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Cerebral Protection DuringMitraClip ImplantationInitial Experience at 2 Centers

Christian Frerker, MD,* Michael Schlüter, PHD,y Oscar D. Sanchez, MD,z Sebastian Reith, MD,xMaria E. Romero, MD,zElena Ladich, MD,z Jörg Schröder, MD,x Tobias Schmidt, MD,* Felix Kreidel, MD,* Michael Joner, MD,zRenu Virmani, MD,z Karl-Heinz Kuck, MD*

ABSTRACT

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OBJECTIVES This study sought to assess the feasibility and safety of using a filter-based cerebral protection system

(CPS) during MitraClip implantation and to report on the histopathologic analysis of the captured debris.

BACKGROUND Stroke is one of the serious adverse events associated with MitraClip therapy.

METHODS Between July 2014 and March 2015, 14 surgical high-risk patients (age 75 � 7 years; 7 men; median logistic

EuroSCORE 21%) underwent MitraClip implantation employing cerebral protection with a dual embolic filter system. All

patients had severe mitral regurgitation of predominantly functional origin.

RESULTS All procedures were successfully completed for both CPS deployment/retrieval and MitraClip implantation.

A total of 28 filters (2 from each patient) were analyzed. Microscopically, debris was identified in all 14 patients. The most

common tissue types were acute thrombus and small fragments of foreign material, which were found in 12 patients

(85.7%) each. Organizing thrombus was present in 4 patients (28.6%), valve tissue and/or superficial atrial wall tissue in

9 patients (64.3%), and fragments of myocardium in 2 patients (14.3%). No transient ischemic attacks, strokes, or deaths

occurred peri-procedurally or during a median follow-up interval of 8.4 months.

CONCLUSIONS In this small study of patients undergoing MitraClip treatment with cerebral protection, embolic debris

potentially conducive to cerebrovascular events was found in all patients. Debris was composed most often of acute

thrombus, foreign material likely originating from the hydrophilic device coating, and valve/atrial wall tissue. Further

studies are warranted to assess the impact of cerebral protection on the incidence of cerebrovascular events after

MitraClip therapy. (J Am Coll Cardiol Intv 2016;9:171–9) © 2016 by the American College of Cardiology Foundation.

M itral regurgitation (MR) is the secondmost common manifestation of valvularheart disease in adults (1). Since the first

MitraClip (Abbott Vascular, Santa Clara, California)

m the *Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Ge

VPath Institute, Inc., Gaithersburg, Maryland; and the xDepartment of Ca

chen, Germany. Dr. Frerker has received lecture honoraria fromAbbott Vascu

noraria from OrbusNeich, Abbott Vascular, Boston Scientific, and Biotronik; a

Sensors International, SinoMedical, Terumo Corporation, CeloNova, W.L. G

nik.Dr.Virmanihas servedas a consultant to480Biomedical,AbbottVascular,

0 Biomedical, Abbott Vascular, Boston Scientific, Cordis J&J, Lutonix Bard, M

vascular Systems Inc., Meril Life Sciences, and Spectranetics; and has rec

medical, Abbott Vascular, Atrium,BioSensors International, Biotronik, Boston

na, Medtronic, MicroPort Medical, CeloNova, OrbusNeich Medical, ReCore,

re, Spectranetics, Cardiovascular Systems Inc., LutonixBard, Surmodics, andM

dresearch grants fromSt. JudeMedical,Medtronic, andEdwardsLifesciences;

. All other authors have reported that they have no relationships relevant to

nuscript received August 5, 2015; revised manuscript received Septembe

implantation in 2008, several studies have attestedto the safety and effectiveness of this new percuta-neous treatment option in patients with moderate-to-severe or severe MR (2–4). Current guidelines

rmany; yAsklepios Proresearch, Hamburg, Germany;

rdiology, University Hospital of the RWTH Aachen,

lar, Inc., andClaretMedical, Inc. Dr. Joner has received

nd research grants from OrbusNeich, Abbott Vascular,

ore, Medtronic, Microport, Boston Scientific, and Bio-

Medtronic, andW.L.Gore;has receivedhonoraria from

edtronic, Merck, Terumo Corporation, W.L. Gore, Car-

eived institutional grants/research support from 480

Scientific, Cordis Johnson&Johnson, GlaxoSmithKline,

SINO Medical Technology, Terumo Corporation, W.L.

eril Life Sciences.Dr.Kuckhas received consultant fees

andhas received research grants fromAbbott Vascular,

the contents of this paper to disclose.

r 14, 2015, accepted September 24, 2015.

TABLE 1 Baseline Patient Characteristics (N ¼ 14)

Men 7 (50)

Age, yrs 75 � 7

Body mass index, kg/m2 26 � 4

Logistic EuroSCORE, % 21 (18–28)

NT-proBNP, pg/ml 5,673 (1,603–12,160)

Left ventricle

End-diastolic diameter, mm 61 � 9

End-systolic diameter, mm 48 � 15

Ejection fraction, % 37 � 16

NYHA functional class

III 8 (57)

IV 6 (43)

ABBR EV I A T I ON S

AND ACRONYMS

ACT = activated clotting time

CPS = cerebral protection

system

IQR = interquartile range

MR = mitral regurgitation

MRI = magnetic resonance

imaging

MVARC = Mitral Valve

Academic Research Consortium

TAVR = transcatheter aortic

valve replacement

TIA = transient ischemic attack

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consider the MitraClip system to be a treat-ment option for high-surgical-risk patients(evidence class IIb) (5,6). Occurrence of astroke or a transient ischemic attack (TIA) isone of the potential complications duringa MitraClip procedure. Incidences of 0.2% to2.6% have been reported (2,3,7). Blazek et al.(8) showed that the MitraClip procedureresulted in new ischemic cerebral lesions ondiffusion-weighted magnetic resonance im-aging (MRI) in 23 (85.7%) of 27 patientsstudied.

Arterial hypertension 11/13 (85)

Hyperlipidemia 9 (64)

Diabetes mellitus 5 (36)

SEE PAGE 180

Cerebral embolic protection devices for

COPD 5 (36)

Pulmonary hypertension 7 (50)

Atrial fibrillation 8 (57)

Chronic renal insufficiency 7 (50)

Coronary artery disease 7 (50)

Previous cardiac surgery 2 (14)

Peripheral arterial disease 3 (21)

Prior stroke 2 (14)

MR etiology

Degenerative 3 (21)

Functional 11 (79)

MR severity

Severe 14 (100)

Values are n (%), mean � SD, or median (interquartile range).

COPD ¼ chronic obstructive pulmonary disease; EuroSCORE ¼ European Systemfor Cardiac Operative Risk Evaluation; MR ¼ mitral regurgitation; NT-proBNP ¼N-terminal pro-brain natriuretic peptide; NYHA ¼ New York Heart Association.

the prevention of cerebrovascular events have beenintroduced for transcatheter aortic valve replacement(TAVR) procedures (9). Van Mieghem et al. (10) re-ported on the histopathologic characteristics of debriscaptured and retrieved from a filter-based cerebralembolic protection device in 30 (75%) of 40 patientsundergoing TAVR. The present study assessed thefeasibility and safety of using a filter-based cerebralprotection device during MitraClip implantation andreports on the histopathologic analysis of the debriscaptured.

METHODS

PATIENTS. Between July 2014 and March 2015, a totalof 14 surgical high-risk patients underwent a Mitra-Clip procedure that employed cerebral protectionwith the dual-filter Sentinel system (Claret Medical,Santa Rosa, California) at 2 German sites (Hamburg[n ¼ 10] and Aachen [n ¼ 4]). The Hamburg patientswere treated consecutively in 2 series of 6 and 4 pa-tients; the Aachen patients were selected according tothe patient’s propensity for thromboembolic eventsdue to echocardiographically detected thrombusmaterial on pacemaker or defibrillator leads. Fourpatients (29%) had an internal cardiac defibrillator(2 of them as a cardiac resynchronization therapy)and 1 patient (7%) had a two-chamber pacemaker.No patient had a porcelain aorta. Pertinent baselinepatient characteristics are given in Table 1.

All patients had severe MR of predominantlyfunctional origin. Left ventricular function wasimpaired, with a mean ejection fraction of 37%, andall patients presented with reduced physical capacity(New York Heart Association functional class III orIV). A history of atrial fibrillation and prior stroke waspresent in 8 (57%) and 2 (14%) patients, respectively.No patient was found to have a thrombus in the leftatrial appendage or the left ventricle. Nine patients

were on oral anticoagulation (phenprocoumon, n ¼ 4;direct oral anticoagulants, n ¼ 5) without interruptionof the anticoagulation during the MitraClip inter-vention; 5 patients had dual antiplatelet therapy withaspirin and clopidogrel. Patients on dual antiplatelettherapy received a 300-mg loading dose of clopidog-rel after the MitraClip procedure. Written informedconsent was obtained from all patients.

CEREBRAL PROTECTION DEVICE. The SentinelCerebral Protection System (CPS) comprises 2 bag-like embolic filters attached back-to-back to the tipof a single 6-F compatible catheter, which isdelivered from the right arm via radial or brachialartery access over a standard 0.014-inch coronaryguidewire (Figure 1). The filter bags are made ofpolyurethane film with 140-mm laser-drilled holes,and each filter is mounted on a self-expandingnitinol wire loop. The system is advanced underfluoroscopic guidance such that the larger proximalfilter (loop diameter: 9 to 15 mm) is deployed in thebrachiocephalic trunk, and the smaller distal filter(loop diameter: 6.5 to 10 mm), which is in an

FIGURE 1 The Cerebral Protection Device Used in This Study

(A) Photograph of the Sentinel Cerebral Protection System (CPS) consisting of 2 filters for simultaneous protection of both the right side

(proximal filter) and the left side (distal filter) of the brain. (B) Schematic of the CPS in place, with the proximal filter deployed in the bra-

chiocephalic trunk and the distal filter in the left common carotid artery.

TABLE 2 Procedural Details and Outcome Parameters (N ¼ 14)

Hospitalization, days 7.4 � 5.0

ICU stay, days 1 (1–2) [n ¼ 6]

Activated clotting time, s 289 � 48

Contrast agent, ml 12.5 (10–20) [n ¼ 10]

Tamponade 0 (0)

Severe bleeding 0 (0)

Vascular complication 1 (7)

Stroke 0 (0)

TIA 0 (0)

Values are mean � SD, median (interquartile range), or n (%).

ICU ¼ intensive care unit; TIA ¼ transient ischemic attack.

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articulating sheath inside the proximal filter, isplaced in the left common carotid artery.

MITRACLIP IMPLANTATION. A standardized anti-coagulation regimen with heparin was initiated with aloading dose of 70 IU/kg aiming at an activated clot-ting time (ACT) between 250 and 300 s. The bolusof heparin was given after the puncture of all pe-ripheral vessels. Deployment of the cerebral protec-tion device was subsequently performed in allpatients via right radial access—that is, before thetransseptal puncture required for MitraClip implan-tation. Left heart catheterization was not performedafter placement of the CPS.

The procedural details of percutaneous mitralvalve repair using the MitraClip have been describedbefore (2). All procedures were performed undergeneral anesthesia in a hybrid operating room. Pro-cedural success was defined as discharge MR ofmaximally moderate severity. Procedural details aregiven in Table 2.

After MitraClip implantation, the embolic filterswere withdrawn into the catheter and removed fromthe patient. Outside, the filters were cut and stored in10% neutral buffered formalin solution and shippedto the CVPath Institute (Gaithersburg, Maryland) foranalysis.

HISTOPATHOLOGIC ASSESSMENT OF CAPTURED

DEBRIS. A total of 28 filters (2 from each patient)were analyzed. The filters were photographed (Canon

EOS Rebel XSi; Canon U.S.A., Melville, New York),examined grossly for visible debris, then cut open; allcontents were filtered through a 40-mm nylon cellstrainer (BD Falcon/Corning, Durham, North Car-olina). The majority of particles detected wereadherent to the filter, with only a small number ofimmersed particles retrieved from the fixative. Thecell-strainer disc was photographed to documentsuccessful debris transfer, and measurements of theretrieved debris were performed. The specimenswere dehydrated in a graded series of alcohols andembedded in paraffin, and sections of 5 to 6 mmthickness were cut, with 2 sections mounted on eachglass slide. The sections were stained with hematox-ylin and eosin and Movat’s pentachrome.

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The sections were evaluated for the presence ofthrombus, valve and atrial wall tissue, vascularstructures with or without atherosclerotic changes,myocardial fragments, calcification, and foreignmaterial. Thrombus was classified as acute if itshowed platelets and fibrin with entrapped red bloodcells and acute inflammatory cells, or as chronic if thethrombus showed the presence of spindle-shapedcells with or without macrophages that lined thethrombus, infiltrated it, or had any organization withmatrix deposition interspersed between the fibrin/platelet thrombus. Two pathologists reviewed theslides independently, and the final diagnosis wasbased on unanimous agreement.

Histopathologic slides were scanned using a digitalslide scanner (Axion Scan.Z1, Carl Zeiss, Thornwood,New York), and the morphometric analysis was per-formed using HALO digital image analysis software(Version 1, Indica Labs, Corrales, New Mexico).Quantitative measurements were performed on the20 largest particles identified in each cross section.The cumulative area of debris was quantitated in eachcross section using an internal algorithm for auto-mated particle detection and was expressed as thecumulative area per case. Minimum and maximumdiameters of individual particles were alsodetermined.

STATISTICAL ANALYSIS. Continuous variables aredescribed as mean � SD if normally distributed, or asmedian (interquartile range [IQR]) if not. The Mann-Whitney U test was used to assess between-groupdifferences in maximum particle diameter, withp < 0.05 considered statistically significant. Categor-ical variables are described with absolute and relativefrequencies.

RESULTS

PROCEDURAL OUTCOMES. The mean ACT in the 14procedures was 289 � 48 s. All procedures were suc-cessfully completed for both CPS deployment/retrieval and MitraClip implantation; 6 patients weredischarged with no or trace residual MR, 5 had mildMR, and 3 patients were discharged with moderateMR. A single clip was implanted in 7 patients (Hamburgn ¼ 5, Aachen n ¼ 2); the other 7 patients received 2clips each. The mean transmitral pressure gradientafter clip implantation was 3.3 � 1.4 mmHg (range: 1 to6 mm Hg).

The procedures lasted for a mean of 91 � 43 min(range: 40 to 200 min), with a fluoroscopy time of30� 16min (range: 11 to 70min). The total device time—the time from transseptal puncture to withdrawal of

the clip delivery system from the left atrium—

amounted to 58 � 31 min (range: 15 to 130 min).There were no peri-procedural TIAs or strokes.

A single vascular complication occurred in a patientin whom the supra-aortic arteries were insufficientlyvisualized by angiography; the patient experiencedbleeding from a small thyroid artery, which wastreated conservatively by administration of prot-amine at the end of the procedure. During a medianfollow-up period of 8.4 months (IQR: 3.5 to 10.3months), no patient died or experienced out-of-hospital TIA or stroke.

HISTOPATHOLOGY. Microscopically, debris wasidentified in all 14 patients. The morphometric anal-ysis of a total of 515 sections (242 from proximal, 273from distal filters) revealed a median cumulativeparticle area per patient of 2.46 (IQR: 0.44 to 3.67)mm2 and a median maximum particle diameter of 295(IQR: 104 to 509) mm; cumulative areas of debriscaptured in proximal and distal filters were 1.35 (0.30to 2.09) mm2 and 1.07 (IQR: 0.13 to 2.21) mm2,respectively, with maximum diameters of 346 (IQR:211 to 555) mm and 217 (IQR: 63 to 442) mm, respec-tively (p < 0.0001). The most common tissue typeswere acute thrombus (Figure 2A) and small fragmentsof nonpolarizable basophilic foreign material(Figure 3) that was morphologically consistent withhydrogel, which were found in 12 patients (85.7%)each. Organizing thrombus (Figure 2B) was present in4 patients (28.6%), and 2 patients were devoid of anythrombus. Fibroelastic tissue with proteoglycandeposition, consistent with either valve tissue and/orsuperficial atrial wall tissue (Figure 4), was found in atotal of 9 patients (64.3%). Two patients (14.3%)showed minute fragments of myocardium. Tissueparticles exhibiting calcification were not observed inany of the filters.

Differentiations of histopathologic findings ac-cording to the number of clips implanted and thestudy site are given in Tables 3 and 4, respectively. Nodifference in the distribution of debris type wasapparent in either analysis. However, the maximumparticle diameters were statistically significantlylarger in patients treated with 2 clips (median 402 vs.134 mm [1 clip], p < 0.0001) and in patients treatedin Aachen (median 411 vs. 262 mm [Hamburg],p < 0.0001).

The various combinations of types of debris asfound in the individual patients are shown in Figure 5.The debris was composed of thrombus, valve/atrialwall tissue, and foreign material in 8 patients (57%),and of thrombus plus foreign material without anyvalve/atrial wall tissue in 3 patients (21%). In 1 patient

FIGURE 2 Type of Thrombus

(A) Acute thrombus with platelet and fibrin (hematoxylin and eosin stained section). (B) Organizing thrombus with matrix deposition of

proteoglycan (yellow arrowheads) (Movat’s pentachrome stained section).

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each the constituents of debris were thrombus andmyocardial fibers, foreign material and myocardial fi-bers, and valve/atrial wall tissue only.

The debris was contained in all 14 proximal and all14 distal filters. The type of debris captured at the 2filter locations is shown in Figure 6. Note the simi-larity of the distributions, with most filters at bothlocations containing acute thrombus and foreignmaterial, followed by valve/atrial wall tissue. Twofilters at either location contained organizingthrombus, and myocardial fibers were detected onlyin 2 distal filters.

FIGURE 3 Foreign Material

(A, B) Basophilic foreign material (yellow arrows) intermingled with acu

(hematoxylin and eosin stained sections).

DISCUSSION

MAIN FINDINGS. The main findings of this smallstudy of using a dual-filter CPS during MitraClipimplantation are as follows:

� Using the CPS during a MitraClip procedure isfeasible and safe.

� Debris was found in all patients, with larger parti-cles identified in proximal filters, in patientstreated with 2 clips, and in patients at an increasedrisk of thromboembolic events.

te fibrin-rich thrombus, rare neutrophils, and thrombocytes

FIGURE 4 Valve Tissue

(A and C) Fibroelastic tissue with proteoglycan deposition corresponding to valve tissue and foreign material (blue arrows). (B) High-power

magnification of the boxed area in A. (D) High-power magnification of the boxed area in C. (A, B, C: hematoxylin and eosin stained section; D:

Movat’s pentachrome stained section).

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� The most prevalent types of debris were acutethrombus and foreign material consistent withhydrogel coating.

CLINICAL RELEVANCE. It has been shown thatpercutaneous interventional procedures bear the risk

TABLE 3 Histopathologic Analysis According to Number of

Clips Implanted

1 Clip(n ¼ 7)

2 Clips(n ¼ 7)

Type of debris in filters

Thrombus 6 (86) 6 (86)

Acute 6 (86) 6 (86)

Organizing 2 (29) 2 (29)

Foreign material 6 (86) 6 (86)

Valve/atrial tissue 4 (57) 5 (71)

Myocardium 2 (29) 0 (0)

Morphometry

Cumulative particle area,mm2

0.81 (0.36–2.06)[n ¼ 7]

3.45 (2.80–6.80)[n ¼ 7]

Maximum particle diameter,mm

134 (56–336)[n ¼ 261]

402 (275–589)[n ¼ 254]

Values are n (%) or median (interquartile range).

of new peri-procedural cerebral ischemic events (11).In a recent consensus document, the Mitral ValveAcademic Research Consortium (MVARC) stated thatstroke and TIA are “clinical endpoints to be collectedin all trials of mitral valve therapies” (12). The inci-dence of stroke or TIA after a MitraClip procedure ofup to 2.6% (7) justifies any attempt to prevent suchcomplications.

In this study, the Claret Sentinel device wasused for cerebral protection during MitraClip pro-cedures. Except for 1 minor vascular complication,no complications occurred while using this CPS.The overall procedure duration of 91 min comparesfavorably with procedure times reported in the Pi-lot European Sentinel MitraClip Registry (138 min),the MitraClip post-approval ACCESS-EU registry(100 min), and the German transcatheter mitralvalve interventions (TRAMI) registry (103 min)(3,4,13).

In our series of patients without any peri-procedural cerebrovascular events, the filterscaptured debris in all patients. A recent diffusion-weighted MRI study of patients after MitraClip

TABLE 4 Histopathologic Analysis According to Study Site

Hamburg(n ¼ 10)

Aachen(n ¼ 4)

Type of debris in filters

Thrombus 9 (90) 3 (75)

Acute 9 (90) 3 (75)

Organizing 3 (30) 1 (25)

Foreign material 8 (80) 4 (100)

Valve/atrial tissue 8 (80) 1 (25)

Myocardium 1 (10) 1 (25)

Morphometry

Cumulative particle area,mm2

2.24 (0.44–3.45)[n ¼ 10]

5.00 (1.13–8.47)[n ¼ 4]

Maximum particle diameter,mm

262 (89–442)[n ¼ 374]

411 (206–647)[n ¼ 141]

Values are n (%) or median (interquartile range).

FIGURE 6 Type of Captured Debris by Filter Location

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implantation without cerebral protection revealed an86% incidence of newly acquired microemboliccerebral lesions (8), suggesting a strong relationshipbetween embolic debris captured in filters duringMitraClip implantation with cerebral protection andischemic cerebral lesions detected by MRI afterMitraClip implantation without cerebral protection.

FIGURE 5 Distribution of Debris Captured in 14 Patients

Debris was captured by the cerebral protection system’s filters

in all patients. Pie chart segments represent numbers (and

percentages) of patients with different compositions of debris.

Most often found was a combination of thrombus, valve/atrial

wall tissue, and foreign material (n ¼ 8; light blue segment)

and of thrombus and foreign material without valve/atrial wall

tissue (n ¼ 3; light brown segment). Thrombus plus myocar-

dium, foreign material plus myocardium, and valve/atrial wall

tissue only was found in 1 patient each.

(A) Debris found in the 14 proximal filters protecting the

brachiocephalic trunk. The majority of filters (12 [86%] and 9

[64%], respectively) contained acute thrombus and foreign

material; valve/atrial wall tissue was present in 7 filters

(50%), and organizing thrombus was identified in 2 filters

(14%). (B) Debris found in the 14 distal filters protecting the

left common carotid artery. As in the proximal filters, the

majority of distal filters (11 [79%] and 10 [71%], respectively)

contained acute thrombus and foreign material; valve/atrial

wall tissue was present in 5 filters (36%), and organizing

thrombus and myocardial fibers were identified in 2 filters

(14%) each.

Although most of the MRI-detected embolic lesionsremained clinically silent, other studies have shownthat clinically silent cerebral lesions were associatedwith neurocognitive impairment and the develop-ment of dementia (14,15).

POTENTIAL ORIGINS OF EMBOLI DURING TRANS-

CATHETER MITRAL VALVE REPAIR. Feld et al. (16)have shown that the Brockenbrough transseptalneedle generates particles when advanced throughthe dilator and transseptal sheath. The particles inthat study were not examined further for the type ofmaterial generated. In our study, foreign particlesfound in the filters consisted of nonpolarizablebasophilic material that was morphologicallyconsistent with hydrogel. To date, no evidence has

PERSPECTIVES

WHAT IS KNOWN? MitraClip implantation is a

valid therapeutic option to relieve symptoms in

elderly patients with significant MR who are

deemed inoperable or at high surgical risk.

Stroke has been observed, if rarely, in associa-

tion with MitraClip therapy, and diffusion-

weighted MRI studies have revealed a high

incidence of new cerebral ischemic lesions after

the intervention.

WHAT IS NEW? The present study of a dual-filter

cerebral protection system employed during MitraClip

therapy has shown that embolic debris, composed

predominantly of acute thrombus and foreign material

likely originating from the hydrophilic device coating,

was released in all patients.

WHAT IS NEXT? Our findings warrant further

studies to assess the impact of cerebral protection

on the incidence of cerebrovascular events and

possibly identify patients in whom cerebral protec-

tion should be mandatory during MitraClip

implantation.

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been found of foreign material arising from theSentinel filter itself and/or its coating. Even after wemanually scraped the surface of filters, no foreignmaterial was observed under high-magnificationmicroscopy.

Hydrophilic coating is frequently used on medicaldevices for interventional procedures to decreasefriction between sheaths or catheters and vesselwalls (17). Mehta et al. (18) identified hydrophilicpolymer emboli in 9 patients who underwentvarious vascular interventions using differentcoated devices. Furthermore, multiple findings ofhydrophilic-coating material in different organshave been described (19–21). For the MitraClip pro-cedure several catheters coated with hydrophilicmaterials are used, such as the transseptal sheathfor transseptal puncture and the guide catheter forthe MitraClip system. However, it is unknown fromwhich catheter the majority of foreign materialoriginated.

The MVARC stated that transcatheter mitral valvetherapies may predispose patients to the formation ofthrombus (12). Acute thrombus could develop at thetransseptal sheath as well as at the guiding catheterand the clip delivery system due to their thrombo-genic nature. Maleki et al. (22) reported up to 9%thrombus formation on regular transseptal sheathsdespite adequate anticoagulation. In our study, anti-coagulation was adequate (as reflected by a mean ACTof 289 s throughout the procedures). In a cohort of81 patients who underwent TAVR, thrombotic mate-rial was found in 74% of patients (23). However,in that trial the ACT was suboptimal at a mean of230 s (23).

The origin of the valve and atrial wall tissuecaptured in 9 patients (64%) could be generatedfrom the transseptal puncture and the advancementof the MitraClip into the left ventricle acrossthe mitral valve. Furthermore, during grasping ofthe mitral leaflets some valve tissue might beembolized.

Calcific debris was not found in any of the filtersanalyzed in our study. This finding appears to beconsistent with the MRI study by Blazek et al. (8) whoreported no impact of mitral valve calcification on theoccurrence of embolic lesions.

STUDY LIMITATIONS. The number of patientsenrolled in this study was low. Most patients (11 of 14;79%) had functional MR. Degenerative MR might beassociated with more valve-related debris. We madeno differentiation with respect to the type of MR. Nobrain imaging or assessment of neurocognitive func-tion before and after the intervention was performed.

Both methodological additions to the study protocolas well as a comparison with a matched cohort ofpatients undergoing MitraClip implantation withoutcerebral protection would have been desirable.

CONCLUSIONS

In this study of 14 patients undergoing MitraCliptreatment using a CPS, embolic debris potentiallyconducive to cerebrovascular events was found in allpatients. The debris was composed most often ofacute thrombus, foreign material likely originatingfrom the hydrophilic device coating, and valve/atrialwall tissue. No peri- or post-procedural strokes orTIAs occurred. Further studies are warranted toassess the impact of cerebral protection on the inci-dence of cerebrovascular events after MitraCliptherapy.

ACKNOWLEDGMENT The authors thank TorieSamuda, PA, for her assistance in the histopathologicanalyses.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Christian Frerker, Department of Cardiology, AsklepiosKlinik St. Georg, Lohmühlenstr. 5, 20099 Hamburg, Ger-many. E-mail: c.frerker@asklepios.com.

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RE F E RENCE S

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KEY WORDS cerebral protection,embolization, MitraClip, mitral regurgitation,transcatheter mitral valve repair