By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports he is a consultant for Alnylam Pharmaceuticals and Akcea Therapeutics.

SYNOPSIS: In patients with low-flow, low-gradient aortic stenosis and severe left ventricular dysfunction, transcatheter aortic valve replacement was associated with significant improvement in left ventricular ejection fraction and similar mortality compared to patients with milder left ventricular dysfunction.

SOURCE: Maes F, Lerakis S, Barbosa Ribeiro H, et al. Outcomes from transcatheter aortic valve replacement in patients with low-flow, low-gradient aortic stenosis and left ventricular ejection fraction less than 30%: A substudy from the TOPAS-TAVI Registry. JAMA Cardiol 2018; Dec 19. doi: 10.1001/jamacardio.2018.4320. [Epub ahead of print].

Management of low-flow, low-gradient aortic stenosis (LFLG AS), typically defined as an aortic valve area < 1.0 cm2 with a mean transvalvular gradient ≤ 40 mmHg and reduced stroke volume, can be challenging. When evaluating candidacy for aortic valve replacement, dobutamine stress echocardiography (DSE) is used often to distinguish true-severe from pseudo-severe AS and to assess contractile reserve. In patients with LFLG AS and severely reduced left ventricular ejection fraction (LVEF), data regarding outcomes after transcatheter aortic valve replacement (TAVR) and the utility of DSE for predicting post-TAVR outcomes are lacking.

Maes et al performed a substudy of the True or Pseudo-Severe Aortic Stenosis-TAVI (TOPAS-TAVI) registry of patients undergoing TAVR for LFLG AS, defined as a mean transvalvular gradient < 35 mmHg with effective orifice area < 1.0 cm2 and LVEF ≤ 40%. Patients were divided into two groups: very low LVEF (< 30%) and low LVEF (30-40%). The primary outcomes were change in LVEF over time, periprocedural complications, and late mortality. Most patients with very low LVEF underwent DSE before TAVR. The association between presence of contractile reserve (defined as an increase in stroke volume of 20% or greater with dobutamine) and post-TAVR outcomes also was assessed.

Of 293 patients included in the analysis, 128 had very low LVEF and 165 low LVEF. The mean LVEF in the very low LVEF group was 22%. There was no difference in periprocedural complications or 30-day mortality (4.1% vs. 4.7%; P = 0.65) between patients with very low vs. low LVEF. Over a median follow-up of 23 months, there was no difference in long-term survival (hazard ratio, 0.96 for very low vs. low LVEF; P = 0.88). Patients with very low LVEF demonstrated a greater improvement in LVEF at one-year follow-up (11.9% vs. 3.6% in the low EF group; P < 0.001).

Of the 92 patients with very low LVEF who underwent pre-TAVR DSE, 49% did not demonstrate contractile reserve. Lack of contractile reserve was not related to survival or change in LVEF after TAVR. The authors concluded that in patients with LFLG AS and severe LV dysfunction, TAVR is associated with similar outcomes compared to patients with milder LV dysfunction. Further, they determined that assessment of contractile reserve is not useful for predicting survival or change in LVEF.


Among patients referred for surgical aortic valve replacement, presence of LFLG AS with left ventricular dysfunction is associated with higher perioperative risk and worse long-term survival. On the other hand, the authors of the TOPAS-TAVI registry previously reported that patients with LFLG AS and reduced LVEF experience acceptable outcomes after TAVR. In this substudy of TOPAS-TAVI, Maes et al demonstrated that even patients with LFLG AS and severely reduced LVEF demonstrate similar post-TAVR survival compared to those with milder reductions in LVEF. Furthermore, these patients experienced the largest improvement in systolic function after TAVR. As TAVR volumes increase and eligibility criteria continue to expand, studies evaluating challenging patient groups such as LFLG AS and severely reduced LVEF are crucial to guide appropriate patient selection.

DSE is a frequently used test to distinguish true-severe from pseudo-severe aortic stenosis. Contractile reserve, the ability to augment stroke volume in response to dobutamine, also is used to predict recovery of LV function after correction of aortic stenosis. The absence of contractile reserve has been associated with poor outcomes following surgical aortic valve replacement. The original TOPAS-TAVI registry revealed no association between presence of contractile reserve and outcomes in patients with LFLG AS and LVEF < 40%. The authors of this substudy extended these findings to patients with severely reduced LVEF, showing that even patients with LVEF < 30% can recover LV systolic function following TAVR, regardless of contractile reserve. While DSE still plays a role for differentiating true-severe vs. pseudo-severe AS, the utility of assessing contractile reserve in these patients is less clear now. Although the authors demonstrated acceptable TAVR outcomes in LFLG AS with LV dysfunction, it is important to remember the mortality rate was approximately 40% in both LVEF groups during the median 23-month follow-up period. This highlights the overall poor prognosis associated with LFLG AS and may be helpful for patients trying to decide whether to pursue TAVR.

There were several important limitations to this registry study. Although the baseline clinical characteristics appeared similar between the very low and low LVEF groups, it is possible that selection bias (particularly among those with very low LVEF) led to unidentified differences between the groups. Approximately one-quarter of patients with very low LVEF did not undergo DSE prior to TAVR. The relatively small number of patients may have limited the ability to detect differences in outcomes. When taking these limitations into consideration, the authors’ conclusion that “these results support the use of TAVR for LFLG AS, irrespective of the severity of left ventricular dysfunction and DSE results” may be a bit strong.

However, it is reasonable to say that LVEF < 30% and lack of contractile reserve should not be considered contraindications to TAVR in patients with LFLG AS. Hopefully, others will study this challenging patient population further to help refine patient selection for TAVR.