OBJECTIVES: Mitral valve prolapse (MVP) is associated with arrhythmias and sudden death. Some studies suggest that abnormalities of the autonomic nervous system (ANS) may contribute to these arrhythmias. In a family investigation with genetic analysis of patients carrying a MVP, we performed a Holter study to define the autonomic profile of MVP. METHODS AND RESULTS: A 24-hour digitized 3-lead Holter ECG was recorded in 30 patients with MVP and in two control groups, a group of 30 healthy relatives and a group of 31 healthy volunteers. We studied especially heart rate variability (HRV) and QT dynamicity. The slope of the relationship between ventricular repolarization and heart rate was studied separately during day and night. There was no difference in HRV (SDNN, rMSSD) among the three groups. On the contrary, QT interval duration was increased in patients with MVP as compared to healthy relatives (QT end: 409+/-52 ms vs 372+/-23 ms, P<0.05; QT apex: 319+/-42 ms vs 286+/-23 ms, P<0.01) and to healthy volunteers (QT end: 409+/-52 ms vs 376+/-25 ms, P=0.004; QT apex: 319+/-42 ms vs 289+/-23 ms, P<0.01). Nocturnal ventricular repolarization rate dependence was increased in MVP as compared to healthy relatives (0.16+/-0.06 vs 0.13+/-0.04, P<0.05) and to healthy volunteers (0.16+/-0.06 vs 0.11+/-0.06, P<0.001) whereas the 24-hour and diurnal QT-R-R slope was not disturbed. CONCLUSION: In MVP, QT is increased and the circadian modulation of QT end/RR slope is disturbed with an increased nocturnal rate dependence. These abnormalities of ventricular repolarization might explain the risk of arrhythmic events in MVP.