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New technological advances propel the field of arrhythmia disorders
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For patients with arrhythmia disorders, technology to help manage their conditions is evolving so rapidly that concepts that appeared impossible just a few years ago are now a reality.
Among the groundbreaking technologies new to the market or in clinical trials are leadless pacemakers, subcutaneous implantable cardioverter defibrillators, subcutaneous implantable loop recorders and tools to make ablation more effective.
Vivek Y. Reddy, MD, presented 1-year data
from the LEADLESS study at the Heart Rhythm
Society Annual Scientific Sessions.
Source: Mount Sinai
Underlying the advancements is the ability to make procedures to diagnose and treat arrhythmia disorders far easier on the patient than previously, reducing complications and the need for repeat procedures.
“Cardiac electrophysiology has traditionally been a technology-driven field,” Rahul Doshi, MD, FACC, FHRS, associate professor of medicine and director of clinical cardiac electrophysiology at the Keck School of Medicine of the University of Southern California, told Cardiology Today. “As technologic advancements continue, we are seeing advancements in all areas of electrophysiology, from pure basic science all the way to mechanical and electrical engineering. It has evolved so quickly over my career and that of others like me who have been doing this for some time.”
Leadless pacemakers
Arguably the most-hyped breakthrough is the leadless pacemaker, which can be implanted without surgery. Instead, the devices, which are approximately 90% smaller than a traditional pacemaker, are implanted directly inside the heart by a catheter-based procedure via the femoral artery.
“From my standpoint, the leadless pacemaker is one of the most exciting technological advances that we’ve seen over the past 10 years,” Andrea M. Russo, MD, FACC, FHRS, professor of medicine at Cooper Medical School of Rowan University, Camden, N.J., said in an interview.
Andrea M. Russo
“It’s a very promising technology. The transvenous lead has been considered the weakest link in ICD and pacing systems. My guess is within 5 or 10 years down the line, we will be using many more leadless systems. In the absence of a subcutaneously implanted pulse generator, there is also no risk for erosion. Anytime you have a transvenous lead of any sort, whether it be an ICD or pacemaker lead, there is a real risk for infection,” said Russo, who also is director of cardiac electrophysiology and arrhythmia services and director of electrophysiology fellowship at Cooper University Hospital, Camden, N.J.
Two single-unit leadless pacemakers are in development: the Nanostim (St. Jude Medical) and the Micra (Medtronic). The LEADLESS study demonstrated that the Nanostim was safe and effective in early testing of 33 patients, with an implant success rate of 97% and a complication-free rate of 94% at 90 days and at 1 year. The LEADLESS II study of approximately 670 patients, which will serve as the pivotal trial for FDA approval, began enrollment in February. The Micra global pivotal clinical trial, which will enroll up to 780 patients, began in December. Ninety-day results from the first 60 patients will be reported in the second half of 2014, according to a Medtronic press release.
The Nanostim received a CE mark approval in October and is available in Europe. Neither Nanostim nor Micra are currently available in the United States.
The driving force behind the development of leadless pacemakers is the desire to reduce complications, Vivek Y. Reddy, MD, director of electrophysiology services at The Mount Sinai Hospital and principal investigator of the LEADLESS studies, told Cardiology Today.
“Over time, [pacemakers] have gotten smaller and smaller, but they’ve always retained the same basic configuration: a pulse generator and a lead,” he said. “The problem is, the lead has always been the weak link in the system. You can get lead fractures, the lead can get incorporated into the wall of the vein, and if you’re unable to remove it, it can lead to complications; lead extraction also has potential complications.
“The idea of having a leadless pacemaker is to deal with all these issues,” Reddy added. “It is all encapsulated in one very small unit that is positioned directly within the heart itself. There are no incisions, and that will presumably decrease the risk for infection and also improve cosmesis and post-procedure discomfort. Also, by not having the lead, you don’t have the potential lead-related tricuspid valve damage and regurgitation/leakage.”
“They’re both good concepts,” Reddy said. Micra is approximately 30% smaller than Nanostim, according to Medtronic.
One year and beyond
At the Heart Rhythm Society Annual Scientific Sessions in May, Reddy presented 1-year data from the LEADLESS study. Data showed no further complications of the device between 90 days and 1 year, including no evidence of device migration or dislodgement, ventricular arrhythmias, infection, device malfunction or early battery depletion. In addition, performance of the device remained consistent (see Table).
“It behaved just like we expected,” Reddy said at a press conference. “It continues to sense and pace appropriately, the battery voltage is as we expected, there are no additional complications and, fundamentally, the device seems to work.”
Besides providing results that could be the basis for FDA approval, the LEADLESS II study will also allow investigators to hone the implantation process, according to Daniel Cantillon, MD, FACC, FHRS, cardiac electrophysiologist at Cleveland Clinic and a member of the LEADLESS II steering committee.
Daniel Cantillon
“As we go along implanting these devices, we are gaining a greater experience with the deployment,” he told Cardiology Today . “It’s very different from traditional pacemaker surgery. If the device should gain FDA approval … obviously we would share our experiences in what we’ve learned in implanting this device from a technical standpoint with our colleagues, so that hopefully those physicians have a similarly safe experience providing this for patients. So far, in the very early phases of the trial, things have gone very smoothly.”
The data and safety monitoring board will meet twice in 2014 to review data from all centers and get a sense of outcomes and complications, Cantillon said.
The one failed implant in LEADLESS occurred because of cardiac perforation during device implantation, and more perforations have been reported in Europe since the device was approved there, Reddy noted at the press conference.
“What we need to understand is how frequently this will happen,” he said. “We know that there are complications related to implantation, even with traditional leads. We also know that with any new technology, there is going to be some amount of complications related to the procedure. As one could anticipate, there have been such complications.
“Is it an initial learning curve issue, which we sort of expect, or is it something that can be sustained long term? At this point, we don’t believe it’s going to be the latter, but only time will tell,” Reddy said.
For simple pacing needs
The first generation of leadless pacemakers will be best suited to those with simple pacing needs, according to Dwight W. Reynolds, MD, FACC, FHRS, FAHA.
“The leadless devices of the current early iteration … are only applicable in the ventricle of the heart,” said Reynolds, who is professor of medicine and chief of the cardiovascular section at University of Oklahoma Health Sciences Center. He also is chairman of the steering committee for the Micra global pivotal clinical trial.
“Currently, we are only using these devices in patients in whom a single-chamber ventricular pacemaker would be a reasonable consideration. The ideal population would be those patients who have atrial fibrillation, who have pauses in their heart rhythm or have complete heart block associated with AF that can be paced as effectively with ventricular-only pacing as they could be with either dual-chamber systems or atrial-only systems. It is also likely that this will be a reasonable consideration for those patients who very infrequently need pacing support,” Reynolds said.
Another company, EBR Systems Inc., has a leadless technology, Wics, to pace the heart through wireless transmission of energy. It does not yet have a CE mark or FDA approval.
“There is a generator, which can emit ultrasound pulses, that is placed in the chest wall,” Reddy said. “Then there are very small pellets that are positioned in the left ventricle. The ultrasound impulses travel to the left ventricle, and then that little pellet paces the ventricle. It’s also a leadless device, but is not encapsulated into a single unit” as with the Nanostim and Micra devices.
In 2013, results for the first three patients in WISE-CRT, the first-in-human study for the Wics device, were reported. Mean LV ejection fraction improved from 23.7% to 39% (P<.017), and all three patients improved in NYHA functional class.
Leadless pacemakers could hit the US market in as soon as 18 months, but it could be longer, given the unpredictability of the FDA process. “Very optimistically, I think a year-and-a-half to 2 years from now may see the first FDA approval,” Reddy said. “The patients [in LEADLESS II] will be followed for 7 years, but the data will be submitted to the FDA long before that.”
Although the leadless pacemakers being tested perform only single-chamber cardiac pacing, future iterations will incorporate features seen in traditional pacemakers.
“One of the limitations of the current leadless pacemaker is that it can only provide single-chamber pacing, which is the most basic form of cardiac pacing,” Cantillon said. “There are already very early efforts underway to explore the possibility of dual-chamber pacing and potentially biventricular pacing with these devices. That’s the next frontier.”
Reynolds agreed. “Most of us believe that as the technology continues to evolve, we’ll have atrial-capable leadless devices as well as dual-chamber devices. Communication between leadless atrial and ventricular devices is a hurdle that has to be overcome, but many of us believe it will eventually be accomplished.”
Subcutaneous ICDs
As with leadless pacemakers, the subcutaneous ICD (S-ICD System, Boston Scientific) was designed to eliminate lead-related complications. Rahul DoshiImage: Jon Nalick Keck, Medicine of USC; reprinted with permission
Rahul Doshi
Image: Jon Nalick
Keck, Medicine of
USC; reprinted with
permission
“It does have a lead, but the difference is that the lead is going into the subcutaneous tissue plane, not into the body or veins,” Doshi told Cardiology Today. “Traditional leads are placed transvenously, and that is a distinct disadvantage from a variety of standpoints. The biggest one is that if you have any issues with the device itself, such as an infection or when you change the device because the batteries have run out, you need to remove the lead. Lead extraction is a high-risk procedure with a real mortality rate, let alone morbidity.”
This is important because patients with ICDs are living longer and getting them implanted at younger ages because of improvements in the technology and expanded indications for it, he noted.
“This, of course, increases the likelihood of having infection … or lead malfunction, related to longevity or the long-term duration of the system,” Doshi said. “So we’re exposing more and more patients to the risk of lead removal or extraction with transvenous implantable devices. Many leads are placed in the right ventricle, and thus have to cross the tricuspid valve. Long-term lead placement across the tricuspid valve can be associated with tricuspid valve dysfunction. This is not often clinically appreciated, but in select patients it can lead to chronic failure of the valve and subsequent symptoms. The subcutaneous ICD system completely avoids these as risks. If you need to remove these leads, it is very simple and doesn’t pose a great risk to the patient.”
The theory has been borne out by early results from the EFFORTLESS S-ICD registry of 472 patients, in which the complication-free rate was 97% at 30 days and 94% at 1 year.
“[A] group of patients that we should seriously consider for a subcutaneous device are women,” Russo said. “There are data to support potential underutilization of devices in women. In the NCDR ICD registry, women who received standard ICDs had a higher complication rate than men. According to data from the IDE study of the subcutaneous device, there are no gender differences in complication rates, in contrast to endocardial systems. We should certainly consider women as one of the groups to focus on.”
Similar to the early versions of leadless pacemakers, the first version of the S-ICD System has simpler functions than conventional devices, including no ability for remote monitoring. “This is a system that does not pace,” Doshi said. “We currently only can place a subcutaneous ICD system in someone that needs ICD protection but does not require pacing in any way, shape or form.”
In contrast to the leadless pacemakers, however, the S-ICD System is larger than conventional ICDs. However, most patients have been able to tolerate its size, Doshi said.
Future versions will be smaller and will have remote monitoring capabilities, he said. “Both of these things are essentially addressed and will likely go through the regulatory process. The next generation of the device will be considerably smaller, just related to battery and capacitor technology. Remote monitoring technology already exists, it’s just a question of having it put into the devices. Also, in a newer iteration, the device will be capable of backup pacing, if a patient needs it.”
Aside from patients who do not need pacing or remote monitoring, those well suited for the first generation of the S-ICD System include younger people who are expected to have an implant for a very long time, those with renal failure or diabetes for whom venous access may be difficult, those who have previously had infections from ICDs, and those with genetic abnormalities placing them at high risk for sudden cardiac death, Doshi said.
Implantable loop recorders
Implantable loop recorders, which continuously monitor and detect arrhythmias, have been around since the late 1990s, but have undergone extensive changes in design. The Reveal LINQ (Medtronic), at approximately 1 cc, is the smallest implantable cardiac monitoring device available for patients and is more than 80% smaller than other insertable cardiac monitors, according to a Medtronic press release. The device received FDA clearance in February.
Andrea Natale
“The old system was big enough that the patient perceived it as another surgery,” Andrea Natale, MD, FHRS, FACC, FESC, cardiac electrophysiologist and executive medical director at the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, told Cardiology Today. “In the past, we were really not able to convince patients to use this, except for a few sporadic cases. Now that the device is miniaturized, the patient accepts it.”
Inserted under the skin in a procedure that takes about 30 seconds, the LINQ works for up to 3 years and is indicated for patients who require long-term monitoring.
“I no longer have to have [patients] try to catch a symptom with an external monitor or a cumbersome monitor that they have to wear,” John Rogers, MD, FACC, director of cardiac pacing and tachyarrhythmia device therapy at Scripps Clinic, La Jolla, Calif., said. “The device has the capability to communicate with a cellphone-based type monitor that’s plugged in next to [the patient’s] bed. If any alerts have been triggered, it’s going to communicate with that bedside monitor, which then sends an alert to me via Medtronic’s CareLink network.”
Rogers said two types of patients are well suited for the LINQ monitor. The first group is “those with syncope or near syncope or palpitations that are quite symptomatic but not frequent enough to pick up on a 24-hour Holter monitor or another shorter-term monitor. The patients that have symptoms every day or multiple symptoms a week are not going to be indicated for this monitor. But those who have less-frequent symptoms would get this monitor.”
The other group, Rogers said, is patients with cryptogenic stroke or transient ischemic attack. “After they’ve been through an extensive workup for why they’ve had a stroke or a TIA and the neurologists still don’t have a good explanation, our concern is that it could be AF, so the monitors are implanted to watch those patients for AF.”
The CRYSTAL AF study, presented at the International Stroke Conference in February, showed the efficacy of implantable loop recorders compared with standard cardiac monitoring in patients with cryptogenic stroke. At 6 months, AF was detected in 8.9% of patients who received the LINQ’s predecessor, the Reveal XT, compared with 1.4% of patients who received standardized cardiac monitoring (HR=6.43; 95% CI, 1.9-21.74). At 1 year, AF was detected in 12.4% of patients in the Reveal XT arm vs. 2% of the control arm (HR=7.32; 95% CI, 2.57-20.81). At 36 months, AF was detected in 30% of those assigned Reveal XT vs. 3% assigned control monitoring (HR=8.78; 95% CI, 3.47-22.19).
“And that’s with the old monitor, where if they had symptoms it was downloaded or it would get interrogated once a month,” Rogers said. “The new device would allow us to see on a daily basis if those patients had AF, reducing their risk for recurrent stroke.”
Ablation catheter with sensors
Technology also has progressed for ablation procedures. Notably, the FDA in February approved the ThermoCool SmartTouch catheter (Biosense Webster), the first device that enables direct and real-time measurement of contact force during catheter ablation procedures.
“The ablations that we do rely on achieving permanent lesions in the areas we can see are abnormal and responsible for the rhythm problem,” Natale, who was primary investigator for the SMART-AF trial that led to approval, said in an interview. “And what makes a good lesion is good contact between the catheter and the cardiac tissue. In the past, we really had no sort of way to measure that besides tactile feedback or other sorts of indirect information like temperature impedance and quality of the electrogram, which are not very reliable.”
In the SMART-AF trial, freedom from recurrent AF was 77% when the procedure was performed within the operators’ selected pressures at least 80% of the time compared with 62% when performed out of the selected range (P=.03). “It’s a very important advancement to the technology that we use every day for ablation procedures, specifically for those procedures where we target … multiple spots for AF and ventricular tachycardia,” Natale said.
Advancements in mapping systems also have made AF ablation procedures more effective, and the LINQ now has a role in the process as well, Natale said.
“The LINQ can become part of this process because it’s a more accurate way of finding out if we’ve done a good job with the [AF ablation] procedure,” he said. “The SmartTouch and the LINQ have become part of an array of tools that we use to do the procedure and verify the outcome of what we have done.”
Work is never done
As these new technologies are adopted and new iterations develop, it is possible that they will be deployed in concert with one another, Russo said.
“We could even use leadless pacemakers with ICDs that are totally subcutaneous,” she said. “If someone has a previously implanted totally subcutaneous ICD system and they subsequently require pacing, you wouldn’t need to remove the whole system and completely replace it with a totally transvenous ICD lead system.”
Despite all of the recent advances, there is still more work to be done, including better identification of patients who are at risk for sudden cardiac death and need some sort of intervention, experts said.
“There is a huge amount of potential advancement identifying patient populations that are not currently indicated or are not being protected,” Doshi said. “We only protect a very small subset of patients who actually have sudden cardiac death in the current indications. The melding of genetics and electrophysiology are making very, very significant advances. Genetics in electrophysiology will be the next big wave of identifying patients at high risk.” – by Erik Swain
Bernstein R. Plenary Session III: Abstract LB11. Presented at: International Stroke Conference 2014; Feb. 12-14, 2014; San Diego.
Lambiase PD. Eur Heart J. 2014;doi:10.1093/eurheart/ehu112.
Natale A. Abstract LB02-03. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 8-11, 2013; Denver.
Reddy VY. Abstract LB02-01. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 8-11, 2014; San Francisco.
Reddy VY. Circulation. 2014;129:1466-1471.
Daniel Cantillon, MD, FACC, FHRS, can be reached at Cleveland Clinic, 9500 Euclid Ave., Desk J2-2, Cleveland, OH 44195; email: cantild@ccf.org.
Rahul Doshi, MD, FACC, FHRS, can be reached at 1510 San Pablo St., Suite 322, Los Angeles, CA 90033; email: rahul.doshi@med.usc.edu.
Andrea Natale, MD, FHRS, FACC, FESC, can be reached at Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, 3000 N. Interregional Highway 35, Suite 720, Austin, TX 78705; email: dr.natale@gmail.com.
Vivek Y. Reddy, MD, can be reached at One Gustav L. Levy Place, Box 1030, New York, NY 10029; email: vivek.reddy@mountsinai.org.
Dwight W. Reynolds, MD, FACC, FHRS, FAHA, can be reached at 825 NE 10th St., Suite 2500, Oklahoma City, OK 73104; email: dwight-reynolds@ouhsc.edu.
John Rogers, MD, FACC, can be reached at 10666 N. Torrey Pines Road, La Jolla, CA 92037; email: rogers.john@scrippshealth.org.
Andrea M. Russo, MD, FACC, FHRS, can be reached at Cooper University Hospital, Dorrance Building, 4th Floor, 1 Cooper Plaza, Camden, NJ 08103; email: russo-andrea@cooperhealth.edu.
Disclosures: Cantillon reports consulting for Cardionomic and St. Jude Medical and past consulting for Medtronic. Natale reports receiving speaker honoraria from Biosense Webster and Medtronic and serving on an advisory board for Biosense Webster. Reddy is a consultant to and advisory board member for St. Jude Medical and in 2013 received one-time financial compensation from St. Jude Medical in the form of an option buyout relating to the company’s acquisition of Nanostim. Reynolds reports advising and consulting for Medtronic. Rogers reports financial ties with Biotronik, Boston Scientific, Medtronic and St. Jude Medical. Russo was an investigator for the IDE trial and postmarket study for the S-ICD System and reports receiving research support and honoraria/consulting fees from Biotronik, Boston Scientific, Medtronic and St. Jude Medical. Doshi reports no relevant financial disclosures.