Reduction in Contrast Nephropathy From Coronary Angiography and Percutaneous Coronary Intervention With Ultra-Low Contrast Delivery Using an Automated Contrast Injector System

Abstract: Objective. To evaluate the incidence of contrast-induced nephropathy (CIN) following coronary angiography and percutaneous coronary intervention (PCI) utilizing a novel ultra-low contrast delivery (ULCD) technique. Background. Current techniques for reducing contrast volumes during angiographic and PCI procedures require the use of advanced coronary imaging methods, such as intravascular ultrasound and coronary flow wires. We propose the use of the ACIST CVi automated contrast injector system (Bracco Diagnostics) with a novel programming technique that significantly reduces contrast volumes and CIN development. Methods. From 2013 to 2014, a total of 123 patients with stage III or higher chronic kidney disease (CKD) underwent coronary angiography, PCI, or a combined procedure using the ULCD technique. A retrospective analysis was conducted to evaluate contrast volumes and rate of CIN development. Patients developing CIN were compared using tests of proportions. Results. The median contrast volume was 17.9 mL (n = 123). The study cohorts comprised diagnostic (15.2 mL; n = 72), PCI (17.1 mL; n = 30), and PCI + diagnostic groups (27.9 mL; n = 21). The incidence of CIN observed in the entire cohort through day 7 was 3.3% (4/123). Seventy-five percent of the CIN cases occurred following diagnostic angiography alone. Longitudinal follow-up at 21 days identified an additional 5 cases of CIN. Compared to literature data, the ULCD technique delivers less contrast per case. Conclusion. The adaptation of the ULCD technique for coronary procedures significantly reduces contrast volume delivery when compared with conventional practice or previously described low-contrast techniques. The ULCD appears to be an efficacious method of limiting CIN development in a susceptible population with CKD.

J INVASIVE CARDIOL 2016;28(11):446-450. Epub 2016 July 15.

Key words: contrast nephropathy, CIN, percutaneous coronary intervention

Contrast-induced nephropathy (CIN) is caused by intravascular iodinated contrast exposure. The contemporary definition is a >25% relative increase or an absolute increase of >0.5 mg/dL in serum creatinine at 48-72 hours following contrast exposure.¹ However, observational data from diagnostic angiography suggest that the peak creatinine rise occurs between 3-6 days following contrast exposure.^1,2De novo CIN development is associated with adverse clinical outcomes, including increased mortality, subsequent cardiovascular events, prolonged hospitalization, and progression to end-stage renal disease.^2-4 CIN is the third leading cause of acute kidney injury in hospitalized patients, representing 14% of cases.^5,6 

Patients with renal failure who require coronary procedures are particularly vulnerable, with CIN incidence often exceeding 15% when using conventional angiographic techniques.⁷ Although numerous therapies have been tested to avert CIN development, the only successful preventative strategies have involved either aggressive fluid administration, the use of iso-osmolar/non-ionic contrast media, or a contrast volume reduction to a volume to creatinine clearance ratio of <3.7.^8,9

The ultra-low contrast delivery (ULCD) technique was implemented into clinical practice in 2006 at the Sanford Cardiovascular Institute in South Dakota. This protocol was subsequently described in 2010.¹⁰ It is a relatively simple and time-efficient procedure that any technician and cardiologist can perform. We evaluated the patient demographics, total contrast use during angiographic and percutaneous coronary intervention (PCI) cases, and the CIN development rate in consecutive patients with preexisting renal disease in whom this technique was employed between 2013 and 2014.

Methods 

The automated contrast injector system (ACIS) has been used at our institution since 2006. Between January 2013 and February 2014, a total of 160 patients with ≥ stage III chronic kidney disease (CKD) undergoing diagnostic coronary angiography and PCI were treated using the ULCD technique administered with the ACIST CVi device (Bracco Diagnostics). Thirty-seven patients already undergoing dialysis were subsequently excluded. This CKD cohort was chosen to evaluate the effect of ultra-low contrast volumes on CIN development rates. Informed written consent was obtained. The data were obtained retrospectively through electronic medical records review. 

All patients received 3-4 hours of preprocedure and postprocedure intravenous saline hydration (1 cc/kg/hr). All angiographic procedures were performed using non-ionic, iso-osmolar, iodine-based contrast media. The quality of imaging was deemed adequate in all cases by the experienced interventional cardiologists. Creatinine measurements and glomerular filtration rate (GFR) calculations were obtained at baseline and at 3, 7, and 21 days post procedure. GFR was calculated using the modification of diet in renal disease (MDRD) equation. Total volumes of contrast were recorded for diagnostic, PCI, or PCI + diagnostic coronary angiographic procedures. The observed incidence of CIN and its correlation with contrast volumes was examined. Increases in serial values of serum creatinine by magnitudes of 25% over baseline or an absolute increase of 0.5 mg/dL was considered significant. CIN was considered to have occurred if a significant creatinine change was present within the first week following the angiographic procedure.

Statistical methods. Data were examined for unusual values. Proportions of cases developing CIN in various conditions were calculated and confidence intervals obtained using normal approximation to the binomial distribution. Tests of proportions were used to compare the low and normal groups for development of CIN. Logistic regression was used to examine factors considered to be of importance in the development of CIN in a multivariate test. All analyses were performed with SAS v. 9.4.

ULCD technique summary. The successful implementation of our ULCD technique (defined as ≤15 cc) is dependent upon six key elements (Table 1). 

The use of an ACIS protocol for contrast delivery leads to the minimization of contrast exposure without sacrificing angiographic quality.¹⁰ The ACIS programming protocols are shown separately for the left coronary artery (Figure 1) and the right coronary artery (Figure 2).¹¹ The protocol for the left coronary artery requires the assessment of both the artery size (divided into large, average, and small) and assessment of flow (characterized as brisk or medium/slow flow). This is initially accomplished using a small-volume injection of 0.5 mL, referred to as the “spill over.” Once the arterial size and flow have been characterized, the ACIS programming settings for the two subsequent diagnostic injections can be derived from the protocol figure. Settings are provided in the following sequence: volume (mL); flow (mL/s); rise time (s); and pressure (psi). The spill-over technique is imaged with single-plane fluoroscopy and the subsequent diagnostic injections with biplane cineography starting with caudal and finishing with cranial projections. Imaging the right coronary artery also starts with the spill-over technique; however, the diagnostic component is accomplished using only a single contrast injection with biplane imaging in the straight left anterior oblique and cranial right anterior oblique views. 

Results

After screening cases, a total of 123 patients were identified who fulfilled the research criteria and had undergone either a diagnostic, PCI, or PCI + diagnostic angiogram during the defined study period. Of these patients, none had developed a significant increase in serum creatinine within 72 hours of an angiographic procedure. Only 4 out of 123 patients (3.3%) were identified in the cohort who had a CIN-defining increase in GFR within 7 days. An additional 5 out of 123 patients (4.1%) developed CIN by the end of week 3. The incidence of CIN during the total 30-day follow-up period was 7.3% (9 out of 123). Interestingly, 5 out of 9 patients (55%) with a CIN-defining illness by week 3 had undergone a diagnostic angiogram alone (Figure 3). 

Logistical regression did not identify any significant increased risk of CIN development associated with variations in demographics or biomorphologic characteristics (Table 2).

Median contrast volumes were low in the diagnostic (15.2 cc; n = 72), PCI (17.1 cc; n = 30), and PCI + diagnostic cohorts (27.9 cc; n = 21) (Table 3). Procedural access site, whether through the groin or radial artery, did not significantly affect the averaged contrast volume delivered (groin, 18 mL; radial, 17 mL) (Table 2).

Discussion

The use of an ACIS programming protocol facilitates the delivery of ultra-low contrast volumes during both diagnostic and interventional coronary procedures. Limitation in contrast exposure substantially reduces the development of CIN in at-risk populations.^7,11,12 There is a predisposition to developing this syndrome in patients with co-morbid conditions (eg, diabetes, heart failure, age >70 years, hemodynamic instability, and stage III-IV CKD).^13-15 Of these, preexisting renal disease has the most unfavorable prognosis with the development of CIN, conferring a 14.9% hospital mortality rate and 27.5% requirement for dialysis.^16,17

The minimization of contrast use during coronary imaging has been used with increasing prevalence in angiography suites. One recent meta-analysis suggests that when compared with hand injection technique, ACIS use is associated with a 15% decrease in CIN and a 45 mL relative reduction in contrast volumes.¹⁸ Another technique has been described that limits contrast volume to 15 mL. However, this technique utilizes hand injectors and requires the use of intravascular ultrasound (IVUS).⁷ More recently, the MOZART trial demonstrated promising outcomes, confirming that contrast limitation decreased the incidence of CIN development.¹² However, this technique also required the use of IVUS. In contrast, our ULCD technique requires only catheter modification and ACIS specific programming.¹¹ This approach appears to be more time efficient, reproducible, easy to follow by technicians, and available to non-interventional cardiologists, who are not trained in the use of IVUS. 

Compared with conventional diagnostic angiography or PCI, contrast volumes for our ULCD technique and CIN development rates are significantly lower. Our data also support a previous observation that CIN development may exhibit a lag-time effect, occurring outside of the currently defined 72 hour post contrast window with peak incidence occurring at 7-21 days.⁷ 

The ULCD technique has effectively reduced the contrast volume delivered to patients during angiographic procedures. We continue to successfully utilize this protocol and limit contrast exposure to patients with the highest risk of developing CIN. Our protocol effectively reduces the development of CIN and contrast volumes when compared with a previously described low-contrast volume protocol applied to patients with CKD.⁷ One major advantage to our technique is that the ACIS programming protocol is standardized and can be easily utilized by other institutions. 

Study limitations. The limitations of our study include its retrospective nature and localization to a single cardiovascular center. Furthermore, the quality of angiographic images produced using this technique was judged by the two interventional cardiologists who developed this technique, not by a core laboratory. Finally, although our study suggests that contrast volume limitation leads to a minimization of CIN development, further multicenter prospective trials are required to prove concept and demonstrate reproducibility of this technique. 

Conclusion

The ULCD technique using an ACIS device is an effectual means of limiting contrast delivery during coronary angiography and PCI. It can be implemented for both groin and radial approaches without significantly increasing the averaged delivered contrast volume. It appears to decrease CIN in a high-risk patient population with CKD and should be considered for study and adaptation into future catheterization protocols. 

References

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From the Departments of ¹Cardiology and ²Biostatistics, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted March 18, 2016, provisional acceptance given April 19, 2016, final version accepted May 3, 2016.

Address for correspondence: Dr Adam Stys, 1301 West 18th Street, Route 6004, Sioux Falls, SD 57105. Email: Adam.Stys@Sanfordhealth.org