Exploring the role of percutaneous coronary intervention for chronic total occlusions Elias, J.

UvA-DARE (Digital Academic Repository) Exploring the role of percutaneous coronary intervention for chronic total occlusions Elias, J. Link to publication Citation for published version (APA): Elias, J. (2018). Exploring the role of percutaneous coronary intervention for chronic total occlusions General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) Download date: 10 Mar 2019

CHAPTER 1 Introduction and outline of the thesis 9

INTRODUCTION Patients with coronary artery disease (CAD) have an increased mortality and morbidity risk. A chronic total occlusion (CTO) is present in about 20% of stable CAD patients and in 10-15% of patients presenting with ST-segment elevation myocardial infarction (STEMI) 1 2. A CTO is defined as a 100% (complete) chronic coronary artery blockage, present for at least 3 months 2. In CTO patients the myocardium distal of the occluded artery becomes completely dependent on alternative perfusion from collateral vessels. Collateral vessels are interarterial connections that supply blood flow to the obstructed tissue to maintain perfusion and preserve function and viability 3. Over time the myocardium will adapt to the chronic flow reduction in order to prevent infarction but this will lead to a decrease in contractile function (hibernation). Percutaneous coronary intervention (PCI) is commonly performed in the treatment of stable CAD as well as STEMI patients. In STEMI patients with multi-vessel disease randomized trials showed that (staged) multi-vessel PCI compared to culprit-only PCI has a beneficial effect on the combined endpoint of recurrent MI, revascularization and mortality 4-6. However, in those trials CTO lesions were mainly excluded. Although CTO patients have a worse outcome and frequently experience disabling (angina) symptoms, revascularization of CTO is infrequently attempted (<10%) 7. Perceptions of lower procedural success rates, higher complication risks and presence of a sufficient alternative collateral network have probably led to this rather conservative strategy. Although the collateral flow to the myocardium supplied by the CTO may be adequate in resting conditions, it fails during exercise and patients will experience ischemia reducing their exercisecapacity and quality of life 3. Observational data suggests that successful (staged) PCI of the CTO leads to improvement of left ventricular (LV) function, a reduction in adverse events and a decreased mortality 8-11. However, all these studies were not randomized and the comparison with a conservative control (no-cto PCI) is lacking. The optimal treatment of (post-stemi) CTO lesions therefore remains controversial. Our research group initiated the first global multicentre randomized controlled trial on the effect of CTO PCI on LV function; the Evaluating Xience and LV Function in PCI on Occlusions after STEMI (EXPLORE) trial. In the EXPLORE trial, STEMI patients with a concurrent CTO were randomized to either routine early CTO PCI within 7 days after the primary PCI or no-cto PCI for at least 4 months. The rationale for the EXPLORE trial is based on two mechanisms: (1) recanalization of the CTO will restore the contractile function of the hibernating myocardium. And (2) revascularization of the CTO will improve the myocardial perfusion of the infarct border area, where the myocardium of the infarct-related artery and the CTO are contiguous or overlapping, leading to improved healing of this border area. These effects will attenuate the remodeling process, which would theoretically lead to a better global LV function and improved survival 12. In the thesis presented we evaluate the role of routine invasive treatment of CTO lesions in the post-stemi setting on global and regional LV function and on clinical outcome. Furthermore, we explore the influence of location of the CTO and the value of the quality of the collateral circulation on the effect of CTO PCI. 10

OUTLINE OF THESIS Part I of this thesis consist of the short-and long-term results of the randomized EXPLORE trial. In chapter 2, 13 we present the effect of additional CTO PCI post-stemi on the combined primary endpoints LV ejection fraction (LVEF) and LV end-diastolic volume (LVEDV) measured,14 15 on cardiovascular magnetic resonance imaging (CMR) at 4 months follow-up. In chapter 3 we evaluate the impact of recanalization of the CTO on mid- and long-term clinical outcome. Furthermore, the effect of CTO PCI on 1-year LV function and functional outcome, angina status and dyspnea status was assessed. Part II focuses on the impact of the location of the concurrent CTO. In general, STEMI patients with the culprit lesion located in the left anterior descending artery (LAD) have a higher mortality, probably because the LAD supplies the major part of left the ventricle 16. However, prognosis might also vary according to the anatomical location of the concurrent CTO. Even more, in STEMI patients with a CTO, there is both an acutely and chronically occluded coronary artery. In chapter 4,17 we therefore evaluate the long-term prognosis of STEMI patients with a concurrent CTO based on the location of the culprit lesion in combination with the location of the CTO. In elective setting the effect of CTO PCI on clinical outcomes varied with the anatomical location 18. In previous studies mortality was reduced after successful CTO treatment in the LAD and left circumflex artery, but not after CTO PCI of the right coronary artery 19. In chapter 5,20 we perform an in-depth analysis of the recovery of LVEF and LVEDV from baseline to 4 month followup in the patients included in the EXPLORE trial. In 180 patients with serial CMR we evaluated the impact of CTO location on success rates and effect of CTO PCI compared to no-cto PCI. Part III evaluates the influence of the quality of the collateral capacity of the collateral vessels supplying the myocardium distal of the CTO. Well-developed collateral vessels have been suggested to be able to reduce infarct size, improve LVEF and survival in stable CAD patients as well as in STEMI 21 22. The prognostic value of collateral vessels to the CTO in STEMI patients is however unknown. Therefore, in chapter 6,23 we examine the effect of well-developed versus poorly-developed collateral vessels to a CTO on long term clinical outcome in STEMI patients undergoing primary PCI. In chapter 7,24 we investigate the impact of collateral vessels to the CTO in STEMI patients on LV function. We also evaluate whether the presence of well-developed- or poorly developed collateral vessels has a different effect of CTO PCI on LV function and long-term clinical outcome. Although the collateral circulation has prognostic implications, it is unknown whether collateral vessels are modifiable markers or just prognostic indicators of outcome. Our research group showed that patients with high versus low coronary collateral capacity display different expression of cellular mirnas 25. This suggests new possibilities for therapeutic stimulation of the development of collateral vessels (arteriogenesis), which is a form of vascular remodeling where pre-existing collateral arterioles transform into functional collateral vessels 26. However, new angiogenesis interventions also require sufficient means of collateral vessel detection and monitoring. CMR has great versatility and has the capacity to obtain morphologic and functional information 27. Therefore in chapter 8,28 we study the detective value of CMR 1 INTRODUCTION AND OUTLINE OF THE THESIS 11

semi-quantitative and quantitative perfusion to distinguish the collateral-perfused from the antegrade-perfused myocardium in CTO patients. Furthermore, we evaluate the correlation between intracoronary measured collateral flow indices, and CMR perfusion parameters. Part IV evaluates the effect of CTO PCI on regional left ventricular function. CMR is a noninvasive high-resolution imaging technique which has the ability, with a single test, to accurately assess and reproduce qualitative myocardial perfusion, viability, regional and functional LV function 29. The primary endpoints of EXPLORE were CMR-derived global LVEF and LVEDV, which are parameters that are affected by many other factors, especially in the early post-stemi phase. A possible treatment effect of CTO PCI will however be most pronounced in the CTO territory. We therefore performed an in-depth quantitative analysis of the regional function of the myocardium using CMR, which allows for accurate analysis of regional segmental function (segmental wall thickening). In chapter 9,30 we evaluate the effect of CTO PCI compared to no- CTO PCI on the recovery of regional LV function, particularly in the CTO territory. LV function (LVEF) and infarct size often serve as surrogate endpoints for prediction of clinical outcome in (STEMI) patients 31. However, subtle but important contractile changes may not be detected, as this does not always lead to global LVEF decline. Therefore, myocardial strain is gaining more interest as it is able to detect more subtle myocardium deformation and is less dependent on performer experience 32. By defining the relative length change of the myocardial segment following the border tracking over time CMR-based feature tracking (FT) provides fast and accurate strain assessment 33. We use FT-CMR to assess global and regional strain recovery over time and the effect of CTO PCI on strain recovery in chapter 10,34. Furthermore, we investigate the prognostic value of strain parameters incremental to standard CMR parameters. 12

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