Valvular Heart Disease PDF

Valvular Heart Disease Jodi Taylor, PharmD, BCPS, BCCCP, FASHP  Guidelines & Statements 2022 CHEST Guideline: Perioperative Management of Antithrombotic Therapy CHEST 2022; doi:10.1016/j.chest.2022.07.025 Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines fo...

Valvular Heart Disease Jodi Taylor, PharmD, BCPS, BCCCP, FASHP  Guidelines & Statements 2022 CHEST Guideline: Perioperative Management of Antithrombotic Therapy CHEST 2022; doi:10.1016/j.chest.2022.07.025 Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS Guidelines for the Management of Valvular Heart Disease. European Heart J 2021;00:1-72 Wilson WR, Gewitz M, Lockhart PB, et al. Prevention of Viridans Group Streptococcal Infective Endocarditis. Circulation 2021;143:e963-978 Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease. A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation 2020; 143: doi: 10.1161/CIR.0000000000000923 Kumar KR, Antunes MJ, Beaton A, et al. Contemporary diagnosis and management of rheumatic heart disease: Implications for closing the gap. A scientific statement from the American Heart Association. Circulation 2020;142: DOI: 10.1161/CIR.0000000000000921 Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals from the American Heart Association Circulation 2015:132:1435-1486  Learning Objectives Compare and contrast valvular stenosis and regurgitation. Recognize and construct appropriate antithrombotic regimens for patients after heart valve intervention procedures [both surgical and catheter-based]. Recognize and construct appropriate regimens for valve thrombosis. Relay important safety considerations for patients receiving thrombolytic therapy for valve thrombosis. Appropriately adjust antithrombotic regimens after valve thrombosis. Discuss the use of antithrombotic therapy in infective endocarditis. Recognize and construct appropriate antithrombotic regimens for patients with rheumatic mitral valve disease without surgical or catheter-based intervention. Identify patient factors that indicate secondary prevention of RHD and prolong total treatment time. Identify the drug of choice for secondary prevention of RHD. Purpose of Keep blood moving in the correct direction the Heart Necessary because of pressure changes within the Valves chambers of the heart https://www.heartfoundation.org.nz/your-heart/heart-conditions/heart-valve-disease. Accessed 10/18/19.  Chordae Tendinae Upon ventricular contraction, the papillary muscles contract to prevent backflow of blood into the atria Bungard TJ, et al. Pharmacother. 2011;31(1):76-91.  AHA: Watch, Learn and Live https://watchlearnlive.heart.org/ ?moduleSelect=hrtvlv Optional interactive tutorial available for free Animations on valve anatomy, blood flow, endocarditis, prolapse, stenosis, valve repair and valve replacement  Stenosis Regurgitation Hardened valve that restricts a.k.a. valvular insufficiency forward blood flow Leaky valve that does not close properly https://www.heartfoundation.org.nz/your-heart/heart-conditions/heart-valve-disease. Accessed 10/18/19.  Origins of Valvular Disease Congenital Valvular Disease Aortic Valve Stenosis Ebstein’s Anomaly Pulmonary Valve Stenosis Tricuspid Atresia Acquired Valvular Disease Cardiovascular conditions [i.e. HTN, CHF, Atherosclerosis, AMI] Infections [i.e. rheumatic fever and endocarditis] Other causes [i.e. autoimmune disorders, Marfan’s syndrome, radiation therapy] Medications https://www.nhlbi.nih.gov/health-topics/heart-valve-disease Accessed 11/13/19. https://www.heart.org/en/health-topics/congenital-heart-defects. Accessed 11/13/19.  Age Male gender VHD Risk Cigarette smoking Factors Hypertension Elevated LDL cholesterol  Medication-Induced Valvular Disease “fen-phen” diet fad – fenfluramine derivative + phentermine fenfluramine, dexfenfluramine withdrawn from market 1997 no reported cases with phentermine alone Ergotamine, methysergide Pergolide, cabergoline MDMA (ecstasy) Bhattacharyya S, et al. Lancet 2009;374:577 Incidence & Implication Incidence increases with increasing age.  Overall survival rates lower in those with valvular disease than those without. Nkomo VT, et al. Lancet 2006;368:1005  Diagnosis Transthoracic Echocardiography (“echo”, TTE) is the gold standard for diagnosis. Other techniques may be employed if studies are inadequate or difficult or multiple diagnoses could be accomplished with one test: Transesophageal echocardiography (“TEE”) Cardiac MRI Heart catheterization Image from: https://www.nhlbi.nih.gov/health-topics/echocardiography. Accessed 11/13/19. Mrsic Z, et al. Prim Care Clin 2018;45:81  Most Common Types of VHD AR Aortic Regurgitation Allows blood to flow back into the left ventricle AS Aortic Stenosis Narrowing of the aortic valve orifice MR Mitral Regurgitation Allows blood flow back into the left atrium and pulmonary veins MS Mitral Stenosis Narrowing of the mitral valve orifice Nishimura, et al. Circulation 2014;129:e521  Symptoms Associated with VHD AR AS MR MS HF symptoms Angina HF symptoms HF symptoms Angina Syncope Decreased Decreased HF symptoms exercise exercise Decreased tolerance tolerance exercise tolerance Nishimura, et al. Circulation 2014;129:e521  AHA Classification of Valvular Disease Stages of Progressive VHD Stage Definition Symptoms A Risk factors present Absent B Progression Absent C Asymptomatic severe Absent C1: LV or RV remains compensated C2: LV or RV decompensation D Symptomatic severe Present Nishimura, et al. Circulation 2014;129:e521  Surgical Intervention Valve Repair Treatment Valve Replacement Bioprosthetic Options for Mechanical Advanced Catheter-Based Procedure VHD Valvuloplasty (aka valvotomy) Transcatheter MV Repair Transcatheter MV Replacement (TMVR) Transcatheter AV Replacement (TAVR) Surgical interventions  Bioprosthetic Valve Replacement Considerations Cons Pros Re-intervention risk (50% failure Preferred if > 70 yrs rate at 15 years) Preferred if medication non- Potential for size mismatch adherence is a concern Only requires short term VKA if no other indication Types of Bioprosthetic Valves: Xenograft (Porcine or Bovine) Autograft (Ross Procedure) Homograft Bungard TJ, et al. Pharmacother 2011;31:76 Nishimura, et al. Circulation 2017;135:e1159 Crawford MH, ed. Current Diagnosis and Treatment: Cardiology, Third Edition. McGraw-Hill.  Mechanical Valve Replacement Considerations Cons Pros Requires life-long VKA Preferred if < 50 yrs Sound may be bothersome to Preferred if additional VKA patient indication present Greater prosthesis longevity Decreased risk of re-intervention Types of Mechanical Valves: First Generation [ball and cage] – no longer implanted Second Generation [single tilting disc] Third Generation [Bileaflet tilting disc] Third generation with separate considerations: On-X valve Bungard TJ, et al. Pharmacother 2011;31:76 Nishimura, et al. Circulation 2017;135:e1159 Crawford MH, ed. Current Diagnosis and Treatment: Cardiology, Third Edition. McGraw-Hill.  Bioprosthetic Valves Image from: https://www.researchgate.net/figure/A-composite-of-bioprosthetic-valves-from-each-of- the-four-major-manufacturers_fig3_269037425. Accessed 11/4/22  Mechanical Heart Valves Image from: https://www.researchgate.net/figure/Different-heart-valve-design-types- top-left-StarrEdwards-silicone-rubber-ball-in_fig2_292306650. Accessed 11/4/22.  Valve Recommended Antithrombotic Regimen Aortic, Warfarin (INR goal 2.5) for at least 3 months and up to 6 months if low bleed risk Antithrombotic Bioprosthetic ASA 75-100 mgTherapy Following daily after initial Surgical therapy or in place of warfarinReplacement if high bleed risk Aortic, Warfarin (INR goal 2.5) for life if no RF for TE complications (no bridge) Mechanical Warfarin (INR goal 3.0) for life if RF£ for TE complications (bridge) Warfarin (INR goal 3.0) for caged ball prosthesis (bridge) Concomitant ASA 75-81 mg daily if ASA indication is present and bleed risk is low Dabigatran contraindicated. All other DOACs not recommended. On-X AVR prosthesis: ASA daily + warfarin INR goal range of 1.5-2 is reasonable after first 3 months if no TE risk factors DOACs not recommended. Mitral, Warfarin (INR goal 2.5) for at least 3 months and up to 6 months if low bleed risk Bioprosthetic ASA 75-100 mg daily after initial therapy or in place of warfarin if high bleed risk Mitral, Warfarin (INR goal 3) for life (bridge) Mechanical Concomitant ASA 75-81 mg daily if ASA indication is present and bleed risk is low Dabigatran contraindicated. All other DOACs not recommended. £ TE RF: AF, hypercoagulable state, LV dysfunction, previous thromboembolism. Severe LV dysfunction may also increase TE risk. TE RF: AF, hypercoagulable state, LV dysfunction, previous thromboembolism Bleeding risk considerations: history of GIB, ASA hyperresponse with excessively prolonged bleeding times, poorly controlled HTN, Age > 75, multiple medications or frequent antibiotic use, irratic INR control Otto CM, et al. Circulation 2020;143:e72-e227 Burchart EG, et al. Eur Heart J 2005;26:2463 TE = thromboembolic  Bridging Therapy Highest risk for thrombosis with mechanical valves All mechanical MVR Older generation AVR Mechanical AVR + thromboembolism RF Bridge with either UFH or LMWH during periods of warfarin interruption Stop UFH 4-6 hours preoperatively Stop LMWH 12 hours preoperatively Resume warfarin ASAP Avoid interruption for minor procedures Nishimura, et al. Circulation 2017;135:e1159  PROACT Trial (On-X Mechanical AVR) Low Risk ALL patients received warfarin [INR 2-3] + ASA 81 mg for first High Risk Group (n=201) 3 months postoperatively Group (n=375) Standard Standard Low-Dose DAPT Warfarin Warfarin Warfarin Low Risk Group (none of the following RF for TE risk factors) LVEF < 30% LA dimension > 50 mm Spontaneous echo contrast in the LA Significant vascular disease History of neurological events in the past year Hypercoagulability left or right ventricular aneurysm Women on estrogen replacement therapy Platelet unresponsiveness to ASA or Plavix (urine thromboxane Chronic AF assay) Puskas JD, et al. J Am Coll Cardiol 2018;71:2717  PROACT Trial (On-X Mechanical AVR) Primary Endpoint was a composite of death, any bleeding (major or minor), and any TE and valve thrombosis event. For Low-Risk, Primary Composite outcome favored warfarin due to less TE events For High-Risk, no difference in Primary Composite outcome but less bleeding with low-dose warfarin Puskas JD, et al. J Am Coll Cardiol 2018;71:2717-26 Catheter-based Interventions  TAVI Options Evolut R SAPIEN 3 Trileaflet, porcine valve Bovine valve on metal frame Self-expands Requires balloon expansion Larger surface area creates better Bottom skirt minimizes paravalvular leak seal and more interference with cardiac conduction system  Antithrombotic Therapy for Catheter-Based Procedures Procedure Type Recommended Antithrombotic Regimen Transcatheter MV repair MD discretion: Single antiplatelet therapy vs. DAPT vs. warfarin Transcatheter AV Implantation (TAVI)* DAPT or VKA (INR goal 2.5) for 3 months in low bleed risk ASA 75 – 100 mg for life Low dose rivaroxaban + ASA associated with higher risk of death and TE events v. DAPT¥ *Warfarin in TAVI recommendation only for patients with low bleeding risk. Guidelines do not address therapy modification for high-risk patients, patients with compelling indications for anticoagulation, or if SAPT or DAPT should be selected for candidates for VKA. Otto CM, et al. Circulation 2020;143:e72-e227 ¥ Galileo trial. Giustino G, et al. Cardiovasc Res 2020;116:e39 Readjusting Therapy: Events AFTER Valvular Intervention  Events after Valvular Intervention Thromboembolic Valvular event (TE) Thrombosis TE event: CVA or Thrombi form on the systemic embolic valve event  TE Events After Intervention Valve Location, Type Therapy Adjustment Aortic, If INR within range at time of TE, increase INR goal to 3.0 (2.5-3.5) or add ASA 75-100 mg daily mechanical Mitral, If INR within range at time of TE, increase INR goal to 4.0 (3.5-4.0) or add ASA 75-100 mg daily mechanical Bioprosthetic If on ASA at time of TE, change to VKA Documentation of INR goal adjustments is critical!! TE=thromboembolic  Acute Valve Thrombosis Valve Location, Type Therapy Patient Presentation Left-sided, Urgent evaluation Mechanical Emergency surgery or fibrinolytic infusion→ Symptoms Present *Fibrinolytic infusion is an acceptable alternative for those with high surgical risk and small thrombus burden, mild HF symptoms, and low bleeding risk. Absence of surgical expertise should also be considered. Right-sided, IV heparin Mechanical Bioprosthetic VKA if no CI to OAC HD stable Left side = Mitral, Aortic valve; Right side = Pulmonic, Tricuspid Valve Otto CM, et al. Circulation 2020;143:e72-e227 Nishimura, et al. Circulation 2017;135:e1159  Thrombolytic Therapy ▪ Absolute Contraindications Relative Contraindications - Prior intracranial hemorrhage – Poorly controlled or chronic sustained HTN (SBP > - Known structural cerebral vascular lesion 180 mmHg) - Known malignant intracranial neoplasm – Ischemic stroke within 3 months – Dementia or other intracranial pathology - Ischemic stroke within 3 months – Traumatic or prolonged CPR (> 10 min) - Suspected aortic dissection – Major surgery within 3 weeks - Active bleeding – Noncompressible vascular puncture - Bleeding diathesis – Pregnancy - Significant closed-head or facial trauma – Active peptic ulcer within 3 months – Current use of anticoagulants – Risk of ICH > 4%  Thrombolytic Therapy Dosing ▪Hold anticoagulant and initiate thrombolytics when INR < 2.5 (warfarin) or aPTT < 50 sec (UFH) ▪Alteplase dosing varies, most common: Phase I: Alteplase 25 mg IV over 25 hours, then Phase II: 6-hr infusion of UFH (70 unit/kg bolus and 16 unit/kg/hr, target aPTT 1.5-2.0x control) ▪Response assessed by TEE Partial resolution → repeat alteplase can be considered Complete resolution → transition to warfarin with bridging ▪Ensure NO IM INJECTIONS!! Ozkan M, et al. Am Heart J 2015;170:409 Otto CM, et al. Circulation 2020;143:e72-e227  Reassessing your patient… After Valve Thrombosis, you must reassess your regimen ▪ VKA therapy ▪ Carefully and intentionally document INR goals ▪ Assess adherence and TTR ▪ Document interventions Otto CM, et al. Circulation 2020;143:e72-e227 VHD and AF  Valvular AF: Historical Perspective Eikelboom JW, et al. N Engl J Med 2013;369:1206-1214  Valvular Heart Disease: Historical Perspective Subsequent to the results of RE-ALIGN, DOAC phase III trials excluded patients with: Mechanical prosthetic heart valves Moderate to severe mitral stenosis (usually of rheumatic origin) Inconsistent definitions and unclear labeling have led to the development of a new categorization  Evaluated Heartvalves, Rheumatic or Artificial (EHRA) ▪EHRA Type 1 Refers to patients with VHD needing OAC therapy with VKA Mechanical prosthetic heart valve or moderate – severe mitral stenosis ▪EHRA Type 2 Refers to patients with VHD needing OAC with either VKA or DOAC All other native valve stenoses and insufficiencies, mitral valve repair patients, bioprosthetic valve replacements, and transaortic valve interventions (TAVI) Steffel J, et al. Eur Heart J 2018;39:1330-1393  AF + Bioprosthetic Heart Valves DOAC is an effective alternative to VKA if  3 months have passed since implantation ▪ Exception: those who have rheumatic mitral stenosis should not receive DOAC ▪ Anticoagulation Qualification: AF AC indication based on CHADSVASc score Otto CM, et al. Circulation 2020;143:e72-e227 Infective Endocarditis  Infective Endocarditis (IE) Modified Duke Criteria Major Criteria Blood culture positive (2 separate cultures or persistently Evidence of endocardial involvement positive) Minor Criteria Predisposition or IVDA Fever > 38⁰C Vascular phenomena Immunological phenomena Microbiological evidence Definite IE Possible IE Rejected Microorganisms demonstrated by culture or 1 major and 1 minor Firm alternative diagnosis histological examination or a vegetation criteria Pathological lesions confirmed by histological 3 minor criteria Resolution of IE with antibiotic therapy for < 4 examination days 2 major criteria No pathological evidence at surgery or autopsy with antibiotic therapy < 4 days 1 major and 3 minor criteria Does not meet criteria for possible IE 5 minor criteria  IE Treatment Do not give antibiotics prior to blood cultures for patients with known VHD and unexplained fever Bactericidal agents preferred Start counting days of therapy on first day blood cultures are negative Culture every 24-48 hours until bloodstream infection has cleared Native valve usually 4 weeks of therapy Prosthetic valve usually 6 weeks of therapy Agent recommendations in guidelines by pathogen Patients with IE associated with IVDA should be referred for addiction treatment Left-sided IE [streptococcus, E. faecalis, S. aureus, or CONS] that is stable after initial IV antibiotics TEE to exclude paravalvular infection Transition to oral antibiotics Follow-up TEE 1-3 days prior to completion of antibiotic course Otto CM, et al. Circulation 2020;143:e72-e227 IVDA=IV drug abuse TEE=transesophageal echocardiography Baddour LM, et al. Circulation 2015;132:1435-1486 CONS=coagulase negative staphylococcus  Infective Endocarditis Prophylaxis in Patients with VHD Specific Dental Procedures Highest Risk Conditions Gingival manipulation Prosthetic cardiac valve or valve material Periapical tooth region manipulation Previous, relapse, or recurrent IE Mucosal perforation Congenital heart disease Cardiac transplant patients with valvulopathy Route/Allergy Antibiotic (single dose) Oral Amoxicillin 2 g No oral access Ampicillin 2 g IV/IM, Cefazolin 1 g IM/IV, Ceftriaxone 1 g IM/IV PCN Allergy Cephalexin 2 g, Azithromycin 500 mg, Clarithromycin 500 mg, Doxycycline 100 mg PCN Allergy + No oral Cefazolin 1 g IV/IM, Ceftriaxone 1 g IV/IM access Wilson WR, et al. Circulation 2021;143:e963  IE: No Role for Anticoagulation! ▪ Addition of antithrombotic therapy does not reduce the incidence of embolic events and increases the rate of neurologic complications related to cerebral hemorrhage. Patients should not routinely be given antiplatelet/anticoagulant medications for the sole indication of IE. ▪ In patients with IE and evidence of cerebral embolism or stroke, regardless of other indications for anticoagulation, it is reasonable to temporarily discontinue anticoagulation COR 2a, LOE B-NR ▪ In patients receiving VKA anticoagulation at the time of IE diagnosis, temporary discontinuation of VKA may be considered COR 2b, LOE B-NR ▪ Separate indications for antiplatelet/anticoagulant medications should be carefully considered for risks and benefits. Whitlock RP, et al. Chest 2012;141:e576S  Rheumatic Heart Disease Global Burden of Rheumatic Heart Disease  Anticoagulation Considerations Rheumatic mitral valve disease (RMVD) RMVD carries the greatest risk of systemic thromboembolism of any common form of acquired valvular disease. Presence of risk factors for thrombosis warrants addition of warfarin (INR goal 2.5): Previous embolus Hypercoagulable state AF LA thrombus Large LA diameter(> 55 mm) Whitlock RP, et al. CHEST 2012;141(2)(Suppl):e576S-3600S  What about FXA inhibitors??? Retrospective Review of Insurance Database in Korea AF + Mitral Stenosis (n=2330) Off-Label Warfarin DOAC ICH ICH TE Annual TE Annual Occurrence Occurrence Rate 2.22% Rate 4.19% 0.49% 0.93% Kim JY, et al. J Am Coll Cardiol 2019;73:1123  Rivaroxaban for AF + RHD? Primary Efficacy Outcome: Composite of Stroke, Systemic Embolism, MI or Death from Vascular or Unknown cause ▪ Lower in warfarin group (Kaplan-Meier ) ▪ Lower rate of Stroke with warfarin ▪ Lower rate of Death with warfarin AF + RHD (n=4531) Primary Safety Outcome: Major Bleeding (ISTH definition) ▪ No difference between groups Rivaroxaban Warfarin INVICTUS trial. Connolly SJ, et al. N Engl J Med 2022. DOI: 10.1056/NEJMoa2209051  Secondary Penicillin Prophylaxis ARF: 2-4 weeks after GAS infection → fever, acute joint symptoms, skin manifestations, elevated inflammatory markers Evaluation for carditis, occurs during ARF and is characterized by lesions including pericarditis and valvulitis. Provision of Secondary Prophylaxis to Reduce Progression to RHD Presentation Recommendation No documented history of ARF No secondary prophylaxis ARF, no carditis Total 5 years or until age 21, whichever is longer Benzathine penicillin G is the drug of ARF, resolved carditis Total 10 years or until age 21, whichever is longer choice for secondary prevention, given IM every 3-4 weeks. ARF, severe chronic RHD (including Total 10 years or until age 40 (or life) after surgical intervention) GAS=group A streptococcus; ARF=acute rheumatic fever; RHD=rheumatic heart disease Practice Problems Uploaded to Canvas!  References 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 Otto CM, Kumbhani DJ, Alexander KP, et al. 2017 ACC expert consensus decision pathway for transcatheter aortic valve replacement in the management of adults with aortic stenosis. J Am Coll Cardiol 2017;69:1313-46 Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association. Circulation 2007;116:1736-54 Kalich BA, Allender JE, Hollis IB. Medication management of patients undergoing transcatheter aortic valve replacement. Pharmacotherapy 2018;38:122-38 Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018;154:1121-1201 Bungard TJ, Sonnenberg B. Valvular Heart Disease: A Primer for the Clinical Pharmacist. Pharmacother. 2011;31:76-91. Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines, Ninth Edition. CHEST. 2012;141:e576S-e600S Crawford MH, editor. Current Diagnosis and Treatment: Cardiology, Third Edition. McGraw-Hill. Others as referenced on slides. Valvular Heart Disease Jodi Taylor, PharmD, BCPS, BCCCP, FASHP