https://orcid.org/0000-0002-9482-411X
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This Issue opens with a Viewpoint article ‘The Year in Cardiovascular Medicine 2024: the top 10 papers in valvular heart disease’ by Helmut Baumgartner from the University Hospital Muenster in Germany, and colleagues.1 With further increasing numbers of publications this year including an unusually high number of randomized controlled trials, the authors had a difficult task to select the 10 ‘best’ papers on valvular heart disease in their contribution to this successful series of articles (Figure 1).
The top 10 papers in valvular heart disease in 2024. AS, aortic stenosis; BE, balloon expandable; EF, ejection fraction; GDMT, guideline-directed medical therapy; HFrEF, heart failure with reduced ejection fraction; MR, mitral regurgitation; M-TEER, mitral transcatheter edge-to-edge repair; RCT, randomized controlled trial; TAVI, transcatheter aortic valve implantation; TR, tricuspid regurgitation; T-TEER, tricuspid transcatheter edge-to-edge repair; TTVR, transcatheter tricuspid valve replacement. RCTs: 
means superiority and 
no difference between groups; registry: means superiority, 
benefit in subgroups, and 
no difference.1
The Issue continues with a focus on cardiac and vascular surgery and arrhythmias. The mechanisms of abdominal aortic aneurysm (AAA) are poorly known, and their management is complex.2–7 In a Clinical Research article entitled ‘Sex-specific differences in alive hospital discharge following infrarenal abdominal aortic aneurysm repair’ Anna Louise Pouncey from the Imperial College London, UK, and colleagues investigated sex-specific differences in, and drivers of, the rate of alive hospital discharge.8 They performed an examination of elective AAA patients in the UK National Vascular Registry (UK NVR), 2014–19, and the Swedish National Patient Registry (SE NPR), 2010–18, for endovascular (EVAR) or open aneurysm repair (OAR). Cox models assessed sex-specific difference in the rate of alive hospital discharge, adjusting for comorbidity, anatomy, standard of care, post-operative complications, and year, with in-hospital death as the competing risk. A total of ∼30 000 AAA repairs were assessed. For EVAR, the unadjusted rate of alive hospital discharge was ∼25% lower for women (UK NVR: hazard ratio [HR] 0.75, P < .001; SE NPR: HR 0.75, P < .001). Following adjustment, the sex-specific HR remained significant. For OAR, the rate of alive hospital discharge was lower for women (UK NVR: HR 0.73, P < .001; SE NPR: HR 0.77, P < .001).
The authors conclude that women have a 25% lower rate of alive discharge after aortic surgery, despite adjustment for pre-/peri- and post-operative parameters. Efforts to increase the rate of alive hospital discharge for women should be made. This manuscript is accompanied by an Editorial by Chiara Lomazzi, Jasper de Kort, and Santi Trimarchi from the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico in Milan, Italy.9 The authors note that while clinical advancements are crucial, healthcare systems should adapt practices to account for the needs of the populations they serve. By incorporating sex-specific considerations into clinical practice and health policy, we can move closer to a truly equitable healthcare environment that ensures optimal outcomes for everyone, regardless of sex or other demographic factors.
Coronary artery bypass grafting (CABG) plays a key role in the management of coronary artery disease,10–13 while the optimal technique remains controversial.14,15 No-touch saphenous vein harvesting may enhance graft patency and improve clinical outcomes after CABG. In a Clinical Research article entitled ‘No-touch vein grafts in coronary artery bypass surgery: a registry-based randomized clinical trial’, Stefan Thelin from Uppsala University Hospital in Sweden, and colleagues performed a registry-based, randomized trial; patients undergoing CABG were randomly assigned to no-touch or conventional harvesting. The primary composite outcome was the proportion of patients with occluded/stenosed >50% vein graft on coronary computed tomography angiography, or who underwent percutaneous coronary intervention to a vein graft, or who died. Secondary outcomes included clinical outcomes and leg wound complications.16 A total of 902 patients were enrolled with a mean total number of distal vein anastomoses of 2.0. The primary endpoint occurred in 20% of patients randomized to no-touch and in 24% of patients randomized to the conventional technique (P = .15) at a mean follow-up time of 3.5 years. The composite of death, myocardial infarction, or repeat revascularization at 4.4 years occurred in 13% and 10% in the no-touch and conventional groups, respectively (P NS). Leg wound complications were significantly more common in patients assigned to no-touch harvesting at 3 months (25% vs. 14%).
The authors conclude that no-touch vein graft harvesting for CABG is not superior to conventional open harvesting in reducing vein graft failure or clinical events after CABG while it increases leg wound complications. The primary outcome requires cautious interpretation due to a lower than expected number of primary events. The manuscript is accompanied by an Editorial by Mario Gaudino and Sigrid Sandner from Weill Cornell Medicine in New York, NY, USA.17 The authors highlight that at this stage of the available knowledge, a critical and granular evaluation of the totality of the evidence is needed. They hope that the SWEDEGRAFT investigators will join them, and the authors of previous trials in an individual patient data meta-analysis that will provide critical and definitive data on the role of no-touch vein graft in contemporary CABG surgery to the cardiovascular community and, most importantly, to our patients.
There is growing interest in the contribution of cardiovascular risk factors and diseases to the pathogenesis of dementia.18–20 It remains unknown whether the brain glymphatic system, which is driven by the heartbeat-driven pulsation of arteries and is responsible for cerebral waste clearance, is impaired in atrial fibrillation (AF) and mediates cognitive dysfunction related to AF. In a Clinical Research article entitled ‘Atrial fibrillation catheter ablation, brain glymphatic function, and cognitive performance’, Jiahuan Guo from Capital Medical University in Bejing, China, and colleagues, sought to assess brain glymphatic alterations in AF, their role in cognitive function, and whether catheter ablation can improve glymphatic activity.21 In this case–control and prospective before-and-after study, patients with AF and healthy controls (HCs) were enrolled. Participants underwent brain magnetic resonance imaging and a comprehensive neuropsychological battery. Glymphatic activity was quantified by the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Magnetic resonance imaging was repeated after ablation. Overall, 87 patients with AF and 44 HCs were enrolled. Compared with HCs, patients with AF had a lower ALPS index (P = .016). A lower ALPS index was associated with worse scores of tests assessing cognitive performance (all P < .05). Mediation analyses revealed that glymphatic activity was a mediator between AF and cognitive decline. Among the 50 patients who underwent ablation therapy, the DTI-ALPS index improved after surgery (P = .015) (Figure 2).
The brain glymphatic activity is impaired in patients with atrial fibrillation (AF), correlates with cognitive function, and mediates the relationship between AF and cognitive decline. Glymphatic activity was improved after catheter ablation in patients with AF. HCs, health controls; PAF, paroxysmal AF; nPAF, non-paroxysmal AF; DTI-ALPS, diffusion tensor image analysis along the perivascular space.21
The authors conclude that brain glymphatic function measured by the DTI-ALPS index is impaired in patients with AF, mediates the association between AF and cognitive decline, and is improved after ablation therapy. The manuscript is accompanied by an Editorial by T. Jared Bunch from the University of Utah, USA.22 The author notes that there is mounting evidence that the timing, type, and efficiency of rhythm control strategies can impact long-term brain health in patients with AF. This evidence is complementary to data that highlight a similar benefit with the timing, type, and efficiency of anticoagulation in patients with AF at risk of thromboembolism. There remains a critical need for powered randomized controlled trials to determine which therapies are preferred, with cognitive decline and dementia as primary endpoints. The author believes that we must pursue opportunities to mitigate risk amongst the broad spectrum of brain injuries in patients with AF to truly improve both their quality and quantity of life.
Life-threatening arrhythmias are a well-established consequence of reduced cardiac sodium current (INa). Gene therapy approaches to increase INa have demonstrated potential benefits to prevent arrhythmias. However, the development of such therapies is hampered by the large size of sodium channels. In a Translational Research article entitled ‘SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias’, Jianan Wang from the University of Amsterdam, The Netherlands, and colleagues evaluated SCN10A-short (S10 s), a short transcript encoding the C-terminal domain of the human neuronal sodium channel, as a gene therapy target to increase INa and prevent arrhythmias.23 Adeno-associated viral vector overexpressing S10 s was injected into wild-type and Scn5a-haploinsufficient mice on which patch–clamp studies, optical mapping, electrocardiogram analyses, and ischaemia reperfusion were performed. In vitro and in silico studies were conducted to further explore the effect of S10 s gene therapy in the context of human hearts. Overexpression of cardiac S10 s increased cellular INa, maximal action potential upstroke velocity, and action potential amplitude in Scn5a-haploinsufficient cardiomyocytes. S10 s gene therapy rescued conduction slowing in Scn5a-haploinsufficient mice and prevented ventricular tachycardia induced by ischaemia–reperfusion in wild-type mice. Overexpression of S10 s increased maximal action potential upstroke velocity in human inducible pluripotent stem cell-derived cardiomyocytes and prevented inducible arrhythmias in simulated human heart models.
The authors conclude that S10 s gene therapy may be effective to treat cardiac conduction abnormalities and associated arrhythmias. The manuscript is accompanied by an Editorial by Patrick Lugenbiel from the University Hospital Heidelberg in Germany.24 The author concludes that future research should focus on improving vector design, delivery methods, and gene editing techniques. Combining gene therapy with other treatments, such as pharmacotherapy and ablation, could provide synergistic benefits. Ongoing clinical trials will shed light on the feasibility and effectiveness of these approaches in humans.
The pathogenic p.(Arg14del) variant in the phospholamban (PLN) gene can cause a severe cardiomyopathy characterized by a high burden of malignant ventricular arrhythmias (MVAs). In a Rapid Communications article entitled ‘Epicardial adipose tissue and malignant ventricular arrhythmias in phospholamban p.(Arg14del) variant carriers’, Belend Mahmoud from the University of Groningen, The Netherlands, and colleagues note that the pathogenic p.(Arg14del) variant in the PLN gene is known to cause a severe form of cardiomyopathy, characterized by a high burden of MVAs.25 A considerable, yet poorly understood heterogeneity in the burden of arrhythmias is observed among individuals with this variant. Unravelling the factors that drive these life-threatening arrhythmias is paramount, not only for the management of PLN cardiomyopathy, but also to enhance our comprehension of these MVAs. Epicardial adipose tissue (EAT) has recently emerged as a potential driver of arrhythmogenicity, but its association with ventricular arrhythmias remains unclear. In this study, the authors retrospectively investigated the relationship between EAT volume and MVAs in two independent cohorts (a primary and a validation cohort) comprising patients with the pathogenic PLN p.(Arg14del) variant. They measured ventricular EAT volume on cardiac magnetic resonance imaging scans and correlated it with the incidence of MVAs during follow-up, which was defined as either sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter defibrillator shock intervention. After multiple multivariable Cox regression adjustment models, they found that EAT accumulation was associated with the incidence of MVAs in both the primary and the validation cohort. Moreover, EAT volume demonstrated an excellent discriminative ability for MVAs, equivalent to that of the current risk prediction model that yields four different variables.
The authors conclude that this study is among the first and largest to identify an association between EAT volume and the incidence of life-threatening MVAs, suggesting that EAT may play a role in the genesis of ventricular arrhythmias.
The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Double counting in meta-analyses: a statistical complication in cardiovascular medicine trials’, Shivani Mehta and Ernesto Calderon Martinez from Washington University of Health and Science in Belize, and the National Autonomous University of Mexico commented on the recent publication ‘Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials’, by A. Oraji et al. from McMaster University in Canada.26,27 Oraji et al. respond in a separate comment.28
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, enarini outside the submitted work.
With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.
