In this interview, EP Lab Digest speaks with electrophysiologist John N. Catanzaro, MD, FACC, FESC, FHRS from the University of Florida Jacksonville about his experience with a new bio envelope created specifically for use with subcutaneous implantable cardioverter-defibrillators (S-ICDs).
Tell us about your EP program at the University of Florida College of Medicine – Jacksonville.
I am an assistant professor of medicine at the UF College of Medicine - Jacksonville. We have a comprehensive EP program, ranging from treatment of atrial fibrillation with different energy modalities, to lead management including laser-assisted and mechanical lead extractions, as well as a structural heart program including LAA closure. In addition, we implant pacemakers as well as transvenous and subcutaneous defibrillators. I am involved in active research within the S-ICD on defibrillation thresholds, DFT vectors, and shock impedance. We will be enrolling in MADIT S-ICD in the near future.
What can you tell us about the CanGaroo ECM Envelope and design?
The “ECM” of the CanGaroo ECM Envelope is an abbreviation for extracellular matrix, which derives from the submucosa of pig intestines. Tissue is decellularized, which prevents any immune response from being activated once it comes into contact with an antigen or some other type of tissue. On a basic science level, when a foreign body is implanted, there is a type 1 macrophage inflammation cascade that occurs. Once the inflammatory response happens, the cascade usually leads to scar, which forms in the shape of a capsule around the cardiac implantable electronic device (CIED). However, once this ECM makes physical contact with the tissue, the type 1 inflammatory cascade is not activated; instead, a type 2 cascade mimics a regenerative response, in which the cells actually recognize this bio envelope as its own tissue. The benefits of this include: 1) formation of a capsule with no scar, 2) resistance to calcification over time, and 3) absence of an inflammatory response, thus promoting a natural healing environment. There has even been evidence of angiogenesis in animals. For example, studies performed implanting pacemakers in rabbits showed blood vessels forming in the capsule, retaining a natural environment. An inflammatory response, on the other hand, would trigger formation of an avascular capsule. This avascular capsule may have the potential to either harbor a subthreshold level of bacterial infection or promote the accumulation of calcium. Scar formation with calcium deposition around the generator could potentially impact defibrillation threshold testing.
Tell us about your experience with the Aziyo Biologics bio envelope.
When I started using it, the CanGaroo was used to promote a stable pocket for the transvenous pacemaker or defibrillator, which is, for the most part, placed under the clavicle in the subcutaneous space. When implanting the S-ICD, there was a need for a custom-made envelope that would fit around the device. The thought of doing this was not to mimic what is being done with transvenous devices. Instead, the goal is to promote a healthy environment around the can and coil, which serve as vectors. It is important for the implant to be optimal with respect to the coil and can. This refers to the ability of tunneling down to the sternum and placing the can onto the latissimus muscle in the formation where the can is tilted posteriorly and not anteriorly. This buttresses the pouch against the muscle, essentially preventing anterior migration of the device, which is beneficial for preserving DFT vector at implant. We also know that a few millimeters of sternal fat can exponentially increase the energy required to successfully defibrillate the heart using shock impedance as a surrogate.
In addition, select patient populations that are candidates for the S-ICD, chronic kidney disease or hemodialysis patients, can have high rates of calcification within the pocket. If that calcium deposition builds up, the energy delivered when the device is required to defibrillate could be absorbed by that calcium or by the scarred capsule, and the energy that reaches the heart would not be enough to effectively defibrillate.
I believe there is more than meets the eye when it comes to merging the field of regenerative medicine and electrophysiology. This technology will serve as a springboard to other applications in the field of electrophysiology.
When did you begin using the bio envelope? How many implants have you performed thus far?
Our center participated in the SECURE registry, in which we enrolled approximately 40 patients. Since then, I’ve implanted the new XXL in two patients: one with Long QT syndrome, and the other in a young patient with idiopathic ventricular fibrillation.
What techniques or technologies for minimizing pocket infection were you using prior to the CanGaroo envelope?
The standard of care is to give peri-operative antibiotics during the procedure. If a patient is at high risk for infection, another method would be to use the absorbable synthetic antibacterial envelope. However, I think that the move toward using a natural-based extracellular matrix has several advantages, including avoiding antibiotic resistance and worsening renal function, as well as avoiding an inflammatory response within the pocket itself. All patients will eventually need generator changes or device extractions at some time, and these can be facilitated by a healthy environment, which is promoted by the ECM. There previously was not a pouch available for the subcutaneous ICD, which provided the opportunity to look into this further. The primary reason for the XXL was to help preserve the defibrillation vector at implant and allow for the lowest shock impedance possible for effective defibrillation. There can be many barriers to effective defibrillation, so we want to give patients the best chance at saving their life when defibrillation is ultimately needed. If we can preserve the defibrillation vector at implant, that is a great start. We will be starting some longer term studies to see if these results can be shown beyond S-ICD implantation.
What are some of the challenges associated with S-ICD implantation (compared to transvenous ICDs)?
The procedure takes a little bit longer, and the BMI of the patient can contribute to the complexity of the case. I find that the length of the lead for the subcutaneous ICD can also be an issue. If the patient has a BMI >35, tunneling the lead from the sternum into the pocket can limit the length of the lead. If there is a limited length to the lead, that can limit the ability to use the device. In addition, the device itself has two suture holds, allowing only the top of the device to be sutured. In many of these cases, we perform the procedure with the patient lying in the supine position; however, this does not simulate real-life activity, so I do expect some migration of the device once the patient gets up and moves around. In addition, I had a recent case where a device was implanted for a secondary prevention indication at another facility; this device then migrated and came completely off of the muscle, so if the device would have detected VF, it would have shocked the patient and had a high probability of not effectively defibrillating the patient. I was able to revise the pocket using the ECM, and anchor the anterior portion and the posteriorly directed inferior aspect of the can to the muscle itself. If the can migrates anterior or moves out of position, the DFT vector is essentially completely changed and unpredictable.
Are you doing an increased number of S-ICD implants? What would you estimate is the percentage of your device implants for S-ICDs (compared to transvenous ICDs)?
When I see a patient, no matter what their age or comorbidity, I take into account their history and physical occupation as well as their age. If there is no pacing indication or requirement of anti-tachycardia pacing (ATP), then I consider choosing between a single-chamber transvenous or subcutaneous device. I have a discussion with the patient regarding both, and we make a joint decision, knowing that whatever type of system is used, we go over the advantages and disadvantages of each. The advantage of the S-ICD is that the system does not come into contact with the myocardium or endovascular milieu, so if there is ever an infection and lead extraction is needed, these patients are spared that risk. Whereas, with a transvenous system, there is the possibility of an infection with the presence of sepsis and bacteria either attaching via biofilm to the endovascular leads or, in worse cases, spreading to the cardiac valves. That is one of the aspects of transvenous devices that I explain to patients — if they acquire a bloodborne infection with an indwelling transvenous system, the likelihood of that infection clearing, especially as they age, is lower than with a subcutaneous system.
How do you see the future of this technology? Will further clinical research be done at your facility?
It’s an exciting time to embrace the concept of merging regenerative medicine and electrophysiology in regard to CRM and subcutaneous devices. Further studies will be performed at UF Health Jacksonville evaluating the efficacy of using the bio envelope to preserve shock impedance over time. Over time, we hope to conduct a multicenter trial to further explore questions that are unanswered regarding subcutaneous defibrillation. I believe that the platform for subcutaneous defibrillation will become larger, and using the bio envelope as an adjunct with any subcutaneous device may offer the opportunity to not only achieve effective defibrillation, but possibly achieve ATP with lower pacing thresholds given the absence of scar formation within the pocket.
Disclosure: Regarding the content herein, Dr. Catanzaro reports he is an advisor for CorMatrix. Outside the submitted work, he reports grants and non-financial support from Boston Scientific and Abbott.