A 70-year-old man with a single-chamber implantable
cardioverter-defibrillator (ICD) presented because his ICD was nearing
the end of battery life. The ICD, implanted 8 years ago for primary
prevention of sudden cardiac death (SCD), has not delivered any
appropriate therapies. His left ventricular ejection fraction (EF),
which was 30% at the time of ICD implantation, has improved to 45%
since then. Is the ICD generator replacement justified?
Approximately 30,000 ICD generator replacement procedures are performed
in the US annually for nearing the end of battery life (ERI),
constituting 28% of all ICD procedures.1,2 While it
is common practice to routinely replace ICDs that reach ERI, several
factors may limit or accentuate their future potential benefit: First,
patients presenting for ICD generator replacement are older and have
more comorbidities than those having initial ICD implant, increasing the
competing risks of death from non-cardiovascular causes. Indeed, 10% of
the patients who underwent ICD replacement die after one year and up to
50% die after five years from causes that the ICD therapies cannot
treat.1 Second, they may have had appropriate ICD
therapies for ventricular tachycardia or ventricular fibrillation
(VT/VF), increasing the likelihood of future VT/VF. The patients who had
appropriate ICD therapy are usually considered to have a secondary
prevention indication for ICD from that point on. Third, they may have
had an improvement in left ventricular ejection fraction (EF) since ICD
implantation, reducing the likelihood of future
VT/VF.3,4
Left ventricular EF is the cornerstone of the criteria used in the
decision for ICD implantation for primary prevention of SCD.
Professional society practice guideline statements recommend ICD
implantation in patients with EF ≤35% and mild to moderate heart
failure symptoms while taking optimal medical therapy. However, 30-40%
of the patients with a primary-prevention ICD experience an improvement
in their EF to the extent that they are no longer eligible for ICD when
they present for generator replacement.3,4 Patients
who experience an improvement in EF are younger, more likely to be
women, more likely to be taking heart failure medications, and more
likely to have non-ischemic cardiomyopathy.3,4 While
there is a close audit of indications at initial ICD implantation
routine re-assessment of ICD indications is not mandated when these
patients present for ICD generator replacement. Identifying the patients
who are least likely to benefit from continued ICD therapy may
significantly reduce procedure-related risks and cost, by avoiding
unnecessary ICD generator replacement.
In this issue of the journal, Chang et al. present the results of a
retrospective cohort study evaluating the risk of appropriate ICD
therapies in 423 patients who underwent ICD generator
replacement.5 Notably, all ICDs were implanted for
primary prevention of SCD and no patient had received appropriate ICD
therapies in the past. The analyses were adjusted for competing risk of
death. At the time of generator replacement 38% of the patients had EF
≥35%. The risk of appropriate ICD therapy was 2.13 times higher in
patients whose EF remained <35% in comparison to those with
EF improvement to ≥35% (Fine-Gray adjusted 5-year event rates 25.0%
vs. 12.7%, respectively; p=0.002). While the EF was a poor predictor of
future appropriate ICD therapy (c-index 0.62), risk stratification was
better at EF cutoff 45%. Patients whose EF was <45% had a
4.42 times higher risk of appropriate ICD therapy compared to those with
EF ≥45% (Fine-Gray adjusted 5-year event rates 25.1% vs. 6.4%,
respectively; p<0.001). These associations were also observed
in subgroups with or without ischemic cardiomyopathy and in those with
or without cardiac resynchronization therapy.
These results are in line with prior cohort studies. In a retrospective
cohort study conducted in a similar cohort almost a decade earlier,
Madhavan et al. reported 12% versus 5% annual risk of appropriate ICD
therapy after generator replacement in patients with EF <35%
vs. ≥35%, respectively.6 In other cohort studies
improvement in EF was associated with a significant reduction in the
risk of appropriate ICD therapy, but was not eliminated, ranging from
2.8% to 5% per year.3,4 The persisting risk of
arrhythmias, observed in some patients despite improvement in EF may be
partly explained by the presence of a fixed substrate for ventricular
arrhythmias (e.g., fibrosis, myocardial scar, heterogeneous
repolarization) that does not resolve even when EF improves. However,
none of the prior studies assessed the risk of ICD therapy using an EF
cutoff 45% and none provided event rates adjusted for the competing
risk of mortality. As such, the study by Chang et al.5advances the field significantly.
Do ICDs save lives if the EF has improved to ≥35%? In a secondary
analysis of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Adabag et al. found that both patients with EF improvement to ≥35% and
those whose EF remained <35% accrued a similar relative risk
reduction in mortality with ICD compared to placebo (hazard ratio 0.6 in
both groups), suggesting that ICD generator replacement may reduce
mortality even after EF has improved to ≥35%.7However, post-hoc analyses of old randomized trial data cannot replace
the need for prospective randomized controlled trials.
At the time ICD reaches ERI, patients and their physicians may use
varying criteria to decide whether to undergo/perform generator
replacement, considering the patient’s age, comorbidities, and competing
risks of death. While the risk of future VT/VF is never zero, each
individual patient may have their own threshold of risk below which they
would choose to forgo generator replacement. Ideally, the possibility of
not replacing the ICD generator when the device reaches ERI should be
introduced at the initial implantation.
Patients who present for ICD generator replacement should be
re-evaluated for the appropriateness of continued ICD therapy. The
evaluation should exclude any potential contraindications, such as
advanced malignancy or dementia, that may have developed since the
initial implant. A validated mortality risk prediction score may
facilitate the discussion by providing an objective estimate of the
patient’s mortality risk.8,9 A frank discussion to
learn the patient’s wishes for end-of-life care in relation to continued
ICD therapy is of utmost importance to help guide the decision and to
clarify potential misconceptions. Older patients who have developed
competing risks of death due to new comorbidities (e.g., renal failure)
or those with frailty, disability or cognitive dysfunction should have
an opportunity to reevaluate continued ICD therapy with an extensive
discussion of goals of care.10
We propose an algorithm to guide ICD generator replacement decision
(Figure). At the time of ERI, we recommend replacement of the generator
if the original indication for ICD was secondary prevention of SCD. The
risk of appropriate ICD therapy is higher (10%/year versus 5%/year) if
the ICD was implanted for secondary prevention of SCD. We also recommend
generator replacement if there was an appropriate ICD therapy (shock or
anti-tachycardia pacing) in the past. Patients whose EF remains ≤ 35%
continue to be at SCD risk and should undergo generator replacement if
they wish to continue ICD therapy. On the other hand, patients with EF
improvement deserve a fair discussion of whether the SCD risk warrants
continuation of ICD therapy. Some patients with normalized or
close-to-normal EF may not have sufficiently high risk of VT/VF to
benefit from continued ICD therapy. Patients with non-ischemic
cardiomyopathy have a lower risk of SCD and may not benefit from ongoing
ICD therapy if EF has improved.11 On the other hand,
patients with a prior myocardial scar may continue to benefit from ICD
even if their EF is better.
Despite the informative results from the present and prior studies, some
questions remain regarding the management of patients with improved EF
presenting for ICD generator replacement. Does the use of modern-day
heart failure therapy, specifically sacubitril/valsartan and
sodium-glucose transporter-2 inhibitors, confer even lower risk of ICD
therapy? The field continues to evolve. In this regard, data from the
study by Chang et al.5 will be very valuable, to
facilitate the discussion between patients and their physicians.