Frontiers of interventional cardiology: plaque imaging, thrombus load, and bifurcation lesions

Download the Issue @ a Glance podcast Subscribe to the EHJ Podcast It has now been half a century since the first coronary bypass graft surgery, with the first percutaneous coronary intervention following just over a decade later.1,2 The relative merits of percutaneous coronary intervention as compared with coronary bypass graft surgery for stable coronary artery disease have continued to be debated ever since and have been the focus of ∼20 randomized trials and numerous registry studies, systematic reviews, and meta-analyses,3,4 as well as recent ESC Guidelines.5 David Holmes and David Taggart from the Mayo Clinic in Rochester USA and the Radcliffe Hospital in Oxford provide a comprehensive review on the topic ‘Revascularization in stable coronary artery disease: CABG vs. PCI. A combined cardiologyand surgery perspective’. He identifies areas of agreement, disagreement, and uncertainties on the role of percutaneous coronary intervention and coronary bypass graft surgery in patients with stable coronary artery disease with the aim of providing the basis for more appropriate patient selection within the HeartTeam.6 The primary culprit of clinical events in patients with coronary artery disease is the vulnerable plaque.7,8 Its structure and biology determine whether plaque rupture9 or erosion10 occurs, leading to thrombus formation and eventually acute coronary syndromes. Until recently, the clinical assessment of plaques proved very difficult. Carlo Di Mario and colleagues from the Royal Brompton in London discuss in their review ‘Invasive coronary imaging: any role in primary and secondary prevention?’ new modalities of non-invasive and invasive coronary imaging in an effort to optimize risk stratification of such patients, and to identify subgroups at high risk that may benefit from an aggressive, personalized approach.11 Of particular interest in this context are novel invasive imaging techniques such as near infra-red spectroscopy and optical coherence tomography that can reliably identify thin-capped fibroatheromas.12,13 Multiple trials are exploring the feasibility of these techniques to guide patient management. A novel issue is the treatment of non-flow-limiting lesions at high risk of destabilization and coronary occlusion. Asymptomatic patients at high risk of cardiovascular ischaemic events may also be considered, with the intermediate step of a wider application of calcium score and angiography with multislice computed tomography and the selective use of invasive imaging in those with suspicious findings. Plaque destabilization due to activation of inflammatory pathways8 is commonly associated with thrombus formation;14,15 and, indeed, without thrombus formation coronary arteries do not occlude. Thus, it appeared evident to most interventionists that catheter-based removal of the thrombus in patients with acute coronary syndromes will be beneficial—until proven otherwise by large trials.16,17 In the FAST TRACK ‘Myocardial blush and microvascular reperfusion following manual thrombectomy during percutaneous coronary intervention for ST elevation myocardial infarction: insights from the TOTAL trial’, Christopher Overgaard and colleagues from the Peter Munk Cardiac Centre in Toronto provided another analysis of the TOTAL trial that randomized 10 732 patients to routine manual thrombectomy or percutaneous coronary intervention alone in ST-segment elevation myocardial infarction.18 In the current angiographic substudy, they investigated if thrombectomy improved microvascular perfusion as measured by myocardial blush grade. Of the 10 732 patients, 1610 randomly selected angiograms were analysable for the primary outcomes of myocardial blush grade and TIMI flow grade. Secondary outcomes included distal embolization and complications of the intervention. Again, surprisingly for many, final myocardial blush and TIMI flow were similar in the two groups. However, thrombectomy was associated with a reduced incidence of distal embolization compared with percutaneous coronary intervention alone. Interestingly, distal embolization was an independent predictor of mortality, with a hazard ratio of 3.0, while myocardial blush grade was not. Thus, routine thrombectomy—as performed with current catheter-based tools—during primary percutaneous coronary intervention does not result in improved myocardial blush grade or flow grade, but did reduce distal embolization. Distal embolization may be an easily assessed angiographic endpoint to evaluate reperfusion strategies in future studies in such patients. The paper is accompanied by an interesting Editorial by William Wijns from the OLV Hospital in Aalst, Belgium.19 Access for percutaneous coronary interventions has been heavily discussed lately, with the publication of an increasing body of evidence favouring the radial approach,20 particularly in those at risk for bleeding. In the paper entitled ‘The comparative efficacy of bivalirudin is markedly attenuated by use of radial access: insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)’, Hitinder Singh Gurm from the University of Michigan in Ann Arbor, MI, USA evaluated the relative impact of bivalirudin on bleeding outcomes associated with transradial interventions in patients treated in 47 hospitals of the Blue Cross Blue Shield of Michigan Cardiovascular Consortium.21 Among patients undergoing transfemoral interventions, the use of bivalirudin was associated with a reduction in bleeding from 3.46% to 1.67% compared with glycoprotein IIb/IIIa inhibitors and from 1.76% to 1.26% compared with heparin. Among patients undergoing transradial interventions, there was a more modest reduction in bleeding with bivalirudin compared with glycoprotein IIb/IIIa inhibitors from 1.41% to 0.79%, and no difference in bleeding compared with heparin. The authors conclude that bivalirudin is primarily efficacious in reducing bleeding in patients undergoing transfemoral interventions, while it provides little benefit in those undergoing transradial interventions. Given its lower cost and comparable outcomes, heparin should be the preferred anticoagulation strategy in those undergoing radial percutaneous coronary intervention. Kaplan–Meier graphs showing clinical outcome. Clinical outcomes at 30 days (left panel) and 6 months (right panel). HR, hazard ratio; ITT, intention-to-treat; MACE, major adverse cardiac events; PH, proportional hazards (from Nazir SA, McCann GP, Greenwood JP, Kunadian V, Khan JN, Mahmoud IZ, Blackman DJ, Been M, Abrams KR, Shipley L, Wilcox R, Adgey AA, Gershlick AH. Strategies to attenuate microvascular obstruction during primary percutaneous coronary intervention: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial. See Pages 1910–1919). A 44-year-old woman undergoing multi-slice computed tomography non-invasive coronary angiography because of partially atypical chest pain. The severe serial lesions in the left anterior descending artery detected with computed tomography are confirmed with invasive angiography and optical coherence tomography, showing a very severe circumferential thin capped fibroatheroma (lesion site, A). Despite multiple risk factors including smoking and severe hypercholesterolaemia, the 10-year cardiovascular risk was 0 based on conventional parameters (from Di Mario C, Moreno PR. Invasive coronary imaging: any role in primary and secondary prevention? See Pages 1883–1890). Outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction have improved incrementally through the implementation of evidence-based practice as outlined in the ESC Guidelines.22 Nevertheless, event rates remain important, among others due to suboptimal perfusion in the microvascular bed23 despite restoring normal patency in the infarct-related artery. Microvascular obstruction occurs in at least 40–70% of the patients and is associated with adverse left ventricular remodelling, diminished recovery of left ventricular function, and worse clinical outcomes, independently of infarct size.24 Conceptually, a number of pharmacological tools should attenuate microvascular obstruction, such as adenosine and sodium nitroprusside. However, heterogeneous trial design and the lack of reliable tools to detect microvascular obstruction have led to conflicting results. Cardiac magnetic resonance imaging sensitively detects both microvascular obstruction and myocardial necrosis.25 Thus, in their paper entitled ‘Strategies to attenuate microvascular obstruction during primary percutaneous coronary intervention: the Randomized REperfusion Facilitated by Local Adjunctive Therapy in ST elevation Myocardial Infarction (REFLO-STEMI) trial’, Anthony H. Gershlick and colleagues from Glenfield Hospital in Leicester, UK assessed 247 patients presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset in a randomized design, as to whether intracoronary adenosine or sodium nitroprusside, administered locally to the infarct-related artery, impacts on microvascular obstruction and infarct size as measured by cardiac magnetic resonance imaging.26 Unfortunately, neither adenosine nor sodium nitroprusside reduced infarct size or microvascular obstruction. What is worse, adenosine was associated with increased adverse clinical outcomes driven by early heart failure, infarct size, and reduced ejection fraction. Thus, adenosine and sodium nitroprusside should not be used in the setting of primary percutaneous coronary intervention. The manuscript is accompanied by an interesting Editorial by James A. de Lemos from UT Southwestern Medical Center in Dallas, Texas.27 While stenting of large coronary segments today is a simple procedure with a very low complication rate, the management of bifurcation lesions remains challenging.28 Randomized trials of coronary bifurcation stenting have shown better outcomes of a simple, i.e. provisional, strategy rather than a complex approaches using stenting of both branches. In their paper entitled ‘Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study’, Miles William Behan from the Edinburgh Heart Centre in Scotland, UK, investigated the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation stenting trials, i.e. the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study.29 Both trials compared simple, provisional T-stenting with complex, i.e. culotte, crush, and T-stenting techniques,30 using drug-eluting stents. With 3.8%, 5-year mortality was lower among patients who underwent a simple compared with 7.0% of those undergoing a complex strategy. The authors conclude that for coronary bifurcation lesions, a provisional single stent approach appears to be associated with lower long-term mortality than systematic dual stenting. The paper is accompanied by an insightful Editorial by Antonio Colombo from EMO GVM Centro Cuore Columbus in Milan, Italy.31 The editors hope that readers of this issue of the European Heart Journal will find it of great interest.