Limb Ischemia: Cardiovascular Diagnosis and Management from Head to Toe
- 693 Downloads
Peripheral arterial disease (PAD) affects an estimated 27 million people in Europe and North America. Limb ischemia, defined as ischemic rest pain, ischemic ulcerations, or ischemic gangrene, represents the most severe manifestation of PAD and is associated with significant cardiovascular and limb morbidity and mortality. Critical limb ischemia (CLI), defined as limb ischemia symptoms for greater than 2 weeks, is characterized by a cascade of hemodynamically significant macrovascular atherosclerotic obstruction and microvascular changes culminating in decreased muscle perfusion, disrupted muscle energy metabolism, and inflammation. In contrast, acute limb ischemia (ALI) is defined as limb ischemia symptoms characterized by sudden onset of less than 2 weeks duration resulting in hemodynamically compromised limb perfusion. Diagnosis of both ALI and CLI is dependent on history, physical examination, and a combination of anatomic and hemodynamic assessment of the limb. Given that the risk factors for ALI and CLI overlap with risk factors for atherosclerotic coronary and neurovascular disease, the management of limb ischemia is focused on both endovascular or surgical limb salvage and cardiovascular risk factor control. Despite advancements in endovascular and surgical revascularization techniques, limb morbidity remains high; clinical trials of angiogenic and cell-based therapies are ongoing. Cardiovascular risk reduction in patients with limb ischemia also remains suboptimal and future studies will focus on novel antiplatelet agents.
KeywordsCritical limb ischemia Acute limb ischemia Peripheral artery disease Revascularization Wound care Cardiovascular risk reduction
Compliance with Ethics Guidelines
Conflict of Interest
Sreekanth Vemulapalli reports grants from Boston Scientific and personal fees from Medtronic and Abbott Vascular.
Manesh R. Patel reports grant support from Astra Zeneca and personal fees from Medtronic.
W. Schuyler Jones reports grants from American Heart Association, AstraZeneca, Daiichi Sankyo, and Boston Scientific Corporation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 6.Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, et al. Acc/aha 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; Transatlantic Inter-society Consensus; and Vascular Disease Foundation. Circulation. 2006;113:e463–654.PubMedCrossRefGoogle Scholar
- 14.Patel MR, Conte MS, Cutlip DE, Dib N, Geraghty P, Gray W et al. Consensus definitions for evaluation of patients with lower extremity peripheral artery disease: the peripheral academic research consortium (parc). J Am Coll Cardiol. in pressGoogle Scholar
- 15.••Mills JL Sr., Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN et al. The society for vascular surgery lower extremity threatened limb classification system: risk stratification based on wound, ischemia, and foot infection (wifi). J Vasc Surg. 2014;59:220–234 e221-222. This manuscript describes the WIFI risk classification system for limb ischemia, as well as its predictive ability for major adverse limb events.Google Scholar
- 19.Rocha-Singh KJ, Jaff M, Joye J, Laird J, Ansel G, Schneider P, et al. Major adverse limb events and wound healing following infrapopliteal artery stent implantation in patients with critical limb ischemia: the xcell trial. Catheter Cardiovasc Interv Off J Soc Card Angiograph Interv. 2012;80:1042–51.CrossRefGoogle Scholar
- 22.Bradbury AW, Adam DJ, Bell J, Forbes JF, Fowkes FG, Gillespie I, et al. Bypass versus angioplasty in severe ischaemia of the leg (basil) trial: an intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy. J Vasc Surg. 2010;51:5S–17S.PubMedCrossRefGoogle Scholar
- 26.Iida O, Nanto S, Uematsu M, Ikeoka K, Okamoto S, Dohi T, et al. Importance of the angiosome concept for endovascular therapy in patients with critical limb ischemia. Catheter Cardiovasc Interv Off J Soc Cardiac Angiograph Interv. 2010;75:830–6.Google Scholar
- 31.•Armstrong EJ, Chen DC, Westin GG, Singh S, McCoach CE, Bang H, et al. Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease. J Am Heart Assoc. 2014;3:e000697. This study describes the efficacy of medical therapy for cardiovascular event prevention in patients with PAD.PubMedCentralPubMedCrossRefGoogle Scholar
- 33.Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159–219.PubMedCrossRefGoogle Scholar
- 37.Patel MR, Becker RC, Wojdyla DM, Emanuelsson H, Hiatt WR, Horrow J et al. Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: data from the plato trial. Eur J Prevent Cardiol. 2014Google Scholar
- 39.Jones WS, Tricoci P, Huang Z, Moliterno DJ, Harrington RA, Sinnaeve PR, et al. Vorapaxar in patients with peripheral artery disease and acute coronary syndrome: insights from thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (tracer). Am Heart J. 2014;168:588–96.PubMedCrossRefGoogle Scholar
- 44.Powell RJ, Goodney P, Mendelsohn FO, Moen EK, Annex BH, Investigators HGFT. Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the hgf-0205 trial. J Vasc Surg. 2010;52:1525–30.PubMedCrossRefGoogle Scholar
- 45.Powell RJ, Simons M, Mendelsohn FO, Daniel G, Henry TD, Koga M, et al. Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation. 2008;118:58–65.PubMedCrossRefGoogle Scholar
- 47.Gabr H, Hedayet A, Imam U, Nasser M. Limb salvage using intramuscular injection of unfractionated autologous bone marrow mononuclear cells in critical limb ischemia: a prospective pilot clinical trial. Exp Clin Transplant Off J Middle East Soc Org Transplant. 2011;9:197–202.Google Scholar
- 52.•Korabathina R, Weintraub AR, Price LL, Kapur NK, Kimmelstiel CD, Iafrati MD, et al. Twenty-year analysis of trends in the incidence and in-hospital mortality for lower-extremity arterial thromboembolism. Circulation. 2013;128:115–21. This study describes the changing epidemiology of acute limb ischemia in the United States.PubMedCrossRefGoogle Scholar
- 54.Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The stile trial. Ann Surg. 1994;220:251–266; discussion 266–258Google Scholar
- 60.Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, et al. Sustained safety and effectiveness of paclitaxel-eluting stents for femoropopliteal lesions: 2-year follow-up from the zilver ptx randomized and single-arm clinical studies. J Am Coll Cardiol. 2013;61:2417–27.PubMedCrossRefGoogle Scholar
- 65.•Duval S, Keo HH, Oldenburg NC, Baumgartner I, Jaff MR, Peacock JM, et al. The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the friends registry. Am Heart J. 2014;168:577–87. This manuscript describes a single center description of the epidemiology of limb ischemia as well as the importance of time to treatment for outcomes in acute limb ischemia.PubMedCrossRefGoogle Scholar
- 67.Alonso-Coello P, Bellmunt S, McGorrian C, Anand SS, Guzman R, Criqui MH, et al. Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141:e669S–90S.PubMedCentralPubMedCrossRefGoogle Scholar
- 76.Goodney PP, Tarulli M, Faerber AE, Schanzer A, Zwolak RM. Fifteen-year trends in lower limb amputation, revascularization, and preventive measures among medicare patients. JAMA Surg. 2014Google Scholar
- 77.Subherwal S, Patel MR, Tang F, Smolderen KG, Jones WS, Tsai TT, et al. Socioeconomic disparities in the use of cardioprotective medications among patients with peripheral artery disease: an analysis of the American College of Cardiology’s Ncdr Pinnacle Registry. J Am Coll Cardiol. 2013;62:51–7.PubMedCentralPubMedCrossRefGoogle Scholar
- 78.•Vemulapalli S, Greiner MA, Jones WS, Patel MR, Hernandez AF, Curtis LH. Peripheral arterial testing before lower extremity amputation among medicare beneficiaries, 2000 to 2010. Circ Cardiovasc Qual Outcomes. 2014;7:142–50. This manuscript describes incomplete use of guideline directed vascular testing prior to lower extremity amputation.PubMedCrossRefGoogle Scholar
- 79.Jollis JG, Roettig ML, Aluko AO, Anstrom KJ, Applegate RJ, Babb JD, et al. Reperfusion of Acute Myocardial Infarction in North Carolina Emergency Departments I. Implementation of a statewide system for coronary reperfusion for ST-segment elevation myocardial infarction. Jama. 2007;298:2371–80.PubMedCrossRefGoogle Scholar