Determinants and outcomes of left ventricular dysfunction across aortic stenosis phenotypes
I Rodrigues, F Nunes, F Sousa, L Moura, A Goncalves, M Almeida, A Lobo, I Neves, M Leite, R Teixeira, R Fontes-CarvalhoAbstract
Background
Left ventricular (LV) systolic dysfunction in aortic stenosis (AS) may arise from distinct pathophysiological pathways. While chronic valvular pressure overload can directly impair myocardial function, reduced LV ejection fraction may also result from coexisting comorbidities. The mechanisms underlying LV dysfunction can also differ across hemodynamic AS phenotypes.
Purpose
This study aimed to characterize contributing factors to LV dysfunction in patients with high-gradient (HG) versus low-flow low-gradient (LFLG) AS and to compare survival outcomes between these groups.
Methods
Patients with moderate-to-severe AS and reduced LV ejection fraction (LVEF<50%) were retrospectively identified. Patients with HG severe AS (mean gradient (MG) ≥40 mmHg and aortic valve area (AVA) ≤1,0cm2) and patients with LFLG AS (AVA≤1 cm2, MG <40mmHg, and stroke volume index ≤35ml/m2) were analysed. The aetiology of LV dysfunction (valvular, ischemic, desynchrony, cardiomyopathy and other) was determined using additional diagnostic modalities available for each patient (electrocardiography, coronary angiography, computed tomography, and cardiac magnetic resonance imaging). Survival differences between the two groups were assessed using time-to-event analyses.
Results
A total of 282 patients were included, of whom 111 had LFLG AS and 37 had HG AS. Baseline characteristics were comparable between groups, except for coronary artery disease, more frequent in the LFLG group (48.6% vs 35.1%, p=0.056) and beta-blocker use, less common in the HG patients (29.7% vs 70.3%, p<0.001). Median LVEF was also lower in the LFLG group (40,7% vs 49%, p<0,001). In the LFLG group, 73.9% of patients had at least one concomitant contributor of LV dysfunction beyond AS, most commonly ischemic heart disease (47.7%), followed by desynchrony (18%), and cardiomyopathies (2%). Only 17.1% had AS as the sole mechanism of LV dysfunction. In contrast, LV dysfunction was attributed exclusively to AS in 54.1% of HG patients (p<0.001), while 45.9% had at least one additional contributing factor (p=0.002). Kaplan–Meier analysis showed significantly worse survival in the LFLG group (median survival of 3.8 vs 8.7 years, log-rank p < 0.001). In multivariable Cox regression, LFLG status remained independently associated with mortality (HR 2.23; 95% CI 1.30–3.81; p=0.004) (Figure 1).
Conclusion
Among patients with AS and reduced LVEF, LFLG patients more frequently had concomitant non-valvular mechanisms of LV dysfunction and had significantly worse survival than HG patients, even after multivariable adjustment for comorbid conditions.Cox regression analysisFor image description, please refer to the figure legend and surrounding text.