Minimal Defibrillation Threshold in Patients with a Subcutaneous Implantable-Defibrillator.

Implantable cardioverter defibrillators (ICDs) have proven to be effective in
treating life-threatening ventricular arrhythmias. For Transvenous ICDs
(TV-ICD) many studies have been performed on defibrillation treshold (DFT) and
programming a shock output with a safety margin of 10J above the DFT is
considered safe and effective (9). The relatively new subcutaneous ICD (S-ICD)
is implanted entirely extracardiac. Due to the extracardiac design the S-ICD
requires a higher energy output compared with the TV-ICD. The shock output of
the S-ICD is based on the results of defibrillation thresholds (DFT) tests in
two early acute studies with temporarily implanted S-ICDs following a step-down
protocol. The average DFT was 32.5J ± 17.0J determined by testing 61 patients
in the first study and 36.6J ± 19.8J determined by testing 49 patients in the
second study. Based on these results, the default shock output of the S-ICD was
set at 80J, which is higher than in TV-ICDs.

Since the first, and only, S-ICD DFT studies were performed, significant
progress has been made in the understanding of factors which influence the DFT
in S-ICD patients. Three of the major components are the amount of fat tissue
underneath the coil, the amount of fat tissue under the can and the placement
of the S-ICD generator towards anterior on the thoracic wall. Multivariable
analysis showed a high Body Mass Index (BMI) as the only predictor for failing
a DFT test. With this knowledge implanting physicians have improved their
technique of implantation and are taking these factors into consideration.
Besides this acquired knowledge on DFT testing in S-ICD patients, a learning
curve was demonstrated for both implanters and institutions with a significant
higher complication rate, including failed DFTs, in the first 15 patients. The
effect of the improved implant technique on the average DFT has not been
examined.

As the DFT in S-ICD patients is higher than in TV-ICD patients, higher output
is required. However the DFT in S-ICD patients is expected to be lower than in
the first studies due to the improvements in S-ICD implant technique. This is
relevant and valuable information as with a lower average DFT , a lower shock
output is required. A lower programmed shock output, could result in an
increased battery longevity. Moreover, for a high shock output a large battery
is required. To accommodate the S-ICDs* larger battery size the S-ICD generator
is 59.5 cc. The average TV-ICD generator has a volume of 30-40 cc with a shock
output ranging from 36J to 46J. When lower shock output is required, battery
size can be reduced, providing an opportunity for the development of smaller
S-ICD generators in the future.

In this study, we assess the lowest energy which successfully converts the
induced ventricular arrhythmia following a predetermined step-down protocol, to
explore whether the average DFT in S-ICD patients is lower than previously
reported in the first acute S-ICD implants(4).

To determine the lowest energy which successfully converts induced ventricular
arrhythmias in S-ICD patients.

Type of study
This study is a prospective non-randomized single-arm study. In this study a
standardized step-down DFT protocol will be used to obtain accurate DFT data
with the use of a minimal number of shocks. Performing a step-down DFT protocol
is a commonly used method during implant, which does not expose patients to an
increased risk. The specific steps in the step-down protocol have been
pre-determined for this study.

Sample size and power calculation
To determine the average DFT in S-ICD patients we will included 12 patients in
this single arm study. A sample size of 12 patients is recommended in studies
for which no prior information is available to base a sample size on.
Therefore twelve patients will provide sufficient information on mean and
variance.

Study intervention
There will be no new intervention in this study. Patients will be tested with
lower shock output than current standard of practice of two conversion tests at
65J according to the step-down protocol determined for this study. Patients
receive a first conversion test with 30J. If 30J shock is not successful the
patient will be converted by an external defibrillator. The next energy tested
will be increased by 20J to 50J, after which a 40J test will performed if the
50J test is successful. In case of failure at 50J, the next step will be to
test at 70J. If conversion fails with 70J the patient will be treated according
to standard of care in patients with failed conversion tests.
Standard of care in these cases will include a chest X-ray to determine whether
air is trapped around the S-ICD coil or generator and determine if the device
needs to be repositioned.

Study materials
- No additional study materials will be used in this study as all patients were
already scheduled to undergo defibrillation testing.

Follow-up
Follow-up in this acute study design stops at discharge.

Statistical analysis
Continuous variable are tested for normality. Values presented are means with
standard deviations or median with interquartile ranges. Dichotomous data are
presented as proportions and compared with the Fisher*s exact test. Statistical
significance is set at an alpha-level of 0.05. Statistical analysis are perform
in R 3.3.3., R Foundation, Vienna, Austria.

Benefits and risks
The participant will not benefit directly from this study, although a lower
defibrillation threshold could mean that the shock output will be programmed
lower than 80J in the future, which is currently standard of practice. Battery
longevity increases with lower shock output if S-ICD therapy is given. There
are no additional limitations or visits required for this study. The study does
not increase the risks associated with ICD implantation or generator
replacement nor does it increase the radiation burden. ICD implantation and
subsequent defibrillation threshold testing are done as part of routine
clinical care, the total shock output of defibrillation testing in this study
protocol will be lower than the standard of 2 x 65J currently considered
standard of practice. Additional defibrillation tests will be performed
following a step-down protocol as shown in figure 3. For the majority of
patients two shocks will be required, with a lower total output than the
current standard of practice, which is 2 shocks of 65J, a total of 130J. In a
small percentage of patients three of four shocks will be required to determine
the minimal defibrillation threshold, however, the total amount of energy
according to the study protocol will not exceed 150J.

Risks discussed with the participants:
What will be discussed with the patient is: that defibrillation testing is
being performed as routinely during implantation of the S-ICD. In this study
protocol we will determine the actual defibrillation threshold using a
step-down protocol instead of performing two defibrillation tests at 65J. For
the majority of patients this will require two conversion tests at lower output
than 65J. A small proportion of patients will require three or four conversion
test to determine the actual defibrillation threshold. In these patients the
maximum amount of energy given will not exceed 150J.