Precise quantification of extravascular fluid and oedema severity in heart failure
Authors: Gurfinkel Y.U , Matskeplishvili S , Sasonko M , Shirshin E , Yakimov B 
Published: November 2020

Abstract

Early diagnosis of heart failure (HF) severity and prediction of acute decompensation is complicated due to the absence of specific symptoms and objective measurable criteria. Here we present a new indicator of the HF severity based on the soft tissue optical imaging in nail-fold capillaries.

Material and methods
One hundred and twenty nine (129) adults we enrolled in the study, including 79 patients with NYHA I–III functional classes of HF, and 50 healthy volunteers without history or risk factors for cardiovascular disease. All patients with HF underwent a standard clinical and laboratory examination including comprehensive echocardiography for evaluation of heart chambers and intracardiac haemodynamics, systolic and diastolic function of the left ventricle (LV). The left ventricular ejection fraction (LVEF) was estimated by the ratio of LV stroke volume (Doppler calculation of aortic systolic flow) to the LV end-diastolic volume (Simpson's method) according to the ESC recommendations for management of patients with HF.
Vital digital capillaroscopy (VDC) of the nail-fold was performed in all patients and healthy volunteers following a 12-hour overnight fasting in a temperature-controlled room in the seated position and the left arm at heart level. Nail-fold capillaries and pericapillary tissue were assessed on fingers of the left hand gently fixed into the device using a digital capillaroscope equipped with a high speed CCD-camera. We used VDC to measure the linear size (in mm) of perivascular zone (PZ) around nail-fold capillaries. Two-photon tomography with fluorescence lifetime imaging (FLIM) was used to investigate PZ composition.

Results
We observed significant differences in the linear size of the PZ in patients with HF and control group. The absolute dimension of PZ strongly correlated with the functional class of HF and outperformed standard echocardiographic parameters used in evaluation of patients. Only in patients with moderate-severe HF (functional class III) there was an echocardiographic evidence of systolic LV dysfunction with reduced LVEF (42±12%). This was confirmed by the distribution of subjects in the control and HF groups by the PZ size and bivariate density analysis. FLIM confirmed that the PZ size is mostly determined by accumulation of extravascular free water.

Results
The simple measurement of the linear size of nail-fold perivascular zone has high sensitivity and specificity in identification of patients with different NYHA classes of HF. The positive predictive value of this parameter exceeds that for all other non-invasive parameters, namely, LVEF. Dimension of the PZ is determined by amount of extravascular free water as confirmed by the fluorescence lifetime imaging. This approach could be of interest for differential diagnosis of HF and monitoring its treatment, providing important possibility to predict HF decompensation with very early diagnosis of the interstitial fluid retention.
Patient distribution: PZ size and LVEF

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Russian Science Foundation