The rate of warfarin embryopathy is reduced (<3%) but not eliminated if the daily dose of warfarin is 5 mg/d.3,6.16,18,23,25,36,37 In most women, the effective dose of warfarin typically does not vary significantly during pregnancy.38 For women who require a dose 5 mg/d, continua- tion of low-dose warfarin throughout pregnancy poses the lowest combined risk to mother and The number of reported pregnancies on low-dose warfarin is relatively small, and not all publications have found improved fetal out- comes on low-dose warfarin,11 so caution should be exercised until more data are available. 9. If warfarin is taken in doses >5 mg/d during the first trimester of pregnancy, there is a >30% risk of fetal loss or embryopathy. For women who require >5 mg/d to maintain a therapeutic INR, replac- ing warfarin with dose-adjusted LWMH during the first trimester reduces fetal loss.3,6,10,15,16,23,39,40 While the patient is taking LMWH, anti-Xa levels should be monitored at least weekly and the dose adjusted accordingly. Fixed dosing is never appro- priate, because it is associated with high maternal morbidity and mortality.41 After the first trimester, the fetal toxicity of warfarin is substantially lower, so switching back to warfarin for the second and third trimesters results in a reasonable balance between maternal safety and fetal safety. 10. In regions where LMWH is unavailable or cost-pro- hibitive, or if anti-Xa levels cannot be monitored, continuous infusion of UFH can be used as an alternative to LMWH during the first trimester for women who require a warfarin dose of >5 mg/d.37 If UFH is used during the first trimester, the dose should be adjusted to maintain an aPTT 2 times control.


In regions where LMWH is unavailable or cost-pro- hibitive, or if anti-Xa levels cannot be monitored, continuous infusion of UFH can be used as an alternative to LMWH during the first trimester for women who require a warfarin dose of >5 mg/d.37 If UFH is used during the first trimester, the dose should be adjusted to maintain an aPTT 2 times control. There are several disadvantages to UFH compared with LMWH: Women are at greater risk for line infections, osteoporosis, and hepa- rin-induced thrombocytopenia, so UFH should be reserved for situations where dose-adjusted LMWH is not feasible.10 Intermittent subcutane- ous injection of UFH is not an acceptable alterna- tive because it is associated with prohibitive rates of valve thrombosis.42 UFH is associated with very high rates of valve thrombosis, stroke, and death in pregnant women with mechanical heart valves during the second and third trimesters.3,4,43 11. In carefully selected women with thrombosis of a mechanical heart valve during pregnancy, low- dose, slow-infusion, tissue-type plasminogen acti- vator (tPA) can be an alternative to surgical valve replacement. Women who are optimal candidates are hemodynamically stable and have obstructive prosthetic valve thrombosis, valve thrombosis with embolic complications, or nonobstructive valve thrombosis with a thrombus >10 mm.44 Given the high rates of fetal loss with cardiac surgery during pregnancy, thrombolysis is an attractive alterna- tive for appropriately selected, hemodynamically stable women with mechanical valve thrombosis. 12. Although the teratogenicity of warfarin is high- est during the first trimester, there is still a risk of pregnancy loss or fetal hemorrhage when warfarin is taken during the second and third trimesters. Therefore, after appropriate counsel- ing, some women may choose to avoid warfarin entirely throughout pregnancy. For these women, dose-adjusted LMWH throughout pregnancy is the safest alterative.


For these women, dose-adjusted LMWH throughout pregnancy is the safest alterative. LMWH throughout preg- nancy is associated with a higher rate of throm- botic complications than warfarin. However, many of the thrombotic events occur when LMWH is administered improperly or monitored erratically or if patients are nonadherent.8,14,15,39 When administered and monitored meticulously, LMWH can be safe.12 Effective dose monitoring includes weekly measurements of anti factor Xa levels, with additional monitoring after dose Measurement of trough levels to maintain a trough Xa level >0.6 IU/mL may help women maintain therapeutic anticoagulation while on LMWH.12,13 13. When warfarin is taken at a dose 5 mg/d, the risk of warfarin embryopathy is reduced but not entirely eliminated. Some women, after discussion with their physicians, may choose to substitute CLINICAL STATEMENTS AND GUIDELINES LMWH for low-dose warfarin during the first tri- mester to eliminate the risk of warfarin embry- opathy. This choice improves fetal outcomes but at the cost of increased maternal thrombotic 14. Low-dose aspirin is regarded as safe during preg- nancy and can be continued in women with mechanical heart valves if needed for other indi- cations. There may be noncardiac indications for aspirin in pregnant women, such as prevention of 15. Studies using subcutaneous LMWH at a fixed dose without monitoring of anti-Xa levels in preg- nant patients with mechanical prostheses found a high risk of valve thrombosis and maternal death. In pregnant women treated with dose-adjusted LMWH, the dose of LMWH required to maintain an adequate anti-Xa level 4 to 6 hours after admin- istration increases throughout pregnancy.9,15,39,41 16.


In pregnant women treated with dose-adjusted LMWH, the dose of LMWH required to maintain an adequate anti-Xa level 4 to 6 hours after admin- istration increases throughout pregnancy.9,15,39,41 16. A randomized clinical trial of dabigatran in non- pregnant patients with mechanical heart valves showed an increased rate of thromboembolic and bleeding complications with dabigatran com- pared with warfarin.45 The safety and effective- ness of anti-Xa direct oral anticoagulants has not been established in patients with mechanical heart valves. Additionally, the safety of anti-Xa direct oral anticoagulants in pregnancy is unknown.30 32 17. Anti-Xa direct oral anticoagulants have not been shown to be safe in patients with mechani- cal heart valves, so they should not be used in pregnancy. 14. SURGICAL CONSIDERATIONS Concomitant surgical procedures may be appropriate at the time of intervention for VHD in the interest of re- ducing periprocedural risk (eg, treatment of significant CAD) or for optimizing long-term outcomes (eg, adding a maze procedure for AF treatment). Consideration may also be given to treating moderate disease in the inter- est of obviating the need for subsequent reoperation for example, treating aortic dilation in the presence of a BAV. This is particularly true when one can anticipate particular difficulty in the conduct of a subsequent re- operation, as may be the case for mitral valve interven- tion after AVR or in a patient with prior mediastinal ir- radiation for whom postoperative adhesions are often severe. The benefits of such concomitant procedures must be balanced against the potential impact on peri- procedural risk due to added complexity. In particular, interventions that add significantly to aortic cross-clamp time may be discouraged in patients with poor LV func- tion or significant pulmonary hypertension. Prolonga- tion of cardiopulmonary bypass time may increase renal injury, particularly among those with preexisting renal dysfunction.


Prolonga- tion of cardiopulmonary bypass time may increase renal injury, particularly among those with preexisting renal dysfunction. More complex procedures may also pose a particular risk in patients with fragile tissue integrity or general frailty, and the additional dissection that may be required in a reoperative setting may tip the balance away from imposing additional risk by performing con- comitant procedures. 14.1. Evaluation and Management of CAD in Patients With VHD 14.1.1. Management of CAD in Patients Undergoing TAVI Recommendations for Management of CAD in Patients Undergoing TAVI Referenced studies that support the recommendations are summarized in Online Data Supplement 45. COR LOE Recommendations In patients undergoing TAVI, 1) contrast- enhanced coronary CT angiography (in patients with a low pretest probability for CAD) or 2) an invasive coronary angiogram is recommended to assess coronary anatomy and guide revascularization. In patients undergoing TAVI with significant left main or proximal CAD with or without angina, revascularization by PCI before TAVI is In patients with significant AS and significant CAD (luminal reduction >70% diameter, fractional flow reserve <0.8, instantaneous wave-free ratio <0.89) consisting of complex bifurcation left main and/or multivessel CAD with a SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score >33, SAVR and CABG are reasonable and preferred over TAVI and PCI.3,4 Synopsis CAD is common among patients presenting with AS, particularly the elderly. In the surgical experience, con- comitant revascularization impacts long-term survival in a favorable way and is commonplace, as is preoperative coronary imaging. Similarly, there is an argument to be made for coronary revascularization among patients un- dergoing TAVI, although the effects on late outcomes are less well defined and may not be the same as for SAVR, given the different demographics and comorbid- ities of the TAVI versus SAVR populations.


Similarly, there is an argument to be made for coronary revascularization among patients un- dergoing TAVI, although the effects on late outcomes are less well defined and may not be the same as for SAVR, given the different demographics and comorbid- ities of the TAVI versus SAVR populations. Nonetheless, at this point, diagnostic imaging and consideration of revascularization are appropriate (Figure 19). Recommendation-Specific Supportive Text 1. The prevalence of CAD in patients with severe AS ranges between 15% and 80%.5 and varies depending on the definition of CAD used and the The impact of CAD on outcomes is controversial,7,8 although one report CLINICAL STATEMENTS AND GUIDELINES singled out severe CAD (defined by a SYNTAX score >22) and incomplete revascularization as the only independent predictors of death after TAVI.9 Assessment of the coronary anatomy is important in patients with severe AS to rule out obstructive CAD. Invasive coronary angiography is commonly performed. In patients with a low pretest prob- ability of CAD, contrast-enhanced coronary CT has an excellent negative predictive In patients with normal renal function, an option is to combine contrast-enhanced coro- nary CT angiography with CT assessment of the peripheral circulation and heart structure as an ini- tial imaging test, reserving coronary angiography for the event that the contrast-enhanced coronary CT angiography is nondiagnostic or significant CAD is found. Invasive functional assessment of coronary lesions in TAVI candidates by using frac- tional flow reserve or instantaneous wave-free ratio is safe and feasible.13 15 Instantaneous wave- free ratio may be particularly attractive because it does not require the administration of a vaso- dilator and is less influenced by the effect of the stenotic aortic valve, although randomized clinical trials validating the utility of both are ongoing. 2.


Invasive functional assessment of coronary lesions in TAVI candidates by using frac- tional flow reserve or instantaneous wave-free ratio is safe and feasible.13 15 Instantaneous wave- free ratio may be particularly attractive because it does not require the administration of a vaso- dilator and is less influenced by the effect of the stenotic aortic valve, although randomized clinical trials validating the utility of both are ongoing. 2. There are no RCTs to inform clinical practice on the benefits and timing of PCI in patients under- going TAVI. The decision to perform PCI is there- fore driven by myriad clinical factors (eg, presence of angina or ischemia, ability to take dual-anti- platelet therapy before TAVI) and anatomic fac- tors (eg, lesion location and complexity, technical feasibility) and should be individualized. Overall, nonrandomized studies suggest that PCI before TAVI is safe and feasible,1 even in patients with left main disease.2 Conceptually, pre-TAVI PCI also allows a safer procedure and circumvents future post-TAVI PCI, which can be occasionally challenging. Staged PCI before TAVI is a common strategy in clinical practice and is associated with lower contrast volume and renal failure than is the strategy of TAVI with concomitant PCI,1 although the timing of pre-TAVI PCI remains controversial. 3. Multiple RCTs have been conducted to define the optimal management of CAD in patients with- out VHD based on the SYNTAX score to define Figure 19. Management of CAD in patients undergoing valve interventions. Colors correspond to Table 2. *Including men age >40 years and postmenopausal women. AVR indicates aortic valve replacement; CAD, coronary artery disease; CABG, coronary artery bypass graft; CT, computed tomography; LV, left ventricular; MR, mitral regurgitation; PCI, percutaneous coronary intervention; SYNTAX, Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery; and TAVI, transcatheter aortic valve implantation.


AVR indicates aortic valve replacement; CAD, coronary artery disease; CABG, coronary artery bypass graft; CT, computed tomography; LV, left ventricular; MR, mitral regurgitation; PCI, percutaneous coronary intervention; SYNTAX, Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery; and TAVI, transcatheter aortic valve implantation. CLINICAL STATEMENTS AND GUIDELINES those least amenable to percutaneous treatment. Subsets of patients shown to have superior free- dom from major adverse cardiac events include those with complex left main disease and those with a SYNTAX score >33.3 Accordingly, a surgical approach is reasonable in this subset of patients. Among SAVR patients, revascularization for those with significant CAD (>50% stenosis) has been shown to impact late risk of mortality favorably.4 14.1.2. Management of CAD in Patients Undergoing Valve Surgery Recommendations for Management of CAD in Patients Undergoing Valve Surgery Referenced studies that support the recommendations are summarized in Online Data Supplement 45. COR LOE Recommendations In patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, history of CAD, or coronary risk factors (including men >40 years of age and postmenopausal women), invasive coronary angiography is indicated before valve In patients with chronic severe secondary MR, invasive coronary angiography should be performed as part of the evaluation.9 11 In selected patients with a low to intermediate pretest probability of CAD, contrast-enhanced coronary CT angiography is reasonable to exclude the presence of significant obstructive In patients undergoing valve repair or replacement with significant proximal CAD ( 70% reduction in luminal diameter in major coronary arteries or 50% reduction in luminal diameter in the left main coronary artery and/or physiologically significance), CABG is reasonable for selective patients.19,20 Synopsis Coronary imaging in the setting of VHD defines anat- omy that may be at risk during surgery or interven- tion.


COR LOE Recommendations In patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, history of CAD, or coronary risk factors (including men >40 years of age and postmenopausal women), invasive coronary angiography is indicated before valve In patients with chronic severe secondary MR, invasive coronary angiography should be performed as part of the evaluation.9 11 In selected patients with a low to intermediate pretest probability of CAD, contrast-enhanced coronary CT angiography is reasonable to exclude the presence of significant obstructive In patients undergoing valve repair or replacement with significant proximal CAD ( 70% reduction in luminal diameter in major coronary arteries or 50% reduction in luminal diameter in the left main coronary artery and/or physiologically significance), CABG is reasonable for selective patients.19,20 Synopsis Coronary imaging in the setting of VHD defines anat- omy that may be at risk during surgery or interven- tion. Given their similar demographic profiles, CAD and VHD frequently coexist, and in the case of sec- ondary MR they have a pathophysiological link. Re- vascularization, in turn, can impact periprocedural risk or long-term outcome. In the case of secondary MR, revascularization may positively impact the valve dis- ease via reverse remodeling of the LV. In the surgical setting, where repeat intervention is at high cost to the patient, efforts are typically made to correct all surgically correctable disease present at the index op- eration. Accordingly, an aggressive approach to revas- cularization is appropriate. In the setting of percutane- ous interventions, however, the option of sequential interventions with interval tests of improvement may be appropriate. In either case, less invasive imaging via contrast-enhanced coronary CT angiography is in- creasingly adopted. Recommendation-Specific Supportive Text 1.


In either case, less invasive imaging via contrast-enhanced coronary CT angiography is in- creasingly adopted. Recommendation-Specific Supportive Text 1. CAD is frequently present among patients with and may contribute to angina pecto- ris among those with aortic valve disease.3,4 Knowledge of coronary anatomy contributes to risk stratification, in addition to directing concom- itant coronary revascularization. There is a very low prevalence of CAD among men <40 years of age and premenopausal women with no athero- sclerotic risk factors2,5 7 or history of mediastinal 2. Functional MR occurs in patients with structur- ally normal valve leaflets and chordae because of LV dysfunction, including regional wall motion abnormalities or global dilation with displace- ment of the papillary muscles, leaflet tethering, annular dilation, and decreased closing forces from reduced contractility.9 11 Because this LV dys- function may be attributable to CAD and accom- panying myocardial ischemia, the assessment of coronary anatomy status is necessary to complete the diagnosis and allow evaluation of revascular- ization options. 3. Contrast-enhanced coronary CT angiography is an alternative to coronary angiography among selected patients who are at low to intermediate pretest probability of CAD before valve surgery.12 This does not include patients who have active symptoms of angina, those with documented ischemia, or those with a prior history of CAD, all of whom should have selective coronary angi- ography. Recent studies, most often in the set- ting of a pre-TAVI evaluation, have demonstrated diagnostic sensitivity of >90%, specificity of 60% and accuracy of >90%.21 Contrast- enhanced coronary CT angiography may be safer than coronary angiography in selected patient populations, such as those with IE and vegeta- tions on the aortic valve.


Recent studies, most often in the set- ting of a pre-TAVI evaluation, have demonstrated diagnostic sensitivity of >90%, specificity of 60% and accuracy of >90%.21 Contrast- enhanced coronary CT angiography may be safer than coronary angiography in selected patient populations, such as those with IE and vegeta- tions on the aortic valve. However, a positive con- trast-enhanced coronary CT angiogram, defined as the presence of epicardial CAD, requires con- firmation with invasive coronary angiography to establish the need for and extent of CABG. The risk of radiation exposure and renal failure because of the contrast injection should be taken into consideration. 4. The presence of uncorrected CAD has been shown to negatively impact both perioperative22,23 and late outcomes of surgery for VHD.19 . Accordingly, concomitant CABG has been favored. These stud- ies of concomitant CABG at the time of valve surgery have demonstrated little or no adverse impact on the acute perioperative mortality rate, despite increased cross-clamp and cardiopulmo- nary bypass times. Moreover, combined CABG CLINICAL STATEMENTS AND GUIDELINES and valve surgery reduces the rate of perioperative myocardial infarction, and incomplete revascular- ization is associated with greater postoperative LV systolic dysfunction and a reduced survival rate after surgery as compared with patients who receive complete revascularization. For more than a decade, improved myocardial preservation tech- niques have been associated with reduced overall operative mortality rates, and it has become stan- dard practice to bypass all significant coronary artery stenoses, when possible, in patients under- going valve surgery. In patients with a significant stenosis of the left anterior descending artery, a left internal thoracic artery graft should be used if possible. Hybrid PCI followed by surgical valve repair or replacement has been reported favor- ably but is restricted to patients at high risk with a combined surgical approach.20 14.2.


Hybrid PCI followed by surgical valve repair or replacement has been reported favor- ably but is restricted to patients at high risk with a combined surgical approach.20 14.2. Intervention for AF in Patients With VHD Recommendations for Intervention for AF in Patients With VHD Referenced studies that support the recommendations are summarized in Online Data Supplement 46. COR LOE Recommendations In patients with VHD and AF for whom surgical intervention is planned, the potential symptomatic benefits and additional procedural risks of adjunctive arrhythmia surgery at the time of cardiac valvular surgery should be discussed with the patient.1 11 For symptomatic patients with paroxysmal or persistent AF who are undergoing valvular surgery, surgical pulmonary vein isolation or a maze procedure can be beneficial to reduce symptoms and prevent recurrent For patients with AF or atrial flutter who are undergoing valve surgery, LA appendage ligation/excision is reasonable to reduce the risk of thromboembolic events.16 19 In patients undergoing LA surgical ablation of atrial arrhythmias and/or LA appendage ligation/excision, anticoagulation therapy is reasonable for at least 3 months after the 3: Harm B-NR For patients without atrial arrhythmias who are undergoing valvular surgery, LA appendage occlusion/exclusion/amputation is potentially Synopsis For patients undergoing valve surgery with symptom- atic AF or atrial flutter, concomitant maze procedure with or without atrial appendage occlusion/exclusion/ amputation is a proven treatment for the atrial arrhyth- mia but requires postoperative anticoagulation for at least 3 months after the procedure (Figure 20). Recommendation-Specific Supportive Text 1.


COR LOE Recommendations In patients with VHD and AF for whom surgical intervention is planned, the potential symptomatic benefits and additional procedural risks of adjunctive arrhythmia surgery at the time of cardiac valvular surgery should be discussed with the patient.1 11 For symptomatic patients with paroxysmal or persistent AF who are undergoing valvular surgery, surgical pulmonary vein isolation or a maze procedure can be beneficial to reduce symptoms and prevent recurrent For patients with AF or atrial flutter who are undergoing valve surgery, LA appendage ligation/excision is reasonable to reduce the risk of thromboembolic events.16 19 In patients undergoing LA surgical ablation of atrial arrhythmias and/or LA appendage ligation/excision, anticoagulation therapy is reasonable for at least 3 months after the 3: Harm B-NR For patients without atrial arrhythmias who are undergoing valvular surgery, LA appendage occlusion/exclusion/amputation is potentially Synopsis For patients undergoing valve surgery with symptom- atic AF or atrial flutter, concomitant maze procedure with or without atrial appendage occlusion/exclusion/ amputation is a proven treatment for the atrial arrhyth- mia but requires postoperative anticoagulation for at least 3 months after the procedure (Figure 20). Recommendation-Specific Supportive Text 1. Surgical ablations, including pulmonary vein isola- tion and atrial maze at the time of valvular surgery and other open cardiac operations, have been dem- onstrated in multiple studies to reduce the recur- rence of AF.5 11 Various approaches to pulmonary vein isolation and modified left atrial, right atrial, and bi-atrial maze procedures entail longer proce- dure times, with higher risks of operative complica- tions and permanent pacemaker implantation.1 4 These adverse outcomes, coupled with the lack of large randomized trial data confirming mortality and stroke benefit, should be examined with the patient. 2.


Surgical ablations, including pulmonary vein isola- tion and atrial maze at the time of valvular surgery and other open cardiac operations, have been dem- onstrated in multiple studies to reduce the recur- rence of AF.5 11 Various approaches to pulmonary vein isolation and modified left atrial, right atrial, and bi-atrial maze procedures entail longer proce- dure times, with higher risks of operative complica- tions and permanent pacemaker implantation.1 4 These adverse outcomes, coupled with the lack of large randomized trial data confirming mortality and stroke benefit, should be examined with the patient. 2. The atrial maze procedure properly refers to a specific bi-atrial lesion set performed by a cut- and-sew technique or with tissue ablation tech- nologies, including cryoenergy or radiofrequency. Of note, the term maze is often loosely applied to many variations of the original lesion set that may be less effective. When performed with com- plete encirclement of the pulmonary veins, most commonly in combination with mitral valve repair or replacement but also with aortic or tricuspid valve procedures, the maze procedure affords freedom from AF with an efficacy similar to that of catheter-based approaches.1,2,12 15 Patients undergoing combined atrial maze procedure at the time of operation for MR have a greater free- dom from recurrent AF than those who did not have a maze procedure.11 In patients with recur- rent AF who are to undergo surgical correction of MR, catheter ablation is best deferred in favor of a concomitant surgical maze, thereby avoiding the potential complications of a catheter maze and a second procedure for the patient. 3.


When performed with com- plete encirclement of the pulmonary veins, most commonly in combination with mitral valve repair or replacement but also with aortic or tricuspid valve procedures, the maze procedure affords freedom from AF with an efficacy similar to that of catheter-based approaches.1,2,12 15 Patients undergoing combined atrial maze procedure at the time of operation for MR have a greater free- dom from recurrent AF than those who did not have a maze procedure.11 In patients with recur- rent AF who are to undergo surgical correction of MR, catheter ablation is best deferred in favor of a concomitant surgical maze, thereby avoiding the potential complications of a catheter maze and a second procedure for the patient. 3. A reduction in thromboembolism has been demon- strated by LA ligation/excision, although the ben- efit is less evident in those patients who maintain Discontinuation of oral antico- agulation has also been associated with late stroke, highlighting that the LA appendage is not the exclusive source of all thrombi in patients with AF. Therefore, there are insufficient data to support rou- tine discontinuation of anticoagulation in patients with AF who are undergoing LA ligation/excision. 4. Ablation with radiofrequency/cryoenergy or atrial suture lines provides an endocardial thrombo- genic milieu, and in addition, surgical LA append- age occlusion can be incomplete.20 22 In the context of atrial arrhythmias, manipulation of the LA, and post-cardioversion/defibrillation stun- ning, atrial mechanical function can be slow to recover. The resultant stasis and thrombogenic endocardial lesions provide a nidus for thrombus development, placing this group of patients at CLINICAL STATEMENTS AND GUIDELINES risk of stroke.


The resultant stasis and thrombogenic endocardial lesions provide a nidus for thrombus development, placing this group of patients at CLINICAL STATEMENTS AND GUIDELINES risk of stroke. Nonrandomized registry data indi- cate that stroke in the first 3 months after cath- eter ablation is driven chiefly by discontinuation of oral anticoagulation.21 Both US and European guideline statements on catheter ablation rec- ommend (on the basis of expert opinion alone) anticoagulation during this periprocedural phase while the endocardium heals from the ablation. By analogy, patients who have had surgical abla- tion should be managed with at least 3 months of anticoagulation, regardless of their CHA2 - VASc risk score. Subsequent anticoagulation should be based on evaluation of arrhythmia recurrence in the context of their CHA2 -VASc score. Anticoagulation should also be given for at least 3 months after LA ligation/excision. For patients receiving bioprostheses, a VKA would be the preferred method of anticoagulation for the first 3 months (see Section 2.4.3). 5. A higher incidence of early AF in all patients after LA appendage occlusion/exclusion has been dem- Together with the recognition that most patients do not develop AF after surgery, pre- emptive LA appendage occlusion in patients with- out preexisting AF cannot be recommended. No stroke benefit has been observed in this group of patients with no preemptive history of AF. 15. NONCARDIAC SURGERY IN PATIENTS WITH VHD 15.1. Diagnosis of Patients With VHD Undergoing Noncardiac Surgery Recommendation for Diagnosis in Patients With VHD Undergoing Noncardiac Surgery COR LOE Recommendation In patients with clinically suspected moderate or greater degrees of valvular stenosis or regurgitation who are undergoing noncardiac surgery, preoperative echocardiography is recommended. Synopsis The evaluation of patients with VHD who are undergo- ing noncardiac surgery is dependent on the type and Figure 20. Intervention for AF in patients with VHD.


Synopsis The evaluation of patients with VHD who are undergo- ing noncardiac surgery is dependent on the type and Figure 20. Intervention for AF in patients with VHD. Colors correspond to Table 2. AF indicates atrial fibrillation; LA, left atrial, and VHD, valvular heart disease. CLINICAL STATEMENTS AND GUIDELINES severity of VHD, including 1) the presence or absence of symptoms, 2) the severity of VHD, 3) the risk of noncar- diac intervention, 4) the response of the LV and/or RV to the overload caused by VHD, and 5) the pulmonary artery systolic pressure. If the patient meets standard criteria for a cardiac intervention, it is prudent to de- fer elective noncardiac procedures and proceed to valve However, in emergency situations, noncardiac surgery may be necessary in the presence of uncorrected severe valve disease. All patients with severe VHD who are undergoing noncardiac surgery benefit from an evaluation by a Heart Team consisting of a cardiologist, cardiac anesthesiologist, and cardiac surgeons, in conjunction with the surgeon performing the procedure. In patients with severe VHD who are un- dergoing low-risk surgical procedures or in patients with mild to moderate VHD, noninvasive monitoring in con- sultation with a cardiovascular anesthesiologist may be all that is needed. In patients with severe VHD who are undergoing elevated-risk noncardiac surgery, decisions should be made as to whether to proceed with the non- cardiac surgery and whether invasive hemodynamic or TEE imaging monitoring should be performed intraop- eratively and postoperatively in an intensive care setting. Recommendation-Specific Supportive Text 1.


In patients with severe VHD who are undergoing elevated-risk noncardiac surgery, decisions should be made as to whether to proceed with the non- cardiac surgery and whether invasive hemodynamic or TEE imaging monitoring should be performed intraop- eratively and postoperatively in an intensive care setting. Recommendation-Specific Supportive Text 1. After a careful clinical evaluation and preopera- tive resting 12-lead ECG, patients being evalu- ated for noncardiac surgery who have known or suspected VHD of moderate or greater degree benefit from TTE.5 If there has been no change in clinical course, an echocardiogram within the past 12 months can be used. Most adverse events have occurred because the diagnosis of VHD was not known to the surgical team. The echocardio- graphic evaluation should quantify the severity of valve stenosis or regurgitation, calculate sys- tolic function, estimate diastolic function, evalu- ate LV size and myocardial structure, estimate RV size and function, and estimate pulmonary artery AS is present in 1% to 2% of all patients >65 years of age and 3% to 8% of all patients >75 years of age. Severe AS is asso- ciated with an increased risk during noncardiac surgery, depending on the specific degree of valve narrowing, LV systolic function, concurrent CAD, type of surgery, and other risk factors associated with surgery. Rheumatic MS may also be poorly tolerated during the altered hemodynamics of anesthesia and noncardiac surgery. Left-sided regurgitant lesions are better tolerated but still convey increased risk, particularly if the anesthesi- ologist and surgeon are unaware of the diagnosis or severity of valve disease.


Left-sided regurgitant lesions are better tolerated but still convey increased risk, particularly if the anesthesi- ologist and surgeon are unaware of the diagnosis or severity of valve disease. 15.2.Management of the Symptomatic Patient Recommendation for Management of the Symptomatic Patient With VHD Undergoing Noncardiac Surgery COR LOE Recommendation In patients who meet standard indications for intervention for VHD (replacement and repair) on the basis of symptoms and disease severity, intervention should be performed before elective noncardiac surgery to reduce perioperative risk if possible, depending on the urgency and risk of the noncardiac Synopsis Symptomatic patients with severe VHD benefit from valve intervention before noncardiac surgery, if possible. Recommendation-Specific Supportive Text 1. Noncardiac surgery patients with symptom- atic severe AS have the highest risk of cardiac complications; the estimated rate of cardiac complications in patients with undiagnosed severe AS undergoing noncardiac surgery is 10% to 30%. AVR (SAVR, TAVI) performed before elective elevated-risk noncardiac sur- gery in symptomatic patients with severe AS will prevent hemodynamic instability during, as well as after, noncardiac surgery.1 7 In AS patients who are undergoing noncardiac sur- gery, there is lack of data on the efficacy or safety of TAVI,8 but TAVI is a reasonable option to avoid delay of semi-urgent noncardiac sur- gery.


AVR (SAVR, TAVI) performed before elective elevated-risk noncardiac sur- gery in symptomatic patients with severe AS will prevent hemodynamic instability during, as well as after, noncardiac surgery.1 7 In AS patients who are undergoing noncardiac sur- gery, there is lack of data on the efficacy or safety of TAVI,8 but TAVI is a reasonable option to avoid delay of semi-urgent noncardiac sur- gery. In hemodynamically unstable patients at high to prohibitive surgical risk for AVR, bal- loon aortic valvuloplasty as a bridging strategy may be an option.9 11 Symptomatic patients with rheumatic MS (the pathophysiology and implications of rheumatic MS and AS are simi- lar) or patients with pulmonary artery systolic pressure >50 mm Hg benefit from valvular intervention before elective noncardiac surgery according to recommendations for rheumatic MS. Left-sided regurgitant lesions also convey increased cardiac risk during noncardiac sur- Although these lesions are generally better tolerated than stenotic valvular disease, in patients with MR and AR who are undergo- ing elective elevated-risk (ie, intermediate- or high-risk) noncardiac surgery and who meet standard indications for intervention, mitral or aortic valve surgery (repair or replacement) optimally should be performed before noncar- diac surgery. CLINICAL STATEMENTS AND GUIDELINES 15.3. Management of the Asymptomatic Patient Recommendations for Management of the Asymptomatic Patient With VHD Undergoing Noncardiac Surgery Referenced studies that support the recommendations are summarized in Online Data Supplement 47. COR LOE Recommendations In asymptomatic patients with moderate or greater degrees of AS and normal LV systolic function, it is reasonable to perform elective In asymptomatic patients with moderate or greater degrees of rheumatic MS with less than severe pulmonary hypertension (pulmonary artery systolic pressure <50 mmHg), it is reasonable to perform elective noncardiac surgery.


COR LOE Recommendations In asymptomatic patients with moderate or greater degrees of AS and normal LV systolic function, it is reasonable to perform elective In asymptomatic patients with moderate or greater degrees of rheumatic MS with less than severe pulmonary hypertension (pulmonary artery systolic pressure <50 mmHg), it is reasonable to perform elective noncardiac surgery. In asymptomatic patients with moderate or greater degrees of MR and normal LV systolic function with less than severe pulmonary hypertension (pulmonary artery systolic pressure <50 mmHg), it is reasonable to perform elective noncardiac surgery.4 7 In asymptomatic patients with moderate or greater degrees of AR and normal LV systolic function, it is reasonable to perform elective Synopsis In asymptomatic patients with significant VHD who do not meet standard criteria for intervention, the risk as- sociated with the noncardiac procedure can be mini- mized by choosing an anesthetic approach that is ap- propriate to the valve lesion and ensuring a higher level of intraoperative (and perioperative) monitoring, taking into account the underlying valvular abnormality, its ef- fect on LV function, and comorbidities. In patients with VHD, the cardiovascular risk of noncardiac surgery is also impacted by other cardiovascular conditions, such as LV and RV dysfunction, CAD, pulmonary hyperten- sion, and peripheral artery disease. In patients with moderate or greater degrees of AS, the hemodynamic effects of anesthesia and surgery are poorly tolerated; predictors of adverse outcomes include severity of AS, coexisting MR, pulmonary hypertension, and CAD. However, these comorbidities also increase the risk of AVR. Data are limited, but the risk benefit ratio con- tinues to favor managing asymptomatic patients with severe AS who are undergoing noncardiac surgery with hemodynamic monitoring and optimization of load- ing conditions, rather than considering prophylactic AVR.


Data are limited, but the risk benefit ratio con- tinues to favor managing asymptomatic patients with severe AS who are undergoing noncardiac surgery with hemodynamic monitoring and optimization of load- ing conditions, rather than considering prophylactic AVR. The patient with rheumatic MS who is undergo- ing noncardiac surgery is treated in a manner similar to the patient with AS. Regurgitant lesions also convey an increased risk of cardiac complications in patients undergoing noncardiac surgery and thus require careful evaluation and hemodynamic monitoring. Recommendation-Specific Supportive Text 1. Asymptomatic patients with severe AS and a normal LVEF can undergo noncardiac sur- gery with acceptable risk, particularly in the absence of severe CAD.1 3 Thus, pre-operative evaluation to exclude severe CAD with CT or angiographic imaging may be useful. In these patients with severe asymptomatic AS, cardiac complications can be reduced by periprocedural continuous optimization of loading conditions, thereby avoiding hypotension and tachycardia. Sinus rhythm with normal heart rate should be maintained. Tachycardia and systemic hypoten- sion may result in decreased coronary perfusion pressure, development of arrhythmias or isch- emia, myocardial injury, cardiac failure, or death. Periprocedural hemodynamic monitoring with a right-heart catheter or intraoperative TEE may be particularly useful to allow continuous opti- mization of loading conditions. Intraoperative and postoperative monitoring of blood pressure and intracardiac volume are implemented start- ing in the preoperative period and continuing until hemodynamics are stable, up to 24 to 48 hours after the procedure. General anesthetics are well tolerated, and the anesthetic agents should be chosen to maintain sinus rhythm and normotension. Phenylephrine or norepineph- rine can be used to increase blood pressure in patients with no significant CAD.9,10 In case of systemic hypertension, arterial dilators, such as short-acting calcium channel blockers, are pre- ferred.


Phenylephrine or norepineph- rine can be used to increase blood pressure in patients with no significant CAD.9,10 In case of systemic hypertension, arterial dilators, such as short-acting calcium channel blockers, are pre- ferred. Epidural or spinal anesthetic interven- tions should be modified to avoid rapid changes in systemic pressure, using only high-dilution neuraxial local anesthetic agents in combination 2. In asymptomatic patients with moderate or greater degrees of rheumatic MS with a pul- monary artery systolic pressure <50 mm Hg, elevated-risk noncardiac surgery can be per- formed with invasive hemodynamic monitoring to optimize loading conditions. Maintenance of LV preload and sinus rhythm should be the targets in the perioperative period. Preload should be maintained at a level high enough to allow an adequate forward cardiac output across the stenotic mitral valve but low enough to avoid pulmonary edema. Preload attain- ment can be challenging and requires mea- surement of cardiac output and pulmonary wedge pressure. Of particular concern is judi- cious intravenous fluid administration, so as to avoid increases in the LA pressure and pul- monary capillary pressure that may precipitate CLINICAL STATEMENTS AND GUIDELINES acute pulmonary edema. Tachycardia should be avoided because of the shortened diastolic LV filling time across the stenotic mitral valve, resulting in an increase in LA pressure.15 17 In asymptomatic patients with significant rheu- matic MS and with a pulmonary artery systolic pressure >50 mm Hg, the risk of elective inter- mediate- to high-risk noncardiac surgery is considerably higher, so these patients should be evaluated and treated as outlined in the rheumatic MS section (Section 6.2).6,7,18 3.


Tachycardia should be avoided because of the shortened diastolic LV filling time across the stenotic mitral valve, resulting in an increase in LA pressure.15 17 In asymptomatic patients with significant rheu- matic MS and with a pulmonary artery systolic pressure >50 mm Hg, the risk of elective inter- mediate- to high-risk noncardiac surgery is considerably higher, so these patients should be evaluated and treated as outlined in the rheumatic MS section (Section 6.2).6,7,18 3. In asymptomatic patients with significant MR and normal LV systolic function with a pulmo- nary artery systolic pressure <50 mm Hg who are undergoing elective noncardiac surgery, the overall hemodynamic goals are avoidance of both increased afterload and bradycardia by choosing the appropriate anesthetic scheme. Left-sided regurgitant lesions convey chronic LV volume overload and increased cardiac risk during noncardiac surgery but are better toler- ated than is stenotic valvular disease.11 Patients with significant MR undergoing noncardiac surgery had higher rates of postoperative HF and myocardial infarction than did controls The combination of neuraxial local anesthetics and opioids produces a favor- able systemic vasodilation for patients with regurgitant valve lesions. Patients with regur- gitant lesions will also do well with general anesthesia, which also lowers systemic vas- cular resistance. However, preload should be Invasive hemodynamic and/ or intraoperative TEE monitoring allows for continuous optimization of LV filling pressures and LV function during and after the opera- tive procedure. Patients should be admitted to an intensive monitoring setting for up to 24 to 72 hours after the procedure.15 In functional MR, especially in these patients for whom very careful attention to afterload control and fluid balance is crucial, anesthetic considerations should also include management of the under- lying heart disease (ie, ischemic heart disease, hypertrophic cardiomyopathy). 4.


Patients should be admitted to an intensive monitoring setting for up to 24 to 72 hours after the procedure.15 In functional MR, especially in these patients for whom very careful attention to afterload control and fluid balance is crucial, anesthetic considerations should also include management of the under- lying heart disease (ie, ischemic heart disease, hypertrophic cardiomyopathy). 4. Patients with severe AR are prone to hemody- namic instability because of the detrimental effects of increased volume on myocardial wall stress. The perioperative stress associated with noncardiac surgery may lead to hypotension, arrhythmias, HF, or even death. Patients with sig- nificant AR undergoing noncardiac surgery had a higher in-hospital mortality rate and higher mor- bidity rate, including postoperative myocardial infarction, stroke, pulmonary edema, intubation >24 hours, and major arrhythmias, than those of case-matched controls without AR. Decreased LV systolic function, elevated serum creatinine >2 mg/dL, and intermediate- to high-risk non- cardiac surgery were predictors of higher risk of cardiopulmonary complications and death.8 Avoid bradycardia when AR is present because of the increase in total diastolic time. These patients are monitored with invasive systemic arterial and venous catheters and/or TEE and are admitted postoperatively to an intensive moni- toring setting. 16. EVIDENCE GAPS AND FUTURE DIRECTIONS Many recommendations for the evaluation and man- agement of VHD continue to be based on clinical ex- perience and observational studies, with prospective RCTs limited mostly to new devices. We recommend that research on valve disease span the spectrum from basic science to prospective randomized trials, includ- ing medical therapy, and that studies focus on each stage of the disease process, from the patient at risk to the patient with end-stage disease.


We recommend that research on valve disease span the spectrum from basic science to prospective randomized trials, includ- ing medical therapy, and that studies focus on each stage of the disease process, from the patient at risk to the patient with end-stage disease. Newer approaches, such as artificial intelligence and machine learning, as well as imaging and engineering advances, may pro- vide sophisticated tools for diagnosis and therapeutics. Research should be patient centered, with patients in- cluded at every stage of the research process to ensure that questions and outcomes important to patients are included in the study design, implementation, and re- porting. 16.1. Prevention of Valve Disease: Stage A On a worldwide basis, rheumatic fever remains the pri- mary cause of VHD; global health systems outcomes studies are needed to identify impediments to success- ful primary and secondary prevention of rheumatic heart disease. Other approaches to prevention, such as vaccine development, and delaying disease progres- sion once valve damage is present should also be ex- plored. Disease prevention in patients at risk of other types of valve disease is needed, including the control of known cardiovascular risk factors. Some subgroups at risk of calcific AS can be identified, such as those with a congenital BAV or elevated lipoprotein(a) lev- els. However, there are no known therapies to pre- vent valve dysfunction in these patients. Basic science studies on the genetic and pathobiological causes of valve dysfunction will provide insight into mechanisms of disease that might allow identification of patients at risk and allow early intervention to prevent disease CLINICAL STATEMENTS AND GUIDELINES 16.2. Medical Therapy to Treat or Prevent Disease Progression: Stage B In patients with early VHD, including those with cal- cific or myxomatous disease, there are currently no therapies to prevent disease progression in the valve leaflets.


Medical Therapy to Treat or Prevent Disease Progression: Stage B In patients with early VHD, including those with cal- cific or myxomatous disease, there are currently no therapies to prevent disease progression in the valve leaflets. Instead, current recommendations are di- rected toward patient monitoring, with the intent to intervene once severe disease is present that results in symptoms or abnormal cardiovascular function. Basic science studies are needed to identify potential tar- gets for prevention of progressive VHD. Focused trans- lational studies using sensitive, advanced imaging markers of disease progression may allow more rapid clinical implementation and better design of RCTs for promising new therapies. There also has been little consideration of the interaction of valvular, ventricu- lar, and vascular involvement in the disease process. Additional studies are needed on therapies that might prevent the adverse consequences of VHD, such as LV dysfunction and pulmonary hypertension. Most im- portantly, patient education and empowering patients to be active participants in managing their health con- ditions and participating in shared decision-making 16.3. Optimal Timing of Intervention: Stage C Current approaches to identifying the optimal timing of intervention in patients with progressive valve disease are suboptimal. Symptom onset is a subjective measure and may occur too late in the disease course for optimal long-term outcomes. Despite the availability of sophisti- cated approaches for measurement of LV volumes, sys- tolic function, diastolic function, and other measures of myocardial performance, recommendations continue to rely on simple linear dimensions used in published se- ries, with data that may not reflect contemporary clini- cal outcomes. Studies are urgently needed that evalu- ate the value of newer measures of LV size, function, and myocardial structure in predicting outcomes after valve intervention, especially in patients with chronic severe AR.


Studies are urgently needed that evalu- ate the value of newer measures of LV size, function, and myocardial structure in predicting outcomes after valve intervention, especially in patients with chronic severe AR. However, LV enlargement and dysfunction are late consequences of valve dysfunction; as more durable approaches to restoring normal valve function are developed, the benefit risk balance for intervention will shift to earlier in the disease. Studies examining the role of earlier markers of myocardial dysfunction, such as strain and strain-rate imaging, diastolic dysfunction, circulating blood markers, and other novel approaches to defining the optimal timing of intervention, also are needed. Few studies have included adequate numbers of older adults to make specific recommendations for this group of patients, for whom particular concerns, such as cognitive function, frailty, and mobility challenges, may change the decision algorithms. In addition, wom- en and minorities often are underrepresented in clinical trials. Directed efforts are needed to ensure all patient groups are included with numbers adequate to perform separate data analysis. Given the relatively low risk associated with inter- vention in otherwise healthy patients and the improved options for valve repair or replacement, RCTs of inter- vention for severe asymptomatic VHD will be important and are in progress for some conditions, such as severe AS. Other specific conditions where clinical equipoise exists are asymptomatic severe AR with normal LV sys- tolic function, severe primary MR with normal LV func- tion and a high likelihood of valve repair, and the role of intervention for TR. Data from large, carefully designed registries are also needed for defining and improving quality of care. Long-term follow-up will be needed to ensure the lifetime risks of a prosthetic valve or valve repair are balanced against any benefits attributable to 16.4.


Long-term follow-up will be needed to ensure the lifetime risks of a prosthetic valve or valve repair are balanced against any benefits attributable to 16.4. Better Options for Intervention: Stage D Better options are needed for valve repair and replace- ment. The timing of intervention is based on the bal- ance between outcomes with native valve disease and the risk and long-term durability of the valve after in- tervention. As valve repair and replacement options improve, the balance will shift toward earlier interven- tion. A valve substitute is needed that can be safely and reliably implanted, is nonthrombogenic, has hemody- namics similar to a normal native valve, and is dura- ble. Transcatheter valve procedures offer the promise of safe implantation and excellent hemodynamics, but long-term durability beyond 5 years is not yet known. In patients who require mechanical valve replacement, oral therapy is needed that provides effective anticoag- ulation with a low risk of complications and no negative impact on quality of life. Moderate to severe VHD is present in 2.5% of the US population and increases in prevalence with age. The disease affects between 4% and 9% of those 65 to 75 years of age and 12% to 13% of those >75 years of age. Many of these patients require surgical or in- terventional procedures. However, even with interven- tion, overall survival is lower than expected, and the risk of adverse outcomes attributable to VHD is high, because of both limited options for restoring normal valve function and failure to intervene at the optimal time point in the disease course. Research is urgently needed on almost every aspect of VHD to ensure that patients who already have VHD receive optimal thera- py and to prevent VHD in those at risk.


Research is urgently needed on almost every aspect of VHD to ensure that patients who already have VHD receive optimal thera- py and to prevent VHD in those at risk. Approaches to improving outcomes in patients with VHD include 1) CLINICAL STATEMENTS AND GUIDELINES national and international registries and RCTs, 2) con- tinuous evaluation of outcomes data at each Compre- hensive and Primary Heart Valve Center, and 3) focus on patient-centric care, with involvement of the patient in the decision-making process (Table 26). More acces- sible quality and outcome data are also needed from Comprehensive Valve Centers to assist cardiologists and patients to make well-informed choices.1 3 Table 26. Evidence Gaps and Future Directions for Patients With VHD Evidence Gaps Future Directions Identification of patients at risk and valve disease prevention (Stage A) Disease mechanisms Basic science to identify specific targets for medical therapy Rheumatic heart disease Primary and secondary prevention Calcific valve disease Identification of patients at risk Risk factor intervention Prevention of disease initiation Medical therapy for progressive valve disease (Stage B) Disease mechanisms Basic science to identify specific targets to slow or reverse disease progression Medical intervention Targeted therapy using advanced imaging endpoints to study disease mechanisms Ventricular and vascular interactions Dynamic interplay between valve disease severity and changes in ventricular anatomy and function Modulation of ventricular and vascular dysfunction in patients with VHD Optimal timing of intervention (Stage C) Improved measures of disease severity Validation of newer measures of LV size (eg, volumes instead of dimension) and function (eg, strain) for timing of intervention decisions.


Evidence Gaps and Future Directions for Patients With VHD Evidence Gaps Future Directions Identification of patients at risk and valve disease prevention (Stage A) Disease mechanisms Basic science to identify specific targets for medical therapy Rheumatic heart disease Primary and secondary prevention Calcific valve disease Identification of patients at risk Risk factor intervention Prevention of disease initiation Medical therapy for progressive valve disease (Stage B) Disease mechanisms Basic science to identify specific targets to slow or reverse disease progression Medical intervention Targeted therapy using advanced imaging endpoints to study disease mechanisms Ventricular and vascular interactions Dynamic interplay between valve disease severity and changes in ventricular anatomy and function Modulation of ventricular and vascular dysfunction in patients with VHD Optimal timing of intervention (Stage C) Improved measures of disease severity Validation of newer measures of LV size (eg, volumes instead of dimension) and function (eg, strain) for timing of intervention decisions. Evaluation of nonimaging parameters (serum markers and other novel approaches) Timing of intervention Timing of intervention in asymptomatic patients with valve regurgitation Intervention for asymptomatic severe AS Intervention for moderate AS with LV dysfunction Identification of patients with secondary MR who benefit from intervention Patient-centered research Involvement of patients in identifying research questions, study design, and definition of outcomes Inclusion of diverse patient groups Adequate representation of diverse patient populations in RCTs for VHD Decision aids Development and validation of improved decision aids for shared decision-making with patients Implementation and validation of decision algorithms for physicians and Heart Valve Teams Intervention options and long-term management (Stage D) Improved prosthetic valves Durability of TAVI valves Nonthrombogenic durable surgical and transcatheter valves Optimal antithrombotic therapy Alternatives to VKA anticoagulation for mechanical valves Management of anticoagulation during pregnancy Optimal antithrombotic therapy after TAVI Medical therapy after AVR Medical therapy to address ventricular and vascular function Optimal blood pressure targets after valve intervention Lower procedural risk Approaches to lower surgical morbidity and mortality rates Prevention of postoperative AF Noninvasive approaches for correction of valve dysfunction Prevention of complications Approaches to avoid need for permanent pacing after SAVR or TAVI Better prevention, diagnosis and treatment of endocarditis.


Evaluation of nonimaging parameters (serum markers and other novel approaches) Timing of intervention Timing of intervention in asymptomatic patients with valve regurgitation Intervention for asymptomatic severe AS Intervention for moderate AS with LV dysfunction Identification of patients with secondary MR who benefit from intervention Patient-centered research Involvement of patients in identifying research questions, study design, and definition of outcomes Inclusion of diverse patient groups Adequate representation of diverse patient populations in RCTs for VHD Decision aids Development and validation of improved decision aids for shared decision-making with patients Implementation and validation of decision algorithms for physicians and Heart Valve Teams Intervention options and long-term management (Stage D) Improved prosthetic valves Durability of TAVI valves Nonthrombogenic durable surgical and transcatheter valves Optimal antithrombotic therapy Alternatives to VKA anticoagulation for mechanical valves Management of anticoagulation during pregnancy Optimal antithrombotic therapy after TAVI Medical therapy after AVR Medical therapy to address ventricular and vascular function Optimal blood pressure targets after valve intervention Lower procedural risk Approaches to lower surgical morbidity and mortality rates Prevention of postoperative AF Noninvasive approaches for correction of valve dysfunction Prevention of complications Approaches to avoid need for permanent pacing after SAVR or TAVI Better prevention, diagnosis and treatment of endocarditis. Better prevention of thromboembolic events. Promoting equity Identify and address disparities in outcomes and survival across diverse patient populations Develop novel, cost-effective approaches for long-term management in rural settings Expand access to therapies for valvular dysfunction AF indicates atrial fibrillation; AS, aortic stenosis; AVR, aortic valve replacement; LV, left ventricular; MR, mitral regurgitation; RCT, randomized controlled trial; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation; VHD, valvular heart disease; and VKA, vitamin K antagonist.


Promoting equity Identify and address disparities in outcomes and survival across diverse patient populations Develop novel, cost-effective approaches for long-term management in rural settings Expand access to therapies for valvular dysfunction AF indicates atrial fibrillation; AS, aortic stenosis; AVR, aortic valve replacement; LV, left ventricular; MR, mitral regurgitation; RCT, randomized controlled trial; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation; VHD, valvular heart disease; and VKA, vitamin K antagonist. CLINICAL STATEMENTS AND GUIDELINES ACC/AHA JOINT COMMITTEE MEMBERS Patrick T. O Gara, MD, MACC, FAHA, Chair; Joshua A. Beckman, MD, MS, FAHA, Chair-Elect; Glenn N. Levine, MD, FACC, FAHA, Immediate Past Chair*; Sana M. Al-Khatib, MD, MHS, FACC, FAHA*; Anastasia Arm- bruster, PharmD, AACC; Kim K. Birtcher, PharmD, MS, AACC; Joaquin Ciggaroa, MD, FACC*; Anita Deswal, MD, MPH, FACC, FAHA; Dave L. Dixon, PharmD, FACC; Lee A. Fleisher, MD, FACC, FAHA*; Lisa de las Fuentes, MD, MS, FAHA, FASE; Federico Gentile, MD, FACC*; Zachary D. Goldberger, MD, MSc, FACC, FAHA; Bu- lent Gorenek, MD, FACC, FESC; Norrisa Haynes, MD, MPH; Adrian F. Hernandez, MD, MHS; Mark A. Hlatky, MD, FACC, FAHA*; Jos A. Joglar, MD, FACC, FAHA; W. Schuyler Jones, MD, FACC; Joseph E. Marine, MD, FACC*; Daniel Mark, MD, MPH, FACC, FAHA; Latha Palaniappan, MD, MS, FAHA, FACC; Mariann R. Piano, RN, PhD, FAHA; Erica S. Spatz, MD, MHS, FACC; Jac- queline Tamis-Holland, MD, FACC; Duminda N. Wijey- sundera, MD, PhD*; Y. Joseph Woo, MD, FAHA, FACC PRESIDENTS AND STAFF American College of Cardiology Athena Poppas, MD, FACC, President Cathleen Gates, Chief Executive Officer John S. Rumsfeld, MD, PhD, FACC, Chief Science and Quality Officer MaryAnne Elma, MPH, Senior Director, Science, Education, Quality, and Publishing Grace D. Ronan, Team Lead, Clinical Policy Publications Timothy W. Schutt, MA, Clinical Policy Analyst American College of Cardiology/ American Heart Association Thomas S. D. Getchius, Director, Guideline Strategy and Operations Abdul R. Abdullah, MD, Director, Guideline Science and Methodology Laura Mitchell, Guideline Advisor American Heart Association Mitchell S.V.


CLINICAL STATEMENTS AND GUIDELINES ACC/AHA JOINT COMMITTEE MEMBERS Patrick T. O Gara, MD, MACC, FAHA, Chair; Joshua A. Beckman, MD, MS, FAHA, Chair-Elect; Glenn N. Levine, MD, FACC, FAHA, Immediate Past Chair*; Sana M. Al-Khatib, MD, MHS, FACC, FAHA*; Anastasia Arm- bruster, PharmD, AACC; Kim K. Birtcher, PharmD, MS, AACC; Joaquin Ciggaroa, MD, FACC*; Anita Deswal, MD, MPH, FACC, FAHA; Dave L. Dixon, PharmD, FACC; Lee A. Fleisher, MD, FACC, FAHA*; Lisa de las Fuentes, MD, MS, FAHA, FASE; Federico Gentile, MD, FACC*; Zachary D. Goldberger, MD, MSc, FACC, FAHA; Bu- lent Gorenek, MD, FACC, FESC; Norrisa Haynes, MD, MPH; Adrian F. Hernandez, MD, MHS; Mark A. Hlatky, MD, FACC, FAHA*; Jos A. Joglar, MD, FACC, FAHA; W. Schuyler Jones, MD, FACC; Joseph E. Marine, MD, FACC*; Daniel Mark, MD, MPH, FACC, FAHA; Latha Palaniappan, MD, MS, FAHA, FACC; Mariann R. Piano, RN, PhD, FAHA; Erica S. Spatz, MD, MHS, FACC; Jac- queline Tamis-Holland, MD, FACC; Duminda N. Wijey- sundera, MD, PhD*; Y. Joseph Woo, MD, FAHA, FACC PRESIDENTS AND STAFF American College of Cardiology Athena Poppas, MD, FACC, President Cathleen Gates, Chief Executive Officer John S. Rumsfeld, MD, PhD, FACC, Chief Science and Quality Officer MaryAnne Elma, MPH, Senior Director, Science, Education, Quality, and Publishing Grace D. Ronan, Team Lead, Clinical Policy Publications Timothy W. Schutt, MA, Clinical Policy Analyst American College of Cardiology/ American Heart Association Thomas S. D. Getchius, Director, Guideline Strategy and Operations Abdul R. Abdullah, MD, Director, Guideline Science and Methodology Laura Mitchell, Guideline Advisor American Heart Association Mitchell S.V. Elkind, MD, MS, FAAN, FAHA, President Nancy Brown, Chief Executive Officer Mariell Jessup, MD, FAHA, Chief Science and Medical Officer Radhika Rajgopal Singh, PhD, Vice President, Office of Science, Medicine and Health Paul St. Laurent, DNP, RN, Senior Science and Medicine Advisor, Office of Science, Medicine and Health Jody Hundley, Production and Operations Manager, Scientific Publications, Office of Science Operations ARTICLE INFORMATION This document was approved by the American College of Cardiology Clinical Policy Approval Committee in August 2020, the American Heart Association Science Advisory and Coordinating Committee in August 2020, and the Ameri- can Heart Association Executive Committee in September 2020.


Elkind, MD, MS, FAAN, FAHA, President Nancy Brown, Chief Executive Officer Mariell Jessup, MD, FAHA, Chief Science and Medical Officer Radhika Rajgopal Singh, PhD, Vice President, Office of Science, Medicine and Health Paul St. Laurent, DNP, RN, Senior Science and Medicine Advisor, Office of Science, Medicine and Health Jody Hundley, Production and Operations Manager, Scientific Publications, Office of Science Operations ARTICLE INFORMATION This document was approved by the American College of Cardiology Clinical Policy Approval Committee in August 2020, the American Heart Association Science Advisory and Coordinating Committee in August 2020, and the Ameri- can Heart Association Executive Committee in September 2020. The Comprehensive RWI Data Supplement table is available with this article Supplemental materials are available with this article at https://www. This article has been copublished in Journal of the American College of Cardiology. Copies: This document is available on the websites of the American College of Cardiology (www.acc.org) and the American Heart Association (https://professional.heart.org). A copy of the document is also available at https://professional.heart.org/statements by selecting the Guidelines & Statements button. To purchase additional reprints, call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com. The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit professional.heart.org/statements. Select the Guidelines & Statements drop-down menu near the top of the webpage, then click Pub- lication Development. Permissions: Multiple copies, modification, alteration, enhancement, and/ or distribution of this document are not permitted without the express permis- sion of the American Heart Association. Instructions for obtaining permission are located at https://www.heart.org/permissions. A link to the Copyright Per- missions Request Form appears in the second paragraph (https://www.heart. org/en/about-us/statements-and-policies/copyright-request-form). REFERENCES Preamble 1. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine (US).


Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine (US). Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011. 2. Committee on Standards for Systematic Reviews of Comparative Ef- fectiveness Research, Institute of Medicine (US). Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: National Academies Press; 2011. 3. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Prac- tice Guidelines. Circulation. 2014;129:2329 45. 4. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Available at: https://professional.heart.org/-/media/phd-files/guidelines-and-state- August 19, 2020. 5. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the ACC/ AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;133:1426 8. 6. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with cardio- vascular disease and comorbid conditions: from the American Heart As- sociation, American College of Cardiology, and U.S. Department of Health and Human Services. Circulation. 2014;130:1662 7. 7. Levine GN, O Gara PT, Beckman JA, et al. Recent innovations, modifica- tions, and evolution of ACC/AHA clinical practice guidelines: an update for our constituencies: a report of the American College of Cardiology/ *Former Joint Committee member; current member during the writing effort. CLINICAL STATEMENTS AND GUIDELINES American Heart Association Task Force on Clinical Practice Guidelines. Cir- culation. 2019;139:e879 86. 1.4. Scope of the Guideline 1. Bonow RO, Carabello BA, Kanu C, et al.


Scope of the Guideline 1. Bonow RO, Carabello BA, Kanu C, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease). Developed in collaboration with the Society of Cardiovascular Anesthesiologists. Cir- culation. 2006;114:e84 231. 2. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:e521 643. 3. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused up- date of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiol- ogy/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135:e1159 95. 4. Hiratzka LF, Creager MA, Isselbacher EM, et al. Surgery for aortic dilatation in patients with bicuspid aortic valves: a statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;133:680 6. 5. Zoghbi WA, Adams D, Bonow RO, et al. Recommendations for noninva- sive evaluation of native valvular regurgitation: a report from the Ameri- can Society of Echocardiography. Developed in collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017;30:303 71. 6. Lancellotti P, Moura L, Pierard LA, et al. European Association of Echocar- diography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echo- cardiogr. 2010;11:307 32. 7. Fuster V, Ryden LE, Cannom DS, et al.


2010;11:307 32. 7. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Developed in col- laboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257 354. 8. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guide- line for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:e199 267. 9. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused up- date of the 2014 AHA/ACC/HRS guideline for the management of pa- tients with atrial fibrillation: a report of the American College of Cardiol- ogy/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Developed in collaboration with the Society of Thoracic Surgeons. Circulation. 2019;140:e125 51. 10. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e698 800. 11. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr. 2009;10:1 25. 12. Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echo- cardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr. 2017;30:372 92. 13. Zoghbi WA, Asch FM, Bruce C, et al.


2017;30:372 92. 13. Zoghbi WA, Asch FM, Bruce C, et al. Guidelines for the evaluation of valvular regurgitation after percutaneous valve repair or replacement: a report from the American Society of Echocardiography. Developed in col- laboration with the Society for Cardiovascular Angiography and Interven- tions, Japanese Society of Echocardiography, and Society for Cardiovascu- lar Magnetic Resonance. J Am Soc Echocardiogr. 2019;32:431 75. 14. Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evalu- ation of prosthetic valves with echocardiography and Doppler ultrasound: a report from the American Society of Echocardiography s Guidelines and Standards Committee and the Task Force on Prosthetic Valves. Developed in conjunction with the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2009;22:975 1014. 15. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124:e783 831. 16. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology/American Heart Associa- tion Joint Committee on Clinical Practice Guidelines. Circulation. 2020: In press. 17. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J. 2011;32:3147 97. 18. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC guidelines for the management of cardiovascular diseases during preg- nancy.


2018 ESC guidelines for the management of cardiovascular diseases during preg- nancy. Eur Heart J. 2018;39:3165 241. 19. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e576S 600S. 20. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33:2451 96. 21. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739 91. 22. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137 61. 1.5. Class of Recommendation and Level of Evidence 1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Available at: https://professional.heart.org/-/media/phd-files/guidelines-and-state- August 19, 2020. 2. GENERAL PRINCIPLES 2.3. Diagnosis and Follow-Up 2.3.1. Diagnostic Testing: Initial Diagnosis 1. Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr. 2009;10:1 25. 2. Zoghbi WA, Adams D, Bonow RO, et al. Recommendations for noninva- sive evaluation of native valvular regurgitation: a report from the Ameri- can Society of Echocardiography. Developed in collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017;30:303 71. 3. Lancellotti P, Moura L, Pierard LA, et al. European Association of Echocar- diography recommendations for the assessment of valvular regurgitation.


European Association of Echocar- diography recommendations for the assessment of valvular regurgitation. Part 2: mitral and tricuspid regurgitation (native valve disease). Eur J Echo- cardiogr. 2010;11:307 32. 4. Baumgartner H, Hung J, Bermejo J, et al. Recommendations on the echo- cardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr. 2017;30:372 92. 5. Medvedofsky D, Maffessanti F, Weinert L, et al. 2D and 3D echocardiog- raphy-derived indices of left ventricular function and shape: relationship with mortality. JACC Cardiovasc Imaging. 2018;11:1569 79. CLINICAL STATEMENTS AND GUIDELINES 6. Quinones MA, Otto CM, Stoddard M, et al. Recommendations for quantifica- tion of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15:167 84. 7. Currie PJ, Seward JB, Reeder GS, et al. Continuous-wave Doppler echocar- diographic assessment of severity of calcific aortic stenosis: a simultane- ous Doppler-catheter correlative study in 100 adult patients. Circulation. 1985;71:1162 9. 8. Thaden JJ, Tsang MY, Ayoub C, et al. Association between echocardiogra- phy laboratory accreditation and the quality of imaging and reporting for valvular heart disease. Circ Cardiovasc Imaging. 2017;10:e006140. 2.3.2. Diagnostic Testing: Changing Signs or Symptoms 1. Carabello BA, Crawford FA Jr. Valvular heart disease. N Engl J Med. 1997;337:32 41. 2. Enriquez-Sarano M, Basmadjian AJ, Rossi A, et al. Progression of mitral regurgitation: a prospective Doppler echocardiographic study. J Am Coll Cardiol. 1999;34:1137 44. 3. Gaasch WH, John RM, Aurigemma GP. Managing asymptomatic patients with chronic mitral regurgitation. Chest. 1995;108:842 7. 4. Lancellotti P, Rosenhek R, Pibarot P, et al. ESC Working Group on Valvular Heart Disease position paper heart valve clinics: organization, structure, and experiences. Eur Heart J. 2013;34:1597 606. 5.


ESC Working Group on Valvular Heart Disease position paper heart valve clinics: organization, structure, and experiences. Eur Heart J. 2013;34:1597 606. 5. Otto CM. Timing of aortic valve surgery. Heart. 2000;84:211 8. 6. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Car- diol. 1989;13:545 50. 7. Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in as- ymptomatic severe mitral regurgitation. Circulation. 2006;113:2238 44. 2.3.3. Diagnostic Testing: Routine Follow-Up 1. Bonow RO, Lakatos E, Maron BJ, et al. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic re- gurgitation and normal left ventricular systolic function. Circulation. 1991;84:1625 35. 2. Carabello BA, Crawford FA Jr. Valvular heart disease. N Engl J Med. 1997;337:32 41. 3. Enriquez-Sarano M, Basmadjian AJ, Rossi A, et al. Progression of mitral regurgitation: a prospective Doppler echocardiographic study. J Am Coll Cardiol. 1999;34:1137 44. 4. Gaasch WH, John RM, Aurigemma GP. Managing asymptomatic patients with chronic mitral regurgitation. Chest. 1995;108:842 7. 5. Lancellotti P, Rosenhek R, Pibarot P, et al. ESC Working Group on Valvular Heart Disease position paper heart valve clinics: organization, structure, and experiences. Eur Heart J. 2013;34:1597 606. 6. Otto CM. Timing of aortic valve surgery. Heart. 2000;84:211 8. 7. Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in as- ymptomatic severe mitral regurgitation. Circulation. 2006;113:2238 44. 8. Enriquez-Sarano M, Tajik AJ, Schaff HV, et al. Echocardiographic predic- tion of left ventricular function after correction of mitral regurgitation: results and clinical implications. J Am Coll Cardiol. 1994;24:1536 43. 9. Otto CM, Salerno CT. Timing of surgery in asymptomatic mitral regurgita- tion. N Engl J Med. 2005;352:928 9. 10. Pellikka PA, Sarano ME, Nishimura RA, et al.


2005;352:928 9. 10. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during pro- longed follow-up. Circulation. 2005;111:3290 5. 11. Rosenhek R, Iung B, Tornos P, et al. ESC Working Group on Valvular Heart Disease position paper: assessing the risk of interventions in patients with valvular heart disease. Eur Heart J. 2012;33:822 8, 8a, 8b. 12. Taniguchi T, Morimoto T, Shiomi H, et al. Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol. 2015;66:2827 38. 13. Kang D-H, Park S-J, Rim JH, et al. Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. Circulation. 2010;121:1502 9. 14. Genereux P, Stone GW, O Gara PT, et al. Natural history, diagnostic ap- proaches, and therapeutic strategies for patients with asymptomatic se- vere aortic stenosis. J Am Coll Cardiol. 2016;67:2263 88. 2.3.4. Diagnostic Testing: Cardiac Catheterization 1. Nishimura RA, Carabello BA. Hemodynamics in the cardiac catheterization laboratory of the 21st century. Circulation. 2012;125:2138 50. 2. Nishimura RA, Grantham JA, Connolly HM, et al. Low-output, low-gradi- ent aortic stenosis in patients with depressed left ventricular systolic func- tion: the clinical utility of the dobutamine challenge in the catheterization laboratory. Circulation. 2002;106:809 13. 2.3.5. Diagnostic Testing: Exercise Testing 1. Aviles RJ, Nishimura RA, Pellikka PA, et al. Utility of stress Doppler echocar- diography in patients undergoing percutaneous mitral balloon valvotomy. J Am Soc Echocardiogr. 2001;14:676 81. 2. Messika-Zeitoun D, Johnson BD, Nkomo V, et al. Cardiopulmonary exercise testing determination of functional capacity in mitral regur- gitation: physiologic and outcome implications. J Am Coll Cardiol. 2006;47:2521 7. 3. Lancellotti P, Lebois F, Simon M, et al. Prognostic importance of quantita- tive exercise Doppler echocardiography in asymptomatic valvular aortic stenosis. Circulation. 2005;112:I377 82. 4.


Prognostic importance of quantita- tive exercise Doppler echocardiography in asymptomatic valvular aortic stenosis. Circulation. 2005;112:I377 82. 4. Mar chaux S, Hachicha Z, Bellouin A, et al. Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis. Eur Heart J. 2010;31:1390 7. 5. Otto CM, Pearlman AS, Kraft CD, et al. Physiologic changes with maxi- mal exercise in asymptomatic valvular aortic stenosis assessed by Doppler echocardiography. J Am Coll Cardiol. 1992;20:1160 7. 6. Pierard LA, Lancellotti P. Stress testing in valve disease. Heart. 2007;93:766 72. 7. Magne J, Mahjoub H, Dulgheru R, et al. Left ventricular contrac- tile reserve in asymptomatic primary mitral regurgitation. Eur Heart J. 2014;35:1608 16. 8. Donal E, Mascle S, Brunet A, et al. Prediction of left ventricular ejection fraction 6 months after surgical correction of organic mitral regurgita- tion: the value of exercise echocardiography and deformation imaging. Eur Heart J Cardiovasc Imaging. 2012;13:922 30. 9. Wahi S, Haluska B, Pasquet A, et al. Exercise echocardiography predicts development of left ventricular dysfunction in medically and surgically treated patients with asymptomatic severe aortic regurgitation. Heart. 2000;84:606 14. 10. Gentry JL 3rd, Parikh PK, Alashi A, et al. Characteristics and outcomes in a contemporary group of patients with suspected significant mitral stenosis undergoing treadmill stress echocardiography. Circ Cardiovasc Imaging. 2019;12:e009062. 11. Lancellotti P, Dulgheru R, Go YY, et al. Stress echocardiography in patients with native valvular heart disease. Heart. 2018;104:807 13. 2.4. Basic Principles of Medical Therapy 1. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137 61. 2.


2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137 61. 2. Gati S, Malhotra A, Sharma S. Exercise recommendations in patients with valvular heart disease. Heart. 2019;105:106 10. 3. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140:e596 646. 2.4.1. Secondary Prevention of Rheumatic Fever 1. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scien- tific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardio- vascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation. 2009;119:1541 51. 2.4.2. IE Prophylaxis 1. Glenny A-M, Oliver R, Roberts GJ, et al. Antibiotics for the prophy- laxis of bacterial endocarditis in dentistry. Cochrane Database Syst Rev. 2013;CD003813. 2. Mougeot FKB, Saunders SE, Brennan MT, et al. Associations between bacteremia from oral sources and distant-site infections: tooth brushing versus single tooth extraction. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119:430 5. CLINICAL STATEMENTS AND GUIDELINES 3. Sherman-Weber S, Axelrod P, Suh B, et al. Infective endocarditis following orthotopic heart transplantation: 10 cases and a review of the literature. Transpl Infect Dis. 2004;6:165 70. 4. Lockhart PB, Brennan MT, Sasser HC, et al. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117:3118 25. 5.


Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117:3118 25. 5. Geist S-MRY, Fitzpatrick S, Geist JR. American Heart Association 2007 guidelines on prevention of infective endocarditis. J Mich Dent Assoc. 2007;89:50 6. 6. Duval X, Alla F, Hoen B, et al. Estimated risk of endocarditis in adults with predisposing cardiac conditions undergoing dental procedures with or without antibiotic prophylaxis. Clin Infect Dis. 2006;42:e102 7. 7. The 2015 ESC Guidelines for the management of infective endocarditis. Eur Heart J. 2015;36:3036 7. 8. Horstkotte D, Rosin H, Friedrichs W, et al. Contribution for choosing the optimal prophylaxis of bacterial endocarditis. Eur Heart J. 1987;8:379 81. 9. Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study. Ann Intern Med. 1998;129:761 9. 10. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocar- ditis. Recommendations by the American Heart Association. Circulation. 1997;96:358 66. 11. Guarner-Argente C, Shah P, Buchner A, et al. Use of antimicrobials for EUS-guided FNA of pancreatic cysts: a retrospective, comparative analysis. Gastrointest Endosc. 2011;74:81 6. 12. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocardi- tis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplin- ary Working Group. Circulation. 2007;116:1736 54. 13. Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Manage- ment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3036 7. 14.


2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Manage- ment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3036 7. 14. Prophylaxis Against Infective Endocarditis: Antimicrobial Prophylaxis Against Infective Endocarditis in Adults and Children Undergoing Inter- ventional Procedures. Available at: https://www.ncbi.nlm.nih.gov/books/ NBK554353/. Accessed October 12, 2020. 15. Thornhill MH, Gibson TB, Cutler E, et al. Antibiotic prophylaxis and inci- dence of endocarditis before and after the 2007 AHA recommendations. J Am Coll Cardiol. 2018;72:2443 54. 16. Desimone DC, Tleyjeh IM, Correa de Sa DD, et al. Incidence of infective endocarditis caused by viridans group streptococci before and after pub- lication of the 2007 American Heart Association s endocarditis prevention guidelines. Circulation. 2012;126:60 4. 17. Dayer MJ, Jones S, Prendergast B, et al. Incidence of infective endocardi- tis in England, 2000 13: a secular trend, interrupted time-series analysis. Lancet. 2015;385:1219 28. 18. Duval X, Delahaye F, Alla F, et al. Temporal trends in infective endocardi- tis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol. 2012;59:1968 76. 19. Pasquali SK, He X, Mohamad Z, et al. Trends in endocarditis hospitaliza- tions at US children s hospitals: impact of the 2007 American Heart As- sociation antibiotic prophylaxis guidelines. Am Heart J. 2012;163:894 9. 20. Pant S, Patel NJ, Deshmukh A, et al. Trends in infective endocarditis in- cidence, microbiology, and valve replacement in the United States from 2000 to 2011. J Am Coll Cardiol. 2015;65:2070 6. 21. Thornhill MH, Dayer MJ, Forde JM, et al. Impact of the NICE guideline rec- ommending cessation of antibiotic prophylaxis for prevention of infective endocarditis: before and after study. BMJ. 2011;342:d2392. 22. Strom BL, Abrutyn E, Berlin JA, et al.


2011;342:d2392. 22. Strom BL, Abrutyn E, Berlin JA, et al. Risk factors for infective endocarditis: oral hygiene and nondental exposures. Circulation. 2000;102:2842 8. 23. Amat-Santos IJ, Messika-Zeitoun D, Eltchaninoff H, et al. Infective endo- carditis after transcatheter aortic valve implantation: results from a large multicenter registry. Circulation. 2015;131:1566 74. 24. Mangner N, Woitek F, Haussig S, et al. Incidence, predictors, and outcome of patients developing infective endocarditis following transfemoral trans- catheter aortic valve replacement. J Am Coll Cardiol. 2016;67:2907 8. 25. Karavas AN, Filsoufi F, Mihaljevic T, et al. Risk factors and management of endocarditis after mitral valve repair. J Heart Valve Dis. 2002;11:660 4. 26. Gillinov AM, Faber CN, Sabik JF, et al. Endocarditis after mitral valve repair. Ann Thorac Surg. 2002;73:1813 6. 27. Botoman VA, Surawicz CM. Bacteremia with gastrointestinal endoscopic procedures. Gastrointest Endosc. 1986;32:342 6. 28. Low DE, Shoenut JP, Kennedy JK, et al. Risk of bacteremia with endoscopic sphincterotomy. Can J Surg. 1987;30:421 3. 29. Low DE, Shoenut JP, Kennedy JK, et al. Prospective assessment of risk of bacteremia with colonoscopy and polypectomy. Dig Dis Sci. 1987;32:1239 43. 30. Wolf JS, Bennett CJ, Dmochowski RR, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008;179:1379 90. 2.4.3. Anticoagulation for AF in Patients With VHD 1. Pan K-L, Singer DE, Ovbiagele B, et al. Effects of non-vitamin K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and valvular heart disease: a systematic review and meta-analysis. J Am Heart Assoc. 2017;6:e005835. 2. Lip GYH, Jensen M, Melgaard L, et al. Stroke and bleeding risk scores in patients with atrial fibrillation and valvular heart disease: evaluating valvular heart disease in a nationwide cohort study. Europace. 2019;21: 33 40. 3. Vora AN, Dai D, Matsuoka R, et al.


2019;21: 33 40. 3. Vora AN, Dai D, Matsuoka R, et al. Incidence, management, and associ- ated clinical outcomes of new-onset atrial fibrillation following transcath- eter aortic valve replacement: an analysis from the STS/ACC TVT registry. JACC Cardiovasc Interv. 2018;11:1746 56. 4. Seeger J, Gonska B, Rodewald C, et al. Apixaban in patients with atrial fibrillation after transfemoral aortic valve replacement. JACC Cardiovasc Interv. 2017;10:66 74. 5. Jochheim D, Barbanti M, Capretti G, et al. Oral anticoagulant type and outcomes after transcatheter aortic valve replacement. JACC Cardiovasc Interv. 2019;12:1566 76. 6. Mangner N, Crusius L, Haussig S, et al. Continued versus interrupted oral anticoagulation during transfemoral transcatheter aortic valve implanta- tion and impact of postoperative anticoagulant management on outcome in patients with atrial fibrillation. Am J Cardiol. 2019;123:1134 41. 7. Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran ver- sus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206 14. 8. De Caterina R, Renda G, Carnicelli AP, et al. Valvular heart disease patients on edoxaban or warfarin in the ENGAGE AF-TIMI 48 trial. J Am Coll Car- diol. 2017;69:1372 82. 9. Carnicelli AP, De Caterina R, Halperin JL, et al. Edoxaban for the preven- tion of thromboembolism in patients with atrial fibrillation and biopros- thetic valves. Circulation. 2017;135:1273 5. 10. Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in comparison with war- farin in patients with atrial fibrillation and valvular heart disease: find- ings from the Apixaban for Reduction in Stroke and Other Thromboem- bolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2015;132: 624 32. 11. Guimar es PO, Pokorney SD, Lopes RD, et al. Efficacy and safety of apixa- ban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: insights from the ARISTOTLE trial. Clin Cardiol.


Efficacy and safety of apixa- ban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: insights from the ARISTOTLE trial. Clin Cardiol. 2019;42:568 71. 12. Vinereanu D, Wang A, Mulder H, et al. Outcomes in anticoagulated pa- tients with atrial fibrillation and with mitral or aortic valve disease. Heart. 2018;104:1292 9. 13. Breithardt G, Baumgartner H, Berkowitz SD, et al. Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban. Heart. 2016;102:1036 43. 14. Breithardt G, Baumgartner H, Berkowitz SD, et al. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease par- ticipating in the ROCKET AF trial. Eur Heart J. 2014;35:3377 85. 15. Siontis KC, Yao X, Gersh BJ, et al. Direct oral anticoagulants in patients with atrial fibrillation and valvular heart disease other than significant mitral stenosis and mechanical valves: a meta-analysis. Circulation. 2017;135:714 6. 16. Andrade JG, Meseguer E, Didier R, et al. Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients with bioprosthetic valves. Ex- pert Rev Cardiovasc Ther. 2018;1 6. 17. Renda G, Ricci F, Giugliano RP, et al. Non-vitamin K antagonist oral antico- agulants in patients with atrial fibrillation and valvular heart disease. J Am Coll Cardiol. 2017;69:1363 71. 18. Briasoulis A, Inampudi C, Akintoye E, et al. Safety and efficacy of novel oral anticoagulants versus warfarin in Medicare beneficiaries with atrial fibrillation and valvular heart disease. J Am Heart Assoc. 2018;7:e008773. CLINICAL STATEMENTS AND GUIDELINES 19. Philippart R, Brunet-Bernard A, Clementy N, et al. Oral anticoagulation, stroke and thromboembolism in patients with atrial fibrillation and valve bioprosthesis. The Loire Valley Atrial Fibrillation Project. Thromb Haemost. 2016;115:1056 63. 20. Duraes AR, de Souza Roriz P, de Almeida Nunes B, et al.