Commentary and Review

Preventing or Minimizing Acute Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Replacement

Anwar Tandar, MD1; Vikas Sharma, MD2; Mark Ibrahim, MD1; Tara Jones, MD1; David Morgan, MD3; Candice Montzingo, MD3; James Lee, MD3; Nathaniel Birgenheier, MD3; Natalie Silverton, MD3; Anu Abraham, MD1; Frederick G.P. Welt, MD1; Jason P. Glotzbach, MD2

Anwar Tandar, MD1; Vikas Sharma, MD2; Mark Ibrahim, MD1; Tara Jones, MD1; David Morgan, MD3; Candice Montzingo, MD3; James Lee, MD3; Nathaniel Birgenheier, MD3; Natalie Silverton, MD3; Anu Abraham, MD1; Frederick G.P. Welt, MD1; Jason P. Glotzbach, MD2


Background. Transcatheter aortic valve implantation (TAVI) is now routinely performed in patients with aortic stenosis with low mortality and complication rates. Although periprocedural risks have been substantially minimized, procedure- and contrast-induced acute kidney injury (AKI) remains a major concern. AKI remains a frequent complication of contrast-guided interventional procedures and is associated with a significantly adverse prognosis. We review the currently available clinical data related to AKI, with emphasis on contrast-induced nephropathy (CIN), and discuss a novel, integrated approach aiming to minimize AKI risk in high-risk patients. A stepwise algorithm is also proposed for the management of these complex patients.

J INVASIVE CARDIOL 2021;33(1):E32-E39.

Key words: acute kidney injury, aortic stenosis, contrast-induced nephropathy, double J-tip wire, transcatheter aortic valve replacement

Aortic stenosis is a common valvular heart disease with an incidence that ranges from 2.8%-4.6% for patients older than 75 years old.1 With an aging population, aortic stenosis represents an increasing health burden. In addition, increasing recognition of low-gradient, low-stroke-volume aortic stenosis (D3 classification) has further increased the number of patients who warrant consideration for intervention.2 With expanding indications from prohibitive or high surgical risk to intermediate risk in 2016 and low risk in 2019, transcatheter aortic valve replacement (TAVR) is becoming one of the most widely used treatment modalities for severe aortic stenosis.3

Valvular heart disease progresses more rapidly in patients with end-stage renal disease, especially in patients on hemodialysis.4,5 Based on data from the PARTNER trial, the incidence of severe renal deficiency (glomerular filtration rate [GFR] ≤30 mL/min) in patients undergoing TAVR is estimated at 12%.6 Furthermore, patients being evaluated for TAVR often undergo repeated contrast exposure as part of the preprocedural evaluation and during the TAVR procedure itself. Acute kidney injury (AKI) in patients undergoing TAVR has been associated with poor short- and long-term outcomes.6,7 The Valve Academic Research Consortium (VARC)-2 consensus document defines AKI based on urine output and creatinine measurements,8 whereas the risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria include broader patient factors.9 Regardless of the criteria, multiple risk factors have been reported to impact the incidence of AKI in patients undergoing TAVR, including patient comorbidities (especially diabetes), hypotension during the procedure, concomitant use of medications such as non-steroidal anti-inflammatory drugs, and total contrast volume. Patients with AKI have higher in-hospital (21%) and 30-day mortality (29%) when compared with non-AKI patients.7

While the exact pathophysiology of contrast-induced nephropathy (CIN) remains complex and poorly understood, exposure to contrast has been repeatedly associated with AKI after procedures and tests using contrast, including non-invasive imaging tests such as computed tomography scans as well as invasive procedures such as coronary angiograms.10,11 CIN is defined as the impairment of renal function — measured as either a 25% increase in serum creatinine (SCr) from baseline or a 0.5 mg/dL (44 µmol/L) increase in absolute SCr value — within 48-72 hours after intravenous contrast administration.12 Multiple pathophysiologic mechanisms have been proposed, including interarterial vasoconstriction, generation of radical oxygen species, and direct tubular damage.13 Several strategies to reduce CIN have been studied; however, limiting total contrast volume and the use of intravenous hydration are the only strategies that have repeatedly demonstrated efficacy.14,15 This becomes challenging, as patients with severe aortic stenosis often have some degree of congestive heart failure, and maintaining euvolemia is an important tenet of clinical management. Marenzi et al reported that the use of furosemide with matched hydration significantly reduces the risk of CIN and may be associated with improved in-hospital outcomes.16,17 Despite early evidence of efficacy, the protective effect of n-acetylcysteine has been questioned.18,19 Fenoldopam has also been tested, but did not reduce CIN.20 Given the paucity of definitive studies, currently accepted best practice emphasizes maximizing periprocedural hydration and limiting administered contrast volume as the most effective strategies to minimize CIN.21

In this review, we summarize multiple strategies to reduce AKI from contrast exposure during the work-up and periprocedural period of TAVR. Patients who are evaluated for a TAVR procedure undergo several steps that provide an opportunity to minimize the risk of CIN. We will consider strategies to minimize the risk of AKI in the preprocedure, procedure, and postprocedure phases.

Preprocedural Phase

TAVR patients are routinely evaluated by both interventional/structural cardiologists and cardiothoracic surgeons for shared decision making and assessment. This is most commonly conducted in the outpatient setting, which provides the opportunity to evaluate conditions that may contribute to increased risk of CIN and implement ways to minimize contrast exposure. It also provides the opportunity to discuss potential risks with the patient to initiate collaboration with the patient and other disciplines, such as nephrology, to reduce the risk. Our approach to mitigating CIN risk in the preprocedural phase is detailed below and depicted in Figure 1A.

Identify risk factors (comorbidities) predisposing to AKI. Important preoperative risk factors to be considered are age, known chronic kidney disease, peripheral vascular disease, heart failure, cerebrovascular accident, atrial fibrillation, diabetes mellitus, acute hypovolemia, nephrotoxic drugs such as angiotensin-converting enzyme inhibitors, and non-steroidal anti-inflammatory drugs. Based on these factors, we divided patients into 2 broad categories: patients with pre-existing severe renal dysfunction (GFR <30 mL/min) but not yet on hemodialysis in whom contrast must be avoided, and those at high risk for renal dysfunction (GFR 30-50 mL/min or multiple risk factors), in whom contrast should be minimized.

Close collaboration with a nephrologist when a patient is identified to have high risk of AKI/CIN following TAVR is highly recommended. It is not uncommon that the patient will be at risk for temporary or permanent hemodialysis. Calculating the risk using a validated risk score can help with patient counseling and education. Mehran et al described a simple online risk calculator to predict the risk of CIN as well as risk for hemodialysis;22 it takes into consideration age, gender, hemodynamic status, the use of an intra-aortic balloon pump, diabetes status, and contrast volume.

Pre-TAVR imaging. Computed tomography angiography (CTA) has become the standard of care for procedural planning to assess the aortic valve annulus, coronary ostia height, peripheral vasculature/access options, and coplanar angle. Intravenous contrast utilized during the CTA study contributes significantly to the AKI risk. Appendix 1 describes our modified CTA protocol using limited contrast, which enables scanning of the chest through the pelvis with a single contrast bolus. Despite this low-dose protocol, any amount of intravenous contrast can induce CIN, especially in patients with severe baseline chronic kidney disease. For this reason, alternative options for preprocedural imaging have been proposed.

Transesophageal echocardiography (TEE). TEE was used in the initial PARTNER trial to size the aortic annulus for the transcatheter heart valve (THV). The relatively high rate of paravalvular leak (PVL) observed in this early experience translated to higher mortality.23 The proposed etiology for higher incidence of PVL was underestimation of the aortic annulus diameter by TEE measurement. With increasing experience, technical expertise, and the use of 3-dimensional (3D) measurements, TEE has recently been comparable to CTA in the measurement of the aortic annulus in specialized centers.24 Vaquerizo et al, however, reported that aortic annulus measurements for preprocedural TAVR assessment by 3D-TEE are significantly smaller than multislice computed tomography (MSCT). In this study, such discrepancy would have resulted in up to 50% of all patients receiving the wrong THV size.

Accurate measurement of the aortic annulus distance to the coronary ostia is also an essential aspect of TAVR preprocedural imaging, as coronary ostial occlusion by the native aortic valve leaflets is a catastrophic complication.25 Recognition of this risk may alter the procedural approach, as protection can be provided by pre-emptively achieving wire access into the coronary artery with or without advancement of an undeployed stent into the coronary artery before valve deployment. TEE has been reported to be as accurate as CT in measuring the distance of the coronary ostia to the aortic annulus and can be used as a substitute for CTA.26

Despite the limitations of TEE (such as inability to detect aortic tortuosity), it remains an attractive alternative to MSCT angiogram in TAVR evaluation, especially if contrast use is to be minimized or avoided and should be considered an option when CTA is not feasible.27

Non-contrast cardiovascular magnetic resonance (CMR) imaging.  Renker et al reported the feasibility of a novel, non-contrast, free-breathing, self-navigated 3D (SN3D) MR sequence for imaging of the aortic root to the iliofemoral run-off in comparison with non-contrast 2-dimensional (2D) balanced steady-state free-precession (bSSFP) imaging.28 Non-contrast 3D-CMR may be considered as an alternative to CTA, as it has been shown to be comparable to CTA in the assessment of aortic annular sizing with adequate image quality in small patient cohorts.29 Non-contrast MRI has also proved to be a feasible and accurate method of assessing the aorto-iliac vessels when compared to CTA.30

While non-contrast CMR is a very attractive alternative to CTA, it may not be readily available at many medical institutions. Moreover, the validation studies have used 1.5 T scanners and may not be extrapolated to 3.0 T scanners. Appendix 2 summarizes the general cardiac MRI protocol used at our institution. Validation studies with a modified protocol are currently ongoing, and our results will be reported in subsequent manuscripts. An example of a non-contrast MRA of a normal aortic valve using our modified protocol is provided (Figure 2).

Intravascular ultrasound (IVUS) for lower-extremity assessment. IVUS has been utilized to assess the distal aorto-iliofemoral artery. Essa et al completed a study of 15 patients who underwent distal aortography, bilateral iliac and femoral arteriography, and IVUS assessment.31 Measurements of vascular tortuosity, minimum lumen diameter, and cross-sectional area demonstrated accuracy comparable to those obtained by CTA.31

Coronary CTA. In certain patients where CT is unavoidable, the use of coronary CTA can serve both to assess the aortic annulus and coronary artery anatomy (Figure 3), potentially avoiding the need for invasive coronary angiography. It is worth noting that while coronary CTA can assess for the presence or absence of disease, invasive coronary angiography is often necessary for further evaluation if coronary calcification or plaque is noted on coronary CTA. Data are lacking regarding the need to perform coronary angiogram with or without percutaneous coronary intervention (PCI) for pre-TAVR evaluation. The common practice of performing coronary angiogram with or without PCI before TAVR is not based on randomized clinical trial data, but rather on established clinical trial protocols.32 The timing of PCI in symptomatic pre-TAVR patients is also a matter of debate.33 The use of non-contrast CT to evaluate coronary calcium has been suggested, but data are lacking and it is probably insufficient as a standalone modality. The additional use of IVUS or fractional flow reserve (FFR) with very limited use of contrast may help in the decision making for coronary intervention, especially for proximal and high-risk lesions (left main, proximal left anterior descending coronary artery, proximal right coronary artery). The use of coronary CT-FFR for pre-TAVR coronary evaluation is currently being investigated with the FORTUNA trial (NCT03665389).

Carbon dioxide (CO2) angiography. The property of CO2 as negative contrast agent was reported in 1956 by Barrera et al.34 CO2 has been reported to be the only safe substitute for contrast in patients with renal insufficiency and those who are allergic to contrast.35 With the improvement of digital subtraction angiography, CO2 angiography has been deemed to be safe for below-the-diaphragm angiography in combination with CT.36  In animal experiments, Burko reported the safety of CO2 injection into the coronary artery.37 There are no data regarding the safety and technicality of CO2 coronary angiography in humans. Shafaruddin et al elegantly reviewed the technical and utilization of CO2 angiography, but limited to below-the-diaphragm angiography due to the neurotoxicity of the CO2.38 This technology is not widely available at this time. The improvement of non-contrast MRA technology may also affect the decision regarding the use of CO2 angiography technology.

In 2018, Castriota et al reported a single-center experience including  20 patients who underwent non-contrast TAVR where CO2 angiography was used to assess the below-the-diaphragm vasculature. The TAVR procedure itself was also conducted without contrast, with techniques similar to those described in the current manuscript.39 The authors feel that the use of <20 mL of contrast in our technique would not make a significant impact on the incidence of CIN, but provide fewer possible complications from TAVR (ie, coronary obstruction).

Procedural Phase

Minimizing contrast. While there are several preprocedural imaging alternatives to limit contrast exposure, avoidance of contrast during the TAVR procedure presents a challenge. Although the exact pathophysiology of AKI and CIN remain elusive, reducing the total administered contrast volume is likely the most important modifiable factor to reduce the risk of CIN.16 Prehydration should be administered cautiously given that concomitant heart failure is often present, and a left ventricular end-diastolic pressure-guided strategy for procedural hydration should be considered, as reported by Brar et al.40

There have been several proposals to avoid the use of excessive contrast during the TAVR procedure. Here, we describe the strategies we have implemented at our institution (Figure 1B).

Cusp localization with double J-tip wire and pigtail for coplanar assessment. During the TAVR procedure, it is important for the operator to verify the coplanar angle for valve positioning. Balloon-expandable valve strategy typically depends on the initial coplanar angle, whereas the strategy for self-expanding valve varies significantly across operators. The most common strategy to achieve coplanar visualization for self-expanding valves is to increase the caudal displacement from the initial coplanar angle until the parallax of the self-expanding valve has been removed.41 The following technique is most advantageous for use with balloon-expandable valves, but can be used as an adjunct in all TAVR procedures to minimize contrast.

This technique was first described during personal Twitter exchanges among the authors and multiple structural/interventional cardiologists. First, two 0.035˝ J-tipped wires and a pigtail catheter are used to verify the coplanar angle. After bilateral femoral access is obtained, the angled pigtail catheter typically used for contrast injection is placed in the right coronary cusp. From the contralateral large-bore femoral access, two 0.035˝ soft J-tip wires are advanced into the left and non-coronary cusps (occasionally, a Judkins Right [JR] coronary catheter is needed to engage the left coronary cusp). With wires in both the left and non-coronary cusps and the pigtail in the right coronary cusp, a precise coplanar angle can be obtained without performing a contrast aortogram (Figure 4). Once the coplanar angle is verified, both J wires are removed and the TAVR procedure is conducted in the usual manner, utilizing only 1 limited (<20 mL) contrast injection before deployment to confirm the position of the valve.

TEE. In centers with expertise, TEE can be used to guide the TAVR procedure and does provide some advantages. TEE guidance during TAVR procedures has been associated with shorter fluoroscopic time, a reduced need for additional aortograms, and a trend toward less-frequent occurrence of post-TAVR AKI.42 However, TEE as the sole imaging modality does not allow for assessment of the coplanar angle for valve deployment. Additionally, the use of TEE during TAVR adds to the complexity of the procedure as general anesthesia is required. Conscious sedation has been shown to lower complications, cost, and also possibly mortality.43,44 Given the trend away from general anesthesia to monitored anesthesia care and conscious sedation at many centers, routine TEE is less attractive.

Avoiding the post-valve deployment aortogram. Routine post-valve deployment aortogram may not be necessary. TEE or transthoracic echocardiogram can be used to determine the degree of PVR post TAVR deployment. Echocardiography can also be used to indirectly assess coronary artery patency by assessing wall motion and ventricular function. Late occlusion of a coronary artery following TAVR has been reported, but it is beyond the scope of this manuscript.45,46

Avoiding the distal aortogram. Distal aortogram post TAVR deployment is routinely used to assess the patency of the aorto-iliofemoral arterial vessels after large-bore sheath removal. Early-generation TAVR technology utilized larger-bore delivery systems (24 Fr) and thus were associated with an increased risk of vascular complications. With contemporary delivery systems, the sheath and catheter sizes have become significantly smaller (14-16 Fr size), which has reduced the incidence of vascular complications.47 The utilization of arterial Doppler to assess the distal arterial vessels (posterior tibialis and/or dorsalis pedis arteries) before and after TAVR can further reduce the procedural contrast load by eliminating the need to perform an iliofemoral angiogram after removal of the delivery sheath and percutaneous closure.

Prevention of prolonged hypotension. Intraoperative hypotension has been well documented as one of the contributors for AKI.48 Hence, preventing prolonged periods of hypotension during TAVR in high-risk patients for renal injury is paramount. Early recognition and treatment of possible complications (eg, pericardial effusion, vascular bleeding complications, drug reactions, valve embolization) that may lead to prolonged hypotension post TAVR is crucial.

Pacing need. Balloon-expandable valve deployment requires rapid pacing, while self-expanding valve technologies may not require rapid pacing. Valve choice should be based on the experience and expertise of the team at each center to minimize the duration of hypotension. In our experience, we have observed longer periods of hypotension (systolic blood pressure <70 mm Hg) during valve deployment using the self-expanding valve platform, mostly due to the need for repositioning and recapturing the valve. Registry data may contribute to the decision-making process.49

General anesthesia vs conscious sedation. While there is variability across institutions, the induction of general anesthesia may increase the chance of post-TAVR complications. Hyman et al compared TAVR under conscious sedation vs under general anesthesia using National Cardiovascular Data Registry/Transcatheter Valve Therapy Registry data. Despite a higher procedural success rate with general anesthesia (98.6% vs 97.9% with conscious sedation; P<.001), conscious sedation for the TAVR procedure is associated with reduced use of inotropes, shorter intensive care unit stay, shorter hospital length of stay, and reduction in combined 30-day death/stroke rate (4.8% vs 6.4% with general anesthesia; P<.001).44

RenalGuard technology. RenalGuard (RenalGuard Solutions) is a new technology that was developed under the understanding that maintaining high urine output may reduce the incidence of CIN. The RenalGuard system entails the use of diuretic to maintain urine output with the measurement of urine output. It has the ability to measure a real-time urine output and to be matched with normal saline infusion. In 2015, Barbanti et al reported a benefit with RenalGuard technology in preventing AKI during TAVR. The incidence of AKI rate was lower in the RenalGuard group than in the control group (n = 3 [5.4%] vs n = 14 [25.0%], respectively; P=.01). In this study, the average SCr was 0.97-1.0 mg/dL.50 The benefit of RenalGuard in patients with abnormal renal function is not known. RenalGuard has received the CE Mark in Europe, but it is under investigational use in the United States.

Using the above techniques, we have completed a series of balloon-expandable transfemoral TAVR procedures in 10 patients with high risk of AKI (average GFR, 20 mL/m2) using an average of 15 ± 6 mL of contrast (iopamidol 370 mgI/mL), which has avoided the worsening of renal function or the need for hemodialysis. At our institution, the rate of new hemodialysis is 0%.

Postprocedure Phase

There are several opportunities in the postprocedural phase to minimize the risk of AKI (Figure 1C). Prevention and early recognition of any complications, such as hypotension from any cause (especially hypovolemia and bleeding), heart block, stroke, arrhythmias, and the avoidance of nephrotoxic drugs, are all very important aspects of postprocedure care. Close monitoring of renal function is very important during this phase, as CIN may peak at 72 hours post procedure.10,51 Avoidance of exposure to contrast should take priority unless it is absolutely necessary. Continuing consultation with renal medicine during this phase may help further reduce the risk.


TAVR remains a complex procedure despite technological advances. AKI remains a relatively common and important source of morbidity following TAVR, and strategies to reduce the occurrence should be implemented. CIN is perhaps the most modifiable cause of post-TAVR AKI, and clinical protocols to reduce CIN are needed. Diligent planning in the preprocedure phase, as well as modifications of the procedural steps to minimize contrast exposure along with continued monitoring post procedure, can potentially reduce the risk of AKI from CIN in TAVR patients. Future technological improvements, especially in non-contrast cardiac MRI may play a significant role in mitigating this complication. A multidisciplinary heart team approach is critically important to achieve best possible outcomes for TAVR patients.

From the Divisions of 1Cardiovascular Medicine, 2Cardiothoracic Surgery, and 3Cardiac Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Tandar is a proctor and speaker for Edwards LifeScience; consultant for W.L. Gore Medical; speaker for Volcano; and member of the medical advisory board for Boston Scientific. Dr Welt is a member of the medical advisory board for Medtronic. Dr Glotzbach is a speaker for Edwards LifeScience. The remaining authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted May 22, 2020.

Address for correspondence: Anwar Tandar, MD, Division of Cardiovascular Medicine, University of Utah School of Medicine, 50 N. Medical Drive, Salt Lake City, UT 84132. Email:

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