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    2020 | Genetic Testing for Diagnosis of Hypertrophic Cardiomyopathy Mimics: Yield and Clinical Significance

     150 150 sabrina.agostini@uhn.ca

    Authors: Sara Hoss, Manhal Habib, Josh Silver, Melanie Care, Raymond H. Chan, Kate Hanneman, Chantal F. Morel, Robert M. Iwanochko, Michael H. Gollob, Harry Rakowski, Arnon Adler 

    Short Description: Genetic testing is helpful for diagnosis of hypertrophic cardiomyopathy (HCM) mimics. Little data are available regarding the yield of such testing and its clinical impact. The HCM genetic database at our center was used for identification of patients who underwent HCM-directed genetic testing including at least 1 gene associated with an HCM mimic (GLA, TTR, PRKAG2, LAMP2, PTPN11, RAF1, and DES). Charts were retrospectively reviewed and genetic and clinical data extracted.

    Interest: Fabry Disease, Genetic Testing, Genetics, Hypertrophic Cardiomyopathy

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    2020| Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): Study Design and Methodology for an International, Adaptive Bayesian Randomized Controlled Trial

     150 150 fraser.amos@uhn.ca

    Authors: Brett L Houston, Patrick R Lawler, Ewan C Goligher, Michael E Farkouh, Charlotte Bradbury, Marc Carrier, Vlad Dzavik, Dean A Fergusson, Robert A Fowler, Jean-Phillippe Galanaud, Peter L Gross, Emily G McDonald, Mansoor Husain, Susan R Kahn, Anand Kumar, John Marshall, Srinivas Murthy, Arthur S Slutsky, Alexis F Turgeon, Scott M Berry, Robert S Rosenson, Jorge Escobedo, Jose C Nicolau, Lindsay Bond, Bridget-Anne Kirwan, Sophie de Brouwer, Ryan Zarychanski

    Short Description: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care.

    Interest: Anti-thrombotic therapy, COVID-19, cardiac injury, venous thromboembolism, myocardial infarction, ischemic stroke

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    2021 | Development and Validation of a Clinical Predictive Model for Identifying Hypertrophic Cardiomyopathy Patients at Risk for Atrial Fibrillation: The HCM-AF Score

     150 150 sabrina.agostini@uhn.ca

    Authors: Richard T. Carrick, Martin S. Maron, Arnon Adler, Benjamin Wessler, Sara Hoss, Raymond H. Chan, Aadhavi Sridharan, Dou Huang, Craig Cooper, Jennifer Drummond, Harry Rakowski, Barry J. Maron, Ethan J. Rowin

    Short Description: Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), associated with impaired quality of life, risk for embolic stroke, and unpredictable onset. We sought to create a predictive model to identify risk for AF development in HCM.

    Interest: Atrial Fibrillation, Hypertrophic Cardiomyopathy

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    2021 | Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy: Equivalent Detection by Magnetic Resonance Imaging and Contrast Echocardiography

     150 150 sabrina.agostini@uhn.ca

    Authors: Deacon Z.J. Lee, Raymond H. Chan, Mahdi Montazeri, Sara Hoss, Arnon Adler, Elsie T. Nguyen, Harry Rakowski 

    Short Description: Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Left Ventricular Apical Aneurysm, Medical Imaging

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    2021 | Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

     150 150 sabrina.agostini@uhn.ca

    Authors: Manhal Habib, Arnon Adler, Kimia Fardfini, Sara Hoss, Kate Hanneman, Ethan J. Rowin, Martin S. Maron, Barry J. Maron, Harry Rakowski, Raymond Chan

    Short Description: Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM. This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Medical Imaging

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    2021 | Recurrent Myocarditis Induced by Immune-Checkpoint Inhibitor Treatment Is Accompanied by Persistent Inflammatory Markers Despite Immunosuppressive Treatment

     150 150 admpmccbiobank

    Authors: Nazanian Aghel, Dakota Gustafson, Ashley Di Meo, Milena Music, Ioannis Prassas, Michael A. Seidman, Aaron R. Hansen, Paaladinesh Thavendiranathan, Eleftherios P. Diamandis, Diego Delgado, Jason E. Fish

    Short Description: A case report of recurrent myocarditis in a patient previously treated with a programmed death ligand I inhibitor, an immune checkpoint inhibitor that blocks the binding of PD-L1 to programmed cell death protein 1 and CD80.

    Interest: Cancer, Cardio-Oncology, Cardiology, Heart disease, Myocarditis

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    2022 | Cardiovascular Signatures of COVID-19 Predict Mortality and Identify Barrier Stabilizing Therapies

     150 150 admpmccbiobank

    Authors: Dakota Gustafson, Michelle Ngai, Ruilin Wu, Huayun Hou, Alice Schoffel, Clara Erice, Serena Mandla, Filio Billia, Michael D. Wilson, Milica Radisic, Eddy Fan, Uriel Trahtemberg, Andrew Baker, Chris McIntosh, Chun-Po S. Fan, Claudia C. dos Santons, Kevin C. Kain, Kate Hanneman, Paaladinesh Thavendiranathan, Jason E. Fish, Kathryn L. Howe

    Short Description: Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe COVID-19, indicating that the vasculature is affected during the acute stages of SARS-CoV-2 infection. Results from this study indicated that multiple inflammatory and EC activation biomarkers were associated with mortality in COVID-19 patients and in severity-matched SARS-CoV-2-negative patients, while dysregulation of specific microRNAs at presentation was specific for poor COVID-19-related outcomes and revealed disease-relevant pathways.

    Interest: COVID-19, Respiratory Disease, Stroke and Cardiovascular, Vascular

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    2022 | Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Deacon Z.J. Lee, Mahdi Montazeri, Roxana Bataiousu, , Sara Hoss, Arnon Adler, Elsie T. Nguyen, Harry Rakowski, Raymond H. Chan

    Short Description: Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype. The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms.

    Interest: Cardiac Imaging, Hypertrophic Cardiomyopathy, Medical Imaging

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    2022 | Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock

     150 150 sabrina.agostini@uhn.ca

    Authors: Fernando L. Scolari,  Sagi Abelson, Darshan H. Brahmbhatt, Sagi Abelson, Jessie J.F. Medeiros, Chun-Po S. Fan, Nicole L. Fung, Vesna Mihajlovic,  Markus S. Anker, Madison Otsuki, Patrick R. Lawler, Heather J. Ross, Adriana C. Luk, Stefan Anker, John E. Dick, Filio Billia

    Short Description: Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre.

    Interest: Cardiogenic Shock, Genomics, Heart Disease, Heart Failure, Molecular Biology

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    2022 | Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients

     150 150 sabrina.agostini@uhn.ca
    FIGURE. Survival analysis in orthotopic heart transplantation recipients according to the presence of clonal hematopoiesis gene mutations. CH, clonal hematopoiesis

     

    Authors: Fernando L. Scolari; Darshan H. Brahmbhatt; Sagi Abelson; Jessie J. F. Medeiros; Markus S Anker; Nicole L. Fung; Madison Otsuki; Oscar Calvillo-Argüelles; Patrick R. Lawler; Heather J. Ross; Adriana C. Luk; Stefan Anker; John E. Dick; Filio Billia

    Short Description: Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival.

    Interest: Genomics, Heart Transplantation, Cardiology, Molecular Biology

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    2022 | Combined Cardiac Fluorodeoxyglucose-Positron Emission Tomography/Magnetic Resonance Imaging Assessment of Myocardial Injury in Patients Who Recently Recovered From COVID-19

     150 150 admpmccbiobank

    Authors: Kate Hanneman, Christian Houbois, Alice Schoffel, Dakota Gustafson, Robert M. Iwanochko, Bernd J. Wintersperger, Rosanna Chan, Jason E. Fish, Kathryn L. Howe, Paaladinesh Thavendiranathan

    Short Description: There is limited understanding of changes with myocardial metabolism in patients who have recovered from acute COVID-19. In this paper, we examine myocardial metabolic changes early after recovery from COVID-19 using fluorodeoxyglucose-positron emission tomography (PET) and associate these changes to abnormalities in cardiac magnetic resonance imaging (MRI)-based function and tissue characterization measures and inflammatory blood markers.

    Interest: Cardiac Imaging, COVID-19, Medical Imaging, Myocardial Injury, Respiratory Disease

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    2022 | Importance of newer cardiac magnetic resonance–based risk markers for sudden death prevention in hypertrophic cardiomyopathy: An international multicenter study

     150 150 sabrina.agostini@uhn.ca

     

    Authors: Ethan J. Rowin, Martin S. Maron, Arnon Adler, Alfred J. Albano, Armanda M. Varnava, Danna Spears, Dana Marsy, Stephen B. Heitner, Emilie Cohen, Kevin M.W. Leong, Stephen L. Winters, Matthew W. Martinez, Benjamin C. Koethe, Harry Rakowski, Barry J. Maron

    Short Description: The sudden death (SD) risk stratification algorithm in hypertrophic cardiomyopathy (HCM) has evolved, underscored recently by novel cardiac magnetic resonance (CMR)–based risk markers (left ventricular apical aneurysm, extensive late gadolinium enhancement, and end-stage disease with systolic dysfunction) incorporated into the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) HCM guidelines. The purpose of this study was to assess the specific impact of newer, predominantly CMR-based risk markers in a large multicenter HCM population that underwent primary prevention implantable cardioverter-defibrillator (ICD) implants.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Medical Imaging, Risk Stratification, Sudden Death

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    2022 | Temporal Changes in Cardiac Morphology and Its Relationship with Clinical Characteristics and Outcomes in Patients with Hypertrophic Cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Manhal Habib, Arnon Adler, Sara Hoss, Kate Hanneman, Olga Katz, Hadeel Halloun Habib, Kimia Fardfini, Harry Rakowski, Raymond H. Chan

    Short Description:  In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8 ± 2.1 years.

    Interest: Hypertrophic Cardiomyopathy

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    2023 | Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Rafik Tadros, Sean L. Zheng,  Christopher Grace, Paloma Jordà, Catherine Francis, Sean J. Jurgens, Kate L. Thomson,  Andrew R. Harper, Elizabeth Ormondroyd, Dominique M. West, Xiao Xu, Pantazis Theotokis, Rachel J. Buchan, Kathryn A. McGurk, Francesco Mazzarotto, Beatrice Boschi, Elisabetta Pelo, Michael Lee, Michela Noseda, Amanda Varnava, Alexa Mc Vermeer, Roddy Walsh, Ahmad S. Amin, Marjon A van Slegtenhorst, Nicole Roslin, Lisa J. Strug, Erika Salvi, Chiara Lanzani, Antonio de Marvao, Hypergenes InterOmics Collaborators, Jason D. Roberts, Maxime Tremblay-Gravel, Genevieve Giraldeau, Julia Cadrin-Tourigny, Philippe L’Allier, Patrick Garceau, Mario Talajic, Yigal Pinto, Harry Rakowski, Antonis Pantazis, John Baksi, Brian P. Halliday, Sanjay K. Prasad, Paul Jr Barton, Declan P. O’Regan, Stuart A. Cook, Rudolf A. de Boer, Imke Christiaans, Michelle Michels, Christopher Kramer, Carolyn Y. Ho, Stefan Neubauer, HCMR Investigators, Paul M. Matthews, Arthur A. Wilde, Jean-Claude Tardif, Iacopo Olivotto, Arnon Adler, Anuj Goel, James S. Ware, Connie R. Bezzina, Hugh Watkins

    Short Description: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) as sociated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants cause HCM. Mendelian randomization analyses support a causal role of increased LV contractility in both obstructive and non-obstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, the findings significantly increase our understanding of the genetic basis and molecular mechanisms of HCM, with potential implications for disease management.

    Interest: Cardiac Magnetic Resonance Imaging, Cardiac Imaging, Genetics, Genetic Testing, Hypertrophic Cardiomyopathy

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    2023| Myocardial Inflammation at FDG PET/MRI and Clinical Outcomes in Symptomatic and Asymptomatic Participants after COVID-19 Vaccination

     150 150 fraser.amos@uhn.ca

    Authors: Constantin Arndt Marschner, Paaladinesh Thavendiranathan, Dakota Gustafson, Kathryn L. Howe, Jason E. Fish, Robert M. Iwanochko, Rachel M. Wald, Husam Abdel-Qadir, Slava Epelman, Angela M. Cheung, Rachel Hong, Kate Hanneman

    Short Description: As of August 2022, more than 5.3 billion people worldwide have received at least one dose of a COVID-19 vaccine (1). Several adverse events have been reported, including myocarditis and pericarditis, following the administration of mRNA-based COVID-19 vaccines (2,3). The overall incidence of myopericarditis following COVID-19 vaccines is low, estimated at 18 per 1 million vaccine doses, with the highest risk in adolescent and young adult males (4). However, many more patients experience cardiac symptoms after vaccination, including shortness of breath, palpitations, and chest pain, yet do not meet diagnostic criteria for acute myopericarditis (5). The cause of these symptoms and the natural history of these patients remains unknown.

    Cardiac MRI plays an important role in the assessment of myocardial tissue changes (6). Cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET provides complementary physiologic information, allowing for the assessment of changes in myocardial metabolism (7,8). Several recent case series have reported cardiac MRI findings in patients with myocarditis following COVID-19 vaccination (9,10). However, there are limited data on patients who present with new-onset cardiac symptoms following COVID-19 vaccination but do not meet diagnostic criteria for myopericarditis (5). There are also limited data evaluating potential subclinical myocardial tissue changes in asymptomatic individuals after vaccination.

    The purpose of this study was to identify cardiac sequelae of COVID-19 vaccination and relate patient-reported cardiac symptoms to myocardial tissue changes identified with cardiac FDG PET/MRI, circulating biomarkers of cardiac injury and systemic inflammation, health-related quality of life, and adverse cardiac events at 2-month follow-up. Our goal was to inform guidelines for cardiac investigations after COVID-19 vaccination and the potential need for longer-term follow-up.

    Interest: Myocardial Inflammation, COVID-19, Vaccination, Molecular Imaging, MR Imaging

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    2024 | Clonal haematopoiesis is associated with major adverse cardiovascular events in patients with hypertrophic cardiomyopathy

     150 150 fraser.amos@uhn.ca

    Authors: Fernando L. Scolari, Darshan Brahmbhatt, Sagi Abelson, Deacon Lee, Raymond H. Kim, Ali Pedarzadeh, Ali Sakhnini, Arnon Adler, Raymond H. Chan, John E. Dick, Harry Rakowski, and Filio Billia

    Short Description: Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder, affecting 1 in 500 individuals. However, germline pathogenic or likely pathogenic (P/LP) genetic variants, such as MYH7 and MYBPC3 genes, are identified in only 25–40% of patients. A wide heterogeneity and distinct morphologies of left ventricular (LV) hypertrophy are described, even amongst family members carrying similar genetic variants. Interestingly, interstitial fibrosis is detected in 40–70% of patients and is associated with sudden cardiac death (SCD). Although HCM can be well tolerated, a subset of patients may require advanced treatments such as orthotopic heart transplant (OHT) and LV assist devices. The underlying mechanisms involved in the heterogeneous clinical presentation of HCM patients are not well understood. Clonal haematopoiesis (CH) has emerged as a new risk factor for the development of atherosclerosis, heart failure and cardiogenic shock and is associated with worse outcomes.

    Interest: Cardiac magnetic resonance imaging, Clonal haematopoiesis, Fibrosis, Hypertrophic cardiomyopathy, Inflammation

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    2025 | Heart Failure Decompensation with Cardiogenic Shock Exhibits Distinct Sequential Inflammatory Profiles

     150 150 fraser.amos@uhn.ca

    Authors: Darshan H. Brahmbhatt, Fernando Luis Scolari, Nicole L. Fung, Madison Otsuki, Patrick R. Lawler, Heather J. Ross, Uros Kuzmanov, Anthony O. Gramolini, Adriana C. Luk, Filio Billia

    Short Description: Cardiogenic shock (CS) is the most severe form of acute heart failure (HF) characterized by severely reduced cardiac output and inadequate end-organ perfusion leading to tissue hypoxia. Patients with CS suffer significant morbidity and mortality1 with in-hospital mortality reaching up to 50%.2 The pathophysiological underpinnings of CS remain to be fully elucidated, but inflammation is thought to play a key role.3 One of the several potential mechanisms for worsening of the shock state has been proposed to occur through the release of inducible nitric oxide and its mediators, resulting in inappropriate vasodilatation.4 Additionally, the development of systemic inflammatory response syndrome (SIRS) is seen in up to a third of patients at presentation and portends a more severe clinical syndrome associated with worse outcomes.5

    The inflammatory profile associated with CS is now being studied in greater detail. However, the majority of studies have focused on CS following acute myocardial infarction (AMI-CS). In AMI-CS, an acute ischaemic insult leads to an immediate drop in cardiac output, which may then be compounded by the ischaemia–reperfusion injury associated with acute revascularization.6 In contrast to this, CS caused by acute decompensated HF (ADHF-CS) often has a heterogeneous trajectory, even before presentation. This realization is important in that these patients may have a different clinical profile and outcomes after discharge.7 The HF state has its own heightened inflammatory state, which is also known to affect outcomes.8 Thus far, the inflammatory profile of patients with ADHF-CS has not been fully characterized nor has the transition from a clinically stable, outpatient-managed HF state to ADHF-CS, and it is unclear if there are changes in the inflammatory profile that occur during this clinical deterioration.

    This retrospective, cross-sectional study was designed to investigate the profile and prognostic significance of circulating cytokines and cellular inflammatory profiles in patients with ADHF-CS admitted to a cardiac intensive care unit (CICU) and to define the association between circulating cytokines in outpatients with HF and those admitted with CS.

    Interest: cardiogenic shock, heart failure, cytokines, mechanical circulatory support, biomarkers, chemokines

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    2025 | Multiomic Landscape of Extracellular Vesicles in Human Carotid Atherosclerotic Plaque Reveals Endothelial Communication Networks

     150 150 fraser.amos@uhn.ca

    Authors: Sneha Raju, Mandy E. Turner, Christian Cao, Majed Abdul-Samad, Neil Punwasi, Mark C. Blaser, Rachel M.E. Cahalane, Steven R. Botts, Kamalben Prajapati, Sarvatit Patel, Ruilin Wu, Dakota Gustafson, Natalie J. Galant, Lindsey Fiddes, Melody Chemaly, Ulf Hedin, Ljubica Matic, Michael A. Seidman, Vallijah Subasri, Sasha A. Singh, Elena Aikawa, Jason E. Fish, and Kathryn L. Howe

    Short Description: Carotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque.

    Our findings indicate that EVs may drive dynamic changes in plaques through EV–vascular cell communication and effector functions that typify vulnerability to rupture, precipitating symptomatic disease. The discovery of endothelial-directed angiogenic processes mediated by EVs creates new therapeutic avenues for atherosclerosis.

    Interest: Arteriosclerosis, Thrombosis, and Vascular Biology

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    2025 | Pretreatment Circulating Vascular Biomarkers Predict Cancer Therapy-Related Cardiac Dysfunction During HER2+ Breast Cancer Treatment

     150 150 fraser.amos@uhn.ca

    Authors: Dakota Gustafson, Priya Mistry, Crizza Ching, Inbar Nardi-Agmon, Christopher Yu, Chun-Po Steve Fan, Christian Houbois, Eitan Amir, Thomas Marwick, Husam Abdel-Qadir, Chris McIntosh, Paaladinesh Thavendiranathan, Jason E Fish

    Short Description:Blood biomarkers to predict cancer therapy-related cardiac dysfunction (CTRCD) risk remain limited. The aim of this study was to identify circulating biomarkers associated with CTRCD risk in HER2+ breast cancer patients. Pretreatment endothelial-centric and inflammatory biomarkers outperformed both clinical and CMR measures in predicting CTRCD during chemotherapy.

    Interest: angiopoeitin-2, biomarkers; breast cancer; cancer therapy–related cardiac dysfunction; cardio-oncology; endothelium; inflammation; machine learning; microRNA; myeloperoxidase; vascular

    Click Here to Read the Full Publication

    2026| Blood-Based Epigenetic Instability Linked to Human Aging and Disease

     150 150 fraser.amos@uhn.ca

    Authors: Salman Basrai, Ido Nofech-Mozes, Rajesh Detroja, Fernando L. Scolari, Mehran Bakhtiari, Andrea Arruda, Tracy Murphy, Scott V. Bratman, Steven M. Chan, Mark D. Minden, Jae Sook Ahn, Dennis D. H. Kim, Robert Kridel, Filio Billia, Sagi Abelson

    Short Description: The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG loci exhibiting highly consistent methylation profiles in the blood of young, healthy individuals. We assess alterations at these epigenetically stable loci in 8,886 individuals across 29 diverse cohorts, including those with hematological cancers (n = 3159), cardiovascular complications (n = 2788), and healthy controls (n = 2939). Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden dynamics and mutation frequency throughout leukemia treatment. In non-cancer cohorts, we observe that methylation levels at epigenetically stable loci become increasingly variable with age, a shift linked to higher cardiovascular disease risk and lower survival rates. This study highlights DNA methylation instability as a blood-based biomarker for both hematological cancer and cardiovascular disease and uncovers a mechanistic link between methylation dynamics and the expansion of maladaptive hematopoietic clones.

    Interest: Epigenetics, DNA Methylation, Cardiogenic Shock, Transcription Factors

    Click Here to Read the Full Publication

    By Interest

    • All
    • Atrial Fibrillation
    • Biomarkers
    • COVID-19
    • CTRCD
    • Cancer
    • Cancer Therapy–Related Cardiac Dysfunction
    • Cardiac Imaging
    • Cardiac Magnetic Resonance Imaging
    • Cardio-Oncology
    • Cardiogenic Shock
    • Cardiology
    • Cardiomyopathy
    • Carotid
    • Clonal Hematopoiesis
    • Echocardiography
    • Fabry Disease
    • Genetic Testing
    • Genetics
    • Genomics
    • Heart Disease
    • Heart Failure
    • Heart Transplantation
    • Hypertrophic Cardiomyopathy
    • Left Ventricular Apical Aneurysm
    • Left Ventricular Assist Devices
    • Mechanical Circulatory Support
    • Medical Imaging
    • Molecular Biology
    • Multiomic
    • Myocardial Injury
    • Myocarditis
    • Plaque
    • Publications
    • Respiratory Disease
    • Risk Stratification
    • Stroke and Cardiovascular
    • Sudden Death
    • Transplantation
    • Vascular
    • Vascular Surgery

    2020 | Genetic Testing for Diagnosis of Hypertrophic Cardiomyopathy Mimics: Yield and Clinical Significance

     150 150 sabrina.agostini@uhn.ca

    Authors: Sara Hoss, Manhal Habib, Josh Silver, Melanie Care, Raymond H. Chan, Kate Hanneman, Chantal F. Morel, Robert M. Iwanochko, Michael H. Gollob, Harry Rakowski, Arnon Adler 

    Short Description: Genetic testing is helpful for diagnosis of hypertrophic cardiomyopathy (HCM) mimics. Little data are available regarding the yield of such testing and its clinical impact. The HCM genetic database at our center was used for identification of patients who underwent HCM-directed genetic testing including at least 1 gene associated with an HCM mimic (GLA, TTR, PRKAG2, LAMP2, PTPN11, RAF1, and DES). Charts were retrospectively reviewed and genetic and clinical data extracted.

    Interest: Fabry Disease, Genetic Testing, Genetics, Hypertrophic Cardiomyopathy

    Click Here to Read the Full Publication

    2020| Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC): Study Design and Methodology for an International, Adaptive Bayesian Randomized Controlled Trial

     150 150 fraser.amos@uhn.ca

    Authors: Brett L Houston, Patrick R Lawler, Ewan C Goligher, Michael E Farkouh, Charlotte Bradbury, Marc Carrier, Vlad Dzavik, Dean A Fergusson, Robert A Fowler, Jean-Phillippe Galanaud, Peter L Gross, Emily G McDonald, Mansoor Husain, Susan R Kahn, Anand Kumar, John Marshall, Srinivas Murthy, Arthur S Slutsky, Alexis F Turgeon, Scott M Berry, Robert S Rosenson, Jorge Escobedo, Jose C Nicolau, Lindsay Bond, Bridget-Anne Kirwan, Sophie de Brouwer, Ryan Zarychanski

    Short Description: Mortality from COVID-19 is high among hospitalized patients and effective therapeutics are lacking. Hypercoagulability, thrombosis and hyperinflammation occur in COVID-19 and may contribute to severe complications. Therapeutic anticoagulation may improve clinical outcomes through anti-thrombotic, anti-inflammatory and anti-viral mechanisms. Our primary objective is to evaluate whether therapeutic-dose anticoagulation with low-molecular-weight heparin or unfractionated heparin prevents mechanical ventilation and/or death in patients hospitalized with COVID-19 compared to usual care.

    Interest: Anti-thrombotic therapy, COVID-19, cardiac injury, venous thromboembolism, myocardial infarction, ischemic stroke

    Click Here to Read the Full Publication

    2021 | Development and Validation of a Clinical Predictive Model for Identifying Hypertrophic Cardiomyopathy Patients at Risk for Atrial Fibrillation: The HCM-AF Score

     150 150 sabrina.agostini@uhn.ca

    Authors: Richard T. Carrick, Martin S. Maron, Arnon Adler, Benjamin Wessler, Sara Hoss, Raymond H. Chan, Aadhavi Sridharan, Dou Huang, Craig Cooper, Jennifer Drummond, Harry Rakowski, Barry J. Maron, Ethan J. Rowin

    Short Description: Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), associated with impaired quality of life, risk for embolic stroke, and unpredictable onset. We sought to create a predictive model to identify risk for AF development in HCM.

    Interest: Atrial Fibrillation, Hypertrophic Cardiomyopathy

    Click Here to Read the Full Publication

    2021 | Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy: Equivalent Detection by Magnetic Resonance Imaging and Contrast Echocardiography

     150 150 sabrina.agostini@uhn.ca

    Authors: Deacon Z.J. Lee, Raymond H. Chan, Mahdi Montazeri, Sara Hoss, Arnon Adler, Elsie T. Nguyen, Harry Rakowski 

    Short Description: Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Left Ventricular Apical Aneurysm, Medical Imaging

    Click Here to Read the Full Publication

    2021 | Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

     150 150 sabrina.agostini@uhn.ca

    Authors: Manhal Habib, Arnon Adler, Kimia Fardfini, Sara Hoss, Kate Hanneman, Ethan J. Rowin, Martin S. Maron, Barry J. Maron, Harry Rakowski, Raymond Chan

    Short Description: Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM. This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Medical Imaging

    Click Here to Read the Full Publication

    2021 | Recurrent Myocarditis Induced by Immune-Checkpoint Inhibitor Treatment Is Accompanied by Persistent Inflammatory Markers Despite Immunosuppressive Treatment

     150 150 admpmccbiobank

    Authors: Nazanian Aghel, Dakota Gustafson, Ashley Di Meo, Milena Music, Ioannis Prassas, Michael A. Seidman, Aaron R. Hansen, Paaladinesh Thavendiranathan, Eleftherios P. Diamandis, Diego Delgado, Jason E. Fish

    Short Description: A case report of recurrent myocarditis in a patient previously treated with a programmed death ligand I inhibitor, an immune checkpoint inhibitor that blocks the binding of PD-L1 to programmed cell death protein 1 and CD80.

    Interest: Cancer, Cardio-Oncology, Cardiology, Heart disease, Myocarditis

    Click Here to Read the Full Publication

    2022 | Cardiovascular Signatures of COVID-19 Predict Mortality and Identify Barrier Stabilizing Therapies

     150 150 admpmccbiobank

    Authors: Dakota Gustafson, Michelle Ngai, Ruilin Wu, Huayun Hou, Alice Schoffel, Clara Erice, Serena Mandla, Filio Billia, Michael D. Wilson, Milica Radisic, Eddy Fan, Uriel Trahtemberg, Andrew Baker, Chris McIntosh, Chun-Po S. Fan, Claudia C. dos Santons, Kevin C. Kain, Kate Hanneman, Paaladinesh Thavendiranathan, Jason E. Fish, Kathryn L. Howe

    Short Description: Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe COVID-19, indicating that the vasculature is affected during the acute stages of SARS-CoV-2 infection. Results from this study indicated that multiple inflammatory and EC activation biomarkers were associated with mortality in COVID-19 patients and in severity-matched SARS-CoV-2-negative patients, while dysregulation of specific microRNAs at presentation was specific for poor COVID-19-related outcomes and revealed disease-relevant pathways.

    Interest: COVID-19, Respiratory Disease, Stroke and Cardiovascular, Vascular

    Click Here to Read the Full Publication

    2022 | Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Deacon Z.J. Lee, Mahdi Montazeri, Roxana Bataiousu, , Sara Hoss, Arnon Adler, Elsie T. Nguyen, Harry Rakowski, Raymond H. Chan

    Short Description: Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype. The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms.

    Interest: Cardiac Imaging, Hypertrophic Cardiomyopathy, Medical Imaging

    Click Here to Read the Full Publication

    2022 | Clonal haematopoiesis is associated with higher mortality in patients with cardiogenic shock

     150 150 sabrina.agostini@uhn.ca

    Authors: Fernando L. Scolari,  Sagi Abelson, Darshan H. Brahmbhatt, Sagi Abelson, Jessie J.F. Medeiros, Chun-Po S. Fan, Nicole L. Fung, Vesna Mihajlovic,  Markus S. Anker, Madison Otsuki, Patrick R. Lawler, Heather J. Ross, Adriana C. Luk, Stefan Anker, John E. Dick, Filio Billia

    Short Description: Cardiogenic shock (CS) with variable systemic inflammation may be responsible for patient heterogeneity and the exceedingly high mortality rate. Cardiovascular events have been associated with clonal haematopoiesis (CH) where specific gene mutations in haematopoietic stem cells lead to clonal expansion and the development of inflammation. This study aims to assess the prevalence of CH and its association with survival in a population of CS patients in a quaternary centre.

    Interest: Cardiogenic Shock, Genomics, Heart Disease, Heart Failure, Molecular Biology

    Click Here to Read the Full Publication

    2022 | Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients

     150 150 sabrina.agostini@uhn.ca
    FIGURE. Survival analysis in orthotopic heart transplantation recipients according to the presence of clonal hematopoiesis gene mutations. CH, clonal hematopoiesis

     

    Authors: Fernando L. Scolari; Darshan H. Brahmbhatt; Sagi Abelson; Jessie J. F. Medeiros; Markus S Anker; Nicole L. Fung; Madison Otsuki; Oscar Calvillo-Argüelles; Patrick R. Lawler; Heather J. Ross; Adriana C. Luk; Stefan Anker; John E. Dick; Filio Billia

    Short Description: Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival.

    Interest: Genomics, Heart Transplantation, Cardiology, Molecular Biology

    Click Here to Read the Full Publication

    2022 | Combined Cardiac Fluorodeoxyglucose-Positron Emission Tomography/Magnetic Resonance Imaging Assessment of Myocardial Injury in Patients Who Recently Recovered From COVID-19

     150 150 admpmccbiobank

    Authors: Kate Hanneman, Christian Houbois, Alice Schoffel, Dakota Gustafson, Robert M. Iwanochko, Bernd J. Wintersperger, Rosanna Chan, Jason E. Fish, Kathryn L. Howe, Paaladinesh Thavendiranathan

    Short Description: There is limited understanding of changes with myocardial metabolism in patients who have recovered from acute COVID-19. In this paper, we examine myocardial metabolic changes early after recovery from COVID-19 using fluorodeoxyglucose-positron emission tomography (PET) and associate these changes to abnormalities in cardiac magnetic resonance imaging (MRI)-based function and tissue characterization measures and inflammatory blood markers.

    Interest: Cardiac Imaging, COVID-19, Medical Imaging, Myocardial Injury, Respiratory Disease

    Click Here to Read the Full Publication

    2022 | Importance of newer cardiac magnetic resonance–based risk markers for sudden death prevention in hypertrophic cardiomyopathy: An international multicenter study

     150 150 sabrina.agostini@uhn.ca

     

    Authors: Ethan J. Rowin, Martin S. Maron, Arnon Adler, Alfred J. Albano, Armanda M. Varnava, Danna Spears, Dana Marsy, Stephen B. Heitner, Emilie Cohen, Kevin M.W. Leong, Stephen L. Winters, Matthew W. Martinez, Benjamin C. Koethe, Harry Rakowski, Barry J. Maron

    Short Description: The sudden death (SD) risk stratification algorithm in hypertrophic cardiomyopathy (HCM) has evolved, underscored recently by novel cardiac magnetic resonance (CMR)–based risk markers (left ventricular apical aneurysm, extensive late gadolinium enhancement, and end-stage disease with systolic dysfunction) incorporated into the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) HCM guidelines. The purpose of this study was to assess the specific impact of newer, predominantly CMR-based risk markers in a large multicenter HCM population that underwent primary prevention implantable cardioverter-defibrillator (ICD) implants.

    Interest: Cardiac Imaging, Cardiac Magnetic Resonance Imaging, Hypertrophic Cardiomyopathy, Medical Imaging, Risk Stratification, Sudden Death

    Click Here to Read the Full Publication

    2022 | Temporal Changes in Cardiac Morphology and Its Relationship with Clinical Characteristics and Outcomes in Patients with Hypertrophic Cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Manhal Habib, Arnon Adler, Sara Hoss, Kate Hanneman, Olga Katz, Hadeel Halloun Habib, Kimia Fardfini, Harry Rakowski, Raymond H. Chan

    Short Description:  In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8 ± 2.1 years.

    Interest: Hypertrophic Cardiomyopathy

    Click Here to Read the Full Publication

    2023 | Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy

     150 150 sabrina.agostini@uhn.ca

    Authors: Rafik Tadros, Sean L. Zheng,  Christopher Grace, Paloma Jordà, Catherine Francis, Sean J. Jurgens, Kate L. Thomson,  Andrew R. Harper, Elizabeth Ormondroyd, Dominique M. West, Xiao Xu, Pantazis Theotokis, Rachel J. Buchan, Kathryn A. McGurk, Francesco Mazzarotto, Beatrice Boschi, Elisabetta Pelo, Michael Lee, Michela Noseda, Amanda Varnava, Alexa Mc Vermeer, Roddy Walsh, Ahmad S. Amin, Marjon A van Slegtenhorst, Nicole Roslin, Lisa J. Strug, Erika Salvi, Chiara Lanzani, Antonio de Marvao, Hypergenes InterOmics Collaborators, Jason D. Roberts, Maxime Tremblay-Gravel, Genevieve Giraldeau, Julia Cadrin-Tourigny, Philippe L’Allier, Patrick Garceau, Mario Talajic, Yigal Pinto, Harry Rakowski, Antonis Pantazis, John Baksi, Brian P. Halliday, Sanjay K. Prasad, Paul Jr Barton, Declan P. O’Regan, Stuart A. Cook, Rudolf A. de Boer, Imke Christiaans, Michelle Michels, Christopher Kramer, Carolyn Y. Ho, Stefan Neubauer, HCMR Investigators, Paul M. Matthews, Arthur A. Wilde, Jean-Claude Tardif, Iacopo Olivotto, Arnon Adler, Anuj Goel, James S. Ware, Connie R. Bezzina, Hugh Watkins

    Short Description: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) as sociated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants cause HCM. Mendelian randomization analyses support a causal role of increased LV contractility in both obstructive and non-obstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, the findings significantly increase our understanding of the genetic basis and molecular mechanisms of HCM, with potential implications for disease management.

    Interest: Cardiac Magnetic Resonance Imaging, Cardiac Imaging, Genetics, Genetic Testing, Hypertrophic Cardiomyopathy

    Click Here to Read the Full Publication

    2023| Myocardial Inflammation at FDG PET/MRI and Clinical Outcomes in Symptomatic and Asymptomatic Participants after COVID-19 Vaccination

     150 150 fraser.amos@uhn.ca

    Authors: Constantin Arndt Marschner, Paaladinesh Thavendiranathan, Dakota Gustafson, Kathryn L. Howe, Jason E. Fish, Robert M. Iwanochko, Rachel M. Wald, Husam Abdel-Qadir, Slava Epelman, Angela M. Cheung, Rachel Hong, Kate Hanneman

    Short Description: As of August 2022, more than 5.3 billion people worldwide have received at least one dose of a COVID-19 vaccine (1). Several adverse events have been reported, including myocarditis and pericarditis, following the administration of mRNA-based COVID-19 vaccines (2,3). The overall incidence of myopericarditis following COVID-19 vaccines is low, estimated at 18 per 1 million vaccine doses, with the highest risk in adolescent and young adult males (4). However, many more patients experience cardiac symptoms after vaccination, including shortness of breath, palpitations, and chest pain, yet do not meet diagnostic criteria for acute myopericarditis (5). The cause of these symptoms and the natural history of these patients remains unknown.

    Cardiac MRI plays an important role in the assessment of myocardial tissue changes (6). Cardiac fluorine 18 (18F) fluorodeoxyglucose (FDG) PET provides complementary physiologic information, allowing for the assessment of changes in myocardial metabolism (7,8). Several recent case series have reported cardiac MRI findings in patients with myocarditis following COVID-19 vaccination (9,10). However, there are limited data on patients who present with new-onset cardiac symptoms following COVID-19 vaccination but do not meet diagnostic criteria for myopericarditis (5). There are also limited data evaluating potential subclinical myocardial tissue changes in asymptomatic individuals after vaccination.

    The purpose of this study was to identify cardiac sequelae of COVID-19 vaccination and relate patient-reported cardiac symptoms to myocardial tissue changes identified with cardiac FDG PET/MRI, circulating biomarkers of cardiac injury and systemic inflammation, health-related quality of life, and adverse cardiac events at 2-month follow-up. Our goal was to inform guidelines for cardiac investigations after COVID-19 vaccination and the potential need for longer-term follow-up.

    Interest: Myocardial Inflammation, COVID-19, Vaccination, Molecular Imaging, MR Imaging

    Click Here to Read the Full Publication

    2024 | Clonal haematopoiesis is associated with major adverse cardiovascular events in patients with hypertrophic cardiomyopathy

     150 150 fraser.amos@uhn.ca

    Authors: Fernando L. Scolari, Darshan Brahmbhatt, Sagi Abelson, Deacon Lee, Raymond H. Kim, Ali Pedarzadeh, Ali Sakhnini, Arnon Adler, Raymond H. Chan, John E. Dick, Harry Rakowski, and Filio Billia

    Short Description: Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disorder, affecting 1 in 500 individuals. However, germline pathogenic or likely pathogenic (P/LP) genetic variants, such as MYH7 and MYBPC3 genes, are identified in only 25–40% of patients. A wide heterogeneity and distinct morphologies of left ventricular (LV) hypertrophy are described, even amongst family members carrying similar genetic variants. Interestingly, interstitial fibrosis is detected in 40–70% of patients and is associated with sudden cardiac death (SCD). Although HCM can be well tolerated, a subset of patients may require advanced treatments such as orthotopic heart transplant (OHT) and LV assist devices. The underlying mechanisms involved in the heterogeneous clinical presentation of HCM patients are not well understood. Clonal haematopoiesis (CH) has emerged as a new risk factor for the development of atherosclerosis, heart failure and cardiogenic shock and is associated with worse outcomes.

    Interest: Cardiac magnetic resonance imaging, Clonal haematopoiesis, Fibrosis, Hypertrophic cardiomyopathy, Inflammation

    Click Here to Read the Full Publication

    2025 | Heart Failure Decompensation with Cardiogenic Shock Exhibits Distinct Sequential Inflammatory Profiles

     150 150 fraser.amos@uhn.ca

    Authors: Darshan H. Brahmbhatt, Fernando Luis Scolari, Nicole L. Fung, Madison Otsuki, Patrick R. Lawler, Heather J. Ross, Uros Kuzmanov, Anthony O. Gramolini, Adriana C. Luk, Filio Billia

    Short Description: Cardiogenic shock (CS) is the most severe form of acute heart failure (HF) characterized by severely reduced cardiac output and inadequate end-organ perfusion leading to tissue hypoxia. Patients with CS suffer significant morbidity and mortality1 with in-hospital mortality reaching up to 50%.2 The pathophysiological underpinnings of CS remain to be fully elucidated, but inflammation is thought to play a key role.3 One of the several potential mechanisms for worsening of the shock state has been proposed to occur through the release of inducible nitric oxide and its mediators, resulting in inappropriate vasodilatation.4 Additionally, the development of systemic inflammatory response syndrome (SIRS) is seen in up to a third of patients at presentation and portends a more severe clinical syndrome associated with worse outcomes.5

    The inflammatory profile associated with CS is now being studied in greater detail. However, the majority of studies have focused on CS following acute myocardial infarction (AMI-CS). In AMI-CS, an acute ischaemic insult leads to an immediate drop in cardiac output, which may then be compounded by the ischaemia–reperfusion injury associated with acute revascularization.6 In contrast to this, CS caused by acute decompensated HF (ADHF-CS) often has a heterogeneous trajectory, even before presentation. This realization is important in that these patients may have a different clinical profile and outcomes after discharge.7 The HF state has its own heightened inflammatory state, which is also known to affect outcomes.8 Thus far, the inflammatory profile of patients with ADHF-CS has not been fully characterized nor has the transition from a clinically stable, outpatient-managed HF state to ADHF-CS, and it is unclear if there are changes in the inflammatory profile that occur during this clinical deterioration.

    This retrospective, cross-sectional study was designed to investigate the profile and prognostic significance of circulating cytokines and cellular inflammatory profiles in patients with ADHF-CS admitted to a cardiac intensive care unit (CICU) and to define the association between circulating cytokines in outpatients with HF and those admitted with CS.

    Interest: cardiogenic shock, heart failure, cytokines, mechanical circulatory support, biomarkers, chemokines

    Click Here to Read the Full Publication

    2025 | Multiomic Landscape of Extracellular Vesicles in Human Carotid Atherosclerotic Plaque Reveals Endothelial Communication Networks

     150 150 fraser.amos@uhn.ca

    Authors: Sneha Raju, Mandy E. Turner, Christian Cao, Majed Abdul-Samad, Neil Punwasi, Mark C. Blaser, Rachel M.E. Cahalane, Steven R. Botts, Kamalben Prajapati, Sarvatit Patel, Ruilin Wu, Dakota Gustafson, Natalie J. Galant, Lindsey Fiddes, Melody Chemaly, Ulf Hedin, Ljubica Matic, Michael A. Seidman, Vallijah Subasri, Sasha A. Singh, Elena Aikawa, Jason E. Fish, and Kathryn L. Howe

    Short Description: Carotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque.

    Our findings indicate that EVs may drive dynamic changes in plaques through EV–vascular cell communication and effector functions that typify vulnerability to rupture, precipitating symptomatic disease. The discovery of endothelial-directed angiogenic processes mediated by EVs creates new therapeutic avenues for atherosclerosis.

    Interest: Arteriosclerosis, Thrombosis, and Vascular Biology

    Click Here to Read the Full Publication

    2025 | Pretreatment Circulating Vascular Biomarkers Predict Cancer Therapy-Related Cardiac Dysfunction During HER2+ Breast Cancer Treatment

     150 150 fraser.amos@uhn.ca

    Authors: Dakota Gustafson, Priya Mistry, Crizza Ching, Inbar Nardi-Agmon, Christopher Yu, Chun-Po Steve Fan, Christian Houbois, Eitan Amir, Thomas Marwick, Husam Abdel-Qadir, Chris McIntosh, Paaladinesh Thavendiranathan, Jason E Fish

    Short Description:Blood biomarkers to predict cancer therapy-related cardiac dysfunction (CTRCD) risk remain limited. The aim of this study was to identify circulating biomarkers associated with CTRCD risk in HER2+ breast cancer patients. Pretreatment endothelial-centric and inflammatory biomarkers outperformed both clinical and CMR measures in predicting CTRCD during chemotherapy.

    Interest: angiopoeitin-2, biomarkers; breast cancer; cancer therapy–related cardiac dysfunction; cardio-oncology; endothelium; inflammation; machine learning; microRNA; myeloperoxidase; vascular

    Click Here to Read the Full Publication

    2026| Blood-Based Epigenetic Instability Linked to Human Aging and Disease

     150 150 fraser.amos@uhn.ca

    Authors: Salman Basrai, Ido Nofech-Mozes, Rajesh Detroja, Fernando L. Scolari, Mehran Bakhtiari, Andrea Arruda, Tracy Murphy, Scott V. Bratman, Steven M. Chan, Mark D. Minden, Jae Sook Ahn, Dennis D. H. Kim, Robert Kridel, Filio Billia, Sagi Abelson

    Short Description: The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG loci exhibiting highly consistent methylation profiles in the blood of young, healthy individuals. We assess alterations at these epigenetically stable loci in 8,886 individuals across 29 diverse cohorts, including those with hematological cancers (n = 3159), cardiovascular complications (n = 2788), and healthy controls (n = 2939). Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden dynamics and mutation frequency throughout leukemia treatment. In non-cancer cohorts, we observe that methylation levels at epigenetically stable loci become increasingly variable with age, a shift linked to higher cardiovascular disease risk and lower survival rates. This study highlights DNA methylation instability as a blood-based biomarker for both hematological cancer and cardiovascular disease and uncovers a mechanistic link between methylation dynamics and the expansion of maladaptive hematopoietic clones.

    Interest: Epigenetics, DNA Methylation, Cardiogenic Shock, Transcription Factors

    Click Here to Read the Full Publication

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