Abstract

Recent data indicate that survival of patients with autonomic neuropathy (AN) is reduced compared to those without AN. Reduced survival in patients with AN is found in both insulin-dependent diabetes mellitus (IDDM) and alcoholic liver disease; two very different diseases commonly associated with AN. The reason for an increased death rate in patients with AN is unknown. However, sudden death due to major arrhythmias seems to have an important role. Corrected QT-interval (QTc) prolongation is thought to be one of triggers for ventricular arrhythmias. Corrected QT-interval (QTc) prolongation is thought to be one of triggers for ventricular arrhythmias. This study evaluated the correlation between the presence of AN and QTc interval in 162 patients with IDDM (mean age 33.2 years, range 14-57 years, mean diabetes duration of 13 years) and in 83 non-diabetic patients with alcohol related cirrhosis (mean age of 48.3 years, range 28-69 years). Five standard tests of cardiovascular autonomic function were studied: heartrate response to deep breathing, standing, Valsalva maneuver, and blood pressure response to standing and sustained handgrip. The QTc interval was determined using Bazett's formula. Classification of the severity of AN was based on the number of abnormal cardiovascular autonomic test results. A statistically significant linear regression was found between QTc interval prolongation and severity of AN in both diabetics and alcoholics (p<0.001). Prolonged QTc interval (> 440 ms) was seen significantly more often in patients with AN compared to those with normal autonomic function (p<0.001). The correlation between QTc interval prolongation and abnormal cardiovascular autonomic reflexes was analyzed separately. All five cardiovascular autonomic reflexes were significantly correlated with QTc interval prolongation in IDDM as well as in alcoholic cirrhotics (p<0.001), except the sustained handgrip test in IDDM (p<0.01). QTc interval prolongation correlated significantly with abnormalities in both parasympathetic and sympathetic cardiovascular reflexes, indicating that besides the established role of sympathetic dysfunction, parasympathetic damage may contribute to the development of QTc interval prolongation.

Keywords: autonomic neuropathy, QT interval, parasympathetic and sympathetic function, cardiovascular reflex test, alcohol-related cirrhosis