Aims: We sought to evaluate the impact of flow and gradient patterns as assessed by cardiac catheterization on functional improvement, clinical outcome and ventricular remodeling in patients with aortic stenosis (AS) and normal left ventricular ejection fraction (LVEF) treated with transcatheter aortic valve implantation (TAVI).

Methods: Between 2007 and 2017, 752 patients had a full pre-procedural right and left heart catheterization in a single-center registry. Of those, 386 patients with an invasively-defined severe AS (indexed aortic valve area calculated with Gorlin equation (iAVA) ≤0.6 cm²) had an LVEF ≥ 50%. We identified four groups: normal flow, high-gradient (n= 113, NF-HG: stroke volume index (SVI) ≥35 mL/m², mean gradient (MG) ≥40mmHg), low-flow, high gradient (n=190, LF-HG: SVI<35 mL/m², MG≥40mmHg), normal-flow low-gradient (n= 50, NF-LG: SVI≥35 mL/m², MG<40mmHg) and low-flow, low-gradient (n= 83, LF-LG: SVI<35 mL/m², MG<40mmHg). Long-term mortality was the principal endpoint of the study. We further analyzed evolution of NYHA class and NT-proBNP levels after TAVI. Ventricular remodeling was assessed by cardiac magnetic resonance (CMR) performed at baseline and 6 months in a subgroup of 178 patients. 

Results: Compared to patients with NF, patients with LF were older (81.9±6 vs. 80.1±6; p=0.004), had higher incidence of atrial fibrillation (45.8% vs. 27.6%, p<0.001) and had a higher logistic EuroScore (p=0.002). At baseline, median NT-proBNP value was 1746 (IQR 663-3339) pg/ml in the LF population and 936 (IQR 436-2221) pg/ml in the NF group (p<0.001) and didn't differentiations between HG and LG groups (p=0.97). The invasive assessment revealed that the LF population presented hemodynamic signs of heart failure: lower cardiac output, higher total peripheral resistance and higher incidence of pulmonary hypertension (67% vs. 55.2%; p=0.014). Following TAVI, significant amelioration of NYHA class was observed in all subgroups at 1 year. At 30 days post-TAVI, NT-pro-BNP decreased significantly in all groups, while at 12 months levels continued to decrease in the NF-HG subgroup, remained stable in LF-HG, and increased slightly in LF-LG and NF-LG subgroups. At a median follow-up period of 36 (IQR: 23-51) months, all-cause mortality was significantly lower in HG compared to LG population (HR 0.68 95%CI 0.49-0.95; log-rank p= 0.024) and did not differ between LF and NF (HR 1.02 95%CI 0.75-1.34; log-rank p=0.87). After multivariate analysis, age, NYHA functional class III/IV, previous stroke, atrial fibrillation, higher PCPW and lower gradient remained independent predictors of all-cause mortality at follow-up. 
In the CMR subgroup, significant decrease of LV mass was observed in NF-HG, LF-HG and LF-LG but not in NF-LG patients. Relative wall mass decreased significantly in LF-HG (p=0.002) and LF-LG groups (0.026). Similar increase in EF was observed in all subgroups and no significant change in end diastolic volume was noted. 

Conclusion: In patients with severe symptomatic AS and normal ejection fraction, the presence of low-flow in the invasive evaluation was common (62.6%), and these patients are older and have higher incidence of atrial fibrillation with more pulmonary hypertension and higher NT-pro-BNP levels. Despite clinical improvement and reduction in NT-proBNP levels, LG patients had less pronounced ventricular remodeling and higher long-term mortality after TAVI, whereas flow status did not impact long-term outcome.