Indications for anticoagulation in native mitral valve disease

Indications for anticoagulation in native mitral valve disease

As per earlier reports, anticoagulation in native valvular heart disease was considered when there is chronic or paroxysmal atrial fibrillation, in those with a very large left atrium, those with severe left ventricular dysfunction or heart failure and when there is a previous history of thromboembolism [1]. Anticoagulation for mitral regurgitation with atrial fibrillation will usually follow the guidelines in non-valvar atrial fibrillation which excludes moderate or more rheumatic mitral stenosis and prosthetic valve. Those two mandate the use of vitamin K antagonists for anticoagulation as of now.

As per the 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease, Class I recommendation is there for anticoagulation with vitamin K antagonist in rheumatic mitral stenosis with atrial fibrillation, prior embolic event or left atrial thrombus [2]. Anticoagulation with vitamin K antagonists decreases the incidence of thromboembolic events in these situations.

Anticoagulation in rheumatic mitral stenosis with sinus rhythm based on left atrial enlargement or spontaneous echo contrast noted on transesophageal echocardiography is mentioned as controversial in the 2020 ACC/AHA Guideline. One study of 848 patients with rheumatic mitral stenosis in sinus rhythm showed left atrial thrombus on transesophageal echo in 56 (6.6%) [3]. On univariate analysis, there was a trend toward thrombus formation in the study in those above 44 years, and in those with inferoposterior left atrial diameter more than 6.9 cm, mean mitral gradient more than 18 mm Hg and dense spontaneous echo contrast. But none of these factors predicted clot formation on multivariate analysis.

Those with very large left atria in rheumatic mitral stenosis with sinus rhythm have more spontaneous echo contrast and lower left atrial appendage velocities, which have been associated with higher rate of embolic events. Body size indexed left atrial volume of more than 60 ml per square meter has good sensitivity, but low specificity for high thromboembolic risk [4].

Non-vitamin K oral anticoagulation has not been studied in randomized controlled trials in patients with rheumatic mitral stenosis. These patients were excluded from the randomized atrial fibrillation trials. There is much higher risk of embolization with rheumatic valvular heart disease compared to those of other etiologies. It is thought that rheumatic process also affects the atrial muscle, increasing the risk of blood flow stasis and thrombosis in left atrial appendage and body [2].

A retrospective analysis using observational insurance database has reported benefit with off-label use of direct oral anticoagulants (DOACs) in rheumatic mitral stenosis with atrial fibrillation [5]. They mentioned that their data is hypothesis generating and needs to be replicated in a randomized trial. But an accompanying editorial cautions us about the difference between such retrospective data and rigorous randomized controlled trials (RCT). Details like severity and etiology of the disease are often not available in such databases. Reporting of clinical outcomes relying on diagnosis codes submitted by a large variety of health care providers will have greater variability than the blinded endpoint adjudication by a panel of independent experts in an RCT [6].

References

1. Chesebro JH, Adams PC, Fuster V. Antithrombotic therapy in patients with valvular heart disease and prosthetic heart valves. J Am Coll Cardiol. 1986 Dec;8(6 Suppl B):41B-56B. doi: 10.1016/s0735-1097(86)80006-7. PMID: 3537070.
2. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O’Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021 Feb 2;143(5):e35-e71. doi: 10.1161/CIR.0000000000000932. Epub 2020 Dec 17. Erratum in: Circulation. 2021 Feb 2;143(5):e228. Erratum in: Circulation. 2021 Mar 9;143(10):e784. PMID: 33332149.
3. Manjunath CN, Srinivasa KH, Panneerselvam A, Prabhavathi B, Ravindranath KS, Rangan K, Dhanalakshmi C. Incidence and predictors of left atrial thrombus in patients with rheumatic mitral stenosis and sinus rhythm: a transesophageal echocardiographic study. Echocardiography. 2011 Apr;28(4):457-60. doi: 10.1111/j.1540-8175.2010.01361.x. Epub 2011 Mar 23. PMID: 21426392.
4. Keenan NG, Cueff C, Cimadevilla C, Brochet E, Lepage L, Detaint D, Himbert D, Iung B, Vahanian A, Messika-Zeitoun D. Usefulness of left atrial volume versus diameter to assess thromboembolic risk in mitral stenosis. Am J Cardiol. 2010 Oct 15;106(8):1152-6. doi: 10.1016/j.amjcard.2010.06.024. PMID: 20920656.
5. Kim JY, Kim SH, Myong JP, Kim YR, Kim TS, Kim JH, Jang SW, Oh YS, Lee MY, Rho TH. Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis. J Am Coll Cardiol. 2019 Mar 19;73(10):1123-1131. doi: 10.1016/j.jacc.2018.12.047. PMID: 30871695.
6. Giugliano RP, O’Gara PT. DOACs in Patients With Mitral Stenosis and Atrial Fibrillation: Time for a Randomized Clinical Trial. J Am Coll Cardiol. 2019 Mar 19;73(10):1132-1134. doi: 10.1016/j.jacc.2018.12.048. PMID: 30871696.