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TCTAP 2023

Routine Functional Testing or Standard Care in High-Risk Patients after PCI

Lack of Evidence for Routine Functional Testing after PCI Duk-Woo Park, MD Asan Medical Center, Korea (Republic of) The effectiveness of regular stress functional testing after percutaneous coronary intervention (PCI) in improving clinical outcomes is uncertain. The 2019 European guidelines recommend non-invasive stress testing 6 months after high-risk PCI and coronary angiography 3-12 months later, and non-invasive stress testing 1 year after general PCI. However, the recommendations are weak (Class IIB recommendation, Level of evidence C), relying on expert opinions, and the 2021 ACC/AHA guidelines do not mention them. POST-PCI Trial: Routine Functional Testing vs. Standard Care after High-Risk PCI From November 2017 to September 2019, the POST-PCI investigators randomly assigned 1,706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI (849 patients), or to standard care alone (857 patients). The primary outcome was a composite of death from any cause, myocardial infarction (MI), or hospitalization for unstable angina at 2 years. The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.61-1.35; P=0.62) (Figure 1). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, -0.01-5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, -0.22-4.68). Figure 1. Time-to-event curves for the primary composite outcome and the components of the primary composite outcome Further, a landmark analysis performed between 1 and 2 years showed a more than twofold higher incidence of coronary angiography (8.2% vs. 3.3%; HR, 2.57; 95% CI, 1.62-4.09) and revascularization (5.8% vs. 2.4%; HR, 2.44; 95% CI, 1.43-4.16) in the functional-testing group compared with the standard-care group. Yet, there were still no meaningful between group-differences in the rate of death or MI (Figure 2). Figure 2. Landmark analysis for outcomes Despite more testing and repeat procedures based on the regular functional testing results, hard clinical endpoints such as death or MI were not reduced. The result was consistent with the recent ISCHEMIA study, which showed that an initial invasive strategy, as compared with an initial conservative strategy, did not reduce mortality or ischemic events among stable patients with myocardial ischemia. The POST-PCI trial results also showed that more aggressive and invasive testing and treatment did not provide additional clinical benefits over a conservative strategy based on guideline-directed medical therapy. In this multicenter, pragmatic, randomized trial of high-risk patients who had undergone PCI, routine functional testing did not result in a lower risk of ischemic cardiovascular events or death from any cause at 2 years. Therefore, routine surveillance stress testing for post-PCI patients is not recommended unless they exhibit clinical signs or symptoms of stent failure. Clinical Science Late-Breaking Clinical Trials 2023 in Asia-Pacific Monday, May 08, 9:30 AM - 10:50 AM Presentation Theater 1, Vista 3, B2 CHECK THE SESSION

May 06, 2023 1701

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TCTAP 2023

PREVENT Trial

Seung-Jung Park, MD Asan Medical Center, Korea (Republic of) Acute coronary syndrome is commonly caused by the rupture of vulnerable plaque, which often has a mild angiographic appearance. Although systemic pharmacologic management is considered a standard therapy for stabilizing vulnerable plaque, the role of the local treatment to prevent plaque rupture has not yet been determined and has only been tested in small trials. The PREVENT trial is designed to compare the effectiveness of preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) to OMT alone in patients with functionally insignificant, high-risk vulnerable plaques. The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized clinical trial (Figure 1). Patients with at least one angiographically significant stenosis (diameter stenosis >50%) without functional significance (fractional flow reserve [FFR] >0.80) and vulnerable plaque characteristics in intracoronary imaging are eligible for enrollment. Target lesions should have at least two of four intracoronary imaging criteria for vulnerable plaque; (1) minimal lumen area (MLA) 70%; (3) maximal lipid core burden index (LCBI) in a 4 mm segment >315 by near-infrared spectroscopy (NIRS); and (4) thin cap fibroatheroma (TCFA) as determined by optical coherent tomography (OCT) or virtual histology (VH). Enrolled patients were randomly assigned in a 1:1 ratio to either a preventive PCI on vulnerable plaque using bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is a target-vessel failure, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, and hospitalization for unstable or progressive angina at 2 years. Figure 1. The study design of the PREVENT trial. Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results will be available by early 2024. The PREVENT trial is the first, a large-scale randomized trial, with adequate power for clinical outcomes to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. The results of this trial will provide compelling evidence to determine whether preventive PCI of focal vulnerable plaques on top of OMT improves patient outcomes compared to OMT alone. Clinical Science Future Perspective on Ongoing Trials from AMC Monday, May 08, 11:00 AM - 12:20 AM Presentation Theater 1, Vista 3, B2 CHECK THE SESSION

May 06, 2023 1709

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TCTAP 2023

OCTIVUS Trial

Do-Yoon Kang, MD Asan Medical Center, Korea (Republic of) The clinical value of intracoronary imaging for percutaneous coronary intervention (PCI) guidance is widely acknowledged. Although optical coherence tomography (OCT) and intravascular ultrasound (IVUS) are the most commonly used intravascular imaging methods for guiding and optimizing PCI in daily clinical practice, there are limited data on head-to-head comparison between OCT-guided and IVUS-guided PCI concerning clinical endpoints. Prior studies (ILUMIEN-3, OPINION, etc.) which compared the two imaging modalities might have been hampered by the use of surrogate imaging endpoints, limited patient numbers, and strict inclusion criteria including relatively simple lesions. Future clinical trials should focus on a large, unselected patient population that is more representative of routine clinical practice. The OCTIVUS trial is an investigator-initiated, multicenter, open-label, pragmatic randomized controlled trial comparing the efficacy and safety of OCT-guided versus IVUS-guided PCI strategies in an all-comers population with minimal exclusion criteria (Figure 1). Due to the lack of stringent exclusion criteria, a large proportion of patients with acute coronary syndrome, multivessel disease, or complex lesions, such as left main, bifurcation, long, or restenotic lesions, the patients who represented those undergoing PCI in contemporary clinical practice, could be enrolled in this trial. PCI optimization criteria are predefined using a common algorithm for online OCT or IVUS. The primary endpoint was target-vessel failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization) at 1 year, which was tested for both noninferiority and superiority. Figure 1. The study design of the OCTIVUS trial. From April 2018 through January 2022, a total of 2,000 patients were enrolled. This year, the primary results will be available. It is anticipated to provide valuable clinical evidence regarding the comparative efficacy and safety of OCT-guided versus IVUS-guided PCI strategies in a broad population of patients undergoing PCI. Clinical Science Future Perspective on Ongoing Trials from AMC Monday, May 08, 11:00 AM - 12:20 AM Presentation Theater 1, Vista 3, B2 CHECK THE SESSION

May 06, 2023 1877

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TCTAP 2023

30 Years History of FFR: From the Concept to Current Status - Legend's Perspective

Nico Pijls, MD Catharina Hospital, Netherlands In the early days of coronary intervention, some pioneers in coronary intervention recognized the value of coronary artery pressure measurement. However, reliable techniques and devices to measure coronary pressure did not accurately exist at that time. With the development of the true pressure wire and hyperemic method, fractional flow reserve (FFR) was introduced in the 1990s. FFR is a fraction of mean distal coronary pressure (Pd) to mean aortic pressure (Pa) at maximal coronary hyperemia. Today, FFR is used widely in clinical practice. Furthermore, many non-hyperemic methods to measure coronary pressure also have been developed to avoid the inconvenience that occurs during hyperemic stimulation. However, there are clear distinctions between FFR and non-hyperemic indices. FFR is linearly related to maximum achievable blood flow and this linearity is only present under maximum hyperemic circumstances. Clinically, leaving out hyperemia can miss significant stenosis, especially in younger patients with proximal lesions in large coronary arteries. FFR has a sound scientific basis and experimental validation, is accurate and reproducible with an unequivocal normal value and a clear-cut-off with a narrow gray zone, and is easy to perform. FFR is the link amid stenosis severity, maximal blood flow, perfusion territory, and myocardial ischemia. FFR can assess the severity of many complex lesions and functional improvement after percutaneous coronary intervention (PCI) (Figure 1). Figure 1. FFR calculated by ratio of mean Pd to mean Pa Numerous clinical trials have investigated the role of FFR-guided PCI in comparison with angiography alone, medical treatment, or coronary artery bypass grafting (CABG). For instance, the FAME trial showed lower stent use and lower major adverse cardiac events (MACE) in the FFR-guided PCI group compared to the angio-guided PCI group. The FAME-2 trial showed better clinical outcomes in the FFR-guided PCI group than in the medical therapy group. The FAME-3 trial demonstrated that FFR-guided PCI using current-generation drug-eluting stents (DES) did not meet the criteria for noninferiority compared with CABG among patients with angiographic three-vessel disease. In conclusion, anatomy alone is insufficient to understand the physiologic significance of coronary artery disease. FFR provides superior insight into coronary pathophysiology and greatly improves the correct diagnosis of coronary artery disease. There is incontrovertible evidence for improved outcomes of coronary disease and revascularization by the systematic use of FFR. Opening of TCTAP 2023 & Key Note Lectures Sunday, May 07, 9:30 AM - 10:16 AM Main Arena, Walker Hall, Level 1 CHECK THE SESSION

May 06, 2023 1948

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TCTAP 2023

Upfront 2-Stent; New Concept in LM Bifurcation PCI

Andrejs Erglis, MD Pauls Stradins Clinical University Hospital, Latvia The popularity of percutaneous coronary intervention (PCI) for the treatment of unprotected left main (ULM) lesions has increased in the past few years due to the advances in stent technologies and adjunctive pharmacotherapies. However, PCI of complex bifurcation lesions is still challenging in the drug-eluting stent (DES) era, and the results are worse compared with the simple coronary lesions. Although the provisional stent (PS) strategy is generally considered as the default strategy for bifurcation lesions, there are scenarios in which the two-stent strategy is initially necessary to improve the patency of both the main branch and the side branch. Unfortunately, the high occurrence of in-stent restenosis (ISR) of the left circumflex artery (LCx) ostium is a major limitation of the 2-stent strategy for ULM lesion, with a recent study reporting that an ISR rate of 25.4% with this strategy (majority in the LCx ostium) versus a rate of 6.3% with a PS strategy. Bioresorbable vascular scaffolds (BVS) has the unique ability to restore vascular physiology and anatomical integrity, such as native tortuosity and angulation, with only a temporary scaffold necessary to maintain the patency of the vessel after the intervention. Studies have shown a complete resorption of scaffold struts at five-years. Therefore, it may provide a novel way to treat ULM distal bifurcation lesions, that would benefit from a two-stent strategy at the time of intervention but leave nothing behind to preclude later surgical revascularization or noninvasive imaging. The study aimed to investigate the long-term outcomes of a two-stent strategy in patients with LM bifurcation lesions involving the ostium of the LCx artery, utilizing a DES in the LM extending into the left anterior descending artery (LAD) and a BVS in the LCx ostium (Figure 1). The primary outcome at four-years was the composite of deaths, myocardial infarction, stroke, and target lesion revascularization (TLR). Figure 1. Methods of study At four-years, the primary outcome was identified in nine patients (19.6%) (Figure 2). All events were TLRs except one myocardial infarction due to BVS thrombosis. Seven of the eight TLRs were a result of side branch BVS restenosis. Univariate predictors of the four-year outcome were higher LDL cholesterol and BVS size ¡Â2.5 mm. On multivariate analysis, LCx lesion preparation with a cutting balloon and post-procedure use of intravascular ultrasound for optimization was found to be independent protective factors of major adverse cardiovascular events (MACE). Figure 2. Four-year clinical outcomes of 2-stent strategy in LM bifurcation PCI In selected patients with LM distal bifurcation disease, an imaging-guided two-stent strategy with DES in the LM and BVS in the LCx ostium was technically successful in all patients and was reasonably safe and effective for four years. Meet the Experts over Breakfast All Bifurcation PCI Monday, May 08, 7:00 AM - 08:00 AM Presentation Theater 1, Vista 3, B2 CHECK THE SESSION

May 06, 2023 1562

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TCTAP 2023

Left Main Revascularization; Consensus and Gaps in 2023

David Joel Cohen, MD Cardiovascular Research Foundation, USA For decades, coronary artery bypass grafting (CABG) has been the standard choice of revascularization for significant left main coronary artery (LMCA) disease. However, with remarkable advancements in device technology and adjunctive pharmacology, percutaneous coronary intervention (PCI) offers a more expeditious approach with rapid recovery and is a safe and effective alternative in appropriately selected patients with LMCA disease. Several landmark randomized clinical trials (RCTs) have shown that PCI with drug-eluting stents for LMCA disease is a safe option with similar long-term survival rates to CABG surgery, especially in those with low and intermediate anatomic risk. Should CABG be preferred for most patients? The most recent individual patient-level meta-analysis incorporating long-term follow-up results from key RCTs (SYNTAX, PRECOMBAT, NOBLE, and EXCEL trials) showed no statistical difference in 5-year all-cause death between PCI and CABG, although a Bayesian approach suggested a difference probably exists favoring CABG (Figure 1). Spontaneous myocardial infarction and repeat revascularization were more common with PCI than with CABG. Overall, there was no difference in the risk of stroke between PCI and CABG, but the risk was lower with PCI in the first year after randomization. A Heart Team approach to communicate expected outcome differences might be useful to assist patients in reaching a treatment decision. Figure 1. 5-year all-cause death between PCI and CABG in meta-analysis Role of mechanical circulatory support If the Heart Team decides to proceed with PCI as a revascularization method, several technical aspects of the PCI strategy should be considered to optimize PCI outcomes. Left main PCI should be performed as much as possible by experienced operators in catheterization laboratories with intracoronary imaging, invasive coronary physiology, and mechanical circulatory support (MCS). MCS use remained low but increased from 0.2% to 0.6% of high-risk elective PCIs between 2007 and 2017, and unprotected left main PCI was the main high-risk feature associated with prophylactic MCS use. Patients with normal left ventricular function rarely require planned MCS. When the left main anatomy is complex (distal bifurcation lesion, severe calcification requiring atheroablation) and cardiac reserve is limited (ejection fraction 30 mmHg), MCS should be considered for unprotected left main PCI. 1-stent vs. 2-stent strategies An up-front 2-stent strategy for bifurcation lesions has been deemed inferior to provisional stenting; nevertheless, the optimal stent strategy for LMCA bifurcation lesions remains unknown. The DKCRUSH-V trial demonstrated that PCI for true distal LMCA bifurcation lesions using a planned double-kissing crush 2-stent strategy resulted in a lower rate of target lesion failure at 1 year than the provisional stenting strategy. In contrast, the EBC-MAIN trial demonstrated that the stepwise layered provisional approach was associated with numerically fewer major adverse cardiac events than planned dual stenting. Currently, the initial single-stent crossover and provisional side branch approach is recommended for LMCA bifurcation lesions. However, the choice of strategy should be based on angiographic features (vessel size, side branch involvement, lesion length), as well as operator expertise. A more detailed evaluation of the anatomic severity can be obtained by intracoronary imaging, which is essential for pre-interventional lesion assessment and post-interventional stent optimization. TCTAP Workshops LM & Multi-Vessel Diseases and Bifurcation & CTO After ISCHEMIA Study Saturday, May 6, 10:30 AM ~ 12:30 PM Valve & Endovascular Theater, Vista 1, B2 CHECK THE SESSION

May 06, 2023 1681

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COMPLEX PCI 2022

[COMPLEX PCI] Guideline and concept changes: revascularization for non-LM bifurcations in 2022

Rolling back unnecessary revascularizations for non-left main (LM) bifurcation lesions is a priority to improve outcomes, an expert said, since optimized medical therapy is ¡°good enough¡± for most patients with stable ischemic heart disease (SIHD). ¡°Clinical outcomes of percutaneous coronary intervention (PCI) for non-LM bifurcation lesions are clearly related to the status of the main branch (MB),¡± Seung-Jung Park, MD, PhD(Asan Medical Center, Seoul, South Korea) said on Nov 24 at COMPLEX PCI, which ran for two days at the Grand Walkerhill Seoul in South Korea. ¡°The major concept is avoiding the side branch (SB) if small – before or after the procedure – which pertains to about 80% of non-LM bifurcations.¡± Seung-Jung Park, MD, PhD presents major guideline and concept changes for revascularization in non-LM bifurcation lesions at COMPLEX PCI at the Grand Walkerhill Seoul in South Korea on Nov 24. Emphasis on less is more in non-LM bifurcation PCIs stems partly from the ISCHEMIA study – deemed as the ¡°most impactful trial since COURAGE¡± – and the ISCHEMIA-EXTEND follow-up study that reported no significant difference between guideline-directed medical therapy (GDMT)-based conservative care (n=2,591) and invasive revascularization with either coronary artery bypass surgery (CABG) or PCI (n=2,588) in patients with stable coronary disease and moderate or severe ischemia. The simple rule is to treat – if and only if – there are ischemic symptoms and treat large SBs (>2.5 mm). Seung-Jung Park, MD, PhD. At median follow-up of 3.2 years, ISCHEMIA found no survival or ischemic benefits (composite of CVD death, MI or hospitalization for unstable angina, HF, or resuscitated cardiac arrest) with initial invasive revascularization over conservative care (invasive-strategy group 5.3% vs. conservative-strategy group 3.4%; difference 1.9%p; 95% CI; 0.8-3.0). At 5 years, rates for cumulative events (invasive group 16.4% vs. conservative 18.2%; difference −1.8%p; -4.7-1.0), all-cause mortality (invasive 9.0% vs. conservative 8.3%; difference 0.7; -1.6-3.1) and MI (10.3% vs. 11.9%; difference -1.6; -3.9-0.7) were statistically non-significant. ISCHEMIA-EXTEND (median follow-up 5.7 years) relayed the same message, reporting no significant difference for the all-cause mortality outcome at 7-years between the initial invasive strategy and conservative strategy groups (12.7% vs. 13.4%; aHR 1.00; 95% CI; 0.85-1.18). The findings were pertinent as coronary computed tomography angiography (CCTA) assessment showed more than 75% of the ISCHEMIA population had multivessel disease (MVD) and stenosis over 50%, Park said: ¡°GDMT was good enough for the majority of SIHD patients, so the focus is on reducing unnecessary revascularizations, especially for PCI.¡± Individualizing treatment strategies according coronary artery disease (CAD) severity based on ¡°ISCHEMIA criteria,¡± he added, is also an important consideration to reduce excess revascularizations. Analysis of ISCHEMIA findings stratified by CAD and ischemia severity showed revascularization with either PCI or CABG and GDMT was reasonable for high-risk patients with significant stenosis (¡Ã70%) in 3 vessels (3VD); any revascularization with GDMT was suitable for high-risk patients with significant stenosis (¡Ã70%) in 2 vessels (2VD) and the proximal left anterior descending (LAD) artery; medical therapy alone was sufficient for intermediate-risk (2VD >70%; 3VD>50%; or >70% pLAD) and low-risk patients (1VD with >70% stenosis; 3VD >50%; or any 1VD >50%). ¡°Although studies have shown better outcomes with revascularization for patients with large ischemic burden – when fractional myocardial mass (FMM) is greater than 10% – analysis shows non-LM bifurcation PCIs do not improve survival for patients with large ischemic burden in real-world practice because the supplied myocardial mass is often too small, only a minority of stable PCI patients meet ISCHEMIA criteria, and small SBs have small ischemic burden.¡± Without symptoms, leave the small side branch (2.5 mm) had FMM greater than 10% (roughly ¡°1.2-vessel disease¡±), which paled in comparison to the high FMM rates found in LM and 2-vessel disease. Upfront 2-stenting vs provisional stenting When deciding between upfront 2-stenting and provisional stenting, the main vessel (MV) status and SB size are crucial considerations, Park said. ¡°Upfront 2-stenting, with either Double-Kissing (DK) Crush or Culotte techniques, is better than provisional stenting for all complex bifurcations with large SB (>2.5 mm),¡± he said. ¡°Small SBs (2.5 mm) with the upfront 2-stent technique (

January 02, 2023 3539

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COMPLEX PCI 2022

US guidance on CABG vs contemporary PCI in MVD partly driven by ¡®misunderstandings, limitations¡¯ o...

The issue of an optimal revascularization strategy for multivessel disease (MVD) prevailed at COMPLEX PCI 2022 in Seoul, South Korea, with strong claims challenging the major but controversial recommendations from American guidelines that largely endorsed surgery over stenting. For MVD patients, Seung-Jung Park, MD, PhD(Asan Medical Center, Seoul, South Korea) advocated an approach that combined invasive revascularization – with either contemporary, state-of-the-art percutaneous coronary intervention (PCI) or conventional coronary artery bypass grafting (CABG) – and guideline-directed medical therapy (GDMT), provided the strategy was tailored to the individual. ¡°It¡¯s a field with very limited data, especially PCI-wise,¡± Park said during the featured lecture session on Nov 25 at the Grand Walkerhill Seoul. Seung-Jung Park, MD, PhD (Asan Medical Center, Seoul, South Korea) explains the impact of evidence and guideline recommendations for MVD in clinical practice at the COMPLEX PCI 2022 conference held at the Grand Walkerhill Seoul in South Korea on Nov 25. In 2018, the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines strongly recommended CABG for triple-vessel disease (3VD) regardless of diabetes status or SYNTAX scores (Class I, A). PCI obtained a Class I (A) recommendation for 3VD patients with low SYNTAX scores (0-22) and a weak Class IIb (A) recommendation for diabetic 3VD patients with low SYNTAX scores. PCI was contraindicated in 3VD patients with intermediate-to-high SYNTAX scores >22 regardless of diabetes status. In 2021, the American College of Cardiology, American Heart Association and Society of Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guidelines strongly recommended CABG for multivessel coronary artery disease (MVCAD) patients with anatomy suitable to PCI or CABG and ischemic cardiomyopathy defined as left ventricular ejection fraction (LVEF)

December 29, 2022 7002

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