Vasoreactivity of the Radial Artery After Transradial Catheterization

The radial artery provides a safer alternative for left heart catheterization compared to femoral or brachial arteries, and also allows early mobilization without the need for closure devices.¹ However, due to the similar dimensions of radial arteries and catheterization sheaths, significant injury of the vessel wall becomes a matter of concern, especially when considering the use of this artery for repeated cardiac procedures, as a bypass conduit, or dialysis fistulas. Although radial artery occlusion is the most common clinical expression of damage induced by catheterization, another, frequently overlooked effect is progressive intimal thickening and negative vessel remodeling as suggested by intravascular ultrasound.² Quantification of local damage to the radial artery is difficult to obtain by imaging techniques. In addition, progressive narrowing may not occur until several weeks after catheterization, while the decision to use the artery as a bypass conduit is usually made soon after angiography. Accordingly, it would be of great interest to identify those cases at major risk for intimal thickening before planning bypass surgery strategy. Based on restenosis models, deendothelization and injury of the internal elastic laminae and tunica media are necessary elements for the development of neointimal proliferation and arterial remodeling.^3,4 In this work, the functional response of the catheterized radial arteries was assessed by ultrasound. We hypothesized that endothelium-dependent and endothelium-independent dysfunction could act as surrogates for the development of significant damage induced by cannulation. Methods Patients. The study group consisted of 18 patients referred for elective cardiac catheterization. Patients were selected according to the following criteria: agreement with the study protocol and willingness to return for follow-up examination, lack of previous transradial catheterization, appropriate radial pulse and a normal Allen’s test. Predefined exclusion criteria were: poor visualization of the radial artery by the screening ultrasound, puncture or cannulation failure and recent (Ultrasound assessment of radial artery function. Radial artery vasoreactivity was assessed a few hours before catheterization, at 24 hours, after 1 week and after 1 month. Endothelial-dependent vasodilation of the radial artery was studied according to previous published guidelines.⁵ In brief, the diameter of the radial artery is calculated by ultrasound before and after 4 minutes of ischemia for the evaluation of endothelial-mediated vasodilation. For the assessment of endothelial-independent vasodilation, arterial diameter is measured before and after 0.4 mg of sublingual nitroglycerin. Patients were fasting for at least 6 hours before ultrasound examination. Intravenous and transdermal nitrates were withdrawn for at least 1 hour before functional ultrasound studies and oral nitrates for 12 hours. According to the study protocol, treatment with other cardiovascular drugs was permitted. Imaging was obtained with a Hewlett-Packard Sonos 5500 ultrasound equipment with a special ultraband linear-array transducer designed for intraoperative ultrasound studies (15–6 L, Philips Medical Systems, Groenewoudseweg, Netherlands; 6–15 MHZ). All studies were performed in a room with a quiet environment and controlled temperature (21–23ºC). Before vasoreactivity studies, patients were laying in rest for at least 10 minutes with the studied arm positioned comfortably over a special support manufactured specifically for these procedures. This device is also equipped with an articulated mechanical arm to stabilize the position of the ultrasound probe and to avoid involuntary movement during examination. After this initial 10-min bed-rest phase, longitudinal sections of the radial artery just proximal to the presumed puncture site were taken with special care for obtaining maximal diameters and clear visualization of the luminal surface. After adjusting for gain and compression settings, the images were acquired and archived in magneto-optical disk for later measurements. After baseline imaging, a pneumatic cuff was inflated on the proximal forearm to 300 mmHg and the absence of flow through the artery was assured by Doppler interrogation. The cuff was kept inflated for 4 minutes. Images of the radial artery were recorded 60 sec after cuff deflation. Flow velocity curves were also recorded. Endothelium-independent vasodilation was assessed 10–15 minutes after hyperemia studies. A second baseline recording was performed and then sublingual nitroglycerin (0.4 mg) was administered. The response to nitroglycerin was calculated as the percent increment in radial artery diameter at 3.5 min. Measurements of arterial diameter were made at the peak of the R wave. The mean value of 4 different measurements along the longitudinal section within the same cardiac cycle was used. All studies were performed by the same operator. The ultrasound imaging was performed without knowledge of the details of catheterization (sheath size and number of catheters used). Long-term intraobserver variability (3-month interval) for repeated measurements or radial artery diameter with this technique and the same operator is 0.02 ± 0.14 mm in our laboratory, which is similar to previous published values for brachial artery vasoreactivity.^6,7Catheterization procedures. The physicians performing left heart catheterization procedures were unaware of the radial artery baseline ultrasound results. Radial artery puncture was performed with a 20G venous cannulae (Arrow International Inc., Reading, Pennsylvania). Sheaths used were either 4 French (Radifocus, Terumo, Hyogo, Tokyo, Japan) for diagnostic procedures or 6 French for angioplasty (Ultimum, St. Jude, Minnetonka, Minnesota). Only short sheaths were used (7 cm long for 4 French and 12 cm long for 6 French), with no hydrophilic coating. In all cases a spasmolytic cocktail containing verapamil 2.5 mg and unfractioned heparin 5,000 Units was administered intraarterially through the sheath inmediately after insertion. Additional heparin was administered as needed for ad hoc coronary angioplasty. The sheaths were removed immediately after catheterization and conventional hemostasia was accomplished with a compressive bandage left in place for 2 hours in case of diagnostic procedures and 4 hours in case of angioplasty procedures. Six-month follow-up study. Ultrasound examination of the radial artery was repeated 6 months after catheterization to obtain resting arterial diameter and assess possible long-term complications, such as progressive narrowing or occlusion. For these studies a similar methodology and equipment were used. All follow-up studies were performed by the same operator that performed functional studies. Statistical analysis. Continuous variables are presented as mean ± standard deviation, unless specified. Comparison of continuous variables determined from the same case at different time frames was performed by analysis of variance for repeated measurements (general linear model). Differences were considered significant if p Patients and catheterization procedures. Baseline clinical and procedural data are summarized in Table 1. All catheterization procedures were performed sucessfully. There were no vascular complications derived from catheterization or physiologic ultrasound studies. In 5 cases, the 4 French sheath used for diagnostic studies were exchanged for a 6 French sheath for coronary intervention. Vasoreactivity studies and radial artery diameters. Ultrasound radial artery diameter values and changes after hyperemia and nitroglycerin are expressed in Table 2. At baseline, mean radial artery diameter was 2.56 ± 0.45 mm. Mean diameter significantly increased to 2.86 ± 0.48 mm at 24 hours (p = 0.001). At 1 week it was 2.75 ± 0.44 mm (p = 0.03, compared to baseline measurements). At 1 month, radial artery diameter was similar to baseline (2.60 ± 0.27 mm; p = 0.95). Maximal diameter, achieved after 0.4 mg sublingual nitroglycerin, was similar along study period (Table 2). Endothelium-dependent vasodilation. Overall, there was a small vasodilatory response to post-ischemic hyperemia (2.7 ± 4.7% at baseline), suggesting a high prevalance of endothelial dysfunction in this population. This response did not change significantly along the study period (Table 2 and Figure 1). Nitroglycerin-induced vasodilation. Radial artery diameter increased by 14.1 ± 7.9% after sublingual nitroglycerin before catheterization. Nitroglycerin-induced vasodilation decreased significantly at 24 hours and showed a trend to return to baseline values at 7 days and 1-month (Table 2 and Figure 1). Radial artery diameter at 6-month follow-up. No patient presented late occlusion of the radial artery. Radial artery diameters were similar to baseline values (mean diameter at 6-month follow-up 2.59 ± 0.51 mm; p = 0.68). Radial artery diameters for the 18 cases at baseline and at follow-up examination are expressed in Figure 2. The majority of patients showed nonsignificant variations in diameter (within two standard deviations of intraobserver variability assessment). In two cases the diameter decreased by 0.35 and 0.36 mm, while in three cases the radial artery diameter increased by 0.34, 0.38 and 0.39 mm. Discussion The main finding of this study is that radial artery physiology appears altered soon after cannulation for left heart catheterization but generally recovers after a few weeks. The alteration seen is more profound for nitroglycerin-induced vasodilation and is probably related to the local trauma provoked by sheath insertion. Endothelial function was abnormal at baseline in this study (1,8,9 However, given the close ratio between outer sheath and radial artery diameter, some degree of damage seems inevitable after cannulation.¹⁰ Although radial artery narrowing or occlusion are not considered severe complications of transradial catheterization, it may have consequences for patients in whom repeated procedures are expected or need coronary artery bypass surgery. Apart from occlusion, which can be clinically obvious, evidence for more subtle late effects of transradial cannulation comes from ultrasound serial studies.^2,11,12 Transcutaneous ultrasound revealed diffuse stenosis in 22% of the cases, at 1–6 month follow-up assessment, in the study of Nagai et al.¹¹ Importantly, the sheath outer diameter was estimated to be greater than radial artery diameter in approximately 50% of the cases of this series and greater sheath-to-artery ratio was an independent predictor of late narrowing or occlusion. In another study, diffuse narrowing was not so frequent after transradial procedures, a difference that was probably related to the smaller sheaths used for diagnostic procedures (5 French).¹² One limitation for serial ultrasound assessment of the radial artery is the difficulty in obtaining good-quality images in such a small vessel (frequently 5Additional problems are related to the great susceptibility of the radial artery to external stimuli, such as environmental temperature changes, stress and pharmacological intervention. In this study, we tried to overcome imaging difficulties using a special probe designed for epicardial ultrasound (15 MHZ), which allows better focus of superficial structures compared to most available vascular probes. All studies were performed after a period of adaptation, with 10 minutes of bed rest in a room with controlled temperature, rendering serial diameter calculations more reliable. Wakeyama et al.,² used intravascular ultrasound to evaluate posible late consequences of transradial procedures. The comparison of patients with a first catheterization with a different group with repeated transradial procedures showed that intima-media thickness was greater and luminal area was smaller in the group with repeated procedures. The differences among studied groups were more evident at the distal radial artery, where diameters are usually smaller due to the normal distal tapering of the vessel¹² and where the sheath is contacting, and in some cases even stretching the arterial wall. The present findings are in agreement with previous observations in that radial artery cannulation can induce vessel injury, as reflected by the attenuated response to nitroglycerin early after catheterization. Interestingly, maximal achieved diameters (post-nitroglycerin) remained stable during the study period (Table 1) and, in contrast to previous studies, mean resting radial artery diameter increased 24 hours after cannulation. The underlying mechanism could be temporal loss of the normal physiologic vascular tone induced by mechanical stretch of the vessel. Accordingly, reduced nitroglycerin-mediated dilatation at 24 hours would be simply the reflection of a reduced vasodilatory reserve, since pre-nitroglycerin diameters at the 24-hour study were close to maximal attainable diameters. There were no cases of diffuse narrowing or late vessel occlusion at 6-month follow-up in this study. Nevertheless, based on the transient alteration of arterial vasoreactivity seen, some degree of permanent vessel damage can not be ruled out and is a strong possibility especially in those cases in which normal dilatation did not recover even 1 month after the procedure. Endothelial layer is, by logic, the most vulnerable part of the vessel to catheter manipulation. Unfortunately, we were not able to demonstrate a significant change in local endothelial function after catheterization, basically because most patients showed a small or null response to endothelial stimuli even at the baseline study. The high prevalence of atherosclerotic disease helps to explain these findings. Non-invasive assessment of intimal damage after transradial procedures would require a population with a baseline normal endothelial response. An important limitation of this study is the small number of cases included, especially with large sheaths, that precluded detailed analysis of the long-term consequences of transradial procedures, although systematic assessment of late stenosis or occlusion after catheterization was not the main objective of the present work. Additionally, we cannot overlook the fact that noninvasive endothelial assessment is less well validated in the radial artery as compared to the brachial artery.,SUP>5 In conclusion, radial artery vasodilatory response is attenuated early after transradial heart catheterization, although complete recovery is possible a few weeks after catheter manipulation. Physiologic impairment might reflect local damage and should be taken into account if plans are done to use the radial artery for surgical revascularization.

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