Summary Background Whether surgery is beneficial for patients with asymptomatic carotid stenosis is controversial. Better methods of identifying patients who are likely to develop stroke would improve the risk–benefit ratio for carotid endarterectomy. We aimed to investigate whether detection of asymptomatic embolic signals by use of transcranial doppler (TCD) could predict stroke risk in patients with asymptomatic carotid stenosis. Methods The Asymptomatic Carotid Emboli Study (ACES) was a prospective observational study in patients with asymptomatic carotid stenosis of at least 70% from 26 centres worldwide. To detect the presence of embolic signals, patients had two 1 h TCD recordings from the ipsilateral middle cerebral artery at baseline and one 1 h recording at 6, 12, and 18 months. Patients were followed up for 2 years. The primary endpoint was ipsilateral stroke and transient ischaemic attack. All recordings were analysed centrally by investigators masked to patient identity. Findings 482 patients were recruited, of whom 467 had evaluable recordings. Embolic signals were present in 77 of 467 patients at baseline. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack from baseline to 2 years in patients with embolic signals compared with those without was 2·54 (95% CI 1·20–5·36; p=0·015). For ipsilateral stroke alone, the hazard ratio was 5·57 (1·61–19·32; p=0·007). The absolute annual risk of ipsilateral stroke or transient ischaemic attack between baseline and 2 years was 7·13% in patients with embolic signals and 3·04% in those without, and for ipsilateral stroke was 3·62% in patients with embolic signals and 0·70% in those without. The hazard ratio for the risk of ipsilateral stroke and transient ischaemic attack for patients who had embolic signals on the recording preceding the next 6-month follow-up compared with those who did not was 2·63 (95% CI 1·01–6·88; p=0·049), and for ipsilateral stroke alone the hazard ratio was 6·37 (1·59–25·57; p=0·009). Controlling for antiplatelet therapy, degree of stenosis, and other risk factors did not alter the results. Interpretation Detection of asymptomatic embolisation on TCD can be used to identify patients with asymptomatic carotid stenosis who are at a higher risk of stroke and transient ischaemic attack, and also those with a low absolute stroke risk. Assessment of the presence of embolic signals on TCD might be useful in the selection of patients with asymptomatic carotid stenosis who are likely to benefit from endarterectomy. Funding British Heart Foundation.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(10)70120-4.pdf

Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study

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.

Clinically Silent Microemboli in Patients With Artificial Prosthetic Aortic Valves Are Predominantly Gaseous and Not Solid

The advent of implantable blood recirculating devices has provided life-saving solutions to patients with severe cardiovascular diseases. Recently it has been reported that ventricular assist devices are superior to drug therapy. The implantable total artificial heart is showing promise as a potential solution to the chronic shortage of available heart transplants. Prosthetic heart valves are routinely used for replacing diseased heart valves. However, all of these devices share a common problem--significant complications such as hemolysis and thromboembolism often arise after their implantation. Elevated flow stresses that are present in the nonphysiologic geometries of blood recirculating devices, enhance their propensity to initiate thromboembolism by chronically activating the blood platelets. This, rather than hemolysis, appears to be the salient aspect of blood trauma in devices. Limitations in characterizing and controlling relevant aspects of the flow-induced mechanical stimuli and the platelet response, hampers our ability to achieve design optimization for these devices. The main objective of this article is to describe state-of-the-art numerical, experimental, and in vivo tools, that facilitate elucidation of flow-induced mechanisms leading to thromboembolism in prosthetic devices. Such techniques are giving rise to an accountable model for flow-induced thrombogenicity, and to a methodology that has the potential to transform current device design and testing practices. It might lead to substantial time and cost savings during the research and development phase, and has the potential to reduce the risks that patients implanted with these devices face, lower the ensuing healthcare costs, and offer viable long-term solutions for these patients.

/pdf/research-approaches-for-studying-flow-induced-thromboembolic-2oqr32258o.pdf

Research approaches for studying flow-induced thromboembolic complications in blood recirculating devices.

Background and Purpose Carotid angiography is associated with a 1% risk of major stroke. Recently, transcranial Doppler ultrasonography (TCD) has shown cerebral microemboli during carotid angiography. To determine their significance, we correlated the number of microemboli during angiography with clinical characteristics, angiography findings, and preangiography and postangiography cerebral magnetic resonance imaging (MRI).

Methods One middle cerebral artery was monitored with TCD in 24 patients during angiography for carotid territory ischemia. The number of microemboli was correlated with angiographic and clinical characteristics. T2-weighted cerebral MRI was performed before and ≤48 hours after angiography, and the number of new ischemic lesions was determined in a blinded review.

Results Microemboli were seen in all patients, with an average of 51 per procedure (range, 12 to 154). The majority of microemboli had signal characteristics typical of air. Sixteen of the 24 patients had both preangiography and postangiography MRI. One of 24 patients had an angiographic stroke, with a single new thalamic lesion on MRI. No other patient had a new lesion. The microembolus count correlated with the angiographic contrast volume ( P <.001) but not with any other radiological or clinical characteristic.

Conclusions This study confirmed the presence of numerous cerebral microemboli during carotid angiography. The microembolic signal characteristics and the correlation with contrast volume indicate that introduced air is the cause. These microemboli are usually clinically silent and do not lead to new changes on cerebral MRI.

Microemboli During Carotid Angiography Association With Stroke Risk Factors or Subsequent Magnetic Resonance Imaging Changes

Background and Purpose— Transcranial Doppler ultrasound can reliably detect both gaseous and solid cerebral emboli. However, conventional equipment is unable to discriminate between gaseous and solid emboli. This is a major limitation in situations in which the 2 coexist, because they may have very different clinical relevance. Recently, a novel Embo-Dop system, using insonation at 2 ultrasound transducer frequencies, has been developed. An initial study with a small sample size suggested it provided excellent discrimination. We performed a validation study in subjects with embolic signals of known nature. Methods— Gaseous embolic signals were obtained in 7 patients with known patient foramen ovale by intravenous injection of agitated saline injections. Solid embolic signals were obtained in patients with symptomatic carotid stenosis (N=23). Discrimination of the 2 using the Embo-Dop system dual-frequency system was assessed. It was compared with discrimination using embolic signal maximum intensity with ...

Can Transcranial Doppler Discriminate Between Solid and Gaseous Microemboli?: Assessment of a Dual-Frequency Transducer System

Doppler emboli detection is an established technique, but the nature of the underlying embolic material remains unclear. The intensity and spectral distribution of emboli signals could help to distinguish between signals arising from formed and gaseous emboli. We undertook this study to develop and evaluate a differentiation algorithm based on the spectral characteristics of emboli signals. Subsequently the algorithm was applied to patients with mechanical prosthetic cardiac valves.

Emboli signals detected in patients with carotid disease, acute stroke, and atrial fibrillation were used as formed emboli data, and signals detected in patients undergoing cardiac catheterization studies were used as gaseous emboli data. For each embolus signal, the maximal amplitude, the sum of amplitudes, and the spectral intensity distribution were calculated. Two hundred emboli signals from each category were used to develop a differentiation algorithm, which was subsequently evaluated on 501 additional solid and 995 gaseous emboli signals. The same algorithm was used to analyze 5958 emboli signals detected in 60 patients with mechanical prosthetic valves.

The best results were obtained with an algorithm based on both the maximal amplitude and the sum of amplitudes (sensitivity, 99%; specificity, 96.5%). On subsequent evaluation, the sensitivity and specificity of the algorithm were 99.6% and 89.8%, respectively. Of the 5958 emboli signals detected in prosthetic valve patients, 92.4% were classified as gaseous.

Differentiation between gaseous and formed emboli signals, as detected by transcranial Doppler in vivo, is feasible by means of spectral analysis. Application of the differentiation algorithm in prosthetic valve patients suggests that the embolic material in these patients is gaseous. The possibility of distinguishing between different formed embolic materials with this technique remains to be evaluated.

Differentiation between gaseous and formed embolic materials in vivo. Application in prosthetic heart valve patients.

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Differentiation between gaseous and formed embolic materials in vivo. Application in prosthetic heart valve patients.