A Review Of Clinical Trials On LARIAT Device
Payam Safavi-Naeini, MD, Abdi Rasekh, MD, FACC
Department Of Cardiology (Drs.Abdi Rasekh And Safavi-Naeini), Texas Heart Insitute .Department Of Cardiology (Dr.Abdi Rasekh), Baylor College Of Medicine, Houston, Texas.
The risk of embolic stroke is 5 times higher among patients with atrial fibrillation (AF) compared with those without AF. More than 90% of thrombi form in the left atrial appendage (LAA) in AF. The purpose of this review is to determine the efficacy and safety of the left atrial appendage (LAA) closure via a percutaneous LAA ligation approach, thus preventing a stroke among patients with AF and contraindication to oral anticoagulant therapy
Correspondence to: Dr.Abdi Rasekh, MD, FACC
Department Of Cardiology Texas Heart Insitute,Texas.
Atrial fibrillation (AF), an abnormal heart rhythm characterized by uncoordinated atrial activation due to multiple reentry circuits with consequent deterioration of atrial mechanical function, is the most common type of sustained arrhythmia.1 In 2010, AF had an estimated prevalence of between 2.7 to 6.1 million, a frequency that is projected to increase to between 5.6 to 12 million by the year 2050.2 Its prevalence increases with age, rising from 0.1% in individuals younger than 50 years old, to 5.9% in those older than 65 years, and reaching to 10% after age 75.3,4,5 Stagnation of blood in upper chambers during AF increases the propensity of thrombus formation and makes a person 4-5 times more likely to have a ischemic stroke.2 Patients with paroxysmal AF should be considered as having a stroke risk similar to individuals with persistent or permanent AF.6 Left atrial appendage (LAA) is the main site of clot formation, and more than 90% of thrombus are related to left atrial appendage dysfunction.7 AF is associated with increased risk of stroke severity, and patients with AF-related stroke have twofold the risk of mortality and threefold the risk of recurrent stroke within 1 year compared with patients without AF.8 The annual rate of ischemic stroke in patients with AF is approximately 5%, which is responsible for about 15% of strokes in the United States.9 AF-related stroke is a substantial economic burden and costs Medicare about $8 billion annually.10 Oral anticoagulation (OAC), with warfarin or new alternative antithrombotic agents (e.g.: apixaban, dabigatran, and rivaroxaban), is the current standard therapy for stroke prevention in patients with AF.11
Nevertheless, many patients (up to 40%) with AF do not receive appropriate preventive therapy for stroke.12,13 The drug–drug and drug–food interactions, variable drug metabolism and the difficulty of keeping patients in therapeutic range, the hardship of need for regular monitoring, and increasing risk of bleeding are serious concerns in using OAC. When using OAC, the rate of major bleeding is around 3% per year, and there is no major difference between warfarin or new OAC.14,15 In patients with AF at high risk of stroke, who either had contraindications to OAC therapy or previous failure of OAC therapy, utilizing a percutaneous LAA closure device (LARIAT snare device; SentreHEART, Inc., Palo Alto, California) is an alternative approach in order to prevent stroke.16
Percutaneous Suture Ligation For LAA Closure
LARIAT Suture Delivery Device (SentreHEART, Redwood City, California) is a new approach to LAA exclusion in patients who are high risk for stroke and contraindicated to or intolerant of standard oral anticoagulation therapy. The LARIAT procedure is performed under general anesthesia and the device consists of 3 components: 1) a 20-mm compliant balloon catheter (EndoCATH®), 2) 0.025” and 0.035” opposite-pole magnet-tipped guide wires (FindrWIRZ), and 3) a 12F suture delivery device.16
A 0.025-inch magnet-tipped guide wire (FindrWIRZ; SentreHEART, Inc.), is placed in the apex of the LAA through the transseptal sheath. A 0.035-inch magnet-tipped guide wire is then directed to the LAA via the pericardial space through the epicardial guide cannula (SentreHEART, Inc.) and is manipulated until its magnetic tip binds to the 0.025-inch magnet-tipped endocardial guide wire. After connecting the two magnetic wires, the LARIAT snare is advanced over the epicardial magnet-tipped wire and placed on the proximal portion of the LAA. The LARIAT suture delivery device places and tightens a loop stich around the base of the LAA with a pre-tied suture loop. The suture is released and tightened after confirmation of complete closure by the LAA Doppler (flow less than 5 mm on cross section) and the LARIAT snare is removed from the
pericardial space. The surgical suture permanently seals the LAA off from
the rest of the heart and the excluded LAAs will shrink thereafter.16
Table 1. Published procedure outcomes: Acute success rate, Complications and efficacy to prevent stroke.
et al (19)
||Rasekh , et al(16)
||Pershad, et al (18)
|<90day Closure w TEE
|Mean CHADS2 Score
||An average of 352 ±143
days (range 50 to 600)
||An average of 4.0±3.4
months (range 0.1-12.7
Selection Criteria For Lariat Procedure Among Patients
With Atrial Fibrillation
The Inclusion Criteria Included:17
1) CHADS2 score ≥ 2 or CHADS2VASc score ≥ 3,
2) Contraindicated to or intolerant of standard oral anticoagulation
(OAC) therapy (due to history of internal or external bleeding, or
high risk for bleeding),
3) Failure of OAC (embolic event despite OAC),
4) Intolerance or difficulty in using OAC.
The Exclusion Criteria Included:11
1) History of cardiac surgery,
2) Myocardial infarction within the previous 3 months,
3) Embolic events within the past 30 days,
4) New York Heart Association class IV heart failure symptoms,
5) History of thoracic radiation therapy,
6) A superior oriented LAA or one larger than 40 mm.
Our initial experience at Texas Heart Institute of LAA exclusion
by LARIAT in a cohort of patients with high risk of embolic events
and contraindicated to or intolerant of standard oral anticoagulation
demonstrated < 90% acute success rate. Transesophageal
echocardiography (TEE) at 2 to 3 months follow-up showed 100%
In addition to our experiment, two other studies have been
published.16,18,19 The safety and efficacy trends of the LARIAT
continue to be maintained in these two independent studies. Both
patient groups were at high risk of stroke and contraindicated to
OAC therapy. This appears to be the real-world compatibility of the
LARIAT in treating patients with limited options for protection.
In these studies, there were no device related complications using
the LARIAT. Access related complications tended to be related to
pericardial access, and the majority of them were not major and selfresolved
during or shortly after the procedure. Furthermore, in these
studies, only three deaths occurred during the follow-up, which were
unrelated to the procedure.
Meanwhile, preliminary data analysis showed promising results
at our center’s one-year follow-up. Among 40 patients, at 3 months
follow-up with TEE, we observed 2 leaks (one <1 mm and the other
around 2-3 mm) and one blood clot, which resolved by OAC therapy.
No CVA detected at 12 months follow-up with Questionnaire for
Verifying Stroke-Free Status (QVSFS)20 and only one patient had
stroke at 18 months after the procedure with no evidence of blood
clot in afterward follow-up TEE. We are submitting a multi-centric
follow-up study, which will provide us with profound insight into
the long-term effectiveness of the LARIAT procedure in preventing
Proposed Multi-Centric Cohort Studies
The purpose of this prospective, multi-center, randomized (1:1)
trial study is to assess the effectiveness of the LARIAT Suture
Delivery Device to reduce the risk of stroke and thromboembolic
complications in patients with non-valvular atrial fibrillation who are at risk for embolic events and are unable to use standard oral
Primary Efficacy Outcome: To assess time to the composite endpoint
(first event of ischemic/hemorrhagic stroke or systemic embolism)
in participants randomized to the LAA exclusion procedure
using the LARIAT Suture Delivery Device compared to participants
in the Control Group.
Primary Safety Outcome: To assess the incidence of major bleeding
events in participants randomized to the LAA exclusion procedure
using the LARIAT Suture Delivery Device compared to participants
in the Control Group.
Sentreheart Feasibility IDE (Investigational Device Exemptions).
This is a feasibility study to demonstrate the technical ability of
the LARIAT device to electrically isolate left atrial appendage as an
initial step in the treatment of patients with persistent or longstanding
persistent atrial fibrillation.
Technical Success: The ability of the LARIAT device to be successfully
placed around the left atrial appendage to achieve electrical
isolation defined as a reduction in LAA voltage amplitude of at least
50% of baseline voltage.
Procedural Success: The ability to achieve technical success without
any device related serious adverse events through 30 days post
Af Success: AF Burden shall be evaluated at 1, 3, 6, 12 months post
Pulmonary Vein Isolation (PVI) procedure.
Is It Possible To Increase The Efficacy Rates Of AF Ablation
With Concomitant LAA Exclusion?
Two studies examine the possibility of this hypothesis. In one
study, Han et al. reported that, there was a significant reduction in
the mean LAA voltage after successful LAA ligation procedure (64
out of 68 patients). Unipolar and bipolar pre-ligation voltage reported
1.1 ± 0.53 mV and 4.7 ± 2.83 mV respectively comparing to
unipolar (0.3 ± 0.38 mV) and bipolar (0.6 ± 0.27 mV) post-ligation voltage.21
The other study showed that the atrial arrhythmia burden de- creased from 81% to 47% (p<0.01) at 3 months follow-up among
18 patients with AF and a cardiac device, who had the LARIAT
procedure.22 A new multi-center FDA approved clinical trial (AMAZE Trial) was just initiated to evaluate the possible role of LAA closure by lariat to increase the success rate of AF ablation in patients with persistent or longstanding persistent AF.
Prevention of atrial fibrillation-related stroke has a great role in
The promising acute success rate of the LAA closure with
LARIAT (< 90%), and low incidence of embolic events in high risk
patients following the LAA ligation, suggests that LAA ligation with
LARIAT device may be a protective option in preventing strokes in
patients who have contraindications to oral anticoagulation.
The results of aforementioned proposed trials will extend our
knowledge about the efficacy of LARIAT to prevent strokes or the
possible role of concurrent LARIAT to increase the success rate of