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Reply from authors: Attempting to solve the puzzle—How to unveil the truth about the origin of stroke in postcardiotomy extracorporeal life support?

Open AccessPublished:April 21, 2022DOI:https://doi.org/10.1016/j.xjon.2022.04.023
      Reply to the Editor:
      D.W. is proctor for Abbott and Scientific advisor for Fresenius/Xenios. All other authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
      In our series of patients on postcardiotomy extracorporeal life support (ECLS), we described predominantly right hemispheric strokes in patients cannulated via the axillary artery. In accordance with our results, Grunfeld and colleagues
      • Grunfeld M.
      • Kai M.
      • Ohira S.
      Mechanism of stroke in the setting of postcardiotomy veno-arterial extracorporeal membrane oxygenation support.
      shared their experience and stress the role of primary procedure in the likelihood of developing ECLS-related stroke. Furthermore, they described a case of innominate artery occlusion in a patient with axillary artery ECLS cannulation recovering cardiac function, shifting interest on the flow phenomena in the watershed zone during weaning, and possible relation to stroke.
      Because patients on postcardiotomy ECLS are an especially complex subset of cardiac surgical patients, there are various possible sources for stroke. Mechanisms can be divided into 3 possibilities: (1) Strokes taking place during the primary procedure. These strokes may be diagnosed during ECLS but are not attributable to ECLS. (2) Stroke related to embolism from an intracardiac source occurring during ECLS—with varying likelihood for intracardiac thrombus formation depending on primary procedure, and potentially cannulation site-related flow patterns. (3) Thromboembolism from the circuit and/or cannulation site—it remains difficult to clearly distinguish the origin of stroke; whereas in certain cases it may seem rather clear, in others it might not.
      Ohira and colleagues
      • Ohira S.
      • Spielvogel D.
      • Malekan R.
      • Goldberg J.B.
      • Spencer P.J.
      • Lansman S.L.
      • et al.
      Impact of mitral valve prosthesis on stroke after insertion of veno-arterial membrane oxygenation for postcardiotomy shock.
      report an increased incidence of stroke associated with mitral valve replacement. We agree that the likelihood of intracardiac thrombus formation on ECLS is likely dependent on the primary procedure, and we included the primary procedure of all patients with stroke in our cohort in Table 1. It would be of interest whether, in the study by Ohira colleagues,
      • Ohira S.
      • Malekan R.
      • Goldberg J.B.
      • Lansman S.L.
      • Spielvogel D.
      • Kai M.
      Axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation support in cardiogenic shock.
      ECLS was prolonged in patients undergoing mitral valve replacement or whether the greater stroke rate was independent of longer support durations, and whether ECLS duration was included in the multivariable analysis. As there is obviously more time for intracardiac thrombus formation to occur with increasing ECLS duration, this may support that these patients should be weaned off ECLS as soon as possible.
      Table 1Characterization of all strokes (n = 48) with timing and clinical indication for CCT, preceding ECLS-related events, and possible causes, now including the type of initial surgery and preoperative left ventricular function
      Cannulation site groupPatient #Timing of CCTIndication for CCTHemorrhagic/ischemicmRS score at dischargeLikely cause of strokePrimary procedurePreoperative LVEF
      Axillary artery1Respiratory weaning/after explantReduced vigilanceHemorrhagic1UnknownHTXPreoperative LVAD
      2Respiratory weaning/after explantLeft-sided hemiplegiaIschemic4ECLSAVR + annular reconstruction (endocarditis)45
      3Respiratory weaning/after explantLeft-sided hemiparesisIschemic4ECLSAscending aortic aneurysm repair + CABG15
      4Respiratory weaning/after explantcomaHemorrhagic6ECLSAVR + MV repair15
      5Directly after explantSudden-onset fixed dilated pupilsHemorrhagic6ECLS explantBentall procedure15
      62 days after explantLeft-sided hemiplegia, decrease of right-sided near-infrared spectroscopy to 29% directly after ECLS explantIschemic4ECLS explantAVR + CABG + aortic arch repair60
      7Respiratory weaning/after explantReduced vigilanceIschemic2ECLSAVR25
      8Respiratory weaning/after explantcomaIschemic4ECLSAVR + MV repair + CABG25
      9After extubationParesis of right armIschemic2ECLS or surgery related (type A aortic dissection)Aortic dissection repair (aortic arch replacement)45
      102 weeks after ECLS explant, on regular ward before dischargeVisual field lossIschemic1Unknown/patient also had type A dissectionAortic dissection repair (aortic reconstruction with patch + CABG)60
      11during ECLS run (day 6)Sudden onset fixed dilated pupils on day 6 during ECLS runHemorrhagic6ECLSHTXPreoperative LVAD
      12Respiratory weaning/after explantReduced vigilanceIschemic1Unknown, patient also underwent perioperative CPRHTXPreoperative LVAD
      13Respiratory weaning/after explantLeft-sided hemiplegiaIschemic4Patient also had mechanical mitral valve thrombosisMV replacement (thrombosed mechanical mitral valve)40
      14During ECLS run (day 3)Sudden onset anisocoria at day 3 of ECLSIschemic6ECLSAVR + MV – replacement + tricuspid valve repair + maze30
      15Respiratory weaning/after explantComa, left-sided hemiplegia, embolectomy of right brachial artery after ECLS explantIschemic6ECLS related: CCT at beginning of ECLS normal, embolectomy right brachial artery after explantAVR + CABG50
      16Respiratory weaning/after explantTetraparesisIschemic5ECLSMV repair + tricuspid valve repair25
      17Respiratory weaning/after explantTetraplegia and comaIschemic6Known left atrial thrombus and systemic embolism, also to left legAVR + MV replacement + CABG + MAZE>50
      18Respiratory weaning/after explantUnknownIschemic3UnknownHTX15
      19Before hospital dischargeVisual field lossIschemic1Unknown, patient underwent concomitant right-sided carotid endarterectomyAVR + CABG + carotid endarteriectomy73
      20During ECLS run (day 3)Sudden onset fixed dilated pupils at day 3 of ECLSHemorrhagic6On ECLSMV repair + TV repair60
      21Respiratory weaning/after explantHemiplegiaIschemic4ECLSAVR + myectomy + annular augmentation60
      22During ECLS run (day 4)Sudden onset anisocoria on day 4 of ECLSHemorrhagic6On ECLSAortic dissection repair (Bentall procedure + aortic arch replacement)55
      23Respiratory weaning/after explantNCSEIschemic5Unknown, also underwent CPRMV replacement + CABGunknown
      24Respiratory weaning/after explantAphasia, left-sided HemiparesisIschemic3ECLS explanted because of device thrombosis despite adequate anticoagulationAortic dissection repair (ascending aortic replacement + CABG)Unknown
      25Respiratory weaning/after explanthemiplegiaIschemic4ECLS, arterial cannula was changed due to thrombus formationMV repair + CABG25
      26During ECLS runSeizureIschemic2ECLSAVR+TV replacement + myectomy + LAA closure60
      27Respiratory weaning/after explantReduced vigilanceIschemic1UnknownAVR + aortic root replacement (Freestyle) + CABG60
      28Respiratory weaning/after explantLeft-sided hemiplegia and dysphagiaIschemic4Patient had normal CCT 2 days before ECLS explant, large right sided ischemic stroke in CCT 3 days after ECLS explantMV repair + CABG45
      29After arterial cannula change (same day)Sudden onset anisocoria after cannula exchangeHemorrhagic6Normal CCT 2 days before explant, onset of anisocoria after arterial cannula change due to thrombus formationBentall procedure45
      30Respiratory weaning/after explantMyocloniaIschemic5Unknown, potentially ECLS relatedAVR+MV repair65
      31Respiratory weaning/after explantReduced vigilance, positive Babinski right sideIschemic4ECLSMV repair + TV repair + LAA closure65
      32Directly after explantfixed dilated pupils after explant, thrombus in arterial cannulaIschemic62 days after explant, occlusion of the right internal carotid artery was diagnosed and patient underwent thrombectomy; however, patient developed a fatal stroke. Thrombotic material in the arterial cannula was noted at the time of explantMV replacement + TV repair60
      33On ECLS (day 3)Sudden onset fixed dilated pupilsHemorrhagic6ECLSAVR+CABG45
      34Respiratory weaning/after explantComaIschemic6Unknown, 30 min CPRMV repair + TV repair + CABG + LAA closure + maze60
      35During ECLS (day 5)SeizureIschemic1ECLSPV-replacement60
      36On ECLS (day 3), after revision for mediastinal bleedingSudden onset fixed dilated pupilsHemorrhagic6Hypertensive phase during revision for bleeding; fixed unresponsive pupils after revision→CCTHTXPreoperative LVAD
      37Respiratory weaning/after explantReduced vigilance and seizureIschemic3UnknownHTXPreoperative LVAD
      38During ECLS run (day 24)unknownIschemic6ECLSVentricular rupture repairunknown
      39Respiratory weaning/after explantHemiparesis and aphasia after extubationIschemic4ECLSMV repair + TV repair + LAA closure + maze60
      40During ECLS (day 17)Seizures, dilated pupilsHemorrhagic6ECLSMV repair + CABG15
      41Respiratory weaning/after explantUnknownischemic1Unknown, also had aortic dissectionAortic dissection repair (Bentall + aortic arch repair)31-50
      Femoral artery1Respiratory weaning/after explantReduced vigilanceIschemic1ECLSAVR+CABG25
      2Respiratory weaning/after explantReduced vigilanceIschemic4Embolic? Patient also underwent CPR before implantMV repair + CABG55
      3Respiratory weaning/after explantUnknownIschemic1Watershed infarct, CPR before implantChronic type a dissection repair (ascending aortic replacement)60
      4During ECLS run (day 6)AnisocoriaIschemic6On ECLS, cannulation site was changed from femoral to axillary artery 4 days before the eventCABG55
      5Respiratory weaning/after explantHemiparesisIschemic3Unknown, perioperative CPRCABG16-30
      6On ECLS (day 8)Anisocoria during ECLS runIschemic6ECLS, cannulation site was changed from femoral to axillary artery on day 4 after implantBentall procedure31-50
      7On ECLS (day 7)Evaluation for durable left ventricular assist device implantationIschemic6Mechanical mitral valve thrombosisAVR+MV replacement49
      Table adopted from Table E6 of the original manuscript. CCT, Cerebral computed tomography; ECLS, extracorporeal life support; mRS, modified Rankin Scale; LVEF, left ventricular ejection fraction; HTX, heart transplantation; LVAD, left ventricular assist device; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; MV, mitral valve; CPR, cardiopulmonary resuscitation; TV, tricuspid valve; NCSE, nonconvulsive status epilepticus; PV, pulmonary valve; LAA, left atrial appendage.
      A considerable issue in axillary cannulation seems to be right hemispheric stroke diagnosed shortly after ECLS explantation, suggesting thromboembolism from the cannulation site at the time of decannulation as the most likely mechanism. This is a mutual finding in our study
      • Schaefer A.K.
      • Distelmaier K.
      • Riebandt J.
      • Goliasch G.
      • Bernardi M.H.
      • Zimpfer D.
      • et al.
      Access site complications of postcardiotomy extracorporeal life support.
      and the study of Ohira and colleagues,
      • Ohira S.
      • Malekan R.
      • Goldberg J.B.
      • Lansman S.L.
      • Spielvogel D.
      • Kai M.
      Axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation support in cardiogenic shock.
      who report 5 cases of stroke to right middle cerebral artery territory after decannulation in patients with axillary arterial cannulation. In our experience, in some patients, even thrombotic appositions in the circuit or even device stop were described in advance of catastrophic neurologic events. This leads to the conclusion that great care must be taken at the time of decannulation, especially after a long run duration, as thrombus formation at the site of cannulation may have occurred.
      We further hypothesize that in cases of hemorrhagic stroke, small subclinical embolic lesions in the brain, caused by embolism from the ECLS circuit or cannulation site, in combination with ECLS-related flow alterations might be a mechanism of hemorrhagic stroke.
      We feel this topic deserves further attention, and investigations of flow characteristics in the cerebral circulation depending on cannulation sites and flow rates and possible influence of cannulation site location on likelihood of stroke from an intracardiac origin are warranted.

      References

        • Grunfeld M.
        • Kai M.
        • Ohira S.
        Mechanism of stroke in the setting of postcardiotomy veno-arterial extracorporeal membrane oxygenation support.
        J Thorac Cardiovasc Surg Open. April 12, 2022; ([Epub ahead of print])
        • Ohira S.
        • Spielvogel D.
        • Malekan R.
        • Goldberg J.B.
        • Spencer P.J.
        • Lansman S.L.
        • et al.
        Impact of mitral valve prosthesis on stroke after insertion of veno-arterial membrane oxygenation for postcardiotomy shock.
        J Heart Lung Transplant. 2021; 40: S407
        • Ohira S.
        • Malekan R.
        • Goldberg J.B.
        • Lansman S.L.
        • Spielvogel D.
        • Kai M.
        Axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation support in cardiogenic shock.
        J Thorac Cardiovasc Surg Tech. 2021; 5: 62-71
        • Schaefer A.K.
        • Distelmaier K.
        • Riebandt J.
        • Goliasch G.
        • Bernardi M.H.
        • Zimpfer D.
        • et al.
        Access site complications of postcardiotomy extracorporeal life support.
        J Thorac Cardiovasc Surg. November 25, 2021; ([Epub ahead of print])

      Linked Article

      • Mechanism of stroke in the setting of postcardiotomy venoarterial extracorporeal membrane oxygenation support
        JTCVS OpenVol. 11
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          With great interest we read the study by Schaefer and colleauges,1 who conducted a detailed analysis of the outcomes of postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) support focusing on stroke and cannulation-related complications. The stroke rate of right axillary (RAX) VA-ECMO was greater than that of femoral cannulation. In both axillary and femoral VA-ECMO, the right hemisphere was the most common stroke location (64.5% in RAX and 50% in femoral). This stroke laterality trend in RAX cannulation was similar in our experiences.
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