Medical Device Daily Senior Staff Writer

It's not uncommon for heart failure patients to receive an implanted medical device for their condition, but the devices typically used in these cases are pacemakers and defibrillators. Medtronic (Minneapolis) is trying to find out if a different type of device – a spinal cord stimulation (SCS), or neurostimulation device – might be an option for heart failure patients.

The company has launched a clinical trial, Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure (Defeat-HF), to study the use of SCS to improve clinical signs and symptoms of heart failure.

The concept of treating heart failure with an SCS device is completely new, Douglas Zipes, MD, an investigator in the study from Indiana University School of Medicine (Indianapolis), told Medical Device Daily.

"This arose some years ago when Medtronic asked me to do some studies on spinal cord stimulation in animals to try to understand why it helped reduce angina," Zipes said. "The clinical demonstration of the benefit in angina had been shown in Europe some years ago and the mechanism of the benefit was never established."

Further animal studies Zipes conducted showed that SCS increases vagal tone to the heart and/or decreases sympathetic activity to the heart. The next study he did showed, in dogs, that SCS markedly reduced the incidents of ventricular fibrillation, as he had expected. But, much to Zipes' surprise, he confesses, that study also showed that heart failure was significantly reversed in those dogs.

A second group of dogs with a longer follow up confirmed that the reversal of heart failure was "dramatic," he said. In fact, the SCS dogs did better than a group of dogs that were just treated with the usual drugs, Zipes added.

"So I said, 'Medtronic, look at what we've got here. Albeit it's an animal study, but the need for clinical studies in heart failure are just achingly severe with 5 million people with heart failure, 500,000 new patients yearly, with very little that we can do for them.' Medtronic finally agreed [to do the study]," Zipes said.

Heart failure stimulates the sympathetic nervous system further progressing the disease. The Defeat-HF study will evaluate whether SCS can restore the natural balance between the sympathetic and parasympathetic nervous systems to improve blood flow, reduce inflammation and restore the heart's dimensions and function, Medtronic said.

Zipes said he told the company, "I can do more animal studies with variations of this, we can do pigs . . . but at some point we're going to have to bite the bullet and try it in patients. After all, the patient is the final denominator as to whether anything is going to be useful or not and I think there's sufficient information from the animal studies to warrant a small clinical investigation."

The study will be conducted under an investigational device exemption in the U.S.

"The unique collaboration of cardiologists and neurosurgeons on this novel feasibility trial has the potential to identify new technologies to treat more heart failure patients and specifically slow the deterioration of patients with advanced heart failure," said Cecilia Linde, MD, PhD, Defeat-HF investigator and cardiologist at the Karolinska University Hospital (Stockholm, Sweden), who enrolled the first patient. The implantation was performed by neurosurgeons Bengt Linderoth, MD, and Goran Lind, MD.

Neurostimulation uses an implantable pulse generator, or neurostimulator, similar to a cardiac pacemaker, with a lead, or thin wire, connecting the device to the spinal cord to deliver low-intensity electrical pulses. The procedure includes percutaneous placement of the leads in the spinal column and the stop-watch-sized neurostimulator is typically implanted in the abdomen.

"This clinical trial will explore the potential for neurostimulation to help physicians provide additional device therapy options for the growing population of heart failure patients," said Pat Mackin, president of the Cardiac Rhythm Disease Management business and senior VP at Medtronic. "Medtronic is proud to continue our leadership in the heart failure therapy and diagnostic market and is uniquely positioned to evaluate this disruptive technology."

Medtronic already has SCS technology for chronic back and leg pain, and it has neurostimulation therapies approved under humanitarian device exemptions for severe obsessive-compulsive disorder and the nausea and vomiting associated with severe gastroparesis. Also, according to the company, there are more than 20 years of literature supporting SCS for cardiovascular applications.

Defeat-HF will be a prospective, randomized, feasibility trial, expected to enroll NYHA Class III systolic heart failure patients at up to 15 centers worldwide. All patients will be implanted with a Medtronic PrimeAdvanced neurostimulator (currently approved for severe chronic pain including back and leg pain, complex regional pain syndrome and painful neuropathy) and followed for 12 months. In this trial, the device delivers stimulation for 12 hours a day.

Medtronic said the trial will measure improvement in heart failure metrics such as heart size and muscle wall thickness, the heart's efficiency in carrying oxygen, and HF symptoms like fatigue, shortness of breath, and quality of life. Metrics will be measured throughout the trial.

"If we can reduce heart failure that's incredible," Zipes said. "By reducing heart failure we'll reduce sudden death, but over and above that we've shown that this does have antiarrhythmic effects . . . so this really has multi-potential for patients and I'm extremely excited because we have such frustration in taking care of heart failure patients."

Amanda Pedersen, 309-351-7774;

amanda.pedersen@ahcmedia.com

Published  July 30, 2010