Abstracts

Rationale:
Epidemiologic studies indicate that risk of death due to sudden cardiac arrest is 3-fold greater in patients with epilepsy than in the general population.  Prior work by our group and others has demonstrated that patients with chronic epilepsy exhibit postmortem evidence of cardiac damage and antemortem elevations in electrocardiographic (EKG) markers of lethal arrhythmia risk, that is, an “Epileptic Heart,” defined as “a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction” [Verrier et al doi: 10.1016/j.yebeh.2020.106946].  In a population study [Kentta et al doi: 10.1016/j.hrthm.2015.11.035], R-wave and T-wave heterogeneity (RWH, TWH), were shown to be independent predictors of sudden cardiac death.  We hypothesized that these markers would detect the “Epileptic Heart” condition in patients with chronic refractory epilepsy at EMU admission.
Method:
Patients referred to the EMU were prospectively enrolled.  On admission day, resting 12-lead EKGs were obtained, and RWH and TWH were assessed by second central moment analysis to determine the splay in the mean R-wave and T-wave morphologies of beats simultaneously recorded in adjoining precordial leads V4, V5, and V6.  Figure 1 illustrates the capacity of RWH and TWH to detect arrhythmia risk in cardiomyopathy patients with ventricular tachycardia (VT) [Tan et al doi: 10.1111/jce.13288].
Results:
Of 22 patients, 16 had chronic epilepsy while 6 had only psychogenic nonepileptic seizures (PNES) and no history of epileptic seizures.  On admission day, maximum interictal RWH was elevated in all patients with chronic epilepsy to 252±25.1 µV (with no seizures), 319±77.2 µV (with focal seizures, FS), and 324±62.9 µV (with generalized tonic clonic seizures, GTCs), all of which exceeded the 160-µV cutpoint of RWH abnormality (Figure 2, red dashed line).  In addition, all patients with epilepsy showed TWH levels well above the 80-µV cutpoint of abnormality (red dashed line), at 158±41.4 µV (with FS), and 193±26.7 µV (with GTCs), and without seizures (132±19.2 µV).  RWH and TWH in patients with GTCs approach levels in cardiomyopathy patients with VT.  Patients with PNES did not have elevated RWH (157±38.2 µV) or TWH levels (68±9.45 µV).
Conclusion:
This is the first study to our knowledge to demonstrate significant RWH and TWH levels in 12-lead EKGs on EMU admission day, reflecting cumulative seizure-induced cardiac damage.  RWH and TWH levels were positively correlated with occurrence of epileptic seizures, particularly GTCs, in the EMU patients with chronic, drug-resistant epilepsy, shedding light on an important potential mechanism of SUDEP.  Data also suggest these novel biomarkers could differentiate between patients with refractory epilepsy and those with only PNES.  Cardiac screening in patients with epilepsy is not standard of care, but use of 12-lead EKGs with these cardiac markers may help to identify patients who may be at higher risk for sudden cardiac death to decrease mortality in epilepsy.
Funding:
:Neurology Department, BIDMC.