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7. Interpretable ECG classification via a query-based latent space traversal (qLST)

Author

Vessies, Melle B., Vadgama, Sharvaree P., van de Leur, Rutger R., Doevendans, Pieter A., Hassink, Rutger J., Bekkers, Erik, and van Es, René

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Electrical Engineering and Systems Science - Signal Processing
Abstract

Electrocardiography (ECG) is an effective and non-invasive diagnostic tool that measures the electrical activity of the heart. Interpretation of ECG signals to detect various abnormalities is a challenging task that requires expertise. Recently, the use of deep neural networks for ECG classification to aid medical practitioners has become popular, but their black box nature hampers clinical implementation. Several saliency-based interpretability techniques have been proposed, but they only indicate the location of important features and not the actual features. We present a novel interpretability technique called qLST, a query-based latent space traversal technique that is able to provide explanations for any ECG classification model. With qLST, we train a neural network that learns to traverse in the latent space of a variational autoencoder trained on a large university hospital dataset with over 800,000 ECGs annotated for 28 diseases. We demonstrate through experiments that we can explain different black box classifiers by generating ECGs through these traversals., Comment: Machine Learning for Health (ML4H) - Extended Abstract

Published
2021

8. ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy

Author

van de Leur, Rutger R., de Brouwer, Remco, Bleijendaal, Hidde, Verstraelen, Tom E., Mahmoud, Belend, Perez-Matos, Ana, Dickhoff, Cathelijne, Schoonderwoerd, Bas A., Germans, Tjeerd, Houweling, Arjan, van der Zwaag, Paul A., Cox, Moniek G.P.J., Peter van Tintelen, J., te Riele, Anneline S.J.M., van den Berg, Maarten P., Wilde, Arthur A.M., Doevendans, Pieter A., de Boer, Rudolf A., and van Es, René

Published
2024
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17. The circadian clock remains intact, but with dampened hormonal output in heart failure

Author

Crnko, Sandra, Printezi, Markella I., Zwetsloot, Peter-Paul M., Leiteris, Laurynas, Lumley, Andrew I., Zhang, Lu, Ernens, Isabelle, Jansen, Tijn P.J., Homsma, Lilian, Feyen, Dries, van Faassen, Martijn, du Pré, Bastiaan C., Gaillard, Carlo A.J.M., Kemperman, Hans, Oerlemans, Marish I.F.J., Doevendans, Pieter A.F.M., May, Anne M., Zuithoff, Nicolaas P.A., Sluijter, Joost P.G., Devaux, Yvan, and van Laake, Linda W.

Published
2023
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18. Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction

Author

Delewi, Ronak, Vogel, Rosanne F., Wilschut, Jeroen M., Lemmert, Miguel E., Diletti, Roberto, van Vliet, Ria, van der Waarden, Nancy W.P.L., Nuis, Rutger-Jan, Paradies, Valeria, Alexopoulos, Dimitrios, Zijlstra, Felix, Montalescot, Gilles, Angiolillo, Dominick J., Krucoff, Mitchell W., Doevendans, Pieter A., Van Mieghem, Nicolas M., Smits, Pieter C., and Vlachojannis, Georgios J.

Published
2023
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21. Induced Pluripotent Stem Cells

Author

van Mil, Alain, Neef, Klaus, Balk, Geerthe M., Buikema, Jan Willem, Sluijter, Joost P. G., Doevendans, Pieter A. F. M., Baars, Hubert F., editor, Doevendans, Pieter A. F. M., editor, Houweling, Arjan C., editor, and van Tintelen, J. Peter, editor

Published
2020
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29. Automatic triage of twelve-lead electrocardiograms using deep convolutional neural networks: a first implementation study

Author

Cardiologie, Arts Assistenten Cardiologie, Gezonde Vaten, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Team Onderzoek, van de Leur, Rutger R., van Sleuwen, Meike T.G.M., Zwetsloot, Peter Paul M., van der Harst, Pim, Doevendans, Pieter A., Hassink, Rutger J., van Es, René, Cardiologie, Arts Assistenten Cardiologie, Gezonde Vaten, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Team Onderzoek, van de Leur, Rutger R., van Sleuwen, Meike T.G.M., Zwetsloot, Peter Paul M., van der Harst, Pim, Doevendans, Pieter A., Hassink, Rutger J., and van Es, René

Published
2024

30. ECG-only explainable deep learning algorithm predicts the risk for malignant ventricular arrhythmia in phospholamban cardiomyopathy

Author

Cardiologie, Genetica, Genetica Groep Van Tintelen, Cancer, Child Health, Circulatory Health, Regenerative Medicine and Stem Cells, Team Medisch, Team Onderzoek, van de Leur, Rutger R., de Brouwer, Remco, Bleijendaal, Hidde, Verstraelen, Tom E., Mahmoud, Belend, Perez-Matos, Ana, Dickhoff, Cathelijne, Schoonderwoerd, Bas A., Germans, Tjeerd, Houweling, Arjan, van der Zwaag, Paul A., Cox, Moniek G.P.J., Peter van Tintelen, J., te Riele, Anneline S.J.M., van den Berg, Maarten P., Wilde, Arthur A.M., Doevendans, Pieter A., de Boer, Rudolf A., van Es, René, Cardiologie, Genetica, Genetica Groep Van Tintelen, Cancer, Child Health, Circulatory Health, Regenerative Medicine and Stem Cells, Team Medisch, Team Onderzoek, van de Leur, Rutger R., de Brouwer, Remco, Bleijendaal, Hidde, Verstraelen, Tom E., Mahmoud, Belend, Perez-Matos, Ana, Dickhoff, Cathelijne, Schoonderwoerd, Bas A., Germans, Tjeerd, Houweling, Arjan, van der Zwaag, Paul A., Cox, Moniek G.P.J., Peter van Tintelen, J., te Riele, Anneline S.J.M., van den Berg, Maarten P., Wilde, Arthur A.M., Doevendans, Pieter A., de Boer, Rudolf A., and van Es, René

Published
2024

31. In-hospital mortality of patients with acute coronary syndrome (ACS) after implementation of national health insurance (NHI) in Indonesia

Author

Team Onderzoek, Healthcare Innovation & Evaluation, Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Qalby, Nurul, Arsyad, Dian S., Qanitha, Andriany, Cramer, Maarten J., Appelman, Yolande, Pabittei, Dara R., Doevendans, Pieter A., Mappangara, Idar, Muzakkir, Akhtar Fajar, Team Onderzoek, Healthcare Innovation & Evaluation, Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Qalby, Nurul, Arsyad, Dian S., Qanitha, Andriany, Cramer, Maarten J., Appelman, Yolande, Pabittei, Dara R., Doevendans, Pieter A., Mappangara, Idar, and Muzakkir, Akhtar Fajar

Published
2024

32. On the design and development of a handheld electrocardiogram device in a clinical setting

Author

Team Innovatie Research MTKF, Cluster MTKF, Team Ontwikkeling MTKF, Other research (not in main researchprogram), Team Onderzoek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Zepeda-Echavarria, Alejandra, Ratering Arntz, Niek C M, Westra, Albert H, van Schelven, Leonard J, Euwe, Froukje E, Noordmans, Herke Jan, Vessies, Melle, van de Leur, Rutger R, Hassink, Rutger J, Wildbergh, Thierry X, van der Zee, Rien, Doevendans, Pieter A, van Es, René, Jaspers, Joris E N, Team Innovatie Research MTKF, Cluster MTKF, Team Ontwikkeling MTKF, Other research (not in main researchprogram), Team Onderzoek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Zepeda-Echavarria, Alejandra, Ratering Arntz, Niek C M, Westra, Albert H, van Schelven, Leonard J, Euwe, Froukje E, Noordmans, Herke Jan, Vessies, Melle, van de Leur, Rutger R, Hassink, Rutger J, Wildbergh, Thierry X, van der Zee, Rien, Doevendans, Pieter A, van Es, René, and Jaspers, Joris E N

Published
2024

33. Left Ventricle Myocardial Work Correlated with Functional Capacity in Severe Rheumatic Mitral Stenosis with Preserved Left Ventricular Ejection Fraction

Author

Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Rudiktyo, Estu, Cramer, Maarten J., Yonas, Emir, Teske, Arco J., Siswanto, Bambang Budi, Doevendans, Pieter A., Soesanto, Amiliana M., Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Rudiktyo, Estu, Cramer, Maarten J., Yonas, Emir, Teske, Arco J., Siswanto, Bambang Budi, Doevendans, Pieter A., and Soesanto, Amiliana M.

Published
2024

34. Stress hyperglycemia and poor outcomes in patients with ST-elevation myocardial infarction: a systematic review and meta-analysis

Author

Team Onderzoek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Alkatiri, Abdul Hakim, Qalby, Nurul, Mappangara, Idar, Zainal, Ahmad Taufik F., Cramer, Maarten J., Doevendans, Pieter A., Qanitha, Andriany, Team Onderzoek, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Alkatiri, Abdul Hakim, Qalby, Nurul, Mappangara, Idar, Zainal, Ahmad Taufik F., Cramer, Maarten J., Doevendans, Pieter A., and Qanitha, Andriany

Published
2024

35. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Published
2024

36. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation ( i.e., a slow and fast cooling approach to -196 °C and -150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024

39. Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department

Author

Onderzoek Vrouw Hart & Vaatziekten, Experimentele Afd. Cardiologie 1, Arts Assistenten Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Zorgeenheid Vaatchirurgie Medisch, Infection & Immunity, Ho, Andrew Fu Wah, Yau, Chun En, Ho, Jamie Sin Ying, Lim, Swee Han, Ibrahim, Irwani, Kuan, Win Sen, Ooi, Shirley Beng Suat, Chan, Mark Y., Sia, Ching Hui, Mosterd, Arend, Gijsberts, Crystel M., de Hoog, Vince C., Bank, Ingrid E.M., Doevendans, Pieter A., de Kleijn, Dominique P.V., Onderzoek Vrouw Hart & Vaatziekten, Experimentele Afd. Cardiologie 1, Arts Assistenten Cardiologie, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Zorgeenheid Vaatchirurgie Medisch, Infection & Immunity, Ho, Andrew Fu Wah, Yau, Chun En, Ho, Jamie Sin Ying, Lim, Swee Han, Ibrahim, Irwani, Kuan, Win Sen, Ooi, Shirley Beng Suat, Chan, Mark Y., Sia, Ching Hui, Mosterd, Arend, Gijsberts, Crystel M., de Hoog, Vince C., Bank, Ingrid E.M., Doevendans, Pieter A., and de Kleijn, Dominique P.V.

Published
2024

40. A Cardioprotective perfusion protocol limits myocardial functional decline during ex situ heart perfusion

Author

Arts Assistenten CTC, Innovatie CTC, Secretariaat en overig CTC, Experimentele Afd. Cardiologie 2, Circulatory Health, Infection & Immunity, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Team Medisch, CTC, Vervoorn, Mats T., Ballan, Elisa M., van Tuijl, Sjoerd, de Jager, Saskia C.A., Kaffka genaamd Dengler, Selma E., Sluijter, Joost P.G., Doevendans, Pieter A., van der Kaaij, Niels P., Arts Assistenten CTC, Innovatie CTC, Secretariaat en overig CTC, Experimentele Afd. Cardiologie 2, Circulatory Health, Infection & Immunity, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Team Medisch, CTC, Vervoorn, Mats T., Ballan, Elisa M., van Tuijl, Sjoerd, de Jager, Saskia C.A., Kaffka genaamd Dengler, Selma E., Sluijter, Joost P.G., Doevendans, Pieter A., and van der Kaaij, Niels P.

Published
2024

41. Hemofiltration Improves Blood Perfusate Conditions Leading to Improved Ex Situ Heart Perfusion

Author

Arts Assistenten CTC, Experimentele Afd. Cardiologie 2, Secretariaat en overig CTC, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Team Medisch, CTC, Kaffka Genaamd Dengler, Selma E, Mishra, Mudit, Vervoorn, Mats T, Kernkamp, Jord, van Tuijl, Sjoerd, de Jager, Saskia C A, Sluijter, Joost P G, Doevendans, Pieter A, van der Kaaij, Niels P, Arts Assistenten CTC, Experimentele Afd. Cardiologie 2, Secretariaat en overig CTC, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Regenerative Medicine and Stem Cells, Team Medisch, CTC, Kaffka Genaamd Dengler, Selma E, Mishra, Mudit, Vervoorn, Mats T, Kernkamp, Jord, van Tuijl, Sjoerd, de Jager, Saskia C A, Sluijter, Joost P G, Doevendans, Pieter A, and van der Kaaij, Niels P

Published
2024

43. On the design and development of a handheld electrocardiogram device in a clinical setting.

Author

Zepeda-Echavarria, Alejandra, Ratering Arntz, Niek C. M., Westra, Albert H., van Schelven, Leonard J., Euwe, Froukje E., Noordmans, Herke Jan, Vessies, Melle, van de Leur, Rutger R., Hassink, Rutger J., Wildbergh, Thierry X., van der Zee, Rien, Doevendans, Pieter A., van Es, René, and Jaspers, Joris E. N.

Subjects
CARDIOVASCULAR disease diagnosis, ACADEMIC medical centers, MEDICAL technology, RESEARCH funding, PRODUCT design, NEW product development, QUALITY control, ELECTROCARDIOGRAPHY, COMMERCIAL product evaluation, MEDICAL equipment, NEW product development laws
Abstract

Cardiovascular diseases (CVDs) are a global burden that requires attention. For the detection and diagnosis of CVDs, the 12-lead ECG is a key tool. With technological advancements, ECG devices are becoming smaller and available for home use. Most of these devices contain a limited number of leads and are aimed to detect atrial fibrillation (AF). To investigate whether a four-electrode arrangement could provide enough information to diagnose other CVDs, further research is necessary. At the University Medical Center Utrecht in a multidisciplinary team, we developed the miniECG, a four-electrode ECG handheld system for scientific research in clinical environments (TRL6). This paper describes the process followed during the development of the miniECG. From assembling a multidisciplinary team, which includes engineers, cardiologists, and clinical physicians to the contribution of team members in the design input, design, and testing for safety and functionality of the device. Finally, we detail how the development process was composed by iterative design steps based on user input and intended use evolution. The miniECG is a device compliant for scientific research with patients within Dutch Medical Centers. We believe that hospital-based development led to a streamlined process, which could be applied for the design and development of other technologies used for scientific research in clinical environments. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and Meta-analysis

Author

Ambari, Ade M., primary, Radi, Basuni, additional, Dwiputra, Bambang, additional, Arityanti, Dean, additional, Rikl, Thomas, additional, Inggriani, Maria P., additional, Qhabibi, Faqrizal Ria, additional, Susilowati, Eliana, additional, Makes, Indira Kalyana, additional, Rudiktyo, Estu, additional, Cramer, Maarten J., additional, Doevendans, Pieter, additional, Setianto, Budhi, additional, and Santoso, Anwar, additional

Published
2024
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46. Detection of Acute Coronary Occlusion with A Novel Mobile ECG Device: A Pilot Study

Author

Zepeda-Echavarria, Alejandra, primary, van de Leur, Rutger R, additional, Vessies, Melle, additional, de Vries, Nynke M, additional, van Sleuwen, Meike, additional, Hassink, Rutger J, additional, Wildbergh, Thierry X, additional, van Doorn, J L, additional, van der Zee, Rien, additional, Doevendans, Pieter A, additional, Jaspers, Joris E N, additional, and van Es, René, additional

Published
2024
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47. 52 Genetic Loci Influencing Myocardial Mass

Author

van der Harst, Pim, van Setten, Jessica, Verweij, Niek, Vogler, Georg, Franke, Lude, Maurano, Matthew T, Wang, Xinchen, Leach, Irene Mateo, Eijgelsheim, Mark, Sotoodehnia, Nona, Hayward, Caroline, Sorice, Rossella, Meirelles, Osorio, Lyytikäinen, Leo-Pekka, Polašek, Ozren, Tanaka, Toshiko, Arking, Dan E, Ulivi, Sheila, Trompet, Stella, Müller-Nurasyid, Martina, Smith, Albert V, Dörr, Marcus, Kerr, Kathleen F, Magnani, Jared W, Del Greco M., Fabiola, Zhang, Weihua, Nolte, Ilja M, Silva, Claudia T, Padmanabhan, Sandosh, Tragante, Vinicius, Esko, Tõnu, Abecasis, Gonçalo R, Adriaens, Michiel E, Andersen, Karl, Barnett, Phil, Bis, Joshua C, Bodmer, Rolf, Buckley, Brendan M, Campbell, Harry, Cannon, Megan V, Chakravarti, Aravinda, Chen, Lin Y, Delitala, Alessandro, Devereux, Richard B, Doevendans, Pieter A, Dominiczak, Anna F, Ferrucci, Luigi, Ford, Ian, Gieger, Christian, Harris, Tamara B, Haugen, Eric, Heinig, Matthias, Hernandez, Dena G, Hillege, Hans L, Hirschhorn, Joel N, Hofman, Albert, Hubner, Norbert, Hwang, Shih-Jen, Iorio, Annamaria, Kähönen, Mika, Kellis, Manolis, Kolcic, Ivana, Kooner, Ishminder K, Kooner, Jaspal S, Kors, Jan A, Lakatta, Edward G, Lage, Kasper, Launer, Lenore J, Levy, Daniel, Lundby, Alicia, Macfarlane, Peter W, May, Dalit, Meitinger, Thomas, Metspalu, Andres, Nappo, Stefania, Naitza, Silvia, Neph, Shane, Nord, Alex S, Nutile, Teresa, Okin, Peter M, Olsen, Jesper V, Oostra, Ben A, Penninger, Josef M, Pennacchio, Len A, Pers, Tune H, Perz, Siegfried, Peters, Annette, Pinto, Yigal M, Pfeufer, Arne, Pilia, Maria Grazia, Pramstaller, Peter P, Prins, Bram P, Raitakari, Olli T, Raychaudhuri, Soumya, Rice, Ken M, Rossin, Elizabeth J, Rotter, Jerome I, Schafer, Sebastian, Schlessinger, David, and Schmidt, Carsten O

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Genetics, Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, Biotechnology, Human Genome, 2.1 Biological and endogenous factors, Animals, Cardiomegaly, Genetic Loci, Genome-Wide Association Study, Humans, electrocardiogram, genetic association study, heart failure, left ventricular hypertrophy, QRS, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundMyocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.ObjectivesThis meta-analysis sought to gain insights into the genetic determinants of myocardial mass.MethodsWe carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.ResultsWe identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo.ConclusionsTaken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.

Published
2016

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