Continuing Education Activity

Chronic total occlusion (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. CTO revascularization has not shown benefit in rates of all-cause mortality, myocardial infarction, stroke, and repeat revascularization and is commonly performed to improve a patient's quality of life by reducing their angina symptoms. This activity reviews the evaluation and treatment of chronic total occlusion of the coronary artery and highlights the role of the interprofessional team in evaluating and treating this condition.

Objectives:

• Describe the histopathology of a chronic total occlusion (CTO) lesion.
• Review the risk factors for developing chronic total occlusion (CTO) lesions.
• Outline the typical presentation of a patient with chronic total occlusion (CTO) lesions.
• Explain the importance of improving care coordination amongst the interprofessional team( primary care physician, cardiologist, and interventionist) to enhance the delivery of care for patients with chronic total occlusion (CTO).

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

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]

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]

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.