Ross Procedure Shows Durable Benefit at 25 Years

When done by experienced surgeons, the Ross procedure can offer young and middle-age adults a durable alternative to aortic valve replacement, with 25-year survival that matches what’s seen in the general population, according to a new analysis.

The results from the Ross Registry, which launched in 1988 and is prospectively tracking patients at 10 centers, add further weight to recent findings from a 1,500-patient retrospective, multicenter cohort study that also showed low mortality and steady hemodynamic outcomes over the long term.

With the Ross procedure, the aortic valve is removed and then replaced with the patient’s own pulmonary valve. The latter is then replaced with a donor valve.

Senior author Stephan Ensminger, MD, DPhil (University Hospital Schleswig-Holstein and German Center for Cardiovascular Research [DZHK], Lübeck, Germany), said the point of the Ross Registry is not to persuade surgeons and patients to pursue a Ross procedure. “It’s not to advertise the Ross procedure,” he stressed to TCTMD. Rather, the idea is to improve how the surgery is being done and to see if it provides a long-solution for patients expected to live for decades.

“We want to give a solid database [about] how this procedure works long-term, in a sense of a lifelong therapy,” he said.

If young patients were to have TAVR or receive a surgically implanted biological valve, they would likely need reintervention after around 5 to 7 years, said Ensminger, “so that doesn’t work.” This leaves surgically implanted mechanical valves, which require a patient to indefinitely stay on anticoagulation, or the Ross procedure as the remaining options, he noted.

The paper, with Anas Aboud, MD (University Hospital Schleswig-Holstein and DZHK), as lead author, was published online in the Journal of the American College of Cardiology.

Reintervention Rates Below 1% per Patient-Year

Aboud and colleagues looked at data on 2,444 adult patients (mean age 44.1 years; 75.8% men) who were treated for the Ross procedure between 1988 and 2018 at one of 10 European centers. The surgical technique was subcoronary in 36.5%, root replacement without additional reinforcement procedures in 19.6%, and root replacement plus additional reinforcement procedures in 43.9%.

Median follow-up was 9.2 years. Early mortality (within 30 days after surgery or in-hospital) was 1.0%. By 25 years, estimated survival was 75.8% for the Ross-treated patients, similar to that for sex- and gender-matched controls, although slight deviation started to occur after 13 years, which the researchers say warrants further investigation.

Ross-related reinterventions were done in 9.2% of patients, at a median of six and a half years later. The risk of autograft reintervention amounted to just 0.69% per patient-year. For right ventricular outflow tract reintervention, the risk was 0.62% per patient-year.

Complications were rare. Incidences of major bleeding, valve thrombosis, permanent stroke, and endocarditis were 0.15%, 0.07%, 0.13%, and 0.36% per patient-year, respectively, and lower than what’s typically seen after mechanical valves and xenografts, investigators note.

There was no difference in survival between the two Ross techniques that now predominate: subcoronary and root replacement plus reinforcement. Today, root replacement without reinforcement is rarely done, said Ensminger.

Expertise, Experience Required

As noted in the paper, a well-designed randomized trial could be done to confirm these observational findings, but Ensminger is skeptical that such a trial is possible. Follow-up would need to last at least 15 years and, more importantly, the difference between what’s being asked of patients in the two treatment arms would be so great. “In one case you have lifelong anticoagulation, and in the other case you have an obviously more-complex procedure but no anticoagulation for the rest of your life more or less,” he said. In speaking with patients, he’s learned that “they have their own opinion and their referring physician has a certain bias one way or another,” so would be unwilling to be randomized.

Another difficulty is that the “Ross procedure is only performed by a relatively small number of centers and a limited number of surgeons,” added Ensminger, emphasizing that this expertise is crucial: “It should be done by expert centers with high case load and one to three expert surgeons [like] the ones included in our registry.”

Registries naturally have limitations, he acknowledged. “But I think this will help and we will try to expand and include more centers even, because I think for the foreseeable future this will be the best evidence you could get probably.”

Ensminger said he hopes the European guidelines begin to look more favorably at the Ross procedure as evidence accumulates. That said, a strong recommendation could backfire if it led to rapid expansion, he cautioned. “It will be limited to expert centers. Otherwise it’s not good for the patient.”

In the United States, the 2020 valvular heart disease guidelines give it a class IIb recommendation (level of evidence B), specifying that the intervention “typically is reserved for younger patients with appropriate anatomy and tissue characteristics in whom anticoagulation is either contraindicated or undesirable, and it is performed only at Comprehensive Valve Centers by surgeons experienced in this procedure.” The 2017 European guidelines make no mention of the Ross procedure.

New Optimism

In an accompanying editorial, Ismail El-Hamamsy, MD, PhD (Mount Sinai Hospital, New York, NY), and colleagues note that the Ross procedure was first performed in 1967. “Since then, there is surely no other cardiac operation for which enthusiasm for its adoption has waxed and waned to such a profound degree, particularly in the United States,” they note. These results, added to what’s known, make a strong case for the approach.

“The ability to provide patients in their 40s with normal life expectancy and a reoperation rate of 1% per year over the first two decades after surgery is very encouraging and offers new optimism for young adults with aortic valve disease,” they write.

“Furthermore,” they add, “despite the large number of surgeons involved, overall operative mortality of 1% in a cohort dating back to 1988 . . . confirms the safety of the operation in high volume centers. Nowadays, with modern bypass circuits and myocardial protection techniques, an operative mortality < 1% should be the expectation.”

To ensure the field moves forward safely, surgical experts and professional societies should specify “clear training pathways, roadmaps for starting Ross programs, and a commitment to prospective data collection and analysis,” as has been done by the Ross Registry,” the editorialists conclude.