Review
Biochemistry & Molecular Biology
Hamza El Hadi, Anne Freund, Steffen Desch, Holger Thiele, Nicolas Majunke
Summary: Cardiomyopathies are a diverse group of heart muscle disorders with potentially fatal consequences such as arrhythmias and heart failure. They are a leading cause of heart transplantation worldwide. Recent advancements in understanding the molecular basis and diagnostic evaluation have paved the way for targeted therapies. However, further research is needed to improve risk assessment and prevention strategies for sudden cardiac death.
Review
Medicine, General & Internal
Enrica Chiti, Marco Paolo, Emanuela Turillazzi, Anna Rocchi
Summary: MiRNAs are small non-coding RNAs involved in regulating biochemical pathways in the human body; their levels can be altered due to pathophysiological mechanisms, making them potential biomarkers for cardiac diseases and other pathological conditions. This review summarizes findings of miRNA biomarkers in the three most common structural cardiomyopathies.
Review
Pharmacology & Pharmacy
Ekaterina Podyacheva, Yana Toropova
Summary: Neoplasm is a major cause of morbidity and mortality worldwide. The use of cytotoxic drugs, such as doxorubicin, in cancer treatment is associated with cardiovascular complications. Defects in intercalated disc proteins can lead to cardiovascular diseases, including doxorubicin-induced cardiomyopathy. Activation of SIRT1 may provide cardioprotection by improving cellular and mitochondrial functions, reducing oxidative stress, and protecting intercalated disc structures.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yukinobu Ito, Makoto Yoshida, Hirotake Masuda, Daichi Maeda, Yukitsugu Kudo-Asabe, Michinobu Umakoshi, Hiroshi Nanjo, Akiteru Goto
Summary: This study investigated morphological differences in intercalated discs (ICDs) in patients with DCM, and found that reduced N-cadherin immunostaining intensity and ICD scattering were specific to DCM. The results suggest that disorganized ICDs contribute to the development of DCM and that N-cadherin immunostaining is useful for pathological diagnosis.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Xuebin Zhang, Yu Duan, Xiao Zhang, Mengyuan Jiang, Wanrong Man, Yan Zhang, Dexi Wu, Jiye Zhang, Xinglong Song, Congye Li, Jie Lin, Dongdong Sun
Summary: Microvascular complications in diabetes patients, including coronary microvascular injury, are associated with a higher risk of adverse outcomes. This study investigated the mechanisms underlying diabetic coronary microvascular hyperpermeability and found that Adipsin plays a vital role in maintaining the integrity of cardiac microvascular endothelial cells.
Article
Biology
Giuseppina Mastrototaro, Pierluigi Carullo, Jianlin Zhang, Beatrice Scellini, Nicoletta Piroddi, Simona Nemska, Maria Carmela Filomena, Simone Serio, Carol A. Otey, Chiara Tesi, Fabian Emrich, Wolfgang A. Linke, Corrado Poggesi, Simona Boncompagni, Marie-Louise Bang, Nuno Guimaraes-Camboa
Summary: Palladin (PALLD) is a protein associated with actin and immunoglobulin in the heart. Its role in the heart has been unclear due to embryonic lethality in knockout mice. However, a study found that PALLD is necessary for normal cardiac function, as its deletion in adult mice led to cardiac abnormalities and dysfunction. Additionally, PALLD interacts with other proteins such as CARP/Ankrd1 and FHOD1. This research sheds light on the importance of PALLD in the heart.
Review
Medicine, General & Internal
Giulia Mattesi, Alberto Cipriani, Barbara Bauce, Ilaria Rigato, Alessandro Zorzi, Domenico Corrado
Summary: ACM is an inherited heart muscle disease that can lead to sudden cardiac arrhythmias and death, with a focus on right ventricular involvement, although recent studies have shown left ventricular involvement as well. Different gene mutations are associated with different phenotypic expressions of ACM.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Paloma Jorda, Laurens P. Bosman, Alessio Gasperetti, Andrea Mazzanti, Jean-Baptiste Gourraud, Brianna Davies, Tanja Charlotte Frederiksen, Zoraida Moreno Weidmann, Andrea Di Marco, Jason D. Roberts, Ciorsti MacIntyre, Colette Seifer, Antoine Deliniere, Wael Alqarawi, Deni Kukavica, Damien Minois, Alessandro Trancuccio, Marine Arnaud, Mattia Targetti, Annamaria Martino, Giada Oliviero, Daniel C. Pipilas, Corrado Carbucicchio, Paolo Compagnucci, Antonio Dello Russo, Iacopo Olivotto, Leonardo Calo, Steven A. Lubitz, Michael J. Cutler, Philippe Chevalier, Elena Arbelo, Silvia Giuliana Priori, Jeffrey S. Healey, Hugh Calkins, Michela Casella, Henrik Kjaerulf Jensen, Claudio Tondo, Rafik Tadros, Cynthia A. James, Andrew D. Krahn, Julia Cadrin-Tourigny
Summary: This study validated a 5-year risk prediction model for ARVC patients, demonstrating its superior performance in guiding ICD implantation decisions compared to other published guidelines and consensus statements. The findings support the use of this model for shared decision making in the primary prevention of SCD in ARVC patients.
EUROPEAN HEART JOURNAL
(2022)
Review
Medicine, General & Internal
Emanuele Monda, Marta Rubino, Giuseppe Palmiero, Federica Verrillo, Michele Lioncino, Gaetano Diana, Annapaola Cirillo, Adelaide Fusco, Francesca Dongiglio, Martina Caiazza, Ippolita Altobelli, Alfredo Mauriello, Natale Guarnaccia, Alessandra Scatteia, Arturo Cesaro, Giuseppe Pacileo, Berardo Sarubbi, Giulia Frisso, Barbara Bauce, Antonello D'Andrea, Santo Dellegrottaglie, Maria Giovanna Russo, Paolo Calabro, Giuseppe Limongelli
Summary: Arrhythmogenic cardiomyopathy (ACM) is a broad term for myocardial diseases characterized by progressive fibrotic or fibrofatty replacement, which leads to ventricular tachyarrhythmias and ventricular dysfunction. Arrhythmogenic left ventricular cardiomyopathy (ALVC) is a specific subtype that exclusively affects the left ventricle. Diagnosis of ALVC requires a combination of family history, clinical, electrocardiographic, and imaging features, with genetic testing for confirmation. Multimodality imaging techniques, such as echocardiography, cardiac magnetic resonance, and cardiac nuclear imaging, are essential for diagnosis, differential diagnosis, risk stratification, and management of ALVC.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Julia Cadrin-Tourigny, Laurens P. Bosman, Anna Nozza, Weijia Wang, Rafik Tadros, Aditya Bhonsale, Mimount Bourfiss, Annik Fortier, Oyvind H. Lie, Ardan M. Saguner, Anneli Svensson, Antoine Andorin, Crystal Tichnell, Brittney Murray, Katja Zeppenfeld, Maarten P. van den Berg, Folkert W. Asselbergs, Arthur A. M. Wilde, Andrew D. Krahn, Mario Talajic, Lena Rivard, Stephen Chelko, Stefan L. Zimmerman, Ihab R. Kamel, Jane E. Crosson, Daniel P. Judge, Sing-Chien Yap, Jeroen F. van der Heijden, Harikrishna Tandri, Jan D. H. Jongbloed, Marie-Claude Guertin, J. Peter van Tintelen, Pyotr G. Platonov, Firat Duru, Kristina H. Haugaa, Paul Khairy, Richard N. W. Hauer, Hugh Calkins, Anneline S. J. M. te Riele, Cynthia A. James
Summary: We developed a prediction model for incident VA/SCD in ARVC patients using readily available clinical parameters, which accurately distinguished patients with and without events and showed superior clinical benefit compared to current ICD placement algorithms.
EUROPEAN HEART JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Thomas Zegkos, Theofilos Panagiotidis, Despoina Parcharidou, Georgios Efthimiadis
Summary: This article discusses the importance of phenotypic and genotypic analysis in dilated cardiomyopathy with arrhythmic burden, and emphasizes early preventive measures for sudden cardiac death, with special attention given to the overlap with left dominant arrhythmogenic cardiomyopathy.
HEART FAILURE REVIEWS
(2021)
Article
Medicine, General & Internal
Riccardo Bariani, Maria Bueno Marinas, Ilaria Rigato, Paola Veronese, Rudy Celeghin, Alberto Cipriani, Marco Cason, Valeria Pergola, Giulia Mattesi, Petra Deola, Alessandro Zorzi, Giuseppe Limongelli, Sabino Iliceto, Domenico Corrado, Cristina Basso, Kalliopi Pilichou, Barbara Bauce
Summary: This study analyzed a series of childbearing women affected by arrhythmogenic left ventricular cardiomyopathy (ALVC) and found that pregnancy had no significant influence on disease progression and degree of electrical instability in ALVC patients without previous episodes of heart failure.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Alex Horby Christensen, Pyotr G. Platonov, Anneli Svensson, Henrik K. Jensen, Christine Rootwelt-Norberg, Pia Dahlberg, Trine Madsen, Tanja Charlotte Frederiksen, Tiina Helio, Kristina H. Haugaa, Henning Bundgaard, Jesper H. Svendsen
Summary: This study describes the complications associated with implantable cardioverter-defibrillators (ICD) treatment in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The results show that during long-term follow-up, approximately 41% of patients experienced potentially life-saving ICD therapy, while 27% had complications requiring surgery, mainly lead-related complications.
Article
Emergency Medicine
Leen Alblaihed, Christine Kositz, William J. Brady, Tareq Al -Salamah, Amal Mattu
Summary: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the myocardium that can cause ventricular arrhythmia and sudden cardiac death. Early recognition of the disease by emergency clinicians is crucial to prevent subsequent death, as it is a significant cause of arrhythmic death among young people and athletes. This publication reviews the pathophysiology, classification, clinical presentations, and appropriate approach to diagnosis and management of ARVC.
AMERICAN JOURNAL OF EMERGENCY MEDICINE
(2023)
Article
Medicine, General & Internal
Nadine Molitor, Firat Duru
Summary: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibro-fatty replacement of the right ventricle, which can lead to ventricular tachyarrhythmias and sudden cardiac death. Diagnosis is challenging due to its variable expressivity, incomplete penetrance, and lack of specific diagnostic criteria. Other cardiac diseases may mimic the clinical phenotypes of ARVC, leading to misdiagnosis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Letter
Cardiac & Cardiovascular Systems
L. H. Lehmann, F. Stein, D. Jaeger, N. Frey
CLINICAL RESEARCH IN CARDIOLOGY
(2022)
Letter
Clinical Neurology
Brigitte Wildemann, Sven Jarius, Lorenz H. Lehmann, Florian Andre, Norbert Frey, Paul Schnitzler, Laura Jaeger, Christoph Gumbinger, Andrea Viehover
JOURNAL OF NEUROLOGY
(2022)
Article
Medicine, General & Internal
Omid Shirvani Samani, Johannes Scherr, Elham Kayvanpour, Jan Haas, David H. Lehmann, Weng-Tein Gi, Karen S. Frese, Rouven Nietsch, Tobias Fehlmann, Steffi Sandke, Tanja Weis, Andreas Keller, Hugo A. Katus, Martin Halle, Norbert Frey, Benjamin Meder, Farbod Sedaghat-Hamedani
Summary: This study investigates the specificity of serum microRNAs as biomarkers for myocardial infarction by examining their behavior during strenuous exercise. The results show that some microRNAs associated with myocardial infarction have similar kinetics during exercise, suggesting limited diagnostic specificity. However, combining certain microRNAs with cardiac troponin within a multi-marker strategy may enhance diagnostic accuracy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Pablo Binder, Binh Nguyen, Lucy Collins, Min Zi, Wei Liu, Foteini Christou, Xiaojing Luo, Susanne S. Hille, Norbert Frey, Elizabeth J. Cartwright, Jonathan Chernoff, Oliver J. Mueller, Kaomei Guan, Xin Wang
Summary: This study identifies a novel regulator of Nrf2, Pak2, and elucidates the potential therapeutic significance of Pak2-mediated regulation of Nrf2 homeostasis in alleviating ER stress and heart failure.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biology
Nicolas A. Geis, Anna Goebbel, Michael M. Kreusser, Tobias Taeger, Hugo A. Katus, Norbert Frey, Philipp Schlegel, Philip W. Raake
Summary: This study aimed to assess the impact of TEER using the MitraClip(TM) device on ventricular arrhythmias and ICD therapies. The results showed that TEER significantly reduced ventricular arrhythmias and the need for ICD therapies.
Article
Pathology
Osman Yilmaz, Amaya Pankaj, Azfar Neyez, Steffen Rickelt, Martin Taylor, Evan R. Lang, Lieve Leijsen, Anne Dinaux, Stuti G. Shroff, Rory Crotty, M. Lisa Zhang, Sandra Cerda, Qing Zhao, Cristina Ferrone, David T. Ting, Deepa T. Patil, Omer Yilmaz, David Berger, Vikram Deshpande
Summary: The expression of PD-L1 in colon carcinoma is associated with prognosis. High expression of PD-L1 is correlated with favorable pathological features and strong correlation with immune cells.
Article
Biochemistry & Molecular Biology
Farbod Sedaghat-Hamedani, Sabine Rebs, Elham Kayvanpour, Chenchen Zhu, Ali Amr, Marion Mueller, Jan Haas, Jingyan Wu, Lars M. Steinmetz, Philipp Ehlermann, Katrin Streckfuss-Boemeke, Norbert Frey, Benjamin Meder
Summary: In this study, a combination of genetic testing, iPSC-CMs and nanopore long-read sequencing was used to identify the causal variant in a multi-generational pedigree of DCM. The study highlighted the importance of precise diagnostics in the clinical management and workup of cardiomyopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ingmar Soren Meyer, Xue Li, Carina Meyer, Oksana Voloshanenko, Susann Pohl, Michael Boutros, Hugo Albert Katus, Norbert Frey, Florian Leuschner
Summary: This study tested the therapeutic potential of the Wnt secretion inhibitor LGK-974 in a model of ischemia/reperfusion injury and found that LGK-974 can attenuate inflammatory response, improve heart function, and potentially be used for immunomodulatory approaches to improve cardiac remodeling after myocardial infarction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Amr Abdin, Johann Bauersachs, Samira Soltani, Matthias Eden, Norbert Frey, Michael Boehm
Summary: Heart failure remains a global healthcare challenge despite significant developments in pharmacotherapies. There are concerns regarding low medication dosages and incomplete drug classes in real-world settings, and current guidelines lack detailed recommendations. A practical approach algorithm is proposed to assist physicians in treating HF patients.
Article
Cell Biology
Kristen J. Tomaszewski, Azfar Neyaz, Kenan Sauder, Steffen Rickelt, M. Lisa Zhang, Omer Yilmaz, Rory Crotty, Stuti Shroff, Robert Odze, Anthony Mattia, Deepa T. Patil, Vikram Deshpande
Summary: Aimsp53 is an independent risk stratification marker in Barrett's esophagus (BE), but there is no universally accepted definition for abnormal p53 staining. This study assessed p53 staining in two cohorts to define abnormal p53 staining in BE-related dysplasia and evaluate the sensitivity and specificity of this cut-point for diagnosing dysplasia. The results showed that a single strongly positive p53 gland is highly sensitive and specific for dysplasia.
Article
Pharmacology & Pharmacy
Panagiotis Xynogalos, Ann-Kathrin Rahm, Sebastian Fried, Safak Chasan, Daniel Scherer, Claudia Seyler, Hugo A. Katus, Norbert Frey, Edgar Zitron
Summary: This study analyzed the effect of the antiarrhythmic drug verapamil on the inwardly rectifying potassium current of cardiomyocytes. The results showed that verapamil inhibited the Kir2.1, Kir2.2, and Kir2.3 channels, with the inhibition of Kir2.3 being a previously unknown finding. Further experiments revealed that the inhibition of Kir2.3 by verapamil was dependent on specific binding sites and interference with PIP2 activation. This finding provides a potential target for the development of selective antiarrhythmic drugs targeting Kir2.3 channels.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Oncology
Noor Jailkhani, Karl R. Clauser, Howard H. Mak, Steffen Rickelt, Chenxi Tian, Charles A. Whittaker, Kenneth K. Tanabe, Stephen R. Purdy, Steven A. Carr, Richard O. Hynes
Summary: Metastases, which are difficult to detect and treat, are the leading cause of cancer-related deaths. There is a clinical need for therapies specifically targeting metastases. This study focuses on developing nanobodies against extracellular matrix (ECM) proteins expressed in human metastases as potential vehicles for targeted delivery of imaging and therapeutic agents. By using phage-display libraries and proteomics, the researchers identified a conserved set of ECM proteins that are abundantly expressed in metastases from TNBC and colorectal cancer. They successfully isolated nanobodies against one of these proteins, tenascin-C (TNC), and demonstrated their specificity in binding TNBC tumors and metastases. The study suggests that generic nanobodies against tumors and metastases have great potential as cancer-agnostic tools for delivering therapeutics to the tumor microenvironment.
Article
Cell Biology
Azfar Neyaz, Rory Crotty, Steffen Rickelt, Amaya Pankaj, Marija Stojanova, Theodoros P. Michelakos, Yurie Sekigami, Filippos Kontos, Paige H. Parrack, Deepa T. Patil, Christopher M. Heaphy, Cristina R. Ferrone, Vikram Deshpande
Summary: Immunohistochemistry for ARX and ALT FISH status can predict the aggressive behavior of nonfunctional PanNETs. This information can help identify patients who may benefit from surgical intervention.
Meeting Abstract
Medicine, General & Internal
Lara Kluemper, Matthias Lutz, Norbert Frey
Article
Cardiac & Cardiovascular Systems
Stefan Frantz, Stefan Anker, Johann Bauersachs, Michael Boehm, Jana Boer, Sonia Busch, Norbert Frey, Christian A. Perings, Tanja K. Rudolph, Stephan von Haehling, P. Christian Schulze
Summary: Heart failure is a syndrome with high morbidity and mortality. The new ESC guidelines provide the current standard for diagnosing and treating acute and chronic heart failure. The most significant change is the altered first-line treatment for heart failure with reduced ejection fraction.