CRT-D versus CRT-P
CRT, as a treatment of HF, has been demonstrated the efficacy and safety
in patients with impaired LV function and a wide QRS duration
[4,28]. In clinical practice, a high proportion of death among HF
patients are due to electrical disturbances, which occur suddenly and
unexpectedly. ICD therapy is also recommended in those HF patients for
primary prevention to reduce the risk of sudden cardiac death and
all-cause mortality [7]. Due to the overlapped indication between
two therapies, combined treatment (CRT-D) are going to mainstream
gradually. Although no specific recommendation was given to clinicians
in choice of CRT-D or CRT-P, the majority patients of US underwent
implantation of CRT-D [29]. However, the only randomized trial
(COMPANION) did not show a significant difference in mortality between
CRT-D and CRT-P directly [4]. A recent meta-analysis, which pooled
unadjusted relative risk, revealed an association of additional ICD and
lower risk of all-cause mortality in CRT patients [5]. Nevertheless,
it is not confident to draw this conclusion unless significant
differences in clinical characteristics have been fully considered.
Moreover, rate of SCD declined substantially among HF patient with
reduced ejection fraction due to increasing use of evidence-based
pharmacotherapies [30]. It remains conflicting whether additional
ICD can still benefit HF patient receiving CRT.
Due to the absence of strong randomized evidences and recent
controversial results, we performed this meta-analysis using adjusted HR
to minimize the influence of patient selection bias. In included
studies, patients undergoing CRT-P are generally older, less often male
gender and less ICM, and these differences are all be corrected by Cox
multivariate analysis. Our work indicated a similar result which approve
the advantage of additional ICD on CRT patients, but the extent of
benefit is decreased compared with previous meta-analysis. Due to the
lack of guidance on device selection, clinical practice varies widely
around the countries and centers. A cause-of-death analysis of patients
with CRT by Marijon et al reported that no statistically difference in
SCD incidence between CRT-P and CRT-D, where only 13% patients
implanted CRT-D in secondary prevention. In our subgroup analyses, no
benefit was observed when we restricted CRT-D indication to primary
prevention [20]. A large observational study by Barra et al
suggested a low absolute risk of SCD among CRT patients [11], and
Ruwald et al reported a lower risk of ventricular arrhythmias in
responders to CRT [31]. Hence, as the cost add-on and inappropriate
shock therapy of ICD was brought to consideration [32,33], it may
suggest the unnecessity of ICD for CRT patients who did not experience a
ventricular arrhythmia causing haemodynamic instability, especially in
super-responders. In all included studies with less than 5 years
follow-up duration, CRT-D keeps benefits in mortality and there is small
amount of heterogeneity across the studies. Limited by few studies
reported long-term outcome and nonnegligible heterogeneity, it is still
unclear about the performance of CRT-D on long-term (≥5 years). More
studies are needed to illustrate it, which can provide clinical
implications to patients with long life expectancy. Although CRT-D did
not present an advantage in all-cause mortality in non-European
countries, we are more inclined to attribute this difference to
inconsistence of indication worldwide rather than racial difference
[34].
In recent studies, propensity score matching technique has been used in
observational studies to adjust for the influence of differences in the
clinical characteristics. With more consistent baseline characteristics
between CRT-D and CRT-P group, the pooled effect from four included
studies did not indicate a lower mortality in patients with CRT-D.
However, only part of studies reported HR after propensity matching, and
those studies also concluded insignificant results by using adjusted HR.
There may be a certain degree of publication bias at all. In addition,
another study including 11 925 CRT-P recipients and 59 534 CRT-D
recipients suggested no difference in survival between CRT-P and CRT-D
recipients, which used instrumental variable analysis to eliminate the
influences of confounders [35]. Different results from different
statistic methods offered us an assumption that additional ICD therapy
may not benefit CRT patients. As those methods can only eliminate
confounders we have known, strong evidence from randomized controlled
trials are urgently needed. We are anticipating the result of RESET-CRT
clinical trial (ClinicalTrials.gov number NCT03494933), which randomized
heart failure patients with LVEF≤35% and a CRT indication to either
CRT-D or CRT-P implantation.