Clin Res Cardiol (2022).

Patients with paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) gain the least benefit from TAVI among all hemodynamic subtypes
M. Puls1, B. E. Beuthner1, R. Topci1, N. Paul2, K. Toischer1, T. Seidler1, C. Jacobshagen3, G. Hasenfuß1
1Herzzentrum, Klinik für Kardiologie und Pneumologie, Universitätsmedizin Göttingen, Göttingen; 2Institut für Medizinische Statistik, Universitätsmedizin Göttingen, Göttingen; 3Klinik für Kardiologie, Intensivmedizin und Angiologie, St. Vincentius-Kliniken, Karlsruhe;
Background and Aims:
Substantial controversy exits regarding the clinical benefit of PLF-LG AS patients from TAVI. Therefore, we examined post-TAVI mortality (all-cause, cardiovascular (CV) and sudden cardiac death (SCD)), clinical improvement of heart failure symptoms and cardiac reverse remodelling in guideline-defined AS subtypes.

Between 1/2017 and 7/2019, we prospectively included 250 consecutive patients scheduled for transfemoral TAVI. TTE, 6mwt distance, MLHFQ, NYHA status and NT-proBNP were recorded. A clinical FU visit with TTE and re-evaluation of heart failure measures was scheduled for 6 months. Regular telephone FU was performed to assess mortality and causes of death (last in 6/2021).

107 individuals suffered from normal EF, high-gradient AS (NEF-HG AS) (LV-EF ≥50%, vmax ≥4 m/s or Pmean ≥40 mmHg, AVA ≤1.0 cm²), 36 from low EF, high-gradient AS (LEF-HG AS) (LV-EF<50%, vmax ≥4 m/s or Pmean ≥40 mmHg, AVA ≤1.0 cm²), 52 from low EF, low-gradient AS (“classic” low-flow, low-gradient AS) (LEF-LG AS) (LV-EF<50%, vmax <4 m/s and Pmean <40 mmHg, AVA ≤1.0 cm², SVI <35 ml/m²), and 38 from paradoxical low-flow, low-gradient AS (PLF-LG AS) (LV-EF ≥50%, vmax <4 m/s and Pmean <40 mmHg, AVA ≤1.0 cm² and indexed AVA ≤0.6 cm²/ m², SVI <35 ml/m²). 17 patients were classified as “moderate-to-severe AS” (MAS).
Baseline characteristic differed significantly in AS subtypes (table 1), with NEF-HG representing the healthiest and LEF-LG the sickest group. Prevalence of atrial fibrillation was highest in PLF-LG (74%).

Regarding mortality, significant differences between AS subtypes were observed particularly for CV mortality and SCD (Kaplan-Meier curves in fig. 1), with PLF-LG patients exhibiting the poorest survival (HR 3.6, P=0.0008 for CV mortality and HR 6.2, P=0.003 for SCD in comparison with NEF-HG).


6 months FU was 73% complete (11% of patients had already died, 4% were too sick to attend FU, and 12% refused the visit).
NYHA-status at 6m (fig. 2A) differed significantly, with >50% of PLF-LG patients dead or in NYHA classes 3 or 4 (possible indicator of treatment futility). TAVI lead to a significant decrease in MLHFQ score and NT-proBNP levels in all subtypes except for PLF-LG (fig. 2 B, C). Only 6mwt distances increased significantly in all groups (fig. 2D).

Fig. 2:

Regarding reverse remodelling, a significant increase in EF and decrease in LVEDV was present only in subtypes with reduced BL EF, whereas a significant decrease in left ventricular mass index (LVMI) and LAVI could be observed in all subtypes except for PLF-LG (fig. 3).

Fig. 3:


PLF-LG patients exhibit the highest mortality (particularly CV and SCD), the poorest symptomatic benefit and the least reverse cardiac remodelling after TAVI among all subtypes. Thus, this cohort seems to gain the least benefit from TAVI.