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Three Part Question

In [an adult patient whose ICD has discharged] is [a rise in troponin] suggestive of [an ischaemic cardiac event precipitating ICD discharge or defibrillation induced myocyte damage]?

Clinical Scenario

A 50-year-old man presents to the emergency department having been woken from sleep by his implanted cardioverter-defibrillator (ICD) firing; it has fired twice more since that time. He is in sinus rhythm and has no acute signs or symptoms. A recent angiogram showed no significant coronary artery disease (CAD). You speak to the Cardiology Registrar who advises that troponin levels should be checked. You wonder if there is any evidence for this and, further, how you might interpret the result.

Search Strategy

Ovid MEDLINE(R) 1946 to November Week 3 2013: ((defibrillators.af. AND implantable.af.) OR exp Defibrillators, Implantable/ OR implantable defibrillator$.af.) AND troponin.af. OR exp Troponin/ Results limited to English language and studies in humans.

The Cochrane Library Issue 12 of 12 December 2013: MeSH descriptor: [Troponin] explode all trees AND ICD:ti,ab,kw (Word variations have been searched) OR MeSH descriptor: [Pacemaker, Artificial] explode all trees

Google Scholar December 2013: >8000 search results.

Search Outcome

Ovid search retrieved 38 papers of which 11 were relevant. PubMed clinical queries: No additional papers identified. Cochrane search retrieved three papers, none of which were relevant. Two additional papers of note identified from first 100 best matches in Google Scholar. No paper directly answered the question posed. The relevant papers are summarised in the following table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Davoodi et al. 2013 Iran	133 patients undergoing ICD insertion and 130 patients undergoing PPM insertion	Prospective cohort study (2b)	Cardiac biomarkers	Troponin rise from myocardial injury is likely due to DFT rather than device insertion	Inconsistencies between cohorts
Toh et al. 2012 Japan	50 patients undergoing elective ICD insertion and DFT (half LVEF >45%, half LVEF < 45%)	Prospective study (2b)	Cardiac biomarkers	No troponin rise above upper limit of normal in either LVEF < 45% or LVEF > 45% group up to 4 hours	1) Small study 2) Short period of follow up (only 4 hours)
Francis et al. 2012 USA	31 patients undergoing first time elective ICD insertion and DFT	Prospective study (2b)	Cardiac biomarkers	Relationship between Troponin I & BNP rise post ICD DFT therefore discharge causes subtle injury and left ventricular dysfunction (p<0.0001)	1) No control group 2) Only followed for maximum of 12 hours 3) No allied assessment of ventricular function i.e. echocardiography 4) Presumably low sensitivity Troponin I assay (1.5ng/ml upper limit normal)? 5) Small study
			Cardiac biomarkers	One patient had Troponin rise above the study’s upper limit of normal
Bhavnani et al. 2010 USA	1372 patients undergoing ICD implantation and DFT with or without subsequent shocks	Retrospective Study (2b)	Hospitalisation for ADHF	Appropriate shock causes increased risk of admission for ADHF (LVEF <35% - AHR 1.66 p<0.002, LVEF > 35% - AHR 4.11 p=0.002).	Only first shock included in study – no note if patient had additional shocks
			Death	Appropriate shock causes increased risk of death (AHR 2.09, P<0.001)
			Death and hospitalisation for ADHF	Inappropriate shocks did not increase risk of death or hospitalisation from ADHF
Blendea et al. 2009 USA	174 patients who received either spontaneous (66) or induced ICD discharges (108)	Prospective study (2b)	Death	Troponin T rise after ICD discharge is an independent risk factor for mortality (p<0.001)	1) Study uses Troponin T not I 2) Single late Troponin level (12-24 hours post discharge)
Alaiti et al. 2009 USA	Review including 34 studies and 1608 patients	Review	Various	1) 2.9% of patients had Troponin I levels above the normal limit post internal cardioversion 2) 32% of patients had Troponin I levels above the normal limit post DFT	Inter-study inconsistencies
Daubert et al. 2008 USA	719 patients who had ICD implanted	Prospective study (2b)	Death	Inappropriate and appropriate shock causes increased risk of death (AHR 4.08, P<0.01)	Number of shocks not recorded
			Death	Inappropriate shock alone causes increased risk of death (AHR 2.29, P=0.02)
			Death	Appropriate shock only causes increased risk of death (AHR 3.36, P<0.01)
Hasdemir et al. 2002 USA	35 patients admitted post spontaneous ICD discharge	Retrospective Study (2b)	Cardiac biomarkers	Troponin rise in 43% of patients without ACS	1) Small study 2) No mention if all patients were admitted 3) Possibly late sampling missing some Troponin rises
			Cardiac biomarkers	22% of Patients with known CAD had proven ACS
			Cardiac biomarkers	Acute ECG changes present in 25% of patients with clinically interpretable ECGs
			Cardiac biomarkers	14% of all patients had ACS
			Cardiac biomarkers	Troponin rise related to number of shocks and delivered energy (p<0.05)
Poole et al. 2008 USA	128 patients with heart failure receiving spontaneous ICD discharges	RCT (1b)	Death	Increased risk of death if had discharge of any cause (appropriate/inappropriate) (p=≤0.002)	Minor device related data loss
Schlüter et al. 2001 Germany	14 patients undergoing elective ICD insertion and DFT	Prospective study (2b)	Cardiac biomarkers	Majority Troponin I peaks at 4 hours	Very small study
			Cardiac biomarkers	21% of patients had Troponin I rise above clinical cut off level with ≥ 2 shocks
Rao et al. 1999 USA	6 patients undergoing ICD insertion and DFT	Prospective study (2b)	Cardiac biomarkers	No Troponin I rise	Very small study
Hurst et al. 1999 Germany	49 patients undergoing elective ICD insertion and DFT	Prospective study (2b)	Cardiac biomarkers	14% of patients had Troponin I levels above clinical cut off level	Small study
			Cardiac biomarkers	Troponin I rise related to number of shocks (p=0.04)
Joglar et al. 1999 USA	12 patients undergoing elective ICD insertion and DFT	Prospective cohort study (2b)	Cardiac biomarkers	50% of patients had Troponin I levels above clinical cut off level and all peaked within 12 hours	Very small study

Comment(s)

The majority of papers deal with defibrillator threshold testing (DFT) rather than spontaneous discharge, and use a variety of troponin assays. From the above research it can be seen that myocyte damage from an ICD discharge alone can raise troponin levels, and the more shocks, the higher the rise. There is no proven difference in level of troponin rise due to whether the discharge was appropriate, inappropriate or from DFT, but a positive troponin level is more common in spontaneous discharges. A small but significant proportion of patients whose ICD discharges on a background of CAD will have acute coronary syndrome (ACS). There is limited data in these studies to suggest that likely non-ACS related rises tend to peak earlier than those from ACS which confirms expert clinical experience that myocardial ischaemia causes a more prolonged troponin release compared to the discrete insult of an ICD discharge for arrhythmia. Interrogation of any recently discharged ICD should be requested on all patients. Whether to employ a troponin level test depends on the patient's history of CAD and the clinical evaluation of ACS. Any patient with a confirmed absence of CAD (all patients with ICD will have had imaging of their coronary arteries) and who presents without symptoms of ACS does not require troponin level evaluation. So in the clinical scenario, the patient could be considered for discharge once ICD interrogation has been arranged. Any patient symptomatic of ACS should be managed as per local ACS protocol with a troponin assay. Any patient with known CAD but without symptoms of ACS should be discussed promptly with an electrophysiologist or, if this is not possible, have a 6–12 h troponin assay (depending on local policy). If the troponin assay is negative, the patient can be considered for discharge once ICD interrogation has been arranged. If the troponin assay is positive, the patient should be managed as per local ACS protocol.

Editor Comment

ACS, acute coronary syndrome; ADHF, acute decompensated heart failure; AHR, adjusted HR; BNP, brain natriuretic peptide; CAD, coronary artery disease; DFT, defibrillator threshold testing; ICD, implanted cardioverter defibrillator; LVEF, left ventricular ejection fraction; RCT, randomised controlled trial.

Clinical Bottom Line

The number of implanted cardioverter defibrillator (ICD) discharges must be taken into account when evaluating any troponin level rise. Overall, a positive troponin assay post-ICD discharge is independently associated with an increased mortality.

References

1. Davoodi G, Mohammadi V, Shafiee A et al. Detection of myocardial injury due to defibrillation threshold checking after insertion of implantable cardioverter/defibrillators. Acta Cardiologica 2013;68:167–72.
2. Toh N, Nishii N, Nakamura K et al. Cardiac dysfunction and prolonged hemodynamic deterioration after implantable cardioverter-defibrillator shock in patients with systolic heart failure. Circ Arrhythm Electrophysiol. 2012;5:898–905.
3. Francis CK, Kuo YH, Azzam I et al. Brain natriuretic peptide and biomarkers of myocardial ischemia increase after defibrillation threshold testing. Pacing Clin Electrophysiol. 2012;35:314–19.
4. Bhavnani SP, Kluger J, Coleman CI et al. The prognostic impact of shocks for clinical and induced arrhythmias on morbidity and mortality among patients with implantable cardioverter-defibrillators. Heart Rhythm. 2010;7:755–60.
5. Blendea D, Blendea M, Banker J et al. Troponin T elevation after implanted defibrillator discharge predicts survival. Heart 2009;95:1153–8.
6. Alaiti MA, Maroo A, Edel TB Troponin levels after cardiac electrophysiology procedures: review of the literature. Pacing & Clinical Electrophysiology 2009;32:800–10.
7. Daubert JP, Zareba W, Cannom DS et al. Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact. J Am Coll Cardiol. 2008;51:1357–65.
8. Hasdemir C, Shah N, Rao AP et al. Analysis of troponin I levels after spontaneous implantable cardioverter defibrillator shocks. J Cardiovasc Electrophysiol. 2002;13:144–50.
9. Poole JE, Johnson GW, Hellkamp AS et al. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med. 2008;359:1009–17.
10. Schlüter T, Baum H, Plewan A et al. Effects of implantable cardioverter defibrillator implantation and shock application on biochemical markers of myocardial damage. Clin Chem. 2001;47:459–63.
11. Rao SP, Miller S, Rosenbaum R et al. Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablations, and defibrillator implantations. Am J Cardiol. 1999;84:470, A9.
12. Hurst TM, Hinrichs M, Breidenbach C et al. Detection of myocardial injury during transvenous implantation of automatic cardioverter-defibrillators. J Am Coll Cardiol. 1999;34:402–8.
13. Joglar JA, Kessler DJ, Welch PJ et al. Effects of repeated electrical defibrillations on cardiac troponin I levels. Am J Cardiol. 1999;83:270–2.