Publications

Showing 21–40 of 2058 publications.

• Heart-derived factors and organ cross-talk in settings of health and disease: new knowledge and clinical opportunities for multimorbidity
  Sen, Melodi Gizem; Chooi, Roger; McMullen, Julie R.
  Journal of Physiology (Vol. ) – 2025
  Cardiovascular disease affects millions of people worldwide and often presents with other conditions including metabolic, renal and neurological disorders. A variety of secreted factors from multiple organs/tissues (proteins, nucleic acids and lipids) have been implicated in facilitating organ cross-talk that may contribute to the development of multimorbidity. Secreted proteins have received the most attention, with the greatest body of research related to factors released from adipose tissue (adipokines), followed by skeletal muscle (myokines). To date, there have been fewer studies on proteins released from the heart (cardiokines) implicated with organ cross-talk. Early evidence for the secretion of cardiac-specific factors facilitating organ cross-talk came in the form of natriuretic peptides which are secreted via the classical endoplasmic reticulumGolgi pathway. More recently, studies in cardiomyocyte-specific genetic mouse models have revealed cardiac-initiated organ cross-talk. Cardiomyocyte-specific modulation of microRNAs (miR-208a and miR-23-27-24 cluster) and proteins such as the mediator complex subunit 13 (MED13), G-protein-coupled receptor kinase 2 (GRK2), mutant ?-myosin heavy-chain (?MHC), ubiquitin-like modifier-activating enzyme (ATG7), oestrogen receptor alpha (ER?) and fibroblast growth factor 21 (FGF21) have resulted in metabolic and renal phenotypes. These studies have implicated a variety of factors which can be secreted via the classical pathway or via non-classical mechanisms including the release of extracellular vesicles. Cross-talk between the heart and the brain has also been described (e.g. via miR-1 and an emerging concept, interoception: detection of internal neural signals). Here we summarize these studies taking into consideration that factors may be secreted in both settings of health and in disease. (Figure presented.). 2025 The Authors. The Journal of Physiology 2025 The Physiological Society.
• Rationale, objectives, and design of the HEart failuRe ObsErvational Study of the Polish Cardiac Society (HEROES)
  Dro?d?, Jaroslaw; Morawiec, Robert; Drozd, Marcin D.; Krzesi?ski, Pawel; Wo?akowska-Kap?on, Beata; Grabowski, Marcin; Leszek, Przemys?aw; Kuch, Marek; Kasprzak, Jaros?aw Damian; Janion, Marianna; Grucha?a, Marcin; Pawlak, Agnieszka; Nessler, Jadwiga Maria; Pruszczyk, Piotr; Straburzy?ska-Migaj, Ewa; Mitkowski, Przemys?aw P.; Gierlotka, Marek J.; Ga?sior, Mariusz; Hryniewiecki, Tomasz T.; Ka?mierczak, Jaroslaw; Witkowski, Adam Ryszard; Zdrojewski, Tomasz R.; Niewada, Maciej; Opolski, Grzegorz; Polo??ski, Lech; Jankowska, Ewa Anita; Maggioni, Aldo Pietro; McMurray, John JV; Coats, Andrew J.S.; Metra, Marco; Rosano, Giuseppe Massimo Claudio; Seferovic, Petar M.; Ponikowski, Piotr P.
  Kardiologia Polska (Vol. 83/3) – 2025
  [No abstract available]
• Changes in natriuretic peptide levels following patiromer-enabled optimization of medical therapy in heart failure: A post hoc analysis of the DIAMOND study
  Kalogeropoulos, Andreas P.; Hameed, Ishaque; Anker, Stefan D.; Bay-Gen, Antoni; Bm, Michael; Budden, Jeffrey J.; Cleland, John G.F.; Coats, Andrew J.S.; Ezekowitz, Justin A.; Filippatos, Gerasimos S.; Goudev, Assen Rachev; Khan, Muhammad Shahzeb; Lindenfeld, Jo Ann M.; Lund, Lars H.; Merkely, Ba Peter; Mentz, Robert J.; Metra, Marco; Moutchia, Jude Suh; Perrin, Amandine; Ponikowski, Piotr P.; Priest, Elisa Lynne; Rossignol, Patrick; Senni, Michele; Shaver, Courtney N.; Waechter, Sandra; Weir, Matthew R.; Pitt, Bertram A.; Butler, Javed J.
  European Journal of Heart Failure (Vol. ) – 2025
  Aims: In the DIAMOND (Patiromer for the Management of Hyperkalaemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial, the potassium binder patiromer enabled optimization of reninangiotensinaldosterone system inhibitors (RAASi) for patients with heart failure and a reduced ejection fraction (HFrEF) and current or recent hyperkalaemia. In this post-hoc analysis, we evaluated the effect of patiromer-enabled RAASi optimization on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, an established surrogate endpoint for clinical outcomes in HFrEF. Methods and results: During screening, 539 (61.4%) of the 878 subsequently randomized patients had NT-proBNP ?1000 pg/ml, measured prior to a 12-week run-in period on single-blinded patiromer during which RAASi were optimized. Among these patients, 165/266 (62%) in the patiromer and 172/273 (63%) in the placebo arm had follow-up NT-proBNP. For these 337 patients, we evaluated the change in NT-proBNP from screening to week 18 after randomization. NT-proBNP declined by ?53% (95% confidence interval ?59% to ?46%; p < 0.001) in both arms combined (median absolute change: ?731 [?1832, 107] pg/ml), with no significant difference between the two arms (p = 0.135). A >30% NT-proBNP reduction was observed in 93/165 (56%) patiromer and 88/172 (51%) placebo patients (p = 0.38), whereas 60/165 (36%) and 53/172 (31%), respectively, achieved NT-proBNP levels <1000 pg/ml at week 18 (p = 0.30). Conclusions: In this post-hoc analysis of DIAMOND, patients with HFrEF and elevated (>1000 ng/ml) NT-proBNP at screening experienced clinically meaningful NT-proBNP reductions following a RAASi optimization strategy that included patiromer during the run-in phase, with no significant differences observed between patiromer and placebo groups during the randomized withdrawal phase. 2025 European Society of Cardiology.
• Intravenous ferric carboxymaltose in heart failure with iron deficiency (FAIR-HF2 DZHK05 trial): Sex-specific outcomes
  Karakas, Mahir; Friede, Tim; Butler, Javed J.; Talha, Khawaja Muhammad; Placzek, Marius; Asendorf, Thomas; Diek, Monika; Nosko, Anna; Stas, Adriane; Kluge, Stefan; Jarczak, Dominik; DeHeer, Geraldine; Rybczynski, Meike; Bay-Gen, Antoni; Bm, Michael; Coats, Andrew J.S.; Edelmann, Frank; Filippatos, Gerasimos S.; Hasenfuss, Gerd; Haverkamp, Wilhelm L.; Lain?ak, Mitja; Landmesser, Ulf E.; Macdougall, Iain C.; Merkely, Ba Peter; Pieske, Burkert Mathias; Pinto, Fausto J.; Rassaf, Tienush; Visser-Rogers, Jennifer K.; Rosano, Giuseppe Massimo Claudio; Volterrani, Maurizio; von Haehling, Stephan; Anker, Markus S.; Doehner, Wolfram; Ince, Hus?eyin Sefa; Koehler, Friedrich; Savarese, Gianluigi; Khan, Muhammad Shahzeb; Krnert, Ursula Rauch; Gori, Tommaso; Trenkwalder, Teresa; Akin, Ibrahim; Paitazoglou, Christina; Kobielusz-Gembala, Iwona; Kuthi, Luca Katalin; Frey, Norbert; Licka, M. B.; Kb, Stefan; Laugwitz, Karl Ludwig; Ponikowski, Piotr P.; Anker, Stefan D.
  European Journal of Heart Failure (Vol. ) – 2025
  Aims: Intravenous iron has emerged as a guideline-recommended therapy in patients with heart failure and iron deficiency, but the potential sex-related differences in efficacy are unknown. We aimed to assess sex-specific outcomes in the Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR-HF2-DZHK05) trial. Methods and results: FAIR-HF2 included 1105 heart failure patients with a left ventricular ejection fraction ?45% and iron deficiency. A total of 368 women (mean age 68.7 13.0 years) and 737 men (mean age 70.5 11.0 years) were randomized to intravenous ferric carboxymaltose or placebo. The three primary endpoints were (i) time to cardiovascular death or first heart failure hospitalization, (ii) total heart failure hospitalizations, and (iii) time-to-first event of cardiovascular death or heart failure hospitalization only in patients with transferrin saturation <20% at baseline. The hazard ratio (HR) for the first primary outcome was 1.07 (95% confidence interval [CI] 0.631.82, p = 0.80) in women and 0.74 (95% CI 0.570.95, p = 0.016) in men, while the rate ratios (RRs) for the second primary outcome were 1.06 (95% CI 0.552.05, p = 0.86) and 0.79 (95% CI 0.581.08, p = 0.136), respectively, and the HRs for the third primary outcome event were 1.21 (95% CI 0.622.36, p = 0.58) and 0.73 (95% CI 0.550.97, p = 0.028), respectively. Regarding safety outcomes, the HR for all-cause mortality was 1.46 (95% CI 0.782.76, p = 0.24) in women, suggesting increased mortality risk under iron supplementation, in contrast to 0.86 (95% CI 0.641.16, p = 0.33) in men (p for interaction = 0.13). Conclusions: This analysis indicates relevant differential efficacy of intravenous iron in heart failure across both sexes. While men receiving ferric carboxymaltose experienced a clinically relevant reduction in cardiovascular death and heart failure hospitalizations, women did not derive similar benefits. The results are clinically relevant and prompt validation in other large outcome trials of intravenous iron supplementation in heart failure. Clinical Trial Registration: ClinicalTrials.gov NCT03036462. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• Atrial cardiomyopathy: From healthy atria to atrial failure. A clinical consensus statement of the Heart Failure Association of the ESC
  Weerts, Jerremy; ?ica, Otilia Anca; Aranyo, Jia; Basile, Christian; Borizanova-Petkova, Angelina; Borovac, Josip Andjelo; Camilli, Massimiliano; Eichenlaub, Martin; Fiori, Emiliano; van Loon, Tim; Withaar, Coenraad; Zakarkaite, Diana; Zink, Matthias Daniel H.; Adamo, Marianna; Aimo, Alberto; Arbelo, Elena; Bisbal van Bylen, Felipe; Farmakis, Dimitrios T.; Dobrev, Dobromir; ?elutkiene, Jelena; Bm, Michael; Coats, Andrew J.S.; Metra, Marco; Rosano, Giuseppe Massimo Claudio; Ruschitzka, Frank T.; Bay-Gen, Antoni; Kotecha, Dipak
  European Journal of Heart Failure (Vol. ) – 2025
  The importance of atrial cardiomyopathy (AtCM) as a specific clinical entity is increasingly recognized. Past definitions have varied, and the lack of consistent cut-offs for imaging parameters and biomarkers have limited clinical utility to diagnose and track AtCM progression. While research has mainly focused on AtCM in the context of atrial fibrillation, emerging evidence underscores its relevance in remodelling and development of heart failure. The aim of this consensus document was to provide a contemporary framework for AtCM, evolve the definitions of AtCM and atrial failure for more widespread clinical use, and help to direct emerging research and future clinical trials. Supporting the work of early career researchers, this consensus document evaluates diagnostic markers and summarizes the underpinning mechanisms, clinical characteristics and prognostic impact of AtCM. Our objective was to bring together new translational scientific progress, catalyse future research and enable clinical application to facilitate better management, for example in patient groups where aggressive control of risk factors or comorbidities could prevent AtCM progression. We redefined AtCM as a graded disorder that includes electrical dysfunction of the atria along with evidence of either mechanical atrial dysfunction, atrial enlargement and/or atrial fibrosis. Atrial failure is the end-stage manifestation of AtCM, characterized by progressive structural, electrophysiological and functional changes. Earlier identification, risk stratification and ongoing research into therapeutic options have the potential to prevent the clinical consequences of AtCM and atrial failure, including adverse patient outcomes and poor quality of life associated with atrial fibrillation and heart failure. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• Management of patients with heart failure at high risk of hyperkalaemia: The CARE-HK in HF registry
  Greene, Stephen J.; Sauer, Andrew J.; Bm, Michael; Bozkurt, Biykem; Butler, Javed J.; Cleland, John G.F.; Coats, Andrew J.S.; Desai, Nihar R.; Grobbee, Diederick E Egbertus; Kelepouris, Ellie; Pinto, Fausto J.; Rosano, Giuseppe Massimo Claudio; Donachie, Vicky; Fabien, Solenn; Waechter, Sandra; Crespo-Leiro, Mar Generosa; Hsmann, Martin P.; Kempf, Tibor; Pfister, O.; Pouleur, Anne Catherine M.; Saxena, Manish; Schulz, Martin; Volterrani, Maurizio; Anker, Stefan D.; Kosiborod, Mikhail N.
  European Journal of Heart Failure (Vol. ) – 2025
  Aims: Patients with heart failure (HF) at high risk for hyperkalaemia are underrepresented in prospective HF registries. The CARE-HK in HF registry sought to characterize prospectively the clinical profile, management, and outcomes for patients with HF at high risk of hyperkalaemia. Methods and results: CARE-HK in HF was a multinational prospective registry of outpatients with HF (regardless of left ventricular ejection fraction [LVEF]) treated with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptorneprilysin inhibitor (ACEI/ARB/ARNI) and either receiving or potential candidate for a mineralocorticoid receptor antagonist (MRA). All patients were at increased risk of hyperkalaemia, defined as hyperkalaemia at baseline, prior hyperkalaemia, or estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Outcomes included frequency of hyperkalaemic events (defined by clinician report with associated potassium value), achievement of reninangiotensin system inhibitor (RASi) optimization (defined as ?50% target doses for ACEI/ARB/ARNI and MRA), medication changes following hyperkalaemic episodes, and clinical events. Overall, 2558 patients from 111 sites across nine countries were included. Median (25th75th) age was 73 (6580) years, 32% were women, 61% had LVEF ?40%, and 40% had prior laboratory evidence of hyperkalaemia. Median baseline eGFR and serum potassium were 44 (3360) ml/min/1.73 m2 and 5.0 (4.45.3) mEq/L, respectively. Over a median follow-up of 12.3 (9.418.1) months, 29% of patients had a hyperkalaemic event, and 7% had multiple events. In characterizing treatment prescribed for most of follow-up, 29% of patients received optimal RASi/MRA therapy, 69% received suboptimal RASi/MRA therapy, and 3% received no RASi/MRA. In the 30 days following the first hyperkalaemic event, RASi/MRA was down-titrated or discontinued in 3.6% of cases. Potassium binder use was low (patiromer 9.1%, sodium zirconium cyclosilicate 5.9%). Compared with patients without a hyperkalaemic event, patients experiencing a hyperkalaemic event had similar risk of all-cause mortality (hazard ratio [HR] 1.22, 95% confidence interval [CI] 0.921.62, p = 0.16) and a higher risk of subsequent hospitalization (HR 1.59, 95% CI 1.351.86, p < 0.001). Conclusions: In this contemporary multinational prospective registry of patients with HF at high risk for hyperkalaemia, hyperkalaemic events were common but infrequently associated with RASi/MRA modification or potassium binder use. Fewer than one in three patients received optimal RASi/MRA therapy for the majority of follow-up, and hyperkalaemic events were associated with higher risk of adverse clinical outcomes. Clinical Trial Registration: ClinicalTrials.gov NCT04864795. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• SEC61B regulates calcium flux and platelet hyperreactivity in diabetes
  Kong, Yvonne X.; Rehan, Rajan; Moreno, Cesar Llogari; Madsen, S.; Zhang, Yunwei; Zhao, Huiwen; Qi, Miao; Houlahan, Callum B.; Cartland, Si; Robertshaw, Declan; Trang, Vincent; Ong, Frederick Jun Liang; Liu, Michael; Cheng, Edward; Alwis, Imala D.; Dupuy, Alexander; Cielesh, Michelle E.; Cooke, Kristen C.; Potter, Meg; Stkli, Jacqueline; Morahan, Grant E.; Kalev-Zylinska, Maggie L.; Rondina, Matthew T.; Schulman, Sol; Yang, Jean Yee Hwa; Neely, G. Gregory; Schoenwaelder, Simone M.; Jackson, Shaun P.; James, David Ernest; Kavurma, Mary M.; Hocking, Samantha L.; Twigg, Stephen Morris; Weaver, James C.; Larance, Mark; Passam, Freda H.; Passam, Freda H.
  Journal of Clinical Investigation (Vol. 135/16) – 2025
  Platelet hyperreactivity increases the risk of cardiovascular thrombosis in diabetes and failure of antiplatelet drug therapies. Elevated basal and agonist-induced calcium flux is a fundamental cause of platelet hyperreactivity in diabetes; however, the mechanisms responsible for this remain largely unknown. Using a high-sensitivity, unbiased proteomic platform, we consistently detected over 2,400 intracellular proteins and identified proteins that were differentially released by platelets in type 2 diabetes. We identified that SEC61 translocon subunit ? (SEC61B) was increased in platelets from humans and mice with hyperglycemia and in megakaryocytes from mice with hyperglycemia. SEC61 is known to act as an endoplasmic reticulum (ER) calcium leak channel in nucleated cells. Using HEK293 cells, we showed that SEC61B overexpression increased calcium flux into the cytosol and decreased protein synthesis. Concordantly, platelets in hyperglycemic mice mobilized more calcium and had decreased protein synthesis. Platelets in both humans and mice with hyperglycemia had increased ER stress. ER stress induced the expression of platelet SEC61B and increased cytosolic calcium. Inhibition of SEC61 with anisomycin decreased platelet calcium flux and inhibited platelet aggregation in vitro and in vivo. These studies demonstrate the existence of a mechanism whereby ER stressinduced upregulation of platelet SEC61B leads to increased cytosolic calcium, potentially contributing to platelet hyperreactivity in diabetes. 2025, Kong et al.
• Machine learning-based risk factor analysis and prediction model construction for mortality in chronic heart failure
  Xu, Qian; Yu, Ruicong; Cai, Xue; Chen, Guanjie; Zheng, Yueyue; Xu, Cuirong; Sun, Jing
  Journal of Global Health (Vol. 15) – 2025
  Background Given the high global mortality burden of chronic heart failure (CHF) and the limitations of traditional risk prediction tools in accuracy and comprehensiveness, along with the potential of machine learning (ML) to improve prediction performance and the ability of a health ecology framework to systematically identify multi-dimensional risk factors, we aimed to develop an ML-based mortality risk prediction model for CHF and analyse its risk factors using a health ecology framework. Methods We enrolled 489 CHF patients from the Jackson Heart Database, with all-cause mortality during a 10-year follow-up period designated as the outcome measure. Guided by a five-layer health ecology framework (individual traits, behavioural characteristics, interpersonal relationships, work/ living conditions, and macro policies), we selected 58 variables for analysis. The cohort was split into 7:3 training/validation sets. Random forest (RF) and k-nearest neighbour (KNN) models identified mortality predictors after five oversampling techniques addressed data imbalance before modelling. We trained seven ML algorithms, validated them via 10-fold cross-validation, and compared them using accuracy, the area under the curve (AUC), and other metrics. Results We identified 24 key factors: 19 for individual traits (age, body mass index (BMI), antihypertensive medication, hypoglycaemic medication, antiarrhythmic medication, systolic blood pressure, glycated haemoglobin, glomerular filtration rate, left ventricular ejection fraction, left ventricular diastolic diameter, left ventricular mass, high-density lipoproteins, low-density lipoproteins, triglycerides, total cholesterol, cardiovascular surgical history, mitral annular early diastolic peak velocity of motion); three for individual behavioural characteristics (dark greens intake, egg intake, and night-time sleep duration); and two for living and working conditions (favourite food shop at three-kilometre radius, proportion of poor people in the place of residence). The model constructed using synthetic minority over-sampling technique combined with edited nearest neighbours (SMOTE-ENN) processing and applying extreme gradient boosting (XGBoost) model was optimal, with an accuracy of 81.58%, an AUC value of 0.83, a precision of 0.87, a recall of 0.84, and an F1 value of 0.86 for the prediction of mortality at 10-year follow up. Conclusions We systematically categorised CHF mortality risk factors by integrating health ecology theory and ML. The SMOTE-ENN and XGBoost model demonstrated high accuracy, though further optimisation is needed to enhance clinical utility in CHF risk prediction. 2025 The Author(s)
• Rapid Glass-Substrate Digital Light 3D Printing Enables Anatomically Accurate Stroke Patient-Specific Carotid Artery-on-Chips for Personalized Thrombosis Investigation
  Zhao, Yunduo Charles; Wang, Zihao; Nasser, Arian; Sun, Allan; Wang, Zhao; Zhang, Yingqi; Ren, Jianfang; Zhao, Haimei; Yap, Nicole Alexis; Wang, Yinyan; Li, Zhiyong; Butcher, Kenneth S.; Passam, Freda H.; Ang, Timothy E.; Ju, Lining Arnold
  Advanced Materials (Vol. ) – 2025
  Translating patient-specific vascular geometries into functional microfluidic devices remains challenging due to fabrication limitations and lengthy processing times. Here, an ultrafast microfabrication platform is introduced using glass-substrate digital light processing 3D printing for creating patient-specific carotid artery-on-a-chipdevices. The optimized protocol employs treated glass slides as printing substrates and custom-designed mechanical clamping, reducing manufacturing time from over 10h to under 2h with ?100% success rate. The system accurately reproduces complex anatomical features from CT angiography data of stroke patients, including stenoses, bifurcations, and ulcerations that conventional reconstruction methods often miss. Computational fluid dynamics validation confirms preserved hemodynamic similarity between patient-scale and chip-scale geometries, with matched wall shear rates maintaining physiological relevance despite 30-fold size reduction. The platform supports endothelialization and blood perfusion, enabling real-time visualization of thrombotic processes. Integration with laser ablation technology allows controlled endothelial injury modeling at patient-specific vulnerable sites. Quantitative analysis reveals 710-fold higher platelet translocation in the high shear zone (>1000s?1), demonstrating the platform's capability to capture shear-dependent thrombotic mechanisms. This rapid biomanufacturing approach represents a significant advance in patient-specific organ-on-a-chip technology, with applications in personalized medicine and vascular device development. 2025 The Author(s). Advanced Materials published by Wiley-VCH GmbH.
• A culturally grounded framework for co-designing policy with Aboriginal and Torres Strait Islander peoples
  Fono, Margaret Apolima; Chapman, Felicity; Parter, Carmen; Knight, Jodi; Sherriff (Wotjobaluk), Simone Louise; Christie, Vita; Gwynne, Kylie G.
  Policy Design and Practice (Vol. 8/4) – 2025
  Policy development in Australia has often overlooked Aboriginal and Torres Strait Islander knowledge systems, leading to policies that fail to address their unique needs and aspirations. Modern initiatives, such as the National Agreement on Closing the Gap, mark a transformative shift toward integrating Indigenous voices and experiences into policymaking. The existing evidence underscores the importance of co-design in Indigenous policy, underpinned by shared power, strong leadership, and culturally grounded principles. The literature suggests that co-designing policy with Aboriginal and Torres Strait Islander peoples can bridge the gap between Indigenous knowledge systems and policy development, fostering trust and creating meaningful, lasting change. We aim to develop a culturally grounded framework for co-designing policy with Aboriginal and Torres Strait Islander peoples by employing a framework synthesis approach and yarning methods. Our research question informs our purposive selection and appraisal of culturally relevant studies, data extraction, synthesis and interpretation to produce our framework. Humphrey etal.s Aboriginal basket weaving framework underpins our framework synthesis method. Our proposed framework aims to amalgamate Indigenous perspectives into policy co-design, ensuring inclusive, effective and culturally informed policies. Our study contributes to the growing body of literature in co-designs public policy domain by introducing an Indigenised model for integrating Aboriginal and Torres Strait Islander ways of knowing, being and doing into modern policy design practices to generate culturally responsive policy. Future framework iterations can inform practical resources to support Aboriginal and Torres Strait Islander peoples and policymakers in meaningful policy co-design. 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
• Implications and limitations of the CLEAR-SYNERGY trial for the use of low-dose colchicine in cardiovascular disease
  Misra, Ashish K.; Psaltis, Peter James; Mondal, Amandeep Rashid; Nelson, Adam James; Nidorf, Stefan Mark
  Nature Cardiovascular Research (Vol. 4/3) – 2025
  Low-dose colchicine is the only anti-inflammatory drug approved for secondary prevention of coronary disease. The CLEAR-SYNGERY trial of colchicine in acute myocardial infarction challenges the results of previous colchicine trials; however, clinicians should be aware of how its design and the COVID-19 pandemic affected the trial outcome. Springer Nature Limited 2025.
• Sericin improves alginate-gelatin hydrogels mechanical properties, porosity, durability, and viability of fibroblasts in cardiac spheroids
  Tarsitano, Martine; Ming, Clara Liu Chung; Idais, Dana; Mahmodi, Hadi; Wyllie, Kaitlin; Isella, Benedetta; Cox, Thomas R.; Kabakova, Irina V.; Paolino, Donatella; Gentile, Carmine
  International Journal of Bioprinting (Vol. 11/1) – 2025
  Biofabrication of cardiac patches is a challenging strategy proposed as an alternative to transplantation for end-stage heart failure patients. The optimization of the bioink used for this strategy can be limited by costs, properties, and biocompatibility of its building blocks. Lately, sericin has emerged within a wide range of natural proteins, thanks to its bioadhesive and biocompatibility potential. In this study, we assessed for the first time the effects of adding silk sericin on alginate-gelatin hydrogels, proposed for cardiac applications. To this aim, we first biofabricated sericin-containing hydrogels with increasing protein concentrations. Thus, we characterized hydrogels mechanical behavior, porosity and structure through rheology, Brillouin microspectroscopy, and scanning electron microscopy. Then, we bioprinted the formulated hydrogels and evaluated their effects on human cardiac spheroids (CSs) in vitro. Our mechanical characterization demonstrated that adding sericin significantly enhanced the elasticity and the viscosity of alginate-gelatin hydrogels. Sericin also modified hydrogels swelling behavior and their pore size, increasing by 20%, 62%, and 92% in Ser1%, Ser2%, and Ser3%, respectively. Although Ser1% did not exhibit significant effects on CSs, Ser2% and Ser3% enhanced cardiac cell viability for up to 14 days compared to the sericin-free hydrogel by acting on the fibroblast population. Sericin-based bioinks showed better printability and durability with +33% and +28% intact patches after 28 days of culture at 37C compared to alginate-gelatin. Taken together, our results validated the use of sericin as a promising component for the optimization of bioink intended for cardiac applications. 2024 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution, and reproduction in any medium, provided the original work is properly cited.
• Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms
  Aye, San Seint; Fang, Zhongqi; Wu, Mike C.L.; Lim, K. S.; Ju, Lining Arnold
  Biomaterials Science (Vol. 13/5) – 2025
  Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of in vitro thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment. 2025 The Royal Society of Chemistry.
• Photochemistry as a tool for dynamic modulation of hydrogel mechanics
  Major, Gretel S.; Joukhdar, Habib; Choi, Yu Suk; Rnjak-Kovacina, Jelena; Wise, Steven G.; Ju, Lining Arnold; Cox, Thomas R.; Xu, Chun; Yeo, Giselle C.; Young, Jennifer L.; Lim, K. S.
  Cell Reports Physical Science (Vol. 6/1) – 2025
  Photochemistry has emerged as a powerful tool for manipulating the dynamic and heterogeneous properties of hydrogel microenvironments in tissue engineering and mechanobiology. Enhanced spatiotemporal control over hydrogel mechanical properties can be achieved by incorporating an array of photosensitive functional groups within polymer networks and controlling photokinetics through light illumination. This review explores how light-stimulated photocleavage, addition, exchange, and isomerization reactions are utilized to generate hydrogels that soften and stiffen in situ, enabling precise control over cell functionality in tissue-engineered constructs. Advancements in polymer design and biofabrication platforms that have enhanced control over these reactions and that permit local modulation of mechanical properties within larger microenvironments are discussed. The applications of these dynamic hydrogels in understanding cellular mechanosensation, investigating fibrotic disease, and directing stem cell differentiation and tissue formation are examined. While significant progress has been made toward on-demand platforms that switch between multiple mechanical conditions, this review highlights the need for materials that undergo progressive dynamic stiffening. The review also explores emerging applications of photochemistry in intracellular environments and its potential integration with advanced force spectroscopy techniques for live-cell mechanobiology studies. Overall, using light as a stimulus for reactions within hydrogels has enhanced tunability, reaction kinetics, and spatiotemporal control compared to other stimuli-driven systems, opening new avenues for biomimetic material design and mechanobiological investigations. 2024 The Author(s)
• Optical coherence tomography assessment of the impact of colchicine on non-culprit coronary plaque composition after myocardial infarction
  Psaltis, Peter James; Nguyen, Mau T.; Singh, Kuljit; Sinhal, Ajay R.; Wong, Dennis T.L.; Alcock, Richard F.; Rajendran, Sharmalar; Dautov, Rustem F.; Barlis, Peter; Patel, Sanjay; Salagaras, Thalia; Marathe, Jessica A.; Bursill, C. A.; Montarello, Nicholas Joseph; Nidorf, Stefan Mark; Thompson, Peter Lindsay; Butters, Julie; Cuthbert, Alana R.; Yelland, Lisa Nicole; Ottaway, Juanita L.; Kataoka, Yu; Di Giovanni, Giuseppe A.; Nicholls, Stephen J.
  Cardiovascular Research (Vol. 121/3) – 2025
  Aims Low-dose colchicine reduces the risk of cardiovascular events after myocardial infarction (MI). The purpose of this study was to assess the effect of colchicine post-MI on coronary plaque morphology in non-culprit segments by optical coherence tomography (OCT). Methods COCOMO-ACS was a double-blind, placebo-controlled trial that randomized 64 patients (median age 61.5 years; 9.4% female) with and results acute non-ST-segment elevation MI to colchicine 0.5 mg daily or placebo for a median of 17.8 months in addition to guideline-recommended therapy. Participants underwent serial OCT imaging within a matched segment of non-culprit coronary artery that contained at least one lipid-rich plaque causing ?20% stenosis. The primary outcome was the change in minimum fibrous cap thickness (FCT) in non-culprit segments from baseline to final visit. Of those randomized, 57 (29 placebo, 28 colchicine) had evaluable imaging at baseline and follow-up. Overall, colchicine had no effect on relative (placebo +48.0 35.1% vs. colchicine +62.4 38.1%, P = 0.18) or absolute changes in minimum FCT (+29.2 20.9 m vs. + 37.2 21.3 m, P = 0.18), or change in maximum lipid arc (?38.8 32.2 vs. ?54.8 46.9, P = 0.18) throughout the imaged non-culprit segment. However, in patients assigned colchicine, cap rupture was less frequent (placebo 27.6% vs. colchicine 3.6%, P = 0.03). In post hoc analysis of 43 participants who had been followed for at least 16 months, minimum FCT increased to a greater extent in the colchicine group (placebo +38.7 25.4% vs. colchicine +64.7 34.1%, P = 0.005). Conclusion In this study, OCT failed to detect an effect of colchicine on the minimum FCT or maximum lipid arc of plaques in non-culprit segments post-MI. The post hoc observation that minimum FCT increased to a greater extent with colchicine after more prolonged treatment suggests that longer-term studies may be required to detect the effect of anti-inflammatory therapies on plaque morphology by OCT. The Author(s) 2024.
• Development of supramolecular anticoagulants with on-demand reversibility
  Dockerill, Millicent; Ford, Daniel J.; Angerani, Simona; Alwis, Imala D.; Dowman, Luke J.; Ripoll-Rozada, Jorge; Smythe, Rhyll E.; Liu, Joanna Shu Ting; Pereira, Pedro JosBarbosa; Jackson, Shaun P.; Payne, Richard J.; Winssinger, Nicolas
  Nature Biotechnology (Vol. 43/2) – 2025
  Drugs are administered at a dosing schedule set by their therapeutic index, and termination of action is achieved by clearance and metabolism of the drug. In some cases, such as anticoagulant drugs or immunotherapeutics, it is important to be able to quickly reverse the drugs action. Here, we report a general strategy to achieve on-demand reversibility by designing a supramolecular drug (a noncovalent assembly of two cooperatively interacting drug fragments held together by transient hybridization of peptide nucleic acid (PNA)) that can be reversed with a PNA antidote that outcompetes the hybridization between the fragments. We demonstrate the approach with thrombin-inhibiting anticoagulants, creating very potent and reversible bivalent direct thrombin inhibitors (K<inf>i</inf> = 74 pM). The supramolecular inhibitor effectively inhibited thrombus formation in mice in a needle injury thrombosis model, and this activity could be reversed by administration of the PNA antidote. This design is applicable to therapeutic targets where two binding sites can be identified. The Author(s) 2024.
• Finerenone and left ventricular hypertrophy in chronic kidney disease and type 2 diabetes
  Filippatos, Gerasimos S.; Anker, Stefan D.; Bakris, George L.; Rossing, Peter R.; Ruilope, Lu Miguel; Coats, Andrew J.S.; von Haehling, Stephan; Ponikowski, Piotr P.; Rosano, Giuseppe Massimo Claudio; Brinker, Meike D.; Farjat, Alfredo E.; Roberts, Luke; Pitt, Bertram A.
  ESC Heart Failure (Vol. 12/1) – 2025
  Aims: Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline. Methods and results: A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR)?57% from baseline over ?4weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (P<inf>interaction</inf>=0.1075 for composite CV outcome and P<inf>interaction</inf>=0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (P<inf>interaction</inf>=0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups. Conclusions: In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF. 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• The importance of assessing and correcting hydration status prior to right heart catheterisation: a pilot study
  Ratwatte, Seshika D.; Cordina, Rachael Louise; Baker, David William; Lau, Edmund M.T.; Celermajer, David S.
  Internal Medicine Journal (Vol. 55/2) – 2025
  We evaluated whether fluid status could be accurately assessed (and corrected if necessary) prior to right heart catheterisation (RHC), to diagnose accurately post-capillary pulmonary hypertension (PHT) in patients with left heart disease risk factors. A non-invasive measure of fluid status prior to RHC identified fluid-depleted patients. Baseline RHC measurements were performed, and a novel provocation technique (passive leg raise) was compared to a one-dose-fits-all fluid challenge and found to be equivalent. 2024 Royal Australasian College of Physicians.
• State- and territory-based differences that impede the establishment of a harmonised national registry
  Lloyd, Larissa K.; Nicholson, Calum; Strange, G. A.; Celermajer, David S.
  Australian Health Review (Vol. 49/2) – 2025
  Objective: This paper aims to identify and describe legislative and administrative barriers to hospital participation and national data linkage for the National Australian Congenital Heart Disease (CHD) Registry. Methods: A narrative review based on the National Australian CHD Registry experience of establishing participating hospital sites and national linkages associated with each jurisdiction. Results: There were numerous identified barriers that could be overcome with additional resources/time, and barriers that could not be overcome, reported by jurisdiction. Conclusions: There is a pressing need for greater harmonisation of state-based legislation governing research and harmonisation of administration to reduce duplication. Substantial state-based differences hinder the establishment of a truly national registry. 2025 The Author(s) (or their employer(s)).
• Atrial fibrillation burden in clinical practice, research, and technology development: a clinical consensus statement of the European Society of Cardiology Council on Stroke and the European Heart Rhythm Association
  Doehner, Wolfram; Boriani, Giuseppe; Potpara, Tatjana S.; Blomstr-Lundqvist, Carina M.; Passman, Rod Stuart; Sposato, Luciano A.; Dobrev, Dobromir; Freedman, Ben; van Gelder, Isabelle C.; Glotzer, Taya V.; Healey, Jeff S.; Karapanayiotides, Theodoros; Lip, Gregory Y.H.; Merino, JosLuis; Ntaios, George C.; Schnabel, Renate B.; Svendsen, Jesper Hastrup; Svennberg, Emma; Wachter, Rolf; Haeusler, Karl Georg; Camm, Alan John
  Europace (Vol. 27/3) – 2025
  Atrial fibrillation (AF) is one of the most common cardiac diseases and a complicating comorbidity for multiple associated diseases. Many clinical decisions regarding AF are currently based on the binary recognition of AF being present or absent with the categorical appraisal of AF as continued or intermittent. Assessment of AF in clinical trials is largely limited to the time to (first) detection of an AF episode. Substantial evidence shows, however, that the quantitative characteristic of intermittent AF has a relevant impact on symptoms, onset, and progression of AF and AF-related outcomes, including mortality. Atrial fibrillation burden is increasingly recognized as a suitable quantitative measure of intermittent AF that provides an estimate of risk attributable to AF, the efficacy of antiarrhythmic treatment, and the need for oral anticoagulation. However, the diversity of assessment methods and the lack of a consistent definition of AF burden prevent a wider clinical applicability and validation of actionable thresholds of AF burden. To facilitate progress in this field, the AF burden Consensus Group, an international and multidisciplinary collaboration, proposes a unified definition of AF burden. Based on current evidence and using a modified Delphi technique, consensus statements were attained on the four main areas describing AF burden: Defining the characteristics of AF burden, the recording principles, the clinical relevance in major clinical conditions, and implementation as an outcome in the clinic and in clinical trials. According to this consensus, AF burden is defined as the proportion of time spent in AF expressed as a percentage of the recording time, undertaken during a specified monitoring duration. A pivotal requirement for validity and comparability of AF burden assessment is a continuous or near-continuous duration of monitoring that needs to be reported together with the AF burden assessment. This proposed unified definition of AF burden applies independent of comorbidities and outcomes. However, the disease-specific actionable thresholds of AF burden need to be defined according to the targeted clinical outcomes in specific populations. The duration of the longest episode of uninterrupted AF expressed as a time duration should also be reported when appropriate. A unified definition of AF burden will allow for comparability of clinical study data to expand evidence and to establish actionable thresholds of AF burden in various clinical conditions. This proposed definition of AF burden will support risk evaluation and clinical treatment decisions in AF-related disease. It will further promote the development of clinical trials studying the clinical relevance of intermittent AF. A unified approach on AF burden will finally inform the technology development of heart rhythm monitoring towards validated technology to meet clinical needs. The European Society of Cardiology 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.