Guidewire Withdrawal in Ascending Aorta Increases Cerebral Microembolism During Coronary Angiography — A Randomized Comparison of Two Guidewire Techniques

Abstract: Background. Microemboli are frequently detected entering the middle cerebral arteries during coronary angiography (CA). Recent studies have reported that cerebral microemboli, especially particulate cerebral microemboli, may cause silent ischemic cerebral lesions. Aims. To investigate whether the occurrence of particulate cerebral microemboli during diagnostic CA is influenced by which guidewire technique is used. Methods. Patients with stable angina pectoris or non-ST elevation acute coronary syndrome, referred for CA, were randomized to initial advancement of catheters with a leading guidewire over the aortic arch or to initial guidewire withdrawal in the descending aorta with advancement of catheters alone. After completed CA (part 1), new catheters and guidewires were advanced with guidewire technique contrary to the one first used (part 2). Patients were continuously monitored with transcranial Doppler (TCD), and cerebral microemboli were automatically counted and differentiated. Results. Statistical analysis was performed on 41 patients. The results in part 1 were confirmed in part 2. The median number (interquartile range) of particulate cerebral microemboli was significantly higher when catheters were advanced with, compared to without, a guidewire over the aortic arch; overall, 6 (IQR, 1-9) vs 1 (IQR, 0-3); P=.01. Conclusions. Advancement of catheters with a leading guidewire over the aortic arch with subsequent flushing in the ascending aorta consistently generated more particulate cerebral microemboli, implying that the choice of guidewire technique has an impact on the risk for cerebral lesions during CA. 

J INVASIVE CARDIOL 2014;26(1):1-6

Key words: coronary angiography, transcranial Doppler, cerebral microemboli, ascending aorta, guidewire

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Today, overt stroke during coronary angiography is a rare complication, seen in less than 0.3% of patients examined.¹ Recently, however, it has been reported that the incidence of small, clinically silent cerebral lesions caused by microemboli may be considerably higher, ranging between 5%-22%, ^2-6 and furthermore, that they may be associated with cognitive impairment.^2,7 This high incidence of silent cerebral lesions implies that the safety of diagnostic coronary angiography may be overestimated. Increasing patient safety is essential and the assessment of the role that procedural techniques may have in causing cerebral complications is, therefore, important.

Currently, two guidewire techniques are used for coronary angiography. One is the original Judkins technique where the guidewire is withdrawn and catheters are flushed in the descending aorta,⁸ while in the other technique, catheters are advanced with a leading guidewire over the aortic arch with subsequent flushing in the ascending aorta.⁹ The choice of technique is governed by local traditions.

In a previous report, the incidence of cerebral microemboli was higher when the guidewire was withdrawn in the ascending aorta.¹⁰ The transcranial Doppler (TCD) method then used could not, however, differentiate gaseous from particulate cerebral microemboli,¹⁰ the former constituting the majority and occurring mainly during catheter flushing, while the latter are considered to be more detrimental since they are more likely to permanently occlude cerebral vessels, causing small ischemic lesions.² It is plausible that catheters advanced over the aortic arch without a leading guidewire dislodge more aortic debris. Consequently, using a TCD method capable of differentiating cerebral microemboli may show that the incidence of gaseous microemboli is lower, but that there is no difference in the incidence of particulate microemboli when the guidewire is withdrawn in the descending aorta.

This study was designed to test the hypothesis that the choice of guidewire technique does not influence the occurrence of particulate cerebral microemboli during coronary angiography. 

Methods

Patients. Eligible patients were those with stable angina pectoris or non-ST elevation acute coronary syndrome (NSTEACS) referred for coronary angiography at Karolinska University Hospital. Exclusion criteria were ST-elevation myocardial infarction, a history of coronary artery bypass surgery, or advanced kidney failure with estimated creatinine clearance below 30 mL/min according to the Cockroft-Gault formula. The regional ethics committee approved the study and all participating patients gave written informed consent.

Coronary angiography. Coronary angiography was performed via right femoral approach. Ultimum 6 Fr sheaths (St Jude Medical), 0.035˝ 150 cm straight-tip guidewires (Boston Scientific), 6 Fr JL 4 (Boston Scientific) and JR 4 catheters (Boston Scientific) were used during the procedure. All guidewires and catheters were heparinized prior to use. After withdrawal of the guidewire, all catheters were flushed with 20 mL of heparinized saline after >10 mL of blood was discarded. A standard contrast medium, Visipaque 320 mg/mL (GE Healthcare) was used. 

Study design. The study design is shown in Figure 1. In part 1 of the study patients were randomized to group A, in which coronary angiography was performed with the advancement of catheters with a leading guidewire over the aortic arch and flushing of the catheter in the ascending aorta, or to group B, in which coronary angiography was performed with the withdrawal of the guidewire and flushing of catheters in the descending aorta, followed by the advancement of the catheter alone over the aortic arch to the ascending aorta. Examination of the left and right coronary arteries was executed during part 1. Part 2 of the study was executed to confirm the findings of part 1. However, for ethical reasons, a complete coronary angiography was not performed. A new set of right and left catheters as well as guidewires were advanced and flushed with saline using the technique contrary to the one used in part 1, but no contrast was injected during part 2. Percutaneous coronary intervention (PCI), intracoronary pressure measurement, intracoronary ultrasound, ventriculography or aortography was performed when indicated, but always after completion of the study protocol. Sheaths were withdrawn immediately after the procedure.

Transcranial Doppler monitoring. Using a specially designed head brace, two dual-frequency probes (2.0 and 2.5 MHz) were fixated bilaterally over the temporal ultrasonic windows. Both middle cerebral arteries (MCA) were continuously monitored using a multifrequency Doppler system (Embo-Dop; DWL Elektronische Systeme GmbH). Emboli passing the insonated vessel result in increases in the reflected ultrasound beam and are detected as high-intensity transient signals (HITS). These cerebral microemboli were automatically identified, counted, and differentiated as gaseous or particulate,^11-13 as shown in Figure 2. The TCD monitoring was discontinued prior to all coronary interventions. The data analysis was performed after completion of the study by an investigator who was not present in the cath lab during the procedures and was thus blinded.

Statistical methods. Values not following normal distribution are presented as median and interquartile range (IQR, q1-q3) and in figures as median (IQR), whereas normally distributed values are presented as mean ± standard deviation (SD). The Mann-Whitney U-test was used for the overall comparison and for group-wise comparison of part 1 and part 2, respectively, regarding the number of cerebral microemboli detected using each guidewire technique. The number of cerebral microemboli between operators was compared using the Kruskal-Wallis test. All tests were two-sided, the level of statistical significance was P<.05, and all statistical analyses were performed using SPSS version 19 (IBM Corporation).

In a previous report, a mean of 6.9 ± 4.7 particulate microemboli was detected when catheters were advanced with a guidewire to the ascending aorta.¹⁴ For this study, we hypothesized a mean of 2.5 particulate microemboli in the group with guidewire withdrawal in the descending aorta with a similar standard deviation. Calculating on a mean difference of ≥4.4 particulate microemboli between the groups, adjusted for non-normally distributed data using Pitman efficiency,¹⁵ twenty-one patients in each group were needed to detect a statistical difference between the groups (80% power, P<.05).

Results

From May to June 2009, a total of 44 out of the 102 patients screened at that time were included in the study. Since 3 of the patients had incomplete TCD recordings, 41 patients were finally analyzed. Twenty-one patients were randomized to initial advancement of the catheters with a guidewire over the aortic arch and flushing in the ascending aorta, and 20 patients to initial guidewire withdrawal and flushing of catheters in the descending aorta.

Patients. Baseline characteristics were similar in both groups (Table 1). The majority of the patients (95%) were medicated with aspirin. Half of the patients had a preliminary diagnosis of NSTEACS and were treated with fondaparinux. In group A, 1 patient with a final diagnosis of NSTEACS did not receive fondaparinux, and in group B, 1 patient was discharged without an NSTEACS diagnosis. In accordance with local routines, 90% of the patients had been given clopidogrel prior to coronary angiography to enable ad hoc percutaneous coronary intervention if so indicated. Patients with stable angina pectoris did not receive heparin. No overt stroke, transient ischemic attack, or other neurological symptoms were observed before patient discharge.

Coronary angiography. Six interventional cardiologists performed the coronary angiography. The diagnostic results of no significant stenosis, one-vessel, two-vessel, or three-vessel disease were evenly distributed between the groups (Table 1). Procedure times did not differ between group A and B for part 1 (P=.99) or for part 2 (P=.34; Table 1). Neither technique necessitated the re-insertion of the catheters due to twisting or bending.

Overall TCD outcome. Cerebral microemboli were detected in all patients. There were no differences in occurrence between the left and the right middle cerebral artery (MCA) or between the interventional cardiologists performing the procedures (data not shown). There was no significant difference in the occurrence of cerebral microemboli in relation to the angiographic results of no stenosis, or one-, two-, or three-vessel disease (data not shown).

Overall, more particulate cerebral microemboli were detected when the catheters were advanced with a leading guidewire over the aortic arch compared with when the guidewire was withdrawn in the descending aorta 6 (IQR, 1-9) compared with 1 (IQR, 0-3) (P=.01), independent of allocation group (Figure 3A). The results for gaseous cerebral microemboli were similar, 38 (IQR, 19-57) compared with 13 (IQR, 3-30) (P<.001; Figure 3B).

Subanalysis of transcranial Doppler outcome. As expected, a higher number of cerebral microemboli was detected in part 1 than in part 2 of the study: particulate 6 (IQR, 1.5-9.5) compared with 1 (IQR, 0-3); (P<.001) and gaseous 34 (IQR, 21-56) compared with 13 (IQR, 3.5-32.5); (P<.001), respectively. 

In part 1 of the study, including coronary artery examination, more particulate cerebral microemboli were detected when the catheters were advanced with a guidewire over the aortic arch compared with when the guidewires were withdrawn in the descending aorta; 9 (IQR, 5-12) compared with 3 (IQR, 1-6); (P=.02; Figure 4A; Table 1). Likewise, more gaseous microemboli were detected when catheters were advanced with a guidewire over the aortic arch 48 (IQR, 32-81) compared with 27 (IQR, 12-39); (P=.01; Table 1).

The results in part 2 were similar to part 1. Particular cerebral microemboli during advancement of catheters with a guidewire over the aortic arch were 2 (IQR, 1-7) compared with 0 (IQR, 0-2) if the guidewire was withdrawn in the descending aorta (P=.02; Figure 4B; Table 1) and gaseous cerebral microemboli were 31 (IQR, 12-53) compared with 4 (IQR, 2-13) (P<.001; Table 1).

There was no statistical difference in the occurrence of particulate cerebral microemboli between patients who had received fondaparinux compared to patients who had not received fondaparinux prior to coronary angiography 9.5 (IQR, 3.75-18.25) compared with 7 (IQR, 4-12) (P=.28).

Discussion

In this randomized study we compared two guidewire techniques currently used during coronary angiography from the perspective of their effect on the occurrence of cerebral microemboli. Advancing catheters over the aortic arch with a leading guidewire consistently generated significantly more particulate cerebral microemboli than when the guidewire was withdrawn in the descending aorta. As expected, fewer cerebral microemboli were detected during part 2 since no contrast was injected and the sequence was therefore much shorter. The outcome was, however, still the same as in part 1. The results imply that the choice of guidewire technique does have an impact on the incidence of particulate cerebral microemboli.

In 1967, when Judkins introduced his percutaneous femoral technique for coronary angiography, he recommended that the catheters should be flushed in the descending aorta before being carefully advanced over the aortic arch, in order to avoid cerebral embolism.⁸ Today, however, the standard technique in many cath labs is advancing catheters with a guidewire protruding from the distal end all the way to the ascending aorta and flushing them in the vicinity of the coronary ostia.⁹ The rationale is primarily to facilitate the placement of the catheters in the correct position. Furthermore, advancing catheters over the aortic arch with a leading guidewire is believed to release less aortic debris, thus decreasing the risk for cerebral embolism.¹⁶ However, the results of this study show the opposite; the withdrawal of guidewires and flushing of catheters in the descending aorta consistently generated less cerebral microemboli than when the catheters were advanced over the aortic arch with a leading guidewire and flushed in the ascending aorta. These results confirm previous findings¹⁰ and support Judkins’ recommendation.

Particulate cerebral emboli probably have different origins. In a population-based cohort of the same ages as the patients included in this study, 62.2% had arteriosclerotic plaques in the aortic arch.¹⁸ The prevalence is reported to increase with age and with hypertension.¹⁹ Particulate embolization may be related to the extent of arteriosclerotic plaque in the aortic arch. Judkins modified the catheters into a less traumatic shape, with the tips pointing to the rear while advancing over the aortic arch, so that direct contact between their sharp edges and the aortic wall was avoided.⁸ When catheters are straightened by a guidewire, the tip points forward instead and may have the effect of a sharp slicer scraping the aortic wall and dislodging aortic debris. The accumulation of dislodged aortic debris in catheters advanced with a guidewire over the aortic arch has previously been reported.^20,21 Catheters and guidewires are both highly prothrombotic materials, known to cause endothelial damage and reduced thromboresistance during coronary angiography.²² Consequently, another source may be clots formed in and around the catheters. Irrespective of the origin, guidewire withdrawal and flushing of catheters in the ascending aorta subsequently entails a higher risk for cerebral embolization. 

The clinical significance of cerebral microemboli is debated. Particulate cerebral microemboli are considered to be more detrimental since they are more likely to permanently occlude cerebral vessels, causing small ischemic lesions.² However, in a small study, gaseous microemboli were linked to cerebral bioelectrical disturbances reflecting increased brain reactivity.¹⁷ It has previously been reported that silent cerebral lesions are associated with a steeper cognitive decline, thus entailing an increased risk for dementia.⁷ Recent prospective studies with diffusion-weighted magnetic resonance imaging have detected new small ischemic cerebral lesions after coronary angiography, with the incidence ranging between 5%-22%.^2-6 In three of these studies, the occurrence of cerebral microemboli was confirmed using TCD,^2,3,5 and in one study, neuropsychological tests indicated a causal link between microemboli and cognitive impairment.² 

Asymptomatic cerebral lesions possibly causing cognitive impairment are a complication that has, as yet, not been explored. The incidence might be high, which would indicate that the safety of coronary angiography may currently be overestimated. 

Today, coronary angiography is frequently used as a diagnostic tool in a continually older and more fragile patient group. Increasing patient safety during coronary angiography is pertinent. Although the standard technique used in our cath lab is guidewire withdrawal in the ascending aorta, the interventional cardiologists participating in this study had no difficulty in using the original Judkins technique. Choosing guidewire withdrawal in the descending aorta could, consequently, constitute an easy-to-execute contribution to minimize the risk for cerebral complications.

Study limitations. This study has several limitations. One is the small number of patients included. Although this is not an entire crossover study since a complete CA was not done in part 2, both techniques were tested in each patient. This doubles the number of examinations performed, which strengthens the findings. Another limitation is that the effect of different guidewire types was not examined. Straight-tip guidewires are standard in our cath lab, as well as in other cath labs in Sweden and worldwide. To date, there are no randomized studies comparing straight-tipped with J-shaped guidewires. A further limitation is that the clinical relevance of cerebral microemboli was not examined. Several MRI studies have already reported a correlation between cerebral microemboli and new small cerebral lesions. However, their effect on cognitive functions is, as yet, less penetrated. Cognitive tests were not performed in this study and regarding the clinical relevance, the results are hypothesis generating. Larger studies on the relationship between different techniques and materials and cerebral complications are warranted.

Conclusion

Advancing catheters with a leading guidewire over the aortic arch with subsequent flushing in the ascending aorta generated significantly more particulate cerebral microemboli than when the guidewire was withdrawn in the descending aorta. The choice of guidewire technique does have an impact on the occurrence of cerebral microemboli, implicating an increased risk for asymptomatic cerebral lesions during diagnostic CA.

Acknowledgments. This work was supported by the Swedish Heart and Lung Foundation, and through regional agreement on medical training and clinical research (ALF) between Stockholm county council and the Karolinska Institutet, Stockholm, Sweden.

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From the ¹Cardiology Unit, Department of Medicine Solna, Karolinska University Hospital ²Department of Clinical Science and Education, Södersjukhuset, ³Department of Molecular Medicine and Surgery and Department of Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, all at Karolinska Institutet, Stockholm, Sweden.

Funding: This work was supported by the Swedish Heart and Lung Foundation, and through regional agreement on medical training and clinical research (ALF) between Stockholm county council and the Karolinska Institutet, Stockholm, Sweden.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted May 29, 2013, provisional acceptance given July 2, 2013, final version accepted August 19, 2013.

Address for correspondence: Juliane Jurga, MD, Department of Cardiology, Karolinska University Hospital/Solna, N3:05, SE 171 76 Stockholm, Sweden. Email: juliane.jurga@karolinska.se