Measures of left atrial structure and function predict cardiovascular death in patients with heart failure with reduced ejection fraction

Abstract Background The role of the left atrium (LA) is increasingly recognized as a predictor of cardiovascular health outcomes. This study aimed to investigate the prognostic value of LA strain in relation to cardiovascular (CV) death in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods In this retrospective cohort analysis, patients diagnosed with stable HFrEF and free from atrial fibrillation at baseline were included. All patients had a Left Ventricular Ejection Fraction (LVEF) of 45% or below at the time of referral. Baseline clinical and echocardiographic parameters were collected from the database of the HF outpatient clinic, and data on CV death was gathered through the Danish National Patient Registry. LA function was assessed by means of LA emptying fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA conduit strain (LACS). Uni- and multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics were used to determine the association between LA parameters and CV death. Cubic splines were used to identify cutoff values for LA parameters corresponding to a HR of 1. Results The study population consisted of 495 patients (mean age 66 ±11.5 years, 71% males). During a follow-up of 10.9 years [IQR: 6.2; 13.4], 134 (27%) patients reached the outcome of CV death. At baseline, patients who died of CV death were generally older (70.7±9.7 years vs. 64.2±11.7, p<0.001), had a higher prevalence of diabetes (25.4% vs. 13.9%, p=0.004), and a higher prevalence of moderate or severe valve disease (11.2% vs. 3.9%, p=0.004), as well as a lower LVEF (25.1%±8.5 vs. 29.4±8.9, p<0.001). Among LA parameters, the patients who met the outcome had a significantly lower LAEF (30.5% [IQR: 18.0; 42.0] vs. 38.9% [IQR: 29.0; 49.3], p<0.001), PALS (18.2% [IQR: 12.7; 24.4] vs. 23.0% [IQR: 18.3; 29.9], p<0.001), PACS (7.7% [IQR: 2.9; 13.6] vs. 11.7% [IQR: 7.9; 16.4], p<0.001), and LACS (9.4% [IQR: 7.2 ; 12.4] vs. 11.9% [IQR: 8.8; 15.0], p<0.001). Lower levels of all LA parameters were associated with an increased risk of CV death in univariable analysis (p<0.0001 for all parameters). However, in multivariable analysis, only LAEF (HR 0.99 per 1% increase, 95% CI 0.973-0.999, p=0.039), PALS (HR 0.96 per 1% increase, 95% CI 0.931–0.991, p=0.011), and PACS (HR 0.94 per 1% increase, 95% CI 0.90–0.98, p=0.002) remained significant. Splines for LAEF, PALS, and PACS were constructed with identified cutoff points for higher CV death risk (Figure 1), which were utilized to generate Kaplan-Meier curves (Figure 2). Conclusion Lower LA parameters, including LAEF, PALS, and PACS, are associated with increased risk of CV death in patients with HFrEF.Spline curves for LAEF, PALS, and PACS.Kaplan-Meier survival estimates for CVD