Scientific Advisory Committee on Medical Devices used in the Cardiovascular System Summary of Proceedings April 8, 2022

April 8, 2022

Core committee members: John Ducas (Chair), Alan Menkis, Barry Rubin, Chris Feindel, Eric Cohen, Jillianne Code, Raymond Yee

Regrets: Anita Asgar, Brent Mitchell, Joaquim Miró, John Webb, Marino Labinaz, Renzo Cecere

Guest speakers: Jacqueline Saw, Interventional Cardiologist, Vancouver General Hospital and St Paul’s Hospital, and Raymond Yee, Professor of Medicine, Schulich School of Medicine & Dentistry and the University of Western Ontario

Guest discussant: Bernard Thibault, Cardiologist, Montreal Heart Institute and Associate Professor at the Université de Montréal

Observers: Gino De Angelis, Yannick Auclair

Health Canada staff: David Boudreau, Karen Tso, Kathy Soltys, Emanuela Fedele, Kevin Day, Anber Ikram, Marianne Ariganello, Ben Elliott, Bisi Lawuyi, Chris Schmidt, Elaine Wong, Elham Aghbashi, Ellen Fraser, Firdous Hadj-Moussa, Geoffrey Green, Jianming Hao, Julie Proulx, Julie Taing, Karen Kennedy, Kathleen O’Callaghan, Lanyi Xu, Mark Korchinski, Martina Buljan, Maurice Sylvain, M'omena Dawood, Monica Forero, Myriam Gauthier, Natalia Mavrinskaya, Nathalie Duval, Peggy Seely, Renate Kandler, Roy Masters

Opening remarks (David Boudreau)

The Director General of the Medical Devices Directorate welcomed attendees to the SAC-MDUCS meeting and observers from the Canadian Agency for Drugs and Technologies and the Institut national d’excellence en santé et en services sociaux. Mr. Boudreau identified the 2 meeting topics: left atrial appendage occlusion devices and leadless pacemakers. He then provided updates within the Medical Devices Directorate before handing the meeting over to the chair:

• ongoing efforts to facilitate access to COVID-19 medical devices through interim orders
• the agile licensing for medical devices initiative
• the advanced therapeutic products pathway
• recent consultations on the guidance for medical device meetings and for clinical evidence requirements

Review of the agenda and declaration of affiliations and interests (John Ducas)

The Chair thanked and welcomed the meeting attendees. He requested declarations of actual or potential conflicts of interest. There were none that restricted SAC-MDUCS members from participating.

Summary of previous advice used and general considerations for the meeting (Kevin Day)

Mr. Day described the committee’s recommendations on topics from 3 previous meetings:

• renal denervation and hypertension treatments (June 2021)
• atherectomy devices in calcified lesions, and the use and performance of transcatheter mitral valve repair (November 2020)
• use of the Special Access Program (SAP) for first human use and associated clinical ethics (March 2019)

He explained how Health Canada used the recommendations to inform decisions about medical device licensing and to help in its assessments of clinical trials and SAP.

Presentation #1: Left atrial appendage occlusion devices (Jacqueline Saw)

Dr. Saw presented clinical data on how left atrial appendage (LAA) occlusion devices are performing in Canada and worldwide, with Amulet and Watchman (including the new version, Watchman FLX) being the most commonly used. She highlighted the current indications for LAA closure in Canada. Using randomized control trial and large registry data, Dr. Saw:

• explored safety and effectiveness endpoints in populations who are contraindicated to long-term oral anticoagulation
• compared device usage with post-implant antithrombotic therapy
• discussed the use of combination therapy with ablation, oral anticoagulation and transcatheter aortic valve replacement

She also presented on the safety issues of these devices, including pericardial effusion, device migration/embolization, device-related thrombus and peri-device leakage.

Overall, Dr. Saw indicated that LAA closure can be performed safely, with good technical success and with effective long-term results. However, as is generally the case with invasive procedures, females have worse complication rates than males.

Dr. Saw also noted that a minimalist approach is being taken to LAA closure through same-day discharge and avoiding general anesthesia. Looking forward, she described some of the devices on the horizon, including new devices (such as single lobe design and lobe and disc design) and new iterations of current devices (such as improved seals).

A discussion followed on these and related topics, including the following:

• device positioning (need for pre-imaging and considering placement depth)
• device usage among patients in Canada (subject to provincial approval and funding)
• hemodynamic changes due to occlusion devices (no adverse effects reported)
• clinical evidence requirements for new devices seeking approval in Canada (need for randomized clinical trials demonstrating non-inferiority to a licensed device)
• use of other therapies after use of LAA occlusion devices (possible to ablate after implanting an LAA occlusion device)

Presentation #2: Leadless pacemakers (Raymond Yee)

Dr. Yee gave an update on leadless pacemakers with contributions from guest discussant Dr. Bernard Thibault. Dr. Yee described the primary rationale for using leadless pacemakers, which is to reduce the risk of complications associated with the lead. He also provided an overview of devices for which we have the most clinical experience (Nanostim/Aveir SJM/Abbott, Micra Medtronic, WiCS EBR).

Dr. Yee compared pre-market data with post-market data for leadless pacemakers (Micra’s investigational device exemption versus its post-market approval registry) and found that success rates were sustained in the real world, meaning that these devices implant well and safely. He also compared data on leaded and leadless pacemakers, noting that major complication rates continue to increase over time for leaded pacemakers but plateau for leadless pacemakers. Leadless pacemakers also appear to show stable electrical properties over time (for example, pacing thresholds) and lower rates of infection compared to leaded systems.

Finally, Dr. Yee described the progression of leadless pacemakers since early clinical use (Micra and Nanostim), including safety data over time indicating good short- to early mid-term results. He emphasized that more long-term data is needed to understand the long-term benefits and risks (for example, long-term extraction of chronic devices). He also emphasized that current leadless pacemakers do not offer physiologic pacing options (for example, His bundle or left bundle branch), which is becoming increasingly common in leaded systems. It was acknowledged that the use of leadless pacemakers in Canada remains fairly low (<5% at his facility).

Dr. Yee went on to address 3 blocks of questions, with discussion interspersed throughout, including comments on patient experiences of leadless pacemakers:

• implantation and retrieval of leadless pacemakers, for example:
  • type of patients chosen for leadless implantation versus traditional pacing systems
  • such patients are at high risk for infection
  • optimal implant location
• involvement of leadless pacemakers in patients needing more than single -chamber pacing, for example:
  • use of transvenous system when the patient requires other active implantable medical device therapies
• future considerations, for example:
  • comparing strengths and weaknesses of available and emerging leadless pacemaker technologies
  • discussion of clinical evidence requirements for future pivotal trials

Next steps, closing remarks and adjournment of meeting (John Ducas)

The Chair asked members for their preference for virtual, in-person or hybrid meetings in the future. During that discussion, the next meeting date was proposed and members were encouraged to submit meeting topics. The Chair advised that a high-level summary would be posted on Health Canada's website. He thanked the members for their contributions and closed the meeting.