SAN FRANCISCO — Among patients with symptomatic, severe native aortic regurgitation at high surgical risk, the JenaValve Trilogy transcatheter heart valve system (JenaValve Technology) met its primary safety and efficacy endpoints, achieving a 1-year all-cause mortality rate of 7.8%.
New pacemaker implantation was 24%, similar to previously reported outcomes.
Vinod Thourani, MD, Piedmont Heart Institute in Atlanta, presented initial outcome results of the ALIGN-AR trial here at Transcatheter Cardiovascular Therapeutics (TCT) 2023.
Thourani concluded that the Trilogy system provides the first dedicated transcatheter aortic valve replacement options “for symptomatic patients with moderate to severe or severe aortic regurgitation or at high risk for surgery and is well positioned to become the preferred therapy upon approval for this population.”
Currently, Trilogy is not approved by the US Food and Drug Administration in the United States and is for investigational use only.
Untreated, severe symptomatic aortic regurgitation (AR) is associated with high mortality, especially for those with NYHA class 3 or 4 symptoms, Thourani explained. “While surgery remains the only recommended intervention for patients with native severe AR, there are a multitude of high-risk patients who are not offered therapy.”
Off-label use of transcatheter valves for AR has been associated with “higher rates of complications, including paravalvular regurgitation and embolization,” he noted.
Thourani described the unique features of the JenaValve Trilogy valve. The system has a set of three “locators” in its own sheath that allows it to be rotated to align with the three cusps of the native aortic valve, falling into the sinuses and securely anchored to the native valve leaflets, and then the valve is deployed. Inside a self-expanding nitinol frame is porcine pericardial tissue. A sealing ring provides sufficient anchoring while conforming to the annulus.
ALIGN-AR was a multicenter, single arm, non-blinded trial with follow-up out to 5 years involving patients with 3-plus or greater AR at high risk for surgical aortic valve replacement. Exclusion criteria included an aortic root diameter greater than 5 cm, a previous prosthetic aortic valve, mitral regurgitation greater than moderate, or coronary artery disease requiring revascularization.
After Trilogy valve implantation, patients were followed for 1, 6, and 12 months, and annually out to 5 years. Safety and efficacy endpoints were compared with prespecified performance goals. Of 180 patients enrolled, 177 were successfully implanted with the Trilogy device.
Patients had an average age of 75.5 years, 47.2% were women, 67.2% were in NYHA class III/IV, 82.8% were hypertensive, and one third were frail. Severe AR was present in 62.4%, and 31.7% had moderate to severe AR.
The primary composite safety endpoint included all-cause mortality, any stroke, major vascular complication, major bleeding, a new pacemaker, acute kidney injury, valve dysfunction, or any intervention related to the device. The primary efficacy endpoint was all-cause mortality at 12 months.
The performance goal for primary efficacy was a weighted average of 25%, derived mainly from 1-year mortality figures for NYHA class I/II and class II/IV with conservative management.
Non-inferiority Margin Met
With a 25% prespecified non-inferiority margin for the primary efficacy endpoint, “We have observed a rate of 7.8%,” Thourani reported during a late-breaking clinical trials session. “The non-inferiority margin was met for the primary efficacy endpoint with a P value of less than .0001.
“With a 40.5% prespecified non-inferiority margin of our primary safety endpoint, with a Trilogy [heart valve] we have observed a rate of 26.7%,” he said. “At 30 days there was a 2.2% mortality and a 2.2% stroke rate. There was a 26.7% primary safety endpoint, mainly driven by the 24% new pacemaker implantation rate. Without pacemaker implantation, the rate of safety events was less than 8%,” (P noninferiority < .0001).
Procedure technical success was 95%, device success 96.7%, and procedure success 92.8%. There was one ascending aortic dissection (0.6%). Moderate or greater paravalvular regurgitation also occurred in one patient. There were four cases of valve embolization.
Pacemaker implants occurred in 30% of patients in the first tercile enrolled and decreased to 14% for the third tercile enrolled. “Lower rates are most likely due to the change in the insertion technique, placing locators above the nadir of the native cusps, reduction in oversizing, and also evolution in the management of periprocedural conduction abnormalities,” Thourani proposed.
The hemodynamics of the valve improved from a gradient of 8.7 mm Hg at baseline to 3.9 mm Hg at 30 days and remained fairly stable out to 1 year. Paravalvular regurgitation was absent in 80.8% of patients at 30 days and mild in 18%. It improved over time, being absent in 93.5% at 6 months and in 92.2% at 1 year.
Left ventricular (LV) remodeling occurred over one year, with LV end systolic diameter, LV end systolic volume, LV mass, and LV mass index all decreasing significantly from baseline to one year (all P < .0001). Importantly to patients, NYHA class improved, from 32% class II, 63% class III, and 5% class IV at baseline to 54% class I, 37% class II, and 10% class III at 30 days and improving slightly out to 1 year.
These improvements resulted in better quality of life as reflected in a 21.8-point improvement in the self-reported Kansas City Cardiomyopathy Questionnaire Overall Summary Score, with a score of 77.6 at 1 year, indicating self-perceived good health.
Encouraging Data
During the session, Robert Bonow, MD, of Northwestern University Feinberg School of Medicine in Chicago, commented that Thourani presented very encouraging data from the ALIGN-AR trial of high-risk surgical patients with significant aortic regurgitation. However, he had a couple of questions for Thourani.
One related to the efficacy data being compared with historical survival data. “So, are you planning to do a randomized study of these patients? You could argue, unlike aortic stenosis, where there’s no medical therapy, there could be medical therapies for the patients.” He noted that one third of the patients are only in NYHA functional class II, so those patients “might do well over the long haul, with medical therapy as an agent.”
Thourani said it was an excellent question. “Doing a randomized trial with a high-risk patient [is] probably less likely,” he said. “I think there is a lot of interest among physicians on the cardiology side and on the surgery side of looking at lower-risk patients, and this could include those that are intermediate and or low risk.”
He said he believes investigators and leadership of the ALIGN-AR trial have conceived of such a trial involving all comers. “I think that’s warranted if we go into younger patients,” he said.
Bonow then asked if there was significant aortic valve calcification in the study population because it is common with regurgitation, “which is why standard approaches are not effective…And how does this device behave in calcified valves?” But Thourani said calcification was an exclusion criterion for this trial.
He said, “deep dives are going to come,” looking at the ventricular outcomes and also looking at a lot of the echocardiographic parameters.
Bonow related this study’s findings on ventricular remodeling to what is seen with surgical aortic valve replacement, where the ventricle decompresses within days. “And that’s predictive of good outcome if you have early data and these patients show how the ventricle remodels quickly,” he said.
The trial was supported by JenaValve. Thourani has received grant/research support from Abbott Vascular, Artivion, Atricure, Boston Scientific, CroiValve, Edwards Lifesciences, JenaValve, Medtronic, and Trisol; consultant fees/honoraria from Abbott Vascular, Artivion, Atricure, Boston Scientific, Croivalve, and Edwards Lifesciences; and has an executive role/ownership interest in DASI Simulations. Bonow had no disclosures.
Transcatheter Cardiovascular Therapeutics 2023: Presented October 24, 2023.
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