Outcome Improvement in Acute Stroke Revascularization Procedures
See related article, pages 695–699.
Mechanical thrombectomy, intra-arterial thrombolysis, and intracranial stenting procedures are increasingly used in patients with symptoms of acute brain ischemia and usually within the first 12 hours after the beginning of symptoms. The rational underlying these acute interventions is to expand the therapeutic time window, because the number of patients presenting within the first 3 hours remains limited.1 Despite more than a decade of experience, the efficacy of these interventions is not firmly established, and they are associated with a substantial risk of complications, such as brain infarction or hemorrhage, arterial dissection, and death. The risk of procedural complications ranges between 5% and 29%, with an average stroke and death rate of ≈10% in recent series.2–7
In an effort to reduce complications, investigators have aimed at identifying clinical risk factors associated with adverse outcomes2 and have also tried to improve patient selection. Patients with posterior circulation arterial stenoses2 or with a blood glucose level >200 mg/dL6 have a relatively high risk. Procedures performed at medical centers with low volumes or by interventionalists with limited experience are associated with a higher risk of complications. Furthermore, patients with large mismatches between diffusion and perfusion on brain neuroimaging studies are more likely to benefit from the procedures and are better candidates.8 The introduction of these variables in patient selection may improve results.
The clinical approach presented in the preceeding paragraph has the advantage of identifying patients with the best risk–benefit profile before any procedure is performed. Another approach to improve outcome is to monitor the different steps of each procedure, to identify the causes of adverse events in vivo, and, hopefully, to correct them when they occur. Ideally, these events should be detected early, before they cause irreversible brain damage. Interventional procedures are not black boxes and an improved understanding of what can go wrong during the course of each procedure should improve interventional techniques and help develop new technologies.
In this issue of Stroke, Rubiera et al9 present data from their study of a relatively small group of acute stroke patients who received continuous transcranial Doppler ultrasound (TCD) monitoring during reperfusion procedures.9 The local hemodynamic effects of thrombolysis, mechanical thrombectomy, balloon angioplasty, and stenting are reviewed. Particulate and gaseous microembolic signals, resulting from arterial manipulations, were detected frequently. Reocclusion was observed in 27% of cases (in 19% during the intra-arterial procedure and in 8% after the latter was completed), prompting recatheterization and additional reperfusion procedures. Artery-to-artery microembolism occurred in 4% of cases after procedure completion, also prompting additional treatment. Intraluminal thrombi were detected. Hyperperfusion was detected in 13% of cases.
The study by Rubiera et al is certainly of interest to the curious scientist. Are the findings of the study clinically relevant? The short answer is a qualified “no.” In their discussion, Rubiera et al present their observations, recognize their potential applications, and wisely refrain from making clinical recommendations. Although their observations describe hemodynamic and embolic findings that have been associated with poor clinical outcomes by others,10 their study did not address specific clinical outcomes. It also did not address the impact of interventions, based on data obtained from TCD monitoring, on clinical outcome. Note that other investigators11 have also used TCD to monitor acute stroke patients previously.
The study by Rubiera et al is important, however, in that it identifies specific intra-arterial adverse events that can lead to tissue damage and clinically detectable complications in the context of interventional procedures. The detection of these events is based on the ability of TCD to continuously and noninvasively monitor procedures. Several of these intra-arterial events can be clinically relevant. For example, during mechanical embolectomy with the Penumbra or Merci devices, TCD can instantly identify recanalization. This is important because it can prompt the interventionalist to refrain from further probing and aspirating or performing a control angiogram to verify arterial patency. Severe microembolism to the brain, another adverse event, can occur during balloon angioplasty, stenting, or embolectomy; this can be treated with antiplatelet agents, such as GpIIb/IIIa inhibitors in selected cases, because it incurs hemorrhagic risk.12 In addition, identification of very elevated mean flow velocities after a recanalization procedure, indicative of a hyperperfusion syndrome, may prompt immediate lowering of blood pressure to prevent hemorrhage.
Whether interventions based on the preceding TCD detected intra-arterial events can be effective in improving outcomes remains unknown at this time. Future research needs first to refine TCD variables and then to test the effect of specific intraprocedural interventions, prompted by the detection of these variables, on clinical outcomes. For example, the ideal mean flow velocity range that would optimize perfusion but prevent reperfusion hemorrhage remains to be defined. The limits of this range and their correlation with blood pressure would be helpful in identifying blood pressure targets. Well-designed studies need to subsequently test the impact of blood pressure treatment on clinical outcome. Only then will we know whether these observations are clinically relevant.
Limitations of TCD include the lack of continuous access to the technology and ultrasonographer expertise in the angiography suite. Most stroke centers do not have the luxury of “24/7” TCD monitoring availability. Waiting for TCD technologists and equipment may force further delays to recanalization at medical centers with limited staff. At centers where TCD is not readily available, or if TCD monitoring is eventually found to be ineffective, other technologies such as intravascular ultrasound, electroencephalography, and cerebral oximetry can be utilized. At the end of the day, the adjunctive technology used is not important. The goal is to improve the procedure’s outcome.
The notion of quality control and outcome assessment are not new to interventional or surgical procedures. Previous investigators have investigated improving outcome after revascularization procedures in acute stroke,13 and the available scientific knowledge base remains limited. Quality control and outcome-directed research have also been important concerns for internal carotid artery stenting and endarterectomy. In these areas also, more information also will be useful. Surgical and interventional procedures evolve over time, and it may be worthwhile noting that the first carotid revascularization procedures of the 1950s were technically quite different from the endarterectomies practiced today. Similarly, intracranial revascularizations are expected to evolve, and they will be substantially influenced by technological developments. The evolution from angioplasty to stenting and then to drug-eluting stents14 is an illustration of this progress. Knowledge gained from monitoring can influence the evolutionary process.
A 32% in-hospital mortality rate in the series by Rubiera et al illustrates the severity of illness in these patients and the need to rapidly develop effective and reasonably safe interventional techniques and other medical treatments. Better selection of acute ischemic stroke patients for intervention based on clinical and neuroimaging criteria and continued enrollment in randomized trials, such as the Interventional Management Study III trial or MR and Recanalization of Stroke Clots Using Embolectomy, are important practical steps in our progress. We expect intraoperative monitoring with TCD or other technologies to influence the interventional and surgical techniques, potentially improving outcome. The study of Rubiera et al is a solid step forward in the path of our progress.
The opinions in this editorial are not necessarily those of the editors or of the American Heart Association.
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