Portal de Periódicos da CAPES

Evaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial

2021; Lippincott Williams & Wilkins; Volume: 14; Issue: 9 Linguagem: Inglês

10.1161/circinterventions.121.011074

1941-7632

Georg Fröhlich, Matthias Endres, Volkmar Falk, Lisa Steinbeck, Aslihan Erbay, Verena Stangl, Jochen Wöhrle, Tanja K. Rudolph, Tobias Geisler, Henryk Dreger, David M. Leistner, Christian H. Nolte, Axel Unbehaun, Axel Linke, Jochen B. Fiebach, Charles B.L.M. Majoie, Guido Knapp, Karl Georg Hæusler, Roxana Mehran, Stephan Windecker, George Dangas, Ulf Landmesser,

Cardiac Imaging and Diagnostics

HomeCirculation: Cardiovascular InterventionsVol. 14, No. 9Evaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBEvaluation of Cerebral Thromboembolism After Transcatheter Aortic Valve Replacement (EARTH TAVR): A Serial Magnetic Resonance Imaging Evaluation as Substudy of the GALILEO Trial Georg Marcus Fröhlich, MD Matthias Endres, MD Volkmar Falk, MD Lisa Steinbeck, MD Aslihan Erbay, MD Verena Stangl, MD Jochen Wöhrle, MD Tanja K. Rudolph, MD Tobias Geisler, MD Henryk Dreger, MD David Manuel Leistner, MD Christian H. Nolte, MD Axel Unbehaun, MD Axel Linke, MD Jochen B. Fiebach, MD Charles Majoie, MD; PhD Guido Knapp, MSc Karl Georg Haeusler, MD Roxana Mehran, MD Stephan Windecker, MD George D. Dangas, MD, PhD Ulf LandmesserMD Georg Marcus FröhlichGeorg Marcus Fröhlich Correspondence to: Georg Marcus Fröhlich, MD, Department of Cardiology, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5059-3770 , Matthias EndresMatthias Endres https://orcid.org/0000-0001-6520-3720 , Volkmar FalkVolkmar Falk https://orcid.org/0000-0002-7911-8620 , Lisa SteinbeckLisa Steinbeck , Aslihan ErbayAslihan Erbay https://orcid.org/0000-0002-9159-4929 , Verena StanglVerena Stangl , Jochen WöhrleJochen Wöhrle https://orcid.org/0000-0002-9915-1815 , Tanja K. RudolphTanja K. Rudolph https://orcid.org/0000-0001-8839-7476 , Tobias GeislerTobias Geisler , Henryk DregerHenryk Dreger , David Manuel LeistnerDavid Manuel Leistner https://orcid.org/0000-0002-4351-420X , Christian H. NolteChristian H. Nolte https://orcid.org/0000-0001-5577-1775 , Axel UnbehaunAxel Unbehaun , Axel LinkeAxel Linke , Jochen B. FiebachJochen B. Fiebach https://orcid.org/0000-0002-7936-6958 , Charles MajoieCharles Majoie https://orcid.org/0000-0002-7600-9568 , Guido KnappGuido Knapp , Karl Georg HaeuslerKarl Georg Haeusler , Roxana MehranRoxana Mehran https://orcid.org/0000-0002-5546-262X , Stephan WindeckerStephan Windecker https://orcid.org/0000-0003-2653-6762 , George D. DangasGeorge D. Dangas and Ulf LandmesserUlf Landmesser Originally published3 Sep 2021https://doi.org/10.1161/CIRCINTERVENTIONS.121.011074Circulation: Cardiovascular Interventions. 2021;14:e011074Ischemic stroke is an important complication in 2% to 6% of patients within 90 days following transcatheter aortic valve replacement (TAVR).1 The mechanism of cerebral embolism may differ according to the early time period (procedure related within 48 hours of TAVR), or later (nondirectly procedure related, eg, atrial fibrillation [AF] or valve leaflet thrombosis).1 In the PARTNER trial (The Placement of Aortic Transcatheter Valves), 62.5% of the major strokes occurred within the first 48 hours post-TAVR, 25% between days 5 and 30, and 1 stroke was noted after the first month.2 Mobilization of debris from the calcified native aortic valve or the aorta during the implant procedure may explain a significant proportion of early strokes.3 It is well known that TAVR, like surgical aortic valve replacement, may trigger new-onset AF, albeit less frequently. In a series of pivotal trials, 9.1% to 11.7% of patients were diagnosed with new-onset AF within 30 days following the implant, which was associated with increased risk of stroke.4The authors declare that all supporting data are available within the article. The aim of the present study was to evaluate the occurrence and extent of cerebral embolization (total new lesion volume on diffusion-weighted imaging [DWI] and fluid-attenuated inversion recovery imaging) in patients early and 90 days post-TAVR as compared with before TAVR in low- to intermediate-risk patients. Cerebral magnetic resonance imaging (MRI) scans were performed before TAVR, within 48 hours post-TAVR, and after 90 days. Two experienced neuroradiologists (J.B.F. and C.M.) assessed cerebral lesion number and volume, as well as intracerebral microbleedings. DWI hyperintense lesions at baseline were diagnosed as acute infarctions. Lacunar and territorial infarct patterns, either necrosis or hyperintense lesions, were diagnosed as chronic strokes. At post-TAVR MRI, new DWI lesions (compared with baseline) were diagnosed as new acute infarction and associated to the TAVR procedure. At 3-month examination, DWI hyperintense lesions and additional fluid-attenuated inversion recovery hyperintense lesions that were not diagnosed at screening (acute or chronic lesions) were diagnosed as new lesions. The difference between lesion post-TAVR MRI and 3-month MRI represents new lesions. The study was approved by the responsible authority (Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, Bonn, Germany) and an institutional review committee (Landesamt f. Gesundheit und Soziales, Berlin, Germany). All subjects gave informed consent.For continuous variables, means and SDs are reported. For binary variables, absolute numbers and percentages are given. For the primary MRI variables, the medians with 95% nonparametric bootstrap CIs are reported.Between November 2016 and May 2018, 33 patients could finally be included. The mean age was 79.4±5.8 years. Thirteen patients (39%) were men. Eight patients (24%) were diabetic, and 13 patients (39%) were known for congestive heart failure. Ten patients (30%) were known for coronary artery disease. Three patients (9%) had a previous stroke. According to EuroScore II, 26 patients (79%) had a low ( 48 hours post-TAVR and the 90-day follow-up.The primary end point demonstrated no difference in new DWI lesion volume but an increase of the fluid-attenuated inversion recovery lesions +3.5 (95% nonparametric bootstrap CI, 2–7) and the fluid-attenuated inversion recovery lesion volume of 0.11 cm3 (0.06–0.34) 90 days after TAVR if compared with baseline (Figure). On average, 5.5 (3–9) new lesions per patient were detected post-TAVR on DWI-MRI scans in comparison to the baseline scan pre-TAVR. While periprocedural cerebral embolism was common following TAVR (DWI lesion volume, 0.32 [0.12–0.67]), no additional lesions were documented at 90 days post-TAVR (Figure). Microbleedings are reasonably viewed as potential safety concern during post-TAVR antithrombotic therapy. We found, however, no concerning associations in our present study.Download figureDownload PowerPointFigure. Cerebral magnetic resonance imaging (MRI) at baseline and post-transcatheter aortic valve replacement (TAVR).A, Fluid-attenuated inversion recovery (FLAIR) cerebral MRI at baseline (red), post-TAVR (green), and after 90 d (blue). Diffusion-weighted imaging (DWI) post-TAVR. B, MRI outcomes. Numbers are presented as median and 95% nonparametric bootstrap CI (NBCI). FUP indicates follow-up.In the GALILEO trial (Global Study Comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes), >90% of patients had a low-to-intermediate perioperative risk score.5 Previous post-TAVR cerebral MRI studies reported a higher ischemic brain lesion volume of 1.5 to 4.3cm3 in up to 77% of patients, if compared with our results in a low surgical risk population.1Potential limitations of this study may be the small sample size, a change in the medical regimen in patients with new-onset AF, and a heterogeneity of procedures (several valve-in-valve procedures, use of protection devices in some patients).In summary, in low- to intermediate-risk TAVR patients without an established indication for an oral anticoagulation, cerebral thromboembolic events as assessed by MRI occurred primarily during the periprocedural phase and rarely from the post-TAVR period to 90 days.AcknowledgmentsThe Charité University Hospital Berlin was responsible for the study design and conduct of the study. The Clinical Research Organization (CRO) Cardialysis, Rotterdam, the Netherlands, was responsible for data management. The MRI core lab (Nicolab, Amsterdam, the Netherlands) was responsible for collection and blinded analysis of all cerebral MRI scans.Sources of FundingThis work was supported by Bayer Vital GmbH, Leverkusen.Disclosures Dr Fröhlich reports research grants from Bayer (significant) and speaker honoraria from Amgen and Boehringer Ingelheim (modest). Dr Rudolph reports speaker's honoraria from Boston Scientific, Edwards Lifesciences, Medtronic, and Abbot (modest). Dr Unbehaun has served as proctor to Boston Scientific. Dr Landmesser reports grants from Bayer (significant) and personal fees from Bayer, Boehringer, Daiichy Sankyo, and Pfizer, outside the submitted work (modest). Dr Falk reports consulting fees from Philips; speaker fees from Medtronic, Edwards, St. Jude Medical, and Aesculap; and research funding from Philips, Valtech, Medtronic, Biotronik, and Boston Scientific. Dr Windecker reports personal fees from AstraZeneca and grants from Boston Scientific, Terumo, Abbott, St. Jude, Edwards, and Medtronic. Dr Dangas reports research/research grants from Abbott Laboratories (significant); other from Boston Scientific Corporation; and last stock option payment for Claret (all fully divested; significant). Dr Mehran: Boston Scientific (modest); ownership/partnership/principal: Claret, bought by Boston Scientific (significant); research/research grants from Bayer Healthcare Pharmaceuticals (significant), AstraZeneca Pharmaceuticals (significant), CSL Medtronic (significant), Abbott Laboratories (significant), and Bristol Myers Squibb Company (significant). Dr Geisler reports being on scientific advisory board meetings for Bayer Healthcare, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, and Boehringer Ingelheim; Speakers Bureau (commercial) for Bristol Myers Squibb, Pfizer, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Medtronic, and Daiichy Sankyo; and funding for travel or speaker honoraria from Bristol Myers Squibb, AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Medtronic, Daiichy Sankyo, and Edwards Lifescience. Dr Leistner reports speaker honoraria and research grants from Bayer (modest). Dr Nolte has received consulting and lecture fess from Boehringer Ingelheim (honoraria for lectures, modest), W. L. Gore and Associates (honoraria for lectures, modest), Bristol Myers Squibb (honoraria for lectures, modest), Pfizer (honoraria for lectures, modest), and Sanofi (honoraria for lectures, modest). Dr Endres reports grants from Bayer and fees paid to Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, Sanofi, Novartis, and Pfizer, all outside the submitted work. Dr Fiebach has received consulting, lecture, and advisory board fees from Boehringer Ingelheim (modest). Dr Georg Haeusler reports study grants by Bayer Healthcare (significant), a study grant by Sanofi-Aventis (significant), lecture fees from Bayer Healthcare (modest), Sanofi-Aventis (modest), Pfizer, and Bristol Myers Squibb, as well as a consultant relationship with Bayer Healthcare (modest), Pfizer, and Edwards Lifesciences (modest). Dr Linke reports research support from Novartis; consulting fees/honoraria from Medtronic, Abbot, Edwards Lifesciences, Boston Scientific, AstraZeneca, Novartis, Pfizer, Abiomed, Bayer, Boehringer, major stock shareholder: Claret Medical, Picardia, and Transverse Medical. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 984.Correspondence to: Georg Marcus Fröhlich, MD, Department of Cardiology, Charité University Hospital Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Email georg.[email protected]deReferences1. Mohammed Imran G, Alexandra L. Understanding neurologic complications following TAVR.Interv Cardiol. 2018; 13:27–32. doi: 10.15420/icr.2017:25:1CrossrefMedlineGoogle Scholar2. Miller DC, Blackstone EH, Mack MJ, Svensson LG, Kodali SK, Kapadia S, Rajeswaran J, Anderson WN, Moses JW, Tuzcu EM, et al.; PARTNER Trial Investigators and Patients; PARTNER Stroke Substudy Writing Group and Executive Committee. Transcatheter (TAVR) versus surgical (AVR) aortic valve replacement: occurrence, hazard, risk factors, and consequences of neurologic events in the PARTNER trial.J Thorac Cardiovasc Surg. 2012; 143:832–843.e13. doi: 10.1016/j.jtcvs.2012.01.055CrossrefMedlineGoogle Scholar3. Schmidt T, Akdag O, Wohlmuth P, Thielsen T, Schewel D, Schewel J, Alessandrini H, Kreidel F, Bader R, Romero M, et al.. Histological findings and predictors of cerebral debris from transcatheter aortic valve replacement: the ALSTER experience.J Am Heart Assoc. 2016; 5:e004399. doi: 10.1161/JAHA.116.004399LinkGoogle Scholar4. Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK, Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, et al.; PARTNER 2 Investigators. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.N Engl J Med. 2016; 374:1609–1620. doi: 10.1056/NEJMoa1514616CrossrefMedlineGoogle Scholar5. Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, Makkar RR, Herrmann HC, Giustino G, Baldus S, et al.; GALILEO Investigators. A controlled trial of rivaroxaban after transcatheter aortic-valve replacement.N Engl J Med. 2020; 382:120–129. doi: 10.1056/NEJMoa1911425CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails September 2021Vol 14, Issue 9Article InformationMetrics Download: 188 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.121.011074PMID: 34474587 Originally publishedSeptember 3, 2021 Keywordsinfarctionbrain ischemiaaortic valvethrombosisischemic strokePDF download SubjectsCerebrovascular Disease/StrokeAortic Valve Replacement/Transcatheter Aortic Valve ImplantationIschemic StrokeImagingMagnetic Resonance Imaging (MRI)