Clinically Silent Microemboli in Patients With Artificial Prosthetic Aortic Valves Are Predominantly Gaseous and Not Solid
Background and Purpose Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood.
Methods Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber.
Results Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa).
Conclusions The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.
Microembolic signals (MES) are frequently observed in transcranial Doppler (TCD) recordings of patients with prosthetic heart valves.1 2 3 4 5 6 These embolic signals are longer in duration and higher in relative intensity increase than those in patients who are embolizing from a carotid artery stenosis.1 These different ultrasound characteristics are related to the composition and size of the embolic material. Since at present the precise nature of high-intensity signals in patients with prosthetic cardiac valves is unknown, different etiologies are under debate: (1) local activation of the coagulation system by the prosthetic valve, resulting in the generation of thrombus; (2) local increase of platelet aggregation; (3) gaseous cavitation bubbles; and (4) functional structures such as vortices.
There is a definite need to clarify this question because brain embolism is a major complication after valve insertion,7 8 and the role of MES and TCD for individual risk assessment, prognosis, and prevention strategies remains uncertain despite large-scale clinical and experimental studies.
We hypothesized that the number of MES produced by mechanical valves can be modified by variation of Pao2 if gaseous bubbles are the underlying cause. Therefore, we performed emboli monitoring by TCD under hyperbaric conditions and inspiration of 100% oxygen.
Subjects and Methods
All subjects received a full Doppler and color duplex investigation of their neck arteries, including the periorbital arteries. The intracranial segments of the internal carotid arteries, the middle cerebral arteries, and the anterior and posterior cerebral arteries were examined transcranially. No patient suffered from stenosis or occlusion of the carotid artery or the middle cerebral artery.
The middle cerebral artery was insonated bilaterally through the temporal window. A 2-MHz probe was secured in a head ribbon. A setting guaranteeing optimal embolus discrimination from the background spectrum was used9 with a low sample volume of 5 mm; ultrasound intensity was 20 mW/cm2. This setting was maintained throughout the recording.
The same pulsed TCD device (Multi-Dop X; DWL) was used for all studies. It employed a 64-point fast Fourier transform and used a graded color scale to display the intensity of the received Doppler signal. The Doppler signal was recorded onto a digital audiotape deck recorder (DTC-690; Sony Germany GmbH) with normal speed. The tapes (DM120; Maxell Europe Ltd) were given numbers to allow blinded off-line analysis. The observers' analysis of MES constituted (1) listening to the signal through a headphone (MDR CD250; Sony Germany GmbH) and (2) watching the signal on the screen at highest speed. The definitions of Spencer10 11 for MES were used: typical visible and audible (click, chirp, whistle) short-duration, high-intensity signal within and sometimes also outside the Doppler flow spectrum, occurring at random in the cardiac cycle. A unanimous decision of two observers (M.K. and I.K.) was applied as the gold standard.
In addition to the aforementioned off-line analysis, the multigated embolus detection software TCD-8 for MDX (version 8.00 K) was used on-line. The distance between the two sample volumes was set at 5 mm. The relative intensity increase was calculated by the machine from the deeper sample volume, ie, the one first passed by an embolus during its migration to the periphery. The decibel values determined by this software differed from other decibel specifications. In contrast to manual calculation of the relative intensity increase of MES compared with the adjacent background spectrum intensity, this automatic calculation uses the entire screen as a background. This includes spectrum-free areas of low intensity. Consequently, the decibel values of MES detected during this approach were higher than those calculated in previous studies. On the basis of recent experience (M.K. et al, unpublished data, 1996), events corresponding to intensity fluctuations of the normal Doppler spectrum could readily be detected in artifact-free periods of normal people with a detection threshold of lower than 11 dB. Therefore, a detection threshold of 11 dB was used in all studies. We chose this low value to include as many signals as possible and to postpone the definition of an appropriate intensity increase cutoff level between events corresponding to intensity fluctuations of the normal Doppler spectrum and MES. The software recorded all events at and above the preset intensity increase threshold and indicated the calculated spatial distance between the two sample volumes. Fig 1⇓ illustrates the method of operation of the software.
Patients With Prosthetic Aortic Valves
Three men and two women, aged 58 to 75 years, were investigated 8 months to 5 years after aortic valve implantation (all Carbomedics). Bilateral TCD monitoring was performed at first with the patient resting in a supine position for 30 minutes (21% oxygen, atmospheric pressure). During the next 30 minutes, patients breathed 100% oxygen by a face mask that was not close fitting. Pao2 was measured during both procedures (air respiration, 100% oxygen) by a capillary probe. All patients were on oral anticoagulation. Two patients had concomitant coronary heart disease, and one had a pacemaker.
A 59-year-old man with an artificial prosthetic aortic valve (Carbomedics 23) for 4 years, determined to be fit for hyperbaric exposure, was recorded in a hyperbaric multiplace chamber. The hyperbaric chamber (HAUX Starmed 2200/5.5) is based at Hyperbares Zentrum Norddeutschland, Friedrich-Ebert-Krankenhaus, Neumünster, Germany, and is normally used for hyperbaric oxygen therapy. During emboli detection, the patient was in a sitting position and monitored noninvasively (transcutaneous Po2 measurements, electrocardiogram, and blood pressure). Two physicians participated in the hyperbaric exposure procedure. During the recordings the ultrasound device was outside the hyperbaric chamber, and the leads of the probes were placed through a specially designed transmural access.
The experiment began with inspiration of normobaric air and continued with the patient breathing 100% oxygen for another 30 minutes using a close-fitting face mask. The descent was performed under compressed air at a rate of 0.1 kPa/min and took 15 minutes. At a constant pressure of 2.5 kPa (in reference to seawater depth of 15 m), 100% oxygen was administered for another 30 minutes. This was followed by an ascent phase to 1.75 kPa, also at a rate of 0.1 kPa/min. After a 10-minute period in which the patient did not breathe oxygen (to minimize oxygen toxicity), another interval of 30 minutes with inspiration of 100% oxygen followed. The final ascent was also performed at a rate of 0.1 kPa/min. After a return to 1 kPa, the study was completed with a second monitoring period for 20 minutes under normobaric pressure.
The number of MES was calculated in counts per minute to compensate for different monitoring durations (ie, 20 minutes of emboli monitoring under 100% oxygen and 2.5 kPa versus 30 minutes under 21% oxygen and normobaric pressure). The evaluation of data was descriptive. Statistical analysis was not performed because of the small number of patients. The approval of the local ethics committee and informed consent were obtained for the study.
Oxygen Application Under Normobaric Conditions
Under resting conditions, the five patients showed a total of 96 events (5, 9, 2, 25, and 55; median, 9; range, 2 to 55) within 30 minutes of bilateral monitoring. During 100% oxygen breathing, the total number dropped to 2 MES ( 2, 0, 0, 0, and 0, respectively; median, 0; range, 0 to 2) per 30 minutes. Interobserver agreement was 97%. The mean Pao2 increase under inspiration of 100% oxygen was 48.6 mm Hg, ranging from 3 to 149 mm Hg (median, 39 mm Hg).
Hyperbaric Chamber Investigation
During breathing of normobaric air (1 kPa), a rate of 1.4 MES per minute was recorded (Fig 2⇓), which dropped to 0.3 MES per minute under inspiration of 100% oxygen (1 kPa). Increasing the pressure to 2.5 kPa during breathing of compressed air resulted in an increase to 1.46 MES per minute.
The following phase of oxygen breathing (100%, 2.5 kPa) again showed a decrease to 0.9 MES per minute. A second phase of oxygen breathing at 1.75 kPa resulted in another decrease to 0.3 MES per minute. After hyperbaric exposure, the rate of MES returned to resting values identical to the embolic counts at the start of the experiment.
Our study demonstrates that the rate of MES in patients with prosthetic cardiac valves depends on arterial oxygen pressure. This finding provides strong evidence that the MES found in these patients are predominantly caused by gaseous particles. Inhalation of 100% oxygen increases the oxygen concentration and simultaneously decreases nitrogen concentration in the blood. The solubility of oxygen in blood is 4.8 times higher than that of nitrogen. Therefore, oxygen gas bubbles formed by the cavitation process dissolve much better in blood and have a shorter life span. Thus, fewer gaseous microemboli enter the cerebral circulation.
In contrast, increasing the pressure to 2.5 kPa in a hyperbaric chamber raises the concentration of dissolved oxygen 8 to 10 times compared with normobaric conditions. With a higher oxygen concentration, cavitation is much more effective under a hyperbaric environment and the rate of MES increases. This interference would not be expected if microemboli consisted of solid platelet aggregates or atherothrombotic, thrombotic, or atherosclerotic material. Two other aortic valve patients undergoing hyperbaric compression have been described recently.12 The first patient revealed an increase in bubble count under hyperbaric compression, which is in agreement with our results. The decrease of MES in the second patient is difficult to explain, because data regarding partial pressures of oxygen in the blood before and during the hyperbaric experiment are lacking. The author hypothesized a reduction in diameter and number of gas bubbles under hyperbaric compression. However, the opposite applies, because bubble signals increase as a result of much higher oxygen concentration.
Under oxygen inhalation, MES could only be recorded in one patient. However, a relevant elevation of Pao2 could not be achieved in this patient, probably because of chronic obstructive lung disease and insufficient oxygen inspiration.
If the composition of microemboli is known, estimation of size is possible. The gaseous nature of MES indicates a bubble size of approximately 3 to 4 μm. This allows passage through the capillary bed without blockade of microcirculation. In contrast, signals of a similar relative intensity increase, if caused by a solid material, would indicate a particle size of much more than 10 μm (D. Russell, conversation, 1996), which is critical in terms of capillary blockade.13 This explains why as many as 1500 MES per hour occur in some patients without any obvious neurological or neurophysiological deficits and why MES could not be related to a history of neurological deficit, cardiac rhythm, or intensity of coagulation.4 14 Our results also do not support the theory of hemodynamic vortices as the underlying cause of MES.15
The ability of prosthetic valves to produce cavitation bubbles can be observed in bench models16 and during transesophageal echocardiography. Furthermore, it has been demonstrated that there is a striking difference in prevalence and quantity of MES rates among different valve types.5 Most of these gas bubbles have a very short life span and dissolve on their way to the brain. This is confirmed by the finding that the rate of MES detected in the internal carotid artery of aortic valve patients is much higher than in the middle cerebral artery.12 In any case, some gas bubbles are stable enough to enter the cerebral circulation, as demonstrated in patients with patent foramen ovale who received agitated saline intravenously for diagnostic purposes.
Patients with prosthetic aortic valves are prone to concomitant cardiac disorders, which are potential embolic sources. Therefore, it cannot be ruled out that MES in these patients are due to a mixture of gaseous and solid particles or platelet aggregates induced by gas bubbles. However, the rate of embolic counts in patients with cardiac diseases such as atrial fibrillation or myocardial infarction is surprisingly much lower. Therefore, microemboli formation appears to predominantly be a result of cavitation, which depends on concentration and solubility of blood gases.
In conclusion, our findings indicate a benign nature of microemboli that arise from prosthetic cardiac valves. Because these gas bubbles are small, it seems unlikely that they are associated with a high immediate risk of neurological deficit. Moreover, our results are not in favor of MES as a useful predictor of stroke risk in patients with prosthetic cardiac valves.
We gratefully acknowledge the support of S. Ladwig, E. Prill, and M. Stirnal during the hyperbaric chamber experiment.
- Received September 12, 1996.
- Revision received November 4, 1996.
- Accepted November 18, 1996.
- Copyright © 1997 by American Heart Association
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