Adverse Events With Intravascular Lithotripsy After Peripheral and Off-Label Coronary Use: A Report From the FDA MAUDE Database

Background. Currently only the peripheral intravascular lithotripsy (IVL) device is approved for use in the United States. We queried the United States Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database from January 1, 2016 to December 14, 2020 for all reports of adverse events and modes of failure related to the peripheral IVL device, when used for on- and off-label indications. There were 20 reports of use in peripheral artery disease interventions and 3 reports of off-label use in coronary interventions. Device malfunction in 13 of 23 patients (56.5%) was the most common adverse event reported. Partial balloon or catheter dislodgment was the most common mode of IVL device failure in 12 of 20 patients (60%), followed by balloon rupture in 3 of 20 patients (15%). Coronary use was rare, and associated with balloon perforation in 1 of 3 patients, bradycardia in 1 of 3 patients, and aortocoronary dissection in 1 of 3 patients. In summary, IVL use carries risk of complications; hence, continued vigilance and postmarketing monitoring are warranted.

J INVASIVE CARDIOL 2021;33(12):E974-E977.

Key words: intravascular lithotripsy, peripheral artery disease

Early studies indicate that intravascular lithotripsy (IVL; Shockwave Medical) can modify heavily calcified lesions and has been available for peripheral use in the United States  since 2016. More recently, IVL is being used off label in percutaneous coronary intervention (PCI). IVL is easy to use and appears to have a favorable safety profile^1-5 compared with other atherectomy devices; however, published data are limited.

The Manufacturer and User Facility Device Experience (MAUDE) database is an online database created by the United States Food and Drug Administration that compiles adverse events for approved medical devices. Reporting is submitted by both mandatory (manufacturers, device-user facilities) and voluntary reporters (healthcare professionals). The reports serve as a tool to monitor device performance and detect adverse events.

We searched the MAUDE database from January 1, 2016 to December 14, 2020 with the phrase “Shockwave Medical” under the manufacturer tab and “Shockwave” under the brand name tab. This period was expected to capture all of the relevant reports for the devices. Multiple mechanisms of failure or adverse events were possible for a single IVL catheter. The MAUDE database is publicly available and deidentified; thus, no institutional review board approval was required.

We found 24 unique reports of adverse events, 1 of which was excluded as it lacked clarity. Of the 23 included reports, there were 3 reports of off-label use of the peripheral IVL catheter for PCI, 1 report of treating peripheral in-stent restenosis, 1 report of treating carotid artery disease, and 18 reports of peripheral arterial interventions (Table 1, Part 1; Table 1, Part 2). The adverse events reported were categorized as death (n = 1; 4.3%), injury (n = 9; 39.1%), and device malfunction (n = 13; 56.5%).

The most commonly reported modes of IVL failure when used for peripheral vascular disease were: error alarm (2/20), partial balloon or catheter dislodgment upon device withdrawal (6/20), balloon rupture (3/20), balloon rupture and partial balloon dislodgment (6/20), vessel rupture (1/20), stroke (1/20), dissection (1/20), thrombus formation (1/20), and peripheral embolization (1/20). Of the 12 cases of partial balloon or catheter dislodgment,  in 6 cases the dislodged hardware was successfully snared, in 3 cases a stent was placed to trap the fragment against the vessel wall, and in 3 cases the dislodged hardware was retained within the introducer sheath and removed en bloc.

Most reports of balloon rupture were attributed to heavily calcified vessel/lesions, and in some cases when the IVL balloon was inflated to >4 atm (up to 10 atm in 1 case, with resultant rupture). Balloon dislodgments almost always occurred when there was difficulty withdrawing the catheter out of the sheath, requiring force in some cases. There was 1 case of physician error in withdrawing the catheter without deflating the IVL balloon, which resulted in catheter fracture.

The 3 complications of off-label IVL use in PCI were as follows: (1) balloon perforation without clinical consequence in 1 case; (b) bradycardia during IVL therapy leading to therapy termination followed by successful PCI and coronary dissection leading to death in 1 case (it is unclear whether the death was directly related to the IVL device); and (3) aortocoronary dissection that was treated conservatively, in which the patient did well during 7 days of follow-up.

The published complication rates in the IVL approval clinical studies were low. The Disrupt Coronary Artery Disease 3 (DISRUPT CAD 3) trial reported 1 death, 1 dissection, 1 perforation, and 1 acute vessel closure among 384 patients.¹ The Disrupt Peripheral Artery Disease (PAD) 1 trial (femoropopliteal lesions) reported no complications among 35 patients.² The Disrupt PAD 2 trial (femoropopliteal lesions) reported 1 dissection among 60 patients.³ The Disrupt PAD 3 observational study (femoropopliteal lesions) reported 2 dissections and 1 perforation among 200 patients.⁴ The Disrupt BTK trial (below-the-knee lesions) reported 1 dissection among 19 patients.⁵

Our study has limitations. MAUDE reports are not independently verified and may have missing or incomplete data. Additionally, actual adverse event rates cannot be calculated through MAUDE’s dataset as the denominator is not known.

In summary, IVL use carries risk of complications, which can rarely be fatal. Although these events appear to be infrequent and may be related to high complexity of the peripheral and coronary lesions treated with IVL, they suggest the need for continued vigilance and monitoring of IVL use in everyday clinical practice. Furthermore, the frequent reports of balloon dislodgment (12/20 with on-label use and 0/3 with off-label use) warrant added caution from users. With limited clinical experience in the United States, it remains to be seen whether the coronary IVL device will carry similar risks.

From the ¹Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; ²Cleveland Clinic, Cleveland, Ohio; ³Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, University Hospitals, Cleveland, Ohio; ⁴Dallas VA Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas; ⁵Brigham and Women’s Hospital, Boston, Massachusetts; and ⁶Henry Ford Health System, Detroit, Michigan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Khatri reports consulting/speaker honoraria from Abbott Vascular, Boston Scientific, Cardiovascular Innovations Foundation, and Terumo. Dr Shishehbor reports consulting and advisory board for Abbott Vascular, Medtronic, Boston Scientific, Philips, and Terumo. Dr Banerjee reports consulting honoraria from Astra Zeneca, Livmor, American Heart Association (Deputy Editor, Circulation Cardiovascular Interventions), and Cardiovascular Innovations Foundation (Board of Directors); research grants from Boston Scientific Corporation and Chiesi. Dr Croce reports grant/research support from Abbott Vascular, Takeda, Teleflex, and CSI; consulting fees/honoraria from Abbott Vascular, BSCI, Biotronik, Philips, Abiomed, CSI, Takeda, and Cordis; major stock shareholder/equity in Dyad Medical. Dr Garcia reports institutional research grants from Edwards Lifesciences, Abbott Vascular, Gore, and Boston Scientific; consultant for Medtronic, Edwards Lifesciences, Neochord, and Abbott Vascular; proctor for Edwards Lifesciences. Dr Burke is a stockholder in Egg Medical and MHI Ventures. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, American Heart Association (Associate Editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), ControlRad, CSI, Elsevier, GE Healthcare, IMDS, InfraRedx, Medicure, Medtronic, Opsens, Siemens, and Teleflex; owner of Hippocrates LLC; shareholder in MHI Ventures, Cleerly Health. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted February 16, 2021.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 E. 28th Street #300, Minneapolis, MN 55407. Email: esbrilakis@gmail.com

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