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Comparison of Efficacy and Safety of Two Biphasic Defibrillators in Cardioversion of Atrial Fibrillation

U

University National Heart Hospital

Status

Completed

Conditions

Arrythmia
Atrial Fibrillation
Electric Countershock

Treatments

Device: Schiller Defigard Touch 7 - DGT7, Schiller Medical, France
Device: LIFEPAK 15, Physio-Control Inc., Redmond, WA, USA

Study type

Interventional

Funder types

Other

Identifiers

NCT04032678
P4/10.07.2018

Details and patient eligibility

About

Background: Biphasic truncated exponential (BTE) waveforms are standard for cardiac defibrillation and synchronized cardioversion up to date. BTE waveforms differ by design characteristics and technologies for pulse commutation (rectilinear, standard truncated exponential, pulsed). Clinical evaluation of BTE waveforms can be planned during cardioversion (CVS) as a well-established procedure of atrial fibrillation patients who are able to give consent and also present a more controlled population.

Scarce studies have been found to present the relative efficacy and safety of different BTE waveforms during CVS. The validity of significantly deviating results of the pulsed waveform in one CVS study is questionable.

Objective: To compare the CVS efficacy and safety two different biphasic defibrillators - a standard truncated exponential waveform and a pulsed biphasic waveform.

Experimental design: Patients will be recruited at the Intensive Cardiology Care Unit (ICCU), Cardiology Clinic, University National Heart Hospital (NHH), Sofia, Bulgaria, underwent the pre-CVS medical exams and check for eligibility. All eligible patients will sign a written informed consent prior to the CVS and will receive the standard hospital procedures during CVS, accepted in the NHH, and approved by the NHH Local Ethic Committee.

Atrial fibrillation patients will be alternatively randomized to CVS using one of the two defibrillators, following the same energy selection protocol in both defibrillators. The statistical power analysis will consider a non-inferiority comparison between the cumulative energy actually delivered by both defibrillators.

The secondary CVS outcome measures are: the cumulative success rate (measured at 1 minute post-shock) and number of delivered shocks. Delivered energy will be measured during each shock with a dedicated pulse recording device (approved by the NHH Local Ethic Committee). Heart rhythm will be monitoring in continuously recorded peripheral ECG.

The secondary CVS safety outcome measures: Biochemical markers for myocardial necrosis (high sensitive troponin I - hsTnI, creatine kinase MB fraction - CK-MB) will be evaluated on blood samples taken before and 12 hours after cardioversion; ST-segment changes will be measured in lead II (baseline and 10 s post-shock) and 12-lead ECG; Complications after cardioversion will be measured during 2 hours follow-up period in the ICCU.

Full description

Background:

External defibrillators are routinely used for treatment of lethal ventricular arrhythmias (defibrillation) as well as atrial and non-lethal ventricular arrhythmias (synchronized CVS). Commercially available defibrillators generate direct current (DC) shock with various waveforms using distinct technologies. These waveforms are suggested to have different efficacy and safety, aiming at a positive effect with lower cumulative energy, smaller number of shocks, and less post-shock complications and myocardial injury. Therefore, the efficacy and safety of different waveforms has been an object of continuous interest and clinical investigations over the last years. Although the superiority of biphasic over monophasic waveforms is well established, the relative efficacy and safety of the available biphasic waveforms is not clear.

Most defibrillator manufacturers use the biphasic truncated exponential (BTE) waveform. Almost all BTE defibrillators are embedding the impedance compensation technology, which adapts the pulse duration for proper delivery of the selected energy. However, various pulse commutation concepts produce differently shaped waveforms:

  • rectilinear (impedance compensation with constant pulse duration);
  • standard truncated exponential (impedance compensation with constant tilt);
  • pulsed (impedance compensation with constant duty cycle and constant tilt). Clinical studies with patients presenting with shockable life-threatening arrhythmias are difficult to perform for ethical and practical reasons. Several studies have therefore included patients requiring elective CVS for atrial arrhythmias, who are able to give consent and also present a more controlled population. Elective CVS is a standard treatment for patients with atrial arrhythmias and is performed as a day case procedure under general anesthesia. The investigator's bibliographic research found 6 studies from which the dose-response curves of 4 rectilinear, 7 standard truncated exponential and 3 pulsed waveforms have been drawn. Although the major disparities between the studies (success accounted at different delays after CVS, rhythm inhomogeneity, different population sizes, different selected energy levels, etc.) the dose-response curves concentrate within 85-95% success rate and 300-500 joules (J) cumulative energy. More data on the efficacy of the pulsed waveform during CVS are needed.

Various BTE waveforms apply different potential gradients on the thorax that might produce various defibrillation effects. Apart from efficacy, the most important aspect is the patient safety, considering that larger potential gradients in the myocardium lasting longer could potentially induce an electroporation and then a fibrillation. A frequently observed effect of electroporation are the post-shock ST-segment deviations in the surface ECG, representing the potential difference between the normal tissue and sustained depolarized critical mass of myocardium closest to the associated origin of the electrical current. Although ST-segment changes are an easily ignored phenomenon, occurring acutely and resolving during the first few minutes post-shock, their presence in a short-term basis can identify electroporation by dangerously high potential gradients, while the sustained ST-changes in a long-term basis can identify cases with myocardial injury. The most reliable quantification of shock-induced myocardial injuries is based on measurements of the hsTnI biomarker after CVS. The safety of shocks contemplates any other complications after CVS, such as apnea, arrhythmias, etc. The variety of safety outcomes for different BTE waveforms is not clear.

Considering that little published data are available on pulsed waveforms, this study aims to compare the pulsed biphasic waveform to a standard truncated exponential waveform in respect of efficacy and safety in elective CVS of atrial fibrillation.

Methods:

Study population All patients admitted for elective CVS of atrial fibrillation (AFIB) in ICCU- National Heart Hospital (NHH) will be potentially eligible for the study. Informed consent will be obtained from all eligible patients prior to CVS. Patients declining to participate in the study will receive treatment according to the hospital protocol.

Cardiologists in ICCU-NHH will check the eligibility of each patient following the detailed list of inclusion and exclusion criteria in section Eligibility Criteria, based on the documented pre-treatment data (duration of AFIB, concomitant diseases, thyroid dysfunction, transesophageal echocardiographic (TEE) measurements).

Additionally, eligibility will be verified through pre-CVS medical exams and routine blood test within 24 hours before CVS, including hsTnI measurements on the day of CVS:

Study design A prospective randomized trial (alternating design) where eligible patients will be randomized to treatment with two different defibrillators. Following the order of patient admittance in ICCU-NHH, the attending cardiologist will assign the odd and even eligible patients to the defibrillators in arm 1 and arm 2, respectively. The cardiologist cannot control the order of patient admittance in ICCU-NHH. The alternative randomization design will equalize the number of subjects on each treatment. This study is not designed to control for sex, age, comorbidity, type of device used for CVS, cumulative energy delivered during shocks, number of shocks administered. Randomization is performed to limit these and any other confounding factors.

Patient preparation Patients will be consulted prior to CVS in a quiet setting. Any questions will be answered by the attending cardiologist. Patients will be asked to manually sign their informed consent for study participation before further preparations and data collection. If the patient declines to participate, then he/she will receive treatment according to the hospital protocol without data documentation, as further defined in the study.

Demographic data (hospital file ID, age, gender, weight, height, body mass index, body surface area) will be taken.

Pre-treatment data will be read from the patient dossier:

  • All concomitant diseases.
  • All medications during the previous 7 days before CVS.
  • Left atrium dimensions, left ventricle dimensions and volumes, ejection fraction (EF) by transthoracic echocardiography during the last month.
  • TEE will be performed for all patients within 1 to 5 days before CVS (except if contraindications of TEE exist); presence of cardiac thrombus and spontaneous echo contrast will be checked.
  • Duration of index AFIB in days.
  • European Heart Rhythm Association (EHRA) class score of symptoms from index AFIB
  • American Society of Anaesthesiologists Score (ASA)
  • Signs of heart failure before CVS and on the day before CVS. Standard blood test (taken 24h before CVS) will be documented. Appropriate standard anticoagulation with unfractionated heparin (UFH) or acenocoumarol or direct oral anticoagulants (DOAC) is to be applied before and after CVS.

The patient will be in fasting condition before CVS. If needed, the chest will be shaved before CVS so that the self-adhesive defibrillation pads can be stick intact to the skin.

The anesthesia will be conducted by an anesthesiologist with slow intravenous injection of Propofol, adjusted individually to reach deep sedation. The individual Propofol dose (mg per kg bodyweight) will be documented.

CVS protocol:

The CVS procedure is performed in ICCU by a cardiologist and anesthesiologist. Defibrillator pads are placed according to the manufacturer user guides. Standard self-adhesive defibrillation pads, recommended by specific defibrillator's manufacturer will be used.

Defibrillator use: The time-interval interval between consecutive shocks is ≥ 1 minute; The energy of consecutive shocks follows pre-defined protocol; The protocol stops at successful CVS (sinus rhythm at 1 minute post-shock), otherwise at the last shock of the protocol.

Data collection and Follow up:

  • Defibrillator pulse recorder: The shock waveforms delivered by the studied defibrillators is recorded in real-time during the shock by a dedicated measurement recorder (Defimpulse) connected in the patient circuit. This allows accurate measurement of the delivered energy, which is the primary measured outcome. Additionally, currents, voltages, patient impedances at each shock can be also measured. The device is fully automatic and expert assistance is not needed during the CVS intervention. The use of the Defimpulse has been approved by the NHH Ethical Committee.

  • Blood samples, standard 12-lead ECG, blood pressure and heart rate is obtained at baseline.

  • Continuous ECG in 3 peripheral leads (I, II, III) is recorded during the CVS procedure. ST-segment deviation is measured on the first cardiac complex after 10 s post-shock 80 ms after J point in lead II.

  • Standard 12-lead ECG is recorded (5 minutes) after CVS; 24 h after CVS; at discharge if the discharge day is different from 24 h after CVS.

  • Heart rate and blood pressure are measured 3 times after CVS (immediately, 1 hour and 2 hours after the last shock).

  • Follow-up period in ICCU (2 hours of duration): Potential complications after CVS are recorded:

    1. Presence of apnea
    2. Presence of arrhythmias.
    3. Record of any other medication at CVS and during the follow-up period.
  • Follow-up period in the Cardiology Clinic (24 hours of duration):

    1. blood samples to analyze CK-MB and hsTnI (12 hours +/- 4 hours after CVS).
    2. Clinical exam with heart rate and blood pressure: 2 times on the day of CVS.
    3. ECG and blood pressure on the next day after CVS.
    4. Any complications before discharge.

Statistics:

Primary endpoint: The statistical analysis is designed for a non-inferiority comparison between the two defibrillators in respect of their cumulative energies actually delivered. A non-inferiority margin of 50J is chosen as the absolute difference in cumulative delivered energy at the end of the CVS study. It is estimated that a total of 62 patients (31 per group) allows a study power to show non-inferiority of 80%, with a one-sided type I error rate of 0.05.

Continuous variables (cumulative energy, number of shocks, cardiac troponin levels, etc.) will be expressed as mean value ± standard deviation or median values (inter-quartile range) and compared with Students t-test or equivalent non-parametric test, respectively. Categorical variables (e.g. cumulative success rate) are expressed as percentages and compared using the Chi-square or Fisher's exact test (where appropriate). P ≤ 0.05 is considered statistically significant for all comparisons.

Ethics All patients are signed a written informed consent prior to the CVS and receive the standard hospital procedures during CVS, accepted in the NHH and approved by the NHH Ethical Committee. Both defibrillators included in this study are approved for clinical use and both are used on a daily basis.

Data anonymization policy is respected. In order to ensure the medical confidentiality, no information about the patient (intervention place and date, age, gender, name, diagnosis, etc.) is entered in the defibrillators. An identification number are given to each patient by the dedicated measurement recorder (Defimpulse). This number and the recording data are properties of the principal investigator. Approval from the NHH Ethical Committee concerning the use of the Defimpulse during the CVS intervention has been obtained.

Enrollment

75 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

(indications for elective cardioversion of atrial fibrillation):

Patients > 18 years old and:

  • Symptomatic AFIB with a duration of less than 12 months - EHRA score 2-4
  • Symptomatic first detected AFIB - EHRA score 2-4
  • Persistent AFIB after successful causal therapy

Exclusion criteria

  • The patients are excluded if one of these conditions is present:

    • Patients with atrial flutter
    • Spontaneous HR <60/min
    • Digitalis intoxication
    • Impossibility to maintain sinus rhythm irrespective to antiarrhythmic therapy and frequent cardioversions
    • Conduction disturbances (without fascicular block and AV block 1 degree) in patients without pacemaker
    • Asymptomatic patients with AFIB for > 1 year
    • Thyroid dysfunction: euthyroid status of at least one month is required (TSH is measured).
    • Thrombosis in cardiac cavities, assessment performed using Transesophageal echocardiography (TEE)
    • Spontaneous echo contrast > 2 degree (TEE)
    • Patients with planned cardiac operation in the next three months
    • Patients with embolic event in the last three months
    • Patients <18 years of age
    • Pregnancy

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

75 participants in 2 patient groups

1 (DGT7)
Experimental group
Description:
Cardioversion with a pulsed biphasic waveform Cardioversion is performed by a pulsed biphasic (Multipulse Biowave®) waveform (Schiller Defigard Touch 7 - DGT7, Schiller Medical, France) with recommended by the manufacturer adult pads (FRED-PA1, Schiller) following an energy protocol of 3 consecutive shocks with constant selected energy: 200J, 200J, 200J. The protocol is stopped at successful cardioversion (sinus rhythm at 1 minute post-shock), otherwise after the 3rd shock. Primary endpoint: The cumulative energy delivered by the consecutive defibrillation shocks during cardioversion. Other Name: DGT7
Treatment:
Device: Schiller Defigard Touch 7 - DGT7, Schiller Medical, France
2 (LP15)
Active Comparator group
Description:
Cardioversion with a biphasic truncated exponential waveform Cardioversion is performed by a biphasic truncated exponential waveform (LIFEPAK 15, Physio-Control Inc., Redmond, WA, USA) with recommended by the manufacturer adult pads (Redipak QUICK COMBO, Physio-Control) following an energy protocol of 3 consecutive shocks with constant selected energy: 200J, 200J, 200J. The protocol is stopped at successful cardioversion (sinus rhythm at 1 minute post-shock), otherwise after the 3rd shock. Primary endpoint: The cumulative energy delivered by the consecutive defibrillation shocks during cardioversion. Other Name: LP15
Treatment:
Device: LIFEPAK 15, Physio-Control Inc., Redmond, WA, USA

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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