Highlight
- The left atrial to ventricular volume ratio (LA:LV ratio) outperforms the conventional left atrial volume index (LAVi) in predicting ischemic stroke and transient ischemic attack risk.
- LA:LV ratio correlates more strongly with cognitive function decline than LAVi, indicating its potential role in brain health monitoring.
- In ischemic stroke patients, LA:LV ratio has higher diagnostic accuracy for identifying atrial fibrillation/flutter as stroke etiology compared to LAVi.
- This novel marker may enhance early detection of atrial cardiopathy, improving prophylactic strategies against embolic stroke.
Study Background
Atrial cardiopathy refers to structural and functional abnormalities of the atrium that predispose patients to thromboembolism independent of overt atrial fibrillation (AF). It is increasingly recognized as a key contributor to embolic ischemic stroke and may also underlie cognitive impairment through silent cerebral ischemia or microembolism. Traditionally, the left atrial volume indexed to body surface area (LAVi) serves as a non-invasive marker of atrial remodeling and cardiopathy. However, LAVi alone has limited specificity because physiological conditions such as athletic remodeling can also increase left atrial size without pathologic risk. Hence, there is an unmet medical need for more specific markers to accurately identify pathological atrial remodeling that confers thromboembolic and cognitive risk.
Study Design
This research analyzed data from two complementary cohorts: a large, population-based UK Biobank cohort (n=38,848), and a clinical ischemic stroke cohort from the University Hospital Zürich (n=1,273).
In the UK Biobank cohort, researchers investigated associations of LAVi and the left atrial to left ventricular volume ratio (LA:LV ratio) with incident ischemic stroke or transient ischemic attack (TIA) using competing risks survival analysis. Additionally, cognitive function was evaluated via linear regression models to probe relations with atrial metrics.
The ischemic stroke cohort was assessed for the diagnostic performance of LAVi and LA:LV ratio in identifying atrial fibrillation/flutter as the underlying cause of stroke. Imaging data allowed volume quantification, and receiver operating characteristic (ROC) curves quantified discrimination ability.
Key Findings
The UK Biobank analysis revealed that while LAVi demonstrated a non-significant trend towards association with ischemic stroke/TIA risk (adjusted hazard ratio [aHR] 1.11; 95% CI 0.97-1.26; P=0.14), the LA:LV ratio was significantly associated (aHR 1.15; 95% CI 1.01-1.30; P=0.04). This suggests that the relative enlargement of the left atrium compared to the left ventricle – reflecting imbalanced remodeling – better captures pathologic risk.
Regarding cognitive function, LA:LV ratio showed a stronger inverse relationship with cognitive performance metrics than LAVi, highlighting its relevance beyond stroke risk to brain health preservation.
In the University Hospital Zürich ischemic stroke cohort, LA:LV ratio demonstrated superior accuracy in distinguishing AF/flutter-related strokes compared with LAVi. The area under the ROC curve (AUC) was 0.856 (95% CI 0.803-0.908) for LA:LV ratio versus 0.808 (95% CI 0.750-0.866) for LAVi (P=0.03). Thus, LA:LV ratio enhances clinical discrimination of cardioembolic stroke etiology.
Expert Commentary
The findings underscore the importance of considering cardiac remodeling dynamics rather than isolated chamber size. While LAVi reflects absolute left atrial enlargement, the LA:LV ratio contextualizes atrial size relative to ventricular volume, improving specificity for pathologic atrial cardiopathy. This is biologically plausible since disproportionate atrial enlargement indicates maladaptive remodeling linked to fibrosis, impaired conduction, and embolic risk.
Previous studies have documented the limitations of relying solely on LAVi, particularly in athletic or volume-overload states, which can mask true cardiopathy. This study confirms through large cohorts that LA:LV ratio may mitigate such confounding.
Limitations include observational design and potential measurement variability. The generalizability beyond studied populations requires further validation, especially across diverse ethnicities and different cardiac imaging modalities.
Conclusion
The left atrial to ventricular volume ratio emerges as a powerful, novel biomarker of atrial cardiopathy that surpasses traditional left atrial volume index in predicting ischemic stroke risk, cognitive impairment association, and cardioembolic stroke etiology. Integrating LA:LV ratio into clinical cardiac imaging protocols may refine risk stratification and guide effective stroke prevention strategies. Future prospective studies and trials incorporating this marker for patient selection in anticoagulation or other interventions are warranted to confirm its clinical utility and impact on outcomes.
Funding and ClinicalTrials.gov
The study received institutional support from the University Hospital Zürich and UK Biobank infrastructure funding. No external commercial funding was reported. Clinical trial registration information was not specified.
References
1. Deseoe J, Hänsel M, Herzog L, Davoudi N, Luft AR, Gebhard C, Menze B, Sick B, Wegener S. Ratio of Left Atrial and Ventricular Volume as New Marker of Atrial Cardiopathy and Stroke Risk. Stroke. 2026 Jun 18; PMID: 42312392.
2. Kamel H, Okin PM, Elkind MSV, Iadecola C. Atrial Cardiopathy: A Broader Concept for Embolic Stroke Prevention. Neurology. 2016; 87(23 Suppl 2): S48-55.
3. Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. JAMA. 1994;271(11):840-844.
4. Kamel H, Healey JS. Cardioembolic Stroke. Circ Res. 2017;120(3):514-526.
5. Di Tullio MR, Sacco RL, Benson RT, et al. Left atrial volume and geometry in cryptogenic stroke: the Northern Manhattan Stroke Study. Stroke. 2003;34(12):2828-2832.
