Venous arterialization for chronic limb-threatening ischemia: Past, present, and future

Abstract

Chronic limb-threatening ischemia (CLTI) is a significant facet of atherosclerotic disease that has major medical and functional consequences. With the number of diabetic patients on the rise and improved life expectancy, has also come a greater awareness and wider adoption of endovascular techniques; thus, amputation rates continue to fall.1-3 We expect that patients will be older, have more advanced comorbidities, and will have had more prior interventions. This may translate to a greater proportion of them presenting with no-option CLTI. Venous arterialization may be a viable alternative to preserving these limbs. This thesis starts with a general introduction that provides an update on the history and development of the venous arterialization. After this the thesis consists of three parts: Part 1 is entitled; the open venous arterialization Part 2 is entitled; percutaneous deep venous arterialization (pDVA, LimFlow procedure) Part 3 is entitled; postoperative care and follow-up of the venous arterialization

The first part provides information about the open superficial venous arterialization. In Chapter 2, a superficial venous arterialization cohort and pedal bypass cohort of two Dutch hospitals is analysed, with promising results in a group of patients for whom no other reconstructive treatment options were available. Although the pedal bypass is still the gold standard (if a target artery is present), distal venous arterialization is a good alternative due to comparable results and its simplicity. The current evidence was analysed in a systematic review and meta-analysis in Chapter 3 and suggests that venous arterialization is a valuable treatment option in selected patients with no-option CLTI. These otherwise unsalvageable legs can be treated with acceptable morbidity and mortality. However, optimization and standardization of techniques are needed. The venous arterialization should always be considered in patients without distal arterial outflow vessels.

The second part is about the percutaneous deep venous arterialization (pDVA). In Chapter 4, the first experience with the pDVA in humans is published, applied to a cohort of patients with no-option CLTI. The dual catheters, guided by ultrasound imaging, provide a reliable way to percutaneously create the AVF between a tibial artery and a deep tibial vein. Assisted by a percutaneously introduced valvulotome, arterial blood can now be directed to the veins of the foot. In this small cohort of patients, pDVA appears to be a safe and feasible procedure that effectively improves limb oxygenation, encourages wound healing, and potentially, avoids major amputation.

The experience, after this first publication, from four centers between 2014 and 2018, is analysed in Chapter 5. This study presents midterm results from the largest population of patients with no-option CLTI treated with pDVA using the LimFlow device. In this complex group of patients, the LimFlow device demonstrated high technical success and amputation-free survival rates of 67% coupled with good wound healing at up to 24 months. In selected patients with no-option CLTI, pDVA is a safe and effective treatment to prevent amputation and heal wounds. A new international multicenter prospective study, PROMISE International, has been started to validate these outcomes in a larger cohort, and the protocol is described in Chapter 6.

The last part of this thesis is about the postinterventional care of the venous arterialization. Chapter 7 is the first analysis of duplex ultrasound (DUS) measurements in post-pDVA patients. The venous arterialization needs time to mature before becoming effective. Stenoses or occlusions can frequently occur during this period, and therefore, there is a high need for more insight in DUS interpretation to detect failure of the arteriovenous circuit and preserve the limb. This study showed that surveillance of the arteriovenous circuit can be performed by DUS and we determined cut-off values to define the presence of stenosis or occlusions, but the small sample size of the study does not allow firm conclusions to be drawn. A guideline for post-pDVA care is given in Chapter 8. Based on literature and clinical experience of 24 patients from Alkmaar and Singapore, we summarize the different techniques proposed and provide an algorithm for the challenges that interventionalists can face in the follow-up period after a pDVA. The most important, is the acknowledgement that the pDVA needs 6 weeks to develop before becoming effective. Other key elements are edema treatment, pain control, wound care and a staged amputation strategy. The postprocedural management can be as challenging as the procedure itself but has not been a priority for further investigation.