Abstract
BACKGROUND: Microcirculatory dysfunction (MCD) contributes to systemic hypoperfusion and end-organ damage. Prior studies have shown MCD in heart failure (HF), but comparative data across HF severity and heart replacement therapies remain limited. OBJECTIVES: We aimed to assess MCD across the spectrum of advanced HF. METHODS: We prospectively enrolled adults with stable chronic HF, cardiogenic shock (CS), HeartMate 3 (HM3) left ventricular assist device support, heart transplant (HT), and healthy controls (HCs), between August 2023 and December 2024. Sublingual microcirculation was assessed using handheld vital microscopy and GlycoCheck software. Primary outcomes were between-group differences in: vessel density; capillary blood volume; perfused boundary region; capillary blood flow; and microvascular health score. RESULTS: A total of 376 patients (120 HF, 81 CS, 43 HM3, and 132 HT) and 44 HC were included. The median age was 62 years and one-third were females. Microvascular density was significantly lower in CS and HT vs HF and left ventricular assist device. Flow was higher in HM3 than CS and HT (P = 0.039). CS and HT had lower capillary blood volume than HF (P < 0.01). Perfused boundary region was highest in HT patients. Microvascular health score was significantly lower in all patient cohorts compared to HC (all P < 0.01), with HT also showing lower scores than HM3 (P < 0.001). CONCLUSIONS: MCD is variably expressed across the spectrum of HF and its treatments, with particularly severe impairment in patients resuscitated from CS and postheart transplantation. These results suggest that restoration of macrohemodynamics does not equate to microvascular recovery and underscore the need for further investigation into the mechanisms, prognostic significance, and therapeutic targeting of systemic microvascular health in advanced cardiovascular disease.