European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, and coronary angiography continues to play a pivotal role in clinical decision-making regarding optimal management strategies, including medical therapy, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). A detailed understanding of angiographic findings is essential, particularly in patients with complex coronary anatomy. Multivessel disease is present in more than half of patients with CAD, and chronic total occlusion (CTO) is identified in approximately 16% of cases undergoing coronary angiography.¹˒² Despite its relatively high prevalence, CTO remains one of the most challenging lesion subsets in contemporary interventional cardiology.

Chronic total occlusions are frequently encountered during diagnostic coronary angiography; however, PCI for CTO lesions is performed infrequently. This reluctance is largely attributed to the high technical complexity of the procedure, prolonged procedural time, increased radiation exposure, perceived higher risk of complications, and the historical lack of robust randomized trial data demonstrating clear prognostic benefit. Consequently, CTOs are often managed conservatively, even in symptomatic patients. This discrepancy between prevalence and treatment underscores the ongoing uncertainty surrounding optimal management strategies for CTO.

CTOs are commonly regarded as the “final frontier” for interventional cardiologists because of their complex anatomy and procedural difficulty. Reported prevalence rates of CTOs vary widely, ranging from 16% to as high as 50% among patients with clinically significant CAD, although large registries generally report a prevalence of approximately 20%.³–⁶ Advances in guidewire technology, imaging modalities, and operator expertise have improved procedural success rates over time. Importantly, successful CTO-PCI has been associated with significant improvement in anginal symptoms, enhanced quality of life, improvement in left ventricular function, reduction in the need for subsequent CABG, and potential improvement in long-term survival. In patients presenting with ST-segment elevation myocardial infarction, the presence of a CTO in a non-infarct-related artery has been associated with larger infarct size, increased left ventricular end-diastolic pressure, impaired ventricular function, and worse clinical outcomes.

Evidence comparing revascularization strategies has demonstrated an early survival benefit of CABG over medical therapy alone, primarily in high-risk patients with severe coronary artery disease and impaired left ventricular function.⁷–¹⁰ However, similar survival benefits have not been consistently observed in studies comparing PCI with optimal medical therapy, possibly due to the inclusion of lower-risk populations. Consequently, PCI has traditionally been performed mainly for symptomatic relief rather than prognostic improvement, except in the setting of acute myocardial infarction.¹¹˒¹² This has further fueled debate regarding the role of PCI in the management of CTOs.

Considerable controversy persists regarding whether CTOs should be routinely treated and, if so, which patients are most likely to benefit. Myocardial viability, ischemic burden, symptom severity, and patient comorbidities are often considered when selecting candidates for revascularization.¹³ Although many CTOs develop collateral circulation that supplies blood flow to the distal myocardium, this collateral perfusion is frequently insufficient to prevent ischemia during exertion. The marked disparity between the high prevalence of CTOs and the relatively low rate of invasive treatment reflects not only the technical challenges and perceived procedural risks but also uncertainty regarding patient selection and expected clinical benefit.¹˒¹⁴

A “true” CTO is defined by complete interruption of coronary blood flow with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow, whereas lesions demonstrating minimal contrast penetration without distal vessel opacification are classified as “functional” CTOs with TIMI grade 1 flow.¹⁵ Prior to the widespread use of PCI for acute myocardial infarction, CTOs developed in approximately 30% of patients treated with thrombolytic therapy and in up to 45% of those who did not receive reperfusion therapy.¹⁵ These rates have declined with the advent of primary PCI; however, CTOs may still develop following failed interventions or due to subsequent vessel reocclusion. Understanding the clinical profile, angiographic characteristics, and outcomes of patients with CTO is essential for refining patient selection and optimizing management strategies. Given the evolving techniques and ongoing debate regarding the benefits of CTO revascularization, studies evaluating the clinical presentation and outcomes of CTO patients remain highly relevant.

The present study was undertaken to analyze the clinical profile of patients diagnosed with CTO of the coronary arteries and to describe their baseline demographic and clinical characteristics. It aimed to evaluate patient outcomes with optimal medical therapy, with or without PCI, in order to assess differences in short-term clinical response. The study also sought to characterize the angiographic profile of CTO lesions in this population, including vessel involvement and lesion characteristics. In addition, short-term prognosis was assessed using two-dimensional echocardiography, with particular emphasis on left ventricular systolic function as measured by ejection fraction (EF).

Study Design and Setting This was a prospective observational study conducted at Sri Jayadeva Institute of Cardiovascular Sciences and Research, a tertiary care referral center for cardiovascular diseases. The study included both inpatient and outpatient populations diagnosed with chronic total occlusion (CTO) of the coronary arteries. The study period extended from 1 January 2016 to 31 December 2018. A prospective design was chosen to allow systematic collection of clinical, angiographic, and echocardiographic data and to assess short-term outcomes following treatment. Study Population and Source of Data A total of 75 consecutive patients of either sex diagnosed with CTO were enrolled during the study period. Patients were identified from cardiology outpatient clinics and inpatient services after confirmation of CTO on coronary angiography. Relevant demographic, clinical, angiographic, and echocardiographic data were obtained through direct patient evaluation, medical records, and procedural documentation. All patients were managed according to standard institutional protocols. Definition of Chronic Total Occlusion Chronic total occlusion was defined as complete obstruction of a native coronary artery with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0. The occlusion was considered chronic if its estimated duration was at least three months. Chronicity was determined based on one or more of the following criteria: a documented history of sudden onset chest pain consistent with myocardial ischemia, evidence of a previous myocardial infarction in the territory supplied by the target vessel, or the time interval between CTO diagnosis on coronary angiography and the index procedure or clinical evaluation. Inclusion Criteria Patients were included in the study if they were aged over 18 years, of either sex, and had angiographically confirmed chronic total occlusion of a native coronary artery with TIMI grade 0 flow and an estimated occlusion duration of at least three months. All included patients were receiving optimal medical therapy for coronary artery disease, with or without subsequent percutaneous coronary intervention. Exclusion Criteria Patients were excluded if they had coexisting medical conditions limiting life expectancy to less than six months or likely to compromise protocol adherence, a recent acute myocardial infarction within seven days prior to enrollment, known hypersensitivity to aspirin or clopidogrel, or an increased risk of bleeding, including the need for oral anticoagulation, recent major bleeding, bleeding diathesis, or coagulation disorders. Pregnant or lactating women and patients with chronic kidney disease defined by a serum creatinine level greater than 2.5 mg/dL were also excluded from the study. Clinical and Angiographic Assessment All enrolled patients underwent detailed clinical evaluation, including assessment of cardiovascular risk factors, symptom status, and prior history of coronary artery disease or myocardial infarction. Coronary angiography was performed using standard techniques. Angiographic characteristics of the CTO lesions were documented, including the target vessel involved, extent of coronary artery disease, presence of collateral circulation, and associated non-occlusive lesions. Treatment strategy—optimal medical therapy alone or medical therapy with PCI—was determined by the treating cardiologist based on clinical presentation, angiographic findings, and patient suitability. Echocardiographic Evaluation and Outcome Assessment Two-dimensional transthoracic echocardiography was performed in all patients at baseline and during follow-up to assess left ventricular systolic function. Left ventricular ejection fraction (EF) was calculated using standard methods. Short-term prognosis was evaluated based on changes in echocardiographic parameters, particularly EF, along with clinical outcomes following medical therapy with or without PCI. The duration of short-term follow-up was defined according to institutional practice and clinical feasibility. Data Management All collected data were recorded in a structured proforma and subsequently entered into a computerized database. Continuous variables included age, laboratory values, and echocardiographic parameters, while categorical variables included sex, risk factors, angiographic characteristics, and treatment modality. Data accuracy was ensured through cross-verification with source documents. Statistical Analysis Both descriptive and inferential statistical analyses were performed. Continuous variables were expressed as mean ± standard deviation (SD) along with minimum and maximum values, while categorical variables were summarized as frequencies and percentages. Statistical significance was assessed at a 5% level (p < 0.05). The following assumptions were made for statistical testing: dependent variables were approximately normally distributed, samples were drawn randomly from the population, and observations were independent. The Student’s t-test (two-tailed, independent) was used to compare continuous variables between two groups. Associations between categorical variables were analyzed using the Chi-square test or Fisher’s exact test as appropriate. Fisher’s exact test was applied when expected cell counts were small to ensure validity of the results. All analyses were conducted in accordance with standard statistical practices. Data analysis was performed using Statistical Package for Social Sciences (SPSS) version 18.0 and the R statistical environment version 3.2.2. Microsoft Word and Microsoft Excel were used for data presentation, including generation of tables, graphs, and figures.

The study population comprised 75 patients with chronic total occlusion, with a mean age of 55.85 ± 11.17 years. The majority of patients belonged to the 51–60 year age group (32, 42.7%). Males predominated the cohort, accounting for 57 (76.0%) patients, while females constituted 18 (24.0%), indicating a clear male preponderance among CTO patients.

Table 1: Baseline Demographic Characteristics of the Study Population (N = 75)

Hypertension was the most prevalent comorbidity, observed in 37 (49.3%) patients, followed closely by diabetes mellitus and tobacco smoking, each present in 35 (46.7%) patients. Coexistence of both diabetes and hypertension was noted in 21 (28.0%) patients. Tobacco smoking was exclusively observed among male patients, highlighting its strong association with CTO in this population.

Table 2: Cardiovascular Risk Factors and Comorbid Conditions of the Study Population (N = 75)

Fatigue on exertion was the most common presenting symptom, reported by 31 (41.3%) patients, followed by chest pain in 29 (38.7%) and dyspnea in 15 (20.0%). On diagnostic evaluation, inferior wall myocardial infarction was the most frequent diagnosis, seen in 28 (37.3%) patients, followed by anterior wall myocardial infarction in 23 (30.7%) patients. Acute coronary syndromes in the form of unstable angina or NSTEMI were observed in nearly one-quarter of patients.

Table 3: Clinical Presentation and Final Diagnosis of the Study Population (N = 75)

Right coronary artery involvement was most common, observed in 42 (56.0%) patients, followed by the left anterior descending artery in 32 (42.7%) patients. Triple-vessel disease was present in 27 (36.0%) patients, while single-vessel disease accounted for 26 (34.7%). The majority of patients had a single CTO vessel (64, 85.3%), with multiple CTOs identified in a smaller proportion.

Table 4: Angiographic Profile of Chronic Total Occlusion of the Study Population (N = 75)

Most patients were managed conservatively with optimal medical therapy, accounting for 63 (84.0%) cases, while CABG and PCI were performed in 8 (10.7%) and 4 (5.3%) patients, respectively. Baseline echocardiography showed an ejection fraction between 40–60% in 68 (90.7%) patients. At three-month follow-up, left ventricular function remained stable in 71 (94.7%) patients, with improvement observed in only 3 (4.0%). Mitral regurgitation was present in 26 (34.7%) patients, predominantly mild in severity.

Table 5: Management Strategy and Short-Term Echocardiographic Outcome of the Study Population (N = 75)

Figure 1 shows that mitral regurgitation was more frequently observed among patients with inferior wall myocardial infarction (42.3%) compared to anterior wall myocardial infarction (38.5%); however, this association did not reach statistical significance. The absence of a significant relationship suggests that the occurrence of mitral regurgitation in CTO patients may be influenced by multiple factors beyond infarct location alone, including extent of ischemia and left ventricular remodelling.

Figure 1: Comparison of MI according to Mitral Regurgitation of patients studied

CTOs are frequently encountered in patients with CAD, with a reported prevalence of approximately 10–15%. Almost all patients with CTO demonstrate some degree of collateral filling to the occluded vessel. However, despite angiographically visible collaterals, fewer than 10% of patients exhibit a normal coronary flow reserve, indicating that collateral circulation often fails to adequately protect the myocardium from hypoxia or intermittent ischemia.¹⁶ Consequently, patients with CTO remain vulnerable to ischemic injury, particularly during increased myocardial demand.

Patients with CTO typically belong to an older age group and frequently present with multiple comorbid conditions. In the present study, the majority of patients were middle-aged, with a mean age of approximately 55 years. This is comparable, though slightly younger, than findings from a large Italian cohort where the mean age was reported as 62 years.¹⁷ A male predominance was observed, with 74% of patients being men and 26% women, which aligns with global trends and mirrors observations from a Latvian study that reported nearly 80% male predominance.

Our findings confirm that patients with CTO represent a high-risk subgroup of CAD, characterized by a high burden of traditional cardiovascular risk factors, multivessel coronary disease, and prior myocardial infarction or revascularization, consistent with previous reports.¹⁸ Notably, 14.7% of patients in our cohort had multiple CTOs involving separate coronary vessels, further emphasizing the advanced nature of coronary disease in this population. Previous studies have demonstrated that mortality among CTO patients is highest in those presenting with acute coronary syndromes, particularly ST-segment elevation myocardial infarction, followed by UA/NSTEMI, with the lowest risk observed in patients with stable angina. The adverse prognostic impact of CTO does not appear to differ significantly between coronary vessels; however, proximal CTOs within a given vessel have been associated with worse outcomes compared to distal lesions. Even distal CTOs confer a negative prognosis, supporting the concept that the extent and severity of ischemic burden play a central role in determining clinical outcomes.

The quality of collateral circulation appears to be influenced by microvascular integrity rather than solely by angiographic factors. While it is difficult to attribute collateral quality to specific patient characteristics, diabetes mellitus has been shown to adversely affect the cardiac microvasculature, leading to impaired myocardial contractility and increased ventricular stiffness.¹⁹ This mechanism may partly explain the worse outcomes observed in diabetic patients with CTO.

The true prevalence of CTO in the general population remains uncertain. Earlier studies conducted in small cohorts reported prevalence rates as high as 35–52% among patients with significant CAD.²⁰ In contrast, a Canadian study involving 1,697 patients reported a CTO prevalence of 14.7% among individuals undergoing coronary angiography.²¹ CTO prevalence was notably higher in patients with prior CABG and lower among those presenting with acute coronary syndrome undergoing primary PCI. In our study, most patients had stable angina, although nearly one-quarter (24%) presented with acute coronary syndrome at the time of CTO diagnosis.

A high prevalence of tobacco smoking was observed in our cohort (46.7%), exceeding rates reported in European studies and highlighting tobacco use as a significant modifiable risk factor in the Indian population. Diabetes mellitus and hypertension were also highly prevalent, further reinforcing their role in the pathogenesis of CTO. The right coronary artery was the most commonly affected vessel, followed by the left anterior descending and left circumflex arteries, consistent with prior literature. The proportion of patients with prior myocardial infarction in our study (24%) was lower compared to reports from the National Cardiovascular Data Registry, which reported rates approaching 73%.²²

In terms of management, the majority of patients (84%) in our study were treated conservatively with optimal medical therapy, with a smaller proportion undergoing PCI or CABG. Evidence suggests that successful CTO-PCI improves angina, quality of life, left ventricular function, and exercise tolerance while reducing the need for CABG and long-term cardiac mortality. However, appropriate patient selection remains critical. Assessment of myocardial viability, symptom burden, ischemic territory, and response to medical therapy should guide revascularization decisions. CABG remains preferable in patients with left main disease, complex triple-vessel disease, diabetes with severe left ventricular dysfunction, chronic kidney disease, or high J-CTO scores.

An increased ischemic burden associated with CTO can result in progressive myocardial dysfunction, larger infarct size, and electrophysiological instability. The adverse prognostic impact of CTO is particularly pronounced in patients presenting with STEMI, as demonstrated in prior studies.²³

Gender-based differences in CTO outcomes remain incompletely understood. In our cohort, which included 24 women, no significant differences were observed between men and women in terms of clinical presentation, angiographic profile, or echocardiographic parameters. These findings suggest that CTO confers a similarly adverse prognosis in both sexes. The EXPLORE trial further demonstrated that early CTO-PCI following STEMI did not result in significant improvement in left ventricular ejection fraction or end-diastolic volume at four months when compared to conservative management.²⁴

Although the sample size of our study limits definitive conclusions regarding the comparative effectiveness of different management strategies, our findings, in conjunction with existing literature, suggest that optimal medical therapy remains appropriate for most patients with stable symptoms and no high-risk features.

This prospective study demonstrates that chronic total coronary occlusions predominantly affect middle-aged and elderly males, with a high prevalence of tobacco smoking and traditional cardiovascular risk factors such as diabetes and hypertension. Patients with CTO exhibit a distinct clinical profile characterized by more severe coronary disease and increased non-coronary comorbidities compared to patients with non-occlusive CAD. In resource-limited settings, advanced CTO revascularization techniques are underutilized due to cost constraints and limited operator expertise, resulting in most patients being managed conservatively or referred for CABG, although diffuse disease often limits graftability. These findings underscore the need for stronger preventive strategies, targeted risk-factor modification, and improved training in CTO revascularization techniques. CTO revascularization should not be avoided solely based on historical perceptions of poor success or high resource utilization, but rather guided by careful patient selection and contemporary evidence.

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