Atrial cardiomyopathy: From healthy atria to atrial failure
Authors, Journal, Affiliations, Type, DOI
- Weerts J, Tica OT, Aranyo J, Basile C, et al. (co-first: Weerts & Tica; co-last: Bayes-Genis & Kotecha)
- European Journal of Heart Failure, 2025; 27:2173–2194
- Heart Failure Association (HFA) Committee on Atrial Disorders, European Society of Cardiology
- Type: Clinical Consensus Statement (HFA/ESC); endorsed by ESC Clinical Practice Guidelines Committee
- DOI: https://doi.org/10.1002/ejhf.3782
Overview
This 2025 ESC/HFA consensus statement proposes a new pragmatic diagnostic framework for atrial cardiomyopathy (AtCM) — defined as electrical and mechanical dysfunction of the atria resulting from pathological changes leading to atrial enlargement or fibrosis, with potential for clinical consequences. Diagnosis requires documented electrical atrial dysfunction (P-wave score ≥1) combined with evidence of mechanical atrial dysfunction, atrial enlargement, or excessive atrial fibrosis. The document introduces a P-wave scoring system (0–4), specific imaging cut-offs (LAVi >40 ml/m², LASr <23%), the concept of atrial failure as end-stage AtCM, and reviews molecular mechanisms and emerging biomarkers. It positions AtCM as a pre-emptive diagnostic entity — bridging AF, HFpEF, and stroke — warranting risk factor management before atrial failure develops.
Keywords
Atrial cardiomyopathy • Atrial fibrosis • Heart failure • Atrial fibrillation • Imaging • Electrocardiography
Key Takeaways
Definition and Diagnostic Framework
- AtCM is redefined as: "electrical and mechanical dysfunction of the atria, resulting from underlying pathological changes that lead to atrial enlargement or atrial fibrosis, with the potential to produce clinical consequences"
- Diagnosis requires: electrical atrial dysfunction (P-wave score ≥1) + one of: mechanical atrial dysfunction, atrial enlargement, or excessive atrial fibrosis
- This two-criterion requirement avoids over-diagnosis (many diseases cause isolated atrial disruption)
- AtCM can be primary (no other initial cardiac abnormality) or secondary (to ventricular/valvular disease)
- The 'common soil hypothesis': stressors (ageing, cardiometabolic risk, comorbidities) promote atrial disease via inflammation, endothelial/microvascular dysfunction, fibrosis, hypercoagulability, and atrial stretch
Electrical Atrial Dysfunction — P-wave Score (Table 2)
| Score | P-wave Finding |
|---|---|
| 0 | No changes |
| 1 | Prolonged P-wave duration (≥120 ms standard ECG or ≥150 ms amplified 12-lead ECG); also partial IAB, voltage ≤0.1 mV, axis <0° or >75°, terminal force V1 >40 mm/ms, dispersion >40 ms |
| 2 | Advanced IAB (P-wave ≥120 ms + biphasic morphology in ≥2 inferior leads) without clinical atrial arrhythmia |
| 3 | Advanced IAB with paroxysmal atrial arrhythmia |
| 4 | Persistent atrial arrhythmia |
- Score 1–2: at-risk stage; proactive risk factor management recommended; anticoagulation/antiarrhythmics controversial
- Score ≥3: thromboembolic risk evaluation warranted; anticoagulation/antiarrhythmic strategies per guidelines
Inter-atrial Block (IAB)
- IAB defined as P-wave ≥120 ms; three degrees: partial (≥120 ms, bimodal, positive inferior leads), advanced (≥120 ms + biphasic in ≥2 inferior leads), intermittent
- Advanced IAB = Bayes syndrome when associated with new-onset supraventricular arrhythmias
- AF risk: 2× with partial IAB, 4× with advanced IAB
- Associated with stroke, cognitive impairment, HF, and mortality
Mechanical Atrial Dysfunction — Imaging Cut-offs (Table 3)
| Parameter | Echo (2D) | CMR |
|---|---|---|
| LAVi | >40 ml/m² (>48 ml/m² women >65 yr) | >60 ml/m² |
| LASr (reservoir strain) | <23% | <23% |
| LA booster strain | <8% (all ages) | <8% |
| LA conduit strain | <12% (<9% in >65 yr) | <21% |
| LA emptying fraction | <48% | <46% |
| LA diameter | >40 mm men / >38 mm women | >42 mm men / >41 mm women |
| RA volume indexed | >36 ml/m² men / >30 ml/m² women | — |
- Only LAVi and LASr incorporated in the proposed AtCM diagnostic framework (others lack sufficient evidence)
- LASr more closely associated with stroke and dementia risk than AF itself
- In HFpEF, mechanical atrial dysfunction is an independent and better predictor than AF for adverse outcomes
- Minimal LA volume (not maximal) may be more prognostic in HF patients
- CMR-LGE for atrial fibrosis: LA LGE ≥10–15% predicts arrhythmias/stroke/ablation recurrence; limited by spatial resolution and variable protocols
Atrial Failure (End-Stage AtCM)
- Defined by progressive structural, electrophysiological, and functional changes
- Characterized by: persistent AF or documented HF with dyspnoea, fatigue, and impaired QoL attributable (at least in part) to atrial disease
- Management: therapy for AF and/or HF per respective ESC guidelines; cardiologist with HF or AF expertise recommended
Biomarkers
- BMP10 (bone morphogenetic protein 10): atrial-specific ligand; elevated levels reflect more severely altered atrial structure; higher BMP10 linked to adverse CV events, higher AF recurrence after rhythm control, and late postoperative AF; role as AtCM risk stratifier under investigation
- Mid-regional proANP: emerging specific biomarker for AtCM in HFpEF; thresholds require further research
- ANP: defective synthesis in failing atrium; anti-hypertrophic, anti-arrhythmic, and autophagy-stimulating properties; excessive ANP production can lead to isolated atrial amyloidosis and AtCM
- BNP/NT-proBNP: clinical utility for AtCM unclear; ARCADIA trial (BNP >250 pg/ml as AtCM criterion) stopped early for futility of apixaban vs aspirin
- Natriuretic peptides, corin, and BMP10 require dedicated studies with clinical cut-points
Molecular Mechanisms
- NLRP3 inflammasome: activated by metabolic/cardiovascular disorders; promotes IL-1β/IL-18 release → fibro-inflammatory cycle in atrial cardiomyocytes, immune cells, fibroblasts → AF substrate; clinical trials of colchicine show no significant AF prevention in largest RCTs
- Atrial fibrosis: diverse mechanisms — stretch-activated fibroblasts, inflammatory processes, coagulation factor activation, fibro-fatty infiltrations; diffuse endomysial fibrosis → discontinuous conduction; patchy fibrosis → macro re-entrant circuits
- Electrical remodeling: shortened AERP; novel targets include PDE8B2 inhibition, SK current upregulation, reactive oxygen species-dependent CaMKIIδc activation
- Epicardial adipose tissue: implicated in AF and HFpEF via atrial fat infiltration, pro-inflammatory/pro-fibrotic mediators, oxidative stress, altered ion currents, gap junction modulation, autonomic dysfunction; more atrial epicardial fat when AF co-occurs with HFpEF; negative cardiometabolic effects more pronounced in women
- Ca²⁺ handling: Ca²⁺ handling and structural (not electrical) remodeling in HFrEF; Ca²⁺ triggered activity is major AF trigger in HFrEF; Ca²⁺ cycling abnormalities from reduced cMyBP-C phosphorylation; fatty acid metabolism defects in atrial cardiomyocytes in AF and HFpEF
Risk Factor and Comorbidity Management
- In clinical AF: class I recommendations for reducing recurrence include control of hypertension, diabetes, obesity, exercise capacity, alcohol restriction (2024 ESC AF-CARE approach)
- In AtCM (without AF): diligent comorbidity management may slow remodelling and prevent AF/HF onset; no dedicated RCTs yet
- Gender gap: women have higher prevalence of LA low-voltage zones than men, suggesting more advanced AtCM at time of diagnosis; sex-dependent mechanisms warrant investigation
Key Evidence Gaps
- No validated clinical trials for AtCM prevention of progression
- Anticoagulation role in AtCM without AF: unresolved (requires RCTs)
- Ablation strategy in advanced atrial failure: not established
- Reproducibility of imaging parameters in the presence of AF: limited data
- Right heart dysfunction's role in AtCM: understudied
Limitations of the Document
- Diagnostic cut-points are consensus-based approximations, not validated against hard endpoints
- Most evidence derived from advanced IAB and late-stage AtCM; early detection markers lack robust prognostic validation
- Limited histological validation of CMR-LGE atrial fibrosis detection
- P-wave measurement challenging in low-amplitude atrial signals; amplified ECG not universally available
- Gender-specific data and diverse population data limited
- Clinical trials in AtCM are essentially non-existent; framework built on observational/mechanistic data
Key Concepts Mentioned
- concepts/Atrial-Cardiomyopathy — primary subject; new ESC/HFA diagnostic framework
- concepts/Atrial-Failure — end-stage AtCM; new clinical entity defined
- concepts/Inter-Atrial-Block — key ECG marker for electrical atrial dysfunction; P-wave scoring
- concepts/Left-Atrial-Strain — LASr <23% threshold; primary imaging marker for AtCM
- concepts/Late-Gadolinium-Enhancement — atrial fibrosis detection via CMR-LGE; limited by resolution
- concepts/HFpEF — AtCM/atrial failure predicts outcomes independently of AF in HFpEF
- concepts/Atrial-Myopathy-in-HCM — primary atrial myopathy as subset of AtCM
- concepts/AF-CARE — referenced for comorbidity management parallels
- concepts/AF-Staging — AtCM framework extends beyond current AF staging
Key Entities Mentioned
- entities/Atrial-Fibrillation — key consequence and manifestation of advanced AtCM; also potential cause
- entities/Heart-Failure — end-stage consequence; bidirectional relationship with AtCM
Wiki Pages Updated
- Created: wiki/concepts/Atrial-Cardiomyopathy.md
- Created: wiki/concepts/Atrial-Failure.md
- Updated: wiki/entities/Atrial-Fibrillation.md
- Updated: wiki/concepts/HFpEF.md
- Updated: wiki/concepts/Late-Gadolinium-Enhancement.md
- Updated: wiki/sourceindex.md
- Updated: wiki/wikiindex.md
- Appended: log.md