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Atrial cardiomyopathy: Pathophysiology and clinical implications

  • Antonella Tufano
    Correspondence
    Corresponding author.
    Affiliations
    Department of Clinical Medicine and Surgery, Federico II University Hospital, Via S. Pansini, 5, Naples 80131, Italy
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  • Patrizio Lancellotti
    Affiliations
    Department of Cardiology, GIGA Cardiovascular Sciences, CHU SartTilman, University of Liège Hospital, Avenue de L'Hôpital 1, Liège 4000, Belgium

    Cardiology Departments, Gruppo Villa Maria Care and Research, Maria Cecilia Hospital, Italy and Anthea Hospital, Cotignola Bari, Via Corriera, 1, 48033 Cotignola RA, Via Camillo Rosalba, 35/37, Bari 70124, Italy
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Published:March 11, 2022DOI:https://doi.org/10.1016/j.ejim.2022.03.007

      Highlights

      • In recent years there has been growing interest in better evaluating left atrial dilation and myocardial fibrosis as a substrate for AF.
      • Easily accessible parameters at transthoracic echocardiography such as abnormal left atrial volume/function, integrated with the currently used clinical scores could substantially improve thromboembolic risk prediction in AF.
      • Detection of atrial cardiomyopathy could also improve the evaluation of the duration of anticoagulant therapy after ablation, and also the identification of individuals for whom ablation therapy will fail.
      • Detection of atrial cardiomyopathy might be useful for guiding the selection of the appropriate antiarrhythmic drugs, rhythm maintenance and rate control therapy, by identifying patients who are likely to experience therapy failures.

      Keywords

      The term atrial cardiomyopathy appears sporadically in the medical literature, and generally has been used in conjunction with atrial fibrillation (AF), or as “atrial fibrotic cardiomyopathy”, a pathological determinant of AF, caused by a primary cardiomyopathic process, independent of the arrhythmic disorder [
      • Kottkamp H.
      Fibrotic atrial cardiomyopathy: a specific disease/syndrome supplying substrates for atrial fibrillation, atrial tachycardia, sinus node disease, AV node disease, and thromboembolic complications.
      ,
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ].
      The definition of atrial cardiomyopathy as: “Any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically-relevant manifestations” was proposed for the first time in a consensus document produced in 2016 by the European Heart Rhythm Association (EHRA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latino americana de Estimulacion Cardiaca y Electrofisiología (SOLAECE), in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA) [
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ]. A histologically based classification is used in this experts’ consensus documents, with the acronym EHRAS (for EHRA/HRS/APHRS/SOLAECE), including four classes: (I) principal cardiomyocyte changes, (II) principally fibrotic changes, (III) combined cardiomyocyte-pathology/fibrosis, (IV) primarily non-collagen infiltration (with/without cardiomyocyte changes) [
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ].
      This is the first histopathological classification of atrial cardiomyopathy, that might be useful primarily to describe pathological changes of the atria, to correlate these changes to the results of imaging procedures, and, in the future, to help defining a tailored management of patients with AF. However, an important limitation of this purely descriptive classification is the absence of progression in severity from EHRAS class I to EHRAS class IV, in contrast with other clinically useful classifications, such as the New York Heart Association functional class (NYHA class) [
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ]. Moreover, the different atrial cardiomyopathies (lone AF, atrial amyloidosis, muscular dystrophies, congestive heart failure, obstructive sleep apnea, AF-induced remodeling, drug-induced, myocarditis, high blood pressure, obesity, age, diabetes and valvular heart disease) can have features of multiple EHRAS classes, with the only exception of atrial amyloidosis in the IV class [
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ,
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ].
      Regardless of the limits of the classification, we believe that the detection of atrial cardiomyopathy may have potential important practical clinical implications: (1) to guide ischemic stroke prevention in patients with or (2) without AF, (3) to guide antiarrhythmic therapy, rhythm maintenance and rate control in AF patients [
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ].
      In recent years there has been growing interest in better evaluating left atrial dilation and myocardial fibrosis, causing left atrial dysfunction and electromechanical conduction delay, as a substrate for AF. Indeed, the 2020 ESC Guidelines for the diagnosis/management of AF [
      • Hindricks G.
      • Potpara T.
      • Dagres N.
      • Arbelo E.
      • Bax J.J.
      • Blomström-Lundqvist C.
      • Boriani G.
      • Castella M.
      • Dan G.A.
      • Dilaveris P.E.
      • Fauchier L.
      • Filippatos G.
      • Kalman J.M.
      • La Meir M.
      • Lane D.A.
      • Lebeau J.P.
      • Lettino M.
      • Lip G.Y.H.
      • Pinto F.J.
      • Thomas G.N.
      • Valgimigli M.
      • Van Gelder I.C.
      • Van Putte B.P.
      • Watkins C.L.
      ESC Scientific Document Group
      2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC.
      ] included for the first time a structured characterization of AF, with clinical assessment of stroke risk, symptom status, burden of AF, and evaluation of substrate, with a clear indication to detect atrial cardiomyopathy, for the optimal management of AF patients [
      • Hindricks G.
      • Potpara T.
      • Dagres N.
      • Arbelo E.
      • Bax J.J.
      • Blomström-Lundqvist C.
      • Boriani G.
      • Castella M.
      • Dan G.A.
      • Dilaveris P.E.
      • Fauchier L.
      • Filippatos G.
      • Kalman J.M.
      • La Meir M.
      • Lane D.A.
      • Lebeau J.P.
      • Lettino M.
      • Lip G.Y.H.
      • Pinto F.J.
      • Thomas G.N.
      • Valgimigli M.
      • Van Gelder I.C.
      • Van Putte B.P.
      • Watkins C.L.
      ESC Scientific Document Group
      2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC.
      ,
      • Boriani G.
      • Vitolo M.
      • Lane D.A.
      • Potpara T.S.
      • Lip G.Y.
      Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology.
      ]. The guidelines state that the diagnosis of atrial cardiomyopathy could be based on easily accessible parameters (e.g. etiology, prothrombotic state, and abnormal left atrial -LA- volume/function) [
      • Hindricks G.
      • Potpara T.
      • Dagres N.
      • Arbelo E.
      • Bax J.J.
      • Blomström-Lundqvist C.
      • Boriani G.
      • Castella M.
      • Dan G.A.
      • Dilaveris P.E.
      • Fauchier L.
      • Filippatos G.
      • Kalman J.M.
      • La Meir M.
      • Lane D.A.
      • Lebeau J.P.
      • Lettino M.
      • Lip G.Y.H.
      • Pinto F.J.
      • Thomas G.N.
      • Valgimigli M.
      • Van Gelder I.C.
      • Van Putte B.P.
      • Watkins C.L.
      ESC Scientific Document Group
      2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC.
      ].
      Easily accessible parameters at transthoracic echocardiography (TTE), such as abnormal LA volume/function, integrated with the currently used clinical scores could substantially improve thromboembolic risk prediction in AF. This in particular in patients at intermediate risk according to the CHA2DS2VASc (congestive heart failure, arterial hypertension, age > 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category) score: CHA2DS2VASc classes 1 if males and 2 if females [
      • Tufano A.
      • Galderisi M.
      Can echocardiography improve the prediction of thromboembolic risk in atrial fibrillation? Evidences and perspectives.
      ,
      • Sulzgruber P.
      • Wassmann S.
      • Semb A.G.
      • Doehner W.
      • Widimsky P.
      • Gremmel T.
      • Kaski J.C.
      • Savarese G.
      • Rosano G.M.C.
      • Borghi C.
      • Kjeldsen K.
      • Torp-Pedersen C.
      • Schmidt T.A.
      • Lewis B.S.
      • Drexel H.
      • Tamargo J.
      • Atar D.
      • Agewall S.
      • Niessner A.
      Oral anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1: a current opinion of the European society of cardiology working group on cardiovascular pharmacotherapy and European society of cardiology council on stroke.
      ].
      Among the TTE measurements, the parameter of choice for this purpose could incorporate a combination of LA size and function. The LA strain is increasingly used to assess LA (LA reservoir, conduit and contractile function), although it remains subject to limited availability and inter-vendor variability [
      • Tufano A.
      • Galderisi M.
      Can echocardiography improve the prediction of thromboembolic risk in atrial fibrillation? Evidences and perspectives.
      ]. P-wave to A′ duration on tissue Doppler imaging (PA-TDI, reflecting total atrial conduction time) is also a surrogate marker of LA function [
      • Delgado V.
      • Di Biase L.
      • Leung M.
      • Romero J.
      • Tops L.F.
      • Casadei B.
      • Marrouche N.
      • Bax J.J.
      Structure and function of the left atrium and left atrial appendage: AF and stroke implications.
      ]. The evaluation of LA emptying fraction (LAEF) by the easy measurement of LA maximal and minimal LA volumes [(LA maximal volume – LA minimal volume) / LA maximal volume x 100], using 2D and, even better, 3D echocardiography, may also be a good estimate of the global capacity of LA to fill the left ventricle (LA ejection fraction). This index probably represents more than a simple surrogate of LA strain and could be therefore utilized and further investigated [
      • Tufano A.
      • Galderisi M.
      Can echocardiography improve the prediction of thromboembolic risk in atrial fibrillation? Evidences and perspectives.
      ]. Studies have demonstrated that LAEF is reduced in patients with AF [
      • Tufano A.
      • Galderisi M.
      Can echocardiography improve the prediction of thromboembolic risk in atrial fibrillation? Evidences and perspectives.
      ]. Future prospective studies are needed to confirm the prognostic power of LA functional (in combination with LA size) assessment in predicting thromboembolic risk in AF patients. The European Association of Cardiovascular Imaging has planned an international multi-center registry designed to explore the possible additional value of standard and advanced TTE parameters to CHA2DS2VASc score in AF patients [
      • Galderisi M.
      • Donal E.
      • Magne J.
      • Lo Iudice F.
      • Agricola E.
      • Sade L.E.
      • Cameli M.
      • Schwammenthal E.
      • Cardim N.
      • Cosyns B.
      • Hagendorf A.
      • Neskovic A.N.
      • Zamorano J.L.
      • Lancellotti P.
      • Habib G.
      • Edvardsen T.
      • Popescu B.A.
      Rationale and design of the EACVI AFib echo Europe registry for assessing relationships of echocardiographic parameters with clinical thrombo-embolic and bleeding risk profile in non-valvular atrial fibrillation.
      ].
      There is also suggestion that atrial remodeling, evaluated with LAEF, not only can predispose to AF, but itself may be associated with an increased risk of systemic thromboembolism. In this perspective, AF is not only a risk factor for thromboembolism for but also a marker of atrial cardiomyopathy, which could explain sometimes the lack of temporal relationship observed between detected AF and stroke [
      • Killu A.M.
      • Granger C.B.
      • Gersh B.J.
      Risk stratification for stroke in atrial fibrillation: a critique.
      ,
      • Shin H.Y.
      • Jeong I.H.
      • Kang C.K.
      • Shin D.J.
      • Park H.M.
      • Park K.H.
      • Sung Y.H.
      • Shin D.H.
      • Noh Y.
      • Lee Y.B.
      Relation between left atrial enlargement and stroke subtypes in acute ischemic stroke patients.
      ,
      • Shaikh Q.
      • Ahmed B.
      • Ahmed M.
      • Mahar J.H.
      • Ahmad M.
      • Ahmed A.
      • Majeed F.
      • Ali F.S.
      • Khan M.
      • Kamal A.K.
      Left atrial volumes and associated stroke subtypes.
      ,
      • Boriani G.
      • Vitolo M.
      • Diemberger I.
      • Proietti M.
      • Valenti A.C.
      • Malavasi V.L.
      • Lip G.Y.H.
      Optimizing indices of atrial fibrillation susceptibility and burden to evaluate atrial fibrillation severity, risk and outcomes.
      ,
      • Freedman B.
      • Camm J.
      • Calkins H.
      • Healey J.S.
      • Rosenqvist M.
      • Wang J.
      • Albert C.M.
      • Anderson C.S.
      • Antoniou S.
      • Benjamin E.J.
      • Boriani G.
      • Brachmann J.
      • Brandes A.
      • Chao T.F.
      • Conen D.
      • Engdahl J.
      • Fauchier L.
      • Fitzmaurice D.A.
      • Friberg L.
      • Gersh B.J.
      • Gladstone D.J.
      • Glotzer T.V.
      • Gwynne K.
      • Hankey G.J.
      • Harbison J.
      • Hillis G.S.
      • Hills M.T.
      • Kamel H.
      • Kirchhof P.
      • Kowey P.R.
      • Krieger D.
      • Lee V.W.Y.
      • Levin L.Å.
      • Lip G.Y.H.
      • Lobban T.
      • Lowres N.
      • Mairesse G.H.
      • Martinez C.
      • Neubeck L.
      • Orchard J.
      • Piccini J.P.
      • Poppe K.
      • Potpara T.S.
      • Puererfellner H.
      • Rienstra M.
      • Sandhu R.K.
      • Schnabel R.B.
      • Siu C.W.
      • Steinhubl S.
      • Svendsen J.H.
      • Svennberg E.
      • Themistoclakis S.
      • Tieleman R.G.
      • Turakhia M.P.
      • Tveit A.
      • Uittenbogaart S.B.
      • Van Gelder I.C.
      • Verma A.
      • Wachter R.
      • Yan B.P.
      AF-screen collaborators. screening for atrial fibrillation: a report of the AF-screen international collaboration.
      ,
      • Vitolo M.
      • Imberti J.F.
      • Maisano A.
      • Albini A.
      • Bonini N.
      • Valenti A.C.
      • Malavasi V.L.
      • Proietti M.
      • Healey J.S.
      • Lip G.Y.
      • Boriani G.
      Device-detected atrial high rate episodes and the risk of stroke/thrombo-embolism and atrial fibrillation incidence: a systematic review and meta-analysis.
      ]. It should also be noted that, in patients with chronic heart failure, the CHA2DS2VASc score is predictive of thromboembolic risk in the absence of AF history [
      • Wolsk E.
      • Lamberts M.
      • Hansen M.L.
      • et al.
      Thromboembolic risk stratification of patients hospitalized with heart failure in sinus rhythm: a nationwide cohort study.
      ]. Moreover, the CHA2DS2-VASc score correlates with the presence of LA spontaneous echo contrast (sludge) in patients with rheumatic mitral stenosis and, again, without AF history. These patients are at risk of LA thrombus formation and systemic thromboembolism, despite sinus rhythm [
      • Belen E.
      • Ozal E.
      • Pusuroglu H.
      Association of the CHA2DS2-VASc score with left atrial spontaneous echo contrast: a cross-sectional study of patients with rheumatic mitral stenosis in sinus rhythm.
      ].
      The concept that a “diseased atrium” is fundamental to the pathogenesis of thrombus formation and ischemic stroke should be considered and emphasized [
      • Smietana J.
      • Plitt A.
      • Halperin J.L.
      Thromboembolism in the absence of atrial fibrillation.
      ,
      • Reiffel J.A.
      The interaction among atrial thromboembolism, atrial fibrillation, and atrial cardiomyopathy.
      ]. If atrial cardiomyopathy is considered as a stroke risk factor, independent of AF, it could be used to identify patients with sinus rhythm who might have thromboembolic events that could be prevented by oral anticoagulation. This hypothesis would need to be tested in prospective randomized trials.
      Detection of atrial cardiomyopathy could also improve the evaluation of the duration of anticoagulant therapy after ablation, and also the identification of individuals for whom ablation therapy will fail, considering the frequent risk of long-term recurrences after the procedure. Indeed, failure of ablation procedures may be caused by progression of atrial cardiomyopathy [
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ]. However, the real impact of atrial cardiomyopathy on the success of catheter ablation has not been clearly elucidated, likely because specific cardiomyopathies may differentially affect ablation procedures [
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ]. A cardiovascular risk factor intervention (correction of obesity, optimal treatment of arterial hypertension) can also improve outcomes after ablation by prevention/reversal of atrial remodeling and atrial cardiomyopathy [
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ,
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ]. Finally, detection of atrial cardiomyopathy might be useful for guiding the selection of the appropriate antiarrhythmic drugs, rhythm maintenance and rate control therapy, by identifying patients who are likely to experience therapy failures [
      • Guichard J.B.
      • Nattel S.
      Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
      ,
      • Goette A.
      • Kalman J.M.
      • Aguinaga L.
      • Akar J.
      • Cabrera J.A.
      • Chen S.A.
      • Chugh S.S.
      • Corradi D.
      • D'Avila A.
      • Dobrev D.
      • Fenelon G.
      • Gonzalez M.
      • Hatem S.N.
      • Helm R.
      • Hindricks G.
      • Ho S.Y.
      • Hoit B.
      • Jalife J.
      • Kim Y.H.
      • Lip G.Y.
      • Ma C.S.
      • Marcus G.M.
      • Murray K.
      • Nogami A.
      • Sanders P.
      • Uribe W.
      • Van Wagoner D.R.
      • Nattel S.
      EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
      ].
      In conclusion, the practical clinical value of the detection of atrial cardiomyopathy may be extremely important but remains to be better elucidated. A great effort is needed in evaluating specific atrial cardiomyopathy imaging/etiologic features in large-scale multi-center trials. At the same time, further studies are also needed to validate the EHRAS classification and to assess its practical role in the management of patients with or without AF.

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      References

        • Kottkamp H.
        Fibrotic atrial cardiomyopathy: a specific disease/syndrome supplying substrates for atrial fibrillation, atrial tachycardia, sinus node disease, AV node disease, and thromboembolic complications.
        J Cardiovasc Electrophysiol. 2012; 23 (Jul): 797-799
        • Guichard J.B.
        • Nattel S.
        Atrial cardiomyopathy: a useful notion in cardiac disease management or a passing fad?.
        J Am Coll Cardiol. 2017; 70 (Aug 8): 756-765
        • Goette A.
        • Kalman J.M.
        • Aguinaga L.
        • Akar J.
        • Cabrera J.A.
        • Chen S.A.
        • Chugh S.S.
        • Corradi D.
        • D'Avila A.
        • Dobrev D.
        • Fenelon G.
        • Gonzalez M.
        • Hatem S.N.
        • Helm R.
        • Hindricks G.
        • Ho S.Y.
        • Hoit B.
        • Jalife J.
        • Kim Y.H.
        • Lip G.Y.
        • Ma C.S.
        • Marcus G.M.
        • Murray K.
        • Nogami A.
        • Sanders P.
        • Uribe W.
        • Van Wagoner D.R.
        • Nattel S.
        EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication.
        Europace. 2016; 18 (Oct): 1455-1490
        • Hindricks G.
        • Potpara T.
        • Dagres N.
        • Arbelo E.
        • Bax J.J.
        • Blomström-Lundqvist C.
        • Boriani G.
        • Castella M.
        • Dan G.A.
        • Dilaveris P.E.
        • Fauchier L.
        • Filippatos G.
        • Kalman J.M.
        • La Meir M.
        • Lane D.A.
        • Lebeau J.P.
        • Lettino M.
        • Lip G.Y.H.
        • Pinto F.J.
        • Thomas G.N.
        • Valgimigli M.
        • Van Gelder I.C.
        • Van Putte B.P.
        • Watkins C.L.
        • ESC Scientific Document Group
        2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-thoracic surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European society of cardiology (ESC) developed with the special contribution of the European heart rhythm association (EHRA) of the ESC.
        Eur Heart J. 2021; 42 (Feb 1): 373-498
        • Boriani G.
        • Vitolo M.
        • Lane D.A.
        • Potpara T.S.
        • Lip G.Y.
        Beyond the 2020 guidelines on atrial fibrillation of the European society of cardiology.
        Eur J Intern Med. 2021; 86 (Apr): 1-11
        • Tufano A.
        • Galderisi M.
        Can echocardiography improve the prediction of thromboembolic risk in atrial fibrillation? Evidences and perspectives.
        Intern Emerg Med. 2020; 15 (Sep): 935-943
        • Sulzgruber P.
        • Wassmann S.
        • Semb A.G.
        • Doehner W.
        • Widimsky P.
        • Gremmel T.
        • Kaski J.C.
        • Savarese G.
        • Rosano G.M.C.
        • Borghi C.
        • Kjeldsen K.
        • Torp-Pedersen C.
        • Schmidt T.A.
        • Lewis B.S.
        • Drexel H.
        • Tamargo J.
        • Atar D.
        • Agewall S.
        • Niessner A.
        Oral anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1: a current opinion of the European society of cardiology working group on cardiovascular pharmacotherapy and European society of cardiology council on stroke.
        Eur Heart J Cardiovasc Pharmacother. 2019; 5 (Jul 1): 171-180
        • Delgado V.
        • Di Biase L.
        • Leung M.
        • Romero J.
        • Tops L.F.
        • Casadei B.
        • Marrouche N.
        • Bax J.J.
        Structure and function of the left atrium and left atrial appendage: AF and stroke implications.
        J Am Coll Cardiol. 2017; 70 (Dec 26): 3157-3172
        • Galderisi M.
        • Donal E.
        • Magne J.
        • Lo Iudice F.
        • Agricola E.
        • Sade L.E.
        • Cameli M.
        • Schwammenthal E.
        • Cardim N.
        • Cosyns B.
        • Hagendorf A.
        • Neskovic A.N.
        • Zamorano J.L.
        • Lancellotti P.
        • Habib G.
        • Edvardsen T.
        • Popescu B.A.
        Rationale and design of the EACVI AFib echo Europe registry for assessing relationships of echocardiographic parameters with clinical thrombo-embolic and bleeding risk profile in non-valvular atrial fibrillation.
        Eur Heart J Cardiovasc Imaging. 2018; 19: 245-252
        • Killu A.M.
        • Granger C.B.
        • Gersh B.J.
        Risk stratification for stroke in atrial fibrillation: a critique.
        Eur Heart J. 2019; 40 (Apr 21Erratum in: Eur Heart J. 2019 Apr 21;40(16):1286. PMID: 30508086): 1294-1302
        • Shin H.Y.
        • Jeong I.H.
        • Kang C.K.
        • Shin D.J.
        • Park H.M.
        • Park K.H.
        • Sung Y.H.
        • Shin D.H.
        • Noh Y.
        • Lee Y.B.
        Relation between left atrial enlargement and stroke subtypes in acute ischemic stroke patients.
        J Cerebrovasc Endovasc Neurosurg. 2013; 15: 131-136
        • Shaikh Q.
        • Ahmed B.
        • Ahmed M.
        • Mahar J.H.
        • Ahmad M.
        • Ahmed A.
        • Majeed F.
        • Ali F.S.
        • Khan M.
        • Kamal A.K.
        Left atrial volumes and associated stroke subtypes.
        BMC Neurol. 2013; 13: 149
        • Boriani G.
        • Vitolo M.
        • Diemberger I.
        • Proietti M.
        • Valenti A.C.
        • Malavasi V.L.
        • Lip G.Y.H.
        Optimizing indices of atrial fibrillation susceptibility and burden to evaluate atrial fibrillation severity, risk and outcomes.
        Cardiovasc Res. 2021; 117 (Jun 16Erratum in: Cardiovasc Res. 2022 Jan 05): 1-21
        • Freedman B.
        • Camm J.
        • Calkins H.
        • Healey J.S.
        • Rosenqvist M.
        • Wang J.
        • Albert C.M.
        • Anderson C.S.
        • Antoniou S.
        • Benjamin E.J.
        • Boriani G.
        • Brachmann J.
        • Brandes A.
        • Chao T.F.
        • Conen D.
        • Engdahl J.
        • Fauchier L.
        • Fitzmaurice D.A.
        • Friberg L.
        • Gersh B.J.
        • Gladstone D.J.
        • Glotzer T.V.
        • Gwynne K.
        • Hankey G.J.
        • Harbison J.
        • Hillis G.S.
        • Hills M.T.
        • Kamel H.
        • Kirchhof P.
        • Kowey P.R.
        • Krieger D.
        • Lee V.W.Y.
        • Levin L.Å.
        • Lip G.Y.H.
        • Lobban T.
        • Lowres N.
        • Mairesse G.H.
        • Martinez C.
        • Neubeck L.
        • Orchard J.
        • Piccini J.P.
        • Poppe K.
        • Potpara T.S.
        • Puererfellner H.
        • Rienstra M.
        • Sandhu R.K.
        • Schnabel R.B.
        • Siu C.W.
        • Steinhubl S.
        • Svendsen J.H.
        • Svennberg E.
        • Themistoclakis S.
        • Tieleman R.G.
        • Turakhia M.P.
        • Tveit A.
        • Uittenbogaart S.B.
        • Van Gelder I.C.
        • Verma A.
        • Wachter R.
        • Yan B.P.
        AF-screen collaborators. screening for atrial fibrillation: a report of the AF-screen international collaboration.
        Circulation. 2017; 135 (May 9): 1851-1867
        • Vitolo M.
        • Imberti J.F.
        • Maisano A.
        • Albini A.
        • Bonini N.
        • Valenti A.C.
        • Malavasi V.L.
        • Proietti M.
        • Healey J.S.
        • Lip G.Y.
        • Boriani G.
        Device-detected atrial high rate episodes and the risk of stroke/thrombo-embolism and atrial fibrillation incidence: a systematic review and meta-analysis.
        Eur J Intern Med. 2021; 92 (Oct): 100-106
        • Wolsk E.
        • Lamberts M.
        • Hansen M.L.
        • et al.
        Thromboembolic risk stratification of patients hospitalized with heart failure in sinus rhythm: a nationwide cohort study.
        Eur J Heart Fail. 2015; 17: 828-836
        • Belen E.
        • Ozal E.
        • Pusuroglu H.
        Association of the CHA2DS2-VASc score with left atrial spontaneous echo contrast: a cross-sectional study of patients with rheumatic mitral stenosis in sinus rhythm.
        Heart Vessels. 2016; 31: 1537-1543
        • Smietana J.
        • Plitt A.
        • Halperin J.L.
        Thromboembolism in the absence of atrial fibrillation.
        Am J Cardiol. 2019; 124 (Jul 15): 303-311
        • Reiffel J.A.
        The interaction among atrial thromboembolism, atrial fibrillation, and atrial cardiomyopathy.
        Am J Cardiol. 2019; 124 (Oct 15): 1317