Reassessing the role of QTc in the diagnosis of autonomic failure among patients with diabetes: a meta-analysis.

OBJECTIVE: A 1992 consensus statement on autonomic testing portrayed Bazett's heart rate-corrected QT interval (QT) prolongation as a specific yet insensitive indicator of diabetic autonomic failure. At that time, only a few small studies had evaluated the accuracy of QTc. To date, even fewer studies have evaluated whether its accuracy is influenced by patient characteristics. RESEARCH DESIGN AND METHODS: We critically appraised 17 studies reporting the sensitivity and specificity of QTc for diabetic autonomic failure. The studies represented 4,584 patients with diabetes (mean age 34.9 years, 46% female, 92% with type 1 diabetes, mean duration of diabetes 14.5 years). We summarized the accuracy of QTc prolongation for diabetic autonomic failure as an odds ratio (OR) (95% CI) and determined whether patient and study design characteristics influenced the accuracy of QTc prolongation by comparing summary receiver operating characteristic curves. RESULTS: Autonomic failure, defined as or =1.2+/-0.4 (mean +/- SD) abnormal of 2.0+/-1.6 administered cardiovascular reflex tests, was found in 26% (25-28) of patients. The pooled sensitivity and specificity of QTc 441+/-8 ms for autonomic failure were 28% (26-29) and 86% (85-87), respectively. Autonomic failure was 2.26 times (1.90-2.70) more likely to be present in patients with than in patients without QTc prolongation. At 86% specificity, the sensitivity of QTc prolongation was 46 vs. 12% for men versus women (P = 0.0077), respectively, and, after adjustment for sex, 66 vs. 17% among patients aged 25 vs. 55 years (P = 0.1902) and 61 vs. 27% at thresholds of 420 vs. 460 ms, respectively (P = 0.2964). CONCLUSIONS: QTc prolongation is a specific albeit insensitive indicator of autonomic failure. Although QTc prolongation is relatively accurate for men, accuracy may be even greater for young men at low QTc thresholds.