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Electrical storm in patients with implantable cardioverter-defibrillator in the era of catheter ablation: Implications for better rhythm control
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Electrical storm in patients with implantable cardioverter defibrillator in The Era of Catheter Ablation. Implications for better rhythm control Sotirios Nedios MD, FHRS, Angeliki Darma MD, Chiara Stevanello MD, Sergio Richter MD, Michael Doering MD, Sascha Rolf MD, Philipp Sommer MD, FHRS, Gerhard Hindricks MD, FHRS, Andreas Bollmann MD, PhD, Arash Arya MD www.elsevier.com/locate/buildenv
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S1547-5271(15)01010-3 http://dx.doi.org/10.1016/j.hrthm.2015.07.034 HRTHM6377
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Heart Rhythm
Cite this article as: Sotirios Nedios MD, FHRS, Angeliki Darma MD, Chiara Stevanello MD, Sergio Richter MD, Michael Doering MD, Sascha Rolf MD, Philipp Sommer MD, FHRS, Gerhard Hindricks MD, FHRS, Andreas Bollmann MD, PhD, Arash Arya MD, Electrical storm in patients with implantable cardioverter defibrillator in The Era of Catheter Ablation. Implications for better rhythm control, Heart Rhythm, http://dx.doi. org/10.1016/j.hrthm.2015.07.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Electrical storm in patients with implantable cardioverter defibrillator in the era of catheter ablation. Implications for better rhythm control.
Sotirios Nedios, MD, FHRS, Angeliki Darma, MD, Chiara Stevanello, MD, Sergio Richter, MD, Michael Doering, MD, Sascha Rolf, MD, Philipp Sommer, MD, FHRS Gerhard Hindricks, MD, FHRS, Andreas Bollmann, MD, PhD, Arash Arya, MD
Department of Electrophysiology, Heart Center, University of Leipzig, Germany Running title: Predictors and therapy of electrical storm Words: abstract: 236 manuscript: 4570 = 4806
Address for correspondence: Sotirios Nedios, MD Department of Electrophysiology Heart Center Leipzig Strümpellstr. 39 04289 Leipzig, Germany Phone: +49 341 865 1413 Fax:
+49 341 865 1460
Email: [email protected]
1
Conflicts of interest: none
Abstract Background: The modern era of cardiology has changed the population of implantable cardioverter defibrillator (ICD) recipients. Identifying predictors of electrical storm (ES) in contemporary ICD patients could improve risk-stratification, therapeutic strategies and mortality. Objective: We aimed to address these points in a real-world setting. Methods: In 330 consecutive patients (65±11 years, 81% male, LVEF 29±9%), with implanted ICD due to ischemic (n=204) or non-ischemic dilated cardiomyopathy (n=126), we analyzed the prevalence, predictors and outcome of ES (≥3 separate VT/VF episodes within 24 hours) therapy. Results: During a median of 21 (17-36) months, 23 (7%) patients had ES. Secondary prevention (61% vs. 24%, p<0.01), single-chamber devices (57% vs. 38%, p=0.02), prior appropriate (96% vs. 24%, p<0.001) and inappropriate (30% vs. 9%, p=0.004) therapies were more prevalent in these patients. In ES patients first appropriate therapy occurred more often in the first year after implantation than in the rest of the cohort (85% vs. 45%, p=0.008) and mortality was significantly higher (22% vs. 2%, p<0.001). Multivariate cox-regression analysis showed that secondary prevention (HR: 2.83, 95%CI: 1.216.61, p=0.016), prior appropriate (HR: 88.99, 95%CI: 11.73-675, p<0.001) and inappropriate (HR: 2.83, 95%CI: 1.14-7.0, p=0.04) therapies were independent predictors of ES. Conclusion: ES is not uncommon in ICD recipients. A secondary prevention indication and the occurrence of both appropriate and inappropriate ICD therapies increase the risk for ES. Prompt initiation of aggressive treatment, especially catheter ablation, should be considered for these patients.
Keywords: catheter ablation, electrical storm, ICD, shocks, predictors. 2
Abbreviations: CRT= cardiac resynchronization therapy; ES = electrical storm; EF = ejection fraction; DCM/ICM = dilated non-ischemic/ischemic cardiomyopathy; ICD = implantable cardioverter-defibrillator; VT/VF = ventricular tachycardia/fibrillation
Introduction Electrical storm (ES) is a devastating, life-threatening event that has become more common in today’s clinical practice. Characterized by multiple episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), ES represents an unstable condition that remains challenging in terms of management and prevention. Thanks to the wide use of implantable cardioverterdefibrillator (ICD) and modern therapy improvements, ICD-recipients nowadays survive longer and run a higher risk for recurrent arrhythmias.1-3 ICD recipients with impaired systolic function or previous history of arrhythmias are at increased risk of ES and cardiac death.4 Whether ES is a causal factor or just an epiphenomenon is still unclear, though it is undisputable that repetitive shocks may provoke myocardial damage and contribute to further deterioration of the underlying disease. Nevertheless, ES exposes patients to great physical and psychological stress, whose impact on the clinical outcome should not be underestimated.1-3 Therefore, identifying ES predictors in a real-world setting would facilitate risk stratification and clinical therapy of these patients. Previous studies have tried to identify ES predictors, including secondary prevention, atrial fibrillation, ejection fraction (EF), renal insufficiency or other potential triggering factors like worsening of heart failure, emotional stress, alcohol excess, electrolyte abnormalities and
3
myocardial ischaemia. 5-10 However, no independent predictors have been reproducibly identified and the role of prior ICD therapies has not been sufficiently adressed yet. 3, 4 Therefore, we aimed to identify ES predictors in ICD recipients in a real-world setting, with a focus on prior ICD therapies and their impact on outcome and prognosis in the era of VT catheter ablation.
Methods Patients Consecutive patients (n=337) undergoing an ICD implant in 2009-2011 were included in our institutional registry. Patients with hypertrophic-obstructive cardiomyopathy (n=5) and channelopathy (n=2) were excluded, so that the final study population comprised of 330 patients with ischemic (ICM, n=204, 62%) or non-ischemic dilated cardiomyopathy (DCM, n=126, 38%). ICM was defined as a reduced left ventricular ejection fraction (LV-EF) associated with a significant coronary vessel obstruction, a history of myocardial infarction or a history of coronary intervention. DCM was defined as a reduced LV-EF in the absence of ischemic, hypertrophic or other clear aetiology of cardiomyopathy. All data were collected in accordance with the Declaration of Helsinki and the institutional research committee approved the study.
Echocardiography Transthoracic echocardiography data were acquired prior to the ICD implantation using a commercially available system (Vivid-9 General Electric Vingmed, Milwaukee, USA). Left ventricular end-diastolic and end-systolic volumes were assessed from the apical 2- and 4chamber images and LV-EF was calculated according to the Simpson method.
4
Implantable cardioverter defibrillator programming Device interrogation was performed regularly (every 4-6 months) or on demand after ICD shocks or after a symptomatic event in an outpatient clinic. Rhythm adjudications were performed based on rate analyses, onset, stability, regularity, morphology and atrioventricular disassociation by two experienced physicians (S.R., M.D.). Implantable cardioverter defibrillators were programmed according to the current manufacturer recommendations for the optimal arrhythmia detection and therapy, including discrimination algorithms when available: Morphology Discrimination plus AV Rate Branch (St. Jude Medical), PR logic and Wavelet (Medtronic), SMART (Biotronik) or Rhythm ID (Boston Scientific and Guidant). The ICD therapy was defined as either antitachycardia pacing (ATP) or ICD shock. The ventricular fibrillation (VF) zone was typically set to >200 beats/min with at least one train of ATP prior to shock while the ventricular tachycardia (VT) zone was typically >170 beats/min with at least three trains of ATP prior to shock. The monitor zone was set to >150 beats/min and atrial arrhythmia detection to >170 beats/min with tachycardia discriminators enabled (according to the Pain-FREE trial) as previously described.11 An ICD therapy delivered for VT or VF was defined as appropriate, and all other episodes were deemed as inappropriate. Device programming remained unchanged in all patients until therapies were delivered or an ablation procedure was preformed, at which point patient-specific programming changes were implemented.
Electrical storm definition and therapy ES was defined as ≥3 separate episodes of VT/VF within 24 hours, separated by bouts of normal rhythm after a successful therapy, either ATP or shock.1 To qualify as ES, the 3 episodes could not be continuous VT/VF in which device therapy was unsuccessful or VT below detection that is untreated. 5
ES treatment was based on physician’s preference and when possible on the treatment of reversible causes. Conservative treatment included admission to the intensive care unit, electrolyte substitution, recompensation, revascularization, beta-blocker and antiarrhythmic drugs (AAD) as necessary. Amiodarone or lidocaine were the first-choice in the acute phase and oral amiodarone or sotalol were preferred for chronic management. Hypokalemia was preferably treated by substitution, whereas premature ventricular contractions (PVCs) were rather ablated. Catheter ablation procedure VT ablation was performed for patients not responding to AAD or as a first-choice for recurrent or incessant arrhythmias, as previously described.12, 13 After a signed, informed consent patients were studied under deep propofol sedation with continuous invasive monitoring of arterial blood pressure and oxygen saturation. The left ventricle was accessed through a transseptal approach, using a steerable introducer (Agilis, SJM, St. Paul, MN, USA). Electroanatomical maps were obtained in sinus rhythm (Carto 3, Biosense Webster Inc., CA, USA or EnSite, St. Jude Medical, MN, USA) and ablation was performed using 3.5 mm saline-irrigated catheters (Navistar Thermocool, Biosense Webster, or Celsius Thermocool, Biosense Webster, 40-50 W, 30 ml/min) and a multichannel recording system (Prucka Cardiolab, GE, Milwaukee, WI, USA). Isovoltage maps were constructed and areas with healthy tissue (>1.5 mV), dense scar (<0.5 mV) or fragmented, late potentials were annotated. If not incessant, VT was induced with programmed stimulation and activation or entrainment mapping was performed to locate exit sites and critical isthmuses. In hemodynamically unstable VTs activation and pace-mapping were used and substrate modification was based on local potentials. Epicardial approach was used in one case after an unsuccessful prior endocardial ablation. Ablation endpoints were elimination of the clinical (partial acute success) or any induced VT (complete acute success).
6
In order to calculate the impact of ES therapy on ICD therapies, the total follow-up time (3.4±1.1 years) was divided into a period from ICD implantation until the ES therapy (0.8±0.7 years) and into a period from thereon (2.5±1.3 years) to the most recent follow-up, the next ES, an additional AAD or AF ablation. In order to mitigate the bias of a reduced AF burden on the incidence of appropriate therapies after an AF ablation, patients were censored at the time of the procedure (in 2 cases after 0.8±0.7 years). These patients had previously received both appropriate and inappropriate (due to AF) ICD therapies.
Statistics Continuous variables are reported as means and standard deviations if normally distributed (Kolmogorov-Smirnov test) and as proportions for categorical variables. Continuous variables were compared using the Student’s t-test, while categorical variables were compared using the chi-square test. To determine the predictive factors of device therapy, univariate and multivariate analyses were performed. Variables with a p-value ≤0.1 in univariate analysis were then included in the multivariate cox-regression regression analysis for determination of the hazard ratio (HR) and its 95% confidence interval (CI). A p-value of ≤0.05 was considered statistically significant. Positive (PPV) and negative predictive values (NPV) were calculated for each dichotomous predictor. Survival and event-free rates from ES were calculated and depicted with the KaplanMeier method. All analyses were performed using SPSS v20.0 (SPSS Inc., Chicago, IL, USA).
7
Results Patient population and ICD therapies Patient data are summarized in Table 1. Devices included 129 (39%) single-chamber, 48 (15%) dual-chamber and 153 (46%) defibrillators with cardiac resynchronisation (CRT-D). During follow-up 33 (10%) patients had inappropriate therapies due to AF (n=19, 6%), supraventricular tachycardia (n=11, 3%) or T-wave oversensing (n=3, 1%). Some patients with ICM (n=7) and DCM (n=3) died after a median of 9 and 22 months (p=0.18) and were censored at that time.
Electrical storm predictors After a median of 21 (17-36) months 23 (7%) patients had ES. Secondary prevention indication (61% vs. 24%, p<0.01), single-chamber devices (57% vs. 38%, p=0.02), prior appropriate (96% vs. 24%, p<0.001) and prior inappropriate (30% vs. 9%, p=0.004) therapies were more prevalent in these patients. In patients with ES first appropriate therapy occurred more often in the first year after implantation than in the rest of the cohort (85% vs. 45%, p=0.008). Mortality of ES patients was significantly increased (22% vs. 2%, p<0.001). Multivariate cox-regression analysis showed that secondary prevention indication (HR: 2.83, 95%CI: 1.21-6.61, p=0.016), appropriate (HR: 88.99, 95%CI: 11.73-675.00, p<0.001) and inappropriate (HR: 2.83, 95%CI: 1.14-7.00, p=0.04) therapies prior to the ES episode were independent predictors of ES (Figure 1). Kaplan-Meier curves illustrate that freedom from ES in ICD patients was significantly lower for patients with secondary prevention, appropriate or inappropriate therapies (Figure 2). In patients with CRT-D (supplementary Table s1), those with electrical storm (n=5) during follow-up had a higher incidence of secondary indication (60% vs. 14%, p=0.03) and more often appropriate therapies (100% vs. 18%, p<0.001), especially in the first year after implantation 8
(60% vs. 16%, p=0.04), despite a frequent use of antiarrhythmic drugs (60% vs. 10%, p=0.01). The low number of ES cases though prohibited regression analysis from revealing statistically significant predictors.
Electrical storm therapy Conservative therapy was chosen in 11 patients, of which 5 patients were treated with amiodarone and 5 stabilized after electrolyte substitution, beta-blocker dose-increase and cardiac re-compensation. One patient rapidly deteriorated due to hemodynamically ongoing VTs despite AADs and finally deceased, before VT ablation was performed. VT ablation was performed in 12 (52%) patients; 2 with ongoing VT, 2 with non-inducible and 8 with inducible VTs. In 2 patients ventricular premature beats were initially targeted as presumptive triggers for the clinical VTs and then further ablation of inducible VTs was pursued. Non-inducibility of any VT (acute complete success) was achieved in 8 (67%) patients, whereas elimination of the clinical tachycardia only (acute partial success) was achieved in 4 (33%). At discharge all patients were prescribed beta-blockers and 5 (42%) had an additional AAD (4 on amiodarone, 1 on sotalol). One patient (8%) experienced a second electrical storm after 40 months and was prescribed amiodarone at that point. Additionally, 4 patients underwent a second ablation due to sustained VT (n=3) or symptomatic VES (n=1). Patients with polymorphic VT or primary VF (n=6) often had hypokalemia as a primary cause and could be effectively treated conservatively rather than undergo an ablation (83% vs. 16%, p=0.069). Patients with monomorphic VT (n=15) were distributed similarly to both treatments (40% vs. 60%, p=0.4) whereas patients with primary initiating PVCs (n=3) were selected for ablation (p=0.48). The difference in indications for ES treatment though between ablated and non-ablated patients did not reach statistical significance (p>0.05). 9
Considering the total number of appropriate device therapies applied, a significant reduction was observed. During follow-up, 119.4±175.9 appropriate therapies per patient-year were administrated prior to ES as opposed to 5.2±7.1 during 2.5±1.3 years after ES therapy (P=0.009). There was no significant reduction of inappropriate therapies (Figure 3). Patients with conservative treatment had a tendency for reduction of appropriate therapies per patient-year (18±11 vs. 5±8, p=0.05), whereas patients that underwent VT ablation experienced a significant reduction (202±205 vs. 5±7, p=0.01). Ablated patients had initially more appropriate therapies (p=0.016) and experienced a higher reduction (197±205 vs. 13±17 therapies/patientyear, p=0.014). However, other clinical characteristics and follow-up time (before and after ES) were similar between the two groups. Mortality was 8% (1/12) in the ablated patients and 18% (2/11) in the conservative treatment group (p=0.09).
Discussion Main findings This study demonstrates that secondary prevention and previous ICD therapies, both appropriate and inappropriate, signify a higher risk for electrical storm in the future. In this cohort of realworld patients, appropriate therapies occurred in 7% over a median follow-up of 21 months. Appropriate treatment of ES cause can reduce the number of appropriate ICD therapies and VT ablation is an effective rhythm therapy, especially for those patients with high VT burden. Since ES is associated with higher mortality, catheter ablation could carry a survival benefit that surely deserves further investigation in comparison to a pharmacological treatment.
10
Electrical storm prevalence and mortality The occurrence of electrical storm is a life-threatening event that is not rare in everyday clinical practice. Initial studies have shown that ES occurs in 10-28% of ICD recipients and is associated with increased mortality.1-8 This could be explained by different factors: i) myocardial injury and ventricular remodeling due to neurohormonal activation, caused directly by the shocks,14 ii) the adverse effects of a heavy pharmacological regimen or iii) ES could just be a relatively “innocent bystander” in a rapidly deteriorating cardiac condition. Our study confirms this association between ES and mortality despite the lower incidence of ES in the era of VT ablation.15 This could be attributed to the changing characteristics of ICD recipients in the recent years. Since advanced medical treatment, improved revascularization and ablation techniques are now widely available, the number of patients that experience recurrent arrhythmias declines. Only the very sick suffer an ES and their prognosis remains poor. Therefore, our findings apply better to today's patient population and could have important implications for reduction of mortality rates.
Electrical storm predictors The clinical factors and mechanisms predisposing to ES initiation remain incompletely understood. In the SHIELD trial, a precipitating cause could be identified in 13% of the cases and mostly consisted of worsening HF and electrolyte disturbances.4 This could be identified in 21% of our study patients who were effectively treated with conservative therapy. Although some studies have reported similar data3, 5-7 or other clinical predictors (e.g. EF, QRS-duration),8 in the vast majority of patients there is no clear ES trigger and the potential role of appropriate and inappropriate therapies has not been adequately studied yet.
11
Our findings revealed that secondary prevention and prior ICD therapies remain the most significant predisposing factors. An increased susceptibility to ventricular arrhythmias as well as the ICD therapies per se, represent a pro-arrhythmic burden. Similarly, Baensch et al. showed that VT inducibility is an independent predictor of ES in DCM patients.5 Therefore, ES is a result of interplay between i) preexisting pathological conditions creating a vulnerable substrate, ii) patient-specific initiating factors and finally maybe iii) the ICD therapy itself. As such, the tendency to develop sustained ventricular arrhythmias before or soon after implantation should lead to a strict follow-up and possibly to the introduction of an adequate prophylactic antiarrhythmic therapy, in order not only to avoid VT-burden but ICD therapies too. Our study showed that inappropriate ICD therapies, delivered mostly during high-rate episodes of AF or SVT, are also independent ES predictors. There is a known association between AF and VT occurrence,16, 17 as well as between AF history prior to ICD implantation and ES occurrence in DCM patients.18 AF might have a negative impact on the ventricles through rapid ventricular rate, short-long-short sequences, decreased cardiac output or increased cardiac filling.16-18 To date though, no study has evaluated the role of inappropriate therapies in ES. Interestingly, AF or SVT alone in our study were not directly associated with the occurrence of ES. According to our findings, inappropriate ICD shocks have per se a detrimental effect on the prognosis, as they carry the same problems associated with appropriate therapies, especially when this concerns shocks. Consequently, special attention should be paid in ICD recipients with recurrent therapies and aggressive rhythm control should be initiated in a timely matter.
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The impact of catheter ablation Choosing the right therapy (conservative or invasive) and the proper time to treat an electrical storm could have an important impact on clinical outcome. Successful ES ablation has been recently associated with reduced ES recurrence and mortality. Sra et al. reported on the catheter ablation of 19 ES patients with only 11% ES recurrence and no death over 26-weeks follow-up.19 A prospective study with ablation of 95 ES patients also showed a cumulative success of 92% over 22 months.20 Similarly, Deneke et al. reported 94% acute success and 9% mortality during 15 months of follow-up of 32 ES patients.21 Two further cohort studies of catheter ablation for ES also showed high acute success rate and significant survival benefit.22, 23 In agreement with these data, we found that ES ablation has an acute and long-term success of 92%. Moreover, despite the fact that mortality of ES patients is increased; there is a tendency of reduced mortality when ablated patients are compared to a conservative therapy. Considering the impact of appropriate and inappropriate therapies on ES, one could also advocate a prophylactic ablation. Although data are scarce, there is some encouraging evidence of ICD therapy reduction in patients with prior myocardial infarction. The SMASH-VT Trial24 showed that prophylactic ablation (without AADs) could reduce ICD shocks from 31% to 9% over a mean follow-up of 23±5 months. The VTACH trial25 randomized patients with prior MI and a stable VT to either ablation or conservative treatment and also found a higher reduction of appropriate therapies in the ablation-group. Since most trials reported on ICM, it is not clear though whether the outcome would be similar for nonischemic patients. Dinov et al.13 showed that in patients with DCM and recurrent sustained VTs a catheter ablation with complete VT noninducibility is associated with better long-term success and reduced mortality. In our study, ablated patients (50% with DCM) experienced a significant reduction of appropriate therapies and a trend for lower mortality despite carrying a higher VT-burden in comparison to those 13
treated conservatively. A prophylactic ablation on an earlier stage of multiple appropriate therapies might have drawn a different picture. Therefore, the merits and the optimal timing of catheter ablation in comparison to the pharmacologic management of ES remain to be proven by a randomized controlled trial.
Limitations This is a single-center study with the limitations of a retrospective analysis. However, we included consecutive patients with regular and thorough interrogations to obtain a comprehensive dataset. ES treatment was not randomised but the indications for the ES therapy were similar between ablated and non-ablated patients. A selection bias though could not be excluded since ablated patients had a higher VT burden that could explain the greater subsequent reduction. Since VT or VES ablation today is a more common treatment-option, this may have prevented the occurrence of ES and thus resulted in a limited number of ES patients, that reflect in our opinion a trend towards earlier diagnosis and intervention in contemporary ICD patients. Moreover, in order to exclude bias and simplify statistical analysis, the follow-up time was abridged with strict criteria, including ES recurrence and AF/VT ablation, leading to a reduced follow-up period and to high standard variation. Finally, the wide variety of manufacturers, devices and discriminating algorithms, hampered a direct comparison of programming within the cohort. However, the fact that every individual patient served as his own control may have minimized that kind of bias. Due to the low number of events, mortality difference (1/12 vs. 2/11) between the two treatments showed a trend but did not reach statistical significance. Certainly, the significance of these findings will need further evaluation in bigger prospective cohorts with longer follow-up period and randomized comparison of different therapy strategies.
14
Conclusion Electrical storm is not uncommon in patients with ICDs. A secondary prevention indication and the occurrence of both appropriate and inappropriate ICD therapies increase the probability for electrical storm. Prompt initiation of aggressive antiarrhythmic treatment, especially catheter ablation, should be considered to reduce the incidence of ES in this population.
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Kosiuk J, Nedios S, Darma A, Rolf S, Richter S, Arya A, Piorkowski C, Gaspar T, Sommer P, Husser D, Hindricks G, Bollmann A. Impact of single atrial fibrillation catheter ablation on implantable cardioverter defibrillator therapies in patients with ischaemic and non-ischaemic cardiomyopathies. Europace Sep 2014;16:1322-1326.
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18
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CLINICAL PERSPECTIVES
The modern era of cardiology has changed the characteristics of ICD-recipients by increasing their survival and their long-term risk for recurrent arrhythmias. The present study examined a contemporary cohort of ICD-patients and systematically analyzed the significance of baseline characteristics and ICD-therapies during follow-up for the occurrence of electrical storm (ES). We found that ES is not uncommon (n=23, 7%) in the first two years and correlates with a higher mortality. A secondary prevention and previous ICD therapies, both appropriate and inappropriate, signify the patients with increased risk for ES in the future. Therefore, a timely and more aggressive antiarrhythmic treatment should be considered for these patients. According to our findings, appropriate treatment of ES cause can reduce the number of appropriate ICD therapies and VT ablation is an effective rhythm therapy, especially for those patients with high VT burden. Since ES is associated with higher mortality, catheter ablation could carry a survival benefit that certainly deserves further investigation in comparison to a conservative treatment in a randomized controlled manner.
19
Table 1. Characteristics of ICD-patients with and without electrical storm. Total Number of patients, n
330
Age, (years)
65±10
Males, n (%)
Electrical Storm No (307)
P
Yes (23)
65±10
68±12
0.14
268 (81)
248 (81)
20 (87)
0.34
29±9
28±9
29±9
0.72
Diabetes mellitus, n (%)
136 (41)
129 (42)
7 (30)
0.38
Hypertension, n (%)
268 (81)
248 (81)
20 (87)
0.59
AF, n (%)
150 (50)
137 (45)
13 (57)
0.29
Persistent AF, n (%)
73 (22)
67 (22)
6 (26)
0.53
NYHA class I, n (%)
38 (12)
35 (11)
3 (13)
0.71
NYHA class II, n (%)
128 (39)
120 (39)
9 (39)
NYHA class III, n (%)
146 (44)
135 (44)
11 (48)
NYHA class IV, n (%)
17 (5)
17 (6)
-
Amiodaron/sotalol, n (%)
29 (9)
25 (8)
4 (7)
0.13
Secondary prevention, n (%)
87 (26)
73 (24)
14 (61)
<0.001
Ischemic cardiomyopathy, n
203 (62)
189 (62)
14 (61)
0.55
Single chamber device, n (%)
129 (39)
116 (38)
13 (57)
0.02
CRT-D, n (%)
153 (46)
148 (48)
5 (22)
0.06
Appropriate therapies, n (%)
94 (24)
72 (24)
22 (96)
<0.001
Single, n (%)
32 (10)
31 (10)
1 (4)
<0.001
Multiple, n (%)
63 (14)
42 (14)
21 (92)
<0.001
158 (48%)
138 (45)
20 (85)
0.008
33 (10)
26 (9)
7 (30)
0.004
Body mass index, (kg/m2)
During first year, n (%) Inappropriate therapies, n (%)
20
Mortality, n (%)
10 (3)
5 (2)
5 (22)
<0.001
LV-EF, (%)
29±9
28±9
28±8
0.98
LVEDD, mm
61±9
62±9
60±9
0.52
Heart rate, bpm
71±17
71±18
70±18
0.38
QRS duration, ms
123±31
124±31
114±41
0.14
Creatinin, mmol/l
108±52
108±54
111±36
0.81
AF= atrial fibrillation; CRT-D= cardiac resynchronization therapy-defibrillator; LV-EF= left ventricular ejection fraction; LVEDD= left ventricular end-diastolic diameter.
Figure 1. Multivariable cox-regression regression analysis for the predictors of electrical storm (ES) in ICD patients. The figure presents graphically the hazard ratios (HR) for ES with the corresponding 95% confidence intervals (95% CI) and p values.
21
Firgure 2. Kaplan-Meier curves for freedom form electrical storm in ICD patients according to A. the indication of implantation, B. the occurrence of inappropriate or C. appropriate therapies. 22
Firgure 3. Number of ICD therapies per patient year prior to electrical storm (ES, blue) in comparison to the period after the appropriate ES therapy (red). Therapies for ES were excluded from the analysis.
23
Electrical storm in patients with implantable cardioverter defibrillator in The Era of Catheter Ablation. Implications for better rhythm control Sotirios Nedios MD, FHRS, Angeliki Darma MD, Chiara Stevanello MD, Sergio Richter MD, Michael Doering MD, Sascha Rolf MD, Philipp Sommer MD, FHRS, Gerhard Hindricks MD, FHRS, Andreas Bollmann MD, PhD, Arash Arya MD www.elsevier.com/locate/buildenv
PII: DOI: Reference:
S1547-5271(15)01010-3 http://dx.doi.org/10.1016/j.hrthm.2015.07.034 HRTHM6377
To appear in:
Heart Rhythm
Cite this article as: Sotirios Nedios MD, FHRS, Angeliki Darma MD, Chiara Stevanello MD, Sergio Richter MD, Michael Doering MD, Sascha Rolf MD, Philipp Sommer MD, FHRS, Gerhard Hindricks MD, FHRS, Andreas Bollmann MD, PhD, Arash Arya MD, Electrical storm in patients with implantable cardioverter defibrillator in The Era of Catheter Ablation. Implications for better rhythm control, Heart Rhythm, http://dx.doi. org/10.1016/j.hrthm.2015.07.034 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Electrical storm in patients with implantable cardioverter defibrillator in the era of catheter ablation. Implications for better rhythm control.
Sotirios Nedios, MD, FHRS, Angeliki Darma, MD, Chiara Stevanello, MD, Sergio Richter, MD, Michael Doering, MD, Sascha Rolf, MD, Philipp Sommer, MD, FHRS Gerhard Hindricks, MD, FHRS, Andreas Bollmann, MD, PhD, Arash Arya, MD
Department of Electrophysiology, Heart Center, University of Leipzig, Germany Running title: Predictors and therapy of electrical storm Words: abstract: 236 manuscript: 4570 = 4806
Address for correspondence: Sotirios Nedios, MD Department of Electrophysiology Heart Center Leipzig Strümpellstr. 39 04289 Leipzig, Germany Phone: +49 341 865 1413 Fax:
+49 341 865 1460
Email: [email protected]
1
Conflicts of interest: none
Abstract Background: The modern era of cardiology has changed the population of implantable cardioverter defibrillator (ICD) recipients. Identifying predictors of electrical storm (ES) in contemporary ICD patients could improve risk-stratification, therapeutic strategies and mortality. Objective: We aimed to address these points in a real-world setting. Methods: In 330 consecutive patients (65±11 years, 81% male, LVEF 29±9%), with implanted ICD due to ischemic (n=204) or non-ischemic dilated cardiomyopathy (n=126), we analyzed the prevalence, predictors and outcome of ES (≥3 separate VT/VF episodes within 24 hours) therapy. Results: During a median of 21 (17-36) months, 23 (7%) patients had ES. Secondary prevention (61% vs. 24%, p<0.01), single-chamber devices (57% vs. 38%, p=0.02), prior appropriate (96% vs. 24%, p<0.001) and inappropriate (30% vs. 9%, p=0.004) therapies were more prevalent in these patients. In ES patients first appropriate therapy occurred more often in the first year after implantation than in the rest of the cohort (85% vs. 45%, p=0.008) and mortality was significantly higher (22% vs. 2%, p<0.001). Multivariate cox-regression analysis showed that secondary prevention (HR: 2.83, 95%CI: 1.216.61, p=0.016), prior appropriate (HR: 88.99, 95%CI: 11.73-675, p<0.001) and inappropriate (HR: 2.83, 95%CI: 1.14-7.0, p=0.04) therapies were independent predictors of ES. Conclusion: ES is not uncommon in ICD recipients. A secondary prevention indication and the occurrence of both appropriate and inappropriate ICD therapies increase the risk for ES. Prompt initiation of aggressive treatment, especially catheter ablation, should be considered for these patients.
Keywords: catheter ablation, electrical storm, ICD, shocks, predictors. 2
Abbreviations: CRT= cardiac resynchronization therapy; ES = electrical storm; EF = ejection fraction; DCM/ICM = dilated non-ischemic/ischemic cardiomyopathy; ICD = implantable cardioverter-defibrillator; VT/VF = ventricular tachycardia/fibrillation
Introduction Electrical storm (ES) is a devastating, life-threatening event that has become more common in today’s clinical practice. Characterized by multiple episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), ES represents an unstable condition that remains challenging in terms of management and prevention. Thanks to the wide use of implantable cardioverterdefibrillator (ICD) and modern therapy improvements, ICD-recipients nowadays survive longer and run a higher risk for recurrent arrhythmias.1-3 ICD recipients with impaired systolic function or previous history of arrhythmias are at increased risk of ES and cardiac death.4 Whether ES is a causal factor or just an epiphenomenon is still unclear, though it is undisputable that repetitive shocks may provoke myocardial damage and contribute to further deterioration of the underlying disease. Nevertheless, ES exposes patients to great physical and psychological stress, whose impact on the clinical outcome should not be underestimated.1-3 Therefore, identifying ES predictors in a real-world setting would facilitate risk stratification and clinical therapy of these patients. Previous studies have tried to identify ES predictors, including secondary prevention, atrial fibrillation, ejection fraction (EF), renal insufficiency or other potential triggering factors like worsening of heart failure, emotional stress, alcohol excess, electrolyte abnormalities and
3
myocardial ischaemia. 5-10 However, no independent predictors have been reproducibly identified and the role of prior ICD therapies has not been sufficiently adressed yet. 3, 4 Therefore, we aimed to identify ES predictors in ICD recipients in a real-world setting, with a focus on prior ICD therapies and their impact on outcome and prognosis in the era of VT catheter ablation.
Methods Patients Consecutive patients (n=337) undergoing an ICD implant in 2009-2011 were included in our institutional registry. Patients with hypertrophic-obstructive cardiomyopathy (n=5) and channelopathy (n=2) were excluded, so that the final study population comprised of 330 patients with ischemic (ICM, n=204, 62%) or non-ischemic dilated cardiomyopathy (DCM, n=126, 38%). ICM was defined as a reduced left ventricular ejection fraction (LV-EF) associated with a significant coronary vessel obstruction, a history of myocardial infarction or a history of coronary intervention. DCM was defined as a reduced LV-EF in the absence of ischemic, hypertrophic or other clear aetiology of cardiomyopathy. All data were collected in accordance with the Declaration of Helsinki and the institutional research committee approved the study.
Echocardiography Transthoracic echocardiography data were acquired prior to the ICD implantation using a commercially available system (Vivid-9 General Electric Vingmed, Milwaukee, USA). Left ventricular end-diastolic and end-systolic volumes were assessed from the apical 2- and 4chamber images and LV-EF was calculated according to the Simpson method.
4
Implantable cardioverter defibrillator programming Device interrogation was performed regularly (every 4-6 months) or on demand after ICD shocks or after a symptomatic event in an outpatient clinic. Rhythm adjudications were performed based on rate analyses, onset, stability, regularity, morphology and atrioventricular disassociation by two experienced physicians (S.R., M.D.). Implantable cardioverter defibrillators were programmed according to the current manufacturer recommendations for the optimal arrhythmia detection and therapy, including discrimination algorithms when available: Morphology Discrimination plus AV Rate Branch (St. Jude Medical), PR logic and Wavelet (Medtronic), SMART (Biotronik) or Rhythm ID (Boston Scientific and Guidant). The ICD therapy was defined as either antitachycardia pacing (ATP) or ICD shock. The ventricular fibrillation (VF) zone was typically set to >200 beats/min with at least one train of ATP prior to shock while the ventricular tachycardia (VT) zone was typically >170 beats/min with at least three trains of ATP prior to shock. The monitor zone was set to >150 beats/min and atrial arrhythmia detection to >170 beats/min with tachycardia discriminators enabled (according to the Pain-FREE trial) as previously described.11 An ICD therapy delivered for VT or VF was defined as appropriate, and all other episodes were deemed as inappropriate. Device programming remained unchanged in all patients until therapies were delivered or an ablation procedure was preformed, at which point patient-specific programming changes were implemented.
Electrical storm definition and therapy ES was defined as ≥3 separate episodes of VT/VF within 24 hours, separated by bouts of normal rhythm after a successful therapy, either ATP or shock.1 To qualify as ES, the 3 episodes could not be continuous VT/VF in which device therapy was unsuccessful or VT below detection that is untreated. 5
ES treatment was based on physician’s preference and when possible on the treatment of reversible causes. Conservative treatment included admission to the intensive care unit, electrolyte substitution, recompensation, revascularization, beta-blocker and antiarrhythmic drugs (AAD) as necessary. Amiodarone or lidocaine were the first-choice in the acute phase and oral amiodarone or sotalol were preferred for chronic management. Hypokalemia was preferably treated by substitution, whereas premature ventricular contractions (PVCs) were rather ablated. Catheter ablation procedure VT ablation was performed for patients not responding to AAD or as a first-choice for recurrent or incessant arrhythmias, as previously described.12, 13 After a signed, informed consent patients were studied under deep propofol sedation with continuous invasive monitoring of arterial blood pressure and oxygen saturation. The left ventricle was accessed through a transseptal approach, using a steerable introducer (Agilis, SJM, St. Paul, MN, USA). Electroanatomical maps were obtained in sinus rhythm (Carto 3, Biosense Webster Inc., CA, USA or EnSite, St. Jude Medical, MN, USA) and ablation was performed using 3.5 mm saline-irrigated catheters (Navistar Thermocool, Biosense Webster, or Celsius Thermocool, Biosense Webster, 40-50 W, 30 ml/min) and a multichannel recording system (Prucka Cardiolab, GE, Milwaukee, WI, USA). Isovoltage maps were constructed and areas with healthy tissue (>1.5 mV), dense scar (<0.5 mV) or fragmented, late potentials were annotated. If not incessant, VT was induced with programmed stimulation and activation or entrainment mapping was performed to locate exit sites and critical isthmuses. In hemodynamically unstable VTs activation and pace-mapping were used and substrate modification was based on local potentials. Epicardial approach was used in one case after an unsuccessful prior endocardial ablation. Ablation endpoints were elimination of the clinical (partial acute success) or any induced VT (complete acute success).
6
In order to calculate the impact of ES therapy on ICD therapies, the total follow-up time (3.4±1.1 years) was divided into a period from ICD implantation until the ES therapy (0.8±0.7 years) and into a period from thereon (2.5±1.3 years) to the most recent follow-up, the next ES, an additional AAD or AF ablation. In order to mitigate the bias of a reduced AF burden on the incidence of appropriate therapies after an AF ablation, patients were censored at the time of the procedure (in 2 cases after 0.8±0.7 years). These patients had previously received both appropriate and inappropriate (due to AF) ICD therapies.
Statistics Continuous variables are reported as means and standard deviations if normally distributed (Kolmogorov-Smirnov test) and as proportions for categorical variables. Continuous variables were compared using the Student’s t-test, while categorical variables were compared using the chi-square test. To determine the predictive factors of device therapy, univariate and multivariate analyses were performed. Variables with a p-value ≤0.1 in univariate analysis were then included in the multivariate cox-regression regression analysis for determination of the hazard ratio (HR) and its 95% confidence interval (CI). A p-value of ≤0.05 was considered statistically significant. Positive (PPV) and negative predictive values (NPV) were calculated for each dichotomous predictor. Survival and event-free rates from ES were calculated and depicted with the KaplanMeier method. All analyses were performed using SPSS v20.0 (SPSS Inc., Chicago, IL, USA).
7
Results Patient population and ICD therapies Patient data are summarized in Table 1. Devices included 129 (39%) single-chamber, 48 (15%) dual-chamber and 153 (46%) defibrillators with cardiac resynchronisation (CRT-D). During follow-up 33 (10%) patients had inappropriate therapies due to AF (n=19, 6%), supraventricular tachycardia (n=11, 3%) or T-wave oversensing (n=3, 1%). Some patients with ICM (n=7) and DCM (n=3) died after a median of 9 and 22 months (p=0.18) and were censored at that time.
Electrical storm predictors After a median of 21 (17-36) months 23 (7%) patients had ES. Secondary prevention indication (61% vs. 24%, p<0.01), single-chamber devices (57% vs. 38%, p=0.02), prior appropriate (96% vs. 24%, p<0.001) and prior inappropriate (30% vs. 9%, p=0.004) therapies were more prevalent in these patients. In patients with ES first appropriate therapy occurred more often in the first year after implantation than in the rest of the cohort (85% vs. 45%, p=0.008). Mortality of ES patients was significantly increased (22% vs. 2%, p<0.001). Multivariate cox-regression analysis showed that secondary prevention indication (HR: 2.83, 95%CI: 1.21-6.61, p=0.016), appropriate (HR: 88.99, 95%CI: 11.73-675.00, p<0.001) and inappropriate (HR: 2.83, 95%CI: 1.14-7.00, p=0.04) therapies prior to the ES episode were independent predictors of ES (Figure 1). Kaplan-Meier curves illustrate that freedom from ES in ICD patients was significantly lower for patients with secondary prevention, appropriate or inappropriate therapies (Figure 2). In patients with CRT-D (supplementary Table s1), those with electrical storm (n=5) during follow-up had a higher incidence of secondary indication (60% vs. 14%, p=0.03) and more often appropriate therapies (100% vs. 18%, p<0.001), especially in the first year after implantation 8
(60% vs. 16%, p=0.04), despite a frequent use of antiarrhythmic drugs (60% vs. 10%, p=0.01). The low number of ES cases though prohibited regression analysis from revealing statistically significant predictors.
Electrical storm therapy Conservative therapy was chosen in 11 patients, of which 5 patients were treated with amiodarone and 5 stabilized after electrolyte substitution, beta-blocker dose-increase and cardiac re-compensation. One patient rapidly deteriorated due to hemodynamically ongoing VTs despite AADs and finally deceased, before VT ablation was performed. VT ablation was performed in 12 (52%) patients; 2 with ongoing VT, 2 with non-inducible and 8 with inducible VTs. In 2 patients ventricular premature beats were initially targeted as presumptive triggers for the clinical VTs and then further ablation of inducible VTs was pursued. Non-inducibility of any VT (acute complete success) was achieved in 8 (67%) patients, whereas elimination of the clinical tachycardia only (acute partial success) was achieved in 4 (33%). At discharge all patients were prescribed beta-blockers and 5 (42%) had an additional AAD (4 on amiodarone, 1 on sotalol). One patient (8%) experienced a second electrical storm after 40 months and was prescribed amiodarone at that point. Additionally, 4 patients underwent a second ablation due to sustained VT (n=3) or symptomatic VES (n=1). Patients with polymorphic VT or primary VF (n=6) often had hypokalemia as a primary cause and could be effectively treated conservatively rather than undergo an ablation (83% vs. 16%, p=0.069). Patients with monomorphic VT (n=15) were distributed similarly to both treatments (40% vs. 60%, p=0.4) whereas patients with primary initiating PVCs (n=3) were selected for ablation (p=0.48). The difference in indications for ES treatment though between ablated and non-ablated patients did not reach statistical significance (p>0.05). 9
Considering the total number of appropriate device therapies applied, a significant reduction was observed. During follow-up, 119.4±175.9 appropriate therapies per patient-year were administrated prior to ES as opposed to 5.2±7.1 during 2.5±1.3 years after ES therapy (P=0.009). There was no significant reduction of inappropriate therapies (Figure 3). Patients with conservative treatment had a tendency for reduction of appropriate therapies per patient-year (18±11 vs. 5±8, p=0.05), whereas patients that underwent VT ablation experienced a significant reduction (202±205 vs. 5±7, p=0.01). Ablated patients had initially more appropriate therapies (p=0.016) and experienced a higher reduction (197±205 vs. 13±17 therapies/patientyear, p=0.014). However, other clinical characteristics and follow-up time (before and after ES) were similar between the two groups. Mortality was 8% (1/12) in the ablated patients and 18% (2/11) in the conservative treatment group (p=0.09).
Discussion Main findings This study demonstrates that secondary prevention and previous ICD therapies, both appropriate and inappropriate, signify a higher risk for electrical storm in the future. In this cohort of realworld patients, appropriate therapies occurred in 7% over a median follow-up of 21 months. Appropriate treatment of ES cause can reduce the number of appropriate ICD therapies and VT ablation is an effective rhythm therapy, especially for those patients with high VT burden. Since ES is associated with higher mortality, catheter ablation could carry a survival benefit that surely deserves further investigation in comparison to a pharmacological treatment.
10
Electrical storm prevalence and mortality The occurrence of electrical storm is a life-threatening event that is not rare in everyday clinical practice. Initial studies have shown that ES occurs in 10-28% of ICD recipients and is associated with increased mortality.1-8 This could be explained by different factors: i) myocardial injury and ventricular remodeling due to neurohormonal activation, caused directly by the shocks,14 ii) the adverse effects of a heavy pharmacological regimen or iii) ES could just be a relatively “innocent bystander” in a rapidly deteriorating cardiac condition. Our study confirms this association between ES and mortality despite the lower incidence of ES in the era of VT ablation.15 This could be attributed to the changing characteristics of ICD recipients in the recent years. Since advanced medical treatment, improved revascularization and ablation techniques are now widely available, the number of patients that experience recurrent arrhythmias declines. Only the very sick suffer an ES and their prognosis remains poor. Therefore, our findings apply better to today's patient population and could have important implications for reduction of mortality rates.
Electrical storm predictors The clinical factors and mechanisms predisposing to ES initiation remain incompletely understood. In the SHIELD trial, a precipitating cause could be identified in 13% of the cases and mostly consisted of worsening HF and electrolyte disturbances.4 This could be identified in 21% of our study patients who were effectively treated with conservative therapy. Although some studies have reported similar data3, 5-7 or other clinical predictors (e.g. EF, QRS-duration),8 in the vast majority of patients there is no clear ES trigger and the potential role of appropriate and inappropriate therapies has not been adequately studied yet.
11
Our findings revealed that secondary prevention and prior ICD therapies remain the most significant predisposing factors. An increased susceptibility to ventricular arrhythmias as well as the ICD therapies per se, represent a pro-arrhythmic burden. Similarly, Baensch et al. showed that VT inducibility is an independent predictor of ES in DCM patients.5 Therefore, ES is a result of interplay between i) preexisting pathological conditions creating a vulnerable substrate, ii) patient-specific initiating factors and finally maybe iii) the ICD therapy itself. As such, the tendency to develop sustained ventricular arrhythmias before or soon after implantation should lead to a strict follow-up and possibly to the introduction of an adequate prophylactic antiarrhythmic therapy, in order not only to avoid VT-burden but ICD therapies too. Our study showed that inappropriate ICD therapies, delivered mostly during high-rate episodes of AF or SVT, are also independent ES predictors. There is a known association between AF and VT occurrence,16, 17 as well as between AF history prior to ICD implantation and ES occurrence in DCM patients.18 AF might have a negative impact on the ventricles through rapid ventricular rate, short-long-short sequences, decreased cardiac output or increased cardiac filling.16-18 To date though, no study has evaluated the role of inappropriate therapies in ES. Interestingly, AF or SVT alone in our study were not directly associated with the occurrence of ES. According to our findings, inappropriate ICD shocks have per se a detrimental effect on the prognosis, as they carry the same problems associated with appropriate therapies, especially when this concerns shocks. Consequently, special attention should be paid in ICD recipients with recurrent therapies and aggressive rhythm control should be initiated in a timely matter.
12
The impact of catheter ablation Choosing the right therapy (conservative or invasive) and the proper time to treat an electrical storm could have an important impact on clinical outcome. Successful ES ablation has been recently associated with reduced ES recurrence and mortality. Sra et al. reported on the catheter ablation of 19 ES patients with only 11% ES recurrence and no death over 26-weeks follow-up.19 A prospective study with ablation of 95 ES patients also showed a cumulative success of 92% over 22 months.20 Similarly, Deneke et al. reported 94% acute success and 9% mortality during 15 months of follow-up of 32 ES patients.21 Two further cohort studies of catheter ablation for ES also showed high acute success rate and significant survival benefit.22, 23 In agreement with these data, we found that ES ablation has an acute and long-term success of 92%. Moreover, despite the fact that mortality of ES patients is increased; there is a tendency of reduced mortality when ablated patients are compared to a conservative therapy. Considering the impact of appropriate and inappropriate therapies on ES, one could also advocate a prophylactic ablation. Although data are scarce, there is some encouraging evidence of ICD therapy reduction in patients with prior myocardial infarction. The SMASH-VT Trial24 showed that prophylactic ablation (without AADs) could reduce ICD shocks from 31% to 9% over a mean follow-up of 23±5 months. The VTACH trial25 randomized patients with prior MI and a stable VT to either ablation or conservative treatment and also found a higher reduction of appropriate therapies in the ablation-group. Since most trials reported on ICM, it is not clear though whether the outcome would be similar for nonischemic patients. Dinov et al.13 showed that in patients with DCM and recurrent sustained VTs a catheter ablation with complete VT noninducibility is associated with better long-term success and reduced mortality. In our study, ablated patients (50% with DCM) experienced a significant reduction of appropriate therapies and a trend for lower mortality despite carrying a higher VT-burden in comparison to those 13
treated conservatively. A prophylactic ablation on an earlier stage of multiple appropriate therapies might have drawn a different picture. Therefore, the merits and the optimal timing of catheter ablation in comparison to the pharmacologic management of ES remain to be proven by a randomized controlled trial.
Limitations This is a single-center study with the limitations of a retrospective analysis. However, we included consecutive patients with regular and thorough interrogations to obtain a comprehensive dataset. ES treatment was not randomised but the indications for the ES therapy were similar between ablated and non-ablated patients. A selection bias though could not be excluded since ablated patients had a higher VT burden that could explain the greater subsequent reduction. Since VT or VES ablation today is a more common treatment-option, this may have prevented the occurrence of ES and thus resulted in a limited number of ES patients, that reflect in our opinion a trend towards earlier diagnosis and intervention in contemporary ICD patients. Moreover, in order to exclude bias and simplify statistical analysis, the follow-up time was abridged with strict criteria, including ES recurrence and AF/VT ablation, leading to a reduced follow-up period and to high standard variation. Finally, the wide variety of manufacturers, devices and discriminating algorithms, hampered a direct comparison of programming within the cohort. However, the fact that every individual patient served as his own control may have minimized that kind of bias. Due to the low number of events, mortality difference (1/12 vs. 2/11) between the two treatments showed a trend but did not reach statistical significance. Certainly, the significance of these findings will need further evaluation in bigger prospective cohorts with longer follow-up period and randomized comparison of different therapy strategies.
14
Conclusion Electrical storm is not uncommon in patients with ICDs. A secondary prevention indication and the occurrence of both appropriate and inappropriate ICD therapies increase the probability for electrical storm. Prompt initiation of aggressive antiarrhythmic treatment, especially catheter ablation, should be considered to reduce the incidence of ES in this population.
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before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. Lancet Jan 2 2010;375:31-40.
CLINICAL PERSPECTIVES
The modern era of cardiology has changed the characteristics of ICD-recipients by increasing their survival and their long-term risk for recurrent arrhythmias. The present study examined a contemporary cohort of ICD-patients and systematically analyzed the significance of baseline characteristics and ICD-therapies during follow-up for the occurrence of electrical storm (ES). We found that ES is not uncommon (n=23, 7%) in the first two years and correlates with a higher mortality. A secondary prevention and previous ICD therapies, both appropriate and inappropriate, signify the patients with increased risk for ES in the future. Therefore, a timely and more aggressive antiarrhythmic treatment should be considered for these patients. According to our findings, appropriate treatment of ES cause can reduce the number of appropriate ICD therapies and VT ablation is an effective rhythm therapy, especially for those patients with high VT burden. Since ES is associated with higher mortality, catheter ablation could carry a survival benefit that certainly deserves further investigation in comparison to a conservative treatment in a randomized controlled manner.
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Table 1. Characteristics of ICD-patients with and without electrical storm. Total Number of patients, n
330
Age, (years)
65±10
Males, n (%)
Electrical Storm No (307)
P
Yes (23)
65±10
68±12
0.14
268 (81)
248 (81)
20 (87)
0.34
29±9
28±9
29±9
0.72
Diabetes mellitus, n (%)
136 (41)
129 (42)
7 (30)
0.38
Hypertension, n (%)
268 (81)
248 (81)
20 (87)
0.59
AF, n (%)
150 (50)
137 (45)
13 (57)
0.29
Persistent AF, n (%)
73 (22)
67 (22)
6 (26)
0.53
NYHA class I, n (%)
38 (12)
35 (11)
3 (13)
0.71
NYHA class II, n (%)
128 (39)
120 (39)
9 (39)
NYHA class III, n (%)
146 (44)
135 (44)
11 (48)
NYHA class IV, n (%)
17 (5)
17 (6)
-
Amiodaron/sotalol, n (%)
29 (9)
25 (8)
4 (7)
0.13
Secondary prevention, n (%)
87 (26)
73 (24)
14 (61)
<0.001
Ischemic cardiomyopathy, n
203 (62)
189 (62)
14 (61)
0.55
Single chamber device, n (%)
129 (39)
116 (38)
13 (57)
0.02
CRT-D, n (%)
153 (46)
148 (48)
5 (22)
0.06
Appropriate therapies, n (%)
94 (24)
72 (24)
22 (96)
<0.001
Single, n (%)
32 (10)
31 (10)
1 (4)
<0.001
Multiple, n (%)
63 (14)
42 (14)
21 (92)
<0.001
158 (48%)
138 (45)
20 (85)
0.008
33 (10)
26 (9)
7 (30)
0.004
Body mass index, (kg/m2)
During first year, n (%) Inappropriate therapies, n (%)
20
Mortality, n (%)
10 (3)
5 (2)
5 (22)
<0.001
LV-EF, (%)
29±9
28±9
28±8
0.98
LVEDD, mm
61±9
62±9
60±9
0.52
Heart rate, bpm
71±17
71±18
70±18
0.38
QRS duration, ms
123±31
124±31
114±41
0.14
Creatinin, mmol/l
108±52
108±54
111±36
0.81
AF= atrial fibrillation; CRT-D= cardiac resynchronization therapy-defibrillator; LV-EF= left ventricular ejection fraction; LVEDD= left ventricular end-diastolic diameter.
Figure 1. Multivariable cox-regression regression analysis for the predictors of electrical storm (ES) in ICD patients. The figure presents graphically the hazard ratios (HR) for ES with the corresponding 95% confidence intervals (95% CI) and p values.
21
Firgure 2. Kaplan-Meier curves for freedom form electrical storm in ICD patients according to A. the indication of implantation, B. the occurrence of inappropriate or C. appropriate therapies. 22
Firgure 3. Number of ICD therapies per patient year prior to electrical storm (ES, blue) in comparison to the period after the appropriate ES therapy (red). Therapies for ES were excluded from the analysis.
23