Publications

Showing 261–280 of 2058 publications.

• Comorbidities and Symptom Status in Moderate and Severe Aortic Stenosis: A Multicenter Clinical Cohort Study
  Playford, David A.; Schwarz, Nisha; Chowdhury, Enayet K.; Williamson, Anna Emilie; Duong, Myngan Ngan; Kearney, Leighton G.; Stewart, S.; Strange, G. A.
  JACC: Advances (Vol. 2/4) – 2023
  Background: Symptoms associated with severe aortic stenosis (AS) are used to guide management. Objectives: The purpose of this study was to examine the pattern of symptoms, comorbidities, and cardiac damage in moderate and severe AS. Methods: A total of 846,198 echocardiographic investigations from 330,940 individuals aged >18 years were selected for the most recent echocardiogram, moderate or severe AS (mean gradient 20.0-39.9 mm Hg, aortic valve peak gradient 3.0-3.9 m/s and aortic valve area >1.0 cm2; or ?40.0 mm Hg, ?4.0 m/s or ?1.0 cm2, respectively), and a cardiologist consultation. Natural Language Processing was applied to letters to extract comorbidities, dyspnea, chest pain, and syncope. Patients with prior aortic valve replacement were excluded. Results: 2,213 patients (0.7% overall, 32.8% females) had moderate and 3,416 (1.0%, 47.3% females) had severe AS. Comorbidities were common, including hypertension, (56.6% moderate AS, 53.1% severe AS, P = 0.01), coronary disease (46.0% and 46.8%, respectively, P = 0.58) and atrial fibrillation (29.6% and 34.8%, respectively, P < 0.001). Symptoms were also common in both moderate (n = 915, 41.3%) and severe (n = 1,630, 47.7%) AS (P < 0.001). Comorbidities were more likely in symptomatic vs asymptomatic patients (P < 0.001). Dyspnea was more likely in severe AS, whereas angina and syncope were similar in moderate vs severe AS. In multivariable analysis, only dyspnea was associated with severe (vs moderate) AS (OR: 1.73, 95% CI: 1.41-2.13, P < 0.001). In both adjusted and unadjusted models, the degree of cardiac damage did not relate to presence of any symptoms but was associated with AS severity. Conclusions: Dyspnea is common in both moderate and severe AS, is associated with comorbidities and is not related to the degree of cardiac damage. Symptom-guided management decisions in AS may need revision. 2023 The Authors
• The Role of Oxidants in Percutaneous Coronary Intervention-Induced Endothelial Dysfunction: Can We Harness Redox Signaling to Improve Clinical Outcomes?
  Wolhuter, Kathryn; Kong, Stephanie M.Y.; Stanley, Christopher P.; Kovacic, Jason C.
  Antioxidants and Redox Signaling (Vol. 38/13) – 2023
  Significance: Coronary artery disease (CAD) is commonly treated using percutaneous coronary interventions (PCI). However, PCI with stent placement damages the endothelium, and failure to restore endothelial function may result in PCI failure with poor patient outcomes. Recent Advances: Oxidative signaling is central to maintaining endothelial function. Potentiation of oxidant production, as observed post-PCI, results in endothelial dysfunction (ED). This review delves into our current understanding of the physiological role that endothelial-derived oxidants play within the vasculature and the effects of altered redox signaling during dysfunction. We then examine the impact of PCI and intracoronary stent placement on oxidant production in the endothelium, which can culminate in stent failure. Finally, we explore how recent advances in PCI and stent technologies aim to mitigate PCI-induced oxidative damage and improve clinical outcomes. Critical Issues: Current PCI technologies exacerbate cellular oxidant levels, driving ED. If left uncontrolled, oxidative signaling leads to increased intravascular inflammation, restenosis, and neoatherosclerosis. Future Directions: Through the development of novel biomaterials and therapeutics, we can limit PCI-induced oxidant production, allowing for the restoration of a healthy endothelium and preventing CAD recurrence. 2023 Mary Ann Liebert, Inc.
• Participation in a clinical trial is associated with lower mortality but not lower risk of HF hospitalization in patients with heart failure: observations from the ESC EORP Heart Failure Long-Term Registry
  Kapelios, Chris J.; Benson, Lina; Crespo-Leiro, Mar Generosa; Anker, Stefan D.; Coats, Andrew J.S.; Chioncel, O. Dragomir; Filippatos, Gerasimos S.; Lain?ak, Mitja; McDonagh, Theresa A.; Mebazaa, Alexandre; Metra, Marco; PIEPOLI, MASSIMO Francesco; Rosano, Giuseppe Massimo Claudio; Ruschitzka, Frank T.; Savarese, Gianluigi; Seferovi?, Petar M.; Volterrani, Maurizio; Maggioni, Aldo Pietro; Lund, Lars H.
  European Heart Journal (Vol. 44/17) – 2023
  [No abstract available]
• An interactive geographic information system to inform optimal locations for healthcare services
  Nicholson, Calum; Hanly, Mark J.; Celermajer, David S.
  PLOS Digital Health (Vol. 2/5) – 2023
  Large health datasets can provide evidence for the equitable allocation of healthcare resources and access to care. Geographic information systems (GIS) can help to present this data in a useful way, aiding in health service delivery. An interactive GIS was developed for the adult congenital heart disease service (ACHD) in New South Wales, Australia to demonstrate its feasibility for health service planning. Datasets describing geographic boundaries, area-level demographics, hospital driving times, and the current ACHD patient population were collected, linked, and displayed in an interactive clinic planning tool. The current ACHD service locations were mapped, and tools to compare current and potential locations were provided. Three locations for new clinics in rural areas were selected to demonstrate the application. Introducing new clinics changed the number of rural patients within a 1-hour drive of their nearest clinic from 44.38% to 55.07% (79 patients) and reduced the average driving time from rural areas to the nearest clinic from 2.4 hours to 1.8 hours. The longest driving time was changed from 10.9 hours to 8.9 hours. A de-identified public version of the GIS clinic planning tool is deployed at https://cbdrh.shinyapps.io/ACHD_Dashboard/. This application demonstrates how a freely available and interactive GIS can be used to aid in health service planning. In the context of ACHD, GIS research has shown that adherence to best practice care is impacted by patients accessibility to specialist services. This project builds on this research by providing opensource tools to build more accessible healthcare services. : 2023 Nicholson et al.
• Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model
  Lay, Angelina J.; Dupuy, Alexander; Hagimola, Lejla; Tieng, Jessica; Larance, Mark; Zhang, Yunwei; Yang, Jean Yee Hwa; Kong, Yvonne X.; Chiu, Joyce; Gray, Emilia; Qin, Zihao; Schmidt, Diana; Maclean, Jessica A.A.; Hofma, Benjamin R.; Ellis, Marc L.; Kalev-Zylinska, Maggie L.; Argon, Yair; Jackson, Shaun P.; Hogg, Philip J.; Passam, Freda H.
  Blood Advances (Vol. 7/9) – 2023
  Extracellular protein disulfide isomerases (PDIs), including PDI, endoplasmic reticulum protein 57 (ERp57), ERp72, ERp46, and ERp5, are required for in vivo thrombus formation in mice. Platelets secrete PDIs upon activation, which regulate platelet aggregation. However, platelets secrete only ~10% of their PDI content extracellularly. The intracellular role of PDIs in platelet function is unknown. Here, we aim to characterize the role of ERp5 (gene Pdia6) using platelet conditional knockout mice, platelet factor 4 (Pf4) Cre+/ERp5floxed (fl)/fl . Pf4Cre+/ERp5fl/fl mice developed mild macrothrombocytopenia. Platelets deficient in ERp5 showed marked dysregulation of their ER, indicated by a twofold upregulation of ER proteins, including PDI, ERp57, ERp72, ERp46, 78 kilodalton glucose-regulated protein (GRP78), and calreticulin. ERp5-deficient platelets showed an enhanced ER stress response to ex vivo and in vivo ER stress inducers, with enhanced phosphorylation of eukaryotic translation initiation factor 2A and inositol-requiring enzyme 1 (IRE1). ERp5 deficiency was associated with increased secretion of PDIs, an enhanced response to thromboxane A2 receptor activation, and increased thrombus formation in vivo. Our results support that ERp5 acts as a negative regulator of ER stress responses in platelets and highlight the importance of a disulfide isomerase in platelet ER homeostasis. The results also indicate a previously unanticipated role of platelet ER stress in platelet secretion and thrombosis. This may have important implications for the therapeutic applications of ER stress inhibitors in thrombosis. 2023 by The American Society of Hematology.
• Obstacles in establishing a national disease registry in Australia: lessons from the development of the CHAANZ Congenital Heart Disease Registry
  Lloyd, Larissa K.; Nasir, Reeja F.; Nicholson, Calum; Strange, G. A.; Celermajer, David S.
  Australian Health Review (Vol. 47/4) – 2023
  Objectives: To provide insights into the obstacles which pose challenges to the set-up of any National Registry in Australia. Methods: An analysis of our experience in executing a Multi-Institutional Agreement (MIA) and obtaining ethics and governance approvals, post-award of a large Medical Research Futures Fund grant in June 2020. Results: From July 2020, our timeline to an executed MIA was 283 days, despite full-time staff working towards this goal. Subsequently, after lead site ethics approval, time to site governance approvals ranged from 9 to 291 days. A total of 214 emails were sent during the MIA development and signing. There were 11-71 emails sent to individual governance offices and the number of requested points of additional information ranged from 0 to 31 queries. Conclusions: There were considerable time delays in executing the initial (pre-research) stages of a National Federal Government funded Registry project which required substantial time and resources. We report a wide variation in requirements between different states and institutions. We propose several strategies which could be implemented to facilitate a more streamlined approach to research ethics and governance. This centralised approach would allow for better use of funding and facilitate better progress in medical research. 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of AHHA.
• Mechano-covalent protection of coagulation factor VIII by von Willebrand factor
  Butera, Diego; Wang, Haoqing Jerry; Woon, Heng Giap; Zhao, Yunduo Charles; Ju, Lining Arnold; Hogg, Philip J.
  Blood Advances (Vol. 7/10) – 2023
  von Willebrand factor (VWF) is the protective carrier of procoagulant factor VIII (FVIII) in the shear forces of the circulation, prolonging its half-life and delivering it to the developing thrombus. Using force spectroscopy, VWF-FVIII complex formation is characterized by catch-bond behavior in which force first decelerates then accelerates bond dissociation. Patients with mutations in VWF at the FVIII binding site phenocopies hemophilia A and the most common mutations are of cysteine residues involving multiple disulfide bonds. From differential cysteine alkylation and mass spectrometry experiments, 13 VWF disulfide bonds at the FVIII binding site were found to exist in formed and unformed states, and binding of FVIII results in partial formation of 12 of the VWF bonds. Force spectroscopy studies indicate that the VWF-FVIII bond stiffens in response to force and this feature of the interaction is ablated when VWF disulfide bonds are prevented from forming, resulting in slip-only bond behavior. Exposure of VWF to pathological fluid shear forces ex vivo and in vivo causes partial cleavage of all 13 disulfide bonds, further supporting their malleable nature. These findings demonstrate that FVIII binding to VWF involves dynamic changes in the covalent states of several VWF disulfides that are required for productive interaction in physiological shear forces. 2023 by The American Society of Hematology.
• Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology
  Metra, Marco; Tomasoni, Daniela; Adamo, Marianna; Bay-Gen, Antoni; Filippatos, Gerasimos S.; Abdelhamid, Magdy A.; Adamopoulos, Stamatis N.; Anker, Stefan D.; Antohi, Laura E.; Bm, Michael; Braunschweig, Frieder; Ben-Gal, Tuvia; Butler, Javed J.; Cleland, John G.F.; Cohen-Solal, Alain; Damman, Kevin; Gustafsson, Finn; Hill, Loreena Michelle; Jankowska, Ewa Anita; Lain?ak, Mitja; Lund, Lars H.; McDonagh, Theresa A.; Mebazaa, Alexandre; Moura, Brenda; Mullens, Wilfried; PIEPOLI, MASSIMO Francesco; Ponikowski, Piotr P.; Rakisheva, Amina G.; Risti?, Arsen D.; Savarese, Gianluigi; Seferovi?, Petar M.; Sharma, Rajan; Tocchetti, Carlo G.; Yilmaz, Mehmet Birhan; Vitale, Cristiana A.; Volterrani, Maurizio; von Haehling, Stephan; Chioncel, O. Dragomir; Coats, Andrew J.S.; Rosano, Giuseppe Massimo Claudio
  European Journal of Heart Failure (Vol. 25/6) – 2023
  Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice. 2023 European Society of Cardiology.
• Bioinspired Approaches to Engineer Antithrombogenic Medical Devices for Vascular Intervention
  Hong, Jun Ki; Waterhouse, Anna
  Arteriosclerosis, Thrombosis, and Vascular Biology (Vol. 43/6) – 2023
  Medical devices form a critical component of health care systems for treating and maintaining patient health. However, devices exposed to blood are prone to blood clotting (thrombosis) and bleeding complications leading to device occlusion, device failure, embolism and stroke, and increased morbidity and mortality. Over the years, developments in innovative material design strategies have been made to help reduce the occurrence of thrombotic events on medical devices, but complications persist. Here, we review material and surface coating technologies that have taken bioinspiration from the endothelium to reduce medical device thrombosis, either by mimicking aspects of the glycocalyx to prevent adhesion of proteins and cells to the material surface or mimicking the bioactive function of the endothelium through immobilized or released bioactive molecules to actively inhibit thrombosis. We highlight newer strategies that take inspiration from multiple aspects of the endothelium or are stimuli responsive, only releasing antithrombotic biomolecules when thrombosis is triggered. Emerging areas of innovation target inflammation to decrease thrombosis without increasing bleeding, and interesting results are coming from underexplored aspects of material properties, such as material interfacial mobility and stiffness, which show that increased mobility and decreased stiffness are less thrombogenic. These exciting new strategies require further research and development before clinical translation, including consideration of longevity, cost, and sterilization, but show capacity for the development of more sophisticated antithrombotic medical device materials. 2023 Lippincott Williams and Wilkins. All rights reserved.
• A hidden problem: peripheral artery disease in women
  Kavurma, Mary M.; Boccanfuso, Lauren M.; Cutmore, Carina; Passam, Freda H.; Patel, Sanjay; Hennessy, Annemarie; Loa, Jacky; Figtree, Gemma A.; Golledge, Jonathan; Robinson, David A.; Aitken, Sarah Joy
  European Heart Journal - Quality of Care and Clinical Outcomes (Vol. 9/4) – 2023
  Peripheral artery disease (PAD) has a huge social and economic burden and is an important contributor to the global health burden. Sex differences in PAD are apparent, with recent data suggesting equal if not greater prevalence in women, and women having worse clinical outcomes. Why this occurs is not clear. To identify underlying reasons for gender inequalities in PAD, we executed a deeper exploration through a social constructive perspective. A scoping review was conducted using the World Health Organization model for analysis of gender-related needs in healthcare. Complex interacting factors, including biological, clinical, and societal variables, were reviewed to highlight gender-related inequities in the diagnosis, treatment, and management of PAD. Current gaps in knowledge were identified and insights into future directions aimed at improving these inequalities were discussed. Our findings highlight the multi-level complexities that need to be considered for strategies to improve gender-related needs in PAD healthcare. 2023 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
• Patient phenotype profiling in heart failure with preserved ejection fraction to guide therapeutic decision making. A scientific statement of the Heart Failure Association, the European Heart Rhythm Association of the European Society of Cardiology, and
  Anker, Stefan D.; Usman, Muhammad Shariq; Anker, Markus S.; Butler, Javed J.; Bm, Michael; Abraham, William T.; Adamo, Marianna; Chopra, Vijay Kumar; Cicoira, Mariantonietta; Cosentino, Francesco; Filippatos, Gerasimos S.; Jankowska, Ewa Anita; Lund, Lars H.; Moura, Brenda; Mullens, Wilfried; Pieske, Burkert Mathias; Ponikowski, Piotr P.; Gzalez-Juanatey, JosRam; Rakisheva, Amina G.; Savarese, Gianluigi; Seferovi?, Petar M.; Teerlink, John R.; Tsche, Carsten; Volterrani, Maurizio; von Haehling, Stephan; Zhang, Jian; Zhang, Yuhui; Bauersachs, Johann; Landmesser, Ulf E.; Zieroth, Shelley R.; Tsioufis, Konstantinos P.; Bay-Gen, Antoni; Chioncel, O. Dragomir; Andreotti, Felicita; Agabiti- Rosei, Enrico; Merino, JosLuis; Metra, Marco; Coats, Andrew J.S.; Rosano, Giuseppe Massimo Claudio
  European Journal of Heart Failure (Vol. 25/7) – 2023
  Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodiumglucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype-based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence-based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy. 2023 European Society of Cardiology.
• Novel Movable Typing for Personalized Vein-Chips in Large Scale: Recapitulate Patient-Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis
  Zhao, Yunduo Charles; Zhang, Yingqi; Wang, Zihao; Jiang, Fengtao; Kyanian, Kiarash; Aye, San Seint; Hong, Tianbo; Vatankhah, Parham; Nasser, Arian; Sun, Allan; Moldovan, Laura; Su, Qian Peter; Cho, Ann-Na; Wang, Yao; Passam, Freda H.; Ang, Timothy E.; Ju, Lining Arnold
  Advanced Functional Materials (Vol. 33/23) – 2023
  The Vein-Chip recapitulates CVST Virchow's triad and enables systematic characterization of venous thrombogenesis with respect to fibrin formation and platelet aggregation. Distinct from the arterial setting, platelets universally adhere across the entire CVS Vein-Chip independent of stenotic geometry and flow disturbance. Intriguingly, fibrin propagates along with the flow direction, but exclusively deposits to the inner vessel wall. Upon inflammatory endothelial injury, fibrin deposition mirrors to the outer vessel wall, but still not in the lumen. Together, the Vein-Chip promises future applications for personalized thrombotic assessment and monitoring. 2023 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH.
• Prevalence of pulmonary hypertension in mitral regurgitation and its influence on outcomes
  Ratwatte, Seshika D.; Strange, G. A.; Playford, David A.; Stewart, S.; Celermajer, David S.
  Open Heart (Vol. 10/1) – 2023
  Objective Pulmonary hypertension (PHT) commonly coexists with significant mitral regurgitation (MR), but its prevalence and prognostic importance have not been well characterised. In a large cohort of adults with moderate or greater MR, we aimed to describe the prevalence and severity of PHT and assess its influence on outcomes. Methods In this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction >50% and with moderate or greater MR were included (n=9683). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes was evaluated (median follow-up of 3.2 years, IQR 1.3-6.2 years). Results Subjects were aged 7612 years, and 62.6% (6038) were women. Overall, 959 (9.9%) had no PHT, and 2952 (30.5%), 3167 (32.7%), 1588 (16.4%) and 1017 (10.5%) patients had borderline, mild, moderate and severe PHT, respectively. A typical left heart disease' phenotype was identified with worsening PHT, showing rising E:e?, right and left atrial sizes increasing progressively, from no PHT to severe PHT (p<0.0001, for all). With increasing PHT severity, 1- and 5-year actuarial mortality increased from 8.5% and 33.0% to 39.7% and 79.8%, respectively (p<0.0001). Similarly, adjusted survival analysis showed the risk of long-term mortality progressively increased with higher eRVSP levels (adjusted HR 1.20-2.86, borderline to severe PHT, p<0.0001 for all). A mortality inflection was apparent at an eRVSP level >34.00 mm Hg (HR 1.27, CI 1.00-1.36). Conclusions In this large study, we report on the importance of PHT in patients with MR. Mortality increases as PHT becomes more severe from an eRVSP of 34 mm Hg onwards. 2023 BMJ Publishing Group. All rights reserved.
• Integrative processing of untargeted metabolomic and lipidomic data using MultiABLER
  Lee, Ian C.H.; Tumanov, Sergey; Wong, Jason Wing Hon; Stocker, Roland; Ho, Joshua W.K.
  iScience (Vol. 26/6) – 2023
  Mass spectrometry (MS)-based untargeted metabolomic and lipidomic approaches are being used increasingly in biomedical research. The adoption and integration of these data are critical to the overall multi-omic toolkit. Recently, a sample extraction method called Multi-ABLE has been developed, which enables concurrent generation of proteomic and untargeted metabolomic and lipidomic data from a small amount of tissue. The proteomics field has a well-established set of software for processing of acquired data; however, there is a lack of a unified, off-the-shelf, ready-to-use bioinformatics pipeline that can take advantage of and prepare concurrently generated metabolomic and lipidomic data for joint downstream analyses. Here we present an R pipeline called MultiABLER as a unified and simple upstream processing and analysis pipeline for both metabolomics and lipidomics datasets acquired using liquid chromatography-tandem mass spectrometry. The code is available via an open-source license at https://github.com/holab-hku/MultiABLER. 2023 The Authors
• Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome
  King, Gregory; Buratto, Edward; Daley, Michael; Iyengar, Ajay J.; Alphonso, Nelson D.; Grigg, Leeanne Elizabeth; Cordina, Rachael Louise; d'Udekem, Yves A.; Konstantinov, Igor E.
  Annals of Thoracic Surgery (Vol. 116/1) – 2023
  Background: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome. Methods: We performed a retrospective study of 1731 patients who survived the Fontan operation from the Australia and New Zealand Fontan Registry between 1975 and 2020. Results: We identified 188 patients with hypoplastic left heart syndrome, including 99 (53%) with aortic atresia. Overall transplant-free survival and freedom from failure of Fontan circulation at 15 years was 91% (95% CI, 86%-96%) and 79% (95% CI, 71%-88%), respectively. The cumulative incidence of AVV operation at 15 years of age for patients with aortic atresia and aortic stenosis was 28% (95% CI, 19%-38%) and 14% (95% CI, 7%-22%; P =.03), respectively. The cumulative incidence of AVV failure (moderate or greater regurgitation or AVV operation) at 15 years of age for patients with aortic atresia and aortic stenosis was 50% (95% CI, 37%-61%) and 30% (95% CI, 19%-42%; P =.01). Patients with AVV failure were at increased risk of having moderately, or worse, decreased systolic ventricular function (odds ratio 6.7; 95% CI, 1.7-33; P =.01) and failure of Fontan circulation (hazard ratio 3.7; 95% CI, 1.5-9.1; P <.01). Conclusions: In patients with hypoplastic left heart syndrome, there is no significant difference in transplant-free survival after Fontan operation between patients with aortic atresia and patients with aortic stenosis. However, patients with aortic atresia have a much higher burden of AVV failure than patients with aortic stenosis. Atrioventricular valve failure is associated with failure of Fontan circulation. 2023
• Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry
  Shahim, Bahira; Shahim, Angiza; Adamo, Marianna; Chioncel, O. Dragomir; Benson, Lina; Crespo-Leiro, Mar Generosa; Anker, Stefan D.; Coats, Andrew J.S.; Filippatos, Gerasimos S.; Lain?ak, Mitja; McDonagh, Theresa A.; Mebazaa, Alexandre; PIEPOLI, MASSIMO Francesco; Rosano, Giuseppe Massimo Claudio; Ruschitzka, Frank T.; Savarese, Gianluigi; Seferovi?, Petar M.; Volterrani, Maurizio; Crespo-Leiro, Marisa G.; Segovia-Cubero, Javier; Amir, Offer; Palic, B.; Maggioni, Aldo Pietro; Metra, Marco; Lund, Lars H.
  European Journal of Heart Failure (Vol. 25/7) – 2023
  Aims: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). Methods and results: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.231.67), and MAVD (adjusted HR 1.37, 95% CI 1.071.74) but not AR (adjusted HR 1.13, 95% CI 0.961.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. Conclusions: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category. 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
• Focal Anticoagulation by Somatic Gene Transfer: Towards Preventing Cardioembolic Stroke
  Kadian, Megha; Kok, Cindy Y.; Ravindran, Dhanya; Passam, Freda H.; Pasalic, Leonardo; Kizana, Eddy
  Heart Lung and Circulation (Vol. 32/7) – 2023
  Cardioembolic stroke (CS) has emerged as a leading cause of ischaemic stroke (IS); distinguished by thrombi embolising to the brain from cardiac origins; most often from the left atrial appendage (LAA). Contemporary therapeutic options are largely dependent on systemic anticoagulation as a blanket preventative strategy, yet this does not represent a nuanced or personalised solution. Contraindications to systemic anticoagulation create significant unmedicated and high-risk cohorts, leaving these patients at risk of significant morbidity and mortality. Atrial appendage occlusion devices are increasingly used to mitigate stroke risk from thrombi emerging from the LAA in patients ineligible for oral anticoagulants (OACs). Their use, however, is not without risk or significant cost, and does not address the underlying aetiology of thrombosis and CS. Viral vector-based gene therapy has emerged as a novel strategy to target a spectrum of haemostatic disorders, achieving success through the adeno-associated virus (AAV) based therapy of haemophilia. Yet, thrombotic disorders, such as CS, have had limited exploration within the realm of AAV gene therapy approachespresenting a gap in the literature and an opportunity for further research. Gene therapy has the potential to directly address the cause of CS by localised targeting of the molecular remodelling that serves to promote thrombosis. 2023
• Prevalence, clinical characteristics and outcomes of heart failure patients with or without isolated or combined mitral and tricuspid regurgitation: An analysis from the ESC-HFA Heart Failure Long-Term Registry
  Adamo, Marianna; Chioncel, O. Dragomir; Benson, Lina; Shahim, Bahira; Crespo-Leiro, Mar Generosa; Anker, Stefan D.; Coats, Andrew J.S.; Filippatos, Gerasimos S.; Lain?ak, Mitja; McDonagh, Theresa A.; Mebazaa, Alexandre; PIEPOLI, MASSIMO Francesco; Rosano, Giuseppe Massimo Claudio; Ruschitzka, Frank T.; Savarese, Gianluigi; Seferovi?, Petar M.; Shahim, Angiza; Popescu, Bogdan Alexandru; Iung, Bernard; Volterrani, Maurizio; Maggioni, Aldo Pietro; Metra, Marco; Lund, Lars H.
  European Journal of Heart Failure (Vol. 25/7) – 2023
  Aim: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum. Methods and results: The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.600.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.410.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.360.49), and combined MR/TR (OR 0.59; 95% 0.500.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.612.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR. Conclusion: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome. 2023 European Society of Cardiology.
• Acute heart failure and valvular heart disease: A scientific statement of the Heart Failure Association, the Association for Acute CardioVascular Care and the European Association of Percutaneous Cardiovascular Interventions of the European Society of
  Chioncel, O. Dragomir; Adamo, Marianna; Nikolaou, Maria Stella; Parissis, John T.; Mebazaa, Alexandre; Yilmaz, Mehmet Birhan; Hassager, Christian; Moura, Brenda; Bauersachs, Johann; Harjola, Veli Pekka; Antohi, Elena Laura; Ben-Gal, Tuvia; Collins, Sean P.; Iliescu, Vlad Anton; Abdelhamid, Magdy A.; ?elutkiene, Jelena; Adamopoulos, Stamatis N.; Lund, Lars H.; Cicoira, Mariantonietta; Masip, Josep; Skouri, Hadi N.; Gustafsson, Finn; Rakisheva, Amina G.; Ahrens, Ingo G.; Mortara, Andrea; Janowska, Ewa A.; Almaghraby, Abdallah Mostafa; Damman, Kevin; MirAndreu, car; Huber, Kurt H.; Risti?, Arsen D.; Hill, Loreena Michelle; Mullens, Wilfried; Chieffo, Alaide; Bartek, Jozef J.; Paolisso, Pasquale; Bay-Gen, Antoni; Anker, Stefan D.; Price, Susanna; Filippatos, Gerasimos S.; Ruschitzka, Frank T.; Seferovi?, Petar M.; Vidal-Perez, Rafael Carlos; Vahanian, Alec S.; Metra, Marco; McDonagh, Theresa A.; Barbato, Emanuele; Coats, Andrew J.S.; Rosano, Giuseppe Massimo Claudio
  European Journal of Heart Failure (Vol. 25/7) – 2023
  Acute heart failure (AHF) represents a broad spectrum of disease states, resulting from the interaction between an acute precipitant and a patient's underlying cardiac substrate and comorbidities. Valvular heart disease (VHD) is frequently associated with AHF. AHF may result from several precipitants that add an acute haemodynamic stress superimposed on a chronic valvular lesion or may occur as a consequence of a new significant valvular lesion. Regardless of the mechanism, clinical presentation may vary from acute decompensated heart failure to cardiogenic shock. Assessing the severity of VHD as well as the correlation between VHD severity and symptoms may be difficult in patients with AHF because of the rapid variation in loading conditions, concomitant destabilization of the associated comorbidities and the presence of combined valvular lesions. Evidence-based interventions targeting VHD in settings of AHF have yet to be identified, as patients with severe VHD are often excluded from randomized trials in AHF, so results from these trials do not generalize to those with VHD. Furthermore, there are not rigorously conducted randomized controlled trials in the setting of VHD and AHF, most of the data coming from observational studies. Thus, distinct to chronic settings, current guidelines are very elusive when patients with severe VHD present with AHF, and a clear-cut strategy could not be yet defined. Given the paucity of evidence in this subset of AHF patients, the aim of this scientific statement is to describe the epidemiology, pathophysiology, and overall treatment approach for patients with VHD who present with AHF. 2023 European Society of Cardiology.
• Near-Infrared Autofluorescence (NIRAF) in Atherosclerotic Plaque Dissociates from Intraplaque Hemorrhage and Bilirubin
  Chen, Weiyu; Nadel, James; Tumanov, Sergey; Stocker, Roland
  International Journal of Molecular Sciences (Vol. 24/13) – 2023
  Near-infrared autofluorescence (NIRAF) in unstable atherosclerotic plaque has been suggested as a novel imaging technology for high-risk atherosclerosis. Intraplaque hemorrhage (IPH) and bilirubin, derived from the subsequent degradation of heme, have been proposed as the source of NIRAF, although their roles and the underlying mechanism responsible for NIRAF remain unclear. To test the proposed role of bilirubin as the source of NIRAF in high-risk atherosclerosis, Biliverdin reductase a gene and apolipoprotein E gene double-knockout (Bvra?/?Apoe?/?) mice were subjected to the Western diet and tandem stenosis (TS) surgery, as a model of both bilirubin deficiency and plaque instability. Human coronary arteries containing atherosclerotic plaques were obtained from heart transplant recipients. The NIRAF was determined by in vivo fluorescence emission computed tomography, and ex vivo infrared imaging. The cholesterol content was quantified by HPLC with UV detection. In Bvra+/+Apoe?/? TS mice, the NIRAF intensity was significantly higher in unstable plaque than in stable plaque, yet the NIRAF in unstable plaque was undistinguishable in Bvra+/+Apoe?/? and littermate Bvra?/?Apoe?/? TS mice. Moreover, the unstable plaque in TS mice exhibited a lower NIRAF compared with highly cellular plaque that lacked most of the features of unstable plaque. In human coronary arteries, the NIRAF associated with cholesterol-rich, calcified lesions, rather than just cholesterol-rich lesions. The NIRAF in atherosclerotic plaque can be dissociated from IPH and bilirubin, such that the compositional meaning of an elevated NIRAF remains obscure. 2023 by the authors.