Article
Cardiac & Cardiovascular Systems
Nadav Willner, Ian G. Burwash, Luc Beauchesne, Vince Chan, Branka Vulesevic, Kathy Ascah, Thais Coutinho, Steve Promislow, Ellamae Stadnick, Kwan L. Chan, Thierry Mesana, David Messika-Zeitoun
Summary: This study evaluated the progression rate of mitral annular calcification (MAC) and the development of calcific mitral valve disease (CMVD). The results showed that a considerable number of MAC patients progressed to severe MAC and frequently developed CMVD. Female patients had higher progression rates. The study emphasizes the importance of a better understanding of the pathophysiology of MAC to develop effective preventive medical therapies.
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
(2022)
Review
Cardiac & Cardiovascular Systems
Jeffrey J. Silbiger
Summary: As life expectancy increases, mitral annular calcification is becoming more prevalent and can lead to valve stenosis, traditional methods for measuring mitral valve area may not be suitable for calcific MS, flow-independent methods should be used to assess the severity of the lesions.
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
(2021)
Review
Cardiac & Cardiovascular Systems
Timothy W. Churchill, Evin Yucel, Sebastien Deferm, Robert A. Levine, Judy Hung, Philippe B. Bertrand
Summary: Mitral annular calcification is associated with adverse clinical outcomes, and its impact on mitral valve dysfunction is underestimated. This review summarizes the epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes an integrative definition and approach to this clinical condition.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Mark C. Blaser, Simon Kraler, Thomas F. Luescher, Elena Aikawa
Summary: Calcific aortic valve disease is expected to almost triple in prevalence over the next 3 decades and currently lacks effective pharmacotherapy to halt its progression. Invasive aortic valve replacement remains the only treatment option, highlighting a substantial gap in care due to limited understanding of disease mechanisms and complex valvular microenvironment. Multiomics approaches, single-cell resolution studies, and systems biology strategies hold promise in shedding new light on valvular disease pathogenesis and identifying potential drug targets.
CIRCULATION RESEARCH
(2021)
Article
Cardiac & Cardiovascular Systems
Giampaolo Morciano, Simone Patergnani, Gaia Pedriali, Paolo Cimaglia, Elisa Mikus, Simone Calvi, Alberto Albertini, Carlotta Giorgi, Gianluca Campo, Roberto Ferrari, Paolo Pinton
Summary: This observational study aims to establish the trend of autophagy in CAVS patients, analyze the involvement of other determinants impacting mitochondrial quality control mechanisms, and explore potential pharmacological interventions. The results show deficiencies in mitochondrial respiration, ATP production, and alterations in biogenesis and mitophagy pathways in the calcified valves, suggesting a rapamycin-based therapeutic strategy to revert pathological phenotypes. Boosting autophagy and mitophagy could potentially counteract cell death and sustain cell functions in the long term.
CARDIOVASCULAR RESEARCH
(2022)
Review
Cardiac & Cardiovascular Systems
Nikolaos Anousakis-Vlachochristou, Dimitra Athanasiadou, Karina M. M. Carneiro, Konstantinos Toutouzas
Summary: This study reviews the alterations of structural native extracellular matrix proteins involved in the development of calcific aortic valve stenosis (CAVS) and highlights its link to deregulated biomechanical function.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Subramanian Dharmarajan, Mei Y. Speer, Kate Pierce, Jake Lally, Elizabeth M. Leaf, Mu-En Lin, Marta Scatena, Cecilia M. Giachelli
Summary: In this study, it was found that aVICs and sinus wall cells give rise to Runx2+ osteochondrogenic cells in diseased mouse aortic valves. Conditional depletion of Runx2 in specific cells led to decreased osteochondrogenic gene expression and improved aortic valve function in a mouse model of CAVD with high prevalence of hemodynamic valve dysfunction. Leaflet hinge and sinus wall calcification were significantly decreased following Runx2 depletion, suggesting a potential causal role in valve dysfunction.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Ezequiel Guzzetti, Jin Kyung Oh, Mylene Shen, Marc R. Dweck, Kian Keong Poh, Amr E. Abbas, Ramy Mando, Gregg S. Pressman, Daniel Brito, Lionel Tastet, Tania Pawade, Mariano Luis Falconi, Diego Perez de Arenaza, William Kong, Edgar Tay, Philippe Pibarot, Jae-Kwan Song, Marie-Annick Clavel
Summary: This study aimed to validate the accuracy of sex-specific thresholds of aortic valve calcification (AVC) in Asians. The results showed that the AVC thresholds defining severe aortic stenosis (AS) were comparable between Asian and Caucasian populations, and similar to those proposed in the guidelines. However, the accuracy of AVC to identify severe AS, especially in Asian women, was sub-optimal. Therefore, the use of AVC-density is preferable in Asians.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2022)
Article
Cardiac & Cardiovascular Systems
Eddy Barasch, John S. Gottdiener, William Tressel, Traci M. Bartz, Petra Buzkova, Daniele Massera, Christopher deFilippi, Mary L. Biggs, Bruce M. Psaty, Jorge R. Kizer, David Owens
Summary: This study found that aortic valve sclerosis, mitral annular calcification, and aortic annular increased reflectivity are associated with the risk of developing aortic stenosis. The study also revealed that aortic annular increased reflectivity has a particularly strong association with incident aortic stenosis, suggesting its potential use in identifying individuals at risk.
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
(2023)
Article
Cardiac & Cardiovascular Systems
Hee Jeong Lee, Jiwon Seo, Seo-Yeon Gwak, Kyu Kim, Iksung Cho, Geu-Ru Hong, Jong-Won Ha, Chi Young Shim
Summary: This study investigated the associating factors and clinical implications of Mitral Annular Calcification (MAC) progression. The results showed that MAC progression is associated with structural substrate and hemodynamic loads, resulting in mechanical stress. Patients with progressive MAC have poor outcomes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cardiac & Cardiovascular Systems
Kensuke Hirasawa, Steele C. Butcher, Ana Rita Pereira, Maria Chiara Meucci, Jan Stassen, Philippe van Rosendael, Nina Ajmone Marsan, Jeroen J. Bax, Victoria Delgado
Summary: This study investigated the association between the severity of mitral annular calcification (MAC) quantified by computed tomography (CT) and changes in mean transmitral gradient (mTMG), mitral valve area (MVA), and stroke volume index (SVi) following transcatheter aortic valve implantation (TAVI). The results showed that mTMG increased significantly following TAVI in patients with different degrees of MAC severity, with greater changes associated with increasing MAC severity. In contrast, MVA and SVi did not change significantly following TAVI.
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
(2023)
Article
Biophysics
Mohammadreza Soltany Sadrabadi, Mona Eskandari, Heidi P. Feigenbaum, Amirhossein Arzani
Summary: The study investigated the effects of aging and calcification on aortic valve dynamics through a computational growth and remodeling framework. The results revealed patterns of geometric orifice area reduction and an increase in valve stress during global and local growth and remodeling of the aortic valve.
JOURNAL OF BIOMECHANICS
(2021)
Article
Biochemical Research Methods
Melissa Mendoza, Mei-Hsiu Chen, Peter Huang, Gretchen J. Mahler
Summary: A three-dimensional microfluidic device was developed to simulate the characteristics of calcific aortic valve disease. The presence of high shear stress and endothelial cells was found to contribute to the formation of calcified nodules.
Article
Cardiac & Cardiovascular Systems
Jules Mesnier, Marina Urena, Caroline Chong-Nguyen, Quentin Fischer, John Kikoine, Jose Luis Carrasco, Zaven Terzian, Eric Brochet, Bernard Iung, Dominique Himbert
Summary: MAC is present in nearly half of patients undergoing TAVI, but MAC-MS is less common. Severe MAC itself does not impact outcomes, while MAC-MS is an independent predictor of all-cause mortality at 1 year. Measurement of mean transmitral gradient can assist in identifying high-risk MAC patients after TAVI.
AMERICAN JOURNAL OF CARDIOLOGY
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Suya Wang, William T. Pu
Summary: Valve replacement is currently the only treatment for calcific aortic valve disease, but research on genetic forms of the disease and machine learning-driven compound screens offer promising potential for disease management.
NATURE REVIEWS CARDIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Nicolas Perrot, Sebastien Theriault, Christian Dina, Hao Yu Chen, S. Matthijs Boekholdt, Sidwell Rigade, Audrey-Anne Despres, Anthony Poulin, Romain Capoulade, Thierry Le Tourneau, David Messika-Zeitoun, Mikael Trottier, Michel Tessier, Jean Guimond, Maxime Nadeau, James C. Engert, Kay-Tee Khaw, Nicholas J. Wareham, Marc R. Dweck, Patrick Mathieu, Philippe Pibarot, Jean-Jacques Schott, George Thanassoulis, Marie-Annick Clavel, Yohan Bosse, Benoit J. Arsenault
Article
Cardiac & Cardiovascular Systems
Riyaz S. Patel, Vinicius Tragante, Amand F. Schmidt, Raymond O. McCubrey, Michael Holmes, Laurence J. Howe, Kenan Direk, Axel Akerblom, Karin Leander, Salim S. Virani, Karol A. Kaminski, Jochen D. Muehlschlegel, Hooman Allayee, Peter Almgren, Maris Alver, Ekaterina Baranova, Hassan Behloui, Bram Boeckx, Peter S. Braund, Lutz P. Breitling, Graciela Delgado, Nubia E. Duarte, Marie-Pierre Dube, Line Dufresne, Niclas Eriksson, Luisa Foco, Markus Scholz, Crystel M. Gijsberts, Charlotte Glinge, Yan Gong, Jaana Hartiala, Mahyar Heydarpour, Jaroslav A. Hubacek, Marcus Kleber, Daniel Kofink, Salma Kotti, Pekka Kuukasjarvi, Vei-Vei Lee, Andreas Leiherer, Petra A. Lenzini, Daniel Levin, Leo-Pekka Lyytikainen, Nicola Martinelli, Ute Mons, Christopher P. Nelson, Kjell Nikus, Anna P. Pilbrow, Rafal Ploski, Yan Sun, Michael W. T. Tanck, W. H. Wilson Tang, Stella Trompet, Sander W. van der Laan, Jessica Van Setten, Ragnar O. Vilmundarson, Chiara Viviani Anselmi, Efthymia Vlachopoulou, Lawien Al Ali, Eric Boerwinkle, Carlo Briguori, John F. Carlquist, Kathryn F. Carruthers, Gavino Casu, John Deanfield, Panos Deloukas, Frank Dudbridge, Thomas Engstrom, Natalie Fitzpatrick, Kim Fox, Bruna Gigante, Stefan James, Marja-Liisa Lokki, Paulo A. Lotufo, Nicola Marziliano, Ify R. Mordi, Joseph B. Muhlestein, Christopher Newton-Cheh, Jan Pitha, Christoph H. Saely, Ayman Samman-Tahhan, Pratik B. Sandesara, Andrej Teren, Adam Timmis, Frans Van de Werf, Els Wauters, Arthur A. M. Wilde, Ian Ford, David J. Stott, Ale Algra, Maria G. Andreassi, Diego Ardissino, Benoit J. Arsenault, Christie M. Ballantyne, Thomas O. Bergmeijer, Connie R. Bezzina, Simon C. Body, Eric H. Boersma, Peter Bogaty, Michiel L. Bots, Hermann Brenner, Jasper J. Brugts, Ralph Burkhardt, Clara Carpeggiani, Gianluigi Condorelli, Rhonda M. Cooper-DeHoff, Sharon Cresci, Nicolas Danchin, Ulf de Faire, Robert N. Doughty, Heinz Drexel, James C. Engert, Keith A. A. Fox, Domenico Girelli, Diederick E. Grobbee, Emil Hagstrom, Stanley L. Hazen, Claes Held, Harry Hemingway, Imo E. Hoefer, G. Kees Hovingh, Reza Jabbari, Julie A. Johnson, J. Wouter Jukema, Marcin P. Kaczor, Mika Kahonen, Jiri Kettner, Marek Kiliszek, Olaf H. Klungel, Bo Lagerqvist, Diether Lambrechts, Jari O. Laurikka, Terho Lehtimaki, Daniel Lindholm, B. K. Mahmoodi, Anke H. Maitland-van der Zee, Ruth McPherson, Olle Melander, Andres Metspalu, Anna Niemcunowicz-Janica, Oliviero Olivieri, Grzegorz Opolski, Colin N. Palmer, Gerard Pasterkamp, Carl J. Pepine, Alexandre C. Pereira, Louise Pilote, Arshed A. Quyyumi, A. Mark Richards, Marek Sanak, Agneta Siegbahn, Tabassome Simon, Juha Sinisalo, J. Gustav Smith, John A. Spertus, Steen Stender, Alexandre F. R. Stewart, Wojciech Szczeklik, Anna Szpakowicz, Jean-Claude Tardif, Jurrien M. ten Berg, Jacob Tfelt-Hansen, George Thanassoulis, Joachim Thiery, Christian Torp-Pedersen, Yolanda van der Graaf, Frank L. J. Visseren, Johannes Waltenberger, Peter E. Weeke, Pim Van der Harst, Chim C. Lang, Naveed Sattar, Vicky A. Cameron, Jeffrey L. Anderson, James M. Brophy, Guillaume Pare, Benjamin D. Horne, Winfried Marz, Lars Wallentin, Nilesh J. Samani, Aroon D. Hingorani, Folkert W. Asselbergs
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2019)
Article
Cardiac & Cardiovascular Systems
Riyaz S. Patel, Amand F. Schmidt, Vinicius Tragante, Raymond O. McCubrey, Michael Holmes, Laurence J. Howe, Kenan Direk, Axel Akerblom, Karin Leander, Salim S. Virani, Karol A. Kaminski, Jochen D. Muehlschlegel, Marie-Pierre Dube, Hooman Allayee, Peter Almgren, Maris Alver, Ekaterina Baranova, Hassan Behlouli, Bram Boeckx, Peter S. Braund, Lutz P. Breitling, Graciela Delgado, Nubia E. Duarte, Line Dufresne, Niclas Eriksson, Luisa Foco, Crystel M. Gijsberts, Yan Gong, Jaana Hartiala, Mahyar Heydarpour, Jaroslav A. Hubacek, Marcus Kleber, Daniel Kofink, Pekka Kuukasjarvi, Vei-Vei Lee, Andreas Leiherer, Petra A. Lenzini, Daniel Levin, Leo-Pekka Lyytikainen, Nicola Martinelli, Ute Mons, Christopher P. Nelson, Kjell Nikus, Anna P. Pilbrow, Rafal Ploski, Yan Sun, Michael W. T. Tanck, W. H. Wilson Tang, Stella Trompet, Sander W. van der Laan, Jessica van Setten, Ragnar O. Vilmundarson, Chiara Viviani Anselmi, Efthymia Vlachopoulou, Eric Boerwinkle, Carlo Briguori, John F. Carlquist, Kathryn F. Carruthers, Gavino Casu, John Deanfield, Panos Deloukas, Frank Dudbridge, Natalie Fitzpatrick, Bruna Gigante, Stefan James, Marja-Liisa Lokki, Paulo A. Lotufo, Nicola Marziliano, Ify R. Mordi, Joseph B. Muhlestein, Chris Newton Cheh, Jan Pitha, Christoph H. Saely, Ayman Samman-Tahhan, Pratik B. Sandesara, Andrej Teren, Adam Timmis, Frans Van de Werf, Els Wauters, Arthur A. M. Wilde, Ian Ford, David J. Stott, Ale Algra, Maria G. Andreassi, Diego Ardissino, Benoit J. Arsenault, Christie M. Ballantyne, Thomas O. Bergmeijer, Connie R. Bezzina, Simon C. Body, Peter Bogaty, Gert J. de Borst, Hermann Brenner, Ralph Burkhardt, Clara Carpeggiani, Gianluigi Condorelli, Rhonda M. Cooper-DeHoff, Sharon Cresci, Ulf de Faire, Robert N. Doughty, Heinz Drexel, James C. Engert, Keith A. A. Fox, Domenico Girelli, Emil Hagstrom, Stanley L. Hazen, Claes Held, Harry Hemingway, Imo E. Hoefer, G. Kees Hovingh, Julie A. Johnson, Pim A. De Jong, J. Wouter Jukema, Marcin P. Kaczor, Mika Kahonen, Jiri Kettner, Marek Kiliszek, Olaf H. Klungel, Bo Lagerqvist, Diether Lambrechts, Jari O. Laurikka, Terho Lehtimaki, Daniel Lindholm, Bakhtawar K. Mahmoodi, Anke H. Maitland-van der Zee, Ruth McPherson, Olle Melander, Andres Metspalu, Witold Pepinski, Oliviero Olivieri, Grzegorz Opolski, Colin N. Palmer, Gerard Pasterkamp, Carl J. Pepine, Alexandre C. Pereira, Louise Note, Arshed A. Quyyumi, A. Mark Richards, Marek Sanak, Markus Scholz, Agneta Siegbahn, Juha Sinisalo, J. Gustav Smith, John A. Spertus, Alexandre F. R. Stewart, Wojciech Szczeklik, Anna Szpakowicz, Jurrien M. ten Berg, George Thanassoulis, Joachim Thieiy, Yolanda van der Graaf, Frank L. J. Visseren, Johannes Waltenberger, Pim Van der Harst, Jean-Claude Tardif, Naveed Sattar, Chim C. Lang, Guillaume Pare, James M. Brophy, Jeffrey L. Anderson, Winfried Maerz, Lars Wallentin, Vicky A. Cameron, Benjamin D. Horne, Nilesh J. Samani, Aroon D. Hingorani, Folkert W. Asselbergs
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2019)
Editorial Material
Cardiac & Cardiovascular Systems
Ernesto L. Schiffrin, James C. Engert
EUROPEAN HEART JOURNAL
(2019)
Article
Cardiac & Cardiovascular Systems
Hao Yu Chen, Benjamin J. Cairns, Aeron M. Small, Hannah A. Burr, Athithan Ambikkumar, Andreas Martinsson, Sebastien Theriault, Hans Markus Munter, Brian Steffen, Richard Zhang, Rebecca T. Levinson, Christian M. Shaffer, Jian Rong, Emily Sonestedt, Line Dufresne, Johan Ljungberg, Ulf Naslund, Bengt Johansson, Dilrini K. Ranatunga, Rachel A. Whitmer, Matthew J. Budoff, Albert Nguyen, Ramachandran S. Vasan, Martin G. Larson, William S. Harris, Scott M. Damrauer, Ken D. Stark, S. Matthijs Boekholdt, Nicholas J. Wareham, Philippe Pibarot, Benoit J. Arsenault, Patrick Mathieu, Vilmundur Gudnason, Christopher J. O'Donnell, Jerome I. Rotter, Michael Y. Tsai, Wendy S. Post, Robert Clarke, Stefan Soderberg, Yohan Bosse, Quinn S. Wells, J. Gustav Smith, Daniel J. Rader, Mark Lathrop, James C. Engert, George Thanassoulis
Article
Cardiac & Cardiovascular Systems
Nicolas Perrot, Sebastien Theriault, Sidwell Rigade, Hao Yu Chen, Christian Dina, Andreas Martinsson, S. Matthijs Boekholdt, Romain Capoulade, Thierry Le Tourneau, David Messika-Zeitoun, James C. Engert, Nicholas J. Wareham, Marie-Annick Clavel, Philippe Pibarot, J. Gustav Smith, Jean Jacques Schott, Patrick Mathieu, Yohan Bosse, George Thanassoulis, Benoit J. Arsenault
Article
Cardiac & Cardiovascular Systems
Mehdi Afshar, Jian Rong, Yang Zhan, Hao Yu Chen, James C. Engert, Allan D. Sniderman, Martin G. Larson, Ramachandran S. Vasan, George Thanassoulis
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2020)
Article
Cardiac & Cardiovascular Systems
Haoyu Wu, Jian'an Luan, Vincenzo Forgetta, James C. Engert, George Thanassoulis, Vincent Mooser, Nicholas J. Wareham, Claudia Langenberg, J. Brent Richards
Summary: PRS for Lp(a) and ApoB can help identify individuals unlikely to have elevated levels, reducing the need for testing as per current lipid guidelines. The PRS for Lp(a) was highly predictive, while the PRS for ApoB was less so compared to actual measurements, suggesting potential for reducing unnecessary testing.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Hao Yu Chen, Christian Dina, Aeron M. Small, Christian M. Shaffer, Rebecca T. Levinson, Anna Helgadottir, Romain Capoulade, Hans Markus Munter, Andreas Martinsson, Benjamin J. Cairns, Linea C. Trudso, Mary Hoekstra, Hannah A. Burr, Thomas W. Marsh, Scott M. Damrauer, Line Dufresne, Solena Le Scouarnec, David Messika-Zeitoun, Dilrini K. Ranatunga, Rachel A. Whitmer, Amelie Bonnefond, Garoar Sveinbjornsson, Ragnar Danielsen, David O. Arnar, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Hilma Holm, Jonas Ghouse, Morten Salling Olesen, Alex H. Christensen, Susan Mikkelsen, Rikke Louise Jacobsen, Joseph Dowsett, Ole Birger Vesterage Pedersen, Christian Erikstrup, Sisse R. Ostrowski, Christopher J. O'Donnell, Matthew J. Budoff, Vilmundur Gudnason, Wendy S. Post, Jerome Rotter, Mark Lathrop, Henning Bundgaard, Bengt Johansson, Johan Ljungberg, Ulf Naslund, Thierry Le Tourneau, J. Gustav Smith, Quinn S. Wells, Stefan Soderberg, Kari Stefansson, Jean-Jacques Schott, Daniel J. Rader, Robert Clarke, James C. Engert, George Thanassoulis
Summary: This study conducted a genome-wide meta-analysis and discovered 17 loci associated with calcific aortic stenosis. The integration of functional, expression, and cross-phenotype data revealed the mechanisms of this disease. Dyslipidemia, inflammation, calcification, and adiposity were identified as important factors in the etiology of calcific aortic stenosis.
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Nicolas Perrot, Vincenza Valerio, Donato Moschetta, S. Matthijs Boekholdt, Christian Dina, Hao Yu Chen, Erik Abner, Andreas Martinsson, Hasanga D. Manikpurage, Sidwell Rigade, Romain Capoulade, Elvira Mass, Marie-Annick Clavel, Thierry Le Tourneau, David Messika-Zeitoun, Nicholas J. Wareham, James C. Engert, Gianluca Polvani, Philippe Pibarot, Tonu Esko, J. Gustav Smith, Patrick Mathieu, George Thanassoulis, Jean-Jacques Schott, Yohan Bosse, Marina Camera, Sebastien Theriault, Paolo Poggio, Benoit J. Arsenault
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2020)