Complex Coronary Artery Lesions

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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 to stent even difficult lesions. There are, however, some lesions that present challenges via the conventional PCI route. These lesions, termed complex coronary lesions, are categorized as such based upon various 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, or stenosis of the saphenous vein graft. 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.


  • Review the types of complex coronary artery lesions.
  • Describe the presentation of a patient with coronary artery disease.
  • Summarize the treatment of complex coronary lesions.
  • Explain the clinical evaluation of complex coronary artery lesions and the role of the health professional team in coordinating the care of patients with this condition.


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 to stent even difficult lesions. There are, however, some lesions that present challenges via the conventional PCI route. These lesions, termed complex coronary lesions, are categorized as such based upon various 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, or stenosis of the saphenous vein graft.[1] Each of these lesions presents unique challenges, and the approach to such lesions is individualized. Specialized techniques, as well as cardiologists with more advanced skill sets, have improved the successful treatment of such lesions.[2]

Conventional PCI may not adequately resolve these lesions, and some may require advanced techniques. One such subset of advanced catheter-oriented interventions is termed: complex high-risk and indicated PCI (CHIP). Such techniques are reserved for individuals who are at very high risk for complications. Examples of 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 have a positive impact on mortality.  Some studies, such as one from Habib et al., cite CABG as a more effective modality towards addressing these lesions.[4]

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

  • Bifurcation lesions- This type of lesion arises at or adjacent to the separation of a major coronary artery. These lesions subdivide into three anatomic portions. The three portions are the proximal main branch, distal main branch, and side branch. A bifurcation lesion is one with significant stenosis (over 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 in each of these locations. 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 that is active, regulated, and involves atherosclerotic as well as inflammatory and hormonal disease processes. Coronary artery calcification (CAC) involved 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 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 there is a bypass graft supplying the left anterior descending artery or the left circumflex artery.
  • Ostial lesion- An ostial lesion is one that starts within 3 mm of the origin of a major coronary artery.[9] These may be challenging to stent due to their proximity to the aorta.
  • Stenosis of saphenous vein graft (SVG)- This type of stenosis occurs commonly, with some reports up to 20% of patients within 1 year. PCI of SVG contains a significant risk for myocardial infarction or diminished anterograde flow.[10] Atherosclerotic disease within graft results in a high restenosis rate as well.


Each complex coronary artery lesion has a unique set of etiologies. For example, bifurcation lesions are primarily anatomic-based.[11] Coronary artery calcifications can result from inherent inflammatory processes, as well as the activity of osteoblastic activity.[12] The presence of thrombus can often result from plaque disruption before or during PCI.[13] Saphenous vein graft occlusion is thought to be a process of intimal vessel smooth muscle proliferation.[14] 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.[15] Each process has an individual process that contributes to its etiology. 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 all complex lesions.


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.[16]

  • Coronary artery calcification is a nonspecific term, and the amount of calcification can vary greatly. The majority of the population has some degree of calcification and atherosclerosis, though it may not be significant enough to cause significant stenosis.[17] One large study noted calcifications to be present in 50% of individuals age 40 to 49. This number rose 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 aged over 70 years and 77% for women aged greater than 70.[19]
  • Chronic total occlusions (CTO) are extremely common as well. CTOs are present in 20% of individuals undergoing non-urgent angiography.[20] The incidence is even higher in higher-risk individuals. CTOs are found in 47% of individuals who present with an acute coronary syndrome and in 89% of individuals with prior coronary artery bypass grafting.[21]
  • Estimates for unprotected left main coronary artery (ULMCA) disease vary. One study cited its prevalence in 5% of individuals who underwent coronary angiography.[22] Another study estimated its prevalence at less than 2% of individuals who underwent coronary angiography.[23]
  • Approximately 300000 individuals undergo coronary artery bypass grafting (CABG) in the United States annually. Among those with 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. About 50% of individuals have saphenous vein graft failure within 10 years of surgery.[24]

History and Physical

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

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

Physical examination findings will vary based upon 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 in completely different ways. Thus, it is important to evaluate each case distinctly when doing a physical exam. Some items 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 should include:

  • Lab Studies - Lab studies are often not as specific in identifying one of the discussed. If one of the lesions has resulted in an acute coronary syndrome, one can expect elevation in white blood cell count. Cardiac-specific biomarkers such as troponin T and troponin I will be elevated 4 to 8 hours after injury and will peak between 12 and 24 hours.[25]
  • 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 ST-depressions and t-wave inversions. Of course, if these lesions have resulted in an unstable plaque, one would look for signs of an acute coronary syndrome and specifically 2 mm ST-elevations in contiguous leads (STEMI). Reciprocal changes in the opposite lead to the increased specificity of this diagnosis.[26] QTc prolongation is another finding that is present in those with transmural ischemia.[27]
  • Stress Testing – Those suspected of undergoing acute coronary syndrome should have coronary angiography and possible PCI. Those in whom the diagnosis is unclear and considered stable should experience some form of stress testing. Exercise ECG is the procedure of choice in individuals with no resting ST-segment anomalies. Ischemic changes may present in this form of testing.[28] In individuals who cannot exercise, a pharmacologic stress test (dobutamine, adenosine) is an alternative.[29] Increasingly, myocardial perfusion scintigraphy test is utilized. These are effective in the localizing area 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 one to evaluate the anatomy and extent of diseased vessels. Coronary angiography does have some limitations, including vessel overlap and visualization limited to the vessel lumen.[30] This modality is still the best one in terms of evaluating the degree of stenosis and if any lesions are amenable to stenting.[31] In some cases, these 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 when compared to native coronary arteries.[32] Degeneration of saphenous vein grafts is believed to be due to stress and shearing factors from higher impact arterial flow. 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 with regards to procedural success, reduction in angiographic restenosis, and decreased major adverse cardiovascular events (MACE).[33]  The RRISC trial was one such study that showed sirolimus-eluting stents decreased target lesion revascularization and late loss.[34] The DELAYED RRISC study, however, revealed a similar need for target lesion revascularization at 36 months.[35] Very few studies have shown drug-eluting stents (DES) to be an effective treatment and support the use of DES over BMS in SVG stenosis, with the best evidence in those with stenosis less than 3.5mm, and in those with diabetes.[33]
  • Bifurcation lesions- Many studies have shown the superiority of DES over BMS. DES specifically have demonstrated decreased rates of restenosis.[36] The majority of trials have not shown any advantage of using two stents versus one stent in bifurcation lesions.[37] Namely, the Nordic IV and European Bifurcation Club 2 trials revealed no difference with regards to MACE between provisional and 2-stent strategies.[38] Despite these results which show the efficacy of provisional side branch stenting strategy, various advanced techniques are still in use when approaching such lesions. Some of these advanced approaches include crush, T-stenting, and kissing balloon angioplasty, and there are some promising data regarding the use of crush technique and double kissing (DK) technique if double stenting is desired.[39] The classic crush technique involves wiring and pre-dilating of both vessels, followed by deployment of the side branch stent, removal of 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).[40] The DK-Crush II trial revealed less target revascularization in the double kissing crush technique at 12 months versus provisional stenting.[41] 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.[42] One other commonly used technique which 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 of the side branch. The final step in this technique is kissing balloon dilatation.[43]
  • Chronic total occlusions (CTO)- These lesions continue to be the most challenging lesions to treat. It is uncertain what the optimal approach is to address these lesions. The DECISION-CTO trial showed noninferiority of medical therapy compared to medical therapy with PCI concerning death, myocardial infarction, cerebrovascular accident, and the need for repeat revascularization.[44] However, some studies have highlighted improved symptoms and lower incidence of myocardial infarction with PCI of CTO.[45] Before approaching a CTO PCI, it is necessary to consider the lesion anatomy. Favorable outcomes of CTO PCI have their basis in the short duration of CTO, shorter length of CTO, the absence of bridging adjacent to occlusion, and a tapered stump at the proximal cap. The most challenging aspect of CTO’s is accessing the distally occluded lesion; this requires the use of antegrade or retrograde approaches. These highly specialized techniques necessitate the use of a specific guiding catheter which may be different based on whether the lesion is in the right versus left coronary circulation.[46] 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. The use of a microcatheter also can provide further support to the guidewire when trying to move across the CTO.[47]A retrograde approach is reserved for CTO lesions which are not amenable to the antegrade approach. Other advanced techniques such as laser and rotational atherectomy have been utilized in CTOs to help create micro-channels. However, atherectomy techniques are risky due to their increased risk of perforation and dissection especially in the false lumen and are not routinely used.[48] CABG  is another option for patients with CTO if there is viable myocardium and if multi-vessel disease is present and bypassing the CTO is an essential aspect of revascularization.[49]
  • Left Main Coronary Artery (LMCA) stenosis- These critical lesions have high mortality given that the LMCA supplies the majority of the myocardium. In individuals with stable angina, CABG has been the standard of care in these individuals with unprotected LMCA stenosis. The 2013 European Society of Cardiology Guidelines did highlight the role of PCI in individuals with a low (less than 22) Syntax score.[50] In those experiencing ACS 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.[51] CABG is preferable in those with concurrent valvular disease, diabetics, those with 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 pump may make these lesions easier to treat if surgeons refuse CABG. These devices can provide hemodynamic support while pursuing PCI.

Differential Diagnosis

  • Aortic dissection
  • Acute cholecystitis
  • Asthma exacerbation
  • Anxiety attack
  • Biliary colic
  • Costochondritis
  • Choledocholithiasis
  • Chronic obstructive pulmonary disease (COPD) exacerbation
  • Dyspepsia
  • Esophageal spasms
  • Esophagitis
  • Gastroesophageal reflux disease (GERD)
  • Myocarditis
  • Panic attack
  • Peptic ulcer
  • Pericarditis
  • Prinzmetal angina
  • Pneumonia
  • Pulmonary embolism
  • Spontaneous or tension pneumothorax


Complex coronary lesions carry higher overall mortality in patients with stable angina than those with non-complex lesions. These complex lesions are often associated with diabetes, lower ventricular ejection fraction, lower HDL-C. The SYNTAX Score and SYNTAX Score II are frequently the means to decide on the best revascularization approach. Studies have shown SYNTAX Score II to be superior to the SYNTAX score as a tool of prognosis. The 4-year mortality showed an adequate correlation between score and mortality in patients with low and medium SYNTAX Score II, however, found that a high SYNTAX Score II underestimated mortality at four years.[52]


  • 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, which depends on the degree of dissection and the effect that it has on flow.
  • Intramural hematoma – Coronary intramural hematoma develops when blood accumulates in the vessel media; this can be best identified with intravascular ultrasound (IVUS), although it can also be seen on coronary angiography. These lesions can present as acute coronary syndromes following a previous PCI.[53]
  • Perforation – Perforation of coronary arteries can result from guidewires, atherectomy devices, and balloons. 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.[54]

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, as well as 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 adequately screen for acute coronary syndromes. 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 which may be necessary during these processes. Cath lab staff also play an essential role. Cath lab techs, as well as 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. At times, interventional cardiologists may need to utilize advanced techniques in high-risk patients. [Level 5]

Article Details

Article Author

Syed Iftikhar

Article Editor:

Patrick Hu


7/26/2021 12:46:26 AM



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