Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

BACKGROUND AND AIMS: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology. METHODS: Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome. RESULTS: Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle. CONCLUSIONS: These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Perivascular Macrophages Regulate Blood Flow Following Tissue Damage.

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Crural Index and extensive atherosclerosis of crural vessels are associated with long-term cardiovascular mortality in patients with symptomatic peripheral artery disease.

BACKGROUND AND AIMS: Limited data exist on the association of the anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments with life expectancy. We recently presented a new classification of the extent of atherosclerosis in crural vessels and showed that Crural Index (CIx) was associated with mid-term survival of symptomatic peripheral artery disease (PAD) patients. This study evaluates the significance of the extent of crural atherosclerosis on long-term cardiovascular mortality. METHODS: 887 consecutive patients with PAD, admitted for digital subtraction angiography (DSA) at Turku University Hospital Department of Vascular Surgery (Turku, Finland) between January 1st, 2009 and July 30th, 2011, were retrospectively analysed. Each crural angiographic image was graded according to CIx criteria. Aorto-iliac and femoro-popliteal arterial segments were similarly graded according to modified TASC II criteria. CIx was used as the categorical variable for the extent of atherosclerosis in crural vessels for survival analysis. Survival was also evaluated with respect to which arterial segment was most severely affected. Causes of death were provided by the Cause of Death Registry of Statistics Finland, updated on January 23rd, 2017. RESULTS: Altogether, 408 (46%) patients died during follow-up. The majority of deaths were due to cardiovascular causes (n = 246, 60%). Cardiovascular mortality was strongly associated with a high CIx (CIx III (Hazard ratio (HR) 2.16, Confidence interval (CI) 95% 1.23-3.80, p = 0.007)) and CIx IV (HR 3.513, 95% CI 1.93-4.565, p < 0.001), as compared to CIx 0. In patients having the crural segment as the most severely affected arterial segment, cardiovascular mortality was significantly increased (HR 2.321, 95% CI 1.45-3.73, p < 0.001), as was overall mortality (HR 2.177, 95% CI 1.53-3.10, p < 0.001). CONCLUSIONS: High Crural Index and extensive crural vessel atherosclerosis are associated with long-term cardiovascular mortality, and both may serve as useful indicators of survival among patients with symptomatic PAD.

Data on amputation free survival of patients with lower limb peripheral artery disease classified according TASC II classification and a new crural index.

The results of amputation free survival (AFS) of a cohort of 887 caucasian patients is shown. The data is based on further analyses of data presented in Jalkanen et al. (2016) [1]. The 36-month amputation free survival of patients divided in new crural vessel disease classification (Crural Index), aortoiliac TASC II classification, femoropopliteal TASC II classification and most severe segment is presented. Also, in depth demographic data is presented for each Crural Index group Jalkanen et al., 2016 [1].

The extent of atherosclerotic lesions in crural arteries predicts survival of patients with lower limb peripheral artery disease: A new classification of crural atherosclerosis.

BACKGROUND AND AIMS: Several studies report correlation of ankle brachial index (ABI) values and mortality. However, no studies exist on the predictive value of anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments on life expectancy. The aim of the present study was to evaluate the significance of both extent and localisation of atherosclerotic lesions to mid-term patient survival. METHODS: Digital subtraction angiography (DSA) images of 887 consecutive patients admitted to the Department of Vascular Surgery at Turku University Hospital (Turku, Finland) were retrospectively analysed. Each angiography was classified according to the TASC II classification for aorto-iliac and femoro-popliteal segments, and a similar four-grade index was created for crural arteries. Patients were followed until 36-months post DSA. RESULTS: During 36-month follow-up 295 (33%) deaths occurred. Death during follow-up was strongly associated with extensive crural disease, but not with extensive proximal disease (Crural Index III-IV, p = 0.044 and < 0.001, respectively). In a Cox regression analysis incorporating baseline variables, Crural Index IV and most severe atherosclerosis on crural vessels were the strongest predictors of poor prognosis (HR 2.20 95% CI 1.3-3.7, p = 0.003 and HR 2.45 95% CI 1.5-4.0, p < 0.001 respectively). CONCLUSIONS: The extent of crural atherosclerosis is independently associated with poor mid term life expectancy. Therefore, a classification of the extent of crural atherosclerosis could serve as an indicator of mortality among PAD patients and aid in clinical decision making.