Antithrombotic Treatment in Cardiomyopathies

Author(s): Georgia Vogiatzi*, Antonios Pantazis, Dimitris Tousoulis

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 23 , 2020

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Cardiomyopathies are a heterogeneous group of heart muscle diseases and important cause of heart failure with reduced or preserved ejection fraction. Although there is an increasing body of evidence on the incidence, pathophysiology, and natural history of heart failure (HF) in cardiomyopathies, certain aspects of the therapeutic strategies remain unclear. More particularly, there is no consensus if to whether antithrombotic therapy has a favorable risk: benefit ratio in reducing thromboembolic event rate in patients with cardiomyopathies without suffering from primary valvular disease or atrial fibrillation. Although the observational data on increased venous thromboembolic risk are supported by multiple pathophysiological mechanisms, the role of antithrombotic therapy in these patients remains unclear. This review article provides an overview of epidemiologic, pathophysiologic, clinical, and therapeutic data for the prevention of thromboembolism in heart failure due to cardiomyopathies.

Keywords: Cardiomyopathies, heart failure, antithrombotic, anticoagulation, anti-platelets, thromboembolism.

Pinto YM, Elliott PM, Arbustini E, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J 2016; 37(23): 1850-8.
[] [PMID: 26792875]
Yamamoto K, Ikeda U, Furuhashi K, Irokawa M, Nakayama T, Shimada K. The coagulation system is activated in idiopathic cardiomyopathy. J Am Coll Cardiol 1995; 25(7): 1634-40.
[] [PMID: 7539015]
Jessup M, Brozena S. Heart failure. N Engl J Med 2003; 348(20): 2007-18.
[] [PMID: 12748317]
Jafri SM, Ozawa T, Mammen E, Levine TB, Johnson C, Goldstein S. Platelet function, thrombin and fibrinolytic activity in patients with heart failure. Eur Heart J 1993; 14(2): 205-12.
[] [PMID: 8449196]
Sirajuddin RA, Miller AB, Geraci SA. Anticoagulation in patients with dilated cardiomyopathy and sinus rhythm: a critical literature review. J Card Fail 2002; 8(1): 48-53.
[] [PMID: 11862583]
Fuster V, Rydén LE, Asinger RW, et al. ACC/AHA/ESC 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 and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology. Eur Heart J 2001; 22(20): 1852-923.
[] [PMID: 11601835]
Chesebro JH, Ezekowitz M, Badimon L, Fuster V. Intracardiac thrombi and systemic thromboembolism: detection, incidence, and treatment. Annu Rev Med 1985; 36: 579-605.
[] [PMID: 3888065]
Kubo SH, Rector TS, Bank AJ, Williams RE, Heifetz SM. Endothelium-dependent vasodilation is attenuated in patients with heart failure. Circulation 1991; 84(4): 1589-96.
[] [PMID: 1914099]
Chung I, Lip GY. Platelets and heart failure. Eur Heart J 2006; 27(22): 2623-31.
[] [PMID: 17028108]
Erne P, Wardle J, Sanders K, Lewis SM, Maseri A. Mean platelet volume and size distribution and their sensitivity to agonists in patients with coronary artery disease and congestive heart failure. Thromb Haemost 1988; 59(2): 259-63.
[] [PMID: 3388297]
Serebruany V, McKenzie M, Meister A, et al. Whole blood impedance aggregometry for the assessment of platelet function in patients with congestive heart failure (EPCOT Trial). Eur J Heart Fail 2002; 4(4): 461-7.
[] [PMID: 12167384]
Sbarouni E, Bradshaw A, Andreotti F, Tuddenham E, Oakley CM, Cleland JG. Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J 1994; 127(3): 607-12.
[] [PMID: 8122609]
Levine TB, Levine AB. Regional blood flow supply and demand in heart failure. Am Heart J 1990; 120(6 Pt 2): 1547-51.
[] [PMID: 2248211]
Ikeda U, Yamamoto K, Shimada K. Biochemical markers of coagulation activation in mitral stenosis, atrial fibrillation, and cardiomyopathy. Clin Cardiol 1997; 20(1): 7-10.
[] [PMID: 8994731]
Casaclang-Verzosa G, Gersh BJ, Tsang TS. Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation. J Am Coll Cardiol 2008; 51(1): 1-11.
[] [PMID: 18174029]
Dries DL, Rosenberg YD, Waclawiw MA, Domanski MJ. Ejection fraction and risk of thromboembolic events in patients with systolic dysfunction and sinus rhythm: evidence for gender differences in the studies of left ventricular dysfunction trials. J Am Coll Cardiol 1997; 29(5): 1074-80.
[] [PMID: 9120162]
Loh E, Sutton MS, Wun CC, et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336(4): 251-7.
[] [PMID: 8995087]
Kozdag G, Ciftci E, Ural D, et al. Silent cerebral infarction in chronic heart failure: ischemic and nonischemic dilated cardiomyopathy. Vasc Health Risk Manag 2008; 4(2): 463-9.
[] [PMID: 18561522]
Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986; 314(24): 1547-52.
[] [PMID: 3520315]
Pfeffer MA, Braunwald E, Moyé LA, et al. The SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med 1992; 327(10): 669-77.
[] [PMID: 1386652]
Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325(5): 293-302.
[] [PMID: 2057034]
Pfeffer MA, et al. [Effect of captopril on mortality and morbidity in patients with dysfunction of the left ventricle after myocardial infarction. Results on survival and hypertrophic studies] Kardiologiia 1993; 33(12): 14--23, 3...
CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316(23): 1429-35.
[] [PMID: 2883575]
Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK. HELAS investigators. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail 2006; 8(4): 428-32.
[] [PMID: 16737850]
Mujib M, Rahman AA, Desai RV, et al. Warfarin use and outcomes in patients with advanced chronic systolic heart failure without atrial fibrillation, prior thromboembolic events, or prosthetic valves. Am J Cardiol 2011; 107(4): 552-7.
[] [PMID: 21185004]
Massie BM, Collins JF, Ammon SE, et al. WATCH Trial Investigators. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation 2009; 119(12): 1616-24.
[] [PMID: 19289640]
Graham S, Ye S, Qian M, et al. WARCEF Investigators. Cognitive function in ambulatory patients with systolic heart failure: insights from the warfarin versus aspirin in reduced cardiac ejection fraction (WARCEF) trial. PLoS One 2014; 9(11)e113447
[] [PMID: 25426862]
Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Committee for Practice Guidelines (CPG). ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29(19): 2388-442.
[] [PMID: 18799522]
Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126(3)(Suppl.): 483S-512S.
[] [PMID: 15383482]
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016; 18(8): 891-975.
[] [PMID: 27207191]
Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002; 287(10): 1308-20.
[] [PMID: 11886323]
Maron BJ, Casey SA, Hauser RG, Aeppli DM. Clinical course of hypertrophic cardiomyopathy with survival to advanced age. J Am Coll Cardiol 2003; 42(5): 882-8.
[] [PMID: 12957437]
Robinson K, Frenneaux MP, Stockins B, Karatasakis G, Poloniecki JD, McKenna WJ. Atrial fibrillation in hypertrophic cardiomyopathy: a longitudinal study. J Am Coll Cardiol 1990; 15(6): 1279-85.
[] [PMID: 2329232]
Ho CY, Seidman CE. A contemporary approach to hypertrophic cardiomyopathy. Circulation 2006; 113(24): e858-62.
[] [PMID: 16785342]
Seferović PM, Polovina M, Bauersachs J, et al. Heart failure in cardiomyopathies: a position paper from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019; 21(5): 553-76.
[] [PMID: 30989768]
Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013; 381(9862): 242-55.
[] [PMID: 22874472]
Kubo T, Kitaoka H, Okawa M, et al. Clinical impact of atrial fibrillation in patients with hypertrophic cardiomyopathy. Results from Kochi RYOMA Study. Circ J 2009; 73(9): 1599-605.
[] [PMID: 19590139]
Elliott PM, Anastasakis A, Borger MA, et al. Authors/Task Force members. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35(39): 2733-79.
[] [PMID: 25173338]
Guttmann OP, Pavlou M, O’Mahony C, et al. Hypertrophic Cardiomyopathy Outcomes Investigators. Prediction of thrombo-embolic risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA). Eur J Heart Fail 2015; 17(8): 837-45.
[] [PMID: 26183688]
Guttmann OP, Rahman MS, O’Mahony C, Anastasakis A, Elliott PM. Atrial fibrillation and thromboembolism in patients with hypertrophic cardiomyopathy: systematic review. Heart 2014; 100(6): 465-72.
[] [PMID: 24014282]
Dominguez F, Climent V, Zorio E, et al. Direct oral anticoagulants in patients with hypertrophic cardiomyopathy and atrial fibrillation. Int J Cardiol 2017; 248: 232-8.
[] [PMID: 28811092]
Maron MS, Finley JJ, Bos JM, et al. Prevalence, clinical significance, and natural history of left ventricular apical aneurysms in hypertrophic cardiomyopathy. Circulation 2008; 118(15): 1541-9.
[] [PMID: 18809796]
Shenoy C, Maron MS. Hypertrophic cardiomyopathy with left ventricular apical aneurysm in brothers. Am J Cardiol 2011; 108(4): 612-3.
[] [PMID: 21684510]
Holloway CJ, Betts TR, Neubauer S, Myerson SG. Hypertrophic cardiomyopathy complicated by large apical aneurysm and thrombus, presenting as ventricular tachycardia. J Am Coll Cardiol 2010; 56(23): 1961.
[] [PMID: 21109122]
Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic Cardiomyopathy With Left Ventricular Apical Aneurysm: Implications for Risk Stratification and Management. J Am Coll Cardiol 2017; 69(7): 761-73.
[] [PMID: 28209216]
Towbin JA, et al. HRS expert consensus statement on evaluation,risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm 2019; 2019
Homma S, Thompson JL, Pullicino PM, et al. WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012; 366(20): 1859-69.
[] [PMID: 22551105]
Lip GY, Ponikowski P, Andreotti F, et al. ESC Task Force. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm. A joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Eur J Heart Fail 2012; 14(7): 681-95.
[] [PMID: 22611046]
Wlodarska EK, Wozniak O, Konka M, Rydlewska-Sadowska W, Biederman A, Hoffman P. Thromboembolic complications in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Europace 2006; 8(8): 596-600.
[] [PMID: 16760233]
January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline 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. J Am Coll Cardiol 2014; 64(21): e1-e76.
[] [PMID: 24685669]
Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg 2016; 50(5): e1-e88.
[] [PMID: 27663299]
Muchtar E, Blauwet LA, Gertz MA. Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circ Res 2017; 121(7): 819-37.
[] [PMID: 28912185]
Abboud J, Murad Y, Chen-Scarabelli C, Saravolatz L, Scarabelli TM. Peripartum cardiomyopathy: a comprehensive review. Int J Cardiol 2007; 118(3): 295-303.
[] [PMID: 17208320]
Lampert MB, Lang RM. Peripartum cardiomyopathy. Am Heart J 1995; 130(4): 860-70.
[] [PMID: 7572598]
Nishi I, Ishimitsu T, Ishizu T, et al. Peripartum cardiomyopathy and biventricular thrombi. Circ J 2002; 66(9): 863-5.
[] [PMID: 12224827]
Amos AM, Jaber WA, Russell SD. Improved outcomes in peripartum cardiomyopathy with contemporary. Am Heart J 2006; 152(3): 509-13.
[] [PMID: 16923422]
Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62(16): e147-239.
[] [PMID: 23747642]
Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of peripartum cardiomyopathy: a position statement from the Heart Failure Association of the European Society of Cardiology Working Group on peripartum cardiomyopathy. Eur J Heart Fail 2010; 12(8): 767-78.
[] [PMID: 20675664]
Bhattacharyya A, Basra SS, Sen P, Kar B. Peripartum cardiomyopathy: a review. Tex Heart Inst J 2012; 39(1): 8-16.
[PMID: 22412221]
Mandal D, Mandal S, Mukherjee D, et al. Pregnancy and subsequent pregnancy outcomes in peripartum cardiomyopathy. J Obstet Gynaecol Res 2011; 37(3): 222-7.
[] [PMID: 21114580]
Hilfiker-Kleiner D, Haghikia A, Berliner D, et al. Bromocriptine for the treatment of peripartum cardiomyopathy: a multicentre randomized study. Eur Heart J 2017; 38(35): 2671-9.
[] [PMID: 28934837]
McNamara DM, Elkayam U, Alharethi R, et al. Clinical Outcomes for Peripartum Cardiomyopathy in North America: Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol 2015; 66(8): 905-14.
[] [PMID: 26293760]
Sheppard R, Rajagopalan N, Safirstein J, Briller J. An update on treatments and outcomes in peripartum cardiomyopathy. Future Cardiol 2014; 10(3): 435-47.
[] [PMID: 24976479]
Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006; 113(14): 1807-16.
[] [PMID: 16567565]
Gati S, Chandra N, Bennett RL, et al. Increased left ventricular trabeculation in highly trained athletes: do we need more stringent criteria for the diagnosis of left ventricular non-compaction in athletes? Heart 2013; 99(6): 401-8.
[] [PMID: 23393084]
Gati S, Papadakis M, Van Niekerk N, Reed M, Yeghen T, Sharma S. Increased left ventricular trabeculation in individuals with sickle cell anaemia: physiology or pathology? Int J Cardiol 2013; 168(2): 1658-60.
[] [PMID: 23582434]
Gati S, Papadakis M, Papamichael ND, et al. Reversible de novo left ventricular trabeculations in pregnant women: implications for the diagnosis of left ventricular noncompaction in low-risk populations. Circulation 2014; 130(6): 475-83.
[] [PMID: 25006201]
Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol 2000; 36(2): 493-500.
[] [PMID: 10933363]
Fazio G, Corrado G, Zachara E, et al. Anticoagulant drugs in noncompaction: a mandatory therapy? J Cardiovasc Med (Hagerstown) 2008; 9(11): 1095-7.
[] [PMID: 18852579]
Aras D, Tufekcioglu O, Ergun K, et al. Clinical features of isolated ventricular noncompaction in adults long-term clinical course, echocardiographic properties, and predictors of left ventricular failure. J Card Fail 2006; 12(9): 726-33.
[] [PMID: 17174235]
Stöllberger C, Blazek G, Dobias C, Hanafin A, Wegner C, Finsterer J. Frequency of stroke and embolism in left ventricular hypertrabeculation/noncompaction. Am J Cardiol 2011; 108(7): 1021-3.
[] [PMID: 21784395]
Lofiego C, Biagini E, Pasquale F, et al. Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction. Heart 2007; 93(1): 65-71.
[] [PMID: 16644854]

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Year: 2020
Page: [2762 - 2768]
Pages: 7
DOI: 10.2174/1381612826666200429230726
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