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SAN FRANCISCO -- The investigational Evoque transcatheter tricuspid valve replacement (TTVR) prosthesis appeared safe and beneficial in initial pivotal trial data.

The major adverse event rate of 27.4% was less than the expected 43.8% (based on isolated TVR surgery from Medicare claims) and an "acceptable safety profile in a highly comorbid patient population," according to Susheel Kodali, MD, of Columbia University Irving Medical Center in New York City, presenting at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation.

While the main 1-year outcomes data from the full 400-patient TRISCEND II trial are still pending, the 6-month data on the first 150 patients supported effectiveness in reducing tricuspid regurgitation (TR) and improving functional and quality of life outcomes.

TR grade dropped from severe, massive, or torrential in all patients to moderate or less in 98.8% of treated patients compared with 21.6% among those on optimal medical therapy alone at 6 months (P<0.001), drawing applause from the late-breaking trial session attendees.

Indeed, 77.8% of the TTVR group had no more than trace TR at 6 months.

The findings come atop further positive results with tricuspid transcatheter edge-to-edge repair (TEER) results at the same meeting from the TRILUMINATE trial, promising multiple transcatheter options approaching the cath lab for inoperable TR patients.

"This is clearly a landmark study," commented Yousif Ahmad, MD, PhD, of Yale School of Medicine in New Haven, Connecticut. "The landscape for tricuspid valve intervention is changing. ... We'll have potentially two RCT-[randomized controlled trial] proven therapies to offer these patients. It's very encouraging for the field."

While the number of isolated tricuspid repair surgeries is only approximately 600 per year in the U.S., perhaps a million and a half have significant TR disease, noted Wayne Batchelor, MD, of the Inova Heart and Vascular Institute in Falls Church, Virginia, a panelist at the TCT press conference. "This is clearly an unmet need."

The trial randomized patients 2:1 to Evoque with continuation of preprocedural optimal medical therapy for at least 3 months afterward or to receive their pre-study optimal medical therapy alone.

The procedure was done via transfemoral access under general anesthesia. No concomitant procedures were allowed.

As expected, the patient population was predominantly female (75-82%), with an average age of 79 and a Society of Thoracic Surgeons (STS) surgical risk score for mitral valve replacement of 9-10%. Nearly all had atrial fibrillation, and about 40% had leads in place from a pacemaker or implantable-cardioverter defibrillator, which the Evoque device "jails" in place.

TR was secondary in around 77%, with about one-third having torrential severity and about 40% having severe TR. Four procedures were aborted due to anatomy or poor imaging. Two patients converted to surgery due to right ventricle perforation from the wire (2.1%).

After excluding patients with a preexisting cardiac device, the rate of pacemaker implantation for new conduction abnormalities was 14%.

The win ratio favored the procedure for improved outcomes on a composite hierarchical comparison between pairs of patients for achieving at least a 10-point improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, one class reduction in New York Heart Association (NYHA) symptoms, and at least a 30-meter improvement in 6-minute walk distance. Evoque got 60% of wins, compared with 13% for medical therapy alone, yielding a win ratio of 4.6 (P<0.001).

Compared with medication alone, TTVR improved KCCQ by 15.8 more points over baseline at 30 days and 17.8 more points at 6 months, which is considered a large improvement. Fully 90% of intervention patients dropped to NYHA class I/II by 6 months compared with 34.2% in the medical arm.

Three patients died of cardiovascular causes. Two were clearly procedure-related with severe worsening of right ventricular dysfunction afterward that went into multiorgan failure. The other was from continued heart failure and acute respiratory distress.

One-year clinical and echocardiographic endpoints, including mortality and heart failure hospitalization, are awaited from the full cohort of 400 patients, which has already enrolled, Kodali noted.

However, the device has breakthrough status and an FDA panel will be convened in January to review the existing trial data. Kodali noted that approval could come as soon as 2024.

He acknowledged, though, that 1 year might be too soon to see a mortality or other hard outcome impact in this heterogenous population. Follow-up is planned for 5 years.

Worse TR has been linked to poorer survival in observational studies, but "whether that elimination [of TR] will translate to an improvement in survival is what we need to see," he said.

"Even if it doesn't ... quality of life from a patient perspective is an important outcome," Kodali said. But he acknowledged, "The question of how you control for placebo in these trials without a sham control is a consideration. We have to acknowledge there's going to be some component of placebo effect."

He suggested that the FDA, and clinicians, will have to look at the totality of evidence -- whether all components of hard outcomes are trending in the right direction, and whether there's a decrease in right ventricular size and other measures of remodeling.

Even so, "we need to show at least some evidence of a clinical outcome like [reduction in] hospitalization for heart failure," argued TCT press conference moderator Roxana Mehran, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

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