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Implantable cardioverter-defibrillators shock paradox

An article from the e-journal of ESC Council for Cardiology Practice

Shock delivery by implantable cardioverter defibrillator (ICD) is a life-saving measure in ventricular tachyarrhythmia. Nevertheless ICD shocks have been related to increased mortality in recent studies, when compared to ICD patients without documented shocks. This review takes a look at this "shock paradox".

Ventricular Arrhythmias and Sudden Cardiac Death (SCD)


Background

Although shock delivery by implantable cardioverter-defibrillators (ICD) is a life-saving measure in cases of ventricular tachyarrhythmia, there have been a few notable effects since it was first discovered in the 80's:

  • In 1988, external defibrillation was shown to lead to energy-dependent macroscopic myocardial damage and to short-term reduction of systolic left ventricular function in an animal model. (1)
  • Ten years later, a decrease of 10% in cardiac index was also found to be "dose-dependent" after increasing shock energy. (2) 
  • Recently, microscopic myocardial damage (electroporation) was documented along endocardial (3) and epicardial (4) ICD leads after intracardiac shock delivery. 
  • Humoral cardiac markers (troponin T, CK-MB and myoglobine) increased significantly after intracardiac defibrillation. (5)

Interestingly, intracardiac shocks during defibrillation threshold (DFT) testing lead to a significant reduction in cardiac index only in patients with a reduced LVEF <30% (6), thus suggesting a loss of systolic function especially in previously damaged myocardium.
In 2008, a correlation was found between ICD shocks and mortality, and was labeled the shock paradox in ICD therapy. 

Shock paradox

  • Increased mortality in patients with primary preventive ICD implantation: In 2008, the SCD-HeFT subanalysis on 811 patients of the Poole et al. study was the first data to reveal a significantly increased mortality in patients with primary preventive ICD implantation and at least one documented intracardiac shock delivery. (7) Over the median follow-up period of nearly 4 years, this fact endured for both appropriate and inappropriate shocks. When focusing on patients surviving the first 24 hours after their first shocks, an increase in all-cause mortality was still observed for appropriate but not for inappropriate shocks. Interestingly, patients with definitely appropriate (with or without inappropriate) shocks had a lower median LVEF (20% EF) than patients with exclusively inappropriate shocks or without any shock (25% EF). The most common cause of death among patients with any ICD shock was progressive heart failure.
  • Patients treated with intracardiac shock showed increased mortality: In 2010, a meta-analysis of 4 prospective trials (PainFREE I + II, EMPIRIC and PREPARE) investigating the prevention of ICD shocks by preferential anti-tachycardia pacing (ATP) pooled the data from 2,100+ patients: (8) ventricular tachyarrhythmia treated by ATP had no impact on mortality when compared to patients without ventricular arrhythmia, whereas patients treated with intracardiac shock showed increased all-cause mortality, when compared to those without documented shock. In patients with only inappropriate shocks, this deleterious effect was no longer found.
  • Negative effect of appropriate shocks on survival is only evident within the first 4 years after ICD implantation: A smaller single center analysis of 561 patients with heart failure and primary preventive ICD observed the clinical outcome over a median follow-up period of 4 years. (9) The authors concluded that the negative effect of appropriate shocks on survival is only evident within the first 4 years after ICD implantation. Appropriate shocks after the median follow-up period and inappropriate shocks occurring at any time revealed no impact on survival. Remarkably, the deleterious effect of intracardiac shocks was seen only in patients with ischemic heart failure, supporting the theory of higher mortality based on the underlying cardiac disease.
  • The adverse prognosis after first shock appears to be more related to the underlying arrhythmia than to an adverse effect from the shock itself: A recent subanalysis of the ALTITUDE registry focused on the "survival by rhythm" in more than 7,400 patients. (10) Significantly higher all-cause mortality was found in patients with appropriate shocks for ventricular arrhythmia as well as in patients with inappropriate shocks caused by atrial fibrillation/flutter, but not those with inappropriate shocks due to other supraventricular tachycardia, noise/artifacts or oversensing. The authors concluded that "the adverse prognosis after first shock appears to be more related to the underlying arrhythmia than to an adverse effect from the shock itself". Unfortunately, this manuscript didn't provide any data on heart failure parameters such as LVEF or NYHA class. Nevertheless, a correlation between mortality and heart failure may be presumed, as ventricular tachyarrhythmia and atrial fibrillation are well known to be more frequent in patients with reduced left ventricular function.

Accelerated ventricular tachyarrhythmia and mortality

Accelerated tachyarrhythmia was associated with significantly higher all-cause mortality: Our own single center analysis on a collective of 1,170 ICD patients over a mean follow-up of 5 years was the first to focus on accelerated ventricular tachyarrhythmia, defined as acceleration (or induction) of a ventricular arrhythmia with a decrease of 10% of the initial cycle length caused by ATP or shock delivery (11). Indeed, in previous publications, the incidence of accelerated ventricular arrhythmias ranged between 1% and 5% within follow-up periods of 2 years maximum. (12-16) Acceleration was documented in 8.5% of all patients and in 17% of patients with documented ATP during this longer follow-up period. Almost all ventricular accelerations were induced by predominantly appropriate ATP (97%) and were in the end, terminated with a shock (99%). Occurrence and recurrence of accelerated tachyarrhythmia were significantly correlated with reduced systolic left ventricular function (LVEF <40%). Most notably, accelerated tachyarrhythmia was associated with significantly higher all-cause mortality. In the multivariable analysis, accelerated ventricular tachyarrhythmia and LVEF <40% were independent predictors for all-cause mortality. In patients with documented ATP, acceleration was an independent mortality predictor as well. Therefore, we found once more a significant correlation between shock delivery and mortality.

However, progressive deterioration of systolic heart failure was likely to be the underlying cause for increased mortality in ICD patients (see next paragraph). The detailed interrelations we found in our collective are summarised in the following figure.

Figure: Parameters with influence on all-cause mortality in patients with ICD (provided by author from reference 11).

Local injury currents

Patients with stable heart failure NYHA-class I-III revealed local injury currents: A recent investigation on DFT testing in 310 patients with stable heart failure NYHA-class I-III revealed local injury currents (LIC) in the post-shock intracardiac ECG as a clue for pre-damaged myocardium. (17) These LIC are late-potential-like abnormalities of the right ventricular ECG. First, the presence of LIC during DFT testing resulted in a significantly higher adverse event rate (i.e. death, or hospitalisation for deterioration of heart failure). Remarkably, a significant correlation between a higher event rate and the occurrence of ICD shocks was only found in patients with documented LIC. On the other hand, a missing LIC leads to an identical adverse event rate in patients with or without ICD shock.

Thus, local injury currents reflecting a pre-damaged myocardium in patients with progression of systolic heart failure might be the missing link between ICD shock delivery and increased mortality.

Conclusion

The presented "shock paradox" is a chicken-and-egg question in cardiology: can ICD shocks be lethal in the long term, or, are patients with a higher risk of death supposed to undergo shocks?
Intracardiac shocks are saving lives in cases of ventricular tachyarrhythmia, but a significant correlation between shocks and mortality was reported in several studies on ICD therapy. In conclusion, shock delivery is most likely a surrogate parameter, reflecting higher all-cause mortality based on progressive deterioration of the underlying chronic heart failure with reduced ejection fraction. 

References


1 - Death and damage caused by multiple direct current shocks: studies in an animal model. Wilson CM, Allen JD, Bridges JB, Adgey AA. Eur Heart J. 1988;9(11):1257-65.
2 - Effect of ventricular shock strength on cardiac hemodynamics. Tokano T, Bach D, Chang J, Davis J, Souza JJ, Zivin A, Knight BP, Goyal R, Man KC, Morady F, Strickberger SA. J Cardiovasc Electrophysiol. 1998;9(8):791-7.
3 - Spatial distribution and extent of electroporation by strong internal shock in intact structurally normal and chronically infarcted rabbit hearts. Kim SC, Vasanji A, Efimov IR, Cheng Y. J Cardiovasc Electrophysiol. 2008;19(10):1080-9.
4 - Atria are more susceptible to electroporation than ventricles: implications for atrial stunning, shock-induced arrhythmia and defibrillation failure. Fedorov VV, Kostecki G, Hemphill M, Efimov IR. Heart Rhythm. 2008;5(4):593-604.
5 - Myocardial injury after electrical therapy for cardiac arrhythmias assessed by troponin-T release. Runsiö M, Kallner A, Källner G, Rosenqvist M, Bergfeldt L. Am J Cardiol. 1997;79(9):1241-5.
6 - Hemodynamic deterioration during ICD implant: predictors of high-risk patients. Steinbeck G, Dorwarth U, Mattke S, Hoffmann E, Markewitz A, Kaulbach H, Tassani P. Am Heart J. 1994;127(4 Pt 2):1064-7.
7 - Prognostic importance of defibrillator shocks in patients with heart failure. Poole JE, Johnson GW, Hellkamp AS, Anderson J, Callans DJ, Raitt MH, Reddy RK, Marchlinski FE, Yee R, Guarnieri T, Talajic M, Wilber DJ, Fishbein DP, Packer DL, Mark DB, Lee KL, Bardy GH. N Engl J Med. 2008;359(10):1009-17.
8 - Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in ICD patients. Sweeney MO, Sherfesee L, DeGroot PJ, Wathen MS, Wilkoff BL. Heart Rhythm. 2010;7(3):353-60.
9 - Impact of shocks on mortality n patients with ischemic or dilated cardiomyopathy and defibrillators implanted for primary prevention. Streitner F, Herrmann T, Kuschyk J, Lang S, Doesch C, Papavassiliu T, Streitner I, Veltmann C, Haghi D, Borggrefe M. PLoS One. 2013;8(5):e63911.
10 - Survival afters hock therapy in implantable cardioverter-defibrillator and cardiac resynchronisation therapy-defibrillator recipients according to rhythm shocked. Powell BD, Saxon LA, Boehmer JP, Day JD, Gilliam FR 3rd, Heidenreich PA, Jones PW, Rousseau MJ, Hayes DL.  The ALTITUDE survival by rhythm study. J Am Coll Cardiol. 2013;62(18):1674-9.

11 - Impact of accelerated ventricular tachyarrhythmias on mortality in patients with ICD therapy. Schukro C, Leitner L, Siebermair J, Pezawas T, Stix G, Kastner J, Schmidinger H. Int J Cardiol. 2013;167(6):3006-10.
12 - Empirical versus tested antitachycardia pacing in implantable cardioverter defibrillators: a prospective study including 200 patients. Schaumann A, von zur Mühlen F, Herse B, Gonska BD, Kreuzer H. Circulation 1998;97:66-74.
13 - Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease. Wathen MS, Sweeney MO, DeGroot PJ, et al.; PainFREE Investigators. Circulation 2001;104:796-801.
14 - Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial. Wathen MS, DeGroot PJ, Sweeney MO, et al.; PainFREE Rx II Investigators. Circulation 2004;110:2591-2596.
15 - Optimizing implantable cardioverter-defibrillator treatment of rapid ventricular tachycardia: antitachycardia pacing therapy during charging. Schoels W, Steinhaus D, Johnson WB, et al.; EnTrust Clinical Study Investigators. Heart Rhythm 2007;4:879-885.
16 - A randomized study to compare ramp versus burst antitachycardia pacing therapies to treat fast ventricular tachyarrhythmias in patients with ICD: the PITAGORA ICD trial. Gulizia MM, Piraino L, Scherillo M, et al.; PITAGORA ICD Study Investigators. Circ Arrhythm Electrophysiol 2009;2:146-153.
17 - Transient local injury current in right ventricular electrogram after implantable cardioverter-defibrillator shock predicts heart failure progression. Tereshchenko LG, Faddis MN, Fetics BJ, Zelik KE, Efimov IR, Berger RD. J Am Coll Cardiol. 2009;54(9):822-8.

Notes to editor


Christoph Schukro, MD, PhD, FESC. 
Medizinische Universität Wien
Univ.Klinik für Innere Medizin II
Abteilung für Kardiologie

Author's disclosures: None declared. 

Other resources
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The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.