Publications

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

 150 150 fraser.amos@uhn.ca
By:
0

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

 150 150 fraser.amos@uhn.ca
By:
0

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

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

 150 150 sabrina.agostini@uhn.ca
By:
0

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

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

 150 150 sabrina.agostini@uhn.ca
By:
0

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
By:
0
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 | Clinical Characteristics and Prognostic Importance of Left Ventricular Apical Aneurysms in Hypertrophic Cardiomyopathy

 150 150 sabrina.agostini@uhn.ca
By:
0

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

 150 150 sabrina.agostini@uhn.ca
By:
0

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

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
By:
0

 

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

 150 150 admpmccbiobank
By:
0

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

 150 150 admpmccbiobank
By:
0

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

  • 1
  • 2
Privacy Preferences

When you visit our website, it may store information through your browser from specific services, usually in the form of cookies. Here you can change your Privacy preferences. It is worth noting that blocking some types of cookies may impact your experience on our website and the services we are able to offer.

Click to enable/disable Google Analytics tracking code.
Click to enable/disable Google Fonts.
Click to enable/disable Google Maps.
Click to enable/disable video embeds.
Our website uses cookies, mainly from 3rd party services. Define your Privacy Preferences and/or agree to our use of cookies.