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Ann Thorac Surg 2006;81:112-119
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Radial Artery Angiographic String Sign: Clinical Consequences and the Role of Pharmacologic Therapy

Senri Miwa, MD, PhD, Nimesh Desai, MD, Tadaaki Koyama, MD, PhD, Emily Chan, BS, Eric A. Cohen, MD, MS, Stephen E. Fremes, MD, MS * , Radial Artery Patency Study Investigators

Divisions of Cardiovascular Surgery and Cardiology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada

Accepted for publication June 8, 2005.

* Address correspondence to Dr Fremes, Division of Cardiovascular Surgery, Schulich Heart Centre, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Ave, Room H410, Toronto, ON M4N 3M5, Canada (Email: stephen.fremes{at}sw.ca).

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
BACKGROUND: The radial artery is an increasingly important graft for coronary artery bypass surgery. Postoperative angiographic studies have shown that a proportion of radial grafts become diffusely narrowed but not occluded, or string signs.

METHODS: Four hundred forty patients receiving a radial artery graft enrolled in a large clinical trial underwent postoperative angiography at 1 year. Angiograms were analyzed visually and quantitatively. A complete string sign was defined as diffuse narrowing along the full length of the graft, while a partial string sign was defined as segmental narrowing. Angiographic findings were correlated with medication compliance and clinical sequelae.

RESULTS: Thirty-one patients (7.0 %) had radial artery graft string signs versus 4 patients (0.9%) with a saphenous vein graft string sign (p = 0.001). Complete string signs were present in 28 cases, and the mean diameter was 0.76 ± 0.14 mm (mean ± SD), whereas 3 cases had a partial string sign with a diameter of 0.89 ± 0.14 mm. Fifteen radial arteries showed Thrombolysis in Myocardial Infarction Study (TIMI) 1 flow, 3 cases showed TIMI 2 flow, and 13 cases showed TIMI 3 flow. There was no difference in incidence of radial string sign between patients taking nifedipine versus diltiazem postoperatively. Multivariate analysis revealed the presence of radial artery string sign was closely related to the perioperative use of alpha-adrenergic agonists and target vessels stenosis less than 90%. Postoperative symptoms were associated with radial artery string signs with TIMI 1 flow (p = 0.0045).

CONCLUSIONS: In the Radial Artery Patency Study, radial artery string sign was present in 7% of patients. Despite diffuse narrowing, 52% of grafts had TIMI 2 flow or better.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 
Initial angiographic results using the radial artery as a graft for coronary artery bypass grafting (CABG) were unsatisfactory [1, 2]. In 1989, Acar and coworkers [3] reintroduced the use of the radial artery for CABG, with encouraging initial findings. Acceptable results were subsequently reported from several groups, and the radial artery has become an increasingly important graft for coronary artery bypass surgery.

While arterial grafting is broadly recommended for coronary surgery [4], arterial grafts still occasionally fail, often as a diffuse narrowing seen on angiography as a "string sign." Only a few published reports of radial grafting have focused on angiographic string sign, and the conclusions of the studies are limited owing to the retrospective nature of the investigations or the small number of patients evaluated [5, 6].

To definitively assess the role of the radial artery as a coronary bypass conduit, we initiated a randomized trial, the multicenter Radial Artery Patency Study (RAPS), in 1996 [7] (see Appendix). The primary results were reported in 2004 [8]. Altogether 561 patients were enrolled, of whom 440 underwent postoperative angiography. Although radial artery patency was substantially superior to saphenous vein graft patency, there were several instances of patent radial arteries demonstrating angiographic string sign. The purpose of this study was to define the etiology and clinical consequences of radial artery angiographic string signs.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 Acknowledgments
 References
 
Details of the study design have been previously published [7]. Patients received both a radial artery and a saphenous vein graft, randomly anastomosed to two different coronary territories. The primary study objective was to determine the angiographic patency of radial artery grafts compared with saphenous vein grafts at 8 to 12 months after surgery. Elective, primary isolated coronary bypass surgery patients with graftable triple vessel disease and preserved left ventricular ejection fraction were candidates for the study. As entry criteria, the left circumflex and the right coronary arteries were required to have proximal lesions with at least 70% stenosis and to be greater than or equal to 1.5 mm in diameter and of acceptable quality according to the visual assessment of the angiogram. Patients with nonpalpable ulnar arteries or a positive Allen's test, an abnormal upper extremity Doppler study or ultrasonogram, and a history of vasculitis or Raynaud's syndrome were ineligible. Patients with bilateral varicose veins or stripping were ineligible. Patients with any condition that would preclude follow-up research angiography on an ethical basis were also excluded.

Study Protocol
The patients signed a consent form approved by the Research Ethics Committee at each participating center. Patients were randomly assigned to one of two graft strategies: (1) the radial artery was used to graft the circumflex territory and a saphenous vein graft was used for the right coronary system; or (2) the radial artery was directed to the right coronary territory and a saphenous vein graft was used for the circumflex system. By protocol, the internal thoracic artery was used for revascularization of the left anterior descending artery. Additional grafts, regardless of conduit used, were optional. The nondominant arm was used exclusively for radial artery harvesting. Details of the surgical technique have been previously published [9]. The radial artery pedicle was dilated in situ by a slow intraluminal injection of 4 to 5 mL of a dilute solution of verapamil and papaverine (5 mg verapamil and 65 mg of papaverine in 16 mL of lactated Ringer's solution). Sequential grafts were performed in two of 440 radial arteries, one to the right coronary territory and one to the circumflex territory. Aortocoronary grafts were performed in 433 of 440 radial artery grafts. Two radial arteries were used as Y-graft extensions, both taken off of nonstudy saphenous vein grafts and anastomosed to the circumflex territory. Five additional radial grafts were anastomosed to vein graft hoods proximally.

Postoperative Management
Patients were given aspirin 325 mg daily starting within 6 hours after surgery and continued indefinitely. By protocol, patients received intravenous nitroglycerin 1 to 10 ug · kg–1 · min–1 during the first 24 hours after surgery in the intensive care unit. Alpha-adrenergic agonist agents such as norepinephrine and neosynephrine were avoided unless other methods to improve hemodynamic status were ineffective. Oral nifedipine was initiated the first postoperative day and continued for 6 months postoperatively. In cases of where patients were intolerant of nifedipine or institutional policy discouraged nifedipine use, diltiazem or amlodipine were offered.

Follow-Up Angiography
Patients were scheduled to undergo follow-up angiography between 8 and 12 months after surgery. The angiogram was not performed if any conditions listed as preoperative exclusions developed in the postoperative period. Angiograms were generally performed on an outpatient basis. Nitroglycerin was injected into each graft prior to filming. At least two orthogonal views of each graft were obtained, and continued exposure was used as required to visualize the distal runoff and the size of the target arteries.

Study Endpoints
The Core Angiographic Committee determined the presence of string signs as a prespecified secondary angiographic end-point. The Core Angiographic Committee consisting of four cardiologists experienced with angiography, reviewed the postoperative angiograms independently in a masked fashion. The films were reviewed by two of the four Committee members with a third review in the case of disagreement.

Secondary clinical endpoints included myocardial infarction and recurrence of anginal symptoms as determined by the Seattle Angina Questionnaire. Serial electrocardiograms were obtained perioperatively.

Definition and Analysis of String Sign
String sign was defined a priori as a patent graft that was diffusely narrowed, with a diameter less than 1 mm according to visual assessment by the Core Angiography Committee. For this study, the diameter of the string graft was directly measured in the proximal, mid-body and distal portions using quantitative coronary analysis with the Inturis CVS Software package (Philips Medical Systems, DA Best, the Netherlands) [10, 11]. Each image was calibrated by selecting a straight segment of the catheter. The manual curve selection tool was used to select the graft portion. In cases where the vessel was not successfully selected, the selection was modified at the user's discretion. For example, when the graft overlaps existing sternal wires, clips, and other coronary vessels, these extraneous objects were excluded from the selection. Once the curve selection was accepted, the mean diameter was collected from the total segment analysis. Empiric determination of interobserver and intraobserver reliability of quantitative angiographic analysis showed that our quantitative coronary analysis of radial artery grafts was highly reliable.

A complete radial artery string sign was defined as diffuse narrowing along the full length of the graft. In addition, we identified several grafts with segmental narrowing of a significant portion of the graft, but not the whole graft, which we defined as partial string signs. Quantitative coronary analysis was performed in the 24 of 31 patients in whom the postoperative angiogram was recorded digitally. Quantitative coronary analysis was also performed in 185 fully patent radials for comparison.

Statistical Analysis
The comparisons between the incidence of graft occlusion or string sign in the radial and saphenous vein grafts were performed with McNemar's test for paired proportional data. Continuous variables, such as graft diameter, were compared using Student's t test with correction for paired analyses where necessary. Dichotomous variables were compared using either the {chi}2 test or Fisher's exact test where indicated.

Multivariable analysis was performed using logistic regression. A logistic regression model to determine risk factors for radial artery occlusion was performed using the following predictor variables: size of target vessel, severity of proximal target vessel stenosis, age, sex, smoking status, diabetes, hypertension, hyperlipidemia, history of vascular disease, intraoperative use of papaverine, perioperative use of alpha-adrenergic agents, calcium-channel blocker use at discharge, and aspirin use at discharge. All analyses were performed using StatView or SAS version 8 (SAS Institute, Cary, North Carolina).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 Acknowledgments
 References
 
Five hundred and sixty-one patients were enrolled in this 13-center clinical trial, and angiography was performed in 440 patients at a mean 10.9 ± 4.3 months after surgery. In these 440 patents, 36 (8.2%) of the radial arteries were completely occluded compared with 60 study saphenous veins (13.6%, p = 0.009; Table 1). The main results of this have been published elsewhere [11]. Among study radial and vein grafts, string signs were seen in 31 of 440 radial arteries and 4 of 440 saphenous vein grafts (p = 0.001; Table 1). Seventeen of the radial artery string grafts were directed to the circumflex system whereas the other 14 were used to bypass the right coronary artery territory (Table 2). Two patients with a radial string sign had a string sign of another graft, one saphenous vein graft and one left internal thoracic artery. In the 31 cases with radial artery string signs, 15 grafts (48%) showed Thrombolysis in Myocardial Infarction Study (TIMI) 1 flow, three grafts (10%) showed TIMI 2 flow, and 13 grafts (42%) showed TIMI 3 flow of the distal native coronary artery (Table 1).


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  		Table 1. Patency and String Signs in All Study Grafts
 

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  		Table 2. Target Vessels of Radial Artery String Signs
 
Quantitative Analysis
Twenty-eight patients had complete string signs, and 3 patients had partial string signs; the distal portion of the graft was affected in each partial string sign case. The mean diameter of the complete radial artery string sign was always less than 1.05 mm (range, 0.46 to 1.04 mm) by quantitative coronary analysis, and the average diameter was 0.76 ± 0.14 mm. By comparison, the average diameter of normal patent radial arteries without any string sign was 2.42 ± 0.78 mm. The diameter of the radial string sign increased nonsignificantly with TIMI flow classification: 0.66 ± 0.12 mm in the TIMI 1 grafts, 0.78 ± 0.16 mm in TIMI 2 grafts, and 0.88 ± 0.10 mm in TIMI 3 grafts. The average diameter of the string portion of radial grafts with a partial string sign was 0.89 ± 0.14 mm, and the average diameter of the nonstring portion was 2.20 ± 0.31 mm. In 9 of the 31 patients, angiographic views of string radial artery grafts were taken before and after the infusion of nitroglycerin. After intragraft nitroglycerin infusion, the graft diameters of these radial string grafts increased slightly from 0.74 ± 13 mm to 0.80 ± 0.12 mm (p = 0.0063).

Impact of Calcium-Channel Blocker Usage
Compliance on calcium-channel blocker therapy among patients who underwent angiography was 95.2% at discharge and 91.1% for the first 6 months after discharge. The incidence of radial artery string sign was 28 of 419 (6.7%) for patients discharged on a calcium-channel blocker and 3 of 21 (14.2%) for those who were not (p = 0.18). When analyzed according the type of calcium-channel blocker prescribed at discharge, the incidence of radial artery string sign was 21 of 292 (7.2%) for nifedipine, 5 of 71 (7.0%) for diltiazem, 2 of 52 (3.9%) for amlodipine, and 0 of 4 (0%) for felodipine (overall p = 0.78). The incidence of radial artery string sign among patient compliant on calcium-channel blocker therapy for 6 months was 26 of 401 (6.5%) versus 5 of 39 (12.8%) for those who were not (p = 0.2).

Predictors of Radial Artery String Signs
The presence of a string sign in radial artery grafts was closely related to the severity of the proximal stenosis of the target coronary artery: 11.8% of the patients with less than 90% proximal narrowing of the target coronary arteries had a radial artery string sign versus 4.1% of the patients with more than 90% proximal narrowing (adjusted odds ratio [OR] 3.1, 95% confidence interval [CI]: 1.4 to 7.0; Table 3). The radial artery string sign occurred in 31.3% of patients who received perioperative alpha-adrenergic agonist infusion, but only in 6.1% of patients without perioperative alpha-adrenergic agonists (adjusted OR 8.2, 95% CI: 2.4 to 28.6; Table 3). There was no meaningful difference in the predictors of radial artery string sign whether all patients undergoing angiography or only patients with patent radial artery grafts were included in the regression model. The predicted risk of radial string sign was 2.7% in patients without either risk factor, 21.5% in patients receiving perioperative alpha-adrenergic agents, 8.3% in patients with radial arteries grafted to target vessels with less than 90% stenosis, and 46.6% in patients with both risk factors according to the risk-adjusted multivariate model. There was no relationship between the use of other recommended medical therapies and the occurrence of radial artery string signs (Table 3).


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  		Table 3. Predictors of Radial Artery String Signs
 
Clinical Consequences of Radial Artery String Signs
Four patients died perioperatively and a further 4 patients died between 30 days and 1 year. None of these patients had angiography; there was one postmortem examination performed that showed both study grafts patent. Myocardial infarction occurred in 3 of 31 patients (9.7%) with a radial artery string sign and 39 of 373 patients (10.5%) with a patent radial artery graft (p = 0.8). All three perioperative myocardial infarctions in the patients with radial artery strings occurred in the inferior territory; 2 of those patients had radials to the circumflex territory and 1 to the right coronary artery territory (Tables 4 and 5). Go Postoperative symptoms of angina at 3 or 12 months were not associated with the presence or absence of radial strings overall; however, TIMI flow was an important determinant of angina at 12 months after surgery in the 31 radial string patients (Tables 4 and 5). Angina occurred in 4 of 15 radial artery string patients with TIMI 1 flow, whereas none of the 16 patients with TIMI 2 or 3 flow had postoperative angina (p = 0.0045; Tables 4 and 5).


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  		Table 4. Postoperative Symptoms
 

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  		Table 5. Postoperative Symptoms in Radial String Sign Patients
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 Acknowledgments
 References
 
In a large angiographic trial of radial artery grafting, we identified 31 cases of radial artery string sign in 440 patients. Previous reports of the radial artery string sign have been limited with respect to patient numbers and study design (Table 6) [11–18]. The cumulative percentage of radial artery strings in these earlier studies was, however, very similar to the findings of this study. In keeping with previous studies, string signs occurred much more frequently in radial artery grafts rather than saphenous vein grafts, which were typically completely obstructed rather than diffusely narrowed.


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  		Table 6. Recent Studies of Radial Artery String Sign
 
Most cases of radial string signs involved the entire graft, which we defined as a total string sign. Only 3 of 31 stringed radial grafts had a partial string sign, and the distal portion was narrowed in all of these three cases (Fig 1). We did not include reactive focal narrowing of the radial arterial grafts at the proximal anastomosis in the definition of radial string, as these changes likely reflect catheter tip spasm and do not represent any graft dysfunction. By protocol, all study grafts were required to receive intragraft injections of nitroglycerin before filming, to minimize graft spasm related to the procedure, and prevent identification of false positive radial artery strings. In 9 patients with radial artery string signs, radial artery angiograms were performed both before and after intragraft nitroglycerin. Nitroglycerin dilated each of the 9 grafts, although the magnitude of vasodilatation was minimal. It remains speculative whether longer nitroglycerin infusions or direct administration of drugs such as verapamil or adenosine may be associated with further vasodilatation.



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  		Fig 1. The left photo shows a complete string sign (arrows) with diffuse narrowing along the full length of the graft. The right photo shows a partial string sign (arrows) with segmental narrowing involving the distal half of the graft, while the proximal half of this graft is almost normal in diameter.

 
The Core Angiographic Committee identified radial artery string signs for grafts that were diffusely narrowed and estimated to be less than 1 mm in diameter. By quantitative coronary analysis, all grafts were in fact less than 1.05 mm, and less than 40% of the diameter of the normal fully patent radial graft. The Core Angiography Committee also determined TIMI flow. Patients with radial string signs had various distal coronary flow patterns, of whom nearly 50% had TIMI 3 flow. Patients with radial artery string signs and TIMI 3 flow appeared less likely to suffer recurrent angina. The numbers of patients involved are small, but suggest that the flow reserve of the TIMI 3 string radial artery grafts was adequate.

Multivariate analysis revealed two factors that were closely related to the occurrence of postoperative radial string signs. Patients with less than 90% proximal stenosis in the target coronary artery by visual assessment had an increased risk of radial string sign. The inclusion criteria for the trial stipulated that the right coronary and circumflex territory lesions needed to be greater than 70%, as we aimed to place the radial grafts in high demand situations with limited competitive flow from the native coronary artery. Our study demonstrated that the threshold coronary stenosis for the radial artery string sign is greater than 70%, and that directing the radial artery to coronary vessels with very high grade proximal lesions was associated with a much lower incidence of radial artery string sign. We previously identified this same relationship for radial graft occlusion [8]. While the mechanism by which flow competition from the native vessels leads to graft narrowing is unclear, it has been previously shown that reduced flow in arterial conduits may lead to low shear stress, inducing graft dysfunction [19, 20].

The second major risk factor was the use of alpha-adrenergic agents in the early postoperative period. The protocol recommended that these agents be avoided. Overall, alpha-adrenergic agents were only used in 25 of 561 enrolled patients, 16 of whom underwent angiography and 5 of whom had radial artery string sign. We are consequently unable to accurately estimate the magnitude of risk (CI: 2.4 to 28.6). Because radial arteries are known to have a significantly increased force of contraction when exposed to alpha-adrenergic agents versus other conduits [21, 22], it seems prudent to minimize the exposure of patients to high doses of these drugs after radial grafting.

To mitigate perioperative vasospasm. papaverine buffered in lactated ringers was used for radial graft preparation in 92% of patients, but did not influence the occurrence of string signs. Other perioperative pharmacologic treatment described in the protocol included nitroglycerin infusion in the intensive care unit and calcium-channel blockers (usually nifedipine) starting on the first postoperative day. Other methods of radial preparation have been described; Buxton and coworkers [23] reported on the use of milrinone, and Taggart and colleagues [24] described phenoxybenzamine. Alternative perioperative preparation of radial grafts may reduce the incidence of strings or occluded grafts. Corvera and colleagues [25] have recently shown that the vasoconstrictive response of the radial artery to alpha-adrenergic agents can be completely abolished using phenoxybenzamine.

The optimization of calcium-channel blockade after radial artery grafting remains controversial. In this trial, compliance with calcium-channel blocker therapy was more than 90% at 6 months, and although radial artery string sign tended to be more common in patients who were not on calcium-channel blockers, our study was not designed or powered to assess this relationship. Gaudino and coworkers [26] have previously shown that calcium-channel blockade with diltiazem does not affect radial graft patency or clinical and scintigraphic results. In vitro experiments on human radial artery segments have shown a superior relaxation and resistance to contractive stimuli with the use of nifedipine or amlodipine, dihydropyridine calcium-channel antagonists, rather than agents such as diltiazem, a 1-5 benzothaizapine calcium-channel antagonist [27, 28]. Although the protocol specified nifedipine use, several institutions preferentially discharged patients on a regimen of diltiazem, and less commonly, amlodipine or felodipine, allowing for comparison of the different calcium-channel blocking agents. Our study found no difference in the incidence of radial graft string signs according to the type of calcium-channel blocker used.

This study has certain limitations. Although this study is larger than any of the previous reports, a sample of 31 string signs did restrict our ability to perform multiple analyses. These are 1-year findings; midterm angiographic follow-up of the study population 5 to 6 years postoperatively is in progress. It is our intention to restudy the string sign patients in addition to patients with fully patent grafts.

In conclusion, radial artery string signs occurred in 7% of patients in this randomized clinical trial. Risk factors for radial artery string signs were perioperative alpha-adrenergic agonists and grafting a coronary vessel with a proximal lesion less than 90%. The presence of a radial artery string sign was for the most part well tolerated clinically; however, patients with radial artery string signs with TIMI 1 flow were more likely to be symptomatic postoperatively. Vigilant postoperative surveillance of radial grafts in patients requiring perioperative alpha-adrenergic support is warranted as these grafts appear to be at exceptionally high risk for string sign formation. Although the type of calcium-channel blocker used had little influence, use of calcium-channel blockers generally may be associated with a reduced incidence of the angiographic string sign.


   Appendix
 
Radial Artery Patency Study Group
The members of the Radial Artery Patency Study Group are as follows (all institutions are in Canada unless otherwise specified): Executive Committee—S. E. Fremes, E. A. Cohen, C. D. Naylor, N. D. Desai, R. Feder-Elituv; Manuscript Committee—N. D. Desai, E. A. Cohen, C. D. Naylor, S. E. Fremes; Steering Committee—S. E. Fremes, E. A. Cohen, C. D. Naylor, M. Carrier, G. Cote, D. Doyle, O. Gleaton, R. Masters, L. Higginson, L. Errett, K. Watson, S. Lichtenstein, R. Carere, M. L. Myers, D. Almond; Participating Cardiologists—D. Almond (Victoria Hospital, London, Ontario), C. Buller (University of British Columbia, Vancouver), F. Charbonneau (McGill University, Montreal), E. A. Cohen (University of Toronto, Toronto), C. Constance (McGill University, Montreal), G. Cote (Montreal Heart Institute, Montreal), J. Ducas (Health Sciences Centre, Winnipeg, Manitoba), O. Gleeton (Hopital Laval, Sainte-Foy, Quebec), L. Higginson (University of Ottawa Heart Institute, Ottawa), L. Schwartz (University of Toronto, Toronto), W. Tymchak (University of Alberta Hospital, Edmonton), R. Watson (University of Toronto, Toronto), G. Devlin (Waikato Hospital, Hamilton, New Zealand); Data Committee—N. D. Desai, H. R. Mallidi, R. Feder-Elituv (all at University of Toronto, Toronto); Statisticians—J. P. Szalai, M. Katik, K. Sykora, A. Kiss (all at University of Toronto, Toronto); Angiographic Committee—E. A. Cohen, J. Dubbin, S. Radhakrishnan, A. Adelman (deceased), L. Schwartz (all at the University of Toronto, Toronto); Clinical End-Points Committee—Z. Sasson (University of Toronto, Toronto), P. Dorian (University of Toronto, Toronto), K. Teoh (McMaster University, Hamilton, Ontario); Electrocardiogram Committee—G. Newton, Z. Wullfart, R. Myers, E. Crystal (all at the University of Toronto, Toronto); Data and Safety Monitoring Committee—S. Brister, C. Morgan, S. Logan (all at the University of Toronto, Toronto); Investigators (the number of patients recruited is in parentheses): Hopital Laval, Sainte-Foy, Quebec: D. Doyle (2), D. Desaulniers (2), R. Baillot (1), G. Raymond (6), M. Lemieux (6), P. Cartier (deceased) (2); Institute de Cardiologie de Montreal, Montreal: R. Cartier (2), M. Carrier (6), Y. Leclerc (1); London Health Sciences Center—University Campus, London, Ontario: A. Menkis (4), D. Boyd (24), R. Novick (2); London Health Sciences Center—Victoria Campus, London, Ontario: M. L. Myers (20); Montreal General Hospital, Montreal: D. Shum-Tim (1), J. F. Morin (48); Sunnybrook and Women's College Health Sciences Centre, Toronto: B. Goldman (14), C. Cutrara (32), G. Bhatnagar (39), S. E. Fremes (108), G. T. Christakis (43), L. Abouzhar (16); Health Sciences Centre, Winnipeg, Manitoba: D. Del Rizzo (10); St. Michael's Hospital, Toronto: D. Bonneau (6), D. Latter (23), L. Errett (11); Toronto General Hospital, Toronto: C. Peniston (4), H. Scully (1), R. Weisel (22), R. J. Cusimano (1), S. Brister (3), T. Ralph-Edwards (1), T. Yau (9); University of Alberta Hospital, Edmonton: E. Gelfand (8), P. Penkoske (2); University of Ottawa Heart Institute, Ottawa: F. Rubens (26); Vancouver Hospital and Health Sciences Centre, Vancouver, B. C.: G. Fradet (25), L. Burr (14), D. Thompson (2); Waikato Hospital, Hamilton, New Zealand: R. Ullal (14); Site Coordinators—M. Aleggretti, A. M. Powel, H. Brochu, R. Feder-Elituv, R. Fox, L. Lepicq, G. Keuen, C. Jessina, S. Finlay, E. Reeves, A. MacDonald, M. El-Tawil, L. Paul, M. A. James, L. Verreault, B. Weller, C. Nacario, J. Wilson, D. Penny, F. Denis, A. Munoz, L. Montebruno.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
Acknowledgments
 References
 
DR BRIAN BUXTON (Melbourne, Victoria, Australia): Doctor Miwa, thank you very much for an excellent presentation and I commend you on the clarity of your results. In the same way that you have had a problem with the radial artery string sign, our dilemma is whether to regard this as a failure or success. A stenosis greater than 90% is one factor in determining competitive flow. Unfortunately, there is no simple method of assessing competitive flow, and therefore, a high-grade native vessel stenosis is only a surrogate of collateral or competitive flow and is not always reliable. For instance, it is possible to have a total occlusion of the circumflex with a large collateral and yet have a highly competitive situation.

Regarding the vasodilators, I noticed they were only used in a very small number of patients. Would you consider bending your rule regarding the use of norepinephrine if the patient presented with extreme vasodilatation, which can occur after bypass surgery or after using a vasodilator?

DR MIWA: Thank you, Dr Buxton. About the vasoconstrictors, from our protocol we defined vasoconstrictor agents as pure alpha-adrenergic agonists, that means norepinephrine or neosynephrine. Sometimes we have to use these vasoconstrictors, but if we can avoid it, for example, by using an intra-aortic balloon pump or other methods to support the patient's condition, we do. Of course, sometimes we have to use these vasoconstrictors, but this paper strongly shows the relationship between vasoconstrictors and radial artery string sign.

So if we have to use vasoconstrictors in the perioperative period, the most important thing is that we pay special attention to the medical care of the patient after surgery and we have to follow them more closely. I think that is the main suggestion from these results.

DR BUXTON: I have one follow-up question regarding the string sign. What do you think will happen at the 5-year angiography? Do you think the flow reserve, the lumen diameter, and the patency will increase, or is it too early to tell?

DR MIWA: Can you ask again?

DR BUXTON: I will ask Dr Desai to comment on that.

DR TOM ORSZULAK (Rochester, MN): I enjoyed your talk. I think radial arteries have a place in coronary revascularization. At our institution, based on published laboratory data by Dave Cable, we found that nitrates alone prevented a lot of radial artery spasm. You seem to avoid using nitrates in people that have radial artery grafts. We have generally put everyone on nitrates for a short term. I am not sure I know the answer to how long nitrates should be given in radial arteries, but have you considered using nitrates for some period of time to prevent some of the spasm or "string sign"?

DR MIWA: In this study we strongly recommended the use of nitrates after surgery. I do not have any convincing evidence regarding how long we have to use nitrates after surgery.

DR FRANK SELLKE (Boston, MA): But you put everybody on some agent, a calcium-channel blocker or a nitrate?

DR MIWA: Yes. In this study more than 90% of the patients received a calcium-channel blocker and, of course, aspirin upon discharge. Regarding the calcium-channel blockers, more than 90% of the patients took a calcium-channel blocker for at least 3 to 6 months.

DR SULAIMAN HASAN (Charleston, WV): I want to congratulate you on your wonderful study and very well presented. My question is, do you consider discontinuing things like angiotensin-converting enzyme (ACE) inhibitors 1 or 2 days before so that you might avoid the use of vasoconstrictors postoperatively?

DR MIWA: In our results, ACE inhibitors, beta blockers, or other antithrombotic medicines did not have any significant relationship with the formation of radial artery string sign. So our data do not show that ACE inhibitor use really affected the incidence of radial artery string sign.

DR HASAN: My question was that if you were to stop an ACE inhibitor 1 or 2 days before, your chance of having to use, say, Levophed or norepinephrine might be less after the operation. Do you do that or not? Do you stop the ACE inhibitors?

DR MIWA: In this multicenter study, we did not have any data regarding preoperative cessation of the ACE inhibitors or other ways to avoid vasoconstrictors. It was not in the protocol. Our clinical practice, generally, is to stop ACE inhibitors the night before the operation.

DR DESAI: I am one of Dr Miwa's coauthors. I can address a couple of these questions. For Dr Buxton's question about the long-term survival of the string radial grafts, it is our impression that the grafts that have TIMI I flow will likely occlude over time. Those with good flow reserve are less likely to do so.

Regarding Dr Orszulak's and Dr Sellke's questions about nitrates, as stipulated in the protocol, all of our patients received intravenous nitroglycerin infusion for the first night postoperatively, provided the patient's hemodynamics could tolerate it. Use of oral nitrates was not required or common after surgery.

DR ALISTAIR G. ROYSE (Melbourne, Australia): I have a 10-year experience with the radial artery, and our published and to-be published data has 90 to 92% patency, which is the same as yours. I would use vasoconstrictors in at least 60% of my patients. I remind you that the duration of action of these vasoconstrictors such as noradrenaline or metaraminol is measured in minutes—not months or years. The notion that a transient use of a short-term acting agent causes permanent irreversible spasm is not logical and not supported by pharmacological evidence. I am unconvinced that there is sufficient robustness in your data to make the association between perioperative use of vasoconstrictors and graft failure so confidently.

DR MIWA: This study included follow-up of both asymptomatic patients and symptomatic patients. From these data, we found a strong relationship between vasoconstrictors, that is, alpha-adrenergic agonists, and the radial artery string sign. I think this makes biological sense and that the relationship between vasoconstrictors and radial string sign is indeed real.


   Acknowledgments
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
References
 
This study was supported by Canadian Institutes of Health Research Grants MT-13833 and MCT 52681.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 Acknowledgments
 References
 

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