Stroke Prophylaxis by Percutaneous Closure of Patent Foramen Ovale and Left Atrial Appendage
The REDUCE study is currently enrolling patients, who will be followed for up to five years. The final results are not to be expected before 2015.25
Figure 2: AMPLATZER® Cardiac Plug for the Closure of the Left Atrial Appendage
This study includes cryptogenic stroke or TIA patients, but unlike the CLOSURE I study, the TIA has to be confirmed by magnetic resonance imaging (MRI) to qualify the patient for inclusion. Of note, a device different from that used in the CLOSURE I is evaluated in the study. Thus, REDUCE may show the impact of this device on the overall comparison between medical treatment and percutaneous PFO closure. The primary end-point is freedom from recurrent ischaemic stroke, TIA confirmed by MRI, or death due to stroke.
In 2011, results are expected from the RESPECT study. The study will eventually enrol a total of 900 patients randomising them to either medical treatment or interventional therapy. The primary end-point is recurrence of non-fatal stroke, post-randomisation mortality, or fatal ischaemic stroke. This study started enrollment in 2003 and has a follow-up period of eight years.
Device-based PFO closure has the aim of long-term prevention for recurrent stroke. Therefore, the initial lack of clinical benefit due to periprocedural complications may be compensated by better long-term stroke prevention. As this will only be confirmed by long- term follow-up, the currently ongoing REDUCE and RESPECT studies will certainly add to our knowledge regarding percutaneous PFO closure. Moreover, the use of slightly different inclusion criteria and other devices will broaden our understanding regarding patient selection, procedural aspects and device selection.
Left Atrial Appendage Occlusion in Atrial Fibrillation Patients
Atrial Fibrillation, Left Atrial Appendage and Stroke Patients with AF are at increased risk for stroke.4–6
The first-choice
therapy in these patients is OAC that is recommended by the current guidelines.12
However, many aspects of OAC including a narrow therapeutic window, long half-life, intra- and inter-patient response variability and the dependence on several factors, such as food and drugs, create management difficulties. This therapy is also associated with the risk of bleeding, which may be relatively low, but potentially fatal particularly in case of cerebral haemorrhage.
Moreover, it requires periodic monitoring. New anticoagulation drugs are being developed and tested,26,27
but the associated
bleeding risk is still existing. In addition, OAC is underused in AF patients, as shown by observational studies. Most frequently, this is due to a physician’s underestimation of the therapeutic benefits and overestimation of the associated risk and patient noncompliance.28 These considerations have prompted the development of non-pharmacological approaches for stroke prevention in AF patients, not as a full alternative to OAC but as a new option for selected patients at risk for stroke who have contraindication to OAC and are not suitable for this therapy.
The thrombogenic role of the LAA in patients with AF is well established. In the absence of a regular contraction, the fibrillating atria are prone to thrombus formation. In patients with AF, echocardiography and autopsy studies have shown that more than 90% of atrial thrombi are formed in the LAA.29,30 lobed and trabeculated cul-de-sac structure31
Its tubular, often multi- is a predisposing factor
for blood stasis and thrombus formation. It therefore has received the definition of the ‘most lethal human appendage’.32
INTERVENTIONAL CARDIOLOGY
This estimates the stroke risk based on a number of well-established risk factors, including congestive heart failure, hypertension, age over 75 years, diabetes and previous stroke or TIA.
Stratification of stroke risk in AF patients is often based on the CHADS2 score.37
In 64 patients with paroxysmal AF who were followed for five years after percutaneous LAA closure, an annual stroke/TIA rate of 3.8% was observed, whereas the CHADS2 predicted rate was 6.6% per year.38 Similarly, in 71 patients in whom the LAA was occluded with this technique, Park et al. observed no stroke during a two-year follow-up. The calculated annual stroke rate based on the CHADS2 score in this population was 5%.39
Similar results were found in other observational studies on transcatheter occlusion of the LAA in AF patients.40,41
The Embolic protection in patients with atrial fibrillation (PROTECT AF) trial compared the percutaneous LAA occlusion with OAC for stroke prophylaxis in non-valvular AF patients.42
The study randomised 707
patients who were candidates for long-term OAC to either percutaneous LAA occlusion with subsequent discontinuation of warfarin (463 patients) or to OAC (244 patients). The primary composite end-point was stroke, cardiovascular death and systemic embolisation. A lower efficacy event rate was demonstrated in the intervention group compared to the warfarin therapy group (3 and 4.9% per year, respectively), leading to the conclusion that the interventional treatment was not inferior to OAC. The higher event rate in the intervention treatment group was of some concern (7.4% per patient/year versus 4.4%). In most cases, these events were procedure-related complications.
69
In view of its role in the formation of potentially fatal atrial thrombi, LAA surgical exclusion or excision was introduced as a stroke reduction measure.30,32–34
Indeed, LAA surgical resection in patients undergoing mitral valve surgery is recommended by current guidelines.35
Percutaneous Left Atrial Appendage Closure Transcatheter closure of the LAA (see Figure 2) was first reported by Sievert et al. in 2002.36
Following this initial report, a number of
non-randomised studies reported lower stroke rates in AF patients undergoing percutaneous LAA occlusion compared to that expected according to their stroke risk factors.
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