Catheterization and Cardiovascular Interventions 87:101–106 (2016)
VASCULAR BIOLOGY Original Studies Time-Course of Vascular Dysfunction of Brachial Artery After Transradial Access for Coronary Angiography Jerson Munoz-Mendoza,1* MD, Abhijit Ghatak,2 MD, Veronica Pinto Miranda,3 MD, Shaka Bahadu,3 MD, Eduardo De Marchena,2 MD, Alexandre C. Ferreira,2,4 MD, and Cesar E. Mendoza,4 MD Background: Prior studies have demonstrated endothelial and smooth muscle brachial artery dysfunction after transradial cardiac catheterization for diagnostic coronary angiography. The duration of this vascular dysfunction is unknown. Objective: To determine the time-course of endothelial and smooth muscle cell dysfunction in the upstream brachial artery after transradial cardiac catheterization. Methods: We studied 22 consecutive patients with suspected coronary artery disease (age 64.4 6 7.7 years) undergoing diagnostic transradial cardiac catheterization. Using high-resolution vascular ultrasound, we measured ipsilateral brachial artery diameter changes during reactive hyperemia (endothelium-dependent dilatation) and administration of sublingual nitroglycerin (endothelium-independent dilatation). The measurements were taken at baseline (before cardiac catheterization), 6 h, 24 h, 1 week, and 1 month postprocedure. The contralateral brachial artery served as a control. Results: Ipsilateral brachial artery diameter during endothelium-dependent dilatation decreased significantly compared with the contralateral diameters at 6 h and 24 h after transradial cardiac catheterization (3.22 vs. 4.11 and 3.29 vs. 4.11, respectively, P < 0.001). The administration of nitroglycerin did not affect this difference. At 1 week and 1 month postprocedure there was no significant difference in diameter of the ipsilateral versus the contralateral brachial artery. As expected the contralateral brachial artery showed no significant changes in diameter. Conclusion: Our results showed that transradial cardiac catheterization causes transient vascular endothelial and smooth muscle dysfunction of the ipsilateral brachial artery, which resolves within 1 week postprocedure. These findings strongly suggest the absence of systemic vascular dysfunction after transradial catheterization both immediately postprocedure as well as 1 week postprocedure. VC 2015 Wiley Periodicals, Inc.
Key words: radial artery; peripheral catheterization; cardiac catheterization; vascular injuries
1
Department of Medicine, Division of Cardiology, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, Bronx, New York 2 Department of Medicine, Division of Cardiology, University of Miami Miller School of Medicine, Miami, Florida 3 Department of Medicine, University of Miami/Jackson Memorial Hospital, Miami, Florida 4 Cardiovascular Division, Jackson Memorial Hospital, Miami, Florida Conflict of interest: Nothing to report. C 2015 Wiley Periodicals, Inc. V
*Correspondence to: Jerson Munoz-Mendoza, MD, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA. E-mail: [email protected] Received 20 April 2015; Revision accepted 20 May 2015 DOI: 10.1002/ccd.26070 Published online 29 June 2015 in Wiley Online Library (wileyonlinelibrary.com)
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INTRODUCTION
Endothelial dysfunction is an altered endothelial phenotype characterized by loss of vasodilator and antithrombotic factors and an increase in vasoconstrictor and prothrombotic factors [1]. It may coexist with dysfunction of the vascular smooth muscle manifested as a lack of response to the vasodilator factors produced by the endothelium [2]. Multiple cardiovascular diseases are associated with chronic or persistent endothelial and smooth muscle cell dysfunction, and they are usually measured noninvasively with flow mediated dilatation (FMD) and nitroglycerin mediated dilatation (NMD) responses in the brachial artery. Previous studies have demonstrated that transradial catheterization may lead to vascular dysfunction of the upstream brachial artery, including narrowing of the brachial artery immediately after the procedure [3] and impaired brachial artery FMD [4]. However, there is limited data regarding its time course. The aim of our study was to evaluate the duration of brachial artery endothelial dysfunction after transradial cardiac catheterization for coronary angiography. MATERIALS AND METHODS Population
The study population consisted of consecutive patients with suspected coronary artery disease (CAD) undergoing transradial cardiac catheterization for diagnostic coronary angiography at our institution. Patients were excluded from the study if they had undergone previous radial cannulation or had an abnormal Allen test result consistent with insufficient ulnar collateral supply. Other exclusion criteria were contraindications to antiplatelet agent, previous use of nitrates, serious renal disease (for potential radial artery damage), malignancies, New York Association Heart Failure Functional class III to IV and failure to successfully cannulate the radial artery. Written informed consent was obtained from all patients before the study. The review committee of this institution’s ethics board approved the study. Transradial Artery Cardiac Catheterization
The right radial artery was cannulated in all cases. Local anesthesia with 2 to 3 mL of subcutaneous lidocaine 1% solution was administered at the skin entry point. After radial access was achieved using a modified Seldinger technique, a 7-cm highly tapered hydrophilic sheath (Terumo Cardiovascular, Somerset, NJ) was inserted. Once the sheet was in place, all the patients received 200 lg of nitroglycerin, 2.5 mg of verapamil and 3,000 units of unfractionated heparin in a combined manner through the access sheath. Single
specially shaped catheters (Terumo Cardiovascular, Somerset, NJ) were initially used to obtain both left and right coronary angiograms as well as left ventricular angiography. The choice of using additional catheters due to difficult cannulation of the coronary arteries or of the left ventricle was at the discretion of the operator. At the end of the procedure, the sheath was removed immediately and postprocedural hemostasis was applied by placing a radial compression device (Terumo Cardiovascular, Somerset, NJ), and following the manufacturer’s recommendations. Procedures Following the guidelines for ultrasonic assessment of brachial FMD, subjects were asked to abstain from strenuous physical activity, tobacco products, and vitamin supplementation for at least 6 h before the vascular examination [5]. Baseline heart rate and blood pressure were recorded. The right brachial artery was visualized longitudinally above the antecubital crease using high resolution ultrasound with an 11 MHz linear array transducer (SonoSite MicroMaxx, SonoSite, Inc, Bothell, WA). We induced reactive hyperemia by inflation of a blood pressure cuff at the forearm to 20 mm Hg above systolic arterial pressure for 5 min. Upon cuff release, the maximum brachial artery diameter within 90 s after cuff deflation was recorded. Sublingual nitroglycerin at a dose of 0.4 mg was administered and the maximum diameter after blood pressure cuff deflation was recorded in order to measure the endothelium-independent smooth muscle response to nitroglycerin. The brachial artery of the opposite arm was measured in the same fashion and used as control. Measurements during reactive hyperemia and following the administration of sublingual nitroglycerin were performed before transradial cardiac catheterization, and 6 h, 24 h, 1 week, and 1 month later by the same experienced vascular technician. The experimental setup is displayed in Figure 1. Statistical Analysis
Statistical analysis was perfomed with SPSS 19.0 software. All continuous variables were expressed as the mean value 6 standard deviation (interquartile range) and its comparisons were perfomed using the two-tailed t test. Overall P value less than 0.05 was considered statistically significant for all calculations. RESULTS
A total of 22 patients (age 64.4 6 7.7 years) were included in the study. The baseline and clinical characteristics of the study population are summarized in Table I. Eleven patients had three comorbidities out of
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Brachial Artery After Transradial Access
four associated with endothelial dysfunction (hypertension, dyslipidemia, diabetes mellitus, and current smoking status), the mean numbers of comorbidities were 2.4 6 0.9. Eight patients underwent percutaneous coro-
Fig. 1. Schematic of experimental setup: after cannulation of the right radial artery, a coronary angiographic catheter is advanced through the right radial and brachial arteries and coronary angiography is performed. Vascular ultrasound of right and left brachial arteries is performed 6 h, 24 h, 1 week, and 1 month after the procedure. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
TABLE I. Baseline Demographics and Clinical Characteristics of the Study Population 64.1 7.8 14 (66.7) 12 (57.1) 17 (81) 8 (38.1) 14 (66.7) 25.4 1.4 193 81.6 43 6.5 106 19
Age (yr) Male, n (%) Hypertension, n (%) Dyslipidemia, n (%) Diabetes mellitus, n (%) Current smoker, n (%) BMI (kg/m2) Triglycerides (mg/dL) HDL (mg/dL) LDL (mg/dL) Medications, n (%) Betablocker CCB ACEI or ARB Statin ASA Plavix Diuretics
8 (38.1) 1 (4.8) 14 (66.7) 15 (71.4) 18 (85.7) 4 (19) 1 (4.8)
HDL ¼ high-density lipoprotein cholesterol, LDL ¼ low-density lipoprotein cholesterol, CCB ¼ calcium channel blocker, ACEi ¼ angiotensinconverting enzyme, ARB ¼ angiotensin receptor blocker.
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nary intervention. The mean catheterization time was 21.1 6 11 and 53.8 6 11 min in patients undergoing diagnostic catheterization only and in those who also had percutaneous coronary intervention, respectively. Eighteen patients used two or three catheters and more than three catheters were used in four patients. No vascular complications including bleeding or vasospasm occurred in the patients. Endothelial Dysfunction in Brachial Artery After Transradial Catheterization Before cardiac catheterization, the maximum diameters of the ipsilateral and contralateral brachial arteries during reactive hyperemia were 4.09 6 0.36 and 4.11 6 0.35 mm, respectively (P 5 0.068). Maximum brachial artery diameter during reactive hyperemia was decreased from the baseline measurement in the ipsilateral brachial artery of all the patients by 21.9 6 9.1%, 6 h after the procedure (P < 0.05). The diameter of the contralateral brachial artery showed no significant change in diameter (P > 0.05) (Table II). The ipsilateral brachial artery diameter started to increase back to its baseline within 24 h postprocedure in 20 patients (90.9%), whereas in the remaining patients (patients 1 and 5) continued to decrease to reach a maximum reduction of 11.3% and 14.3% of baseline at 24 h postprocedure. One week after cardiac catheterization, the ipsilateral brachial artery diameter was at least 90% of baseline in 20 patients, and four patients had recovered at least 99% of the baseline diameter. One month after cardiac catheterization all patients had a brachial artery diameter during reactive hyperemia of at least 95% of the baseline diameter. Seventeen patients had at least 99% of the baseline diameter. The diameter in the contralateral artery did not change significantly over throughout the study (Table II). Of note, the two patients (1 and 5) whose brachial diameter continued to decline at 24 h, used three catheters (while the others used 4). They differed in that Patient 1 had no cardiovascular comorbidities opposed to Patient
TABLE II. Maximum Diameters (in mm) of Both Brachial Arteries During Reactive Hyperemia and Nitroglycerine Induced Vasodilatation
RBA Hyperemia NTG LBA Hyperemia NTG
Baseline
6h
24 h
1 week
1 month
4.09 0.36 4.09 0.36
3.22 0.57a 3.2 0.61a
3.29 0.6a 3.41 0.71a
3.88 0.44b 3.82 0.55b
4.05 0.37b 4.02 0.47b
4.11 0.35 4.13 0.34
4.11 0.36b 4.14 0.36b
4.11 0.36b 4.14 0.36b
4.1 0.36b 4.14 0.37b
4.13 0.36b 4.14 0.35b
RBA ¼ right brachial artery, LBA ¼ left brachial artery, NTG ¼ after sublingual nitroglycerine. a P < 0.05 versus baseline reading before catheterization b P > 0.05 versus baseline reading before catheterization. Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
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Fig. 2. Maximum brachial artery diameter as a response to reactive hyperemia and sublingual nitroglycerin. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
5 who had three (including smoking). Patient 1 underwent diagnostic cardiac catheterization whereas Patient 5 underwent percutaneous cardiovascular intervention. The patients that recovered their baseline diameters the fastest had heterogeneous features as well. These changes in the brachial artery diameter during reactive hyperemia in the ipsilateral arm were not associated with the number of cardiovascular comorbidities, type of cardiac catheterization performed (diagnostic versus therapeutic), the time of cardiac catheterization, nor the number of catheters used. Smooth Muscle Dysfunction in Brachial Artery After Transradial Catheterization Figure 2 shows that during nitroglycerin induced vasodilation, the maximal diameter in the ipsilateral brachial artery was significantly smaller at 6 h and 24 h after transradial catheterization (21.8 and 16.7% of baseline, respectively) with subsequent normalization by 1 week after postprocedure (93.4% of baseline). This diameter did not change in the contralateral brachial artery. DISCUSSION
This study assesses the changes over time in the vasomotor function of the brachial artery after transradial catheterization using high resolution vascular ultrasound. Our study’s findings demonstrate that there are transient changes in the brachial artery diameter after ipsilateral transradial cardiac intervention, which con-
sists of decreased brachial artery diameter during reactive hyperemia and after sublingual nitroglycerin administration, compared with the contralateral artery. These findings suggest impaired endothelial and smooth muscle cell function of the upstream brachial artery after transradial cardiac catheterization with recovery within 1 week postprocedure. The changes in the physiology and morphology of the brachial artery after transradial catheterization have been scarcely studied; of note, there is only one study that assessed endothelial and smooth muscle cell dysfunction in the brachial artery over time in 30 patients with suspected coronary artery disease undergoing diagnostic coronary angiography. In this study, the resting diameter of the ipsilateral brachial artery did not decrease after cardiac catheterization but was slightly larger at 6 h and 24 h after transradial catheterization (101.8 and 104.5% of baseline, respectively) [4]. These findings clearly differ from our results. We did not record resting diameters of the brachial artery. We opted to measure the diameter during reactive hyperemia as a surrogate marker of endothelial dysfunction; the fact that the diameters during reactive hyperemia were decreased in our study, reflects that the resting brachial artery diameters were decreased as well. The reason for this discrepancy is not well understood at this time. Of note, the above-mentioned study found that flow-mediated dilatation at 6 h was significantly reduced in the ipsilateral brachial artery, and remained impaired at 24 h in smokers, which suggests that there are local endothelial dysfunction in upstream brachial artery after transradial cardiac catheterization.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Brachial Artery After Transradial Access
Results of our study suggest that this is a temporary phenomenon that resolves within 1 week in most of the subjects. Discordant results have also been found in the resting diameter of the radial artery itself after transradial cardiac intervention. Two small studies have shown that the resting diameter of the radial artery increases slightly after cardiac catheterization [4,6] (up to 110% of the baseline diameter at 24 h). However, Shen et al. in a larger study of 621 patients established that the mean radial diameter significantly decreases 1 day after coronary artery procedures using the radial approach. Importantly, the measurements were performed using high-resolution ultrasound biomicroscopy, which has much better resolution compared with the standard Doppler ultrasound [7]. The literature supports the decreased diameter of a cannulated artery after coronary artery interventions. One study showed worsened endothelial and smooth muscle compartment dysfunction of the brachial artery after transradial catheterization as demonstrated with impaired FMD and NMD [4]. Another study demonstrated narrowing of the upstream brachial artery immediately after transradial catheterization, decreasing more than 50% in a 17% of the subjects; unfortunately these findings were not followed over time [3]. While in another study, the diameter of the radial artery 1 day after cannulation was also found to be significantly smaller in patients who had undergone transradial catheterization previously versus patients who were naive to the procedure [8]. The brachial artery is part of the conduit used during transradial cardiac catheterization and has itself multiple current and potential clinical uses including measurement of flow-mediated dilatation [9], coronary and carotid artery stenting [10], intra-aortic balloon pumping [11], coil embolization for cerebral aneurysms [12], among other interventional procedures when aortic or peripheral arterial conditions limit the transfemoral approach [12]. Its structure and function can be preserved in order to decrease the risk of minor or major complications. The transient worsening of vascular dysfunction is most probably due to subcellular or molecular changes affecting the production of local vasodilators and its response, however, those mechanisms have not been characterized in the brachial artery yet. The relatively small number of patients could represent a limitation of the present study, since it precluded the analysis looking for possible confounders or performing subgroup analysis. Another limitation is that we did not measure baseline vascular dysfunction in our cohort of patients, who had on average two cardiovascular diseases associated with endothelial dysfunction, and therefore were expected to have some degree
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of measurable vascular dysfunction. Such measurement could have been made through estimation of FMD in the brachial artery before cardiac catheterization. It would have been interesting to measure FMD over time and determine if it correlates with the diameter in the brachial artery during reactive hyperemia. Despite these limitations, the strength of this study is that it followed the function of the upstream brachial artery after transradial catheterization over time for the first time, using a standardized technique. Further studies with larger samples are warranted to confirm our results. The timing for repeated transradial catheterization is neither established nor addressed by the current clinical guidelines [13,14]. It would not be advisable to cannulate the radial and brachial arteries until transient vascular dysfunction resolves to baseline. Although this study is not adequately powered to determine the appropriate timing to repeat an ipsilateral transradial catheterization, it suggests than 1 week waiting period may be reasonable. CONCLUSION
In conclusion, our findings suggest that transradial cardiac catheterization leads to transient endothelial and smooth muscle cell dysfunction to the upstream brachial artery with recovery within 1 week postprocedure. We believe that prospective randomized control studies with large sample sizes are the next step to definitively confirming our results. REFERENCES 1. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003;42:1149–1160. 2. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, et al. Nitroglycerine-induced vasodilation for assessment of vascular function: A comparison with flow-mediated vasodilation. Arterioscler Thromb Vasc Biol 2013;33:1401–1408. 3. Lin YJ, Liu YB, Chu CC, Tsai CW. Predictors of brachial artery spasm during transradial cardiac catheterization. Acta Cardiol Sin 2006;22:134–141. 4. Heiss C, Balzer J, Hauffe T, Hamada S, Stegemann E, et al. Vascular dysfunction of brachial artery after transradial access for coronary catheterization. JACC Cardiovasc Interv 2009;2: 1067–1073. 5. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39:257–265. 6. Sanmartin M, Goicolea J, Ocaranza R, Cuevas D, Calvo F. Vasoreactivity of the radial artery after transradial catheterization. J Invasive Cardiol 2004;16:635–638. 7. Shen H, Zhou YJ, Liu YY, Du J, Liu XL, et al. Assessment of early radial injury after transradial coronary intervention by
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
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high-resolution ultrasound biomicroscopy: Innovative technology application. Chin Med J (Engl) 2012;125:3388–3392. Nie B, Zhou YJ, Yang Q, Cheng WJ, Wang ZJ, et al. Safety and feasibility of repeated percutaneous transradial coronary intervention in the same route. Chin Med J (Engl) 2012;125: 221–225. Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, et al. The assessment of endothelial function: from research into clinical practice. Circulation 2012;126:753– 767. Ventoruzzo G, Biondi-Zoccai G, Maioli F, Liistro F, Bolognese L, et al. A tailored approach to overcoming challenges of a bovine aortic arch during left internal carotid artery stenting. J Endovasc Ther 2012;19:329–338. Datt B, Miner S. Anatomical advantage to percutaneous insertion of the intra-aortic balloon through the left brachial ar-
tery over the right brachial artery. J Extra Corpor Technol 2013; 45:51–54. 12. Iwata T, Mori T, Tajiri H, Miyazaki Y, Nakazaki M, et al. Initial experience of a novel sheath guide for transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation. Neurosurgery 2013;72:15–19; discussion 19-20. 13. Scanlon PJ, Faxon DP, Audet AM, Carabello B, Dehmer GJ, et al. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions. J Am Coll Cardiol 1999;33:1756–1824. 14. Caputo RP, Tremmel JA, Rao S, Gilchrist IC, Pyne C, et al. Transradial arterial access for coronary and peripheral procedures: executive summary by the Transradial Committee of the SCAI. Catheter Cardiovasc Interv 2011;78:823–839.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
VASCULAR BIOLOGY Original Studies Time-Course of Vascular Dysfunction of Brachial Artery After Transradial Access for Coronary Angiography Jerson Munoz-Mendoza,1* MD, Abhijit Ghatak,2 MD, Veronica Pinto Miranda,3 MD, Shaka Bahadu,3 MD, Eduardo De Marchena,2 MD, Alexandre C. Ferreira,2,4 MD, and Cesar E. Mendoza,4 MD Background: Prior studies have demonstrated endothelial and smooth muscle brachial artery dysfunction after transradial cardiac catheterization for diagnostic coronary angiography. The duration of this vascular dysfunction is unknown. Objective: To determine the time-course of endothelial and smooth muscle cell dysfunction in the upstream brachial artery after transradial cardiac catheterization. Methods: We studied 22 consecutive patients with suspected coronary artery disease (age 64.4 6 7.7 years) undergoing diagnostic transradial cardiac catheterization. Using high-resolution vascular ultrasound, we measured ipsilateral brachial artery diameter changes during reactive hyperemia (endothelium-dependent dilatation) and administration of sublingual nitroglycerin (endothelium-independent dilatation). The measurements were taken at baseline (before cardiac catheterization), 6 h, 24 h, 1 week, and 1 month postprocedure. The contralateral brachial artery served as a control. Results: Ipsilateral brachial artery diameter during endothelium-dependent dilatation decreased significantly compared with the contralateral diameters at 6 h and 24 h after transradial cardiac catheterization (3.22 vs. 4.11 and 3.29 vs. 4.11, respectively, P < 0.001). The administration of nitroglycerin did not affect this difference. At 1 week and 1 month postprocedure there was no significant difference in diameter of the ipsilateral versus the contralateral brachial artery. As expected the contralateral brachial artery showed no significant changes in diameter. Conclusion: Our results showed that transradial cardiac catheterization causes transient vascular endothelial and smooth muscle dysfunction of the ipsilateral brachial artery, which resolves within 1 week postprocedure. These findings strongly suggest the absence of systemic vascular dysfunction after transradial catheterization both immediately postprocedure as well as 1 week postprocedure. VC 2015 Wiley Periodicals, Inc.
Key words: radial artery; peripheral catheterization; cardiac catheterization; vascular injuries
1
Department of Medicine, Division of Cardiology, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, Bronx, New York 2 Department of Medicine, Division of Cardiology, University of Miami Miller School of Medicine, Miami, Florida 3 Department of Medicine, University of Miami/Jackson Memorial Hospital, Miami, Florida 4 Cardiovascular Division, Jackson Memorial Hospital, Miami, Florida Conflict of interest: Nothing to report. C 2015 Wiley Periodicals, Inc. V
*Correspondence to: Jerson Munoz-Mendoza, MD, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA. E-mail: [email protected] Received 20 April 2015; Revision accepted 20 May 2015 DOI: 10.1002/ccd.26070 Published online 29 June 2015 in Wiley Online Library (wileyonlinelibrary.com)
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INTRODUCTION
Endothelial dysfunction is an altered endothelial phenotype characterized by loss of vasodilator and antithrombotic factors and an increase in vasoconstrictor and prothrombotic factors [1]. It may coexist with dysfunction of the vascular smooth muscle manifested as a lack of response to the vasodilator factors produced by the endothelium [2]. Multiple cardiovascular diseases are associated with chronic or persistent endothelial and smooth muscle cell dysfunction, and they are usually measured noninvasively with flow mediated dilatation (FMD) and nitroglycerin mediated dilatation (NMD) responses in the brachial artery. Previous studies have demonstrated that transradial catheterization may lead to vascular dysfunction of the upstream brachial artery, including narrowing of the brachial artery immediately after the procedure [3] and impaired brachial artery FMD [4]. However, there is limited data regarding its time course. The aim of our study was to evaluate the duration of brachial artery endothelial dysfunction after transradial cardiac catheterization for coronary angiography. MATERIALS AND METHODS Population
The study population consisted of consecutive patients with suspected coronary artery disease (CAD) undergoing transradial cardiac catheterization for diagnostic coronary angiography at our institution. Patients were excluded from the study if they had undergone previous radial cannulation or had an abnormal Allen test result consistent with insufficient ulnar collateral supply. Other exclusion criteria were contraindications to antiplatelet agent, previous use of nitrates, serious renal disease (for potential radial artery damage), malignancies, New York Association Heart Failure Functional class III to IV and failure to successfully cannulate the radial artery. Written informed consent was obtained from all patients before the study. The review committee of this institution’s ethics board approved the study. Transradial Artery Cardiac Catheterization
The right radial artery was cannulated in all cases. Local anesthesia with 2 to 3 mL of subcutaneous lidocaine 1% solution was administered at the skin entry point. After radial access was achieved using a modified Seldinger technique, a 7-cm highly tapered hydrophilic sheath (Terumo Cardiovascular, Somerset, NJ) was inserted. Once the sheet was in place, all the patients received 200 lg of nitroglycerin, 2.5 mg of verapamil and 3,000 units of unfractionated heparin in a combined manner through the access sheath. Single
specially shaped catheters (Terumo Cardiovascular, Somerset, NJ) were initially used to obtain both left and right coronary angiograms as well as left ventricular angiography. The choice of using additional catheters due to difficult cannulation of the coronary arteries or of the left ventricle was at the discretion of the operator. At the end of the procedure, the sheath was removed immediately and postprocedural hemostasis was applied by placing a radial compression device (Terumo Cardiovascular, Somerset, NJ), and following the manufacturer’s recommendations. Procedures Following the guidelines for ultrasonic assessment of brachial FMD, subjects were asked to abstain from strenuous physical activity, tobacco products, and vitamin supplementation for at least 6 h before the vascular examination [5]. Baseline heart rate and blood pressure were recorded. The right brachial artery was visualized longitudinally above the antecubital crease using high resolution ultrasound with an 11 MHz linear array transducer (SonoSite MicroMaxx, SonoSite, Inc, Bothell, WA). We induced reactive hyperemia by inflation of a blood pressure cuff at the forearm to 20 mm Hg above systolic arterial pressure for 5 min. Upon cuff release, the maximum brachial artery diameter within 90 s after cuff deflation was recorded. Sublingual nitroglycerin at a dose of 0.4 mg was administered and the maximum diameter after blood pressure cuff deflation was recorded in order to measure the endothelium-independent smooth muscle response to nitroglycerin. The brachial artery of the opposite arm was measured in the same fashion and used as control. Measurements during reactive hyperemia and following the administration of sublingual nitroglycerin were performed before transradial cardiac catheterization, and 6 h, 24 h, 1 week, and 1 month later by the same experienced vascular technician. The experimental setup is displayed in Figure 1. Statistical Analysis
Statistical analysis was perfomed with SPSS 19.0 software. All continuous variables were expressed as the mean value 6 standard deviation (interquartile range) and its comparisons were perfomed using the two-tailed t test. Overall P value less than 0.05 was considered statistically significant for all calculations. RESULTS
A total of 22 patients (age 64.4 6 7.7 years) were included in the study. The baseline and clinical characteristics of the study population are summarized in Table I. Eleven patients had three comorbidities out of
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Brachial Artery After Transradial Access
four associated with endothelial dysfunction (hypertension, dyslipidemia, diabetes mellitus, and current smoking status), the mean numbers of comorbidities were 2.4 6 0.9. Eight patients underwent percutaneous coro-
Fig. 1. Schematic of experimental setup: after cannulation of the right radial artery, a coronary angiographic catheter is advanced through the right radial and brachial arteries and coronary angiography is performed. Vascular ultrasound of right and left brachial arteries is performed 6 h, 24 h, 1 week, and 1 month after the procedure. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
TABLE I. Baseline Demographics and Clinical Characteristics of the Study Population 64.1 7.8 14 (66.7) 12 (57.1) 17 (81) 8 (38.1) 14 (66.7) 25.4 1.4 193 81.6 43 6.5 106 19
Age (yr) Male, n (%) Hypertension, n (%) Dyslipidemia, n (%) Diabetes mellitus, n (%) Current smoker, n (%) BMI (kg/m2) Triglycerides (mg/dL) HDL (mg/dL) LDL (mg/dL) Medications, n (%) Betablocker CCB ACEI or ARB Statin ASA Plavix Diuretics
8 (38.1) 1 (4.8) 14 (66.7) 15 (71.4) 18 (85.7) 4 (19) 1 (4.8)
HDL ¼ high-density lipoprotein cholesterol, LDL ¼ low-density lipoprotein cholesterol, CCB ¼ calcium channel blocker, ACEi ¼ angiotensinconverting enzyme, ARB ¼ angiotensin receptor blocker.
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nary intervention. The mean catheterization time was 21.1 6 11 and 53.8 6 11 min in patients undergoing diagnostic catheterization only and in those who also had percutaneous coronary intervention, respectively. Eighteen patients used two or three catheters and more than three catheters were used in four patients. No vascular complications including bleeding or vasospasm occurred in the patients. Endothelial Dysfunction in Brachial Artery After Transradial Catheterization Before cardiac catheterization, the maximum diameters of the ipsilateral and contralateral brachial arteries during reactive hyperemia were 4.09 6 0.36 and 4.11 6 0.35 mm, respectively (P 5 0.068). Maximum brachial artery diameter during reactive hyperemia was decreased from the baseline measurement in the ipsilateral brachial artery of all the patients by 21.9 6 9.1%, 6 h after the procedure (P < 0.05). The diameter of the contralateral brachial artery showed no significant change in diameter (P > 0.05) (Table II). The ipsilateral brachial artery diameter started to increase back to its baseline within 24 h postprocedure in 20 patients (90.9%), whereas in the remaining patients (patients 1 and 5) continued to decrease to reach a maximum reduction of 11.3% and 14.3% of baseline at 24 h postprocedure. One week after cardiac catheterization, the ipsilateral brachial artery diameter was at least 90% of baseline in 20 patients, and four patients had recovered at least 99% of the baseline diameter. One month after cardiac catheterization all patients had a brachial artery diameter during reactive hyperemia of at least 95% of the baseline diameter. Seventeen patients had at least 99% of the baseline diameter. The diameter in the contralateral artery did not change significantly over throughout the study (Table II). Of note, the two patients (1 and 5) whose brachial diameter continued to decline at 24 h, used three catheters (while the others used 4). They differed in that Patient 1 had no cardiovascular comorbidities opposed to Patient
TABLE II. Maximum Diameters (in mm) of Both Brachial Arteries During Reactive Hyperemia and Nitroglycerine Induced Vasodilatation
RBA Hyperemia NTG LBA Hyperemia NTG
Baseline
6h
24 h
1 week
1 month
4.09 0.36 4.09 0.36
3.22 0.57a 3.2 0.61a
3.29 0.6a 3.41 0.71a
3.88 0.44b 3.82 0.55b
4.05 0.37b 4.02 0.47b
4.11 0.35 4.13 0.34
4.11 0.36b 4.14 0.36b
4.11 0.36b 4.14 0.36b
4.1 0.36b 4.14 0.37b
4.13 0.36b 4.14 0.35b
RBA ¼ right brachial artery, LBA ¼ left brachial artery, NTG ¼ after sublingual nitroglycerine. a P < 0.05 versus baseline reading before catheterization b P > 0.05 versus baseline reading before catheterization. Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
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Fig. 2. Maximum brachial artery diameter as a response to reactive hyperemia and sublingual nitroglycerin. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
5 who had three (including smoking). Patient 1 underwent diagnostic cardiac catheterization whereas Patient 5 underwent percutaneous cardiovascular intervention. The patients that recovered their baseline diameters the fastest had heterogeneous features as well. These changes in the brachial artery diameter during reactive hyperemia in the ipsilateral arm were not associated with the number of cardiovascular comorbidities, type of cardiac catheterization performed (diagnostic versus therapeutic), the time of cardiac catheterization, nor the number of catheters used. Smooth Muscle Dysfunction in Brachial Artery After Transradial Catheterization Figure 2 shows that during nitroglycerin induced vasodilation, the maximal diameter in the ipsilateral brachial artery was significantly smaller at 6 h and 24 h after transradial catheterization (21.8 and 16.7% of baseline, respectively) with subsequent normalization by 1 week after postprocedure (93.4% of baseline). This diameter did not change in the contralateral brachial artery. DISCUSSION
This study assesses the changes over time in the vasomotor function of the brachial artery after transradial catheterization using high resolution vascular ultrasound. Our study’s findings demonstrate that there are transient changes in the brachial artery diameter after ipsilateral transradial cardiac intervention, which con-
sists of decreased brachial artery diameter during reactive hyperemia and after sublingual nitroglycerin administration, compared with the contralateral artery. These findings suggest impaired endothelial and smooth muscle cell function of the upstream brachial artery after transradial cardiac catheterization with recovery within 1 week postprocedure. The changes in the physiology and morphology of the brachial artery after transradial catheterization have been scarcely studied; of note, there is only one study that assessed endothelial and smooth muscle cell dysfunction in the brachial artery over time in 30 patients with suspected coronary artery disease undergoing diagnostic coronary angiography. In this study, the resting diameter of the ipsilateral brachial artery did not decrease after cardiac catheterization but was slightly larger at 6 h and 24 h after transradial catheterization (101.8 and 104.5% of baseline, respectively) [4]. These findings clearly differ from our results. We did not record resting diameters of the brachial artery. We opted to measure the diameter during reactive hyperemia as a surrogate marker of endothelial dysfunction; the fact that the diameters during reactive hyperemia were decreased in our study, reflects that the resting brachial artery diameters were decreased as well. The reason for this discrepancy is not well understood at this time. Of note, the above-mentioned study found that flow-mediated dilatation at 6 h was significantly reduced in the ipsilateral brachial artery, and remained impaired at 24 h in smokers, which suggests that there are local endothelial dysfunction in upstream brachial artery after transradial cardiac catheterization.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Brachial Artery After Transradial Access
Results of our study suggest that this is a temporary phenomenon that resolves within 1 week in most of the subjects. Discordant results have also been found in the resting diameter of the radial artery itself after transradial cardiac intervention. Two small studies have shown that the resting diameter of the radial artery increases slightly after cardiac catheterization [4,6] (up to 110% of the baseline diameter at 24 h). However, Shen et al. in a larger study of 621 patients established that the mean radial diameter significantly decreases 1 day after coronary artery procedures using the radial approach. Importantly, the measurements were performed using high-resolution ultrasound biomicroscopy, which has much better resolution compared with the standard Doppler ultrasound [7]. The literature supports the decreased diameter of a cannulated artery after coronary artery interventions. One study showed worsened endothelial and smooth muscle compartment dysfunction of the brachial artery after transradial catheterization as demonstrated with impaired FMD and NMD [4]. Another study demonstrated narrowing of the upstream brachial artery immediately after transradial catheterization, decreasing more than 50% in a 17% of the subjects; unfortunately these findings were not followed over time [3]. While in another study, the diameter of the radial artery 1 day after cannulation was also found to be significantly smaller in patients who had undergone transradial catheterization previously versus patients who were naive to the procedure [8]. The brachial artery is part of the conduit used during transradial cardiac catheterization and has itself multiple current and potential clinical uses including measurement of flow-mediated dilatation [9], coronary and carotid artery stenting [10], intra-aortic balloon pumping [11], coil embolization for cerebral aneurysms [12], among other interventional procedures when aortic or peripheral arterial conditions limit the transfemoral approach [12]. Its structure and function can be preserved in order to decrease the risk of minor or major complications. The transient worsening of vascular dysfunction is most probably due to subcellular or molecular changes affecting the production of local vasodilators and its response, however, those mechanisms have not been characterized in the brachial artery yet. The relatively small number of patients could represent a limitation of the present study, since it precluded the analysis looking for possible confounders or performing subgroup analysis. Another limitation is that we did not measure baseline vascular dysfunction in our cohort of patients, who had on average two cardiovascular diseases associated with endothelial dysfunction, and therefore were expected to have some degree
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of measurable vascular dysfunction. Such measurement could have been made through estimation of FMD in the brachial artery before cardiac catheterization. It would have been interesting to measure FMD over time and determine if it correlates with the diameter in the brachial artery during reactive hyperemia. Despite these limitations, the strength of this study is that it followed the function of the upstream brachial artery after transradial catheterization over time for the first time, using a standardized technique. Further studies with larger samples are warranted to confirm our results. The timing for repeated transradial catheterization is neither established nor addressed by the current clinical guidelines [13,14]. It would not be advisable to cannulate the radial and brachial arteries until transient vascular dysfunction resolves to baseline. Although this study is not adequately powered to determine the appropriate timing to repeat an ipsilateral transradial catheterization, it suggests than 1 week waiting period may be reasonable. CONCLUSION
In conclusion, our findings suggest that transradial cardiac catheterization leads to transient endothelial and smooth muscle cell dysfunction to the upstream brachial artery with recovery within 1 week postprocedure. We believe that prospective randomized control studies with large sample sizes are the next step to definitively confirming our results. REFERENCES 1. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003;42:1149–1160. 2. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, et al. Nitroglycerine-induced vasodilation for assessment of vascular function: A comparison with flow-mediated vasodilation. Arterioscler Thromb Vasc Biol 2013;33:1401–1408. 3. Lin YJ, Liu YB, Chu CC, Tsai CW. Predictors of brachial artery spasm during transradial cardiac catheterization. Acta Cardiol Sin 2006;22:134–141. 4. Heiss C, Balzer J, Hauffe T, Hamada S, Stegemann E, et al. Vascular dysfunction of brachial artery after transradial access for coronary catheterization. JACC Cardiovasc Interv 2009;2: 1067–1073. 5. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002;39:257–265. 6. Sanmartin M, Goicolea J, Ocaranza R, Cuevas D, Calvo F. Vasoreactivity of the radial artery after transradial catheterization. J Invasive Cardiol 2004;16:635–638. 7. Shen H, Zhou YJ, Liu YY, Du J, Liu XL, et al. Assessment of early radial injury after transradial coronary intervention by
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Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
