Arterial thrombo-embolic events in cardiac amyloidosis: a look beyond atrial fibrillation

Abstract Background Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort. Methods and results Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from 5 Italian referral centres were retrospectively evaluated and followed-up for a median time of 19 months. Thirty-one patients (7.6%) suffered from an AE, of whom 10 (32.2%) were in sinus rhythm and had no history of AF. There were no significant differences in terms of age, gender and type of CA between patients with or without AEs. Fourteen (7.6%) of 185 patients on anticoagulation had an AE despite therapy. Anticoagulation therapy did not appear to fully protect from the risk of events (HR 1.23, 95%CI 0.52–2.92, p = .64). The only predictor of AEs, in particular among CA patients in sinus rhythm, was a CHA2DS2-VASC score ≥ 3 (HR 2.84, 95%CI 1.02–7.92, p = .05 in overall population; HR 10.13, 95%CI 1.12–91.19, p = .04 in patients in sinus rhythm). Conclusions In our large, multicentric, real-world cohort, prevalence and incidence rate of AEs was high. A consistent proportion of events occurred despite anticoagulation therapy or in patients in sinus rhythm. A higher CHA2DS2-VASc score might identify patients at risk of AEs also among those in sinus rhythm.

[1]  H. Kamel,et al.  Tailoring the Approach to Embolic Stroke of Undetermined Source: A Review. , 2019, JAMA neurology.

[2]  C. Autore,et al.  Predicting the Unpredictable: How to Score the Risk of Stroke in Cardiac Amyloidosis? , 2019, Journal of the American College of Cardiology.

[3]  M. Maurer,et al.  Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. , 2019, Journal of the American College of Cardiology.

[4]  J. Moon,et al.  High Prevalence of Intracardiac Thrombi in Cardiac Amyloidosis. , 2019, Journal of the American College of Cardiology.

[5]  Roger D. White,et al.  Direct Current Cardioversion of Atrial Arrhythmias in Adults With Cardiac Amyloidosis. , 2019, Journal of the American College of Cardiology.

[6]  G. Lip,et al.  Relation of the CHA2DS2-VASc Score to Risk of Thrombotic and Embolic Stroke in Community-Dwelling Individuals Without Atrial Fibrillation (From The Atherosclerosis Risk in Communities [ARIC] Study). , 2019, The American journal of cardiology.

[7]  R. Kronmal,et al.  The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods , 2018, International journal of stroke : official journal of the International Stroke Society.

[8]  Sung-Soo Yoon,et al.  Serum Free Light Chain Difference and &bgr;2 Microglobulin Levels Are Risk Factors for Thromboembolic Events in Patients With AL Amyloidosis , 2018, Clinical lymphoma, myeloma & leukemia.

[9]  M. Henein,et al.  Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis , 2018, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[10]  Salma I. Patel,et al.  CHA2DS2‐VASc Score: A Predictor of Thromboembolic Events and Mortality in Patients With an Implantable Monitoring Device Without Atrial Fibrillation , 2017, Mayo Clinic proceedings.

[11]  R. Falk,et al.  AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. , 2016, Journal of the American College of Cardiology.

[12]  James C Moon,et al.  Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis , 2016, Circulation.

[13]  J. Saver CLINICAL PRACTICE. Cryptogenic Stroke. , 2016, The New England journal of medicine.

[14]  H. Kamel,et al.  Atrial Fibrillation and Mechanisms of Stroke: Time for a New Model , 2016, Stroke.

[15]  A. Gorst-rasmussen,et al.  Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation. , 2015, JAMA.

[16]  J. Halperin,et al.  Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences. , 2015, Journal of the American College of Cardiology.

[17]  C. Rapezzi,et al.  Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role , 2015, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[18]  F. Salvi,et al.  Cardiac amyloidosis: the great pretender , 2015, Heart Failure Reviews.

[19]  S. Connolly,et al.  Embolic strokes of undetermined source: the case for a new clinical construct , 2014, The Lancet Neurology.

[20]  Mary G. George,et al.  An Updated Definition of Stroke for the 21st Century: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association , 2013, Stroke.

[21]  G. Lip,et al.  Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study , 2012, BMJ Open.

[22]  F. Salvi,et al.  Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. , 2011, JACC. Cardiovascular imaging.

[23]  Matthew W. Martinez,et al.  Intracardiac Thrombosis and Anticoagulation Therapy in Cardiac Amyloidosis , 2009, Circulation.

[24]  Krishnaswamy Chandrasekaran,et al.  Intracardiac Thrombosis and Embolism in Patients With Cardiac Amyloidosis , 2007, Circulation.

[25]  R. Falk,et al.  Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis , 2005, American journal of hematology.

[26]  It Istituto Superiore di Sanit,et al.  Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from th 10th International Symposium on Amyloid an Amyloidosis, Tours, France, 18-22 April 2004 , 2005 .

[27]  J. Seward,et al.  Left atrial myopathy in cardiac amyloidosis: implications of novel echocardiographic techniques. , 2005, European heart journal.

[28]  James B Seward,et al.  Left atrial volume in the prediction of first ischemic stroke in an elderly cohort without atrial fibrillation. , 2004, Mayo Clinic proceedings.

[29]  B. Maron,et al.  Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy. , 2002, Journal of the American College of Cardiology.

[30]  R B D'Agostino,et al.  Left atrial size and the risk of stroke and death. The Framingham Heart Study. , 1995, Circulation.