Five-Year PORTICO IDE Data Reassure on Outcomes, Hemodynamics

PARIS, France—Half a decade on, there is no significant difference in the risk of all-cause mortality or stroke between patients at high or extreme risk for surgery who were treated with the self-expanding Portico (Abbott) transcatheter heart valve as compared to those treated with other commercially available devices, according to results of the PORTICO IDE trial.

In addition to comparable clinical outcomes, the study’s imaging parameters, including mean gradients and aortic-valve areas, were no different between Portico and the other commercially available devices. The need for a new permanent pacemaker, which was significantly higher at 1 year with Portico, remained elevated at 5 years (35.90% vs 20.30% with commercially available devices; P < 0.001).

Raj Makkar, MD (Cedars-Sinai Medical Center, Los Angeles, CA), who presented the results during a hotline session at EuroPCR 2023, said there were some differences identified in post hoc analyses focused on head-to-head comparisons with the valve types. All-cause mortality was comparable between the Portico and Evolut R/PRO valves, but these rates were higher than what was seen with the Sapien 3 device.

The post hoc findings, though, are not meant to be definitive, but “just food for thought,” said Makkar.

Discussant Jonathan Schwartz, MD (Atrium Health, Charlotte, NC), said the new data provide assurances that valve hemodynamics remained stable over time. In particular, he was pleased that reduced leaflet motion (RLM), an unexpected signal that threw the TAVI field into disarray in 2014 when it was identified in a small number of PORTICO IDE patients, didn’t have any impact on valve durability.

Makkar acknowledged, however, that the chapter on RLM isn’t fully closed.

“We need to understand the true significance of reduced leaflet motion, we have to look at the long-term outcomes in patients who are low risk,” he said, referring to the fact that Portico IDE enrolled the highest risk patients. “This was not the right patient population, or it’s limited somewhat at least, because of the increased death rates. The 5-year data in the low-risk studies—both with Evolut and Sapien 3—will be helpful. Also, in these low-risk studies, you were practically prohibited from treating CT findings. You did CTs and the findings were thrown into a black box. We’ll have a greater idea [from the low-risk studies] because that is the natural history of reduced leaflet motion.”

In PORTICO IDE, the majority of patients with RLM were not treated with anticoagulation, but the recommendation wasn’t as rigorous as treatment protocols in the low-risk studies, Makkar told TCTMD.

Moving From 1 to 5 Years

The PORTICO IDE trial, which met its initial primary and safety efficacy definitions of noninferiority at 1 year and formed the basis for US Food and Drug Administration approval in 2021, included 750 patients randomized to either the first-generation Portico valve or other commercially available transcatheter heart valves, among them Sapien 3 (Edwards Lifesciences) and Evolut R/PRO (Medtronic).

Of the TAVI trials, PORTICO is unique in that it was “paused” 9 years ago given concerns over the CT-identified RLM findings. The clinical significance of RLM remains debatable, as Makkar pointed out, with some still questioning the potential long-term consequences of subclinical leaflet thrombosis. In the IDE trial, the PORTICO investigators reported that RLM was not associated with clinical outcomes, including death or stroke. Nor was it associated with any deficiencies in valve function at 1 year.

PORTICO IDE: 5-Year Outcomes

At EuroPCR, Makkar showed that clinical outcomes remain comparable between Portico and the other valves at 5 years. In terms of echocardiographic outcomes, the aortic mean gradients and valve areas also were sustained through follow-up. Paravalvular leak (PVL) deemed moderate or greater was significantly higher at 30 days with Portico, a difference maintained at 1 year, but there was no difference in moderate-or-greater PVL at 5 years. The absence of late difference in the rate of PVL might be more attributable to the nature of this extreme/high-risk patient population.

“At 5 years, the numbers were not higher because a lot of patients had died—almost 50% of the patients had died in both groups,” said Makkar. “If you look at the prevalence of moderate-or-more paravalvular leak, it was 2.8% [with Portico] versus zero in the commercially available valve group.”

A surprise finding was the higher CV mortality rates in the Portico-treated patients.

Darren Mylotte, MD (University Hospitals Galway, Ireland), who chaired the hotline session, asked whether this might be the result of the higher PVL and permanent pacemaker rates “coming back to haunt us or if it was a play of chance.”

Makkar said it’s likely a combination of both. While these were older, high/extreme-risk patients, it’s becoming clearer that higher pacemaker rates do have an impact on mortality, said Makkar. Valve reinterventions, specifically TAV-in-TAV procedures, were higher in patients treated with Portico, he added, but this higher rate of reintervention would be expected to ameliorate the potential risks of death and other adverse outcomes associated with PVL, he said.

Looking Into Valve Durability

Looking into valve durability, researchers reported that rates of structural valve deterioration were not statistically different between the devices. Additionally, the overall rate of nonstructural valve deterioration was comparable between Portico and the other transcatheter valves (37.5% vs 40.1%, respectively; P = 0.34). However, the rate of nonstructural valve deterioration between valves differed in patients with moderate-or-greater PVL. In this subgroup of patients, 17.5% of patients treated with Portico had evidence of nonstructural deterioration compared with 5.1% of patients treated with the other valves (P < 0.0001).

On the other hand, valve durability was significantly better with Portico in patients with moderate-or-greater patient-prothesis mismatch (PPM).

With respect to RLM, Makkar reported that it did not significantly impact the mean aortic gradient, although there was a trend toward smaller aortic valve areas in the 51 patients with CT evidence of impaired motion. However, there was no significant difference in the risk of all-cause mortality or stroke among patients with and without RLM at 30 and/or days. There was also no impact of RLM on bioprosthetic valve dysfunction or failure at 5 years.

Schwartz said that despite limitations of the first-generation device, the 5-year data are “impressive.” Earlier this year, the FDA approved a second-generation Portico transcatheter valve, Navitor, with an upgraded valve cuff for better sealing, the aim being reduced PVL rates. Makkar said there are data from small series suggesting this new device is indeed better at preventing PVL. Additionally, it’s hoped that the device’s delivery system will help more accurately place the valve, which should have a positive effect on pacemaker rates.