Advances in interventional cardiology are reflected in the increased complexity of percutaneous coronary interventions (PCI). This leads to an increasing use of fluoroscopic guidance in these procedures with a concomitant increase in concern regarding radiation exposure of patients and staff.1 An increased level of radiation exposure has been reported to be associated with operator experience, radial (compared with brachial) vascular approach, previous coronary artery bypass grafting (CABG), and complex vessel and lesion characteristics including chronic total occlusions, bifurcation lesions, and severely calcified lesions.2–10
The relationship between radiation exposure and the outcomes of patients undergoing PCI has not been specifically addressed. Fluoroscopic time is an observable surrogate for radiation exposure. We therefore evaluated short-term prognosis and resource utilization of consecutive patients treated with PCI as a function of fluoroscopy time.
Patients and Methods
Patient population. Demographic, clinical and angiographic data, as well as records on fluoroscopy time, procedure time, contrast media volume and resource utilization on consecutive patients undergoing PCI using a femoral approach in Lenox Hill Hospital from 2000 through 2004 entered in the prospective PCI database were retrospectively analyzed. For patients who underwent more than one revascularization procedure during the study period, only the first intervention was analyzed. Patients undergoing multivessel angioplasty or primary PCI for acute myocardial infarction (MI) were excluded. The primary endpoint was the rate of in-hospital major adverse cardiac events (MACE) including death, any MI, and/or emergent repeat revascularization. All adverse events were source-documented. The study was approved by the hospital’s Institutional Review Board.
Angiography and procedures. All procedures were performed in 5 procedure rooms; 4 of them contained Philips H-5000 image intensifier systems and one Philips F-10 flat-panel system. Qualitative and quantitative coronary angiographic analysis was performed according to previously described standard methodology and definitions.11,12 Lesions were classified according to the AHA/ACC grading system.13 PCI was performed using standard techniques. The specific type of revascularization procedure (i.e., balloon angioplasty, atherectomy, stenting) was at the operator’s discretion. All patients received aspirin 325 mg daily ≥ 24 hours pre-PCI and indefinitely afterwards. Patients who underwent stenting were treated with clopidogrel 75 mg daily for 4 weeks. Heparin was administered during the procedure to maintain an activated clotting time of 250–300 seconds. All other treatments, including platelet glycoprotein IIb/IIIa receptor inhibitors, were at the discretion of the physicians. All patients underwent 12-lead electrocardiography before and after the procedure to detect procedure-related ischemic changes. Pre- and postprocedure creatine kinase (CK) and CK-MB values were routinely obtained.
Definitions. Q-wave myocardial infarction (MI) was an elevated creatine kinase (CK) or CK-MB > 2 times the upper limit of normal with new pathological Q-waves in ≥ 2 contiguous leads. Postprocedural non-Q-wave MI was defined as a CK-MB isoenzyme elevation at least 5 times the upper limit of normal without new Q-waves. Procedural hypotension was a decrease in systolic blood pressure to < 80 mmHg requiring vasopressor and/or intra-aortic balloon pump support. Chronic renal insufficiency (CRI) was a baseline creatine ≥ 2 mg/dl.
Statistical analysis. For the purpose of this study, patients were divided into two groups based on fluoroscopy time: patients with a fluoroscopy time within or above the 75th percentile of the entire study population (Figure 1). The latter were selected based on the value of the cutoff point (in this case, fluoroscopy time) that corresponded to the most significant relation with outcome (in-hospital MACE). Continuous variables are expressed as mean ± 1SD and compared using the Student’s t-test. Categorical data are presented as frequencies and compared using Chi-square statistics. The nonparametric Kruskal-Wallis test was used for comparison of ordinal variables.
Multivariate predictors of prolonged fluoroscopy time and MACE were determined using multivariate linear regression with entry/stay criteria of 0.2/0.1. Stepwise selection was used to select variables from the list of candidate predictors, which included age, gender, prior MI, prior CABG, peripheral vascular disease, hypertension, diabetes, hyper-cholesterolemia, prior smoking, target vessel, intervention on a saphenous vein graft (SVG), ostial location of the target lesion, bifurcation, lesion eccentricity, lesion type based on the ACC/AHA classification, calcification, thrombus, and Thrombolysis in Myocardial Infarction (TIMI) grade flow. Fluoroscopic time was included in a list of candidate predictors for multivariate analysis of MACE predictors. The discriminative ability of the models was quantified by the c-statistic.
A total of 9,650 patients undergoing single-vessel PCI on 14,104 lesions were analyzed. The mean fluoroscopy time in the entire study population was 18.3 ± 12.2 minutes, the median time (interquartile range) was 15.1 (9.9 to 23.0) minutes. The mean procedure time was 81.6 ± 60.6 minutes, the median time (interquartile range) was 72.0 (53.0 to 98.0) minutes.
Baseline characteristics. As shown in Table 1, compared to patients within the 75th percentile of fluoroscopy time (control group, fluoroscopy time ≤ 23 minutes), those with prolonged fluoroscopy time were older, more frequently presented with unstable angina, had a higher prevalence of prior CABG, chronic renal insufficiency and peripheral arterial disease, and had lower left ventricular ejection fractions and higher TIMI risk scores.
Baseline angiographic characteristics of the patients are presented in Table 2. Prolonged fluoroscopic time was associated with intervention on the right coronary artery, left internal mammary artery and SVG, as well as excessive calcification, longer lesion length, higher degree of target vessel diameter stenosis, ostial and distal lesion location, bifurcation lesion, eccentric lesion, lesion bend > 45º, multiple (tandem) lesions, in-stent restenotic lesion, thrombus-containing lesion, worse TIMI flow grade, and more severe lesion type according to AHA/ACC classification. Figure 2 shows a significant increase in the proportion of lesions B2/C, calcified lesions, bifurcation lesions, and eccentric lesions with increments of fluoroscopy time when the study population was further stratified into quartiles (1st quartile corresponded to fluoroscopy time < 9.9 minutes; 2nd quartile, a fluoroscopy time of ≥ 9.9 minutes to < 15.1 minutes; 3rd quartile, a fluoroscopy time of ≥ 15.1 minutes and < 23.0 minutes; and 4th quartile, a fluoroscopy time of ≥ 23.0 minutes). In addition, TIMI flow grade 0 was significantly more frequent at baseline, with increments of fluoroscopy time (5.2%, 9.1%, 9.9% and 15.8%, for 1st, 2nd, 3rd and 4th quartiles, respectively; p < 0.0001). The same was true with regard to target lesion length (12.4 ± 5.7, 12.8 ± 6.6, 13.2 ± 7.4 and 13.5 ± 7.6 mm; p < 0.0001).
Procedural and in-hospital outcomes. In the entire cohort, the majority of lesions (71.0%) were treated with stent(s), while 29.0% of the lesions were treated solely with plain balloon angioplasty. Adjunctive rotational atherectomy was performed in 2.6% of the lesions. Patients with prolonged fluoroscopy times had higher rates of rotational atherectomy (5.2% vs. 1.4%, respectively; p < 0.0001) and thrombectomy (1.3% vs. 0.4%; p < 0.0001) compared to the control group. Other procedure-related data are summarized in Table 3. Prolonged fluoroscopy time was associated with less frequent achievement of final TIMI grade flow 3, higher incidence of final dissection, coronary artery perforation, and the slow-flow or no-flow phenomenon. Platelet glycoprotein IIb/IIIa receptor inhibitors were administered significantly more frequently to patients with prolonged fluoroscopy time. As expected, resource utilization including the number of guide catheters, balloons, and stents was significantly higher in patients with prolonged fluoroscopy time compared with controls.
In-hospital outcomes are detailed in Table 4. The rate of in-hospital death, emergent CABG, retroperitoneal hematoma, and drops in hematocrit ≥ 15% compared with the preprocedure value, and hypotension was significantly higher in patients with prolonged fluoroscopy time than in controls. The incidence of stroke, acute stent thrombosis, and blood product transfusion also tended to be higher in patients with prolonged fluoroscopy time.
A significant trend towards an increase in the in-hospital MACE rates was observed with increments of fluoroscopy time from 0.7% in the lowest quartile to 1.0%, 2.4%, and 5.7% in the higher quartiles, respectively (chi square for trend p < 0.0001) (Figure 3). Independent predictors of in-hospital MACE included fluoroscopic time and history of MI (OR 1.04 [1.02, 1.06]; p = 0.008; OR 2.82 [1.18, 6.72]; p = 0.019). The c-index showed good discriminative power of this model (c-index = 0.81).
A significant correlation existed between prolonged fluoroscopy time and increased amount of contrast media (r = 0.36). We therefore speculated as to whether contrast volume was also related to worse in-hospital outcome. However, there was no significant change in the rates of in-hospital MACE across quartiles of contrast amount (2.5%, 0.8%, 2.6%, and 3.1% in groups of patients who were administered < 200, ≥ 200 to < 250, ≥ 250 to < 350, and ≥ 350 ml of contrast media, respectively; Ptrend = 0.33).
By multivariate analysis, prolonged fluoroscopy time (> 75th percentile) was most strongly associated with prior CABG, peripheral arterial disease, ostial lesion location, severe lesion calcification and eccentricity, and baseline TIMI grade flow 0–2 (Figure 4). The c-index for this model was 0.76.
The use of fluoroscopy is a major source of radiation exposure during PCI, and correlates with direct measurements of radiation exposure such as dose area product.5,7,14 In this study, prolonged fluoroscopy time was defined as being above the 75th percentile of the entire study population. Based on a large consecutive series of PCI patients, the current study shows that prolonged fluoroscopy time is associated with increased rates of procedural complications including early mortality, emergent CABG, increased resource utilization, and a trend towards an increased incidence of neurologic complications and need for blood product transfusions.
In this analysis, prior CABG and peripheral arterial disease were the only clinical predictors of prolonged fluoroscopy time. Performance of diagnostic and interventional procedures on bypass grafts is a known factor prolonging fluoroscopy time due to graft origin search and increased time necessary to fill the grafts.3 Peripheral arterial disease may prolong procedural and/or fluoroscopic time due to difficulties in gaining vascular access. Prolonged fluoroscopy time was also associated with several important angiographic characteristics of the treated vessel/lesions (calcification, eccentricity, ostial location, and preprocedure TIMI flow 0–2). A proportion of several unfavorable lesion characteristics steadily increased with increments of fluoroscopy time. Not surprisingly, more complex vessel/lesion anatomy resulted in prolonged fluoroscopy time due to technically difficult procedures and/or related complications. One therefore may consider fluoroscopy time as a rough surrogate of procedure complexity.
This is in full agreement with previous studies indicating that anatomical factors stratified by AHA/ACC grading criteria significantly influence fluoroscopy time.2–5 A complexity index was proposed for the assessment of vessel and/or lesion characteristics based on the sum of the integer scores assigned for severe vessel tortuosity, bifurcation lesions, ostial lesions, and chronic total occlusions.5 The described index was shown to correlate significantly with prolonged radiation exposure assessed either directly or by fluoroscopy time.5
In our study, in-hospital mortality was 4.7 times higher and emergent CABG was performed 7 times more frequently in patients who required prolonged fluoroscopy time compared with control patients. Once again, higher incidence of in-hospital MACE in patients with prolonged fluoroscopy time is likely due to more complex and complicated procedures in this group. By multivariate analysis, longer fluoroscopy time as an indicator of procedural complexity and associated procedural complications was one of the predictors of in-hospital MACE.
Deterioration of renal function post-PCI was clearly related to prolonged fluoroscopy time in this analysis. It was consistent with larger amounts of contrast media and a higher incidence of hemodynamic instability during the index procedure, both factors that are known to increase the risk of contrast-induced nephropathy. Several studies indicated that contrast-induced nephropathy is a significant predictor of mortality post-PCI.15,16 Of interest, however, despite a significant correlation between fluoroscopy time and contrast volume, there was no significant relationship between the amount of contrast used and in-hospital outcomes. This allows us to hypothesize that fluoroscopy time is probably a more reliable predictor of short-term prognosis than volume of contrast media.
Finally, neurological complications and blood transfusion requirements also tended to be higher in patients with prolonged fluoroscopy time. Fluoroscopy time reflects more factors than radiation use. Several important issues need to be addressed, given the correlation between fluoroscopy time and clinical outcomes. These include justifying individual procedures both in terms of expected radiation use and the anticipated rate of immediate procedural complications. Both patients and referring physicians should also be appropriately informed and aware of the possibilities of radiation and clinical complications. The detrimental effect of radiation per se is an extremely important issue in patients with prolonged radiation exposure, especially in those who undergo multiple procedures. More than 70 cases of skin injuries have been reported in the literature.17,18 Retrospective analysis of patients with radiation-induced skin injuries showed significant prolongation of fluoroscopy time in these cases.
The factors that prolong fluoroscopy time are an important concern for certain PCIs, and are associated with increased risk of procedural and short-term complications along with increased resource utilization. This consideration should be specifically taken into account by the physician and properly explained to patients in the assessing the risk/benefit ratio of applicable techniques (PCI vs. medical therapy vs. CABG). Any effort to reduce the amount of radiation exposure should be considered in catheterization laboratories. Operators should monitor radiation dose and fluoroscopy time, analyze reasons for prolonged radiation exposure, and carefully consider the risks versus benefits of continuing prolonged procedures. Each prolonged fluoroscopy-guided PCI has to be assessed for potential radiation injury and contrast-induced nephropathy. Fluoroscopy time has a clear relationship with procedure complexity, and may provide a useful surrogate of this variable for operators as part of their interprocedural risk-benefit analysis. Personal or institutional fluoroscopic time guidance levels could be established as a function of anticipated complexity. Further studies should address relationships between fluoroscopy time, procedural complexity, and operator skills.
- Cusma JT, Bell MR, Wondrow MA, et al. Real-time measurement of radiation exposure to patients during diagnostic coronary angiography and percutaneous interventional procedures. J Am Coll Cardiol 1999;33:427–435.
- Bell MR, Berger PB, Menke KK, Holmes DR Jr. Balloon angioplasty of chronic total coronary artery occlusions: What does it cost in radiation exposure, time, and materials? Cathet Cardiovasc Diagn 1992;25:10–15.
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- Bernardi G, Padovani R, Morocutti G, et al. Clinical and technical determinants of the complexity of percutaneous transluminal coronary angioplasty procedures: Analysis in relation to radiation exposure parameters. Catheter Cardiovasc Interv 2000;51:1–9.
- Katritsis D, Efstathopoulos E, Betsou S, et al. Radiation exposure of patients and coronary arteries in the stent era: A prospective study. Catheter Cardiovasc Interv 2000;51:259–264.
- den Boer A, de Feijter PJ, Serruys PW, Roelandt JR. Real-time quantification and display of skin radiation during coronary angiography and intervention. Circulation 2001;104:1779–1784.
- Yo S, Chino M, Hasegawa T, Isshiki T. Actual state of radiation exposure during coronary angioplasty: A multicenter study in the nationwide database for cost analysis of percutaneous transluminal coronary angioplasty in Japan. Circ J 2003;67:676–681.
- Larrazet F, Dibie A, Philippe F, et al. Factors influencing fluoroscopy time and dose-area product values during ad hoc one-vessel percutaneous coronary angioplasty. Br J Radiol 2003;76:473–477.
- Sandborg M, Fransson SG, Pettersson H. Evaluation of patient-absorbed doses during coronary angiography and intervention by femoral and radial artery access. Eur Radiol 2004;14:653–658.
- Lansky AJ, Popma JJ. Quantitative angiography. In: Topol EJ (ed). Textbook of Interventional Cardiology. Philadelphia: W.B. Saunders. 1999, pp. 725–747.
- TIMI Study Group: The Thrombolysis in Myocardial Infarction (TIMI) trial: Phase I findings. N Engl J Med 1985;312:932.
- Ryan TJ, Faxon DP, Gunnar RM, et al. Guidelines for percutaneous transluminal coronary angioplasty: A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol 1988;12:529–545.
- Miller DL, Balter S, Cole PE, et al for the RAD-IR study. Radiation doses in interventional radiology procedures: The RAD-IR study: Part I: Overall measures of dose. J Vasc Interv Radiol 2003;14:711–727.
- Dangas G, Iakovou I, Nikolsky E, et al. Contrast-induced nephropathy after percutaneous coronary interventions in relation to chronic kidney disease and hemodynamic variables. Am J Cardiol 2005;95:13–19.
- Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: Development and initial validation. J Am Coll Cardiol 2004;44:1393–1399.
- Koenig TR, Wolff D, Mettler FA, Wagner LK. Skin injuries from fluoroscopically guided procedures: Part 1, Characteristics of radiation injury. Am J Roentgenol 2001;177:3–11.
- Koenig TR, Mettler FA, Wagner LK. Skin injuries from fluoroscopically guided procedures: Part 2, Review of 73 cases and recommendations for minimizing dose delivered to patient. Am J Roentgenol 2001;177:13–20.