EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: Definition, characterization, and clinical implication

Abstract

The atria provide an important contribution to cardiac function [1], [2]. Besides their impact on ventricular filling, they serve as a volume reservoir, host pacemaker cells and important parts of the cardiac conduction system (e.g. sinus node, AV node), and secrete natriuretic peptides like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) that regulate fluid homoeostasis. Atrial myocardium is affected by many cardiac and non-cardiac conditions [3] and is, in some respects, more sensitive than ventricular [4]. The atria are activated, besides the three specialised intermodal tracts [5], [6], through working cardiomyocytes, so that any architectural or structural change in the atrial myocardium may cause significant electrophysiological disturbances. In addition, atrial cells (both cardiomyocytes and non-cardiomyocyte elements like fibroblasts, endothelial cells, and neurons) react briskly and extensively to pathological stimuli [3] and are susceptible to a range of genetic influences [7]. Responses include atrial cardiomyocyte hypertrophy and contractile dysfunction, arrhythmogenic changes in cardiomyocyte ion-channel and transporter function, atrial fibroblast proliferation, hyperinnervation, and thrombogenic changes [2]. Thus, atrial pathologies have a substantial impact on cardiac performance, arrhythmia occurrence, and stroke risk [1], [8]. Ventricular cardiomyopathies have been well classified; however, a definition and detailed analysis of ‘atrial cardiomyopathy’ is lacking from the literature. The purpose of the present consensus report, prepared by a working group with representation from the European Heart Rhythm Association (EHRA), the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and Sociedad Latino Americana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE), was to define atrial cardiomyopathy, to review the relevant literature, and to consider the impact of atrial cardiomyopathies on arrhythmia management and stroke. 1.1. Definition of atrial cardiomyopathy The working group proposes the following working definition of atrial cardiomyopathy: ‘Any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically-relevant manifestations’ (Table 1). Table 1 Definition of atrial cardiomyopathy. Many diseases (like hypertension, heart failure, diabetes, and myocarditis) or conditions (like ageing and endocrine abnormalities) are known to induce or contribute to an atrial cardiomyopathy. However, the induced changes are not necessarily disease-specific and pathological changes often share many similarities [9], [10]. The extent of pathological changes may vary over time and atrial location, causing substantial intraindividual and interindividual differences. In addition, while some pathological processes may affect the atria very selectively (e.g. atrial fibrillation-induced remodelling), most cardiomyopathies that affect the atria also involve the ventricles to a greater or lesser extent. There is no presently accepted histopathological classification of atrial pathologies. Therefore, we have proposed here a working histological/ pathopysiological classification scheme for atrial cardiomyopathies (Table 1; Fig. 1). We use the acronym EHRAS (for EHRA/HRS/ APHRS/SOLAECE), defining four classes: (I) principal cardiomyocyte changes [11], [12], [13], [14], [15]; (II) principally fibrotic changes [10], [14], [16]; (III) combined cardiomyocyte-pathology/fibrosis [9], [11], [12]; (IV) primarily non-collagen infiltration (with or without cardiomyocyte changes) [17], [18], [19]. This simple classification may help to convey the primary underlying pathology in various clinical conditions. The EHRAS class may vary over time and may differ at atrial sites in certain patients. Thus, this classification is purely descriptive and in contrast to other classifications (NYHA class, CCS class etc.), there is no progression in severity from EHRAS class I to EHRAS IV (Table 2). The classification may be useful to describe pathological changes in biopsies and to correlate pathologies with results obtained from imaging technologies etc. In the future, this may help to define a tailored therapeutic approach in atrial fibrillation (AF) (Fig. 1, Fig. 2, Fig. 3). Fig. 1 Histological and pathopysiological classification of atrial cardiomyopathies (EHRA/HRS/APHRS/SOLAECE): EHRAS classification. The EHRAS class may vary over time in the cause of the disease and may differ at various atrial sites. Of note, the nature of ... Fig. 2 (A) EHRAS Class I (biopsy): there are severe changes affecting ‘primarily’ the cardiomyocytes in terms of cell hypertrophy and myocytolysis; fibrosis is much less evident than myocyte modifications. (B) EHRAS Class II (biopsy): cardiomyocyte ... Fig. 3 EHRAS Class IV (autopsy heart): this image shows a myocardial interstitial with some fibrosis but prominent amyloid (AL type) deposition (left-hand side, congo red staining under regular light microscope; right-hand side, congo red staining under polarised ... Table 2 EHRAS classification of atrial cardiomyopathy. 2. Anatomical considerations and atrial muscular architecture 2.1. Normal atrial structures 2.1.1. Gross morphology Each atrium has a morphologically characteristic atrial body and appendage (Fig. 4). In the body, there is a venous component with the orifices of the systemic or pulmonary veins (PVs) and a vestibular component that surrounds the atrial outlet [20]. The interatrial septum (IAS) separates the atrial bodies. The venous component of the left atrium (LA) is located posterosuperiorly and receives the PVs at the four corners, forming a prominent atrial dome. The LA is situated more posteriorly and superiorly than the right atrium separated by the obliquity of the plane of the IAS [21]. Fig. 4 Schematic representations and heart dissections to show the arrangement of the myocardial strands in the superficial parts of the walls. (A) The dissection viewed from the anterior aspect display the interatrial muscle Bachmann bundle and its bifurcating ... The LA appendage (LAA) is smaller than the right atrium appendage (RAA). Narrower and with different shapes has a distinct opening to the atrial body and overlies the left circumflex coronary artery. Its endocardial aspect is lined by a complex network of muscular ridges and mem-branes [22], [23]. Different LAA morphologies have been described, and it appears that LAA morphology correlates with the risk of thrombogenesis [24]. Bachmann׳s bundle is a broad epicardial muscular band running along the anterior wall of both atria (Fig. 4). The rightward arms extend superiorly towards the sinus node and inferiorly towards the right atrioventricular groove, while the leftward arms blend with deeper myofibres to pass around the neck of the LAA and reunite posteriorly to join the circumferential vestibule of the LA. The walls of LA are non-uniform in thickness (1–15 mm) and thicker than the right atrium [25].