Sophia Z. Massin

Background: Peripheral arterial disease (PAD) is a chronic atherosclerotic disease characterized by atheromatous plaque buildup within arteries of the lower limbs. It can lead to claudication, skin ulcerations, and, in severe cases, chronic limb-threatening ischemia, requiring amputation. There are several plasma protein biomarkers that have been suggested as prognostic markers for adverse events, including major adverse cardiovascular and limb events. However, the clinical benefit and ability to clinically adapt these biomarkers remains uncertain due to inconsistent findings possibly related to heterogenous study designs and differences in methodology. Objectives: This review aims to evaluate the current literature on the prognostic value of plasma protein biomarkers for PAD, their predictive ability for PAD-related adverse outcomes, and their potential roles in guiding PAD management. Methods: To address these challenges, we conducted a systematic review of MEDLINE, Embase, and Cochrane CENTRAL libraries of the current literature (2010–2024). Results: We found 55 studies that evaluated the prognostic value of 44 distinct plasma proteins across various pathophysiological processes. These included markers of immunity and inflammation, markers of metabolism, cardiac biomarkers, markers of kidney function, growth factors and hormones, markers of coagulation and platelet function, extracellular matrix and tissue remodeling proteins, and transport proteins. This review summarizes the existing evidence for prognostic protein plasma biomarkers for PAD and their association with adverse events related to PAD. Conclusions: With this review, we hope to provide a comprehensive list of the prognostic markers and their value as prognostic biomarkers to guide clinical decision making in these patients.

INTRODUCTION: Epicardial adipose tissue (EAT) is often associated with atrial fibrosis, and both can provide the substrate for atrial fibrillation (AF). However, most AF patients have no evidence of left atrial (LA) fibrosis based on bipolar voltage mapping. We determined whether EAT differs in AF patients without LA fibrosis compared to matched controls without AF. METHODS: Patients undergoing cardiac CT before first-time AF catheter ablation were prospectively enrolled. LA bipolar voltage mapping was performed, and patients were divided into -LVZ (LA low voltage zones < 5% of LA surface area; no fibrosis) and +LVZ (LA low voltage zones ≥ 5%; fibrosis). A control group without AF was matched to -LVZ patients. EAT was quantified on CT using standard signal thresholding to quantify total and regional volumes. AF patients were followed for 1-year postablation to assess atrial arrhythmia (AA) recurrence. RESULTS: -LVZ (n = 50) had higher total EAT volumes than matched controls (n = 48) (79 [58-109] vs. 51 [37-73] cm³, p < 0.001), higher LA EAT (9 [6.3-12] vs. 4.2 [2.9-5.8] cm³, p < 0.001), higher posterior LA EAT (9.7 [6.4-12] vs. 5.9 [2.8-7.2] cm³, p < 0.001) and higher right atrial EAT (7.3 [5.1-9.9] vs. 4.8 [3.2-6.5] cm³, p < 0.001). These differences remained even after correcting EAT for BMI and LA volumes. There were no significant differences in EAT volumes between -LVZ and +LVZ (n = 25). There was no significant association between EAT and AF recurrence postablation. CONCLUSION: EAT volume is greater in AF patients without evidence of LA fibrosis compared to matched controls without AF. These findings support an association of EAT with AF pathogenesis even in the absence of LA fibrosis.

INTRODUCTION: An important substrate for atrial fibrillation (AF) is fibrotic atrial myopathy. Identifying low voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional dependency of wave propagation. Our objective was to evaluate directionally independent unipolar voltage mapping, but with far-field cancellation, to identify low-voltage regions during AF. METHODS: In 12 patients undergoing pulmonary vein isolation for AF, high-resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20-pole circular catheter. Bipolar electrograms (EGMs) (Bi) < 0.5 mV in sinus rhythm identified low-voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni-res) and without (uni-orig) far-field cancellation using a novel, validated least-squares algorithm. RESULTS: Uni-res voltage was ~25% lower than uni-orig for both low voltage and normal atrial regions. Far-field EGM had a dominant frequency (DF) of 4.5-6.0 Hz, and its removal resulted in a lower DF for uni-orig compared with uni-res (5.1 ± 1.5 vs. 4.8 ± 1.5 Hz; p < .001). Compared with Bi, uni-res had a significantly greater area under the receiver operator curve (0.80 vs. 0.77; p < .05), specificity (86% vs. 76%; p < .001), and positive predictive value (43% vs. 30%; p < .001) for detecting low-voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni-res versus uni-orig. CONCLUSION: Far-field EGM can be reliably removed from uni-orig using our novel, least-squares algorithm. Compared with Bi and uni-orig, uni-res is more accurate in detecting low-voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study.