Visualising and quantifying microvascular structure and function in patients with heart failure using optical coherence tomography

Abstract

Heart failure (HF) is characterised by abnormal conduit and resistance artery function in humans. Microvascular function in HF is less well characterised, due in part to the lack of tools to image these vessels in vivo. The skin microvasculature is a surrogate for systemic microvascular function and health and plays a key role in thermoregulation, which is dysfunctional in HF. We deployed a novel optical coherence tomography (OCT) technique to visualise and quantify microvascular structure and function in 10 subjects with HF and 10 age- and sex-matched controls. OCT images were obtained from the ventral aspect of the forearm, at baseline (33°C) and after 30 min of localised skin heating. At rest, OCT-derived microvascular density (20.3 ± 8.7%, P = 0.004), diameter (35.1 ± 6.0 μm, P = 0.006) and blood flow (82.9 ± 41.1 pl/s, P = 0.021) were significantly lower in HF than CON (27.2 ± 8.0%, 40.4 ± 5.8 μm, 110.8 ± 41.9 pl/s), whilst blood speed was not significantly lower (74.3 ± 11.0 μm/s vs. 81.3 ± 9.9 μm/s, P = 0.069). After local heating, the OCT-based density, diameter, blood speed and blood flow of HF patients were similar (all P > 0.05) to CON. Although abnormalities exist at rest which may reflect microvascular disease status, patients with HF retain the capacity to dilate cutaneous microvessels in response to localised heat stress. This is a novel in vivo human observation of microvascular dysfunction in HF, illustrating the feasibility of OCT to directly visualise and quantify microvascular responses to physiological stimuli in vivo. KEY POINTS: Microvessels in the skin are critical to human thermoregulation, which is compromised in participants with heart failure (HF). We have developed a powerful new non-invasive optical coherence tomography (OCT)-based approach for the study of microvascular structure and function in vivo. Our approach enabled us to observe and quantify abnormal resting microvascular function in participants with HF. Patients with HF were able to dilate skin microvessels in response to local heat stress, arguing against an underlying structural abnormality. This suggests that microvascular functional regulation is the primary abnormality in HF. OCT can be used to directly visualise and quantify microvascular responses to physiological stimuli in vivo.

Keywords: heart failure; microvessels; optical imaging.

Figure 1. Qualitative comparison between OCT speed maps for a selection of HF patients and their matched controls at baseline and after local heating, showing microvasculature over a 5 × 5 mm field of view

Pixel intensity indicates flow speed, with dark red indicating slow flow and orange/yellow indicating faster flow. The baseline scans of those with HF were distinctly darker (indicating lower mean blood speed) than their matched controls. Once heated, the blood speed maps from both the HF patients and their matched controls appeared similar. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2. Mean blood vessel density (%) (A), diameter (μm) (B), blood speed (μm/s) (C), and blood flow (pl/s) (D) for heart failure patients (dark grey, n = 10) and matched controls (light grey, n = 10) at baseline (BL) and after local heating (LH)

Data are means ± SD, individual data overlaid, repeated measures ANOVA (left panels) and paired t‐tests (right panels). LH responses relative to their baseline are shown on right hand panels. *Difference from control group at P < 0.05.