Nonsurgical transcatheter heart valve replacement significantly improved outcomes in patients with severe heart valve diseases — aortic stenosis and tricuspid regurgitation — compared to clinical surveillance and standard care alone, according to two recent clinical trials published in the New England Journal of Medicine.
Charles Davidson, MD, ‘85 GME, professor of Medicine in the Division of Cardiology and vice chair for Clinical Affairs in the Department of Medicine, was a co-author of both studies and lead investigator of the Northwestern Medicine enrollment site.
More than 13 percent of Americans over the age of 75 will develop aortic stenosis, according to the American Heart Association, which occurs when the opening of the aortic valve, which controls blood flow from the left ventricle of the heart into the aorta, narrows and restricts proper blood flow. The condition is most commonly due to increased calcification of the heart with aging, but can also be a congenital abnormality.
Currently, asymptomatic patients with severe aortic stenosis are advised to follow-up with their care team every six to 12 months and, in some cases, or can be recommended for open heart valve replacement surgery. However, early nonsurgical catheter-based interventions have not been indicated for these patients, according to Davidson.
“It’s long been known that severe aortic stenosis is associated with a worse prognosis with increased mortality. Usually within about two years, if the valve is not replaced, about half of patients will die. It’s a mechanical problem and medications have never been shown to lessen mortality risk,” Davidson said.
In the first study, the Early TAVR study, more than 900 patients with asymptomatic severe aortic stenosis enrolled from 75 academic medical centers across the U.S. and Canada were randomly assigned to undergo transcatheter aortic-valve replacement (TAVR) surgery, in which the aortic valve is replaced from a groin artery with a balloon-expandable valve, or routine follow-up appointments every six months.
The average age of patients was 76 years, and the primary endpoint was a composite endpoint of death, stroke or unplanned hospitalization.
Overall, the primary endpoint event occurred in 26.8 percent of patients in the TAVR group and 45.3 percent in the clinical surveillance group. Specifically, death occurred in 8.4 percent of the TAVR patients and 9.2 percent of controls, stroke occurred in 4.2 percent of TAVR patients and 6.7 percent of controls, and unplanned hospitalization occurred in 20.9 percent of TAVR patients and 41.7 percent of controls.
In the clinical surveillance group, after an average of four years of follow-up, 87 percent of patients also underwent aortic valve replacement.
“What we found in this study is that patients often develop symptoms fairly quickly after the onset of severe aortic stenosis and that the tax for waiting was no longer worthwhile. When severe aortic stenosis is present, the safety and benefits are higher with a strategy of early transcatheter aortic valve replacement rather than clinical surveillance,” Davidson said. “This really makes it simpler for patients and referring physicians to manage these patients with a life-threatening problem.”
In the second study, the Triscend II trial, 400 patients with tricuspid valve regurgitation that occurs when the valve located between the right atrium and right ventricle does not close completely, were randomly assigned to undergo either transcatheter tricuspid valve replacement and standard medical therapy or medical therapy alone.
“Prior to this study, patients were treated with medical therapy, which would include diuretics, or water pills. The other treatment is surgical valve replacement or repair, but that is generally reserved for people that are having surgery for other valves. The reason for that is that the surgical risk is generally high in this population due to the comorbidities including liver and kidney disease or have undergone previous cardiac surgery,” Davidson said.
The composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, tricuspid valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 meters on a six-minute walk test.
Overall, patients in the valve-replacement group demonstrated better combined outcomes than the control group in terms of death from any cause (14.8 percent versus 12.5 percent), post index tricuspid-valve intervention (3.2 percent versus 0.6 percent), and improvement in the KCCQ-OS score (66.4 percent versus 36.56 percent), NYHA class change greater than or equal to 1 (78.9 percent versus 24 percent), and six-minute walk distance greater than 30 meters (47.6 percent versus 31.8 percent). Patients in the valve-replacement group, however, demonstrated a higher annualized rate of hospitalization for heart failure than the control group.
According to Davidson, his team has now performed over one hundred transcatheter valve replacement procedures at Northwestern Medicine, both as part of the aforementioned clinical trials and subsequent to the valve’s FDA approval earlier this year.
“This expands the heart population that we can potentially improve their quality of life. Since FDA approval, we are able to treat cohorts that were excluded from the randomized trials, including dialysis dependent and challenging anatomy patients,” Davidson said.
Both studies were supported by Edwards Lifesciences.
