ENHANCED device programming to reduce therapies and improve quality of life in Implantable Cardioverter Defibrillator patients: A prospective, single-arm safety monitoring study

Several studies on primary and secondary prevention of sudden cardiac death
have proved the benefit of implantable cardioverter defibrillator (ICD) therapy
in prolonging life (1-3). However, retrospective analyses of the mile stone
trials for primary prophylactic ICD therapy demonstrated that a reduction in
the incidence of sudden cardiac death was counterbalanced by an increased risk
in subsequent heart failure death (4). Especially patients who received
appropriate ICD therapy for ventricular tachyarrhythmia (VT) were at higher
risk for mortality due to heart failure (5). An ICD shock - whether appropriate
or inappropriate - was an independent risk factor for mortality in the SCD-HeFT
trial (6). A meta-analysis revealed that "ICD shocked" patients had a poorer
survival compared with anti tachycardiac pacing (ATP)-only treated patients
(7). Shocks have also been shown to impact adversely on quality of life and
symptoms of anxiety and depression (8), although the evidence for an adverse
effect of shocks on quality of life and distress is not consistent even in the
major primary and secondary prevention trials that included quality of life as
a secondary outcome measure (9). Moreover, there is increasing evidence that
the psychological status and profile of the ICD patient is an important
determinant of both the onset of VT (10,11) but also survival (12-14).

To improve the prognosis and quality of life of ICD patients, a reduction of
ICD shocks whether appropriate or inappropriate is necessary. One already known
possibility to reduce shocks is programming ATP for fast VT's (15), but in
comparison to shock delivery ATP started without delay and an unknown number of
non-sustained VT's might be unnecessarily treated by the ICD with the risk of
converting the VT into VF. In the shock arm of the PAINFREE II trial 34% of the
fast VT's did not need any ICD therapy because of spontaneous termination
during capacitor charging. In the non-randomized PREPARE study, it was shown
that with the prolonging of the VT/VF detection (30/40) the number of
appropriate and inappropriate shocks could be significantly reduced (16).
However, also in this trial an unknown number of non-sustained fast VT's were
unnecessarily treated because ATP was delivered in less than 10 s. Although
SVT/VT discrimination was enabled, 30% of the shocks were caused by SVT's.

An Enhanced ICD programming strategy, as defined below, might further reduce
ICD-shocks, improve quality of life, and survival of ICD patients:

Enhanced ICD strategy:
• enhanced VT/SVT discrimination
• prolonged VT/VF detection to support spontaneous termination of VT/pVT
• not to treat hemodynamic stable VT's in which ATP may accelerate the VT into
a life-threatening VT or VF

Primary objective:
• To investigate whether Enhanced programming is safe for primary and secondary
prevention patients

Secondary objectives:
• Investigate the impact of Enhanced programming on adverse events (related to
ICD shock with consequences and related to syncopal/near syncopal events)
• Investigate the impact of Enhanced programming on ATPs/shocks
(appropriate/inappropriate; successful/unsuccessful).
• Investigate the impact of Enhanced programming on quality of life and
distress (i.e., anxiety/depression)

The study is set up as a prospective, single-arm safety monitoring study. The
device follow-up assessments will take place at 2-, 6- and 12 months post
implantation, and every 6 months afterwards until the last included patient has
completed the 12 month follow-up. Patients will complete a questionnaire
booklet at baseline (1 week - 1 day prior implantation), 3-, 6- and 12-months
post-implantation.

- Enhanced ICD programming:
VT monitor: > 166/min
fVT: > 182/min; via VF 60/80 intervals (number of intervals to start ATP after
approximately 20 s); 3 x ATP (8 stimuli, 88%, scan 20 ms); shock 1-5: 35 J;
redetection 30/40 intervals
VF: > 250/min; via VF 60/80 intervals (number of intervals to start therapy
after approximately 15 s); 1 x ATP (8 stimuli, 88%) during charging; all
shocks: 35 J; redetection 30/40 intervals

SVT/VT discrimination is turned on, high rate time out is *OFF*
SVT/VT discrimination single chamber: stability, wavelet; SVT upper rate limit:
222/min
SVT/VT discrimination dual/triple chamber: P/R logic, wavelet; SVT upper rate
limit: 222/min
T-wave oversensing and lead noise discrimination is turned on in all devices

1) In patients with known sustained VT*s the VT zone may be programmed to lower
heart rates or ATP/shock therapy may be programmed in the VT zone when
hemodynamic instability is expected.

We expect that the Enhanced programming strategy will lead to a reduction in
ICD therapy with subsequent benefits to the quality of life and well being of
patients. However, because of the longer detection duration, patients with an
the Enhanced programming face a slightly higher chance of feeling heart
palpitations and getting unconscious during fast rhythm disturbances. The risk
associated with participation in the study is therefore estimated to be
moderate. Since the ENHANCED-ICD trial is a safety study, additional unexpected
adverse effects may be possible. However, if there should be a medical
indication for a more conventional ICD programming in a subject with an
Enhanced programming, the programming will be adapted immediately, to ensure
the safety of the patient.