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 a 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 1mm 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 increase 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, 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 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.

• Aortic dissection
• Acute cholecystitis
• Asthma exacerbation
• Anxiety attack
• Biliary colic
• Costochondritis
• Choledocholithiasis
• 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 perforation’s 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]

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.

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.