Transcatheter aortic valve replacement in low-risk patients with symptomatic severe bicuspid aortic valve stenosis

Selected in JACC: Cardiovascular Interventions by M. Alasnag , W.H. Ahmed

In the absence of randomized trials to study TAVR in bicuspid arotic stenosis in low-risk patients, prospective cohort studies such as Low-Risk TAVR provide us with valuable information.

Reviewers

Mirvat Alasnag

@mirvatalasnag

Interventional cardiologist / Cardiologist

King Fahd Armed Forces Hospital - Jeddah, Saudi Arabia

Waqar Ahmed

@Jedicath

Interventional cardiologist / Cardiologist

KFAFH - Jeddah, Saudi Arabia

Our Comment

Why this study – the rationale/objective?

Transcatheter aortic valve replacement (TAVR) in inoperable, high, intermediate and low-risk individuals, has been compared to surgical aortic valve replacement (SAVR) in several randomized studies that paved the way for US FDA approval of this technology. The US FDA approved TAVR for low-risk individuals irrespective of valve morphology despite the fact that the bicuspid morphology was an exclusion criterion in the published randomized trials. To date, we don’t have any randomized data evaluating TAVR in bicuspid aortic valves. The available evidence for TAVR in bicuspid valves is primarily observational.

Although propensity-matched cohorts obtained from the Transcatheter Valve Therapy (TVT) registry did not demonstrate a significant difference in 30-day or 1-year mortality between tricuspid and bicuspid individuals, there was an increase in 30-day stroke rates. The purpose of the Low-Risk TAVR (LRT) trial is to evaluate the feasibility and safety of TAVR in low-risk patients with bicuspid valves. This is the first FDA-approved Investigational Device Exemption (IDE) trial in the US enrolling low-risk patients with bicuspid valves.

How was it executed – the methodology?

The Low-Risk TAVR trial is a prospective, investigator-initiated, multicenter cohort study that included low-risk individuals with stenotic bicuspid valves treated with either balloon expandable (BEV) or self-expanding (SEV) transcatheter aortic valves (at the discretion of the operator).

The primary endpoint was all-cause mortality at 30 days. Baseline and follow-up echocardiography and computed tomography to detect leaflet thickening/thrombosis were analyzed in an independent Core Laboratory. Patients were enrolled into two arms: tricuspid or bicuspid. Clinical endpoints were adjudicated by an independent Clinical Events Adjudication Committee comprising an interventional cardiologist, a cardiothoracic surgeon, and a neurologist using Valve Academic Research Consortium (VARC) 2 definitions. A dilated ascending aorta was an important exclusion criterion for the LRT trial.

What is the main result?

A total of 61 low-risk patients (STS 30-day PROM score 1.5±0.6%) with bicuspid aortic valves were enrolled in the bicuspid arm and underwent TAVR between August 2016 and September 2019. The mean age of the TAVR arm was 68.6 years. In terms of Sievers classification, 78.3% were type 1, 13.3% were type 0 and 3.3% were type 2. The majority (74%) received BEV (Sapien 3, Edwards Lifesciences, Irvine, California) and 26% received a SEV (Evolut R/Pro, Medtronic, Minneapolis, Minnesota). Seventy-nine per cent required a > 26-mm or larger valve. All were performed via transfemoral access.

The mortality and disabling stroke rates at 30 days were zero. New permanent pacemaker implantation at 30 days was 13.1%. (BEV 6.7% and SEV 31.3%). Only one patient had moderate paravalvular leak (PVL) at 30 days, and none had severe PVL. At 30 days, 60 patients underwent contrast-enhanced CT scans and Hypoattenuated Leaflet Thickening (HALT) was present in 6 patients (1 SEV and 5 BEV) and Reduced Leaflet Motion (REM) was found in 4 patients.

Critical reading and the relevance for clinical practice

In the absence of randomized trials to study TAVR in bicuspid aortic stenosis in low-risk patients, prospective cohort studies such as LRT provide us with valuable information.
Although small numbers were enrolled, the study demonstrated safety with a zero mortality and disabling stroke rate. The overall stroke rate in this cohort is numerically low (1.6%), which is higher than that noted in tricuspid valves (0.5%). The TVT registry reported a higher 30-day stroke rate in bicuspid valves (2.5% vs 1.6%). In young low-risk patients any stroke above the accepted rate for SAVR is unjustified.

Low mortality is expected in a low-risk cohort; therefore, it is far more important to assess PVL and the need for permanent pacemakers. The overall rates of PVL and bleeding were comparable to low-risk TAVR in tricuspid valves. However, moderate and severe PVL was numerically higher in bicuspid valves (2%) compared to tricuspid valves in both the LRT (0.5%) and PARTNER 3 trials (0.8%), similar to the TVT registry bicuspid cohort, but lower than the tricuspid patients in the Evolut Low-Risk trial (3.5%). Once again, the rate of PVL in low-risk (young) patients is concerning particularly given the data linking the degree of PVL to mortality.

In addition, there is a notably high permanent pacemaker rate in this cohort. The mean age of this bicuspid population was 5 years younger than those in previously published low-risk tricuspid trials which is not surprising considering the natural history of early degeneration of bicuspid aortic valves. It is difficult to accept a higher rate of permanent pacemakers with their inherent risks in a low-risk young population.

Finally, aortopathy, which is commonly associated with Sievers 0, was an exclusion criterion making it difficult to infer the feasibility of TAVR in this subset.

The small sample size precludes adequate evaluation of the type of transcatheter valve most suitable for a bicuspid pathology. Aside from the small sample size, this is not a randomized study and no long-term inferences can be made on durability. Overall the data shows promise, yet most cardiologists would hesitate to offer TAVR with such rates of stroke, permanent pacemaker and PVL to a young low-risk population.