COMMENTARY

Artificial Hearts: One Size Does Not Fit All #HerHeartToo

Melissa Walton-Shirley, MD

Disclosures

November 22, 2021

Mechelle and Tim Giles started their 35th wedding anniversary celebration in a hospital room. It was especially poignant. Mechelle was hours away from discharge after becoming the first woman to receive an Aeson totally implantable artificial heart.

Tim and Mechelle Giles

Her 10-year journey to this milestone began at a health fair in Adair County, Kentucky, with a surprising diagnosis of diabetes. After a losing battle with fluid buildup and progressive weakness, punctuated by a pacemaker implant and blood clots, she was eventually transferred to University of Louisville Health's Jewish Hospital in Louisville, Kentucky.

Mechelle Giles with one of her surgeons, Mark Slaughter, MD

Many serious conversations followed with her husband, and her cardiothoracic surgeons Mark Slaughter, MD, and Siddharth Pahwa, MD. "They said the LVAD was no longer an option," her husband Tim said, referring to a left ventricular assist device.

"They said there is only one other thing we can do, and that's the mechanical heart. I took his word for it and here I am. I trust him," said Mechelle, referring to Slaughter.

The Aeson artificial heart by Carmat

In a Zoom interview with media, Mechelle sat next to her husband. "I feel great," she said, her smile waning when the device alarmed in the background. When she was assured that nothing was wrong, relief washed over her face. The investigational system manufactured by Carmat produced a rhythmic squeaking noise in the background as we spoke, "like a gerbil barking," as Tim put it.

Amidst the joy and deserved celebration, the uncomfortable truth is that if Mechelle Giles had presented two decades ago, or in other geographic locations, she would have likely died of biventricular failure. Very few female patients are given the option of an artificial heart.

Women as Objects, Not Medical Subjects

Women may be the objects of romantic poetry and Shakespearean odes, but they are rarely the subjects of science and are underrepresented in heart failure trials. Mechelle Giles' story is proof that a lot has changed in the history of advanced heart failure management for women, but then again, some things have stayed the same.

The Jarvik 7 was the first successfully implanted artificial heart. A version 30% smaller  than the original was implanted into Mary Lund in 1985—the first woman in the world to have her heart explanted and replaced by a device. She was bridged for 45 days until she got a heart transplant. She died of multisystem organ failure about 9 months later with her donor heart still working, a testament to the need for better patient selection.

Mary Lund's implant days were spent tethered to a power source the size of a small refrigerator, the term "totally implantable" only yet a dream. The information gathered from her experience no doubt benefits Mechelle Giles today.

Of the 14 recipients of the now-discontinued AbioCor totally implantable artificial hearts (Abiomed), none were women. That device was thought to be too bulky for most women at 4 inches across and nearly 2 pounds in weight. It was difficult to fit into even small-framed men. Cardiothoracic surgeon Rob Dowling, MD, now at Penn State Health, who was part of the team that implanted the first AbioCor at Jewish Hospital, recalled having to improvise. "I stepped out of the OR to the bathroom to think about it," he said by phone. He came up with the idea of incising the diaphragm and using a Gortex graft to allow for more room, proving it could be done.

When I asked him why the device was never offered to any women, he acknowledged that although "it was difficult to make it fit, there is really no good explanation as to why a female was never implanted." He pointed to other devices, such as the investigational BiVACOR artificial heart, which promises to be "small enough for a child, powerful enough for an adult."

Roberta Bogaev Chapman, MD, medical director for heart failure for Abiomed, has an engineering background and a unique perspective on the company's early days of device development. "The engineers were not clinicians. They didn't think about the size implications. It was an afterthought that you had to have a large chest cavity for the device to fit," she said.

The company appears to have done a 180-degree turn. "One of my responsibilities at Abiomed is to drive the women's health initiative that focuses on identifying sex-specific differences in their Impella products…and meeting the unique needs of women with all of our devices," Bogaev Chapman said.

As a practicing physician in 2008, she flew on her own dime to Washington, DC, to champion the US Food and Drug Administration (FDA) approval of the HeartMate II LVAD (Abbott) "because it fit women," she said. "In the early days, the early trials around MCS [mechanical circulatory support] enrolled zero women," Bogaev Chapman said, noting that there are multiple barriers: " Women are often referred late, have additional comorbidities and competing responsibilities."

The SynCardia CardioWest device, currently the only FDA-approved totally implantable artificial heart is indicated as a bridge to transplant. It offers a 50cc option that fits most women and has also been used in children.

Despite the smaller models, only 259 of 2010 patients implanted with the SynCardia device are women. Andrea Rogers, director of global marketing, said by email that their 2000th implant patient was a woman. Recently, another woman was implanted, and in September two female pediatric patients (ages 16 and 11 years) received the device, she added.

Women continue to trail behind men in many areas of heart failure management.

Ventricular assist devices (VADs) make up around 95% of mechanical circulatory support devices, and nearly 80% of LVAD implants in 2016 were in men. Even though LVAD implants in women doubled from 2009 to 2014, men continued to be implanted three times more often than women. As devices evolved, women now have a similar postimplant inpatient mortality rates to men, so they should have equal access.

Heart Transplants: Women Lag Behind

And the disparity is not limited to artificial hearts. The first human heart transplant was famously performed by Christiaan Barnard, MD, in 1967 in South Africa. That's over 50 years ago, yet data from the Scientific Registry of Transplant Recipients shows that between 2004 and 2015, women deemed high-priority candidates (United Network for Organ Sharing status 1) were more likely than men to die waiting for a heart transplant, even after adjustment for more than 20 risk factors.

There have long been calls to enroll more women in cardiovascular research trials. Even so, an article published in the Journal of the American College of Cardiology in 2018 noted that "While women are now well represented in clinical trials for hypertension and atrial fibrillation, they are dramatically under-represented in clinical trials for coronary heart disease and heart failure." And if you think that's because women with heart failure are more likely to have diastolic dysfunction and therefore not meet ejection fraction entry criteria for some trials, the authors debunked that: "Our analyses do not suggest that gender-biased study entry criteria are the main reason for lower enrollment of women in cardiovascular trials," they wrote. They further explained that "Women are less likely to be considered for trials but also less likely to consider participating."

I asked one of the lead authors, Marjorie Jenkins, MD, a professor of medicine at Texas Tech University Health Sciences Center, who also worked for the Office of Women's Health at the FDA, what can be done to change that. By phone, she said, "If the FDA does not mandate change, pharma is not going to do it. If they can get away with not having enough women in trials, they will because time is money."

Jenkins pointed out that industry and the U.S. Congress have the best tools to change the trajectory. "We need a concerted effort, most likely led by women." Given that we have more women in the Senate and the House of Representatives, Jenkins suggested that they require the FDA to demand that industry at least have their trial populations reflect the prevalence of the disease.

She reminded me that "Gender disparity doesn't just apply to women. When you look at osteoporosis, nearly all of the studies are in women. Approved drugs use the T-scale, so men are actually getting the short end of that stick. The same goes for male breast cancer. We have zero chemotherapeutic agents for men."

Even the Research Mice Are Male

Jenkins told me that females are left out of bench research as well. "The research pipeline is totally lined with males, even at the cellular level," she said, explaining that one research team had never used a female animal model even though their disease of interest occurred almost exclusively in women. "Women are 80% of healthcare consumerism. We are 51% of the population… But no one is using females as the normal even with diseases like HFpEF [heart failure with preserved ejection fraction] that are found predominantly in women," she said.

As a cardiology fellow in the early 1990s, I was blessed to have a front-row seat to some of the magnificent advances in heart failure. I was mentored by stalwarts of mechanical circulatory support, including Drs. Laman Gray, Rob Dowling, Al Lansing, and William DeVries. I cared for 1 of the 14 patients to receive an AbioCor artificial heart implant.

Lucille Dixon with her husband Shelby

My most memorable patient with end-stage heart failure was a young woman named Lucille. When I met her in 2004, she was "cold and wet," with low cardiac output and severe bilateral pulmonary edema that was refractory to every pharmacologic measure we had to offer. With no prospect for a timely donor heart, she accepted the offer to be the first patient at Jewish Hospital to receive the HeartMate II.

That device served her well until she bridged to a transplant a year later. She is alive today because of device innovation and the lack of sex disparity in the treatments her advanced heart failure providers recommended.

Staff applaud Mechelle Giles as she leaves University of Louisville Health's Jewish Hospital

 

Mechelle Giles left the hospital with the gift of more time with her husband, children, and grandchildren because of the advances in heart failure therapeutics. Many others will not be so lucky. The playing field has not yet been leveled.

As clinicians, we should vow to practice equal opportunity medicine by taking adequate time to explain all medical options to patients regardless of sex. We can push to legislate equality in funding gender-balanced science. We can pressure our cardiology societies to develop education campaigns for researchers and clinicians to address issues that discourage trial participation for women.

Bogaev Chapman suggested that we focus on the altruistic aspects of trial participation because "women are more willing to benefit if they see a benefit beyond themselves." She highlighted the need for virtual visits and reimbursement for child and elder care.

We owe the 2.6 million Mechelles—U.S. women living with heart failure—equal consideration. On the heels of movements like #MeToo, #BlackLivesMatter and #SeeMe, perhaps cardiac medicine should title our next campaign #HerHeartToo, with the aim to make treatment access and outcomes equal.

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety. In addition to opinion writing, she enjoys spending time with her husband and daughters and sidelines as a backing vocalist for local rock bands.

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