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Chronic Total Occlusion of the Coronary Artery
Introduction
A coronary chronic total occlusion (CTO) is defined as 100% occlusion of a coronary artery for a duration of greater than or equal to 3 months based on angiographic evidence. The TIMI (thrombolysis in myocardial infarction) flow grading system is a scoring classification from 0-3 referring to the levels of coronary blood flow assessed during coronary angiography. The TIMI flow grading system is as below[1]:
- TIMI 0 flow (no perfusion-complete occlusion) - the absence of any forward flow beyond a coronary occlusion.
- TIMI 1 flow (penetration without perfusion) - faint forward flow beyond the occlusion, associated with an incomplete filling of the distal coronary bed.
- TIMI 2 flow (partial reperfusion) - delayed forward flow with complete filling of the distal coronary bed.
- TIMI 3 flow (full perfusion) - normal flow, which fills the distal coronary bed.
A "true" CTO is defined as 100% occlusion of a coronary artery with TIMI 0 flow; whereas a "functional" CTO is defined as severely stenotic, yet, less than a 100% occlusion of the coronary artery with TIMI 1 flow for a duration of greater than or equal to 3 months based on angiographic evidence.[2] Moreover, it is difficult to identify the exact period over which a CTO lesion is present in the absence of serial angiograms. Therefore, it is mostly estimated based on available clinical information related to the timing of the event that caused the occlusion, for example, prior myocardial infarction or sudden change in anginal symptoms with electrocardiogram changes consistent with the location of the occlusion. However, in many patients, the age of the CTO cannot be determined with confidence.
Etiology
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Etiology
Risk factors for CTO lesion in patients are as below[3]:
- Known coronary artery disease or history of myocardial infarction
- Excessive tobacco use
- High LDL cholesterol, low HDL cholesterol
- Diabetes
- Sedentary lifestyle
- Hypertension
- Family history of premature disease
- End-stage kidney disease
- Obesity
- Postmenopausal women
Epidemiology
CTO lesions are found in approximately one-quarter to one-third of patients undergoing diagnostic coronary angiography. The true prevalence, however, in the general population is unknown due to a subset of patients with CTO lesions being asymptomatic or minimally symptomatic and never undergoing diagnostic coronary angiography. Patients with a history of coronary artery bypass graft surgery are found to have CTOs of their native vessels more frequently (50% to 55%). In comparison, patients presenting with ST-elevation myocardial infarction (STEMI) are less likely to have a CTO (9% to 11%).[4][5]
Data from the National Heart, Lung, and Blood Institute (1997–1999) Dynamic Registry showed that CTO lesions are most common in the right coronary artery and least common in the left circumflex artery. Older patients are more likely to have at least one CTO lesion with 37% prevalence in patients under the age of 65 years, 40% in patients between the ages of 65 to 79 years, and 41% in those patients who are older than 85 years.[6]
Pathophysiology
Pathogenesis of coronary artery disease, which can progress to CTO lesions, has multiple contributing factors, which include upregulation of the immunologic and inflammatory markers (cytokines, leukocytes, high sensitivity C-reactive protein), endothelial dysfunction, and cholesterol accumulation. Most commonly, it starts with the collection of smooth muscle cells within the intima, and this progresses to macrophages accumulating in the intima leading to pathologic intimal thickening and progression of lesions.[7][8]
Histopathology
Histopathological attributes of a CTO lesion commonly consist of calcium, lipids (both intracellular and extracellular), smooth muscle cells, an extracellular matrix, and neovascularization. Occlusions typically have a dense concentration of collagen-rich fibrous tissue at the proximal and distal ends contributing to a columnar lesion of calcified, resistant fibrous tissue surrounding a softer core of organized thrombus and lipids. Lesion classification is as soft, hard, or a mixture of both. Soft plaques are more frequent in occlusions less than 12 months of age and consist of cholesterol-laden cells and foam cells. Hard plaques are more prevalent in occlusions that are older than 12 months of age and are characterized by dense fibrous tissue with fibrocalcific regions without neovascular channels.[9]
History and Physical
CTO lesions are diagnosed in patients who are undergoing coronary angiography as part of the evaluation of ischemic heart disease, cardiomyopathy, or valvular heart disease. Patients with ischemic heart disease generally present with typical chest pain symptoms (stable or unstable angina), atypical chest pain, NSTEMI, or STEMI. In contrast, patients with different types of cardiomyopathies or valvular heart disease may present with a variety of symptoms, including decompensated congestive heart failure. Therefore, during history taking in patients suspected of having ischemic heart disease, it is essential to have them describe and subjectively quantify their symptoms.
The history should also include risk factors for cardiovascular disease (diabetes, tobacco abuse, hypertension, hyperlipidemia) and non-cardiac causes of the patient's symptoms, including pulmonary embolism, aortic dissection, pneumothorax, esophageal rupture or perforating peptic ulcer. Physical examination in these patients should include complete auscultation of the heart and lung sounds together with assessment for heart failure signs including jugular venous distention, Kussmaul sign, hepatojugular reflex, ascites, and peripheral edema.
Evaluation
A significant component of an assessment for a patient who presents with signs and symptoms of ischemic heart disease is history and physical exam. These should include vital signs (respiratory rate, blood pressure, temperature, and heart rate), review of the patient's medication list, and an electrocardiogram. During their evaluation, the patient should have an assessment for any underlying or comorbid valvular heart disease or heart failure.
A healthcare provider should consider thyroid function testing, pulmonary function testing, routine blood work, including cardiac enzymes, chest X-ray, and echocardiography as part of their initial evaluation. If the initial assessment and evaluation are performed on an urgent basis, intravenous access should be obtained and, if no contraindication exists, the patient should be administered aspirin (162 to 325 mg) and nitrates. If available, patients should be placed on a cardiac monitor and should be assessed with pulse oximetry for the need for supplemental oxygen.
Treatment / Management
CTO revascularization has not shown to benefit rates of all-cause mortality, myocardial infarction, stroke, or repeat revascularization; however, it has shown to significantly improve patients' quality of life and reduce symptoms of angina.[10][11][12] Nuclear medicine stress test or myocardial viability studies are also used in conjunction with symptoms to objectively demonstrate areas of ischemia or viability supplied by the CTO vessel. Based on current guidelines, patients with single-vessel CTO lesions should undergo coronary artery bypass surgery if they have left main artery disease, proximal LAD disease which supplies a viable anterior wall, or three-vessel disease in a patient with insulin-dependent diabetes, severe left ventricular dysfunction, or chronic kidney disease.[13](A1)
In patients who meet the indication for a CTO PCI, informed consent is necessary before the procedure after an extensive discussion about the risks and benefits of CTO PCI for the patient. Due to the challenging nature of the CTO lesions, a successful outcome for PCI in these lesions is when the procedure obtains TIMI-3 flow, and there is less than 50% of residual stenosis in the vessel.
Multiple scoring systems are available to operators to predict technical success in CTO lesions. One of the most commonly used scoring systems is the J-CTO score, developed using the Chronic Total Occlusion Registry in Japan. A J-CTO score is used to predict the probability of crossing the CTO lesion within 30 minutes, and is inclusive of five independent factors; blunt stump appearance of the proximal cap of the occlusion, occlusion length greater than or equal to 20 mm, calcification detected within the CTO segment, the presence of a greater than 45-degree bend within the CTO segment, and prior failed PCI attempt of the CTO lesion. Each of these independent factors carries 1 point in the J-CTO score; zero is considered easy, a score of one is deemed to be intermediate, two rates as difficult, and greater than or equal to three is considered very difficult, with the probability of crossing within 30 minutes found to be 88%, 67%, 42%, and 10% respectively.[14]
Another commonly used score to predict the technical success of CTO PCI is the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) score. This predictor uses four independent factors to assess the CTO lesion, which includes CTO lesion proximal cap ambiguity, moderate/severe tortuosity of the CTO vessel, Circumflex artery CTO, and the absence of interventional collaterals. Each of these factors carries one point and correlates with technical success. A PROGRESS-CTO score of 0 is associated with 91% technical success, a score of 1 correlates with 74%, a score of 2 is 57% percent, and a score of ≥3 is less than 4.3%.[15](A1)
Differential Diagnosis
- STEMI
- NSTEMI
- Pulmonary embolism
- Aortic dissection
- Pneumothorax
- Esophageal rupture
- Perforating peptic ulcer disease
Prognosis
In addition to causing symptoms, CTOs have correlations with a worse overall prognosis, with higher rates of death and non-fatal adverse cardiovascular events in several populations. Patients with CTOs tend to be older and have more comorbidities and more significant impairment of left ventricular function. Furthermore, patients with non-revascularized CTOs have higher mortality and a higher risk of major adverse cardiovascular events in comparison to patients with multivessel coronary artery disease who are completely revascularized.[16][17]
Complications
Percutaneous coronary intervention (PCI) of a CTO lesion on average requires more fluoroscopy time, higher contrast volume, and carries a lower success rate compared to non-CTO PCI’s. CTO PCIs also have a higher complication rate than non-CTO PCIs with major complications, including myocardial infarction, stroke, vessel perforation, and death. However, vascular access site complications during CTO PCI occur at a similar frequency as routine PCI; these include poorly controlled bleeding, hematoma, acute thrombosis, distal embolization, retroperitoneal hemorrhage, dissection of the access artery, arteriovenous fistula, and pseudoaneurysm. Other potentially serious complications include ventricular tachyarrhythmias, bradycardia, allergic reactions, atheroembolism, and contrast nephropathy.[18][19][20][21][22][23]
Data analysis of the National Cardiovascular Data Registry-Cath PCI Registry in the United States showed higher in-hospital major adverse cardiovascular event frequency (1.6 versus 0.8 percent; p<0.001) which included mortality (0.4 % versus 0.3%; p<0.001), stroke (0.1% versus 0.1 %; p = 0.045), tamponade (0.3% versus 0.1%; p<0.001), MI (2.7% versus 1.9 %; p<0.001), and urgent CABG surgery (0.8% versus 0.4%; p<0.001) in 22,365 patients who underwent CTO PCI compared with 572,145 patients who underwent non-CTO PCI. CTO PCIs also had lower procedural success rate (59% vs. 96%, p < 0.001) in this registry.[24]
Another multicenter registry (OPEN-CTO) from 12 CTO-PCI centers of 1,000 consecutive patients undergoing CTO PCI evaluated success rates, complication rates, and health status benefits at one month. CTO PCIs showed a success rate of 86%, with an in-hospital mortality of 0.9%, 1-month mortality of 1.3%. 4.8% of the patients had coronary perforations requiring treatment. Additionally, major adverse cardiovascular events were 7%, myocardial infarction 2.6%, acute kidney injury 0.7%, and stroke 0%.[12]
Deterrence and Patient Education
Patient education should include resources such as videos and pamphlets. Teaching should focus on risk factor reduction and lifestyle modification such as smoking cessation, blood pressure management based on guidelines, screening for new-onset diabetes, and exercise as tolerated.
Enhancing Healthcare Team Outcomes
Educating patients at risk for coronary artery disease and making a closed-loop communication between them and their cardiologist for primary and secondary prevention can further improve the management of patients at risk of these CTO lesions. Collaboration with shared decision making (between primary care physician, cardiologist, and interventionist) and communication are vital elements for good outcomes in patients with coronary artery disease and CTO lesions.
The interprofessional team care provided to the patient must use an integrated care pathway combined with an evidence-based approach to evaluating CTO lesions. The earlier angiographic and demographic predictors of failure to revascularize are identified in CTO lesions; the better is the prognosis and outcome.
Media
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References
Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987 Jul:76(1):142-54 [PubMed PMID: 3109764]
Level 1 (high-level) evidenceIvanhoe RJ, Weintraub WS, Douglas JS Jr, Lembo NJ, Furman M, Gershony G, Cohen CL, King SB 3rd. Percutaneous transluminal coronary angioplasty of chronic total occlusions. Primary success, restenosis, and long-term clinical follow-up. Circulation. 1992 Jan:85(1):106-15 [PubMed PMID: 1728439]
Hajar R. Risk Factors for Coronary Artery Disease: Historical Perspectives. Heart views : the official journal of the Gulf Heart Association. 2017 Jul-Sep:18(3):109-114. doi: 10.4103/HEARTVIEWS.HEARTVIEWS_106_17. Epub [PubMed PMID: 29184622]
Level 3 (low-level) evidenceFefer P, Knudtson ML, Cheema AN, Galbraith PD, Osherov AB, Yalonetsky S, Gannot S, Samuel M, Weisbrod M, Bierstone D, Sparkes JD, Wright GA, Strauss BH. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter Chronic Total Occlusions Registry. Journal of the American College of Cardiology. 2012 Mar 13:59(11):991-7. doi: 10.1016/j.jacc.2011.12.007. Epub [PubMed PMID: 22402070]
Level 3 (low-level) evidenceClaessen BE, Dangas GD, Weisz G, Witzenbichler B, Guagliumi G, Möckel M, Brener SJ, Xu K, Henriques JP, Mehran R, Stone GW. Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial. European heart journal. 2012 Mar:33(6):768-75. doi: 10.1093/eurheartj/ehr471. Epub 2012 Jan 12 [PubMed PMID: 22240495]
Level 1 (high-level) evidenceCohen HA, Williams DO, Holmes DR Jr, Selzer F, Kip KE, Johnston JM, Holubkov R, Kelsey SF, Detre KM, NHLBI Dynamic Registry. Impact of age on procedural and 1-year outcome in percutaneous transluminal coronary angioplasty: a report from the NHLBI Dynamic Registry. American heart journal. 2003 Sep:146(3):513-9 [PubMed PMID: 12947372]
Kitta Y, Obata JE, Nakamura T, Hirano M, Kodama Y, Fujioka D, Saito Y, Kawabata K, Sano K, Kobayashi T, Yano T, Nakamura K, Kugiyama K. Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. Journal of the American College of Cardiology. 2009 Jan 27:53(4):323-30. doi: 10.1016/j.jacc.2008.08.074. Epub [PubMed PMID: 19161880]
Gawaz M, Neumann FJ, Dickfeld T, Koch W, Laugwitz KL, Adelsberger H, Langenbrink K, Page S, Neumeier D, Schömig A, Brand K. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation. 1998 Sep 22:98(12):1164-71 [PubMed PMID: 9743506]
Stone GW, Kandzari DE, Mehran R, Colombo A, Schwartz RS, Bailey S, Moussa I, Teirstein PS, Dangas G, Baim DS, Selmon M, Strauss BH, Tamai H, Suzuki T, Mitsudo K, Katoh O, Cox DA, Hoye A, Mintz GS, Grube E, Cannon LA, Reifart NJ, Reisman M, Abizaid A, Moses JW, Leon MB, Serruys PW. Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: part I. Circulation. 2005 Oct 11:112(15):2364-72 [PubMed PMID: 16216980]
Level 3 (low-level) evidenceGrantham JA, Jones PG, Cannon L, Spertus JA. Quantifying the early health status benefits of successful chronic total occlusion recanalization: Results from the FlowCardia's Approach to Chronic Total Occlusion Recanalization (FACTOR) Trial. Circulation. Cardiovascular quality and outcomes. 2010 May:3(3):284-90. doi: 10.1161/CIRCOUTCOMES.108.825760. Epub 2010 Apr 13 [PubMed PMID: 20388873]
Level 2 (mid-level) evidenceJoyal D, Afilalo J, Rinfret S. Effectiveness of recanalization of chronic total occlusions: a systematic review and meta-analysis. American heart journal. 2010 Jul:160(1):179-87. doi: 10.1016/j.ahj.2010.04.015. Epub [PubMed PMID: 20598990]
Level 1 (high-level) evidenceSapontis J, Salisbury AC, Yeh RW, Cohen DJ, Hirai T, Lombardi W, McCabe JM, Karmpaliotis D, Moses J, Nicholson WJ, Pershad A, Wyman RM, Spaedy A, Cook S, Doshi P, Federici R, Thompson CR, Marso SP, Nugent K, Gosch K, Spertus JA, Grantham JA. Early Procedural and Health Status Outcomes After Chronic Total Occlusion Angioplasty: A Report From the OPEN-CTO Registry (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures). JACC. Cardiovascular interventions. 2017 Aug 14:10(15):1523-1534. doi: 10.1016/j.jcin.2017.05.065. Epub [PubMed PMID: 28797429]
Stone GW, Reifart NJ, Moussa I, Hoye A, Cox DA, Colombo A, Baim DS, Teirstein PS, Strauss BH, Selmon M, Mintz GS, Katoh O, Mitsudo K, Suzuki T, Tamai H, Grube E, Cannon LA, Kandzari DE, Reisman M, Schwartz RS, Bailey S, Dangas G, Mehran R, Abizaid A, Moses JW, Leon MB, Serruys PW. Percutaneous recanalization of chronically occluded coronary arteries: a consensus document: part II. Circulation. 2005 Oct 18:112(16):2530-7 [PubMed PMID: 16230504]
Level 3 (low-level) evidenceMorino Y, Abe M, Morimoto T, Kimura T, Hayashi Y, Muramatsu T, Ochiai M, Noguchi Y, Kato K, Shibata Y, Hiasa Y, Doi O, Yamashita T, Hinohara T, Tanaka H, Mitsudo K, J-CTO Registry Investigators. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC. Cardiovascular interventions. 2011 Feb:4(2):213-21. doi: 10.1016/j.jcin.2010.09.024. Epub [PubMed PMID: 21349461]
Christopoulos G, Kandzari DE, Yeh RW, Jaffer FA, Karmpaliotis D, Wyman MR, Alaswad K, Lombardi W, Grantham JA, Moses J, Christakopoulos G, Tarar MNJ, Rangan BV, Lembo N, Garcia S, Cipher D, Thompson CA, Banerjee S, Brilakis ES. Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score. JACC. Cardiovascular interventions. 2016 Jan 11:9(1):1-9. doi: 10.1016/j.jcin.2015.09.022. Epub [PubMed PMID: 26762904]
Level 1 (high-level) evidenceHannan EL, Racz M, Holmes DR, King SB 3rd, Walford G, Ambrose JA, Sharma S, Katz S, Clark LT, Jones RH. Impact of completeness of percutaneous coronary intervention revascularization on long-term outcomes in the stent era. Circulation. 2006 May 23:113(20):2406-12 [PubMed PMID: 16702469]
Level 2 (mid-level) evidenceHannan EL, Wu C, Walford G, Holmes DR, Jones RH, Sharma S, King SB 3rd. Incomplete revascularization in the era of drug-eluting stents: impact on adverse outcomes. JACC. Cardiovascular interventions. 2009 Jan:2(1):17-25. doi: 10.1016/j.jcin.2008.08.021. Epub [PubMed PMID: 19463393]
Johnson LW, Lozner EC, Johnson S, Krone R, Pichard AD, Vetrovec GW, Noto TJ. Coronary arteriography 1984-1987: a report of the Registry of the Society for Cardiac Angiography and Interventions. I. Results and complications. Catheterization and cardiovascular diagnosis. 1989 May:17(1):5-10 [PubMed PMID: 2720767]
Dorros G, Cowley MJ, Simpson J, Bentivoglio LG, Block PC, Bourassa M, Detre K, Gosselin AJ, Grüntzig AR, Kelsey SF, Kent KM, Mock MB, Mullin SM, Myler RK, Passamani ER, Stertzer SH, Williams DO. Percutaneous transluminal coronary angioplasty: report of complications from the National Heart, Lung, and Blood Institute PTCA Registry. Circulation. 1983 Apr:67(4):723-30 [PubMed PMID: 6218938]
Kennedy JW. Complications associated with cardiac catheterization and angiography. Catheterization and cardiovascular diagnosis. 1982:8(1):5-11 [PubMed PMID: 7060118]
Noto TJ Jr, Johnson LW, Krone R, Weaver WF, Clark DA, Kramer JR Jr, Vetrovec GW. Cardiac catheterization 1990: a report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I). Catheterization and cardiovascular diagnosis. 1991 Oct:24(2):75-83 [PubMed PMID: 1742788]
Laskey W, Boyle J, Johnson LW. Multivariable model for prediction of risk of significant complication during diagnostic cardiac catheterization. The Registry Committee of the Society for Cardiac Angiography & Interventions. Catheterization and cardiovascular diagnosis. 1993 Nov:30(3):185-90 [PubMed PMID: 8269487]
Wyman RM, Safian RD, Portway V, Skillman JJ, McKay RG, Baim DS. Current complications of diagnostic and therapeutic cardiac catheterization. Journal of the American College of Cardiology. 1988 Dec:12(6):1400-6 [PubMed PMID: 2973480]
Brilakis ES, Banerjee S, Karmpaliotis D, Lombardi WL, Tsai TT, Shunk KA, Kennedy KF, Spertus JA, Holmes DR Jr, Grantham JA. Procedural outcomes of chronic total occlusion percutaneous coronary intervention: a report from the NCDR (National Cardiovascular Data Registry). JACC. Cardiovascular interventions. 2015 Feb:8(2):245-253. doi: 10.1016/j.jcin.2014.08.014. Epub [PubMed PMID: 25700746]