Hot topics in interventional cardiology: left main disease, heavily calcified coronary stenoses, and physiology-guided percutaneous coronary interventions

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on interventional cardiology and cardiac and vascular surgery contains the ‘2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG’ by Robert Byrne from the RCSI University of Medicine and Health Sciences in Dublin, Ireland, and colleagues.1 Treatment of left main (LM) coronary artery disease remains controversial.2–7 In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with LM disease with low-to-intermediate SYNTAX score (0–32). This followed the withdrawal of support by the EACTS in 2019 for the recommendations about the management of LM disease of the 2018 Guidelines. The Task Force was asked to review all new relevant data including updated aggregated data from the four randomized trials comparing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) vs. coronary artery bypass grafting (CABG) in patients with LM disease. This document represents a summary of the work of the Task Force; suggested updated recommendations for the choice of revascularization modality in patients undergoing myocardial revascularization for LM disease and low-to-intermediate SYNTAX score are included. In a Viewpoint article entitled ‘Redefining the way to perform percutaneous coronary intervention: a view in search of evidence’, Antonio Colombo and Pier Pasquale Leone from the Humanitas University in Milan, Italy note that PCI has long been conceived as the optimal stent implantation since the introduction of the first stents and even more so with DES.8 The logic behind this is clear and supported by many studies. What is also clear is that, despite all refinements, PCI including DES implantation performs inferiorly to CABG in moderately to highly complex lesions. Imaging-guided DES implantation and optimal lesion preparation including better handling of calcified lesions are possible solutions, although not free of complexity, risk of complications, and cost. Solid evidence comparing such an approach vs. CABG is, however, still lacking. Finally, the persistent risk of late stent thrombosis and restenosis after DES implantation, with a 2% hazard per year, is a concern, regardless of lesion complexity. The authors invite the interventional community to a look back, with the aim of offering their forecast to the field of PCI, rather than proposing an immediate change. The authors envisage that the following concept has the potential, if supported by adequate studies, to reshape the way to perform PCI: ‘Performance of optimal lesion dilatation with an adequate result should not be considered a straightforward justification to carry on with DES implantation.’ Indeed, why do we implant DES? If the result after lesion dilatation appears angiographically poor due to recoil or if dissection is judged unstable, DES implantation should follow to avoid impending vessel closure and, possibly, restenosis. If the result after lesion dilatation is satisfactory, why can’t we opt to deliver an anti-restenotic medication via drug-coated balloon (DCB) angioplasty rather than proceeding with DES implantation? In a Fast Track Clinical Research article entitled ‘Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality’, Hao-Yu Wang from the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, and colleagues sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischaemia according to the Murray law-based quantitative flow ratio (μQFR) after LM bifurcation PCI.9 Consecutive patients undergoing LM bifurcation stenting at a large tertiary care centre between January 2014 and December 2016 with available post-PCI μQFR were included. Physiologically significant residual ischaemia was defined by post-PCI μQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCx). The primary outcome was 3-year cardiovascular death. The major secondary outcome was the 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analysable post-PCI μQFR, 155 (13.2%) had residual ischaemia in either the LAD or LCx. Patients with vs. those without residual ischaemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20]. The 3-year risk of BOCE was significantly higher in the residual ischaemia group (17.8% vs. 5.8%; adjusted HR 2.79), driven by a higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (MI; 14.0% vs. 3.3%; adjusted HR 4.06). A significant, inverse association was observed between continuous post-PCI μQFR and the risk of clinical outcomes (per 0.1 μQFR decrease, HR of cardiovascular death 1.27; HR of BOCE 1.29). Wang et al. conclude that after angiographically successful LM bifurcation PCI, residual ischaemia assessed by μQFR is identified in about 13% of patients and is associated with higher risk of 3-year cardiovascular death, indicating the prognostic value of post-PCI physiological assessment. The contribution is accompanied by an Editorial by Nils Johnson and Jung-Min Ahn from the McGovern Medical School at UTHealth and Memorial Hermann Hospital in Houston, TX, USA and Jung-Min Ahn from the University of Ulsan College of Medicine in Seoul, South Korea.10 The authors conclude that while awaiting further evidence, the most important decision for PCI of the LM revolves around the strategy: provisional single stent vs. upfront two stents. A potential resolution to the apparent conflict between DKCRUSH-V—an upfront two-stent strategy is superior—and EBC MAIN—a provisional single stent strategy is superior—is that both are correct. For more complex, true LM bifurcation disease, make a two-stent plan; for less complex scenarios, begin with a single crossover stent. Wise selection of the strategy involves a thoughtful evaluation of the side branch (usually the LCx), and intravascular imaging brings the most clarity, although intracoronary physiology and anatomical features can help too. Since the publication of the 2015 EAPCI consensus on rotational atherectomy, the number of PCIs performed in patients with severely calcified coronary artery disease has grown substantially. In the Fast Track Clinical contribution entitled ‘Management strategies for heavily calcified coronary stenoses: an EAPCI clinical consensus statement in collaboration with the EURO4C-PCR group’, Emanuele Barbato from Sapienza University in Rome, Italy and colleagues note that on the one hand, this has been prompted by the clinical demand for the continuous increase in life expectancy, the sustained expansion of the primary PCI networks worldwide, and the routine performance of revascularization procedures in elderly patients.11 On the other hand, the availability of new and dedicated technologies such as orbital atherectomy and intravascular lithotripsy, as well as the optimization of the rotational atherectomy system, has increased operators’ confidence in attempting more challenging PCI. This current EAPCI clinical consensus statement prepared in collaboration with the EURO4C-PCR group describes the comprehensive management of patients with heavily calcified coronary stenoses, starting with how to use non-invasive and invasive imaging to assess calcium burden and inform procedural planning. Objective and practical guidance is provided on the selection of the optimum interventional tool and technique based on the specific calcium morphology and anatomic location. Finally, the specific clinical implications of treating these patients are considered, including the prevention and management of complications and the importance of adequate training and education. Overview of the process to determine the volume–outcome relationship and the optimal annual case volume in surgery for acute type A aortic dissection. Grey line, first quartile; yellow line, second quartile; blue line, third quartile; and red line, fourth quartile. ATAAD, acute type A aortic dissection.16 The treatment of aortic dissection is challenging.12–15 In the Fast Track Congress article entitled ‘Type A aortic dissection: optimal annual case volume for surgery’, Michal Kawczynski from Maastricht University Medical Center in the Netherlands, and colleagues proposes a novel volume–outcome (V–O) meta-analytical approach to determine the optimal annual hospital case volume threshold for cardiovascular interventions in need of centralization. The authors indicate that this novel method is applied to surgery for acute type A aortic dissection (ATAAD) as an illustrative example.16 A systematic search was applied to three electronic databases (1 January 2012 to 29 March 2023). The primary outcome was early mortality in relation to annual hospital case volume. Data were presented by volume quartiles (Qs). Restricted cubic splines were used to demonstrate the V–O relationship, and the elbow method was applied to determine the optimal case volume. For clinical interpretation, numbers needed to treat (NNTs) were calculated. One hundred and forty studies were included, comprising 38 276 patients. A significant non-linear V–O effect was observed (P < .001), with a notable between-quartile difference in early mortality rate [10.3% (Q4) vs. 16.2% (Q1)]. The optimal annual case volume cut-off was determined at 38 cases/year (NNT to save a life in a centre with the optimal volume vs. 10 cases/year = 21). More pronounced between-quartile survival differences were observed for long-term survival [10-year survival (Q4) 69% vs. (Q1) 51%, P < .01, adjusted HR 0.83 per quartile, NNT to save a life in a high-volume (Q4) vs. a low-volume centre (Q1) = 6] (Figure 1). The authors conclude that using this novel approach, centralization of ATAAD care to high-volume centres may lead to improved outcomes. This method can be applied to various other cardiovascular procedures requiring centralization. The contribution is accompanied by an Editorial by Tim Berger, Martin Czerny, and Maximilian Kreibich from the University Hospital Freiburg in Bad Krozingen, Germany.17 The authors note that ATAAD is among the cardiovascular diseases with the highest immediate mortality of 0.5% per hour in medically managed patients. After diagnosis is made, two questions need to be addressed. Is the patient stable enough for transfer to a high-experience centre with a substantial caseload? Also, even if this is the case, does the patient even benefit by being transferred and operated on in one of these centres? To date, both questions could not be properly answered due to the lack of existing data. In the study by Kawczynski and colleagues, important insights were obtained regarding the most relevant volume-related outcomes, i.e. short- and long-term mortality as well as stroke. These new data will improve the triaging of patients with ATAAD. Instantaneous wave-free ratio (iFR) is a non-hyperaemic pressure index measured in the wave-free period in diastole. Fractional flow reserve (FFR) is the ratio between mean aortic pressure (Pa) and distal coronary pressure (Pd) during hyperaemia. The increased rate of major adverse cardiovascular events is driven by the higher all-cause mortality in the iFR arm. The pooled analysis was conducted by digitalizing the Kaplan–Meier curves with the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). CI, confidence interval; HR, hazard ratio; PCI, percutaneous coronary intervention.24 The functional assessment of coronary stenoses plays a key role in PCI planning.18–22 Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia.23 Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR- with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. In a Fast Track Congress article entitled ‘Five-year major cardiovascular events are increased when coronary revascularization is guided by instantaneous wave-free ratio compared with fractional flow reserve: a pooled analysis of iFR-SWEDEHEART and DEFINE-FLAIR trials’, Ashkan Eftekhari from the Aalborg University Hospital in Denmark and colleagues note that the aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038).24 The composite of major adverse cardiovascular events (MACE) and its individual components (all-cause death, MI, and unplanned revascularization) were analysed. Raw Kaplan–Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package. In total, iFR- and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group (50.0%) vs. the FFR group (45.2%) (P = .001). In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI were 8.3, 21.5, 10.4, and 5.5% vs. 6.3, 18.6, 10.7, and 5.4% in the FFR group. HR estimate for MACE was 1.18, for all-cause mortality 1.34, for unplanned revascularization 0.99, and for MI 1.02 (Figure 2). Eftekhari et al. conclude that 5-year all-cause mortality and MACE rates are increased with revascularization guided by iFR compared with FFR. Rates of unplanned revascularization and MI are equal in the two groups. The manuscript is accompanied by an Editorial by Mirvat Alasnag from the King Fahd Armed Forces Hospital in Jeddah, Saudi Arabia.25 Alasnag notes that at this juncture it is important to consider whether it is time to revisit the current Guidelines. In the meantime, it is wise to use non-hyperaemic pressure indices judiciously and consider FFR-guided revascularization the gold standard strategy for intracoronary pressure measurement. Finally, the results of this meta-analysis do not diminish previously reported evidence confirming that FFR-guided PCI remains superior to angio-guided PCI. The issue is also complemented by a Rapid Communications article entitled ‘Coronary revascularization guided by instantaneous wave-free ratio compared with fractional flow reserve: pooled 5-year mortality in the DEFINE-FLAIR and iFR-SWEDEHEART trials’ by Colin Berry from the University of Glasgow, and colleagues.26 This second meta-analysis of DEFINE-FLAIR and iFR-SWEDEHEART trials provides results similar to that of Eftekhari and colleagues, confirming the superiority of revascularization guided by FFR compared with iFR. The Editors decided to publish these two overlapping meta-analyses because they will probably lead to a modification of a Class 1 recommendation in current Guidelines, and they find it reassuring to have these new data confirmed by two independent groups. The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.