BACKGROUND: Congenital ventricular septal defects (VSDs) are considered to have benign long-term outcome when treated correctly in childhood. However, abnormal parameters are described in younger adults, including impaired heart rate variability (HRV). It is not known whether such abnormalities will deteriorate with age. Therefore, HRV and cardiac events, such as premature ventricular contraction, were evaluated in patients aged >40 years with congenital VSDs and compared with healthy peers. METHODS AND RESULTS: A total of 30 surgically closed VSDs (51±8 years, repair at median age 6.3 years with total range 1.4– 54 years) with 30 healthy controls (52±9 years) and 30 small, unrepaired VSDs (55±12 years) with 30 controls (55±10 years) were all equipped with a Holter monitor for 24 hours. Compared with healthy peers, surgically closed patients had lower SD of the normal-to-normal (NN) interbeat interval (129±37 versus 168±38 ms; P<0.01), SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording (116±35 versus 149±35 ms; P<0.01) and 24-hour triangular index (31±9 versus 44±11; P<0.01). SD of the NN intervals, SD of the average NN intervals for each 5-minute segment of a 24-hour HRV recording, and triangular index were comparable between unrepaired VSDs and healthy peers. SD of the NN intervals was <100 ms in 22% of surgically closed and 10% of unrepaired VSDs, whereas controls were within normal ranges. A high number of premature ventricular contractions (>200 events) was registered in 57% of surgical patients compared with 3% of controls (P<0.01), and 53% of unrepaired VSDs compared with 10% in controls (P<0.01). CONCLUSIONS: Adults aged >40 with congenital VSDs demonstrate impaired HRV, mainly among surgically closed VSDs. More than half demonstrated a high number of premature ventricular contractions. These novel findings could indicate long-term cardiovascular disturbances. This necessitates continuous follow-up of VSDs throughout adulthood.