Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study

Abstract

Background: Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan.

Method: We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m²), Mild (52-62 ml/m²), Moderate (63-73 ml/m²) and Severe (> 73 ml/m²). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality.

Results: The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m². In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death.

Conclusion: LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.

Keywords: Biplane area-length method; Cardiac magnetic resonance; Left atrial volume; Mortality.

Fig. 1

Two (a) and four (b) chamber CMR left ventricular view tracing of left atrium (LA). The LA appendage and pulmonary veins are excluded from area planimetry. Length is drawn as a perpendicular line from mid-point of the straight line connecting the mitral annulus

Fig. 2

Bland-Altman and unity plots for intra-observer and inter-observer reproducibility analysis of LA volume index (LAVi) measurement

Fig. 3

Time to event Kaplan-Meier curve presenting the association of all-cause mortality with increasing LAVi. Normal = left atrial volume indexed: 21 to 52 ml/m²; Mild = 52 to 62 ml/m²; Moderate = 63 to 73 ml/m²; Severe = greater than 73 ml/m²

Fig. 4

Risk of all-cause mortality in patients with severe LA enlargement in various sub-groups. Hazard ratios for each sub-group were calculated using multivariate models. Age < 60 = adjusted for hypertension, LVEF, LV scar; Age > 60 = adjusted for hypertension, diabetes mellitus, atrial fibrillation, LVEF, RVEF, LV mass, LV scar; Non-hypertensive = adjusted for age, diabetes mellitus; Hypertensive = adjusted for age, atrial fibrillation, diabetes mellitus, myocardial infarction, LVEF, RVEF, LV mass, LV scar; Non-diabetic = adjusted for age, hypertension, atrial fibrillation, LVEF, RVEF, LV scar; Diabetic = adjusted for age, hypertension, LVEF; Preserved LVEF (> 50%) and Reduced LVEF (< 50%) = adjusted for age, hypertension, diabetes mellitus, RVEF, LV scar; No Left-sided Valvulopathy = adjusted for age, hypertension, diabetes mellitus, LVEF; Left-sided Valvulopathy = adjusted for age, hypertension, LVEF; eGFR > 60 ml/min = adjusted for age, hypertension, diabetes mellitus, LVEF, LV scar; eGFR < 60 ml/min = adjusted for age, hypertension, diabetes mellitus, LVEF

Fig. 5

Hazard ratios for LAVi as a continuous variable. Restricted cubic spline model of hazard ratios for left atrial volume indexed. The 3 curves represent the hazard ratio and the upper and lower bounds of the 95% confidence interval at any given LAVi. The transition point of the lower bound of the 95% confidence interval occurs at 52 ml/m² which also correspond to the upper limit of normal LA size derived by standard deviations. Hazard ratios after 73 ml/m² tend to even out as the gradient of the curve plateaus