Transcatheter Aortic Valve Replacement for Pure Aortic Insufficiency

Corresponding Author

Although less prevalent than aortic stenosis, aortic regurgitation (AR) remains a frequently encountered clinical problem in the adult population, with an estimated prevalence of at least moderate AR of 2.2% in patients older than age 70 years (1). Surgical aortic valve repair or replacement has been the preferred therapeutic option for patients with severe AR; however, many patients with this pathology are not candidates for surgery because of elevated surgical risk.

Transcatheter aortic valve replacement (TAVR) has been extensively performed in patients with symptomatic aortic stenosis with similar, and in some studies superior, results when compared to surgical valve replacement, and it is currently accepted as a valid treatment alternative for the majority of patients in the entire risk spectrum (2, 3, 4, 5, 6, 7, 8). Based on this successful experience, clinicians began to explore expanding the role of TAVR to the treatment of patients with severe pure AR not eligible for surgery; however, this has proven to be a rockier road. Early experience demonstrated poorer outcomes with TAVR for AR when compared to TAVR for aortic stenosis, with higher mortality, device embolization, second valve implantation, and significant residual post-procedure paravalvular leaks (PVL) rates observed (9,10). This is not surprising, given the particular anatomic challenges imposed by AR, such as the lack of annular/leaflet calcification, irregular orifice geometry, and frequently associated ascending aorta pathology, all of which negatively affect the ability to deploy a stable TAVR system without significant PVL. Self-expanding valves, particularly the CoreValve transcatheter heart valve (THV) (Medtronic, Minneapolis, Minnesota) were favored initially, because it was thought to facilitate safe anchoring by oversizing without increased risk for annular disruption—unfortunately, with disappointing results (11). The use of next-generation balloon-expandable and self-expanding TAVR systems demonstrated improved outcomes in patients with at least intermediate risk for surgery; however, higher than acceptable procedural complications and mortality rates were observed (12).

In this issue of JACC: Case Reports, Ng et al. (13) describe the case of a 66-year-old man with prohibitive risk for surgery who presented with severe aortic insufficiency secondary to post-infectious leaflet perforation complicated by cardiogenic shock who underwent successful TAVR using the JenaValve THV (JenaValve Technology, Inc., Irvine, California). This THV system was used under an emergency use protocol, because it is not currently approved for use in the United States. The procedure was successfully performed via a transfemoral approach, with trace residual paravalvular leak and minimal residual gradients, and the patient experienced a remarkably expeditious recovery.

The JenaValve THV comprises a self-expanding nitinol stent with a porcine pericardial valve. Of particular interest in its design is the presence of “locators” attached to the valve frame that clip onto the leaflets upon deployment, facilitating anchoring without relying on annular calcification or the need for oversizing. Additional positive features of this TAVR system are: 1) the supra-annular location of the actual valve, theoretically improving hemodynamics; and 2) the presence of large cells at its aortic end and the possibility of anatomically correct alignment with native sinuses, facilitating coronary access. A potentially negative feature is the lack of a dedicated sealing skirt, which might increase the risk for significant post-procedure PVL.

Early European experience using the JenaValve THV for pure severe AR was encouraging, with the valve being successfully implanted via a transapical approach in more than 96% of patients without at least moderate post-procedure PVL or coronary occlusion. Of note, despite the high procedural success and preserved valve function, with mean aortic prosthesis gradients in the single digits, a high mortality of 20% was observed in these cohorts of patients at 1 year of follow-up, perhaps a reflection of increased comorbidities and interventions performed late in the course of the disease (14,15). This experience was expanded in the multicenter observational AR TAVR registry reporting the results of 331 patients with prohibitive surgical risk who underwent treatment of native severe AR using early- and new-generation TAVR valve systems, of whom 64 were treated with the JenaValve (12). Compared to the early-generation Medtronic CoreValve THV, the JenaValve THV had a significantly lower incidence of second valve implantation (9.4% vs. 26.4%; p = 0.007) and a lower incidence of at least moderate post-procedure PVL (1.6% vs. 18.2%; p = 0.001), without significant differences on new permanent pacemaker insertion rates between the 2 TAVR systems. Of concern, the JenaValve THV was associated with a higher risk for stroke at 30 days when compared to the Medtronic CoreValve THV (7.8% vs. 0.9%). A major drawback on the early generations of the JenaValve THV is the need for transapical access, which is known to increase the morbi-mortality of TAVR. However, a JenaValve THV transfemoral system was recently tested in 11 patients with severe aortic stenosis with encouraging results (16). Although the procedural success rate was slightly lower (93.3%) than that previously reported for transapical access, there were no patients with at least moderate post-procedure PVL.

Unquestionably, TAVR for severe AR has proven to be more difficult than when performed in patients with severe aortic stenosis. Based on its unique features and early encouraging results, there are high hopes in the medical community for the JenaValve THV becoming a safe and effective option for the treatment of patients with severe AR who are not candidates for surgery, which is currently an unmet need. This concept is currently being tested in the ALIGN-AR EFS (Safety and Effectiveness/Performance of the Transfemoral JenaValve Pericardial TAVR System in the Treatment of Patients With Symptomatic Severe Aortic Regurgitation) trial evaluating the safety and effectiveness/performance of the transfemoral JenaValve in the treatment of patients with symptomatic severe AR (NCT02732704). The results of this study might get us to cross the next frontier in TAVR.

Funding Support and Author Disclosures

The author has reported that he has no relationships relevant to the contents of this paper to disclose.