When I first starting writing for CLD in 2006, I asked the question, “How much contrast media is enough in patients at risk for contrast-induced nephropathy (CIN)?”1 Once the clinical indication for angiography exists, and the patient understands the risks and benefits, the requirement for important diagnostic information trumps the amount of contrast to be used. However, any unnecessary or excessive use of contrast beyond the minimum needed incurs a risk to the patient. Different procedures require different amounts of contrast material to obtain the minimal diagnostic information. A patient with angina undergoing only native coronary angiography may require as little as 20-40 mL compared to a patient with claudication after coronary bypass graft surgery, who may need over 150 mL of contrast for coronary, graft, aortic, and peripheral angiography. Operators can limit contrast by skillful angiography, withholding ventriculography and other marginally important studies, or employing intravascular ultrasound (IVUS) (but not optical coherence tomography [OCT]) to guide the percutaneous coronary intervention (PCI). Recently, some operators have demonstrated that PCI can be performed with no contrast media at all, using x-ray mapping and IVUS images alone to guide the procedure.2 While this is an exceptional demonstration, we should try to reduce contrast media in all patients and especially in those patients with impaired renal function, diabetes, or congestive heart failure.
Measuring Renal Function
The discussion of how much contrast is safe requires we use a common approach to volume limits. While we have laboratory values of creatinine and BUN, there are two preferred measures of renal function: estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCl or CC). eGFR is normalized to adult body surface area, whereas CrCl, using the Cockcroft-Gault equation, gives an estimate of actual GFR3 (Table 1). This is assessment of renal function is relevant as we compare different studies making recommendations from the ratio of contrast volume (CV) and CrCl. For example, for a patient with a CrCl of 70 cc/min, the CV/CrCl of 3 means that the patient received 3 x 70 or 210 mL of contrast. A CV/CrCl ratio of 1 in the same patient would be 1 x 70 = 70 mL contrast for his angiogram.
Studies on Contrast Volumes
Most prior studies have recommended limiting contrast to less than 3 times the estimated creatinine clearance value (CV/CrCl<3)4 (Table 2). While this is certainly an excellent guide, a number of operators have reported successful PCI using ultra-low contrast volumes, often defined as the ratio of contrast volume (CV) to the patient’s estimated creatinine clearance (CrCl) as CV/CrCl≤1.0.
Azzalini et al5 reduced contrast administration with an ultra-low dose contrast (ULC)-PCI protocol based on the pre-specification of the maximum contrast volume to be administered, IVUS, and/or dextran (not contrast media)-based OCT guidance, and use of diluted contrast media. In 111 patients, 8 had the ULC-PCI protocol used compared to 103 in the conventional group, with similar clinical and angiographic baseline characteristics. Contrast volume was markedly lower in the ULC-PCI group (8.8 mL [range, 1.3-18.5] vs 90 mL [range, 58-140 mL]; P<.001). Importantly, procedures in the ULC-PCI group included the use of rotational atherectomy, two-stent bifurcation PCI, and mechanically supported chronic total occlusion PCI. In 7 of the 8 cases, the ULC-PCI protocol was successful (contrast volume-to-eGFR ratio <1), with a marked reduction of the incidence of contrast-induced acute kidney injury (CI-AKI) (0% vs 15.5% in the ULC-PCI and conventional groups, respectively).
Of particular note, the MOZART (Minimizing cOntrast utilization with IVUS Guidance in coRonary angioplasTy) study6 demonstrated that the aggressive use of IVUS-guided PCI can dramatically reduce the contrast dose. In MOZART, 83 patients meeting the IVUS criteria underwent PCI with standard contrast reduction techniques, with or without additional IVUS-based contrast reduction techniques. The standard contrast reduction techniques were described by Nayak et al7 (Table 3). Standard contrast reduction techniques resulted in a low average contrast dose of 64 mL/procedure (compared with a historical 148 mL/procedure). Adding the IVUS-based contrast reduction techniques cut the average dose by approximately 60%, to a very low 20 mL/procedure (range of 3 to 54 mL, in 41 patients (P<.001). Concerns for the use of IVUS were its requirement for suitable anatomy and increased procedure time (14 minutes), but this seems like a small price to pay for ultra-low dose contrast volumes.
Mehran et al8 reported the use of a device designed to limit the delivery of excess contrast during angiography. The AVERT (Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial tested the efficacy of a contrast-reducing device attached to the contrast manifolds, the Avert system (Osprey Medical), to reduce the contrast media volume used during coronary angiography. The goals of the study included preserved image quality and prevention of CI-AKI in patients at risk for CI-AKI. Patients undergoing coronary angiography with planned or possible PCI were randomized to hydration plus the Avert system (n=292) or hydration only (n=286). Avert significantly reduced contrast media volume, with the extent of contrast volume reduction correlating with procedural complexity (Figure 1). No significant differences in CI-AKI were observed with Avert in this trial. Additional trials will have to determine whether the degree of contrast volume reduction as demonstrated provides clinical benefit beyond hydration alone in patients at high risk for CI-AKI requiring large contrast volume use.
Most recently, Gurm et al9 described the prevalence and outcomes associated with ultra-low contrast volume administration among 75,392 patients undergoing PCI in Michigan from July 2014 to 2017 from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium database. The distribution of CV/CrCl was divided into those with ratios of ≤1, 1-3, and >3. The ultra-low contrast volume group, CV/CrCl ≤1, comprised 13% of cases, while 68% had CV/CrCl between 1 and 3, and 18% had CV/CrCl ratios >3. The use of ultra-low volume contrast was associated with significantly lower incidence of AKI (odds ratio 0.682, P<.001) and lower need for dialysis (odds ratio 0.341, P=.003). These benefits are most evident in patients with highest baseline risk of CIN. Gurm et al9 concluded that a small but clinically significant number of patients can be treated with ultra-low contrast volume, and that these patients had significant reduction in incidence of CIN or need for dialysis. Operators should consider using a new contrast volume threshold (CV/CrCl<1.0) when performing PCI in patients at risk for CIN.
While the information of Gurm et al9 clearly identified the prevalence and potential benefit of reduced contrast administration, the data reflected practices across the entire state of Michigan and compromise the experience of both academic and community hospitals. This blending of the academic and community practices does make this study more generalizable, but limited, in that not every hospital measured renal function post-procedure systematically and that only the highest post PCI value was recorded. In real-world experience, many patients are discharged before the maximal serum creatinine is obtained and therefore, the findings may underestimate the true occurrence of AKI.
The Bottom Line — Use All Methods to Reduce Contrast Administration
We should all employ contrast reduction strategies for our patients with borderline renal function (Tables 3-4). Most labs already use low and/or iso-osmolar contrast media known to be associated with reduced nephrotoxicity. From Society of Cardiovascular Angiography and Interventions (SCAI) and other society recommendations, we should consider stopping a procedure as we approach the CV/CrCl ratio >3). Contrast volume minimization and appropriate hydration are the only evidence-based methods to reduce the incidence of CIN. Let’s go low with contrast until we find a better way to protect the patients at risk of CIN.
Disclosures: Dr. Morton Kern reports he is a consultant for Abiomed, Abbott Vascular, Philips Volcano, ACIST Medical, Opsens Inc., and Heartflow Inc.
- Kern MJ. Letter from the Editor: Contrast-induced nephropathy in the cardiac cath lab. Cath Lab Digest. 2006 Apr; 14(4). Available online at https://www.cathlabdigest.com/content/contrast-induced-nephropathy-cardiac-cath-lab. Accessed July 11, 2019.
- Ali ZA, Galougahi KK, Nazif T et al. Imaging- and physiology-guided percutaneous coronary intervention without contrast administration in advanced renal failure: a feasibility, safety, and outcome study. Eur Heart J. 2016 Oct 21; 37(40): 3090-3095.
- Cockcroft D, Gault M. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31-41.
- Mavromatis K. The imperative of reducing contrast dose in percutaneous coronary intervention. JACC Cardiovasc Interv. 2014 Nov; 7(11): 1294-1296.
- Azzalini L, Laricchia A, Regazzoli D, et al. Ultra-low contrast percutaneous coronary intervention to minimize the risk for contrast-induced acute kidney injury in patients with severe chronic kidney disease. J Invasive Cardiol. 2019 Jun; 31(6): 176-182.
- Mariani J Jr, Guedes C, Soares P, et al. Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention: the MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coronary angioplasTy) randomized controlled trial. JACC Cardiovasc Interv. 2014 Nov; 7(11): 1287-1293.
- Nayak KR, Mehta HS, Price MJ, et al. A novel technique for ultra-low contrast administration during angiography or intervention. Catheter Cardiovasc Interv. 2010 Jun 1; 75(7): 1076-1083.
- Mehran R, Faggioni, Chandrasekhar J, et al. Effect of a contrast modulation system on contrast media use and the rate of acute kidney injury after coronary angiography. JACC Cardiovasc Interv. 2018 Aug 27; 11(16): 1601-1610.
- Gurm HS, Seth M, Dixon SR, et al. Contemporary use of and outcomes associated with ultra-low contrast volume in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv. 2019 Feb 1; 93(2): 222-230.