Synergic interaction between coronary flow reserve and left atrial diameter as a risk factor for major adverse cardiovascular events in patients with nonobstructive coronary artery disease

Abstract Background Left atrial diameter (LAD) is one of the parameters which indicate left ventricular diastolic disorders (DD) and associated with poor prognosis. Previous studies have reported the relationship between DD and coronary microvascular dysfunction (CMD) but the impact of coexisting DD and CMD on prognosis is unknown. Methods and results This study included 330 patients who underwent intracoronary physiological assessment including CFR for suspected myocardial ischemia without significant stenosis in the epicardial coronary artery from December 2019 to March 2023. Of 330 patients (female: n=96 [29%], age: 70±11 years), 109 (33%) had CMD (CFR<2.5) and 93 (28%) had DD (LAD>40 mm). Patients were classified into 4 groups based on the cut-off values of CFR and LVMI: group 1 (no CMD nor DD n=160); group 2 (only DD, n=61); group 3 (only CMD, n=77) and group 4 (both CMD and DD, n=32). Clinical follow-up was performed for major adverse cardiovascular events (MACE) including cardiovascular death, acute coronary syndrome and hospitalization for heart failure. During a median follow-up of 715 days, the cumulative MACE-free survival rate at 2 year were 97.9%, 100.0%, 95.5% and 75.1% in groups 1 to 4. Group 4 showed significantly higher MACE rate compared with other 3 groups (hazard ratio [HR] 14.3; 95% confidence interval [CI] 3.8-53.9; p<0.001, HR 14.25; 95% CI 1.8-114.4; p=0.01 and HR 4.7; 95% CI 1.4-15.8; p=0.01 respectively). Notably, Bonferroni's multiple comparison showed that Group 4 had the highest incidence of heart failure hospitalization compared with other 3 groups (p=<0.001, p=0.002, p=0.01 respectively). Cox proportional hazards model revealed that CMD and DD had synergic interaction as a risk factor for MACE (HR 9.1; 95% CI 3.4-24.4; p<0.001). Conclusion Patients with both CMD and DD showed significantly higher risk for MACE, especially for heart failure hospitalization. The combined classification based on CFR and LAD would identify the high-risk patients for MACE.MACE-free survival curveheart failure-free survival curve