be helpful in making management decisions about intervention when other data are conflicting. LVEF is used as a key determi- nant of LV function in timing MR intervention. Unfortunately, LVEF is load dependent and often overestimates LV function in MR. Global longi- tudinal strain, although also load dependent, appears more sensitive to LV dysfunction in patients with chronic MR and, as such, might give warning that LV function is declining before LVEF Thus, novel markers of LV systolic function, such as global longitudi- nal strain, may be useful adjuncts in assessing LV function in patients with chronic MR. 7.2.2.4. Diagnostic Testing: Cardiac Catheterization Left ventriculography and hemodynamic measurements are useful when clinical assessment and noninvasive tests are inconclusive or discordant with regard to 1) se- verity of MR, 2) LV function, or 3) the need for surgery.1 Noninvasive imaging is adequate for evaluation of MR in most cases. However, invasive hemodynamic evalu- ation may be necessary in some cases, especially when there is a clinical discrepancy between symptomatic sta- tus and noninvasive testing. Elevated filling pressures support a cardiac cause of dyspnea and may indicate severely abnormal pathophysiology even when the pa- tient claims to be asymptomatic. Conversely, a normal invasive hemodynamic examination in a symptomatic CLINICAL STATEMENTS AND GUIDELINES patient with what appears to be less than severe MR suggests a noncardiac cause for the symptoms. Hemo- dynamic evaluation can be especially helpful in patients with concomitant lung disease. Normal LA (or pulmo- nary artery wedge) pressure and a large transpulmonary gradient suggest pulmonary hypertension that is attrib- utable to lung disease rather than mitral valve disease. Left ventriculography may also be of diagnostic benefit. Whereas echocardiographic-Doppler interrogation of the mitral valve measures flow velocity, ventriculography uses the density of contrast to determine the amount of blood flow from the LV to the LA. Although only semi- quantitative, a carefully performed ventriculogram can help in quantifying MR severity. Additional hemodynam- ic interventions, such as exercise or leg raising, may be helpful when the resting information is equivocal. 7.2.2.5. Diagnostic Testing: Exercise Testing Recommendation for Diagnostic Testing: Exercise Testing for Chronic Primary MR Referenced studies that support the recommendation are summarized in Online Data Supplement 28. COR LOE Recommendation In patients with primary MR (Stages B and C) and symptoms that might be attributable to MR, hemodynamic exercise testing using Doppler echocardiography or cardiac catheterization or cardiopulmonary exercise testing is reasonable.1 4 Synopsis In a subset of apparently asymptomatic patients with se- vere primary MR, exercise testing with hemodynamics can provide additional diagnostic and prognostic information. Recommendation-Specific Supportive Text 1. The onset of symptoms represents a key develop- ment in severe MR. However, some patients may not recognize their symptoms, may deny them, or may alter their lifestyle to remain asymptomatic. A formal treadmill exercise test can establish true exercise tolerance and can also form the base- line for future symptom assessment. Additional information about a cardiac or noncardiac limita- tion can be obtained from oxygen consumption measurements during exercise. When patients do complain of symptoms, they usually complain of dyspnea with exertion, yet noninvasive evaluation is usually made at rest. Exercise echocardiography or exercise invasive hemodynamics may add addi- tional prognostic value beyond conventional exer- cise treadmill testing in patients with asymptomatic moderate or severe chronic primary MR.1 4 MR may worsen during exercise, or filling pressures may become markedly abnormal, helping to demon- strate MR as the cause of the patient s dyspnea.1 4 7.2.3. Medical Therapy Recommendations for Medical Therapy for Chronic Primary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 29. COR LOE Recommendations In symptomatic or asymptomatic patients with severe primary MR and LV systolic dysfunction (Stages C2 and D) in whom surgery is not possible or must be delayed, GDMT for systolic dysfunction is reasonable.1 3 Benefit B-NR In asymptomatic patients with primary MR and normal LV systolic function (Stages B and C1), vasodilator therapy is not indicated if the patient is normotensive.4 8 Synopsis In patients with primary MR, there is no convincing evidence that vasodilator therapy reduces MR severity. However, GDMT for LV systolic dysfunction or systemic hypertension should be implemented as in any patient with these conditions. Recommendation-Specific Supportive Text 1. Patients with MR and LV dysfunction experience myocardial damage and HF. With onset of LV systolic dysfunction, surgery is usually indicated. However, in those patients in whom surgery (or transcatheter repair) is not performed or will be delayed, medical therapy for systolic dysfunction may be helpful to treat the LV dysfunction alone. Although data specific to patients with MR with LV dysfunction are sparse, treatment of such patients would consist of the standard regimen for HF, including beta-adrenergic blockade, ACE inhibitors or ARBs, and possibly aldosterone antagonists.1 3 Perhaps the best data exist for the use of beta which reverse LV dysfunction in experi- Patients who are receiving beta block- ers may have better surgical outcomes and delayed onset of LV dysfunction as compared with those not taking these medications.3 ACE inhibition has not been effective in experimental MR with LV dysfunction. Because aldosterone antagonism is thought to work in part by inhibiting fibrosis, its role in MR, where little fibrosis occurs, is unclear. 2. Because vasodilator therapy appears to be effec- tive in acute severe symptomatic MR, it seems rea- sonable to attempt afterload reduction in chronic asymptomatic MR with normal LV function in an effort to forestall the need for surgery. However, the results from the limited number of trials addressing this therapy have been disappointing, demonstrating little or no clinically important ben- Conversely, because vasodilators decrease LV size and mitral closing force, they may increase CLINICAL STATEMENTS AND GUIDELINES mitral valve prolapse, worsening rather than decreasing severity of MR.6 The foregoing does not apply to patients with concomitant hypertension. Hypertension must be treated because of the well- known morbidity and mortality associated with that condition and because increased LV systolic pressure by itself increases the systolic transmitral gradient and worsens severity of MR. Recommendations for Intervention for Chronic Primary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 30. COR LOE Recommendations In symptomatic patients with severe primary MR (Stage D), mitral valve intervention is recommended irrespective of LV systolic In asymptomatic patients with severe primary MR and LV systolic dysfunction (LVEF 60%, LVESD 40 mm) (Stage C2), mitral valve surgery is recommended.3 10 In patients with severe primary MR for whom surgery is indicated, mitral valve repair is recommended in preference to mitral valve replacement when the anatomic cause of MR is degenerative disease, if a successful and durable repair is possible.11 15 In asymptomatic patients with severe primary MR and normal LV systolic function (LVEF 60% and LVESD 40 mm) (Stage C1), mitral valve repair is reasonable when the likelihood of a successful and durable repair without residual MR is >95% with an expected mortality rate of <1%, when it can be performed at a Primary or Comprehensive In asymptomatic patients with severe primary MR and normal LV systolic function (LVEF >60% and LVESD <40 mm) (Stage C1) but with a progressive increase in LV size or decrease in EF on 3 serial imaging studies, mitral valve surgery may be considered irrespective of the probability of a successful and durable repair.16 In severely symptomatic patients (NYHA class III or IV) with primary severe MR and high or prohibitive surgical risk, transcatheter edge-to- edge repair (TEER) is reasonable if mitral valve anatomy is favorable for the repair procedure and patient life expectancy is at least 1 year.17,18 In symptomatic patients with severe primary MR attributable to rheumatic valve disease, mitral valve repair may be considered at a Comprehensive Valve Center by an experienced team when surgical treatment is indicated, if a durable and successful repair is likely.19 3: Harm B-NR In patients with severe primary MR where leaflet pathology is limited to less than one half the posterior leaflet, mitral valve replacement should not be performed unless mitral valve repair has been attempted at a Primary or Comprehensive Valve Center and Synopsis Anterior and/or bileaflet primary mitral valve disease re- quires a complex and extensive repair,20,23 26 and durabil- ity of the repair is less certain than for simple posterior leaflet intervention. Freedom from reoperation is approxi- mately 80%, and freedom from recurrent moderate or severe MR is 60% at 15 to 20 years in complex cases. These results are superior to the results of mitral valve re- placement if the repair is performed at high-volume valve even in elderly patients.30,31 Repair should also be attempted, if possible, with other causes of severe MR, such as papillary muscle rupture, IE, and cleft mitral valve. However, the results of very complex repair in younger patients may be matched by the re- sults of durable mechanical mitral valve replacement with careful management of anticoagulation. The Heart Valve Team should assign complex repairs to experienced mitral valve surgeons with established excellent operative and long-term outcomes. The probability of mitral valve repair rather than mitral valve replacement and overall outcome correlate with surgeon-specific mitral volumes.21,27 The hospital mortality rate is 50% lower, on average, in the highest-volume hospitals that perform 50 repairs per year. However, some low-volume hospitals outperform the median high-volume hospitals. This overlap suggests that hospital- or surgeon-specific volumes should not be used as a surrogate for actual surgeon-specific repair rates and outcomes (Figure 8). The management of patients with combined severe primary MR and AS is discussed in the Mixed Valve Disease section (Section 10.2.2). Recommendation-Specific Supportive Text 1. Primary MR is a mechanical problem of the leaflet coaptation that has only a mechanical solution that of mitral valve mechanical intervention. The onset of symptoms that results from severe MR worsens prognosis even when LV function appears to be normal,1,2 and the negative prognosis extends even to mild symptoms.2 Thus, the onset of symp- toms is an indication for prompt mitral valve surgery. 2. The goal of therapy in MR is to correct it before the onset of LV systolic dysfunction and its sub- sequent adverse effect on patient outcomes. The ideal time for mitral valve surgery is when the patient s LV approaches but has not yet reached the parameters that indicate systolic dysfunction Because symptoms do not always coincide with LV dys- function, imaging surveillance is used to plan surgery before severe dysfunction has occurred. If moderate LV dysfunction is already present, prog- nosis is worse after mitral valve operation.5 7,9,10,16 Thus, further delay (although symptoms are absent) will lead to greater LV dysfunction and a CLINICAL STATEMENTS AND GUIDELINES still worse prognosis. Because the loading condi- tions in MR allow continued late ejection into a lower-impedance LA, a higher cutoff for nor- mal LVEF is used in MR than in other types of heart disease. Although it is clearly inadvisable to allow patients LV function to deteriorate beyond the benchmarks of an LVEF 60% or LVESD 40 mm, some recovery of LV function can still occur even if these thresholds have been crossed.5,32 3. Repair success increases with surgical volume and expertise, which is a principle guiding surgical However, mitral valve replacement is preferable to a poor repair. The results of a mini- mally invasive approach may be similar to those of a full median sternotomy if the minimally inva- sive operation is performed by highly experienced When leaflet dysfunction is limited so that only annuloplasty and repair of the pos- terior leaflet are necessary, an operative mortality rate of <1%, long-term survival rate equivalent to that of the age-matched general population, approximately 95% freedom from reoperation, and >80% freedom from recurrent moderate or severe MR at 15 to 20 years after operation are exp 4. The onset of symptoms, LV dysfunction, or pul- monary hypertension worsens the prognosis for MR. Careful surveillance may result in timing of valve surgery before these negative sequelae occur. However, an attractive alternative strat- egy for treating severe chronic primary MR is to perform early mitral repair before these trig- gers are reached. Early mitral repair avoids the need for intensive surveillance and also obvi- ates the possibility that patients might become lost to follow-up or delay seeing their clini- cian until advanced LV dysfunction has already For the early mitral repair strat- egy to be effective, a durable repair must be provided. An unwanted valve replacement and its attendant risks, or a failed repair necessitat- ing reoperation, could be a complication of this Figure 8. Primary MR. Colors correspond to Table 2. *See Prosthetic Valve section (11.1.2) for choice of mitral valve replacement if mitral valve repair is not possible. CVC indicates Com- prehensive Valve Center; ERO, effective regurgitant orifice; ESD, end-systolic dimension; LVEF, ejection fraction; MR, mitral regurgitation; MV, mitral valve; MVR, mitral valve replacement; RF, regurgitant fraction; RVol, regurgitant volume; and VC, vena contracta. CLINICAL STATEMENTS AND GUIDELINES approach. Thus, there must be a high degree of certainty that a durable repair can be performed. This certainty comes from the track record of the surgical team in operating on the specific type of lesion under consideration. Thus, asymptomatic patients should be treated in a Comprehensive In excellent hands, patients with severe MR from flail leaflets who undergo early operation as opposed to watchful waiting have a lower risk of developing HF and lower 5. MR may lead to progressively more severe MR as the initial level of MR causes LV dilation, which increases stress on the mitral apparatus, caus- ing further damage to the valve apparatus, more severe MR, and further LV dilation thus initiating a perpetual cycle of ever-increasing LV volumes and MR. Longstanding volume overload leads to irreversible LV dysfunction and a poorer progno- sis. Patients with severe MR who develop an LVEF <60% or LVESD 40 mm have already developed LV systolic dysfunction.5,6 One study has sug- gested that for LV function and size to return to normal after mitral valve repair, the LVEF should Thus, when lon- gitudinal follow-up demonstrates a progressive decrease of LVEF toward 60% or a progressive increase in LVESD approaching 40 mm, it is rea- sonable to consider intervention.41 In severe MR, TTE is recommended at 3- to 6-month intervals or more frequently as the ventricle enlarges. 6. Mitral transcatheter edge-to-edge repair (TEER) with the anterior and posterior leaflets clipped together at 1 locations is safe and effective in treating severely symptomatic patients with pri- mary MR who are at high or prohibitive surgi- Studies of TEER with a mitral valve clip have demonstrated improved symptoms and a reduction in MR by 2 to 3 grades, leading to reverse remodeling of the LV. Superior outcomes were shown with surgery versus TEER, and thus it is only the patients who are at high or prohibitive risk for surgery for whom TEER is performed. 7. Rheumatic mitral valve disease is less suitable for mitral repair compared with complex degenera- tive disease. Durability of the repair is limited by thickened or calcified leaflets, extensive subval- vular disease with chordal fusion and shortening, and progression of rheumatic disease. Freedom from reoperation at 20 years, even in experienced hands, is in the 50% to 60% range. In a large series from Korea, repair was accomplished in 22% of patients operated on for rheumatic dis- One-third of these patients who underwent repair had significant stenosis or regurgitation at 10 years. Repair of rheumatic mitral valve disease should be limited to patients with less advanced disease in whom a durable repair can be accom- plished or to patients in whom a mechanical pros- thesis cannot be used because of anticoagulation 8. Mitral valve repair is the procedure of choice for isolated severe primary MR limited to less than one-half of the posterior leaflet, and mitral valve replacement is inappropriate unless mitral valve repair has been attempted and was unsuccess- Surgical repair of primary MR has been remarkably successful. Repair of isolated degenerative mitral disease, when leaflet dys- function is sufficiently limited that only annu- loplasty and repair of the posterior leaflet are necessary, has led to outcomes distinctly supe- rior to those with biological or mechanical mitral Repair is associated with an operative mortality rate of <1%, long-term survival rate equivalent to that of age-matched general population, approximately 95% free- dom from reoperation, and >80% freedom from recurrent moderate or severe ( 3) MR at As much as one-half of the posterior leaflet may be excised, plicated, or resuspended. Posterior leaflet repair has become sufficiently standardized in this situation so that repair, rather than mitral valve replacement, is the standard of care. Execution of this procedure with a success rate 95% should be the expectation of every cardiac sur- geon who performs mitral valve procedures. 7.3. Chronic Secondary MR 7.3.1. Stages of Chronic Secondary MR In chronic secondary MR, the mitral valve leaflets and chords usually are normal or minimally thickened. In- stead, MR is associated with severe LV dysfunction caused by CAD (ischemic chronic secondary MR) or id- iopathic myocardial disease (nonischemic chronic sec- ondary MR). The abnormal and dilated LV causes papil- lary muscle displacement, which in turn results in leaflet tethering with associated annular dilation that prevents adequate leaflet coaptation. Secondary MR may also develop because of LA dilation and enlargement of the mitral annulus, which often occurs with AF and other cardiomyopathies. There are instances in which both primary and secondary MR are present. The best ther- apy for chronic secondary MR is not clear because MR is only one component of the disease, and restoration of mitral valve competence is not curative. The optimal criteria for defining severe secondary MR have been controversial. Compared with primary MR, adverse out- comes in secondary MR are associated with a smaller CLINICAL STATEMENTS AND GUIDELINES calculated ERO; the severity of secondary MR may in- crease over time because of adverse remodeling of the LV or mitral annulus; and Doppler methods for calcula- tions of ERO area by the flow convergence method may underestimate severity because of the crescentic shape of the regurgitant orifice.1,2 Even so, on the basis of the criteria used for determination of severe MR in RCTs of surgical intervention for secondary MR,3 6 the recom- mended definition of severe secondary MR is now the same as for primary MR (ERO 0.4 cm2 and regurgitant volume 60 mL) (Table 18). 7.3.2. Diagnosis of Chronic Secondary MR Recommendations for Diagnosis of Secondary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 31. COR LOE Recommendations In patients with chronic secondary MR (Stages B to D), TTE is useful to establish the etiology and to assess the extent of regional and global LV remodeling and systolic dysfunction, severity of MR, and magnitude of pulmonary In patients with chronic secondary MR (Stages B to D), noninvasive imaging (stress nuclear/ PET, CMR, or stress echocardiography), coronary CT angiography, or coronary arteriography is useful to establish etiology of MR and to assess myocardial viability. In patients with chronic secondary MR with severe symptoms (Stage D) that are unresponsive to GDMT who are being considered for transcatheter mitral valve interventions, TEE is indicated to determine suitability for the procedure.3 8 In patients with chronic secondary MR undergoing transcatheter mitral valve intervention, intraprocedural guidance with TEE is recommended.4,7,9 13 Synopsis In symptomatic patients with chronic secondary MR, TTE is the initial diagnostic modality. Assessment of the coro- nary anatomy and myocardial viability may be helpful in management if ischemic MR is suspected. If transcatheter mitral valve intervention is contemplated, TEE determines suitability for the procedure and guides the procedure.1 Recommendation-Specific Supportive Text 1. TTE is essential in patients with MR to identify patients with primary MR and those with sec- ondary forms of MR. In general, in patients with LV systolic dysfunction and symptoms of HF, the presence of chronic secondary MR of any sever- ity is associated with a worse prognosis than that seen in the absence of MR. Most patients with secondary MR have global LV dysfunction, but in some patients, a limited but strategically placed wall motion abnormality may also cause chronic secondary MR. An initial TTE helps establish the cause of chronic secondary MR and also serves as a baseline for future comparisons. In patients with secondary MR, severe MR is defined as an , but outcome studies have shown poor prognosis in those with moderate MR (ERO 2. Prognosis is poor for both ischemic and non- ischemic MR, but ischemic MR lends itself to the possibility of revascularization and potential improvement in LV function if CAD has led to large areas of hibernating viable myocardium. Long-term results of the STICH (Surgical Treatment for Ischemic Heart Failure) trial demonstrated an improved 10-year survival rate in patients with ischemic cardiomyopathy and LVEF <35% who underwent CABG plus GDMT as compared with those randomized to GDMT alone. CT angiog- raphy is usually adequate to rule out significant CAD and thus rule out ischemic MR. If CAD is detected and noninvasive testing demonstrates areas of viability, coronary arteriography is pur- sued to better define the anatomy for potential Although the presence of myocardial viability did not determine the effect of revascularization on survival in the STICH trial, there is a subset of patients with viable myocar- dium in whom the ischemic MR will respond to 3. Clinical trials have identified anatomic consid- erations, detectable by TEE, that can identify patients with secondary MR who have a valve morphology amenable to TEER. In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial of patients with secondary MR and HF, exclusion criteria included vertical coaptation length <2 mm in valves with leaflet tethering, evidence of calci- fication in the grasping area of the A2 or P2 scal- lops, presence of a significant cleft of A2 or P2 scallops, and lack of both primary and secondary chordal support. These are similar criteria to the earlier EVEREST trial. TEE is standard preproce- dural imaging to determine suitability for TEER.3 8 4. During mitral TEER, TEE assists in guiding posi- tioning of the clip(s), assessing success of the procedure, determining whether more than a single clip is necessary to reduce MR, and assur- ing that the clip(s) has not created MS.4,7,9 13 CLINICAL STATEMENTS AND GUIDELINES 7.3.3. Medical Therapy Recommendations for Medical Therapy for Secondary MR Referenced studies that support the recommendations are summarized in Online Data Supplement 31. COR LOE Recommendations Patients with chronic severe secondary MR (Stages C and D) and HF with reduced LVEF should receive standard GDMT for HF, including ACE inhibitors, ARBs, beta blockers, aldosterone antagonists, and/or sacubitril/valsartan, and biventricular pacing as indicated.1 11 In patients with chronic severe secondary MR and HF with reduced LVEF, a cardiologist expert in the management of patients with HF and LV systolic dysfunction should be the primary MDT member responsible for implementing and monitoring optimal Synopsis GDMT for HF with reduced LVEF in patients with se- vere secondary MR should be provided, in conjunc- tion with a cardiology expert, in the management of HF. Recommendation-Specific Supportive Text 1. Chronic secondary MR usually develops as a result of LV systolic dysfunction. Thus, standard GDMT for HF forms the mainstay of therapy. Diuretics, beta blockers, ACE inhibitors or ARBs, and aldo- sterone antagonists help improve symptoms and/ or prolong life in patients with HF in general and probably do so even when HF is complicated by chronic secondary MR. GDMT can reduce LV volumes (reverse remodeling) in many patients, which reduces severity of secondary MR.1 11 2. Secondary MR is often responsive to GDMT (including coronary revascularization or car- diac resynchronization therapy in appropriate patients). Optimization of GDMT should be under the supervision of a cardiologist expert in the treatment of patients with HF to achieve optimal results and to determine with the MDT when symptoms are truly refractory to GDMT before decisions are made for surgical or transcatheter Table 18. 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. 