The 2020 guideline for the management of patients with valvular heart disease replaces the American Heart Association/American College of Cardiology (AHA/ACC) 2014 guideline and the 2017 focused update. The following is Part 3 of 3 key perspectives regarding mixed valve disease, prosthetic valves, infective endocarditis (IE), and pregnancy and valvular heart disease:

Mixed Valve Disease

1. Management of mixed valve disease should follow the guidelines for the predominant lesion. For ambiguous symptoms, use of biomarkers or invasive hemodynamics at rest or exercise should be considered as adjuncts to traditional imaging. For patients with mixed moderate aortic stenosis/aortic regurgitation who have developed left ventricular (LV) dysfunction (LV ejection fraction [LVEF] <50%), surgical aortic valve replacement (SAVR) is indicated (Class 1).

Prosthetic Valves

2. Following an initial post-procedure transthoracic echocardiogram (TTE), surveillance imaging is recommended at 5 and 10 years, then annually. When there is a change in clinical symptoms or signs suggesting valve dysfunction, additional imaging such as transesophageal echocardiography (TEE), fluoroscopy, or cardiac computed tomography (CT) is recommended. For a bioprosthetic transcatheter aortic valve implantation (TAVI), annual TTE is reasonable.
3. Antithrombotic therapy for prosthetic valves:
   • Mechanical valves: Anticoagulation with vitamin K antagonists (VKAs) is recommended to achieve varying international normalized ratios (INRs) dependent on valve characteristics and patient risk factors (all Class 1).
   • For mechanical AVR with thromboembolic risk factors (hypercoagulable state, LV dysfunction, prior thromboembolism) or an older-generation prosthesis: INR of 3.0.
   • For mechanical bileaflet or current-generation single-tilting disk AVR with no risk factors: INR of 2.5.
   • For mechanical On-X AVR and no thromboembolic risk factors: A lower INR of 1.5-2.0, starting 3 months after surgery with addition of aspirin (ASA) 75-100 mg daily (Class 2b).
   • For mechanical mitral valve replacement: INR of 3.0.
   • Bioprosthetic TAVI/SAVR or mitral valve replacement: ASA 75-100 mg is reasonable (Class 2a).
   • Bioprosthetic SAVR or mitral valve replacement: Anticoagulation with VKA to an INR of 2.5 is reasonable for 3-6 months postoperatively (Class 2b).
   • Mechanical valve prosthesis: The use of direct thrombin inhibitors (dabigatran) or anti-Xa direct oral anticoagulants remains a Class 3 contraindication.
   • Bridging of a mechanical bileaflet aortic valve without other risk factors is not required, while those with mechanical AVR with thromboembolic risk factors, older-generation mechanical AVRs, or mechanical mitral valve replacements, all need bridging anticoagulation therapy (Class 2a).
4. For high surgical risk patients with prosthetic valve dysfunction (stenosis or valve regurgitation), a transcatheter valve-in-valve procedure is reasonable at a Comprehensive Valve Center (Class 2a). For high surgical risk patients with paravalvular regurgitation with intractable hemolysis or New York Heart Association (NYHA) class III or IV symptoms, a catheter-based percutaneous repair is reasonable (Class 2a).

Infective Endocarditis

5. Patients with IE should be managed by a multispecialty Heart Valve Team including an infectious disease specialist, as well as a neurologist for those who have had neurologic events. In patients with suspected IE, initial TTE is recommended to evaluate for the presence of a vegetation and its possible effects on valvular function (Class 1). Subsequent TEE is indicated when TTE is nondiagnostic, or when complications are suspected, or when intracardiac device leads are present (Class 1). TEE is reasonable in patients with S. aureus bacteremia without a known source, as well as patients with prosthetic valves and persistent fever without bacteremia (Class 2a). The newer imaging modality of 18F-fluorodeoxyglucose positron emission tomography /CT is now considered a valuable adjunct for patients classified by Modified Duke Criteria as having "possible IE" (Class 2a), particularly when prosthetic valves are not optimally visualized on standard TTE or TEE imaging.
6. Appropriate antibiotic therapy should be initiated after obtaining blood cultures and then tailored to antibiotic sensitivity data. Stable patients with left-sided IE caused by streptococcus, E. faecalis, S. aureus, or coagulase negative staph without evidence of paravalvular infect ion on TEE, can change to oral antibiotic therapy after initial intravenous (IV) therapy. A follow-up TEE is recommended 1-3 days prior to completion of the antibiotic course (Class 2b).
7. Early surgical intervention (during initial hospitalization and before completion of full therapeutic course of antibiotics) is recommended for patients with the following characteristics: heart failure symptoms; left-sided IE caused by S. aureus, fungal organism, or other highly resistant organisms; persistent bacteremia or fevers >5 days; recurrent emboli and persistent vegetation; native left-sided valve IE with a mobile vegetation >10 mm in length. In patients with prosthetic valve IE and relapsing infection after completion of an antibiotic course, surgery is recommended (Class 1).
8. In patients with IE with an indication for surgery who suffered a stroke without intracranial hemorrhage, surgery without delay may still be considered. However, if there has been extensive neurologic damage or intracranial hemorrhage, it is advised to wait ≥4 weeks (Class 2b).

Pregnancy and Valvular Heart Disease

9. Women with severe valve disease (Stages C and D) considering pregnancy should undergo pre pregnancy counseling and appropriate testing by a cardiologist with expertise in managing valvular heart disease in pregnancy with subsequent monitoring at a tertiary care center with a dedicated Heart Valve Team (Class 1).
10. In asymptomatic women considering pregnancy with either severe rheumatic mitral stenosis (MS) (mitral valve area ≤1.5 cm², Stage C1) or severe aortic stenosis (aortic velocity ≥4.0 m/s or mean pressure gradient ≥40 mm Hg), valve intervention prior to conception is reasonable. For MS, a percutaneous mitral balloon commissurotomy should be considered if there is favorable valve morphology (Class 2a). If there is severe mitral regurgitation (Stage C1), and the valve is suitable to repair, this should be considered (Class 2b). For women undergoing valve replacement prior to pregnancy, the choice of the type of valve should be made through a shared decision-making process.
11. In pregnant women with either severe rheumatic MS, severe aortic stenosis, or severe mitral regurgitation with NHYA class III or IV symptoms refractory to medical therapy, intervention during pregnancy is reasonable (Class 2a).
12. Women with mechanical prosthetic valves have high-risk pregnancies and should be monitored closely. During the first trimester, warfarin is associated with the lowest likelihood of maternal complication but highest likelihood of miscarriage, fetal death, and congenial malformation, especially when the warfarin dose exceeds 5 mg/day.
13. Ideally, a switch to low molecular weight heparin (LMWH) (with target anti-Xa level of 0.8-1.2 U/ml 4-6 hours after dose) or IV unfractionated heparin (UFH) (with activated partial thromboplastin time [aPTT] 2x control) is made ≥1 week before planned delivery, followed by a switch to UFH ≥36 hours before planned delivery. UFH should be stopped ≥6 hours before planned vaginal delivery (Class 1). If urgent delivery via C-section is required, anticoagulation should be reversed first.
14. If warfarin <5 mg/day is required to maintain a therapeutic INR, continuation of warfarin for all three trimesters is reasonable (Class 2a), or dose-adjusted LMWH ≥2x/day during the first trimester, followed by warfarin for the second and third trimesters may be considered. If >5 mg/day is required, dose-adjusted LMWH during the first trimester, followed by warfarin for the second and third trimester, may be considered (Class 2a) or with continuation of LMWH for the second and third trimesters (Class 2b). The use of direct thrombin inhibitors and anti-Xa direct oral anticoagulants is still not recommended (Class 3).

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Cardiac Surgery and VHD, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound, Mitral Regurgitation

Keywords: Anticoagulants, Antithrombins, Aortic Valve Insufficiency, Aortic Valve Stenosis, Cardiac Surgical Procedures, Diagnostic Imaging, Echocardiography, Echocardiography, Transesophageal, Endocarditis, Endocarditis, Bacterial, Fibrinolytic Agents, Fibrinolytic Agents, Fluorodeoxyglucose F18, Geriatrics, Heart Defects, Congenital, Heart Valve Diseases, Heart Valve Prosthesis, Heparin, Low-Molecular-Weight, Mitral Valve Insufficiency, Mitral Valve Stenosis, Pregnancy, Secondary Prevention, Tomography, Transcatheter Aortic Valve Replacement, Warfarin

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