Atrial cardiomyopathy revisited-evolution of a concept: a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS)

Abstract

Aims: The concept of "atrial cardiomyopathy" (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on atrial cardiomyopathy in 2016 (EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication). Subsequently, publications on AtCM have increased progressively.

Methods and results: The present consensus document elaborates the 2016 AtCM document further to implement a simple AtCM staging system (AtCM stages 1-3) by integrating biomarkers, atrial geometry, and electrophysiological changes. However, the proposed AtCM staging needs clinical validation. Importantly, it is clearly stated that the presence of AtCM might serve as a substrate for the development of atrial fibrillation (AF) and AF may accelerates AtCM substantially, but AtCM per se needs to be viewed as a separate entity.

Conclusion: Thus, the present document serves as a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) to contribute to the evolution of the AtCM concept.

Keywords: Atrial fibrillation; Cardiomyopathy; Fibrosis; Mechanisms; Pathophysiology; Stroke; Atrium.

Figure 1

Number of papers published annually on atrial cardiomyopathy since first use of the term in 1972. Obtained with a Medline Search for articles with the search term “‘Atrial cardiomyopathy’ OR ‘atrial myopathy’”. A progressive increase in the number of publications has occurred since the appearance of the ERA/HRS/APHRS/LAHS consensus report on atrial cardiomyopathy in 2016.

Figure 2

Age-related changes in atrial tissue structure. Commonly found age-related changes in atrial tissue structure (Masson's trichrome staining) which represent the structural bases of atrial ageing. yo, years old.

Figure 3

(A) Light microscopy image (Masson's trichrome stain) of atrial tissue with normal intercellular space (41 yo) and (B) cardiomyocyte loss with expansion of interstitial fibrous tissue (82 yo). (C) and (D): myofibrillar loss and fibrotic replacement in the aged left atrium. yo, years old.

Figure 4

Histological factor associated with atrial structural remodelling characterized by electroanatomic mapping. The upper panel shows light microscopy images of atrial biopsy samples obtained from patients with non-valvular atrial fibrillation. The lower panel shows examples of high-density bipolar voltage map of the left atrium created during high right atrial pacing at 100 beats per minute. Not only fibrosis, but also increased intercellular space preceding fibrosis, myofibrillar loss, decrease in myocardial nuclear density, and amyloid deposition are associated with the progression of atrial structural remodelling. The rightmost image in the upper panel shows Congo Red staining, the second from the right shows haematoxylin and eosin staining, and the others show Masson's trichrome staining. The colour gradation in the lower panel voltage maps indicates differences in voltage amplitude from purple at 1.5 mV to grey at 0.1 mV, as shown in the colour bar. AtCM, atrial cardiomyopathy (see Table 2 for explanation of AtCM stages).

Figure 5

Microphotographs captured from left atrial biopsies belonging to patients suffering from long-lasting atrial fibrillation associated with severe mitral-valve regurgitation. These histopathological sections have been stained with a combined Weigert/Van Gieson dye where cardiomyocytes are highlighted in yellow-brown, collagen fibres in red, and elastic fibres in black. (A) Medium-power view of a developing Early-Stage histopathological remodelling (ATCM stage 1) where multiple foci of interstitial fibrosis (arrowheads) stem from the adventitia of a penetrating coronary branch (asterisk). (B) Low-power view of an incipient Early-Stage histopathological remodelling with multiple interstitial fibrosis foci (arrowheads) originating from a longitudinally oriented blood vessel (asterisks). (C) An initial Early-Stage AtCM histopathological remodelling with a fibroelastotic endocardial thickening (asterisk) from which newly deposed collagen fibres enlarge the adventitia of subendocardial blood vessels (arrowheads). (D) Incipient Early-Stage histopathological remodelling interstitial fibrosis (arrowheads) stemming from an endocardium thickened by fibroelastosis which had also enlarged local blood vessel adventitia (asterisk). (E) Early-Stage histopathological remodelling characterized by multiple foci of interstitial fibrosis (arrowheads) that had originated from sparse penetrating blood vessel adventitias (asterisks). (F) Another type of Intermediate-Stage histopathological remodelling (AtCM stage 2) compound interstitial fibrosis (arrowheads) which takes origin from two blood vessels and a thickened endocardium (asterisks). (G) Advanced-Stage histopathological remodelling characterized by confluent myocardiosclerotic foci (asterisks). H. Compact and diffuse areas of interstitial fibrosis (Very Advanced-Stage histopathological remodelling; AtCM stage 3). Staining. (A-G) Weigert/Van Gieson combined dye. Original magnifications. (A): ×20 (scale bar is 150μm); (B-G): ×10 (scale bar in (B) is 300μm).

Figure 6

Atrial size and function during the cardiac cycle: volume (A) and strain (B) curve analysis. Precise calculations: Total EF = [(maxAV − minAV)/ maxAV]; Expansion Volume = [(maxAV − minAV)/minAV]; Passive EF = [(maxAV − preAV)/maxAV]; Active EF = [(preAV − minAV)/preAV]. Abbreviations: maxAV, Maximal Atrial Volume; minAV, Minimal Atrial Volume; preAV, Pre–atrial contraction Volume; EF, Emptying Fraction.

Figure 7

Manhattan plot showing known loci and novel loci associated with atrial fibrillation. A total of 34 740 186 genetic variants (each represented by a dot) were tested, comparing 60 620 atrial fibrillation cases and 970 216 controls free of atrial fibrillation. The x axis represents the genome in physical order, and the y axis represents P values (−log10(P value)) of association. The black horizontal dotted line represents a Bonferroni-corrected threshold of statistical significance corresponding to 1 000 000 independent tests (P < 5 × 10−8). Reprinted by permission from Nielsen et al.

Figure 8

Although chronological age progresses at an immutable rate, biological ageing, measured by epigenetic age in this article, is modifiable by various exposures and life experiences. Thus, establishing a relationship between epigenetic age and atrial fibrillation (AF) risk gives a unique insight into modifiable ageing associated atrial fibrillation risks. Reprinted from Ward-Caviness et al.

Figure 9

Interaction of risk factors, atrial cardiomyopathy, occurrence of atrial fibrillation and outcome. AtCM, atrial cardiomyopathy; AF, atrial fibrillation; CV, cardiovascular; TIA, transient ischaemic attack.