Procedural Strategies to Reduce the Incidence of Contrast-Induced Acute Kidney Injury During Percutaneous Coronary Intervention

JACC: CARDIOVASCULAR INTERVENTIONS

VOL.

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ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

STATE-OF-THE-ART REVIEW

Procedural Strategies to Reduce the Incidence of Contrast-Induced Acute Kidney Injury During Percutaneous Coronary Intervention Marcel Almendarez, MD,a,b Hitinder S. Gurm, MD,c José Mariani, JR, MD,d,e,f Matteo Montorfano, MD,a Emmanouil S. Brilakis, MD, PHD,g Roxana Mehran, MD,h Lorenzo Azzalini, MD, PHD, MSCa

ABSTRACT Contrast-induced acute kidney injury (CI-AKI) is a potentially serious complication following coronary angiography and percutaneous coronary intervention (PCI). The incidence of CI-AKI is particularly high in patients with advanced chronic kidney disease (defined as an estimated glomerular filtration rate <30 ml/min/1.73 m2). Although much effort has been dedicated to the identification and implementation of preventive measures for this complication at the pre-intervention stage, much less has been investigated on the procedural strategies and techniques to decrease the risk of CI-AKI during PCI. The mainstay of such approaches relies on the minimization of contrast volume by means of specific strategies or dedicated devices. Invasive imaging, such as intravascular ultrasound or non–contrast-based optical coherence tomography, is another pillar of any ultra-low-contrast-volume PCI protocol. Finally, an array of miscellaneous ancillary measures can be implemented to decrease the risk of CI-AKI, which includes the use of radial access, remote ischemic conditioning, and hemodynamic support in high-risk patients. The present review analyzes the technical aspects as well as the scientific evidence supporting these novel techniques, with the goal to improve the outcomes of patients at high risk for CI-AKI undergoing PCI. (J Am Coll Cardiol Intv 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.

From the aInterventional Cardiology Division, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy; b

Interventional Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; cDivision of Cardiovascular

Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; dDepartment of Interventional Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; eHospital Israelita Albert Einstein, São Paulo, Brazil; fSanta Casa de São Paulo, São Paulo, Brazil; gCenter for Advanced Coronary Interventions, Minneapolis Heart Institute, Minneapolis, Minnesota; and the hInterventional Cardiovascular Research and Clinical Trials, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Gurm received honoraria for consulting from Osprey Medical; and research funding from the National Institutes of Health and Blue Cross Blue Shield of Michigan. Dr. Brilakis received consulting/speaker honoraria from Abbott Vascular, the American Heart Association (associate editor of Circulation), Boston Scientific, Cardiovascular Innovations Foundation (board of directors), CSI, Elsevier, GE Healthcare, InfraRedx, and Medtronic; research support from Regeneron and Siemens; is a shareholder of MHI Ventures; and is on the board of trustees of the Society of Cardiovascular Angiography and Interventions. Dr. Mehran has received institutional research grant support from The Medicines Company, Bristol Myers-Squibb, AstraZeneca, Abbott Vascular, Bayer, Beth Israel Deaconess, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich, Osprey Medical, PLC/Renal Guard, and Lilly/Daiichi Sankyo; is on the advisory board for Janssen (Johnson & Johnson), Medtelligence, and PLx Opco/PLx Pharma; serves on a data and safety monitoring board for Watermark Research Partners; and has received consulting fees and honoraria from Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Medscape/WebMD, Siemens Medical Solutions, Philips/Volcano/Spectranetics, Roivant Sciences, Sanofi, Bracco Group, Janssen (Johnson & Johnson), and Merck. Dr. Mehran’s spouse is a consultant for Abiomed and The Medicines Company. Dr. Azzalini has received honoraria from Abbott Vascular, Guerbet, Terumo, and Sahajanand Medical Technologies; and research support from ACIST Medical Systems, Guerbet, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received February 25, 2019; revised manuscript received April 4, 2019, accepted April 23, 2019.

ISSN 1936-8798/$36.00

https://doi.org/10.1016/j.jcin.2019.04.055

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ABBREVIATIONS

DEFINITION, EPIDEMIOLOGY, AND

AND ACRONYMS

AIM OF THE REVIEW

CKD = chronic kidney disease CI-AKI = contrast-induced

Contrast-induced

acute

kidney

HIGHLIGHTS

injury

(CI-AKI) is defined as the development

acute kidney injury

of

CM = contrast media

acute

kidney

injury

(AKI)

following

contrast media (CM) administration, in the

CV = contrast volume

absence of an alternative etiology (1). There

CV/CrCl = contrast-volume-tocreatinine-clearance

eGFR = estimated glomerular filtration rate

are

several

definitions

for

CI-AKI,

but

currently one of the most widely adopted is the Kidney Disease Improving Global Outcomes definition: an increase in serum

IVUS = intravascular

creatinine by $0.3 mg/dl within 48 h after

ultrasound

MARCE = major adverse renal

CM exposure, or an increase to $50% within

and cardiovascular events

7 days (2).

OCT = optical coherence

The incidence of CI-AKI in patients un-

tomography

dergoing percutaneous coronary interven-

OR = odds ratio

tion (PCI) shows ample variations (3.3% to

PCI = percutaneous coronary

14.5%) (3,4). The development of CI-AKI has

intervention

been associated with worse outcomes, such as increased hospital stay and costs, irreversible kidney injury, need for dialysis, and death (1). Recently, the composite endpoint of major adverse renal and cardiovascular events (MARCE) has been proposed to account for the multifaceted nature of CI-AKI–related adverse outcomes, such as renal failure with dialysis, myocardial infarction, stroke, heart failure, renal/cardiac hospitalization, or death (5,6). Once CI-AKI is established, there is no specific treatment, hence the goal is prevention. Although much research has been conducted to identify, compare, and implement different pharmacological strategies

for

CI-AKI

prevention

at

the

pre-

procedural level (1,7), less has been investigated on nonpharmacological

procedural

strategies

to

decrease the risk of such a complication. The focus of this review is therefore to discuss the currently available

evidence

supporting

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Procedural Strategies to Reduce the Incidence of CI-AKI During PCI

these

novel


The incidence of contrast-induced acute kidney injury (CI-AKI) is particularly high (>25%) in patients with advanced chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI), and has been associated with increased risk for in-hospital dialysis and mortality.
Implementing contrast-sparing protocols may reduce the risk for CI-AKI in patients with advanced CKD undergoing coronary angiography and PCI.
Additional components of an ultra-lowcontrast-volume PCI protocol include strong reliance on intravascular imaging, device-based interventions, and ancillary measures.
Prospective (ideally randomized) studies should evaluate whether the implementation of the procedural recommendations discussed herein can lead to decreased rates of CI-AKI, need for dialysis, and mortality in high-risk patients undergoing PCI. Besides direct CM effects, there are several other procedural factors compounding the development of CI-AKI, such as embolization of atheromatous debris from the aorta during femoral catheterization (8), as well as periprocedural hypotension and bleeding, which cause ischemic kidney injury. These mechanisms alone can trigger AKI, and amplify the deleterious effects of CM, particularly in complex and high-risk PCI (7).

techniques.

RISK FACTORS FOR CI-AKI

PATHOPHYSIOLOGY OF CI-AKI

In patients with advanced chronic kidney disease (CKD), defined as an estimated glomerular filtration

The pathophysiology of CI-AKI is complex (Figure 1).

rate (eGFR) <30 ml/min/1.73 m 2, the incidence of CI-

CM induces the release of endothelin and adenosine,

AKI can be as high as 27%, and such a degree of

and a reduction in the availability of nitric oxide and

renal impairment confers a more than 3-fold increase

prostaglandins,

in the adjusted risk of CI-AKI, compared with a

which

triggers

vasoconstriction.

Furthermore, this hypoperfusion leads to hypoxia of

normal renal function (9).

the outer medulla—which is very vulnerable to

Renal hypoperfusion also plays a pivotal role, with

ischemia—and tubular cells (1,7). Moreover, CM exerts

all conditions associated with hypotension repre-

direct toxic effects on the tubular cells (osmotic

senting a risk factor for CI-AKI: cardiogenic shock,

nephrosis) and its viscosity impairs blood oxygen

acute heart failure, acute coronary syndrome, etc.

delivery at the tubular cell level. These mechanisms

(9,10). Other factors that have been consistently

trigger the release of reactive oxygen species thereby

associated with CI-AKI are advanced age (>75 years),

increasing oxidative stress (1,7).

diabetes, anemia, and low ejection fraction (1,7,10).

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F I G U R E 1 Pathophysiology of Contrast-Induced Acute Kidney Injury

Volume depletion also represents a major risk factor

PRE-PROCEDURAL STRATEGIES TO

for the development of CI-AKI, because it increases

PREVENT CI-AKI

CM concentration in the tubules and slows down its clearance (1,11). Finally, the timing between cumula-

The single most important pre-procedural measure to

tive renal injuries might play a role in the develop-

reduce the occurrence of CI-AKI is hydration before

ment

undergoing

and after the procedure. This should be based on the

coronary artery bypass graft surgery within 1 day of

intravenous administration of normal saline, because

coronary angiography have a 2-fold increase in the

no advantages have been demonstrated for other so-

risk

lutions (e.g., bicarbonate, half-normal saline) (1).

of

of

CI-AKI,

MARCE,

because

compared

patients

with

those

who

wait $5 days (6).

Also, several studies have shown that tailoring hy-

CI-AKI risk assessment is of paramount impor-

dration rate (and hence the total volume adminis-

tance in patients at increased risk for CI-AKI. This

tered) to the left ventricular end-diastolic pressure

can be performed using validated scores, such as the

(13), central venous pressure (14), or bioimpedance

one proposed by Mehran et al. (10), the Blue Cross

vector analysis (11) will lead to decreased rates of CI-

Blue Shield of Michigan Cardiovascular Collaborative

AKI, compared with a standard hydration protocol.

(BMC2) model (12), or the National Cardiovascular Data

Registry

Cath-PCI

registry

AKI

There has been a multitude of small randomized

prediction

trials showing benefit of several pharmacological

model (9), which incorporate the aforementioned

agents (e.g., N-acetylcysteine, bicarbonate, trimeta-

predictors.

zidine, fenoldopam, among others), often with large

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F I G U R E 2 Procedural Strategies to Reduce Contrast Volume

(A) Impella-assisted left anterior descending (LAD) chronic total occlusion (CTO) PCI. (a) LAD CTO from a previous angiogram (red circle). (b) Engagement of the left main coronary artery using a wire, avoiding test injections. (c) Final angiogram obtained using 50%-diluted contrast media. (B) Comparison of coronary angiograms performed with (a) undiluted and (b) 50%-diluted contrast media. (C) StentBoost Enhanced Visualization Software (Philips) stent enhancing technology. (D) Metallic roadmapping. To provide geographic identification of the (a) area of interest (red circle), (b) a wire was advanced into the marginal branch. (E) Dynamic Coronary Roadmap (Philips). (a) LAD CTO (red circle). (b) An electronic silhouette of the left coronary is created by the software upon first contrast injection, which guides subsequent wiring.

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F I G U R E 3 Intravascular Imaging to Guide Ultra-Low-Contrast-Volume PCI

(A) Zero-contrast percutaneous coronary intervention (PCI) using intravascular ultrasound (IVUS) guidance. (a) In-stent restenosis on the proximal left anterior descending (red circle; from a previous angiogram). (b) IVUS is performed, (c) showing stent underexpansion. (d) Final result after cutting and drug-eluting balloon angioplasty, with good stent expansion and minimal stent area (MSA). (B) Dextran-based optical coherence tomography (OCT) to guide an ultra-low-contrast-volume PCI. (a) Distal left main bifurcation disease involving both branches (red circle; from a previous angiogram). (b) OCT is performed using dextran to flush blood, (c) showing severely calcified disease. (d) Final OCT result after rotational atherectomy and stent deployment, displaying good stent expansion and MSA.

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C E NT R AL IL L U ST R AT IO N Measures to Decrease the Risk of CI-AKI Before and During PCI

Almendarez, M. et al. J Am Coll Cardiol Intv. 2019;-(-):-–-. CI-AKI ¼ contrast-induced acute kidney injury; FFR ¼ fractional flow reserve; iFR ¼ instantaneous wave-free ratio; IVUS ¼ intravascular ultrasound; OCT ¼ optical coherence tomography.

effect sizes attributable to alpha error or imbalanced

and patients with acute coronary syndrome [16]),

randomization. When subjected to large randomized

periprocedural administration of rosuvastatin led to a

clinical trials, every agent tested to date has failed to

relative decrease of up to 62% in the risk of devel-

prevent CI-AKI (7). The only exception is represented

oping CI-AKI, compared with standard of care.

by potent statins (mainly rosuvastatin) immediately

Finally, if PCI is planned, it is ideal to discontinue

before and after CM exposure. Due to their pleiotropic

any potentially nephrotoxic medications at least 48 h

effects, statins act as stabilizers of the renal vascular

before exposure to CM (1,7).

endothelium, enhancing nitric oxide production; they also reduce endothelin secretion, and have antioxi-

PROCEDURAL STRATEGIES TO

dant, anti-inflammatory, and antithrombotic effects.

PREVENT CI-AKI

In 2 randomized controlled trials including patients undergoing coronary angiography and PCI at high-

Strategies to reduce the risk of CI-AKI during

risk for CI-AKI (subjects with diabetes and CKD [15],

PCI are outlined in Figure 2, Figure 3, and in

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Procedural Strategies to Reduce the Incidence of CI-AKI During PCI

to reduce CV while maintaining acceptable image

T A B L E 1 Contrast-Sparing Strategies for PCI

quality (21). Numerous other “tricks” can be utilized

Use 5-F catheters with no side holes for coronary angiogram

to minimize CV during diagnostic angiography and

Display previous coronary angiograms on cath lab monitors (if available) to avoid acquiring new diagnostic images

PCI (Table 1, Figure 2) (20,21), which include, among others, using previous angiograms as reference, using

Use biplane angiography Limit the volume of contrast per injection (ideally, 2 ml/injection) Use diluted contrast media Test injections should be avoided:
Enter coronary artery ostium with guidewire to confirm guiding catheter engagement
If unable to wire side branches, use intravascular ultrasound in live-view mode Use stent enhancement techniques (e.g., StentBoost [Philips, Best, the Netherlands], ClearStent [Siemens Healthcare, Erlangen, Germany]) Use increased acquisition rates (15 or 25 frames/s) to improve image quality during diagnostic angiogram and to evaluate the final result

biplane angiography and stent-enhancing technology, wiring key side branches to create a metallic roadmap, and maximizing the use of intravascular imaging. Dedicated devices to reduce overall CV have been developed. The DyeVert PLUS system (Osprey Medical, Minneapolis, Minnesota) is a device that is connected

between

the

injection

syringe

and

the

manifold via a 4-way stopcock, allowing diversion of excess contrast during manual injection. The fraction of CM that would not contribute to coronary opacification, but rather would reflux into the aortic root, is

Allow for elimination of contrast from guiding catheter by backbleeding or aspirating before entering equipment

diverted into a reservoir chamber. In a recent trial

Use additional guidewires to create a roadmap of the target vessel and its side branches, or use dedicated software (e.g., Dynamic 3D Roadmap, Philips)

angiography and/or PCI were randomized to the

(22), 587 high-risk patients undergoing coronary DyeVert system or standard of care. Mean eGFR was

Extensive use of intravascular ultrasound, dextran-based optical coherence tomography, and coronary physiology testing

45.6 ml/min/1.73 m 2 in both groups. Patients in the

In zero-contrast PCI, perform a transthoracic echocardiogram to look for pericardial effusion, before and after the procedure

CV (85.6  50.5 ml vs. 101.3  71.1 ml; p ¼ 0.02). There

DyeVert system arm had a 15.5% relative reduction of were no differences in the rates of CI-AKI, which

PCI ¼ percutaneous coronary intervention.

might have been related to the small difference in CV between the 2 arms. Simulation studies have sug-

the Central Illustration. It is fundamental that explicit consideration about CI-AKI risk be made during the pre-procedural “time-out,” so that all health care professionals involved in the case are aware of the issue and appropriate measures are taken. This involves mentioning the patient’s eGFR, type of CM and % of dilution, intravascular imaging modality used, and the maximum contrast volume (CV) allowed (in case of ultra-low-contrast-volume PCI). Therefore, a team effort and meticulous procedural planning are required to minimize the risk of CI-AKI.

pronounced dysfunction.

its with

deleterious increasing

A

effects degrees

(12). The next-generation DyeVert system was evaluated in a multicenter single-arm pilot study, in which up to 40% of CV was saved (p < 0.0001) (23). Future research is needed to assess whether this reduction in CV translates into clinically meaningful benefit. Another approach to excess contrast removal is represented by coronary sinus aspiration immediately following contrast injection. A nonrandomized study in 43 diabetic patients with CKD undergoing sheath and standard of care (24). With each contrast injection, aspiration was simultaneously performed.

The volume of CM is proportional to the risk of CI-AKI and

needed to demonstrate clinically meaningful benefits

PCI compared coronary sinus aspiration with an 8.5-F

CM REDUCTION STRATEGIES

(4,17),

gested that larger reductions in CV (>30%) will be

are

more

of

renal

contrast-volume-to-creatinine-

clearance (CV/CrCl) ratio >2 has been identified as an independent predictor of CI-AKI in patients with an eGFR <30 ml/min/1.73 m2 (18). In such a patient population, a CV/CrCl <1 is ideal to minimize the risk for CI-AKI (19,20) and has thus been identified as

CV aspirated was 34  16 ml, which constituted 39  10% of the total CV administered. The CI-AKI rate was lower in the coronary sinus aspiration group (5.5% vs. 36%; p ¼ 0.03). However, eGFR and CV/CrCl were not reported, complicating the evaluation of the CI-AKI risk profile of the study population. Moreover, such an approach is limited by increased procedural times and the technical challenges and risks associated with coronary sinus cannulation.

a distinctive characteristic of ultra-low-contrast-

INTRAVASCULAR IMAGING. Intravascular imaging is

volume PCI protocols.

another pillar of any zero-/ultra-low-contrast-vol-

In vulnerable patients, using diluted contrast

ume PCI protocol (Figure 3). Traditionally, this has

(usually 50% with normal saline) is a simple measure

been achieved with intravascular ultrasound (IVUS).

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In the MOZART (Minimizing cOntrast utiliZation

RENALGUARD

with IVUS guidance in coRonary angioplasTy) trial (21), 83 patients were randomized to angiography-

The RenalGuard system (RenalGuard Solutions, Mil-

guided PCI or IVUS-guided PCI to reduce overall

ford, Massachusetts) is a device that allows the

CV. Operators were encouraged to follow the previ-

maximization of intravenous hydration by matching

ously mentioned contrast-sparing measures (Table 1,

the infused volume to the patient’s urine output. One

Figure 2) in both study arms. Total CV was 20 ml

hour before the procedure, an intravenous bolus of

(interquartile range: 12.5 to 30 ml) in the IVUS group

isotonic saline and a dose of furosemide are admin-

versus 64.5 ml (interquartile range: 42.8 to 97 ml) in

istered. When a urine output of 300 ml/h is achieved,

the angiography group (p < 0.001). There were no

PCI is started. Matched hydration is continued for 4 h

differences in CI-AKI rates, although the study was

after PCI. By achieving a high urine output, CM is

not powered for such an outcome, and baseline renal

diluted, and consequently, its deleterious effects in

function was normal in the majority of patients. The

the kidney are reduced. Randomized trials comparing

MOZART II trial (Minimizing Contrast Utilization

matched hydration with RenalGuard to standard hy-

With IVUS Guidance in Coronary Angioplasty to

dration protocols showed a reduction of 53% to 78%

Avoid Acute Nephropathy; NCT02743156), powered

in CI-AKI rates in patients with moderate-to-severe

to

CKD undergoing coronary angiography and PCI

evaluate

differences

in

CI-AKI

rates,

is

currently ongoing.

(29,30). RenalGuard use should therefore be consid-

Ali et al. (25) proposed a sophisticated protocol to

ered in patients at high risk for CI-AKI.

perform PCI without CM in 31 subjects with a mean eGFR of 16  8 ml/min/1.73 m 2, a few days after ultra-

REMOTE ISCHEMIC CONDITIONING

low-contrast-volume coronary angiogram (median 13 ml). This was based on extensive IVUS imaging, as

The mechanism underlying how remote ischemic con-

well as coronary physiology testing and metallic

ditioning works remains largely unknown. One theory is

roadmapping (Figure 3). Fractional flow reserve and

that the increase in circulating bradykinins, nitric oxide,

coronary flow reserve were recorded at baseline to

and erythropoietin reduces renal ischemia/reperfusion

confirm the physiological relevance of the lesions,

injury, thus decreasing the risk of CI-AKI (31). A protocol

and after stenting to evaluate the final result. IVUS

of pre-conditioning with 4 cycles of alternating 5-min

was used to identify proximal and distal landing

inflation and 5-min deflation of an upper-arm blood

zones, to guide stent choice and post-dilatation, and

pressure cuff to the patient’s systolic blood pressure plus

to confirm the final result. This approach resulted in

50 mm Hg was tested in a small randomized trial by Er

successful PCI and no MARCE at short-term follow-up

et al. (31). They randomized 100 patients with an eGFR <60 ml/min/1.73 m2 undergoing coronary angiog-

in all patients. Compared with IVUS, optical coherence tomography

raphy with/without intervention to remote ischemic

(OCT) offers superior resolution and definition of certain

preconditioning versus standard of care. Preconditioning

structures (e.g., calcium). However, OCT requires blood

was associated with an absolute reduction of 28% in CI-

flush from the vessel lumen during acquisition, which is

AKI risk (odds ratio [OR]: 0.21; 95% confidence interval:

usually achieved with CM. The feasibility of performing

0.07 to 0.57; p ¼ 0.002). In another randomized trial

OCT using an alternative agent, such as low-molecular-

including 225 patients with non–ST-elevation myocardial

weight dextran, has been previously reported (26).

infarction

Dextran-based OCT results in comparable image quality

conditioning was performed by inflating/deflating the

and almost equal measurements (a correction coefficient

stent balloon for 30 s after stenting the culprit lesion. A

must be used to account for differences in the refractory

reduction in the rate of CI-AKI was observed (12.4% vs.

properties of CM and dextran) (Figure 3). Only anecdotal

29.5%; p ¼ 0.002). However, the feasibility of imple-

experience with zero-/ultra-low-contrast-volume PCI

menting remote ischemic conditioning into routine clin-

performed with dextran-based OCT has been reported

ical practice remains to be proven.

undergoing

PCI

(32),

ischemic

post-

(20,27). Dextran is thought not to be nephrotoxic in the volumes

used

in

dextran-based

OCT-guided

PCI

VASCULAR ACCESS SITE

(<100 ml), although there have been reports of dextraninduced AKI with larger amounts (>1 l) (28). Other side

Radial access is associated with lower rates of major

effects include anaphylactic reactions and coagulopathy

bleeding and, consequently, hemodynamic instability

(26). Therefore, the safety of such an approach must be

during PCI, compared with femoral access. It can also

definitely evaluated before a recommendation on its

reduce atheroma embolization to the renal arteries by

widespread adoption can be made.

avoiding manipulating the abdominal aorta. Data

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from 6 observational studies were evaluated in a

HEMODYNAMIC SUPPORT

meta-analysis comparing vascular access site and risk of CI-AKI in 26,185 patients undergoing PCI. Radial

Patients undergoing high-risk PCI (e.g., with hypo-

access was associated with lower risk of CI-AKI (OR:

tension, cardiogenic shock, or heart failure, particu-

0.51;

0.67;

larly if requiring aggressive techniques, such as

p < 0.0001) (33). However, the meta-analysis was

rotational atherectomy) present a very high incidence

limited by the heterogeneous nature of CI-AKI defi-

of CI-AKI (9). Hemodynamic support with a percuta-

nition across studies and differences in baseline

neous left ventricular assist device such as Impella

comorbidities and treatment between the transradial

(Abiomed, Danvers, Massachusetts), is a feasible

and transfemoral groups. The MATRIX-Access (Mini-

strategy for maintaining hemodynamic stability dur-

95%

confidence

interval:

0.39

to

mizing Adverse Haemorrhagic Events by Transradial

ing high-risk PCI. Impella can significantly reduce the

Access Site and Systemic Implementation of Angiox)

episodes of transient hypotension that are particu-

trial randomized 8,210 patients with acute coronary

larly deleterious for kidney perfusion and can trigger

syndrome undergoing PCI to radial versus femoral

AKI. Besides anecdotal case reports (37), only 1 cohort

access (8). AKI occurred in fewer patients in the radial

study investigated whether hemodynamic support

access arm (15.4% vs. 17.4%; OR: 0.87; 95% confi-

with Impella could decrease the risk of CI-AKI. In their

dence interval: 0.77 to 0.98; p ¼ 0.02). There was a

retrospective single-center study, Flaherty et al. (38)

positive interaction in patients at the highest risk for

included 230 patients with left ventricular ejection

AKI, such as those with reduced eGFR, advanced

fraction #35% (115 subjects supported with Impella 2.5

Killip class, or high Mehran score, in whom a greater

and 115 unsupported matched control patients) un-

benefit of radial access was observed. Therefore, the

dergoing high-risk PCI. CI-AKI was observed in 5.2% of

available evidence supports the use of radial access

Impella-supported subjects vs. 27.8% in the unsup-

over femoral access, when feasible, to decrease the

ported group (adjusted OR: 0.13; 95% confidence in-

risk of AKI.

terval: 0.09 to 0.31; p < 0.001). Impella use was associated with lower incidence of all stages of AKI,

CONTRAST MEDIA TYPE

including AKI requiring dialysis. In unsupported patients with baseline CKD, the incidence of CI-AKI was

There are conflicting data regarding the risk of CI-AKI

greater and correlated with the severity of CKD. By

according to iso-osmolar versus low-osmolar CM.

contrast, there was no association between CKD

McCullough et al. (34) conducted a patient-level

severity and CI-AKI in Impella-supported patients.

meta-analysis in 2,727 patients from 16 randomized

These promising data warrant confirmation in large

trials to compare the safety of iodixanol versus low-

prospective registries.

osmolar CM. They indicated that CKD patients had lower rates of CI-AKI when iso-osmolar iodixanol was

CONCLUSIONS AND SUMMARY

used, compared with low-osmolar CM (2.8% vs. 8.4%;

OF RECOMMENDATIONS

p ¼ 0.001). However, these findings were derived from studies performed 2 decades ago, which did not

Despite

implement

preventive

recommended preventative measures, CI-AKI re-

measures. Another meta-analysis suggested that the

mains a frequent complication of CM exposure during

relative safety of iodixanol may vary depending on

coronary angiography and intervention. Patients with

the specific low-osmolar CM used as comparator, but

advanced CKD are at high risk of CI-AKI and are

overall, iodixanol was not considered superior to low-

therefore exposed to a significant burden of morbidity

osmolar CM (35). A more recent meta-analysis

and mortality. Novel and creative procedural strate-

including only patients with CKD undergoing PCI

gies to minimize the risk of CI-AKI are warranted, of

included 2,839 subjects from 10 randomized trials,

which decreasing CV is the single most important

and showed no significant benefit of iodixanol in

measure.

preventing CI-AKI (OR: 0.72; 95% confidence interval:

strongly relies on intravascular imaging, diluted CM,

0.50 to 1.04; p ¼ 0.08) (36). Finally, a recent large

and metallic roadmapping with guidewires. Radial

observational study compared the risk of CI-AKI

should be the default access route to decrease the risk

across 4 different low-osmolar CM and iodixanol

of bleeding and embolization of atheromatous debris

and found no differences between low-osmolar CM

into the renal arteries. The use of hemodynamic sup-

and iodixanol (17). At present, there is therefore no

port in high-risk settings and remote ischemic pre-/

evidence to recommend iodixanol over low-osmolar

post-conditioning holds interest, but further studies

CM for CI-AKI prevention.

are needed to confirm the efficacy of such approaches.

current

guideline-directed

the

implementation

of

guideline-

Zero-/ultra-low-contrast-volume

PCI

9

10

Almendarez et al.

-, NO. -, 2019

JACC: CARDIOVASCULAR INTERVENTIONS VOL.

- 2019:-–-

Procedural Strategies to Reduce the Incidence of CI-AKI During PCI

Future large multicenter studies should seek validation of these strategies to improve the outcomes of this

ADDRESS

vulnerable patient population.

Azzalini, Interventional Cardiology Division, Cardio-

FOR

CORRESPONDENCE:

Dr. Lorenzo

Thoracic-Vascular Department, San Raffaele Scientific ACKNOWLEDGMENT The authors are thankful to

Institute, Via Olgettina 60, 20132 Milan, Italy. E-mail:

Dr. Soledad Ojeda for her support with figure

[email protected].

preparation.

@mariani_jr, @esbrilakis, @Drroxmehran.

Twitter:

@lorenzo2509,

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KEY WORDS chronic kidney disease, contrast-induced acute kidney injury, contrast-induced nephropathy, intravascular ultrasound, optical coherence tomography, percutaneous coronary intervention

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