3.3 High rate versus delayed therapy
Basal characteristics of the two randomized groups did not differ
between the groups (supplementary table 1). Patients in the high-rate
programming group had more frequently obstructive sleep apnea (19%
versus 5%, p=0.040) and less frequently history of stroke or TIA (6%
versus 21%, p=0.038). No other characteristics differ between the
groups.
Regarding primary endpoint, no programming strategy was better than the
other (HR 0.901, 95% CI 0.311-2.614, p=0.849 for delayed detection
programming). Also, for secondary endpoints no differences were found.
DISCUSSION
The concept of optimal ICD programming has evolved in recent years from
quick detection and treatment of VT/VF to a more permissive strategy, in
order to reduce avoidable shocks11. Demonstration of
an increased defibrillation threshold when VF was
prolonged14, concerns about undersensing and
underdetection of VF and its use in secondary prevention patients with a
higher risk of arrhythmic events were responsible for the idea of
programming of short interval for detection and treatment of rapid
tachycardia.
Nowadays, concepts have changed and the adverse effects of avoidable
therapies were emphasized. As such, an evidence-based programming is
recommended11. However, manufacturer-specific
translations of recommendations into clinical practice is not
straightforward and obtaining a universal (or almost universal)
programming to apply in clinical practice is not easy. However, for
clinicians who deal with defibrillator programming on a daily basis, it
would be more practical to have only one programming that could be used
across all manufacturers.
We have shown in the present study, that it was possible to program
defibrillators from all the five manufacturers with one of two
tachycardia configurations, based on high-rate or delayed detection.
Both strategies were effective and safe. As expected, due to the reduced
number of patients assigned in each arm no conclusion about the benefit
of one programming over the other could be obtained. Despite this fact,
when comparing the new programming group with a historical group of
patients treated in the same institution, some conclusions were drawn.
When comparing our interventional group (new programming) with our
historical group (conventional programming), the primary outcome (all
therapies) was significantly reduced by the new programming strategy. By
analyzing secondary outcomes, the reduction in the number of appropriate
ATP mostly accounted for these results. However, all shocks (appropriate
and inappropriate together) were also reduced. There was a trend for a
benefit regarding inappropriate shocks (HR 0.155, p=0.079), while
appropriate shocks were not minimized.
“Appropriate” ATPs were reduced in the new programming group. This is
expectable since ATPs were exclusively delivered in the FV zone (figure
1) while charging and it is also consistent with previous
studies4-10. Despite the fact that ATP can be
effective and avoids shocks15, it can also be
responsible for acceleration and degeneration to polymorphic VT or VF.
According to previous studies, ATP programming can cause acceleration of
VT or degeneration to VF in 1.2% to 21% of
patients15-16, being responsible for shock delivery
and even incessant electrical storm. The potential adverse effects of
using ATP only during charge, such as syncope, did not occur.
Avoidable” ATPs were almost eradicated in the new programming group,
suggesting that many episodes of nonsustained VT that would have
terminated spontaneously were treated prematurely in the conventional
programming group.
Inappropriate shocks affected 4% of patients in the new programming
group, a proportion similar to other studies3-9,
comparing to 9% in the conventional programming group. There was a
trend for a reduction in inappropriate shocks with the new programming
(HR 0.155, p=0.079), which would be expected considering previous
studies3-9. The absence of statistical significance is
probably related to the reduced number of events.
The total number of shocks was significantly reduced, but not the number
of appropriate shocks, which occurred in 5.6% of all patients. The rate
was independent of the programming, probably because they are
unavoidable, since these patients are at a high risk of SCD. The same
occurred in other studies, in which a minority of patients received
appropriate ICD shocks (3-6%) and no significant difference in the risk
of appropriate shocks was observed with new
programming3-9.
On the other hand, some reports raised the question of ineffectiveness
of ICD when specific tachycardia configurations are used. Differences in
sensing and detection methods among manufacturers may limit the
applicability of generic programming recommendations. An update of the
previous expert consensus statement was released in
201913, including manufacturer-specific translations
into clinical practice. Despite these recent concerns and the fact that
many patients were programmed with tachycardia configuration different
from those used in randomized trials, potential adverse effects did not
occur. The risks of applying these tachycardia settings, such as syncope
and arrhythmic death, were minimal. No syncopal episodes were detected
but two sudden deaths occurred, one of them in the new programming
group. In both patients it was not possible to have access to the EGM
and autopsy was not performed, so an arrhythmic cause for death was
possible but not certain. The patient belonging to the new programming
group was randomized to the high rate arm so his tachycardia
configuration was in accordance with MADIT-RIT, which efficacy and
safety have been previously demonstrated. Togerson et al reported that
in most patients in whom failure of ICDs to treat VF occurred, ICD
programming deviated from values validated in manufacturer-specific
clinical trials, although complying with the more generic
recommendations of the Consensus Statement12. This is
not what happened in our case since the patient had a programming in
accordance with a previous randomized trial4-5. In the
patient who died suddenly in the conventional programming group, it was
not possible to access tachycardia settings.
The number of deaths was high in our study (18%), comparing with
previous ones. Our population was older and had a higher incidence of
hypertension, diabetes and AF, which can explain this result. However,
the majority of patients died from non-cardiovascular causes. Probably
related to this fact, we found no benefits in mortality with new
programming. Others had found otherwise10 and
hypothesized that the significant reduction in appropriate and
inappropriate ATP and shocks may have contributed to the observed
mortality reduction. In fact, these studies change our concepts about
tachycardia programming by demonstrating a benefit in mortality rates
with ICD programming. In the present study, such an observation could
not be done. Nevertheless, the benefit of the reduction of all therapies
is per si enough to advice for such programming. Although not
translating into a survival benefit in our study, inappropriate shocks
are painful and associated with increased anxiety and
depression17, so every effort should be made to reduce
them.
Finally, the role of medical therapy in reducing the risk of SCD is well
established. Thus, recent studies highlighting the benefit of
defibrillators are influenced by the increasing use of these drugs
comparing to studies performed some years ago18. In
the present study, patients were receiving adequate medical therapy:
96% were taking ACEI/ARB/ARNI; 90% beta-blockers, 46%
mineralocorticoid receptor antagonists (MRA). These proportions are
comparable to controlled trials and better than recent
registries19. Only the proportion of patients under
MRA was higher in the new programming group (55% versus 37%, p=0.016).
Although MRA reduce the risk of SCD20, this difference
is unlikely to influence our results in what concerns device therapies.
The present study highlights the
benefits of having a structured protocol to program all patients with a
defibrillator implanted for primary prevention. Our principal finding is
that it was possible to program tachycardia settings across all device
manufacturers, while the reduction of all defibrillator therapies
without safety concerns was achieved.
LIMITATIONS
It was not a pure prospective study since it was performed a comparison
with historical controls in which the tachycardia settings were unknown
and not standard. However, since patients from the historical control
group were included after 2014, the ICD programming was probably in line
with the programming guidelines published in 201511.
It’s entirely possible that a proportion of the patients in this group
already received some form of contemporary programming, so the
difference between the conventional and novel program in groups could be
underestimated. If the historical group had been earlier, the benefit
would probably have been higher.
Also, in order to avoid selection bias that might result from the
exclusion of the so called “good patients” (namely those without
previous therapies), some of our study patients were also included in
the early historical control group. However, even with the inclusion of
these patients, who had defibrillators for a longer time and were free
from previous episodes of ICD therapies, we had found significant
differences in the studied endpoints.
It was not possible to determine the total number of ventricular events
for each group in order to understand if the number of ICD therapies has
been reduced due to less arrhythmic events or because of the new
programming configurations. This information was not available in the
conventional programming group.
Finally, due to the small number of randomized patients the analyses of
the relationship between device programming and endpoints in the high
rate and delayed detection groups had limited power.