New pieces to the jigsaw of antiplatelet treatment after acute coronary syndrome, and a focus on leadless pacing

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on arrhythmias, thrombosis, and antithrombotic treatment contains a Great Debate article entitled ‘Great debate: default duration of dual antiplatelet treatment after percutaneous coronary intervention in acute coronary syndrome should be 12 months’ by Felicita Andreotti from Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.1 Taken together, the data are leading us to consider a shortened dual antiplatelet treatment (DAPT) duration after acute coronary syndrome, followed by a strong P2Y12 inhibitor after a single month of DAPT or by any kind of antiplatelet agent after 3 months of DAPT. Many questions, however, remain: when should the temporal transition occur? Should shortened DAPT apply to all or only to those more vulnerable to bleeding? Does vulnerability to bleeds include all older patients? How does shortened DAPT reconcile with the benefits of prolonged intensified antithrombotic therapy in high ischaemic risk patients?2 The authors of the ‘Contra’ section in this Debate raise concerns over the strong recommendation in the latest European Society of Cardiology guidelines regarding the 12 month default duration of DAPT for the management of acute coronary syndrome (ACS). In the ‘Pro’ section of the Debate, selected guideline authors explain the reasons for their recommendation. Both teams argue robustly. Over the past decade, leadless pacing has undergone a rapid evolution, resulting in multiple leadless pacemaker (LPM) devices that offer advancements such as atrioventricular synchronized pacing, atrial stimulation, dual-chamber pacing, and improved battery longevity.3 In a State of the Art Review article entitled ‘Leadless pacing: a comprehensive review’, Shmaila Saleem-Talib from Haga Teaching Hospital in The Netherlands, and colleagues looked at studies comparing LPMs with transvenous pacemakers (TVPMs) and show a lower rate of device-related complications with LPMs.4 In the near future, LPMs could be combined with other devices such as non-transvenous implantable cardioverter-defibrillators to provide antitachycardia pacing or bradycardia pacing. Future prospectives for leadless cardiac resynchronization therapy and leadless conduction system pacing are being investigated. As LPMs continue to improve, their applications are anticipated to expand further, improving patient outcome, and promising a bright future for leadless pacing. In this review, the past, present, and future of leadless pacing are discussed, with a focus on cutting-edge implantation techniques, clinical outcomes, and modern advancements of LPMs (Figure 1). An overview of the past, present, and future of leadless pacing: comparison of different leadless pacemakers (LPMs) and their size in millimetres, with the Nanostim in the past, and the Micra VR/AV and AVEIR with an atrial module in the present. Furthermore, an overview of the different pacing modes: single-chamber pacing VVI/VDD mode, dual-chamber pacing DDD mode, cardiac resynchronization therapy (CRT) (it is not clear how this will be implemented, an LPM in the left ventricle is not desirable), conduction system pacing with an LPM in the interventricular septum activating the conduction system, and an LPM combined with a subcutaneous implantable cardioverter-defibrillator (S-ICD), which can deliver shock therapy. Different pacing locations with the right ventricular (RV) apex in the past, given the higher risk of pericardial effusion and the broader paced QRS complex. The vascular access with the femoral vein (FV) in the past, given more vascular complications, and the internal jugular vein (IJV) in the future with fewer vascular complications and easier access to the RV septum. Different pacing indications in the very young and the very old. Long-term complications in LPMs vs. transvenous pacemakers (TVPMs), showing lower overall complications, lower infection rate, lower device revision rate, and a lower heart failure (HF) hospitalization rate for LPMs. On the other hand, more cardiac perforations and a higher all-cause mortality rate for LPMs. AVB, atrioventricular block; RVOT, RV outflow tract4 Dual antiplatelet therapy plays a key role in the management of myocardial infarction (MI).5 Oral P2Y12 receptor inhibitor pre-treatment defines the systematic drug administration prior to coronary angiography, as opposed to a more selective administration at the time of percutaneous coronary intervention (PCI). In the setting of suspected non-ST-elevation ACS (NSTE-ACS), the purpose of pre-treatment is to prevent (recurrent) MI prior to coronary angiography as well as PCI complications. In a Viewpoint article entitled ‘Oral P2Y12 inhibitor pre-treatment for percutaneous coronary intervention in non-ST-elevation acute coronary syndromes: evolving notions in ESC guidelines’, Marco Roffi from University Hospitals, Geneva, Switzerland, and Gilles Montalescot from Pitié-Salpêtrière Hospital in Paris, France look at risks of pre-treatment including peri-procedural bleeding, related or not to vascular access as well as increased bleeding and treatment delay in the case of emergent/urgent coronary artery bypass surgery.6 From 2020 on, ESC guidelines took a position against routine P2Y12 inhibitor pre-treatment for NSTE-ACS patients undergoing early invasive strategy, a position that the authors fully embrace, while leaving the door open for pre-treatment on a case-by-case basis if coronary angiography is delayed. While an adequately powered randomized trial comparing pre-treatment vs. no pre-treatment with ticagrelor in a broad spectrum of delays to coronary angiography—now allowed according to the ESC guidelines—is warranted, it is unlikely that this will happen following the premature termination of DUBIUS. In a Viewpoint article entitled ‘The year in cardiovascular medicine 2024: the top 10 papers in thrombosis and antithrombotic treatment’, Felicita Andreotti from Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy, and colleagues give their contribution to the successful series of articles on the top 10 papers published in 2024 in different fields of cardiovascular medicine.7 The prediction and management of life-threatening ventricular arrhythmias are challenging.8–13 Accurate near-term prediction of life-threatening ventricular arrhythmias would enable pre-emptive actions to prevent sudden cardiac arrest/death. Artificial intelligence is playing a key role in different areas of cardiovascular medicine.14–19 A deep learning-enabled single-lead ambulatory electrocardiogram (ECG) may identify an ECG profile of individuals at imminent risk of sustained ventricular tachycardia (VT). In a Clinical Research article entitled ‘Near-term prediction of sustained ventricular arrhythmias applying artificial intelligence to single-lead ambulatory electrocardiogram’, Laurent Fiorina from Hôpital privé Jacques Cartier in Massy, France and colleagues performed a retrospective study which included about 250 000 patients undergoing, 14 day ambulatory ECG recordings from six countries.20 The first 24 h were used to identify patients who experienced sustained VT occurrence (primary outcome) in the subsequent 13 days using a deep learning-based model. In the internal and external validation sets, the model achieved an area under the receiver operating characteristic curve of 0.957 and 0.948, respectively. For a specificity fixed at 97%, the sensitivity reached 71% and 66% in the internal and external validation sets, respectively. Saliency maps suggested the role of premature ventricular complex burden and early depolarization time as predictors for VT. The authors conclude that a novel deep learning model utilizing dynamic single-lead ambulatory ECGs accurately identifies patients at near-term risk of ventricular arrhythmias. It also uncovers an early depolarization pattern as a potential determinant of ventricular arrhythmias. The manuscript is accompanied by an Editorial by Konstantinos C. Siontis and Paul A. Friedman from the Mayo Clinic in Rochester, MN, USA.21 The authors note that Fiorina et al. are to be congratulated for a study that offers invaluable insights while also highlighting the remaining challenges that sudden cardiac death prediction will continue to pose. Nonetheless, ‘well begun is half done’ in the uphill battle to reduce the burden of sudden cardiac death with artificial intellegence-enabled ambulatory ECG. Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of ACS. Recent data suggest a harmful association of DAPT compared with single antiplatelet therapy following SCAD. This study investigated independent predictors of major adverse cardiovascular events (MACEs) and recurrence in patients with SCAD. In a Clinical Research article entitled ‘The Australian–New Zealand spontaneous coronary artery dissection cohort study: predictors of major adverse cardiovascular events and recurrence’, Quan M. Dang from the University of Sydney, Australia, and colleagues, performed a multicentre cohort study involving 23 Australian and New Zealand sites which included patients aged ≥18 years with an ACS due to SCAD confirmed on core laboratory adjudication.22 Multivariable Cox proportional hazard models analysed predictors for the primary MACE outcome. Among 586 patients with SCAD, mean age was 52 years, and 89% were female. At long-term follow-up (median 21 months), MACE and SCAD recurrence occurred in 8.6% and 3.6% of patients, respectively. Oral anticoagulation on discharge (adjusted hazard ratio [aHR] 3.8, P = .003), ticagrelor combined with aspirin (aHR 1.8, P = .037), fibromuscular dysplasia (aHR 2.2, P = .037), and history of stroke (aHR 3.8, P = .03) were independently associated with higher rate at follow-up. Fibromuscular dysplasia (aHR 3.9, P = .01), ticagrelor combined with aspirin (aHR 2.6, P = .01), and history of stroke (aHR 6.2, P = .01) were also associated with higher SCAD recurrrence rate (Figure 2). Findings from the Australian–New Zealand Spontaneous Coronary Artery Dissection Registry study22 The authors conclude that the findings support the notion that SCAD is primarily caused by intramural bleeding, with a harmful association of more potent antiplatelet therapy and anticoagulation with adverse cardiovascular outcomes. This manuscript is accompanied by an Editorial by Marysia S. Tweet and Jason C. Kovacic from the Mayo Clinic College of Medicine in Rochester, MN, USA, and the Icahn School of Medicine at Mount Sinai in New York, NY, USA.23 The authors highlight that the best practice for acute care of SCAD patients is a work in progress and will evolve as future studies are performed. Key take-aways from the study of Dang et al. suggest that if DAPT is to be used, the preference perhaps should be for less potent P2Y12 inhibition with clopidogrel, and limiting the use of anticoagulation to situations when it is clearly indicated. Fibromuscular dysplasia and history of stroke were also associated with increased risk, giving insight into predicting outcomes. Fortunately, research on SCAD has expanded drastically over the past decade but has generated even more questions. A broader grasp of genetic predisposition, mechanisms, predictors, and treatment strategies among SCAD patients will inform strategies towards reducing and ultimately preventing adverse outcomes, thereby creating a safer and more certain future for SCAD patients and their families. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Increased heart rate in HFpEF—a sensible way to go?’, Payel Sen, Oana Sorop, and Daphne Merkus from the University Clinic Munich, Germany, and Erasmus University Medical Center, Rotterdam, The Netherlands, commented on the recent publication ‘Rate acceleration in heart failure with preserved ejection fraction: towards different strokes for different folks’ by Tim van Loon, Kevin Vernooy, and Joost Lumens from Maastricht University in The Netherlands.24,25 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.