Discussion
In this prospective cohort of patients with heart failure and classic
indication for CRT, with a high number of individuals with Chagas
cardiomyopathy, upgraded therapy was independently associated with
worsened 1-year survival after CRT implantation. Besides that, CC was
also associated with worse prognosis in follow-up.
Patients submitted to the upgraded CRT implantation had similar
clinical, echocardiographic and demographic characteristics when
compared to the population of De novo CRT, only differing with a higher
prevalence of Chagas cardiomyopathy. We observed a high prevalence of
patients with advanced HF, with a mean LVEF below 25% and most patients
classified as NYHA III-IV. There was no loss of follow-up and use of
evidence-based medical therapies was higher than most previous
CRT-trials. 7-8 Furthermore, the indication for CRT
was consistent with guideline-based recommendations, with almost all
patients presenting with LBBB (induced or spontaneous) and
QRS> 150ms. Unlike previous studies comparing De novo CRT
vs upgraded, we found no difference regarding the prevalence of atrial
fibrillation or QRS duration between both groups. 5,9
In general, CRT was effective in improving systolic performance with a
significant increase in LVEF. This left ventricular reverse remodeling
occurred consistently in both groups, and it is in accordance with a
recently published meta-analysis that demonstrated similar rates of
improvement in LVEF in patients undergoing upgraded and de
novo -CRT. 10
We observed a high overall mortality in 1-year follow-up of 30.1%,
mainly in the upgraded-CRT group. In univariate analysis, Chagas disease
and upgraded-CRT were directly associated with overall mortality in
1-year. The principal find of our study was that in the multivariate
model, upgraded therapy was the only variable associated with the
primary outcome. This result, and the excessive mortality-rate in the
upgraded group, is consistent with the study of Vamos M et al, that
followed 552 CRT implantations, including 177 upgrade procedures, and
found a 1.65-fold increased mortality.5 Similarly, the
cohort of Beca B et al, found a long-term mortality rate 2.86-fold
increased.11 On the other hand, this data differs from
previously mentioned meta-analysis, and the European CRT survey, that
demonstrated that CRT upgrade is associated with similar risk for
all-cause mortality compared to De novo resynchronization
therapy.9
Some factors may justify these findings, firstly, it has been suggested
that CRT upgrade procedures are associated with increased
peri-procedural complications. In fact, all in-hospital deaths of our
study occurred in the upgraded-CRT group and was directly related to the
procedure. However, our sample size was not sufficient to test this
hypothesis. Data comparing the rates of complications following CRT
upgrade versus de novo CRT are limited and inconsistent. In a
large European CRT Survey of 11088 patients, and 2396 (23.2%) upgrade
procedures, overall peri-procedural complication rates were similar
between upgraded-CRT and De novo CRT.12 In contrast,
Cheung JW et al, using the United States National database, identified a
significantly higher rate of complications in CRT upgrade patients
compared to de novo CRT patients with a two-fold increased risk of
in-hospital mortality.6
Another hypothesis is that patients in the upgrade group had more
advanced heart disease and more comorbidities. In our series, upgraded
patients had a trend to be older, with slightly lower left ventricular
ejection fraction and higher prevalence of NYHA III and IV, despite the
lack of statistical significance when they were compered to De novo CRT
group. Perhaps, the indication for biventricular pacing was too late in
this group and was associated to a worse prognosis.
Finally, the presence of Chagas cardiomyopathy may interfere in patient
survival. CC has more severe heart dysfunction and worse clinical
management, mainly due to its etiopathogenesis and worse ventricular
remodelling, with a higher incidence of death from advanced heart
failure and arrhythmic causes.13-14 Particularly in
patients undergoing CRT, it has been consistently demonstrated that
Chagas cardiomyopathy has a worse prognosis when compared to other
dilated cardiomyopathies. Martinelli et al showed that Chagas disease
had a two-fold higher risk of death in one-year compared to the others
dilated cardiomyopathy.15 Simirlaly, Passos, et al
also demonstrated a worse prognosis in combined events in patients with
Chagas cardiomyopathy after CRT.16
It is important to emphasize that, since intrinsic LBBB in Chagas heart
disease is uncommon, and it is considered an arrhythmogenic
cardiomyopathy characterized by a wide variety of abnormalities of the
conduction, it is expected a higher incidence of upgraded-CRT
implantation in this patients. In fact, in the cohort presented by
Martinelli et al, there was a 73.9% incidence of induced-LBBB in
Chagas’ disease patients undergoing CRT.15 In our
study, 72.7% of patients undergoing upgraded-CRT implantation had
Chagas cardiomyopathy.
This is the first study that analysis the impact of the upgraded-CRT on
mortality in a population where Chagas disease is a prevalent cause of
cardiomyopathy. In fact, it is known by previous publications that CC
was directly associated with an increase in short-term mortality after
CRT implantation. However, after multivariate analysis adjusted for
potential confounders in our analysis, it is suggested that this worse
prognosis may be due to the higher incidence of upgraded-CRT. Studies
with larger cohorts of patients with Chagas cardiomyopathy are necessary
to confirm this hypothesis. Until then, considering the current
scientific evidence, patients with HF secondary to Chagas disease and
previous ventricular pacing, must have the indication for the upgrade
procedure evaluated with great caution.
This study has some limitations. We emphasize the unicentric design of
the study, which may impact in its external validity. Additionally, it
is a non-randomized study that generates hypothesis and is exposed to
confounding bias. Finally, the limited sample size makes the study
vulnerable to type 1 error.