LAARGE is a prospective, multicenter real-world registry, which enrolled patients from 37 centers. It had been designed to compile a large database on daily practice of LAAC and clinical follow-up data. Recruitment started in July 2014, and ended in January 2016. Patients which were scheduled for an LAAC were consecutively included in the LAARGE database. Cases with started procedure and documented LVEF were included in the present subanalysis (as-treated analysis). The indication was set by the attending cardiologist in consideration of the dedicated guidelines [1], and the patients were treated according to the current recommendations and the manufacturer’s instructions with different post-market devices [12]. The postprocedural management including the antithrombotic treatment was at the discretion of the operating physician [13]. The study was carried out according to the principles of the 1975 Declaration of Helsinki, and was approved by the ethics committee of the Landesärztekammer Rheinland-Pfalz. Written informed consent to participate in the registry was obtained from all patients.

LVEF dysfunction was defined as an LVEF 36–55% meaning a moderate reduction (mrLVEF), and ≤ 35% meaning a severe reduction (srLVEF).

Baseline characteristics, imaging, and procedural data as well as intra-hospital complications were reported by each center based on an electronic case report form. Adverse events and complications during the one-year follow-up were registered by the Stiftung Institut für Herzinfarktforschung (IHF) via a standardized phone interview with each patient, and by reports from the implantation centers. In the case of relevant complications, original medical records were reviewed by an event adjudication committee to allow similar assessment of all events. If patients could not be contacted, information was obtained from the residents’ registration offices.

Effectiveness was primarily assessed by the absence of all-cause death and stroke during follow-up, secondarily by the absence of systemic embolism and transient ischemic attacks (TIA). Intra-hospital complications including para-device leaks > 5 mm as well as severe and moderate bleedings, and device dislocations during follow-up constituted the safety outcome measure. Implantation success was defined as a stable device anchorage.

Statistical analyses were performed with SAS^® version 9.4 (SAS Institute, Cary, NC, USA). Continuous data are presented as means with standard deviation, or as medians with interquartile ranges (25th and 75th percentiles), categorical data as frequencies with group-related percentages. Trends across the patient groups were assessed by a Cochran–Armitage test regarding categorical variables, or by an exact Cochran–Armitage test in case of rare events, and by a Jonckheere–Terpstra test regarding metrical variables, as indicated in the tables. In addition, the group with srLVEF was compared with the rest using the Pearson chi-squared test, Fisher’s exact test, or Mann–Whitney–Wilcoxon test for categorical variables, rare events, and metrical variables, respectively. These statistics were based on the available cases.

One-year mortality after the implantation procedure, and the incidence of the combined event of all-cause death or non-fatal stroke were evaluated by means of survival analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression without adjustment, and adjusted for baseline risk factors significantly associated with LV function: age (linear), sex, coronary artery disease, peripheral arterial disease, chronic kidney disease, and diabetes mellitus. Expected yearly rates of non-fatal stroke were calculated from the individual CHA₂DS₂-VASc score, respectively [14]. The follow-up duration was defined as the time span from index discharge to the date of the follow-up contact. p values ≤ 0.05 (two-tailed) were considered significant.

619 patients with documented LVEF were included in this subanalysis. 344 (55.6%) revealed a preserved (p)LVEF, 225 (36.3%) an mrLVEF, and 50 (8.1%) an srLVEF (Table 1). Patients were predominantly older than 64 years of age (91.4%; p = NS). Among srLVEF patients male sex, coronary artery disease, and renal impairment were more prevalent (each p < 0.01). Both CHA₂DS₂-VASc (4.3 ± 1.5, 4.8 ± 1.6, and 5.1 ± 1.5, respectively; p < 0.001 for trend) and HAS-BLED score (3.7 ± 1.1, 4.1 ± 1.2 and 4.2 ± 1.0, respectively; p < 0.001 for trend) were the highest in the srLVEF group. Across all groups, the main indication was a prior bleeding event (80.0%; p = NS for trend).

The LA diameter increased with decreasing LVEF (p < 0.001 for trend; supplemental Table 1). No LAA morphology was predominant in any group.

Implantation success was achieved in 97.9%, and was independent from LVEF (p = NS for trend; Table 2). No peri-device leak > 5 mm was evident. Two interruptions were not related to LAA anatomy: in one patient, the transseptal sheath was destroyed intraprocedurally; the other patient developed an ST-segment elevation myocardial infarction. In an additional two patients, technical success was only achieved in a second procedure. There was no significant trend in the use of device types. 44.6% received a WATCHMAN™ device (Boston Scientific, Marlborough, MA, USA), 27.5% an AMPLATZER™ Cardiac Plug, and 24.9% an AMPLATZER™ Amulet™ (both Abbott, Chicago, IL, USA). Except from dose–area product, which increased with LVEF reduction (p = 0.004 for trend), procedural parameters were statistically indifferent across all groups.

Intra-hospital complications, especially major adverse cardiac and cerebrovascular events (MACCE), and other major complications were throughout infrequent, and showed a balanced distribution (Table 3). Two patients died due to an unknown or a cardiovascular reason other than the implant procedure, respectively, and the cases of death were hence classified as adverse events. Eight dislodged devices could be snared by a catheter (each p = NS for trend). Pursuant to this low number of complications, the period of hospitalization was generally short (median 2 days; p = NS for trend).

12.2% of patients received anticoagulants at hospital discharge (p = NS for trend; supplemental Table 2). Patients who received dual antiplatelet agents were prescribed this therapy for 3–6 months after the procedure (p = NS for trend), while the majority of these patients (59.0%) stayed on this medication for only 3 months.

For 602 patients (97.6% of all patients who had been discharged alive), a follow-up was documented (p = NS for trend; Table 4). The combined primary effectiveness outcome measure, i.e., absence of all-cause death and non-fatal stroke, was reached in 87.7% of patients within 365 days after the procedure (p = 0.067 for trend; Fig. 1). In a simple Cox regression model, an increased incidence of all-cause death or stroke in the srLVEF group compared to the pLVEF group was evident. However, after adjustment for age, sex, chronic kidney disease, coronary artery disease, peripheral arterial disease, and diabetes mellitus, the effect of LVEF on the combined effectiveness outcome measure did not reach statistical significance any more (Table 5). In contrast, chronic kidney disease (HR: 3.18; 95% CI: 1.90–5.32; p < 0.001), coronary artery disease (HR: 1.86; 95% CI: 1.03–3.33; p = 0.038), and peripheral arterial disease (HR: 1.72; 95% CI: 1.04–2.86; p = 0.035) were identified as independent predictors. Thromboembolic events were generally rare: non-fatal ischemic strokes occurred in 0.6% of patients, TIA in 0.4%, and systemic embolisms in 0.2% (each p = NS for trend). This was despite the fact that only 5.9% of patients who persisted on OAC after 1 year (p = NS for trend), whereby the distribution of anticoagulant agents did not differ between the groups (supplemental Table 2). In one pLVEF patient with a WATCHMAN™ device, a device-related thrombus (DRT) was detected after 1.5 months by transesophageal echocardiography (information reported for 217 patients from 20 centers, p = NS between LVEF groups; median time point 1.3 (2.7; 5.7) months). The DRT could be resolved by resumption of phenprocoumon for three months. No further thromboembolic event was registered in this patient during follow-up.

These analyses were based on data of a real-world registry with some inherent limitations. Respecting the observational character of this registry, conduction of the intervention was not influenced by the study investigators, and was based on the operators’ discretions as well as the manufacturers’ recommendations. This individualized decision algorithm might have influenced the outcome measures, but surely reflects the clinical practice. There is no information about the implantation volume per center and per operator during the study period. Adverse events during follow-up were partly self-reported, which might have lessened the detected numbers. The individual reason for a maintained anticoagulation after the procedure could not be extracted from the original data. In addition, the follow-up was limited to one year. However, despite the limitations of this observational registry, it is serving as a data source for a little studied topic.