The brain makes the heart sick - or vice versa?

The heart and brain are closely linked in terms of health. This block of topics bridged neurological, cardiological, and psychological aspects in selected cardiac and cerebral diseases.

Sudden cardiac death (SCD) is among the most common causes of death in patients with epilepsy, accounting for about one-fifth of all mortality, reported Prof. Hanno Tan, MD, of the University of Amsterdam Heart Center. The risk of SCD is about three times higher among patients with epilepsy than in the general population, according to data from the Dutch ARREST registry [1]. The so-called SUDEP cases – Sudden Unexplained Death in Epilepsy – probably only contribute to a small extent to this. The definition SUDEP actually requires a negative autopsy and excludes concomitant cardiac disease, Tan pointed out. However, in our experience, many SUDEP cases do not result in a thorough clarification of the cause of death.

So what accounts for the increased risk of SCD in patients with epilepsy? As expected, the presence of clinically relevant cardiac disease and, in addition, mental impairment were identified as risk factors, Tan reported [2]. In addition, the use of certain antiepileptic drugs, particularly sodium channel inhibitors such as lamotrigine, may be associated with an increased risk of SCD [3]. Corresponding risk increases were found not only in epilepsy patients, but also in patients with neuropathic pain treated with such antiepileptic drugs. “Ion channel disorders and associated congenital arrhythmia syndromes such as prolonged QT syndrome or catecholaminergic ventricular tachycardia may also be important,” Tan said.

The cardiologist recommended closer collaboration between neurologists and cardiologists and more generous use of ECG studies to better prevent SCD in patients with epilepsy.

Takotsubo cardiomyopathy (TAK), or broken heart syndrome, is thought to be caused primarily by emotional triggers such as grief, anger/frustration, or personal conflict. But equally relevant are physical trigger factors such as acute shortness of breath or neurological diseases such as an epileptic seizure, reported Prof. Dr. Christian Templin of the University Heart Center Zurich. According to figures from the international TAK registry (www.takotsubo-registry.com), physical triggers were found in as many as 36% of those affected, emotional triggers in only 27%, and both in 8% [4]. Templin is one of the initiators of the registry, which in Switzerland includes heart centers in Lucerne and Basel as well as Zurich.

The triggering mechanisms of Takotsubo syndrome are not yet clearly understood. The syndrome is most likely triggered by microcirculatory dysfunction, Templin said. Increased stress hormone levels such as catecholamines and activation of the sympathetic nervous system are also important. In the context of TAK, life-threatening arrhythmias can occur, and theoretically, a heart attack could also be triggered, the cardiologist added. And, “Sudden cardiac death can also be the initial manifestation of the syndrome.”

Due to insufficient knowledge about the disease and failures in diagnosis, TAK is often misdiagnosed and the frequency underestimated, according to Templin. According to the estimation of the Swiss cardiologist and the experience at the Zurich Heart Center, about 2-3% of all patients with suspected acute coronary syndromes have Takotsubo syndrome. For women, the proportion is even higher at around 6%. The disease is still considered particularly typical in older women who have suffered a traumatic event, such as losing their partner. Overall, the prevalence of stress cardiomyopathy has increased significantly in recent years, Templin reported.

TAK was first described by Japanese physician Dr. Hikaru Sato in 1991. During coronary angiography, coronary spasm and left ventricular dysfunction were documented in the patient, but no relevant stenoses were found. A few days after the procedure, left ventricular function returned to normal, and the patient had also largely recovered.

For a long time, cardiologists believed that if patients survived the life-threatening acute event with a variety of potential mechanical complications, they had a good prognosis. However, this assessment seems to have been wrong. According to registry data, affected individuals also have a similar long-term poor prognosis as patients with acute coronary syndrome (ACS). Five-year mortality is 65%, Templin reported. However, the data have not yet been broken down by patients’ concomitant diseases, such as neurological diseases, which are of high prognostic importance. However, follow-up studies of 286 TAK patients by a German research group led by Dr. Ingo Eitel of the Heart Center Lübeck confirm the long-term increased mortality. As reported by the authors at the DGK meeting, one-year mortality was 10% and four-year mortality was 25% [5].

Takotsubo syndrome is often not a one-time event. Recurrence occurs in 5-10% of patients, and in about 2% within one year. Four types of TAK are distinguished according to the ejection fraction and angiographic image of the left ventricle, of which the apical type (apical “ballooning” of the left ventricle) is clearly the most common, accounting for more than 80% according to registry data. In second place are midventricular type (15%), followed by basal (2.2%) and focal type (1.5%).

As is well known, Takotsubo syndrome is not the only example of the importance of stress and other negative emotional factors as cardiovascular risk factors in their own right. In various studies, anger, annoyance and aggressiveness have already been correlated with an increased risk of cardiovascular complications and sudden cardiac death [6,7], recalled psychosomatics expert Prof. Dr.Karl-Heinz Ladwig of Helmholtz Zentrum München-Neuherberg. However, not all people are equally at risk. Ladwig: “Those who are better able to handle stress are less likely to suffer sudden cardiac death.”

“Stroke and sudden cardiac death have many overlapping risk factors, such as hypertension, hypercholesterolemia, smoking, obesity, or lack of exercise – so some coincidence of the two events is to be expected,” said Prof. Marc Fatar, M.D., a neurologist at Mannheim University Hospital.

However, in absolute terms, cardiac and neurologic acute complications rarely occur simultaneously. According to figures from the Austrian stroke unit registry on more than 44,000 patients over a six-year period, 1% of patients with ischemic stroke and 0.3% with hemorrhagic stroke were also diagnosed with myocardial infarction in the first three days [8]. Predictors, according to Fatar, were advanced age, severe neurologic deficits, and cardiovascular risk factors and a positive history of infarction. Sudden cardiac death after stroke has been little studied and, based on available data, could affect%-3% all stroke patients, Fatar reported. The association could possibly also be explained causally by unfavorable influence on heart rate and Qt time after cerebral damage, thus promoting arrhythmias.

Source: 83rd Annual Meeting of the German Society of Cardiology in April 2017, D-Mannheim: Symposium “Heart and Brain”, April 21, 2017.

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