Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients

doi:10.1016/j.hrthm.2009.11.027

Heart Rhythm

Volume 7, Issue 3, March 2010, Pages 353-360

https://doi.org/10.1016/j.hrthm.2009.11.027 Get rights and content

Background

Implantable cardioverter-defibrillator (ICD) shocks have been associated with an increased risk of death. It is unknown whether this is due to the ventricular arrhythmia (VA) or shocks and whether antitachycardia pacing (ATP) termination can reduce this risk.

Objective

The purpose of this study was to determine whether mortality in ICD patients is influenced by the type of therapy (shocks of ATP) delivered.

Methods

Cox models evaluated effects of baseline characteristics, ventricular tachycardia (VT; <188 bpm), fast VT (FVT; 188–250 bpm), ventricular fibrillation (VF; >250 bpm), and therapy type (shocks or ATP) on mortality among 2135 patients in four trials of ATP to reduce shocks.

Results

Over 10.8 ± 3.3 months, 24.3% patients received appropriate shocks (50.6%) or ATP only (49.4%), and 6.6% died. Mortality predictors were age (hazard ratio 1.07, 95% confidence interval 1.04–1.08, P <.0001), New York Heart Association class III/IV (3.50 [2.27–5.41]; P <.0001), coronary disease (3.08 [1.31–7.25]; P = .01), and cumulative VA (VT + FVT + VF) episodes shocked (1.20 [1.13, 1.29]; P <.0001). Beta-blockers (0.65, 0.46–0.92; P <.0001) and remote myocardial infarction (0.53, [0.38–0.76] P = .0004) predicted reduced risk. Since 92% of VT and all VF received a single therapy type (ATP and shocks, respectively), the effect of therapy on episode risk could not be established. For FVT (32% shocked, 68% ATP), episode and therapy effects could be uncoupled; ATP-terminated FVT did not increase episode mortality risk, whereas shocked FVT increased risk by 32%. Survival rates were highest among patients with no VA (93.8%) of ATP-only (94.7%) and lowest for shocked patients (88.4%). Monthly episode rates were 80% higher among shocked versus ATP-only patients.

Conclusions

Shocked VA episodes are associated with increased mortality risk. Shocked patients have substantially higher VA episode burden and poorer survival compared with ATP-only-treated patients.

Introduction

Implantable cardioverter-defibrillators (ICDs) reduce mortality by terminating ventricular arrhythmias (VAs) with shocks. Recent evidence indicates an association among appropriate shocks, inappropriate shocks, and increased risks of heart failure (HF) and death.1, 2, 3, 4 While VA episodes and shocks may be markers for higher risk patients, the possibility that shock-induced electrical trauma increases episode mortality risk has not been excluded. Since untreated VA is potentially lethal and shocks are lifesaving, uncoupling these interacting effects is difficult, particularly since almost all episodes in these studies were shocked.

Comparing the effects of antitachycardia pacing (ATP) versus shocks could provide the opportunity to uncouple a harmful shock effect from the VA. We hypothesized that mortality in ICD patients is influenced by the type of therapy (shocks or ATP) delivered.

Section snippets

Methods

Predictors of mortality were analyzed in 2135 patients enrolled in four trials incorporating ATP to reduce shocks (PainFREE Rx,⁵ PainFREE Rx II,⁶ EMPIRIC,⁷ and PREPARE⁸). All patients had Medtronic (Minneapolis, MN) ICDs implanted less than 4 weeks before enrollment. Device programming was standardized in each study with some differences between studies. Detection in the ventricular fibrillation (VF) zone required that 12/16 (PainFREE), 18/24 (PainFREE II, EMPIRIC), or 30/40 (PREPARE) R-R

Statistical methods

Patient characteristics were summarized with standard descriptive statistics. Baseline characteristics associated with mortality risk were established using (1) a shared frailty model⁹ (to account for possible differences in patient selection and treatment between studies) and a (2) stepwise Cox proportional hazards model.¹⁰ Characteristics associated with mortality risk in both models were included in all subsequent models that included episode and therapy type covariates. Episodes were

Baseline characteristics of the study population (Table 1)

Most patients were males with coronary disease (CAD), myocardial infarction (MI), moderately reduced ejection fraction (EF), and mild-moderate HF symptoms, representative of a typical ICD patient population. The reason for ICD was primary prevention in 67% of patients. Average follow-up was slightly <1 year.

Spontaneous arrhythmia episodes

A total of 5376 spontaneous episodes were analyzed. Adjudicated VA accounted for 3934 (73.2%); 1442 (26.8%) were inappropriately detected SVT.

Device detection classification and response to therapy

Most ventricular episodes were potentially

Discussion

This experiment introduces the possibility that electrical therapy type may influence mortality risk in some ICD patients. The main findings are that (1) patients with VA episodes and shocks have higher mortality (≈20% increased risk per shocked episode) than patients with neither or patients with VA treated only with ATP; (2) patients with more VA episodes and more shocks have higher mortality than patients with less of both; (3) VA occurrence rates, durations, and electrical therapy burden of

Clinical implications

Investigations of shock-related myocardial injury have focused on acute effects that may be insufficient to account for reduced survival after appropriate shocks. Other mechanisms may be important. Shocks may activate signaling pathways in the molecular cascade of HF. The clinical consequence may manifest months after shocks. Nonetheless, despite any suggestion that shocks increase risk of death and HF, ICDs prolong survival. Near total reliance on shocks may have underestimated the ICD

Limitations

This was a retrospective analysis with relatively short follow-up. Differences in detection and therapy programming between studies could have influenced the results. Postmortem ICD interrogations and mode of death were not recorded. Episodes without EGMs were excluded. Eventually, all sustained VA receives therapy, and separating therapy effect from episode type becomes impossible. Neither the association between shocks and death in prior studies nor the association between shock-free

Conclusions

Shocked VA episodes are associated with increased mortality risk. Shocked patients have a substantially higher VA episode burden and poorer survival compared with ATP-only-treated patients.

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ClinicalDeviceDifferences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Statistical methods

Baseline characteristics of the study population (Table 1)

Spontaneous arrhythmia episodes

Device detection classification and response to therapy

Discussion

Clinical implications

Limitations

Conclusions

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Resuscitation

J Am Coll Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction

N Engl J Med

Clinical
Device
Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients