Low-Gradient Severe AS: Insights From CURRENT AS Registry-2

Quick Takes

  • In a multicenter registry study of patients with severe aortic stenosis (AS), patients with low gradient (LG) AS with reduced LVEF more often had cardiovascular comorbidities, advanced cardiac damage, and frailty compared to patients with high gradient (HG) AS; and patients with paradoxical low flow low gradient (LFLG) AS more often had atrial fibrillation, advanced cardiac damage, and frailty.
  • After adjusting for confounders, LG AS with reduced LVEF and paradoxical LFLG were independently associated with higher risk for death or heart failure hospitalization compared with HG AS, whereas normal flow low gradient (NFLG) AS was not.

Study Questions:

What are the clinical characteristics and outcomes for patients with low-gradient (LG) aortic stenosis (AS) compared to high-gradient (HG) AS?

Methods:

The CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) Registry-2 is a prospective, multicenter registry that enrolled 3,369 consecutive patients with severe AS at 21 participating centers in Japan between 2018 and 2020. The current study included 3,363 of those patients after excluding patients without indexed stroke volume (n = 5) or left ventricular ejection fraction (LVEF) data (n = 1). Patients were divided into four groups based on AS hemodynamic classification at the time of enrollment: LG AS with reduced LVEF (n = 285); paradoxical low flow LG (LFLG) AS (n = 220); normal flow LG (NFLG) AS (n = 872); and HG AS (n = 1,986). Cardiac damage was assessed echocardiographically using published criteria (Genereux, et al., Eur Heart J 2017;38:3351-8). Of 3,363 patients in the study cohort, 1,621 (48.2%) were managed with an initial conservative strategy and 1,742 (51.8%) with initial surgical (SAVR) or transcatheter aortic valve replacement (TAVR). The median follow-up interval was 763 days (IQR 426-1,059 days). The primary outcome measure was all-cause death or heart failure hospitalization (HFH).

Results:

Initial SAVR or TAVR was used more frequently among patients with HG AS (69%) compared to patients with LG AS with reduced LVEF (37% [p < 0.001]), paradoxical LFLG AS (29% [p < 0.001]), or NFLG AS (22% [p < 0.001]). Compared to patients with HG AS, a) patients with LG AS with reduced LVEF more often had cardiovascular comorbidities, advanced cardiac damage, and frailty, with less severe valve calcification; b) patients with paradoxical LFLG AS more often had atrial fibrillation, advanced cardiac damage, and frailty, with less severe valve calcification; and c) patients with NFLG AS had comparable cardiac damage and frailty with less severe valve calcification. The cumulative 3-year incidence of death or HFH was higher among patients with LG AS with reduced LVEF and those with paradoxical LFLG than among those with HG AS. After adjusting for confounders, LG AS with reduced LVEF and paradoxical LFLG compared with HG AS were independently associated with higher risk for death or HFH (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.49-2.23; p < 0.001, and HR, 1.43; 95% CI, 1.13-1.82; p = 0.003, respectively) but NFLG AS was not (HR, 1.03; 95% CI, 0.88-1.21; p = 0.68).

Conclusions:

The authors conclude that, compared to patients with HG AS, clinical outcomes were significantly worse among patients with LG AS with reduced LVEF and paradoxical LFLG AS, but comparable among patients with NFLG AS.

Perspective:

This multicenter registry study from Japan helps define baseline differences at the time of diagnosis between patients with HG severe AS, LG AS with reduced LVEF, paradoxical LFLG AS, and NFLG AS; and documents worse clinical outcomes in terms of all-cause death or HFH among patients with LG AS with reduced LVEF or paradoxical LFLG AS compared to patients with HG AS. Interestingly, the LG AS with reduced LVEF group appears to be somewhat heterogeneous in that not all patients must have had low flow (mean stroke volume index 34 ± 8 mL/m2). In this observational registry study, there were differences between groups in the rate of utilization of initial SAVR or TAVR (highest among the HFG AS group), and clinical outcome differences between the HG AS group, and the LG with reduced LVEF or the paradoxical LFLG groups were blunted when comparing only patients who underwent intervention. The impact of intervention with SAVR or TAVR in these higher-risk groups ideally should be studied in prospective randomized trials.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Structural Heart Disease

Keywords: Aortic Valve Stenosis, Cardiovascular Surgical Procedures, Heart Valve Diseases, Transcatheter Aortic Valve Replacement


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