High on-treatment platelet reactivity in peripheral arterial disease: A systematic review.

OBJECTIVES: To highlight current evidence pertaining to the measurement methods and prevalence of high on-treatment platelet reactivity (HTPR) in patients with PAD, as well as to evaluate the relationship between HTPR and recurrent adverse cardiovascular and limb events in PAD patients. METHODS: A systematic review of English-language literature on HTPR in patients with PAD. An electronic literature search of PubMed and Medline was performed in May 2021. RESULTS: A total of 29 studies with a total number of 11,201 patients with PAD were identified. HTPR during clopidogrel treatment ranges from 9.8 to 77%, and during aspirin treatment ranges from 4.1 to 50% of PAD patients. HTPR was associated with adverse clinical outcomes. The need for limb revascularisation was higher in patients with HTPR during clopidogrel use. Similarly, HTPR during aspirin use in the PAD population was predictive of adverse cardiovascular events (HR 3.73; 95% CI, 1.43-9.81; p = .007). A wide range of techniques were applied to measure platelet resistance, without consensus on cut-off values. Furthermore, differing patient populations, a variety of antiplatelet regimens, and differing clinical endpoints highlight the high degree of heterogeneity in the studies included in this review. CONCLUSION: No consensus on technique or cut-off values for HTPR testing has been reached. Patients with HTPR are potentially at a greater risk of adverse limb-related and cardiovascular events than patients sensitive to antiplatelet therapy illustrating the need for clinical implementation of HTPR testing. Future research must aim for consistent methodology. Adaptation of antiplatelet therapy based on HTPR results requires further exploration.

Reliability of bedside tests for diagnosing peripheral arterial disease in patients prone to medial arterial calcification: A systematic review.

Background: Medial arterial calcification (MAC), frequently associated with diabetes mellitus (DM) and chronic kidney disease (CKD), is a systemic vascular disorder leading to stiffness and incompressible arteries. These changes impede the accuracy of bedside tests to diagnose peripheral arterial disease (PAD). This review aimed to evaluate the reliability of bedside tests for the detection of PAD in patients prone to MAC. Methods: A systematic search (Pubmed, Embase, Web of Science, Cochrane, and Emcare) was performed according to the PRISMA guidelines to identify relevant studies providing data on the performance of bedside tests for the detection of PAD in patients prone to MAC. Studies were included when bedside test were compared to a reference standard. Primary endpoints were the positive and negative likelihood ratios (PLR, NLR). Methodological quality and risk of bias were evaluated using the QUADAS-2 tool. Findings: In total, 23 studies were included in this review. The most commonly evaluated test was the ankle-brachial index (ABI), followed by toe-brachial index (TBI), toe pressure (TP) measurements, and continuous wave Doppler (CWD). The majority of patients were older, male, and had DM. We found that ABI <0·9 was helpful to diagnose PAD, but failed to rule out PAD (NLR >0·2). The same applied for TP (NLR >0·3) and TBI (5 out of 6 studies revealed an NLR >0·2). CWD (loss of triphasic pattern) is reliable to exclude PAD (NLR 0-0·09), but was only validated in two studies. Overall, methodological quality was poor which led to risk of bias in 20 studies. Interpretation: The diagnosis of PAD in patients prone to MAC remains challenging. The ABI performed reasonably in the diagnosis of PAD, while the CWD (loss of triphasic signal) can be used to rule out PAD. This systematic review showed that test performances were generally poor with serious concerns in methodological quality of the included studies. We therefore counsel against the use of a single bedside test. Funding: None to declare.

Near-infrared fluorescence imaging with indocyanine green for quantification of changes in tissue perfusion following revascularization.

OBJECTIVES: Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion. METHODS: ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform®. Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and the AUC for the egress. The non-treated contralateral leg was used as a control group. RESULTS: Successful revascularization was performed in 32 patients. There was a significant increase for the maximum slope and AUC egress in all three ROIs. The most significant difference was seen for the maximum slope in ROI 3 (3.7%/s to 6.6%/s, p < 0.001). In the control group, no significant differences were seen for the maximum slope and AUC egress in all ROIs. CONCLUSIONS: This study shows the potential of ICG NIR fluorescence imaging in assessing the effect of revascularization procedures on foot perfusion. Future studies should focus on the use of this technique in predicting favorable outcome of revascularization procedures.

Perfusion Patterns in Patients with Chronic Limb-Threatening Ischemia versus Control Patients Using Near-Infrared Fluorescence Imaging with Indocyanine Green.

In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform® (Middenmeer, The Netherlands). The time-intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage.

Perfusion Parameters in Near-Infrared Fluorescence Imaging with Indocyanine Green: A Systematic Review of the Literature.

(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.