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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 16  |  Issue : 4  |  Page : 356-359

Cerebral microembolization in patients with prosthetic valve and anticoagulation assessment using transcranial Doppler ultrasonography


1 Department of Neurology, Al-Azhar Faculty of Medicine, El-Hussein University Hospital, Cairo, Egypt
2 Department of Cardiothorathic Surgery, Al-Azhar Faculty of Medicine, El-Hussein University Hospital, Cairo, Egypt

Date of Submission28-Jun-2018
Date of Acceptance04-Feb-2019
Date of Web Publication23-Apr-2019

Correspondence Address:
Mohamed A Zaki
Department of Neurology, Al-Azhar Faculty of Medicine, El-Hussein University Hospital, Cairo, 31511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_60_18

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  Abstract 


Background Transcranial Doppler detection of microemboli is widely described, and thromboembolism is a major cause of morbidity in patients with prosthetic heart valves. They require lifelong anticoagulation to minimize thrombotic complications. This study was undertaken to assess the clinical relevance of microembolic signals (MESs) and their relation to anticoagulation.
Patients and methods Thirty patients with single mitral mechanical prosthetic valve were included. All of them were selected with low intensity of international normalization ratio (INR). After 2-week interval, INR intensities were stabilized to the recommended levels. Transcranial Doppler monitoring for MES detection was done to the same patients, before and after the stabilization of INR intensities.
Results Microemboli were detected in 86.7% of patients before and after the INR level adjustment, with mean number of 57.63±13.12 before adjust. The numbers were significantly lowered after the adjustment of INR, as the emboli number became 24.1±9.12.
Conclusion Compared with previously thought findings, the study results were different, as there was a significant effect of the anticoagulation on the number of MESs detected in patients with mechanical valve replacement, but without effect in MES incidence, denoting that, there were a variety of MESs rather than thrombotic. Further assessment by MES differentiation to define solid ones will be indicated.

Keywords: anticoagulation, embolism, heart valve prosthesis, microemboli, transcranial Doppler ultrasonography


How to cite this article:
Zaki MA, Moussa ME. Cerebral microembolization in patients with prosthetic valve and anticoagulation assessment using transcranial Doppler ultrasonography. Al-Azhar Assiut Med J 2018;16:356-9

How to cite this URL:
Zaki MA, Moussa ME. Cerebral microembolization in patients with prosthetic valve and anticoagulation assessment using transcranial Doppler ultrasonography. Al-Azhar Assiut Med J [serial online] 2018 [cited 2019 Oct 20];16:356-9. Available from: http://www.azmj.eg.net/text.asp?2018/16/4/356/256761




  Introduction Top


Acute stroke is one of the leading cause of morbidity and mortality worldwide. In developed countries, stroke ranks as either second or third most common cause of death, and embolization is the cause of ischemic stroke in 40–80% of cases [1]. Thromboembolism is a significant complication in patients with prosthetic heart valves, and the risk of thromboembolic complications is greatest during the first 3 months after surgery for both mechanical and bioprosthetic devices [2]. There is a persistent lifelong risk of patients with mechanical valves, which requires lifelong anticoagulation in most patients to minimize postoperative thrombotic complications [3]. Microembolic signals (MESs) have been detected in a number of clinical conditions, such as carotid artery stenosis, aortic arch plaques, atrial fibrillation, myocardial infarction, prosthetic heart valves, patent foramen ovale, valvular stenosis, during carotid surgery, and surgery on open heart [4].

Quantification of subclinical emboli signals may allow more precise estimation of embolic risk and an objective assessment of treatment effects.


  Aim of the study Top


This study was undertaken to assess the clinical relevance of MESs and their relation to anticoagulation.


  Patients and methods Top


This study was conducted in El-Hussein University Hospital, Al-Azhar University. No hospitalized patients were included in this study. A total of 30 patients were recruited from Cardiothoracic Outpatient Clinic, who were following up for postoperative anticoagulation.

All patients were stabilized on warfarin at the time of examination. Only patients who never experienced neurological problems were selected and were not properly adjusted with low intensity of international normalization ratio (INR). Two weeks later, the same patients were examined again after adjustment of the INR intensity (2.5–3.5 for patients with mechanical prosthetic valves) [5].

All the study patients were with single mitral valve (St. Jude bileaflet prosthetic valve), all of them were females, and their mean age was approximately 31.17±8.26 years. Other potential sources of embolization rather than the valve lesion were excluded by echocardiography, ECG, carotid artery duplex, and full neurological history and examination. The study patients before adjustment of INR levels were considered as a control group, and the same patients after adjustment of INR levels were considered as a case group.

TCD monitoring was performed using TCD 8 software in Multi dop ×4 device (2-MHz transducer; DWL, Supplingen, Germany). The right and left middle cerebral arteries (MCAs) were identified simultaneously at a depth between 45 and 55 mm, with the patient in a seated position; after acquiring the optimal signals, the Doppler probes were fixed over the temporal bone with head elastic band (head set) to maintain a constant angle of insonation. Patients in whom no MCAs signal could be identified were excluded [1].

The term MES was used, not HITS (high-intensity transient signal), because MES term is more adequate than the term HITS; furthermore, the term HITS is misleading, as it is also applied to artifacts [6].

Established criteria were used to distinguish between artifact and true emboli signals. MES can be identified as short-lasting, unidirectional intensity increase (>3 db) within the Doppler frequency spectrum; MESs appear randomly within the cardiac cycle and produce a ‘whistle,’ ‘chirping,’ or ‘clicking’ sound when passing through the sample volume [7].

The optimal time for monitoring depends on the clinical entity. In patients with implanted artificial heart valves, monitoring during 30 min will be sufficient. In patients with carotid artery stenosis, Atrial Fibrillation (AF), or other cardiac disease, monitoring over 60 min, which may be extended to 8 h, or repetitive monitoring may be recommended. So the study patients were monitored for 30 min [8],[9].

General and full neurological assessment was done to exclude symptomatic patients. A written consent was taken from all the study cases according to the ethical committee of Al-Azhar University.

Statistical analysis of data

The collected data were organized, tabulated, and statistically analyzed using statistical package for social science, version 16 (SPSS Inc., Chicago, Illinois, USA). Numerical data were presented as mean±SD, whereas categorical data were presented as frequency and percent. Comparison between groups was done by independent samples t test. Comparison between groups of categorical variables was done by χ2 test or Mann–Whitney test when appropriate. P value less than 0.05 was considered significant for interpretation of results.


  Results Top


Thirty women were successfully examined in this study. All of them had single mechanical mitral valve replacement, with no neurological clinical complications. They were just following up for postoperative anticoagulation. Age distribution in the study was 31.17±8.26 years. All the 30 patients were examined by transcranial Doppler ultrasonography for MES detection and counting with monitoring of both MCAs for not less than 30 min before the adjustment of the INR level, and they were considered as the control group. After 2-week interval, with adjustment of the INR levels, patients were monitored again, and they were considered as the patient group. The results of the study compared both groups regarding the count and the incidence of MES, to assess the effect of the different INR level change on the MES.

all variables that might affect the results including valve type, age, sex, absence of the neurological manifestations, and other causes of the embolizations were comparable between the studied patients. There was only, INR was the non comparable variable between the studied patients.

Regarding the number of MES ([Figure 1], red point) monitored and recorded, in group I, the number was 57.6±13.1, and in group II, the number was 24.1±9.12. On comparison, there was a highly significant difference between both the groups (P<0.01) ([Table 1]).
Figure 1 An example of MES (red point directed to the true emolus). MES, microembolic signal.

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Table 1 Comparison between study groups, regarding microembolic signal incidence and number

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Regarding the incidence of MES, in both groups, MES was detected in 26 cases, with incidence of 86.7%, which is the same incidence in the both groups before and after the adjustment of the INR levels, without significant difference.


  Discussion Top


Emboli are common in patients with prosthetic cardiac valves and depend on the type of implanted valve; double valves, mitral and aortic, have the highest incidence, followed by mitral and then aortic valve [6]. The presence of emboli is more in dual valves and in mechanical ones, and this study was designed to fixate and unify factors that may influence the differences between patients, and all patients were with single mitral prosthetic valve [6].

Warfarin was recommended lifelong for patient’s study, and the ideal INR level needed to guard against thromboembolic complications lies between 2.5 and 3.5. To emphasis that, there are no other sources of embolization rather than valve lesion. The patients selected had never experienced any neurological complications. Moreover, the INR levels of the selected patients were less than the recommended [5].

Previous studies stated that in patients with prosthetic heart valve, MESs can be detectable in cerebral circulation ranging from 50 to 90%, so the study patients before INR adjustment were considered as a control group to judge the outcome of the anticoagulation [2],[10]. These emboli did not cause any clinical neurological complication. Most MESs do not produce immediate symptoms, but MESs in cerebral circulation indicate asymptomatic patients with increased stroke risk, and patients with cerebral microemboli have higher cognitive deficits. Cumulative effect of embolism is thought to be the cause [1]. With adjustment of warfarin doses and follow-up till the INR levels became 2.5–3.5, patients were monitored again for microemboli counting, and the both groups were compared [5].

The comparison of the two groups in the number of MESs detected revealed that they were significantly lower in group II, in whom the INR levels were idealized, and this result was in disagreement with Georgiadis et al. [11] and Rams et al. [12], who stated that there is no significance in the number of MES noted among patients at different intensities of anticoagulant. Moreover, they concluded that there is no influence of the intensity of anticoagulation or even with addition of antiplatelets. Moreover, Georgiadis et al. [6] in another study stated that there was no correlation with clinical parameters identified with emboli, and suggested that there are no clinical sequelae to the detected emboli [6]. These results were followed by a long period of unaddressing of this field.

On the contrary, many studies stated that the number of MESs decreases with INR decrease in many diseases like patients with AF and with MCA stenosis, suggesting a great value of MES [5],[13],[14]. Moreover, solid MESs are with high incidence in patients with manifestations [15].

This study was in agreement with Laura et al. [16], who reissued the matter again after an interval of unadressing and stated that the degree of anticoagulation may have greater clinical relevance than previously thought [16]. Regarding the incidence of emboli in the both groups, results did not show any significant difference, as emboli were detected in 86.7% in the both groups. This result was in agreement with all the aforementioned studies, and puts the study here in a contradiction. The explanation was that MES does not disappear completely, but only lowered in number. Some of them responded to the anticoagulants and the other not, denoting that not all MESs are of the same nature.

This is according to Georgiadis et al. [11], who suggested that not all emboli were solid [11]. The lack of correlation between the activity of anticoagulation system and the number of MES suggests that it is not thrombotic, and most MESs in mechanical valve patients are gaseous in nature, and the embolism of gas would cause less circulatory obstruction, and in animal models have demonstrated the ability of gas to pass through the pial arterioles into the venous system. In turn that explain with all this number of emboli there are no clinical manifestations [6],[17]. So with a good differentiation between the types of MES available now in the new versions of TCD machines, the detection of solid MES would be valuable and beneficial [15],[17],[18].

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Vuković-Cvetković V. Microembolus detection by transcranial doppler sonography: review of the literature. Stroke Res Treat 2012; 2012:382361.  Back to cited text no. 1
    
2.
Braeken S, Russell D, Brucher R, Michelsen A, Brosstad F, Svennevig J. Cerebral emboli in prosthetic heart valve patients. Stroke 1994; 25:739.  Back to cited text no. 2
    
3.
Gikelboom J, Connolly S, Brueckmann M, Granger C, Kappetein A, Mack M et al. Dabigatran versus warfarin in patient e mechanical heart valves. N Engl J Med 2013; 369:1206–1214.  Back to cited text no. 3
    
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Bogousslavsky J, Cachin C, Regli CF, Despland P, VanMelle G, Kappenberger L. Cardiac sources of embolism and cerebral infarction clinical consequences and vascular concomitants: the Lausanne Stroke Registry. Neurology 1991; 41:855–859.  Back to cited text no. 4
    
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Schneeweiss S, Gagne J, Patrick AR, Choudhry NK, Avron J et al. Comparative efficacy and safety of new oral anticoaguant in patient with atrial fibrillation. Circ Cardiovascular Qual Outcome 2012; 5:480–486.  Back to cited text no. 5
    
6.
Georgiadis D, Kaps M, Berg J, Mackay T, Dapper F, Faichney A et al. Transcranial Doppler detection of micro-emboli in prasthotic heart valve patients: dependency upon valve type. Eur J Cardio-thorac Surg 1996; 10:253–258.  Back to cited text no. 6
    
7.
Ringelstein R, Droste D, Babikian V et al. Consensus onmicroembolus detection by TCD: international consensus group on microembolus detection. Stroke 1998; 29:725–729.  Back to cited text no. 7
    
8.
Droste D, Ritter M, Kemeny V, Schulte-Altedorneburg G, Ringelstein B. Microembolus detections at follow-up in 19 patients with acute stroke. Correlation with stroke etiology and antithrombotic treatment. Cerebrovasc Dis 2000; 10:272–277.  Back to cited text no. 8
    
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Molloy J, Khan N, Markus H. Temporal variability of asymptomatic embolization in carotid a. stenosis and optimal recording protocols. Stroke 1998; 29:1129–1132.  Back to cited text no. 9
    
10.
Muller H, Burckhardt D, Casty M, Pfisterer M, Buser M. High intensity transcranial Doppler signals (HITS) after prosthetic valve implantation. J Heart Valve Dis 1994; 3:602–606.  Back to cited text no. 10
    
11.
Georgiadis D, Grosset D, Kelman A, Faichney A, Lees K. Prevalence and characteristics of intracranial micro emboli signals in patients in the different types of prosthetic cardiac valve. Stroke 1994; 25:587–592.  Back to cited text no. 11
    
12.
Rams J, Davis A, Lolley M, Spencer M. Detection of micro emboli in patient in the artificial heart valve using transcranial dopller: preliminary observation. J Heart valve Dis 1993; 2:37–41.  Back to cited text no. 12
    
13.
Gao S, Wong K, Handberg T, Lam W, Droste D, Ringelstein E. Microembolic signals predics recurrent cerebral ischemic events in the middle cerebral artery stenosis. Stroke 2004; 35:2832–2836.  Back to cited text no. 13
    
14.
Demir S, Ozdag MF, Kendirli M, Togrol R. What do anticoagulant say about microemboli. J Stroke Cerebrovasc Dis 2015; 24:2474–2477.  Back to cited text no. 14
    
15.
Mona S, Annika M, Frank B, Janl S, Rainer B, David R. Solid cerebral microemboli and cerebrovascular symptoms in patients with prosthetic heart valves. Stroke 2008; 39:1159–1164.  Back to cited text no. 15
    
16.
Laura S, Giuseppe N, Giorgio V, Giuseppe V, Giusseppe B, Riccardo D et al. Microembolic signals in patients with prosthetic valves; relationship with the degree of anticoagulation. Int J Angiol 2002; 11:230–233.  Back to cited text no. 16
    
17.
Loreno G, Bikram Ch, Abu-omar Y. Solid and gaseous cerebral microembolization after bilologic and mechanical aortic valve replacement: investigation with multirange and multifrequency transcranial Doppler ultrasound. J Thorac Cardiovasc Surg 2008; 136:1391–1392.  Back to cited text no. 17
    
18.
Engel A, Horvat Menih I, Hueepfl M, Erdoes G, Kubista B, Ullrich R et al. Detection and differentiation cerebral microemboli in patients undergoing major orthopedic surgery using transcranial Doppler ultrasound. Br J Anaesth 2017; 118:400–406.  Back to cited text no. 18
    


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