Complications in Coronary Chronic Total Occlusion Interventions for Cath Lab: A Systematic Review By MaCalin Mitchell RN, RCIS Devan Shaul Daniel Wilkinson A thesis submitted to the School of Radiologic Sciences in collaboration with a research agenda team In partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN RADIOLOGIC SCIENCES (MSRS) WEBER STATE UNIVERSITY Ogden, Utah December 13, 2024 ii THE WEBER STATE UNIVERSITY GRADUATE SCHOOL SUPERVISORY COMMITTEE APPROVAL of a thesis submitted by MaCalin Mitchell BSN, RN, RCIS Devan Shaul Daniel Wilkinson This thesis has been read by each member of the following supervisory committee and by majority vote found to be satisfactory. ______________________________ Dr. Tanya Nolan, EdD Chair, School of Radiologic Sciences ______________________________ Christopher Steelman, MS Director of MSRS Cardiac Specialist ______________________________ Dr. Laurie Coburn, EdD Director of MSRS RA ______________________________________________________________________ Dr. Robert Walker, PhD Director of MSRS iii THE WEBER STATE UNIVERSITY GRADUATE SCHOOL RESEARCH AGENDA STUDENT APPROVAL of a thesis submitted by MaCalin Mitchell BSN, RN, RCIS Devan Shaul Daniel Wilkinson This thesis has been read by each member of the student research agenda committee and by majority vote found to be satisfactory. Date December 5, 2024 ____________________ ___________________________ MaCalin Mitchell December 5, 2024 ____________________ ___________________________ Devan Shaul December 5, 2024 ____________________ ______________________________ Daniel Wilkinson iv Abstract Coronary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) represents a highly specialized area within interventional cardiology, requiring advanced skills to address the procedural complexity and elevated risk of complications in the catheterization laboratory (cath lab). This thesis systematically reviews the types, causes, and management strategies for CTO PCI complications, categorizing them into coronary, non-coronary cardiac, and non-cardiac complications. With the complexity and potential risks associated with CTO PCI remaining higher than non-CTO PCI, understanding what the most common complications can occur and establishing guidelines for cath lab teams are important for these procedure. These complications contribute significantly to procedural morbidity, highlighting the necessity for targeted management protocols and cath lab team knowledge. Using a case study design and analysis, this study assesses 34 cases to highlight trends in complication types, patient demographics, and management outcomes. This thesis systematically reviews common complications in CTO PCI. The most common complication that was observed in over 50% of the 34 case studies analyzed was coronary perforations. Coronary perforations, frequently resulting from retrograde techniques and guidewire manipulation, were most common in collateral arteries. They often involved septal and epicardial collaterals and led to cardiac hematomas and tamponade. Other complications identified included coronary dissections, sidebranch occlusions, equipment entrapment, and non-coronary issues such as aortic dissections and hypotension, often exacerbated in older patients with complex lesion profiles. Through a case study approach, this research found that cath lab teams’ need for preparedness in managing coronary perforations along with other complications is necessary when being part of these procedures. Recommendations based on these findings include implementing CTO PCI- v specific emergency protocols, ensuring availability of essential equipment like covered stents and balloon occlusion devices, and educating cath lab staff on management options specific to CTOs. This research emphasizes the need for standardized CTO protocols and enhanced training, which could significantly reduce complication rates and improve procedural success, ultimately advancing patient safety and outcomes in CTO PCI. vi Acknowledgements I would like to give a special thanks to Dr. Jared Crisafi for his invaluable advice and insights, which were essential in helping this project reach its full potential. Also, thank you to the Master of Science in Radiologic Sciences cohort, with special appreciation to Chris Steelman, for their invaluable support, guidance, and encouragement throughout this project. Lastly, a thank you to my family and friends that showed continued support and encouragement, without it, I do not think this would have been possible. vii Table of Contents Chapter 1: Introduction ................................................................................................... 1 Background ............................................................................................................... 1 Statement of the Problem .......................................................................................... 2 Research Questions ................................................................................................... 3 Nature of the Study ................................................................................................... 3 Research Method and Design .......................................................................................................... 4 Qualitative Research ....................................................................................................................... 4 Case Study Design........................................................................................................................... 5 Data Collection and Analysis .......................................................................................................... 5 Significance of the Study........................................................................................... 5 Definition of Key Terms............................................................................................ 6 Summary ................................................................................................................... 7 Chapter 2: Clinical Background ...................................................................................... 8 Etiology .................................................................................................................... 8 Epidemiology ............................................................................................................ 8 Pathophysiology ........................................................................................................ 9 History and Physical.................................................................................................. 9 Evaluation ............................................................................................................... 10 Treatment / Management Options ............................................................................ 12 Summary ................................................................................................................. 12 Chapter 3: Literature Review......................................................................................... 13 Introduction ............................................................................................................. 13 Key Factors Contributing to CTO Complications .................................................... 14 CTO Complications ................................................................................................. 15 Coronary Complications .......................................................................................... 15 Coronary perforations ............................................................................................................... 15 Collateral Coronary complications ........................................................................................... 16 Coronary Dissections................................................................................................................. 17 Side-branch Occlusions ............................................................................................................. 18 Equipment Entrapment/Loss ...................................................................................................... 18 No Reflow ................................................................................................................................... 19 Non-coronary Complications ................................................................................... 20 Aortic Dissection ....................................................................................................................... 20 Pericardial Tamponade ............................................................................................................. 20 Mycardial Infarction .................................................................................................................. 20 Hypotension ............................................................................................................................... 21 Arrhythmias................................................................................................................................ 21 Thromboembolic Events............................................................................................................. 22 Non-cardiac Complications ..................................................................................... 22 Vascular Access Complications................................................................................................. 23 Contrast Induced nephropathy/Allergy ...................................................................................... 23 Radiation Injuries ..................................................................................................................... 24 Strategies for Managing CTO Complications .......................................................... 25 Coronary Complication Management.......................................................................................... 26 Non-coronary Complication Management................................................................................... 30 viii Non-cardiac Complication Management ..................................................................................... 32 Summary ................................................................................................................. 34 Chapter 4: Research Method ......................................................................................... 35 Research Methods and Design(s) ............................................................................. 35 Population ............................................................................................................... 36 Sample .................................................................................................................... 36 Data Collection, Processing, and Analysis ............................................................... 36 Assumptions ............................................................................................................ 37 Limitations .............................................................................................................. 37 Delimitations ........................................................................................................... 38 Ethical Assurances .................................................................................................. 38 Summary ................................................................................................................. 39 Chapter 5: Findings ....................................................................................................... 40 Results .................................................................................................................... 40 Evaluation of Findings ............................................................................................ 41 Summary ................................................................................................................. 41 Chapter 6: Implications, Recommendations, and Conclusions ....................................... 42 Implications ............................................................................................................ 42 Recommendations ................................................................................................... 45 Conclusions ............................................................................................................. 47 Appendices ................................................................................................................... 49 References .................................................................................................................... 51 1 Chapter 1: Introduction Chronic total occlusion (CTO) interventions represent a challenging area of coronary artery disease management, often requiring specialized skills and techniques within the catheterization laboratory (cath lab). The prevalence of CTOs diagnosed in patients are 1620%.1,2 With almost a fifth of patients having a CTO, treatment with percutaneous coronary interventions (PCI) is the desired method in about 10-15% of these patients.5 The main indication of a PCI for CTOs is improvement in ischemic symptoms.1 Despite advancements in interventional cardiology, CTO procedures are associated with higher rates of complications compared to other coronary lesions. These complications can range from unsuccessful procedures to major adverse cardiac events (MACE), necessitating a thorough understanding and systematic approach by cath lab teams.2,3 With the complexity and potential risks associated with CTO interventions remaining higher than other PCI, understanding what the most common complications can occur and establishing guidelines for cath lab teams are important for any CTO procedure. These guidelines should include pre-procedural planning, patient selection criteria, procedural techniques, and management of complications.1 By standardizing protocols and optimizing teamwork within the cath lab, guidelines would improve procedural success rates, minimize complications, and enhance patient safety and outcomes. Background CTOs are usually the most challenging PCIs within the field of coronary artery disease management. Interventional cardiologists often face difficulties in treating CTOs due to their complex nature and the associated risks. PCIs are starting to become a common approach to manage CTO symptom management; however, they pose significant challenges compared to 2 interventions that involve non-CTO lesions. CTO PCIs are performed to manage patient symptoms and often times, the risk does not outweigh the benefits.1,2 With continued technology advancement and more experience, these procedures are becoming more common and streamlined within cath labs today.3 CTO PCIs are associated with a higher incidence of complications, including coronary and non-coronary complications. Coronary complications primarily involve issues directly related to the coronary arteries, such as perforation, dissection, Side-branch Occlusions, no reflow, and equipment entrapment/loss, which can lead to immediate risks requiring urgent intervention. Non-coronary complications encompass a broad spectrum of cardiac and systemic issues, extending beyond the coronary arteries. These may include aortic dissection, pericardial tamponade, periprocedural myocardial infarction, arrhythmias, and non-cardiac complications arising from procedural factors.3,4 Statement of Problem The complex nature of CTO interventions, coupled with the potential for complications, validates the importance of understanding what complications can occur and implementing strategies to mitigate risks. Key factors that contribute to CTO complications include patient demographics, lesion characteristics, and procedural factors.2 Also, the lack of standardized training and technical complexity of these procedures further exposes the challenges faced by interventional cardiologists and cath lab staff. While advancements in technology and procedural techniques have improved success rates, complications remain a concern, particularly in less experienced cath labs and new CTO programs.6 Efforts to improve complication preparedness, management, and patient outcomes requires the knowledge, understand, and current recommendations in being prepared during the procedure.4 3 A comprehensive understanding of complications and effective management strategies is important for increasing patient safety and procedural success in CTO PCIs. Therefore, further research is required to explore case studies, common complications, mechanisms, and management of complications during CTO PCIs, with the aim of improving CTO knowledge and developing guidelines from this research. Research Questions Understanding the most common complications that can happen during CTO interventions and the contributing factors is important for any cath lab staff involved. Complications that put the patient at risk acutely can and will eventually happen and are influenced by factors like lesion complexity, operator experience, and patient comorbidities. Identifying and planning for different CTO complications and procedure factors can guide strategies to improve patient safety and success.1 Investigating the correlation between specific CTO complication data, demographics, and rates will allow cath lab staff to develop ideal approaches in helping interventional cardiologists manage these complications effectively and quickly. Research questions that will be addressed in this thesis include: Q1. What are the different types of complications that can occur during CTO PCI? Q2. What are the most commonly occurring complications during CTO PCI? Q3. What can cath lab staff do to prepare to manage CTO complications when they happen? Nature of the Study Establishing guidelines for optimizing CTO PCIs for cath lab staff requires an approach that involves various aspects of interventional cardiology. With an importance based on evidence-based practice, this study uses various techniques including a clinical background and 4 detailed literature review on different CTO complications, current management of CTO complications, review of CTO complication case studies, and recommended guidelines to follow for CTO PCIs. Through a detailed literature review and case study analyses, it will aim to improve cath lab staff knowledge and confidence in managing complications that occur by providing recommended guidelines for the most common complication of CTO PCI. Furthermore, the research aims to focus on the factors influencing CTO treatment decision-making, considering patient demographics, comorbidities, and lesion characteristics. By addressing these different areas, this research contributes to advancing a more thorough understanding and management of one of the most challenging procedures of coronary artery disease (CAD) and educating cath lab teams involved with CTO PCI procedures. Research Method and Design The purpose of this thesis is to consider and discuss the complexities of CTO complications through literature review and case study analysis. The subsequent review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Recognizing the unique aspects of CTO complications and the increased frequency of these procedures being performed, a case study design was chosen as it provides real cases that occurred and opportunity to gain a more comprehensive understanding of the most common CTO complications. Qualitative Research A qualitative method was chosen for its potential to support the different analyses of patients with CTOs and the most common complications. Quantitative studies predominantly offer statistical insights that would be valuable to this thesis to further understand the different 5 aspects of statistical analysis of CTO complications; however, a qualitative approach will allow assessing the entirety of the case studies reviewed. Case Study Design Case studies are particularly helpful when examining occurrences of CTO complications within real-life settings. In this thesis, the case study design facilitates a multi-faceted investigation of CTO complications by incorporating various perspectives and experiences to understand the most commonly occurring complications. Data Collection and Analysis Data will be gathered through careful web-based searches via PubMed, Weber State University’s Stewart Library online database, and Google Scholar utilizing specific keywords. This comprehensive search method provided an extensive search of the available literature and case studies, presenting both conclusions and valuable personalized perspectives of CTO PCI complications. For data analysis, thematic analysis methods were implemented, utilizing a process which involved authors performing multiple reviews of the data, refining information and themes with each assessment. Significance of the Study CTO PCI represents one of the most difficult aspects of CAD management within interventional cardiology.1 As the complexity and risk associated with these procedures are significantly higher than those of other coronary interventions, the need for specialized knowledge and skills is required. This research is significant as it seeks to address the critical knowledge needed for complications and establish guidelines for cath lab staff when involved with CTO PCIs, in hopes of standardizing practices. 6 This research has the potential to enhance the safety and efficacy of CTO procedures by educating cath lab staff. By systematically analyzing the most common complications and best practices for managing complications. This research will provide valuable insights for cath lab teams and the development of evidence-based guidelines will reduce variability in procedural success rates and minimize adverse events. Furthermore, this study contributes to the broader field of interventional cardiology by addressing a gap in the current literature regarding CTO-specific complication management for cath lab staff. With the integration of advanced technologies and a focus on evidence-based practices, this research will draw attention to unmet education for cath lab staff on CTO PCIs. The findings of this thesis are expected to inform both clinical practice and future research. Possibly, this study is an essential step towards advancing the management of one of the most complex and high-risk areas of CAD. Definition of Key Terms Antegrade Approach: A technique in PCI where the guidewire and other instruments are advanced in the direction of normal blood flow, typically from the origin to the end of the occlusion.9 Coronary Artery Disease (CAD): condition characterized by the narrowing or blockage of the coronary arteries1 Chronic Total Occlusion (CTO): A condition characterized by the complete blockage of a coronary artery for a duration of three months or longer, leading to significant challenges in revascularization procedures.36 Collateral Circulation: A network of small blood vessels that develop to bypass a blocked artery, providing an alternative route for blood to reach the affected heart tissue.36 7 CTO Complexity Score: A system used to evaluate the difficulty of a CTO procedure based on factors such as the length of the occlusion, degree of calcification, and tortuosity of the artery.13 Major adverse cardiac events (MACE): include several key events that reflect significant cardiovascular complications.9 Percutaneous Coronary Intervention (PCI): A non-surgical procedure used to treat narrowed or blocked coronary arteries, including those with CTOs, by using techniques such as balloon angioplasty and stent placement.1 Retrograde Approach: A technique in PCI where the guidewire and other devices are advanced in the opposite direction of normal blood flow, often through collateral vessels, to access and treat the CTO from the distal end.9 Subintimal Space: The area between the inner and outer layers of the artery wall, which may be intentionally entered during certain CTO procedures to facilitate the advancement of the guidewire.11 Wire Escalation: A step-by-step approach to advancing progressively more specialized guidewires through a CTO to successfully cross the blockage and achieve revascularization.13 These key terms are fundamental when working in the cath lab, particularly those involved in managing CTOs. They provide a common language to effectively communicate the complexities of these high-risk procedures. Summary This thesis introduces the complexity and challenges associated with CTO PCI, a specialized area within interventional cardiology that requires advanced skills and techniques in 8 the cath lab. Despite technological advancements, CTO procedures carry a higher risk of complications compared to other coronary interventions, making the establishment of standardized guidelines needed for cath lab staff.2 These guidelines will provide all aspects of CTO procedures, from pre-procedural planning to management of the complications, with the aim of improving procedural success rates and patient safety. The goal of this thesis includes research into the most common CTO complications and effective management strategies and the ultimate goal of enhancing cath lab preparedness and managing them when they occur. Chapter 2: Clinical Background Etiology CTOs are a complete obstruction of any coronary artery that has been there for at least three months. The primary etiology is the slow progression of atherosclerosis, the plaque builds up and narrows the coronary arteries over time. Eventually, the artery becomes completely occluded, resulting in no blood flow. Contributing risk factors include smoking, hypertension, diabetes, hyperlipidemia, and a history of myocardial infarction (MI), which predisposes individuals to CTO development. CTOs are associated with a prior MI in 40% of patients and further emphasizes the role of coronary artery disease (CAD).1, 3, 36 Epidemiology The prevalence of CTOs diagnosed in patients are 16-20% as mentioned earlier.1,2 With almost a fifth of patients having a CTO, treatment with PCI is the desired method in about 1015% of these patients.5 The main indication of a PCI for CTOs is improving ischemic symptoms.1 CTOs affect males, 85% to 98%, more commonly and typically occur in older individuals. There is a 37% prevalence of CTOs in patients under the age of 65 years old. There is a 40% prevalence in patients between the ages of 65 to 79 years old and 41% in patients who 9 are older than 85 years.37 The right coronary artery (RCA) is the most commonly affected vessel, around 43% to 55% of CTOs and is followed by the left anterior descending artery (LAD) in about 24% of cases and the left circumflex artery (LCx) being the least common with 7% to 20%.36 Pathophysiology CTOs result from a complete occlusion of a coronary artery due to atherosclerotic plaque building up until the vessel is completely occluded. The plaque becomes fibrotic and calcified over time. The heart and vasculature start to generate bridging arteries called collaterals that grow to supply the affected myocardial areas. Although collateral circulation may develop to supply the affected region, it is often not enough circulation to meet the metabolic demands, especially during physical exertion, leading to ischemic symptoms such as angina. Autopsy studies have shown that thrombus within the occluded coronary arteries become reorganized into collagen-dense fibrous tissue, leading to calcification as the lesion ages.36 Calcified lesions are very difficult to treat and often require specialized equipment and techniques to get past.37 History and Physical Examination CTO lesions are usually diagnosed in patients that have selective coronary angiography done for evaluation of CAD, ischemic heart disease, cardiomyopathy, or valvular heart disease. The history and physical examination will show similar signs and symptoms as patients with CAD. Patients with CAD or ischemic heart disease commonly present with symptoms such as stable or unstable angina, atypical chest pain, or acute coronary syndromes like NSTEMI or STEMI. Patients will often complain of symptoms such as shortness of breath and chest pain or tightness on exertion and relief by resting or medication. When taking a history in patients 10 suspected of CAD or ischemic heart disease, it is important to have them describe their symptoms in detail and severity.36, 37 In addition to symptom characterization, the history should cover risk factors for cardiovascular disease, including diabetes, tobacco use, hypertension, hyperlipidemia, and a sedentary lifestyle. Many patients with CTOs report chronic stable angina, or a history of prior cardiovascular events such as MI or coronary artery bypass grafting (CABG).36, 37 Physical examination should include auscultation of heart and lung sounds, along with an assessment for signs of heart failure. Signs of heart failure may include jugular venous distension, Kussmaul’s sign, hepatojugular reflex, ascites, and peripheral edema. Specific findings in CTO patients can include a displaced apical impulse, indicating left ventricular dysfunction, and pulmonary crackles, suggesting heart failure due to ischemic cardiomyopathy.37 In general, signs of acute ischemia are typically absent unless the patient is presenting with an acute coronary syndrome. The severity of symptoms often depends on the extent of collateral circulation and the degree of occlusion; patients with subtotal occlusions may experience exertional chest pain and fatigue, while those with complete occlusions often have symptoms even at rest, which may be refractory to medical therapy.36, 37 The diagnosis of CTO is based on clinical presentation, risk factors, and imaging modalities such as coronary angiography, cardiac CT, or stress PET/CT. These imaging modalities help assess the extent of coronary occlusion and collateral circulation.36 Evaluation As part of a patient’s initial evaluation, CTOs are assessed using a variety of diagnostic imaging modalities, like those used to evaluate coronary artery disease, with each choice of modality being dependent on the patient’s clinical presentation and examination. An 11 electrocardiogram (ECG) is an easy, yet cost-effective tool that is used to assess the heart’s electrical activity. An ECG provides crucial information regarding acute and chronic cardiac conditions and can show signs such as arrhythmias, ischemia, and ventricular hypertrophy. Echocardiography, a technique based from ultrasound imaging, allows for a more detailed and accurate assessment of heart function, valvular conditions, and the pericardium. Echocardiography is used in both acute and chronic settings which also helps guide certain therapeutic procedures. Cardiac stress testing, which can be performed using both pharmacological stress agents such as dobutamine or through exercise assess the presence of CAD by evaluating abnormal ECG changes or any anginal symptoms that may arise during induced stress on the heart.36, 37 Blood work is a key diagnostic marker in assessing for any acute coronary events. Cardiac enzymes, most common one being troponins and markers such as BNP are used to assess heart damage and heart failure. In chronic CAD management, inflammatory markers such as C-reactive protein (CPR) and lipid levels provide important prognostic information. These markers ultimately can increase the risk of heart attack and plaque formation. Lastly, the gold standard for diagnosing CAD is cardiac catheterization. A cardiac catheterization offers direct imaging of all coronary arteries through a catheter-based angiogram procedure. This procedure is highly accurate; however, it is an invasive procedure and is reserved for high-risk patients and carries some inherent risk.36 12 Treatment/Management Options CTOs in coronary arteries present significant challenges in cardiovascular management. The treatment and management options for CTOs have evolved considerably, focusing on percutaneous and surgical approaches. Treatment choice often depends on the patient's clinical presentation, the occlusion characteristics, and the presence of collateral circulation. Studies indicate that hybrid approaches, combining traditional PCI with adjunctive techniques, can enhance outcomes. For instance, the OPEN-CTO study demonstrated that patients undergoing hybrid procedures experienced better health status and symptom relief than those receiving optimal medical therapy alone. 36 The management of CTOs involves a multifaceted approach that includes percutaneous interventions, surgical options, and emerging endovascular techniques. The choice of treatment should be individualized, taking into account the specific characteristics of the occlusion and the patient's overall health status. Ongoing research and clinical trials will continue to refine these approaches, aiming to improve patient outcomes and quality of life for those affected by CTOs.36 Summary CTOs are the slow progression of atherosclerosis. Risk factors such as smoking, hypertension, diabetes, and a history of myocardial infarction (MI) contribute to their development. CTOs affect up to 20% of patients undergoing coronary angiography, with males and older individuals being more commonly affected.1 The RCA is the most frequently involved vessel. Although collateral circulation can develop to supply blood to the occluded area, it is often insufficient, leading to ischemic symptoms like angina.36, 37 13 Patients with CTOs often present with symptoms similar to CAD, such as stable or unstable angina, shortness of breath, and chest pain, especially during exertion. Physical examination may reveal signs of heart failure, including jugular venous distension or pulmonary crackles. Diagnosis typically relies on coronary angiography, cardiac CT, or stress imaging, which help assess the extent of the occlusion and collateral circulation. While signs of acute ischemia are typically absent unless the patient has an acute coronary syndrome, symptom severity often correlates with the extent of the occlusion.37 Management of CTOs involves a combination of percutaneous and surgical interventions. Hybrid approaches, such as combining PCI with adjunctive techniques, have shown to provide better symptom relief than medical therapy alone. Treatment decisions should be individualized based on the occlusion characteristics and the patient's overall health. Ongoing research continues to refine treatment strategies to improve outcomes for CTO patients. Chapter 3: Literature Review Introduction CTOs exist when a coronary artery is completely blocked for at least three months and are difficult to treat for an interventional cardiologist. Once the patient consents to have a PCI of a CTO, they are extremely more complex and dangerous compared to non-CTO coronary lesions. The field of CTO PCI has many complex aspects and challenges and requires a thorough understanding of various complications that may arise during these procedures as they are more likely to occur. Coronary complications, which occur directly to the coronary arteries, present significant risks and demand careful management. Non-coronary complications extend beyond the coronary arteries, forming a broad spectrum of cardiac complications. On the 14 other hand, non-cardiac complications involve systemic or procedural issues outside the coronary arteries and cardiac system.1 A detailed exploration of the contributing factors and complications are essential for cath lab staff to navigate the intricacies of CTO PCI, prioritize patient safety, and optimize procedural success. Key Factors Contributing to CTO Complications To understand what complications are involved with CTO, it is important to understand key factors contributing to their occurrence. The key contributing factors account for several critical aspects even before the procedure starts. Clinical decision-making allows for better procedural planning, technique selection, and risk mitigation. Patient safety in CTO interventions should be at the forefront of these procedures. Let us discuss the complex nature of interventions, potential for periprocedural complications, and long-term outcomes. With CTO procedures being more complex in nature, the potential for periprocedural complications increases for the patient. CTO PCI has higher complication rates than PCI with major cardiac events: 1.6%-3.3% vs 0.8%-1.4%; death: 0.4%-1.4% vs 0.3%-0.7%. Also, studies reveal longer procedure durations, heightened radiation exposure, and increased resource consumption during CTO PCI. Key challenges that influence the success of these procedures include technical complexity, steep learning curves, and lack of standardized training.3 Before the procedure is performed, an assessment is done with one or more CTO PCI scoring systems to see how safe it would be to continue with the procedure. These scales look at specific patient key contributing factors on looking at complications and feasibility of the PCI. These scales each have their own factors they take into consideration on deciding if the CTO PCI is achievable. Some common factors include >65 years old, female, calcium within 15 the target CTO lesion, location of CTO lesion, left ventricular ejection fraction assessment, coronary tortuosity, lesion proximal cap ambiguity, coronary artery bypass graft surgery, and comorbidities.13 Examples of CTO scores include J-CTO, PROGRESS-CTO, RECHARGE, CASTLE, CTO-COMPLICATIONS, and OPEN-CLEAN.25 Complication rates vary due to patient and procedure factors and further show that many patient aspects should be assessed before the procedure is started.13 CTO Complications Coronary Complications Coronary complications, intrinsic to CTO procedures, have a spectrum of issues. They should be prevented and be able to manage them when they occur. Some complications are more acute than others and should be managed as soon as possible, while some complications require complex decision making for the best management. Coronary Perforations Coronary perforations happen when a hole or tear occurs along any of the coronary vessels. This complication causes blood to leak out of the artery and into the surrounding area. They are associated with a 5-fold increase with in-hospital mortality, 10%-15%, because it can lead to cardiac tamponade and hemodynamic compromise.32 Perforations are classified using the Ellis classification system. It categorizes coronary artery perforations into three classes based on severity. Class I involves a minor perforation with extraluminal crater formation but no significant leakage. Class II is a moderate perforation with contrast leakage into the pericardium or myocardium, creating a "blushing" effect, but without a clear jet of extravasation. Class III is the most severe, with free extravasation of contrast outside the 16 coronary artery, posing a high risk for complications like cardiac tamponade, often requiring urgent intervention.8 Kostantinis et al. mentions a study that analyzed 10,454 CTO PCIs performed on 10,219 patients between 2012 and 2022. The perforation rate was 4.9%, about 500 perforations total. Of those 500 perforations, guidewire exit was the most common cause and retrograde approach was responsible in 47% the perforations.7 The most severe perforations occur in any of the main vessels such as the left main coronary artery (LMCA), left anterior descending artery (LAD), circumflex artery (LCX), and right coronary artery (RCA). Other vessels susceptible to perforations are distal vessels and collateral vessels, such as septal and epicardial vessels.1 Perforations can be one of the most severe complications of CTO PCI and the cath lab team must be assessing for them during any coronary angiography images. Perforations can lead to cardiac hematomas, usually occurring pericardial, intramyocardial, or intracavitary spaces.6 If perforations go unnoticed, the patient is at risk for acute decompensation or if there is a small perforation, symptoms begin to show hours later. As the perforations progress, whether they are large or small, can pressure on the cardiac muscles or block creating serious problems for the patient.9 Collateral Circulation Complications Collateral circulation occurs when new vessels generate to “bypass” the blockage and the interventional cardiologist will sometimes put the guidewire through these to get to the lesion, this is known as retrograde approach.9 Collateral flow can be assessed using angiography. Four grades are used to describe the extent of collateral flow: (0) no visible 17 collateral channels, (1) filling of side branches of the blocked artery, (2) partial filling of the main blocked vessel, and (3) complete filling of the main epicardial vessel. The occurrence of angiographically visible collaterals can be a positive prognosis for the patient. The collaterals are often small and can easily perforate. Any type of mechanical trauma during attempts to cross or treat the occluded segment could perforate or dissect the artery. As mentioned above, 47% of the perforations happened when using a retrograde approach, so collateral attempts are riskier than antegrade approach. If any coronary complications occur in collateral vessels, it is known as donor vessel closure and is very serious complications due to extensive ischemia and hemodynamic decompensation.9 If only collateral circulation is supplying the CTO, closure of it will cut off any blood flow and closure of the entire main vessel as well. Coronary Dissections Coronary dissections are a complication that requires careful evaluation and management to prevent further vessel injury and adverse outcomes, but can also be an intentional strategy to cross the CTO. A dissection occurs when the inner layer, the intima, tears. Blood enters the space between the intima and the middle layer, the media, creating a false lumen, potentially cutting off true lumen flow of the vessel depending on severity. Page et al. studied coronary dissections during PCI procedures between 2014-2019. They found that 141 of 10,278 PCI or 1.4%, had coronary dissections. They most commonly occur due to guidewire advancement and outcomes are better when the guidewire remains positioned across the dissection. Stenting is the most frequent treatment method with MACE occurring in about 1 in 4 patients. 9,10 18 Often, dual injection is used for CTO PCIs to view antegrade and retrograde flow. If a dissection plane is noticed, additional injections against the dissection flap can potentially make the dissection worse from forcing contrast against the dissection layer.9 Dissections can range from minor and easily manageable to severe that have closed off the vessel. Dissections may be utilized to the interventional cardiologist’s advantage. They will often utilize the subintimal space to cross the CTO and enter back into the lumen. These strategies include antegrade dissection-reentry (ADR) and subintimal tracking and re-entry (STAR).9, 10 Side-branch Occlusions A side-branch (SB) occlusion occurs when a smaller artery branching off from the main coronary artery becomes blocked or closed off.2 This complication can happen when a stent is placed in the main artery and causes a “snowplow” effect of the plague to pinch the artery off. Also, one possible mechanism of occlusion is the extension of the dissection plane over a branch due to balloon or stent expansion in a different segment of the bifurcation.12 The presence of SB occlusion in the context of CTO PCI can increase the chances of it occurring. SB occlusion occurs around 25.8–47% during CTO PCI and are often associated with an increased risk of post-PCI myocardial infarction.9,11,12 The occlusion of a single large collateral vessel, like an epicardial vessel, can lead to significant ischemia and hemodynamic instability.9 Equipment Entrapment/loss Equipment delivery in CTO PCI is more difficult due to the severity of calcified and tortuous vessels, as well as advancement of guidewires, microcatheters, balloons, or stents through narrow channels. 13,14 Alexandrou et al. studied the data from Prospective Global Registry for the Study of Chronic Total Occlusion (PROGRESS CTO) and found that 43 19 (0.4%) out of 10713 CTO procedures had equipment entrapment or loss with guidewires and microcatheter having the most occurrences.14 Other factors of equipment entrapment/loss are the meeting points of antegrade and retrograde devices over the same guidewire, and using collaterals during retrograde approaches, which can lead to stent loss, wire entrapment, or wire fractures.21 Additionally, rotating wire knuckles can lead to wire knots, and aggressive use of a rotational atherectomy burr can exacerbate these risks.9,13 The cath lab team needs to determine if it is best to attempt the retrieval of the lost equipment or deploy/crush the lost equipment.6 No Reflow CTO PCI can sometimes lead to a phenomenon known as coronary slow flow (CSF) or no-reflow phenomenon (NRP). This complication occurs when the coronary vessel appears completely patent, but there so little or no blood flow going through it.15,16 NRP is often attributed to factors such as microvascular obstruction, endothelial dysfunction, or arteriolar spasm. It is more prevalent in cases of ST-segment elevation myocardial infarction, PCI of degenerated vein grafts, and the use of atherectomy devices. 9,15,16 Wang et al. discusses that the prevalence of NRP/CSF in patients who underwent PCI are 2-3.2%, while patients with ST elevated myocardial infarction (STEMI) have incidences of 30-40%.16 It is important to rule out other conditions that may mimic no-reflow on angiography. The following complications can mimic no-reflow phenomenon: dissection, air embolism, spasm, pseudo-lesion formation, intramural hematoma, and thrombosis. When true no-reflow is confirmed, pharmacological treatments are recommended to manage the condition such as adenosine, nitroprusside, verapamil, nicardipine, or epinephrine are the medications commonly used.9,16 20 Non-coronary complications Non-coronary complications of CTO PCI extend beyond the coronary arteries that affect the cardiac system. They include a diverse range of challenges such as aortic dissection, pericardial tamponade, myocardial infarction, hypotension, arrhythmias.3,9 Aortic Dissection Aortic dissections occur in about 1% of CTO PCI procedures, often originating from a coronary dissection that extends into the aorta. These dissections are more common during retrograde approaches and frequently involve the right coronary artery (RCA). They can result from deep-seated catheter engagement, aggressive catheter use, or contrast injections. Additional causes include coronary ostium pre-dilation, balloon rupture, or inadvertent retrograde wire advancement into the subintimal space. The risk of guide-induced dissections is higher in CTO PCI due to the need for aggressive catheter support and larger size guide catheters 4,21 Pericardial Tamponade Characterized by the accumulation of fluid in the pericardial sac. Pericardial tamponade requires immediate attention due to the pressure exerted on the heart. Most often, it occurs from coronary perforations that leak into the pericardial space.1 Myocardial Infarction Any complication that involves injuring or damaging cardiac tissue makes the patient susceptible to myocardial infarction (MI) during CTO PCIs. Retrograde CTO PCI has higher rates of cardiac biomarker elevation compared to antegrade-only procedures, but its impact on clinical outcomes remains a question.1 21 It may be common to see small increases in cardiac enzymes during retrograde CTO procedures, often due to ischemia from collateral vessel occlusion. Typically, it is tolerated without ECG changes and minor troponin elevations may not have any clinical significance during the procedure. If a dominant collateral is utilized and the patient experiences significant ischemia or chest pain, the operator should consider an alternative strategy to prevent MI. While postprocedural MI is a potential complication, it is likely underdiagnosed due to a lack of systematic postprocedural cardiac biomarker screening and other major complications are often the acute reason of a MI. 1,9 Hypotension During CTO PCI, hypotensive events can occur due to various complications, and it is important to identify the cause of it in a timely manner. After ruling out false pressure readings such as catheter dampening, equipment issues, the tuohy being open, potential causes of true hypotension should be investigated. These include access site bleeding, aortic insufficiency from catheter use, ischemia due to collateral channel occlusion, donor vessel lesions or ischemia, perforations leading to tamponade, and anaphylaxis.9, 17,21 Careful assessment and appropriate interventions, like correcting catheter position or administering vasodilators, can help manage these complications and stabilize the patient’s condition.21 Arrhythmias Arrhythmias are a possible complication to CTO PCIs and should be addressed during the procedure if it poses a concern to continue on with the PCI. Assaf et al. studied ventricular arrhythmia risk with patients with CTO and found that patients that have had successful PCI may be alleviated by the ventricular arrhythmia or show some improvement. This means the patient may come in with an arrhythmia and should be noted before the procedure begins.24 22 New arrhythmias are an area of concern however. Any underlying conduction abnormality can increase the risk of arrhythmias during CTO PCI. Ischemia or manipulation of collaterals can increase vagal tone and potentially irritate the conduction system. In retrograde CTO PCI with septal collaterals approach, the equipment may block the remaining functional fascicle, resulting in complete heart block. Most commonly, arrhythmias start from inadequate coronary flow or non-coronary complications.9 Thromboembolic Events Thromboembolic events (aortic, iliac, coronary plaque, thrombus, air) can complicate any CTO PCI, so it's important to take steps to minimize the risk of any embolization.4 This can be achieved by carefully aspirating the guide catheters after they have advanced through the aorta. Proper anticoagulation is also essential, especially during retrograde CTO PCI. To prevent catheter thrombus formation and subsequent embolization, it is recommended during antegrade CTO PCI, the activated clotting time (ACT) should be maintained above 300 seconds, and above 350 seconds during retrograde CTO PCI. The ACT should be monitored every 20–30 minutes.9 Prolonged CTO procedures with high levels of anticoagulation, ACT >350 seconds, may increase the risk of noncardiac bleeding, particularly in patients with known or unknown pathologies. This risk should be taken into account if unexplained vasovagal episodes occur during or after the procedure.9 Non-cardiac complications Non-cardiac complications of CTO interventions occur from the area outside the coronary arteries or heart. Non-cardiac complications broaden the scope of considerations for 23 interventional cardiologists, cath lab staff, and other ancillary staff engaged in CTO procedures. Vascular Access Complications This complication is periprocedural in nature and includes vascular access site complications that create bleeding or cause peripheral ischemia, usually from either the radial or femoral arteries. Seven French or greater sheaths and guide sizes are commonly used in these procedures along with dual access in the radial and femoral artery 70-80% of the time.3,18 This creates more opportunities for complications at the access sites. Meijars et al. goes on to report that the reliability of reported incidences in many studies may be underestimated of the true incidence of access site complications and The COLOR trial (Complex Large Bore Radial Access) found a complication rate of 14.9% for femoral artery access and 2.8% for radial artery access in CTO patients.18 This data could suggest that vascular access complications may be the most common complications surrounding CTO PCI if underreporting is true. Contrast Induced Nephropathy/Allergy Contrast-induced nephropathy (CIN) occurs after PCI and is a leading cause of acute renal failure in hospitals, contributing to higher morbidity, mortality, and costs. CIN rates are around 3.4% incidence rate, making it important to assess the patient’s renal function levels before the procedure begins.19 Large amounts of contrast may be used for viewing the coronaries, wire placement, angioplasty, stenting, or any other kind of equipment so CIN is a threat, especially for patients with renal impairment already.4 The total contrast volume should be < 3.7× the 24 creatinine clearance of the patient and often can be prevented with preprocedural hydration.9,19 Allergies to contrast media or iodine can be a serious complication as well. It is vital to assess and discuss the patient’s reaction to contrast media, especially if they have an allergic history to shellfish.20 This will gauge what medications and dosage will be needed to premedicate the patient. It is recommended and common practice to premedicate the patient with contrast media or iodine allergies. Prophylactic medications include steroids, an H1 antihistamine blockers like diphenhydramine, and an H2 antihistamine blockers like pepcid.9,20 Radiation Injury This non-cardiac complication is more common in CTO PCI due to the duration of the procedures. Skin injuries from radiation exposure may present later and are often overlooked. Continuous monitoring of the air kerma measured in Gray (Gy) radiation dose during the procedure is suggested because it correlates with radiation skin injuries. Radiation injuries can occur from continual need for fluoroscopy in one or two working views during the PCI. Only working in one or two views allows the radiation to focus only on those few areas during fluoroscopy. The global CTO crossing algorithm advises terminating the procedure if exceeding 5 Gy, unless the procedure is almost finished.21,22 It is also important to note the threshold for radiation burns. Less than 5 Gy skin injury is unlikely to occur, greater than 10 Gy skin injury is likely, requiring assessment of the case, and greater than 15 G is considered a sentinel event by the Joint Commission and requires reporting to the regulatory authorities in the United States.9 25 With improvements in equipment and techniques, increased use of intravascular imaging, and increasing operator expertise with CTO procedures there has been less usage of radiation from 2012 to 2020.22 This complication adds another layer of consideration that can be forgotten due to the length of the procedures. Strategies for managing CTO complications The management of complications during CTO interventions remains a significant challenge. When a complication occurs, there are various ways to approach the treatment of them and being able to decide on the correct treatment path taken can be a very difficult one. Despite success rates of around 90% in CTO interventions today, they continue to be associated with more complications, including periprocedural mortality and acute coronary complications.1,6 To enhance complication management and improve patient outcomes, several approaches and advancements can be explored. These include the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, training, and preparation. When a complication occurs, understanding the severity of it is important. Specific interventions may not always be necessary in managing minor complications, non-flow limiting dissections, or even small septal artery perforations. In some cases, aggressive treatment could pose greater risks than careful monitoring and continuing the procedure. Deciding whether to complete or stop the procedure in the presence of complications should be based on the relative risks to the patient, considering factors like procedural time, use of any medications, and the current state of the coronary artery. Questions to ask to the physician and other cath lab staff are when minor complications occur are: Will additional 26 procedural time, medications, devices, or coronary ischemia put the patient at additional risk or can you safely leave the coronary artery in the current state?3 Even if the decision is to abort the procedure, methods such as investment strategies can be utilized to make the next CTO PCI attempt achievable. This method involves extra plaque modification such as balloon-assisted subintimal entry, scratch-and-go, and IVUS-guided puncture, parallel wiring or anterior dissection and ADR attempts.26 When a significant complication happens, the critical decision is whether to act immediately or take a moment to evaluate the situation. A good method and proposal are a "60second rule". This method suggests that if it is safe, taking 60 seconds to assess the patient, communicate with the team, confirm the diagnosis, consider treatment options, and seek additional assistance can lead to more successful outcomes than rushing into a poor decision. If immediate action is required, such as in cases of acute hemodynamic collapse or ventricular tachycardia, the priority should be to stabilize the patient before further evaluation.9,17 Current literature on the best practices to manage these complications will always be evolving with more research and experience. Coronary, non-coronary, and non-cardiac complications each have particular management and the cath lab team will need to understand what they are and be ready. Coronary Complication Management Coronary perforations, collateral coronary complications, coronary dissections, sidebranch occlusions, equipment entrapment/loss, and no reflow were all discussed earlier, but let us discuss some management techniques of coronary complications. Coronary perforation management involves a careful approach depending on the hemodynamic stability of the patient and the severity of the perforation.2 If the perforation 27 occurs, efforts are made to wire across the perforated vessel and seal it inflating a balloon directly over or proximally to the perforation to tamponade initially. New equipment is being developed for this purpose; they are called perfusion balloons. While the balloon is inflated and sealing the perforation, the balloon still allows blood flow to the rest of the arteries.33 Assessment focuses on whether the patient is stable after a balloon is inflated and covering the perforation, this determines conservative measures such as multiple echocardiograms to monitor for effusion/tamponade, or if more aggressive interventions like covered stents, pericardiocentesis, microsphere/bead embolization, coils, thrombin, or subcutaneous fat, transfusion, or even surgery are required depending on the vessel size and location. 9, 17, 32 If the patient continues bleeding, the procedure may need to be stopped to prevent further complications, with protamine or other supportive measures provided as needed. When bleeding persists despite interventions, additional methods like balloon tamponade proximal to the perforation or surgical approaches such as coronary artery bypass grafting (CABG) may be necessary. 9,17, 21 It is important to know what perforation intervention may be used for differently located coronary perforations. For distal main vessel perforations, options include microspheres, coils, thrombin, or subcutaneous fat. For distal side-branch perforations, the same techniques are used, but if these fail, covered stents on the main vessel to exclude the side-branch may be necessary. For proximal side-branch perforations, the same options apply, with the possibility of applying covered stents on the side-branch or main vessel to prevent further damage.17, 32 If the perforation occurs in the proximal main vessel, treatment options depend on the presence of bifurcation. If no bifurcation is present, covered stents may be used as well. In the case of 28 bifurcation, surgery may be the safest option; however, further covered stent deployment might be required.32 Managing distal vessel or collateral perforations involves assessing the patient's hemodynamic stability. If stable, balloon tamponade proximal to the perforation can be performed and echocardiogram is used to monitor for effusion or tamponade.2,17 If the patient is unstable, more immediate interventions, such as administering intravenous fluids, performing pericardiocentesis, or arranging for blood transfusion are necessary9 In severe cases, CT surgery may be required. Once balloon tamponade is applied, if the perforation is successfully sealed, the procedure can be stopped, with protamine administration after equipment is removed as needed. If tamponade fails, further strategies like injection of thrombin, use of covered stents, or coils can be employed.17 In certain cases, both antegrade and retrograde occlusion may be necessary to achieve hemostasis, followed by protamine administration to reverse anticoagulation, specifically collateral vessels.2,9,17 Managing coronary dissections begins by determining if the guidewire is through the true lumen of the dissection. If a guidewire is successfully placed, and there is TIMI 3 flow (Thrombolysis in Myocardial Infarction), the next steps involve balloon dilation if the vessel is not fully open. Once the vessel is open, stent implantation is recommended, with considerations like intravascular ultrasound (IVUS) to assess the dissection, using cutting balloons to release large intramural hematomas, and placing stents distal to long dissections.9,17 If wiring through the true lumen is unsuccessful, attempts to cross the dissection with an antegrade or retrograde strategy are considered, such as ADR or STAR techniques.21 If these revascularization attempts fail, options include CABG, conservative management, mechanical circulatory support, or pharmacologic support.9,17,21 29 Managing side branch occlusions during CTO PCI requires a strategic approach for successful recanalization while minimizing damage to the side branch. One method is antegrade wiring of the occluded branch, this can be particularly challenging when dissection/reentry techniques are employed for crossing. Retrograde recanalization is another option, especially if collateral channels exist that supply the occluded branch.21 Intracoronary imaging can assist in identifying the cause of the occlusion such as a subintimal track near the side branch ostium and guide rewiring strategies. When a dissection/reentry strategy is used, subintimal dissection by reentering the true lumen as proximally as possible should be done. Alternatively, the CrossBoss catheter can be employed to minimize the extent of dissection and support reentry efforts.9 In cases where a coronary bifurcation is present at the distal CTO cap, retrograde approach can reduce the risk of side branch occlusion during antegrade crossing attempts, preserving branch integrity.9,21 Managing coronary artery equipment entrapment and loss can involve many different strategies depending on the type of equipment lost or trapped, such as wires, stents, atherectomy burrs, or microcatheters. For wires, if they are intact and externalized, efforts to pull them back using microcatheters, snares, or guide extensions should be done. In cases where the wire breaks or is entrapped in the coronary artery, surgical removal may be necessary if snares are unsuccessful or leaving them in the coronary artery if proven safe.17 Stents can present difficult challenges, particularly if the wire is stuck or threaded through the stent. Options include using snares, deploying the stent in the least harmful position, or retrieving the stent with balloon support.9,17 With atherectomy burrs, intact removal involves manipulating the rotation speeds while pulling the device backward. If the burr 30 becomes stuck, advanced techniques such as wire entanglement or breaking the wire and pinning the burr into the vessel wall may be necessary.1,17 For microcatheters, balloons, or laser tips, management includes pulling the device back with balloons or using wire entanglement methods. In situations where none of these retrieval methods work, abandoning the device and resorting to surgical intervention is the final step.17,21 Managing coronary no-reflow first involves determining if an epicardial obstruction, such as dissection, air embolism, or proximal thrombus, is present. If an obstruction is identified, appropriate treatment depends on the cause. Dissections are managed previously discussed, while air embolism requires 100% oxygen inhalation and aspiration. Proximal thrombus can be treated with aspiration or balloon angioplasty.1,2,17 In the absence of an epicardial obstruction, pharmacologic treatment is started. Medications such as adenosine, verapamil, nicardipine, epinephrine, nitroprusside, and eptifibatide are administered directly into the distal vessel. If flow is restored, the case is completed. If the issue continues, more pharmacologic treatments are considered and methods to improve perfusion pressure, such as diuretics, intra-aortic balloon pump (IABP) use, or circulatory support.9,17 Non-coronary Complication Management Non-coronary complications include aortocoronary dissections, pericardial tamponade, hypotension, arrhythmias, and thromboembolic events that were discussed earlier on what they are, but let us discuss some management techniques of these complications. The best treatment for aortocoronary dissection remains up for debate, as this rare condition lacks a wellestablished management approach. Various strategies, including emergent surgery, coronary artery stenting, and conservative medical treatment, have been suggested.6 More than 40% of 31 cases rapidly progress to involve the ascending aorta if the entry point of the dissection is not sealed promptly.9 Once an aortocoronary dissection occurs, quick invention is needed to prevent rapid progression. Dunning et al. proposed that stenting the entry point of the dissection may be effective when the dissection extends less than 40 mm from the coronary ostium. In contrast, surgical intervention may be needed if the dissection exceeds 40 mm from the ostium.2,21 If the dissection extends beyond 40 mm into the aortic root, causes aortic regurgitation, or involves the supra-aortic vessels, emergent surgery is required.28 Managing hypotension during CTO PCI begins with determining if the drop in blood pressure is real or is technical issues such as guide dampening or equipment malfunction. If the hypotension is real, the next step is to assess whether the patient has a pulse. In the absence of a pulse, cardiopulmonary resuscitation (CPR) is started immediately. If the patient has a pulse, a systematic evaluation of potential causes is done.9,17 Common causes include ischemia or infarct, arrhythmia, cardiac performance issues, vasodilatory or distributive causes, or bleeding. Once the cause of hypotension is identified, the reversibility is assessed. If the cause is quickly reversible, addressing the issue is prioritized, while appropriate hemodynamic support should be started if the condition is not rapidly reversible. Utilization of vasopressors or circulatory mechanical support may be needed.9,17 Pericardial tamponade can be an urgent complication and in hemodynamically unstable patients, an emergent pericardiocentesis is essential. Removing the accumulated fluid is the only way to restore normal ventricular filling and adequate cardiac output. The drain is keeping pressure off the cardiac muscle so it can perfuse.29 For arrhythmias, whether bradycardia or ventricular arrhythmias, management involves rapid identification of the rhythm disturbance, followed by medications such as atropine or 32 anti-arrhythmic agents, and the use of temporary pacing or defibrillation if necessary. In severe cases, advanced cardiac life support (ACLS) protocols should be followed.21 In cases of air embolization, administering 100% oxygen helps with air resorption, and aspiration should be attempted if a large amount of air is present. If the patient experiences cardiac arrest, intracoronary epinephrine may be necessary. Since hemodynamic deterioration can occur rapidly, quick intervention is essential.2, 21 For thrombus or plaque embolization, aspiration can be performed using an aspiration catheter, such as the Export, or through deep guide catheter engagement or a guide catheter extension. If aspiration is unsuccessful, alternative options like laser or other thrombectomy may be used.2,21 Non-cardiac Complication Management Vascular Access complications can commonly occur and should be assessed periodically throughout the procedure and post-procedure as well. Small superficial hematomas typically resolve on their own over time and require only conservative management. Treatment measures may include applying local pressure to the access site, ensuring prolonged bed rest, adjusting or temporarily stopping anticoagulant and antiplatelet medications, maintaining proper hydration, and regularly monitoring blood cell counts.30 In contrast, retroperitoneal hemorrhage is the most severe form of access site bleeding and is clinically associated with higher mortality rates.30 Surgical intervention is required in only a small number of patients with retroperitoneal hematomas, as most cases can be managed with blood transfusions and close hemodynamic monitoring, given that they are typically selflimiting. If a patient remains unstable despite aggressive resuscitation, we recommend starting 33 with a percutaneous approach, reserving open surgery for instances where the bleeding cannot be controlled.2,30,31 Contrast induced nephropathy and allergies should be approached as more preventative for CTO PCI. There is often plenty of time to address these concerns before the procedure ever starts. First, it is important to identify patients at high risk for CIN, as close monitoring of contrast usage is essential. The primary preventive strategy involves limiting the amount of contrast used and avoiding repeated use of contrast within a short time frame. Additional preventive measures may include ensuring adequate hydration, using iso-osmolar contrast agents, and administering sodium bicarbonate.21 For patients with contrast allergies, it is recommended and common practice to premedicate the patient with contrast media or iodine allergies. Prophylactic medications include steroids, an H1 antihistamine blockers like diphenhydramine, and an H2 antihistamine blockers like pepcid.9,20 Radiation injuries should be more preventative as well, it is important to implement a standardized radiation safety program to minimize radiation exposure during CTO PCI. Several measures can be employed to achieve this. Limiting the use of fluoroscopy and cineangiography is key with utilizing low magnification and proper collimation. Employing the lowest frame rate and frequently rotating the image intensifier can also help reduce exposure.9 Attention should be paid to the positioning of both the table and the image intensifier, avoiding steep angles whenever possible. Before starting cine-angiography, injecting the collateral donor vessel can be beneficial. Real-time feedback on radiation exposure can be monitored with radiation monitors, and additional shielding, such as Rad Pads, can offer further 34 protection. Finally, allowing sufficient time between procedural attempts can further minimize radiation risks.9,21 Summary CTO PCI presents unique challenges and complexities within the field of interventional cardiology. The success of these procedures depends on the understanding and effective management of potential complications that may occur during the PCI. From coronary and non-coronary complications involving the heart to non-cardiac complications that occur elsewhere in the body, addressing these challenges requires a multi-disciplined approach. Key factors contributing to CTO complications vary in patient-related and procedural factors, emphasizing the importance of meticulous pre-procedural planning, patient selection criteria, and risk assessment. The selection of specific intervention techniques is of great importance in determining the nature and severity of complications. Whether utilizing antegrade, retrograde, or hybrid approaches, each technique carries its own set of advantages and risks and each member of the cath lab team needs to be ready. In the last few years, CTO PCI has gained popularity with an estimated 90% success rate; however, the complications remain at about 3%.5 Recognition and addressing complications is required for patient care and safety. The implementation of structured decision-making processes for assessing and responding to complications is a highly suggested aspect for any CTO program. The comprehension of complications needs to extend beyond the physician’s understanding and cath lab staff should be trained to understand, recognize, and be able to react to the proper treatment decisions. 35 In summary, as this specific and specialized field continues to evolve with advances in technology and procedural techniques, the importance of recognizing and addressing complications cannot be overstated. Establishing recommended guidelines for complications in CTO PCI is an essential part for the cath lab team to navigate the complexities of these procedures effectively. Being able to understand what is happening during these stressful moments, responding appropriately, and being prepared is prioritizing patient safety and creating a culture of continuous improvement. Chapter 4: Research Method Research Methods and Design A case study review is an effective method for investigating complex issues within reallife settings. It enables researchers to closely examine the different characteristics and factors of a specific case or many different cases. This approach is particularly beneficial when researching different CTO complications, since each complication is unique, but allowed to see commonalities as more cases were reviewed. By comparing the different types of complications, patient demographics, and outcomes across different cases, new insights into what the most common CTO complications were able to be assessed and how they were managed. Additionally, this method can emphasize the impact of being prepared to manage the complications in a timely manner. It is an appropriate approach as a research design for this project due to the lack of established comprehensive guidelines for cath lab teams important for any CTO procedure. A case study review of CTO complications could bridge the gap of challenges cath lab staff encounter when being part of these procedures. 36 Population The population included in this qualitative research consisted of CTO PCI case studies that resulted in and managed complications during procedure. The research aimed to study the most common complications, and analyze key factors such as patient age, gender, location of occlusion and complications, severity, management strategies, and outcomes. Sample The sample for this study was selected using a purposeful sampling method. This technique, common in qualitative research, allowed for the selection of cases based on their relevance to CTO PCI. For this analysis, CTO PCI that resulted in complications case reports were chosen. The sample size was determined by the availability of relevant case reports and studies. In total, 34 cases were selected for analysis. Data Collection, Processing, and Analysis We executed a systematic search for relevant case reports on CTO PCI that resulted in complications. Our main resources were Weber State University’s Stewart Library One Search, NIH, PubMed, and Google Scholar between the years 2014 to 2024 The research was explored by key terms such as “chronic total coronary occlusion complications”, “CTO (the specific complications)”, “CTO complications management”, and “chronic total occlusions.” Data collection included a multifaceted approach, involving retrospective analysis of complications encountered during CTO PCI, review of common and uncommon complications, examination of contemporary issues and challenges in CTO PCI. The authors reviewed the identified studies to ensure alignment with our inclusion and exclusion criteria. The subsequent qualitative review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. To be included, case studies had 37 to meet the following criteria: published between 2014 and 2024, be peer-reviewed, and focus on CTO PCI that resulted in complications. Assumptions It is assumed that reported complications accurately reflect the incidence and severity of adverse events associated with CTO PCI procedures. Furthermore, the assumption is made that these reported complications provide a comprehensive overview of CTO PCI complications, accurately reflecting the most common complications and providing cath lab teams with information to manage them. Additionally, it is assumed that reported complications offer insights into patient safety and procedural challenges, accurately representing underlying trends and associations observed in individual studies. These steps collectively integrate various data sources, collection methodologies, processing techniques, and analytical frameworks to deepen our understanding of complications related to CTO PCI and inform clinical practice in this domain. Limitations Developing protocols and guidelines for managing CTO complications in the cath lab presents several potential limitations. First, the complexity and variability of CTOs pose a significant challenge. CTOs can differ in location, length, vessel size, and degree of calcification, necessitating different approaches for each case. Consequently, creating comprehensive protocols that accommodate this variability while maintaining efficacy and safety may prove to be harder than expected. Second, the rapid and evolving nature of interventional cardiology introduces another limitation. Techniques and technologies for managing CTOs continue to advance while tools or ideas for CTO procedures quickly become outdated. With that, the lack of consensus among 38 experts regarding the optimal approach to CTO intervention further complicates protocol development. This thesis may encounter difficulties in reconciling differing opinions and integrating emerging evidence into the proposed guidelines. Delimitations: When creating protocols and guidelines for managing CTO complications in the cath lab, it is essential to recognize several key delimitations. First, the scope of the thesis should be clearly defined, specifying the types of CTO complications and patient populations, including factors such as complications type and location. Second, it is important to acknowledge the limitations of available resources. This includes considering the equipment and expertise available within the catheterization lab, as well as any constraints related to staffing or budget. These limitations may influence the feasibility of implementing certain protocols or guidelines and should be carefully accounted for throughout this study. Lastly, this study should recognize the dynamic nature of medical practice and technology. Given the rapid advancements in interventional cardiology, any protocols and guidelines developed must be flexible and adaptable to accommodate emerging techniques, equipment, and evidence-based practices. By acknowledging these delimitations, this thesis can focus on developing practical and relevant recommendations for managing CTOs in the cath lab while acknowledging the complexities and risks in real-world clinical practice. Ethical Assurances Ethical considerations arise when developing protocols for invasive procedures like CTO interventions. Balancing the potential benefits of more standardized approaches with patient 39 safety and autonomy is essential. Ensuring that the proposed protocols prioritize patient wellbeing and adhere to ethical principles such as informed consent and risk mitigation is vital. Overall, while creating protocols and guidelines for CTO management in the cath lab is valuable, navigating the complexities of CTOs, keeping pace with advancements, and addressing ethical considerations present significant limitations for this study. Summary This study employs a systematic review to comprehensively inquire existing literature on CTO procedures in cath labs. The population of interest includes both patients undergoing CTO procedures and cath lab staff involved in these interventions, recognizing the important role of all team members in ensuring patient safety and procedural success. Developing protocols and guidelines for CTO management in the cath lab has several limitations. 34 cases studies were chosen, broader research on this group is limited, case studies do not always accurately reflect the broader population, possible biases in the selection of severe or uncommon cases, and complexity and variability of CTOs pose a significant challenge This approach is chosen to address the lack of comprehensive and important guidelines for all cath lab teams regarding CTO procedures. The complexity and variability of CTOs, the rapid advancements in interventional cardiology, and ethical considerations pose major challenges. These limitations show the importance of clearly defining the study scope, considering resource constraints, and acknowledging the dynamic nature of medical practice and technology. By recognizing and addressing these limitations, this study aims to provide practical recommendations for managing CTO PCI complications in the cath lab. 40 Chapter 5: Findings Results The dataset consists of case studies focused on CTO PCIs, analyzing key factors such as patient age, gender, location of occlusion, complications, severity, management strategies, and outcomes. The majority of cases involved male patients, which may reflect broader trends in cardiovascular diseases. The average patient age falls between 60 and 70, typical for CTO procedures. Specifically, patients with occlusions in the right coronary artery (RCA), and left anterior descending (LAD) arteries have an average age of 76 years, while those with occlusions in the left circumflex (LCx) artery average 75 years. CTO complication locations varied across different coronary arteries. Among the 34 case studies analyzed, the average patient age was 66 years, with gender differences of 24 males and 10 females. The RCA was the most frequently affected coronary artery with 17 cases involving it. The next most occurring coronary arteries involved were the collateral arteries with 13, (10 septal collateral arteries and 3 epicardial collateral arteries). The other coronary arteries that were affected were LAD (5 cases) and LCx (2 cases). Some case reports had more than one artery affected by the complication. The most common complication was coronary perforation (18 cases) with cardiac hematomas (7 cases) and coronary dissection (5 cases) following. Specific complications, such as septal vessel perforation leading to septal hematoma, subintimal shift causing side branch occlusion, and epicardial collateral perforation resulting in significant bleeding into the pericardial space, were frequently observed. Perforation and hematoma complications can be explained because they correlate with each other, cardiac hematomas can often develop from coronary perforations. 41 Despite the occurrence of complications, most patients experienced successful recoveries after interventions. Mild and moderate cases tend to have higher success rates, while severe complications result in more varied outcomes. Older patients, especially those between 70 and 80 were more prone to severe complications, though successful recoveries were still possible depending on the severity of the intervention required. Evaluation of Findings The most common complication observed included coronary perforation that involved various locations. The most common locations of coronary perforations during CTO PCI were the collateral arteries (9), 5 septal collaterals and 4 epicardial collaterals. The next most common was the RCA (4) followed by LAD (3) and LCx (2). The data shows a clear correlation between complication types and location of it. 50% of the coronary perforations involved were collaterals, either septal or epicardial. Collaterals are specific to CTOs due to the collateral growth when an artery becomes totally occluded. It is important that cath lab staff understand this concept because most other PCI will not involve collateral arteries. Summary The dataset clearly identifies coronary perforations as the most common complication in CTO PCIs, including a male-dominated gender distribution and an average patient age in the 60s to 70s. The RCA was the most frequently occluded vessel; however, it did not have the most perforations involved like the collateral arteries. Other notable complications included coronary dissections and intramural hematomas. Most patients experienced successful outcomes, particularly in mild and moderate cases. However, severe cases often led to more complicated recoveries, especially in older individuals 42 requiring extensive interventions. These findings emphasize the importance of understanding what coronary perforations are, the current strategies to manage them, and what cath lab staff can do pre-procedurally to prevent or be ready, and how cath lab staff can support the physician in treating them when they occur. Chapter 6: Implications, Recommendations, and Conclusions Implications The increasing popularity of performing CTO PCIs, allowed by evolving technologies for faster procedure completion and new CTO programs being developed, is an area that cath lab staff should research. These procedures' better success rate indicates a considerable shift in cardiovascular disease treatment. Despite extensive research on CTO complications and available case studies to analyze, specific data on CTO PCI complications and specific recommended guidelines for cath lab staff is still needed. As these procedures become more common, a disparity between available information and understanding of the challenges faced by the team involved with these procedures will be important to understand. This analysis addresses this gap by exploring CTO PCI complications, current literature on the frequency of them, case study reviews on what specific complications are most common, and exploring the recommended ways cath lab staff can be prepared for complications when they occur. Based on 34 case studies, the authors acknowledge limitations, including inherent variability of CTO PCI complications, the complications are based on case studies and may not be generalizable to all patients, and only a limited number of case studies are published on these complications. Ethical considerations were taken, ensuring transparent and responsible use of previously published case studies while conducting the research with the absence of conflicts of 43 interest. The following section outlines implications, recommendations, and conclusions from this comprehensive CTO PCI complication. What are the different types of complications that can occur during CTO PCI? Chapter 2 covered the potential CTO PCI complications that can occur throughout these procedures. The analysis of case studies highlights a range of potential complications that include what was already discussed. Coronary perforations, the most frequent complication with 18 cases, often result from guidewire manipulation and aggressive techniques like the retrograde approach. Hematomas (7 cases) and dissections (5 cases), reveal the delicate nature of the coronary vessels during these procedures and further stress the need for careful planning, cautious manipulation, and rapid intervention strategies for treatment. Stent related issues such as dislodgement or loss, also pose significant challenges, emphasizing the importance of knowing the capabilities and coronary anatomy that can accommodate the devices. Additionally, less common complications such as side branch occlusions, arteriovenous fistulas, and complete AV block show the diverse risks involved in CTO PCI. These findings all suggest that a comprehensive approach with combining better pre-procedural planning, CTO PCI team education, and recommended guidelines could reduce complications. As CTO PCI increases with popularity, intervention for managing chronic total occlusions will require more education and awareness of what can happen during these procedures. What are the most commonly occurring complications during CTO PCI? In identifying what complications occurred along with other procedural data, we observed that out of 34 cases of CTO PCI in this clinical demographic, 18 cases were coronary perforations. This finding aligns with existing literature, which emphasizes that coronary perforations occur at around 5% of cases.7 The prevalence of perforations in the CTO PCI 44 highlights the necessity for increased awareness and monitoring during the procedure to find the perforation and treat it in a timely manner. Additionally, we discovered that coronary perforations tend to occur more commonly from the use of guidewire and microcatheter as 12 out of the 18 coronary perforations were caused from those mechanisms along with 7 out of the 18 occurring from retrograde approach. This finding is also consistent with the research, which suggests that coronary perforations during CTO PCI are more likely to occur from retrograde approach and can be more clinically significant (required direct treatment).27 This information is significant for cath lab staff and providers as it highlights the need for thorough knowledge and prevalence of coronary perforations occurring, especially when the approach is retrograde. The higher incidence and severity of coronary perforations among CTO PCI patients emphasizes the need for improved procedural protocols and treatment strategies.2,3 Given the potential for severe outcomes coronary perforations can have and the distinct characteristics of which they can be, clinicians should be ready to promptly manage this complication whenever a CTO PCI is performed. Furthermore, these findings can be helpful for healthcare providers, particularly cath lab staff or any other ancillary staff to be aware of the higher risk of coronary perforations in CTO PCI. This knowledge can result in more timely management of coronary perforations with a good possibility of leading to better outcomes. What can cath lab staff do to prepare to manage CTO complications when they happen? With 18 cases out of the 34 being coronary perforations, it is important that cath lab staff understand what the management of this complication is. It is vital to know what emergency equipment to have available, such as quick access to balloons, covered stents, and pericardiocentesis tray if the perforation advanced into pericardial tamponade.9.17 Furthermore, 45 there were multiple other case studies of different CTO PCI complications that the cath lab staff should also know how to manage. Additionally, because complications happen more frequently in older patients with CTOs, cath lab teams should develop protocols designed toward high-risk populations.2 Pre-procedural planning, including a thorough assessment of the patient’s health status and potential risks, can guide the team in anticipating complications and developing a strategy for immediate management. Regular collaboration and communication among the cath lab staff, interventional cardiologists, anesthesiologists, or any other ancillary staff involved can also enhance the effectiveness of response measures. These would minimize the impact of severe complications and improve patient outcomes. Recommendations To effectively manage complications during CTO PCI, cath lab staff must adopt or create a proactive and comprehensive approach. Given the high incidence of coronary perforations, which occurred in over half of the 34 case studies, it is essential that staff are fully trained in the identification and management of this complication (Appendix A), but also a thorough understanding of managing other complications as well. For any new CTO program or developing one, it is highly suggested that being ready for these complications by being prepared with making or adopting some kind of guidelines for CTO PCI. It would first be beneficial and recommended to establish a pre-procedural equipment and resources checklist and having the equipment and resources available before even getting the patient in the cath lab. This allows the cath lab staff to see what equipment or resources they have and if not, may need to even delay the case due to safety reasons. 46 The first step of CTO PCI is having the right support and resources if needed. Within the hospital, access to cardiothoracic surgery and perfusion team backup is essential for cases requiring emergency surgical intervention. It is important to know who you need to call and how to contact them, when CT surgeons are needed, it is usually urgent. Echocardiography services should be available for rapid assessment of cardiac tamponade often resulting from a coronary perforation, detailed cardiac assessments, and post-procedure assessments if needed, knowing the fastest way to contact them is beneficial as well. Next, collaboration with a peripheral vascular specialist is important for managing vascular access complications and is beneficial, as vascular complications can escalate quickly. Finally, transferring patients to an experienced ICU ensures expert care during the recovery phase, particularly in severe complication cases. Implementing these recommendations first will enable cath lab staff to have the support needed to manage PCI complications swiftly and effectively, reducing risks and improving patient outcomes.1,2,9,17,21 After establishing that the cath lab team has the support if needed, it is important that the availability of specific equipment is located easily. It is recommended to establish a CTO cart that has all the equipment needed for specific complications or CTO PCI situations. Key tools should include a pericardiocentesis tray, covered stents, angioplasty balloons in various sizes to occlude perforations, coils, and microcatheters for coil delivery in cases of small vessel bleeding. Additionally, snares are useful for device retrieval, and thrombin or microspheres should be on hand for embolization or bleeding control.1,2,9,17,21 In the procedural room, mechanical circulatory support devices are important for patients experiencing severe hemodynamic instability and should be on standby ready to use. ACLS drugs and a defibrillator must be readily accessible for immediate resuscitation, and contact 47 information for emergency support. The CTO cart should be in the room as well, having all these in the room will allow for a quick remedy to any acute CTO PCI complication that occurs. Asking the interventional cardiologist about specifics of the case will be the last aspect. They may request individual equipment that is special for the CTO they are going to try to cross. 1,2,9,17,21 (Appendix B.) Lastly, continuous education and case reviews are also essential, enabling staff to stay informed about emerging best practices and techniques for managing CTO complications. These efforts, combined with clear communication and team-based strategies, can help minimize the severity of complications and improve patient outcomes in CTO PCI procedures. Utilizing the information in this thesis paper, cath lab staff should be able to understand the most common complications during CTO PCI and be able to be prepared for the occurrence of any acute coronary complication while also having the knowledge of preventing other potential complications. Specifically for coronary perforations, cath lab staff should know the proper treatment options and pathways, highlighted in the attached flow chart. While the interventional cardiologist is very knowledgeable in these procedures, cath lab staff should have knowledge of what can happen and also have information on how to prepare for these high-risk procedures and predict the treatments so equipment can be ready when needed. Conclusion The analysis of CTO PCI complications reveals several important trends and considerations for cath lab staff. The dataset highlights a gender disparity, with a majority of male patients undergoing CTO procedures, and an average patient age between 60 to 70. The RCA and collateral arteries were the most frequently occluded vessels, with complications such as coronary perforation, cardiac hematoma, and coronary dissection being the most common. 48 The correlation between age and complication severity was evident, with older patients, particularly those in their late 70s and 80s, being more prone to severe complications. Despite this, successful recoveries were possible, especially in mild and moderate cases. These findings emphasize the complexity of managing CTO interventions, particularly in older populations, where the severity of complications, rather than age alone, plays a significant role in patient outcomes. Based on these findings, it is important for cath lab teams to be well-prepared with the appropriate equipment, protocols, and multidisciplinary collaboration to manage potential complications. Ensuring that emergency equipment is readily available in an accessible and quick manner can significantly improve patient outcomes. The study reinforces the importance of specific strategies for high-risk populations and careful pre-procedural planning to reduce the risks associated with CTO PCIs. 49 Appendix A 50 Appendix B 51 References 1. Rigger J, Hanratty CG, Walsh SJ. Common and Uncommon CTO Complications [published correction appears in Interv Cardiol. 2019 Feb;14(1):48]. 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