Abstract
Background: Electrical storms (E-storms), defined as multiple fatal ventricular arrhythmias over a short period, negatively affect the prognosis of patients receiving an implantable cardioverter defibrillator or cardiac resynchronization therapy with a defibrillator (ICD/CRT-D). However, the prognostic impact of recurrent E-storms has not been well elucidated.
Methods and Results: We analyzed the association between E-storm recurrences and mortality using data from 1,274 participants in the Nippon Storm Study, a prospective observational study conducted at 48 ICD/CRT-D centers in Japan. Differences in E-storm recurrences by patient characteristics were evaluated using the mean cumulative function (MCF), which is the cumulative number of E-storm episodes per patient as a function of time. Patients with multiple E-storms had a 3.39-fold higher mortality risk than those without E-storms (95% confidence interval 1.82–6.28; P<0.01). However, there was no significant difference in mortality risk between patients with a single E-storm and those without E-storms. The MCF curve exhibited a slower ascent in patients who received primary prevention ICD/CRT-D than in those who received secondary prevention ICD/CRT-D. However, when analyzing only patients with E-storms, the MCF curves demonstrated comparable trajectories in both groups.
Conclusions: E-storm recurrences may have a negative impact on prognosis. Once patients with primary prevention experience an E-storm episode, they face a similar risk of subsequent recurrent E-storms as patients with secondary prevention.
Implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-Ds) have been established therapies for reducing the risk of sudden cardiac death in patients with structural heart disease.1–5 However, 10–20% of patients receiving ICDs/CRT-Ds are known to experience electrical storm (E-storm) episodes, in which multiple ventricular arrhythmias occur in a short period of time.6,7 It has been suggested that patients who develop E-storms have a poor prognosis.7 Therefore, managing the development of E-storms is a clinical concern. Survival analysis using the Kaplan-Meier curves usually addresses non-recurrent events, such as death. However, E-storms are potentially recurrent events in patients receiving ICDs/CRT-Ds.6 Previous studies have focused primarily on the first E-storm event, with subsequent events discarded as censored events.7 Therefore, the prognostic impact of multiple E-storm episodes is unknown. Furthermore, the clinical characteristics of patients who have been experienced multiple E-storm episodes have not been elucidated.
Methods
Registration
Data for this subanalysis were drawn from the Nippon Storm Study.8,9 Details of the overall study design of the Nippon Storm Study have been published elsewhere.8 Briefly, the Nippon Storm Study is an observational study sponsored by the Japanese Heart Rhythm Society and the Japanese Society of Electrocardiology conducted in patients implanted with ICD/CRT-D. Website registration of patients was conducted across 48 Japanese ICD centers (Supplementary Appendix), and the Japanese Heart Rhythm Society collected data from physicians who input the patients’ data. According to the guidelines for implantations of ICDs/CRT-Ds, the indication and purpose for the implantations were determined by the attending cardiologists at each center. Patient enrollment in the Nippon Storm Study began in October 2010, and patients were enrolled by July 2012, with follow-up completed in June 2014. The Nippon Storm study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of each participating institution. All patients provided written informed consent to take part in the study.
Inclusion and Exclusion Criteria
Because the pathophysiology of E-storms with and without underlying cardiac disease differs, they are considered to have different mechanisms underlying their occurrence;10 thus, the present study focused on analysis of patients with structural cardiac disease. Of the 1,570 patients enrolled in the Nippon Storm study, 1,274 with structural heart disease listed on the investigation sheet were included in the present study. Structural heart disease included dilated cardiomyopathy, hypertrophic cardiomyopathy, ischemic heart disease (IHD), congenital heart disease, valvular heart disease, arrhythmogenic right ventricular cardiomyopathy, sarcoidosis, and others (amyloidosis, drug-induced cardiomyopathy, Fabry disease, left ventricular non-compaction, myocarditis). Twenty-one patients with no follow-up data at all were excluded, as were 275 patients with no mention of structural heart disease. These 275 had long QT syndrome, Brugada syndrome, and idiopathic ventricular fibrillation (VF).
ICD Programming
The ICD was programmed at the discretion of the attending physician. Some discrimination algorithms, such as the PR Logic and Wavelet (Medtronic, Minneapolis, MN, USA), Rhythm ID (Boston Scientific, Marlborough, MA, USA), and Morphology Discrimination plus AV Rate Branch (St. Jude Medical, St. Paul, MN, USA), were used. The VF zone was >188–200 beats/min with at least 1 train of antitachycardia pacing (ATP) therapy before the shock; the ventricular tachycardia (VT) zone was >140–160 beats/min with at least 3 trains of ATP before the shock, which was could be modified according to the patient’s background. Physicians managed each E-storm episode according to their own preference. If myocardial ischemia, heart failure, or electrolyte abnormalities triggered the E-storm, the physician immediately corrected it. In E-storm events where an antiarrhythmic drug regimen was deemed necessary, a combination of β-blockers, lidocaine, and Class III antiarrhythmics (amiodarone or sotalol) was administered, sequentially or in combination. In some cases, catheter ablation was performed during the acute phase of the E-storm. These data were collected.
Follow-up
For precise follow-up, we constructed a new tracking system called “Chaser”, which was intended to minimize the loss of follow-up data. Data of interventions from the ICDs were sent at a maximum interval of 6 months to the office of the Japanese Heart Rhythm Society through the website. Each ICD intervention was assessed as an appropriate or inappropriate intervention and classified as an ATP treatment, low-energy shock, or high-energy shock.
Definition of E-Storms
E-storms were defined as the occurrence of at least 3 separate episodes of VT/VF within a 24-h period.6–10 All E-storm episodes were examined through the end of the study, and the number of days from enrollment to each E-storm episode was calculated.
Primary Endpoints
The endpoints of this study were E-storms and all-cause mortality. E-storm events were treated as recurrent event data, which consisted of the times to each repeated event for each individual. All-cause mortality included both cardiovascular and non-cardiovascular deaths; cardiovascular death was defined as death from cardiovascular causes (e.g., myocardial infarction, heart failure, arrhythmia, stroke); sudden cardiac death was also included in the cardiovascular death category.
Analysis of Recurrent Event Data for E-Storm Episodes
Event plots were generated to create a visual representation of the timeline for each E-storm episode. The plots accurately show the days of occurrence of each E-storm episode, as well as the patient’s progress, with a line extending to their last observed status. E-storm episodes could occur multiple times in each patient. In order to evaluate the recurrence of E-storms, a non-parametric recurrent event data analysis was used with the mean cumulative function (MCF) of E-storm episodes. Currently, both the MCF and several extended Cox hazard models are available for analysis of recurrent event data. Although extended Cox hazard models are more powerful statistical tools in etiological studies than the MCF, they were not used in the present study because we believe there is still a lack of clinically interpretable findings regarding the fitting of hazard models to E-storms. The MCF has the advantage of simplicity of concept and ease of visualization of the recurrence process. The basic concept of an MCF was defined by the following model for a population without censoring. At a given time, each population unit had accumulated a total number of recurrence episodes. The distribution at that time had a mean M(t), the mean of the cumulative episodes per unit. The M(t) could be viewed as a continuous function with a derivative m(t) = dM(t) / dt, where m(t) was the mean rate at which the number of recurrences accumulated at time (t) (Supplementary Figure). MCF demonstrated the cumulative number of E-storm episodes per patient as a function of time (unit: E-storm events/patient).11–13 MCF plots were created by plotting MCF values against time. In an analysis of patients with multiple E-storm episodes, we compared MCF plots for the total E-storm episodes with the first E-storm events in order to demonstrate the impact of repeated E-storm events.
Analysis of Factors Influencing E-Storm Recurrence
A survival analysis, typically using the Kaplan-Meier method, was designed to analyze non-recurrent events. E-storms could occur repeatedly; therefore, the Kaplan-Meier method was inappropriate for analyzing the factors that contributed to the recurrence of E-storms over time. Instead, we conducted a recurrent event data analysis to compare 2 of the MCF plots of the binarized variables. That analysis was conducted univariately because a multivariate recurrence event data analysis was not feasible. The extraction and binarization of the suggested factors associated with E-storms were carefully determined with reference to previous studies.6,7,10 The following 5 factors were selected and categorized: age (≥75 or <75 years), sex, left ventricular ejection fraction (LVEF; ≤35% or >35%), underlying heart disease (IHD or non-IHD), and New York Heart Association (NYHA) functional class (≥III or <III). If significant patient characteristics were identified in multiple E-storms, those characteristics were subsequently categorized and included in the analysis. If a statistically significant difference was found between 2 MCF plots, a further analysis was performed on patients who had experienced E-storms.
Statistical Analysis
Continuous baseline variables are presented as the mean±SD, whereas categorical baseline variables are presented as numbers and percentages. When comparing the patient characteristics, we used the χ2
test for categorical variables and Student’s t-test for continuous variables. For the time-to-mortality event outcomes, survival curves were created using the Kaplan-Meier Method. Log-rank tests and Wilcoxon tests were used for statistical hypothesis tests. The effects of covariates were explored with proportional hazard models using the hazard ratio (HR) and 95% confidential interval (95% CI). To evaluate the statistical significance of differences between 2 MCF plots, we examined the variance confidence limits. If the confidence limit for a specific time period did not include 0, then the 2 MCF plots were significantly different during that time period. The results of tests of the significance of differences in MCF plots are presented in 3 levels: no significant difference in all periods (NS); a significant difference in less than 50% of the periods (partial significant difference); and a significant difference in more than 50% of the periods (significant difference). That statistical approach was used to explore factors associated with an E-storm recurrence. Two MCF plots for the presence or absence of selected factors were generated and compared in the manner described above.
Statistical analyses were conducted using JMP Pro 16 software (SAS Institute Inc., Cary, NC, USA), with significance set at a two sided P<0.05.
Results
Baseline Patient Characteristics
Of the 1,570 patients enrolled in the Nippon Storm Study, we focused on 1,274 patients with structural heart disease. Of these 1,274 patients, 482 (38%) had IHD and 342 (27%) had dilated cardiomyopathy. In all, 638 (50%) patients underwent ICD/CRT-D implantations for primary prevention and 636 (50%) underwent ICD/CRT-D implantations for secondary prevention. The mean age of patients was 65±12 years, and 967 (76%) were male. ICDs were implanted in 775 (61%) patients, and CRT-Ds in 499 (39%). The mean LVEF was 38%. The baseline characteristics of the 1,274 patients are presented in Table.
Table.
Patient Characteristics
| |
All
(n=1,274) |
No E-storms
(n=1,190) |
Single E-storm
(n=50) |
Multiple E-storms
(n=34) |
P value |
| Age (years) |
65±12 |
65±12 |
68±10 |
66±11 |
NS |
| Male sex |
967 (76) |
902 (76) |
39 (78) |
26 (77) |
NS |
| Hypertension |
475 (37) |
457 (38) |
13 (26) |
5 (15) |
<0.01 |
| Diabetes |
374 (29) |
348 (29) |
14 (29) |
12 (35) |
NS |
| Hyperlipidemia |
475 (37) |
448 (38) |
16 (32) |
11 (32) |
NS |
| Stroke |
102 (8) |
98 (8) |
2 (4) |
2 (6) |
NS |
| Peripheral artery disease |
28 (2) |
27 (2) |
0 (0) |
1 (3) |
NS |
| Death |
135 (11) |
118 (10) |
6 (12) |
11 (32) |
<0.01 |
| CRT-D |
499 (39) |
465 (39) |
20 (40) |
14 (41) |
NS |
| ICD |
775 (61) |
725 (61) |
30 (60) |
24 (59) |
| Primary prevention |
638 (51) |
611 (51) |
16 (32) |
11 (32) |
<0.01 |
| Underlying heart diseases |
| IHD |
482 (38) |
458 (38) |
15 (30) |
9 (26) |
<0.01 |
| Non-IHD |
792 (62) |
732 (62) |
35 (70) |
25 (74) |
| DCM |
342 (27) |
321 (27) |
12 (24) |
9 (26) |
|
| HCM |
204 (16) |
191 (16) |
8 (16) |
5 (15) |
|
| ARVC |
29 (2) |
22 (2) |
4 (8) |
3 (9) |
|
| Sarcoidosis |
62 (5) |
55 (5) |
3 (6) |
4 (12) |
|
| Others |
155 (12) |
143 (12) |
8 (16) |
4 (12) |
|
| LVEF (%) |
38±17 |
38±17 |
37±15 |
33±15 |
NS |
| Severity of HF symptoms |
| NYHA Class ≥III |
417 (33) |
386 (32) |
19 (38) |
12 (35) |
NS |
| NYHA Class I |
375 (29) |
351 (30) |
14 (28) |
10 (29) |
|
| NYHA Class II |
482 (38) |
453 (38) |
17 (34) |
12 (35) |
|
| NYHA Class III |
365 (29) |
335 (28) |
18 (36) |
12 (35) |
|
| NYHA Class IV |
52 (4) |
51 (4) |
1 (2) |
0 (0) |
|
| Medication |
| β-blocker |
841 (66) |
787 (66) |
33 (66) |
21 (62) |
NS |
| Class III antiarrhythmic drug |
540 (42) |
492 (41) |
27 (54) |
21 (58) |
<0.05 |
| Amiodarone |
513 (40) |
472 (40) |
24 (48) |
17 (50) |
NS |
| ACEi/ARB |
790 (62) |
745 (63) |
28 (56) |
17 (50) |
NS |
Unless indicated otherwise, data are given as the mean±SD or n (%). ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARVC, arrhythmogenic right ventricular cardiomyopathy; CRT-D, cardiac resynchronization therapy with a defibrillator; DCM, dilated cardiomyopathy; E-storm, electrical storm; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, implantable cardioverter defibrillator; IHD, ischemic heart disease; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.
Frequency of E-Storm Events and Patient Characteristics
E-storm episodes were observed in 84 (6.6%) patients over the course of a median follow-up of 28 months (interquartile range 23–33 months), yielding an annual event rate per patient of 2.8%. Fifty patients experienced a single E-storm event and 34 experienced multiple E-storm events during the follow-up period. In patients with multiple E-storm events, the median number of E-storm events was 2 (interquartile range 2–3). The clinical characteristics of patients without E-storms, those with a single E-storm event, and those with multiple E-storm events are presented in the Table. The incidence of IHD and the indication of ICD/CRT-D for primary prevention was lower in patients with multiple E-storms than in patients without E-storms. Of the 91 E-storm events that occurred in patients with multiple E-storm events, 17 events were treated with ATP therapy only. Of the 50 single E-storm events, 10 were treated with ATP alone. Of the 84 patients who experienced at least one E-storm event (n=141 E-storm events in total), 20 patients underwent catheter ablation. Of these 20 procedures, 5 were conducted for primary prevention and 15 for secondary prevention.
Event Plots for E-Storms
Figure 1A shows the event plot for patients with a single E-storm episode. Six of 50 patients (12%) died during the follow-up period. Of the 6 deaths among patients with a single E-storm episode, 3 (50%) were cardiovascular deaths. Three of the 6 patients died within 100 days of the last E-storm episode. Figure 1B shows the event plot for patients with multiple E-storm events. Eleven of 34 patients (32%) died during the follow-up period. Of the patients who experienced multiple E-storms and died, 5 (45%) had experienced 2 or more E-storm events with shock therapy. In contrast, among the patients who experienced multiple E-storms and survived, only 2 (9%) had experienced 2 or more E-storm events with shock therapy. The mortality rate was higher among patients with multiple than single E-storms events. Of the 11 patients who experienced multiple E-storms and died, 4 died within 100 days of the last E-storm event. Of the 11 deaths in the group with multiple E-storm events, 4 (36%) were cardiovascular deaths. Among the 118 deaths in the group without an E-storm event, 50 (42%) were cardiovascular deaths. Among the 118 deaths without an E-storm event, 7 patients died within 100 days of their last E-storm event. Four of these 7 patients died of cardiovascular causes.
Survival Analysis
The Kaplan-Meier curves showed a significantly higher all-cause mortality rate in patients with multiple E-storm events than in those with a single E-storm event and those without E-storms (Figure 2). In the patients with multiple E-storm events, the increase in mortality was particularly pronounced after the middle of the follow-up period. At 1 year, the mortality rate was 6% for patients with multiple E-storm events, 4% for those with a single E-storm event, and 4% for patients without E-storms. At 2 years, the mortality rate was 24% for patients with multiple E-storm events, 11% for patients with a single E-storm event, and 9% for patients without E-storms. Patients with a single E-storm event had a 1.26-fold higher risk of all-cause mortality than those without an E-storm, with a non-significant 95% CI of 0.55–2.85 (P=0.59). Patients with multiple E-storm events had a significantly higher risk of all-cause mortality, with a 3.39-fold increase compared with those without E-storms (95% CI 1.82–6.28; P<0.01). After adjusting for age and sex, the risk of all-cause mortality for patients with a single E-storm event and those with multiple E-storm events was 1.17-fold (95% CI 0.51–2.65; P=0.51) and 3.34-fold (95% CI 1.80–6.21; P<0.01) higher, respectively, compared with those without E-storms.
Among patients with multiple E-storm events, those with 2 or more E-storm events requiring shock therapy (n=7) had an 8.0-fold increased risk of mortality compared with those without E-storms (95% CI 3.26–19.54; P<0.01). Conversely, the hazard for death was not significantly different from that of patients without E-storms in those with ATP-only E-storm events or in those with only 1 E-storm event that required shock therapy.
MCF Plots for the First E-Storm Event and Total E-Storm Events
Figure 3 shows MCF plots for the first E-storm event compared with total E-storm events. Both MCF plots showed a comparable increasing curve during the initial 3–6 months. However, the increase in the MCF plot for total E-storm episodes started to become steeper compared with the MCF plot for the first E-storm episode at 6 months, and that disparity appeared to widen over time (Figure 3). This indicates that the number of patients for whom treatment of the first E-storm event was ineffective increased after 6 months.
Factors Associated With the Recurrence of E-Storms Over Time
Figure 4 shows MCF plots for the total E-storm episodes by each of the 7 selected clinical factors, namely age (≥75 or <75 years), sex, LVEF (≤35% or >35%), underlying heart disease (IHD or non-IHD), NYHA functional class (≥III or <III), purpose of ICD/CRT-D implantation (primary or secondary prevention), and the use or not of Class 3 antiarrhythmic medications. The MCF plot for patients without IHD seemed to exhibit a steeper upward trend compared with the plot for patients with IHD (Figure 4D, Upper panel). The lower panel in Figure 4D shows a significant difference between the 2 MCF plots because the confidence limits of the difference in MCF plots did not include 0 for more than 50% of the time. The MCF plot in patients with secondary prevention ICDs/CRT-Ds seemed to exhibit a steeper upward trend than in patients with primary prevention ICDs/CRT-Ds (Figure 4F, Upper panel). The lower panel in Figure 4F shows a significant difference between the 2 MCF plots. For the remaining 5 parameters, no significant differences were observed between the 2 MCF plots according to analysis with the MCF difference test (Figure 4A–C,E–G). When analyzing solely patients who had experienced at least 1 E-storm event, both MCF plots for IHD and non-IHD patients, as well as patients with ICDs/CRT-Ds for primary and secondary prevention, had comparable upward trends. The difference and the confidence limits between the 2 MCF plots revealed that there were no differences in the MCF between IHD and non-IHD patients, or between patients with ICDs/CRT-Ds for primary and secondary prevention (Figure 5).
Discussion
Main Findings
Our results indicated that repeated episodes of E-storms may have a negative impact on the prognosis of patients with ICDs/CRT-Ds. Recurrent E-storms more commonly occurred in patients with ICDs/CRT-Ds for secondary prevention than for primary prevention. However, when analyzing only patients who had experienced E-storms, the time course of recurrent E-storms was comparable between patients with ICDs/CRT-Ds for primary prevention and secondary prevention. These findings suggest that once an E-storm event has occurred in a patient with an ICD/CRT-D for primary prevention, they may be at the same risk for a subsequent recurrent E-storm as patients with ICDs/CRT-Ds for secondary prevention. Our findings also showed the difficulty in predicting patients at high risk of recurrent E-storms using indicators such as the LVEF and NYHA class at baseline.
Repeated E-Storms and a Poor Prognosis
The results of this study showed that patients with multiple episodes of E-storms had an approximately 3-fold higher risk of all-cause mortality than those who did not experience E-storm events. However, there was no significant difference in mortality between patients who had only one E-storm event and those who did not experience E-storm events. These findings suggest an association between the cumulative number of E-storms and mortality. However, the event plots indicated that death occurred several months after the most recent E-storm event in most cases. Therefore, we speculated that the effect of E-storms on mortality was primarily indirect rather than direct. Koizumi et al. reported data suggesting that an E-storm is one of the key events that occur as a natural course of worsening heart failure.14 The accumulation of E-storm events may have adversely affected the patient’s mental and physical health, resulting in an increased risk of death.
Recurrence of E-Storms
In the Nippon Storm Study, approximately 40% of patients with E-storms experienced multiple E-storms, suggesting that approaches to prevent the next E-storm were not highly effective at that time. The cumulative recurrence of E-storms may vary depending on device settings, such as tachycardia detection, and non-device therapies, such as antiarrhythmic drugs and non-pharmacologic therapies. Therefore, it is important to consider the historical differences in device settings and therapeutic interventions when interpreting our data. No new antiarrhythmic drugs have been approved since the publication of the Nippon Storm Study, and clinical practice has not changed significantly with respect to antiarrhythmic drug therapy.15 Conversely, there have been notable changes in interventions with catheter ablation. In the early 2000s, when the Nippon Storm Study was conducted, catheter ablation to control VT/VF had limited efficacy, but since then there has been marked progress in catheter ablation technologies and the procedure has been widely and effectively performed.16–18 Therefore, multiple E-storms may now be inhibited by interventions with catheter ablation, which may lead to different results from those of our study. However, the results of the present study are valuable in that we can confirm the impact of E-storms in a setting where catheter ablation interventions are rarely used.
Our results indicate that the prognosis of patients with multiple E-storm events is worse than that of patients with only 1 E-storm event. However, it remains controversial whether controlling E-storms with catheter ablation improves prognosis.19–24
Although angiotensin receptor-neprilysin inhibitor, a useful pharmacotherapy for heart failure,25 has been reported to be effective in suppressing ventricular arrhythmias,25 it was not approved at the time of this study.
Factors Associated With E-Storm Recurrences
The cumulative incidence of E-storms showed a similar increasing trend in IHD and non-IHD patients during the first 18 months after ICD/CRT-D implantation. However, after 18 months, the cumulative incidence of E-storms in the 2 groups gradually started to diverge, with E-storms occurring more frequently in non-IHD patients than in IHD patients. This phenomenon could be interpreted as the number of non-IHD patients who acquired an arrhythmic substrate after 18 months starting to increase. It has been suggested that structural heart disease can cause arrhythmogenic remodeling with the development of myocardial scar or fibrosis that can form the basis of re-entry, or by an impaired expression and function of ion channels and changes in calcium handling.26 Therefore, the risk of E-storms increases when the progression of structural myocardial disease and myocardial conduction/repolarization derangements coincide. According to the guidelines, LVEF ≤35% remains the primary selection criterion for ICD placement for the primary prevention of sudden cardiac death in patients with non-IHD.27–29 Although some studies have identified reduced LVEF as a risk factor for the development of E-storms,30,31 other studies, including our study, did not identify reduced LVEF as a specific predictor of E-storms.6,32,33 Cardiac magnetic resonance imaging studies have shown that a reduction in LVEF does not necessarily coincide with myocardial scar formation.34 These findings suggest that there are limitations in using baseline LVEF to predict recurrent E-storms.
The cumulative recurrence of E-storms was more common in patients with ICD/CRT-D implantation for secondary prevention than for primary prevention. However, more than 3 months after ICD/CRT-D implantation, the trend of increasing E-storm recurrence appeared to be similar in both groups. Furthermore, focusing only on patients who experienced at least 1 E-storm event, the cumulative recurrence of E-storms was comparable between the primary and secondary prevention groups. These findings provide strong evidence for the efficacy of ICDs/CRT-Ds implantation for primary prevention in Japanese patients. To avoid the underuse of ICDs/CRT-Ds for primary prevention, the indication for ICDs/CRT-Ds should be reconsidered with the progression of the underlying heart disease.
Study Limitations
This study has some limitations. Its prospective observational design and the multicenter registry led to a lack of randomization, which could have resulted in a potential confounding bias. This includes the clinical management of E-storms, such as the administration of antiarrhythmic medications, sympathetic blockade, catheter ablation, and device programming. Although it is important to exercise caution when extrapolating our results to other geographic settings, especially to patients in Western countries, our cohort accurately reflects the real-world clinical setting of Asian patients with ICDs, particularly those with non-ischemic cardiomyopathy. This study was conducted during a time when ablation for E-storms was not common; therefore, the frequency of recurrent E-storms may have been higher than today. Our results did not identify a prognostic difference of E-storms in patients with and without IHD and ICDs/CRT-Ds implanted for primary vs. secondary prevention. This may be driven, in part, by the low overall E-storm event rates. Prognosis may differ between patients with multiple E-storms requiring shock therapies and those with E-storms in which ATP therapies were effective. However, these results should be interpreted in light of the limited number of patients included in the study. We believe that patients with multiple E-storm events do not have a large variability in the number of events. However, the possibility cannot be ruled out that the small number of patients in the target population may have created a bias that allowed certain cases with a higher frequency of events to influence the results. Finally, a higher rate of detection and longer duration interval were used in the primary prevention patients compared with the secondary prevention patients. This could have potentially increased the incidence of E-storms due to the administration of excess ICD therapies for self-terminating VT/VF events.
Conclusions
Repeated episodes of E-storms may have had a negative effect on the prognosis of ICD/CRT-D patients. Once patients with ICDs/CRT-Ds for primary prevention experience an E-storm event, they face a similar risk of subsequent E-storm recurrence over time as patients with ICDs/CRT-Ds for secondary prevention. This suggests the potential existence of a highly established arrhythmic substrate in patients with ICDs/CRT-Ds for primary prevention.
Acknowledgments
The authors gratefully acknowledge all 48 Japanese ICD centers involved in this study and the office of the Japanese Heart Rhythm Society, especially Yoko Sato, for data collection. The authors also thank Naohiko Aihara and Keisuke Shioji for confirming (in a blinded manner) E-storm episodes based on intracardiac electrograms at the time of each event.
Sources of Funding
No financial support was received for this study from any specific company, except the Japan Arrhythmia Device Industry Association.
Disclosures
The authors declare no other relationships with industry and no specific unapproved use of any compound or product.
IRB Information
This study was approved by the Institutional Review Board of Kindai University, Osaka, Japan (Reference no. 22-068).
Data Availability
The deidentified participant data associated with this study will not be shared.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-24-0390
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