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Mortality and Heart Failure Hospitalization in Patients With Conduction Abnormalities After Transcatheter Aortic Valve Replacement
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 12, NO. 1, 2019
ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Mortality and Heart Failure Hospitalization in Patients With Conduction Abnormalities After Transcatheter Aortic Valve Replacement Troels H. Jørgensen, MD,a Ole De Backer, MD, PHD,a Thomas A. Gerds, DRRERNAT,b Gintautas Bieliauskas, MD,a Jesper H. Svendsen, MD, DMSC,a,c Lars Søndergaard, MD, DMSCa,c
ABSTRACT OBJECTIVES The aim of this study was to assess mortality and rehospitalization in patients with new bundle branch block (BBB) and/or permanent pacemaker (PPM) after transcatheter aortic valve replacement (TAVR). BACKGROUND Previous studies have provided inconsistent results on the clinical impact of new BBB or new PPM after TAVR. METHODS A total of 816 consecutive patients without pre-procedural BBB or PPM undergoing TAVR between 2007 and 2017 were followed for 5 years or until data extraction in September 2017. Data on vital status and hospitalization were obtained through national registries. RESULTS Within 30 days post-TAVR, new BBB without PPM and new PPM occurred in 247 (30.3%) and 132 (16.2%) patients, respectively, leaving 437 patients (53.6%) without conduction abnormalities. Median follow-up was 2.5 years (interquartile range: 1.0 to 4.9 years). One-year all-cause mortality was increased for new BBB (hazard ratio [HR]: 2.80; 95% confidence interval [CI]: 1.18 to 3.67) but not for new PPM (HR: 1.64; 95% CI: 0.72 to 3.74) compared with patients with no conduction abnormalities. The risk for late all-cause mortality ($1 year after TAVR) was higher both for patients with new BBB (HR: 1.79; 95% CI: 1.24 to 2.59) and for those with new PPM (HR: 1.58; 95% CI: 1.01 to 2.46) compared with patients with no conduction abnormalities. Patients with new BBB (HR: 1.47; 95% CI: 1.02 to 2.12) and new PPM (HR: 1.66; 95% CI: 1.09 to 2.54) had a higher risk for heart failure hospitalization and reduced left ventricular ejection fraction (p < 0.0001 for both groups) during follow-up. CONCLUSIONS New BBB and new PPM developed frequently after TAVR. New BBB was associated with increased early and late all-cause mortality, whereas new PPM was associated with late all-cause mortality. Furthermore, both new BBB and new PPM increased the risk for heart failure hospitalizations. (J Am Coll Cardiol Intv 2019;12:52–61) © 2019 by the American College of Cardiology Foundation.
I
ncreased operator experience and improved
more than mild paravalvular regurgitation (PVR) and
transcatheter heart valve (THV) design are
mortality was an early recognized potential Achilles’
among factors that have reduced the risk for
heel of TAVR (4). As a consequence, both manufac-
transcatheter
aortic
valve
replacement
(TAVR)–
turers and operators have had a strong focus on
related complications (1–3). The association between
reducing the rate of PVR. However, preventive
From the aDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
b
Section of
Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and the cDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Dr. Jørgensen has received a research grant from Edwards Lifesciences. Dr. Sondergaard has received consulting fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. Dr. Svendsen is on the advisory board of Medtronic; has received speaking fees from Medtronic and Biotronik; and has received an institutional research grant from Medtronic, Biotronik, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received August 13, 2018; revised manuscript received October 25, 2018, accepted October 30, 2018.
ISSN 1936-8798/$36.00
https://doi.org/10.1016/j.jcin.2018.10.053
Jørgensen et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 1, 2019 JANUARY 14, 2019:52–61
measures against PVR, such as the introduction of
PPM (patients who underwent PPM implan-
ABBREVIATIONS
sealing skirts, more liberal THV oversizing, and
tation within 30 days after TAVR, regardless
AND ACRONYMS
post-dilation, are risk factors for the development of
of the presence or absence of new BBB).
BBB = bundle branch block
conduction abnormalities (CAs) after TAVR (2,5).
On the basis of the nationwide registries,
This might explain why induction of left bundle
the primary endpoint was all-cause mortality.
branch block (LBBB) and implantation of a permanent
Secondary outcomes were first hospitaliza-
CI = confidence interval
pacemaker (PPM) remain frequent complications af-
tion and recurrent hospitalizations for heart
HR = hazard ratio
ter TAVR, seen in 10% to 30% of patients depending
failure or all-cause admissions. Hospitaliza-
IQR = interquartile range
CA = conduction abnormality
on the type of THV implanted (1,3,5–8). Still, the clin-
tion for heart failure was classified if the
LBBB = left bundle branch
ical impact of TAVR-induced CAs remains controver-
following
block
sial, as new-onset LBBB and post-procedural PPM
Diseases-10th Revision codes were registered
International
Classification
of
have shown inconsistent effects on mortality and
during admission: I11.0, I13.0, I13.2, I42.0,
heart failure after TAVR (5,7,9–19).
I42.1, I42.2, I42.9, and I50. Date and indica-
The aim of the present study was to investigate the incidence of TAVR-induced new-onset bundle branch
tion of PPM implantation were identified through the Danish Pacemaker Registry.
block (BBB) and new PPM implantation as well as
Patients were followed until the date of
their impact on all-cause mortality and hospitaliza-
death or the date of data extraction from the
tion
nationwide registries in September 2017, with
for
heart
53
Complications of TAVR-Induced Conduction Abnormalities
failure
in
an
all-comers
TAVR
population.
a maximum of 5 years of follow-up. SEE PAGE 62
METHODS
LVEF = left ventricular ejection fraction
PPM = permanent pacemaker PVR = paravalvular regurgitation
RBBB = right bundle branch block
RVP = right ventricular pacing TAVR = transcatheter aortic valve replacement
THV = transcatheter heart
STATISTICAL
ANALYSIS. Categorical
vari-
valve
ables are expressed as counts and percentages and were compared using chi-square-tests.
The present study was a prospective single-center
Continuous variables are expressed as mean SD,
study. All consecutive patients who underwent
compared using analysis of variance and paired Stu-
TAVR at Rigshospitalet, Copenhagen University Hos-
dent’s t-tests, or median (interquartile range [IQR]),
pital, Denmark, from 2007 to 2017 were included.
compared using Kruskal-Wallis tests. Time zero for all
Patients with pre-procedural BBB or PPM, those with
survival analyses was set at 30 days post-TAVR. The
missing pre- or post-procedural electrocardiographic
exposure variable (new BBB or new PPM vs. no CAs)
data, and those who emigrated were excluded. The
was defined at time zero. The median follow-up time
study was approved by the Danish Data Agency and
was
Danish Patient Safety Authority.
method (22). All-cause mortality was analyzed using
DATA SOURCE. Baseline and periprocedural charac-
teristics were collected from electronic patient records. Pre- and post-procedural electrocardiographic data were validated in all patients. QRS interval $120 ms was defined as BBB and further classified into LBBB and right BBB (RBBB) (20). All Danish permanent residents are assigned a unique personal identification number, which is linked to nationwide administrative registries (21). In the Civil Registration and National Patient Registry, vital status and hospitalization information on date of admission and discharge, and codes for diagnosis and procedures are registered. Date and indication of PPM implantation are registered in the Danish Pacemaker Registry.
calculated
using
the
reverse
Kaplan-Meier
the Kaplan-Meier method and the log-rank test. The absolute risk for first heart failure hospitalization (with death without heart failure being a competing risk) was analyzed using the Aalen-Johansen method and Gray’s test. Cox regression was used to analyze the association of exposure with all-cause mortality rates and rates of first heart failure hospitalization. The models were adjusted for sex, age at date of TAVR as a continuous variable, history of ischemic heart disease, need for dialysis at admission for TAVR, chronic obstructive pulmonary disease, diabetes mellitus, pre-TAVR left ventricular ejection fraction (LVEF), and type of implanted THV. A landmark analysis was performed for all-cause mortality 1 year after TAVR. The KaplanMeier estimates were computed among 1-year survi-
FOLLOW-UP. Patients were classified into 3 groups:
vors, and the exposure hazard ratio (HR) was allowed
no CAs (patients without BBB on the last available 12-
to change after 1 year in Cox regression. The impor-
lead electrocardiogram or PPM within 30 days after
tance of the exposure time interaction (allowing a
TAVR), new BBB (patients with new-onset LBBB or
change of HR after 1 year) was tested using a likeli-
RBBB on the last available 12-lead electrocardiogram
hood ratio test against the proportional hazard
but no new PPM within 30 days after TAVR), and new
model. In further analysis, Cox regression was used to
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Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 1 Study Profile
Afib ¼ atrial fibrillation; AVB ¼ atrioventricular block; BBB ¼ bundle branch block; CA ¼ conduction abnormalities; ECG ¼ electrocardiogram; LBBB ¼ left bundle branch block; PPM ¼ permanent pacemaker; RBBB ¼ right bundle branch block; SSS ¼ sick sinus node syndrome; TAVR ¼ transcatheter aortic valve replacement.
analyze the association of exposure as a time-
RESULTS
dependent variable with all-cause mortality during the first 30 days after TAVR. Adjusted mean number
STUDY POPULATION. In total, 1,190 consecutive pa-
of recurrent hospitalizations was estimated as pro-
tients had undergone TAVR from 2007 to September
posed by Ghosh and Lin (23) considering death as
2017, of whom 348 were excluded because of pre-
a competing risk. For analysis of last available ven-
procedural BBB
tricular pacing percentage, a similar cutoff value,
graphic data, or emigration. Of the remaining 842
or
PPM, missing
electrocardio-
of #40% and >40%, as in the MOST trial was
patients, 26 had <30 days of follow-up after TAVR,
used (24). The level of statistical significance was set
leaving 816 patients eligible for the primary analyses.
at 5%. All statistical analyses were performed using
In this final study population, 247 patients (30.3%)
SAS Base version 9.4 (SAS Institute, Cary, North
had new BBB without new PPM, 132 (16.2%) had new
Carolina).
PPM, and 437 (53.6%) had no CAs (Figure 1). The
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Complications of TAVR-Induced Conduction Abnormalities
T A B L E 1 Baseline and Procedural Characteristics
No CAs (n ¼ 437)
New BBB (n ¼ 247)
New PPM (n ¼ 132)
Age, yrs
81 (76–85)
81 (75–85)
80 (75–84)
0.47
Male
224 (51.3)
125 (50.2)
60 (45.5)
0.50
p Value
Baseline
Diabetes
88 (20.1)
53 (21.5)
28 (21.2)
0.91
Hyperlipidemia
280 (64.1)
150 (60.7)
74 (56.1)
0.23
Hypertension
343 (78.5)
192 (77.7)
91 (68.9)
0.07
Ischemic heart disease
223 (51.0)
124 (50.2)
52 (39.4)
0.06
Previous infarction
399 (8.7)
28 (11.3)
7 (5.3)
0.14
COPD
92 (21.1)
57 (23.1)
28 (21.2)
0.82
142 (32.5)
86 (34.8)
52 (39.4)
0.34
6 (1.4)
7 (2.8)
5 (3.8)
0.17
63 (14.4)
40 (16.2)
13 (9.9)
0.24
Known atrial fibrillation Dialysis Previous stroke NYHA functional class III or IV STS score, % Pre-procedural LVEF, %
282 (64.5)
159 (64.4)
75 (56.8)
0.25
3.3 (2.3–4.8)
3.1 (2.2–4.7)
3.4 (2.1–5.2)
0.80
55 (45–60)
55 (50–60)
60 (45–60)
0.049
400 (91.5)
233 (94.3)
125 (94.7)
0.27 <0.0001
57 (74.0) 358 (53.1) 22 (33.9) 328/424 (77.4) 100/409 (24.5) 256 (58.6) 27 (26–29)
13 (16.9) 211 (31.3) 23 (35.4) 189/237 (79.8) 54/220 (24.6) 156 (63.2) 29 (26–29)
7 (9.1) 105 (15.6) 20 (30.8) 96/129 (74.4) 25/120 (20.8) 83 (62.9) 27 (26–29)
Procedural Femoral access Prosthesis type Balloon expandable* Self-expanding* Mechanical* Pre-dilation Post-dilation General anesthesia Prosthesis size, mm
0.50 0.69 0.43 0.28
Values are median (IQR), n (%), or n/N (%). *Percentages are row %. BBB ¼ bundle branch block; CA ¼ conduction abnormality; COPD ¼ chronic obstructive pulmonary disease; IQR ¼ interquartile range; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; PPM ¼ permanent pacemaker; STS ¼ Society of Thoracic Surgeons.
median time to last available electrocardiogram after
The hazard rate of early (<1 year) and late ($1 year)
TAVR was 4 days (IQR: 2 to 7 days) for patients with
all-cause mortality was significantly higher for pa-
new BBB or no CAs. PPMs were implanted in 79 pa-
tients with new BBB compared with those with no
tients (59.8%) with new PPM within 1 week after
CAs, whereas only late all-cause mortality was higher
TAVR. New PPM was single-ventricular (VVI/DDD
for patients with new PPM compared with no CAs
device) in 122 patients (92.4%) and biventricular
(Figure 2B). The HRs of all-cause mortality during the
(cardiac resynchronization therapy device) in 9 pa-
first 30 days after TAVR were 4.89 (95% confidence
tients (6.8%); a total of 3 (2.3%) of these also func-
interval [CI]: 1.00 to 23.92) for patients with new BBB
tioned
and 2.21 (95% CI: 0.20 to 24.72) for those with new
as
implantable
cardioverter-defibrillators.
More patients with new BBB (n ¼ 19 [7.7%]) received PPMs later than 30 days after TAVR compared with patient with no CAs (n ¼ 15 [3.4%]) (p ¼ 0.013). Median follow-up was 2.5 years (IQR: 1.0 to 4.9 years). Baseline and procedural characteristics are shown in Table 1. The median age of the total population was 81 years (IQR: 75 to 85 years), and the median Society of Thoracic Surgeons score was 3.2% (IQR: 2.2% to 4.9%). There was no difference in the baseline characteristics between groups, except for the type of implanted THV (p < 0.0001) and baseline LVEF (p ¼ 0.049).
PPM compared with no CAs. HOSPITALIZATIONS. The hazard rate of first heart
failure hospitalization was higher for patients with new BBB and new PPM compared with those with no CAs (Figure 3). In a subanalysis, first heart failure hospitalization was included in the Cox regression model as a time-dependent variable and independently increased the risk for all-cause mortality (HR: 3.32; 95% CI: 2.41 to 4.59; p < 0.0001). The mean number of recurrent heart failure hospitalizations up to 5 years after TAVR was higher for patients with new BBB and new PPM compared
MORTALITY. Five years after TAVR, all-cause mor-
with those with no CAs (Table 2, Online Figure 1).
tality was 48.4% in patients with new BBB, 46.7% in
However, when excluding patients without any
those with new PPM, and 32.8% in those with no CAs
heart failure admissions, there was no difference in
(p ¼ 0.0003) (Figure 2A).
the
mean
number
of
recurrent
heart
failure
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Complications of TAVR-Induced Conduction Abnormalities
JANUARY 14, 2019:52–61
F I G U R E 2 5-Year All-Cause Mortality
(A) Absolute risk for all-cause mortality at 5 years after transcatheter aortic valve replacement for patients with new bundle branch block (BBB), new permanent pacemaker (PPM), or no conduction abnormalities (CA). (B) Landmark analysis of all-cause mortality with cutoff at 1 year. CI ¼ confidence interval.
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Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 3 First Heart Failure Hospitalization
Cumulative incidence of first heart failure hospitalization up to 5 years after transcatheter aortic valve replacement for patients with new bundle branch block (BBB), new permanent pacemaker (PPM), or no conduction abnormalities (CA). CI ¼ confidence interval.
hospitalizations during follow-up. There was no dif-
percentages #40% and >40%, respectively. Both
ference in the mean number of recurrent all-cause
groups had a median backup rate of 60 beats/min
hospitalizations for patients with new BBB and new
(IQR: 60 to 60 beats/min; p ¼ 0.43). In patients with
PPM compared with no CAs (Table 2, Online Figure 2).
pacing percentages #40%, the last available electro-
For patients admitted to the hospital, the median
cardiogram within 30 days post-TAVR (2 patients had
duration of hospital stay was 4.5 days/admission
missing data) showed that 41 patients (67.2%) had
(IQR: 2.0 to 7.0 days/admission) for patients with new
new-onset LBBB, 9 (14.8%) had new-onset RBBB, and
BBB, 4.0 days/admission (IQR: 2.0 to 6.0 days/
11 (18.0%) had no BBB when not paced.
admission) for those with new PPM, and 3.0 days/
Including only patients with single-ventricular
admission (IQR: 1.7 to 6.0 days/admission) for those
pacemakers (VVI/DDD devices), the hazard rate of
with no CAs (p ¼ 0.037).
all-cause mortality was similar for patients with right
The 10 patients with new RBBB had a median
ventricular
pacing
(RVP)
#40%
versus
>40%
follow-up duration of 2.9 years; none of these pa-
(Table 3). The hazard rate of first heart failure hospi-
tients died during follow-up. Exclusion of patients
talization was higher for patients with RVP >40%
with new RBBB from those with new BBB provided
compared with those with RVP #40% (HR: 2.84; 95%
similar results for primary analyses of all-cause mor-
CI: 1.25 to 6.45).
tality and heart failure (Online Figure 3).
CHANGES OF LVEF. In 320 patients (42.1% of patients
PACEMAKER-SPECIFIC OUTCOMES. Data for pacing
at risk), the last available echocardiogram older than
percentage were available for all patients with new
6 months (median time to follow-up 2.0 years [IQR:
PPM except 1. The last available recorded pacing data
1.1 to 4.0 years] with no differences between groups
for patients with new PPM showed that 48.1% (n ¼ 63)
[p ¼ 0.89]) was analyzed for follow-up. LVEF was
and 51.9% (n ¼ 68) of patients had ventricular pacing
similar between groups at discharge (p ¼ 0.73)
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Complications of TAVR-Induced Conduction Abnormalities
T A B L E 2 Ratio Between Mean Numbers of Recurrent Hospitalizations up to 5 Years After
Transcatheter Aortic Valve Replacement Ratio of Repeated Hospitalizations (95% CI) p Value
New PPM
p Value
observed an increased risk for sudden cardiac death for TAVR patients with new LBBB, which increased additionally in an interactive manner during the first 6 months if new LBBB was concomitant with
No CAs*
New BBB
Heart failure hospitalizations
1.00
1.57 (1.28–2.07)
Heart failure hospitalizations, excluding patients with no heart failure hospitalizations
1.00
1.002 (0.76–1.32)
0.99
0.93 (0.68–1.29)
0.68
complete heart block, or ventricular arrhythmias.
All-cause hospitalizations
1.00
1.08 (0.95–1.21)
0.24
1.00 (0.86–1.16)
0.99
chrony, shortening of diastole, and abnormal septal
0.002 1.44 (1.03–2.02) 0.032
LVEF
#40%.
These
results
could
indicate
an
increased risk for early progression to heart failure, LBBB is known to cause interventricular dyssynmotion, reducing LVEF and over time inducing
*No CA group is the comparator for all analyses.
asymmetrical cardiac dilation and hypertrophy, lead-
CI ¼ confidence interval; other abbreviations as in Table 1.
ing to heart failure (25). Several studies have described a reduced immediate and late recovery of LVEF in
(Figure 4). LVEF was significantly reduced from
patients with new LBBB after TAVR (9,11,13) but failed
discharge to follow-up among patients with new BBB
to show an increased risk for heart failure hospitali-
and new PPM (p < 0.0001 for both groups) but not for
zations (9,12). In the present study, heart failure hos-
patients with no CAs. LVEF was significantly different
pitalization was found to be a strong predictor of
between groups at follow-up (p ¼ 0.0001) (Figure 4).
all-cause mortality, and the increased risk for heart failure hospitalization for patients with new BBB
DISCUSSION
might explain the increased risk for late all-cause mortality after TAVR compared with patients with no CAs.
Of 816 patients without BBB or PPM prior to TAVR,
Several of the studies that failed to show an asso-
30.3% patients developed new BBB, and 16.2% had
ciation between new LBBB and all-cause mortality
need for PPM within 30 days after TAVR. The rates of
defined new LBBB as LBBB present at discharge,
new BBB (5–7,10–13) and new PPM (1,3,5,7,14–17) were
included patients with new PPM >48 h post-TAVR or
similar to those previously reported.
after discharge in the comparator group, and had
Compared with patients with no CAs, the risk for
higher baseline risk score compared with the present
early and late all-cause mortality was increased in
study (9,11–13). The inclusion of a higher proportion
patients with new BBB, whereas only the risk for late
of patients with transient LBBB and a higher weight
all-cause mortality was increased in patients with
of comorbidities may attenuate the difference in
new PPM. Furthermore, LVEF was reduced during
clinical outcome in these studies.
follow-up, the risk for heart failure hospitalization
Unlike patients with pre-procedural RBBB, limited
was increased, and the duration of hospitalization
follow-up data exist for patients with new RBBB after
was longer for patients with new BBB or new PPM
TAVR. Similar to what has previously been observed
compared with those with no CAs.
(11), 1.2% of patients developed new RBBB after TAVR
CLINICAL OUTCOMES OF NEW BBB AFTER TAVR.
in the present study. Although none of these patients
In a meta-analysis, new LBBB was found to increase
died during follow-up, further data are needed.
the risk for cardiac death and PPM implantation
CLINICAL OUTCOMES OF NEW PPM AFTER TAVR.
within 1 year after TAVR (7). Further, Urena et al. (6)
In the present study, patients with new PPM only had increased risk for late all-cause mortality, potentially
T A B L E 3 Clinical Outcomes According to Ventricular Pacing
Percentage
being protected from aforementioned risk for early sudden cardiac death seen in patients with new LBBB (6). In the meta-analysis by Regueiro et al. (7), new
All-cause mortality <1 yr $1 yr First heart-failure hospitalization
Hazard Ratio (95% CI)
PPM after TAVR failed to show an association with all-
RVP #40%*
RVP >40%
p Value
cause mortality but had a tendency to protect from
1.00 1.00
2.23 (0.34–14.81) 0.79 (0.34–1.84)
0.41 0.59
1.00
2.84 (1.25–6.45)
0.013
cardiac death up to 1 year after TAVR. However, the analyzed studies included patients with both preprocedural and new BBB (7,15,17,18). It is plausible that the observed protective effect of new PPM was because a significant proportion of the patients
Patients with biventricular pacemakers (cardiac resynchronization therapy devices) were excluded. *Patients with new permanent pacemakers within 30 days after transcatheter aortic valve replacement and RVP percentages #40% were the comparator for all analyses. CI ¼ confidence interval; RVP ¼ right ventricular pacing.
without PPM after TAVR had new LBBB, which was associated with 1-year cardiac death (7). Previous studies with more than 1 year of follow-up failed to show an association between new PPM after
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Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 4 Changes of Left Ventricular Ejection Fraction Over Time
Left ventricular ejection fraction (mean SD) at baseline, discharge, and follow-up. p ¼ 0.049 for comparison between groups at baseline. p ¼ 0.0001 for comparison between groups at follow-up. Change between baseline and discharge within patients with new bundle branch block (BBB) (p < 0.0001), new permanent pacemaker (PPM) (p ¼ 0.023), and no conduction abnormalities (CAs) (p < 0.0001). Change between discharge and follow-up within patients with new BBB (p < 0.0001), new PPM (p < 0.0001), and no CAs (p ¼ 0.23).
TAVR and all-cause mortality. However, these studies
with those with no CAs. Thus, neither new BBB nor
included patients with known or new LBBB in the
new PPM appears benign in the long term, indicating
comparator group (14,15). RVP is known to cause
that prevention is the best long-term treatment of
similar interventricular dyssynchrony, resulting in an
TAVR-induced CAs and that these patients may
analogous pathway to heart failure as seen in patients
benefit from closer follow-up. Balloon-expandable
with LBBB (25). Given that LBBB and RVP increase the
and some self-expanding THVs tend to have a lower
risk for heart failure, the inclusion of patients with
risk for CAs (5), but, the risk for other complications
LBBB in the comparator group might be why previous
such as PVR also needs to be considered when
studies did not identify an association between new
selecting the optimal THV. Reducing the risk for CAs
PPM after TAVR and longer-term mortality (14,15).
with a minimal trade-off for an increased risk for PVR,
OUTCOME OF PROLONGED QRS DURATION. As the
the membranous septum length might function as
indication for TAVR advances to younger patients
patient-specific limit for THV implantation depth (26).
with low surgical risk and longer life expectancy, the
Similar to the results of the MOST trial (24), pa-
long-term safety of TAVR becomes increasingly
tients in the present study with new PPM who were
important. In the present study, PPM implantation
paced >40% of the time had higher risk for heart
seemed beneficial in case of new CAs, maybe pro-
failure
tecting from early sudden cardiac death. However, the
paced #40%. Periodic reassessment of the intrinsic
increased risk for heart failure hospitalization and low
QRS configuration and heart rate for patients with
LVEF at follow-up for both patients with new BBB and
PPM at follow-up could reveal some patients with
new PPM could be a cofactor in the increased risk for
unnecessarily high RVP percentages who might
late mortality observed in these patients compared
benefit from a lower paced backup rate. Cardiac
hospitalizations
compared
with
those
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Complications of TAVR-Induced Conduction Abnormalities
resynchronization therapy has been shown to be
The risk for heart failure hospitalization and late all-
beneficial in case reports of patients with low LVEFs
cause mortality was increased, and the duration of
and persistent LBBB after TAVR (5). However, there
hospitalization was longer for patients with new BBB
are limited data on the systematic implementation of
or new PPM compared with those with no CAs.
cardiac resynchronization therapy devices for TAVR
Although future larger scale, multicenter studies
patients with reduced LVEFs and even more so for
should confirm these results, this study indicates that
preventing deterioration of a normal LVEF, which
TAVR-induced new BBB and new PPM are not just
might be increasingly important for younger low-risk
benign post-TAVR complications.
patients with TAVR-induced CAs. STUDY LIMITATIONS. The diagnosis of heart failure
was based on data from national registries, which contain information on the diagnosis given by the treating physician at discharge. It was not possible to
ADDRESS FOR CORRESPONDENCE: Dr. Troels H.
Jørgensen, Rigshospitalet, The Heart Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: [email protected].
validate diagnoses; however, the national registries provide unselected information, which is mandatory to complete, on all patients every time they are admitted to the hospital. A previous study validating the Danish National Patient Registry found a positive predictive value of 75% for heart failure hospitaliza-
PERSPECTIVES WHAT IS KNOWN? New LBBB and new PPM are frequent complications after TAVR. However, previ-
tions (21). The median time to last available electrocardiogram was 4 days, meaning that some patients might have been misclassified because of only transient BBB. However, analysis with time zero set at 3 months, giving a median time to last available electrocardiogram of 7 days (IQR: 3.0 to 35.0 days), provided similar results for all-cause mortality and heart failure hospitalization (Online Figure 4). Even though baseline differences were minimal and most analyses were multivariate, the observational nature of the study makes it possible that unmeasured confounders might explain the observed results, and external validity might be limited because of the single-center design of the study.
ous studies have reported inconsistent results on their clinical impact. WHAT IS NEW? Both new BBB and new PPM after TAVR are associated with increased all-cause mortality, although new PPM may protect against early death. Similarly, TAVR-induced CAs increase the rate of heart failure hospitalization as well as the duration of hospitalization in general. WHAT IS NEXT? Future studies should confirm these results, separating patients with new-LBBB, those with new PPM, and those without CAs after TAVR. Furthermore, procedural planning and selection of THV may reduce the risk for the development of CAs without increasing the risk for PVR, which
CONCLUSIONS
might be of significant value for long-term outcome
Patients with new BBB had an increased risk for early
after TAVR.
all-cause mortality compared with those with no CAs.
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KEY WORDS bundle branch block, conduction abnormality, pacemaker, transcatheter aortic valve replacement A PP END IX For supplemental figures, please see the online version of this paper.
61
VOL. 12, NO. 1, 2019
ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Mortality and Heart Failure Hospitalization in Patients With Conduction Abnormalities After Transcatheter Aortic Valve Replacement Troels H. Jørgensen, MD,a Ole De Backer, MD, PHD,a Thomas A. Gerds, DRRERNAT,b Gintautas Bieliauskas, MD,a Jesper H. Svendsen, MD, DMSC,a,c Lars Søndergaard, MD, DMSCa,c
ABSTRACT OBJECTIVES The aim of this study was to assess mortality and rehospitalization in patients with new bundle branch block (BBB) and/or permanent pacemaker (PPM) after transcatheter aortic valve replacement (TAVR). BACKGROUND Previous studies have provided inconsistent results on the clinical impact of new BBB or new PPM after TAVR. METHODS A total of 816 consecutive patients without pre-procedural BBB or PPM undergoing TAVR between 2007 and 2017 were followed for 5 years or until data extraction in September 2017. Data on vital status and hospitalization were obtained through national registries. RESULTS Within 30 days post-TAVR, new BBB without PPM and new PPM occurred in 247 (30.3%) and 132 (16.2%) patients, respectively, leaving 437 patients (53.6%) without conduction abnormalities. Median follow-up was 2.5 years (interquartile range: 1.0 to 4.9 years). One-year all-cause mortality was increased for new BBB (hazard ratio [HR]: 2.80; 95% confidence interval [CI]: 1.18 to 3.67) but not for new PPM (HR: 1.64; 95% CI: 0.72 to 3.74) compared with patients with no conduction abnormalities. The risk for late all-cause mortality ($1 year after TAVR) was higher both for patients with new BBB (HR: 1.79; 95% CI: 1.24 to 2.59) and for those with new PPM (HR: 1.58; 95% CI: 1.01 to 2.46) compared with patients with no conduction abnormalities. Patients with new BBB (HR: 1.47; 95% CI: 1.02 to 2.12) and new PPM (HR: 1.66; 95% CI: 1.09 to 2.54) had a higher risk for heart failure hospitalization and reduced left ventricular ejection fraction (p < 0.0001 for both groups) during follow-up. CONCLUSIONS New BBB and new PPM developed frequently after TAVR. New BBB was associated with increased early and late all-cause mortality, whereas new PPM was associated with late all-cause mortality. Furthermore, both new BBB and new PPM increased the risk for heart failure hospitalizations. (J Am Coll Cardiol Intv 2019;12:52–61) © 2019 by the American College of Cardiology Foundation.
I
ncreased operator experience and improved
more than mild paravalvular regurgitation (PVR) and
transcatheter heart valve (THV) design are
mortality was an early recognized potential Achilles’
among factors that have reduced the risk for
heel of TAVR (4). As a consequence, both manufac-
transcatheter
aortic
valve
replacement
(TAVR)–
turers and operators have had a strong focus on
related complications (1–3). The association between
reducing the rate of PVR. However, preventive
From the aDepartment of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
b
Section of
Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; and the cDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Dr. Jørgensen has received a research grant from Edwards Lifesciences. Dr. Sondergaard has received consulting fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. Dr. Svendsen is on the advisory board of Medtronic; has received speaking fees from Medtronic and Biotronik; and has received an institutional research grant from Medtronic, Biotronik, and Gilead. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received August 13, 2018; revised manuscript received October 25, 2018, accepted October 30, 2018.
ISSN 1936-8798/$36.00
https://doi.org/10.1016/j.jcin.2018.10.053
Jørgensen et al.
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measures against PVR, such as the introduction of
PPM (patients who underwent PPM implan-
ABBREVIATIONS
sealing skirts, more liberal THV oversizing, and
tation within 30 days after TAVR, regardless
AND ACRONYMS
post-dilation, are risk factors for the development of
of the presence or absence of new BBB).
BBB = bundle branch block
conduction abnormalities (CAs) after TAVR (2,5).
On the basis of the nationwide registries,
This might explain why induction of left bundle
the primary endpoint was all-cause mortality.
branch block (LBBB) and implantation of a permanent
Secondary outcomes were first hospitaliza-
CI = confidence interval
pacemaker (PPM) remain frequent complications af-
tion and recurrent hospitalizations for heart
HR = hazard ratio
ter TAVR, seen in 10% to 30% of patients depending
failure or all-cause admissions. Hospitaliza-
IQR = interquartile range
CA = conduction abnormality
on the type of THV implanted (1,3,5–8). Still, the clin-
tion for heart failure was classified if the
LBBB = left bundle branch
ical impact of TAVR-induced CAs remains controver-
following
block
sial, as new-onset LBBB and post-procedural PPM
Diseases-10th Revision codes were registered
International
Classification
of
have shown inconsistent effects on mortality and
during admission: I11.0, I13.0, I13.2, I42.0,
heart failure after TAVR (5,7,9–19).
I42.1, I42.2, I42.9, and I50. Date and indica-
The aim of the present study was to investigate the incidence of TAVR-induced new-onset bundle branch
tion of PPM implantation were identified through the Danish Pacemaker Registry.
block (BBB) and new PPM implantation as well as
Patients were followed until the date of
their impact on all-cause mortality and hospitaliza-
death or the date of data extraction from the
tion
nationwide registries in September 2017, with
for
heart
53
Complications of TAVR-Induced Conduction Abnormalities
failure
in
an
all-comers
TAVR
population.
a maximum of 5 years of follow-up. SEE PAGE 62
METHODS
LVEF = left ventricular ejection fraction
PPM = permanent pacemaker PVR = paravalvular regurgitation
RBBB = right bundle branch block
RVP = right ventricular pacing TAVR = transcatheter aortic valve replacement
THV = transcatheter heart
STATISTICAL
ANALYSIS. Categorical
vari-
valve
ables are expressed as counts and percentages and were compared using chi-square-tests.
The present study was a prospective single-center
Continuous variables are expressed as mean SD,
study. All consecutive patients who underwent
compared using analysis of variance and paired Stu-
TAVR at Rigshospitalet, Copenhagen University Hos-
dent’s t-tests, or median (interquartile range [IQR]),
pital, Denmark, from 2007 to 2017 were included.
compared using Kruskal-Wallis tests. Time zero for all
Patients with pre-procedural BBB or PPM, those with
survival analyses was set at 30 days post-TAVR. The
missing pre- or post-procedural electrocardiographic
exposure variable (new BBB or new PPM vs. no CAs)
data, and those who emigrated were excluded. The
was defined at time zero. The median follow-up time
study was approved by the Danish Data Agency and
was
Danish Patient Safety Authority.
method (22). All-cause mortality was analyzed using
DATA SOURCE. Baseline and periprocedural charac-
teristics were collected from electronic patient records. Pre- and post-procedural electrocardiographic data were validated in all patients. QRS interval $120 ms was defined as BBB and further classified into LBBB and right BBB (RBBB) (20). All Danish permanent residents are assigned a unique personal identification number, which is linked to nationwide administrative registries (21). In the Civil Registration and National Patient Registry, vital status and hospitalization information on date of admission and discharge, and codes for diagnosis and procedures are registered. Date and indication of PPM implantation are registered in the Danish Pacemaker Registry.
calculated
using
the
reverse
Kaplan-Meier
the Kaplan-Meier method and the log-rank test. The absolute risk for first heart failure hospitalization (with death without heart failure being a competing risk) was analyzed using the Aalen-Johansen method and Gray’s test. Cox regression was used to analyze the association of exposure with all-cause mortality rates and rates of first heart failure hospitalization. The models were adjusted for sex, age at date of TAVR as a continuous variable, history of ischemic heart disease, need for dialysis at admission for TAVR, chronic obstructive pulmonary disease, diabetes mellitus, pre-TAVR left ventricular ejection fraction (LVEF), and type of implanted THV. A landmark analysis was performed for all-cause mortality 1 year after TAVR. The KaplanMeier estimates were computed among 1-year survi-
FOLLOW-UP. Patients were classified into 3 groups:
vors, and the exposure hazard ratio (HR) was allowed
no CAs (patients without BBB on the last available 12-
to change after 1 year in Cox regression. The impor-
lead electrocardiogram or PPM within 30 days after
tance of the exposure time interaction (allowing a
TAVR), new BBB (patients with new-onset LBBB or
change of HR after 1 year) was tested using a likeli-
RBBB on the last available 12-lead electrocardiogram
hood ratio test against the proportional hazard
but no new PPM within 30 days after TAVR), and new
model. In further analysis, Cox regression was used to
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Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 1 Study Profile
Afib ¼ atrial fibrillation; AVB ¼ atrioventricular block; BBB ¼ bundle branch block; CA ¼ conduction abnormalities; ECG ¼ electrocardiogram; LBBB ¼ left bundle branch block; PPM ¼ permanent pacemaker; RBBB ¼ right bundle branch block; SSS ¼ sick sinus node syndrome; TAVR ¼ transcatheter aortic valve replacement.
analyze the association of exposure as a time-
RESULTS
dependent variable with all-cause mortality during the first 30 days after TAVR. Adjusted mean number
STUDY POPULATION. In total, 1,190 consecutive pa-
of recurrent hospitalizations was estimated as pro-
tients had undergone TAVR from 2007 to September
posed by Ghosh and Lin (23) considering death as
2017, of whom 348 were excluded because of pre-
a competing risk. For analysis of last available ven-
procedural BBB
tricular pacing percentage, a similar cutoff value,
graphic data, or emigration. Of the remaining 842
or
PPM, missing
electrocardio-
of #40% and >40%, as in the MOST trial was
patients, 26 had <30 days of follow-up after TAVR,
used (24). The level of statistical significance was set
leaving 816 patients eligible for the primary analyses.
at 5%. All statistical analyses were performed using
In this final study population, 247 patients (30.3%)
SAS Base version 9.4 (SAS Institute, Cary, North
had new BBB without new PPM, 132 (16.2%) had new
Carolina).
PPM, and 437 (53.6%) had no CAs (Figure 1). The
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Complications of TAVR-Induced Conduction Abnormalities
T A B L E 1 Baseline and Procedural Characteristics
No CAs (n ¼ 437)
New BBB (n ¼ 247)
New PPM (n ¼ 132)
Age, yrs
81 (76–85)
81 (75–85)
80 (75–84)
0.47
Male
224 (51.3)
125 (50.2)
60 (45.5)
0.50
p Value
Baseline
Diabetes
88 (20.1)
53 (21.5)
28 (21.2)
0.91
Hyperlipidemia
280 (64.1)
150 (60.7)
74 (56.1)
0.23
Hypertension
343 (78.5)
192 (77.7)
91 (68.9)
0.07
Ischemic heart disease
223 (51.0)
124 (50.2)
52 (39.4)
0.06
Previous infarction
399 (8.7)
28 (11.3)
7 (5.3)
0.14
COPD
92 (21.1)
57 (23.1)
28 (21.2)
0.82
142 (32.5)
86 (34.8)
52 (39.4)
0.34
6 (1.4)
7 (2.8)
5 (3.8)
0.17
63 (14.4)
40 (16.2)
13 (9.9)
0.24
Known atrial fibrillation Dialysis Previous stroke NYHA functional class III or IV STS score, % Pre-procedural LVEF, %
282 (64.5)
159 (64.4)
75 (56.8)
0.25
3.3 (2.3–4.8)
3.1 (2.2–4.7)
3.4 (2.1–5.2)
0.80
55 (45–60)
55 (50–60)
60 (45–60)
0.049
400 (91.5)
233 (94.3)
125 (94.7)
0.27 <0.0001
57 (74.0) 358 (53.1) 22 (33.9) 328/424 (77.4) 100/409 (24.5) 256 (58.6) 27 (26–29)
13 (16.9) 211 (31.3) 23 (35.4) 189/237 (79.8) 54/220 (24.6) 156 (63.2) 29 (26–29)
7 (9.1) 105 (15.6) 20 (30.8) 96/129 (74.4) 25/120 (20.8) 83 (62.9) 27 (26–29)
Procedural Femoral access Prosthesis type Balloon expandable* Self-expanding* Mechanical* Pre-dilation Post-dilation General anesthesia Prosthesis size, mm
0.50 0.69 0.43 0.28
Values are median (IQR), n (%), or n/N (%). *Percentages are row %. BBB ¼ bundle branch block; CA ¼ conduction abnormality; COPD ¼ chronic obstructive pulmonary disease; IQR ¼ interquartile range; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; PPM ¼ permanent pacemaker; STS ¼ Society of Thoracic Surgeons.
median time to last available electrocardiogram after
The hazard rate of early (<1 year) and late ($1 year)
TAVR was 4 days (IQR: 2 to 7 days) for patients with
all-cause mortality was significantly higher for pa-
new BBB or no CAs. PPMs were implanted in 79 pa-
tients with new BBB compared with those with no
tients (59.8%) with new PPM within 1 week after
CAs, whereas only late all-cause mortality was higher
TAVR. New PPM was single-ventricular (VVI/DDD
for patients with new PPM compared with no CAs
device) in 122 patients (92.4%) and biventricular
(Figure 2B). The HRs of all-cause mortality during the
(cardiac resynchronization therapy device) in 9 pa-
first 30 days after TAVR were 4.89 (95% confidence
tients (6.8%); a total of 3 (2.3%) of these also func-
interval [CI]: 1.00 to 23.92) for patients with new BBB
tioned
and 2.21 (95% CI: 0.20 to 24.72) for those with new
as
implantable
cardioverter-defibrillators.
More patients with new BBB (n ¼ 19 [7.7%]) received PPMs later than 30 days after TAVR compared with patient with no CAs (n ¼ 15 [3.4%]) (p ¼ 0.013). Median follow-up was 2.5 years (IQR: 1.0 to 4.9 years). Baseline and procedural characteristics are shown in Table 1. The median age of the total population was 81 years (IQR: 75 to 85 years), and the median Society of Thoracic Surgeons score was 3.2% (IQR: 2.2% to 4.9%). There was no difference in the baseline characteristics between groups, except for the type of implanted THV (p < 0.0001) and baseline LVEF (p ¼ 0.049).
PPM compared with no CAs. HOSPITALIZATIONS. The hazard rate of first heart
failure hospitalization was higher for patients with new BBB and new PPM compared with those with no CAs (Figure 3). In a subanalysis, first heart failure hospitalization was included in the Cox regression model as a time-dependent variable and independently increased the risk for all-cause mortality (HR: 3.32; 95% CI: 2.41 to 4.59; p < 0.0001). The mean number of recurrent heart failure hospitalizations up to 5 years after TAVR was higher for patients with new BBB and new PPM compared
MORTALITY. Five years after TAVR, all-cause mor-
with those with no CAs (Table 2, Online Figure 1).
tality was 48.4% in patients with new BBB, 46.7% in
However, when excluding patients without any
those with new PPM, and 32.8% in those with no CAs
heart failure admissions, there was no difference in
(p ¼ 0.0003) (Figure 2A).
the
mean
number
of
recurrent
heart
failure
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Complications of TAVR-Induced Conduction Abnormalities
JANUARY 14, 2019:52–61
F I G U R E 2 5-Year All-Cause Mortality
(A) Absolute risk for all-cause mortality at 5 years after transcatheter aortic valve replacement for patients with new bundle branch block (BBB), new permanent pacemaker (PPM), or no conduction abnormalities (CA). (B) Landmark analysis of all-cause mortality with cutoff at 1 year. CI ¼ confidence interval.
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Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 3 First Heart Failure Hospitalization
Cumulative incidence of first heart failure hospitalization up to 5 years after transcatheter aortic valve replacement for patients with new bundle branch block (BBB), new permanent pacemaker (PPM), or no conduction abnormalities (CA). CI ¼ confidence interval.
hospitalizations during follow-up. There was no dif-
percentages #40% and >40%, respectively. Both
ference in the mean number of recurrent all-cause
groups had a median backup rate of 60 beats/min
hospitalizations for patients with new BBB and new
(IQR: 60 to 60 beats/min; p ¼ 0.43). In patients with
PPM compared with no CAs (Table 2, Online Figure 2).
pacing percentages #40%, the last available electro-
For patients admitted to the hospital, the median
cardiogram within 30 days post-TAVR (2 patients had
duration of hospital stay was 4.5 days/admission
missing data) showed that 41 patients (67.2%) had
(IQR: 2.0 to 7.0 days/admission) for patients with new
new-onset LBBB, 9 (14.8%) had new-onset RBBB, and
BBB, 4.0 days/admission (IQR: 2.0 to 6.0 days/
11 (18.0%) had no BBB when not paced.
admission) for those with new PPM, and 3.0 days/
Including only patients with single-ventricular
admission (IQR: 1.7 to 6.0 days/admission) for those
pacemakers (VVI/DDD devices), the hazard rate of
with no CAs (p ¼ 0.037).
all-cause mortality was similar for patients with right
The 10 patients with new RBBB had a median
ventricular
pacing
(RVP)
#40%
versus
>40%
follow-up duration of 2.9 years; none of these pa-
(Table 3). The hazard rate of first heart failure hospi-
tients died during follow-up. Exclusion of patients
talization was higher for patients with RVP >40%
with new RBBB from those with new BBB provided
compared with those with RVP #40% (HR: 2.84; 95%
similar results for primary analyses of all-cause mor-
CI: 1.25 to 6.45).
tality and heart failure (Online Figure 3).
CHANGES OF LVEF. In 320 patients (42.1% of patients
PACEMAKER-SPECIFIC OUTCOMES. Data for pacing
at risk), the last available echocardiogram older than
percentage were available for all patients with new
6 months (median time to follow-up 2.0 years [IQR:
PPM except 1. The last available recorded pacing data
1.1 to 4.0 years] with no differences between groups
for patients with new PPM showed that 48.1% (n ¼ 63)
[p ¼ 0.89]) was analyzed for follow-up. LVEF was
and 51.9% (n ¼ 68) of patients had ventricular pacing
similar between groups at discharge (p ¼ 0.73)
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Complications of TAVR-Induced Conduction Abnormalities
T A B L E 2 Ratio Between Mean Numbers of Recurrent Hospitalizations up to 5 Years After
Transcatheter Aortic Valve Replacement Ratio of Repeated Hospitalizations (95% CI) p Value
New PPM
p Value
observed an increased risk for sudden cardiac death for TAVR patients with new LBBB, which increased additionally in an interactive manner during the first 6 months if new LBBB was concomitant with
No CAs*
New BBB
Heart failure hospitalizations
1.00
1.57 (1.28–2.07)
Heart failure hospitalizations, excluding patients with no heart failure hospitalizations
1.00
1.002 (0.76–1.32)
0.99
0.93 (0.68–1.29)
0.68
complete heart block, or ventricular arrhythmias.
All-cause hospitalizations
1.00
1.08 (0.95–1.21)
0.24
1.00 (0.86–1.16)
0.99
chrony, shortening of diastole, and abnormal septal
0.002 1.44 (1.03–2.02) 0.032
LVEF
#40%.
These
results
could
indicate
an
increased risk for early progression to heart failure, LBBB is known to cause interventricular dyssynmotion, reducing LVEF and over time inducing
*No CA group is the comparator for all analyses.
asymmetrical cardiac dilation and hypertrophy, lead-
CI ¼ confidence interval; other abbreviations as in Table 1.
ing to heart failure (25). Several studies have described a reduced immediate and late recovery of LVEF in
(Figure 4). LVEF was significantly reduced from
patients with new LBBB after TAVR (9,11,13) but failed
discharge to follow-up among patients with new BBB
to show an increased risk for heart failure hospitali-
and new PPM (p < 0.0001 for both groups) but not for
zations (9,12). In the present study, heart failure hos-
patients with no CAs. LVEF was significantly different
pitalization was found to be a strong predictor of
between groups at follow-up (p ¼ 0.0001) (Figure 4).
all-cause mortality, and the increased risk for heart failure hospitalization for patients with new BBB
DISCUSSION
might explain the increased risk for late all-cause mortality after TAVR compared with patients with no CAs.
Of 816 patients without BBB or PPM prior to TAVR,
Several of the studies that failed to show an asso-
30.3% patients developed new BBB, and 16.2% had
ciation between new LBBB and all-cause mortality
need for PPM within 30 days after TAVR. The rates of
defined new LBBB as LBBB present at discharge,
new BBB (5–7,10–13) and new PPM (1,3,5,7,14–17) were
included patients with new PPM >48 h post-TAVR or
similar to those previously reported.
after discharge in the comparator group, and had
Compared with patients with no CAs, the risk for
higher baseline risk score compared with the present
early and late all-cause mortality was increased in
study (9,11–13). The inclusion of a higher proportion
patients with new BBB, whereas only the risk for late
of patients with transient LBBB and a higher weight
all-cause mortality was increased in patients with
of comorbidities may attenuate the difference in
new PPM. Furthermore, LVEF was reduced during
clinical outcome in these studies.
follow-up, the risk for heart failure hospitalization
Unlike patients with pre-procedural RBBB, limited
was increased, and the duration of hospitalization
follow-up data exist for patients with new RBBB after
was longer for patients with new BBB or new PPM
TAVR. Similar to what has previously been observed
compared with those with no CAs.
(11), 1.2% of patients developed new RBBB after TAVR
CLINICAL OUTCOMES OF NEW BBB AFTER TAVR.
in the present study. Although none of these patients
In a meta-analysis, new LBBB was found to increase
died during follow-up, further data are needed.
the risk for cardiac death and PPM implantation
CLINICAL OUTCOMES OF NEW PPM AFTER TAVR.
within 1 year after TAVR (7). Further, Urena et al. (6)
In the present study, patients with new PPM only had increased risk for late all-cause mortality, potentially
T A B L E 3 Clinical Outcomes According to Ventricular Pacing
Percentage
being protected from aforementioned risk for early sudden cardiac death seen in patients with new LBBB (6). In the meta-analysis by Regueiro et al. (7), new
All-cause mortality <1 yr $1 yr First heart-failure hospitalization
Hazard Ratio (95% CI)
PPM after TAVR failed to show an association with all-
RVP #40%*
RVP >40%
p Value
cause mortality but had a tendency to protect from
1.00 1.00
2.23 (0.34–14.81) 0.79 (0.34–1.84)
0.41 0.59
1.00
2.84 (1.25–6.45)
0.013
cardiac death up to 1 year after TAVR. However, the analyzed studies included patients with both preprocedural and new BBB (7,15,17,18). It is plausible that the observed protective effect of new PPM was because a significant proportion of the patients
Patients with biventricular pacemakers (cardiac resynchronization therapy devices) were excluded. *Patients with new permanent pacemakers within 30 days after transcatheter aortic valve replacement and RVP percentages #40% were the comparator for all analyses. CI ¼ confidence interval; RVP ¼ right ventricular pacing.
without PPM after TAVR had new LBBB, which was associated with 1-year cardiac death (7). Previous studies with more than 1 year of follow-up failed to show an association between new PPM after
Jørgensen et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 1, 2019 JANUARY 14, 2019:52–61
Complications of TAVR-Induced Conduction Abnormalities
F I G U R E 4 Changes of Left Ventricular Ejection Fraction Over Time
Left ventricular ejection fraction (mean SD) at baseline, discharge, and follow-up. p ¼ 0.049 for comparison between groups at baseline. p ¼ 0.0001 for comparison between groups at follow-up. Change between baseline and discharge within patients with new bundle branch block (BBB) (p < 0.0001), new permanent pacemaker (PPM) (p ¼ 0.023), and no conduction abnormalities (CAs) (p < 0.0001). Change between discharge and follow-up within patients with new BBB (p < 0.0001), new PPM (p < 0.0001), and no CAs (p ¼ 0.23).
TAVR and all-cause mortality. However, these studies
with those with no CAs. Thus, neither new BBB nor
included patients with known or new LBBB in the
new PPM appears benign in the long term, indicating
comparator group (14,15). RVP is known to cause
that prevention is the best long-term treatment of
similar interventricular dyssynchrony, resulting in an
TAVR-induced CAs and that these patients may
analogous pathway to heart failure as seen in patients
benefit from closer follow-up. Balloon-expandable
with LBBB (25). Given that LBBB and RVP increase the
and some self-expanding THVs tend to have a lower
risk for heart failure, the inclusion of patients with
risk for CAs (5), but, the risk for other complications
LBBB in the comparator group might be why previous
such as PVR also needs to be considered when
studies did not identify an association between new
selecting the optimal THV. Reducing the risk for CAs
PPM after TAVR and longer-term mortality (14,15).
with a minimal trade-off for an increased risk for PVR,
OUTCOME OF PROLONGED QRS DURATION. As the
the membranous septum length might function as
indication for TAVR advances to younger patients
patient-specific limit for THV implantation depth (26).
with low surgical risk and longer life expectancy, the
Similar to the results of the MOST trial (24), pa-
long-term safety of TAVR becomes increasingly
tients in the present study with new PPM who were
important. In the present study, PPM implantation
paced >40% of the time had higher risk for heart
seemed beneficial in case of new CAs, maybe pro-
failure
tecting from early sudden cardiac death. However, the
paced #40%. Periodic reassessment of the intrinsic
increased risk for heart failure hospitalization and low
QRS configuration and heart rate for patients with
LVEF at follow-up for both patients with new BBB and
PPM at follow-up could reveal some patients with
new PPM could be a cofactor in the increased risk for
unnecessarily high RVP percentages who might
late mortality observed in these patients compared
benefit from a lower paced backup rate. Cardiac
hospitalizations
compared
with
those
59
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Jørgensen et al.
JACC: CARDIOVASCULAR INTERVENTIONS VOL. 12, NO. 1, 2019 JANUARY 14, 2019:52–61
Complications of TAVR-Induced Conduction Abnormalities
resynchronization therapy has been shown to be
The risk for heart failure hospitalization and late all-
beneficial in case reports of patients with low LVEFs
cause mortality was increased, and the duration of
and persistent LBBB after TAVR (5). However, there
hospitalization was longer for patients with new BBB
are limited data on the systematic implementation of
or new PPM compared with those with no CAs.
cardiac resynchronization therapy devices for TAVR
Although future larger scale, multicenter studies
patients with reduced LVEFs and even more so for
should confirm these results, this study indicates that
preventing deterioration of a normal LVEF, which
TAVR-induced new BBB and new PPM are not just
might be increasingly important for younger low-risk
benign post-TAVR complications.
patients with TAVR-induced CAs. STUDY LIMITATIONS. The diagnosis of heart failure
was based on data from national registries, which contain information on the diagnosis given by the treating physician at discharge. It was not possible to
ADDRESS FOR CORRESPONDENCE: Dr. Troels H.
Jørgensen, Rigshospitalet, The Heart Centre, Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: [email protected].
validate diagnoses; however, the national registries provide unselected information, which is mandatory to complete, on all patients every time they are admitted to the hospital. A previous study validating the Danish National Patient Registry found a positive predictive value of 75% for heart failure hospitaliza-
PERSPECTIVES WHAT IS KNOWN? New LBBB and new PPM are frequent complications after TAVR. However, previ-
tions (21). The median time to last available electrocardiogram was 4 days, meaning that some patients might have been misclassified because of only transient BBB. However, analysis with time zero set at 3 months, giving a median time to last available electrocardiogram of 7 days (IQR: 3.0 to 35.0 days), provided similar results for all-cause mortality and heart failure hospitalization (Online Figure 4). Even though baseline differences were minimal and most analyses were multivariate, the observational nature of the study makes it possible that unmeasured confounders might explain the observed results, and external validity might be limited because of the single-center design of the study.
ous studies have reported inconsistent results on their clinical impact. WHAT IS NEW? Both new BBB and new PPM after TAVR are associated with increased all-cause mortality, although new PPM may protect against early death. Similarly, TAVR-induced CAs increase the rate of heart failure hospitalization as well as the duration of hospitalization in general. WHAT IS NEXT? Future studies should confirm these results, separating patients with new-LBBB, those with new PPM, and those without CAs after TAVR. Furthermore, procedural planning and selection of THV may reduce the risk for the development of CAs without increasing the risk for PVR, which
CONCLUSIONS
might be of significant value for long-term outcome
Patients with new BBB had an increased risk for early
after TAVR.
all-cause mortality compared with those with no CAs.
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KEY WORDS bundle branch block, conduction abnormality, pacemaker, transcatheter aortic valve replacement A PP END IX For supplemental figures, please see the online version of this paper.
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