In certain subgroups of patients, prolongation of the QTc interval may increase total and cardiovascular mortality due to life-threatening ventricular arrhythmias and sudden death. Nonetheless, whether modest prolongation of the QTc interval in the general population has clinical importance remains unclear.
We conducted a literature search from 1990 forward to identify all published prospective cohort studies evaluating the association between prolonged QTc interval 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.
The 7 prospective cohort studies identified included 36 031 individuals. There were 2677 (8.7%) individuals with prolonged QTc interval, defined as 440 milliseconds or greater. Whereas 1 study reported no association between prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistent associations overall as well as across subgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascular mortality and sudden death were also inconsistent. In the overview, the only consistent findings were for the subgroup of patients with prior cardiovascular disease, in which relative risks ranged from 1.1 to 3.8 for total mortality, from 1.2 to 8.0 for cardiovascular mortality, and from 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absent or greatly attenuated; specifically, relative risks ranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascular mortality, and from 1.3 to 2.4 for sudden death.
There was no consistent evidence for increased risks of total or cardiovascular mortality or of sudden death, 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.