Morphological and functional phenotyping of patients with severe aortic stenosis, preserved ejection fraction and low-flow constellations

Q: What are the key findings of this study?

PLF-LG AS patients had worse right ventricular function and highest 5-year cardiovascular mortality compared to LF-HG and NF-HG AS despite preserved LVEF.

Q: What does this research mean for the field?

Patients with paradoxical low-flow low-gradient aortic stenosis have the highest 5-year cardiovascular mortality and greater heart failure symptoms compared to high-gradient subgroups. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Svante Gersch; Kristin Steinhaus; B E Beuthner; L Wuestefeld; S Uhr; Manar Elkenani; Moritz Schnelle; Elisabeth M. Zeisberg; Miriam Puls; A Schuster; G Hasenfuss; T Lange; Karl Toischer

doi:10.1093/eurheartj/ehaf784.2413

November 1, 2025European Heart Journal

Morphological and functional phenotyping of patients with severe aortic stenosis, preserved ejection fraction and low-flow constellations

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Key result

PLF-LG AS linked to worse RV function and highest 5-year CV mortality despite preserved LVEF.

Why the study?

Data on the clinical characteristics and outcomes of patients with severe aortic stenosis, preserved LVEF, and reduced stroke volume index in high-gradient AS remained scarce.

Does the paradoxical low-flow low-gradient AS phenotype worsen cardiovascular and all-cause mortality compared to high-gradient AS phenotypes in patients with severe AS and preserved LVEF undergoing TAVR?

Key Points

This research investigates the clinical characteristics and outcomes of severe aortic stenosis patients with preserved ejection fraction and reduced stroke volume index.
Included 184 patients undergoing transcatheter aortic valve replacement
Categorized patients into low-flow high-gradient, normal-flow high-gradient, and paradoxical low-flow low-gradient groups
Analyzed using echocardiography, cardiac magnetic resonance imaging, histology, and next-generation sequencing
No baseline differences between low-flow and normal-flow high-gradient subgroups
Paradoxical low-flow low-gradient patients had greater heart failure symptom burden
Right ventricular function was impaired in paradoxical low-flow low-gradient patients compared to high-gradient subgroups
All groups showed similar levels of myocardial fibrosis
Paradoxical low-flow low-gradient patients had the highest 5-year cardiovascular mortality

Structured PICO

Does the paradoxical low-flow low-gradient AS phenotype worsen cardiovascular and all-cause mortality compared to high-gradient AS phenotypes in patients with severe AS and preserved LVEF undergoing TAVR?

P

Population

184 patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) who underwent transcatheter aortic valve replacement (TAVR).

I

Intervention

Paradoxical low-flow low-gradient AS (PLF-LG AS) phenotype

C

Comparator

Low-flow high-gradient AS (LF-HG AS) and Normal-flow high-gradient AS (NF-HG AS) phenotypes

O

Outcome

Cardiovascular and all-cause mortalityhard clinical

Implication

In patients with severe AS and preserved LVEF undergoing TAVR, the paradoxical low-flow low-gradient phenotype is associated with worse right ventricular function and higher 5-year cardiovascular mortality compared to high-gradient phenotypes.

Abstract

Background 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. 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 While there were no relevant differences in baseline characteristics between LF-HG and NF-HG subgroups, PLF- LG AS patients 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) 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 (Figure 1). Conclusion Among AS patients with preserved LVEF, LF-HG and NF-HG had similar clinical profiles and outcomes, indicating a comparable disease course. In contrast, PLF-LG showed more severe right-sided heart failure and the worst long-term prognosis. Thus, reduced SVi may not be a useful marker for risk stratification or patient management in LF-HG AS.

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Cite This Study

Gersch et al. (2025) studied this question. PLF-LG AS patients had worse right ventricular function and highest 5-year cardiovascular mortality compared to LF-HG and NF-HG AS despite preserved LVEF.

synapsesocial.com/papers/698828330fc35cd7a88476aa https://doi.org/10.1093/eurheartj/ehaf784.2413