Scientific Advisory Committee on Medical Devices Used in the Cardiovascular System (SAC-MDUCS) Summary 2020-11-23

November 23, 2020

Core committee members: John Ducas (Chair), John Webb, Renzo Cecere, Anita Asgar, Alan Menkis, Barry Rubin, Brent Mitchell, Chris Feindel, Eric Cohen, Jillianne Code, Raymond Yee

Regrets: Marino Labinaz, Joaquim Miro

Guest speakers: Kunal Minhas, Director, Cardiac Catheterization Laboratory, St. Boniface Hospital, Winnipeg; Vincent Chan, Cardiac Surgeon, University of Ottawa Heart Institute

Health Canada staff: David Boudreau, Saira David, Gaya Jayaraman, Kevin Day, Ben Elliot, Chris Schmidt, Daniel Yoon, Geoffrey Green, Ian Aldous, Jianming Hao, Julia Bairos, Karen Kennedy, Lanyi Xu, Mark Korchinski, Maurice Sylvain, Monica Forero, Peggy Seely, Renate Kandler, Roy Masters

Opening remarks (David Boudreau)

The Director General of the Medical Devices Directorate (MDD) welcomed attendees to the first virtual meeting of SAC-MDUCS during this unprecedented time of the COVID-19 pandemic. He identified the following topics for SAC-MDUCS consideration during the meeting:

• Devices used in the treatment of heavily calcified coronary lesions;
• Transcatheter aortic valve replacement (TAVR) to treat aortic valve disease; and
• Percutaneous mitral valve repair or replacement technologies, including Mitraclip.

He also described how Health Canada has implemented innovative and agile regulatory measures to help prioritize and expedite the regulatory review of in-demand COVID-19 medical devices. He then provided a brief update on activities related to the Medical Devices Action Plan before handing the meeting over to the Chair.

Review of the Agenda and Declaration of Affiliations and Interests (John Ducas)

The Chair outlined the meeting agenda and requested declarations of actual or potential conflicts of interest. There were no declared affiliations and interests that restricted SAC-MDUCS members' participation.

Summary of Previous Advice Used and General Considerations for the Meeting

Kevin Day provided a summary of previous advice used by Health Canada:

• Health Canada believes that there are data to support the use of drug-coated balloons in some patients. Furthermore, the clinical use of drug-coated balloons can be appropriately controlled through the practice of medicine as we continue to monitor uncertainties and outcomes.
• We continue to work towards licensing TAVR replacement in low-risk patient populations.
• Interatrial shunting for heart failure and pulmonary arterial hypertension continue to be of interest within the Special Access Program (SAP) and in clinical trials.

Presentation #1: Atherectomy Devices for the Treatment of Heavily Calcified Coronary Lesions (Kunal Minhas)

Kunal Minhas's presentation focused on the characteristics of severely calcified coronary lesions; the challenges in assessing and treating these lesions; and an assessment of the risks and benefits of devices used to treat severely calcified coronary lesions. He offered a clinical perspective on the clinical performance of devices used in the assessment and treatment of heavily calcified coronary lesions, including current practices in Canada. Dr. Minhas also spoke to the limited use of existing technologies, such as rotational and orbital atherectomy devices, as well as promising features of newer atherectomy technologies. He presented on the benefits and risks associated with the range of available devices and the technologies in development. He also contextualized the most commonly used of these technologies within contemporary treatment decision algorithms. This further highlighted how unique aspects of different technologies can be used to the greatest clinical advantage.

After the presentation, the committee discussed the differences between intravascular lithotripsy and other atherectomy devices that are currently available. The discussion touched on the degree of calcification; particulate embolization; dissection and perforation; the possibility of death, heart attack, and restenosis; and the induction of cardiac ectopics with coronary intravascular lithotripsy.

The committee further considered the potential impact of these factors on Health Canada's regulation of these technologies and the potential authorization of these technologies through SAP. Patient populations that would benefit the most from these technologies include patients with severely calcified lesions and lesions that are difficult to cross or dilate. Health Canada will continue to monitor the usage of these devices and any adverse events associated with them, as these effects could become significant as use broadens.

Presentation #2: Use and access to TAVR devices (John Webb; Renzo Cecere)

John Webb spoke from an interventional cardiological perspective and Renzo Cecere from a surgical perspective. The presentations focused on the use of TAVR for the treatment of aortic valve disease with two main areas of focus. The first was the use of TAVR in low-risk patient groups and whether there are any conditions where the use of TAVR should be limited in these groups. In general, improvements in rates of death and disabling stroke were highlighted for TAVR (using transfemoral access) compared to surgery. In some areas, surgery may be associated with improved outcomes compared to TAVR, such as pacemaker implant rates, structural valve deterioration, and mild paravalvular leakage. The implications of the broader use of TAVR in low-risk patients were also presented. These included considerations for future interventions; the feasibility and risks of valve-in-valve procedures; and the risks associated with alternative access sites, thrombosis, coronary artery occlusion, and calcified left ventricular outflow tract for TAVR.

The discussions highlighted that, given that all valves will fail eventually, maintaining coronary access after a valve-in-valve procedure is a potential problem. Clinicians and Health Canada should consider how the transcatheter valve performs in the context of TAVR-in-TAVR and TAVR-in-surgical aortic valve replacement (SAVR) interventions. Consideration should be given when selecting the first TAVR device (e.g., intra-annular vs. supra-annular, sealed skirt) for implantation, especially in a low-risk patient population. As younger patients with longer life expectancies are implanted with TAVR devices, there may be a need to access the coronary arteries to treat future coronary artery disease after a valve-in-valve re-intervention. Additionally, the committee noted that patient age is not a sole determinate of the best intervention (i.e., TAVR vs. SAVR), and labelling should not restrict use based on age alone. This decision making is the role of the Heart Team.

As TAVR indications expand into lower risk and younger patient population, new transcatheter valves cannot be approved for low-risk patients until long-term durability is assessed in high- and intermediate-risk patients. The committee noted that surgical valve replacement was considered a very good option for young, low-risk patients.

The second focus was on the emergence of new technologies and a comparison to the well-established and more mature TAVR systems currently available. In general, performance of the market-leading technologies should continue to be used as the required clinical performance for market access in Canada. Low-risk patients should be treated with valves for which we have significant clinical data, including long-term follow up.

After the presentation, the committee discussed how practical access to TAVR in Canada is dependent on risk level and the age of patient populations. The evolution of prosthetic heart valve composition (mechanical or tissue) as well as the flexibility, structure, and durability of devices were considered. The committee noted that the choice of TAVR vs SAVR is well-positioned within the practice of medicine in the context of a Heart Team in Canadian health care facilities. The importance of considering patient preference in treatment options was also discussed.

Presentation #3: Emergence of New Transcatheter Mitral Valve Replacement and Transcatheter Mitral Repair Devices (Anita Asgar; Vincent Chan)

Anita Asgar spoke from an interventional cardiological perspective and Vincent Chan from a surgical perspective. The presentations focused on the use of devices to repair or replace leaking mitral valves. While Mitraclip has been on the market for several years, other percutaneous mitral valve repair or replacement technologies have been slow in developing, and many have been associated with poor clinical outcomes. The mitral valve and mitral valve disease are complex, and there are currently many devices under clinical investigation for the treatment of mitral regurgitation (MR).

The presentations provided an update on the clinically acceptable outcomes for different patient populations for a wide range of devices that address leaflet repair (edge-to-edge), annular repair (annuloplasty), chordal repair or replacement, and valve repair and replacement. The presentation proposed ideal characteristics for a percutaneous mitral valve repair system, including transeptal delivery; the ability to reposition the device for proper alignment; non-obstruction of the left ventricular outflow track; avoiding the need for long-term anticoagulation; and an allowance for future interventions.

The presentation also provided guidance on clinical trial design considerations (i.e., trial design, patient population (e.g., primary vs. secondary MR), patient exclusion criteria, control group, and study size). In most cases, trials should be randomized against surgery or the mitral clip for both degenerative and functional MR with endpoints recommended by the Mitral Valve Academic Research Consortium. Exceptions to this include mitral annular calcification, which is not currently well managed with existing therapeutic interventions and might use predefined objective performance criteria that are well matched with the patient population to be studied. It was noted that surgical outcomes for mitral valve replacement and most types of mitral valve repair are quite good and continue to improve, thereby presenting the need for contemporary comparators for clinical trials.

After the presentations, the committee discussed the role of surgeons and interventional cardiologists in the treatment of mitral valve disease and acknowledged the importance of having an interdisciplinary team looking at structural heart disease and heart failure. This is particularly important given the range of treatment options available from medical management to surgical intervention. The importance of site experience (e.g., more than 23 cases per year), long-term outcomes, and patient preference was further discussed.

What Health Canada has heard and Wrap-up (Kevin Day)

Kevin Day thanked the committee for their work and for the excellent discussions of the day. He emphasized that Health Canada strives to ensure timely access to these cardiac medical devices once there is adequate evidence of safety and effectiveness. He noted the importance of accessing clinical trials for emerging technologies and accessing SAP for unmet clinical needs.

While regulating rapidly evolving cardiovascular medical device technologies continues to be challenging, the recommendations and deliberations of the committee provide valuable insight about the safety and effectiveness of these technologies. These committee meetings facilitate an informed assessment of cardiovascular medical devices even in the early stages of clinical data collection and have also helped to contextualize those data.

Next Steps, Closing Remarks and Adjournment of Meeting (John Ducas)

The Chair advised that a high-level summary would be posted on Health Canada's website. He indicated that the next SAC-MDCUS meeting was expected in May or June of 2021. The Chair thanked the members for their contributions and closed the meeting.