Caloric restriction-mimetics for the reduction of heart failure risk in ...

First Of Its Kind 'J-Valve' Surgery Performed At Christ Hospital

A first-of-its-kind surgery is being performed as part of a clinical trial at The Lindner Research Center.The minimally invasive surgery is designed to treat severe native aortic regurgitation and AR-dominant mixed aortic valve disease in patients.The successful procedure was done by Dr. Dean Kereiakes, Dr. Santiago Garcia and the team at The Lindner Research Center at The Christ Hospital Health Network earlier this month.Enrollment for the early feasibility study using the device was announced through a partnership between the Christ Hospital Heart & Vascular Institute and Genesis MedTech, a medical device company. The J-Valve TF System, which was developed by JC Medical, is regarded as a valve that addresses unmet clinical need and has potential to help many, as described by Dr. Garcia, principle investigator for the study at The Christ Hospital Health Network. "Unlike cardiac surgery, our patient did not have general anesthesia and went home the next day," Garcia added. "We are pleased to report that the first Early Feasibility case using a 34mm J-Valve yielded favorable results," Kereiakes, president of the Christ Hospital Heart and Vascular Institute and National Co-Principal Investigator for the study said in a statement. "The J-Valve TF System could potentially revolutionize the treatment of aortic regurgitation, allowing larger annular sizes to be treated." The completion of the implantation is a milestone moment for Genesis MedTech."This achievement demonstrates our dedication to advancing medical technology in the structural heart disease sector. Collaborating with leading TAVR sites across the US and Canada, we hope to demonstrate results that will highlight the unique ability of a dedicated TAVR valve like J-Valve in treating patients with a life-threatening disorder." The North American EFS is part of a broad clinical program that will investigate the treatment of patients with aortic regurgitation," Dr. Mark A. Turco, CEO JC Medical and President of Vascular Intervention North America at Genesis MedTech shared, said in a statement.

CINCINNATI —

A first-of-its-kind surgery is being performed as part of a clinical trial at The Lindner Research Center.

The minimally invasive surgery is designed to treat severe native aortic regurgitation and AR-dominant mixed aortic valve disease in patients.

The successful procedure was done by Dr. Dean Kereiakes, Dr. Santiago Garcia and the team at The Lindner Research Center at The Christ Hospital Health Network earlier this month.

Enrollment for the early feasibility study using the device was announced through a partnership between the Christ Hospital Heart & Vascular Institute and Genesis MedTech, a medical device company.

The J-Valve TF System, which was developed by JC Medical, is regarded as a valve that addresses unmet clinical need and has potential to help many, as described by Dr. Garcia, principle investigator for the study at The Christ Hospital Health Network.

"Unlike cardiac surgery, our patient did not have general anesthesia and went home the next day," Garcia added.

"We are pleased to report that the first Early Feasibility case using a 34mm J-Valve yielded favorable results," Kereiakes, president of the Christ Hospital Heart and Vascular Institute and National Co-Principal Investigator for the study said in a statement. "The J-Valve TF System could potentially revolutionize the treatment of aortic regurgitation, allowing larger annular sizes to be treated."

The completion of the implantation is a milestone moment for Genesis MedTech.

"This achievement demonstrates our dedication to advancing medical technology in the structural heart disease sector. Collaborating with leading TAVR sites across the US and Canada, we hope to demonstrate results that will highlight the unique ability of a dedicated TAVR valve like J-Valve in treating patients with a life-threatening disorder." The North American EFS is part of a broad clinical program that will investigate the treatment of patients with aortic regurgitation," Dr. Mark A. Turco, CEO JC Medical and President of Vascular Intervention North America at Genesis MedTech shared, said in a statement.

Tricuspid Valve Replacement Safe, Effective In Pivotal Trial

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.

Disclosures

Kodali disclosed relationships with Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Vascular, JenaValve, Anteris, Dura Biotech, Shifamed, TRiCares, Phillips, Nyra Medical, Helix Valve Repair, Thubrikar Aortic Valve, Dura Biotech, Supira, MID, TriFlo, Adona, Tioga, xDot, Moray Medical, and Cardiomech.

Mehran disclosed relationships with Abbott Vascular, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, AtriCure, Bayer AG, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cardiawave, CeloNova, Chiesi, Concept Medical, CytoSorbents, Daiichi-Sankyo/Eli Lilly and Company, Element Science, Faraday Pharmaceuticals, Filterlex Medical, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Vivasure, Zoll, Cine-Med Research, Ionis Pharmaceuticals, Vectura, WebMD, Applied Therapeutics, and Elixir Medical.

Ahmad disclosed relationships with Boston Scientific, Cardiovascular Systems, and Shockwave Medical.

Primary Source

Transcatheter Cardiovascular Therapeutics

Source Reference: Kodali SK "TRISCEND II trial: A randomized trial of transcatheter tricuspid valve replacement in patients with severe tricuspid regurgitation" TCT 2023.

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ALIGN-AR: Positive Results For Trilogy Valve In Aortic Regurgitation

SAN FRANCISCO, CA—The Trilogy heart valve system (JenaValve) performs well in patients who have symptomatic aortic regurgitation (AR) and a high surgical risk, according to the results of the ALIGN-AR trial.

The single-arm trial met both safety and efficacy goals established based on historical data, with significant gains observed in NYHA functional class and quality of life through 1 year that were accompanied by "excellent" echocardiographic outcomes, including improvements in various measures of LV remodeling, Vinod Thourani, MD (Piedmont Heart Institute, Atlanta, GA), reported Tuesday at TCT 2023.

Though the overall pacemaker implantation rate overall was 24%, it declined as operators gained experience with the procedure, reaching 14% in the last third of patients enrolled in the trial.

"The TRILOGY THV system provides the first dedicated TAVR option for symptomatic patients with moderate-to-severe or severe aortic regurgitation who are at high risk for surgery and is well positioned to become the preferred therapy upon approval for this population," Thourani said during his presentation.

When untreated, severe symptomatic AR is tied to a high rate of mortality, especially in patients with NYHA III or IV symptoms. SAVR is the only recommended therapy for patients with severe AR, although many high-risk patients are not offered surgery. When TAVI devices are used off-label in this population, there are high rates of complications, including paravalvular regurgitation and embolization, Thourani noted.

The Trilogy system is specifically designed for patients with AR, with three locators that go into the aortic sinuses and, after alignment, anchor onto the leaflets; the valve is then deployed. This implantation technique protects against device embolization. If the Trilogy is ultimately approved by regulators, it will provided a much-needed therapeutic option, experts indicated. The ALIGN-AR trial was designed as a US Food and Drug Administration investigational device exemption trial.

Pinak Shah, MD (Brigham and Women's Hospital, Boston, MA), commenting at a press conference, predicted that uptake would be swift after an approval, downplaying the pacemaker rate because of the lack of alternatives for these patients. "It's a little bit higher than what we see in normal TAVR, but I am very excited to put this to use because we have an unmet need," he said.

ALIGN-AR

The ALIGN-AR trial, conducted at 20 sites, included 180 patients (mean age 75.5 years; 47.2% women) who had symptomatic moderate-to-severe or severe AR (grade ≥ 3), NYHA class II-IV symptoms, and a high risk for surgery as determined by a heart team evaluation. Mean STS score was 4.1%, and one-third of patients had frailty. AR was graded as severe in 64.4%.

General anesthesia was used in 91.1% of procedures, which lasted a mean of 71.8 minutes. Rates of technical, device, and procedure success exceeded 92%. There were no cases of intraprocedural death, annular rupture, ventricular perforation, or coronary obstruction, with low rates of valve embolization (2.2%) and aortic dissection (0.6%).

Primary safety and efficacy endpoints were based on prespecified performance goals established using historical data.

The safety endpoint was a composite of 30-day all-cause mortality, any stroke, major vascular complication, life-threatening/major bleeding, new pacemaker, acute kidney injury, valve dysfunction, and surgery/intervention related to the device. The observed rate was 26.7%, and the upper end of the confidence interval was 34.1%, significantly below the prespecified 40.5% margin for noninferiority (P < 0.001).

The efficacy endpoint was all-cause mortality measured at 1 year. The observed rate was 7.8%, and the upper end of the confidence interval was 12.3%, significantly below the performance goal of 25% (P < 0.0001 for noninferiority).

Safety events were dominated by new pacemaker implants, which declined as the study progressed. Thourani attributed that to changes that were made to insertion technique, less aggressive oversizing of the valve, and advances in the management of periprocedural conduction abnormalities.

He highlighted the angiographic results, which showed that more than 99% of patients had none/trace or mild paravalvular regurgitation at 30 days, with that performance sustained throughout follow-up. At 1 year, in fact, no patients had regurgitation graded as moderate or worse.

Through 1 year, patients saw significant improvements in LV end-systolic diameter, LV end-systolic volume, LV mass, and LV mass index (P < 0.0001 for all). "You see really significant improvements in the ventricle after having the aortic regurgitation obliterated," Thourani said.

In addition, the effective orifice area was large (mean 2.8 cm2 at 1 year), with a significant decline in mean gradient observed from baseline to 1 year (8.7 to 4.3 mm Hg).

Accompanying those changes were improvements in NYHA functional class (all had class II or worse symptoms at baseline versus 40% at 1 year) and Kansas City Cardiomyopathy Questionnaire overall score, which increased from 55.8 at baseline to 77.6 at 1 year.

A Forgotten Disease?

At the TCT press conference, Thourani said the potential population that could be treated by the Trilogy is huge, adding that AR is "a forgotten disease." The number of patients presenting for inclusion in the continued access phase of this trial is greater than the number that were getting enrolled in the initial phase because of increasing awareness that there's now a possible treatment, he indicated. "Once we open this up, I think we'll see this proliferation of a disease managed that we normally have ignored."

Other experts also were encouraged by the findings.

"You're talking about a high-risk patient population that didn't have surgical options, and what you're seeing here is very excellent results," Rebecca Hahn, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), told the media.

Bernard Prendergast, MD (St Thomas' Hospital, London, England), highlighted the differences between patients with AR and those with aortic stenosis, noting that anatomy and rates of aortopathy are distinct. "Therefore, we need a different device. So using currently available TAVR devices off-label to treat aortic regurgitation can be successful, but it is fraught with risk of embolism and other adverse consequences," he said. With the Trilogy, he added, "we now have a very useable device which is specific for aortic regurgitation, and although it's a less common disease than aortic stenosis, it's one with major need. So I'm really excited by these results."

Robert Bonow, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), serving as a discussant after Thourani's presentation, found the data encouraging, as well, but questioned Thourani about whether there is an RCT in the works to pit the Trilogy valve against a comparator in patients with AR. "You could argue unlike aortic stenosis, where there's no medical therapy, there could be medical therapies for these patients," Bonow said, pointing, for example, to the four pillars of heart failure therapy.

Thourani said a randomized trial in high-risk patients is unlikely at this point, but added that there is a lot of interest in exploring the impact of Trilogy in patients with intermediate or low risk and that the ALIGN-AR investigators have mulled an all-comers trial.

"If we go into younger patients . . . A randomized trial is warranted," Thourani said.

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