Monitoring the Effectiveness of Anticoagulative Therapy in Left Atrial Spontaneous Echo Contrast by Cerebral Microemboli Detection
To the Editor:
We observed high-intensive transient signals (HITS) in continuous transcranial Doppler (TCD) sonography in a patient with stroke and massive spontaneous echo contrast in the left atrium. These HITS occurred only when insufficient anticoagulation was present.
HITS detected in continuous transcranial Doppler spectral curves are correlated with embolic conditions and stroke.1 Fulfilling several criteria, they are accepted as cerebral microembolic events. Until now, no influence of anticoagulation on the presence of HITS has been proved.2 Only one case examines the influence of intravenous heparin on the rate of HITS in a patient with stroke, but in this patient no embolic source was found.2 In another published case,3 remitting cerebral ischemia is correlated with the rate of microembolic signals, but there is no relation to anticoagulation with intravenously applied heparin.
The well-known condition of spontaneous echo contrast, shown by transthoracic (TTE) or transesophageal echocardiography (TEE), occurs mainly in the left atrium in cardiac embolic cases. It is explained by aggregations of erythrocytes, indicates a hypercoagulative state, and is associated with a high incidence of left atrial thrombus as well as a higher stroke risk in these patients.4
Our 62-year-old male patient developed persisting atrial flutter for the first time with an embolic occlusion of the left internal carotid artery (ICA) and a consecutive territorial infarction in the area of the left middle cerebral artery (MCA). TEE demonstrated massive spontaneous echo contrast in the left atrium, due to atrial flutter and enlargement of the left atrium. The patient received intravenously heparin with a partial thromboplastin time of about 55 seconds. Three continuous TCDs were performed over the following days, the second without anticoagulation because, unnoticed by nurses and physicians, the patient disconnected the IV line with heparin nearly 1 hour before examination. Only in this examination were significant HITS found in the right MCA. The left MCA showed artifacts in all examinations because of bad bone window and turbulent cross flow over the circle of Willis.
We concluded that the patient’s symptoms were due to the occlusion of the left ICA but that the microembolic events which registered in the right MCA only in a situation without any anticoagulation were the consequence of the embolic cardiac condition visualized as spontaneous echo contrast in the TEE. To our knowledge, this is the first time that an effect of anticoagulation in the treatment of cardiogenic embolic disease has been directly demonstrated through detection of cerebral microembolic signals.
We conclude that the effectiveness of anticoagulant therapy in spontaneous echo contrast can be monitored through detection of microembolic signals. The as-yet unproved influence of anticoagulation in cardiac embolic disease on the occurrence of microembolic signals may result from a too-low detection level for emboli by this method in some cases. However, it might be effective in the special situation of spontaneous echo contrast, which indicates a massive tendency for coagulation and embolic events.
- Copyright © 1999 by American Heart Association
Doppler monitoring of blood flow velocity patterns in the intracranial arteries has been used for several years to detect HITS, which have been prematurely accepted as synonymous with microembolism despite warning hints that this may not always be so.R1
First, the majority of HITS are clinically silent, and reports of associated transient ischemic attacks or strokes are extremely rare (eg, in patients with prosthetic heart valves as many as 1 million HITS per month may be extrapolated without neurological or neuropsychological problems). These HITS have recently been identified as resulting from gaseous artifacts (so-called microcavitations).R2 Others that are less frequently observed in patients with cerebral ischemia are more likely to represent features of ongoing microembolism,R3 eg, in the presence of symptomatic carotid disease; however, neither the constituency of these microembolic particles nor the risk of stroke or transient ischemic attacks associated herewith has been identified so far. Second, the information from the Doppler signal is insufficient for interpretation of the size and composition of microembolic particles because of several physical and physiological problems, as observed in experimental conditions: signals from identical emboli may vary enormously due to the nonuniformity of the ultrasound field inside the skull, only small differences between Doppler signals from surrounding blood versus those from microembolic particles, and unpredictable trajectories of a particular embolus passing the vessel and the ultrasound beam volume.R2 Thus, many attempts to distinguish gaseous from solid microemboli, and in particular to separate different composition and size from patterns of HITS, will always involve a large degree of uncertainty, which supports the caveat against a terminology using HITS and microembolic particles as synonyms.
Several anecdotal observations of patients with identified sources of cerebral embolism, repeated clinical attacks, and HITS detected during TCD monitoring represent an interesting approach to identify the composition of microembolic particles at least in individual subjects by different reactions to agents interfering with their generation and to use this information for a refined and personally stratified therapeutic regimen.
In our article published in Stroke in 1996,R3 the therapeutic regimen at the time of investigation was analyzed to establish its effect on incidence of HITS. Among 148 patients with identified sources of embolism, those without a specific treatment (anticoagulation/platelet inhibition) showed a nonsignificant trend for a higher incidence of HITS than those who were on anticoagulation (eg, 20.9% versus 10.8% in patients with vascular sources of embolism and 8.6% versus 3.6% in patients with cardiac sources of thrombembolism). In a case similar to those reported by Siebler et alR4 and by Eggers et al in their letter, we recently describedR5 a patient with recurrent ischemic attacks in the posterior circulation due to proximal vertebral artery stenosis, who exhibited both HITS and acute embolic lesion patterns demonstrated by MRI. Clinical events occurred despite standard antiplatelet therapy and oral anticoagulation, but they, as well as HITS, stopped when effective intravenous anticoagulation (partial thromboplastin time of 83 seconds) or a combination of anticoagulants (INR of 1.5 to 3.5) and aspirin (50 mg) was administered.
Because the spontaneous course of patients with cerebrovascular diseases varies, anecdotal reports like these cannot be taken for evidence-based therapy. However, these cases challenge the question of whether modification of HITS to individual treatment strategies may become a useful instrument for more efficient secondary stroke prevention, which unfortunately still fails in two thirds of all patients treated according to the results from large clinical trials.
Daffertshofer M, Ries S, Schminke U, Hennerici M. High-intensity transient signals in patients with cerebral ischemia. Stroke.. 1996;27:1844–1849.
Siebler M, Nachtmann A, Sitzer M, Steinmetz H. Anticoagulation monitoring and cerebral microembolis detection. Lancet.. 1994;344:555. Letter.