Published online before print January 3, 2008, doi: 10.1161/STROKEAHA.107.491241
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2008;39:503.)
© 2008 American Heart Association, Inc.
Progress Reviews |
Occurrence and Clinical Impact of Microembolic Signals During or After Cardiosurgical Procedures
From the Department of Neurology (R.D., E.B.R.) and the Leibniz Institute for Atherosclerosis Research (R.D., E.B.R.), University of Muenster, Muenster, Germany.
Correspondence to Ralf Dittrich, MD, Department of Neurology, University Hospital of Muenster, Albert-Schweitzer-Strasse 33, 48129 Muenster, Germany. E-mail dittrir{at}gmx.de
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
Background and Purpose— Microembolic signals (MESs) are detectable within the transcranial Doppler frequency spectrum downstream from vascular atherothrombotic or cardiothrombotic lesions. A frequent occurrence of MESs has also been shown during bypass surgery or after mechanical valve implantation. We sought to compile the knowledge on MES prevalence, the clinical impact of these cardiogenic MESs, and microemboli composition.
Summary of Review— We performed a systematic MEDLINE search and summarized the currently available literature about MESs during or after cardiosurgical procedures for this state-of-the-art report.
Conclusions— The nature of cardiogenic MESs is heterogeneous, and their prevalence is highly variable, reflecting their different origin from a broad spectrum of cardiosurgical conditions. The occurrence and number of MESs during cardiac catheterization and percutaneous coronary angioplasty seem to have a clinical impact but need to be explored further. In patients with prosthetic heart valves, in those with left ventricular assist devices, and during cardiac surgery, the occurrence of MESs has an important clinical impact, and MES monitoring has proven its reliability. Although the data encourage intensifying MES detection in cardiac disorders, their heterogeneous nature does not yet allow the use of MESs as a general surrogate parameter for neuronal damage or cardial thromboembolic risk.
Key Words: cardiac embolism • cardiac surgery • cognitive impairment • tcd • transcranial Doppler • ultrasound
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
In the late 1960s, decompression bubbles in divers were described by means of diagnostic ultrasound,1 as well as arterial aeroembolism during cardiac surgery.2 These clinically silent signals, preferably called microembolic signals (MESs), are detectable within the transcranial Doppler frequency spectrum (TCD). Because of the detection of MESs in patients with artificial heart valves, it became evident that MESs can also originate from the heart itself.3 Their clinical impact depends on the presence of thromboembolic diseases within the heart or other cardiogenic embolic sources, eg, during or after cardiosurgical procedures. Despite the widespread use of TCD monitoring in patients with cardiac sources of embolism, a systematic overview, in particular with respect to cardiac surgical procedures, about this topic is missing. Thus, the goal of the following review is to summarize the present state of knowledge about the cardiosurgical conditions leading to MESs, their prevalence, clinical impact, and microemboli composition.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
We performed a systematic MEDLINE search limited to the English language containing the search terms "microembolic signals," "microemboli," or "high-intensity transient signals." These search terms were combined with the different topics of the review: "heart valves," "prosthetic heart valves," "artificial heart valves," "assist device," "cardiac surgery," "bypass surgery," "coronary angioplasty," and "cardiac catheterization." Comments, reviews, letters, case reports, animal studies, and in vitro studies were not considered. The inclusion criteria were systematic TCD monitoring in homogeneous patient groups providing new findings and scientifically relevant results in the aforementioned topics. We screened and extracted the articles and decided by consensus about their inclusion.
|
MESs in Prosthetic Heart Valves |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
In patients with mechanic heart valves (MHVs), the frequency of MESs4–6 depends on the type of valve installed,7–14 whereas the prevalence of MESs is much lower with bioprostheses13–17 (see Table 1
). The majority of MESs, particularly in MHV carriers, reflect gaseous microemboli due to cavitation at the rim of the MHV18,19 and not to the shedding of thromboembolic material. This hypothesis is supported by the stable number of MESs found during repeated investigations and the lack of patients’ clinical deterioration over time.6 Also, the rate of cardioembolic stroke in these patients does not appear to be correlated with the number of MESs detected.15 No correlation could be identified between the patient’s hemostaseology and either the number of MESs or the type and extent of antithrombotic treatment.20 Similarly, neurologic deficits based on the number of MESs detected in MHV carriers could not be predicted.21,22 No difference could be demonstrated in MESs between symptomatic and asymptomatic MHV carriers.22 The gaseous MESs associated with MHVs are characterized by a higher relative intensity increase over the background speckle as opposed to solid MESs. There is, however, considerable overlap of the "loudness" of these various types of MESs, thereby not allowing a clear differentiation between the 2.23 This is why inhalation of concentrated oxygen has been used to suppress cavitation formation to distinguish solid thromboembolic from gaseous material.14,24,25 Because the solubility of oxygen in blood is 
5 times greater than that of nitrogen, the blood is preferably saturated with oxygen instead of nitrogen. Oxygen cavitation is short-lived, which means that many oxygen bubbles do not reach the brain at all. Most of the oxygen cavitation bubbles have a diameter of 3 to 5 µm, allowing them to easily pass capillaries without doing harm to brain tissue. In patients with MHVs, the number of MESs could significantly be reduced by inhaling oxygen compared with a period without oxygen inhalation.18 Similarly, no effect on the MES rate was seen in patients with solid microemboli derived from atherothrombotic arterial sources during oxygen inhalation.26
|
|
Quite contrary, a higher number of MESs per hour in MHV carriers with a medical history suggestive for stroke60 compared with asymptomatic MHV carriers11 was reported.5 In other studies, impaired working memory could be demonstrated in patients having received MHVs, presumably caused by continuous "showers" of cerebral microembolism.27,28 Also, increased levels of platelet-derived microparticles, an increased procoagulant activity, and an increased rate of MESs were found in MHV carriers symptomatic with cerebrovascular events.29 In 30 patients with bileaflet valves, a reduction of MESs by 16% to 41% after administration of acetylsalicylic acid of 81 to 531 MESs/h was demonstrated.25 Additionally, a higher number of MESs was found in patients with valve obstruction.30 Successful thrombolysis led to a marked decrease of MESs, whereas the number of MESs remained almost stable after unsuccessful thrombolysis. The fact that successful thrombolysis may lead to a higher number of gaseous MESs due to better leaflet mobility and that the authors used a nonvalidated threshold of 400 Hz to differentiate solid from gaseous MESs are limitations of that study. However, the described results indicate that microemboli in MHV carriers are at least in part composed of solid material.
In conclusion, the potential harm due to chronic MESs, particularly in patients with MHVs, seems to be low or negligible because the majority of these microemboli are gaseous and generated by microcavitation. However, owing to their mixed gaseous and solid origin, they cannot be used as an indicator of a thromboembolic threat or event.
|
MESs in LVADs |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
In patients with left ventricular assist devices (LVADs), thromboembolism is 1 of the most frequent complications requiring effective anticoagulation.31 Depending on the device implanted, the MES prevalence ranges from 20% to 100%.32–40 A higher amount of MESs corresponds to thromboembolic events in patients with the Novacor N100 LVAD,32,34,37 but not in patients with a DeBakey device.38,40 Patients with the Novacor N100 device and antithrombotic therapy in addition to anticoagulation (eg, antiplatelet agents) had significantly fewer MESs and thromboembolic events.37 Again, this phenomenon could not be demonstrated in patients with a DeBakey device.38 MESs in DeBakey LVAD carriers could be abolished in part by oxygen inhalation, indicating that a substantial number of these MESs are gaseous in origin38,39 (see also Table 2
). However, the use of time domain analysis to differentiate the mixed composition of gaseous and solid emboli was unsuccessful.39
|
|
A "hidden" procoagulable state is presumably the reason for the higher number of solid MESs in the patients who experience thromboembolic events. In conclusion, the MES load, MES composition, and the relation to thromboembolic events depend strongly on the device installed, the individual thromboembolic risk, and the extent of antithrombotic treatment. The heterogeneity of influencing factors does not allow us to draw a final conclusion about the predictive value of MES monitoring, but it might be possible for each individual type of LVAD.
|
Monitoring of MESs During Cardiac Surgery |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
The number of MESs during open-heart surgery is high, and often showers of MESs are recorded, particularly during clamp placement and removal in cardiopulmonary bypass grafting (CABG).41–46 Also, residual air in the venous cannula increases the number of MESs at the beginning of CABG.47 These intraoperative MESs can cause cognitive impairment. In patients having <200 MESs during their CABG procedure, 8.6% showed postoperative neuropsychological deficits, but this proportion rose to 43% in patients having >1000 MESs.48 Moreover, a higher occurrence of postoperative neurologic complications in patients with a high number of MESs (>60) during CABG was demonstrated.43 In another study, a reduction in postoperative cerebral glucose metabolism was found, correlating with the number of MESs recorded (r=–0.46, P<0.05).49 Although neuropsychological impairment occurred after the surgical procedure, its correlation with the number of MESs or the decrease in cerebral glucose metabolism could not be proven. Lee et al50 demonstrated that a higher number of intraoperative MESs corresponded with an impairment in an auditory verbal learning test 2 weeks and 1 year after CABG (P
0.05). Interestingly, a specific verbal memory decline in patients with predominantly left-sided MESs was observed, whereas a higher number of right-sided MESs was associated with a nonverbal memory deficit after open-heart surgery.51 The correlation of a high number of MESs, particularly during on-pump cardiac surgery, with a relative reduction of prefrontal activation during functional magnetic resonance imaging while performing verbal memory tasks 4 weeks postoperatively could also be demonstrated.52 There are additional reports on cognitive impairment and delayed recovery after CABG due to intraoperative MESs.53–57
The nature of these MESs, either solid or gaseous, is not fully understood. An increased number of MESs during aortal manipulation, especially in the case of severe aortal atherosclerosis, indicated the predominantly solid nature of MESs.44 In another study, the higher number of MESs in patients with valve replacement or CABG was associated with postoperative neuropsychological impairment. A much higher number of MESs (mean, 2083 per case during operation) in patients with valve replacement compared with those with CABG (mean, 50 MESs per case during operation, P0.05) was found. Interestingly, both conditions led to similar severe neuropsychological impairment. The authors concluded that this observation reflected the primarily gaseous nature of the MESs during valve replacement as opposed to the predominantly solid MESs during bypass surgery.54 Similar conclusions were drawn in a larger study with a more simple detection technique despite a lower number of MES detected.58
A considerable proportion of MESs during cardiac surgery appear to be gaseous. These gas bubbles are much larger than the cavitation-induced bubbles and may do harm to the brain. With respect to various surgical steps during CABG, the occurrence of MESs was analyzed.59 During the aortic clamp placement and its removal, more solid MESs were seen (mean MES increase, 1.5±1.5/min). By contrast, during perfusion interventions (eg, blood sampling, drug administration), more gaseous MESs could be registered (mean MES increase, 6.9±4.5/min). The number of MESs was significantly higher during perfusion interventions. Similarly, a higher number of MESs and more severe neuropsychological deficits were found when 
10 perfusion interventions became necessary during the entire course of the operation compared with patients with fewer interventions.60 Reduced purging and the use of continuous infusions instead of bolus injections significantly decreased the number of MESs during the surgical procedure.61 Also, when a large-bore syringe was used, the rate of MESs was significantly lower compared with that seen with a small-bore syringe.62 Moreover, it could be demonstrated that CO2 insufflation in the cardiothoracic wound during open-heart valve surgery reduced the number of gaseous MESs.63
Finally, a dramatic and significant reduction of MESs was achieved with off-pump CABG.50,64–70 Another study group71 not only confirmed the higher number of MESs during on-pump (mean, 335.1) compared with off-pump (mean, 144.7) surgery but also found a significantly lower 6-month postoperative "cognitive impairment-index" in the off-pump patient group, as assessed by counting the number of impaired test performances for each patient in 7 tests. A limitation of these results is the fact that a significant cognitive decline was not related to the number of MESs during operation. Others observed the same phenomenon, but the amount of MESs was not correlated with the S100 protein level, a marker of diffuse cerebral injury.69 In contrast, a significantly higher level of S100 protein in patients undergoing on-pump surgery and a higher intraoperative number of MESs in patients with retinal microvascular damage were reported.70
Further refinement of surgical techniques, like avoidance of aortic side clamping and the use of clampless devices, also reduces the number of solid MESs.46 In that study, automatic software had been used to discriminate between solid and gaseous MES, which could be a potential source of error. The additional use of a sutureless proximal aortic device led to a decrease of MESs during the surgical procedure.72 Arterial filters, in particular leukocyte-depleting filters, fat-removal filters, or an air bubble trap in the arterial line, could also considerably reduce the number of MESs.73–79 Because the number of MESs is higher in cases of longer-duration CABG procedures, shorter operation times may prevent harm due to MESs.80 In left heart valve replacement, the application of a new "dual-vent" de-airing technique could significantly reduce the number of carotid MESs.81 Furthermore, cannulation of the distal aortic arch led to a decrease of MESs compared with conventional cannulation of the ascending aorta.82,83 The use of a straight or curved aortic cannula, or cannulas of different diameters, had no influence on the number of MESs.84 However, optimized positioning in the aorta descendens was not associated with better performance in postoperative cognitive tests.85 The number of MESs again depends on the type of oxygenator device used, even when modern versions are used. The mean number of MES during the whole procedure was 309 for the DIDECO oxygenator but only 143 for the COBE oxygenator (P<0.00001).86
Not all protective efforts lead to a significant decline in MESs during cardiac surgery. A surface-modifying additive during conventional cardiopulmonary bypass surgery did not reduce the number of MESs.87 In addition, there was no difference in MES number when a minimally invasive versus a conventional mitral valve operation was performed.88 Finally, an symmetry connector system, to avoid partial clamping, was followed by an increased number of MESs, presumably due to gaseous microemboli.89
Another point of interest is the hemispheric distribution of MESs during cardiac surgery, but the results are ambiguous so far. Whereas some study groups described a preponderance of left-sided MESs,50,90 others either reported an equal distribution of MESs91 or found a preference for the right hemisphere.49,51 In conclusion, MESs are a common phenomenon during cardiac surgery. The composition of the microemboli is heterogeneous and reflects solid and gaseous particles. So far, it remains controversial which composition of MES represents the majority during cardiosurgical procedures. However, it is indisputable that a large number of MESs during cardiosurgical procedures leads at least to temporary if not permanent neuropsychological deficits due to neuronal damage. The type and degree of the resulting deficit depends on the hemisphere to which the higher number of MESs are channelled. Thus, MES monitoring by TCD is a reliable, easily accessible, noninvasive tool to guide and improve surgical techniques.
|
Monitoring of MESs During Cardiac Catheterization and Percutaneous Coronary Angioplasty |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
Asymptomatic MESs were detected in >50% of patients during left atrial catheterization.92,93 The same phenomenon was discovered during percutaneous transluminal coronary angioplasty.94 The majority (70%) of the 679 MESs occurred after injection of solutions; hence, the authors concluded that these MES were predominately gaseous. Other authors confirmed this finding and detected MESs primarily during contrast agent injection.95 Further evidence for the primarily gaseous origin was the reduction in the number of MESs by using solutions with a low gas content.96 In all of the aforementioned studies, clinically apparent neurologic deficits did not occur after the procedure. The use of a guidewire and different catheter types also influenced the number of MESs.97 In a recent more sophisticated study, the authors verified the primarily gaseous origin of MESs in 47 patients during left heart catheterization by automated software (92.1% gaseous vs 7.9% solid MESs).98 Interestingly, 3 (6.4%) patients had transient neurologic deficits immediately after the procedure, and 7 (16.7%) patients had cognitive impairment as assessed by neuropsychological tests 24 hours after the procedure. Five (15.2%) patients had new cerebral lesions detected by diffusion-weighted magnetic resonance imaging 24 hours after catheterization. This finding coincided with a higher number of solid MESs (P=0.016). These results suggest that the procedural occurrence of MESs during catheterization is potentially harmful; it can damage the brain parenchyma and cause at least transient neurologic symptoms. However, in another study, only 1 of 46 patients developed a new diffusion-weighted imaging lesion after the procedure.99 In conclusion, the clinical impact of MESs during left heart catheterization appears to be clinically relevant but needs to be investigated further with standardized study protocols.
|
Limitations of MES Monitoring |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
Unfortunately, MES monitoring by TCD has general major limitations. Studies conducted so far have used different monitoring times, ultrasound devices, and monitoring protocols, thus hampering the comparability of results. In addition, the overlapping physical properties of the microemboli do not yet allow us to unequivocally differentiate gaseous from solid MESs, despite promising technical progress, like multifrequency TCD,100 a longer sample volume length for gaseous microemboli,101 and Doppler time domain analysis.39 Finally, there is a lack of large, prospective and long-term, follow-up studies in all fields of cardiosurgical procedures. These limitations are the major drawbacks for the validity of MESs as a surrogate parameter that could replace clinical outcome events.
|
Summary |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
The prevalence and number of cardiogenic MESs during all types of cardiac interventions is high but depends strongly on the underlying cardiosurgical condition. The clinical impact is as heterogeneous as the number of settings in which MESs occur. MESs in patients with MHVs are mainly cavitation-based, gaseous in nature, and usually harmless to the brain. Quite contrary, the differing load of solid particles in various cardioembolic disorders allows us to define a hierarchy of embolic risk related to the various diseases and procedures. Showers of solid or large gaseous MESs during cardiac surgery, cardiac catheterization, or percutaneous coronary angioplasty are harmful but are partly preventable by both better technical equipment and improved and meticulous surgical technique. MESs can provide clues to successfully modify surgical interventions, and they may serve as a guide to the choice of timing and technical guidelines of a given intervention. However, MESs during or after cardiosurgical procedures are not yet an accepted surrogate parameter for the prediction of thromboembolic risk or neuronal damage with cognitive decline.
|
Acknowledgments |
|---|
Disclosures
None.
Received May 13, 2007; accepted June 7, 2007.
|
References |
|---|
|
TopAbstractIntroductionMethodsMESs in Prosthetic Heart...MESs in LVADsMonitoring of MESs During...Monitoring of MESs During...Limitations of MES MonitoringSummaryReferences |
|---|
1. Spencer MP, Campbell SD, Sealey JL, Henry FC, Lindbergh J. Experiments on decompression bubbles in the circulation using ultrasonic and electromagnetic flowmeters. Occup Med. 1969; 11: 238–244.
2. Spencer MP, Lawrence GH, Thomas GI, Sauvage LR. The use of ultrasonics in the determination of arterial aeroembolism during open heart surgery. Ann Thorac Surg. 1969; 8: 489–497.[Medline] [Order article via Infotrieve]
3. Berger M, Davis D, Lolley D, Rams J, Spencer MP. Detection of subclinical microemboli in patients with prosthetic heart valves. J Cardiovasc Tech. 1990; 9: 282–283.
4. Grosset DG, Cowburn P, Georgiadis D, Dargie HJ, Faichney A, Lee KR. Ultrasound detection of cerebral emboli in patients with prosthetic heart valves. J Heart Valve Dis. 1994; 3: 128–132.[Medline] [Order article via Infotrieve]
5. Braekken KS, Russell D, Brucher R, Svennevig J. Incidence and frequency of cerebral embolic signals in patients with a similar bileaflet mechanical valve. Stroke. 1995; 26: 1225–1230.
6. Georgiadis D, Kaps M, Siebler M, Hill M, Konig M, Berg J, Kahl M, Zunker P, Diehl B, Ringelstein EB. Variability of Doppler microembolic signal counts in patients with prosthetic cardiac valves. Stroke. 1995; 26: 439–443.
7. Muller HR, Burckhardt D, Casty M, Pfisterer ME, Buser MW. High intensity transcranial Doppler signals (HITS) after prosthetic valve implantation. Heart Valve Dis. 1994; 3: 602–606.
8. Georgiadis D, Grosset DG, Kelman A, Faichney A, Lees KR. Prevalence and characteristics of intracranial microemboli signals in patients with different types of prosthetic cardiac valves. Stroke. 1994; 25: 587–592.[Abstract]
9. Georgiadis D, Kaps M, Berg J, Mackay TG, Dapper F, Faichney A, Wheatley DJ, Lees KR. Transcranial Doppler detection of microemboli in prosthetic heart valve patients: dependency upon valve type. Eur J Cardiothorac Surg. 1996; 10: 253–257;discussion 257–258.
10. Grosset DG, Georgiadis D, Kelman AW, Cowburn P, Stirling S, Lees KR, Faichney A, Mallinson A, Quin R, Bone I, Pettigrew L, Brodie E, MacKay T, Wheatley DJ. Detection of microemboli by transcranial Doppler ultrasound. Tex Heart Inst J. 1996; 23: 289–292.[Medline] [Order article via Infotrieve]
11. Deklunder G, Lecroart JL, Savoye C, Coquet B, Houdas Y. Transcranial high-intensity Doppler signals in patients with mechanical heart valve prostheses: their relationship with abnormal intracavitary echoes. J Heart Valve Dis. 1996; 5: 662–667.[Medline] [Order article via Infotrieve]
12. Lindner A, Georgiadis D, Luhmann A, Stephan M, Preiss M, Zerkowski HR, Zierz S. Time course of high-intensity transient signals in patients undergoing elective heart valve replacement: a prospective study. J Heart Valve Dis. 1997; 6: 527–530.[Medline] [Order article via Infotrieve]
13. Sliwka U, Georgiadis D. Clinical correlations of Doppler microembolic signals in patients with prosthetic cardiac valves: analysis of 580 cases. Stroke. 1998; 29: 140–143.
14. Milano A, D’Alfonso A, Codecasa R, De Carlo M, Nardi C, Orlandi G, Landucci L, Bortolotti U. Prospective evaluation of frequency and nature of transcranial high-intensity Doppler signals in prosthetic valve recipients. J Heart Valve Dis. 1999; 8: 488–494.[Medline] [Order article via Infotrieve]
15. Eicke BM, Barth V, Kukowski B, Werner G, Paulus W. Cardiac microembolism: prevalence and clinical outcome. J Neurol Sci. 1996; 136: 143–147.[CrossRef][Medline] [Order article via Infotrieve]
16. Georgiadis D, Lindner A, Manz M, Sonntag M, Zunker P, Zerkowski HR, Borggrefe M. Intracranial microembolic signals in 500 patients with potential cardiac or carotid embolic source and in normal controls. Stroke. 1997; 28: 1203–1207.
17. Lievense AM, Bakker SL, Dippel DW, Taams MA, Koudstaal PJ, Bogers AJ. Intracranial high-intensity transient signals after homograft or mechanical aortic valve replacement. J Cardiovasc Surg (Torino). 1998; 39: 613–617.[Medline] [Order article via Infotrieve]
18. Georgiadis D, Wenzel A, Lehmann D, Lindner A, Zerkowski HR, Zierz S, Spencer MP. Influence of oxygen ventilation on Doppler microemboli signals in patients with artificial heart valves. Stroke. 1997; 28: 2189–2194.
19. Georgiadis D, Baumgartner RW, Karatschai R, Lindner A, Zerkowski HR. Further evidence of gaseous embolic material in patients with artificial heart valves. J Thorac Cardiovasc Surg. 1998; 115: 808–810.
20. Sturzenegger M, Beer JH, Rihs F. Monitoring combined antithrombotic treatments in patients with prosthetic heart valves using transcranial Doppler ultrasound. Stroke. 1995; 26: 63–69.
21. Kofidis T, Fischer S, Leyh R, Maier H, Deckert M, Haberl R, Haverich A, Reichert B. Clinical relevance of intracranial high intensity transient signals in patients following prosthetic aortic valve replacement. Eur J Cardiothorac Surg. 2002; 21: 22–26.
22. Nadareishvili ZG, Beletsky V, Black SE, Fremes SE, Freedman M, Kurzman D, Leach L, Norris JW. Is cerebral microembolism in mechanical prosthetic heart valves clinically relevant? J Neuroimaging. 2002; 12: 310–315.[Medline] [Order article via Infotrieve]
23. Droste DW, Dittrich R, Hermes S, Kemeny V, Schulte-Altedorneburg G, Hansberg T, Ringelstein EB. Four-gated transcranial Doppler ultrasound in the detection of circulating microemboli. Eur J Ultrasound. 1999; 9: 117–125.[CrossRef][Medline] [Order article via Infotrieve]
24. Kaps M, Hansen J, Weiher M, Tiffert K, Kayser I, Droste DW. Clinically silent microemboli in patients with artificial prosthetic aortic valves are predominately gaseous and not solid. Stroke. 1997; 28: 322–325.
25. Laas J, Kseibi S, Perthel M, Klingbeil A, El-Ayoubi L, Alken A. Impact of high intensity transient signals on the choice of mechanical aortic valve substitutes. Eur J Cardiothorac Surg. 2003; 23: 93–96.
26. Droste DW, Hansberg T, Kemeny V, Hammel D, Schulte-Altedorneburg G, Nabavi DG, Kaps M, Scheld HH, Ringelstein EB. Oxygen inhalation can differentiate gaseous from nongaseous microemboli detected by transcranial Doppler ultrasound. Stroke. 1997; 28: 2453–2456.
27. Deklunder G, Roussel M, Lecroart JL, Prat A, Gautier C. Microemboli in cerebral circulation and alteration of cognitive abilities in patients with mechanical prosthetic heart valves. Stroke. 1998; 29: 1821–1826.
28. Uekermann J, Suchan B, Daum I, Kseibi S, Perthel M, Laas J. Neuropsychological deficits after mechanical aortic valve replacement. J Heart Valve Dis. 2005; 14: 338–343.[Medline] [Order article via Infotrieve]
29. Geiser T, Sturzenegger M, Genewein U, Haeberli A, Beer JH. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles in patients with prosthetic heart valves. Stroke. 1998; 29: 1770–1777.
30. Hiratsuka R, Fukunaga S, Tayama E, Takagi K, Arinaga K, Shojima T, Teshima H, Aoyagi S. High-intensity transient signals due to prosthetic valve obstruction: diagnostic and therapeutic implications. Ann Thorac Surg. 2004; 77: 1615–1621.
31. Pennington DG, McBride LR, Peigh PS, Miller LW, Swartz MT. Eight years’ experience with bridge to cardiac transplantation. J Thorac Cardiovasc Surg. 1994; 107: 472–481.
32. Nabavi DG, Georgiadis D, Mumme T, Schmid C, Mackay TG, Scheld HH, Ringelstein EB. Clinical relevance of intracranial microembolic signals in patients with left ventricular assist devices: a prospective study. Stroke. 1996; 27: 891–896.
33. Moazami N, Roberts K, Argenziano M, Catanese K, Mohr JP, Rose EA, Oz MC. Asymptomatic microembolism in patients with long-term ventricular assist support. ASAIO J. 1997; 43: 177–180.[Medline] [Order article via Infotrieve]
34. Schmid C, Weyand M, Nabavi DG, Hammel D, Deng MC, Ringelstein EB, Scheld HH. Cerebral and systemic embolization during left ventricular support with the Novacor N100 device. Ann Thorac Surg. 1998; 65: 1703–1710.
35. Wilhelm CR, Ristich J, Knepper LE, Holubkov R, Wisniewski SR, Kormos RL, Wagner WR. Measurement of hemostatic indexes in conjunction with transcranial Doppler sonography in patients with ventricular assist devices. Stroke. 1999; 30: 2554–2561.
36. Potapov EV, Nasseri BA, Loebe M, Kukucka M, Koster A, Kuppe H, Noon GP, DeBakey ME, Hetzer R. Transcranial detection of microembolic signals in patients with a novel nonpulsatile implantable LVAD. ASAIO J. 2001; 47: 249–253.[CrossRef][Medline] [Order article via Infotrieve]
37. Nabavi DG, Stockmann J, Schmid C, Schneider M. Hammel D. Scheld HH, Ringelstein EB. Doppler microembolic load predicts risks of thromboembolic complications in Novacor patients. J Thorac Cardiovasc Surg. 2003; 126: 160–167.
38. Thoennissen NH, Schneider M. Allroggen A, Ritter M, Dittrich R, Schmid C, Scheld HH, Ringelstein EB, Nabavi DG. High level of cerebral microembolization in patients supported with the DeBakey left ventricular assist device. J Thorac Cardiovasc Surg. 2005; 130: 1159–1166.
39. Thoennissen NH, Allroggen A, Dittrich R, Ritter M, Schmid C, Scheld HH, Ringelstein EB, Nabavi DG. Can Doppler time domain analysis of microembolic signals discriminate between gaseous and solid microemboli in patients with left ventricular assist device? Neurol Res. 2005; 27: 780–784.[CrossRef][Medline] [Order article via Infotrieve]
40. Thoennissen NH, Allroggen A, Ritter M, Dittrich R, Schmid C, Schmid HH, Ringelstein EB, Nabavi DG. Influence of inflammation and pump dynamic on cerebral microembolization in patients with continuous-flow DeBakey LVAD. ASAIO J. 2006; 52: 243–247.[CrossRef][Medline] [Order article via Infotrieve]
41. Blauth CI. Macroemboli and microemboli during cardiopulmonary bypass. Ann Thorac Surg. 1995; 59: 1300–1303.
42. Baker AJ, Naser B, Benaroia M, Mazer CD. Cerebral microemboli during coronary artery bypass using different cardioplegia techniques. Ann Thorac Surg. 1995; 59: 1187–1191.
43. Clark RE, Brillman J, Davis DA, Lovell MR, Price TR, Magovern GJ. Microemboli during coronary artery bypass grafting: genesis and effect on outcome. J Thorac Cardiovasc Surg. 1995; 109: 249–258.
44. Barbut D, Hinton RB, Szatrowski TP, Hartman GS, Bruefach M, Williams-Russo P, Charlson ME, Gold JP. Cerebral emboli detected during bypass surgery are associated with clamp removal. Stroke. 1994; 25: 2398–2402.[Abstract]
45. Barbut D, Yao FS, Hager DN, Kavanaugh P, Trifiletti PR, Gold JP. Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery. Stroke. 1996; 27: 87–90.
46. Guerrieri Wolf L, Abu-Omar Y, Choudhary BP, Pigott D, Taggart DP. Gaseous and solid cerebral microembolization during proximal aortic anastomoses in off-pump coronary surgery: the effect of an aortic side-biting clamp and two clampless devices. J Thorac Cardiovasc Surg. 2007; 133: 485–493.
47. Rodriguez RA, Rubens F, Belway D, Nathan HJ. Residual air in the venous cannula increases cerebral embolization at the onset of cardiopulmonary bypass. Eur J Cardiothorac Surg. 2006; 29: 175–180.
48. Pugsley W, Klinger L, Paschalis C, Treasure T, Harrison M, Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke. 1994; 25: 1393–1399.[Abstract]
49. Jacobs A, Neveling M, Horst M, Ghaemi M, Kessler J, Eichstaedt H, Rudolf J, Model P, Bonner H, de Vivie ER, Heiss WD. Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events. Stroke. 1998; 29: 660–667.
50. Lee JD, Lee SJ, Tsushima WT, Yamauchi H, Lau WT, Popper J, Stein A, Johnson D, Lee D, Petrovitch H, Dang CR. Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial. Ann Thorac Surg. 2003; 76: 18–26.
51. Bokeriia LA, Golukhova EZ, Breskina NY, Polunina AG, Davydov DM, Begachev AV, Kazanovskaya SN. Asymmetric cerebral embolic load and postoperative cognitive dysfunction in cardiac surgery. Cerebrovasc Dis. 2006; 23: 50–56.[CrossRef][Medline] [Order article via Infotrieve]
52. Abu-Omar Y, Cader S, Guerrieri Wolf L, Pigott D, Matthews PM, Taggart DP. Short-term changes in cerebral activity in on-pump and off-pump cardiac surgery defined by functional magnetic resonance imaging and their relationship to microembolization. J Thorac Cardiovasc Surg. 2006; 132: 1119–1125.
53. Sylivris S, Levi C, Matalanis G, Rosalion A, Buxton BF, Mitchell A. Fitt G, Harberts DB, Saling MM, Tonkin AM. Pattern and significance of cerebral microemboli during coronary artery bypass grafting. Ann Thorac Surg. 1998; 66: 1674–1678.
54. Braekken SK, Reinvang I, Russell D, Brucher R, Svennevig JL. Association between intraoperative cerebral microembolic signals and postoperative neuropsychological deficit: comparison between patients with cardiac valve replacement and patients with coronary artery bypass grafting. J Neurol Neurosurg Psychiatry. 1998; 65: 573–576.
55. Diegeler A, Hirsch R, Schneider F, Schilling LO, Falk V, Rauch T, Mohr FW. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Ann Thorac Surg. 2000; 69: 1162–1166.
56. Browndyke JN, Moser DJ, Cohen RA, O’Brien DJ, Algina JJ, Haynes WG, Staples ED, Alexander J, Davies LK, Bauer RM. Acute neuropsychological functioning following cardiosurgical interventions associated with the production of intraoperative cerebral microemboli. Clin Neuropsychol. 2002; 16: 463–471.[Medline] [Order article via Infotrieve]
57. Stygall J, Newman SP, Fitzgerald G, Steed L, Mulligan K, Arrowsmith JE, Pugsley W, Humphries S, Harrison MJ. Cognitive change 5 years after coronary artery bypass surgery. Health Psychol. 2003; 22: 579–586.[CrossRef][Medline] [Order article via Infotrieve]
58. Neville MJ, Butterworth J, James RL, Hammon JW, Stump DA. Similar neurobehavioral outcome after valve or coronary artery operations despite differing carotid embolic counts. J Thorac Cardiovasc Surg. 2001; 121: 125–136.[CrossRef][Medline] [Order article via Infotrieve]
59. Taylor RL, Borger MA, Weisel RD, Fedorko L, Feindel CM. Cerebral microemboli during cardiopulmonary bypass: increased emboli during perfusionist interventions. Ann Thorac Surg. 1999; 68: 89–93.
60. Borger MA, Peniston CM, Weisel RD, Vasiliou M, Green REA, Feindel CM. Neuropsychologic impairment after coronary bypass surgery: effect of gaseous microemboli during perfusionist interventions. J Thorac Cardiovasc Surg. 2001; 121: 743–749.
61. Rodriguez RA, Williams KA, Babaev A, Rubens F, Nathan HJ. Effect of perfusionist technique on cerebral embolization during cardiopulmonary bypass. Perfusion. 2005; 20: 3–10.
62. Rudolph JL, Tilahun D, Treanor PR, Pochay VE, Mahendrakar MA, Sagar P, Babikian VL. Use of a large bore syringe creates significantly fewer high intensity transient signals (HITS) into a cardiopulmonary bypass system than a small bore syringe. Perfusion. 2006; 21: 67–71.
63. Svenarud P, Persson M, van der Linden J. Effect of CO2 insufflation on the number and behavior of air microemboli in open-heart surgery: a randomized clinical trial. Circulation. 2004; 109: 1127–1132.
64. Bhasker Rao B, Van Himbergen D, Edmonds HL Jr, Jaber S, Ali AT, Pagni S, Koenig S, Spence PA. Evidence for improved cerebral function after minimally invasive bypass surgery. J Card Surg. 1998; 13: 27–31.[CrossRef][Medline] [Order article via Infotrieve]
65. Watters MPR, Cohen AM, Monk CR, Angelini GD, Ryder IG. Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound. Br J Anaesth. 2000; 84: 629–631.
66. Bowles BJ, Lee JD, Dang CR, Taoka SN, Johnson EW, Lau EM, Nekomoto K. Coronary artery bypass performed without the use of cardiopulmonary bypass is associated with reduced cerebral microemboli and improved clinical results. Chest. 2001; 119: 25–30.[Medline] [Order article via Infotrieve]
67. Lund C, Hol PK, Lundblad R, Fosse E, Sundet K, Tennoe B, Brucher R, Russell D. Comparison of cerebral embolization during off-pump and on-pump coronary artery bypass surgery. Ann Thorac Surg. 2003; 76: 765–770.
68. Abu-Omar Y, Balacumaraswami L, Pigott DW, Matthews PM, Taggart DP. Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures. J Thorac Cardiovasc Surg. 2004; 127: 1759–1765.
69. Motallebzadeh R, Kanagasabay R, Bland M, Kaski JC, Jahangiri M. S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004; 25: 409–414.
70. Ascione R, Ghosh A, Reeves BC, Arnold J, Potts M, Shah A, Angelini GD. Retinal and cerebral microembolization during coronary artery bypass surgery: a randomized, controlled trial. Circulation. 2005; 112: 3833–3838.
71. Stroobant N, Van Nooten G, Van Belleghem Y, Vingerhoets G. Relation between neurocognitive impairment, embolic load, and cerebrovascular reactivity following on- and off-pump coronary artery bypass grafting. Chest. 2005; 127: 1967–1976.
72. Scarborough JE, White W, Derilus FE, Mathew JP, Newman MF, Landolfo KP; Neurological Outcome Research Group. Combined use of off-pump techniques and a sutureless proximal aortic anastomotic device reduces cerebral microemboli generation during coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003; 126: 1561–1567.
73. Padayachee TS, Parsons S, Theobold R, Gosling RG, Deverall PB. The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass. Ann Thorac Surg. 1988; 45: 647–649.[Abstract]
74. Eifert S, Reichenspurner H, Pfefferkorn T, Baur B, von Schlippenbach C, Mayer TE, Hamann G, Reichart B. Neurological and neuropsychological examination and outcome after use of an intra-aortic filter device during cardiac surgery. Perfusion. 2003; 18 (suppl 1): 55–60.
75. Schoenburg M, Kraus B, Muehling A, Taborski U, Hofmann H, Erhardt G, Hein S, Roth M, Vogt PR, Karliczek GF, Kloevekorn WP. The dynamic air bubble trap reduces cerebral microembolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2003; 126: 1455–1460.
76. Whitaker DC, Newman SP, Stygall J, Hope-Wynne C, Harrison MJ, Walesby RK. The effect of leucocyte-depleting arterial line filters on cerebral microemboli and neuropsychological outcome following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2004; 25: 267–274.
77. de Vries AJ, Gu YJ, Douglas YL, Post WJ, Lip H, van Oeveren W. Clinical evaluation of a new fat removal filter during cardiac surgery. Eur J Cardiothorac Surg. 2004; 25: 261–266.
78. Perthel M, Kseibi S, Bendisch A, Laas J. Use of a dynamic bubble trap in the arterial line reduces microbubbles during cardiopulmonary bypass and microembolic signals in the middle cerebral artery. Perfusion. 2005; 20: 151–156.
79. Schonburg M, Ziegelhoeffer T, Kraus B, Muhling A, Heidt M, Taborski U, Gerriets T, Roth M, Hein S, Urbanek S, Klovekorn WP. Reduction of gaseous microembolism during aortic valve replacement using a dynamic bubble trap. Gen Physiol Biophys. 2006; 25: 207–214.[Medline] [Order article via Infotrieve]
80. Brown WR, Moody DM, Challa VR, Stump DA, Hammon JW. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke. 2000; 31: 707–713.
81. Milsom FP, Mitchell SJ. A. dual-vent left heart deairing technique markedly reduces carotid artery microemboli. Ann Thorac Surg. 1998; 66: 785–791.
82. Borger MA, Taylor RL, Weisel RD, Kulkarni G, Benaroia M, Rao V, Cohen G, Fedorko L, Feindel CM. Decreased cerebral emboli during distal aortic arch cannulation: a randomized clinical trial. J Thorac Cardiovasc Surg. 1999; 118: 740–745.
83. Mullges W, Franke D, Reents W, Babin-Ebell J. Brain microembolic counts during extracorporeal circulation depend on aortic cannula position. Ultrasound Med Biol. 2001; 27: 933–936.[CrossRef][Medline] [Order article via Infotrieve]
84. Benaroia M, Baker AJ, Mazer CD, Errett L. Effect of aortic cannula characteristics and blood velocity on transcranial Doppler-detected microemboli during cardiopulmonary bypass. Cardiothorac Vasc Anesth. 1998; 12: 266–269.[CrossRef]
85. Mullges W, Franke D, Reents W, Babin-Ebell J, Toyka KV. Reduced rate of microembolism by optimized aortic cannula position does not influence early postoperative cognitive performance in CABG patients. Cerebrovasc Dis. 2003; 15: 192–198.[CrossRef][Medline] [Order article via Infotrieve]
86. Georgiadis D, Stets R, Schorch A, Baumgartner RW, Bernet F, Zerkowski HR. Doppler microembolic signals during cardiopulmonary bypass: comparison of two membrane oxygenators. Neurol Res. 2004; 26: 99–102.[CrossRef][Medline] [Order article via Infotrieve]
87. Rodriguez RA, Watson MI, Nathan HJ, Rubens F. Do surface-modifying additive circuits reduce the rate of cerebral microemboli during cardiopulmonary bypass? J Extra Corpor Technol. 2006; 38: 216–219.[Medline] [Order article via Infotrieve]
88. Schneider F, Onnasch JF, Falk V, Walther T, Autschbach R, Mohr FW. Cerebral microemboli during minimally invasive and conventional mitral valve operations. Ann Thorac Surg. 2000; 70: 1094–1097.
89. Skjelland M, Bergsland J, Lundblad R, Lingaas PS, Rein KA, Halvorsen S, Svennevig JL, Fosse E, Brucher R, Russell D. Cerebral microembolization during off-pump coronary artery bypass surgery with the Symmetry aortic connector device J Thorac Cardiovasc Surg. 2005; 130: 1581–1585.
90. Mullges W, Berg D, Toyka KV. Bilateral cerebral emboli monitoring during extracorporeal circulation. Ultrasound Med Biol. 1999; 25: 755–758.[CrossRef][Medline] [Order article via Infotrieve]
91. Moser DJ, Ferneyhough KC, Bauer RM, Arndt S, Schultz SK, Haynes WG, Staples ED, Alexander J, Davies LK, O’Brien DJ. Unilateral vs. bilateral ultrasound in the monitoring of cerebral microemboli. Ultrasound Med Biol. 2001; 27: 757–760.[CrossRef][Medline] [Order article via Infotrieve]
92. Feerick AE, Church JA, Zwischenberger J, Conti V, Johnston WE. Systemic gaseous microemboli during left atrial catheterization: a common occurrence? J Cardiothorac Vasc Anesth. 1995; 9: 395–398.[CrossRef][Medline] [Order article via Infotrieve]
93. Stygall J, Kong R, Walker JM, Hardman SM, Harrison MJ, Newman SP. Cerebral microembolism detected by transcranial Doppler during cardiac procedures. Stroke. 2000; 31: 2508–2510.
94. Bladin CF, Bingham L, Grigg L, Yapanis AG, Gerraty R, Davis SM. Transcranial Doppler detection of microemboli during percutaneous transluminal coronary angioplasty. Stroke. 1998; 29: 2367–2370.
95. Leclercq F, Kassnasrallah S, Cesari JB, Blard JM, Macia JC, Messner-Pellenc P, Mariottini CJ, Grolleau-Raoux R. Transcranial Doppler detection of cerebral microemboli during left heart catheterization. Cerebrovasc Dis. 2001; 12: 59–65.[CrossRef][Medline] [Order article via Infotrieve]
96. Fischer A, Ozbek C, Bay W, Hamann GF. Cerebral microemboli during left heart catheterization. Am Heart J. 1999; 137: 162–168.[CrossRef][Medline] [Order article via Infotrieve]
97. Braekken SK, Endresen K, Russell D, Brucher R, Kjekshus J. Influence of guidewire and catheter type on the frequency of cerebral microembolic signals during left heart catheterization. Am J Cardiol. 1998; 82: 632–637.[CrossRef][Medline] [Order article via Infotrieve]
98. Lund C, Nes RB, Ugelstad TP, Due-Tonnessen P, Andersen R, Hol PK, Brucher R, Russell D. Cerebral emboli during left heart catheterization may cause acute brain injury. Eur Heart J. 2005; 26: 1269–1275.
99. Hamon M, Gomes S, Oppenheim C, Morello R, Sabatier R, Lognone T, Grollier G, Courtheoux P, Hamon M. Cerebral microembolism during cardiac catheterization and risk of acute brain injury: a prospective diffusion-weighted magnetic resonance imaging study. Stroke. 2006; 37: 2035–2038.
100. Russell D, Brucher R. Online automatic discrimination between solid and gaseous cerebral microemboli with the first multifrequency transcranial Doppler. Stroke. 2002; 33: 1975–1980.
101. Smith JL, Evans DH, Bell PR, Naylor AR. A comparison of four methods for distinguishing Doppler signals from gaseous and particulate emboli. Stroke. 1998; 29: 1133–1138.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||