Sudden unexpected death in epilepsy: impact, mechanisms, and prevention

Patients with refractory epilepsy face an elevated risk of sudden death, with rates as high as 1% per year. This phenomenon, known as sudden unexpected death in epilepsy (SUDEP), is believed to be a seizure-related occurrence, but the exact underlying mechanisms are uncertain. Both pulmonary and cardiac pathophysiologies have been proposed. The cardiac mechanism of greatest interest is the precipitation of arrhythmias by seizure discharges via the autonomic nervous system. SUDEP prevention has centered on effective seizure control, and epilepsy surgery has reduced SUDEP incidence in a number of studies. Additional prophylaxis methods are needed, however, for the large number of patients with treatment-refractory epilepsy. Future research should aim to clarify whether the association between seizures and autonomic dysfunction and cardiac arrhythmias extends to a demonstrable cardiac mechanism for SUDEP.     

Testing an Exercise Intervention to Improve Aerobic Conditioning and Autonomic Function after an Implantable Cardioverter Defibrillator (ICD)

Background: Implantable cardioverter defibrillators (ICDs) are an increasingly common treatment for survivors of sudden cardiac arrest or others with life‐threatening ventricular arrhythmias. Health‐care providers are often reluctant to prescribe exercise for this group because of the belief that it will provoke ventricular arrhythmias and cardiac arrest; patients are often afraid to exercise because of concern over receiving an ICD shock. A social cognitive theory‐driven exercise intervention aimed at stabilizing cardiac arrhythmias and reducing ICD shocks by increasing parasympathetic autonomic nervous system control is described. Methods: The exercise intervention has two phases that include an 8‐week aerobic conditioning component followed by a 16‐week exercise maintenance component. The aerobic exercise intervention is expected to have significant impact on cardiopulmonary function, ventricular arrhythmias, cardiac autonomic function, and self‐efficacy in persons who have an ICD. The exercise intervention is currently being tested using a randomized clinical trial format, the results of which will be available in 2012. Conclusion: The exercise after ICD trial is one of the first clinical trials to test the effects of aerobic exercise on cardiopulmonary outcomes after receiving an ICD for primary or secondary prevention of sudden cardiac arrest. (PACE 2010; 973–980)     

Heart-brain interactions in cardiac arrhythmias: role of the autonomic nervous system

The autonomic nervous system plays an important role in the genesis of ventricular arrhythmias and sudden cardiac death. Evidence is substantial for a neural component in sudden cardiac death. Sympathetic nerve sprouting and regional myocardial hyperinnervation following myocardial injury promote cardiac arrhythmia and sudden cardiac death through several potential mechanisms. Modulating autonomic tone is a potential method to reduce the risk of ventricular arrhythmias. Thoracic spinal cord stimulation is showing promise as a treatment for refractory angina. In addition, spinal cord stimulation has protected against ventricular tachycardia/ventricular fibrillation in animal models of postinfarction heart failure.     

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

Ventricular arrhythmias (VA) can range in presentation from asymptomatic to cardiac arrest and sudden cardiac death (SCD). Sustained ventricular tachycardias/ventricular fibrillation (VT/VF) are a common cause of SCD in the setting of myocardial infarction (MI) and heart failure. A particularly arrhythmogenic cardiac syncytia in these conditions can be attributed to both sympathetic activation and parasympathetic dysfunction, while appropriate neuromodulation has the potential to reduce occurrence of VT/VF. In this review, we outline the components of the autonomic nervous system that play an important role in normal cardiac electrophysiology and function. In addition, we discuss changes that occur in the setting of cardiac disease including adverse neural remodeling and neurohormonal activation which significantly contribute to propensity for VT/VF. Finally, we review neuromodulation strategies to mitigate VT/VF which predominantly rely on increasing parasympathetic drive and blockade of sympathetic neurotransmission.     

Advances in Molecular Imaging: Innervation Imaging

Cardiac autonomic nervous system plays a major role in maintaining hemodynamic and electrophysiological stability to changing demands. There is increasing evidence showing that imaging cardiac autonomic nervous system can evaluate patients with different cardiac conditions, including ischemic heart disease, arrhythmias and heart failure (HF), with high prognostic value, thus providing a potential tool for improving patient management. Excellent reviews on cardiac autonomic imaging with SPECT and PET tracers have been recently published. This review is aimed to bring the reader up-to-date on the subject with particular emphasis on the major findings of recent years.     

Pathophysiologic cardiovascular changes in stress and depression

Fear, anger, and grief may precipitate myocardial ischemia and infarction. The prognosis of patients with inducible ischemia during mental stress is worse than in those without inducible ischemia. The sympathetic nervous system plays an important role in stress-associated changes in cardiovascular regulation and contributes to cardiovascular morbidity and mortality by inducing vasoconstriction and tachycardia, as well as arrhythmia. Hostility--previously termed type A personality--is often associated with sympathetic hyperreactivity to mental stress and carries an increased risk for atherosclerotic vascular disease. As endothelial dysfunction is an early manifestation of atherosclerosis, the impact of mental stress on endothelial function is also important. Acute mental stress induces prolonged endothelial dysfunction in healthy volunteers, which is prevented by selective endothelin A receptor antagonism. This represents an important link between mental stress and atherosclerotic vascular disease. In addition, patients with depression show hypercortisolemia, and changes in platelet function leading to a prothrombotic state. These findings help to explain the increased cardiovascular risk in patients with depression.     

Atrial fibrillation associated with autonomic dysreflexia

Autonomic dysreflexia is an acute disorder of autonomic homeostasis occurring in persons with spinal cord lesions above the major splanchnic sympathetic outflow. Atrial fibrillation is a serious cardiac arrhythmia characterized by disorganized atrial depolarization and an irregular ventricular response. Previously reported complications of autonomic dysreflexia have included seizures, strokes and cardiac arrhythmias other than atrial fibrillation. We present a 60-yr-old man with C-5 incomplete quadriplegia in whom atrial fibrillation was apparently induced by an episode of autonomic dysreflexia. Mechanisms by which autonomic dysreflexia may cause this arrhythmia include altered cardiac autonomic tone as well as atrial distention. The simultaneous occurrence of autonomic dysreflexia and atrial fibrillation poses special diagnostic problems and treatment risks. Atrial fibrillation incidence increases with age in the general population. With the aging of the spinal cord-injured population, we expect to see more episodes of atrial fibrillation associated with autonomic dysreflexia.     

Modulation of the Q-T Interval by the Autonomic Nervous System

Recent investigations have clarified some of the effects of the autonomic nervous system on duration and spatial distribution of the Q-T interval in humans. The use of atrial pacing to fix heart rate or 24-hour continuous electrocardiographic recording to develop a regression formula for individual patients has provided a means to interpret the effects of an intervention that alters both the heart rate and the Q-T interval. Drugs that affect Ihe autonomic nervous system can influence Q-T interval directly or by changing rate. Bazett's formula to correct for rate may be misleading after certain drug interventions. For example, the Q-T interval during sinus rhythm or afrial pacing and the ventricular effective refractory period shorten after atropine plus propranolol, but corrected Q-T interval using Bazetf's formula does not change. No change occurs in the Q-T interval during sinus rhythm or atrial pacing, or in ventricular effective refractory period after administration of propranolol although corrected Q-T interval using Bazett's formula markedly shortens. Q-T interval during sinus rhythm and atrial pacing and ventricular effective refractory period decrease after atropine but correct Q-T interval lengthens. To define further the relationship of the autonomic nervous system on the duration of the Q-T interval we studied the effects of sleep. Fifteen patients receiving no drugs underwent 3–6 days of continuous electrocardiography recordings. The duration of the Q-T interval was longer during sleep in all 15 patients independent of heart rate change. This prolongation of the Q-T interval during sleep may reflect increased parasympathetic tone or decreased sympathetic tone on the ventricle. Further investigation of the relation of the autonomic nervous system to ventricular depolarization and repolarization may delineate some of Ihe trigger mechanisms for the development of lethal ventricular arrhythmias in humans.     

Cardiovascular Manifestations Seen in Obstructive Sleep Apnea

Patients with obstructive sleep apnea (OSA) have an increased prevalence of systemic and pulmonary hypertension, left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunction, and congestive heart failure, increased platelet aggregability, and increased susceptibility to thrombotic and embolic cardiac and cerebrovascular events. Patients with OSA have an increased prevalence of coronary artery disease, myocardial infarction, nocturnal angina, and myocardial ischemia, arrhythmias, and sudden cardiac death. Patients with OSA also have an increased prevalence of stroke. Treatment of OSA with continuous positive airway pressure improves cardiac efficiency in patients with heart failure, causes a reduction in the frequency of nocturnal ischemic ST-segment depression, relieves nocturnal angina, and causes a reduction in the occurrence of new cardiovascular events and an increase in the time to such events.     

Takotsubo or stress cardiomyopathy: role of nuclear cardiology using 123I-MIBG

Takotsubo cardiomyopathy, also known as broken heart syndrome or stress cardiomyopathy, is a very interesting syndrome of acute transient left ventricular dysfunction, usually following significant emotional stress. It was first described in Japan nearly two decades ago and many aspects of its pathogenesis still remain poorly understood. The incidence of out-of-hospital sudden death related to Takotsubo is currently unknown. Excess catecholamines following stress seem to trigger Takotsubo and play an important role. The clinical presentation resembles acute myocardial infarction, including chest tightness and/or dyspnea, ECG changes and elevated cardiac enzymes. However, in contrast to a typical acute myocardial infarction, no significant coronary lesions or thrombi are found on coronary angiography. Differentiating Takotsubo from acute myocardial infarction is important to avoid the unnecessary risks of thrombolytic therapy. Typically, left ventriculography shows marked abnormalities with akinesia in the mid-distal anterior wall and apex (occasionally involving other heart regions), giving a balloon shape to the left ventricle. The name Takotsubo originates from the shape of the left ventricle, which resembles a Japanese octopus-trapping pot. Hospital mortality is low but death can be caused by severe acute heart failure and/or ventricular arrhythmias. Typically, a stressful life event is reported preceding the acute symptoms. Takotsubo is most common in menopausal women although young individuals, including men, can also be affected. The autonomic nervous system has a defined role in the process. In this article, we will review the role of imaging the heart using ¹²³I-meta-iodobenzylguanidine, a radioactive marker allowing mapping of the autonomic nervous system of the heart, in cases of suspected Takotsubo.     

Autonomic mechanisms and sudden death after abrupt coronary occlusion

In spite of recent advances in secondary prevention, sudden cardiac death has remained a major public health problem as the majority of fatalities occur in subjects without a history of severe heart disease. Abrupt rupture of a vulnerable plaque resulting in thrombotic occlusion of a coronary artery is a common cause of sudden death in this population. Coronary occlusion does not, however, invariably lead to sudden death but may cause acute myocardial infarction or exacerbation of chest pain. Extensive studies in experimental animals and increasing clinical evidence indicate that autonomic nervous activity has a significant role in modifying the clinical outcome. Sympathetic hyperactivity favours the genesis of life-threatening ventricular tachyarrhythmias while vagal activation exerts an antifibrillatory effect. Strong afferent stimuli from the ischaemic myocardium impair arterial baroreflex and may lead to dangerous haemodynamic instability. Studies with a human angioplasty model have shown that there is wide interindividual variation in the type and severity of autonomic reactions during the early phase of abrupt coronary occlusion, a critical period for out-of-hospital cardiac arrest. The site of the occlusion is not a significant determinant of the reactions, whereas the severity of a coronary stenosis, adaptation or ischaemic preconditioning, beta-blockade and gender seem to affect the autonomic reactions and occurrence of complex ventricular arrhythmias. Clinical and angiographic factors are, however, poor predictors of autonomic reactions in an individual patient. Recent studies have documented a hereditary component for autonomic function, and genetic factors may also modify the clinical manifestations of acute coronary occlusion.     

Autonomic mechanisms and sudden death after abrupt coronary occlusion.

In spite of recent advances in secondary prevention, sudden cardiac death has remained a major public health problem as the majority of fatalities occur in subjects without a history of severe heart disease. Abrupt rupture of a vulnerable plaque resulting in thrombotic occlusion of a coronary artery is a common cause of sudden death in this population. Coronary occlusion does not, however, invariably lead to sudden death but may cause acute myocardial infarction or exacerbation of chest pain. Extensive studies in experimental animals and increasing clinical evidence indicate that autonomic nervous activity has a significant role in modifying the clinical outcome. Sympathetic hyperactivity favours the genesis of life-threatening ventricular tachyarrhythmias while vagal activation exerts an antifibrillatory effect. Strong afferent stimuli from the ischaemic myocardium impair arterial baroreflex and may lead to dangerous haemodynamic instability. Studies with a human angioplasty model have shown that there is wide interindividual variation in the type and severity of autonomic reactions during the early phase of abrupt coronary occlusion, a critical period for out-of-hospital cardiac arrest. The site of the occlusion is not a significant determinant of the reactions, whereas the severity of a coronary stenosis, adaptation or ischaemic preconditioning, beta-blockade and gender seem to affect the autonomic reactions and occurrence of complex ventricular arrhythmias. Clinical and angiographic factors are, however, poor predictors of autonomic reactions in an individual patient. Recent studies have documented a hereditary component for autonomic function, and genetic factors may also modify the clinical manifestations of acute coronary occlusion.     

Changes in hemodynamics and autonomic nervous activity in patients undergoing laparoscopic cholecystectomy: differences between the pneumoperitoneum and abdominal wall-lifting method

BACKGROUND AND STUDY AIMS: Intraoperative changes in circulatory hemodynamics and autonomic nervous activity were evaluated in 33 patients with cholelithiasis who underwent laparoscopic cholecystectomy. PATIENTS AND METHODS: Of these patients, 18 were treated using a pneumoperitoneum (group G) and 15 using the abdominal wall-lifting method (group WL). Their ECG, blood pressure, arterial oxygen saturation, and expiratory carbon dioxide partial pressure were monitored. Autonomic nervous function was evaluated by spectral analysis of the heart rate. RESULTS: Mean blood pressure increased significantly in group G during surgery, but did not vary in group WL during any stage of surgery. The high-frequency (HF) power, an index of parasympathetic activity, decreased significantly in group G after pneumoperitoneum. However, the HF power did not decrease significantly in group WL. The LF/HF ratio, an index of sympathetic activity, increased significantly in group G after pneumoperitoneum, but did not vary in group WL. In addition, the incidence of ventricular or supraventricular arrhythmias and the severity of the arrhythmias as determined by Lown's classification were higher in group G than in group WL. These findings suggest that intraoperative changes in autonomic nervous activity, due to increased intra-abdominal pressure, were smaller in patients undergoing laparoscopic cholecystectomy using the abdominal wall-lifting method than in those undergoing laparoscopic cholecystectomy using pneumoperitoneum. The results also demonstrated that hemodynamic changes were smaller in patients undergoing the abdominal wall-lifting method than in those undergoing pneumoperitoneum. CONCLUSIONS: It was concluded that hemodynamics should be carefully monitored during pneumoperitoneum, and that the abdominal wall-lifting approach in laparoscopic cholecystectomy is a method worthy of consideration for elderly patients or those with cardiopulmonary complications.     

Autonomic nervous system examinations

Autonomic nervous system plays a critical role in the regulation of cardiovascular system. We reviewed the autonomic nervous system examinations. Time and frequency domain analyses in heart rate variability is obtained from short- and long-term ECG and have predictive values of prognosis in various conditions of heart disease. Baroreflex testing evaluates autonomic modulation of arterial pressure. Baroreflex sensitivity is expressed by the(arterial blood pressure)/(RR interval in ECG) slope in response to infusion of nitroglycerine or phenylephrine. Decrease in baroreflex sensitivity is superior to heart rate variability in identifying patients with poor prognosis in post myocardial infarction. 123I-metaiodobenzylguanidine (MIBG) is an analogue of norepinephrine and hence cardiac 123I-MIBG imaging can visualize cardiac sympathetic nervous system. Defect area in the early phase(15 to 30 min after injection) indicates localization of ventricular denervation. MIBG uptake, measured as a heart to mediastinum activity ratio, had a high predictive vale for survival. Altered MIBG uptake may also play a significant role in the assessment of arrhythmogenic potential in patients with idiopathic ventricular fibrillation or congenital long QT syndrome.     

The epidemiology of out-of-hospital 'sudden' cardiac arrest

It is difficult to assemble data from an out-of-hospital cardiac arrest since there is often lack of objective information. The true incidence of sudden cardiac death out-of-hospital is not known since far from all of these patients are attended by emergency medical services. The incidence of out-of-hospital cardiac arrest increases with age and is more common among men. Among patients who die, the probability of having a fatal event outside hospital decreases with age; i. e. younger patients tend to more often die unexpectedly and outside hospital. Among the different initial arrhythmias, ventricular fibrillation is the most common among patients with cardiac aetiology. The true distribution of initial arrhythmias is not known since several minutes most often elapse between collapse and rhythm assessment. Most patients with out-of-hospital cardiac arrest have a cardiac aetiology. Out-of-hospital cardiac arrests most frequently occur in the patient's home, but the prognosis is shown to be better when they occur in a public place. Witnessed arrest, ventricular fibrillation as initial arrhythmia and cardiopulmonary resuscitation are important predictors for immediate survival. In the long-term perspective, cardiac arrest in connection with acute myocardial infarction, high left ventricular ejection fraction, moderate age, absence of other heart failure signs and no history of myocardial infarction promotes better prognosis. Still there is much to learn about time trends, the influence of patient characteristics, comorbidity and hospital treatment among patients with prehospital cardiac arrest.     

坦度螺酮对伴焦虑抑郁冠心病支架置入术后患者心脏自主神经的影响

目的探讨新型抗焦虑抑郁药物坦度螺酮对伴有焦虑抑郁的冠心病支架置入术后患者心率变异性（HRV）及QT离散度（QTd）的影响。方法对2011年5月-2013年5月冠心病支架置人术后伴焦虑抑郁患者86例给予坦度螺酮治疗6周,观察抗焦虑抑郁治疗前后HRV及QTd的变化情况。结果坦度螺酮治疗6周后HRV各参数明显升高（P〈0．05）,QTd明显缩小（P〈0．01）。结论新型抗焦虑抑郁药物坦度螺酮能显著改善伴焦虑抑郁冠心病支架置入术后患者心脏自主神经功能。且该药的安全性较好,不良反应发生率低。     

Autonomic Effects of Dipyridamole Stress Testing on Frequency Distribution of RR and QT Interval Variability

Transient myocardial ischemia and associated changes in the autonomic nervous system may influence heart rate and ventricular repolarization to variable degrees. This study evaluated the effect of dipyridamole (DIP) induced ischemia on the autonomic balance by spectral analysis of RR and QT intervals variability. Patients with coronary artery disease undergoing DIP stress echocardiography were studied. From high resolution ECG recordings, RR and QT interval measurements were performed by a dynamic template-matching algorithm. A time-variant analysis was used to estimate power in the LF (0.05–0,15 Hz) and in the HF (0.15–0.4 Hz) band of RR and QT interval spectra. Patients were grouped in ischemic and nonischemic subgroups based on the echocardiographic detection of wall-motion abnormalities. In patients without ischemia (n = 28), DIP caused a decrease in LF power and an increase in HF power of the RR and QT interval variability, indicating concordant changes of both intervals. In contrast, patients with inducible ischemia (n = 11) showed a decrease in HF power of the RR interval spectra and an increase of HF power of QT interval spectra. Furthermore, LF power was increased for RR but decreased for QT interval spectra. Our study suggests that DIP induced ischemia causes a loss of autonomic coupling between heart rate and ventricular repolarization for sympathetic and parasympathetic activities. This lability in ventricular repolarization may constitute an arrhythmogenic substrate during acute ischemia in patients with coronary artery disease.     

Cardiac arrhythmias--update 1987

Arrhythmias may result from abnormalities of impulse initiation (automaticity), conduction (slow conduction, block, reentry), or a combination. The central and peripheral nervous systems have an important influence on the genesis of cardiac arrhythmias. Sympathetic and parasympathetic fibers innervate both atria and ventricle. The study of clinical cardiac arrhythmias includes the use of invasive and noninvasive testing procedures. The ECG, ambulatory monitoring, esophageal recording, exercise testing, and signal averaging techniques are the currently used noninvasive tests. Intracardiac electrophysiologic studies and endocardial catheter mapping are invasive techniques. The treatment of cardiac arrhythmias includes the use of antiarrhythmic drugs, cardiac pacing (antibradycardia, antitachycardia), implantable automatic defibrillator, cardiac fulguration, and antitachycardiac surgery. Clinical cardiac arrhythmias are of two types, the bradyarrhythmias and the tachyarrhythmias. The tachyarrhythmia, in turn, may be supraventricular or ventricular. There are clinical syndromes specifically related to arrhythmias: preexcitation syndromes are associated with supraventricular tachyarrhythmias, long Q-T syndromes with ventricular tachyarrhythmias, and sick sinus syndrome with bradyarrhythmias. The "tachycardia-bradycardia syndrome" is a combination of atrial tachyarrhythmias and sinus node dysfunction (some of the patients may also have ventricular tachyarrhythmias). Specific arrhythmias are recognized by their ECG characteristics. These arrhythmias also have specific electrophysiologic features which can be defined during invasive electrophysiologic studies. Cardiac arrhythmias may or may not be accompanied by underlying organic heart disease. Their treatment is related to the specific diagnosis and mechanism of the rhythm disturbance. The presence and extent of underlying organic heart disease is an important factor in the selection of antiarrhythmic therapy (drug, pacemaker, or surgery).     

Psychological factors in cardiac arrhythmias

Autonomic nervous control of the heart and the blood vessels is essential for optimal physical performance. Afferent nerves conduct impulses to the vasomotor and cardioaccelerator and cardioinhibitor centres resulting in efferent sympathetic and vagus output. Information inputs also from the environment and the person's thought processes are mediated from the cortex by the hypothalamus, the limbic system, and the autonomic nervous system to the heart and blood vessels. Emotional factors like anger, anxiety, and fear increase sympathetic output and influence heart rate. On the other hand, fear and the feeling of being in a helpless situation causes intensive vagal activation with ensuing severe bradycardia or asystole and vasovagal syncope. Although psychologic factors can cause extreme grades of tachy- or bradycardia they usually have no acute deleterious effects in the normal heart. In the diseased heart, however, consequences may be hazardous. Emotional factors are known to increase ventricular arrhythmias either directly or indirectly by increasing heart rate and causing ischaemia as in coronary heart disease. In animal experiments ventricular fibrillation threshold is lowered by aversive conditions. In heart diseases with sudden death as a well known complication increased sympathetic activity may give rise to fatal arrhythmias. In man the evidence of psychologic factors as the cause of life-threatening arrhythmias and sudden death is mostly anecdotal or circumstantial. Well designed studies are needed to evaluate the role of psychologic factors in arrhythmias.     

Type of arrhythmia at EMS arrival on scene in out-of-hospital cardiac arrest in relation to interval from collapse and whether a bystander initiated CPR

Outcome after cardiac arrest is strongly related to whether the patient has ventricular fibrillation at the time the emergency medical service (EMS) arrives on the scene. The occurrence of various arrhythmias at the time of EMS arrival among patients with out-of-hospital cardiac arrest was studied in relation to the interval from collapse and whether cardiopulmonary resuscitation (CPR) was initiated by a bystander. The patients studied were all those with out-of-hospital cardiac arrest in Göteborg, Sweden, between 1980 and 1992 in whom CPR was attempted by the arriving EMS and for whom the interval between collapse and the arrival of EMS was known. In all, information on the time of collapse and arrival of EMS was available for 1,737 patients. Among patients for whom EMS arrived within 4 minutes of collapse, 53% were found in ventricular fibrillation/tachycardia. There was a successive decline in the occurrence of such arrhythmias with time. However, when the interval exceeded 20 minutes, ventricular fibrillation/tachycardia was still observed in 27% of cases. Bystander CPR increased the occurrence of such arrhythmias regardless of the interval between collapse and EMS arrival.