Outcomes and Patency of Endovascular Infrapopliteal Reinterventions in Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: Endovascular revascularization is the preferred treatment to improve perfusion of the lower extremity in patients with chronic limb-threatening ischemia (CLTI). Patients with CLTI often present with stenotic-occlusive lesions involving the infrapopliteal arteries. Although the frequency of treating infrapopliteal lesions is increasing, the reintervention rates remain high. This study aimed to determine the outcomes and patency of infrapopliteal endovascular reinterventions. METHODS: This retrospective, multicenter cohort study of 3 Dutch hospitals included patients who underwent an endovascular infrapopliteal reintervention in 2015 up to 2021 after a primary infrapopliteal intervention for CLTI. The outcome measures after the reintervention procedures included technical success rate, the mortality rate and complication rate (any deviation from the normal postinterventional course) at 30 days, overall survival, amputation-free survival (AFS), freedom from major amputation, major adverse limb event (MALE), and recurrent reinterventions (a reintervention following the infrapopliteal reintervention). Cox proportional hazard models were used to determine risk factors for AFS and freedom from major amputation or recurrent reintervention. RESULTS: Eighty-one patients with CLTI were included. A total of 87 limbs underwent an infrapopliteal reintervention in which 122 lesions were treated. Technical success was achieved in 99 lesions (81%). The 30-day mortality rate was 1%, and the complication rate was 13%. Overall survival and AFS at 1 year were 69% (95% confidence interval [CI], 55%-79%) and 54% (95% CI, 37%-67%), respectively, and those at 2.5 years were 45% (95% CI, 33%-56%) and 21% (95% CI, 11%-33%), respectively. Freedom from major amputation, MALE, and recurrent reinterventions at 1 year and 2.5 years were 59% (95% CI, 46%-70%) and 41% (95% CI, 25%-56%); 54% (95% CI, 41%-65%) and 36% (95% CI, 21%-51%); and 68% (95% CI, 55%-78%) and 51% (95% CI, 33%-66%), respectively. A Global Limb Anatomic Staging System score of III showed an increased hazard ratio of 2.559 (95% CI, 1.078-6.072; p=0.033) for freedom of major amputation or recurrent reintervention. CONCLUSIONS: The results of this study indicate that endovascular infrapopliteal reinterventions can be performed with acceptable 30-day mortality and complication rates. However, outcomes and patency were moderate to poor, with low AFS, high rates of major amputations, and recurrent reinterventions. CLINICAL IMPACT: This multicenter retrospective study evaluating outcome and patency of endovascular infrapopliteal reinterventions for CLTI, shows that endovascular infrapopliteal reinterventions can be performed with acceptable 30-day mortality and complication rates. However, the short- and mid-term outcomes of the infrapopliteal reinterventions were moderate to poor, with low rates of AFS and a high need for recurrent reinterventions. While the frequency of performing infrapopliteal reinterventions is increasing with additional growing complexity of the disease, alternative treatment options such as venous bypass grafting or deep venous arterialization may be considered and should be studied in randomized controlled trials.

Detecting Changes in Tissue Perfusion With Hyperspectral Imaging and Thermal Imaging Following Endovascular Treatment for Peripheral Arterial Disease.

PURPOSE: Hyperspectral imaging (HSI) and thermal imaging allow contact-free tissue perfusion measurements and may help determine the effect of endovascular treatment (EVT) in patients with peripheral arterial disease. This study aimed to detect changes in perfusion with HSI and thermal imaging peri-procedurally and determine whether these changes can identify limbs that show clinical improvement after 6 weeks. METHODS: Patients with Rutherford class 2-6 scheduled for EVT were included prospectively. Hyperspectral imaging and thermal imaging were performed directly before and after EVT. Images were taken from the lateral side of the calves and plantar side of the feet. Concentrations of (de)oxyhemoglobin, oxygen saturation, and skin temperature were recorded. Angiographic results were determined on completion angiogram. Clinical improvement 6 weeks after EVT was defined as a decrease ≥ one Rutherford class. Peri-procedural changes in perfusion parameters were compared between limbs with and without good angiographic results or clinical improvement. To identify limbs with clinical improvement, receiver operating characteristic (ROC) curves were used to determine cutoff values for change in HSI. RESULTS: Included were 23 patients with 29 treated limbs. Change in HSI values and temperature was not significantly different between limbs with good and poor angiographic results. Change in peri-procedural deoxyhemoglobin, determined by HSI, at the calves and feet was significantly different between limbs with and without clinical improvement at 6 week follow-up (p=0.027 and p=0.017, respectively). The ROC curve for change in deoxyhemoglobin at the calves showed a cutoff value of ≤1.0, and ≤-0.5 at the feet, which were discriminative for clinical improvement (sensitivity 77%; specificity 75% and sensitivity 62%; specificity 88%, respectively). CONCLUSIONS: HSI can detect changes in perfusion at the calves after EVT in patients with Rutherford class 2-6. Peri-procedural deoxyhemoglobin changes at the calves and feet are significantly different between limbs with and without clinical improvement. Decrease in deoxyhemoglobin directly after EVT may identify limbs that show clinical improvement 6 weeks after EVT.

Reliability assessment of hyperspectral imaging with the HyperView™ system for lower extremity superficial tissue oxygenation in young healthy volunteers.

PURPOSE: Hyperspectral imaging (HSI) is a noninvasive spectroscopy technique for determining superficial tissue oxygenation. The HyperView™ system is a hand-held camera that enables perfusion image acquisition. The evaluation of superficial tissue oxygenation is warranted in the evaluation of patients with peripheral arterial disease. The aim was to determine the reliability of repeated HSI measurements. METHODS: In this prospective cohort study, HSI was performed on 50 healthy volunteers with a mean age of 26.4 ± 2.5 years, at the lower extremity. Two independent observers performed HSI during two subsequent measurement sessions. Short term test-retest reliability and intra- and inter-observer reliability were determined, and generalizability and decision studies were performed. Transcutaneous oxygen pressure (TcPO2) measurements were also performed. RESULTS: The short term test-retest reliability was good for the HSI values determined at the lower extremity, ranging from 0.72 to 0.90. Intra- and inter-observer reliability determined at different days were poor to moderate for both HSI (0.24 to 0.71 and 0.30 to 0.58, respectively) and TcPO2 (0.54 and 0.56, and 0.51 and 0.31, respectively). Reliability can be increased to >0.75 by averaging two measurements on different days. CONCLUSION: This study showed good short term test-retest reliability for HSI measurements, however low intra- and inter-observer reliability was observed for tissue oxygenation measurements with both HSI and TcPO2 performed at separate days in young healthy volunteers. Reliability of HSI can be improved when determined as a mean of two measurements taken on different days.

Tissue perfusion in DIEP flaps using Indocyanine Green Fluorescence Angiography, Hyperspectral imaging, and Thermal imaging.

Flap necrosis continues to occur in skin free flap autologous breast reconstruction. Therefore, we investigated the benefits of indocyanine green angiography (ICGA) using quantitative parameters for the objective, perioperative evaluation of flap perfusion. In addition, we investigated the feasibility of hyperspectral (HSI) and thermal imaging (TI) for postoperative flap monitoring. A single-center, prospective observational study was performed on 15 patients who underwent deep inferior epigastric perforator (DIEP) flap breast reconstruction (n=21). DIEP-flap perfusion was evaluated using ICGA, HSI, and TI using a standardized imaging protocol. The ICGA perfusion curves and derived parameters, HSI extracted oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) values, and flap temperatures from TI were analyzed and correlated to the clinical outcomes. Post-hoc quantitative analysis of intraoperatively collected data of ICGA application accurately distinguished between adequately and insufficiently perfused DIEP flaps. ICG perfusion curves identified the lack of arterial inflow (n=2) and occlusion of the venous outflow (n=1). In addition, a postoperatively detected partial flap epidermolysis could have been predicted based on intraoperative quantitative ICGA data. During postoperative monitoring, HSI was used to identify impaired perfusion areas within the DIEP flap based on deoxyHb levels. The results of this study showed a limited added value of TI. Quantitative, post-hoc analysis of ICGA data produced objective and reproducible parameters that enabled the intraoperative detection of arterial and venous congested DIEP flaps. HSI appeared to be a promising technique for postoperative flap perfusion assessment. A diagnostic accuracy study is needed to investigate ICGA and HSI parameters in real-time and demonstrate their clinical benefit.

Determination of Changes in Tissue Perfusion at Home with Hyperspectral and Thermal Imaging in the First Six Weeks after Endovascular Therapy in Patients with Peripheral Arterial Disease.

The aims of this study were to assess changes in tissue perfusion up to 6 weeks after endovascular therapy (EVT), in hospital and at home, and to determine differences in tissue perfusion between patients with and without clinical improvement or good angiographic result. This single-center prospective cohort study included patients undergoing EVT for Rutherford stages two to six. Hyperspectral and thermal imaging were performed at the dorsal and plantar sides of the foot. These measurements consisted of a baseline measurement pre-EVT, and six follow-up measurements obtained at 1 and 4 h and 6 weeks in hospital, and 1 day, 7 days, and 14 days at home. Clinical improvement was defined as a decrease of one or more Rutherford class or decrease in the wound surface area and a good angiographic result was accomplished when a Transatlantic Inter-Society Consensus for the Management of PAD II C or D lesion was treated and uninterrupted flow continued in at least one below-the-knee artery in continuation with the inframalleolar arteries. The study included 34 patients with 41 treated limbs. Deoxyhemoglobin values were lower 1 h post-EVT compared with baseline and increased over time up to 6 weeks post-EVT. Significant differences in deoxyhemoglobin levels at 7 and 14 days post-EVT were determined between patients with and without clinical or angiographic success. This prospective pilot study shows the feasibility of hyperspectral imaging and thermal imaging post-EVT at home, which may decrease the need for hospital visits.

Laser Doppler Flowmetry Combined with Spectroscopy to Determine Peripheral Tissue Perfusion and Oxygen Saturation: A Pilot Study in Healthy Volunteers and Patients with Peripheral Arterial Disease.

BACKGROUND: In this study, we assessed the ability of the EPOS system (Perimed AB, Järfälla, Stockholm, Sweden) to detect differences in tissue perfusion between healthy volunteers and patients with peripheral arterial disease (PAD) with different severity of disease. METHODS: This single-center prospective pilot study included 10 healthy volunteers and 20 patients with PAD scheduled for endovascular therapy (EVT). EPOS measurements were performed at rest at 32 °C and 44 °C, followed by transcutaneous oxygen pressure (TcPo2) measurements. The measurements were performed on the dorsal and medial side of the foot, as well as the lateral side of the calf. EPOS parameters included hemoglobin oxygen saturation (HbSo2) and speed-resolved red blood cell (RBC) perfusion. RESULTS: HbSo2 at 44 °C was significantly different between the three groups for all measurement locations. The overall speed-resolved RBC perfusion at 44 °C was statistically significant between the groups on the dorsal and medial side of the foot but not on the calf. TcPo2 values were not significantly different between the three groups. CONCLUSIONS: This study demonstrates that the EPOS system can depict differences in tissue perfusion between healthy volunteers, patients with Fontaine class IIb PAD, and those with Fontaine class III or IV PAD but only after heating to 44 °C.

Technical Success and Mid-Term Outcomes of Endovascular Revascularization of Tibio-Peroneal Trunk Lesions.

Tibio-peroneal trunk (TPT) lesions are usually categorized as 'complex' in anatomical classifications, which leads to the perception that endovascular therapy (EVT) will be challenging and the outcome most likely poor. This multicenter, retrospective cohort study investigates the efficacy of the EVT of TPT lesions in patients with chronic limb threatening ischemia (CLTI) or an infrapopliteal bypass at risk. The primary endpoint was limb-salvage. The secondary outcomes were technical success, freedom from clinically driven target lesion revascularization (CD-TLR), overall survival, and amputation-free survival. A total of 107 TPT lesions were treated in 101 patients. At 3 years, the limb-salvage rate was 76.4% (95% CI 66.0-86.8%). Technical success was achieved in 96.3% of cases. The freedom from CD-TLR, amputation-free survival, and overall survival at 3 years were 53.0% (95% CI 38.1-67.9%), 33.6% (95% CI 23.0-44.2%), and 47.7% (95% CI 36.1-59.3%), respectively. Reintervention significantly increased the hazard ratio for amputation by 7.65 (95% CI 2.50-23.44, p < 0.001). Our results show that the EVT of both isolated and complex TPT lesions is associated with high technical success and acceptable limb-salvage rates, with reintervention being a major risk factor for amputation. Moreover, mid-term mortality rate was relatively high. In future revisions of the anatomical grading scales, the classification of TPT lesions as highly complex should be reconsidered.

Telemedicine in patients with peripheral arterial disease: is it worth the effort?

Introduction: For patients with peripheral arterial disease (PAD), the various components of telemedicine, such as telemonitoring, telecoaching, and teleconsultation, could be valuable in daily management. The objective of this review was to give an overview of the current use of telemedicine interventions in PAD. Areas covered: A literature search was performed for studies that evaluated patients with PAD of the aorto-pedal trajectory, who were monitored by telemedicine and acted upon accordingly. The primary outcome was health-related outcomes. The studies that were found focused mainly on wearable activity monitoring and telecoaching in PAD (n = 4) or wound monitoring after vascular surgery (n = 2). Main results indicate that telemedicine interventions are able to detect (post-operative) complications early, improve functional capacity and claudication onset time, and improve PAD patients' quality of life. Expert opinion: The use of telemedicine in PAD patients is still an under-explored area. Studies investigating the use of telemedicine in PAD are very limited and show varying results. Owing to its high potential in improving physical ability, lifestyle coaching, and timely detection of deterioration, future research should focus on proper implementation of telemedicine in PAD patients, including clinical and feasibility outcomes, effect on workload of nurses, and cost-efficiency.

A systematic review of diagnostic techniques to determine tissue perfusion in patients with peripheral arterial disease.

Introduction: Peripheral arterial disease (PAD) may cause symptoms due to impaired tissue perfusion of the lower extremity. So far, assessment of PAD is mainly performed by determination of stenosis or occlusion in the large arteries and does not focus on microcirculation. Several diagnostic techniques have been recently introduced that may enable tissue perfusion measurements in the lower limb; however, most have not yet been implemented in clinical daily practice. This systematic review provides an overview of these diagnostic techniques and their ability to accurately detect PAD by peripheral tissue perfusion. Areas covered: A literature search was performed for articles that described a diagnostic technique to determine tissue perfusion in patients with known PAD compared with healthy controls. Expert opinion: So far, transcutaneous oxygen measurements are most often used to measure tissue oxygenation in PAD patients, but evidence seems too low to define this technique as a gold standard, and implementing this technique for home monitoring is difficult. New potentially suitable diagnostic tests should be non-invasive, contact-free, and quick. Further research is needed for all of these techniques before broad implementation in clinical use is justified, in hospital, and for home monitoring.

Hyperspectral imaging for noninvasive tissue perfusion measurements of the lower leg: review of literature and introduction of a standardized measurement protocol with a portable system.

INTRODUCTION: Hyperspectral imaging (HSI) is a noninvasive technique for transcutaneous measurements of tissue perfusion. This study (1) provides a review of the current literature on HSI for tissue perfusion measurements of the lower leg and (2) introduces a standardized measurement protocol for HSI measurements with a portable system. EVIDENCE ACQUISITION: A literature search was performed for studies on tissue perfusion measurements with HSI in the lower extremity. A standardized protocol was developed to perform HSI measurements in 43 healthy volunteers at the plantar side of the foot and at the lateral side of the calf, with 3 consecutive hyperspectral images at each location. EVIDENCE SYNTHESIS: The literature review identified 9 studies, including 2 of healthy volunteers, 4 of patients with diabetes mellitus, and 3 of patients with peripheral arterial disease. In 5 of 7 patient studies, HSI values were associated with severity of disease or wound healing. In our study, the healthy volunteers' HSI values for oxyhemoglobin, deoxyhemoglobin, and oxygen saturation were (mean±SD) 82.8±24, 55.7±15.7, and 59.2±11.7, respectively, at the plantar surface of the foot, and 40.8±11, 38.0±7.8, and 51.7±10.5, respectively, at the lateral side of the calf. HSI values differed significantly between the calf and plantar locations. Intraoperator reliability between the 3 consecutive images ranged from 81% to 89%. CONCLUSIONS: Limited evidence indicates that HSI is associated with severity of peripheral arterial disease and diabetes mellitus, and with wound healing. Hyperspectral images with a portable system can be taken with high precision when a standardized measurement protocol is used. However, differences exist at several locations at the lower extremity, so each measurement location should be used as its own reference when consecutive measurements are performed during follow-up. More studies with larger patient cohorts should be performed before HSI can be incorporated as standard tool in the diagnostic armamentarium of the vascular specialist.

A sustained decrease in plasma fibrinolytic potential following partial liver resection or pancreas resection.

BACKGROUND: Patients undergoing partial hepatectomy have a substantial risk for postoperative venous thrombosis even in the presence of optimal thromboprophylaxis. Recently we demonstrated a hypercoagulable state following a partial hepatectomy which was related to decreased plasma levels of natural anticoagulants and elevated levels of FVIII. The fibrinolytic status following partial hepatectomy has not been studied, but may display unique features as a result of temporarily decreased synthesis of fibrinolytic proteins. METHODS: We included 17 patients undergoing a partial hepatectomy and determined plasma fibrinolytic potential and measured plasma levels of individual fibrinolytic proteins in serial samples taken perioperatively. Results were compared to ten patients undergoing pancreas resection and twenty-four healthy volunteers. RESULTS AND CONCLUSION: Following both partial hepatectomy and pancreas resection plasma fibrinolytic potential decreased at the end of surgery, normalized on post-operative day 1, and decreased again on post-operative day 3 after which the hypofibrinolytic state gradually resolved. The hypofibrinolytic state on day 1 associated with increased plasma levels of PAI-1 in both groups. Plasma levels of plasminogen, α2-antiplasmin and TAFI all decreased following partial hepatectomy and pancreas resection and levels recovered over time. The kinetics of recovery were different for the different proteins and were slower in the liver resection group, resulting in a unique ratio of pro-to-anti-fibrinolytic proteins at each time point. This may explain the hypofibrinolytic status from day 3 onwards. A sustained plasma hypofibrinolytic state in combination with the hypercoagulable state we previously identified may contribute to the increased risk of thrombotic complications after partial liver resection.