Exercise gas exchange, hemodynamics and clinical outcomes in patients with normal flow low gradient aortic stenosis
T Sugimoto, M Barletta, F Bandera, G Generati, E Alfonzetti, M GuazziAbstract
Background
The 2025 European Guidelines, define normal-flow, low-gradient (NFLG) aortic stenosis (AS) as less likely severe AS. NFLG is regarded as pathophysiologically equivalent to moderate AS with differences in exercise gas exchange and hemodynamic that remain undefined.
Purpose
We sought to examine the exercise gas exchange, and clinical features of less likely severe AS with preserved EF (NFLG ASpEF) compared to moderate ASpEF and true-severe ASpEF.
Methods
88 patients divided in 26 NFLG ASpEF (AVA <1.0 cm2 or AVA index <0.6 cm2/m2, PV <4 m/s or MPG <40 mmHg, SVi >35ml/m2, LVEF ≥50%), 27 moderate ASpEF and 35 severe ASpEF patients underwent CPET imaging.
Results
There were no significant differences in baseline patient characteristics or medication use among the three groups. Although the mean pressure gradient (MPG) during exercise differed significantly across the groups (moderate ASpEF 25±11, NFLG ASpEF 39±10, severe ASpEF 52±22 mmHg, p <0.001), exercise SVi (43±12 ml/m2), heart rate (122±22 bpm), and cardiac output (8.8±2.8 L/min) did not (p >0.05). Indices of left atrial pressure, left atrial stiffness, and right ventricular–pulmonary circulation coupling showed no significant differences at rest as well; however, these parameters worsened significantly during exercise in the severe ASpEF group. As to exercise gas-exchange, a signifcant reduction of the arteriovenous oxygen content difference was observed in the NFLG ASpEF group (moderate ASpEF 15.0±5.9, NFLG ASpEF 11.5±2.8, severe ASpEF 15.9±4.8 mLO2/100ml, p =0.002). During follow-up, aortic valve replacement was performed more frequently in the NFLG ASpEF than in the moderate ASpEF group (moderate AspEF 4%, NFLG ASpEF 31%, severe ASpEF 26%, Log-rank test p =0.034). Over a median follow-up of 926 days, age- and sex-adjusted Cox proportional hazards analyses showed that the hazard ratios for the composite endpoint of heart failure hospitalization and all-cause mortality were comparable among the three groups (p = 0.64).
Conclusions
Data show that the NFLG ASpEF phenotype exhibits an exercise hemodynamic pattern comparable to moderate ASpEF; nonetheless despite a preserved O2 delivery an impaired O2 extraction emerges as peculiar feature of this clinical entity of AS.