DISCUSSION
This study demonstrates that a considerable fluctuation of EF occurs
among patients with EF ≤ 35%, changing their ICD eligibility status
over time. After one year, almost 40% of patients with EF ≤35%
experienced a >10% improvement in EF. But over the next
1.4 years, approximately 25% of those who had an improvement in EF lost
their gains returning back to EF ≤35%. While the fluctuation in EF was
present in both ischemic and non-ischemic cardiomyopathy, a larger
proportion of those with non-ischemic cardiomyopathy had an improvement
in EF and a lower proportion had subsequent reduction. These results may
explain the root cause of continued SCD risk after EF improvement.
Several previous studies have shown that 30-40% of patients with ICD
experience a substantial improvement in EF post-implantation. Our
results support these previous observations.2–4Presumed to be from continued medical therapy, improvement in EF was
associated with a lower incidence of appropriate ICD therapy in
comparison to those whose EF did not change.1,3–6Similar observations were also made among patients with cardiac
resynchronization therapy, suggesting that EF improvement is associated
with better outcomes regardless of its etiology.11These studies raised the question of whether ICD generator should be
replaced at the end of battery life among patients with EF improvement.
Recently, in a post hoc analysis of SCD-HeFT we demonstrated that
patients with a substantial improvement in EF appeared to have a similarsurvival benefit from ICD in comparison to those who did not
demonstrate EF improvement.7 To date, this is the only
comparison of survival in relation to ICD among patients with EF
improvement. The results from the present investigation suggest that
recurrence of cardiomyopathy among patients with recovered EF may be the
culprit for the continued benefit of ICD among these patients.
Cumulatively these results support ICD generator replacement at the end
of battery life regardless of EF.
Recently, Lupón et al. examined the prognostic impact of the
dynamic changes in EF over a 15-year follow-up in a prospective,
consecutive, observational registry of outpatient heart failure
patients.12 They found that the majority of patients
had a marked rise in EF during the first year, maintained up to a
decade, followed by a slow EF decline thereafter. Our findings add to
this literature by showing that fluctuation in EF around the cut-off
35% may influence clinical decisions on ICD therapy. The present data
also showed that while the mean EF was stable between the
1st and 2nd follow-up (31.7% vs.
32.6, respectively). there remained significant fluctuation in
~25% of the cohort, which had potential treatment
implications for those patients.
Patients with non-ischemic cardiomyopathy were more likely to experience
an improvement in EF in this and previous
cohorts.2,3,12 Absence of large myocardial scar volume
may be responsible from this observation.12,13 Lupón
and colleagues showed that while ischemic heart failure patients showed
a modest EF increase during the first year of medical therapy those with
non-ischemic heart failure had a more pronounced
improvement.12 Further, those with non-ischemic heart
failure had a more prolonged increase during follow-up after one year
than ischemic heart failure patients.12 Collectively,
these results may help us understand the lack of survival improvement
with ICD therapy among patients with non-ischemic
cardiomyopathy.14,15
While medical therapy for heart failure is responsible for improvement
in EF, less is known about factors that lead to re-worsening of EF after
an improvement. Recently, the TRED-HF study examined whether patients
with dilated cardiomyopathy could discontinue heart failure medications
after recovery of cardiac function, which was defined as being
asymptomatic, EF increasing from < 40% to >
50%, normalization of left ventricular end diastolic volume, and
decreasing of N-terminal pro-B-type natriuretic peptide to <
250 ng/L.16 These researchers found that
cardiomyopathy relapsed in 44% of the patients following withdrawal of
medical therapy versus in no patients who continued heart failure
medications, suggesting that heart failure treatment should be continued
indefinitely.16 Our analysis adds to these data by
showing that EF trajectory may be volatile even with continued medical
therapy.
Patients with normalization of EF constitute a special subgroup. Based
on limited data the risk of appropriate ICD therapy is very low in these
patients.4,11 However, in a small prospective study,
Cioffi et al. showed EF normalization to be a transient finding in 55%
of their patients, with the effect lasting a mean duration of 15 ± 5
months.17 In our study, only 3% of patients
experienced a rise in EF to >55%. Similar to the Cioffi
study, 56% of our patients had a subsequent drop in EF of
> 10%. This suggests that normalization of EF is not
equivalent to a cure of HF, but rather remission as a significant
proportion of these patients remain at risk for relapse and
SCD.18–20