Is Marfan Syndrome Associated with Primary Structural Changes in the Left Atrium?

Abstract

Marfan syndrome (MFS) is an autosomal-dominant multisystem connective tissue disorder that is based on mutations in the FBN1 gene and variably affects different organs, including the heart. In this study, we investigated cardiac function with a focus on the left atrium (LA) in a relatively large cohort of patients with MFS. After screening of 1165 patients that had been examined in our center between 2016 and 2020, 231 adult MFS patients with and without aortic operation were included in our study and compared to a healthy control group (n = 106). Cardiac function was assessed by transthoracic echocardiography and NT-proBNP was used as a secretory marker. Most (94.8%) of the patients received genetic testing. Left ventricular function was within normal ranges and not impaired. Interestingly, we found that LA size and secretory activity were increased in MFS patients, despite normal left ventricular filling pressures. This finding was even more pronounced in MFS patients with prior aortic surgery. A correlation between LA size or NT-proBNP levels and the type of pathogenic FBN1 variant could not be identified. Right ventricular function and right atrial size were increased only in MFS patients that had undergone aortic surgery. In conclusion, these findings suggest that MFS leads to structural changes in the LA that are not solely resulting from left ventricular dysfunction, but probably can be considered a primary pathology of MFS.

Keywords: Marfan syndrome; NT-proBNP; aorta; aorto-ventricular coupling; biomarkers; cardiac function; cardiomyopathy; echocardiography; left atrium.

Figure 1

LA size in normal and elevated left ventricular filling pressures in healthy controls and patients with MFS with and without prior aortic surgery. Mild outliers that are more than 1.5 IQR below the first or above the third quartile (box) are represented by circles. Extreme outliers that are more than 3 IQR below the first or above the third quartile are represented by asterisks. LA = left atrium. LVFP = left ventricular filling pressure. MFS = Marfan syndrome. * p < 0.05 (Kruskal–Wallis and Bonferroni post hoc tests).

Figure 2

LA size in Relation to left ventricular filling pressure in healthy controls, patients with MFS with and without prior aortic surgery. LA = left atrium. MFS = Marfan syndrome.

Figure 3

NT-proBNP in healthy controls (yellow), patients with MFS with (blue) and without (green) prior aortic surgery. Mild outliers that are more than 1.5 IQR below the first or above the third quartile (box) are represented by circles. MFS = Marfan syndrome, * p < 0.05, ** p < 0.001 (Kruskal–Wallis and Bonferroni post hoc tests).

Figure 4

Genotype–phenotype relationship. Differences in LA size between types of pathogenic FBN1 variant were not significant (Kruskal–Wallis test, p = 0.12). Mild outliers that are more than 1.5 IQR below the first or above the third quartile (box) are represented by circles. Extreme outliers that are more than 3 IQR below the first or above the third quartile are represented by asterisks. LA = left atrium.