https://doi.org/10.1007/s00392-025-02625-4
1Universitätsmedizin Göttingen Herzzentrum, Klinik für Kardiologie und Pneumologie Göttingen, Deutschland; 2Universitätsmedizin Göttingen Institut für klinische Chemie Göttingen, Deutschland; 3Forum Medizin GbR Kardiologie Rosdorf, Deutschland
In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) both high-gradient (HG) and low-gradient (LG) constellations can be associated with a reduced LV stroke volume index (SVi < 35mL/m2). While the prognostic significance of a reduced SVi in paradoxical low-flow, low-gradient AS (PLF-LG AS) is well established, data on the clinical characteristics and outcomes of patients with reduced SVi in HG AS remain scarce. Therefore, this study aimed to comprehensively characterize this subgroup in the context of both HG and LG constellations and explore the prognostic role of a reduced SVi in severe HG AS.
Methods:
The study included 184 patients with severe AS and preserved LVEF who underwent transcatheter aortic valve replacement (TAVR). Three groups were categorized:
(1) Low-flow high-gradient AS (LF-HG AS): LVEF >50%, Vmax ≥4 m/s, Pmean ≥40 mmHg, SVI ≤35 mL/m², AVA ≤1.0 cm²,
(2) Normal-flow high-gradient AS (NF-HG AS): LVEF >50%, Vmax ≥4 m/s, Pmean ≥40 mmHg, SVI>35 mL/m², AVA ≤1.0 cm²,
(3) Paradoxical low-flow low-gradient AS (PLF-LG AS): LVEF >50%, Vmax <4 m/s, Pmean <40 mmHg, AVA ≤1.0 cm², SVI ≤35 mL/m²
Patients were comprehensively analyzed using a multimodal approach, including clinical data, echocardiography, cardiac magnetic resonance (CMR) imaging, multidetector computed tomography, histology and next-generation sequencing (NGS). Cardiovascular and all-cause mortality were defined as primary clinical endpoints.
Results:
45 patients were classified as LF-HG, 88 as NF-HG and 51 as PLF-LG AS. While there were no relevant differences in baseline characteristics between LF-HG and NF-HG subgroups, PLF-LG AS patients were significantly older (LF-HG: 80.1±6.1; NF-HG: 78.7±6.0; PLF-LG: 81.4± 5.8; p=0.02) and demonstrated greater symptom burden of heart failure compared to HG subgroups (NT-proBNP: LF-HG: 2328 ± 3370 ng/L; NF-HG: 1623±2398 ng/L; PLF-LG: 2150±1579 ng/L; p=0.007; Minnesota Living with Heart Failure Questionnaire: LF-HG: 32.6±16.5; NF-HG: 27.8±17.7; PLF-LG: 36.8±16.4; p=0.01).
Echocardiography and CMR imaging revealed impaired right ventricular (RV) function in PLF-LG AS patients compared to HG subgroups (TAPSE: LF-HG: 21.4±4.1 mm; NF-HG: 23.2±4.3 mm; PLF-LG: 19.4±4.3 mm; p=0.01; RVEF: LF-HG: 56.9% (47.8;61.4%); NF-HG: 57.6% (53.1;63.5%) PLF-LG: 49.3% (42.8;58.8%); p=0.027; RV GLS: LF-HG: -27.8% (-21.3;-31.6%); NF-HG: -31.1% (-25.6;-35.3%); PLF-LG: -25.8% (-22.3;-28.8%); p=0.007). Assessing myocardial fibrosis, there were no significant differences among all three groups neither in histological analyses (LF-HG: 12.3±14.3 %; NF-HG: 14.7±13.7 %; PLF-LG: 16.8±13.7 %; p=0.55), circulating biomarkers (CITP:MMP1: LF-HG: 2.6±1.3; NF-HG: 2.5±1.9; PLF-LG: 2.6±1.3; p=0.38) nor in CMR-derived extracellular volume (LF-HG: 24.5% (23.2;25.9%); NF-HG: 25.5 (24.0;26.9%); PLF-LG: 26.6% (24.1;28.0%); p=0.26). Among all subgroups, PLF-LG AS patients had the highest 5-year cardiovascular mortality.
Conclusion:
Amongst AS patients with preserved LVEF, there were no relevant clinical and prognostic differences between patients with LF-HG and NF-HG suggesting a comparable disease trajectory. In contrast, PLF-LG was associated with more pronounced right-sided heart failure compared to HG AS subgroups and showed the poorest long-term outcome. Therefore, in LF-HG AS patients, a reduced SVi might not serve as an appropriate parameter for optimized patient management or risk stratification.
Figure 1: