CLTI prognosis is not decided by the artery alone: this evidence map shows that wound severity, nutrition, frailty, heart failure, dialysis, mobility loss, and biomarkers together define who survives, heals, or loses a limb. The full review explains which clinical scores and warning signals may help identify high-risk patients before revascularization decisions are made.
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Abstract: The aim of this review is to synthesize contemporary evidence regarding the prognostic factors, clinical scoring systems, and long-term outcomes for patients diagnosed with CLTI (Chronic Limb-Threatening Ischemia). The review utilises 74 original studies with 392683 total participants (topic deduplicated ΣN). The mapped evidence indicates that prognosis in CLTI is shaped less by any single anatomical feature and more by the convergence of wound severity, nutritional state, and systemic frailty, with 5-year amputation-free survival ranging from 26.5%–35.4% in high-risk groups to 72.1%–89.5% in low-risk groups. The Wound, Ischemia, and foot Infection (WIfI) classification and nutritional indices such as the Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score emerged as the most recurrent independent predictors across cohorts, while revascularization was associated with improved 1-year amputation-free survival (58.0% versus 45.7% in tissue-loss disease). Recurrent secondary signals included hemodialysis, heart failure with reduced ejection fraction (2-year amputation-free survival 35% versus 61% in preserved ejection fraction), ambulatory decline (1-year survival 86.8% versus 23.9%), calcification burden, depression, and emerging inflammatory, microRNA, and metabolomic biomarkers, suggesting that prognosis is best understood as a multidomain construct rather than a purely vascular one. Clinically, this supports embedding combined wound, nutritional, frailty, and cardiac assessment into routine pre-revascularization workup to identify patients who may benefit from intensified medical optimization or alternative care pathways. The evidence map is, however, dominated by retrospective single-region cohorts with heterogeneous endpoints, which tempers certainty about the relative weight of individual predictors. Future research should prioritize prospective multicenter validation of composite prognostic scores integrating WIfI stage, nutritional indices, frailty, and novel biomarkers, alongside interventional trials testing whether modifying nutrition, depression, or ambulatory decline translates into measurable gains in amputation-free survival.
Final search date and database lock: 2026-05-01 21:24:21 CEST
Plan: Pro (expanded craft tokens; source: Semantic Scholar)
Source: Semantic Scholar
Total Abstracts/Papers: 1063802
Downloaded Abstracts/Papers: 1000
Included original and non-original Abstracts/Papers (all): 81
Included original Abstracts/Papers (Vote counting by direction of effect): 74
Reference Index (links used in paper): 69
Total participants (topic deduplicated ΣN): 392683
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The Evidence Object JSON is a separate machine-readable evidence product: a concentrated synthesis of results, topic-level evidence, and discussion across original and non-original studies. It can be directly input into your LLM, agent, or RAG workflow.
[2] Comparison of Prognosis in Chronic Limb Threatening after Revascularisation Versus Non-revascularisation Treatment: Analysis of Japanese Regional Insurance Claims. — https://doi.org/10.1016/j.ejvs.2025.05.036
[3] Long-term prognosis after bypass surgery versus endovascular therapy in chronic hemodialysis patients with peripheral artery disease -10-year follow-up study — https://doi.org/10.1093/eurheartj/ehaf784.3027
[6] Poor limb prognosis of patients with chronic limb-threatening ischemia on hemodialysis: A retrospective observational study based on the Global Limb Anatomic Staging System (GLASS). — https://doi.org/10.1016/j.avsg.2023.11.049
[9] Influence of Malignant Neoplasms on Limb Prognosis in Patients with Peripheral Arterial Disease: A Real World Analysis Based on a Nationwide Database. — https://doi.org/10.1016/j.ejvs.2026.01.037
[11] The CHADS2 score may be a useful predictor of prognosis in chronic limb-threatening ischemia patients after endovascular intervention with and without AF — https://doi.org/10.1093/eurheartj/ehad655.2054
[12] Association of cardiac prognosis in chronic limb-threatening ischemia patients after endovascular intervention and wound, ischemia, and foot infection clinical stage — https://doi.org/10.1093/eurheartj/ehac544.1962
[13] Prognostic Nutritional Index as a Predictor of Prognosis in Patients with Chronic Limb Threatening Ischemia Who Underwent Endovascular Revascularization Therapy — https://doi.org/10.55503/2790-6744.1209
[16] Influence of heart failure on the clinical outcomes of patients with chronic limb-threatening ischemia after infrainguinal revascularization. — https://doi.org/10.1016/j.jvs.2025.04.002
[18] Endovascular Treatment for Calcified Femoropopliteal Peripheral Artery Disease and Risk Factor Identification: Two Year Outcomes of the Evolusion Study. — https://doi.org/10.1016/j.ejvs.2025.10.002
[19] Clinical outcomes in patients with chronic limb-threatening ischemia with or without hyperpolypharmacy after revascularization. — https://doi.org/10.1016/j.avsg.2025.08.035
[20] The systemic immune-inflammation index is an independent predictive factor in predicting major amputation in chronic limb-threatening ischemia — https://doi.org/10.1177/17085381251327174
[21] Risk factor management over two decades in hospitalised patients with chronic limb-threatening ischaemia with and without diabetes mellitus — https://doi.org/10.1177/20420188251362729
[22] Prognostic Factors After Bone Marrow-Derived Mononuclear Cell Implantation in No-Option Chronic Limb-Threatening Ischemia Patients with Atherosclerotic Lower Extremity Artery Disease. — https://doi.org/10.1536/ihj.24-440
[24] Sciatic nerve atrophy as a risk factor for impaired wound healing in patients with chronic limb-threatening ischemia. — https://doi.org/10.1016/j.jvs.2025.02.008
[25] Risk factors of incident acute limb ischemia after contemporary femoropopliteal endovascular revascularization from a multicenter registry: A retrospective observational study — https://doi.org/10.1177/20480040251325412
[29] Limb Salvage and Survival in Chronic Limb-Threatening Ischemia: The Need for a Fast-Track Team-Based Approach — https://doi.org/10.3390/jcm12186081
[30] Potential applications of artificial intelligence and machine learning on diagnosis, treatment, and outcome prediction to address health care disparities of chronic limb-threatening ischemia. — https://doi.org/10.1053/j.semvascsurg.2023.06.003
[33] Poor short-term outcomes for prognostic high-risk patients with chronic limb-threatening ischemia undergoing endovascular therapy — https://doi.org/10.1186/s42155-024-00443-9
[34] Nationwide Study of the Outcome of Treatment of Lower Extremity Atherosclerotic Lesions With Endovascular Surgery With or Without Drug Eluting Methods in Patients With Diabetes — https://doi.org/10.1177/15266028241241967
[35] Prognostic factors and outcomes of chronic limb threatening ischaemia in patients post kidney transplant: a systematic review — https://doi.org/10.1007/s44337-024-00106-7
[36] Abstract 2036: Prognostic Impact Of Pfkfb3 Expression In Endothelial Cells Insights From Peripheral Arterial Disease Patients And The Effects Of Supervised Exercise — https://doi.org/10.1161/atvb.44.suppl_1.2036
[38] Association between High Bleeding Risk and 2-Year Mortality in Patients with Chronic Limb-Threatening Ischemia — https://doi.org/10.5551/jat.64157
[39] Impact of ambulatory status change on survival in patients with chronic limb-threatening ischemia undergoing infrainguinal surgical or endovascular revascularization. — https://doi.org/10.1016/j.jvs.2023.03.024
[40] The Prognostic Value of the WIfI Classification in Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-Analysis. — https://doi.org/10.1016/j.ejvs.2019.03.040
[42] Peak aortic valve jet velocity is an independent predictor of mortality of dialysis patients undergoing open surgery for chronic limb threatening ischemia. — https://doi.org/10.1016/j.avsg.2023.09.090
[44] Evaluation of three nutritional indices as predictors of 2-year mortality and major amputation in patients with chronic limb-threatening ischemia — https://doi.org/10.1177/17085381221102801
[45] Risk Stratification for 2-Year Mortality in Patients with Chronic Limb-Threatening Ischemia Undergoing Endovascular Therapy — https://doi.org/10.5551/jat.57711
[46] Serum Metabolic Signatures of Chronic Limb-Threatening Ischemia in Patients with Peripheral Artery Disease — https://doi.org/10.3390/jcm9061877
[47] Comparison of clinical outcomes, including the wound healing rate, between inframalleolar bypass to the pedal artery and that to the pedal branch artery in the modern endovascular era. — https://doi.org/10.1016/j.jvs.2022.01.138
[49] Bypass Surgery Provides Better Outcomes Compared with Endovascular Therapy in the Composite Endpoint Comprising Relief from Rest Pain, Wound Healing, Limb Salvage, and Survival after Infra-inguinal Revascularisation in Patients with Chronic Limb Threatening Ischaemia. — https://doi.org/10.1016/j.ejvs.2021.12.043
[50] Sarcopenia as a Possible Negative Predictor of Limb Salvage in Patients with Chronic Limb-Threatening Ischemia — https://doi.org/10.3400/avd.oa.18-00167
[51] Risk stratification and mortality prediction in octo- and nonagenarians with peripheral artery disease: a retrospective analysis — https://doi.org/10.1186/s12872-021-02177-1
[53] Baseline and Updated Information on Nutritional Status in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation. — https://doi.org/10.1016/j.ejvs.2020.11.036
[56] Elevated Remnant Lipoprotein Related to Adverse Events in Patients with Chronic Limb Threatening Ischemia after Endovascular Therapy for Below the Knee Lesions. — https://doi.org/10.1016/j.avsg.2022.01.024
[60] Dynamic changes in WIfI classification as a prognostic indicator for midterm outcomes in CLTI patients undergoing infrapopliteal endovascular revascularization — https://doi.org/10.1186/s40001-025-03728-4
[61] Contemporary in-hospital and long-term prognosis of patients with acute ST-elevation myocardial infarction depending on renal function: a retrospective analysis — https://doi.org/10.1186/s12872-023-03084-3
[64] Derivation and Validation of Risk Score Including Nutritional Status Among Patients With Chronic Limb-threatening Ischemia: Insight From I-PAD NAGANO Registry. — https://doi.org/10.1177/15266028251314691
[67] Absolute Lymphocyte Count Predicts Bypass Surgery Outcomes in Patients with Chronic Limb-Threatening Ischemia — https://doi.org/10.3400/avd.oa.23-00088
[68] Impact of Controlling Nutritional Status Score on Comprehensive Clinical Outcomes in Patients With Chronic Limb-Threatening Ischemia in a Local Area of Super-Aged Society — https://doi.org/10.1177/15266028241259396
[69] The Association of Comorbid Depression on Mortality and Amputation Risk in Patients with Chronic Limb Threatening Ischemia. — https://doi.org/10.1016/j.jvs.2023.09.001
[72] The Dutch chronic lower limb-threatening ischemia registry (THRILLER): A study protocol for popliteal and infrapopliteal endovascular interventions — https://doi.org/10.1371/journal.pone.0288912
[74] Circumferential degree of tibial artery calcification is associated with infrapopliteal endovascular revascularization outcomes in patients with chronic limb-threatening ischemia. — https://doi.org/10.23736/s0392-9590.23.05130-1
[75] Abstract 15047: The Probability of miRNA Derived From Extracellular Vesicles as Functional Biomarkers for Patients With Lower Extremity Artery Disease — https://doi.org/10.1161/circ.148.suppl_1.15047
[76] WIfI Classification-Based Analysis Of Risk Factors For Outcomes In Patients With Chronic Limb-Threatening Ischemia After Endovascular Revascularization Therapy. — https://doi.org/10.1016/j.ejvs.2022.12.027
[77] Prognostic value of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification in patients with no‐option chronic limb‐threatening ischemia — https://doi.org/10.1016/j.jvs.2018.02.028
[78] Validation of the GLASS staging systems in patients with chronic limb-threatening ischemia undergoing de novo infrainguinal revascularization. — https://doi.org/10.1016/j.avsg.2021.09.054
[79] Impact of Preoperative Symptoms and Revascularized Arterial Segment in Patients With Chronic Limb-Threatening Ischemia — https://doi.org/10.1177/1538574419834765
[80] Association Between Wound Healing and the Japanese Below-the-Knee Chronic Total Occlusion Score in Patients With Chronic Limb-Threatening Ischemia After Endovascular Therapy. — https://doi.org/10.1177/15266028241296044
