From the Departments of Neurology, Universities of Halle and Jena, Halle
and Jena, Germany.
Correspondence to D. Georgiadis, MD, Department of Neurology, University of Halle, D-060129 Halle, Germany. E-mail dimitrios.georgiadis{at}medizin.uni-halle.de
Methods—Transcranial Doppler monitoring for MES
was performed over the middle cerebral arteries for 30 to 60 minutes
per patient. Prevalence of neurological complications was evaluated
with a standard neurological questionnaire in patients carrying the
valve implant longer than 3 months (n=369).
Results—Significant differences in MES prevalence and counts were
noted among the 580 patients depending on valve type (presented with
medians and [95% confidence intervals]): St Jude Medical, n=200,
72%, 4 [3 to 6]; Björk Shiley Monostrut, n=99, 92%, 133 [93
to 181]; Medtronic Hall, n=80, 47%, 1 [2 to 5]; ATS, n=61, 52%, 3
[2 to 5]; Tecna, n=38, 71%, 2 [1 to 4]; Carbomedics, n=37, 81%, 8
[5 to 13]; Carpentier-Edwards supraannular, n=54, 39%, 1 [0 to 3];
Sorin biological, n=11, 9%, 0 [0 to 0]. No relation between MES
counts and valve size, international normalized ratio, patients' age,
cardiac rhythm, or implant duration was noted. No significant
differences in MES counts or prevalence (22 [3 to 68] versus 5 [3 to
6] and 63% versus 69%, both P>.05), in valve
duration, valve position, valve type, patients' age, sex, cardiac
rhythm, or international normalized ratio were evident between
neurologically symptomatic (n=42) and
asymptomatic patients.
Conclusions—MES in patients with prosthetic cardiac
valves depend on the type and, in certain valve types, the position of
the valve implant and possess no direct clinical significance.
MES were recognized according to standard criteria: characteristic
sound, random appearance in the cardiac cycle, intensity increase at
least 3 dB above background, and unidirectionality within the
Doppler spectrum.5
The following data were collected from all patients: age, duration,
type and size of valve implant, cardiac rhythm, antihemostatic
treatment, and occurrence of neurological complications. This
assessment was based on a standard neurological questionnaire
evaluating the occurrence of limb weakness and speech or visual
deficit. Patients monitored within 3 months of valve insertion were
included in the study but not in the evaluation of the influence of MES
on neurological symptoms.
Two-sample t test was used for comparison of normally
distributed data and the Mann-Whitney U test for nonnormally
distributed data. Correlation of nonparametric data were
evaluated with the Spearman-Rank test. The
Valve Position
Valve Size
Cardiac Rhythm
Neurological Complications
Prevalence of neurological complications was significantly higher in
patients with mechanical valves compared with those with porcine valves
(12.3% versus 4.4%; P<.05,
Clinical Parameters
To date, three studies with patient numbers adequate for statistical
analysis were published concerning the clinical relevance of
MES (Sliwka et al3 [n=179], Braekken et al2
[n=92], and Georgiadis et al4 [n=257]). Patients were
examined within the first week after surgery and 10 to 13 months after
valve implantation by Sliwka et al; 1 week, 1 year, and 5 years after
valve implantation by Braekken et al; and between 3 days and 10 years
after implantation by Georgiadis et al. The study of Braekken et al
evaluated patient numbers that were too small (total of 14
symptomatic patients) and acquired marginally significant
differences between symptomatic and
asymptomatic patients2 ; their results therefore
could be coincidental. Sliwka et al also described significantly higher
MES counts in symptomatic patients, but this was true only
for the subgroup examined one week after surgery, whereby this result
was based on 7 symptomatic patients.3 No
significant differences in MES counts were demonstrated in the study of
Georgiadis et al,4 which is in agreement with our current
results.
The demonstrated lack of clinical correlations lends further
support to the hypothesis that the underlying embolic material in
patients with prosthetic cardiac valves is gaseous. Several
previous observations also argue for gaseous embolic material:(1) the
lack of influence of the intensity and mode of anticoagulation on MES
counts,2 3 10 11 (2) the lack of relation of MES counts to
D-dimer, thrombin-antithrombin, and antithrombin III serum
levels,12 (3) the generation of MES in a hydrodynamic
function tester with mechanical valves and degassed saline as
circulating medium,13 (4) the significant changes in MES
counts in valve patients after decompression14 or oxygen
inhalation,15 and (4) the evidence on changes of the
reflecting frequency of MES in valve patients under multifrequency
insonation.16 Whereas the generation of cavitation bubbles
by artificial heart valves is a generally accepted phenomenon widely
described in circulatory mock-loops,17 18 these are
supposed to implode within milliseconds and therefore not enter the
systemic circulation. However, it is possible that interactions between
cavitation bubbles and blood components prolong their life span.
Additionally, a portion of these bubbles has been described to be
bigger, and thus energetically more stable,19 so that their
detection in the MCA appears feasible.
MES in patients with porcine valves could not be caused by cavitation,
because the energy thresholds are not reached by native valves. We
assume that MES in these patients are instead caused by formed material
associated with interactions between blood elements and the biological
valve. As these patients were older compared with those with mechanical
valves, MES could also arise from coexisting cardiac or aortic embolic
sources.
Our failure to provide evidence for a relation between MES counts and
prevalence of neurological complications does not necessarily suggest
that these have no impact on brain function, because the continuous
embolization could be causing more subtle deficit that might only
become evident by the application of neuropsychological testing.
Unfortunately, only preliminary results20 are available in
this intriguing issue.
In conclusion, our results strongly argue against any clinical
significance of MES in patients with prosthetic cardiac valves
and suggest that routine TCD monitoring for emboli is not warranted in
these patients.
Received May 15, 1997;
revision received September 8, 1997;
accepted October 6, 1997.
© 1998 American Heart Association, Inc.
Original Contributions
Clinical Correlations of Doppler Microembolic Signals in Patients With Prosthetic Cardiac Valves
Analysis of 580 Cases
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—The clinical relevance of
Doppler microembolic signals (MES) in patients with
prosthetic cardiac valves was evaluated by merging and
statistically reanalyzing patient data from four research institutions
(Departments of Neurology, Universities of Aachen, Halle, and
Münster, Germany; Department of Medicine and Therapeutics,
University of Glasgow, Scotland, and Department of Cardiothoracic
Surgery, Western Infirmary, Glasgow, Scotland).
Key Words: embolism • heart valve prosthesis • ultrasonics
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Six years after the
first description of Doppler MES in patients with
prosthetic cardiac valves,1 no conclusive evidence
has been produced concerning their clinical relevance. Results of
recently published articles were contradictory.2 3 4 In an
attempt to clarify this intriguing issue, databases from four research
institutions (Departments of Neurology, Universities of Aachen, Halle,
and Münster, Germany; Department of Medicine and Therapeutics,
University of Glasgow, Scotland, and Department of Cardiothoracic
Surgery, Western Infirmary, Glasgow, Scotland) were merged and the
results statistically reanalyzed.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Ultrasound devices used were Trans-Scan, EME (Aachen); Multi-Dop
X-4, DWL (Halle); TC-2000, EME (Glasgow); and Pioneer 4040, EME
(Münster). Bilateral monitoring was performed for 1 hour in
patients monitored in Halle, but results of the right MCA were used for
further analysis. Unilateral TCD monitoring (30 minute
duration) was performed in all other patients. MES counts were
expressed as counts per hour. 
2 test was
used for comparison of frequencies. Significance was declared at
P<.05 level.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Valve Type
MES counts and their prevalence were significantly higher in
patients with mechanical valves compared with those with porcine valves
(6 [5 to 7.5] versus 0 [0 to 1] and 26.2% versus 70.3%,
respectively; both P<.01, Mann-Whitney U test
and 2 test, Table 1
).
Additionally, MES counts were significantly higher in patients with BSM
valves compared with all other valve types (all P<.01,
Mann-Whitney U test, Table 1) and in patients with
Carbomedics compared with those with SJM, MH, Tecna, and ATS valves
(all P<.05, Mann-Whitney U test).
View this table:
[in a new window]
Table 1. Clinical Details and Results of TCD Monitoring in
580 Patients With Prosthetic Heart Valves
Overall, MES counts were significantly higher in patients with
dual valve replacement compared with those with sole aortic or sole
mitral valve replacement (P<.002 and P<.04,
respectively; Table 2). The same was true
for patients with SJM and BSM valves (all P<.01,
Mann-Whitney U test; Table 2). Additionally, in patients
with ATS valves, significantly higher MES counts were noted when
comparing aortic with mitral position (P<.001, Mann-Whitney
U test; Table 2).
View this table:
[in a new window]
Table 2. Dependence of MES on Valve Position
There was no correlation between MES counts and valve size on
evaluation of all patients or when separately evaluating aortic and
mitral positions in patients with BSM, MH, and SJM valves (BSM, mitral
position r=-0.18, aortic position r=0.03; SJM,
aortic position r=0.1, mitral position r=0.03;
MH, aortic position r=-0.3, mitral position
r=-0.02).
Cardiac rhythm was sinus in 426 patients and atrial fibrillation
in 146 patients, whereas 8 patients carried a pacemaker. No relation
between MES counts and cardiac rhythm was found in the examined
patients or in any subgroups (overall MES counts in patients in sinus
rhythm and atrial fibrillation 5 [4 to 6.5] and 5.5 [3.4 to 10],
respectively).
Two hundred eleven patients were examined within the first 3
months after cardiac surgery and thus excluded from further
analysis as far as neurological deficit was concerned.
Forty-two of the remaining patients (11.4%) had experienced a
neurological event 3±0.5 months (mean±SE, minimum 1 week, maximum 11
months) before examination (transient ischemic attack, n=17;
amaurosis fugax, n=3; ischemic stroke, n=22; Table 3). Mean time between occurrence of
neurological symptoms and valve insertion was 37±5 months.
View this table:
[in a new window]
Table 3. MES Prevalence and Counts in Neurologically
Asymptomatic Symptomatic Patients 2 test). The
same was true for patients with BSM, MH, and Tecna, compared with
remaining mechanical valve implants. No differences in MES counts or
prevalence were evident between neurologically symptomatic
and asymptomatic patients (all P>.05,
Mann-Whitney U test and 2 test, Table 3
).
Type and site of neurological events in relation to each valve are
listed in Table 3.
No relation between patient's age, sex, and duration of valve
implant to the number or prevalence of MES was found in the examined
patients or in any subgroups.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
The present study represents the largest collection of
patients with prosthetic cardiac valves monitored with
transcranial Doppler, regarding both number of examined
patients and different valve types. It must be stressed that because a
limited number of valve types is used in each cardiothoracic
department, recruitment of patients from different institutions was
essential. The resulting use of various Doppler equipment and
evaluation of MES counts by more than one observer constitute a
weakness of the present study. However, as the interobserver
variability in MES counts in patients with prosthetic valves is
low,6 particularly through the high MES intensity in these
patients,7 this limitation is not likely to have greatly
influenced our results. The performance of unilateral
monitoring in 79% of cases, and the fact that neurologically
symptomatic patients were not routinely monitored over the
cerebral vessel supplying the affected territory or immediately after
onset of neurological symptoms, constitute further methodological
weaknesses. The insignificant differences between right and left MCA
demonstrated in the present study, which are in agreement with the
report of Grosset et al8 in prosthetic valve
patients and Georgiadis et al9 in patients with potential
cardioembolic source, suggest that whereas bilateral monitoring
provides more accurate results, it would hardly improve our findings.
Obviously, monitoring prosthetic valve carriers immediately
after symptom onset would be preferable. Still, the report of
Georgiadis et al,6 who found .insignificant differences in
MES counts in 50 patients examined on three different occasions within
one year, suggests that the MES-generating mechanism is stable, and
thus the methodology of the present study acceptable.
Selected Abbreviations and Acronyms
BSM
=
Björk Shiley Monostrut
MCA
=
middle cerebral artery
MES
=
microembolic signals
MD
=
Medtronic Hall
SJM
=
St Jude Medical
TCD
=
transcranial Doppler
Acknowledgments
Mr A. Faichney, Department of Cardiothoracic Surgery, Western
Infirmary, Glasgow, Scotland; Professor H.R. Zerkowski, Department of
Cardiothoracic Surgery, University of Halle; Dr F. Schöndube,
Department of Cardiothoracic Surgery, University of Aachen; and
Professor H.H. Scheld, Department of Cardiac and Vascular Surgery,
University of Münster, provided valuable help in patient
recruitment. Dr K.R. Lees and Dr D.G. Grosset, Acute Stroke Unit,
University Department of Medicine and Therapeutics, and Dr A.
Mallinson, Department of Hematology, Western Infirmary, Glasgow,
Scotland; Professor J. Noth, Department of Neurology, University of
Aachen; and Professor Zierz and Dr Lindner, Department of Neurology,
University of Halle, actively supported parts of this project. We
are also indebted to Professor D.J. Wheatley and Dr T.G. Mackay,
Department of Cardiac Surgery, University of Glasgow, Scotland;
Professor M. Kaps, Department of Neurology, University of Lübeck;
and Professor H. Reul, Helmholtz Institute for Biomedical Engineering,
Aachen, for their constructive comments concerning
microembolic signals in valve patients. Finally, we
would like to thank a number of medical students who were actively
involved in parts of this research project: B. Meyer and F.
Schöndube in Aachen; S. Stirling and P. Coburn in Glasgow; A.
Lühmann and A. Wenzel in Halle; and T. Mumme, M. Hill, and M.
König in Münster.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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