Predictors of rapid disease progression include older age, more severe valve calcification, and a faster rate of hemodynamic progression on serial studies. In patients with an aortic velocity >4 m/s in addition to predictors of rapid disease progres- sion, symptom onset is likely in the near future, so there is less benefit to waiting for symptom onset. Thus, elective AVR may be considered if the sur- gical risk is low and after consideration of other clinical factors and patient preferences. In adults with initially asymptomatic severe AS, the rate of sudden death is low (<1% per year). However, an aortic velocity 5 m/s or an LVEF <60% each is associated with higher all-cause and cardiovascular mortality rates in the absence A multivariate analysis of predictors of death in a large cohort (>500 patients) showed a >4-fold higher risk of cardiovascular death for those with an LVEF <60% than for those with a A progressive decrease in LVEF is most likely in those with an LVEF <60% before AS becomes Evaluation for other causes of a decline in LVEF is appropriate, particularly when AS is not yet severe, but a progressive decline in LV systolic function is of concern and should prompt more frequent evaluation; and consider- ation of AVR when repeat studies show a progres- sive decline in LVEF without other cause with a lack of response to medical therapy. The presence of at least 3 serial imaging studies showing a con- sistent decline in LVEF ensures that the changes seen are not simply attributable to recording, measurement, or physiological variability.8 11 Hemodynamic progression eventually leading to symptom onset occurs in nearly all asymptom- atic patients with AS.


The presence of at least 3 serial imaging studies showing a con- sistent decline in LVEF ensures that the changes seen are not simply attributable to recording, measurement, or physiological variability.8 11 Hemodynamic progression eventually leading to symptom onset occurs in nearly all asymptom- atic patients with AS. The survival rate during the asymptomatic phase is similar to age-matched controls, with a low risk of sudden death (<1% per year) when patients are followed prospec- tively and when patients promptly report symp- tom onset. The rate of symptom onset is strongly dependent on the severity of AS, with an event- free survival rate of about 75% to 80% at 2 years in those with a jet velocity <3.0 m/s, compared with only 30% to 50% in those with a jet veloc- ity 4.0 m/s. Patients with asymptomatic AS require periodic monitoring for development of symptoms and progressive disease (Section 3.1). In patients with moderate calcific AS undergoing cardiac surgery for other indications, the risk of progressive VHD is balanced against the risk of repeat surgery or TAVI (Sections 4.3.3 and 10). This decision must be individualized on the basis of the specific operative risk in each patient, clini- cal factors such as age and comorbid conditions, valve durability, and patient preferences.13,49,62 64 3.2.4. Choice of Intervention 3.2.4.1. Choice of Mechanical Versus Bioprosthetic AVR Recommendations for Choice of Mechanical Versus Bioprosthetic AVR Referenced studies that support the recommendations are summarized in Online Data Supplements 11 and 12.


Choice of Mechanical Versus Bioprosthetic AVR Recommendations for Choice of Mechanical Versus Bioprosthetic AVR Referenced studies that support the recommendations are summarized in Online Data Supplements 11 and 12. COR LOE Recommendations In patients with an indication for AVR, 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 AVR for whom VKA anticoagulant therapy is contraindicated, cannot be managed appropriately, or is not desired, a bioprosthetic AVR 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 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 pros- thetic valve type is influenced by several factors, CLINICAL STATEMENTS AND GUIDELINES including patient age, values, and preferences; ex- pected bioprosthetic valve durability, avoidance of pa- tient prosthesis mismatch, and the potential need for and timing of reintervention; and the risks associated with long-term VKA anticoagulation with a mechani- cal valve replacement.


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 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 pros- thetic valve type is influenced by several factors, CLINICAL STATEMENTS AND GUIDELINES including patient age, values, and preferences; ex- pected bioprosthetic valve durability, avoidance of pa- tient prosthesis mismatch, and the potential need for and timing of reintervention; and the risks associated with long-term VKA anticoagulation with a mechani- cal valve replacement. Despite the significantly higher rate of bioprosthetic structural valve deterioration ob- served in younger versus older patients,7 11,14,15 many patients choose to avoid a mechanical prosthesis be- cause they are unwilling to consider long-term VKA therapy because of the inconvenience 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 involve very high risk (eg, those with prior ra- diation exposure). The availability of TAVI has changed the dynamics of the discussion of the trade-offs be- tween mechanical and bioprosthetic valves in younger (Table 22). Recommendation-Specific Supportive Text 1.


The availability of TAVI has changed the dynamics of the discussion of the trade-offs be- tween mechanical and bioprosthetic valves in younger (Table 22). 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 structural dete- rioration of a bioprosthesis is greater in younger patients, but the risk of bleeding from anticoagu- lation is higher in older patients. In patients with shortened longevity and/or multiple comorbidi- ties, 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.


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 valve 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.14 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 thromboem- bolic events favors the choice of a mechanical valve in patients <50 years of age, unless antico- agulation 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 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 survival advantage with a mechanical prosthesis in this age group.


Several studies have shown a survival advantage with a mechanical prosthesis in this age group. Alternatively, large retrospec- tive observational studies have shown similar long-term survival rates in patients 50 to 69 years of age undergoing mechanical versus biopros- thetic valve replacement.22 24 In general, patients with mechanical valves experience a higher risk of bleeding caused by anticoagulation, whereas individuals who receive bioprosthetic valves expe- rience a higher rate of reoperation because of structural deterioration of the prosthesis, as well as perhaps a decrease in survival rate.6,25 27 There are several other factors to consider in the choice of type of valve prosthesis (see Section 11.1). Ultimately, the choice of mechanical versus bio- prosthetic valve replacement for all patients, but especially for those between 50 and 65 years of age, is a shared decision-making process that must account for the trade-offs between dura- bility (and the need for reintervention), bleeding, 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 CLINICAL STATEMENTS AND GUIDELINES risk of bleeding complications related to VKA therapy and more often require interruption of VKA therapy for noncardiac surgical and inter- ventional 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. 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.


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 for whom anticoagulation is either contraindicated or undesirable, and it is performed only at Comprehensive Valve Centers by surgeons experienced in this procedure.11 13,32 3.2.4.2. Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate Recommendations for Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate Referenced studies that support the recommendations are summarized in Online Data Supplement 11 to 13.


Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate Recommendations for Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate Referenced studies that support the recommendations are summarized in Online Data Supplement 11 to 13. COR LOE Recommendations For symptomatic and asymptomatic patients with severe AS and any indication for AVR who are <65 years of age or have a life expectancy >20 years, SAVR is recommended.1 3 For symptomatic patients with severe AS who are 65 to 80 years of age and have no anatomic contraindication to transfemoral TAVI, either SAVR or transfemoral TAVI is recommended after shared decision-making about the balance between expected patient longevity and valve durability.1,4 8 For symptomatic patients with severe AS who are >80 years of age or for younger patients with a life expectancy <10 years and no anatomic contraindication to transfemoral TAVI, transfemoral TAVI is recommended in preference to SAVR.1,4 10 In asymptomatic patients with severe AS and an LVEF <50% who are 80 years of age and have no anatomic contraindication to transfemoral TAVI, the decision between TAVI and SAVR should follow the same recommendations as for symptomatic patients For asymptomatic patients with severe AS and an abnormal exercise test, very severe AS, rapid progression, or an elevated BNP (COR 2a indications for AVR), SAVR is recommended in preference to TAVI.1 3,11 For patients with an indication for AVR for whom a bioprosthetic valve is preferred but valve or vascular anatomy or other factors are not suitable for transfemoral TAVI, SAVR is For symptomatic patients of any age with severe AS and a high or prohibitive surgical risk, TAVI is recommended if predicted post- TAVI survival is >12 months with an acceptable quality of life.12,13,14,15 For symptomatic patients with severe AS for whom predicted post-TAVI or post-SAVR survival is <12 months or for whom minimal improvement in quality of life is expected, palliative care is recommended after shared decision-making, including discussion of patient preferences and values.


COR LOE Recommendations For symptomatic and asymptomatic patients with severe AS and any indication for AVR who are <65 years of age or have a life expectancy >20 years, SAVR is recommended.1 3 For symptomatic patients with severe AS who are 65 to 80 years of age and have no anatomic contraindication to transfemoral TAVI, either SAVR or transfemoral TAVI is recommended after shared decision-making about the balance between expected patient longevity and valve durability.1,4 8 For symptomatic patients with severe AS who are >80 years of age or for younger patients with a life expectancy <10 years and no anatomic contraindication to transfemoral TAVI, transfemoral TAVI is recommended in preference to SAVR.1,4 10 In asymptomatic patients with severe AS and an LVEF <50% who are 80 years of age and have no anatomic contraindication to transfemoral TAVI, the decision between TAVI and SAVR should follow the same recommendations as for symptomatic patients For asymptomatic patients with severe AS and an abnormal exercise test, very severe AS, rapid progression, or an elevated BNP (COR 2a indications for AVR), SAVR is recommended in preference to TAVI.1 3,11 For patients with an indication for AVR for whom a bioprosthetic valve is preferred but valve or vascular anatomy or other factors are not suitable for transfemoral TAVI, SAVR is For symptomatic patients of any age with severe AS and a high or prohibitive surgical risk, TAVI is recommended if predicted post- TAVI survival is >12 months with an acceptable quality of life.12,13,14,15 For symptomatic patients with severe AS for whom predicted post-TAVI or post-SAVR survival is <12 months or for whom minimal improvement in quality of life is expected, palliative care is recommended after shared decision-making, including discussion of patient preferences and values. In critically ill patients with severe AS, percutaneous aortic balloon dilation may be considered as a bridge to SAVR or TAVI.


In critically ill patients with severe AS, percutaneous aortic balloon dilation may be considered as a bridge to SAVR or TAVI. Synopsis In patients considering a bioprosthetic AVR, the next step is the choice between SAVR and TAVI. In patients with a high or prohibitive risk for SAVR (see Section 2.5), decision-making focuses on TAVI versus pallia- tive care. When surgical risk is not high or prohibitive, procedure-specific impediments are assessed (Fig- ure 3). When both SAVR and TAVI are options, a prime consideration is the limited data about TAVI durabil- ity. SAVR has been used for more than 50 years, with ample durability data available for specific valve types across different age groups. Currently, robust durabil- ity data for TAVI extend to only about 5 years. SAVR valve deterioration typically occurs after >10 years, so longer-term TAVI durability data are needed. A key factor in decision-making is the ratio of patient life expectancy to known valve durability, with patient age often used as a surrogate for life expectancy. For a woman in the United States, the average additional expected years of life are 25 at age 60 years, 17 at age 70 years, and 10 at age 80 years. For a man, expected additional years of life are 22 at age 60 years, 14 at age 70 years, and 8 at age 80 years. The age break- points shown in these recommendations reflect these Recommendations for Choice of SAVR Versus TAVI for Patients for Whom a Bioprosthetic AVR Is Appropriate (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES Figure 3. Choice of SAVR versus TAVI when AVR is indicated for valvular AS. Colors correspond to Table 2. *Approximate ages, based on US Actuarial Life Expectancy tables, are provided for guidance.


*Approximate ages, based on US Actuarial Life Expectancy tables, are provided for guidance. The balance between expected patient longevity and valve durability varies 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 years, leading to uncertainty about longer-term outcomes. The decision about valve type should be individualized on the basis of patient-specific factors that might affect expected longevity. Placement of a transcatheter valve requires vascular anatomy that allows transfemoral delivery and the absence of aortic root dilation that would re- quire surgical replacement. Valvular anatomy must be suitable for placement of the specific prosthetic valve, including annulus size and shape, leaflet number and calcification, and coronary ostial height. See ACC Expert Consensus Statement.20 AS indicates aortic stenosis; AVR, aortic valve replacement; LVEF, left ventricular ejection fraction; QOL, quality of life; SAVR, surgical aortic valve replacement; STS, Society of Thoracic Surgeons; TAVI, transcatheter aortic valve implantation; TF, transfemoral; and VKA, vitamin K antagonist. CLINICAL STATEMENTS AND GUIDELINES statistical averages and serve as the starting point for shared decision-making, not as absolute values for chronological age. Some younger patients with comorbid conditions have a limited life expectancy, whereas some older patients have a longer-than-av- erage life expectancy. Decision-making should be indi- vidualized on the basis of patient-specific factors that affect longevity or quality of life, such as comorbid cardiac and noncardiac conditions, frailty, dementia, and other factors.


Decision-making should be indi- vidualized on the basis of patient-specific factors that affect longevity or quality of life, such as comorbid cardiac and noncardiac conditions, frailty, dementia, and other factors. In addition, the choice of implanta- tion approach is based on a shared decision-making process that accounts for the patient s values and pref- erences and includes discussion of the indications for and against each approach and the potential need for and risks associated with valve reintervention.16 19 Recommendation-Specific Supportive Text 1. SAVR has demonstrated excellent durability and outcomes for both mechanical and bioprosthetic valves. Earlier RCTs comparing SAVR and TAVI in patients with a higher surgical risk included only older patients, with a mean age in the mid-80s. More recent RCTs that included patients at low to intermediate surgical risk had a mean age in the mid-70s, but there were very few patients <65 years of age, so the evidence base cannot be extrapolated to these patients. In addition, valve durability is of higher priority in younger patients, who typically have a longer life expec- tancy and lower surgical risk. As longer-term data on TAVI valve durability become available, the age range for recommending TAVI may shift, but at this time the most prudent course, based on the published evidence, is to recommend SAVR for adults <65 years of age unless life expectancy is limited by comorbid cardiac or noncardiac condi- tions. The final choice of implantation approach is based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indications for and against each approach and the potential need for and risks associated with valve reintervention. There are no data for the use of TAVI in patients 2.


There are no data for the use of TAVI in patients 2. Both SAVR and TAVI are effective approaches to AVR in adults 65 to 80 years of age. Patients enrolled in RCTs of TAVI versus SAVR had high- velocity severe AS (Stage D1). However, less robust data from observational studies and regis- try data are encouraging with regard to TAVI for symptomatic patients with low-flow, low-gradi- ent severe AS (Stages D2 and D3). Thus, these guidelines make the same recommendations for symptomatic patients with confirmed severe AS regardless of flow rate. TAVI has a slightly lower mortality risk and is associated with a shorter hos- pital length of stay, more rapid return to normal activities, lower risk of transient or permanent AF, less bleeding, and less pain than SAVR. On the other hand, SAVR is associated with a lower risk of paravalvular leak, less need for valve reinterven- tion, and less need for a permanent pacemaker. When the choice of SAVR or TAVI is being made in an individual patient between 65 and 80 years of age, other factors, such as vascular access, comorbid cardiac and noncardiac conditions that affect risk of either approach, expected functional status and survival after AVR, and patient values and preferences, must be considered. The choice of mechanical or bioprosthetic SAVR (Section 11) versus a TAVI is an important consideration and is influenced by durability considerations, because durability of transcatheter valves beyond 5 to 6 years is not yet known.2 3. TAVI is a safe and effective procedure for treat- ment of severe symptomatic AS in all adults regardless of estimated surgical risk. The mortality rate for transfemoral TAVI is lower than that for SAVR, with a HR of 0.88 and a 95% CI of 0.78 to 0.99 in a meta-analysis of RCTs.


The mortality rate for transfemoral TAVI is lower than that for SAVR, with a HR of 0.88 and a 95% CI of 0.78 to 0.99 in a meta-analysis of RCTs. TAVI also is asso- ciated with a lower risk of stroke (HR: 0.81; 95% CI: 0.68 0.98; P=0.028), major bleeding, and AF, as well as a shorter hospital length of stay, less pain, and more rapid return to normal activities.3 Compared with SAVR, TAVI results in higher rates of vascular complications, paravalvular regurgita- tion, permanent pacemaker implantation, and valve intervention, but most patients will consider that the advantages of TAVI outweigh these dis- advantages. TAVI valves are durable to at least 5 years, and the limited data on TAVI durability are of less concern to most patients >80 years of age because the valve durability is likely to be longer than the patient s life expectancy.22 If significant valve deterioration does occur, a second TAVI within the first prosthesis, (called a valve-in-valve TAVI), is likely to be possible. When a transfemo- ral approach is not possible, other factors, such as alternative vascular access, comorbid cardiac and noncardiac conditions, expected functional status and survival after AVR, and patient values and preferences, must be considered. The spe- cific choice of a balloon-expandable valve or self- expanding valve depends on patient anatomy and 4. An LVEF <50% in a patient with severe AS is a COR 1 indication for AVR, so the choice of TAVI versus SAVR in these patients is based on the same considerations as in patients with symptoms CLINICAL STATEMENTS AND GUIDELINES attributable to severe AS.


An LVEF <50% in a patient with severe AS is a COR 1 indication for AVR, so the choice of TAVI versus SAVR in these patients is based on the same considerations as in patients with symptoms CLINICAL STATEMENTS AND GUIDELINES attributable to severe AS. From a pathophysiolog- ical point of view, the reasons for thinking that TAVI might be especially beneficial with severe AS and a low LVEF are the avoidance of myocardial ischemia with an open surgical procedure and the greater reduction in afterload with a larger effective valve area. However, outcome data from RCTs show that a low LVEF also is a risk factor for adverse outcomes even with TAVI.29 The final choice of implantation approach is based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indications for and against each approach and the potential need for and risks associated with valve reintervention. Studies on the potential benefit of TAVI in patients with moderate AS and LV systolic dysfunction are in progress. 5. Published RCTs comparing TAVI and SAVR included only patients with symptoms attrib- utable to severe AS. Asymptomatic patients with COR 2a indications for AVR should either undergo SAVR or wait until a COR 1 indication is present before intervention. The recommen- dation for SAVR in preference to TAVI includes asymptomatic patients for whom AVR is being considered because of an abnormal exercise blood pressure response, an elevated serum BNP level, rapid hemodynamic progression, or very severe AS with a velocity of 5 m/s.


The recommen- dation for SAVR in preference to TAVI includes asymptomatic patients for whom AVR is being considered because of an abnormal exercise blood pressure response, an elevated serum BNP level, rapid hemodynamic progression, or very severe AS with a velocity of 5 m/s. The final choice of implantation approach is based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indications for and against each approach and the potential need for and risks associated with valve reintervention.30 32 6. Published RCTs have focused primarily on TAVI via the transfemoral vascular access route. The mortality rate has been higher with TAVI by nonfemoral access routes than with SAVR, possibly because of the access approach itself, but more likely because of the higher comor- bidity burden and risk in patients with vascular disease severe enough to preclude transfemo- ral access. When transfemoral TAVI is not fea- sible, SAVR or palliative care options should be included in the shared decision-making discus- sion. The final choice of implantation approach is based on a shared decision-making process that accounts for the patient s values and pref- erences and includes discussion of the indica- tions for and against each approach and the potential need for and risks associated with 7. TAVI was compared with standard medical therapy in a prospective RCT of patients with severe symptomatic AS who were deemed inop- The rate of all-cause death at 2 years was lower with TAVI (43.3%) (HR: 0.58; medical therapy (68%).12,14,34 Standard therapy included percutaneous aortic balloon dilation in 84%. There was a reduction in repeat hospital- ization with TAVI (55% versus 72.5%; P<0.001).


There was a reduction in repeat hospital- ization with TAVI (55% versus 72.5%; P<0.001). In addition, only 25.2% of survivors were in New York Heart Association (NYHA) class III or IV 1 year after TAVI, compared with 58% of patients receiving standard therapy (P<0.001). However, the rate of major stroke was higher with TAVI than with standard therapy at 30 days (5.05% versus 1.0%; P=0.06) and remained higher at vascular complications occurred in 16.2% with TAVI versus 1.1% with standard therapy Similarly, in a nonrandomized study of 489 patients with severe symptom- atic AS and extreme surgical risk treated with a self-expanding TAVI valve, the rate of all-cause death at 12 months was 26% with TAVI, com- pared with an expected mortality rate of 43% if patients had been treated medically.13 The final choice of TAVI versus palliative care is based on a shared decision-making process that accounts for the patient s values and preferences and includes discussion of the indication, risks, and benefits for and against each approach. 8. The survival and symptom reduction benefit of TAVI is seen only in appropriately selected patients. Baseline clinical factors associated with a poor outcome after TAVI include advanced age, frailty, smoking or chronic obstructive pulmonary disease, pulmonary hypertension, liver disease, prior stroke, anemia, and other systemic condi- tions. The STS estimated surgical risk score pro- vides a useful measure of the extent of patient comorbidities and may help identify which patients will benefit from TAVI.


The STS estimated surgical risk score pro- vides a useful measure of the extent of patient comorbidities and may help identify which patients will benefit from TAVI. Patients with a mechanical impediment to SAVR, such as a por- celain aorta or prior chest radiation damage, may have better outcomes after TAVI than do frail patients or those with moderate to severe disease in more than one other organ system.12,14,34 The likely benefits and risks of TAVI are considered in weighing the risk benefit ratio of intervention in an individual patient. TAVI is not recommended in patients with 1) a life expectancy of <1 year even with a successful procedure or 2) those with a chance of survival with benefit of <25% at 2 years. CLINICAL STATEMENTS AND GUIDELINES 9. Percutaneous aortic balloon dilation has a role in treating children, adolescents, and young adults with AS, but its role in treating older patients is very limited. The mechanism by which bal- loon dilation modestly reduces the severity of stenosis in older patients is fracture of calcific deposits within the valve leaflets and, to a minor degree, stretching of the annulus and separa- tion of the calcified or fused commissures. Immediate hemodynamic results include a Table 14.


The mechanism by which bal- loon dilation modestly reduces the severity of stenosis in older patients is fracture of calcific deposits within the valve leaflets and, to a minor degree, stretching of the annulus and separa- tion of the calcified or fused commissures. Immediate hemodynamic results include a Table 14. A Simplified Framework With Examples of Factors Favoring SAVR, TAVI, or Palliation Instead of Aortic Valve Intervention Favors SAVR Favors TAVI Favors Palliation Age/life expectancy* Younger age/longer life expectancy Older age/fewer expected remaining years of life Limited life expectancy Valve anatomy BAV Subaortic (LV outflow tract) calcification Rheumatic valve disease Small or large aortic annulus Calcific AS of a trileaflet valve Prosthetic valve preference Mechanical or surgical bioprosthetic valve preferred Concern for patient prosthesis mismatch (annular enlargement might be considered) Bioprosthetic valve preferred Favorable ratio of life expectancy to valve durability TAVI provides larger valve area than same size SAVR Concurrent cardiac conditions Aortic dilation Severe primary MR Severe CAD requiring bypass grafting Septal hypertrophy requiring myectomy AF Severe calcification of the ascending aorta ( porcelain aorta) Irreversible severe LV systolic dysfunction Severe MR attributable to annular calcification Noncardiac conditions Severe lung, liver, or renal disease Mobility issues (high procedural risk with sternotomy) Symptoms likely attributable to noncardiac conditions Severe dementia Moderate to severe involvement of 2 other organ systems Frailty Not frail or few frailty measures Frailty likely to improve after TAVI Severe frailty unlikely to improve after TAVI Estimated procedural or surgical risk of SAVR or TAVI SAVR risk low TAVI risk high TAVI risk low to medium SAVR risk high to prohibitive Prohibitive SAVR risk (>15%) or post- TAVI life expectancy <1 y Procedure-specific impediments Valve anatomy, annular size, or low coronary ostial height precludes TAVI Vascular access does not allow transfemoral TAVI Previous cardiac surgery with at-risk coronary grafts Previous chest irradiation Valve anatomy, annular size, or coronary ostial height precludes TAVI Vascular access does not allow transfemoral TAVI Goals of Care and patient preferences and values Less uncertainty about valve durability Avoid repeat intervention Lower risk of permanent pacer Life prolongation Symptom relief Improved long-term exercise capacity and QOL Avoid vascular complications Accepts longer hospital stay, pain in recovery period Accepts uncertainty about valve durability and possible repeat intervention Higher risk of permanent pacer Life prolongation Symptom relief Improved exercise capacity and QOL Prefers shorter hospital stay, less postprocedural pain Life prolongation not an important goal Avoid futile or unnecessary diagnostic or therapeutic procedures Avoid procedural stroke risk Avoid possibility of cardiac pacer *Expected remaining years of life can be estimated from US Actuarial Life Expectancy tables.


The balance between expected patient longevity and valve durability varies 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 only to 5 y, leading to uncertainty about longer-term outcomes. The decision about valve type should be individualized on the basis of patient-specific factors that might affect expected longevity. A large aortic annulus may not be suitable for currently available transcatheter valve sizes. With a small aortic annulus or aorta, a surgical annulus-enlarging procedure may be needed to allow placement of a larger prosthesis and avoid patient prosthesis mismatch. Dilation of the aortic sinuses or ascending aorta may require concurrent surgical replacement, particularly in younger patients with a BAV. AF indicates atrial fibrillation; AS, aortic stenosis; BAV, bicuspid aortic valve; CAD, coronary artery disease; LV, left ventricular; MR, mitral regurgitation; QOL, quality of life; SAVR, surgical aortic valve replacement; and TAVI, transcatheter aortic valve implantation. Modified from Burke et al.16 CLINICAL STATEMENTS AND GUIDELINES moderate reduction in the transvalvular pressure gradient, but the postdilation valve area rarely . Despite the modest change in valve area, an early symptomatic improvement usually occurs. However, serious acute compli- cations, including acute severe AR, restenosis, and clinical deterioration, occur within 6 to 12 months in most patients. Therefore, in patients with AS, percutaneous aortic balloon dilation is not a substitute for AVR.


Therefore, in patients with AS, percutaneous aortic balloon dilation is not a substitute for AVR. Some clinicians contend that, despite the procedural morbid- ity and mortality rates and limited long-term results, percutaneous aortic balloon dilation can have a temporary role in the management of some symptomatic patients, such as those patients with severe AS and refractory pulmo- nary edema or cardiogenic shock, who might benefit from percutaneous aortic balloon dila- tion as a bridge to TAVI or SAVR. However, this approach is used less frequently given the availability and success of immediate TAVI even in very high-risk patients (Table 14).35 38 4. AORTIC REGURGITATION 4.1. Acute Aortic Regurgitation Acute aortic regurgitation (AR) may result from abnor- malities of the valve, most often endocarditis, or abnor- malities of the aorta, primarily aortic dissection. Acute AR may also occur as an iatrogenic complication of a transcatheter procedure or after blunt chest trauma. The acute volume overload on the LV usually results in severe pulmonary congestion, as well as a low forward cardiac output. Urgent diagnosis and rapid intervention are lifesaving. 4.1.1. Diagnosis of Acute AR TTE or TEE is indispensable in confirming the pres- ence, severity, and etiology of acute AR; determining whether there is rapid equilibration of the aortic and LV diastolic pressures; visualizing the aortic root; and evaluating LV size and systolic function.1,2 A short deceleration time on the aortic flow velocity curve and early closure of the mitral valve are indicators of markedly elevated LV end-diastolic pressure. A pres- sure half-time of <300 ms on the AR velocity curve indicates rapid equilibration of the aortic and LV diastolic pressures. The degree of holodiastolic flow reversal in the aortic arch, in comparison with the forward systolic flow, provides a quick semiquantita- tive estimate of regurgitant fraction.


The degree of holodiastolic flow reversal in the aortic arch, in comparison with the forward systolic flow, provides a quick semiquantita- tive estimate of regurgitant fraction. Acute severe AR caused by aortic dissection is a surgical emergency. CT imaging is the primary approach for diagnosis of acute aortic dissection because it is highly accurate and continuously available at most medical centers. MRI is rarely used in the acute setting because of pa- tient instability. TEE may be used when CT imaging is unavailable and is helpful in intraoperative assess- ment of aortic valve function before and after the surgical intervention. The sensitivity and specificity of TTE for diagnosis of Type A3 aortic dissection are only 60% to 80%, whereas TEE has a sensitivity of 98% to 100% and a specificity of 95% to 100%. Angiog- raphy should be considered only when the diagno- sis cannot be determined by noninvasive imaging or when the differential diagnosis is an acute coronary syndrome. 4.1.2. Intervention for Acute AR In patients with acute severe AR resulting from IE or aortic dissection, medical therapy to reduce LV afterload may allow temporary stabilization, but surgery should not be delayed, especially if there is hypotension, pulmonary edema, or evidence of Intra-aortic balloon counterpulsation is contraindicated in patients with acute severe AR.5 Beta blockers are often used in treating aortic dis- section. However, these agents should be used very cautiously, if at all, for other causes of acute AR be- cause they will block the compensatory tachycardia and could precipitate a marked reduction in blood pressure. 4.2. Stages of Chronic AR The most common causes of chronic severe AR in the United States and other high-income countries are BAV disease and primary diseases of the ascend- ing aorta or the sinuses of Valsalva.


Stages of Chronic AR The most common causes of chronic severe AR in the United States and other high-income countries are BAV disease and primary diseases of the ascend- ing aorta or the sinuses of Valsalva. Rheumatic heart disease is the leading cause of AR in many low- to middle-income countries. With calcific valve disease, regurgitation often accompanies AS, but the degree of regurgitation usually is mild to moderate, not se- vere. In most patients with AR, the disease course is chronic and slowly progressive, with increasing LV volume overload and LV adaptation via chamber dila- tion and hypertrophy. Management of patients with AR depends on an accurate diagnosis of the cause and stage of the disease process. Table 15 shows the stages of AR, ranging from patients at risk of AR (Stage A) or with progressive mild to moderate AR (Stage B) to severe asymptomatic (Stage C) and symptomatic (Stage D) AR. Each of these stages is defined by valve anatomy, valve hemodynamics, se- verity of LV dilation, and LV systolic function, as well as by patient symptoms. CLINICAL STATEMENTS AND GUIDELINES Table 15.


Each of these stages is defined by valve anatomy, valve hemodynamics, se- verity of LV dilation, and LV systolic function, as well as by patient symptoms. CLINICAL STATEMENTS AND GUIDELINES Table 15. Stages of Chronic AR Stage Definition Valve Anatomy Valve Hemodynamics Hemodynamic Consequences Symptoms A At risk of AR BAV (or other congenital valve anomaly) Aortic valve sclerosis Diseases of the aortic sinuses or ascending aorta History of rheumatic fever or known rheumatic heart disease IE AR severity: none or trace None None B Progressive AR Mild to moderate calcification of a trileaflet valve BAV (or other congenital valve anomaly) Dilated aortic sinuses Rheumatic valve changes Previous IE Mild AR: Jet width <25% of LVOT Vena contracta <0.3 cm Regurgitant volume <30 mL/ beat Regurgitant fraction <30% Angiography grade 1 Moderate AR: Jet width 25% 64% of LVOT Vena contracta 0.3 0.6 cm Regurgitant volume 30 59 mL/ beat Regurgitant fraction 30% to Angiography grade 2 Normal LV systolic function Normal LV volume or mild LV dilation None C Asymptomatic severe AR Calcific aortic valve disease Bicuspid valve (or other congenital abnormality) Dilated aortic sinuses or ascending aorta Rheumatic valve changes IE with abnormal leaflet closure or perforation Severe AR: Jet width 65% of LVOT Vena contracta >0.6 cm Holodiastolic flow reversal in the proximal abdominal aorta Regurgitant volume 60 mL/ beat Regurgitant fraction 50% Angiography grade 3 to 4 In addition, diagnosis of chronic severe AR requires evidence of LV dilation and mild to moderate LV dilation (LVESD <50 mm) C2: Abnormal LV systolic function with depressed LVEF ( 55%) or severe LV dilation (LVESD >50 mm or ) None; exercise testing is reasonable to confirm symptom status D Symptomatic severe AR Calcific valve disease Bicuspid valve (or other congenital abnormality) Dilated aortic sinuses or ascending aorta Rheumatic valve changes Previous IE with abnormal leaflet closure or perforation Severe AR: Doppler jet width 65% of LVOT Vena contracta >0.6 cm Holodiastolic flow reversal in the proximal abdominal aorta Regurgitant volume 60 mL/ beat Regurgitant fraction 50% Angiography grade 3 to 4 In addition, diagnosis of chronic severe AR requires evidence of LV dilation Symptomatic severe AR may occur with normal systolic function (LVEF >55%), mild to moderate LV dysfunction (LVEF 40% to 55%), or severe LV dysfunction (LVEF Moderate to severe LV dilation is present Exertional dyspnea or angina or more severe HF symptoms AR indicates aortic regurgitation; BAV, bicuspid aortic valve; ERO, effective regurgitant orifice; HF, heart failure; IE, infective endocarditis; LV, left ventricular; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; and LVOT, left ventricular outflow tract.


CLINICAL STATEMENTS AND GUIDELINES 4.3. Chronic AR 4.3.1. Diagnosis of Chronic AR Recommendations for Diagnostic Testing of Chronic AR Referenced studies that support the recommendations are summarized in Online Data Supplement 14. COR LOE Recommendations In patients with signs or symptoms of AR, TTE is indicated for assessment of the cause and severity of regurgitation, LV size and systolic function, prognosis, and timing of valve In patients with a BAV or with known dilation of the aortic sinuses or ascending aorta, TTE is indicated to evaluate the presence and severity In patients with moderate or severe AR and suboptimal TTE images or a discrepancy between clinical and TTE findings, TEE, CMR, or cardiac catheterization is indicated for the assessment of LV systolic function, systolic and diastolic volumes, aortic size, and AR severity.20 25 Synopsis TTE provides diagnostic information about the etiology and mechanism of AR (including valve reparability), se- verity of regurgitation, morphology of the ascending aorta, and LV response to the increases in preload and afterload. Imaging with TEE, CMR, or aortic angiogra- phy provides additional information when needed. Recommendation-Specific Supportive Text 1. Although qualitative measures of AR severity are adequate in many situations, when AR is signifi- cant (Stages B and C), quantitative measures of regurgitant volume and effective regurgitant orifice (ERO) area1 are better predictors of clini- Measures of LV systolic function (LVEF or fractional shortening) and LV end-systolic dimension (LVESD) or LV end-systolic volume are predictive of the development of HF symptoms or death in initially asymptomatic patients (Stages B and C1) and are significant determinants of survival and functional results after surgery in asymptomatic and symptomatic patients (Stages Symptomatic patients (Stage D) with normal LVEF have a significantly better long- term postoperative survival rate than those with depressed systolic function. 2.


Although qualitative measures of AR severity are adequate in many situations, when AR is signifi- cant (Stages B and C), quantitative measures of regurgitant volume and effective regurgitant orifice (ERO) area1 are better predictors of clini- Measures of LV systolic function (LVEF or fractional shortening) and LV end-systolic dimension (LVESD) or LV end-systolic volume are predictive of the development of HF symptoms or death in initially asymptomatic patients (Stages B and C1) and are significant determinants of survival and functional results after surgery in asymptomatic and symptomatic patients (Stages Symptomatic patients (Stage D) with normal LVEF have a significantly better long- term postoperative survival rate than those with depressed systolic function. 2. Auscultation has high specificity for detecting AR but low sensitivity and diagnostic accuracy.27 TTE can identify AR in patients who have been deemed to be at risk on the basis of the presence of known aortic dilation or a condition associated with abnormal aortic valve function, such as a BAV. 3. TTE and CMR are useful for evaluating patients in whom there is discordance between clinical assessment and severity of AR by TTE or when TTE images are suboptimal. CMR imaging pro- vides accurate and reproducible measures of regurgitant volume and regurgitant fraction in patients with AR, as well as assessment of aortic morphology, LV volume, and LV systolic func- tion. Cardiac catheterization with LV and aortic angiography, as well as quantitation of regurgi- tation severity, is another option.20 25,28 30 4.3.2. Medical Therapy Recommendations for Medical Therapy of Chronic AR Referenced studies that support the recommendations are summarized in Online Data Supplement 14.


Medical Therapy Recommendations for Medical Therapy of Chronic AR Referenced studies that support the recommendations are summarized in Online Data Supplement 14. COR LOE Recommendations In asymptomatic patients with chronic AR (Stages B and C), treatment of hypertension (systolic blood pressure >140 mmHg) is In patients with severe AR who have symptoms and/or LV systolic dysfunction (Stages C2 and D) but a prohibitive surgical risk, GDMT for reduced LVEF with ACE inhibitors, ARBs, and/or sacubitril/valsartan is Synopsis There is no evidence that vasodilating drugs reduce se- verity of AR or alter the disease course in patients with significant AR in the absence of systemic hypertension. Recommendations for GDMT for hypertension and HF apply to patients with chronic asymptomatic AR, as for the general population. Recommendation-Specific Supportive Text 1. Severe AR is associated with a wide pulse pres- sure, such that systolic blood pressure is higher than in patients without AR even when systemic vascular resistance is normal. Transaortic stroke volume increases further with medications that lower heart rate, such as beta blockers, which may result in a paradoxical apparent increase in blood pressure. Vasodilating drugs, such as ACE inhibitors or ARBs, do not affect heart rate and thus may reduce systolic blood pressure without a substantial reduction in diastolic blood pres- sure in patients with chronic AR.1,2,5 8 2. In symptomatic patients who are candidates for surgery, medical therapy is not a substitute for AVR. However, medical therapy is help- ful for alleviating symptoms in patients who are considered to be at very high surgical risk because of concomitant comorbid medical CLINICAL STATEMENTS AND GUIDELINES 4.3.3. Timing of Intervention Recommendations for Timing of Intervention for Chronic AR Referenced studies that support the recommendations are summarized in Online Data Supplement 15 to 17.


Timing of Intervention Recommendations for Timing of Intervention for Chronic AR Referenced studies that support the recommendations are summarized in Online Data Supplement 15 to 17. COR LOE Recommendations In symptomatic patients with severe AR (Stage D), aortic valve surgery is indicated regardless of LV systolic function.1 7 In asymptomatic patients with chronic severe AR and LV systolic dysfunction (LVEF 55%) (Stage C2), aortic valve surgery is indicated if no other cause for systolic dysfunction is In patients with severe AR (Stage C or D) who are undergoing cardiac surgery for other indications, aortic valve surgery is indicated. In asymptomatic patients with severe AR and normal LV systolic function (LVEF >55%), aortic valve surgery is reasonable when the LV is severely enlarged (LVESD >50 mm or indexed ) (Stage C2).10,11,13 24 In patients with moderate AR (Stage B) who are undergoing cardiac or aortic surgery for other indications, aortic valve surgery is reasonable. In asymptomatic patients with severe AR and normal LV systolic function at rest (LVEF >55%; Stage C1) and low surgical risk, aortic valve surgery may be considered when there is a progressive decline in LVEF on at least 3 serial studies to the low normal range (LVEF 55% to 60%) or a progressive increase in LV dilation into the severe range (LV end- diastolic dimension [LVEDD] 3: Harm B-NR In patients with isolated severe AR who have indications for SAVR and are candidates for surgery, TAVI should not be performed.29 32 Synopsis Most patients with indications for surgery for chronic severe AR require valve replacement with a mechani- cal or bioprosthetic valve (Figure 4).


In asymptomatic patients with severe AR and normal LV systolic function at rest (LVEF >55%; Stage C1) and low surgical risk, aortic valve surgery may be considered when there is a progressive decline in LVEF on at least 3 serial studies to the low normal range (LVEF 55% to 60%) or a progressive increase in LV dilation into the severe range (LV end- diastolic dimension [LVEDD] 3: Harm B-NR In patients with isolated severe AR who have indications for SAVR and are candidates for surgery, TAVI should not be performed.29 32 Synopsis Most patients with indications for surgery for chronic severe AR require valve replacement with a mechani- cal or bioprosthetic valve (Figure 4). Preservation of the native aortic valve ( valve sparing ) may be pos- sible in selected patients with favorable valve anatomy who are undergoing surgical replacement of the aortic sinuses and/or ascending aorta.33 39 Although advanc- es are occurring in primary aortic valve repair,37,40 42 this approach is not yet generalizable, and durabil- ity is not known. Current recommendations for AVR related to severity of LV dilation are based on mea- surement of LV short-axis diameters. There are limited data demonstrating prognostic value of LV volume measurements in chronic AR using left ventriculogra- Normal limits for LV volumes have been determined, as have criteria for severe LV dilation, but these values differ between 2D echocardiography, 3D echocardiography, and there are insufficient data on the relationship between LV volumes and outcomes of patients with AR. This is an area in need of further investigation. Other markers of LV dysfunction and re- modeling, such as global longitudinal strain and circu- likewise require additional clinical outcome studies. Recommendation-Specific Supportive Text 1.


Other markers of LV dysfunction and re- modeling, such as global longitudinal strain and circu- likewise require additional clinical outcome studies. Recommendation-Specific Supportive Text 1. Symptoms are an important indication for AVR in patients with chronic severe AR, and the most important aspect of the clinical evaluation is tak- ing a careful, detailed history to elicit symptoms or diminution of exercise capacity. Patients with chronic severe AR who develop symptoms have a high risk of death if AVR is not performed,52 and survival and functional status after AVR are related to the severity of preoperative symptoms, assessed either subjectively or objectively with Even among symptomatic patients with a severe reduction in LVEF (<35%), AVR results in improved survival rate.5 7 2. LV systolic function is an important determi- nant of survival and functional status after Outcomes are optimal when surgery is performed before LVEF decreases In asymptomatic patients with LV systolic dysfunction, postoperative out- comes are better if AVR is performed before onset of symptoms.53 3. Patients with chronic severe AR may be referred for other types of cardiac surgery, such as CABG, mitral valve surgery, or surgery for correction of dilation of the aortic root or ascending aorta. In these patients, AVR will prevent both the hemo- dynamic consequences of persistent AR during the perioperative period and the possible need for a second cardiac operation in the near future. Patients undergoing surgical repair or replacement of the aortic root or ascending aorta may be can- didates for aortic valve sparing procedures.33 39 4. LVESD in patients with chronic AR reflects both the severity of the LV volume overload and the degree of LV systolic shortening.54,62 An elevated LVESD often reflects LV systolic dysfunction with a depressed LVEF.


LVESD in patients with chronic AR reflects both the severity of the LV volume overload and the degree of LV systolic shortening.54,62 An elevated LVESD often reflects LV systolic dysfunction with a depressed LVEF. If LVEF is normal, an increased LVESD indicates a significant degree of LV remod- eling and is associated with subsequent develop- ment of symptoms and/or LV systolic dysfunction and an increased mortality rate after AVR.17,20,21 Most studies have used unadjusted LVESD, but indexing for body size is important, particularly in women or small patients.13,19,52 Recent data indi- cate that the LVESD index threshold for optimal postoperative survival may be even smaller than but more outcome data, and ide- ally an RCT, of earlier intervention are needed. CLINICAL STATEMENTS AND GUIDELINES LV volumes may be a more sensitive predictor of cardiac events than LVESD index in asymptomatic but more data are needed to deter- mine the threshold values of LV systolic volume that best predict postoperative outcomes. 5. In patients with moderate AR who are undergo- ing other forms of cardiac surgery, such as CABG, mitral valve surgery, or replacement of the ascend- ing aorta, the decision to intervene on the aortic valve concurrently includes consideration of several factors, including aortic valve anatomy, aortic root size and shape, regurgitant severity, other comor- bidities, and patients preferences and values. Patients undergoing surgical repair or replacement of the aortic root or ascending aorta may be candi- dates for a valve-sparing procedure.33 39 6.


Patients undergoing surgical repair or replacement of the aortic root or ascending aorta may be candi- dates for a valve-sparing procedure.33 39 6. LVEDD, a marker of the severity of LV volume overload in patients with chronic AR, is signifi- cantly associated with clinical outcomes in asymp- tomatic patients, and progressive increases in LVEDD are associated with subsequent need for In asymptomatic patients, it is important to ensure that apparent changes in LV size or LVEF are not due simply to measurement or physiological variability. In addition, confirmation of severe regurgitation by quantitative measures of AR severity with TTE, TEE, or, when needed, CMR provides confidence that AR is the cause of LV dila- tion or decrease in LVEF. When there is an apparent significant fall in EF or increase in LV size, repeat imaging typically is performed at 3- to 6-month intervals unless there is clinical deterioration. 7. TAVI for isolated chronic AR is challenging because of dilation of the aortic annulus and aortic root and, in many patients, lack of sufficient leaflet calcification. Risks of TAVI for treatment of AR include transcatheter valve migration and signifi- cant paravalvular leak.29 32 TAVI is rarely feasible, and then only in carefully selected patients with severe AR and HF who have a prohibitive surgi- cal risk and in whom valvular calcification and annular size are appropriate for a transcatheter approach. Figure 4. Timing of intervention for AR. Colors correspond to Table 2. AR indicates aortic regurgitation; AVR, aortic valve replacement; EDD, end-diastolic dimension; ERO, effective regurgi- tant orifice; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; RF, regurgitant fraction; RVol, regurgitant volume; and VC, vena contracta CLINICAL STATEMENTS AND GUIDELINES 5. BICUSPID AORTIC VALVE 5.1. BAV and Associated Aortopathy 5.1.1. Diagnosis and Follow-Up of BAV 5.1.1.1.


BAV and Associated Aortopathy 5.1.1. Diagnosis and Follow-Up of BAV 5.1.1.1. Diagnostic Testing: Initial Diagnosis Recommendations for Diagnostic Testing: Initial Diagnosis of BAV Referenced studies that support the recommendations are summarized in Online Data Supplement 18. COR LOE Recommendations In patients with a known BAV, TTE is indicated to evaluate valve morphology, measure severity of AS and AR, assess the shape and diameter of the aortic sinuses and ascending aorta, and evaluate for the presence of aortic coarctation for prediction of clinical outcome and to determine timing In patients with BAV, CMR angiography or CT angiography is indicated when morphology of the aortic sinuses, sinotubular junction, or ascending aorta cannot be assessed accurately or fully by echocardiography.4,5 In first-degree relatives of patients with a known BAV, a screening TTE might be considered to look for the presence of a BAV or asymptomatic dilation of the aortic sinuses and ascending aorta.6 Synopsis BAV is a common congenital anomaly that affects 0.5% to 2.0% of adults with a 3:1 male-to-female predomi- Patients with BAV may develop isolated aortic valve disease, including isolated AR, AS, or a combina- tion of the two. Aortic aneurysms have been reported in 20% to 40% of patients with BAV.1 This aortopathy can occur independent of valve function and consists of dilation of the aortic sinuses, the ascending aorta, or the arch. Therefore, patients with BAV require care- ful evaluation of both the aortic valve and the aorta throughout their lifetimes (Figure 5). Recommendation-Specific Supportive Text 1. Many patients with BAV will develop AS or AR over their lifetimes.


Many patients with BAV will develop AS or AR over their lifetimes. In a recent meta-analysis of natural history studies of patients with BAV, 13% to 30% of patients developed moderate or greater AR and 12% to 37% developed moderate or greater AS during follow-up.1 TTE usually is adequate for evaluation of aortic valve anatomy and hemody- namics. TEE provides improved 2D and 3D images if needed. Aortic enlargement at the level of the sinuses or proximal ascending aorta has been reported in 20% to 40% of patients with BAV,1 and some develop severe aneurysmal dilation and are at increased risk of aortic dissection.2,3,7 10 Aortic measurements are reported at the aortic annulus, sinuses of Valsalva, sinotubular junction, and mid-ascending aorta. Doppler interrogation of the proximal descending aorta and abdominal aorta should also be performed to evaluate for the presence of aortic coarctation, which is asso- ciated with BAV in a subset of patients, although a coarctation also can be detected by comparing arm and leg blood pressures. 2. CT angiography or CMR provides better images of the aortic sinuses, sinotubular junction, or ascending aorta when TTE does not adequately visualize the sinus and proximal 5 to 6 cm of the ascending aorta. The choice of CMR versus CT angiography depends on patient preference, insurance coverage, institutional expertise, and consideration of radiation exposure. 3. In about 20% to 30% of patients with a BAV, other family members also have a BAV and/or an associated aortopathy. A specific genetic cause has not been identified, and the patterns of inheritance are variable. Imaging can identify the presence of a BAV and aortic dilation, but there is a paucity of data on the cost-effectiveness of this approach and whether earlier diagnosis would improve long-term clinical outcomes.6,11 5.1.1.2.


Imaging can identify the presence of a BAV and aortic dilation, but there is a paucity of data on the cost-effectiveness of this approach and whether earlier diagnosis would improve long-term clinical outcomes.6,11 5.1.1.2. Diagnostic Testing: Routine Follow-Up Recommendations for Diagnostic Testing: Routine Follow-Up of Patients With a BAV Referenced studies that support the recommendations are summarized in Online Data Supplement 18. COR LOE Recommendations In patients with BAV and a diameter of the aortic sinuses or ascending aorta of 4.0 cm, lifelong serial evaluation of the size and morphology of the aortic sinuses and ascending aorta by echocardiography, CMR, or CT angiography is reasonable, with the examination interval determined by the degree and rate of progression of aortic dilation and by family history.1 5 In patients with a BAV who have undergone AVR, continued lifelong serial interval imaging of the aorta is reasonable if the diameter of the aortic sinuses or ascending aorta is 4.0 Synopsis Patients with BAV with and without associated aortic aortopathy require lifelong surveillance. Because pro- gression of valve disease and growth of the aorta can occur in the absence of symptoms, diagnostic imaging plays an integral role in the surveillance process. Recommendation-Specific Supportive Text 1.


Because pro- gression of valve disease and growth of the aorta can occur in the absence of symptoms, diagnostic imaging plays an integral role in the surveillance process. Recommendation-Specific Supportive Text 1. Aortopathy is present in approximately 20% to 40% of patients with a BAV and is associated with dilation of the aortic sinuses, the ascending aorta, and/or the arch.1 In a retrospective case series of 918 patients with BAV followed for 2 to 12 years CLINICAL STATEMENTS AND GUIDELINES with serial imaging, 47% required valve surgery but only 3.8% required aortic grafting without valve replacement, and <0.1% had aortic dissec- In a systematic review of 13 studies with >11000 patients with a BAV, aortic dilation was present in 20% to 40%, but only 0.4% suffered Aortic imaging at least annually is prudent in patients with BAV and significant aor- tic dilation (>4.5 cm) to determine the appropriate timing of surgical intervention. Patients with risk factors that increase the risk of aortic dissection, such as a rapid rate of change in aortic diameter or a family history of aortic dissection, may also require more frequent monitoring. In patients with milder dilation that shows no change on sequential studies and with a negative family his- tory, a longer interval between imaging studies is 2. In a retrospective review of 1286 patients with a BAV who underwent isolated AVR with a median of 12 years of follow-up, subsequent aortic dissection occurred in 1%, ascending aor- tic replacement surgery was needed in 0.9%, and progressive aortic enlargement was noted in In a smaller cohort of 153 patients with a BAV with prior AVR, 3% required proximal aor- tic surgery after 15 years of follow-up.


In a retrospective review of 1286 patients with a BAV who underwent isolated AVR with a median of 12 years of follow-up, subsequent aortic dissection occurred in 1%, ascending aor- tic replacement surgery was needed in 0.9%, and progressive aortic enlargement was noted in In a smaller cohort of 153 patients with a BAV with prior AVR, 3% required proximal aor- tic surgery after 15 years of follow-up. No cases of aortic dissection were noted.7,10 These stud- ies demonstrate that the aorta may continue to dilate in patients with a BAV who undergo valve 5.1.2. Interventions for Patients With BAV 5.1.2.1. Intervention: Replacement of the Aorta Recommendations for Intervention: Replacement of the Aorta in Patients With a BAV Referenced studies that support the recommendations are summarized in Online Data Supplement 18. COR LOE Recommendations In asymptomatic or symptomatic patients with a BAV and a diameter of the aortic sinuses or ascending aorta >5.5 cm, operative intervention to replace the aortic sinuses and/ or the ascending aorta is recommended.1 3 In asymptomatic patients with a BAV, a diameter of the aortic sinuses or ascending aorta of 5.0 to 5.5 cm, and an additional risk factor for dissection (eg, family history of aortic dissection, aortic growth rate >0.5 cm per year, aortic coarctation), operative intervention to replace the aortic sinuses and/or the ascending aorta is reasonable if the surgery is performed at a Comprehensive Valve Center.3,4 Figure 5. Intervals for imaging the aorta in patients with a BAV. Colors correspond to Table 2. BAV indicates bicuspid aortic valve; CTA, computed tomographic angiography; CMR, cardiac magnetic resonance; TTE, transthoracic echocardiography.


BAV indicates bicuspid aortic valve; CTA, computed tomographic angiography; CMR, cardiac magnetic resonance; TTE, transthoracic echocardiography. CLINICAL STATEMENTS AND GUIDELINES In patients with a BAV with indications for SAVR and a diameter of the aortic sinuses or ascending aorta 4.5 cm, replacement of the aortic sinuses and/or ascending aorta is reasonable if the surgery is performed at a Comprehensive Valve Center.4 7 In patients with a BAV who meet criteria for replacement of the aortic sinuses, valve-sparing surgery may be considered if the surgery is performed at a Comprehensive Valve Center.8,9 In asymptomatic patients with a BAV who are at low surgical risk, have a diameter of the aortic sinuses or ascending aorta of 5.0 to 5.5 cm, and have no additional risk factors for dissection, operative intervention to replace the aortic sinuses and/or the ascending aorta may be considered if the surgery is performed at a Comprehensive Valve Center.4 7,10 14 Synopsis The timing and type of surgery for replacement of the aorta are dependent on the anatomy of the aorta (as demonstrated on imaging), patient characteristics, and institutional expertise (Figure 6). Recommendation-Specific Supportive Text 1. Retrospective studies of patients with a BAV have shown that the incidence of aortic dissection is very low and is estimated to be approximately 0.4% with routine surveillance of the aorta.1 However, data are limited with regard to the degree of aortic dilation at which the risk of dissection is high enough to war- rant operative intervention in patients who do not fulfill criteria for AVR on the basis of severe AS or AR. Thus, an individualized approach to the timing of surgical intervention for a dilated aorta is suggested.


Thus, an individualized approach to the timing of surgical intervention for a dilated aorta is suggested. Surgery is recommended in patients with a BAV with or without symptoms and with a diameter of the aortic sinuses or the ascending aorta of 5.5 cm.2 2. Specific risk factors, including family history of aortic dissection, aortic growth rate >0.5 cm per year, and aortic coarctation, are associated with a greater risk of aortic dissection. In patients with these risk factors, operative intervention to replace the aortic sinuses and/or the ascending aorta is reasonable when the aortic dimension is 5.0 to 5.5 cm, if the surgery is performed at a Comprehensive Valve Center.4,10 12,15 3. In patients with a BAV, data are limited with regard to the degree of aortic dilation at which the risk of dissection is high enough to warrant replacement of the ascending aorta at the time of AVR. The risk of progressive aortic dilation and dissection after AVR in patients with BAV has been the subject of several studies, but definitive data are lacking. In patients undergoing AVR because of severe AS or AR, replacement of the ascending aorta is reason- able when the aortic diameter is >4.5 cm.4 7,10 14 4. There are a limited number of patients with BAV who meet criteria for operative intervention on the aortic sinuses and/or ascending aorta but have a well-functioning aortic valve. Because of the growing experience with valve-sparing surgery on highly selected patients,8,9 surgical replacement of the aorta with aortic valve repair or reimplantation may be considered. However, given the complexity of this procedure, surgery should be performed at a Comprehensive Valve Center. 5.


However, given the complexity of this procedure, surgery should be performed at a Comprehensive Valve Center. 5. Data are limited with regard to the degree of aortic dilation at which the risk of dissection is high enough to warrant operative intervention in patients who do not fulfill criteria for AVR on the basis of severe AS or AR. In asymptomatic patients with a BAV and a diameter of the aortic sinuses and/or ascending aorta of 5.0 to 5.5 cm who are at low surgical risk and have no additional risk factors for aortic dissection, surgery to replace the aortic sinuses and/or ascending aorta may be considered as long as surgery is performed at a Comprehensive Valve Center. Additionally, shared decision-making between the patient and the healthcare team is needed to clearly outline the risks of surgery and weigh them against the potential reduction in future risk of aortic dissection.4 7,10 14 5.1.2.2. Intervention: Repair or Replacement of the Aortic Valve Recommendations for Intervention: Repair or Replacement of the Aortic Valve Referenced studies that support the recommendations are summarized in Online Data Supplement 18. COR LOE Recommendations In patients with BAV and severe AR who meet criteria for AVR, aortic valve repair may be considered in selected patients if the surgery is performed at a Comprehensive Valve Center.1 3 In patients with BAV and symptomatic, severe AS, TAVI may be considered as an alternative to SAVR after consideration of patient- specific procedural risks, values, trade-offs, and preferences, and when the surgery is performed at a Comprehensive Valve Center.4 6 Synopsis The indications for the timing of aortic valve interven- tion in patients with a BAV and AS or AR is similar to those for trileaflet aortic valves. See the respective sec- tions on AS (Section 3.2) and AR (Section 4).


See the respective sec- tions on AS (Section 3.2) and AR (Section 4). The choice of prosthetic valve type in patients with a BAV is similar to that for patients with trileaflet valves. See the sec- tion on prosthetic valve choices (Section 3.2.4.1) for full details. Given the unique nature of BAV, however, there are additional specific considerations. Recommendations for Intervention: Replacement of the Aorta in Patients With a BAV (Continued) COR LOE Recommendations CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. Surgical repair of the aortic valve may be feasible in selected patients, depending on valve and aortic root anatomy and tissue characteristics. Published data suggest that valve repair can be performed safely and effectively by surgeons with training and experience in these techniques.1 3,7 However, given the complexities of patient selection and surgical techniques, such surgeries should be per- formed at a Comprehensive Valve Center. 2. Recent trials have demonstrated the benefits of TAVI in patients with severe, symptomatic AS. However, the early pivotal TAVI trials excluded patients with BAV. Initial studies using early-gener- ation valves suggested a higher rate of paravalvular leak in the BAV population.4,5 Data from the STS/ ACC Transcatheter Valve Therapies Registry, which includes all consecutive TAVI procedures performed in the United States, suggest that with the use of newer-generation prosthetic valves the rate of paravalvular leak is no different in patients with a BAV than in patients with a trileaflet aortic valve. This registry also showed no difference in mortality rate at 30 days and 1 year between the BAV and tricuspid valve groups. However, the stroke rate at 30 days was higher in the BAV group.6 Other con- siderations are the younger age of patients with a BAV, for whom the risk benefit ratio of TAVI versus SAVR needs careful consideration.


However, the stroke rate at 30 days was higher in the BAV group.6 Other con- siderations are the younger age of patients with a BAV, for whom the risk benefit ratio of TAVI versus SAVR needs careful consideration. RCTs are needed to obtain full clarity on the optimal use of TAVI in this population, as well as long-term outcomes. 6. MITRAL STENOSIS The incidence of rheumatic MS is low in high-income countries and has been slowly declining in low- and mid- dle-income countries, but MS remains a major cause of valve disease worldwide. Rheumatic MS is much more common in women (about 80% of cases) than in men. The clinical presentation of rheumatic MS varies, with patients from regions with a high disease prevalence presenting at a young age (teen years to age 30 years) Figure 6. Intervention for replacement of the aorta in patients with a BAV. Colors correspond to Table 2. *Family history of aortic dissection, aortic growth rate 0.5 cm/y, and/or presence of aortic coarctation. BAV indicates bicuspid aortic valve; AVR, aortic valve re- placement; and CVC, Comprehensive Valve Center. CLINICAL STATEMENTS AND GUIDELINES with commissural fusion but pliable noncalcified valve leaflets. In contrast, the presentation in regions with a low disease prevalence occurs more often in older pa- tients (age 50 to 70 years) who present decades after the initial rheumatic fever episode with calcified fibrotic leaf- lets in addition to commissural fusion and subvalvular involvement.


In contrast, the presentation in regions with a low disease prevalence occurs more often in older pa- tients (age 50 to 70 years) who present decades after the initial rheumatic fever episode with calcified fibrotic leaf- lets in addition to commissural fusion and subvalvular involvement. Older patients with MS often have multiple other cardiac and noncardiac comorbidities, such as ath- erosclerotic disease, hypertension, and diastolic dysfunc- tion, all of which need to be taken into consideration in patient evaluation and management.1,2 Although most of MS in the world results from rheumat- ic heart disease, nonrheumatic calcific MS is found with in- creasing frequency in the elderly population in high-income countries Calcific MS is the result of calcification of the mi- tral annulus that extends into the leaflet bases, resulting in both narrowing of the annulus and rigidity of the leaflets.3 5 6.1. Stages of MS The stages of MS are defined by patient symptoms, valve anatomy, valve hemodynamics, and the consequences of valve obstruction on the left atrium (LA) and pulmo- nary circulation (Table 16). Rheumatic valve disease is the primary cause of MS, with anatomic features reflect- ing this disease process. Hemodynamic severity is best characterized by valve area, either directly planimetered by 2D or 3D imaging or calculated from the diastolic The definition of severe MS is based on the severity of symptoms, as well as the sever- ity at which intervention will improve symptoms. Thus, a mitral valve area 1.5 cm2 is considered severe, which typically corresponds to a transmitral mean gradient of >5 mmHg to 10 mmHg at a normal heart rate. How- ever, mean pressure gradient is highly dependent on transvalvular flow rate, the diastolic filling period, and heart rate.


How- ever, mean pressure gradient is highly dependent on transvalvular flow rate, the diastolic filling period, and heart rate. Mitral pressure half-time also has limitations, and is dependent upon LV and LA compliance as well as stenosis severity. Other approaches to calculation of the mitral valve area, such as the continuity equation or Gorlin formula, may be used if discrepancies exist. These pertain primarily to patients with rheumatic MS. 6.2. Rheumatic MS 6.2.1. Diagnosis and Follow-Up of Rheumatic MS 6.2.1.1. Diagnostic Testing: Initial Diagnosis Recommendations for Diagnostic Testing: Initial Diagnosis of Rheumatic MS Referenced studies that support the recommendations are summarized in Online Data Supplement 19. COR LOE Recommendations In patients with signs or symptoms of rheumatic MS, TTE is indicated to establish the diagnosis, quantify hemodynamic severity, assess concomitant valvular lesions, and demonstrate valve morphology (to determine suitability for mitral commissurotomy).1 3 In patients considered for percutaneous mitral balloon commissurotomy (PMBC), TEE should be performed to assess the presence or absence of LA thrombus and to evaluate the severity of MR.4 6 Synopsis For patients with rheumatic MS, TTE is the initial di- agnostic test to determine the severity of the stenosis Table 16.


COR LOE Recommendations In patients with signs or symptoms of rheumatic MS, TTE is indicated to establish the diagnosis, quantify hemodynamic severity, assess concomitant valvular lesions, and demonstrate valve morphology (to determine suitability for mitral commissurotomy).1 3 In patients considered for percutaneous mitral balloon commissurotomy (PMBC), TEE should be performed to assess the presence or absence of LA thrombus and to evaluate the severity of MR.4 6 Synopsis For patients with rheumatic MS, TTE is the initial di- agnostic test to determine the severity of the stenosis Table 16. Stages of MS Stage Definition Valve Anatomy Valve Hemodynamics Hemodynamic Consequences Symptoms A At risk of MS Mild valve doming during diastole Normal transmitral flow velocity None None B Progressive MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Increased transmitral flow velocities Mitral valve area >1.5 cm2 Diastolic pressure half-time Mild to moderate LA enlargement Normal pulmonary pressure at rest None C Asymptomatic severe MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Mitral valve area 1.5 cm2 Diastolic pressure half-time Severe LA enlargement Elevated PASP >50 mm Hg None D Symptomatic severe MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Mitral valve area 1.5 cm2 Diastolic pressure half-time Severe LA enlargement Elevated PASP >50 mm Hg Decreased exercise tolerance Exertional dyspnea The transmitral mean pressure gradient should be obtained to further determine the hemodynamic effect of the MS and is usually >5 mm Hg to 10 mm Hg in severe MS; however, because of the variability of the mean pressure gradient with heart rate and forward flow, it has not been included in the criteria for severity.


Stages of MS Stage Definition Valve Anatomy Valve Hemodynamics Hemodynamic Consequences Symptoms A At risk of MS Mild valve doming during diastole Normal transmitral flow velocity None None B Progressive MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Increased transmitral flow velocities Mitral valve area >1.5 cm2 Diastolic pressure half-time Mild to moderate LA enlargement Normal pulmonary pressure at rest None C Asymptomatic severe MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Mitral valve area 1.5 cm2 Diastolic pressure half-time Severe LA enlargement Elevated PASP >50 mm Hg None D Symptomatic severe MS Rheumatic valve changes with commissural fusion and diastolic doming of the mitral valve leaflets Planimetered mitral valve area Mitral valve area 1.5 cm2 Diastolic pressure half-time Severe LA enlargement Elevated PASP >50 mm Hg Decreased exercise tolerance Exertional dyspnea The transmitral mean pressure gradient should be obtained to further determine the hemodynamic effect of the MS and is usually >5 mm Hg to 10 mm Hg in severe MS; however, because of the variability of the mean pressure gradient with heart rate and forward flow, it has not been included in the criteria for severity. LA indicates left atrial; MS, mitral stenosis; and PASP, pulmonary artery systolic pressure. CLINICAL STATEMENTS AND GUIDELINES and suitability for PMBC. If PMBC is being considered, a TEE can further evaluate the presence and severity of concomitant MR and rule out LA thrombus. Recommendation-Specific Supportive Text 1.


If PMBC is being considered, a TEE can further evaluate the presence and severity of concomitant MR and rule out LA thrombus. Recommendation-Specific Supportive Text 1. TTE is the imaging modality of choice to eluci- date the anatomy and functional significance of rheumatic MS.1 The parasternal long-axis window can identify the characteristic diastolic doming of the mitral valve, whereas short-axis scanning will demonstrate commissural fusion and allow planimetry of the mitral orifice. Use of 3D echocardiography (either TTE or TEE) pro- vides greater accuracy of measurement of the mitral valve area.7,8 Doppler echocardiography mean transvalvular gradients always should be reported with heart rate because a high heart rate will result in overestimation of stenosis severity.9 Estimated RV systolic pressure is obtained from the TR velocity. Concomitant MR should be quan- tified, along with any other valve lesions (Section 7.3.1.1). Several scores are available for evalua- tion of mitral valve morphology and prediction of outcomes with PMBC, and these scores consider valve thickening, mobility, and calcification with subvalvular chordal fusion.10,11 Characterization of commissural morphology and calcification fur- ther predicts suitability for commissurotomy.2,3,12,13 Additional assessment of rheumatic MS includes the mitral pressure half-time, with acknowledg- ment that this parameter is also affected by LA and LV compliance. If the mean gradient does not match the valve area, other methods, such as the continuity equation, should be considered.14 2. TEE offers excellent visualization of the mitral valve and LA and is an alternative approach to assessment of rheumatic MS in patients whose TTE images are technically limited.


TEE offers excellent visualization of the mitral valve and LA and is an alternative approach to assessment of rheumatic MS in patients whose TTE images are technically limited. In patients being considered for PMBC, a TEE can rule out LA cavity and appendage thrombi.4 6 TEE also is use- ful for evaluation of MR severity in patients being considered for PMBC because shadowing of the LA on TTE may result in underestimation of MR severity. MR that is more than mild is a contrain- dication to PMBC. 6.2.1.2. Diagnostic Testing: Changing Signs or Symptoms Patients with an established diagnosis of rheumatic MS may experience a change in symptoms attributable to disease progression related to recurrent episodes of rheu- matic fever leading to further valve damage; progressive narrowing of the mitral valve attributable to leaflet fibro- sis and thickening; progressive pulmonary hypertension; or worsening of concomitant MR or other valve lesions. In addition, symptom status may change with no change in rheumatic MS severity because of an increased he- modynamic load (for example, because of pregnancy), new-onset or rapid AF, fever, anemia, or hyperthyroid- ism, or hemodynamic shifts in the perioperative period of patients undergoing noncardiac surgery. In such cases, a repeat TTE examination can quantify the mitral valve gradient and area, as well as other parameters that may contribute to a change in symptoms. 6.2.1.3. Diagnostic Testing: Routine Follow-Up Rheumatic MS is a slowly progressive disease, char- acterized by a prolonged latent phase between the initial rheumatic illness and the development of valve The latent phase is an interval typically measured in decades in high-income countries but in considerably shorter periods in low- to middle-in- come countries, likely because of recurrent carditis.


Diagnostic Testing: Routine Follow-Up Rheumatic MS is a slowly progressive disease, char- acterized by a prolonged latent phase between the initial rheumatic illness and the development of valve The latent phase is an interval typically measured in decades in high-income countries but in considerably shorter periods in low- to middle-in- come countries, likely because of recurrent carditis. Once mild stenosis has developed, further narrow- ing is slow (decrease in valve area of 0.1 cm2 per year on average), although the rate of progression is highly variable.3 Importantly, progressive enlarge- ment of the RV and a rise in RV systolic pressure can be observed, even in the absence of a decrease in mitral valve area. Accordingly, repeat TTE at intervals dictated by valve area is an important aspect of dis- ease management, even in patients without symp- toms (Table 4). 6.2.1.4. Diagnostic Testing: Cardiac Catheterization In the contemporary era, assessment of MS and associ- ated lesions can be obtained in most patients by TTE, occasionally supplemented by TEE. However, there will be a subset of patients with nondiagnostic studies or for whom there is discordance between the clinical and echocardiographic findings. In older patients, other fac- tors contributing to symptoms may need to be further sorted out, such as concomitant diastolic dysfunction, LA noncompliance, or intrinsic pulmonary vascular dis- ease. Cardiac catheterization is useful in these patients to further characterize rheumatic MS hemodynamics and etiology of symptoms, as it can measure absolute pressures in the LV, LA, and pulmonary circulation at rest and with exercise.


Cardiac catheterization is useful in these patients to further characterize rheumatic MS hemodynamics and etiology of symptoms, as it can measure absolute pressures in the LV, LA, and pulmonary circulation at rest and with exercise. Although the mean pulmonary artery wedge pressure is an acceptable substitute for mean LA pressure, the LV to pulmonary wedge gra- dient will overestimate the true transmitral gradient because of phase delay and delayed transmission of Nonetheless, the absolute mean pulmonary artery wedge pressure and its relationship to the LV diastolic pressure and pulmonary artery pres- sure can provide useful clinical information. The Gorlin equation can be used for an independent calculation of mitral valve area.2,3 CLINICAL STATEMENTS AND GUIDELINES 6.2.1.5. Diagnostic Testing: Exercise Testing Recommendation for Diagnostic Testing: Exercise Testing in Patients With Rheumatic MS COR LOE Recommendation In patients with rheumatic MS and a discrepancy between resting echocardiographic findings and clinical symptoms, exercise testing with Doppler or invasive hemodynamic assessment is recommended to evaluate symptomatic response, exercise capacity, and the response of the mean mitral gradient and pulmonary artery pressure.1 5 Synopsis Exercise testing with either Doppler echocardiography or cardiac catheterization is important when the resting hemodynamics do not match the clinical symptoms in patients with rheumatic MS. Recommendation-Specific Supportive Text 1. Exercise testing with hemodynamics is helpful in the management of rheumatic MS when a patient s symptoms seem significantly greater than or less than would be expected from TTE. Results have been published in which both exercise and dobu- tamine were used with Doppler echocardiography, although exercise is preferred in general as the more Most experience is with tread- mill exercise, with images and Doppler obtained immediately after stress, but bicycle exercise allows data acquisition at various stages of exercise.


Results have been published in which both exercise and dobu- tamine were used with Doppler echocardiography, although exercise is preferred in general as the more Most experience is with tread- mill exercise, with images and Doppler obtained immediately after stress, but bicycle exercise allows data acquisition at various stages of exercise. Bicycle exercise testing during cardiac catheterization can also be performed for direct measurements of pul- monary artery wedge pressure and pulmonary pres- sures at rest and with exercise. Simple functional capacity helps to quantify the patient s symptoms. Changes in valve gradient should be measured, as well as the estimated pulmonary artery systolic pressure. If the patient cannot exercise, increasing the heart rate with maneuvers such as leg lifts or sit-ups may be useful. 6.2.2. Medical Therapy Recommendations for Medical Therapy in Patients With Rheumatic MS Referenced studies that support the recommendations are summarized in Online Data Supplement 20. COR LOE Recommendations In patients with rheumatic MS and 1) AF, 2) a prior embolic event, or 3) an LA thrombus, anticoagulation with a VKA is indicated.1 7 In patients with rheumatic MS and AF with a rapid ventricular response, heart rate control can be beneficial.8 In patients with rheumatic MS in normal sinus rhythm with symptomatic resting or exertional sinus tachycardia, heart rate control can be beneficial to manage symptoms.9 15 Synopsis In patients with rheumatic MS and AF, anticoagulation decreases the incidence of thromboembolic events. An- ticoagulation can also decrease the incidence of throm- boembolic events in patients with rheumatic MS if there has been a prior embolic event or if an LA throm- bus was visualized.


An- ticoagulation can also decrease the incidence of throm- boembolic events in patients with rheumatic MS if there has been a prior embolic event or if an LA throm- bus was visualized. In symptomatic patients with MS who are in normal sinus rhythm and have tachycardia, heart rate control with beta blockers, calcium channel blockers, or ivabradine will lengthen the diastolic fill- ing period and lower LA pressure. However, routine use of heart rate control for patients with rheumatic MS in normal sinus rhythm in the absence of tachycardia may result in chronotropic incompetence, preventing an ad- equate cardiac output response to exercise. Recommendation-Specific Supportive Text 1. Patients with rheumatic MS with AF and prior embolic events are at high risk of arterial embo- lization when AF or an LA thrombus is present. Treatment with VKA anticoagulation will decrease the incidence of these events.3 7,16 It is controver- sial whether long-term anticoagulation should be given to patients with rheumatic MS in normal sinus rhythm on the basis of LA enlargement or spontaneous contrast on TEE.17,18 Patients with very large left atria have more spontaneous echo- cardiographic contrast and lower LA appendage which have been associated with a higher rate of embolic events, but no data directly link large left atria to embolic events. Non vitamin K oral anticoagulation has not been studied in patients with rheumatic MS, and these patients were excluded from the randomized AF trials.


Non vitamin K oral anticoagulation has not been studied in patients with rheumatic MS, and these patients were excluded from the randomized AF trials. In addition to the much higher risk of embo- lization with rheumatic valve disease as compared with other causes of valve disease, there is con- cern that rheumatic disease also affects the atrial muscle, resulting in an increased risk of blood flow stasis and thrombosis in the body of the LA, as well as the LA appendage.1 Further studies are required to confirm these findings.2 2. Patients with rheumatic MS are prone to develop- ing atrial arrhythmias specifically AF. Significant detrimental hemodynamic consequences may be associated with the acute development of AF, pri- marily from the rapid ventricular response, which shortens the diastolic filling period and increases The treatment of acute AF consists of anticoagulation and control of the heart rate response with negative dromotropic agents. If the rate cannot be adequately controlled with medica- tions, cardioversion may be necessary to improve hemodynamics. In the stable patient, the decision CLINICAL STATEMENTS AND GUIDELINES for rate control versus rhythm control is dependent on multiple factors, including the duration of AF, hemodynamic response to AF, LA size, prior epi- sodes of AF, and history of embolic events. It is more difficult to achieve rhythm control in patients with rheumatic MS because the rheumatic process itself may lead to progressive fibrosis and enlargement of the atria, fibrosis of the internodal and interatrial tracts, and damage to the sinoatrial node. 3. The use of negative dromotropic agents for the treatment of symptoms in patients with rheumatic MS in normal sinus rhythm has been controversial.


The use of negative dromotropic agents for the treatment of symptoms in patients with rheumatic MS in normal sinus rhythm has been controversial. Although a reduction in heart rate and prolonga- tion of the diastolic filling period will decrease the transmitral mean gradient, studies have shown that treatment with beta blockade may not improve or may even decrease exercise tolerance, most likely because of the limitation of the cardiac output attributable to a limited stroke volume and Nonetheless, there are now several randomized trials that have exam- ined beta blockers and ivabradine in patients with rheumatic MS and have shown that either drug can increase exercise duration and improve symp- To explain these differences, the earlier trials that found no benefit of beta blockers were performed in older patients with underlying chro- notropic incompetence, whereas the randomized trials showing benefit were performed primarily in younger patients with higher resting and exercise- induced heart rates. Thus, the use of beta blockers or ivabradine to improve symptoms may be effec- tive only in patients who do not have underlying chronotropic incompetence. When medical ther- apy is considered for relief of symptoms in patients with rheumatic MS, it must be remembered that intervention with PMBC relieves symptoms in those patients with an appropriate valve morphology. Recommendations for Intervention for Rheumatic MS Referenced studies that support the recommendations are summarized in Online Data Supplements 21 to 24.