Microvascular blood flow disturbances predict poor outcome of revascularization in CLTI patients

Abstract Background We have recently established hypoxic microvascular remodelling as a critical pathomechanistic factor that limits oxygen diffusion to muscle in chronic limb threatening ischaemia (CLTI). Using animal models of experimental hind limb ischaemia we have also displayed the biological relevance of post-ischaemic microvascular remodelling in skeletal muscle. Our results indicate that differential microvascular changes associate to muscle damage and repair. The natural microvascular dynamics that inherently promote muscle recovery are defected in CLTI patients. Particularly, a progressive arterialization of capillaries in CLTI muscle differentiates the dynamics of the microvasculature from initially assisting muscle regeneration to aggravating ischaemic damage. Methods To establish the clinical relevance of the post-ischaemic microvascular changes in CLTI, we now have studied the effect of microvascular remodelling on the outcome of CLTI patients undergoing surgical or endovascular revascularization. Contrast enhanced ultrasound was used preoperatively to determine the microvascular status of CLTI patients (n=36) scheduled for immediate revascularization. Outcome events such as: hospitalization; reoperation; leg amputation; or death, were postoperatively followed from medical records up to 6 months after revascularization. Patients were grouped according to muscle capillary transit time (Tct) being either similar (n=18) or shorter (n=18) to that in the contralateral legs of the patients, and treatment outcomes were compared between groups. Results The results display consistent increases in postoperative event rates in all measured outcomes in the ShortTct group as compared to controls (at 1 month 8 vs. 2 events (rate ratio 4.00 (95%CI: 0.85-18.84, p=0.080)); at 3 months 13 vs. 4 events (rate ratio 3.25 (95%CI: 1.06-9.97, p=0.039)); at 6 months 17 vs. 9 events (rate ratio 1.89 (95%CI: 0.84-4.24, p=0.123))). For example, 5 vs. 0; 7 vs. 1; and 7 vs. 4 reoperations were detected in the ShortTct group as compared to controls at 1, 3 and 6 months, respectively. By 6 months after initial revascularization also 2 deaths were recorded in the ShortTct group as compared to no deaths in the controls. Conclusions Despite still small samples size in this study, these results suggest that microvascular blood flow disturbances, such as short preoperative muscle capillary transit time, can predict poor outcome of CLTI patients after revascularization. Importantly, the results also identify patients with microvascular blood flow disturbances a subgroup of CLTI patients that should likely receive more specialized care to improve outcomes. The results also call for immediate actions from the scientific community to improve clinical detection of microvascular alterations and to develop strategies to normalize microvascular function in CLTI patients.