Echocardiography-based pressure-volume loop assessment in the evaluation for the effects of indoxyl sulfate on cardiovascular function

Background: Indoxyl sulfate (IS), a uremic toxin, has been reported to have hypertrophic effects on the heart. Previous studies, however, have shown no association between elevated IS levels and cardiovascular outcomes in hemodialysis patients. We hypothesized that, despite left ventricular (LV) hypertrophy, myocardial contractility and ventricular-arterial coupling would remain preserved, and that this would explain the reason for the absence of prognostic impact of IS.

Methods: We evaluated the association of IS with LV structure, contractility, vascular function, and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) in 154 patients on hemodialysis, using echocardiography-based pressure-volume loop assessment.

Results: As expected, subjects in the high IS group (IS ≥ 33.8 μg/mL) had greater LV mass index and end-diastolic volume index compared to subjects in the low IS group (IS < 33.8 μg/mL). These differences remained significant after adjusting for age, sex, body mass index, diabetic nephropathy, duration of hemodialysis, and NT-proBNP levels, suggesting a potential role of elevated IS levels in LV remodeling. However, no differences in LV contractility (preload recruitable stroke work, peak power index, and systolic mitral annular velocity) and mechanical efficiency (ventricular-arterial coupling and stroke work/pressure volume area) were observed between the groups.

Conclusions: Deleterious effects of IS on LV remodeling are not accompanied by impaired LV contractility or mechanical efficiency, which could contribute to the absence of cardiovascular prognostic impact observed in previous studies performed on hemodialysis patients.