Left atrial appendage volume as a prognostic Indicator of long-term mortality in Cancer survivors treated with thoracic radiation

Abstract

Background: Cancer survivors with prior chest radiation therapy (CXRT) frequently present with atrial fibrillation, heart failure, and have higher overall long-term mortality. There are no data examining the utility of left atrial (LA) and LA appendage (LAA) volume-indices to predict clinical outcomes in these patients.

Objectives: We examined the prognostic value of cardiac phase-dependent 3-D volume-rendered cardiac computerized tomography (CT)-derived LA and LAA volume-indices to predict mortality and major adverse cardiac events (MACE) in cancer survivors treated with thoracic irradiation.

Method: We screened 625 consecutive patients with severe aortic stenosis who had undergone transcatheter aortic valve replacement from 2012 to 2017. Based on the gated cardiac CT image quality, we included 184 patients (CXRT:43, non-CXRT:141) for further analysis. We utilized multiplane-3D-reconstructed cardiac CT images to calculate LA and LAA volume-indices, and examined the prognostic role of CCT-derived LA and LAA volume-indices in predicting the all-cause mortality, cardiovascular (CV) mortality, and MACE. We used multivariate cox-proportional hazard analysis to identify the clinical predictors of survival.

Results: Overall, the CXRT group had significantly elevated LAA volume-index compared to non-CXRT group (CXRT:11.2 ± 8.9 ml/m²; non-CXRT:8.6 ± 4.5 ml/m², p = 0.03). On multivariate cox-proportional hazard analysis, the elevated LAA volume and LAA volume-index were the strongest predictors of reduced survival in CXRT group compared to non-CXRT group (LAA volume: RR = 1.03,95% CI 1.0-1.01, p = 0.01; and LAA volume index: RR = 1.05, 95% CI 1.0-1.01, p = 0.03). LAA volume > 21.9 ml was associated with increased mortality. In contrast, LA volume was not a significant predictor of mortality.

Conclusion: We describe a novel technique to assess LA and LAA volume using 3-D volume-rendered cardiac CT. This study shows enlarged LAA volume rather than LA volume carries a poor prognosis in cancer-survivors treated with prior CXRT. Compared to conventionally reported markers, LAA volume of > 21.9 ml was incremental to that of other risk factors.

Keywords: Cancer survivors; Cardiac CT; Left atrial appendage; Mortality; Radiotherapy.

Fig. 1

Volume acquisition and structural view of left atrium (LA) and left atrial appendage (LAA) obtained by using the three-dimensional multi-planar (axial, coronal and sagittal) reconstructions from multi-detector cardiac computer tomography. Determination of LA and LAA volume measures using three-dimension volume threshold-based method highlighted by the green zones. The top right images demonstrate the three-dimensional view of the LA, LAA and pulmonary veins

Fig. 2

Left atrial (LA) volume curve. The x-axis represents the percent change in the cardiac cycle, and y-axis represents the volume change in the LA. The acquisition of LA volume was performed using three-dimensional reconstructions of the multi detector electrocardiographic gated cardiac computed tomography (CT) images obtained at different phases of the cardiac cycle (0 to 80% R-R interval) to reflect incremental volume change per 10% change in cardiac cycle

Fig. 3

Left atrial appendage (LAA) volume curve. The x-axis represents the percent change in the cardiac cycle, and y-axis represents the volume change in the LAA. The acquisition of LAA volume was performed using three-dimensional reconstructions of the multi detector electrocardiographic gated cardiac computed tomography (CT) images obtained at different phases of the cardiac cycle (0 to 80% R-R interval) to reflect incremental volume change per 10% change in cardiac cycle

Fig. 4

Kaplan Meir survival curve for the mortality rate in patients with and without prior chest radiation therapy. Reduced survival in CXRT group with elevated LAA volume of more than 21.9 ml compared to those with LAA volume of less than 21.9 ml adjusted to 40% of the cardiac cycle. The red line denotes patients without prior chest radiation therapy (non-CXRT group) and blue line denotes patients with prior chest radiation therapy (CXRT group)

Fig. 5

Graphical Abstract summarizing the study design, approach, major findings, and their clinical implications