Discussion

Anorexia nervosa is a major eating disorder with a prevalence of 1–3% in adolescents and young adults and has the highest mortality rate (20%) among psychiatric disorders. Approximately one-third of deaths in patients with anorexia nervosa have been attributed to cardiovascular complications, second only to suicide. Cardiac abnormalities are found in up to 80% of patients with anorexia nervosa. ^{Reference Sullivan1–Reference Neumarker7}

The present study showed that sinus bradycardia was a common finding in adolescents with anorexia nervosa, which has been well documented in previous studies. ^{Reference Panagiatopoulos, McCrindle and Hick10–Reference Sweene11} Possible aetiologic factors include increased vagal tone, decreased sympathetic tone, thyroid dysfunction, electrolyte abnormalities, drug side effects, decreased myocardium glycogen content, and muscle atrophy. ^{Reference Casiero and Frishman4,Reference Galetta, Franzoni and Cupisti12,Reference Romano, Chinali and Pasanisi26,Reference Nagueh, Smiseth and Appleto31–Reference Bomba, Corbetta and Gambera35}

Prolongation of the QT and QTc interval was also relatively common, seen in 28% of our patients. Prolongation of the QT interval and increased QT dispersion have been previously reported as well. These abnormalities have been implicated in the onset of arrhythmias and sudden death; however, a causal role has not yet been demonstrated in patients with anorexia nervosa. QT abnormalities in anorexia nervosa are unlikely the result of a channelopathy of the type seen in patients with hereditary long QT syndrome. Proposed mechanisms for QT abnormalities in anorexia nervosa include limitations of the measurement associated with bradycardia, autonomic imbalances, electrolyte disorders, nutritional deficiencies, rapid weight loss, and cardiac atrophy. More interestingly, structural myocardial changes due to starvation such as fibrosis and adipose infiltration possibly leading to non-homogeneous myocardial depolarisation and repolarisation could be the substrate for arrhythmia in anorexia nervosa. ^{Reference Panagiatopoulos, McCrindle and Hick10–Reference Guerrier, Mitan and Wang17}

Structural abnormalities in anorexia nervosa reported by echocardiography include decreased cardiac mass, mitral valve prolapse, pericardial effusions, reduced left ventricular diastolic and systolic dimensions, and decreased cardiac output. Remarkably, these patients do not present congestive heart failure consistent with the observation that fractional shortening and ejection fraction as measured by echocardiography remain normal in most patients. Histological and MRI findings in patients with anorexia nervosa suggest an underlying cause to cardiac muscle dysfunction, despite it not being detected by standard echocardiographic indices such as fractional shortening and ejection fraction. ^{Reference Moodie and Salcedo8,Reference Kalager, Brubakk and Bassoe18–Reference Romano, Chinali and Pasanisi26}

Tissue Doppler imaging has been shown to be a useful tool in the evaluation of systolic and diastolic dysfunction in other cardiomyopathies. ^{Reference Yu, Sanderson and Marwick27} In our series, we found four patients (14.3%) with abnormal tissue Doppler imaging indicating systolic or diastolic dysfunction. Two cases also had severely decreased left ventricular mass, which represented two of three total patients with decreased left ventricular mass in our study. This could be an indication of an association between left ventricular mass and severe diastolic dysfunction as measured by tissue Doppler imaging in anorexia nervosa patients. The patients’ disease duration was not different from the group average. One of these patients also had tissue Doppler imaging abnormalities indicating both systolic and dysfunction. None of these patients presented with QT abnormalities.

In addition, 7 (25.0%) of the remaining patients showed a trend towards decreased systolic or diastolic dysfunction with either tissue Doppler imaging velocities decreased to between −1 and −2 SD, which could represent an early manifestation of myocardial systolic and diastolic dysfunction despite normal fractional shortening and ejection fraction by standard echocardiography techniques.

Other reports of tissue Doppler imaging evaluation in patients with anorexia nervosa have yielded contrasting results. ^{Reference Galetta, Franzoni and Cupisti36} Similar to our findings, the series by Escudero ^{Reference Escudero, Potts and Lam37} showed that despite normal contractility by fractional shortening and ejection fraction the patients have abnormal tissue Doppler imaging indices. This could indicate early myocardial compromise in patients with anorexia nervosa and could prove as a useful marker for aggressive nutritional intervention in these patients. Refeeding has been shown to be an effective treatment in reversing the adverse cardiac effects of anorexia nervosa. ^{Reference Olivares, Vasquez and Fleta9,Reference Sweene11}

Therefore, the finding that tissue Doppler imaging could serve as a tool for identifying myocardial dysfunction over the more standard findings of reduced fractional shortening and ejection fraction values is potentially clinically relevant in anorexia nervosa patients. Abnormal tissue Doppler imaging could indicate abnormal histologic findings as described above which could be the substrate for QT prolongation and other possibly malignant ventricular arrhythmias. Further studies are necessary to evaluate the correction of the observed cardiac abnormalities after aggressive nutritional intervention and to establish a standard threshold using tissue Doppler imaging for such an intervention.

In conclusion, abnormal tissue Doppler imaging findings may be an effective tool in detecting early myocardial compromise which could help to reduce the risk for cardiac complications including arrhythmias and sudden cardiac death in these patients by means of closer monitoring and aggressive and timely nutritional intervention.