A grad school romance led to a med-tech breakthrough that may save the lives of millions of patients suffering from mitral regurgitation
By Daniel Oberhaus
Photos by Mike Madison
On a brisk spring morning in 2018, Saravana ’03 M.S. and Katherine ’03 M.S., ’05 Ph.D. Kumar said goodbye to their two young children and left their home in Minnesota on one of the most high-stakes road trips of their lives. Their destination was a hospital in Quebec City where a 77-year-old patient was preparing to undergo surgery for a chronic heart condition.
The patient had never met the Kumars before, but the husband-and-wife team already knew a lot about him. They knew he was suffering from a condition called mitral regurgitation, a common type of heart valve disease that results in blood leaking backward into the heart each time it pumps. They knew that the condition was leaving the patient tired and out of breath, and if left untreated, would significantly increase his risk of death.
Earlier this year, the Food and Drug Administration granted the AltaValve “Breakthrough Device” status, which accelerated the device’s progress toward pivotal trial, the final regulatory hurdle before it is commercially available to millions of patients in need.
They also knew the man had agreed to undergo a first-in-the-world transcatheter treatment procedure that had been approved through Canada’s special access program, which allows patients to opt-in to receive medical treatments that show promise but have not yet been approved for sale. The procedure was important to him not only because it would reduce the risk of life-threatening complications from his disease; it also meant he’d be able to fully participate in his son’s upcoming wedding.
In the back of their car, Saravana and Katherine Kumar were carrying a new device called the AltaValve that they hoped would provide relief to the patient in Quebec and eventually to millions of other mitral regurgitation patients around the world. Over the previous two years, Saravana, Katherine and a small team of collaborators had started a company called 4C Medical and brought the AltaValve from an idea on the back of a napkin to a prototype built in their garage to a bonafide medical device that had shown remarkable results in animal studies. Now, they were preparing for their biggest test yet: implanting the device in a human patient for the first time.
Together, the Kumars had successfully brought several other medical devices from concept to clinic, but the nerves associated with a first-in-human trial never went away.
“It’s a completely out-of-body experience,” said Saravana Kumar. “You’re nervous, you’re sweating, you know you’re prepared, but you’re about to do something that has never before been attempted.”
The AltaValve is a mesh sphere about the size of a quarter that slightly resembles a Fabergé egg when it is fully deployed in the heart. The prosthetic valve is implanted above the native mitral valve, which regulates the flow of blood out of the heart’s left atrium and is designed to ensure that blood flowing out of the heart doesn’t leak back in as it is pumped into the rest of the body. When the device was first inserted into the patient in the hospital, both Kumars anxiously watched the patient’s echocardiogram — an ultrasound image of the heart — for signs that it had stopped the leak.
“We were looking at it and there was still a leak around it, which wasn’t too bad, but it still wasn’t ideal,” Saravana Kumar said. “But then we fully opened the implant and the echocardiographer running the images was shouting across the room asking where the leak went. Everyone just looked at one another and breathed a sigh of relief — we had completely eliminated the leak. It was at that moment we knew we had something.”
The first treatment with 4C Medical’s AltaValve was, in all respects, a resounding success. The patient was able to attend his son’s wedding, and when he came in for a checkup a few months later, his only complaint was that he was able to shovel snow for only three hours without getting winded. Saravana Kumar still laughs when he thinks about it. “I remember thinking, ‘Man, I’m only 40 years old, and I can’t even shovel snow for three hours.’”
Since that first patient, 4C Medical has implanted its device in more than 100 patients as a part of an early feasibility clinical trial or for compassionate use (for patients with no other treatment options). Earlier this year, the Food and Drug Administration granted the AltaValve “Breakthrough Device” status, which accelerated the device’s progress toward pivotal trial, the final regulatory hurdle before it is commercially available to millions of patients in need.
The Kumars estimate that around 450 patients will receive the AltaValve as part of the pivotal trial and if the device works as well as expected, it means that they will have developed a breakthrough treatment that has eluded some of the world’s largest and most well-funded medical device companies. The reason so many companies have struggled to find a suitable treatment for MR, says Katherine Kumar, is that they applied similar approaches used in other parts of the heart. But the mitral valve is a totally different — and more challenging — environment.
The mitral valve is the “Mount Everest” of valve technologies. It’s by far the largest problem in the cardiovascular space."
Saravana Kumar
The mitral valve regulates the flow of blood out of the left atrium — one of the four chambers of the human heart — as it circulates through the body. If the valve doesn’t close properly when the heart contracts, blood will come streaming back into the pool in the left atrium rather than being pumped into the body by the left ventricle. A common way to treat MR is to replace the patient’s leaky mitral valve with an artificial one, which is inserted directly into the valve’s annulus — a ring-like structure that provides the foundation for the valve — just as it would for any other faulty valve in the heart.
The challenge, however, is that the mitral valve lacks the strong foundation in the annulus that is used to mount artificial valves in other parts of the heart. In addition, the mitral valve experiences the highest blood pressure in the heart, which makes it challenging to keep artificial valves in place. It’s for this reason that Saravana Kumar describes the mitral valve as the “Mount Everest” of valve technologies. “It’s by far the largest problem in the cardiovascular space,” he said. “Despite the number of patients with valve disease on the mitral side outweighing the number of patients with other valve diseases, there isn’t a single replacement valve available for mitral because of how hard this problem is to solve.”
Saravana and Katherine Kumar are, in many ways, the perfect duo to tackle this seemingly impossible challenge, but their road to starting 4C Medical was anything but conventional. Both immigrated to the United States to pursue a master’s degree in mechanical engineering at UNC Charlotte — Saravana moving from India and Katherine from Ukraine — and met after their academic advisor, Robin Coger, then a professor of mechanical engineering, sent them to an academic conference where Katherine was scheduled to speak. At the conference, Saravana helped Katherine practice her talk to help calm her nerves; the pair started dating not long after.
“We’ve now been married for a long time, have two kids and a company together, and we still joke with Dr. Coger that it’s all her fault,” said Katherine Kumar.
After completing their master’s degrees at Charlotte, the Kumars maintained a long-distance relationship while they pursued Ph.D.s — Katherine at Charlotte and Saravana at the University of Minnesota — before reuniting in the Twin Cities where both pursued successful careers in the state’s booming medical devices industry. During this time, Saravana Kumar helped lead a small team inside St. Jude Medical — one of the world’s largest medical device manufacturers — that developed one of the most widely used artificial heart valves in the world while Katherine Kumar led variety of teams at startups and major medical technology companies working on devices for applications ranging from women’s contraception to atherectomy, a procedure for removing plaque from the arteries.
When we formed 4C Medical, we were criticized so much. Everyone told us our idea would never work. We understood their concern, but we never doubted that this would work."
Katherine Kumar
Along the way, the Kumars learned to bring breakthrough medical devices from concept to commercialization from both engineering and regulatory perspectives. Although many of the products they developed have been successful, they saw how painful it could be when a medical device proved unable to help patients. This hard-won experience primed them for a meeting in 2017 with one of Katherine’s longtime colleagues, Minneapolis cardiologist Jeff Chambers, who had patented a new kind of heart valve and wanted their help bringing it to reality.
At the time, Katherine Kumar was eight months pregnant with their second child, but both she and her husband had spent enough time in the medical device industry to know a great idea when they saw one. The insight behind the device that would eventually become the AltaValve was simple: rather than placing the artificial mitral valve inside the annulus like you would with other heart valves, they would anchor the device above the valve, where it would be better able to handle the uniquely challenging and dynamic mitral environment. It had never been done before and when they broached the ideas with colleagues in their field, most cautioned against it.
“When we formed the company, we were criticized so much,” Katherine Kumar said. “Everyone told us our idea would never work. I remember getting pulled aside at a conference by a very famous physician whom I had worked with before and he asked me what the hell I was doing. We understood their concern, but we never doubted that this would work.”
Over the next year and a half, the Kumars balanced building prototypes of the AltaValve in their garage with the demands of raising two young children. Slowly but surely, they advanced toward testing the device in animals until they had enough data to show it was safe and effective enough for trial in humans. The journey was long, but the data speaks for itself. Today, the AltaValve has been implanted in over 100 patients with overwhelmingly positive results, which allowed 4C Medical to raise nearly $90 million in venture financing to bring the device through pivotal trials.
The Kumars are optimistic that their device will be commercially available to the nearly two million people in the United States living with MR before the end of the decade. But first, they’ll need to implant the device in nearly 500 patients as part of a pivotal trial that will show the device is both safe and effective.
“There will be challenges because there are always challenges,” said Katherine Kumar. “I definitely have more gray hair because of this. But the beauty of working in this particular area is that you also get to see immediate relief in the patient’s symptoms suffering from this disease and that’s so rewarding. It gives you the energy you need to keep marching forward.”
Daniel Oberhaus is a freelance writer based in Brooklyn, New York.
Mike Madison is a freelance photographer in Minneapolis, Minnesota.