Dedicated transcatheter aortic valve replacement (TAVR) devices led to better outcomes in high-risk severe native aortic regurgitation (AR) patients than off-label alternatives, according to a new meta-analysis in more than 2,000 patients. However, permanent pacemaker implants were high for severe AR patients receiving TAVR in the study. The findings were published Monday online in JACC: Cardiovascular Interventions and follow the recent development of two dedicated devices for TAVR in pure native AR, the JenaValve Technology’s JenaValve Trilogy and Edwards Lifescience’s J-Valve, acquired as part of its JC Medical takeover in August. Patients with native AR generally receive surgical aortic valve replacement (SAVR), the authors, led by Sahar Samimi, MD, from the Houston Methodist DeBakey Heart and Vascular Center, Texas, noted. However, despite severe AR being a progressive disease associated with a mortality risk exceeding 10% per year if left untreated, severe cases often do not undergo SAVR within the first year of diagnosis because of the high surgical risk often associated. Some go on to receive TAVR as an alternative, although with anatomical challenges associated, including large annulus, aortic root dilation, lack of leaflet calcium to enable anchoring the valve and severe regurgitation jet, leading to potentially unstable valve positioning and risk of valve embolization, the authors noted. Other studies have highlighted high rates of complications and reintervention associated with treating noncalcified AR with transcatheter heart valves (THVs) designed to treat aortic stenosis. Instead, “recent advances have led to the development of 2 dedicated devices, the JenaValve Trilogy […] and J-Valve […], which were specifically designed to maneuver the technical challenges of TAVR in pure native AR,” the researchers noted. “Both devices are equipped with specialized locators that engage with the sinuses of Valsalva, providing stable anchoring and preventing embolization.” The current study aimed to assess the safety and efficacy of these specialty devices vs standard TAVR devices used off-label via a meta-analysis of 34 studies included in PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases through July 11, 2024, with a 30-day all-cause mortality primary endpoint. A total 2,162 patients with a mean age of 75.4 years were included, 42.8% of whom were women. The studies included 1,193 dedicated devices (55.2%) and 969 (44.8%) off-label devices. Off-label devices used included those from Medtronic’s Evolut range and CoreValve, Edwards Lifesciences’ SAPIEN range, Meril Life Sciences’ Myval, Boston Scientific’s Accurate neo and Direct Flow Medical’s Direct Flow. Patients undergoing TAVR with the two dedicated devices had lower 30-day all-cause mortality rates (3% vs 9%; 95% confidence interval [CI]: P< 0.01). Secondary endpoints were also better for the dedicated TAVR device group, including device success (93% vs 82%; 95% CI: P < 0.01), valve embolization/ migration (2% vs 8%; 95% CI: P < 0.01), pacemaker implantation (11% vs 20%; 95% CI: P < 0.01) and reintervention (4% vs 10%; P < 0.01) at 30 days. The risk of AR remaining moderate or worse after procedure was also lower (2% vs 5%; P = 0.03). “These findings support the use of dedicated devices over off-label THVs in fulfilling an unmet need in this high surgical risk patient population with pure native AR,” the authors concluded. While JenaValve is approved by the US Food and Drug Administration, a decision is yet to be made for J-Valve. The authors went on to call for regulatory approval in high surgical-risk patients, and further prospective trials investigating dedicated devices among patients with intermediate and low surgical risk. ‘Unexpectedly high’ pacemaker rate In an accompanying editorial, Tanja K. Rudolph, MD, from the Clinic for General and Interventional Cardiology/Angiology, in Bad Oeynhausen, Germany, highlighted an “unexpected” high rate of permanent pacemaker (PPM) implantation – of 20% to 24% - following transfemoral implantation with the JenaValve Triology. This has “not yet been fully understood and is currently a matter of investigation,” said Rudolph. “Patient-based factors such as higher prevalence of preprocedural conduction disturbances as well as implantation technique and sizing might influence permanent pacemaker rate,” she noted. Pacemaker implants were significantly higher in the JenaValve Triology group than the J-Valve group at 30 days, the researchers added (21% vs 6%; P < 0.01), although it came with a lower incidence of significant residual AR compared to J-Valve (1% vs 3%; P < 0.01). They hypothesized that this could be related to the JenaValve Triology’s “unique anchoring mechanism, which, although effective in securing the valve and preventing significant residual AR, might exert additional pressure on the conduction system.” Rudolph added that PPM implantation was significantly lower (6% vs 21%) in transapically treated patients. “However, it has to be noted that dedicated devices are no longer available as transapical devices.” The researchers speculated that in native AR, leaflets are not calcified as they are in aortic stenosis. This likely leads to the low incidence of stroke rates post-TAVR for native AR patients versus aortic stenosis. However, “lthough calcified leaflets are deemed unfavorable in terms of stroke risk, annular calcification may provide some level of protection for the atrioventricular conduction system,” the authors noted. “Thus, the lack of this protective armor among patients with noncalcified native AR may leave the conduction system more susceptible to injury from the THVs, potentially leading to a higher risk of PPM implantation.” They also stressed that PPM was lower in the JenaValve/J-valve patients overall (11%) compared to the off-label THV group (20%). “The lower tendency for [transcatheter heart valve embolization and migration] and improved device anchoring and positioning with these specific valve systems could potentially explain the lower rate of PPM placement,” they said. “In the case of off-label valves, the risk of device failure to anchor, mispositioning, increased manipulation because of a higher risk of valve migration, and valve oversizing all contribute to a higher risk of PPM implantation for the patient.” Sources: Samimi S, Hatab T, Kharsa C, et al. Meta-Analysis of Dedicated vs Off-Label Transcatheter Devices for Native Aortic Regurgitation. JACC: Cardiovasc Interv 2024; DOI: 10.1016/j.jcin.2024.08.042 Rudolph TK. Transcatheter Heart Valves Devices for Native Aortic Valve Regurgitation: Time for a Change? JACC: Cardiovasc Interv 2024; DOI: 10.1016/j.jcin.2024.09.038 Image Credit: ibreakstock - stock.adobe.com