Stress, the autonomic nervous system, and sudden death

The existence of an important relationship between stress, the autonomic nervous system, and sudden cardiac death (SCD) has been long recognized. In the present essay we review the large number of conditions, acting at individual or at population level, that have been causally associated to SCD and discuss the mechanistic and translational value of the studies exploring such associations. These conditions include external stressors (earthquakes, wars) and internal stressors (anger, fear, loss of a loved one) and emotions of even opposite sign. Most situations confirm the time-honored view that increases in sympathetic activity are proarrhythmic whereas increases in vagal activity are protective; however, we will also show and discuss a condition in which the culprit appears to be the excess of vagal activity. The physiologic rationale underlying the most typical situations is on one hand the profibrillatory effect of the increase in the heterogeneity of repolarization secondary to the release of norepinephrine, and on the other the combined effect of acetylcholine to lower heart rate and to antagonize the cardiac effects of norepinephrine at ventricular level. An interesting facet of this potentially lethal relationship is that the elements involved are by no means always exceptional, and they can actually represent part of our everyday life.