Zeroing on Gadolinium to Complement Intravascular Ultrasound in Zero-Contrast Percutaneous Coronary Interventions

Abstract

Background. Many techniques have been developed to minimize the risk of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) through drastic reductions in iodinated contrast volume and the use of intravascular ultrasound (IVUS). While some of the described techniques completely avoid contrast use and rely on transthoracic echocardiography to check for potential pericardial bleeding, this strategy may miss or delay the treatment of potentially life-threatening complications. We hereby propose the use of group II gadolinium (Gd)-based contrast agents, instead of iodinated contrast, to complement IVUS, in order to achieve the goal of zero-contrast percutaneous coronary intervention, without raising the risk of CIN. These agents have been shown to be relatively safe in the setting of advanced CKD, with an overall reported risk of nephrogenic systemic fibrosis of <0.07% and no significant nephrotoxicity. Combining the use of Gd with the “live IVUS technique” in patients with advanced CKD seems to achieve the goal of high-precision PCI, without significantly compromising procedural safety.

Keywords: contrast-induced nephropathy, gadolinium, intravascular ultrasound, zero-contrast percutaneous coronary intervention

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The risk of contrast-induced nephropathy (CIN) following a percutaneous coronary intervention (PCI) is directly related to baseline renal function and iodinated contrast volume.^1,2 Moreover, persistent CIN is associated with long-term mortality, either after elective PCI or urgent PCI for acute myocardial infarction (AMI).^3,4 Hence, in the last few years, many techniques have been developed to minimize the risk of CIN in patients with chronic kidney disease (CKD), through drastic reductions in iodinated contrast volume and the complementary use of alternative imaging modalities to coronary angiography.^5-9 These techniques can be categorized into 2 different strategies: ultra-low contrast (ULC)-PCI or zero-contrast (ZC)-PCI.

The ULC-PCI strategy^5-7 utilizes a small amount of iodinated contrast after completing the PCI in order to ensure that there is no iatrogenic coronary perforation (stent or distal wire related) and to assess flow dynamics (flow speed, embolization, etc). Neither of these phenomena can be checked with intravascular ultrasound (IVUS). Even though the ULC-PCI strategy quickly ensures the absence of pericardial bleeding, it does involve injecting a small amount of contrast, which may lead to CIN in patients with severe CKD.

The ZC-PCI strategy^8,9 does not use any iodinated contrast and the entire PCI is performed under IVUS guidance. The last recommended step of this technique includes a limited transthoracic echocardiogram to rule out a pericardial effusion as a possible complication. The major advantage of this strategy is the absence of any risk of CIN. The major downside to this approach is the suboptimal sensitivity of an echocardiogram in detecting small distal coronary perforations, and there is concern regarding a potential delay in the identification and management of this life-threatening bleeding complication, since the echocardiogram is usually done 10 minutes after completion of the PCI.

Another major downside is that an echocardiogram performed 10-15 minutes after PCI can give a false sense of security about the absence of a small perforation, while it can still miss a slow, wire-related distal microperforation that takes hours to manifest.

Given these factors, we contend that coronary angiography at the end of an IVUS-guided PCI is still necessary. Our proposed strategy is to perform a coronary angiography at the conclusion of the ZC-PCI utilizing gadolinium, which is radio-opaque (Figure 1). The use of gadolinium within recommended doses allows for a relatively safe evaluation of flow characteristics and coronary perforation without increasing the risk of CIN.

Gadolinium is a silvery-white, iodine-containing heavy metal, which attenuates x-ray photons at a rate of 2/3 relative to iodinated contrast agents (Figure 1).¹⁰ Diluted gadolinium has been used for coronary angiography with acceptable visibility (Figure 2).^10,11 It has also been shown to be an effective and safe alternative contrast agent in other diagnostic and interventional procedures.^12-15Table 1 summarizes pertinent data related to gadolinium use and confirms the lack of significant nephrotoxicity.¹⁰

Gadolinium-based contrast agents (GBCAs) are divided into 3 groups by the American College of Radiology based on their risk of nephrogenic systemic fibrosis (NSF).¹⁶ These groups differ by their molecular class (linear vs macrocyclic) and net charge (ionic vs nonionic).¹⁶

Group I agents (gadodiamide, gadopentetate dimeglumine, gadoversetamide) have the highest reported risk of NSF and are being phased out.

Group II agents (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, gadoteridol) have been proven to be relatively safe in patients with severe CKD (glomerular filtration rate <30 mL/min) and the reported rate of NSF is <0.07% according to the most recent meta-analysis.¹⁷

Group III agents (gadoxetate disodium) are the newest category; thus far, there have been no reported cases of NSF.

These encouraging reports about group II and III GBCAs have led the American College of Radiology and the National Kidney Foundation to publish a consensus document outlining the relative safety of these agents in patients with advanced CKD.¹⁸ The consensus clearly outlines that, depending on the clinical indications, the potential diagnostic harms of withholding group II GBCA for a magnetic resonance imaging study may outweigh the risk of NSF in this population.¹⁸

We propose that, given the very low reported rate of NSF in large cohorts of patients with advanced CKD who had received group II GBCAs,¹⁷ it seems that the risk of adverse events related to recommended doses of these agents is mostly lower than the risk of nephrotoxicity related to the use of iodinated contrast agents in these patients.

In most reported studies, gadolinium was injected either in an undiluted form or diluted with iodinated contrast at varying ratios from 1:1 to 3:1 (Table 1). The delivery of undiluted gadolinium with a power injector in the coronary arteries was rarely associated with the occurrence of ventricular arrhythmias.¹⁹

In order to remain faithful to the ZC-PCI concept, while minimizing the risk of ventricular arrhythmias, we propose diluting group II GBCAs in 0.9% normal saline solution, at a ratio of 1:1, without the use of power injectors. It is absolutely crucial to make sure that the total dose of GBCA does not exceed the recommended standard dose of 0.1 mmol/kg (Figure 1). The vast majority of reported NSF cases related to GBCA occurred in patients who had received a higher dose of gadolinium.¹⁸ For example, a 100 kg patient should not receive more than 10 mL of gadobutrol, which has a concentrationof 1 mmol/mL. If the operator is planning on performing 2 final coronary angiograms, each injection could be performed using less than 5 mL of gadobutrol and an equal volume of 0.9% normal saline.

Conclusion

Finally, the combination of gadobutrol and IVUS has been shown to be feasible in a reported case of complex PCI on a chronic total occlusion in a patient with severe anaphylaxis to iodinated contrast agents.²⁰ We would like to go a step further and suggest the use of the “live IVUS stenting technique,”²¹ which allows for a high degree of precision in stent landing zones, along with a final injection of the recommended dose of the available group II GBCA, which provides necessary angiographic information that complement IVUS data and maintain the highest degree of safety, without compromising on procedural effectiveness.

Affiliations and Disclosures

From Ascension Saint Thomas Heart Rutherford, Murfreesboro, Tennessee.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lichaa is a consultant for Philips, Abbott Vascular, Becton Dickenson and Company, Cordis, and Medicure.

The author reports that patient consent was provided for publication of the images used herein.

Manuscript accepted January 15, 2022.

Address for correspondence: Hady Lichaa, MD, FACC, FSCAI, FSVM, RPVI, Assistant Professor of Medicine, University of Tennessee Health Science Center, Faculty of Medicine, 1840 Medical Center Pkwy, Suite 201, Murfreesboro, TN 37129. Email: Hady.lichaa@gmail.com

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