CardioFit Device Shows Promise in Treating Heart Failure
By Jaimie Lazare
Ongoing research of an implantable device may be the key to treating patients with heart failure for whom the standard of care doesn’t improve symptoms.
Congestive heart failure (CHF) is a leading cause of hospitalization among elderly patients. The management of patients’ CHF includes medication and lifestyle changes. However, for some, that may not be enough to help improve their symptoms. An alternate treatment is being explored in INOVATE-HF (Increase Of VAgal TonE in Heart Failure), a worldwide investigational trial of CardioFit, an implantable electrical device developed by BioControl Medical. The trial is determining the device’s efficacy in heart failure treatment.
“The CardioFit device is a vagal nerve stimulator that uses electrical signals to increase parasympathetic flow to the heart. After implantation, the amount of stimulation is gradually increased because there are on-and-off cycles that provide intermittent stimulation to the vagus nerve. Parasympathetic stimulation of the heart does a variety of good things, such as reduce arrhythmias and apoptosis,” says David E. Lanfear, MD, MS, FACC, a researcher in advanced heart failure and cardiac transplantation and the lead investigator for the INOVATE-HF trial at Henry Ford Health System in Detroit. “Although we don’t fully understand the role of apoptosis in heart failure, cell death occurs in the hearts of people with cardiac failure and arrhythmias.”
“In heart failure, the sympathetic nervous system ramps up heart rate and blood pressure, which is fine in the short term because it’s maintaining adequate blood flow to vital organs. But over the long haul, it actually causes damage to the heart because the heart gets bigger, scar tissue forms in the heart, and the heart just fails even more over time,” says George Sokos, DO, a heart failure cardiologist and principal investigator for the INOVATE-HF trial at Allegheny General Hospital in Pittsburgh. “Beta-blockers are commonly prescribed to heart failure patients because they block part of the sympathetic nervous system. What the CardioFit device does is work from a totally different angle. You still utilize all the medicines, but the device ramps up the parasympathetic nervous system to slow the heart rate down, decrease the amount of work that the heart needs to do, and make the heart work more efficiently.”
Every institution participating in the trial uses a multidisciplinary approach to care. At Massachusetts General, an electrophysiologist and a neurosurgeon are involved with implanting the device, while a heart specialist manages it, according to Parks.
While all patients are monitored throughout the study, the treatment group must be assessed via more frequent monitoring and follow-up. Parks says initially patients with the implanted device return within 10 days so wound healing can be monitored. Those participants are observed frequently because the vagus nerve stimulation must be turned on slowly to avoid side effects that can include voice changes, cough, hoarseness, or nausea, all of which can typically be treated by decreasing the amount of stimulation applied to the nerve. The device is activated three to four weeks after implantation, followed by six visits to increase the level of stimulation, she says.
“In order to qualify for the trial, the person has to be on standard-of-care therapy for heart failure. Because heart failure medicines are good, this trial is really reserved for those people who haven’t responded to traditional therapies. It’s a step-up approach, and we’re comparing it to standard of care. The control group in the trial continues to get their standard medical therapy,” Parks says.
Sokos notes that medications may not have ever worked for some patients. “I mean, a lot of times we’re limited by these medicines that we use for heart failure. One of the limitations that we run into is an inability to add other medications that are proven to work because patients aren’t able to tolerate them,” he says.
“If we get a good response to the medication, people do well for a significant amount of time. Sometimes, as they get older, they start to get a little bit worse despite the best medical management that we have. More than likely, the people who end up utilizing the CardioFit device are people who never got to the point where medications were working to begin with,” Sokos continues. “The likelihood is they’ve had heart failure for some time, and they’ve had physicians try to adjust their medications over a period of time because there really haven’t been many other options.”
Levy says she was informed of adriamycin’s possible side effects, one of which was the development of cardiac problems. In December 2009, she developed CHF. Levy spent several days in the ICU where fluid was drained from her lungs. After her hospital discharge, she visited a local cardiologist who prescribed medication for her CHF. “And it worked for a while; I was very fortunate from 2009 to 2010. In 2011, I was in cardiac rehab, and I was actually quite healthy. There was also no sign of the cancer,” she says.
But one day in 2011, on her way home from work, Levy couldn’t breathe and her husband took her to the local hospital’s emergency department where she learned that her CHF had worsened. “I have never really fully recovered from that particular attack in 2011. I’m really still fighting that,” she says.
In 2012, Levy ended up at Massachusetts General where she met Parks and Jarmeet P. Singh, MD, PhD, director of the Cardiac Resynchronization Therapy Program, director of the Holter and Noninvasive Electrophysiology Laboratory, and an associate professor of medicine at Harvard Medical School. “I was the luckiest woman alive when I wound up in Dr Singh’s office at Mass General, and he introduced me to Dr Parks,” Levy says.
The physicians tried other procedures to help improve Levy’s cardiovascular function, but they didn’t work. “So they suggested that the study might be a good place for me. Dr Singh put the device in, and the procedure went beautifully. It’s just a couple of hours under general anesthesia, and the wound healed up well,” she says. (To learn more about Levy’s experience and the medical team involved in her care, visit http://bit.ly/UVtp9d.)
A Good Fit
“We try to look at anybody with heart failure. They have to have low ejection fraction heart failure, meaning less than or equal to 40%, and have moderate to severe symptoms. People who are doing well on standard medical therapy are not the best candidates for this study. It is for people who are on standard therapy but continue to have fairly significant impairment from heart failure,” Lanfear explains. “We’re looking for people who are still symptomatic but don’t need a transplant or mechanical circulatory support yet such as a left ventricular assist device [LVAD],” he says.
“For older patients where a transplant may not be an acceptable option, this device could potentially be a very useful therapeutic tool. Many institutions have transplant guidelines that include age cutoffs,” he continues. “Although not a hard-and-fast rule, patients who are 70 years old are not considered for transplants. On the other hand, if CardioFit proves to be effective, this could be a good option at 75 to 80 years of age or for those who are even older.
“The tendency is to make inclusion criteria extremely tight to have as homogenous and uncomplicated of a group of patients as possible. This often excludes older patients from participating. It makes it harder for patients to enroll in the study, which not only slows progress but makes the trial findings less applicable to the general population,” Lanfear notes. “For example, if no patients over 75 are enrolled in a trial, once the treatment is approved, how sure are we that it will actually work in older patients? On the other hand, I think the CardioFit trial is much broader than the typical study. In fact, we just changed the criteria to allow a wider variety of patients to enroll, which makes it more applicable to the patients that we typically see. For example, we recently screened a 79-year-old man who will probably enroll in the study.”
“People who have had major neck surgery and radiation to the neck aren’t ideal operative candidates. If your patients have chronic atrial fibrillation or a history of serious arrhythmias, they aren’t good candidates for this trial,” Parks says.
“The ideal candidate for this device would have intact kidney function. We prefer patients not to have diabetes, which is difficult because it’s a common disease process that coexists with heart failure. If they do have it, we’d like it to be controlled simply because you’re implanting a device in a patient with uncontrolled diabetes that could lead to more infections,” Sokos explains.
Patients considered for the device should be able to at least walk and function in everyday life. “We like them to be able to complete a walk test, which is sort of standard protocol in a lot of trials as a measure for minimal functional abilities. A walk test is also useful because it may not just be heart failure that limits your older adult patients’ functional capabilities in everyday life but other comorbidities like arthritis,” Sokos says. “So we try to make the judgment call as is the heart failure the main driving force behind our patients’ limitations? If it’s the heart failure alone and it’s not anything else, that’s a patient we’re trying to push for. But if they have other issues that are limiting their ability to function, even if it would make their heart function better, they’d still be limited; that’s not who we’re looking for.”
“This trial is interesting because it focuses on patients who aren’t so sick that they would be considered for a left ventricular assist device or transplant, but they are already on standard therapy and still have a lot of symptoms. This is a real need for these patients because not everyone can get a transplant or LVAD, but there are still a large number of patients that fall into this category where you have applied all conventional therapies, but they are still not doing as well as they would like,” Lanfear says. “I frequently recommend exercise regimens or cardiac rehab to improve symptoms in my heart failure patients. This can be especially helpful in older adult patients who are deconditioned,” he says.
“Heart failure is the result of other cardiovascular disease. When a person has high blood pressure or coronary heart disease over many years, it will progress into heart failure. So even though the public is well aware of high blood pressure or coronary heart disease, they don’t really understand that the long-term effects of those diseases will ultimately lead to heart failure,” Parks says. “Heart failure is one of the diseases that is increasing in prevalence because it really is a disease of the aging population. For hospitalizations of patients over the age of 65, the No. 1 diagnosis is congestive heart failure. That’s another important thing because a substantial amount of money goes toward managing these patients, and the majority of the cost goes to hospitalization.”
Parks notes that it’s premature to comment about the CardioFit device’s efficacy; however, the hope is that it will allow clinicians to control heart failure and improve symptoms, keeping patients out of the hospital. “By doing so, we not only help the patient, we help the system at large by reducing costs,” she says.
So far the device appears to be improving the lives of heart failure patients enrolled in the trial. “I am now back to work, and the device seems to be working. I feel stronger. Some days I do feel fatigued but not nearly as much as before,” Levy says. “I have hope in my life.”
— Jaimie Lazare is a freelance writer based in Brooklyn, New York.
Key Inclusion and Exclusion Criteria
• LVEF < 40% and LVEDD in the range of 50-80 mm
• Sinus rhythm, average daytime heart rate between 65 and 110 beats/min via 24-hour Holter
• Six-minute walk distance 150-425 m
• NT-ProBNP level 1,000-15,000 pg/mL
• First degree AV block with PR interval > 240 msec, second or third degree AV block, pacemaker dependence with use of unipolar sensing or a minimal postventricular blanking period shorter than 135 msec in all sensed leads
• Hgb ≤ 9.5 g/L, creatinine > 3 mg/dL (265 mcmol/L), total bilirubin level > 1.8 mmol/dL), HgbA1c > 7.5%
• OSA (AHI > 15) unless treated for at least three months
• Systolic blood pressure < 80 mm Hg
— Source: Biocontrol Medical