Arterial Doppler in Diabetes Management

13th August 2022, NIA Diagnostic Imaging

In a 2020 study, 1 in 20 Australians have diabetes mellitus (excludes gestational diabetes), and the primary complications associated with this disease are foot ulcerations and claudication (Australian Institute of Health and Welfare, 2022). Diabetic foot ulcerations can develop due to a number of factors including poor glycaemic control, poor foot care, dry skin, calluses, and foot deformities (Oliver & Mutluoglu, 2022).

However, a common cause for foot ulcerations and claudication is poor circulation due to damaging changes to nerves and blood vessels, and/or an underlying peripheral arterial disease (PAD) – primarily atherosclerosis (AT) (K.S. & Kumar A., 2020).

Risk factors of atherosclerosis:

Age (males greater than 45-years-old and females greater than 55-years-old)
Smoking
Diabetes mellitus
High lipid diet
Sedentary lifestyle
Family history (male family member younger than 55 years and female family member younger than 65 years)
Systemic arterial hypertension

Pathophysiology

AT occurs when the arterial endothelium undergoes injuries (physical or from chemical toxins such as smoking) or dysfunction. These changes to the endothelial cells allow an influx of lipids to easily permeate the vessel layers and adhere to the intima wall. Intima thickening also occurs when smooth muscles cells migrate from media to intima layer. Overtime, more lipids, platelets, necrotic remnants, blood monocytes and lymphocytes, and collagen accumulate to become the visible soft and/or hard plaque seen on ultrasound (Prado dos Santos, et al., 2021).

Imaging and Diagnosis

At NIA Diagnostic Imaging, arterial Doppler/Duplex studies for both upper and lower limbs are a service provided to aid in the assessment of PAD in patients – especially patients with foot ulcerations, claudication, weakness, and numbness in the limbs which are symptoms associated with diabetes mellitus. Arterial Doppler/Duplex studies involves use of colour Doppler – useful in detecting segments that appear stenotic or occlude – and pulsed wave Doppler, which detects flow velocity and degree of severity of the stenoses. The ankle-brachial index (ABI) is also performed with ultrasound guidance prior to commencing the arterial doppler/duplex study to provide an initial diagnosis.

The table below summaries interpretations of ABI values and recommended treatments associated:

Criteria

The criteria used for diagnosing occlusive disease is defined by assessing the:

– Velocity

➢ Velocity increases through stenosis lumen and can return to normal velocity post stenosis

➢ Stenosis is determined by the ratio of velocity through the stenosis lumen to the velocity proximal to the stenosis

➢ Peak velocity is greater than 200 cm/s which indicates haemodynamically significant

– Flow changes

➢ Laminar flow changes from either triphasic or biphasic to monophasic flow (Nasra & Osher, 2021)

The table below is used to help classify the degree of occlusive disease for lower limbs:

Treatment

There are various methods of treatment for PAD and the appropriate treatment is dependent on the severity of the disease.

References:

Aitken, S., 2020. Peripheral artery disease in the lower limbs. Focus, 49(5), pp. 239-244.
Australian Institute of Health and Welfare, 2022. Diabetes: Australian facts, s.l.: Australian Government.
Deane, C. & Goss, D., 2011. Peripheral arteries. In: Clinical Ultrasound. England: Churchill Livingstone, pp. 1197-1226.
Hodgkiss-Harlow, K. & Bandyk, D., 2013. Interpretation of arterial duplex testing of lower-extremity arteries and interventions. Seminars in Vascular Surgery, 26(2-3), pp. 95-104.
Hwang, J. Y., 2017. Doppler ultrasonography of the lower extremity arteries: anatomy and scanning guidelines. Ultrasonography, 36(2), pp. 111-119.
K.S., S. & Kumar A., S., 2020. Assessment of Diabetic Foot through the Developmental Stages of Lower Limb Abnormalities Using Ultrasound, s.l.: IntechOpen.
Nasra, K. & Osher, M., 2021. Sonography Vascular Peripheral Arterial Assessment, Protocols, And Interpretation, Treasure Island, Florida: StatPearls.
Oliver, T. & Mutluoglu, M., 2022. Diabetic Foot Ulcer, Treasure Island, Florida: StatPearls Publishing.
Pahwa, R. & Jialal, I., 2021. Atherosclerosis, Treasure Island, Florida: StatPearls.
Prado dos Santos, V., Pozzan, G., Castelli, Jr, V. & Caffaro, R. A., 2021. Arteriosclerosis, atherosclerosis, arteriolosclerosis, and Monckeberg medial calcific sclerosis: what is the difference?. Jornal Vascular Brasileiro, Volume 20, pp. 1-8.
Stanford Medicine, 2022. Measuring and Understanding the Ankle Brachial Index (ABI). [Online] Available at: https://stanfordmedicine25.stanford.edu/the25/ankle-brachial-index.html [Accessed 11 August 2022].

PFO Closure

Furlan AJ, Reisman M, Massaro J, et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366: 991–

A multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.

Results:

Primary end point was 5.5% in the closure group as compared with 6.8% in the medical-therapy group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P = 0.37)

Conclusion:

“In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure

with a device did not offer a greater benefit than medical therapy alone for the

prevention of recurrent stroke or TIA”

2 Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017; 377: 1022–

A multicenter, randomised, open-label trial ,randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomisation.

Results:

Recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient years, respectively (hazard ratio 0.55; 0.31 – 0.999; P = 0.046)

Conclusion:

“Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up.”

Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013; 368: 1083–

A prospective, multicenter, randomised, event-driven trial, randomly assigned patients to medical therapy alone (anti-platelet or warfarin therapy) or closure of the patent foramen ovale.

Results:

9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 0.22 – 1.11; P = 0.08). The primary analysis of the intentionto- treat cohort showed a nominal 51% hazard rate reduction with closure, but the reduction did not reach significance.

Conclusions:

” …there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischaemic stroke.”

Sondergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med 2017; 377: 1033–

Multinational trial involving patients with a PFO who had had a cryptogenic stroke, randomly assigned patients to undergo PFO closure plus antiplatelet therapy or to receive antiplatelet therapy alone.

Results:

During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 0.09 to 0.62; P=0.002).

Conclusions:

“Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation.”

Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017; 377: 1011–

In a multicenter, randomised, open-label trial patients 16-60 years of age who had had a recent stroke attributed to PFO, to transcatheter PFO closure plus long-term antiplatelet therapy, antiplatelet therapy alone or oral anticoagulation.

Results:

No stroke occurred among patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet- only group (hazard ratio, 0.03; 0 to 0.26; P<0.001). Large number of patients discontinued anti-coagulation in the anti-coagulant group and statistical significance was not analysed because the study was not adequately powered to compare outcomes.

Conclusion:

“Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation.”

Lee PH, Song J-K, Kim JS, et al. Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO Trial. J Am Coll Cardiol 2018; 71: 2335–

Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group.

Results:

No events occurred in the PFO closure group. 12.9% of patients in the medication group had an event (p= 0.023).

Conclusion:

“PFO closure in patients with high-risk PFO characteristics resulted in a lower rate of the primary endpoint as well as stroke recurrence”