Continuing Education Activity

Contemporary treatment of coronary artery disease is highly dependent on percutaneous coronary intervention (PCI) along with medical management. PCI techniques have advanced significantly over time and are used for stenting even challenging lesions. There are, however, some lesions that present challenges via the conventional PCI route. These complex coronary lesions are categorized based on anatomic, physiological, or functional difficulties. Some of these complex lesions in coronary vessels include bifurcation lesions, calcified lesions, chronic total occlusions, unprotected left main coronary artery lesions, ostial lesions, and saphenous vein graft stenosis. This activity describes the clinical evaluation of complex coronary artery lesions and explains the role of the health professional team in coordinating the care of this condition.

Objectives:

• Differentiate between various types of complex lesions, such as bifurcation, calcified, chronic total occlusions, and unprotected left main coronary artery lesions, to tailor treatment strategies effectively.

• Implement state-of-the-art percutaneous coronary intervention techniques to address complex lesions, staying current with technological advancements in interventional cardiology.

• Implement state-of-the-art percutaneous coronary intervention techniques to address complex lesions, staying current with technological advancements in interventional cardiology.

• Collaborate with interdisciplinary healthcare teams, fostering communication and sharing expertise to enhance comprehensive care for patients with complex coronary lesions.

Introduction

Contemporary treatment of coronary artery disease is highly dependent on percutaneous coronary intervention (PCI) along with medical management. PCI techniques have advanced significantly over time and are used for stenting even challenging lesions. There are, however, some lesions that present challenges via the conventional PCI route. These complex coronary lesions are categorized based on anatomic, physiological, or functional difficulties.

Some of these complex lesions in coronary vessels include bifurcation lesions, calcified lesions, chronic total occlusions, unprotected left main coronary artery lesions, ostial lesions, and saphenous vein graft stenosis.[1] Each of these lesions presents unique challenges, and the approach to such lesions is individualized. Specialized techniques and cardiologists with advanced skill sets have improved the successful treatment of such occlusions.[2]

Conventional PCI may not adequately treat these lesions, which may require advanced techniques. One such subset of advanced catheter-oriented interventions is complex, high-risk, and indicated PCI (CHIP). These techniques include laser, rotational, laser atherectomy, various bifurcation stenting techniques, and specialized approaches to chronic total occlusions.[3] These techniques are promising; however, studies are inconclusive if they positively impact mortality. Some studies, such as Habib et al, cite CABG as a more effective modality for addressing these lesions.[4]

A brief explanation of some of the most common complex lesions follows.

• Bifurcation lesions: These arise at or adjacent to the separation of a major coronary artery. They occur when the main coronary arteries divide into two smaller anatomic portions. The three resultant portions are the proximal main branch, distal main branch, and side branch. A bifurcation lesion is one with significant stenosis (> 50%) in a coronary artery involving the origin of a side branch or in a coronary artery adjacent to the origin of the side branch.[5] The Medina classification system assesses and defines the location of stenosis. This system is a simple numeric system that encompasses the main branch, distal branch, and side branch.
• Calcified lesions: Vascular calcification of the coronary arteries is a common process actively regulated and involves atherosclerotic, inflammatory, and hormonal disease processes. Coronary artery calcification (CAC) involves intimal and medial calcification.[6] CAC increases vessel stiffness and increases the potential for cardiovascular events.[7]
• Chronic total occlusions: This is the complete obstruction of a coronary artery. These occlusions must show TIMI 0 or TIMI 1 flow and have a duration of at least 3 months.
• Left main coronary artery (LMCA) disease: Left main coronary artery disease can be problematic given that it is the origin of the majority of the left ventricular coronary supply. An unprotected left main coronary artery leaves the majority of the myocardium susceptible to death if significant stenosis is present.[8] A protected left main coronary artery is such that a bypass graft supplies the left anterior descending artery or the left circumflex artery.
• Ostial lesion: An ostial lesion starts within 3 mm of the origin of a major coronary artery.[9] These may be challenging to stent due to proximity to the aorta.
• Stenosis of saphenous vein graft (SVG): Saphenous vein grafts are the most common vessels used in CABG. This type of stenosis occurs commonly, with some reports of up to 20% of patients developing this within one year. PCI of SVG carries a significant risk of myocardial infarction or diminished flow.[10] Atherosclerotic disease within graft results in a high restenosis rate as well.[11]

Etiology

Each complex coronary artery lesion has a unique set of etiologies. For example, bifurcation lesions are primarily anatomy-based.[12] Coronary artery calcifications can result from inherent inflammatory processes, as well as the activity of osteoblastic activity.[13] The presence of a thrombus can often result from plaque disruption before or during PCI.[14] Saphenous vein graft occlusion is thought to be a process of intimal vessel smooth muscle proliferation.[15] There are disease processes that are common to each disorder. For example, Baris et al. identified diabetes mellitus and advanced age as independent predictors for all complex coronary lesions.[16] Other risk factors for coronary artery disease and atherosclerosis, such as age, hypertension, obesity, male sex, smoking, and hypercholesterolemia, can be inferred but have not directly been identified in any significant studies as independent risk factors for complex lesions.

Epidemiology

Coronary artery calcification is a nonspecific term, and the amount of calcification can vary greatly. Most of the population has some degree of calcification and atherosclerosis, though these may not be significant enough to cause significant stenosis.[17] One large study noted calcification in 50% of individuals aged 40 to 49. This number rises to 80% of individuals aged 60 to 69.[18] Gender and age are significant risk factors for coronary calcification. Studies have reported the incidence of coronary calcification at 93% for men older than 70 years and 77% for women aged older than 70.[19]

Coronary bifurcation lesions are the most common of the complex coronary lesions. Some estimates have reported that these are found in up to 20% of all PCIs.[20] Chronic total occlusions (CTO) are extremely common as well. CTOs are present in 20% of individuals undergoing non-urgent angiography.[21]  CTOs are found in 47% of individuals who present with acute coronary syndrome and in 89% of individuals with prior coronary artery bypass grafting.[22]

Estimates for unprotected left main coronary artery disease vary. One study cited its prevalence in 5% of individuals who underwent coronary angiography.[23] Another study estimated the prevalence at less than 2% of individuals who underwent coronary angiography.[24]

Approximately 300,000 individuals undergo coronary artery bypass grafting (CABG) in the United States annually. Among those with a saphenous venous graft, 8% to 12% experience early occlusion before discharge. Approximately 15% to 30% of saphenous vein grafts experience occlusion within the first year after CABG.[25] About 60% of individuals develop saphenous vein graft failure within 10 years of surgery.[26]

History and Physical

Most individuals with complex coronary artery lesions present similarly. The most common presentation is angina pectoris. Essential history elements include evaluating for risk factors of coronary artery disease. It is crucial to ask the patient questions regarding any history of vascular disease, obesity, diabetes, hypertension, age, hyperlipidemia, smoking, and family history of heart disease. Some of the most common symptoms of these lesions include:

• Chest pain, pressure, tightness, or heaviness (usually substernal or left-sided) radiating to the neck, jaw, left shoulder, or left arm
• Shortness of breath
• Palpitations
• Weakness
• Light-headedness
• Nausea or vomiting
• Sweating
• Feelings of anxiety or impending doom
• Indigestion

Physical examination findings vary based on the status of the patient’s disease. Individuals can have chronic coronary artery disease or an acute unstable plaque, and their physical exam findings will manifest differently. Thus, evaluating each case distinctly during a physical exam is essential. Some signs to look for in the physical exam include:

• Tachycardia
• Hypertension or hypotension
• Fever
• Jugular venous distension
• Crackles
• S4 heart sound
• Mitral systolic murmur
• Displaced apical impulse
• Delayed capillary refill
• Peripheral edema

Evaluation

Evaluation should include the following:

• Laboratory Studies: Laboratory values are not specific in identifying complex coronary lesions. If a blockage results in acute coronary syndrome, one can expect an elevation in cardiac-specific biomarkers; troponin T and troponin I will be elevated 4 to 8 hours after injury and will peak between 12 and 24 hours.[27]
• Electrocardiography (ECG): ECG has variable results in each clinical scenario. Nearly half of individuals with angina pectoris have no acute abnormalities on ECG. The most common findings in those who experience angina pectoris include 1 mm or more ST-depressions and T-wave inversions. If these lesions cause an unstable plaque, acute coronary syndrome can develop and present as 2 mm or more ST-elevations in contiguous leads (STEMI). Reciprocal changes in the opposite leads can increase the specificity of this diagnosis.[28] QTc prolongation is another finding present in those with transmural ischemia.[29]
• Stress Testing: Those suspected of acute coronary syndrome should have coronary angiography and possible PCI. Those in whom the diagnosis is unclear and are considered stable should undergo some form of stress testing. Exercise ECG is the procedure of choice in individuals with no resting ST-segment anomalies.[30] A pharmacologic stress test (dobutamine, adenosine) is an alternative for individuals who cannot exercise.[31] Increasingly, the myocardial perfusion scintigraphy test is utilized. They effectively localize areas of ischemia using thallium and technetium as nuclear markers of uptake.
• Coronary Angiography – Coronary angiography is the gold standard in diagnosing coronary lesions. Coronary angiography allows evaluation of the anatomy and extent of diseased vessels. Coronary angiography does have some limitations, including vessel overlap and visualization limited to the vessel lumen.[32] This modality is the only way to definitely evaluate the degree of stenosis and determine if any lesions are amenable to stenting.[33] Sometimes, complex lesions may not be amenable to stenting and may require medical therapy alone or surgical evaluation.

Treatment / Management

Treatment of primary coronary lesions varies with type:

• Saphenous vein graft stenosis: Saphenous venous grafts have accelerated rates of degeneration compared to native coronary arteries, and these stenoses compose about 10% to 15% of PCIs performed.[34] Degeneration of saphenous vein grafts is believed to be due to stress and shearing factors from high arterial flow paired with venous characteristics. Studies have compared the use of bare metal stents, drug-eluting stents, and balloon angioplasty. The SAVED trial found that bare metal stents (BMS) were superior to balloon angioplasty regarding procedural success, reduction in angiographic restenosis, and decreased major adverse cardiovascular events (MACE).[35] The RRISC trial showed that sirolimus-eluting stents reduced the need for target lesion revascularization and late loss. The relative risk reduction of restenosis was about 60%, and the relative risk reduction of need for revascularization was 80%.[11] However, another study by these same authors, the DELAYED RRISC study, revealed a similar need for target lesion revascularization at about 3 years and a significantly lower mortality rate in the BMS group compared to the DES group.[36] Very few studies have shown drug-eluting stents (DES) to be a more effective treatment than BMS in SVG stenosis, with the best evidence for DES in those with stenosis less than 3.5 mm and those with diabetes.[35] Notably, most of these studies were done on early-generation DES, while newer-generation DES have more biocompatible coatings and may have lower rates of stent thrombosis.[37] 
• Bifurcation lesions- Many studies have shown the superiority of DES over BMS in bifurcating lesions.[37] Most trials have shown no advantage of using 2 stents versus 1 stent in these lesions.[38] Namely, the Nordic IV and European Bifurcation Club 2 trials revealed no difference in major adverse cardiac events between provisional and 2-stent strategies.[39] Despite these results showing the efficacy of a provisional side branch stenting strategy, various advanced techniques are still used when approaching such lesions. These advanced approaches include crush, T-stenting, and kissing balloon angioplasty. There are promising data regarding using the crush and double kissing (DK) techniques if double stenting is desired.[40] The classic crush technique involves wiring and pre-dilating both vessels, followed by deployment of the side branch stent, removal of the side branch balloon and wire, followed by deployment of the main branch stent. This deployment of the main branch stent “crushes” part of the side branch stent. There are also variations of this technique. Such variations include the classic crush, the mini-crush, simultaneous kissing stents (SKS), and the double kissing crush (DK crush).[41] The DK-Crush II trial revealed less target revascularization in the double kissing crush technique at 12 months versus provisional stenting.[42] The DKCRUSH-V trial cited the superiority of a DK crush 2-stent technique over provisional stenting for those with distal left main bifurcation lesions.[43] Another commonly used technique that has shown promising results is the T-stenting technique. This technique is useful for bifurcations with an angle close to 90 degrees. The steps involved include wiring and dilating both vessels simultaneously, stenting the main branch, followed by maintaining the wire and stenting the side branch. The final step in this technique is kissing balloon dilatation. The kissing balloon technique involves using 2 balloons in the side branch and main branches for luminal opening.[44]
• Chronic total occlusions (CTO)- These lesions are the most challenging to treat. The optimal approach to address these lesions is unclear. The DECISION-CTO trial showed the noninferiority of medical therapy compared to medical therapy along with PCI for death, myocardial infarction, cerebrovascular accident, and the need for repeat revascularization.[45] However, some studies have highlighted improved symptoms and a lower incidence of myocardial infarction using PCI.[46] Before approaching a CTO PCI, it is necessary to consider the lesion anatomy. Favorable outcomes of CTO PCI are associated with short CTO duration, shorter CTO length, absence of bridging adjacent to the occlusion, and a tapered stump at the proximal cap. The most challenging aspect of CTOs is accessing the distally occluded lesion; both antegrade and retrograde approaches can accomplish this. These highly specialized techniques necessitate using a specific guiding catheter, which may differ based on whether the lesion is in the right versus left coronary circulation.[47] Guidewire choice is also important. The most common approach is to initially utilize a polymer-coated floppy wire and escalate quickly based on physics to optimize tip load and support. These wires are less stiff and allow safer access to the CTO. Using a microcatheter can also support the guidewire when moving across the CTO.[48] A retrograde approach is reserved for CTO lesions that are not amenable to the antegrade approach. Other advanced techniques, such as laser and rotational atherectomy, have been utilized in CTOs to help create microchannels. However, atherectomy techniques are risky due to the risk of perforation and dissection, especially in the false lumen, and are not routinely used.[49] CABG is another option for patients with CTO if there is viable myocardium and if multi-vessel disease is present. Bypassing the CTO is an essential aspect of revascularization.[50]
• Left main coronary artery (LMCA) stenosis: These critical lesions have high mortality, given that the LMCA supplies most of the myocardium. In individuals with stable angina, CABG has been the standard of care for these individuals with unprotected LMCA stenosis. The 2013 European Society of Cardiology Guidelines highlighted PCI's role in individuals with a low (< 22) SYNTAX score.[51] The SYNTAX score is widely used and has been validated in many studies.[52][53][54][53][52] In those experiencing acute coronary syndrome with LMCA culprit lesions, PCI may be an option in those with cardiogenic shock, isolated LMCA culprit lesions, poor surgical candidates, or those with initial TIMI 0 or 1 flow.[55] CABG is preferable in those with concurrent valvular disease, diabetes, decreased left ventricular ejection fraction, extensively calcified LMCA disease, multi-vessel disease, or high SYNTAX score. Recent advances in hemodynamic support with devices such as intra-aortic balloon pumps may make these lesions easier to treat in cases where CABG is inappropriate. These devices can provide hemodynamic support while pursuing PCI.

• Mechanical circulatory support for high-risk/complex coronary artery lesions: Many of the above-listed lesions carry a high risk of failure and decompensation during the PCI. Veno-arterial extracorporeal membrane oxygenation ( VA-ECMO) support is often used in patients considered extremely high risk for PCI who otherwise are not surgical candidates and may be considered for medical management.[56] Before crossing the high-risk lesion, the patient can be cannulated for VA-ECMO for hemodynamic support during the procedure or continued support after the conclusion of the procedure if cardiogenic shock remains. VA-ECMO allows the patient to have maintained preload and afterload so that the proceduralists have adequate time and hemodynamic support to repair the complex coronary lesion. [57] Having VA-ECMO as a periprocedural support device allows the cardiology team to create a bridge between those patients who would have only received medical management due to their complex coronary artery disease.[58]

• New developments: As noted above, most research has been done on first-generation DES. Newer generation DES stents have significant changes, such as more biocompatible coatings, thinner stent struts, and lower dosages of sirolimus-type drugs; these changes are thought to decrease the inflammatory process and allow intimal healing.[59] Bioresorbable stents also have the potential to improve the outcomes of PCI greatly. These stents are meant to degrade into inert molecules after the coronary artery lumen has been opened, possibly aiding in beneficial vessel remodeling.[37][59]

Differential Diagnosis

The differential of complex cardiac lesions is wide and includes any process causing chest pain, shortness of breath, palpitations, or other signs of cardiac ischemia. Some of these conditions include aortic dissection, acute cholecystitis, anxiety biliary colic, costochondritis, chronic obstructive pulmonary disease (COPD) exacerbation, esophageal spasms, esophagitis, gastroesophageal reflux disease (GERD), myocarditis, pericarditis, Prinzmetal angina, pneumonia, pulmonary embolism, and spontaneous or tension pneumothorax.

Prognosis

Complex coronary lesions carry higher overall mortality in patients with stable angina than those with noncomplex lesions. These complex lesions are often associated with diabetes, lower ventricular ejection fraction, and lower HDL-C. The SYNTAX Score and SYNTAX Score II are frequently the means to decide on the best revascularization approach. These scoring systems are widely used and have been validated in many studies.[52][53][54] Studies have shown SYNTAX Score II to be superior to the SYNTAX score as a prognostic tool. 

Complications

Coronary artery dissection: This complication is related to percutaneous transluminal coronary angioplasty. Certain types of coronary artery dissections are associated with an increased incidence of vessel closure and myocardial infarction, depending on the degree of dissection and the effect on coronary flow.

Intramural hematoma: Coronary intramural hematoma develops when blood accumulates in the vessel media; this can be best identified with intravascular ultrasound (IVUS) but can also be seen on coronary angiography. These lesions can present as acute coronary syndrome following a previous PCI.[60]

Perforation: Perforation of coronary arteries can result from guidewires, atherectomy devices, and balloons. Performations are rare but can be serious. One large review found an incidence of 0.7%, with the majority requiring intervention such as prolonged balloon inflation or anticoagulation reversal; however, overall morbidity and mortality rates were low.[61] The degree of perforation affects prognosis. Class I perforations include an intramural crater without extravasation and carry a very low risk of myocardial infarction. Class II perforations are 1 mm or greater with cavity spilling. Class III lesions correlate with myocardial infarction in up to 50% of lesions.[62]

Deterrence and Patient Education

Patients should be active participants in their care. Given the morbidity and mortality involved with complex coronary lesions, providers should actively discuss the management of these lesions as well as all possible options and the potential complications associated with them. Medical, interventional, and surgical options should be discussed with these individuals.

Enhancing Healthcare Team Outcomes

Management of complex coronary artery lesions requires an interprofessional team approach. Emergency medical personnel are often first responders and must be able to screen for acute coronary syndromes adequately. Nurses must be able to effectively recognize symptoms and decompensation of these patients at the bedside. Nurses and pharmacists are also needed to prepare, dispense, and efficiently administer various medications that may be necessary during these processes. Cardiac catheterization lab staff also play an essential role. Catheterization lab techs and nurses must be readily available to efficiently and effectively deliver care when acute coronary syndromes occur. And, of course, interventional cardiologists play a vital role. Interventional cardiologists must be readily available to diagnose and treat those with complex coronary lesions. Sometimes, interventional cardiologists may need to utilize advanced techniques in high-risk patients.

Managing complex cardiac lesions requires a cohesive and interprofessional healthcare team to provide patient-centered care, enhance outcomes, ensure safety, and optimize team performance. Physicians, nurses, pharmacists, laboratory staff, and interventional cardiology specialists play pivotal roles in this collaborative approach. Effective communication among team members is paramount. Physicians and nurses must promptly recognize signs of cardiac ischemia and initiate appropriate diagnostic testing. Open and clear communication facilitates rapid diagnosis and treatment decisions and ensures a coordinated response.

Patients must be fully educated about the risks and benefits of appropriate interventions, and informed consent is essential, respecting patient autonomy and ensuring beneficence and non-maleficence. Patient preferences are central to decisions, promoting shared decision-making. Education and training keep the team updated on best practices. Ongoing professional development ensures that healthcare practitioners are equipped to respond effectively to cardiac ischemia, which can be an emergency. A patient-centered approach places the patient's well-being and preferences at the forefront of all decisions. In managing complex cardiac lesions, an interprofessional healthcare team ensures a comprehensive response, minimizes complications, and prioritizes patient safety and care quality.