Cardiovascular Revascularization Medicine, 2018-07-01, Volume 19, Issue 5, Pages 553-557, Copyright © 2018 Elsevier Inc. Abstract A 67-year-old man with coronary artery disease and previous coronary underwent successful Guideliner reverse CART percutaneous coronary intervention of a chronic total occlusion of the right coronary artery. He later developed evidence of myocardial ischemia, and imaging, including angiogram, echocardiogram, and cardiac computed tomography revealing active dye extravasation from the previously normal RV marginal branches, in addition to a large subepicardial hematoma. Despite these dramatic findings, the patient remained hemodynamically stable and pain-free, with resolving ECG changes. Thus, with close clinical observation, the patient did not undergo pericardiocentesis or other invasive procedures, and was discharged home safely. This review evaluates the complications of CTO-PCI, with a focus on subepicardial hematomas, discussing diagnosis and management of this highly morbid complication. Highlights With modern techniques, CTO-PCI can be performed with success approaching 90%. It is imperative for CTO operators to appropriately diagnose and manage complications. Subepicardial hematoma is a rare complication of CTO-PCI, with high mortality. This case and review highlight the diagnosis and management of coronary perforation and subepicardial hematoma. Conscientious evaluation of hemodynamics and clinical status should guide patient care. 1 Introduction Traditionally, percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) was performed in relatively few patients, with success rates as low as 70%. However, new data suggests that with modern techniques and emerging technology, CTO-PCI can be performed with success rates approaching 90% . CTOs may be present in up to 30% of patients with CAD in clinical practice, suggesting a potential increase in the number of CTO-PCI procedures . Given the complexity of these occlusions, modern algorithms advocate a thoughtful approach to CTO-PCI, with careful consideration of patient specific factors, lesion characteristics, and collateral circulation, with judicious attempts at antegrade or retrograde approaches. With the increasing number of CTO-PCI being performed, it is imperative for CTO operators to appropriately diagnose and manage potential complications, ranging from access-site hematoma to coronary perforation. 2 Case report A 67-year-old man with a history of diabetes mellitus type 2, hypertension, hyperlipidemia, and coronary artery disease (CAD) presented with persistent, daily exertional dyspnea despite optimal anti-anginal therapy. Thus, he was referred for PCI of a right coronary artery (RCA) CTO. Prior history was notable for coronary artery bypass graft surgery in 2004, with a left internal mammary artery (LIMA) to the left anterior descending artery (LAD), saphenous vein graft (SVG) to the first obtuse marginal (OM1), and SVG to the right posterior descending artery (rPDA). He underwent subsequent PCI of high-grade disease in two separate OM branches in 2013, after coronary angiogram demonstrated occlusion of both SVGs, high grade stenosis in the native left circumflex (LCx), and CTO of the native RCA. At the initial outpatient follow-up after this PCI, symptoms had improved. However, he presented one year later with progressive exertional dyspnea limiting his daily activity, despite escalation of antianginal therapy. His medications included maximum tolerated doses of carvedilol, isosorbide mononitrate, and amlodipine, in addition to aspirin, losartan, furosemide, rosuvastatin, and insulin. Echocardiogram showed normal ejection fraction with no valve abnormalities. Due to his persistent symptoms, the decision was made to perform PCI of the occluded right coronary artery. With bilateral femoral arterial access, the RCA was engaged using an 8F AL-1 guide catheter with a 6F Guideliner while the left main coronary artery (LMCA) was engaged using a 6F EBU 3.5 guide catheter ( Fig. 1/Video 1 ). In general adherence to the hybrid approach (NATO) algorithm , an antegrade wire was advanced beyond the proximal cap to the subintimal space ( Fig. 2/Video 2 ) and a retrograde wire was delivered via a septal perforator to the true lumen of the distal RCA using a Corsair microcatheter. The retrograde wire was exchanged for a 300 cm Pilot 200 guide wire, which was advanced using the “knuckle” technique in the retrograde direction. The Guideliner reverse CART technique was then employed, using an Emerge 3.0 × 30 mm balloon to enable advancement of the retrograde Pilot 200 guide wire and Corsair into the RCA Guideliner and guide catheter ( Fig. 3/Video 3 ). An R350 guide wire was inserted through the Corsair and externalized. Intravascular ultrasound (IVUS) of the RCA revealed a vessel with 4 mm proximal diameter and 3 mm distal diameter. From distal to proximal RCA, three DES were deployed. Repeat IVUS of the entire RCA revealed adequate stent apposition and mild-moderate stenosis of the proximal RCA with a minimal luminal area > 5 mm2. Final angiography confirmed adequate stent apposition, improvement of distal RCA flow from TIMI 0 to TIMI III flow, adequate recruitment of pre-existing RV marginal arteries, and no evidence of acute vessel perforation ( Fig. 4/Video 4 ). After this successful Guideliner reverse CART PCI of the RCA-CTO, the patient's initial post-procedural course was uneventful. Fig. 1/Video 1 Dual-injection coronary angiogram, with an 8 Fr AL-1 guide catheter in the right coronary artery and a 6 Fr EBU 3.5 guide catheter in the left main coronary artery. The angiogram shows chronic total occlusion of the right coronary artery with left-to-right septal collaterals from the left anterior descending artery. Fig. 2/Video 2 Coronary angiogram demonstrating the antegrade wire escalation technique; with micro catheter support, the antegrade wire was advanced beyond the proximal cap of the right coronary artery chronic total occlusion to the subintimal space. Fig. 3/Video 3 Angiogram demonstrating the Guideliner reverse CART technique, using an Emerge 3.0 × 30 mm balloon to enable advancement of the retrograde Pilot 200 guide wire and Corsair into the right coronary artery Guideliner and guide catheter. Fig. 4/Video 4 Final angiography after deployment of three drug eluting stents to the right coronary artery. Angiogram shows adequate stent apposition, improvement from TIMI 0 to TIMI III flow, adequate recruitment of pre-existing right ventricular marginal arteries, and no evidence of acute vessel perforation. Approximately 2 h after PCI, the patient developed chest discomfort, followed by 50-beats of a hemodynamically stable wide-complex tachycardia. The rhythm converted spontaneously to normal sinus, revealing ST-elevation on the subsequent ECG ( Fig. 5 ). The patient was taken emergently back to the cardiac catheterization laboratory. The left main coronary artery system was unchanged ( Fig. 6/Video 5 ). The right coronary artery was patent, but revealed relative straightening of the previous angulations in the proximal and mid-vessel, compared to the prior angiogram. Most notably, the angiogram demonstrated approximately 10 separate points of dye extravasation from the previously normal RV marginal branches ( Fig. 7/Video 6 ). Importantly, no wire or device had been near these points during the RCA PCI earlier in the day. Fig. 5 Electrocardiogram two hours after completion of initial procedure, demonstrating ST elevation. Fig. 6/Video 5 Emergent second angiogram of the left main coronary artery system. Reveals unchanged coronary angiogram without evidence of vessel injury. Fig. 7/Video 6 Emergent second angiogram of the right coronary artery system. The right coronary artery is patent, but there is relative straightening of the previous angulations in the proximal and mid-vessel, compared to the prior angiogram. Most notably, the angiogram demonstrates approximately 10 separate points of dye extravasation from the previously normal right ventricular marginal branches. Urgent bedside echocardiogram at that time was demonstrated a small pericardial effusion with a large adherent thrombus on the RV free-wall ( Fig. 8 ). There was no echocardiographic evidence of tamponade (i.e. no exaggerated mitral or tricuspid inflow variation) and the pulsus paradoxus measured < 10 mmHg. The patient remained hemodynamically stable throughout the procedure, with a normal rhythm and no need for vasopressors or hemodynamic support. Considering this hemodynamic stability and the recent administration of unfractionated heparin, the decision was made to conservatively manage this effusion with admission to the cardiac intensive care unit and close hemodynamic monitoring. The ECG at end of case showed improved ST segment elevation. Fig. 8 Echocardiogram immediately after second angiogram, revealing a large hematoma compressing the right ventricle, with bowing of the interventricular septum into the left ventricle. Cardiac computed tomography performed the same day revealed a loculated fluid collection measuring approximately 9.0 × 6.8 × 10.5 cm, compressing the right ventricle. The collection caused mass effect, with severe compression of the right ventricle and leftward bowing of the intraventricular septum ( Fig. 9 ). The hematoma appeared to be largely contained within the tissue plane between the visceral pericardium and the right ventricular myocardium proper. By initially expanding in this tissue plane, the initial hematoma effectively avulsed the penetrating RV branches from the myocardium, with resultant bleeding from the separated ends. This created a positive feedback loop, wherein bleeding from the avulsed branches further pressurized and expanded the hematoma. Fig. 9 Cardiac computed tomography demonstrating a large loculated fluid collection contained within the tissue plane between the visceral pericardium and the right ventricular myocardium proper. The hematoma measures approximately 9.0 × 6.8 × 10.5 cm, causing compression of the right ventricle and leftward bowing of the intraventricular septum. “*” indicates the hematoma. A stat surgical consult was obtained, but in light of his clinical stability, prior sternotomy, ongoing RV infarct, and potential subepicardial location of the hematoma, a decision was made not to pursue surgical evacuation. Throughout several days of clinical observation, he remained hemodynamically stable and symptom-free, with no further episodes of tachycardia, hypotension, or other markers of clinical deterioration. Repeat echocardiogram 2 weeks after discharge revealed a persistent, organized subepicardial hematoma, with moderate dysfunction and dilation of the RV. At 6 months, the hematoma had completely resolved, though RV function remained compromised. A subsequent echocardiogram 12-months after the procedure showed normal RV size and function ( Fig. 10 ). The patient declined repeat CT angiogram. Fig. 10 Echocardiogram one year after the initial event, demonstrating resolution of the subepicardial hematoma, normal RV size, and normal RV function. 3 Discussion In this patient, we postulate that balloon inflation in the subintimal space, part of the reverse CART procedure, produced a small hematoma in the tissue plane just deep to the RCA and beneath the visceral pericardium. This hematoma was located just within the myocardium. Initial expansion within this space separated the RCA from the myocardium, avulsing a small penetrating branch. This in turn created an active bleeding source that fed and pressurized the space, expanding the hematoma. As it enlarged, additional penetrating branches were pried from the muscle and recruited to the process in a positive feedback loop, until multiple avulsed branches perpetuated the hematoma. By the time of the angiogram 2 h later, 10 separate and distinct extravasation points were visualized in areas that never interacted with any wire or device. CTA confirmed the postulated anatomic relationship, with the RCA and the acute marginal branches substantially separated from the right ventricular myocardium by the expanded hematoma ( Fig. 3/Video 3 ). The patient was discharged one week after the initial event, asymptomatic and in stable condition, with a diagnosis of ST-elevation myocardial infarction due to avulsion of right ventricular marginal branches, in the setting of subepicardial hematoma as a sequela of successful Guideliner reverse CART PCI of an RCA CTO. 4 Review Coronary artery perforation is a rare, but grave, complication of percutaneous coronary intervention, caused by wire exit, balloon injury, or plaque modification. Perforation complicates 0.35% of PCI in contemporary series, though numbers have risen in recent years, despite improvements in technology and technique . Due to a recent increase in the volume of complex cases, rates of coronary perforation increased in 2016, complicating 2.9% of CTO-PCI and 0.45% of all PCI . Coronary artery perforation is an independent predictor of mortality, with rates between 17% and 23% . Risk factors include age, female gender, chronic kidney disease, and non-ST segment elevation myocardial infarction . Management strategies can range from prolonged balloon inflations, vessel embolization, covered stent placement, and emergent coronary artery bypass . Covered stent placement itself incurs additional risk, with higher rates of stent thrombosis and target lesion failure. In 40% of cases, coronary artery perforation can present with hemodynamic collapse from cardiac tamponade . Due to the rapid accumulation of pericardial blood, a relatively small volume can result in significant hemodynamic effect on the right ventricle. In such cases, emergent pericardiocentesis or surgical evacuation of hematoma is often necessary, with commensurate increase in mortality . However, in rare cases, coronary perforation can cause a localized subepicardial hematoma, without a fluid collection that is amenable to percutaneous drainage. Reports of subepicardial hematoma as a complication of PCI began in the early 1990s, noting early morbidity and mortality due to hemodynamic collapse, similar to classic tamponade . In most cases of subepicardial hematoma in the literature, patients suffer significant hemodynamic compromise, cardiogenic shock, and multi-organ system failure, despite maximal resuscitative efforts. In such cases, management often entails emergent surgical evacuation of the hematoma and potential emergent bypass of compromised vessels. Despite these heroic measures, mortality remains high , with only rare cases of survival to discharge after surgery . In cases where perforation is identified before sufficient fluid accumulation to cause tamponade, polytetrafluoroethylene-covered stent may be a possible solution. 5 Conclusion The volume of CTO-PCI procedures is increasing, with higher success rates due to improved techniques and technology. However, complications of CTO-PCI remain an important consideration, including coronary perforation and pericardial tamponade. The formation of a subepicardial hematoma is a rare complication with very high morbidity and mortality. This case demonstrates the clinical course of a subepicardial hematoma complicating RCA CTO-PCI, and is unique in its conservative management and favorable outcome. Despite the large size of the hematoma and evident RV compromise, the patient's clinical stability argued against covered stent placement, pericardiocentesis, or emergent surgery, particularly given the morbidity of these procedures. The right coronary artery remained patent despite RV infarct from avulsion of the marginal branches, and the patient's symptoms and ECG changes improved without further intervention. With a measured approach centered on a stable heart rate, normal blood pressure, and resolution of his symptoms, serial imaging demonstrated resorption of the subepicardial hematoma and improvement in RV function. Thus, with conscientious evaluation of the patient's hemodynamics and clinical stability, he was spared further invasive procedures. Thus, though subepicardial hematoma is typically associated with significant morbidity and mortality, early identification, rapid diagnostic testing, and a thorough evaluation of hemodynamics can allow for conservative management, though urgent surgical management remains the current standard in the majority of cases.