Biomarkers in Cardiology Research

1. Biomarkers in Cardiology Research Shock to the Heart! Electric Current and Cardiac Injury Martin Möckel, M.D., PhD and Julia Searle, M.D. Charité – Universitätsmedizin Berlin Department of Cardiology and Emergency Medicine Unit Berlin, Germany 30th Annual Emergencies in Medicine Conference, March 4 - 8, 2012, Hyatt Escala Lodge, Park City, UT

2. Biomarkers in Cardiology Research Disclosures None 30th Annual Emergencies in Medicine Conference, March 4 - 8, 2012, Hyatt Escala Lodge, Park City, UT

3. Biomarkers in Cardiology Research Electrical injuries • Germany: • ~ 4000 severe electrical injuries/year, 50-60 lethal • Majority are domestic accidents, • mainly due to human failure • ~80 % low voltage (3% lethal), • ~ 20 % high voltage (30% lethal) • Men > women • 20% in children under the age of 7 years • In the U.S.: • > 500 deaths per year, ~50% workplace accidents (4th leading cause of work-related traumatic death • >200 deaths at home /year – mainly malfunction of devices and misuse • >2000 cases of burns in children requiring treatment

4. Biomarkers in Cardiology Research Scientific evidence: Case Reports 3 Case Reports Jensen, P. J., et al. "Electrical injury causing ventricular arrhythmias." Br.Heart J. 57.3 (1987): 279-83. Severe, ongoing ventricular arrhythmia after electrical injury but in all patients onset of arrhythmia with a delay of 8-12 hours after the accident • 43-year old electrician, 3000V current from one hand to the other 12 hours after the incident: Patient collapses playing football Further episodes after 6 days and 6 months

5. Biomarkers in Cardiology Research Scientific evidence: Case Reports • 43-year old woman with electrical injury (380V), electrical current from hand to hand, 8 hours after the incident, the patient experiences dizziness and palpitations, from then on further daily attacks over the next two months. • 34-year old man, electrical current from left hand to right shoulder. After 12 hours chest pain and palpitations. From then on regular ventricular arrhythmias with declining frequency over 2 years.

6. Biomarkers in Cardiology Research Scientific evidence: Clinical trials • 48 patients after high voltage accidents (>1000V) • No serious cardiac arrhythmias in any patient with normal ECG on admission (during the first 24 hours after admission)

7. Biomarkers in Cardiology Research Scientific Evidence: Clinical trials • Arrowsmith et al. 1997 (Swansea, UK) • retrospective review of 145 patients with electrical injury within 5 years (88% low voltage accidents) • 72% with 12-lead ECG, of these 73% with 24-hour cardiac monitoring • 4 patients with arrhythmias: • in 3 patients occasional ectopic beats, settled within 24 hours • in 1 patient atrial fibrillation after high voltage accident, settled after digoxin medication • In all 4 patients ECG changes were present at admission • Initial unconsciousness and high voltage increased risk for arrhythmia Conclusion: In patients with a normal ECG at admission and no history of loss of conciousness, cardiac arrhythmias are not to be expected Arrowsmith, J., R. P. Usgaocar, and W. A. Dickson. "Electrical injury and the frequency of cardiac complications." Burns 23.7-8 (1997): 576-78.

8. Biomarkers in Cardiology Research Scientific Evidence: Clinical trials • Bailey et al. 2007 (Quebec, Canada) • 134 patients from 21 Emergency Departments over a 4-year period with previously identified theoretical risk factors of significant electrical injury • transthoracic current • tetany • loss of consciousness • voltage source > or =1000 V (n=13) • 11% (n=15) patients with abnormal initial ECGs No patient developed potentially lethal late arrhythmia during the 24 hours of cardiac monitoring Asymptomatic patients with transthoracic current/and or do not require cardiac monitoring, whilst patients with high voltage accidents and patients with initial consciousness (sign of arrhythmia) should be monitored Bailey, B., P. Gaudreault, and R. L. Thivierge. "Cardiac monitoring of high-risk patients after an electrical injury: a prospective multicentre study." Emerg.Med.J. 24.5 (2007): 348-52.

9. Biomarkers in Cardiology Research Scientific Evidence: Clinical trials Proposal by Blackwell et al. after 3 year prospective audit of 212 presentations to the ED with low voltage electrical injury Implementation of a new management protocol which led to a massive reduction of hospital admissions Blackwell N, Hayllar J. A three year prospective audit of 212 presentations to the emergency department after electrical injury with a management protocol. Postgrad Med J, 2002

10. Biomarkers in Cardiology Research Guidelines

11. Biomarkers in Cardiology Research Study Hypothesis • Patients after electrical injury • without significant concomitant injuries • without significant ECG changes • without concomitant injuries requiring hospital admission • will not develop further, specifically cardiac complications and are allowed to be discharged • from the Emergency Department

12. Biomarkers in Cardiology Research Study Design All patients of all ages with a main hospital diagnosis ICD-10- Code T 75.4 (Electrocution) admitted to the Charité University Hospital Berlin, Campus Virchow Klinikum between January 2001 and December 2008 Patient chart review: Type of current and severity of electrical injury Complications and concomitant injuries at admission Cardiac monitoring In-hospital complications In-hospital-Outcome 268 patients in an eight-year period

13. Biomarkers in Cardiology Research Patients with electrical injuries were young and of male gender Median age: 23 years (25th percentile 6 years/ 75th percentile 35 years) Minimum Age 10 months Maximum Age 92 years 71% 71% 29% 29%

14. Biomarkers in Cardiology Research 30% of our patients were children under the age of 7 years

15. Biomarkers in Cardiology Research Most electricals accidents occured in the domestic environment 63% 37%

16. Biomarkers in Cardiology Research Current sources • 81% human failure • 10% faulty electrical device

17. Biomarkers in Cardiology Research 50% of our patients made their own way to the ED 24 % 6 %

18. Biomarkers in Cardiology Research Severity of electrical injuries • 94.4% low voltage accidents, 3% high voltage (>500 V) • Entry of electrical current in 94% arm/hand, exit of current in 84% not available Burns: I° burns: 2% II° burns:7% III° burns: 0.7% (n=2) IV° burns: 0.4% (n=1)

19. Biomarkers in Cardiology Research Severity of electrical injuries • 3% (n=8) high voltage accidents (>500 V), n=6 of them work-related • 3 patients with burns (1 x I°, 2 x II°), 2 patients with electrical marks (entry and exit) • 2 patients initially unconscious • 3 patients with serious injuries (head trauma, keratitis photoelectrica, fractures of spine and rib + pneumothorax) • ECG at admission: • 2 patients with tachycardia, 1 patient with bradycardia • 2 patients with unspecified ST deviations • Laboratory at admission: • 3 patients with CK-elevation (1 patients + CK-MB elevation), after 6-12 hours 2 patients with CK-elevation, no CK-MB elevation

20. Biomarkers in Cardiology Research All patients were monitored overnight No patient experienced cardiac arrhythmias during the monitoring period except for one patient with a nocturnal sinus bradycardia

21. Biomarkers in Cardiology Research Findings on admission • 1% (n=2) of our patients had initially been unconscious • ECG at admission: • 1% (n=3) with singular supraventricular extrasystolies • 1% (n=3) with singular ventricular extrasystoles • 1% (n=3) with first degree AV-Block • Laboratory values at admission: • CK increase in 19 % of patients (tested in 78% of patients) • Myoglobin increase in 2 % (n=5) patients (tested in 78% of patients) • Troponin increase in 2 patients (tested in 78% of patients) • CK increase associated with concomitant injuries

22. Biomarkers in Cardiology Research In-hospital findings • Subsequent ECG (available in 61% of patients): • n=1 new incomplete right bundle branch block (RBBB) • n=1 new incomplete RBBB plus singular supraventricular extrasystoles • n=1 new incomplete RBBB plus singular supraventricular extrasystoles plus Couplets • Subsequent laboratory values: • CK increase in 7 % of patients (tested in 38% of patients) • Myoglobin increase in 1 patient (tested in 38% of patients) • Troponin increase in 1 patient (tested in 38% of patients)

23. Biomarkers in Cardiology Research Case Report I: A typical case with mild ECG abnormalities 25 year old, male electrician Electrical injury with a non-insulated power cable (4th electrical injury of his life) No loss of consciousness, no concomitant injuries, no electric mark No symptoms and complaints at presentation to the ED All laboratory values within normal range (including troponin and CK) ECG: unspecific ST-elevation in II, III, V2-V6, new incomplete right bundle branch block in follow-up ECG 6h after admission

24. Biomarkers in Cardiology Research Case Report I ECG at atmission (I,II,III, aVR, aVL, aVF)

25. Biomarkers in Cardiology Research Case Report I ECG at admission (V1-V6)

26. Biomarkers in Cardiology Research Case Report I ECG 6 hours after admission (I,II,III, aVR, aVL, aVF)

27. Biomarkers in Cardiology Research Case Report I ECG 6 hours after admission (V1-V6) New incomplete RBBB Outcome: The patient spent one night at an intensive care unit with continuous cardiac monitoring and was discharged without arrhythmias or complications.

28. Biomarkers in Cardiology Research Case Report VI: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU. Case Report II: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is found unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU. Case Report VI: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU.

29. Biomarkers in Cardiology Research Case Report II: A severe case Case Report VI: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU. ECG at admission Outcome: The patient initially develops multi-organ failure, but no cardiac complications or further arrhythmias. After 2 weeks he is discharged with a mild neurologic deficit.

30. Biomarkers in Cardiology Research Case Report III: An unusual case 15 year old, male patient is admitted to the Emergency Department and reports an “electrical injury” with consecutive syncope. He reports to have fallen against an electrical fence in an animal park and to subsequently having fainted. Extensive medical history with (amongst others) transposition of the great vessels (TGV), switch surgery and known ventricular arrhythmias with intermittent couplets Case Report VI: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU. Outcome: Hospital admission for observation and monitoring. Sinus bradycardia at night (45 bpm) but no ventricular arrhythmias. Multiple PVB and couplets in 24h ECG, probably not related to electrical injury.

31. Biomarkers in Cardiology Research 40 year old, male patient with a domestic electrical injury while repairing a washing machine, voltage unknown (220 or 380 V) No initial unconsciousness, no symptoms or complaints at presentation. Troponin at admission elevated to 0.21 µg/L and mild ST-elevations V2-V6 in the initial ECG. Case Report IV: Biomarker abnormalities

32. Biomarkers in Cardiology Research Case Report IV Outcome: ECG and troponin back to normal after 6 hours. No cardiac arrhythmias in 24h cardiac monitoring, patient is discharged on the next day. ECG at admission

33. Biomarkers in Cardiology Research 18 months old girl Managed to get hold of an electric cable from her cot and to rip the cable out of the wall, the girl is found crying with cable in hand. 3rd and 4th degree burns on right hand, electric marks on 3 fingers. No ECG/cardiac abnormalities at presentation. Case Report V: Burns IV° Outcome: Hospital admission, initially with 24h continuous monitoring. Later during hospital course debridement and skin transplantation. No cardiac arrhythmias throughout hospital stay

34. Biomarkers in Cardiology Research Conclusion: This is one of the few larger scale studies evaluating the occurrence of late arrhythmias after electrical injury. In our cohort, consisting of all 268 patients who were admitted to the Charité Berlin, CVK, Germany, with an electrical injury over an 8 year period, NO patient experienced major cardiac arrhythmias during the continuous monitoring.

35. Biomarkers in Cardiology Research Conclusion: Unless concomitant injuries or other diseases warrant hospital admission, it seems to be safe to discharge patients

36. 24-hour Monitoring after Electrical Injury– Sense or Nonsense? J. Searle, A. Slagman, W. Maass, M. Mockel Charité - Universitätsmedizin Berlin, Department of Cardiology CVK and Emergency Medicine CVK,CCM, Berlin, Germany Introduction: For fear of late arrhythmias, it has become current practice to admit patients after survived electrical injury to intensive care or observation units for continuous cardiac monitoring. Yet, evidence for the necessity of this costly measure has never been established. So far, reports on late cardiac arrhythmias after electrical injury originate from case reports (e.g. Jensen et al. 1987), whereas clinical studies never found a relationship between the two. Yet, all trials so far, investigated low patient numbers (Purdue et al. 1986, 48 pts.; Arrowsmith et al. 1997, 145 pts.; Bailey et al. 2007, 120 pts.). Hypothesis: Patients, who present to the Emergency Department after survived electrical injury without life-threatening arrhythmias or significant ECG-changes at presentation and without concomitant injuries or diseases or injuries will not develop electrical injury-related cardiac complications and therefore do not require hospital admission and continuous cardiac monitoring. Methods: A retrospective case note review was performed of all patients who were admitted to the Charité Campus Virchow Klinikum (CVK), a University hospital in Berlin, Germany after electrical injury. For this, the hospital information system was screened for patients with a main hospital diagnosis ICD-code T75.4 (electrical injury). Thus, 268 patients who were admitted to between 2001 and 2008 with electrical injury were identified. Results I: Patient characteristics A total of 268 patients with electrical injury were enrolled Median Age 23 years (25th %ile 6 years / 75th %ile 35 years), min. 1 year, max. 92 years. 30% of patients were children at an age < 7 years (figure 1). The majority of patients were male (figure 2) • Results III: Cardiac diagnostics at presentation • and during the hospital stay • Only two patients were initially unconscious • A total of 9 patients had an abnormal ECG at presentation • singular supraventricular extrasystoles (n=3) • singular ventricular extrasystoles (=3) • AV-block I° (n=3). • A follow-up ECG was performed in 61% of the patients, 3 patients showed abnormalities: • new incomplete right bundle branch block (n=1) • new RBBB and singular supraventricular ES (n=1) • new RBBB and singular ventricular ES (n=1) • CK was measured in 78% and was elevated in 19% of these patients. • Troponin was measured in 78% and was elevated in 2 of these patients. • Myoglobin was measured in 78% and elevated in 5 patients. Results IV: 94% of the accidents occured with low voltage. Severe injuries were rare in our cohort as is represented by the mode of arrival (figure 5) and the skin alterations caused by the electric current (figure 6); 2% of patients had I° burns, 7% had 2° burns, and only 2 and 1 patients had III° and IV° burns respectively. Results II: Causes for electrical injuries Most electrical accident occur in the domestic environment rather than being work-related (Figure 1). This is reflected by the distribution of causes as shown in figure 2. Figure 1: Age distribution Figure 2: Gender distribution Figure 5: Mode of arrival at the hospital Figure 3: cause of electrical injuries Figure 4: Distribution of specific causes Figure 6: Skin alterations caued by electric´current Results V: Outcome All 268 patients were admitted to an intensive care or observation unit and had 24 hours continuous cardiac monitoring. The only abnormality was a sinus bradycardia of 45bpm during the first night of hospitalization. Case Report I: A typical case with mild ECG abnormalities 25 year old, male electrician Electrical injury with a non-insulated power cable(4th electrical injury of his life) No loss of consciousness, no concomitant injuries, no electric mark No symptoms and complaints at presentation to the ED All laboratory values within normal range (including troponin and CK) ECG: unspecific ST-elevation in II, III, V2-V6, new incomplete right bundle branch block in follow-up ECG 6h after admission Case Report II: An unusual case 15 year old, male patient is admitted to the Emergency Department and reports an “electrical injury” with consecutive syncope. He says he fell against an electrical fence in an animal park and subsequently fainted. Extensive medical history with (amongst others) transposition of the great vessels (TGV), switch surgery, known ventricular arrhythmias with couplets Case Report IV: Biomarker abnormalities 40 year old, male patient with a domestic electrical injury while repairing a washing machine, voltage unknown (220 or 380 V) No initial unconsciousness, no symptoms or complaints at presentation. Troponin at admission elevated to 0.21 µg/L and mild ST-elevations V2-V6 in the initial ECG. Case Report VI: A severe case 33 year old, male patient Domestic electrical injury while repairing a toaster which was purchased on a flee market. Patient is unconscious, at arrival of emergency physician at his home very low ventricular fibrillation, almost asystole. Electric mark on index finger and thumb, right hand. After successful resuscitation, the patient is transferred to the ICU. Outcome: Hospital admission for observation and monitoring. Sinus bradycardia at night (45 bpm) but no ventricular arrhythmias. Multiple VES and couplets in 24h ECG, probably not related to electrical injury. Case Report III: Burns IV° 18 months old girl Managed to get hold of an electric cable from her cot and to rip the cable out of the wall, the girl is found crying with cable in hand. 3rd and 4th degree burns on right hand, electric marks on 3 fingers. No ECG/cardiac abnormalities at presentation. Index ECG ,case report IV Index ECG ,case report I Follow-up ECG, case report I Index ECG , case report VI Index ECG, case report VI Outcome: Hospital admission, initially with 24h continuous monitoring Debridement and skin transplantation. No cardiac arrhythmias throughout hospital stay Outcome: ECG and troponin are back to normal after 6 hours. No cardiac arrhythmias in 24h cardiac monitoring, patient is discharged on the next day. Outcome: The patient initially develops multi-organ failure, but no cardiac complications or further arrhythmias. After 2 weeks he is discharged with a mild neurologic deficit. Outcome: The patient spends one night at an intensive care unit with continuous cardiac monitoring and is discharged without arrhythmias or complications. Conclusion: This is the first larger scale study evaluating the occurrence of late arrhythmias after electrical injury. In our cohort, consisting of all 268 patients who were admitted to the Charité Berlin, CVK, Germany, with an electrical injury over an 8 year period, NO patient experienced major cardiac arrhythmias during the continuous monitoring. Unless concomitant injuries or other diseases warrant hospital admission, it seems to be safe to discharge patients after initial assessment. ESC Congress, Paris, August 2011, Postersession 7, 31/08/2011, Poster Zone C

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