Author + information
- Victor Nauffal, MD,
- Yiyi Zhang, PhD,
- Elena Blasco-Colmenares, MD, PhD,
- David D. Spragg, MD,
- Joseph E. Marine, MD,
- Barbara Butcher, RN,
- Sanaz Norgard, BS,
- Eliseo Guallar, MD, DrPH,
- Gordon F. Tomaselli, MD and
- Alan Cheng, MD∗ ()
- ↵∗Department of Medicine, Division of Cardiology, Johns Hopkins Medical Institutes, 600 North Wolfe Street, Halsted 565, Baltimore, Maryland 21287
Implantable cardioverter-defibrillators (ICDs) reduce arrhythmic sudden death in patients with systolic heart failure (1). Interestingly, ICD therapies (2,3) are associated with an increased risk of death. The reasons for this increased mortality risk remain poorly understood.
We studied 714 patients with baseline cardiac troponin T (cTnT) levels undergoing primary prevention ICD and cardiac resynchronization therapy-defibrillator device implantation (4). ICD therapies delivered at least 5 min apart were counted as independent episodes and were characterized as inappropriate if delivered for nonventricular arrhythmic events or nonsustained ventricular tachycardia (VT) and appropriate if delivered for sustained VT or ventricular fibrillation (VF). Patients who experienced VT/VF storm (≥3 appropriate therapy episodes within 24 h) were excluded from this analysis due to its distinct elevation in mortality (n = 11) (5). Multivariable Cox proportional hazards models were used to calculate the hazard ratios (HRs) associated with the different types of ICD therapy modeled as time-dependent covariates.
Over a median follow-up of 5.3 years, 486 ICD therapies were delivered in 182 patients, including 295 appropriate (VT1 (<200 beats/min), 20%; VT2 (200 to 250 beats/min), 54.9%; and VT3 (>250 beats/min), 25.1%) and 191 inappropriate therapies (57.6% for atrial fibrillation). Among the 182 patients, 85 patients experienced appropriate ICD therapy only, 74 inappropriate ICD therapy only, and 23 both types of therapy. Compared with patients who did not receive any ICD therapy, those who received appropriate ICD therapy only were more likely to be male, have higher body mass index, have lower use of beta-blockers, and have an ICD rather than a cardiac resynchronization therapy-defibrillator device. Patients who received inappropriate therapy only were more likely to have a history of atrial fibrillation.
We found a significant interaction between ICD shocks and baseline cTnT (Figure 1), stratified by the cut-off of 0.01 ng/ml, on the risk of subsequent mortality (p for interaction = 0.04). ICD shocks were significantly associated with increased mortality in patients with cTnT ≥0.01 ng/ml (HR: 2.47, 95% confidence interval [CI]: 1.60 to 3.82; p < 0.001) but not in patients with cTnT <0.01 ng/ml (HR: 1.08, 95% CI: 0.52 to 2.25; p = 0.84). In a subgroup analysis classifying shocks as appropriate or inappropriate and taking into account the number of shocks, the association between a single appropriate ICD shock and mortality was stronger in patients with baseline cTnT ≥0.01 ng/ml (HR: 3.16, 95% CI: 1.67 to 5.99) than in patients with cTnT <0.01 ng/ml (HR: 1.82, 95% CI: 0.65 to 5.05). Furthermore, a similar pattern was observed for the association between multiple appropriate shocks (HR: 6.90, 95% CI: 3.39 to 14.02 in patients with cTnT ≥0.01 ng/ml and HR: 2.57, 95% CI: 0.84 to 7.85 in those with cTnT <0.01 ng/ml). Interestingly, multiple inappropriate shocks were associated with increased mortality among patients with baseline cTnT ≥0.01 ng/ml (HR: 2.67, 95% CI: 1.03 to 6.93) but not among those with baseline cTnT <0.01 ng/ml (HR: 0.55, 95% CI: 0.10 to 4.27). Tests for interaction in subgroup analyses based on type of shock did not reach statistical significance, but the sample size was limited.
In this study, we observed a role for subclinical myocardial injury in modulating the effect of shock therapy on mortality. Specifically, we found that appropriate shocks (single or multiple) and multiple inappropriate shocks increased all-cause mortality, primarily among patients with elevated baseline cTnT.
Our study has several limitations. This is a relatively small cohort and our analysis was limited by the small number of endpoints; thus, our findings should be confirmed in larger multicenter studies. In addition, cTnT levels were only available at baseline and not during follow-up or immediately prior to ICD therapy.
In a cohort of primary prevention defibrillator recipients, we demonstrate a dynamic interplay between ICD shocks and subclinical myocardial injury and identify a subgroup of patients who are more vulnerable to the injurious effects of shock therapy. These findings may be useful in identifying patients at the highest risk for injury from ICD shocks who may benefit most from aggressive ICD programming tailored to reduce ICD shocks or other interventions to decrease the incidence of tachyarrhythmias.
Please note: Funding for this study was provided by the Donald W. Reynolds Foundation, National Institutes of Health (NIH) R01 HL091062 (to Dr. Tomaselli) and NIH R01 HL103946 (to Dr. Cheng). Dr. Nauffal was supported by the Johns Hopkins Murex Research Award and partly supported by Fogarty training grant NIH-FIC-D43TW009118, awarded to the Scholars in Health Research Program. Dr. Spragg has received honoraria from Medtronic and St. Jude Medical for fellows’ education programs and service on advisory councils. Dr. Cheng has received honoraria from Boston Scientific, Medtronic, and St. Jude Medical for participation in fellows’ educational programs and advisory councils; and has served as a consultant to Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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