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The April 2017 issue of the Journal of Innovations in Cardiac Rhythm Management has an excellent paper on why BioSig's PURE EP™ is a superior electrophysiology signal recording and processing system to existing systems and positioned to shake-up the entire EP market when launched in 2018. The paper was published by a team of cardiologists and electrophysiologists at Mayo Clinic, Harvard Medical School, and BioSig Technologies, Inc. (BSGM).

The paper is titled, "Initial Experience with the BioSig PURE EP Signal Recording System: An Animal Laboratory Experience" and is rather technical. Investors wishing to read the paper can simply click on JI-CRM logo and it will pop open the PDF. Below is my summary of the key findings by the team of physicians and what this means for investors in BioSig Technologies.

A Quick Backgrounder

An electrophysiology study (EPS) is a diagnostic procedure performed by a specialized cardiologist, called an electrophysiologist, with the intent to help understand the nature of an abnormal heart rhythm. An arrhythmia is an abnormal heartbeat or a change from the normal sequence of electrical impulses that control the beating (contraction) of the heart. Atrial fibrillation (AF) is the most common form of arrhythmia and affects an estimated 2.7 million Americans.

Medications and cardioversion to control atrial fibrillation are not always effective. In these cases, a cardiologist may perform a procedure to ablate the area of heart tissue that's causing the erratic electrical signals in an effort to restore the heart to a normal rhythm. This is done by the use of specialized catheters that deliver radiofrequency energy or heat to ablate small areas of the heart or connective tissue, either by isolating or destroying the tissue causing the asynchronous signal.

BioSig's PURE EP™ is a novel surface electrocardiogram (EKG) and intracardiac multichannel recording and analysis system designed to assist electrophysiologists during catheter ablation procedures to treat cardiac arrhythmia. For additional information, read this BioNap article from February 2017 → BioSig's PURE EP: Explained.

The Problem

EPS and electroanatomical mapping systems have been around for two decades. In fact, most of the signal processing and recording systems in use today are over a decade old; and, this creates a problem because there has been a tremendous improvement in the understanding of cardiac arrhythmia pathophysiology since the first systems hit the market in 1997.

Large medical device companies like J&J and Boston Scientific have chosen to spend their R&D dollars developing and improving the high-tech electrophysiology catheters used during ablation procedures instead of upgrading the hardware that runs the system. And you can't blame them! The catheters are single use, high cost / high margin consumable products. Large hospitals buy hundreds to thousands per year versus perhaps only a few EPS system components or software upgrades a year. Bioscience Webster is one of the most profitable divisions of J&J and Abbott Labs $25 billion acquisition of St. Jude in 2016 was all about getting into this hot market.

Unfortunately, the success rate of cardiac ablation procedures (defined as the need for no further necessary intervention) is still rather low, estimated at only 30% to 60%. Procedure times are several hours long and the cost of care is increasing, largely due to the use of expensive catheters and repeat surgeries to ablate areas missed on the first attempt. BioSig has developed an alternative. A new signal processing and recording system designed to reduce procedure times and improve the outcome of ablation procedures through enhanced, real-time display of information without the need for egregiously expensive catheters.

Let's Get Technical

Traditional recording systems start with an instrumentation amplifier and then apply variable and fixed gain amplifiers, high-pass and low-pass filters, and notch filters to enhance and improve the signal display. The problem with this approach is that the original raw information generally cannot be recovered. It's like taking a picture with your phone and applying a permanent Instagram filter.

Are you sure you want to do this? Once you apply Vintage 1970's filter it cannot be undone!  

PURE EP is different. It records the unaltered cardiac signal and allows the surgeon to apply multiple display filters in new windows without corrupting the raw data. PURE EP uses a proprietary amplifier topology, which combines a very low-noise instrumentation amplifier and a high-resolution convert on a digital processing module. Importantly, the system has noise suppression from both outside and internal (catheter generated) radio-frequency interference that can result in visualization artifacts. A depiction of the two systems can be seen below.

The JICRM paper highlights some of the important attributes of PURE EP vs. traditional recording systems. One of the problems of traditional systems is saturation artifacts. These occur because of the limitations in the display when both low-amplitude and high-amplitude signals are processed by front-end amplifiers. The large amplitude signals may show up on the display as truncated (see example). The only option is to reduce the system gain, which negatively affects the visualization of small signals. For example, pacing signals present a challenging issue for older generation systems because they are orders of magnitude larger than electrograms.

Another problem associated with saturation is the system recovery time after adjusting the amplifier. Older systems can take as long as 10 seconds to reset after adjustment according to the authors of the paper, whereas PURE EP recovers in about 2 seconds (see data). If one assumes 200 burns per procedure, just this aspect alone saves approximately 20-30 minutes in procedure time.

To navigate these issues, electrophysiologists may deploy a clipping solution to remove overlapping high-amplitude signals from masking low-amplitude signals. The problem with clipping is that it changes the way the signal below the clipping level is interpreted. PURE EP navigates this issue by having a high dynamic range and low background noise performance (1 μV) approximately 10-fold better than the competition.

Another major feature of PURE EP is that it can eliminate or reduce the background noise due to the ablation catheter. Even the most high-end catheters have unbalanced background energy. This creates significant baseline drift. This can push the signal outside the bounds of the display (see example). Older systems try to mitigate this problem by installing front-end filters. PURE EP allows the operator to open up a new window that "pins" each beat to the baseline so that the data can be viewed throughout the ablation procedure without background noise corrupting the analysis.

The development of artifacts that show up as a result of notch filters also creates a visualization problem for the electrophysiologists because conventional notch filters lead to a loss of detail. PURE EP uses a different approach with proprietary adaptive notch filtering that removes the noise without
affecting the base waveform shape (see results). This preserves the integrity of the signal.

- Changing The Landscape -

According to the authors of the paper, "Maintaining good contact with tissue remains one of the greatest challenges in modern electrophysiology." It is one of the key factors that determine procedure success rates. Existing systems requires the use of relatively stiff, force-sensing catheters to display this information. Additionally, the angle of contact and the effect of the intracardiac structures produce significant signal variability. However, with PURE EP, thanks to the expanded frequency and dynamic range, the current of injury (COI) caused by the catheter contact with the tissue provides a good estimate of contact force without the need for stiff catheters.

According to Health Research International, force-sensing catheters generated $365 million in sales in the U.S. in 2016. These catheters are incredibly expensive, over $3,000 per, and the market is expected to eclipse $1 billion in 2020. The cost of these catheters is even resulting in some hospitals reusing (resterilizing) the catheters even though they are designed for single use. BioSig's PURE EP system has to be concerning for market leader Biosense Webster (J&J) because it allows for the type of contact and force sensing without these expensive catheters. Conversely, it probably looks very attractive to players like Boston Scientific that are trying to play catch-up to J&J or expand sales of their standard catheters by installing PURE EP's system. Standard irrigated ablation catheters are still roughly $1,000 a pop!

PURE EP even helps improve catheter visualization, which is extremely important when ablating above and below the aortic value in order to avoid injury to the coronaries. Things like respiratory and cardiac motion, coupled with catheter artifact, result in poor images in this location. PURE EP allows for the application of more than one filter at a time in multiple windows on the display, thus greatly improving catheter position and orientation. It can also aid in distinguishing between healthy, scar, and fatty tissue, providing more precise target ablation. This is the kind of thing that can lead to reduced procedure time and improved patient outcomes, and that's really the goal.

Conclusion

The April 2017 paper published in JICRM by Padmanabhan, D., et al. is an outstanding review of the pre-commercial data with PURE EP and how the system is positioned to potentially change the EP market for good once approved in 2018. Management at BioSig continues to guide to the filing of the U.S. 510(k) application in the second half of 2017. The review time for a predicate device like PURE EP should be rather quick, perhaps only a few months. Once on the market, PURE EP has the potential to shift market share in both the EP recording and mapping market, dominated by players like GE Healthcare, Boston Scientific, and Abbott, and advanced catheter manufacturers like J&J.

The market is asleep on BioSig right now. Perhaps they see an upstart player not capable of competing with behemoths like GE and J&J. Companies like Abbott, Medtronic, and Boston Scientific are all battling for market share. But it is clear that BioSig's market capitalization of $40 million does not remotely come close to fairly valuing the PURE EP system. This is space that has seen significant M&A activity over the past few years. One day, one of these major players is going to wake up and realize that without PURE EP, they may get left behind.