Testing the sympathetic nervous system of the foot has a high predictive value for early amputation in patients with diabetes with a neuroischemic ulcer

Abstract

Objective: There is evidence from the literature that dysfunctionality of the sympathetic nervous system of the foot with subsequent loss of local autoregulation could be a predictor of early amputation in patients with diabetes with a neuroischemic ulcer. To confirm this we tested the functionality of the sympathetic nervous system in the foot in a consecutive group of 31 patients with diabetes with critical limb ischemia and non-healing neuroischemic ulcer.

Research design and methods: Prospective cohort with retrospective analysis after 12 months of routinely acquired clinical data. All patients in the study group underwent angiography of the foot as part of a routine angioplasty procedure. Primary study endpoint was lower extremity amputation-free survival at 12 months. Because of the study design no other endpoints could be analyzed. The functionality of the sympathetic nervous system was tested with perfusion angiography.

Results: Thirty-one patients were followed for 12 months. The Capillary Resistance Index (CRI) was used to measure the response of the sympathetic nervous system. CRI≥0.9 is the cut-off point for a non-responsive sympathetic nervous system. All patients (n=11) with a CRI≥0.9 underwent a major amputation before 12 months. Of all patients with a CRI only 15% underwent major amputation. The positive predictive value for major amputation before 12 months for patients with a CRI ≥ 0.9 was 100%.

Conclusions: A non-responsive sympathetic nervous system of the foot is a strong predictor of early major amputation (log rank p<0.001; HR 14.22; 95% CI 3.64 to 55.51).

Keywords: ischemia; microangiopathy; neuropathy and vascular disease.

Figure 1

Time-density curves of a positive response and non-response to the Tolazoline administration. Yellow curve is foot perfusion before Tolazoline. Blue curve is foot perfusion after 4 mg Tolazoline intra-arterial in mid-popliteal artery. (A) Normal time-density curves. First part parallel and early peak of the blue. CRI=0.7. (B) Non-responsive time-density curves. Curves overlap, no early peak density. CRI=1.0. CRI, Capillary Resistance Index.

Figure 2

Scatter plot of CRI in patients with and without amputation. Fourteen patients did undergo an amputation. Most of these patients (n=11) had a CRI≥0.9 (of which six patients had a CRI=1.0). Three patients had a CRI<0.9 (0.52, 0.62 and 0.74). Seventeen patients did not undergo an amputation. These patients all had a CRI<0.9 (of which two patients with CRI=0.78 and two patients with CRI=0.79). Dotted line indicates a potential cut-off value of CRI=0.9 to separate non-amputated patients with a positive flow reserve from the amputated patients. CRI, Capillary Resistance Index.

Figure 3

Kaplan-Meier curves for amputation-free survival in patients with CRI<0.9 and with CRI≥0.9 (log rank p<0.001; HR 14.22; 95% CI 3.64 to 55.51). Eleven patients with CRI≥0.9. Twenty patients with CRI<0.9. CRI, Capillary Resistance Index.

Figure 4

Kaplan-Meier curves of amputation-free survival in patients who did undergo angioplasty and in patients who did not undergo angioplasty (log rank p=0.407; HR 0.65; 95% CI 0.22 to 1.94). Twenty-three patients did undergo angioplasty, eight patients did not undergo angioplasty.

Figure 5

Kaplan-Meier curves of amputation-free survival in patients who had renal insufficiency or underwent dialysis and in patients with normal renal function (log rank p=0.036; HR 2.88; 95% CI 0.96 to 8.64). Renal insufficiency=eGFR<30 mL/min. eGFR, estimated glomerular filtration rate.