The main finding of the present study is the absence of any differences in echocardiographic or ECG parameters between HC and patients with A-AN who, 20 years after their initial treatment, had recovered normal weight. However, patients with A-AN who had low weight at follow up showed cardiac structural abnormalities such as decreases in the LVEDD, LV mass and left atrium dimensions compared to the HC and the Normal-weight group. Moreover, the percentage of patients with low LV mass indexed by BSA in the Low-Weight group was higher than in the Healthy and Normal-Weight group.
In the present study, significant decreases in the LVEDD, LV mass and left atrium was observed in the Low-Weight group compared with the Normal-Weight group and the HC, but no differences were observed for left ventricular systolic function. These results are in line with previous studies which have found structural abnormalities in AN patients but no differences in systolic function compared with controls (4–6, 8–12). Studying cardiac dimensions and ventricular function in 95 adolescents with AN in comparison with 58 controls, (12) found significant reductions in LV dimensions, LV wall thickness, LV mass and Left atrium dimension in patients with AN. (12). Despite the decreases in LV mass and LV dimensions, resting systolic function in AN patients was unchanged. The differences for the LV mass indexed by BSA between groups did not reach statistical significance; this may have been due to the small sample size in the Low-Weight group, since previous studies with larger samples have reported significant differences (Escudero et al., 2016; Franzoni et al., 2003; Galetta et al., 2003; Mont et al., 2003; Olivares et al., 2005).
One patient in the Low-Weight group presented mild tricuspid regurgitation. This condition has been described in patients with congestive heart failure and severe malnutrition (27). Another patient with AN had a dilated right ventricle; however, it has been suggested that normal right ventricular wall thickness and chamber size may give the impression of a dilated right ventricle when compared to the small left ventricle in patients with malnutrition (28).
We found no differences in any cardiac parameter between HC and Normal-Weight groups, all of which were in the normal range. Taken together, these results indicate that although patients with low weight present cardiac structural abnormalities, they may recover completely when they reach and maintain normal weight. Most studies that have assessed the reversibility of cardiac abnormalities in the short term after refeeding have found similar results (5, 6), though not all (11). Mont et al (2003) compared cardiac parameters of adolescents with AN before and after refeeding and weight normalization (3-18 months later). After refeeding, these authors observed significant increases in the LVEDD, LVESD, left atrium dimension and the LV mass, all of which returned to normal values in the majority of patients. LVEF was normal before and after refeeding for all subjects. The study by Olivares et al (2005) compared cardiac parameters of 40 young women with AN, at baseline and after renutrition (6-18 months), and matched them with 40 healthy controls (6). The authors observed a significant reduction in cardiac cavities and in myocardial mass in patients with AN compared with controls; after treatment and weight recovery, myocardial size and cardiac cavities returned to normal after adjustment for body mass (6). Lastly, Kastner et al (2012) studied 173 adolescents with AN admitted to hospital before and after renutrition and compared them with 40 healthy controls (11), finding that anorexic patients had reduced LVEDD and LVESD in comparison to controls at baseline. They did not observe a relevant increase in LVEDD and LVESD, but the duration of treatment was shorter (1-6 months) and weight gain was lower (mean BMI at recovery 17.12±1.27) than in the other studies that have assessed the reversibility of cardiac abnormalities (5, 6, 11).
Regarding functional changes, we did not find differences between groups in any of the ECG parameters. One patient in the Low-Weight group presented sinus bradycardia, which has been reported as the most frequent arrhythmia in patients with AN (4, 5, 10, 14, 29). None of the patients in the Low-weight group presented prolonged QTc or QT dispersion, findings recorded by some authors in patients with AN (Galetta et al., 2002; Mont et al., 2003; Olivares et al., 2005) though not by others (Bomba et al., 2018; Panagiotopoulos, McCrindle, Hick, & Katzman, 2000; Sachs et al., 2016). Potential causes of these discrepancies include electrolytic disturbances, the use of drugs known to prolong QT interval, ionic channel genetics, idiopathic long QT syndrome, metabolic factors, hormones or decrease in LV mass index.
The main limitation of the study is the small sample size, especially in the Low-Weight group; however, since most adolescent-onset AN who receive treatment recover from the illness, this is inevitable (17). Another relevant limitation is that not all the patients contacted agreed to participate in the study. It is possible that the final sample was composed of patients with a better prognosis or higher motivation to collaborate with studies of this kind.
The main strength of the study is that, to our knowledge, it is the first to compare cardiac parameters in the long term between A-AN after 20 years of initial treatment and healthy controls. Another strength is its comparison of the A-AN sample with a matched sample of HC.