Multicenter Registry on Patients Affected by Electrical Storm
Conditions: Arrhythmias, Cardiac, Tachycardia, Ventricular, Ventricular Fibrillation, Defibrillators, Implantable
Sponsor: Università Politecnica delle Marche

ELECTRA protocol v. 1.4, 04/02/2016 
 
 
 
ELECTRA 
(INTERNATIONAL ELECTRICAL STORM REGISTRY) 
MULTICENTER REGISTRY ON PATIENTS AFFECTED BY  
ELECTRICAL STORM 
 
RESPONSIBLE: DR. FEDERICO GUERRA 
CLINIC OF CARDIOLOGY AND ARRHYTHMOLOGY 
MARCHE POLYTECHNIC UNIVERSITY 
(DIRECTOR: PROF. ALESSANDRO CAPUCCI) 
 
 

ELECTRA protocol v. 1.4, 04/02/2016 
 
1. 
BACKGROUND 
Organized ventricular arrhythmias (ventricular tachycardia (VT), torsades de pointes (TdP) 
and ventricular fibrillation (VF)) represent a major event in the clinical history of a patient 
and they can lead to hemodynamic instability and sudden cardiac death (SCD). 
Organized ventricular arrhythmias may be associated with structural heart disease (either 
with ischemic or non-ischemic etiology), genetic arrhythmic syndromes (Brugada syndrome, 
familial long QT syndrome, right ventricular arrhythmogenic cardiomyopathy) or metabolic 
disorders. Nonetheless, the etiology of ventricular arrhythmias may remain unknown even 
after extensive diagnostic workup. 
In patients at high risk for ventricular arrhythmias, the guidelines of European Society of 
Cardiology1 suggest the implant of an internal defibrillator (ICD), a subcutaneous device that 
can quickly recognize and treat arrhythmias using fast ventricular pacing (ATP) or internal 
shock. 
Patients that have already had an organized ventricular arrhythmia with hemodynamic 
instability are considered at high risk for SCD and ICD implant is therefore suggested 
(secondary prevention). Patients with structural heart disease and severe impairment of 
contractile function are considered as well at high risk for SCD and an ICD implant is 
suggested (primary prevention). 
Recurrences of ventricular arrhythmias and electrical instability have exponentially 
increased in the last decades and a new clinical entity called “electrical storm” (ES) has 
emerged as major morbidity and mortality factor. The ES is defined as a cluster of 3 or more 
sustained ventricular arrhythmias within 24 hours, or a sustained ventricular tachycardia 
lasting 12 hours or more and that does not respond to treatments2. 
Most of the patients presenting ES are already implanted with an ICD. This is due to 3 
factors: first, patients with ICD implant are at higher risk to develop ventricular arrhythmias 
for the cardiac disease that led to the ICD implant. Second, the device records and treats 
also asymptomatic or poor symptomatic arrhythmic episodes that otherwise would not be 
detected. Third, and more important, the device gives the possibility to survive to an 
arrhythmic episode, making it possible for the patient to experience an ES. 
The incidence of ES is debated in different studies and ranges from 10 to 60% in patients 
with ICD for secondary prevention and from 4 to 7% in patients with ICD for primary 
prevention3. 
Despite the wealth of data on ES, there are still gray areas regarding predictors, treatment 
and prognostic implications of such condition, as a consequence of the small samples of the 
                                                          
1 Priori G, Blomström-Lundqvist C, Mazzanti A,et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias 
and the prevention of sudden cardiac death European Heart Journal 2015 , doi/10.1093/eurheartj/ehv316 
2 Credner SC, Klingenheben T, Mauss O, et al. Electrical storm in patients with transvenous implantable cardioverter-defibrillators: 
incidence, management and prognostic implications. J Am Coll Cardiol. 1998 Dec;32(7):1909-15. 
3 Guerra F, Shkoza M, Scappini L, et al. Role of electrical storm as a mortality and morbidity risk factor and its clinical predictors. A 
meta-analysis. Europace 2014; 16:347.353. 

ELECTRA protocol v. 1.4, 04/02/2016 
 
studies available so far.4 Nonetheless, almost all authors agree in considering ES a predictor 
of poor outcome5. 
Finally, in these last years, a great interest has raised on optimal ICD programming to reduce 
unnecessary interventions for ventricular arrhythmias. In this context, some multicentric 
trials, such as MADIT-RIT6, have showed that restricting ICD intervention to longer or faster 
arrhythmias is safe and may reduce patient morbidity and mortality. 
 
 
                                                          
4 Stuber T1, Eigenmann C, Delacrétaz E. Seasonal variations of ventricular arrhythmia clusters in defibrillator recipients. Pacing Clin 
Electrophysiol. 2006 Aug;29(8):816-20.4  
5 Guerra F, Flori M, Bonelli P, et al. Electrical storm and heart failure worsening in implantable cardiac defibrillator patients. Europace. 
2015 Feb;17(2):247-54. 
6 Moss Aj, Shuger C, Beck CA, et al. Reduction in Inappropriate Therapy and Mortality through ICD Programming N Engl J Med 2012; 
367:2275-2283. 2012DOI: 10.1056/NEJMoa1211107 

ELECTRA protocol v. 1.4, 04/02/2016 
 
2. 
AIM OF THE STUDY 
The aim of the ELECTRA registry is twofold: 
a) To create an international registry on clinical features, optimal therapy, ablation 
strategy, prognosis and the effect of ICD programming on patients with ES. 
b) To use the data derived from the registry for a prospective, observational study on 
mortality and rehospitalization rate in patients with ES. 
3. 
REGISTRY DESIGN 
The creation of the present registry is aimed at gathering information on a wide cohort of 
patients affected by ES. All patients will be enrolled for a minimum of three years from the 
protocol approval. There is no pre-specified date for the end of enrollment, which will be 
decided by the study responsible according to the enrollment rate. 
A minimum of 500 patients will be included in the present registry. The exploratory nature 
intrinsic to the registry characteristics does not allow a sample size calculation by statistical 
means. However, the sample presented is based on the estimated enrolment rates of the 
participating centers during a 3-year enrolment period. Moreover, the sample size is large 
enough to postulate specific subgroup analyses. 
REGISTRY INCLUSION CRITERIA: 
- 
Diagnosis of ES (documentation of 3 or more episodes of sustained ventricular 
arrhythmia within 24h or documentation of sustained ventricular tachycardia lasted at 
least 12h).In order to fulfill this criterion, a patient with a previous episode of ES could 
also be enrolled during routine screening. 
- 
Age ≥18 
- 
Written informed consent 
REGISTRY EXCLUSION CRITERIA: 
- 
patient without ICD 
- 
Confirmed or suspected use of drugs or narcotics with known direct pro-arrhythmic 
effect 
- 
Inability to express an informed consent for the study 
At enrollment, each patient will be informed on the aim and the design of the study, and 
the investigations needed. All patients that meet the inclusion criteria will be included in the 
study (attachment #1). All recruited patients will receive the informative form (attachment 
#1) and the informative letter to their general practictioner (attachment #2). 
3.1 
EVALUATION OF ELIGIBILITY 
All patients admitted to the participating centers will be evaluated consecutively by the 
referent investigators. All patients that meet the above-described criteria will be included in 
the registry. 

ELECTRA protocol v. 1.4, 04/02/2016 
 
3.2 
DATA COLLECTION 
No additional procedures are required to the participating centers. Data usually collected in 
the center and necessary for the analysis will be collected by the referent investigator. 
Considering that ICDs record the principal events of the whole life of the device, patients 
with an ES previous to the creation of this registry will be included retrospectively providing 
that: 
1) clinical data from the participating center are complete and accurate and allow to 
check inclusion and exclusion criteria 
2) follow-up is available 
3) ICD has not been replaced, leading to the loss of original data 
4) ECG and echocardiography done in routine practice are available in case of necessity 
5) subject agrees to subscribe the informed consent during the next routine visit in the 
recruiting center 
All data will be used with scientific research purposes only. Data will be saved on a dedicated 
website7 in agreement with current regulations on the treatment of personal data. Electronic 
cards of data collection transmitted to the study responsible will be identified by an 
alphanumeric code. The list of matches between subjects' data and these codes will be 
created and kept by local investigators or delegates. The data manager is the study 
responsible. 
For the type of data requested, see Case Report Form (attachment #3) 
3.3 
 
DATA REPORT 
Collected data will be processed, analysed and reported according the Strengthening the 
Reporting of Observational Studies in Epidemiology (STROBE) Initiative international 
guidelines.8 A descriptive analysis will be perfomed yearly and at the end of enrolment. 
This will include: 
 The prevalence of cardiovascular risk factors (arterial hypertension, diabetes 
mellitus, prior stroke or TIA, atrial fibrillation, peripheral vascular disease) in the 
studied population. 
 The acute and chronic management of ES, regarding pharmacological and non-
pharmacological treatment. 
 Centrality and dispersion measures regarding laboratory, echocolorDoppler and 
electrophysiological parameters. 
 Centrality and dispersion measures regarding ES inherent variables, such as total 
number of arrhythmias, cycle length and ICD programming. 
 
 
                                                          
7 http://clincardio.univpm.it/eulogin.php 
8 on Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines 
for reporting observational studies. PLoS Med 2007. 4(10): e296. 

ELECTRA protocol v. 1.4, 04/02/2016 
 
4. 
OBSERVATIONAL STUDY DESIGN 
Multicente, observational, prospective clinical study. Data from the first 500 patients enrolled 
in the registry will be used for the present analysis. Please see point #3 of the present 
protocol for information regarding registry enrollment criteria and data collection. 
4.1 
PRIMARY ENDPOINT 
- 
All-cause mortality 3 years after the ES 
4.2 
SECONDARY ENDPOINT 
- 
Hospitalization for all causes 3 years after the ES 
4.3 
ANALYSIS OF RELAPSES AND MORTALITY 
Each center will be asked to report every new hospital admission of patients enrolled in the 
study and the cause of hospitalization. Moreover, data about subjects' vital status will be 
asked to be updated every 6 months. 
4.4 
STATISTICAL ANALYSIS 
The primary endpoint will be estimated annually and it will be expressed as absolute and 
relative numbers. Survival curves free from study endpoint, eventually divided into 
subgroups according to variables of interest such as gender, age, underlying heart disease, 
comorbidity and programming mode, will be drawn with Kaplan-Meier method and compared 
by Log-rank test. Basal and follow-up parameters (clinical, electrocardiographic and 
echocardiographic) will be compared by test or by Fisher test if they are discrete; by T-
student test or signed rank test if they are continuous. Every test will be two-tailed and a 
value of p>0.05 will be considered significant. 
According to the number of centers involved we expect to recruit at least 500 patients. 
Considering an annual incidence of the primary endpoint (death from all causes) of 11% 
according to our experience (Guerra et al. Europace 2015), we expect about 55 events at 
the first statistical analysis after one year from the start and we expect about 165 events at 
the end of the follow-up of three years. The statistical analysis will be conducted using the 
SPSS 21.0 for Windows software (SPSS Inc. Chicago, IL, USA). 
 
5. 
INDICATIONS OF EXPECTED RISKS AND BENEFITS FOR SUBJECTS IN THE 
STUDY 
As no procedures or therapies are required there are no expected risks for patients 
participating to the registry. Despite no short-term benefits will be granted to any of 
participating patients, increasing knowledge of ES will bring to future benefits to the 
community, especially concerning the capacity to prevent recurrent shocks in ICD bearers. 
Each subject will be informed both orally and by an appropriate document concerning 
procedures and purposes of the study. It will be clearly explained that participating (or not 

ELECTRA protocol v. 1.4, 04/02/2016 
 
participating) to the study will not change the frequency and type of clinical evaluations 
expected for the subject’s disease. Patients can consult people they trust and they will have 
enough time to identify and ask any criticism and to gather further information; finally, 
patients will be asked to sign the informed consent if they agree to participate to the present 
registry. It will be stated that patient’s participation to the registry is voluntary, free and that 
the consent can be withdrawn at any time and for any reason. 
6. 
COSTS AND CONFLICT OF INTERESTS 
The registry is cost-free as it does not require any further procedure or examination. The 
present protocol is promoted by the Marche Polytechnic University and it is not financed nor 
influenced by subjects with commercial interests in health. Participation in the trial by 
individual centers is free and voluntary and it will not interfere with clinical care activities. 
 
 

ELECTRA protocol v. 1.4, 04/02/2016 
 
Attachment #1 - Informed consent 
 
ELECTRA registry: Informative Form and Declaration of Consent 
 
 
INFORMATIVE FORM 
Mr./Ms., 
In this hospital 
 
, we are conducting a 
medical-scientific research named “ELECTRA” (international electrical storm registry). 
WHAT IS THE AIM OF THE STUDY 
The present registry aims to collect data on patients with an implantable defibrillator that 
develop recurrent ventricular arrhythmias, a clinical condition named electrical storm. The 
increase of knowledge on electrical storm will bring to future benefits to the community, in 
particular about the capacity to prevent recurrent electrical shocks and treat 
hemodynamically unstable patients. 
WHAT DOES YOUR PARTICIPATION IN THE STUDY IMPLY 
In case you decide to take part to the registry, as an observational study, you will not be 
subjected to any different treatment than those provided by your physician for your disease. 
The acceptance of this informed consent allows the collection, protection and sharing of 
your clinical data in an anonymous fashion.  
EXAMINATION YOU COULD BE SUBJECTED TO DURING THE STUDY 
The registry does not require any additional therapies or procedures. You could be 
contacted by the referring physician of this center and be asked about your health state. 
RISKS AND BENEFITS YOU COULD RECEIVE TAKING PART IN THE STUDY 
Participating in the registry will not expose you to any risk as no additional procedures, 
compared to those performed routinely, will be required. Even if it is hard to predict that 
participating in the trial will bring to short-term benefits for any patient, increasing knowledge 
on electrical storm will bring future benefits to the community, especially regarding the 
capacity to prevent recurrent shocks and to manage hemodynamically unstable patients. 
WHAT HAPPENS IF YOU DECIDE NOT TO PARTICIPATE IN THE STUDY 
You are free to decline your participation to the registry. In that case, you will receive all 
standard therapies usually provided for your disease and physicians will continue to follow 
you with due attention care. There will be no changes in the frequency and type of clinical 
evaluation expected for your disease 

ELECTRA protocol v. 1.4, 04/02/2016 
 
INTERRUPTION OF THE STUDY: 
Your consent to this research program is entirely voluntary and you can withdraw from the 
study whenever you want and for any reason. 
PRIVACY OF PERSONAL DATA: 
The use of your personal data will be marked by principles of fairness, lawfulness and 
transparency, defending your privacy and your rights. Your personal data will be collected 
and electronically stored and they will be used for scientific and research purposes only. 
Data access will be protected by the study manager and data will be kept anonymous. The 
results of the study you will participate can be object of scientific publication but your identity 
will always remain anonymous.  
 
DECLARATION OF CONSENT 
 
I, the undersigned 
 
subscribe to have received by Dr.  
 
detailed information about the request to participate to the “ELECTRA” registry, as reported 
in the information schedule attached above and handed me previously. 
I declare to have been allowed to discuss this information, to have been able to question all 
I thought was necessary to know and to have received satisfactory answers. I also have had 
the possibility to talk about the details of the study with a trusted person. 
I freely agree to take part in the study, being aware of the meaning of the request and of the 
risks and benefits involved. 
 
 
    Date 
Patient signature 
 
 
    Date 
Investigator signature 
 
 

ELECTRA protocol v. 1.4, 04/02/2016 
 
Attachment #2 - Letter for the General Practitioner 
 
Studio ELECTRA: Informative Form for the General Practitioner 
 
 
Dear Colleague, 
Your patient has been invited to participate to a clinical registry called: “ELECTRA 
International electrical storm registry”, whose principal investigator for the present Centre is 
Dr. 
__________________, 
phone______________, 
e-
mail____________________________ 
The present registry aims to collect data on patients with an implantable defibrillator that 
develop recurrent ventricular arrhythmias, a clinical condition named electrical storm. The 
increase of knowledge on electrical storm will bring to future benefits to the community, in 
particular about the capacity to prevent recurrent electrical shocks and treat 
hemodynamically unstable patients. 
The participation to the registry implies that your patient will not be subjected to any different 
treatment than those provided for his/her disease. The principal investigator will contact you 
by phone or e-mail only if it will be necessary to know the current vital status of your patient. 
The registry does not require any additional therapies or procedures. Participating in the 
registry will not expose your patient to any risk as no additional procedures, compared to 
those performed routinely, will be required. Even if it is hard to predict that participating in 
the trial will bring to short-term benefits for any patient, increasing knowledge on electrical 
storm will bring future benefits to the community, especially regarding the capacity to prevent 
recurrent shocks and to manage hemodynamically unstable patients. 
The use of you and your patient’s personal data will be marked by principles of fairness, 
lawfulness and transparency, defending your privacy and your rights. The patient’s personal 
data will be collected and electronically stored and they will be used for scientific and 
research purposes only. Data access will be protected by the study manager and data will 
be kept anonymous. The results of the study you will participate can be object of scientific 
publication but your identity will always remain anonymous.  
Thank you for your collaboration, Best Regards, 
 
    Date 
Investigator signature 
 
 

ELECTRA protocol v. 1.4, 04/02/2016 
 
Attachment #3- Case report form 
 
 
 

ELECTRA protocol v. 1.4, 04/02/2016 
 
Attachment #4 – Follow-up requested data for the observational study 
• 
Last follow-up date 
• 
Vital status (alive, sudden cardiac death, non-sudden cardiac death, non-cardiac 
death, dead for unknown reasons) 
• 
Total number of electrical storm recurrences 
• 
First electrical storm recurrence date 
• 
Total number of unclustered ventricular arrhythmia recurrences 
• 
First unclustered ventricular arrhythmia recurrence date 
• 
Total number of rehospitalization for heart failure 
• 
First rehospitalization for heart failure