Prolonged QTc Interval and Risks of Total and Cardiovascular Mortality and Sudden Death in the General Population

Methods: We conducted a literature search from 1990 forwardtoidentifyallpublishedprospectivecohortstudiesevaluatingtheassociationbetweenprolongedQTcinterval and risks of total and cardiovascular mortality as well as sudden death. We reviewed each of the studies individually and then conducted a qualitative overview. Results:The7prospectivecohortstudiesidentifiedincluded 36031individuals.Therewere2677(8.7%)individualswith prolonged QTc interval, defined as 440 milliseconds or greater.Whereas1studyreportednoassociationbetween prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistentassociationsoverallaswellasacrosssubgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascularmortalityandsuddendeathwerealsoinconsistent. In the overview, the only consistent findings were for the subgroupofpatientswithpriorcardiovasculardisease,in which relative risks ranged from 1.1 to 3.8 for total mortality,from1.2to8.0forcardiovascularmortality,andfrom 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absentorgreatlyattenuated;specifically,relativerisksranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascularmortality,andfrom1.3to2.4forsuddendeath. Conclusions:Therewasnoconsistentevidenceforincreased risksoftotalorcardiovascularmortalityorofsuddendeath, except perhaps for patients with prior cardiovascular disease. In the general population, if QTc interval prolongation is associated with any increase in mortality, that risk is likely to be small and difficult to detect reliably. Arch Intern Med. 2004;164:943-948