Peripheral Arterial Interventions with Reduced Contrast Use: The Save Contrast Study

Abstract

Background

Contrast volume is a predictor of the occurrence of radiocontrast nephropathy and is associated with a high rate of in-hospital mortality and morbidity. Several strategies have been outlined to reduce contrast volume in the angiographic laboratory. Peripheral arterial endovascular procedures can be lengthy and tend to be associated with the use of high volumes of contrast. In this study, we tested specific interventions intended to reduce contrast volume in the angiographic laboratory during peripheral arterial procedures.

Materials and Methods

Fifty consecutive procedures (36 patients) who underwent peripheral arterial interventions at a single center were retrospectively reviewed for demographics, clinical, procedural, and major adverse events (MAE) immediately prior to the implementation of a prospective protocol to reduce contrast use in the angiographic laboratory (group A). Following protocol implementation, 50 additional consecutive procedures (42 patients) were prospectively enrolled (group B). The protocol required diluting contrast concentration to a 2:1 dilution for larger vessels and 3:1 for infrapopliteal vessels, the use of selective injections, digital subtraction angiography, a ruler, road mapping, and intravascular ultrasound. The primary endpoint was acute procedural success, defined as achieving <30% residual narrowing with no intraprocedural complications. A primary safety endpoint was MAE at 30 days, which included unplanned amputation, total mortality, or target lesion revascularization. Descriptive and comparative analyses were performed between the two groups.

Results

In groups A and B, 14 and 8 patients had staged procedures, respectively, and were analyzed only once for demographics and clinical characteristics. All patients were analyzed for clinical, angiographic, procedural, and 30-day outcomes. No differences were found in total treated length (mm) or chronic limb-threatening ischemia ( p  = 0.748). More chronic total occlusions were noted in group B than group A (42.3% vs. 24.2%; p  = 0.011). Residual stenosis was significantly more in group B than group A (15.4 ± 23.8% vs. 6.7 ± 6.7%, respectively; p  = 0.015). Contrast use was markedly reduced in group B versus group A (90.4 ± 61.3 cc vs. 221.2 ± 84.7 cc, respectively; p  < 0.001). MAE were similar in both groups.

Conclusion

Contrast use can be significantly reduced during peripheral arterial interventions with the implementation of a few simple measures. A statistically nonsignificant decrease in procedural success and an increase in distal embolizations and perforations were noted in the low contrast group. Larger, randomized studies are needed to determine the overall safety of this low contrast approach in peripheral arterial interventions.

Peripheral arterial disease (PAD) is highly prevalent, affecting over 12 million people in the United States. PAD is a significant marker of heightened cardiovascular events, including myocardial infarction and stroke, and significantly affects a person's quality of life. PAD can progress to limb ischemia and may lead to limb amputation.

The endovascular approach to treat PAD has increased significantly in the past several years, exceeding vascular surgical procedures. Endovascular treatment of infrainguinal arterial disease requires contrast use in the angiographic laboratory, and the amount of contrast varies significantly based on procedure complexity.

While terminology varies, contrast-associated acute kidney injury (CA-AKI) has been noted as a leading cause of iatrogenic acute kidney injury. ^{1 2 3 4 5 6} A larger volume of contrast, particularly in high-risk groups such as diabetics and those with chronic kidney disease, may lead to CA-AKI. Other risk factors include hypertension, heart failure, and critical or acute limb ischemia. Predisposing factors to injury include perioperative hypotension, volume depletion, anemia, and simultaneous exposure to other nephrotoxins. Although the need for renal replacement is rare (1–4%), the incidence of CA-AKI can be as high as 20 to 30% in high-risk patients. ⁷ A low or iso-osmolar dye, and lower volume of contrast have been associated with reduced risk of injury. ^{8 9 10 11} Pre- and postexposure intravenous hydration with isotonic saline is likely to be the best strategy to reduce the risk of AKI. ^{12 13}

The purpose of this study is to test the hypothesis that simple measures can be implemented in the angiographic suite to reduce contrast volume use during peripheral arterial interventions without compromising the acute procedural results or increasing the major adverse events (MAE) at 30 days.

Materials and Methods

This is a retrospective single-center, single-operator study that included an initial chart review from 50 consecutive procedures (36 patients) prior to implementing a protocol to reduce contrast use. Fifty prospective consecutive procedures (42 patients) were then enrolled following an imaging acquisition protocol intended to reduce the utilization of contrast. Follow-up assessments occurred at predischarge from the hospital and at 30 days following the study procedure.

Renal insufficiency was defined as a creatinine of 1.5 mg/dL or higher or a glomerular filtration rate (GFR) of less than 60 mL/minute/1.73 m ² . The peripheral artery calcification scoring system was utilized to define the degree of angiographic calcium in the treated arteries.

The primary effectiveness endpoint was acute procedural outcome, defined as achieving <30% residual narrowing at the end of the procedure with no intraprocedural complications.

The primary safety endpoint was MAE at 30 days, defined as unplanned amputation, total mortality, or target lesion revascularization (TLR) at 30 days.

Secondary outcomes included the following:

1. Use of imaging with intravascular ultrasound (IVUS).

2. In-hospital MAE rate: all-cause mortality, perforation requiring additional treatment, distal embolization requiring additional mechanical or pharmacological treatment, major bleeding as defined by the Thrombolysis in Myocardial Infarction criteria, vascular access site complications requiring transfusion and/or surgical repair, acute stent thrombosis as defined by the Academic Research Consortium, and unplanned major (above the ankle) or minor amputation.

3. Change in ankle-brachial index at 1 month.

4. Contrast amount.

5. Radiation exposure.

6. Fluoroscopic time.

7. Acute renal injury is defined as a rise in creatinine by 0.5 mg/dL on hospital discharge or a drop in creatinine clearance by 25%.

The following steps were introduced prospectively to reduce contrast use:

1. Dilution of the contrast to 1:2 for femoropopliteal arteries and 1:3 for infrapopliteal arteries.

2. Digital subtraction angiography for all infrapopliteal arteries.

3. Selective injection of the infrapopliteal arteries.

4. Use road mapping.

5. Substitute imaging with IVUS to define the proximal and distal ends of lesions and define the vessel size more accurately, and the initial choice of treatment strategy. The use of IVUS was not mandated.

6. Use rulers to mark diseased segments.

Patients were hydrated in the angiographic laboratory during the procedure with intravenous normal saline ranging from 500 to 750 mL and followed with intravenous hydration postprocedure with normal saline at 125 mL/hour for 4 to 5 hours.

All patients who underwent infrainguinal peripheral arterial interventions were enrolled consecutively. All patients received diagnostic computed tomographic angiography preprocedure as a routine practice by the operator. None of the patients received diagnostic angiography or intervention with CO ₂ .

Adverse events were classified as follows:

–MAE:

1. In-hospital MAE rate: all-cause mortality, perforation requiring additional treatment, distal embolization requiring additional mechanical or pharmacological treatment, major bleeding as defined by the Thrombolysis in Myocardial Infarction criteria, vascular access site complications requiring transfusion and/or surgical repair, acute stent thrombosis as defined by the Academic Research Consortium, and unplanned major or minor amputation.

2. MAE rate at 30 days: defined as major or minor unplanned amputation of the treated limb, vascular access site complications requiring transfusion and/or surgical repair, all-cause mortality, acute thrombosis, or clinically-driven target vessel revascularization.

3. Unanticipated or unexpected adverse device effects: any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the protocol or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Statistical Analysis

Analysis was performed per patient, per procedure, and per lesion. Descriptive analysis on all variables was done. Continuous data were presented as mean ± standard deviation (median); Categorical data were given as count/sample (percentage). The Anderson–Darling test was used to test for normality. The Levene test is used to test for equal variances. Kruskal–Wallis test, one-sample and two-sample t -test, and Fisher's exact test were used where appropriate. Statistical significance was determined by a p -value < 0.05. Software used was Minitab 21 (State College, PA) and Cytel Studio 12 (Cambridge, MA).

Results

Fifty consecutive procedures were retrospectively enrolled at baseline and 50 following the implementation of the contrast reduction protocol. In groups A and B, 14 and 8 patients had staged procedures, respectively, and were analyzed only once for demographics and clinical characteristics ( Table 1 ). All patients were analyzed for clinical, angiographic, procedural, and 30-day outcomes ( Tables 2 and 3 ). There were 36 unique patients in the control group (group A) and 42 in the postprotocol group (group B). There were 51 and 54 legs with 79 and 97 lesions in the pre- and postprotocol groups, respectively.

Table 1. Clinical and demographic variables.

	n	Control	n	Per protocol	p -Value
		Mean/percent		Mean/percent
Age (y)	36	73.8 ± 10.1	42	73.9 ± 9.9	0.9120
Body mass index	36	27.8 ± 5.4	42	28.4 ± 7.4	0.6810
Ankle brachial index	28	0.72 ± 0.21	36	0.60 ± 0.23	0.1480
Males	20/36	55.6%	19/42	45.2%	0.3640
Smoking
Never (%)	4/36	11.1%	9/42	21.4%	0.4002
Former (quit >3 mo; %)	11/36	30.6%	9/42	21.4%
Current (%)	21/36	58.3%	24/42	57.1%
Coronary artery disease	19/36	52.8%	19/42	45.2%	0.5070
Race
White	35/36	97.2%	39/42	92.9%	0.1663
Black	0/36	0%	3/42	7.1%
American Indian	1/36	2.8%	0/42	0.0%
Renal insufficiency	22/36	61.1%	23/42	54.8%	0.5720
History of amputation	32/36	88.9%	38/42	90.5%	0.9075
	2/36	5.6%	3/42	7.1%
	1/36	2.8%	1/42	2.4%
	1/36	2.8%	01/42	0.0%
Cerebrovascular disease
No	34/36	94.4%	35/42	83.3%	0.3687
Yes, stroke	1/36	2.8%	4/42	9.5%
Yes, TIA	1/36	2.8%	3/42	7.1%
Hypertension	35/36	97.2%	41/42	97.6%	1.000
Hypercholesterolemia	35/36	97.2%	41/42	97.6%	1.000
Diabetes	16/36	44.4%	17/42	40.5%	0.7240
Rutherford category
III	27/36	54.0%	25/42	50.0%	0.7476
IV	12/36	24.0%	16/42	32.0%
V	9/36	18.0%	8/42	16.0%
VI	0/36	0.0%	1/42	2.0%
Missing	2/36	4.0%	0/42	0.0%

Table 2. Angiographic and procedural variables.

	n	Control	n	Per protocol	p -Value
		Mean/percent		Mean/percent
Procedure time (min)	50	75.7 ± 33.8	50	100.5 ± 61.2	0.077
Total fluroscopy time (min)	50	25.1 ± 13.8	50	37.4 ± 29.4	0.128
Total contrast (cc)	50	221.2 ± 84.7	50	90.4 ± 61.3	0.000
Radiation used: cumulative air kerma (mGray)	49	214.8 ± 165.3	50	272.7 ± 248.1	0.278
Radiation used: DAP (Gy/cm 2 )	39	52.1 ± 41.3	30	62.5 ± 48.9	0.250
Chronic total occlusion (%; per lesion)	19/79	24.1%	41/97	42.3%	0.182
Type of contrast
Omnipaque	13/50	26.0%	14/50	28.0	1.000
Visipaque	36/50	72.0%	36/50	72.0
Isovue	1/50	2.0%	0/50	0.0
Number of lesions treated
1	51/79	64.6%	50/97	51.5%	0.0894
2	22/79	27.8%	27/97	27.8%
3	5/79	6.3%	15/97	15.5%
4	1/79	1.3%	5/97	5.2%
Intravascular ultrasound during the procedure
Yes	20/50	40.0	29/50	58.0	0.087
No	29/50	58.0	21/50	42.0
Missing	1/50	2.0%	0/50	0.0
Calcium (%; per lesion)
Grade 0	0/79	0.0%	1/97	1.0%	0.000
Grade 1	2/79	2.5%	9/97	9.3%
Grade 2	6/79	7.6%	27/97	27.8%
Grade 3/4	17/79	21.5%	49/97	50.5%
Not reported	54/79	68.4%	11/97	11.3%

Table 3. Outcomes.

	n	Control	n	Per protocol	p -Value
		Mean/percent		Mean/percent
Procedural/in-hospital
Procedural success (per lesion)	79/79	100.0%	87/97	89.7%	0.062
Debris in the filter	17/30	56.7	2/2	100	0.345
Distal embolization/perforation
Distal embolization	1/50	2.0%	2/50	4.0%	0.236
Perforation	0/50	0.0%	3/50	6.0%
Dissections
0	46/50	92.0%	45/50	90.0%	0.237
Type A	1/50	2.0%	2/50	4.0%
Type D	3/50	6.0%	3/50	6.0%
Major amputations	0/50	0.0%	0/50	0.0%	NA
Mortality	0/36	0.0%	0/42	0.0%	NA
Major bleeding (per procedure)	0/50	0.0%	0/50	0.0%	NA
Pseudoaneurysm	0/50	2.0%	0/50	0.0%	NA
Change in GFR pre- and postintervention (within 1–6 d postprocedure)		Preprocedure		Postprocedure
Control retrospective group A		52.31 ± 22.28		57.22 ± 21.9
Per protocol, prospective group B		57.41 ± 18.45		69.29 ± 19.71
Postdischarge minus predischarge A vs. B		4.91 ± 7.10		11.88 ± 6.47	0.006
30-d
TLR	0/50	0.0%	0/50	0.0%	NA
Unplanned major amputation of to target limb	0/50	0.0%	0/50	0.0%	NA
Mortality	0/36	0.0%	1/42	2.4%	NA
ABI @30-d minus ABI @baseline	11	0.21 ± 0.29	16	0.38 ± 0.28	0.144

Abbreviations: ABI, ankle brachial index; GFR, glomerular filtration rate; TLR, target lesion revascularization.

The ages in groups A and B were 73.8 ± 10.1 and 73.9 ± 9.9 years, respectively. 55.6% (20/36) and 45.2% (19/42) were males, respectively. In group A, two patients had a history of minor amputation to the target leg (5.6%), one minor amputation to the nontarget leg (2.8%), and one major amputation to the nontarget leg (2.8%). The postprotocol group had three (7.1%), one (2.4%), and zero (0.0%), respectively. 8.3% of patients in group A were on dialysis and 2.4% in group B ( Table 1 ).

Furthermore, there was a significant difference in the calcification of the lesion between pre- and postprotocol, with more moderate to severe calcium seen in group B ( p  < 0.0005). In addition, more chronic total occlusions were present in group B versus group A (42.3% vs. 24.1%, respectively; p  = 0.0110; Table 2 ). Filters were initially used more frequently in our laboratory and quite often in more complex disease and atherectomy (group A). However, this practice changed subsequently, with filter use markedly reduced given the lack of cost-effectiveness data on their use (group B).

The median amount of contrast used in group A was 221.2 ± 84.7 cc and in group B was 90.4 ± 61.3 cc ( p  < 0.0005). There was no difference in the GFR between the two groups. Both baseline lesion stenosis (80.0% vs. 85%, p  = 0.0210) and final lesion assessment residual stenosis (5.0% vs. 10.0%, p  = 0.0150) were significantly different between group A and B, respectively ( Table 2 ). Group B also had three perforations requiring additional treatment and three type D dissections, whereas Group A had no perforations and three type D dissections. Finally, one patient died in Group B on day 3 from atherosclerotic cardiovascular disease, unrelated to the procedure ( Table 3 ). In the subgroup of patients with chronic total occlusions, group A had one distal embolization and three different dissections, and group B had two perforations, one distal embolization, and two type D dissections.

At the 30-day follow-up, one patient in group A had leg cellulitis. In group B, there was one patient who had a planned amputation. Sixteen patients in group A and 17 patients in group B had GFR between days 1 and 6 postprocedure. There was no significant difference in the median creatinine between the two groups (1.08 vs. 0.9 mg/dL; group A vs. group B, respectively; p  = 0.5640). There was no significant difference in the mean GFR at baseline versus postdischarge within each group. However, a significantly higher GFR difference from baseline to postprocedure was seen in group B when compared with group A (11.88 ± 6.47 vs. 4.91 ± 7.10, p  = 0.006; Table 3 ). There were no patients in either group who dropped more than 25% from the baseline to postdischarge.

Discussion

The administration of contrast during imaging or endovascular procedures is associated with AKI, particularly when administered in higher volumes. Currently, preventative treatment to reduce this risk is to minimize the volume of contrast administered and the administration of intravenous hydration with 0.9% normal saline prior to and after the procedure. Other interventions, such as intravenous sodium bicarbonate and oral acetylcysteine, did not show superiority to IV normal saline. ¹⁴

Peripheral arterial procedures can be complex and may require a significant amount of contrast. In this study, we demonstrated that simple steps during the procedure can significantly reduce the amount of contrast administered. Despite a more complex anatomy in group B (CTO, severe calcium) treated under the protocol, a smaller amount of contrast was administered with statistically similar acute procedural outcome and no difference in the 30-day outcome of the patients. The numerically higher perforations and distal embolizations can be attributed to the complexity of the disease treated. It should be noted that the study is not powered to assess mortality or amputation rates at 30 days. Also, the procedural success was numerically lower in group B, and therefore a larger number of patients is needed to determine with certainty the true significance of this difference and whether low contrast volume use was a contributory factor.

There were no differences in GFR postprocedure between the two groups. The overall rate of AKI was low, the number of patients enrolled was small, and the follow-up was limited, all contributing factors to the lack of difference in the GFR between the two groups. Furthermore, although a nonsignificant trend toward a higher postprocedure GFR was seen in both groups when compared with preprocedure, the difference in GFR between pre- and postprocedure was significantly higher in group B when compared with group A ( Table 3 ). It is possible that this finding is secondary to chance or variation in the amount of hydration postprocedure. However, a lower amount of contrast in group B, and therefore less osmotic diuresis, may have accounted for this difference, with higher retention of hydration postprocedure.

Previous studies have shown that the use of lower iodinated contrast concentrations during endovascular interventions did not compromise image quality, which remained diagnostic. ¹⁵ The dilution of contrast volume in our study does yield a lower iodine concentration with statistically no apparent compromise to safety. Numerically higher perforations and distal embolizations were seen in the low contrast group, but this could be explained by the complexity of disease treated in this cohort, although the contribution of low contrast to these events cannot be totally excluded without a larger randomized trial. Several alternative imaging methods have been proposed to reduce contrast during interventions, including CO ₂ angiography. Although the latter can provide adequate imaging for larger proximal arteries, it is generally suboptimal for distal, smaller vessels. ¹⁶ Furthermore, zero-contrast interventions were carried on with IVUS and/or duplex ultrasound ^{17 18} but more data are needed to validate this approach. In this study, the addition of IVUS to low contrast appears to be a promising approach with the addition of precision imaging to low contrast angiography.