Cardiac implantable electronic devices, often referred to as CIEDs, have revolutionised the field of cardiology by providing life-saving interventions for patients with a variety of heart conditions. Due to increased prevalence of cardiovascular disease, driven primarily by an ageing population, the number of CIEDs implanted each year is expected to rise, with an estimated 1.4 million devices being implanted worldwide in 2017¹. Sector & Segment estimates Sector & Segment estimated the Global CIED market to be worth £22.3billion USD in 2023 and predicts it to grow to 35.3 billion by 2033.

CIEDs come in many different forms, including pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy devices (CRTs), each tailored to address specific cardiac issues. Figure 1 displays a short summary of the options currently available.

While CIEDs have transformed the landscape of cardiac care, they are not without their challenges. Traditional CIEDs are comprised of a generator, containing the battery and electronic circuitry responsible for regulating the device, as well as two (three in the case of CRT) thin, insulated leads which carry electrical signals from the generator to the heart. It is these leads which have historically proven the “Achilles’ heel²” of CIEDs, as they are the most common cause of complications. In the rest of this article, we will delve deeper into the enduring concerns surrounding leads, the race towards a lead-free portfolio, the current roadblocks to widespread adoption, and how companies should navigate them.

The weakest link

As mentioned, lead-related complications are the most frequent type of complication CIED patients experience, regardless of CIED type. Kirkfeldt et. al analysed almost 6,000 Danish patients and found that within six months of implantation, 160 patients experienced a lead-related complication³. This accounted for just over 30% of all complications. In almost all cases, lead failures require either replacing the lead, or a full device revision, and can therefore have serious implications for patient health. Barreveld et. al assessed a registry of Dutch patients implanted with an ICD and calculated a mean cost of lead-related complications of €5,800, higher than most other common complications⁴.

There are a large variety of reasons leads can fail, which can broadly be categorised into:

• Infections - Infections at the lead insertion site can result in lead-related issues. In some cases, the infection can spread to the lead, causing lead dysfunction or necessitating lead removal. Kirkfeldt et. al found that roughly 30% of all lead-related complications were infections.
• Mechanical Issues – These include lead fractures, dislodgements, corrosion, loosening, and migration. Causes for such mechanical issues include excessive movement and/or strain, exposure to body fluids, tissue growth near the lead, or design issues.
• Wear & tear– This can be due to both time, such as a breakdown of the lead insulation due to long-term exposure to bodily fluids; as well as external factors, such as exposure to strong electromagnetic fields or radiation therapy.

Further, issues related to the ‘pocket’ created outside the heart where the generator has to be placed, such as infections and hematomas, as well as pulse generator issues, are also common causes of complications in devices involving leads.

The race for leadless devices

Pacemakers

The high costs and health burdens attributable to leads provide a large incentive for companies to develop devices which do not rely on leads. The intuitive  solution is a self-contained device which is small enough to go directly into the heart, eliminating the need for a pocket and leads.  Although such a device was theorised as early as 1970⁵, the first device was not trialled in humans until 2012. Figure 2. shows a timeline of the “race” to developing a leadless pacemaker.

The first company to trial a leadless device was St. Jude Medical in 2012. The pioneering device, Nanostim. was a single-chamber pacemaker. It was inserted by making a small incision in the patient’s groin, inserting a catheter into the femoral vein through the incision, and depositing the device in the patient’s heart. The initial study on 33 patients was promising, as 94% of patients had no complications⁶. Between 2013 and 2016, 1423 Nanostim devices were implanted worldwide⁷. Unfortunately, rare but serious product faults, most notably battery failures between 29- and 37-months post implant, resulted in the device being recalled and discontinued before ever receiving FDA approval.

Despite the recall of Nanostim, the concept gained widespread acceptance, and in 2015 Medtronic launched the now widely adopted Micra, using the same mechanism and method of implementation. Medtronic went on to enjoy a de-facto six-year monopoly, and celebrated implanting their 100,000th Micra⁸ in 2021. During this time, Medtronic also launched Micra AV, a leadless pacemaker which also provides atrioventricular synchrony. This expanded the target population of leadless pacemakers to patients with AV block. Abbott, having acquired St. Jude Medical for $25bn⁹ in 2017,  finally re-entered the market in 2022 with a leadless single-chamber pacemaker, Aveir VR, boasting twice the battery-life of Micra¹⁰. A few months later, Medtronic released the second generation of pacemakers, Micra AV2 and Micra VR2. Both claim to have a 40% increase in battery life compared to previous generations, and the AV2 has an increased upper limit in tracking capability for faster heart rates (115->135 BPM)¹¹. All three new leadless pacemakers received FDA approval the same year.

In 2023, Abbott regained pole position as they were the first to launch and receive FDA approval for a dual-chamber pacemaker, Aveir DR. The system involves two small implants, one placed in the right atrium and the other in the right ventricle, which communicate wirelessly to synchronize the patient’s heartbeat. This expands the target population considerably, as approximately 80% of patients who require a pacemaker require dual-chamber pacing¹².

Meanwhile, Boston Scientific has been attempting to enter the market and differentiate themselves by trialling a leadless pacemaker, Empower, since 2021. Empower can coordinate with their subcutaneous ICD (see next section). In many cases, patients who require an ICD will later require a pacemaker. Initial evidence of both their subcutaneous ICD and leadless pacemaker is positive, meaning that Empower will likely become the default choice for patients already fitted with a subcutaneous ICD.

Implantable Cardioverter-Defibrillators (ICDs)

Leads for ICDs are more complex than pacemaker leads as they require coil(s) to send high-voltage shocks to the heart. As a result, we are not yet able to develop a leadless technology. Instead, Boston Scientific has developed a subcutaneous ICD (s-ICD), Emblem. In the case of s-ICD implantation, the surgeon places the s-ICD under the skin below the patient’s armpit, whilst connecting the device with a lead to an electrode which runs along the breastbone. Not only is this procedure less invasive, but it also means that no leads are placed directly into the heart.

Boston Scientific started trialling Emblem in 2009 and have since built up a strong body of evidence indicating lower rates of complications¹³.  On the other hand, one of the most serious complications of ICDs are unnecessary shocks, which are not only painful and distressing for the patient but have also been shown to correlate with higher healthcare costs and mortality rates^14,15. Unfortunately, Emblem has been shown to have comparable, if not higher, rates of unnecessary shocks when compared to traditional ICDs¹⁶.

Emblem was the only available s-ICD for over a decade and as of 2023, an estimated 120,000 Emblems have been implanted worldwide¹⁷. Boston Scientific’s monopoly is coming to an end however, as in 2023 Medtronic launched a competing system, Aurora, which received a CE mark early in the year. Aurora is half the size of Emblem, which theoretically may provide easier implantation, better longevity, and improved patient comfort.

Cardiac Resynchronization Therapy (CRT)

EBR Systems started working on a leadless CRT device around 2013, WiSE¸ to be used in conjunction with an ICD or pacemaker. The proprietary technology uses ultrasound waves to deliver cardiac resynchronization. Placing of the system initially proved difficult, and the first conducted study was terminated early, with only 13/17 patients having the system successfully implanted. The other 4 patients experienced cardiac perforations, one of which was fatal¹⁸. Recent research and development efforts have proven much more promising, as a 2022 study showed all 31 patients having the device correctly fitted¹⁹.

Attaching a CRT lead to a tiny leadless pacemaker would likely be impossible, so as the adoption of leadless pacemakers and ICDs continues to grow, so does the need and value of leadless CRT. Many patients with a pacemaker or ICD may later develop heart failure and require CRT. A 2021 study combining WiSE with a leadless pacemaker, Micra, provided promising evidence that the two can operate in tandem²⁰. As of October 2023, WiSE remains the only available leadless CRT device on the market.

Battery-free pacing

Scientists have successfully tested a heartbeat-powered pacemaker in living pigs²¹, although extensive further research is required before it can be tested in humans. The device would need to be implanted in the heart during open heart surgery, which is far more invasive than the other leadless technologies discussed and would therefore severely restrict the eligible patient population.

Current roadblocks for leadless devices

Despite Abbott’s relatively late development of a leadless pacemaker, they still hold 30% market share in the market for pacemakers  (Medtronic is the market leader at 46%)²² due to the large number of traditional pacemakers still being implemented. A 2018 survey of 52 centres across Europe which implant pacemakers indicated that although the majority (86%) of centres do implant leadless devices, in 80% of centres leadless devices account for less than 10% of  implanted pacemakers²³.

From figure 3 it is clear that clinicians are very open to new leadless developments, as all centres indicated that they believe in the technology and are able to implant it. There is also no indication of patients opting for a traditional pacemaker. Lack of dual-chamber or CRT pacing was a reason for not implanting in slightly over a quarter of cases, but the commercial release of Aveir DR and WiSE since the study was conducted likely eliminates this concern. It is therefore clear that the overarching barriers of adoption, given the correct indication, are price, reimbursement, and availability.

Keys to successful market adoption

Once safety of a new leadless technology is proven, there are various avenues companies can explore to encourage faster adoption:

Strengthening the research base

Conducting additional research serves as a critical step in demonstrating both the effectiveness and value of leadless devices. Additional RCTs comparing leadless devices with traditional pacemakers not only convey scientific rigor, but also offer a comprehensive and easy-to-understand view of their  performance relative to the traditional offerings. Alternatively, compassionate use studies provide an avenue to gather not only further real-world data, but also patient testimonials which can prove very powerful in conveying tangible QoL improvements. Although HCPs already understand the potential benefits of leadless devices, the aim should be to establish them as a first-line treatment in appropriate patients. This will require a consensus among HCPs of undeniable clinical superiority to traditional pacemakers.

Actively engaging stakeholders

To establish favourable reimbursement policies, insurers and policymakers need to be made aware of the undeniable cost savings which stem from reduced complication rates when using leadless devices. Meanwhile, persuading key opinion leaders (KOLs) will play a crucial role for the inclusion of leadless devices in guidelines and best practices. KOLs need to be made aware of not only the reduced complication rates, but also the importance of the improved patient comfort which leadless devices provide.

Investing in cyber security measures

One of the largest concerns around new technological advancements in CIEDs is the increased potential for cyberattacks which could target and disable the device. Medtronic has previously garnered media attention after it was shown that their devices could potentially be hacked through their internet-based software updating systems. Pre-emptively partnering with leaders in the cyber security space to reassure both stakeholders and patients that any new technology is not only clinically superior, but also the most resistant to hacking, could be another route to faster adoption.

How we can help

Sector & Segment has extensive experience helping companies innovate in both young and more mature markets. Specifically, our experts can provide support to companies in the CIED space through:

• Conducting market analysis and assessing the landscape for CIEDs, including market potential, competitive landscape, and regulatory considerations.
• Conducting feasibility studies and financial analysis to assess the potential ROI and determine the best course of action.
• Researching and quantifying preferences and attitudes of HCPs and payers to determine which product features to highlight and prioritise when developing or marketing new innovations.
• Providing strategic guidance and expertise in the context of mergers and acquisitions, including assessing target companies, conducting due diligence, and identifying synergies to maximize value creation during the deal process.

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