Sudden death: Brain, heart or interactive?

What is the pathogenesis of sudden death? Is sudden death in most cases due to cardiac disease? Or is the brain and it's central autonomic nervous system the culprit? Or even both the brain and the heart?

Transcript

1. Sudden death: Brain, heart or interactive? Peter Sörös Department of Clinical Neurological Sciences University of Western Ontario psoros@uwo.ca
2. Sudden death Sudden death after stroke Epidemiology Pathophysiology Risk stratification
3. Contemporary Reviews in Cardiovascular Medicine Sudden Cardiac Arrest Without Overt Heart Disease Simon Modi, MBBS; Andrew D. Krahn, MD The topic of sudden unexplained cardiac arrest without overt heart disease is a highly emotive and important subject with a rapidly advancing knowledge base. The correct identification of those conditions predisposing to cardiac arrest is paramount, and is part of the role of every practicing cardiologist. This review article is designed to give the practicing cardiologist an up-to-date insight into a subspecial- ized field of cardiac electrophysiology and cardiac genetics. It seeks to help to formulate diagnoses with advanced electro- physiological testing and genetic profiling and also with a reminder of basic clinical presentations and pathophysiolog- ical features of the conditions in question. This article seeks to encapsulate the field in general and at the same time to provide a select amount of useful detail, both contemporary and historical, and to provide references from a resource of excellent reviews in the literature. We hope that the reader will develop confidence in identifying rare causes of cardiac arrest and an insight into the sort of patients that should be referred to subspecialist clinics. Structural or coronary heart disease is by far the most common cause of sudden cardiac arrest.1 Once overt heart disease has been excluded in the cardiac arrest survivor, the differential diagnosis includes manifest or latent primary electrical disease and latent structural causes (Tables 1 and 2). These conditions predispose the patient to recurrent ventric- ular arrhythmia and cardiac arrest without overt heart disease. The overriding immediate concern in these patients is recur- standard testing early in their course, requiring a high index of suspicion to discern. Survivors of cardiac arrest without overt heart disease typi- cally come under the care of an electrophysiologist because of the need for implantation of an implantable cardioverter- defibrillator (ICD). Care is ideally delivered by a team of individuals with expertise in genetics, electrophysiology, and cardiomyopathies, with input from imaging experts as well. This team deals with survivors of cardiac arrest, their family members when an inherited cause is identified, and the less fortunate families when sudden death occurs without overt heart disease and families are sent for screening.3–6 This is often referred to as cascade family screening.4,7 It should be recognized, however, that even when each of the known causes of cardiac arrest without overt heart disease has been systematically excluded with in-depth testing, nearly half of the causes of cardiac arrest in these patients will remain unexplained.2 Investigation of the Sudden Cardiac Arrest Survivor Survivors of cardiac arrest require a comprehensive clinical review with an in-depth sequential testing strategy (Figure 1). This includes a detailed presenting history with witness statements as well as comprehensive family and drug histo- ries. Family history should inquire not only about sudden death, but also about events such as drowning, fatal single- Circulation. 2011;123:2994-3008
4. Definition “Sudden cardiac death (SCD) is defined as natural death from cardiac causes, heralded by abrupt loss of consciousness within 1 hour of the onset of an acute change in cardiovascular status. Preexisting heart disease may or may not have been known to be present, but the time and mode of death are unexpected.” Braunwald's heart disease: a textbook of cardiovascular medicine. Saunders/Elsevier 2008
5. Causes of sudden death 1 5 10 15 20 25 Panel: Primary causes of sudden, unexpected cardiac and non-cardiac death Sudden cardiac death with cardiac arrest Ǧ ”—”“†—ž†—™Š—ž‰Ž˜Š†˜Š Ǧ ž”ˆ†—‰Ž†‘Ž“‹†—ˆ™Ž”“ Ǧ ”—”“†—ž˜•†˜’ Ǧ †—‰Ž”’ž”•†™ŽŠ˜ Ǧ ˜ˆ†Š’Žˆˆ†—‰Ž”’ž”•†™ž Ǧ ž•Š—™—”•Žˆˆ†—‰Ž”’ž”•†™ž Ǧ ——ž™’”ŒŠ“Žˆ—ŽŒ™›Š“™—Žˆš‘†—ˆ†—‰Ž”’ž”•†™ž Ǧ †”™˜š‡”ǩ˜™—Š˜˜Ǫˆ†—‰Ž”’ž”•†™ž Ǧ “Š—Ž™Š‰†——ž™’”ŒŠ“Žˆ‰Ž˜”—‰Š—˜ Ǧ ”“Œǂ†“‰˜”—™ǂ˜ž“‰—”’Š˜ Ǧ —šŒ†‰†˜ž“‰—”’Š Ǧ †™Šˆ”‘†’Ž“Š—ŒŽˆ•”‘ž’”—•Žˆ›Š“™—Žˆš‘†— tachycardia Ǧ š‘’”“†—žŠ’‡”‘Ž˜’ Ǧ Š™†‡”‘ŽˆŽ’‡†‘†“ˆŠ Ǧ ž•Š—†‘†Š’Ž†”—ž•”†‘†Š’Ž† Ǧ ž•”’†Œ“Š˜†Š’Ž† Ǧ “™”Žˆ†™Ž”“ Sudden non-cardiac death Ǧ š•™š—Š‰†”—™Žˆ†“Šš—ž˜’ Ǧ Š˜•Ž—†™”—ž‹†Ž‘š—Š†‹™Š—†˜•Ž—†™Ž”“ Ǧ •Ž‘Š•™Žˆ˜ŠŽŸš—Š Ǧ “™—†ˆ—†“Ž†‘†Š’”——†ŒŠ
6. Heart and autonomic nervous system measured in approximately 4 to 6 weeks after discharge from the hospital to document recovery of cardiac function. Inhospital mortality from ABS is very low and unlikely to be N1% to 2%. Overall, the long-term survival is similar to that of the general age-matched population.35 The subgroup of patients in whom there is a physical trigger such as major surgery or illness appear to have a worse prognosis, most likely related to the underlying condition. The recurrence rate of ABS is no N10%.35 conjunction with a rise in catecholamines.61 Moreover, wall motion abnormalities and depressed ejection frac- tion have been observed in diseases associated with high catecholamines such as a pheochromocytoma62,63 and subarachnoid hemorrhage.64 Wittstein et al25 have reported very high levels of catecholamines in ABS at the time of presentation, which remained elevated for 7 to 9 days. Endomyocardial biopsies in a subset of their patients demonstrated contraction band necrosis, a Figure 5 Proposed pathophysiology of ABS. Prasad, Lerman, and Rihal 413 American Heart Journal Volume 155, Number 3 Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): A mimic of acute myocardial infarction Abhiram Prasad, MD, FRCP, FESC, FACC, Amir Lerman, MD, FESC, FACC, and Charanjit S. Rihal, MD, FACC, Rochester, MN Apical ballooning syndrome (ABS) is a unique reversible cardiomyopathy that is frequently precipitated by a stressful event and has a clinical presentation that is indistinguishable from a myocardial infarction. We review the best evidence regarding the pathophysiology, clinical features, investigation, and management of ABS. The incidence of ABS is estimated to be 1% to 2% of patients presenting with an acute myocardial infarction. The pathophysiology remains unknown, but catecholamine mediated myocardial stunning is the most favored explanation. Chest pain and dyspnea are the typical presenting symptoms. Transient ST elevation may be present on the electrocardiogram, and a small rise in cardiac troponin T is invariable. Typically, there is hypokinesis or akinesis of the mid and apical segments of the left ventricle with sparing of the basal systolic function without obstructive coronary lesions. Supportive treatment leads to spontaneous rapid recovery in nearly all patients. The prognosis is excellent, and a recurrence occurs in b10% of patients. Apical ballooning syndrome should be included in the differential diagnosis of patients with an apparent acute coronary syndrome with left ventricular regional wall motion abnormality and absence of obstructive coronary artery disease, especially in the setting of a stressful trigger. (Am Heart J 2008;155:408-17.) An association between emotional or physical stressful triggers and adverse cardiovascular events such as death and myocardial infarction has been recognized for many years.1,2 At a population level, earthquakes, wars, and major sporting events have all been linked to a surge in cardiovascular mortality.3-6 Among hospitalized patients, noncardiac surgery is one of the most frequent trigger for cardiovascular events, with the highest risk in those undergoing vascular surgery due to coexisting severe coronary artery disease.7 Myocardial dysfunction may occur in critically ill patients with sepsis due to a pathogen-induced proinflammatory immune response,8 and a reversible cardiomyopathy in critically ill patients has also been reported in the absence of sepsis.9 Similarly, neurologists have recognized an association between subarachnoid hemorrhage and a reversible cardiomyo- pathy that has been termed neurogenic stunning, characterized by acute brain injury and the absence of coronary artery disease.10,11 Recently, there has been an increasing awareness of a unique cardiac syndrome that has been described as the apical ballooning syndrome (ABS), Tako-Tsubo cardio- myopathy, and stress or ampulla cardiomyopathy.12-21 It has also been referred to as the Broken Heart Syndrome in the popular press. The syndrome overlaps with the aforementioned conditions in that it is a reversible cardiomyopathy that is frequently precipitated by a stressful event and has a clinical presentation that is indistinguishable from a myocardial infarction. This distinct cardiac syndrome was originally described in 1990 in the Japanese population and was called “Tako- Tsubo cardiomyopathy,” named after the octopus trap- ping pot with a round bottom and narrow neck, which resembles the left ventriculogram during systole in these patients.12 Sporadic case reports followed22 until the last 5 years or so during which several cases series have been reported from around the world, including Europe,18,23 North America,14,16,24-26 and Australia.27 In 2006, the American Heart Association incorporated ABS into its classification of cardiomyopathies as a primary acquired cardiomyopathy.28 Apical ballooning syndrome is underrecognized and often misdiagnosed. It is an important differential diagnosis of an acute myocardial infarction. We review the best evidence regarding the pathophysiology, clinical features, investigation, and management of ABS. Incidence The precise incidence of ABS is unknown due to its novel nature, varied presentation, and evolving From the The Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN. Submitted September 26, 2007; accepted November 2, 2007. Reprint requests: Abhiram Prasad, MD, FRCP, FESC, FACC, Cardiac Catheterization Laboratory, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: prasad.abhiram@mayo.edu 0002-8703/$ - see front matter © 2008, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2007.11.008 Prasad et al. Am Heart J 2008, 155:408-417
7. Northridge earthquake Southern California Earthquake Center www.scec.org lined in the six days after the earthquake (zϭ3.15, Pϭ0.002). l tests were the De- uring the ough 16, ( January in 1991, f the igated by nuary 10 ds. There s, from a ys before hs on the n the day us years, ed by the Fifty per- elated to ease. Not ent cause Disease c cardio- rthquake and 109 during the week of the earthquake. However, analysis of the number of deaths each day that were de- termined to be related to atherosclerotic cardiovascular disease (Fig. 2) revealed a sharp increase, from an av- erage of 15.6Ϯ3.9 deaths per day during the seven days before the earthquake to 51 on the day of the earth- quake (relative risk as compared with the same period in previous years, 2.6; 95 percent confidence interval, Figure 3. Daily Numbers of Sudden Deaths Related to Athero- 0 30 20 10 23 20 17 14 11 January 1994 No. of Deaths sclerotic Cardiovascular Disease from January 10 through 23, 1994. On January 17, the day of the earthquake, there were 24 cases of sudden death related to atherosclerotic cardiovascular dis- ease (zϭ4.41, PϽ0.001). There was a decline in number of sud- den deaths on each of the six days after the earthquake (zϭ1.73, Pϭ0.084). The New England Journal of Medicine ERN ONTARIO on January 12, 2012. For personal use only. No other uses without permission. 996 Massachusetts Medical Society. All rights reserved. Increase in the number of sudden cardiac deaths. 4.6 ± 2.1 (mean ± SD) per day in the preceding week 24 on the day of the earthquake (z = 4.41, P < 0.001). 2.7 ± 1.2 per day in the following week Leor et al. N Engl J Med 1996;334:413-419
8. Sudden death after stroke
9. Epidemiology Silver FL, Norris JW, Lewis AJ, Hachinski VC. Stroke 1984;15:492-496 494 STROKE TABLE 2 Comparison between Mechanisms ofDeath during the First Week and the 2nd to 4th Week in 180 Patients with Supraten- torial Lesions TABLE 3 Funct of Non-cerebral Cause of death Transtentorial herniation Pneumonia Cardiac Pulmonary embolism Sudden death Septicemia Unknown Brain stem extension (of hematoma) Totals Infarction First week 36 0 7 0 2 1 0 46 2-4th week 6 28 17 4 8 4 12 79 Hemorrhage First week 42 1 0 0 0 0 1 1 45 week 2 2 2 0 0 0 3 1 10 Grade I II III IV Totals In Only one pa to death (tabl hemorrhage a day 22. set, 32 were stuporous or comatose, and twenty-two of these patients survived less than 72 hours. In the first week TTH accounted for 42 of the deaths (see table 2) (37 occurring within the first 72 hours). Of six TTH deaths between the fourth and the ninth days, three were clinically attributed to rebleeding and three to edema. Marked edema was seen pathological- ly in two, but none of the autopsies revealed separate hemorrhages of different ages. Two patients with tha- lamic hemorrhages died because of direct extension of blood into the brainstem. One occurred on the twelfth day and autopsy disclosed only fresh hemorrhage, sug- gesting that a second recent hemorrhage must have obliterated the original hematoma. Intraventricular hemorrhage was present in 26 of 36 patients. Infratentorial I This group infarction. Al brainstem les cerebellar infa tion includin hemispheres. Of the 13 de secondary to cerebellar infa were cardiac a the whole 30 d deaths, with s to 21 days. Only two grade I or II infarct and die and dysphagia
10. Pathophysiology Sudden cardiac death after stroke
11. Ventricular fibrillation • 62 patients with ischemic MCA infarct > 30 mm • exclusion criteria: cardiac disorders, arrhythmias at admission, diabetes, medication affecting the autonomic nervous system • Heart monitor during the first 3 days of hospitalization • Ventricular fibrillation in 3 patients Tokgözoglu et al. Stroke 1999;30:1307-1311
12. Asystole scan, and underwent decompressive craniectomy at 36 h. No further asystolic events occurred during the 14 days in the stroke unit. At 3 months, she had recovered partially from her left hemisyndrome and was able to transfer herself, but not to walk without assistance (modified Rankin scale 4). Cardiac arrhythmias are quite common in acute stroke, but asystolia has only rarely been documented.1 Although the Cushing reflex due to intracranial hypertension may result in J Neurol Neurosurg Psychiatry 2008;79:618. doi:10.1136/jnnp.2007.127357 REFERENCES 1. Belvis R, Marti-Vilalta JL. Asystolias in the acute phase of brain stroke. Report of a case. Neurologia 2003;18:170–4. 2. Oppenheimer S. Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance. Clin Auton Res 2006;16:6–11. 3. Wintermark M, Flanders AE, Velthuis B, et al. Perfusion-CT assessment of infarct core and penumbra. Stroke 2006;37:979–85. Figure 1 (A) Acute perfusion CT before asystolia: red, middle cerebral artery infarct; green, penumbra; line, right insular anatomical topography. Note the extensive involvement of the right insula.3 (B) Plain CT after the first episode of asystolia, showing no mass effect. (C) Acute phase ECG showing the third of five episodes of asystolia, lasting about 10 s (paper velocity 25 mm/s). Rey et al. J Neurol Neurosurg Psychiatry 2008;79:618
13. Autonomic nervous system 293 Autonomic Nervous System 3 4 5 2 9 8 10 11 12 13 14 6 15 7 1 Sympathetic and Parasympathetic Nervous Systems A Sympathetic and parasympathetic nervous systems (adapted from Villiger and Ludwig) Eyes Lacrimal glands, salivary glands Blood vessels of the head Heart Lungs Stomach Liver Pancreas Kidneys Intestine Rectum Urinary bladder Genitals Kahle, Color Atlas of Human Anatomy, Vol. 3 © 2003 Thieme All rights reserved. Usage subject to terms and conditions of license. 295 Autonomic Nervous System 8 1 4 6 11 10 5 15 2 9 7 12 13 14 3 Sympathetic and Parasympathetic Nervous Systems A Autonomic nervous system (according to Hirschfeld and Léveillé) Kahle, Color Atlas of Human Anatomy, Vol. 3 © 2003 Thieme All rights reserved. Usage subject to terms and conditions of license. Kahle, Frotscher. Color Atlas of Human Anatomy, Vol. 3. Thieme 2003
14. Cerebral autonomic nervous system Insula Cingulate gyrus Hypothalamus Amygdala Sörös, Hachinski. Lancet Neurol 2012;11:179-188
15. Insular infarct • 150 consecutive patients with non- lacunar MCA infarct • insular involvement in 72 patients (48%) • no isolated insular lesion had major insula infarction, 5 had minor, and 7 had no insula infarction. CORRELATION OF MRI AND CT Eleven patients underwent both MRI and CT within 6 hours. Mean time to first image was 2.8 hours from stroke onset (MRI first in 4); mean time between studies was 2.5 hours. All 6 patients with the CT insular ribbon sign had major insula infarction on DWI. All 5 patients with negative CT scan results had either no or minor insula infarction on DWI. CARDIOVASCULAR EFFECTS OF INSULA INFARCTION Four patients received antihypertensive treatment within the first 48 hours of stroke onset in addition to any usual long-term antihypertensive medications; none had in- sula infarction (P=.15). Minor electrocardiographic changes, predominantly nonspecific ST/T-wave abnor- malities, were present in 29 patients with insula infarc- tion and 23 patients with no insula infarction (P=.16) but were more common with left hemisphere infarction (34 vs 18; P=.01). There was no difference in QTc interval be- tween patients with or without insula infarction of either Figure 1. Isolated insula infarction. Diffusion-weighted image at the level of the insula from a single patient. Table. Insula Involvement vs No Insula Involvement Variable Insula (n = 72) No Insula (n = 78) P Value Lenticulostriate involvement, No. (%) 33 (46) 11 (14) Ͻ.001 More than one third of MCA territory infarction, No. (%) 25 (35) 2 (3) Ͻ.001 Median NIHSS score 13.5 6 Ͻ.001 TOAST mechanism, No. of patients .08 Cardiac source 40 29 Large artery* 24 36 Unknown or other 8 13 Abbreviations: MCA, middle cerebral artery; NIHSS, National Institutes of Health Stroke Scale; TOAST, Trial of Org 10172 in Acute Stroke Treatment.16 *␹2 = 5.11. Figure 2. Composite image at the level of the insula that demonstrates the topography of middle cerebral artery infarctions with major insula involvement. Degree of shading is proportional to frequency of involvement of 5 x 5-mm brain regions. Fink et al. Arch Neurol 2005;62:1081-1085
16. Insula 239 Telencephalon 2 4 5 3 1 6 10 8 9 7 Insula A Insula with the opercula moved apart (according to Retzius) B Cortical areas of the insula (according to Brockhaus) C Mesocortex D Stimulation map of the human insular cortex (according to Penfield and Faulk) Kahle, Color Atlas of Human Anatomy, Vol. 3 © 2003 Thieme All rights reserved. Usage subject to terms and conditions of license. Kahle, Frotscher. Color Atlas of Human Anatomy, Vol. 3. Thieme 2003 Johann Christian Reil. Archiv für die Physiologie 1809, 9:195-208. Caspar David Friedrich. Der Wanderer über dem Nebelmeer, 1818. Kunsthalle Hamburg. “a triangular-shaped prominent cluster of isolated convolutions, the island of Reil” Henry Gray. Anatomy. 1858, p. 459 “The Insula (island of Reil; central lobe) lies deeply in the lateral or Sylvian fissure ... circular sulcus ... triangular eminence” Henry Gray. Anatomy of the human body. 1918
17. Electric stimulation of the insula • electric stimulation of the posterior insula at tachycardia sites in rats • stimulation 100 ms prior to the T wave • widening of the QRS complex • bradycardia • asystolic arrest P~im 2h 3 4h '" "f? 6h 8h A 1 Prestim 8h30 5h30 8h35 3 7h 8h45 7h10 8h55 ,, ,,,-------- 7h15 8h55 11 *t' r 7 h 30 B Fig. 1. A: serial EC(;s obtained during stimulation of the sensorimotor cortex in a control animal. This shows the absence of chan characteristics over an 8 h period, typical of control animals. The stimulus artifact present in all but the prestimulation trace (labelle is identified by the 3 arrows in tracing A5. B: serial ECGs obtained during insular stimulation in an experimental animal. The stim was at the border of the granular insular and somatosensory cortices. These traces illustrate the characteristic pattern of ECG change in all but one of the experimental animals in both the ventilated and unventilated groups. The stimulus artifact is identifiable in prestimulation trace. distribution of the sites from which arrhythm .~ ~:: elicitable is shown in Fig. 2. The average initial norepinephrine and epi Oppenheimer, Wilson, Guiraudon, Cechetto. Brain Res 1991;550:115-121
18. Sudden unexpected death in epilepsy • the most frequent cause of death directly related to epilepsy • suggested pathomechanism includes autonomic imbalance and cardiac arrhythmias R   
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19. Regulation of blood pressure D.F. Cechetto, J.K. Shoemaker / NeuroImage 47 (2009) 795–803 Cechetto, Shoemaker. Neuroimage 2009;47:795-803
20. Risk stratification
21. Predictors of early cardiac morbidity and mortality • 846 patients with ischemic stroke • 12 weeks follow-up • 35 (4%) died from cardiac causes • 161 (19 %) suffered at least one serious cardiac adverse event (including nonfatal episodes of ventricular tachycardia, ventricular flutter, myocardial infarct) Prosser et al. Stroke 2007;38:2295-2302
22. Predictors of early cardiac morbidity and mortality • congestive heart failure • renal failure • diabetes • severe stroke • long QTc or ventricular extrasystoles Prosser et al. Stroke 2007;38:2295-2302
23. Insular lesion • 502 patients with ischemic infarct • 123 patients with insular infarct ity at 2 years. Except for the association between QTc interval and vascular mortality, we found similar results when analysis was performed on the maximum follow- up. Discussion In this study, a wide variety of arrhythmias (AF, SVEBs, and VEBs) and abnormal repolarization were significantly associated with BI. Occurrences of these ECG abnormalities are not easy to explain and have coronary events and free of previous cardiovascular his- tory, the results remained significant. Although some patients without past coronary events may have asymp- tomatic coronary artery disease,18 this suggests that ab- normal repolarization may be, in part, neurogenic in nature. These results should be considered with caution because we analyzed and pooled all types of ST-interval abnormalities and did not adjust on serum potassium, which can modify ST interval. Serum potassium was not available in the database. We also found a 13% Fig 4. Two-year overall (left) and vascular (right) survival curves of brain infarction (BI) cases according to right-sided insular involvement. Black lines indicate noninsular and left-sided insular involvement; gray lines indicate right-sided insular involvement. Abboud et al. Ann Neurol 2006;59:691-699
24. Heart rate variability • 84 patients with ischemic infarct • 24-hour EKG • time domain: R-R variability • frequency domain: power in different frequency bands • abnormal long-term heart rate dynamics (ultra low vs. low frequency) predict mortality Discussion. The main new finding in the present study was that abnormal HR dynamics had prognos- tic power in predicting poststroke mortality. The prognostic significance of abnormal power-law slope ␤ was independent of all other well-recognized risk variables such as age, prior myocardial infarction, and SSS score. Conventional measures of HR variability have been reported to be suppressed in both ischemic and hemorrhagic stroke patients.12-15 The association of these HR variability measures with clinical mea- sures of function in ischemic stroke patients has been recognized.22 Spectral analysis of HR variability has been used as a diagnostic tool in brain death patients and is suggested to provide information not only about the clinical status of critically ill patients but also about their prognosis.23,24 Impaired HR dy- namics is a well-established prognostic indicator of adverse outcome in patients with various cardiovas- cular diseases. To our knowledge, however, this is the first study to report the association of abnormal HR dynamics with survival of stroke patients. Our findings expand the applicability of HR variability measures to the risk stratification of stroke patients. The cardiac autonomic nervous system dysfunc- tion in stroke patients has previously been investi- gated mainly by conventional time and frequency domain measures of HR variability.12-15 These mea- LF, ms 607 Ϯ 670 606 Ϯ 760 VLF, ms 1,300 Ϯ 1,080 1,018 Ϯ 2,149 ULF, ms 13,519 Ϯ 15,426 13,157 Ϯ 14,306 ␤ slope Ϫ1.31 Ϯ 0.16 Ϫ1.44 Ϯ 0.30* ␣ 1.20 Ϯ 0.18 1.06 Ϯ 0.24† Values are means Ϯ SD. * p Ͻ 0.05, † p Ͻ 0.01. GCS ϭ Glasgow Coma Scale score; SSS ϭ Scandinavian Stroke Scale score; CK-MB ϭ myocardium specific creatine kinase; SDNN ϭ standard deviation of R-R intervals; HF ϭ high fre- quency power of HR variability; LF ϭ low frequency power of HR variability; VLF ϭ very low frequency power of HR variability; ULF ϭ ultra low frequency power of HR variability; ␤ slope ϭ power-law slope; ␣ ϭ short-term scaling exponent ␣ of detrended fluctuation analysis. ␣ Ͻ 0.75 2.9 (0.9–10.5) * Hazard ratio assessed by Cox regression analysis. † p Ͻ 0.05, ‡ p Ͻ 0.01, § p Ͻ0.001. SSS ϭ Scandinavian Stroke Scale score; AMI acute myocardial infarction; ␤ slope ϭ power-law slope; ␣ ϭ short-term scaling ex- ponent ␣ of detrended fluctuation analysis; SDNN ϭ standard deviation of R-R intervals. Figure. Kaplan-Meier survival curve for the subjects with the power-law slope ␤ less than Ϫ1.50 or over Ϫ1.50. Esti- mated cumulative survival rate over 7-year period was 67% in those with a slope over Ϫ1.50 and 20% in those with a slope less than Ϫ1.50. 1824 NEUROLOGY 62 May (2 of 2) 2004 Mäkikallio et al. Neurology 2004;62:1822-1826
25. Conclusions 1 5 10 15 20 Review h can be the -cardiac condi- of the aorta, or al arrhythmia sease, such as hy, is the most occurs about men, probably oronary artery th in patients ed by primary mbalance such or drugs with es of sudden osis have been h is caused by mon sequence ycardia, which during hospitalisation. In three patients, sudden death (Right) Insular lesion Parasympathomimetic drugs Parasympathetic overactivity Bradyarrhythmia Tachyarrhythmia Myocardial injury Sympathetic overactivity (Left) Insular lesion Old age Emotional stress Sympathomimetic drugs Asystole Circulatory collapse Pre-existing heart disease Diabetes Renal failure General susceptibility Electrolyte derangement Proarrhytmic medication Ventricular fibrillation Figure : Pathophysiology of sudden death after stroke Relative overactivity of the parasympathetic or sympathetic nervous system can result in circulatory collapse and š‘™Ž’†™Š‘ž˜š‰‰Š“‰Š†™ǩœŽ™Š‡”Š˜Ǫǀ †ˆ™”—˜ˆ”“™—Ž‡š™Ž“Œ™”™Š‰Š›Š‘”•’Š“™”‹†š™”“”’ŽˆŽ’‡†‘†“ˆŠ†“‰ ˆ†—‰Ž†ˆ‰ž˜‹š“ˆ™Ž”“†—Š˜š’’†—Ž˜Š‰Ž“Œ—ŠŠ“‡”Š˜ǀ Sörös, Hachinski. Lancet Neurol 2012;11:179-188
26. Future directions
27. “London Autonomic Scanner” Paula Modersohn-Becker. Otto Modersohn, schlafend, 1906. Paula Modersohn-Becker-Stiftung Bremen EOG EEG EKG
28. What’s inside the box? 1. How do we analyze the data? •Heart rate variability: Which information is most useful? 2. Which additional data needs to be included? •Stroke location: Which lesions are most dangerous? •Clinical data: preexisting heart disease, renal disease, diabetes? •Data at admission: QTc, troponin? •Genetic variants
29. Thank you! Münster