Left atrial thrombus resolution in non-valvular atrial fibrillation or flutter: biomarker substudy results from a prospective study with rivaroxaban (X-TRA)

Figures & data

Figure 1. X-TRA study design. CrCl: creatinine clearance; EOT: end of treatment.

Table 1. Relationship between baseline biomarkers and demographic variables based on multivariate models.

Biomarker	Sex	Age	BMI	R^2	n
log hsCRP				0.000	55
log D-dimer			X	0.055	53
vWF			X	0.056	55
log hsIL-6				0.000	46
log PAI-1		X	X	0.149	55
log F1,2	X		X	0.130	55
log TAT		X		0.055	51

X indicates which demographic variables were used to build the model with the corresponding biomarker.

R² is the coefficient of determination.

BMI: body mass index; F1,2: prothrombin fragment 1 + 2; hsCRP: high-sensitivity C-reactive protein; hsIL-6: high-sensitivity interleukin-6; PAI-1: plasminogen activator inhibitor-1; TAT: thrombin–antithrombin complexes; vWF: von Willebrand factor.

Table 2. Multivariate models of relationships between echocardiograhic characteristics and biomarker levels at baseline.

Echocardiogram parameter at baseline	Biomarker (baseline)	Regression coefficient		95% CI	p-value	n
(a) Linear models (continuous echocardiogram parameter)
LAA peak emptying velocity	log hsCRP	4.301		[−0.41 to 9.01]	.089	28
	log D-dimer	4.602		[−0.55 to 9.75]	.095	28
	vWF	0.037		[−0.01 to 0.08]	.137	28
	log hsIL-6	−9.311		[−16.58 to −2.04]	.021	28
	log TAT	−8.964		[−17.68 to −0.25]	.057	28
LA/LAA thrombus area	log D-dimer	42.550		[−5.49 to 90.59]	.094	31
(b) Logistic models (binary echocardiogram parameter)
			OR
Presence of spontaneous echocontrast	log hsCRP	−1.172	0.310	[0.05 to 1.79]	.190	33
	log D-dimer	3.503	33.212	[1.09 to 1015.30]	.045	33
	log TAT	6.158	472.617	[0.54 to 411305.90]	.075	33

The table shows the results from final multivariate models for the clinical endpoints after Akaike information criteria-based parameter selection.

In addition to above biomarkers other demographic data were also selected as relevant covariates in this selection (Congestive heart failure and prior stroke were relevant covariates with LAA peak emptying velocity; hypertension with LA/LAA thrombus area; BMI and diabetes mellitus with presence of spontaneous echocontrast).

LA: left atrium; LAA: left atrial appendage; OR: odds ratio; CI: confidence interval.

Figure 2. Boxplots of biomarker levels. Values at baseline and end of treatment (descriptive). The red circles are baseline values and the blue crosses are values for the end of treatment. The median is indicated as a solid horizontal line in bold; “+” indicates the mean; the bottom and top of the box are the first and third quartiles (25th and 75th percentile), therefore 50% of the observations lie within this box and the box length is the interquartile range; the upper and lower whiskers are at the lowest and highest observation if they do not exceed 1.5 times the box length (interquartile range). F1:2: prothrombin fragment 1 + 2; hsCRP: high-sensitivity C-reactive protein; hsIL-6: high-sensitivity interleukin-6; PAI-1: plasminogen activator inhibitor-1; TAT: thrombin–antithrombin complexes; vWF: von Willebrand factor.

Table 3. Multivariate logistic models of relationships between thrombus outcomes and biomarker baseline levels.

Thrombus outcome	Biomarker (baseline)	Regression coefficient	OR	95% CI	p-value	n
Thrombus complete resolved	log hsIL-6	1.591	4.909	[1.27 – 19.00]	.021	33
	vWF	−0.011	0.989	[0.98 – 1.00]	.077	33
Thrombus reduced or resolved	log hsCRP	2.210	9.120	[1.16 – 72.00]	.036	31
	vWF	−0.015	0.985	[0.97 – 1.00]	.134	31

The table shows the results from final multivariate models for the clinical endpoints after Akaike information criteria-based parameter selection.

In addition to above biomarkers other demographic data were also relevant covariates as results of this selection (diastolic blood pressure and BMI relevant with thrombus reduced or resolved).

CI: confidence interval; OR: odds ratio.