Printer Friendly

Effects of implantable cardioverter defibrillator implantation and shock application on biochemical markers of myocardial damage.

The Implantation of an implantable cardioverter defibrillator (ICD)[3] is a common approach in patients with ventricular tachycardia or who have survived cryptogenic sudden cardiac death (1). To check for normal ICD function, it is necessary to test the system and to determine the defibrillation threshold. The defibrillation threshold is defined as the lowest energy, in joules (J), for defibrillation of induced ventricular fibrillation (VF). However, repeated episodes of electrical therapy can have disadvantageous effects on myocardial performance (2, 3).

The cardiac isoforms of troponin T (cTnT) and troponin I (cTnI) are highly specific markers for the detection of myocardial damage. After myocardial ischemia but also as a result of other myocardial stress, such as myocarditis, cTnI and cTnT are released into the circulation (4, 5) where they can be detected with sensitive immunoassays (6, 7).

This study assesses the extent of myocardial injury after ICD implantation and testing by the release of the cardiospecific markers cTnT and cTnI in relation to other, not fully cardiospecific, markers of cardiac ischemia: creatine kinase (CK), CK-MB mass concentration, and myoglobin.

Materials and Methods


Between February and November 1998, 14 patients (12 men, 2 women; median age, 63.5 years; range, 44-78 years) with high risk of ventricular tachyarrhythmia and scheduled for implantation of an ICD were included in this study (Table 1). Revascularization steps (angioplasty and stenting, or bypass grafting) had been completed in all patients suffering from coronary artery disease (CAD) before starting the implantation procedure. One patient was rejected because of signs of myocardial ischemia. None of the other 13 patients had stable or unstable angina. Eight patients suffered from CAD, two from cardiomyopathy (CMP), and two from valvular heart disease (VHD). One patient had both CAD and CMP, and another had CMP and VHD. All patients gave their informed consent to participate in this study. Blood samples were collected at four time points: before and 1, 4, and 24 h after intraoperative shock application. The samples before and 1 h after testing were drawn from a radialis catheter (for invasive blood pressure measurements); the samples 4 and 24 h after testing were drawn from peripheral veins.

After clotting and centrifugation, the serum samples were stored at ~70[degrees]C until analysis


Implantation and ICD used. ICD systems from Guidant Corporation, Cardiac Pacemakers (Models 1749, 1782, 1783, and 1849) and from Medtronic, Inc. (Models 7250 and 7227) were used. Tined, steroid-eluting electrodes were used in 10 patients (Medtronic "Sprint" 6942/6932 and Cardiac Pacemakers Endotak Endurance: 145), and tined, non-steroid-eluting electrodes were used in 4 patients (Cardiac Pacemakers Endotak Endurance: 135). In five patients, additional steroid-eluting "screw-in" leads (Medtronic 6940) for atrial sensing were implanted.

Each patient received a 1-J test shock before every testing episode. VF was induced with a shock-on-T induction with 1.2 J. For determining the defibrillation threshold, the verification technique was used. Intermediate energies that successfully defibrillate the patient and provide an adequate energy margin are determined in the verification procedure. This technique is widely accepted because it does not require the subject to be tested with energies that do not defibrillate as the threshold method does (8). If the first shock was effective, the physician could repeat the testing with the same energy or stop further testing. In case of failure, the system automatically applied a second shock with maximum energy. Implantation criteria were met if induced VF could be terminated one time with a shock of ~10-15 J to maximum output or if two subsequently induced VF episodes could be defibrillated successfully with 10-15 J to maximum output.

In case of missing implantation criteria, repositioning of the ventricular lead was performed before retesting. In one patient (patient 5), the physician decided not to reposition the electrode although the second shock after the first repositioning (shock 4) was ineffective and VF had to be terminated with an effective 31-J shock. Instead of repositioning, the physician tested again and defibrillated successfully with 23 J. In another patient (patient 18), the electrode had to be repositioned twice, and the patient received two external 360-J shocks. Three patients received atrial shocks through a additional lead for terminating atrial fibrillation.

To guarantee myocardium recovery between the ischemic episodes produced by VF, care was taken not to induce VF within 5 min after the previous testing episode.

Analytical procedures. cTnT and CK-MB were measured with an electrochemiluminescence immunoassay on an Elecsys[R] 2010 analyzer (Roche Diagnostics). The cTnT assay uses two monoclonal antibodies specific for the cardiac isoform of TnT and has <0.01% cross-reactivity with skeletal muscle troponin T. The CV is 5.1% at the cutoff of 0.1 [micro]g/L for cTnT, and for CK-MB, the CV is 3.9% at 5.98 [micro]g/L; the cutoff is 5 [micro]g/L (9). cTnI was measured on a Dimension[R] [micro]L analyzer (Dade Behring) using the TROP Flex[TM] reagent cassette. This assay uses two monoclonal antibodies specific for two different epitopes on the cTnI molecule. The cross-reactivity with skeletal troponin I is <0.1%. The CV is 9.4% at 0.5 [micro]g/L, and the cutoff is 0.4 [micro]g/L. Myoglobin was measured on a BN 2 analyzer (Dade Behring) using a immunonephelometric assay (N-Latex Myoglobin). The CV is 4.8% at 85 [micro]g/L, and the cutoff is 70 [micro]g/L. Total CK activity was measured on a Vitros[R] 950 IRC (Ortho Clinical Diagnostics) at 25[degrees]C. The CV is 3% at 70 U/L, and the cutoff is 80 U/L for men and 70 U/L for women. All assays were performed according the recommendations of the manufacturers.

Statistics. Analyses were performed using a commercially distributed software package (Astute, Statistics Add-in for Microsoft Excel; DDU Software). To test for the differences in serum markers at baseline and after ICD implantation, the Wilcoxon matched-pairs signed-ranks test was used. Significance was estimated as P <0.05.


The P values for all markers and all patients are shown in Table 2, which compares the serum samples drawn at 1, 4, and 24 h with the serum samples drawn before implantation and testing. Four hours after ICD implantation and testing, all markers showed significant increases compared with the baseline values before testing. In contrast, for cTnT and myoglobin, this was at all three time points after ICD testing.

The individual markers and the biochemical findings of all patients are shown in Table 3. In nine patients, cTnT was detectable. cTnI was detectable in eight patients, all of whom also had detectable cTnT values. cTnI peak concentrations above the cutoff were seen in three patients, two of whom also exceeded the cTnT cutoff. In both patients, we also found CK-MB mass increases over the cutoff. All of the patients with cTnT/cTnI peak concentration above the cutoff received two ventricular shocks; two patients had additional atrial screw-in electrodes, and one of them received three additional atrial shocks with lower energy. No repositioning had to be performed in all of these patients. There was a weak correlation between troponin increase and cumulative energy in all of the patients who received two effective ventricular shocks (r = 0.647 for cTnI and r = 0.636 for cTnT).

CK-MB mass concentrations above the cutoff were seen in four patients. One of these patients received three atrial and seven ventricular shocks (cumulative energy, 194 J). Additionally, the physician applied two external 360-J shocks, and the electrode had to be repositioned twice.

The CK activity increased to >80 U/L in five patients. Patient 18 showed the largest increase (164 U/L); this patient received the largest cumulative energy (194 J) and two external 360-J shocks. In two of the five patients showing CK activity >80 U/L, additional atrial leads were implanted (patients 7 and 18). In all of these five patients, CK showed no peak within 24 h.

Myoglobin concentrations peaked at >70 [micro]g/L in nine patients. In three patients, additional atrial leads were implanted. The very high myoglobin peak concentration for patient 18 (291 [micro]g/L) correlated with the high CK in this patient.

No patient who received only one shock showed detectable cTnT or cTnI values. When we compared the number of shocks and the increases in cTnT and cTnI, only patients receiving two effective shocks showed concentrations above the cutoff. Median peak values postoperatively were 0.08 [micro]g/L (range, 0-2.16 [micro]g/L) for cTnI, 0.023 [micro]g/L (range, 0-0.26 [micro]g/L) for cTnT, and 2.5 [micro]g/L (range, 0-14.93 [micro]g/L) for CK-MB.


Animal experiments have suggested that repeated high-energy direct current shocks produce myocardial damage (3, 4). The way the energy is delivered to the heart is an important factor that influences the release of cardiac markers into circulation. Intracardial applied shocks with rather low energy are probably more damaging than transthoracic shocks with high energy (10). Increasing CK and CK-MB concentrations after transthoracic shocks have been described (11), but it has been found that most of the CK released after transthoracic cardioversion derives from chest wall skeletal muscles, because cardiospecific markers such as cTnT and cTnI show no or minimal increases after transthoracic shock (12-14).

We found increased serum concentrations of all markers, cTnT, cTnI, CK-MB, CK, and myoglobin, after ICD implantation. Patients who received only one shock showed no increases in cTnT, cTnI, and CK-MB mass above the cutoff values. All patients with cTnT and cTnI peak concentrations above the cutoff had received two ventricular shocks.

It is remarkable that patients who received more than two shocks, very high cumulative energy, and repositioning of the electrode (patients 5 and 18) had no (patient 5) or only marginal (patient 18) increases in cTnT and cTnI. Wrong positioning of the electrode leads to a higher number of ineffective shocks; these ineffective shocks therefore do not lead to a release of cTnT and cTnI from the myocardium. One patient received two additional external 360-J shocks. This patient showed only marginal increases in the specific markers cTnT, cTnI, and CK-MB mass, and large increases in the nonspecific markers CK and myoglobin. External shocks may lead only to a release from the thoracic skeletal muscles (11-14), which explains the large increases in CK activity and myoglobin in this patient.

Our results correlate well with those of Hurst et al. (15) and Runsio (10), who also found increased serum concentrations of cTnT and cTnI or cTnT and CK-MB after ICD implantation (Table 4). In contrast to these studies, we found a clearly visible lower postoperative peak value for cTnT, but also lower peak values for cTnI and CK-MB. This discrepancies are attributable to the lower cumulative energy used in our patients, but the assays used for determining the cardiac-specific markers, especially for cTnT, are also important influencing factors. For measuring cTnT, we used a highly specific second-generation assay (9) with negligible cross-reactivity with skeletal muscle troponin T (6). The cTnT assay used by Hurst et al. (15) and Runsio et al. (10) shows 2% cross-reactivity with skeletal muscle troponin T (16), leading to possible false-positive results.

Troponins T and I are structurally bound regulator proteins of the contractile apparatus of the skeletal muscle and myocardium. Only a small portion of both can be found as a soluble portion in the cytoplasm. For cTnT, this is ~6-8%; for cTnI, it is 2.5% (17). The release into the circulation is therefore characterized by two steps. In the first step, the cytoplasmic pool is released simultaneously with other cytoplasmic proteins, such as CK, CK-MB, and myoglobin. After loss of integrity of the contractile apparatus, cTnT and cTnI are released continuously until the infarcted area is healed. The first release can be measured in the blood -4 h after damage, whereas the second release will occur into the serum after 24 h (18). Additionally, the half-time of both cTnT and cTnI is ~2 h (10). As shown in the Results, cTnT, cTnI, and CK-MB show a peak value after 4 h. Therefore, we suggest that the release of cTnT and cTnI is only from the small amount located in the cytoplasm. Cell necrosis would cause a second, additional release of disintegrated structurally bound proteins into circulation, which did not occur in our patients. CK showed additional increases even after 24 h. Each testing episode caused a short skeletal muscle spasm that could explain the further increase of CK after 24 h.

In conclusion, ICD implantation and testing often leads to a short release of cardiac markers into the circulation. The effectiveness of the individual shock, depending on the positioning of the electrode and the position of the heart in the electrical field, seems to influence the release of the cardiac-specific markers. Because the cardiac-specific markers cTnT and cTnI peak after 4 h, theoretically no cell necrosis can occur. It seems to be rather from cytoplasmic origin as a result of a reversible change of permeability of the cellular membrane.

Received September 27, 2000; accepted January 4, 2001.


(1.) Ulbricht LJ, Emmerich K, Probst H, Krakau I, Gulker H. Automated implantable cardioverter/defibrillators. Indications for implantation and clinical results. Z Kardiol 1995;84(Suppl 2):127-36.

(2.) Wilson CM, Allen, JD, Bridges JB, Adgey AAJ. Death and damage caused by multiple direct current shocks: studies in an animal model. Eur Heart J 1988;9:1257-65.

(3.) Doherty PW, McLaughlin PR, Billingham M, Kernoff R, Goris ML, Harison DC. Cardiac damage produced by direct countershock applied to the heart. Am J Cardiol 1979;43:225-32.

(4.) Keffer JH. Myocardial markers in injury. Evolution and insights. Am J Clin Pathol 1996;105:305-20.

(5.) Lauer B, Niederau C, Kuhl U, Schanwell M, Pauschiger M, Strauer BE, Schultheiss HP. Kardiales Troponin T zur Verlaufsbeurteilung bei klinischem Verdacht auf Myokarditis. Dtsch Med Wochenschr 1998;123:409-17.

(6.) Baum H, Braun S, Gerhardt W, Gilson G, Hafner G, Muller-Bardorff M, et al. Evaluation and clinical performance of a second generation cardiospecific assay for troponin T. Clin Chem 1997;43: 1877-84.

(7.) Kuhr L, Baum H, Hafner G, Prellwitz W, Neumeier D. Evaluation of a rapid, quantitative cardiac troponin I immunoassay. Eur J Clin Chem Clin Biochem 1997;35:399-404.

(8.) Hayes JJ, Bardy GH. Various pulses and lead systems to lower defibrillation threshold. In: Naccarelli GV, Veltri EP eds. Implantable card ioverter-defibrillators. Boston: Blackwell Scientific Publications, 1993:321-34.

(9.) Klein G, Kampmann M, Baum H, Rauscher T, Vukovic T, Hallermayer K, et al. Clinical performance of new cardiac markers troponin T and CK-MB on the Elecsys 2010. A multicentre evaluation. Wien Klin Wochenschr Suppl 1998;3:40-51.

(10.) Runsio M, Kallner A, Kallner G, Rosenquist M, Bergfeld L. Myocardial injury after electrical therapy for cardiac arrhythmias assessed by troponin T release. Am J Cardiol 1997;79: 1241-5.

(11.) Jackobsson J, Odmansson I, Norlander R. Enzyme release after cardioversion. Eur Heart J 1990;11:749-52.

(12.) Rao ACM, Naeem N, John C, Collinson PO, Canepa-Anson R, Joseph SP. Direct current cardioversion does not cause cardiac damage: evidence from cardiac troponin T estimation. Heart 1998;80:229-30.

(13.) Bonnefoy E, Chevalier P, Kirkorian G, Guidolet J, Marchand A, Touboul P. Cardiac troponin T does not increase after cardioversion. Chest 1997;111:15-8.

(14.) Allan JJ, Feld RD, Russel AA, Ladenson JH, Rogers MA, Kerber RE, Jaffe AS. Cardiac troponin I levels are normal or minimal elevated after transthoracic cardioversion. J Am Coll Cardiol 1997;30: 1052-6.

(15.) Hurst TM, Hinrichs M, Breidenbach C, Katz N, Waldecker. Detection of myocardial injury during transvenous implantation of automatic card ioverter-defibrillators. J Am Coll Cardiol 1999;34: 402-8.

(16.) Katus HA, Remppis A, Looser S, Hallermeier K, Scheffold T, Kubler W. Enzyme linked immuno assay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol 1989;21:1349-53.

(17.) Christenson RH, Duh S-H, Newby LK, Ohman EM, Califf RM, Granger CB, et al. Cardiac troponin T and cardiac troponin I: relative values in short-term risk stratification of patients with acute coronary syndromes. Clin Chem 1998;44:494-501.

(18.) Katus HA, Remppis A, Scheffold T, Diederich KW, Kuebler W. Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction. Am J Cardiol 1991;67:1360-7.

[3] Nonstandard abbreviations: ICD, implantable cardioverter defibrillator; VF, ventricular fibrillation; cTnT and cTnI, cardiac troponin T and 1; CK-MB, creatine kinase MB; CAD, coronary artery disease; CMP, cardiomyopathy; and VHD, valvular heart disease.


[1] Institut fur Klinische Chemie and Pathobiochemie, and

[2] I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, D-81675 Munich, Germany.

* Address correspondence to this author at: Institut fur Klinische Chemie and Pathobiochemie, Klinikum rechts der Isar, Ismaningerstrasse 22, D-81675 Munchen, Germany. Fax 49-89-4140-4875; e-mail
Table 1. Patient characteristics.

 All patients (a) (n = 14)

Age, years 63.5 (44-78)
Sex, M/F 12/2
LV-EF, (b) % 45(18-70)
Cardiovascular disease
Dilated CMP 4
Cumulative energy, J 38(17-194)
Number of shocks 2(1-10)
Additional leads 5

(a) Data are presented as median and range.

(b) LV-EF, left ventricular ejection fraction.

Table 2. Comparison of significance of deviations.

 After 1 h vs After 4 h vs After 24 h vs
 before before before

cTnT 0.0093 0.0077 0.0094
cTnl NS (a) 0.0186 NS
CK-MB 0.006 0.0043 NS
Myoglobin 0.0029 0.001 0.0012
CK NS 0.02 0.0076

(a) NS, not significant.

Table 3. ICD shocks and resulting biochemical changes.

Patient Atrial Total Atrial Ventr. (a) shocks, J
 electrode energy, J shocks, J

1 Yes 44 4/4 18/18
2 No 23 23
3 Yes 44 2/2/4 18/18
5 No 143 17/31/21/20/31/23
6 No 23 23
7 Yes 36 18/18
8 No 50 25/25
9 No 42 21/21
10 Yes 36 18/18
11 No 40 25/15
16 No 21 21
17 No 17 17
18 Yes 194 2/3/4 21/31/21/31/31/21/29

Patient No. of No. of Peak Time, Peak
 shocks repositionings cTnl, h cTnT,
 [micro]g/L [micro]g/L

1 4 0 0.22 1 0.04
2 1 0 0 0.023
3 5 0 0.53 4 0.076
5 6 1 0 0
6 1 0 0.14 4 0.019
7 2 0 0.27 4 0.034
8 2 0 2.16 4 0.26
9 2 0 0.08 4 0.014
10 2 0 1.11 4 0.131
11 2 0 0 0
16 1 0 0 0
17 1 0 0 0
18 10 2 0.07 4 0.026

Patient Time, Peak CK-MB Time, Peak
 h mass, h myoglobin,
 [micro]g/L [micro]g/L

1 24 2.02 4 40.8
2 1 1.63 1 71.7
3 4 6.3 4 43.3
5 1.9 24 56.8
6 4 2.06 4 209
7 4 2.5 4 315
8 4 14.93 4 144
9 1 4.76 1 171
10 4 9.14 4 104
11 0.73 4 44.5
16 2.79 0 102
17 1.89 4 211
18 4 5.25 4 291

Patient Time, Peak Time, Cardiac
 h CK, U/L h disease

1 4 39 0 CAD
2 24 20 0 CMP
3 4 38 24 VHD
5 4 22 1 CMP
6 4 79 24 CAD
7 4 100 24 CAD
8 4 132 24 CAD
9 1 112 24 VHD
10 4 64 24 VHD/CMP
11 24 39 24 CAD
16 24 56 0 CAD
17 4 92 24 CAD
18 24 164 24 CAD/CMP

(a) Ventr., ventricular.

Table 4. Comparison of our results (a) with the studies of Hurst
et al. (15) and Runsio et al. (10).

 This study Hurst et al.

Peak cTnT, [micro]g/L 0.023 (0-0.26) 0.26 (b) (0.02-6.46)
Peak cTnl, [micro]g/L 0.08 (0-2.16) 0.8 (b) (0.3-5.5)
Peak CK-MB, [micro]g/L 2.5 (0.73-14.93) Not done
Number of shocks 2(1-10) 7.0 [+ or -] 2.5 (d)
Mean cumulative energy, J 38(17-194) 111.2 [+ or -] 62.7 (d)

 Runsio et al.

Peak cTnT, [micro]g/L 0.16 (0.008-0.350) (c)
Peak cTnl, [micro]g/L Not done
Peak CK-MB, [micro]g/L 5.8 (1.0-11.7) (c)
Number of shocks 5(4-8)
Mean cumulative energy, J 114(94-174)

(a) Data are presented as median and range except where otherwise

(b) Mean.

(c) 95% confidence interval.

(d) Mean [+ or -] SD.
COPYRIGHT 2001 American Association for Clinical Chemistry, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2001 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Heart Health and Clinical Laboratory
Author:Schluter, Thomas; Baum, Hannsjorg; Plewan, Andreas; Neumeier, Dieter
Publication:Clinical Chemistry
Date:Mar 1, 2001
Previous Article:Clinical and experimental results on cardiac troponin expression in duchenne muscular dystrophy.
Next Article:Characteristics of an Albumin Cobalt Binding test for assessment of acute coronary syndrome patients: a multicenter study.

Related Articles
InControl's METRIX(TM) System Receives FDA Clearance for U.S. Clinical Trial Expansion and Patient-Activated Therapy
ICD registry scheduled to start on Jan. 1.
Pacing, ICDs are used more aggressively in men than in women.
Electrical storm and implanted defibrillators.
Prevention of death in chronic kidney disease: the role of implantable cardioverter defibrillators.

Terms of use | Copyright © 2017 Farlex, Inc. | Feedback | For webmasters