Introduction

There is limited clinical evidence of pulmonary microvascular disease (PMD) in DM. We hypothesized that (1) a novel echocardiographic marker quantifying the pulmonary transit of agitated colloid contrast bubbles (PTAC) may identify pulmonary capillary disease; and (2) that PTAC may be associated with exercise limitation.

Methods

A repeated measures cross-over trial of sixty participants (40 DM and 20 age/sex-matched controls [C]) receiving sildenafil 50 mg or placebo in randomised order prior to each of two exercise tests (VO_2max and exercise echocardiography) was performed. PMD was assessed by measuring the degree of PTAC traversing the pulmonary vasculature during incremental exercise, injected through a peripheral venous cannula. Bubbles reaching the left ventricle were quantified and categorised as low-PTAC or high-PTAC (see figure). Sildenafil’s effect on VO_2max was observed, as were non-invasive measures of central haemodynamic parameters including cardiac output (CO) and pulmonary artery systolic pressure (PASP) to derive pulmonary vascular resistance (PVR).

Results

DM and C subjects were of similar age (44±13 vs. 43±13 years, p=0.87) and gender (70% vs. 65% male, p=0.7). Mean DM duration was 16 ± 10 years and glycaemic control was moderate (HbA1c: 7.7 ± 1.3%). At peak exercise, low-PTAC was more common in DM than C subjects (41 vs. 12.5%, χ² P=0.041), and there was a trend to low-PTAC in DM subjects with vs. without microvascular complications (55% vs. 26.3%, Χ² P=0.069). Sildenafil increased CO and reduced PVR in DM, without altering the frequency of low-PTAC or improving VO_2max. On multiple regression, neither PTAC nor sildenafil predicted maximal VO₂.

Conclusion

PTAC was lower in DM compared to C subjects thereby suggesting that PTAC may be a novel marker of PMD. However, low-PTAC was not associated with reduced exercise capacity and nor was it influenced by pulmonary vasodilator therapy.