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This Issue opens with the European Society of Cardiology (ESC) President’s Page entitled ‘Looking ahead to an exciting year in 2025’ by Thomas Luscher.1 This ESC President’s page highlights the society’s enthusiastic start to 2025, marked by its 75th anniversary celebration during the ESC Congress in Madrid. The congress will focus on rising cardiovascular disease burdens worldwide, novel risk factors such as environmental hazards, and advancements in obesity management. A major milestone is the EU’s new Cardiovascular Health Plan, developed with ESC support, emphasizing prevention, access to care, and collaborative projects across the 27 EU countries.
The Issue continues with a focus on genetics and valvular heart disease. Genetic studies have revealed hundreds of genetic variants associated with cardiovascular diseases (CVDs) and have allowed the development of polygenic risk scores (PRSs).2–5 In a Special Article entitled ‘Clinical utility and implementation of polygenic risk scores for predicting cardiovascular disease: a clinical consensus statement of the ESC Council on Cardiovascular Genomics, the ESC Cardiovascular Risk Collaboration, and the European Association of Preventive Cardiology’, Heribert Schunkert from the Universitätsklinikum der Technischen Universität München in Germany, and colleagues note that PRSs can capture genetic information in a single metric, hold promise for use in CVD risk prediction,6 and integrate clinical risk scores.7,8 Importantly, PRS information can reflect the causally mediated risk to which the individual is exposed throughout life. Although ESC Guidelines do not currently advocate their use in routine clinical practice, PRSs are commercially available and increasingly sought by clinicians, health systems, and members of the public to inform personalized healthcare decision-making. This clinical consensus statement provides an overview of the scientific basis of PRSs and evidence to date on their role in CVD risk prediction for the purposes of disease prevention. It provides the reader with a summary of the opportunities and challenges for implementation and identifies current gaps in supporting evidence. The document also lays out a potential roadmap by which the scientific and clinical community can navigate any future transition of PRSs into routine clinical care. Finally, clinical scenarios are presented where information from PRSs may hold most value and organizational frameworks to enable responsible use of PRS testing while more evidence is being generated by clinical studies are discussed.
Nucleic acid-based therapies are booming. In a Special Article entitled ‘Translation of genomics into routine cardiological practice: insights from a European Society of Cardiology Cardiovascular Round Table’, Stefanie Dimmeler from the Goethe University in Frankfurt, Germany, and colleagues note that one emerging avenue is genetic therapies, which hold promise for diseases with a monogenic basis.9 Gene silencing techniques using antisense oligonucleotides or RNA interference strategies are currently at the forefront of genetic therapies in CVD, with several RNA-targeted therapies already approved for the treatment of conditions such as familial hypercholesterolaemia and transthyretin amyloidosis. For diseases caused by loss-of-function genetic variants, there is growing interest in gene therapy, applying either gene replacement strategies using adeno-associated virus vectors or gene editing strategies using tools such as the clustered regularly interspaced short palindromic repeats and clustered regularly interspaced short palindromic repeats-associated protein-9 (CRISPR/Cas9) system. Pre-clinical studies have highlighted the potential of this technology in CVD, and promising data are beginning to emerge from early-phase clinical trials. During a European Society of Cardiology Cardiovascular Round Table workshop, the challenges of translating these novel therapeutic strategies to the routine cardiology clinic were discussed. Several key priorities were identified, including the need for disease-specific pre-clinical models, precision diagnostics, adequately powered clinical trials with meaningful endpoints, and enhanced education of healthcare professionals and patients. The Cardiovascular Round Table also considered the role of PRSs in risk stratification and how these can potentially be implemented in clinical practice.
While mitral valve repair is gaining increasing popularity,10,11 aortic valve repair is much less utilized. In a State of the Art Review article entitled ‘Current status of aortic valve repair surgery’, Ruggero De Paulis from the Unicamillus University in Rome, Italy, and colleagues indicate that severe aortic valve regurgitation, if not treated in a timely manner, can significantly impact survival for both tricuspid aortic valve and bicuspid aortic valve patients, with the latter being significantly younger.12 Increased understanding of the root anatomy and its physiology has opened up the way to techniques of aortic valve repair surgery. The techniques mainly relate to re-establishing the correct root and annular geometry and eliminating leaflet prolapse. These techniques are applied in the presence of both a dilated and a normal root, and are equally valid for tricuspid or bicuspid valves. Techniques for repairing a bicuspid valve might vary depending on the different valve phenotypes. Medium- and long-term results appear favourable and potentially superior to those of prosthetic replacement in terms of valve-related complications and quality of life. Optimal surgical treatment, especially in younger and selected patients, should aim to avoid aortic valve replacement and its related complications (Figure 1).
Techniques to reduce annular dimensions. Each technique has several advantages and disadvantages that need to be considered depending on the patients and the surgeon’s experience12
The issue also contains another contribution from the Year in Cardiovascular series, namely ‘The Year in Cardiovascular Medicine 2024: the top 10 papers in dyslipidaemias’ by EHJ Editors Lale Tokgözoglu, Carl Orringer, and Alberico Catapano.13 This year, exciting developments in the lipid field have added novel therapies to our armamentarium of lipid-lowering agents and provided new insight on biomarkers.
Interest in tricuspid valve disease is also increasing due to the recent development of percutaneous treatments.14–16 The association between peri-procedural change in tricuspid regurgitation (TR) and outcomes in patients undergoing mitral transcatheter edge-to-edge repair (M-TEER) is unclear. In a Clinical Research article entitled ‘Tricuspid regurgitation and outcomes in mitral valve transcatheter edge-to-edge repair’, Shingo Matsumoto from the Tokai University School of Medicine in Isehara, Japan and colleagues aimed to examine the prognostic value of TR before and after M-TEER.17 Patients in the OCEAN-Mitral registry were divided into four groups according to baseline and post-procedure echocardiographic assessments: no TR/no TR (no TR), no TR/significant TR (new-onset TR), significant TR/no TR (normalized TR), and significant TR/significant TR (residual TR) (all represent before/after M-TEER). Tricuspid regurgitation ≥ moderate was defined as significant. The primary outcome was cardiovascular death or heart failure hospitalization. The TR pressure gradient was also evaluated. Baseline assessment for TR and TR pressure gradient was not associated with outcomes after M-TEER. In contrast, patients with new-onset TR had the highest adjusted risk for the primary outcome, followed by those with residual TR (compared with no TR as a reference, hazard ratio 1.83 for new-onset TR, 1.45 for residual TR, and 0.82 for normalized TR). Similarly, from baseline to post-procedure, TR pressure gradient changes were associated with subsequent outcomes after M-TEER. New-onset and residual TR incidence were commonly associated with dilated tricuspid annulus diameter and atrial fibrillation (Figure 2).
Change in tricuspid regurgitation and outcome after mitral transcatheter edge-to-edge repair. Change in the tricuspid regurgitation pressure gradient was analysed using a linear mixed model, adjusted for the interaction between the four tricuspid regurgitation categories and visit, with a random intercept and slope per patient. AF, atrial fibrillation; AFL, atrial flutter; CV, cardiovascular; HF, heart failure; M-TEER, mitral transcatheter edge-to-edge repair; TR, tricuspid regurgitation; TRPG, tricuspid regurgitation pressure gradient; TV, tricuspid valve17
The authors conclude that post-procedural TR, but not baseline TR, is associated with outcomes after M-TEER. Careful TR assessment after the procedure would provide an optimal management for concomitant significant TR in patients undergoing M-TEER. The manuscript is accompanied by an Editorial by Domenico Angellotti, Fabien Praz, and Stephan Windecker from the University of Bern in Switzerland.18 The authors note that the most appropriate therapeutic strategy for residual TR in patients undergoing transcatheter mitral valve interventions—concomitant vs staged transcatheter TR intervention—remains uncertain. Since baseline TR was not associated with adverse clinical outcomes and improved in almost half of patients after M-TEER in the present study, watchful waiting with re-evaluation after the procedure, followed by a staged transcatheter tricuspid intervention as needed, may be proposed.
In a Clinical Research contribution entitled ‘Baseline characteristics and outcomes of rheumatic mitral valve disease: the EURObservational Research Programme Valvular Heart Disease II Survey’, Magdy Abdelhamid from Cairo University in Egypt, and colleagues sought to analyse the management of patients with severe native valve disease and those with previous valvular intervention in relation to existing European Society of Cardiology Guidelines.19 The ESC VHD II registry is an international, prospective, longitudinal, multicentre, observational study, which was conducted in 222 centres. The registry included patients with severe native valvular heart disease (VHD) or with previous valvular intervention. Follow-up was undertaken at 6 months at the investigating centre or by telephone. In patients recruited in the ESC VHD II registry, 470 had severe native rheumatic mitral valve disease and 332 had a previous rheumatic mitral valve intervention. In patients with Class I recommendation for intervention, the latter was undertaken in only 70%. Adherence to Guideline recommendations was better in patients with native VHD than in those with previous intervention. Total mortality was 1.5% in hospital and 3.5% at 6 month follow-up. Independent predictors of death at 6 months were age, chronic pulmonary disease, New York Heart Association Classes III and IV at presentation, liver dysfunction, and previous myocardial infarction.
Abdelhamid et al. conclude that compliance with Guideline recommendations for intervention is poor overall in patients with rheumatic VHD. Concerted educational efforts are needed to improve the management of this vulnerable patient cohort. The contribution is accompanied by an Editorial by Ana Mocumbi from Universidade Eduardo Mondlane in Maputo, Mozambique.20 Mocumbi concludes that this study should be used to foster discussion on the uniqueness of rheumatic heart disease (RHD) management, and the determinants for its poor prognosis. Key to this debate is the development of RHD-specific evidence-based guidelines, which may contribute to improve quality of care, reducing the premature mortality and disability associated with this highly preventable disease.
The issue also includes a Rapid Communications contribution entitled ‘A rare splice-site variant in troponin T: the need for ancestral diversity in genomic reference datasets’ by Alexandra Butters from the Garvan Institute of Medical Research and University of New South Wales, and colleagues.21 There is growing interest in inherited cardiomyopathies.22–24 The under-representation of different ancestry groups in large genomic datasets creates difficulties in interpreting the pathogenicity of monogenic variants. Genetic testing for individuals with non-European ancestry results in higher rates of uncertain variants and a greater risk of misclassification. The authors report a rare variant in the cardiac troponin T gene, identified via whole-exome sequencing in two unrelated probands of Oceanian ancestry with cardiac phenotypes.
They conclude that this variant is benign and is not a monogenic cause of disease. Even with ongoing efforts to increase representation in genomics, the authors highlight the need for caution in assuming rarity of genetic variants in largely European datasets. Efforts to enhance diversity in genomic databases remain crucial.
The issue is also complemented by a Discussion Forum contribution entitled ‘Cardiac biomarkers for diagnosing Takotsubo syndrome: keep it simple?’ in which Olivier Gach and Charles Pirlet from CHC MontLégia in Liège, Belgium comment on the recent publication ‘Cardiac biomarkers for diagnosing Takotsubo syndrome’ by Victor Schweiger from the University Hospital Zurich in Switzerland.25,26
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.
