Prognostic stratification by coronary flow reserve and left atrial volume index in patients with non-obstructive coronary artery disease

Background Left atrial volume index (LAVi) is a surrogate marker for left ventricular diastolic dysfunction (LVDD) and is associated with adverse clinical outcomes. Coronary microvascular dysfunction (CMD), primarily assessed using coronary flow reserve (CFR), is a known risk factor for major adverse cardiovascular events (MACE). While previous studies have demonstrated a relationship between LVDD and CMD, the prognostic impact of their coexistence remains unclear. Purpose This study aimed to evaluate whether combining CFR and LAVi improves risk stratification in patients without functional coronary stenosis. Methods This retrospective study included 330 patients who underwent intracoronary physiological assessment, and had no significant epicardial stenosis (fractional flow reserve > 0.80). CMD was defined as CFR < 2.5, assessed using the invasive thermodilution method, while LVDD was defined as LAVi > 34 mm3/m2, assessed by echocardiography. Based on CFR and VAVi, patients were categorized into four groups: Group 1 (normal CFR and LAVi, n=180), Group 2 (elevated LAVi only, n=43), Group 3 (impaired CFR only, n=75), and Group 4 (both impaired CFR and elevated LAVi, n=32). The primary endpoint was MACE, defined as a composite of cardiovascular death (CVD), acute coronary syndrome (ACS), and heart failure (HF) requiring hospitalization. Results Among the 330 patients (31% female, n = 101; mean age: 70 ± 11 years), 107 (32%) had CMD and 75 (23%) had LVDD. During a median follow-up of 759 days, 27 patients experienced the primary endpoint. Kaplan-Meier analysis showed that the two-year MACE-free survival rates for Groups 1 through 4 were 98.8%, 100.0%, 95.4%, and 70.0%, respectively. Group 4 had the highest MACE risk compared to Group 1 (HR 3.2; 95% CI: 1.9–5.3), Group 2 (HR 3.6; 95% CI: 1.3–10.2), and Group 3 (HR 9.7; 95% CI: 2.7–35.2). Notably, HF with preserved ejection fraction was the predominant event in Group 4. Conclusion Patients with both impaired CFR and elevated LAVi had a significantly higher risk of MACE compared to those with either abnormality alone. The combined assessment of CFR and LAVi allows for enhanced risk stratification in patients without functional coronary stenosis, particularly in identifying patients at risk of HFpEF. These findings highlight the potential of integrating CFR and LAVi into clinical practice to refine risk stratification and guide targeted therapeutic strategies.