Does Anyone with Severe Aortic Stenosis Not Benefit from TAVR?
March 1, 2024
By Michael H. Crawford, MD, Editor
SYNOPSIS: A single-center, retrospective study of low-flow low-gradient aortic stenosis patients has shown that a gradient < 20 mmHg identifies a high-risk group because of significant comorbidities that may not benefit from transcutaneous aortic valve replacement.
SOURCE: Ueyama HA, Chopra L, Dalsania A, et al. Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis. Eur Heart J Cardiovasc Imaging 2024;25:267-277.
Low-flow low-gradient aortic stenosis (LGAS) has been shown to have a worse prognosis with transcatheter aortic valve replacement (TAVR) than high-gradient AS, but little is known about how the degree of pressure gradient reduction affects outcomes. Thus, these investigators from Mount Sinai Hospital in New York, NY, conducted a single-center, retrospective study of all patients between 2019 and 2021 who had an aortic valve area (AVA) of ≤ 1.0 cm2, a stroke volume index of ≤ 35 mL/m2, and underwent TAVR or conservative management. These patients were retrospectively classified into three groups by their baseline mean pressure gradient (MPG): very LG (MPG ≤ 20 mmHg), LG (MPG 21 mmHg to 39 mmHg), and high gradient (HG, MPG ≥ 40 mmHg).
The primary endpoint was a composite of all-cause mortality and heart failure hospitalization. Secondary endpoints included the components of the primary endpoint and the 30-day periprocedural complication rates for those who underwent TAVR. Among the 662 patients included in the study, 130 patients had very LG, 339 patients had LG, and 193 patients had HG. At baseline, very LG patients had more comorbidities, such as coronary artery disease, chronic kidney disease, moderate tricuspid valve regurgitation, atrial fibrillation, and the highest average Society of Thoracic Surgeons (STS) score (very LG, 4.5% vs. LG, 3.4% vs. HG, 3.3%; P < 0.001). Also, they were more likely to have drug or device therapy for heart failure. In addition, the prevalence of left ventricular ejection fraction (LVEF) < 50% was higher in the very LG group (60% vs. 35% vs. 23%, respectively; P < 0.001), and they had a larger average AVA (0.76 cm2 vs. 0.69 cm2 vs. 0.55 cm2, respectively; P < 0.001). During the median follow-up of 12 months, 18% of the patients died and 9% of the patients were hospitalized for heart failure. The greatest risk of the primary endpoint was in the lower MPG strata (P < 0.001), which mainly was the result of heart failure rehospitalization (P < 0.001) and not mortality (P = 0.2). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (hazard ratio [HR] = 2.42; 95% confidence interval [CI], 1.29-4.55).
Whereas the LG and HG groups had a decreased risk of the composite endpoint with TAVR compared to conservative management (LG HR, 0.38; 95% CI, 0.24-0.62 and HG HR, 0.15; 95% CI, 0.07-0.33), the very LG group did not (HR = 0.69; 95% CI, 0.35-1.34). However, all-cause mortality was decreased in the very LG group with TAVR (HR, 0.42; 95% CI, 0.18-0.95). The authors concluded that patients with very LGAS are a unique population with significant comorbidities and worse outcomes with or without TAVR.
COMMENTARY
Previous studies have shown that aortic valve replacement by any means in patients with severe AS reduces subsequent mortality, but outcomes in general are worse in those with LGAS compared to HGAS. In TAVR registry studies, LG (but not LVEF) is an independent predictor of mortality and heart failure hospitalizations. Thus, a closer look at the spectrum of LG patients and their response to TAVR in the Ueyama et al study is of interest. The researchers found that very LG patients make up about one-fifth of low-flow severe AS patients, and they have more comorbidities and lower LVEFs. TAVR in their low-flow severe AS patients showed comparable 30-day outcomes across the gradient spectrum, but longer-term outcomes were better as the gradients increased. Very LG was an independent predictor of the primary composite outcome and heart failure hospitalization alone. However, TAVR in the very LG patients did not improve either of these outcomes compared to conservative therapy but did improve all-cause mortality.
Ueyama et al opined that TAVR may not result in long-term benefits in very LG patients. One explanation for this caution in very LG patients is that very LG identifies patients with extensive cardiac and systemic comorbidities that impair outcomes despite TAVR. Thus, very LG is a heterogeneous group where one must carefully weigh and consider the potential risks and benefits of TAVR.
There are weaknesses in the Ueyama et al study. Since it was a retrospective, single-center study, selection biases are likely, although multivariate analyses were performed to mitigate these effects. Also, in less than half of the patients was low-flow LG severe AS verified by dobutamine echocardiography or computed tomography calcium content of the AV. However, an analysis of those with and without verification showed comparable results. In addition, median follow-up was only 12 months. What seems clear is that, like with many procedures, just because you can do a TAVR with low periprocedural complications does not mean that you should. Very LG severe AS may be an example of this axiom.