The Impact of Functional Status on the Outcomes of Endovascular Lower Extremity Revascularization for Critical Limb Ischemia in the Elderly.

BACKGROUND: Functional status is an important predictor of outcomes after infrainguinal bypass surgery. There are little data on the effect of functional status on the outcomes of endovascular lower extremity interventions, especially in the elderly frail population. METHODS: This is a retrospective analysis of the American College of Surgeons - National Surgical Quality Improvement Program files for the years 2011-2013 to assess the impact of functional status on outcome after endovascular intervention for critical limb ischemia (CLI). Elderly patients (age ≥70) undergoing revascularization for CLI were included. The patients were divided into 2 groups based on functional status prior to surgery: independent (IND) or dependent (DEP), which included partially dependent as well as totally dependent patients. The 2 groups were compared with respect to demographics, comorbidities, complications, length of stay, limb loss, and mortality. Statistical analysis was performed using Student's t-test for continuous variables and Fisher's exact test for categorical variables. RESULTS: There were 1,055 patients (DEP = 253, 24%). There was no difference in gender or race but DEP patients were older than IND (P = 0.008). DEP patients were significantly more likely to have history of congestive heart failure (P = 0.003), hypertension (P = 0.042), and diabetes (P <0.001). There was no difference in emergent surgeries between the 2 groups (P = 1.00). DEP patients had more tibial interventions compared with IND (P <0.001). DEP developed more pneumonia (P <0.001) and septic shock (P = 0.016) and had a trend toward more urinary tract infections (P = 0.051) after endovascular revascularization. There was no significant difference in operating time (P = 0.232) or major amputation (P = 0.092). DEP had significantly longer length of hospital stay (P = 0.0068). DEP had significantly higher mortality (5.98% vs. 2.01%, P = 0.002). On multivariate analysis, DEP status, emergency procedure, congestive heart failure, cardiac arrest requiring cardiopulmonary resuscitation, myocardial infarction, sepsis, and septic shock were independently associated with 30 days of mortality. Irrespective of age, DEP functional status was the most significant preoperative predictor of mortality with an odd ratio of 5.16 [1.93-13.83], P = 0.001 (parsimonious model). CONCLUSIONS: Functional status should be carefully assessed when considering endovascular revascularization in the elderly as DEP has significantly higher morbidity and mortality.

A model of the interaction between N-type and C-type inactivation in Kv1.4 channels.

Kv1.4 channels are Shaker-related voltage-gated potassium channels with two distinct inactivation mechanisms. Fast N-type inactivation operates by a ball-and-chain mechanism. Slower C-type inactivation is not so well defined, but involves intracellular and extracellular conformational changes of the channel. We studied the interaction between inactivation mechanisms using two-electrode voltage-clamp of Kv1.4 and Kv1.4ΔN (amino acids 2-146 deleted to remove N-type inactivation) heterologously expressed in Xenopus oocytes. We manipulated C-type inactivation by introducing a lysine-tyrosine point mutation (K532Y, equivalent to Shaker T449Y) that diminishes C-type inactivation. We used experimental data to develop a comprehensive computer model of Kv1.4 channels to determine the interaction between activation and N- and C-type inactivation mechanisms needed to replicate the experimental data. C-type inactivation began at lower voltage preactivated states, whereas N-type inactivation was coupled directly to the open state. A model with distinct N- and C-type inactivated states was not able to reproduce experimental data, and direct transitions between N- and C-type inactivated states were required, i.e., there is coupling between N- and C-type inactivated states. C-type inactivation is the rate-limiting step determining recovery from inactivation, so understanding C-type inactivation, and how it is coupled to N-type inactivation, is critical in understanding how channels act to repetitive stimulation.