Abstract
Introduction: His-Purkinje system (HPS) pacing emerges as an
ideal strategy to restore cardiac synchrony. However, there is
insufficient evidence to confirm the safety of HPS pacing in advanced
age patients who are vulnerable to invasive procedures.
Methods : We aimed to evaluate the short-term feasibility and
safety of HPS pacing in symptomatic bradycardia patients over 85 years
of age by comparing the pacing parameters and clinical outcomes with a
younger cohort. 189 out of 198 consecutive patients underwent HPS pacing
with symptomatic bradycardia were included. Among them 37 and 152 were
aged over 85 years and below 85 years respectively. Peri- and
post-procedure pacing parameters, cardiac function and clinical events
were thoroughly evaluated during follow-up.
Results : Compared with the younger cohort, the elderly had
worse renal function and cardiac function. All 189 patients underwent
successful HPS pacing, among whom 28 were paced at His-bundle. Paced QRS
duration was shortened non-significantly compared with intrinsic, which
showed no difference between cohorts. Pacing threshold and impedance
decreased significantly without difference between cohorts. Lead
dislodgement and pocket hematoma/infection only occurred in 2 (1.3%)
and 4 (0.7%) younger patients, respectively. Through a 10.5±3.0 months
follow-up, A non-significant improvement in cardiac function was
indicated by echocardiographic indices. Clinical events incidences were
comparable, except a higher incidence of myocardial infarction (8.1% vs
0.7%) observed in the advanced age cohort.
Conclusion : Compared with the younger, HPS pacing could safely
restore physiological conduction and reserve cardiac function in
advanced age patients with symptomatic bradycardia.
Keywords : physiological pacing, left bundle branch pacing,
His-bundle pacing, bradycardia, super-aged, elderly, safety.
Introduction
Physiological pacing—the concept of imitating the normal cardiac
conduction pathway—has long been put forward as a means of restoring
atrioventricular synchrony(1). This concept has been
historically redefined since the first His-bundle pacing attempt to
achieve ventricular synchrony in 2000(2). Thereafter,
a growing body of evidence shows the efficacy of His-bundle pacing.
However, most studies utilize advanced pacemakers for a limited
population(3-5), which cannot be generalized to
patients requiring a more cost-effective therapy. In addition, early
battery depletion often occurred as a result of the elevated pacing
threshold, impeding the application of His-bundle
pacing(6). Huang et al. optimized the technique by
pacing at the distal His-bundle(7) or even closer to
the left bundle branch (LBB), presenting a narrow QRS with steady pacing
parameters(8). Based on this observation, in 2017 they
reported the first case of LBB pacing to correct an LBB block in a heart
failure patient with steady pacing parameters(9).
Presently, the evidence indicates that His-Purkinje system (HPS) pacing
poses a promising alternative for correcting
bradycardia(6,10).
Although the criteria of successful His-bundle(11) and
LBB pacing(12) have been well-defined, we still lack
practical experience under specific conditions, such as cardiomyopathy
and myocardial infarction, which are common in super-aged patients.
As the conductive pathway degenerates, bradycardia occurs more
frequently in super-aged patients, which can only be corrected by the
implantation of a pacemaker (13). Nevertheless,
elderly patients have distinctive features compared with the general
population: more tortuous veins(14), lower BMI, and
lower cardiac mass(15). These differences increase the
potential risks of the implantation procedure. Additionally,
comorbidities like hypertension, ischemic heart disease and chronic
renal disease(13) are pervasive in the elderly
population, further worsening the prognosis for pacemaker implantation.
Therefore, super-aged patients should be evaluated with extreme care,
especially when performing HPS pacing, which requires more invasive
manipulation including transseptal lead placement. However, currently no
study has discussed the feasibility and safety of HPS pacing in the
advanced age population.
Our study was designed to validate the safety and prognose of HPS pacing
in patients over 85 with symptomatic bradycardia through comparison with
a younger cohort, in order to provide the preliminary evidence in
advanced age patients.
Methods
Study Sample
From October 2018 to June 2019, 198 consecutive patients were admitted
indicating a need for pacemaker implantation in accordance with the 2013
ESC guidelines(16) , lead failure requiring revision,
or pacemaker replacement due to battery depletion. Among them, 189
patients had symptomatic bradycardia were included, encompassing 37
patients aged over 85 and 152 younger patients. These patients underwent
either permanent His-bundle or LBB pacing. Patients were excluded if
they indicated and underwent cardiac resynchronization therapy (CRT) or
an implantable cardioverter-defibrillator (ICD). Written forms of
consent were acquired from every patient before the procedure. Our study
complied with the Declaration of Helsinki and it was approved by the
local ethical committee.
HPS pacing
His-bundle pacing
The His-bundle pacing procedure was similar to that used in previous
studies(6,8). Briefly, through the left subclavian
vein or axillary vein (Figure 1 A ), an 8.5F sheath was placed
after a fixed curved sheath (C315His, Medtronic) distally advanced
beyond the tricuspid annulus. A Select Secure™ lead (model 3830, 69CM,
Medtronic, Minneapolis, MN, USA) was then cannulated to locate the
His-bundle by capturing the His-bundle potential displayed on
electrocardiogram (ECG, Bard recorder, Bard Electrophysiology Laboratory
System, MA). Subsequently, pacing parameters were monitored and an
eligible site was chosen with criteria described by Su et
al.(8). During implantation, intrinsic QRS duration,
paced QRS duration, and pacing stimulus to LV activation time (p-LVAT)
were all measured.
LBB pacing
For LBB pacing, a similar maneuver to the one described above was
applied to locate His-bundle. Afterwards, under a right anterior oblique
(RAO) 30° view, activation mapping was conducted 1cm anterior to
His-bundle to locate the ideal site—the proximal LBB, where left and
right activations fuse incompletely and show a negative “W” waveform
on lead V1. Then, the electrode was manipulated perpendicularly to the
interventricular septum (IVS) and screwed clockwise until it reached the
LV subendocardium.
An eligible site must meet following criteria:
- LBB potential recorded at the pacing tip
- Unipolar pacing shows RBB block feature on ECG
- Selective or non-selective capture of LBB recorded under different
outputs
To ensure safe and stable pacing, pacing threshold, sensing and
impedance were all measured. A decremental conduction test was then
applied to ensure the correction of conductive lesions. The intrinsic
and paced QRS durations, and p-LVAT were measured, and the pacing site
was optimized with the shortest p-LVAT in order to improve cardiac
function and prognosis (Figure 2 ).
In order to prevent perforation and optimize fixation, we used digital
subtraction angiography (DSA) to approximate the lead depth in the IVS
by injecting contrast media via the puncture sheath and C315 sheath
(Figure 1 D-F ). For patients with II° to III° AV block or
complete LBB block, we placed a temporary pacemaker in case of a
complete AV block resulting from injury of the His-bundle or proximal
LBB.
Device programming
Generally, the pacing lead was connected in accordance with the cardiac
rhythm. For sinus rhythm or chronic AF patients, the lead was connected
to atrial port or ventricular port respectively. Pacing output and AV
delay was adjusted individually to achieve optimal QRS morphology before
discharge. During follow-up, pacing parameters, AV delay and pacing
proportion were routinely monitored.
Follow-up management
In the 1st, 3rd and
12th months following the procedure, patients were
required to have outpatient follow-ups, or inpatient follow-ups if they
were immobilized. Comprehensive medical histories were taken and
physical examinations conducted by experienced cardiologists. Device
programming, 24-hour Holter, and transthoracic echocardiography (TTE)
were evaluated.
Statistical analysis
Continuous parameters were described as a mean ± standard deviation (SD)
if they conformed to normal distribution, while those without a normal
distribution were presented as the median and interquartile ranges
(IQR). The p-value was generated from 2 sample t-tests or a Mann-Whitney
test according to the equality of variance, or singed-rank test if a
normal distribution was not presented. Repeated measures analysis of
variance was applied to analyze the repeated measurements of pacemaker
and echocardiographic parameters. Categorical variables were described
as percentages (%) and p-values were analyzed with χ2tests or Fisher exact tests (when theoretical frequency was lower than
5). A 2-sided P-value of <0.05 was considered statistically
significant. SAS 9.4 software (SAS Institute Inc., Cary, NC, USA) was
used to conduct the analysis.
Results
Sample characteristics
Generally, the elder cohort was 10 years older than the younger. The
indications of pacemaker replacement were similar between cohorts, while
4 (2.6%) younger patients had lead failure necessitated lead revision.
Of note, compared with the younger cohort, the elderly had significantly
deteriorated renal function indicated by estimated glomerular filtration
fraction (eGFR, 54.8±24.3 ml/min/1.73m2 VS 87.1±31.8
ml/min/1.73m2), and worse cardiac function indicated
by higher NYHA (New York Heart Association) grading and proBNP level
despite similar left ventricular ejection fraction (LVEF). The other
comorbidities and medications were similar. Detailed information is
listed in Table 1 .
Periprocedural details
HPS pacing was achieved in all 189 patients with short fluoroscopic
time. Satisfactory electrical synchrony was indicated by narrow paced
QRS wave (107.4±8.8 ms vs 106.6±10.7 ms) and short p-LVAT (75.6±10.2 ms
vs 74.4±8.6 ms), which showed no difference between the young and elder
cohorts. Pacing parameters were similar between cohorts. And no
complications including ventricular perforation were observed. Further
periprocedural details are presented in Table 2 . Fluoroscope
procedures are shown in Figure 1 and ECGs in Figure 2 .
Follow-up
All patients underwent a mean follow-up of
10.5±3.0 months. Comparing pacing
parameters monitored in the 3rd month, threshold and
impedance showed a similar decreasing pattern. Sensing rose
significantly in the younger patients, while it stayed stable in the
elderly (Figure 3 ). Though without a significant difference,
pacemaker-related events only occurred in the younger, including 2
(1.3%) lead dislodgement underwent lead revision, 1 (0.7%) pocket
hematoma underwent drainage and 3 (2.0%) pocket infections requiring
debridement.
The overall prognosis was similar between cohorts, with comparable
mortality (1 (2.7%) elder patient resulted from intestinal obstruction
and 1 (0.7%) younger patient due to ventricular fibrillation). In the
3rd month, However, cardiac events occurred more
frequently in the elderly, including a higher incidence of myocardial
infarction (8.1% vs 0.7%, p=0.03) and a non-significant higher
rehospitalization rate (27.0% vs 13.8%, p=0.05). Follow-up details are
shown in Table 3 .
TTE in the 3rd month completed in 31 young and 12
elder patients revealed similar non-significant improvements of cardiac
function (Figure 4) . Notably, only 1 younger patient had heart
failure with acutely dropped LVEF (from 60% to 24%) which resulted
from pneumonia with massive pleural effusion recovered from
thoracocentesis.
Discussion
Our study compared the clinical profiles of 37 patients aged over 85
with 152 younger patients admitted with symptomatic bradycardia and
underwent HPS pacing, suggesting that in the advanced age population
with symptomatic bradycardia: 1. HPS pacing can also be safely performed
with extensive care, 2. HPS pacing can achieve similar cardiac synchrony
and stability in the short term, 3. The short-term prognosis of HPS
pacing was comparable with younger patients.
Chinese aging population stands out as a major issue, with report
estimating over 150 million Chinese citizens will be over 80 by
2050(17). As in our study, the median age of younger
cohort was 77 years. Besides, bradycardia—resulting from either aging
or potential disease progression—is more pervasive in geriatrics.
Therefore, pacemaker implantation investigating super-aged patients has
long been a focus (13). However, as a community,
elderly patients have more comorbidities, worse general conditions and
limited life expectancy. Pacing strategy necessitates a more
comprehensive consideration compared with younger patients. Although
studies have indicated that conventional physiological pacing (dual
chamber pacing) cannot improve the likelihood of
survival(18) and cost more, less complications and a
better quality of life by physiological pacing should be considered as
well(13).
On one hand, HPS comprises the normal conduction pathway, which is an
ideal site to achieve physiological pacing. Pacing from HPS mimics
routine cardiac conduction to the greatest extent with a narrow QRS
wave. Research has proven that His-bundle pacing improves cardiac
function comparably with RV pacing(19) or
CRT(20). Besides, LBB pacing can also narrow QRS and
reserve cardiac function comparably with RV pacing(21)or CRT(22). In addition, both
His-bundle(8) and LBB(10) pacing can
be performed with stable pacing parameters. Similarly, in our study, we
observed comparable electrical synchrony with narrowed QRS and reserved
cardiac function indicated by LVEF albeit the change was
non-significant. And pacing parameters were kept stable during a
short-term. Moreover, those indices showed no difference between younger
and elder cohorts. Hence, HPS pacing could achieve stable and
physiologic cardiac synchrony in advanced age patients as well.
On the other hand, safety is a major concern for super-aged patients.
Studies on the elderly have shown that elderly patients had more
tortuous veins (as shown in Figure 2 A ), lower BMI and lower
cardiac mass(15), accounting for the higher risk of
complications such as pneumothorax, lead dislodgement and loss of
capture(14). Therefore, pacemaker implantations should
be performed with excessive care.
First, the fluoroscopic time was comparable to that previously
reported(10). Before the procedure, we thoroughly
evaluated patients’ medical histories and conducted examinations like
chest X-rays to reveal any underlying risks. Moreover, as we performed
implantation via the left subclavian or axillary vein, taking extreme
caution, no pneumothorax occurred during follow-up. According to recent
study, alternative puncture sites such as the cephalic and auxiliary
vein should be considered, as well as ultrasonic guidance if the risk of
pneumothorax is high(23). Thus, in order to ensure
safety, we recommend a thorough evaluation of patient profiles before
procedure and careful manipulation when performing pacemaker
implantation in either young or elder patients.
Secondly, lead dislodgement is rare for His-bundle pacing and LBB
pacing, as Vijayaraman et al. reported 3 acute
cases(10) and Wang et al. reported 2 late
ones(21). The manipulation of His-bundle pacing has
been well-described and performed(8). In addition,
ever since 2017 when Huang et al. published the first case of LBB
pacing(9), the maneuver of LBB pacing has been
standardized with less complications. In our study, lead dislodgement
occurred in 2 younger patients underwent His-bundle pacing early in our
center, while no case occurred in the elder cohort. Both had successful
lead repositioned at LBB. Presumably, extensive fibrosis of myocardium
caused by either myocardial infarction or cardiomyopathy render the
fixation of the electrode difficult, as Zhang et al. reported 1 failed
implantation due to fibrosis after an anterior myocardial
infarction(24). However, we currently still lack a
convenient and effective way to evaluate fibrosis and avoid such
complications. Based on our experience, we recommend the criteria to
assess lead depth and minimize the risk of lead dislodgement: 1.
Unipolar pacing impedance at the distal tip should be > 500
Ω (sharp decrement indicates perforation into LV); 2. Once LBB potential
has been recorded and pacing parameters were acceptable, screwing was
halted instantly; 3. Under DSA, we judged the lead depth by continuously
injecting contrast (Figure 2 D-F ). In addition, when retracting
the delivery sheath, we observed a rebound of the distal portion of the
lead, which indicated a steady fixation(12).
Thirdly, ventricular perforation is another major complication. No
extant study has focused on perforations in HPS pacing. Nevertheless,
one study has shown several factors to correlate with ventricular
perforation during conventional pacing, including the use of temporary
pacemakers, use of steroids, use of helical screw leads, BMI of
<20, and old age(15). Their study indicates
that a thinning of the cardiac wall for reasons unknown, and excessive
leads in the RV increase risk of perforation. Inevitably, during HPS
pacing, an active fixation 3830 lead was used and temporary pacemakers
were routinely placed for AVB patients. Furthermore, patients aged over
85 had a more vulnerable cardiac wall, with a higher risk of myocardial
infarction (18.9%) and higher usage of statins (43.2%). We presume
that the risk of perforations during HPS pacing exceeds that of
conventional pacing in advanced age population. Though we observed no
perforation in our sample of 189 patients, which is in parallel with the
incidence rate indicated by current HPS pacing studies (ranging from 0
to 3%(10,21,24,25)), we still need to stress that
manipulation should be managed with extensive care. Most importantly, we
should carefully screw the lead and evaluated the lead depth as
described above. Meanwhile, in the occasion of temporary pacing, the
lead is better fixed at the relatively thick area of the IVS. Although
such maneuvers could empirically prevent perforation, larger studies
focusing on safety are warranted to validate these conclusions. In
conclusion, we believe HPS pacing in elderly patients poses a higher
risk of perforation and extensive caution should be taken during
procedure.
Last but not least, although our study showed HPS pacing can be achieved
safely with satisfactory cardiac synchrony, we should reflect the
necessity of HPS pacing for symptomatic bradycardia population with
advanced age comprehensively. In our study, advanced age patients had
more cardiac events, including higher myocardial infarction incidence
and non-significant higher rehospitalization rate due to cardiovascular
events. We believe the deteriorated cardiac function and higher
proportion coronary heart disease might contribute to the recurrent
cardiovascular symptom. Currently, only a 20-year evidence of pacing in
patients over 90 years old provided similar outcomes of single or dual
chamber pacing(13). Although the evidence is not
adequate to illustrate the necessity of HPS pacing in advanced age
population, it can be a desirable choice in an experienced center with
the premise of safety. More importantly, we should realize that it is
general conditions, rather than age, that directly affect the safety of
the procedure. Therefore, evaluation of general conditions should be
prioritized ahead of age before HPS pacing.
Limitations
First, the conclusion cannot be extrapolated as we only included
patients with symptomatic bradycardia patients. Secondly, although both
His-bundle and LBB pacing can be physiological, the difference between
them was not stressed, which was beyond the scope of this paper. A
well-designed, larger-scaled, comparative study is required. Thirdly,
During the procedure, His-bundle and LBB potentials cannot be recorded
exhaustively, which might result from a complete LBB block or a distal
complete AVB. Moderate to severe tricuspid regurgitation could impede
the recording of His-bundle or LBB potential as well. In addition, the
duration of follow-up examinations was too short to observe long-term
clinical events. Study with a longer follow-up period is necessary to
validate the long-term necessity and benefits of these procedures. Last
but not least, due to immobility and impaired cognitive function,
compliance rates among elderly patients is low (including relatively
younger patients as well), which makes follow-up difficult and often
incomplete. A more considerate follow-up strategy is required for the
aged population.
Conclusion
Compared with a younger cohort, physiological pacing could be achieved
at HPS with a considerable success rate and level of safety in the
elderly population with symptomatic bradycardia. Long-term follow-up is
warranted to validate the benefits of HPS pacing.
Acknowledgment
Great thankfulness to all the work done by electrophysiology team.
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Table 1. Baseline
characteristics of HPS pacing patients.