Update 4 December 2018: The U.S. FDA's advisory committee voted to recommend the Optimizer Smart system for approval.
The medical device sitting in Joan Boyle’s chest looks much like a pacemaker or defibrillator, with a pager-sized machine implanted under the right clavicle and electrodes running out of it into the heart wall. But this device is unlike any currently available in cardiology clinics across the United States.
It doesn’t regulate a slow heartbeat, as pacemakers do. Nor does it work like an implantable defibrillator to send low-energy shocks that can reset a wonky heart rhythm. Rather, the Optimizer Smart system delivers high-energy pulses to faltering heart muscle tissue, helping an ailing ticker contract more strongly and deliver oxygen-rich blood where it’s needed throughout the body.
Boyle received the implantable pulse generator in June through a controlled-access study protocol. Beforehand, “she was struggling, feeling very lethargic, and her breathing was labored,” says Boyle’s granddaughter Jennifer Wagner. “Just going from the car to the house was a difficult task.”
Now, Boyle is on her feet more. The 86-year-old great-grandmother from Philadelphia is back to making ceramics, painting, and baking her signature chocolate chip cookies—and soon millions of other Americans suffering from congestive heart failure could gain access to the Optimizer system, too.
On Tuesday, an advisory committee to the U.S. Food and Drug Administration (FDA) will meet and vote on whether to recommend marketing authorization of the first-of-its-kind device.
Up to one-quarter of all patients with moderate-to-severe heart failure could be candidates for this kind of “cardiac contractility modulation” therapy if they fail to respond adequately to ACE inhibitors, beta blockers, and other drug treatments.
“There’s been a segment of the population that has not had a device available for them,” says Steven Roberts, Boyle’s cardiologist from the Thomas Jefferson University Hospitals in Philadelphia. For these people, “the heart muscle is weak—it doesn’t pump forcefully enough—but the electrical system is still working.”
The device then essentially serves as a personal trainer for wimpy left ventricles, boosting the performance, strength, and pumping power of the enfeebled heart chamber.
Some version of the Optimizer system has been available for over 15 years in Europe, where more than 2,800 patients have received the treatment, according to the device’s Israeli manufacturer, Impulse Dynamics. Optimizers are also now sold in Australia, Brazil, China, India, and several other countries at a cost of around US $30,000 for both the device and the minimally invasive surgical implantation procedure.
But in the United States—where the FDA takes a more stringent approach to device regulation—researchers had to first demonstrate the safety and effectiveness of the system in prospective, randomized studies before it could be made available for everyone else.
Those studies didn’t initially go according to plan, which explains the long delay in getting to this week’s regulatory review.
The first clinical trial ran between 2005 and 2007 and involved 428 patients recruited at dozens of sites across the United States. Half received the Optimizer system, half served as controls.
Those implanted with the device showed significant improvements, both in exercise tolerance (as measured by aerobic metabolism) and on a quality-of-life questionnaire, with no increased rates of hospitalizations or death. But the trial failed to meet its primary efficacy endpoint on a different physiologic measure of exercise ability—which sent researchers back to the drawing board.
They crunched the trial data again and noticed that the device most benefited those study participants whose weakened hearts left some blood—but not too much blood—in the left ventricle after each contraction. Below a certain pumping capacity, the heart muscle seemed too far gone to respond to the therapeutic jolting.
“This is a heart failure treatment, not an end-stage heart failure treatment system,” explains Carsten Tschöpe, a cardiologist at Charité Medical University, in Berlin.
The clinical research team then launched another trial in 2011, this time enrolling only those patients with moderately reduced heart function. And as the trial endpoint, they used the aerobic exercise measure that had shown statistical significance in the earlier study.
As they reported in the October 2018 issue of JACC: Heart Failure, a journal of the American College of Cardiology, the device then hit all its marks.
In real-world observational data from patient registries in Europe, clinicians also showed that the device reduced rates of heart-related hospitalizations by about 75 percent, with sustained improvements in quality of life and functional status that lasted for at least two years following implantation.
Wagner can see those kinds of lasting differences in her grandmother today. “I can tell just by her willingness to do more,” she says.
There’s one time of the week, however, when Boyle doesn’t do much of anything. That’s on Wednesday nights, when she always sits in front of the television set with the Optimizer’s wireless battery charger device draped over her chest. It looks like a royal blue version of the Apple Watch magnetic charging dock. Boyle simply calls it the “gidgee.”
It’s not entirely clear how the device helps people like Boyle. Studies from dogs and rabbits suggest that the pulses alter the activity and expression levels of proteins involved in calcium signaling and contractile forces at the site of signal delivery, eventually leading to long-term remodeling of the heart tissue.
For Boyle and her cardiologist, though, all that really matters is that it’s working. “It is a little mysterious,” muses Roberts. “It certainly is.”