Associations between Sympathetic Nerve Activity and Ischemia in Takotsubo Syndrome and Stable Ischemic Heart Disease

BackgroundPatients with stable ischemic heart disease (IHD) frequently experience ambulatory myocardial ischemia. Takotsubo Syndrome (TTS) often mimics IHD and is associated with heightened sympathetic activity. We hypothesized that skin sympathetic nerve activity (SKNA) differs between participants with prior TTS, stable IHD, and reference controls and that SKNA increases relative to electrocardiographic (ECG) evidence of ischemia. MethodsSimultaneous recordings of SKNA and ECG (neuECG) measured ST height and average SKNA (aSKNA) in ambulatory participants with a history of TTS (n=6), stable IHD (n=7), and reference controls (n=19). Ambulatory ischemia was defined as ischemic ST segment depression [≥]0.5 mm. SKNA burst frequency, duration, amplitude, and total area above the threshold were calculated during ischemic and non-ischemic episodes. ResultsBaseline aSKNA was similar between TTS, IHD, and reference controls (0.980{+/-} 0.061 {micro}V vs 0.916{+/-}0.050 {micro}V vs 1.098{+/-}0.291 {micro}V respectively, p=0.06). Ischemic episodes (n=15) were identified in 2 TTS and 4 IHD participants, while reference controls had none. Among the TTS and IHD groups, ischemic ST depression was associated with increased heart rate and elevated aSKNA from baseline. An analysis of SKNA burst patterns at similar heart rates revealed that SKNA total burst area was significantly higher during ischemic episodes than non-ischemic episodes (0.301{+/-}0.380 {micro}V.s and 0.165{+/-}0.205 {micro}V.s, p=0.023) in both the TTS and IHD participants. ConclusionsCompared with heart rate-matched non-ischemic episodes, ischemic episodes were associated with larger SKNA burst areas in the TTS and IHD groups. The neuECG may be a useful tool in studying the pathophysiology of sympathetic nervous system-related ischemia. Clinical PerspectiveO_LIAmbulatory monitoring with neuECG can assess sympathetic skin nerve activity (SKNA) and electrocardiography simultaneously. C_LIO_LIWe found that ischemic episodes are present not only in patients with stable ischemic heart disease (SIHD) but also those with a history of Takotsubo Syndrome. C_LIO_LISKNA burst activity was greater during ischemic episodes than nonischemic episodes in patients with SIHD and history of Takotsubo Syndrome. C_LIO_LINeuECG may be a noninvasive tool in studying mechanisms of sympathetic nervous system-related ischemia. C_LI