To evaluate the effects of acute reduction in ventricular volume (VV) on QT interval dispersion (QTd), 14 men with heart failure (HF; 74.5 Ϯ 2 yr of age) and 11 healthy male control subjects (68 Ϯ 2 yr of age) were studied. For 15 min, lower body negative pressure (LBNP) was applied at Ϫ15 and Ϫ40 mmHg to reduce venous return. At baseline and during LBNP application, QTd was measured with an 87-lead, body-surfacemapping device; chamber volumes were assessed by radioisotope ventriculography; blood pressure (BP) and heart rate (HR) were continuously monitored; and blood samples were obtained for assessment of norepinephrine (Nor) levels. At Ϫ15 mmHg, LNBP application induced a significant decrease in VV but did not change BP and HR in both groups. In addition, Nor levels increased significantly (P Յ 0.05) in the control group (from 286.7 Ϯ 31.5 to 388.8 Ϯ 41.2 pg/ml) and in HF patients (from 405.8 Ϯ 56 to 477.6 Ϯ 47 pg/ml), and QTd was significantly (P Յ 0.05) decreased in the control group (57.2 Ϯ 3.8 vs. 49.1 Ϯ 3.4 ms) and in HF patients (67.8 Ϯ 6 vs. 63.7 Ϯ 5.9 ms). No additional decreases in VV or QTd were produced by Ϫ40 mmHg LNBP, but Nor levels did increase in both groups and reach 475.5 Ϯ 34 and 586.5 Ϯ 60 pg/ml (P Ͻ 0.05) in the control and HF groups, respectively; BP did not change, but HR also increased in both groups. In conclusion, an acute LBNP-induced reduction in VV caused a decrease in the QTd of elderly men regardless of the existence of HF. Because increased sympathetic activity with more intense LBNP was not accompanied by additional changes in QTd, altered QTd may be better related to changes in VV than to autonomic nervous system activity. lower body negative pressure; cardiomyopathy; cardiac; norepinephrine; ischemic disease HEART FAILURE (HF) is a highly prevalent and important cause of morbidity and mortality in the elderly population (20). Although improvements in HF therapy have lowered mortality caused by disease progression, nearly half of the patients with HF experience sudden death (22,34). Some studies (4,7,12,14,39) have suggested that QT interval dispersion (QTd) could be associated with a higher risk of sudden death. Indeed, some investigators (16, 44) have correlated structural alterations observed in HF with increased QTd and a worse prognosis. Thus a better prognosis due to the use of drugs that attenuate ventricular remodeling [e.g., angiotensin-converting enzyme (ACE) inhibitors] seems to be associated with a more homogeneous repolarization, which leads to a decrease in QTd (3).As a result, research to detect a possible relationship between QTd behavior and factors known to influence the prognosis of HF [e.g., ventricular dysfunction, ventricular volume (VV), and neurohormonal activation] can be very useful (1, 35). Among such factors, VV is the least complex variable to study. One model that induces acute reductions in VV consists of the application of lower body negative pressure (LBNP), whereby cardiac preload is decreased because of a reduction in venous return (10). Thi...