Ann Thorac Surg 2003;75:1414-1421
© 2003 The Society of Thoracic Surgeons
Original article: cardiovascular
Radial artery use is safe in patients with moderate to severe left ventricular dysfunction
Shafie Fazel, MDa,b,
Hari R. Mallidi, MDa,b,
Marc P. Pelletier, MDa,b,
Jeri Y. Severa,b,
George T. Christakis, MDa,b,
Bernard S. Goldman, MDa,b,
Stephen E. Fremes, MDa*
a Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
b Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada
Accepted for publication December 11, 2002.
* Address reprint requests to Dr Fremes, Sunnybrook and Women’s College Health Sciences Centre, 2075 Bayview Ave, Room H410, Toronto, Ontario, Canada M4N 3M5.
e-mail: stephen.fremes{at}swchsc.on.ca
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Abstract
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BACKGROUND: Using radial artery grafts in patients with moderate to severe left ventricular dysfunction (LVD; ejection fraction < 35%) has been discouraged for the fear that postoperative vasopressor support may cause graft spasm and lead to ischemic complications. We, therefore, examined the safety of radial grafts in aortocoronary bypass (ACB) patients with LVD.
METHODS: Data were collected from 5,455 patients who underwent isolated ACB between January 1995 and September 2001. One thousand eight hundred three patients received a radial artery graft (RadACB), and 3,652 patients did not (NoRadACB). Three hundred seven RadACB, and 819 NoRadACB operations were performed in LVD patients. A matched (age, sex, urgency of operation, diabetes, and renal insufficiency) cohort analysis was performed in LVD patients. Univariate and logistic regression analyses were performed in the entire population and the unmatched RadACB and NoRadACB patient subgroups to examine the effect of radial artery use on postoperative death or myocardial infarction rate.
RESULTS: The matched cohort analysis revealed a similar rate of death or myocardial infarction (RadACB, 11 of 242 patients; NoRadACB, 16 of 242 patients; p = 0.32). Left ventricular dysfunction was associated with a higher rate of death or myocardial infarction in both unmatched groups (RadACB, odds ratio, 2.36; 95% confidence interval, 1.38 to 4.58; p = 0.004; NoRadACB, odds ratio, 1.62; 95% confidence interval, 1.18 to 2.24; p < 0.001) and in the entire population (odds ratio, 1.77; 95% confidence interval, 1.32 to 2.35; p = 0.003). An interaction term for patients with LVD and a radial artery graft, which was forced into the logistic regression model for the entire population, was not predictive of death or myocardial infarction (odds ratio, 1.52; 95% confidence interval, 0.75 to 3.10; p = 0.25).
CONCLUSIONS: Left ventricular dysfunction carries similar risk for postoperative death or myocardial infarction in RadACB and NoRadACB patients. The presence of LVD in isolation is not a contraindication to the use of radial grafting.
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Introduction
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The demonstration by the Cleveland Clinic group that the left internal thoracic artery in situ bypass graft to the left anterior descending coronary artery results in improved long-term outcome [1] sparked interest in arterial revascularization. The radial artery is becoming increasingly popular as a third arterial conduit in association with the left and right internal thoracic arteries, or as the second arterial conduit in patients with contraindications to bilateral internal thoracic artery harvesting. The reasons for this popularity are sixfold: (1) ease of harvesting at the time of the internal thoracic artery harvest, (2) low risk of local complications including infections and hand ischemia, (3) adequate length to bypass all coronary artery territories, (4) diameter that closely matches coronary artery diameter, (5) ease of suturing and surgical handling because of its thick muscular media, and (6) reliability of the graft in terms of minimal variability from patient to patient [2].
A major drawback to the use of arterial grafts, and in particular the radial artery, is arterial spasm. In the first series of radial aortocoronary bypass (ACB) operations reported by Carpentier and colleagues in early 1970s [3], radial artery spasm, narrowing, or occlusion was documented in approximately 25% of grafts intraoperatively and 35% of grafts 2 years postoperatively [4]. Similar experience of other surgical groups [5, 6] resulted in the abandonment of the radial artery as a bypass conduit. After the observation by Acar and associates [2] that an originally "occluded" radial graft was patent in a patient 15 years postoperatively, the radial artery was reevaluated as an arterial bypass conduit. Current clinical evidence suggests that the radial artery is a superior bypass conduit in comparison to the saphenous vein graft [2, 7–16].
However, the potential for radial artery spasm remains a problem that may be most relevant in patients who require postoperative vasopressor support. A multitude of in vitro and in vivo studies have documented the robust spasm of the radial artery in reaction to various agents including endothelin, angiotensin, serotonin, and in particular the potent 
-adrenergic agonist norepinephrine [17–24]. Thus, some surgeons have refrained from using the radial artery in patients who may require vasopressor support postoperatively, such as patients with moderate to severe left ventricular dysfunction (LVD).
To determine whether radial artery use is safe in patients with moderate to severe LVD, we undertook the current retrospective analysis. A combination of univariate, matched cohort, and multivariate analyses was performed.
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Patients and methods
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Patients
The Division of Cardiovascular Surgery at Sunnybrook and Women’s College Health Sciences Centre has maintained a prospective database of all patients undergoing cardiac surgical procedures since its inception in 1989. Data on more than 200 demographic, anatomic, preoperative, perioperative, and postoperative variables were collected prospectively on all patients undergoing surgery at Sunnybrook and Women’s College Health Sciences Centre by chart review during the hospital stay and completed shortly after discharge from hospital. Data are managed and maintained in dBASEIV databases. Between January 1995 and September 2001, 5,455 consecutive patients underwent isolated ACB operations at our institution. One thousand eight hundred three patients received a radial artery (RadACB) graft, and 3,652 patients did not (NoRadACB). The use of a radial artery was according to the choice of the individual surgeon, and not by random allocation. A summary of preoperative clinical risk variables and intraoperative details is presented in Table 1.
Definition of terms
Left ventricular grade 1, 2, 3, or 4 was determined by visual assessment of the left ventriculogram and, when not available, by transthoracic echocardiography or nuclear studies, and represents left ventricular ejection fraction more than 50%, 35% to 49%, 20% to 34%, or less than 20%, respectively. Left ventricular dysfunction was defined for patients with left ventricular grade 3 or 4. Renal insufficiency designates patients with creatinine levels greater than 150 µmol/L. Smoking designates patients who are currently smoking, or quit within 3 months of the surgery. Recent myocardial infarction (MI) designates patients with an MI within 1 month of surgery. Hypertension, dyslipidemia, diabetes mellitus, and chronic obstructive pulmonary disease referred to medically treated conditions.
Definition of outcomes
Death is defined as the 30-day mortality or death during the index hospitalization. Myocardial infarction refers to both fatal and nonfatal MIs as evidenced by new Q waves on the electrocardiogram or by a peak in creatine kinase isoenzyme MB level greater than 50 IU/L that represented more than 7% of the total creatine kinase, and was reviewed by a cardiologist. Echocardiographic corroboration of a new MI was routinely sought, but was not necessary for the diagnosis. The primary end point of the study is the variable "death/MI," a composite outcome of any death or nonfatal MI within the first 30 postoperative days or during the index hospitalization. The diagnosis of cerebrovascular accident includes reversible and nonreversible focal neurologic deficits, usually confirmed by computed tomographic scanning and by a neurologist consultation. Low output syndrome refers to patients who required the use of inotropic agents or intraaortic balloon pump support for longer than 30 minutes to maintain a systolic blood pressure more than 90 mm Hg with a cardiac index more than 2.0 L · min-1 · m-2. The use of an intraaortic balloon pump is also reported separately.
Matched cohort selection
Of the 307 RadACB patients who had LVD, 242 patients could be matched 1:1 with 242 of 819 NoRadACB patients with LVD. The matching variables were age ± 1 year, sex, urgency of operation, presence or absence of diabetes, and presence or absence of preoperative renal insufficiency. Each patient in the NoRadACB cohort was assigned a random number, and the cohort was sorted according to the random number. A computer algorithm then searched in the NoRadACB group for patients who matched according to the above variables to a RadACB patient. The algorithm would search until one matching patient was identified or until all NoRadACB patients were screened without a match. A summary of preoperative clinical risk variables is provided in Table 2.
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Table 2. Perioperative Characteristics of the Matched Patients Undergoing Aortocoronary Bypass With or Without Radial Artery Graft Who Have Moderate to Severe Left Ventricular Dysfunctiona
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Surgical method
The modified Allen’s test was used to determine the adequacy of collateral circulation to the hand. Upper extremity Doppler flows and ultrasound tests were performed selectively in patients with borderline Allen’s tests or with manifest peripheral vascular disease. The radial artery was not used if any of the following conditions applied: the Allen’s test was positive; the patient had an abnormal upper-extremity Doppler study; a radial plaque was noted on ultrasound; or the patient had a history of vasculitis or Raynaud’s disease. The nondominant arm was used almost exclusively for radial artery harvesting, which was performed simultaneously with the harvest of all other conduits. The radial artery was harvested as a pedicle with adjacent veins and surrounding fatty tissue. An atraumatic "no-touch" technique was used for harvesting. After anticoagulation with heparin, the artery was gently dilated in situ by slow intraluminal injection of 5 mL of dilute papaverine chloride and verapamil hydrochloride solution (papaverine, 60 mg, and verapamil, 5 mg, in 16 mL of Ringer’s lactate solution). Ex vivo, the artery was immersed in the same solution. The saphenous vein was harvested using conventional methods followed by immersion in papaverine solution. The radial artery was used primarily to graft a major coronary branch with a high-grade proximal stenosis (>70% diameter narrowing) on the lateral (53.0%) or inferior wall (40.8%) of the heart. The most common individual targets for radial grafting were obtuse marginal 1 (31.6%), obtuse marginal 2 (14.2%), intermediate (4.8%), posterior descending (19.7%), right coronary (19.1%), and diagonal 1 (4.6%). Single grafts (one distal anastomosis per graft) as opposed to sequential grafts (more than one distal anastomosis per graft) were constructed. The proximal radial anastomosis was constructed onto the aorta in most cases. We do not routinely measure intraoperative graft flow.
Postoperative management
Electrocardiograms were obtained preoperatively, on day 1 postoperatively, and either at the time of discharge or on day 5 postoperatively. Serial cardiac enzymes were obtained on arrival to the intensive care unit, every 8 hours for 24 hours, and daily for 2 additional days. Patients received intravenous nitroglycerin (1 to 4 µg · kg-1 · min-1) for the first 24 hours after operation provided the systolic blood pressure was greater than 100 mm Hg. Oral nifedipine (Adalat XL 20 to 30 mg daily) was continued for 6 months thereafter, beginning on the first postoperative day. For patients intolerant of nifedipine, diltiazem hydrochloride or amlodipine was substituted. Sublingual nifedipine (10 mg every 6 hours) was used in the intensive care unit only in instances of persistent hypertension (systolic blood pressure > 140 mm Hg) despite adequate doses of intravenous nitroglycerin or sodium nitroprusside. All patients were placed on a regimen of aspirin, 325 mg daily, beginning 6 hours postoperatively and were maintained indefinitely on cholesterol-lowering agents.
Statistical analyses
The SAS for PC (SAS Institute Inc, Cary, NC) was used for statistical analyses. The base line characteristics and hospital outcomes for the two groups of patients were compared using the 
2 analysis or Fisher’s exact test for categorical data and the Student’s t test for continuous variables. Hospital outcomes were evaluated multivariately by stepwise logistic regression analysis. An entry level p value of 0.15 was used. Odds ratios (OR) and their 95% confidence intervals (CI) for hospital events were calculated accordingly. Results are reported as the mean ± standard deviation or as absolute frequencies and proportions in the text, tables, and figures unless not applicable. Length of stay variables are reported as medians with the interquartile range because of a large right-sided tail of values. Statistical significance was defined as a p value of less than 0.05.
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Results
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Of the 5,455 patients undergoing isolated coronary bypass surgery since 1995, 1,803 patients received a radial artery graft. In general, the use of the radial artery at our institution was used for elective ACB patients who were younger with fewer comorbidities than NoRadACB patients. It is of note that 307 (17.0%) of RadACB patients had moderate to severe left ventricular dysfunction. Patient demographics and perioperative details are listed in Table 1.
The morbidity and mortality associated with ACB unadjusted for other risk variables was lower in the RadACB group than in the NoRadACB group (Table 3;
Fig 1).
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Fig 1. outcome by group of all isolated aortocoronary bypass patients from 1995 to 2001. *p < 0.05. (cva = cerebrovascular accident; iabp = intraaortic balloon pump; los = low output syndrome; mi = myocardial infarction; noradacb = aortocoronary bypass without radial artery graft; radacb = aortocoronary bypass with radial artery graft.)
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Matched cohort study
Two hundred forty-two NoRadACB and 242 RadACB patients with LVD could be matched with the variables age, sex, urgency of operation, diabetes, and preoperative renal insufficiency. These matching variables were chosen because independent predictors of postoperative low output syndrome in our patient population were LVD (OR, 2.23; 95% CI, 1.86 to 2.68), renal insufficiency (OR, 1.78; 95% CI, 1.22 to 2.60), female sex (OR, 1.50; 95% CI, 1.23 to 1.81), age more than 70 years (OR, 1.37; 95% CI, 1.14 to 1.65), urgent operation (OR, 1.31; 95% CI, 1.08 to 1.58), and diabetes (OR, 1.21; 95% CI, 1.00 to 1.46). As shown in Table 2, the two groups were similar with respect to most preoperative risk variables. The mortality and morbidity in each of the two groups is summarized in Figure 2.
The occurrence of death, MI, and death/MI were all not significantly greater in the NoRadACB patients (death, 5 of 242 (2.1%) versus 8 of 242 (3.3%), p = 0.40; MI, 6 of 242 (2.5%) versus 9 of 242 (3.7%), p = 0.42; and death/MI: 11 of 242 (4.5%) versus 16 of 242 (6.6%), p = 0.32].
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Fig 2. Outcome, by group, of the matched aortocoronary bypass with radial artery graft (RadACB) and aortocoronary bypass without radial artery graft (NoRadACB) patients. *p < 0.05. (CVA = cerebrovascular accident; IABP = intraaortic balloon pump; LOS = low output syndrome; MI = myocardial infarction.)
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Risk variables for death or myocardial infarction
Univariate analysis of preoperative risk variables in the RadACB patient population revealed that LVD, redo ACB, and an endarterectomy procedure were associated with increased risk of death/MI (Table 4). In multivariate analysis, however, only LVD (OR, 2.36; CI: 1.38 to 4.58) was an independent predictor of death/MI. The multivariate predictors of death/MI in the NoRadACB patients were: LVD (OR, 1.62; 95% CI, 1.18 to 2.24), age more than 70 years (OR, 1.57; 95% CI, 1.16 to 2.11), recent MI (OR, 1.47; 95% CI, 1.02 to 2.10), and hypertension (OR, 1.46; 95% CI, 1.08 to 1.98). The independent predictors of death/MI in the entire ACB population are graphically represented in Figure 3.
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Table 4. Risk Variables for Death or Myocardial Infarction in All Radial Artery Graft (n = 1,798), and No Radial Artery Graft (n = 3,668) Aortocoronary Bypass Patientsa
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An interaction term, Rad&LVD, representing the RadACB patients with LVD, was forced into the model to explore whether this combination of factors predisposed patients to a greater risk of death/MI (Fig 3).
The risk of a poor outcome was not significantly greater (OR, 1.52; 95% CI, 0.75 to 3.10; p = 0.25).
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Fig 3. Multiple logistic regression model identifying independent predictors of death or myocardial infarction in all isolated aortocoronary bypass (ACB) patients from 1995 to 2001. (CCS = Canadian Cardiovascular Society angina functional class; CI = confidence interval; HTN = hypertension; LITA = left internal thoracic artery; LVD = left ventricular dysfunction; OR = odds ratio; RadACB = aortocoronary bypass with radial artery graft; Rad&LVD = interaction term of RadACB patients with LVD.)
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Comment
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In the original paper published by Carpentier and colleagues in 1973 [3], intraoperative spasm of the mechanically dilated and skeletonized radial artery was observed in nearly one quarter of the grafts. Two years postoperatively the incidence of narrowing or occlusion of the radial conduit was observed to be a prohibitive 35% by angiography [4]. Other groups reported similar results of intractable radial artery spasm and poor postoperative patency [5, 6]. Thus, the radial artery graft was abandoned. Discovery of a patent radial artery graft 15 years postoperatively that was initially "occluded" prompted Acar and colleagues [2] to restudy the radial artery for coronary artery bypass grafting. The series of 56 radial artery grafts published in 1992 [2] reported a 100% early patency rate. The report sparked renewed interest in the radial artery as a second or third arterial bypass conduit. The early clinical results and angiographic patency studies of the radial artery graft since that report have been very promising. The early and late patency rates of the radial artery are reported to be 76.9% to 100% and 87.5% to 100%, respectively [2, 7–16]. In fact, many authors advocate using the radial artery as the second arterial conduit of choice [8, 13, 14]. The results of the Radial Artery Patency Study (RAPS), a multicenter, randomized clinical trial [25], are pending.
Basic science investigations have elucidated the mechanism by which radial artery spasm is mediated. Although the nonreceptor-mediated spasm of the artery in response to local tissue acidity is important, as a coronary bypass conduit it is the receptor-mediated response to catecholamines or platelet-derived serotonin, induced by endothelial damage and platelet aggregation, that should be avoided or abrogated. Thus, three major modifications have been made to the original Carpentier technique to minimize radial artery spasm: (1) the harvesting method was modified from a skeletonized technique to a pedicled approach to minimize surgical handling of the artery; (2) mechanical dilatation was substituted by pharmacologic dilatation to minimize endothelial dysfunction; and (3) postoperative vasodilator therapy was adopted in hopes of minimizing postoperative radial artery spasm [7, 26]. The use of -adrenergic agonists, in light of the above findings, during the postoperative period remains controversial. Although spasm of radial grafts with -adrenergic agonists has not been demonstrated in vivo, the onset of spasm may lead to the collapse of the already compromised circulatory system. For this reason surgeons in our institution have cautiously used the radial artery as a bypass conduit in patients at high risk of needing postoperative vasopressor support.
At our institution, the 7-year experience with 307 patients with a radial artery graft who had concomitant moderate to severe LVD has been comparable or better than the NoRadACB patient group. Because the base line characteristics of the RadACB and the NoRadACB populations were different with regard to many of the preoperative risk variables, we had to conduct both matched cohort, as well as multivariate, analysis to level the statistical ground for a fairer comparison.
The 1:1 matched cohort analysis of 242 LVD patients (in each group), who were deliberately matched with regard to five independent predictors of low output syndrome and were similar with regard to most other preoperative variables (Table 2) revealed comparable morbidity and mortality figures in both RadACB and NoRadACB patients with a trend favoring the RadACB patients (Fig 2). It is interesting to note that in the matched analysis, intraaortic balloon pump was used in 40.0% (9 of 23) of RadACB patients who developed low output syndrome versus 28.5% (11 of 38) in the NoRadACB group. This trend does not, however, reach statistical significance (p = 0.41).
Multivariate analysis was performed at two levels: on the entire ACB population with the forced interaction variable Rad&LVD, and at the subset RadACB versus NoRadACB level. As depicted in Figure 3, LVD is an independent predictor of death or MI, and the use of the radial artery is an independent protector of death or MI once controlled for all other variables. The forced interaction variable Rad&LVD had an OR of 1.52 with a CI that crossed unity. This would argue that the presence of a radial artery in a patient with moderate to severe LVD is not a predictor of death or MI. The subset analysis confirms the above results. In both RadACB and the NoRadACB populations, LVD was an independent predictor of death or MI with overlapping CIs. Nonetheless, we have been very careful in our approach to the treatment of early postoperative hypotension in the radial artery patients. Specifically, we seldom use agents such as norepinephrine, phenylephrine, or vasopressin in RadACB patients, and have a lower threshold to resort to intraaortic balloon pump counterpulsation. Preferred inotropic agents are milrinone, dobutamine, and epinephrine in such circumstances. The vasopressors are reserved for patients who suffer from intractable postoperative vasoplegia with supranormal cardiac indices, and even then with careful electrocardiogram monitoring in place. Emphasis is placed on end-organ function as opposed to mean blood pressure, and maximal effort is invested to ensure adequate preload and contractility rather than peripheral vasoconstriction when end-organ hypoperfusion is suspected.
There are limitations to this study. Although the data, fairly extensive in scope, were collected prospectively, the study is retrospective, and certain information relative to this specific question is not available. For example, radial artery spasm was not analyzed directly; instead, we reported the incidence of hard clinical outcomes such as death, MI, and low output syndrome. Also, although the frequency of MI was less in the radial artery patients, we did not record the territory of the new MIs. Because of our institution’s avoidance of vasopressors in the postoperative management of radial artery patients, we could not unequivocally determine the influence of radial grafting in patients with LVD and prolonged -adrenergic agonists. Also, there were few patients who had severe LVD (left ventricular grade 4). Most importantly, the use of the radial artery was according to surgeon preference rather than by random allocation. The RadACB and NoRadACB groups were quite different; we attempted to control for these differences using matched cohort analysis and multivariate techniques. Regrettably, observational studies are prone to both unmeasured bias as well as measured bias.
Nonetheless, the results of our study support a wider application of the radial artery conduit. Namely, an otherwise suitable patient should not be denied the benefits of an additional arterial graft because of the presence of moderate to severe LVD risk in and of itself.
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Acknowledgments
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Supported in part by CIHR grant MT-13883.
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References
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Abstract
Introduction
