Methods
Study population
Based on the registered retrospective study Combining Left Atrial
Appendage Closure with Cryoballoon Ablation in Chinese Population
(CLACBAC, registry No. NCT04185142), from June 2017 to Aril 2019, 117
consecutive patients underwent combined procedure were included.
Patients diagnosed with drug-refractory, non-valvular AF and met at
least one of the following inclusion criteria:
a. CHA2DS2-VASc score≥2 or/and
HAS-BLED score≥3,b. contraindications to long-term oral anticoagulants (OACs)
(active major hemorrhagic diseases, inherited hemorrhagic disorders,
severe side effects under OACs),c. refusal of OACs according
to personal willingness despite comprehensive explanation.
While exclusion criteria were:
a. thrombus in LA or LAA presented and confirmed by TEE,b. oversized left atrium (LA, diameter>65mm) by transthoracic
echocardiography (TTE) or LAA (ostium>35mm) by TEE,c. pericardial effusion (≥ 4mm by TTE or TEE),d. hemodynamic unstable patients,e. patients with active hemorrhagic diseases,f. ischemic or hemorrhagic stroke within 30 days.
The diagnosis of paroxysmal, persistent and long-persistent AF was in
accordance with 2016 ESC guideline (10). The diagnosis of bleeding
events referred to 2011 BARC consensus (11). For every patient, inform
of consent was signed before the procedure with procedural risks and
related complications fully informed. Our study complies with the
declaration of Helsinki and approved by the ethics committee of Shanghai
Tenth People’s Hospital.
Combined procedure
All the procedure was performed under local anesthesia with lidocaine.
Procedure details were as previously described (12). Briefly, following
a transseptal puncture, a 28 mm 2nd generation
cryoballoon (CB, Arctic Front, Medtronic, MN, USA) was cannulated to the
ostium of PV. Once complete occlusion was confirmed by angiography,
cryo-energy was delivered with a time-to-isolation (TTI) guided freezing
strategy (13). Phrenic pacing was applied to prevent phrenic nerve
lesion. Activate clotting time (ACT) was monitored and maintained above
300 seconds during the whole procedure.
LAAC was performed instantly after CB ablation. Either Watchman
(Watchman, Boston Scientific, MA, USA) or LAmbre device (Lifetech
Scientific Co, Ltd, Shenzhen, China) was used. Under TEE (GE Vivid E9
and Siemens ACUSON SC2000) guidance, LAAC device was delivered and
deployed. Before release, stable anchoring was confirmed by tug test and
complete sealing was confirmed by TEE assessment of residual flow. Once
released, TEE was applied again to reconfirm device positioning and
evaluate procedure-related complications.
Post-procedure management
The anti-thrombotic therapy was recommended as follows: 1. 3-month OACs
(Warfarin, dabigatran or rivaroxaban), 2. according to TEE examination
in the 3rd month, double anti-platelet therapy for another 3 months 3.
lifelong single anti-platelet therapy. All patients were required to
have outpatient follow-up in the 1st, 3rd, 6th, 12th month, and every
year after the procedure. TEE was scheduled to perform in the 3rd month
and the 12th month if necessary.
Primary endpoints comprise LAAC related complications (residual flow,
device related thrombosis (DRT)). Secondary endpoints encompass
all-cause death, early (before the 3rd month) and late
atrial arrhythmia (AA) recurrence (recorded atrial tachycardia (AT)
lasting longer than 30s), stroke (confirmed by either computed
tomography (CT) or magnetic resonance imaging (MRI)), major hemorrhagic
events, redo-ablation, cardiovascular intervention, pericardial effusion
rehospitalization due to cardiovascular events.
LAR measurement
For every patient, TEE was performed according to the ASE guideline and
standards (14). Preprocedural, postprocedural and follow-up TEE were
thoroughly collected. LAR profile and LAA ostium were measured on TEE at
45°/90° planes. LAR was recognized as a high-echo band between LAA and
left superior PV (LSPV). The width of LAR was measured as the maximal
length between LAA side and PV side, while the thickness of LAR was
measured from the most proximal site of LAR to the base where a
prominent reduction of echo signal was observed compared with LAR
(Figure 1 ). The outer ostium was measured from the tip of LAR
to the circumflex artery, as the landing zone of plug device (Watchman).
While the inner ostium was measured from the circumflex artery to a
point 1 to 2 cm superiorly within LAR, as the landing zone of pacifier
device (LAmbre) (15). All the images were independently measured on TEE
machine by 3 proficient echocardiologists, and the final LAR width,
thickness, LAA inner and outer ostium diameters were acquired from the
average of 3 measurements.
Statistical analysis
Continuous variables were
described as 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.
Categorical variables were
described as percentages (%), and P value was generated from
χ2 test.
The changes of LAR profile were analyzed using repeated measures
analysis of variance, and the correlation between width and thickness
change was assessed through Spearman correlation analysis. LAR lesion
was divided into mild or severe group by whether the width after
procedure was larger than 2-fold of its original width or not. The
association of LAR lesion size and clinical information and were
evaluated by logistic regression analysis. Further multivariate model
was applied that adjusted for age, gender, body mass index (BMI), LA
diameter, AF type. The influence of LAR lesion on prognosis was analyzed
through survival analysis with Kaplan-Meier estimate, and P value was
generated from Log-Rank test.
2-side P-value < 0.05 was considered significant for all
analysis. SAS 9.4 software (SAS Institute Inc., Cary, NC, USA) and
GraphPad Prism 8.0.2 (GraphPad software Inc., CA, USA) adopted to
conduct all the analysis.