Our data demonstrate that despite the high level of concern for sudden death and cardiac morbidity in patients with AN, few cardiac abnormalities exist among the population of malnourished adolescents admitted for nutritional stabilization. Additionally, observed abnormalities resolve on refeeding and restoration of appropriate body weight.
Most of our sample had sinus bradycardia, consistent with other reports of malnutrition.10,20,21
Reduction in heart rate is likely due to increased vagal tone and the body’s attempt to conserve energy in response to starvation.22
Interestingly, subjects with a longer duration of illness were less likely to be bradycardic. Acute reductions in nutritional intake and rapid weight loss have a more profound effect on metabolic regulation of heart rate than chronic malnourishment. In addition, subjects with a higher BMI at admission were more likely to have a lower heart rate. This finding is confounded by the fact that all subjects in this study met medical criteria for hospitalization; thus, patients with lower heart rates were selected for participation. Despite significant increases in weight between assessments, 4 subjects (22%) returning for a second evaluation remained bradycardic.
Repolarization abnormalities are a common concern of clinicians caring for patients with AN. Prolongation of the QT interval is the ECG abnormality most commonly associated with AN and is the most feared given the association between delayed repolarization and sudden death. Prevalence reports of QTc prolongation in subjects with AN range from 0% to 45%.12,23–26
In our small sample, the distribution of QTc intervals was within the normal range. Subjects who had a longer duration of amenorrhea had a longer QT interval. Measurements of weight alone (BMI, percentage of MBW) were not associated with length of the QT interval, suggesting that changes in the hormonal milieu may have an impact on repolarization apart from the effect of malnutrition alone. Refeeding appears to return any QT interval prolongation to normal over time. The QT dispersion has been shown to increase in subjects with AN compared with control subjects and is associated with longer duration of disease and advancing subject age.24,26,27
In the young women in our study, QT dispersion was within normal limits at both times. In our sample, only 1 subject had a metabolic derangement at the time of ECG; abnormal QTc intervals in the acute setting should be interpreted in the context of serum chemistries and clinical history.
Low aBMD is another well-known complication of AN.28–30
Patients with AN possess numerous risk factors for skeletal deficits, including low body weight, poor nutritional intake, and hormonal abnormalities. In this sample, spinal aBMD was within the normal range for age and sex and was strongly correlated with measures of malnutrition. Interestingly and unexpectedly, higher heart rate at admission predicted lower lumbar spine aBMD. Given the other correlations we found, it is likely that this relationship is mediated through duration of illness; subjects with higher heart rates at admission had longer durations of illness, and thus we would expect a more significant effect on spinal aBMD. We also found that a longer QT interval predicted increased spinal aBMD. This cross-system association emphasizes that the combination of malnutrition and behavior associated with AN results in a multisystem disease.
Myocardial mass decreases as a result of self-induced starvation, similar to reductions in skeletal muscle that are visible evidence of malnutrition.2,10
Reduced LV volumes, LV mass, and cardiac output have all been associated with AN.10,31
We found clinically unimportant decreases in LV mass at presentation. In subjects returning for follow-up, the recovery of LV mass was less than predicted by the increase in body surface area, and LV mass Z
scores decreased between admission and follow-up assessments. The decline in LV mass Z
scores despite weight improvements suggests early sparing of cardiac muscle in the face of moderate malnutrition as well as a relative delay of cardiac muscle restoration. Continued controversy exists as to the etiology of these findings. Possible hypotheses include a direct effect of malnutrition or a secondary effect of preload reduction leading to ventricular atrophy. Despite these decreased measurements, little to no LV dysfunction has been reported,31,32
nor was any noted here. The only truly pathologic observation, a pericardial effusion, was identified in 3 subjects; admission weight was less than 75% of MBW in 2 of the 3 subjects with an effusion. With no intervention other than nutritional rehabilitation, the effusion resolved in 2 of the cases. The outlier in this study who had persistent pericardial effusion and among the lowest LV mass indices had profound malnutrition with a BMI of 12.1 at presentation.
In addition to studying a sample of younger subjects with a shorter duration of illness, we also challenged subjects to perform a treadmill exercise test. This evaluation closely mimics the upright-posture stresses on the cardiovascular system that are associated with typical daily activities, unlike supine exercise tests used previously to assess this population. No significant abnormalities were noted either during acute medical stabilization or at follow-up. No evidence of occult myocardial injury was demonstrated using measurement of cardiac enzymes.
Study limitations deserve acknowledgment and consideration. Our sample is small and thus limits our ability to detect rather rare cardiac abnormalities. Only a subsample underwent cardiac enzyme measurements, which limits our power to detect subtle differences. However, not a single subject had cardiac enzyme results outside the normal range. In this pilot study, we were unable to assess potential hormonal mechanisms that may mediate the effects of malnutrition on cardiac status. All study subjects were at least 2 years post menarche. Results may not be generalizable to premenarchal girls. Lastly, our adolescent subjects were moderately malnourished (median BMI, 15.8). While this sample accurately reflects those patients deemed ill enough to require acute inpatient medical care at our institution, future studies will need to validate our findings in more severely malnourished populations (BMI ≤14.0).
Decreased emphasis on bed rest during hospitalization may be beneficial. Our patients continued to have evidence of orthostatic intolerance throughout their hospitalization. In addition, these patients had evidence of skeletal deficits. There are ample data that bed rest exacerbates both of these observations.5,33
These associations reinforce the implication that AN is a multisystem disorder, further emphasizing the need for creative, multidisciplinary treatment plans.
In conclusion, in a group of acutely malnourished and medically compromised adolescents with AN, few truly pathologic cardiac findings were identified. Most subjects demonstrated sinus bradycardia, which resolved for most with successful refeeding. Mild reductions in LV mass and LV function are seen both at baseline and at follow-up, suggesting early sparing of cardiac muscle in the face of moderate malnutrition as well as a relative delay of muscle restoration. No clinically important arrhythmias were identified. Measurements of spinal aBMD were inversely related to hemodynamic parameters, suggesting a link between skeletal health and the cardiovascular system. While limited, these data are concordant with other studies of the moderately malnourished patient with AN, particularly the careful study by Mont et al.12
Our findings suggest that in the patient with moderate malnutrition, less intensive cardiac monitoring and a more permissive approach to graded physical activity may be reasonable. However, individualized care plans may be needed depending on patient stability and behavioral issues.