{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:29:46Z","timestamp":1790800186113,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/17\/5\/32705"],"award-info":[{"award-number":["PG\/17\/5\/32705"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>About half of hypertrophic and dilated cardiomyopathies cases have been recognized as genetic diseases with mutations in sarcomeric proteins. The sarcomeric proteins are involved in cardiomyocyte contractility and its regulation, and play a structural role. Mutations in non-sarcomeric proteins may induce changes in cell signaling pathways that modify contractile response of heart muscle. These facts strongly suggest that contractile dysfunction plays a central role in initiation and progression of cardiomyopathies. In fact, abnormalities in contractile mechanics of myofibrils have been discovered. However, it has not been revealed how these mutations increase risk for cardiomyopathy and cause the disease. Much research has been done and still much is being done to understand how the mechanism works. Here, we review the facts of cardiac myofilament contractility in patients with cardiomyopathy and heart failure.<\/jats:p>","DOI":"10.3390\/ijms19082234","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T03:10:01Z","timestamp":1533093001000},"page":"2234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Cardiomyopathies and Related Changes in Contractility of Human Heart Muscle"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0859-1082","authenticated-orcid":false,"given":"Petr G.","family":"Vikhorev","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia N.","family":"Vikhoreva","sequence":"additional","affiliation":[{"name":"Heart Science Centre, Magdi Yacoub Institute, Harefield Hospital, London UB9 6JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.4330\/wjc.v7.i4.204","article-title":"Autonomic and endocrine control of cardiovascular function","volume":"7","author":"Gordan","year":"2015","journal-title":"World J. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"MacLeod, K.T. (2016). Recent advances in understanding cardiac contractility in health and disease. F1000Research, 5.","DOI":"10.12688\/f1000research.8661.1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1161\/CIRCRESAHA.117.310230","article-title":"Calcium and Excitation-Contraction Coupling in the Heart","volume":"121","author":"Eisner","year":"2017","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.abb.2016.02.016","article-title":"Structural determinants of muscle thin filament cooperativity","volume":"594","author":"Moore","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6782","DOI":"10.1073\/pnas.1700868114","article-title":"Ca(2+)-induced movement of tropomyosin on native cardiac thin filaments revealed by cryoelectron microscopy","volume":"114","author":"Risi","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cardiores.2004.12.022","article-title":"Regulation of cardiac contractile function by troponin I phosphorylation","volume":"66","author":"Layland","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s12471-014-0590-4","article-title":"Troponin I phosphorylation in human myocardium in health and disease","volume":"22","author":"Wijnker","year":"2014","journal-title":"Neth. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3389\/fphys.2016.00415","article-title":"Why Is there a Limit to the Changes in Myofilament Ca(2+)-Sensitivity Associated with Myopathy Causing Mutations?","volume":"7","author":"Marston","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00424-013-1426-6","article-title":"Structure, sarcomeric organization, and thin filament binding of cardiac myosin-binding protein-C","volume":"466","author":"Craig","year":"2014","journal-title":"Pflugers Arch."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s12551-017-0248-8","article-title":"Pseudophosphorylation of cardiac myosin regulatory light chain: A promising new tool for treatment of cardiomyopathy","volume":"9","author":"Yadav","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"18763","DOI":"10.1073\/pnas.1413922112","article-title":"Myosin binding protein-C activates thin filaments and inhibits thick filaments in heart muscle cells","volume":"111","author":"Kampourakis","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29241","DOI":"10.1074\/jbc.M115.686790","article-title":"Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation","volume":"290","author":"Kumar","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/europace\/eup229","article-title":"The magnitude of sudden cardiac death in the young: A death certificate-based review in England and Wales","volume":"11","author":"Papadakis","year":"2009","journal-title":"Europace"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1136\/hrt.2004.040337","article-title":"New insights into the pathology of inherited cardiomyopathy","volume":"91","author":"Hughes","year":"2005","journal-title":"Heart"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/eurheartj\/ehs397","article-title":"Diagnostic work-up in cardiomyopathies: Bridging the gap between clinical phenotypes and final diagnosis. A position statement from the ESC Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Rapezzi","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/415227a","article-title":"The failing heart","volume":"415","author":"Towbin","year":"2002","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1161\/CIRCRESAHA.117.309711","article-title":"Classification, Epidemiology, and Global Burden of Cardiomyopathies","volume":"121","author":"McKenna","year":"2017","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/0735-1097(89)90293-3","article-title":"The challenge of cardiomyopathy","volume":"13","author":"Abelmann","year":"1989","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1093\/eurheartj\/ehu301","article-title":"Atlas of the clinical genetics of human dilated cardiomyopathy","volume":"36","author":"Haas","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/j.jacc.2016.08.079","article-title":"Clinical and Mechanistic Insights Into the Genetics of Cardiomyopathy","volume":"68","author":"Burke","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1161\/CIRCULATIONAHA.111.023838","article-title":"Epidemiology and genetics of sudden cardiac death","volume":"125","author":"Deo","year":"2012","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1161\/CIRCULATIONAHA.116.025795","article-title":"Ejection Fraction: Misunderstood and Overrated (Changing the Paradigm in Categorizing Heart Failure)","volume":"135","author":"Konstam","year":"2017","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1365-2559.2004.01835.x","article-title":"The pathology of hypertrophic cardiomyopathy","volume":"44","author":"Hughes","year":"2004","journal-title":"Histopathology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00428-007-0505-5","article-title":"Guidelines for autopsy investigation of sudden cardiac death","volume":"452","author":"Basso","year":"2008","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/ERP-16-0037","article-title":"Diagnosis and assessment of dilated cardiomyopathy: A guideline protocol from the British Society of Echocardiography","volume":"4","author":"Mathew","year":"2017","journal-title":"Echo Res. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1530\/ERP-15-0007","article-title":"Diagnosis and management of hypertrophic cardiomyopathy","volume":"2","author":"Pantazis","year":"2015","journal-title":"Echo Res. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.15420\/aer.2013.2.1.36","article-title":"Mimics of Hypertrophic Cardiomyopathy\u2014Diagnostic Clues to Aid Early Identification of Phenocopies","volume":"2","author":"Sankaranarayanan","year":"2013","journal-title":"Arrhythm. Electrophysiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e579","DOI":"10.1161\/CIR.0000000000000455","article-title":"Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1016\/j.jacc.2016.03.590","article-title":"The Diagnosis and Evaluation of Dilated Cardiomyopathy","volume":"67","author":"Japp","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/eurheartj\/ehm342","article-title":"Classification of the cardiomyopathies: A position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"29","author":"Elliott","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","article-title":"Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases","volume":"37","author":"Pinto","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.jacc.2018.03.462","article-title":"Genetic Etiology for Alcohol-Induced Cardiac Toxicity","volume":"71","author":"Ware","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.cardfail.2017.03.003","article-title":"Truncating Titin (TTN) Variants in Chemotherapy-Induced Cardiomyopathy","volume":"23","author":"Linschoten","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bakalakos, A., Ritsatos, K., and Anastasakis, A. (2018). Current perspectives on the diagnosis and management of dilated cardiomyopathy Beyond heart failure: A Cardiomyopathy Clinic Doctor\u2019s point of view. Hellenic J. Cardiol.","DOI":"10.1016\/j.hjc.2018.05.008"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1056\/NEJM200004133421502","article-title":"Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy","volume":"342","author":"Felker","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1001\/jama.296.15.1867","article-title":"Incidence, causes, and outcomes of dilated cardiomyopathy in children","volume":"296","author":"Towbin","year":"2006","journal-title":"JAMA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1056\/NEJMoa1110186","article-title":"Truncations of titin causing dilated cardiomyopathy","volume":"366","author":"Herman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/ng.3719","article-title":"Titin-truncating variants affect heart function in disease cohorts and the general population","volume":"49","author":"Schafer","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/j.jacc.2017.08.063","article-title":"Phenotype and Clinical Outcomes of Titin Cardiomyopathy","volume":"70","author":"Tayal","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e002645","DOI":"10.1161\/JAHA.115.002645","article-title":"Role of Titin Missense Variants in Dilated Cardiomyopathy","volume":"4","author":"Begay","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e001896","DOI":"10.1161\/CIRCGEN.117.001896","article-title":"Outcomes of Contemporary Family Screening in Hypertrophic Cardiomyopathy","volume":"11","author":"Schinkel","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/cge.13157","article-title":"Utility of genetics for risk stratification in pediatric hypertrophic cardiomyopathy","volume":"93","author":"Mathew","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1136\/heartjnl-2014-306387","article-title":"Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy","volume":"101","author":"Lopes","year":"2015","journal-title":"Heart"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.jacc.2004.07.045","article-title":"Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy","volume":"44","author":"Vasile","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1161\/CIRCGENETICS.108.821314","article-title":"Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy","volume":"2","author":"Kaski","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ejmg.2010.07.007","article-title":"Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy","volume":"53","author":"Millat","year":"2010","journal-title":"Eur. J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mazzarotto, F., Girolami, F., Boschi, B., Barlocco, F., Tomberli, A., Baldini, K., Coppini, R., Tanini, I., Bardi, S., and Contini, E. (2018). Defining the diagnostic effectiveness of genes for inclusion in panels: The experience of two decades of genetic testing for hypertrophic cardiomyopathy at a single center. Genet. Med.","DOI":"10.1038\/s41436-018-0046-0"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Authors\/Task Force Members, Elliott, P.M., Anastasakis, A., Borger, M.A., Borggrefe, M., Cecchi, F., Charron, P., Hagege, A.A., Lafont, A., and Limongelli, G. (2014). 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur. Heart J., 35, 2733\u20132779.","DOI":"10.1093\/eurheartj\/ehu284"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/gim.2014.205","article-title":"Results of clinical genetic testing of 2912 probands with hypertrophic cardiomyopathy: Expanded panels offer limited additional sensitivity","volume":"17","author":"Alfares","year":"2015","journal-title":"Genet. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mademont-Soler, I., Mates, J., Yotti, R., Espinosa, M.A., Perez-Serra, A., Fernandez-Avila, A.I., Coll, M., Mendez, I., Iglesias, A., and Del Olmo, B. (2017). Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181465"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s12551-017-0305-3","article-title":"The Sydney Heart Bank: Improving translational research while eliminating or reducing the use of animal models of human heart disease","volume":"9","author":"Lal","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5339\/gcsp.2015.10","article-title":"Exploring cardiac biophysical properties","volume":"2015","author":"Bollensdorff","year":"2015","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00424-004-1363-5","article-title":"Sarcomeric determinants of striated muscle relaxation kinetics","volume":"449","author":"Poggesi","year":"2005","journal-title":"Pflugers Arch."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00424-008-0630-2","article-title":"Insights into the kinetics of Ca2+-regulated contraction and relaxation from myofibril studies","volume":"458","author":"Stehle","year":"2009","journal-title":"Pflugers Arch."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.mex.2016.02.006","article-title":"Instrumentation to study myofibril mechanics from static to artificial simulations of cardiac cycle","volume":"3","author":"Vikhorev","year":"2016","journal-title":"MethodsX"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1073\/pnas.85.9.3265","article-title":"Effect of Ca2+ on cross-bridge turnover kinetics in skinned single rabbit psoas fibers: Implications for regulation of muscle contraction","volume":"85","author":"Brenner","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/cvr\/cvt119","article-title":"Mutations in MYH7 reduce the force generating capacity of sarcomeres in human familial hypertrophic cardiomyopathy","volume":"99","author":"Piroddi","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3389\/fphys.2017.01103","article-title":"Cardiomyocyte Hypocontractility and Reduced Myofibril Density in End-Stage Pediatric Cardiomyopathy","volume":"8","author":"Bollen","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/0735-1097(92)90369-X","article-title":"Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: A multiple logistic regression analysis","volume":"20","author":"Zimmer","year":"1992","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10974-010-9205-x","article-title":"A piece of the human heart: Variance of protein phosphorylation in left ventricular samples from end-stage primary cardiomyopathy patients","volume":"30","author":"Holewijn","year":"2009","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_61","first-page":"15","article-title":"Protein Oxidative Modifications: Beneficial Roles in Disease and Health","volume":"1","author":"Cai","year":"2013","journal-title":"J. Biochem. Pharmacol. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wijnker, P.J.M., Sequeira, V., Kuster, D.W.D., and Velden, J.V. (2018). Hypertrophic Cardiomyopathy: A Vicious Cycle Triggered by Sarcomere Mutations and Secondary Disease Hits. Antioxid. Redox Signal.","DOI":"10.1089\/ars.2017.7236"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1161\/CIRCULATIONAHA.109.904557","article-title":"Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies","volume":"121","author":"Predmore","year":"2010","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bbadis.2014.11.003","article-title":"Sarcomeric protein isoform transitions in cardiac muscle: A journey to heart failure","volume":"1852","author":"Yin","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.yjmcc.2010.06.006","article-title":"Normal passive viscoelasticity but abnormal myofibrillar force generation in human hypertrophic cardiomyopathy","volume":"49","author":"Hoskins","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1161\/CIRCRESAHA.109.202440","article-title":"Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency","volume":"105","author":"Marston","year":"2009","journal-title":"Circ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1161\/CIRCRESAHA.111.300436","article-title":"Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations","volume":"112","author":"Sequeira","year":"2013","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1161\/CIRCHEARTFAILURE.111.963702","article-title":"Contractile dysfunction irrespective of the mutant protein in human hypertrophic cardiomyopathy with normal systolic function","volume":"5","author":"Paalberends","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1113\/jphysiol.2008.155952","article-title":"The familial hypertrophic cardiomyopathy-associated myosin mutation R403Q accelerates tension generation and relaxation of human cardiac myofibrils","volume":"586","author":"Belus","year":"2008","journal-title":"J. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00424-006-0181-3","article-title":"Tension generation and relaxation in single myofibrils from human atrial and ventricular myocardium","volume":"454","author":"Piroddi","year":"2007","journal-title":"Pflugers Arch."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1113\/jphysiol.2014.274571","article-title":"Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation","volume":"592","author":"Ferrara","year":"2014","journal-title":"J. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fphys.2018.00359","article-title":"Burst-Like Transcription of Mutant and Wildtype MYH7-Alleles as Possible Origin of Cell-to-Cell Contractile Imbalance in Hypertrophic Cardiomyopathy","volume":"9","author":"Montag","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.yjmcc.2013.01.001","article-title":"Familial hypertrophic cardiomyopathy: Functional effects of myosin mutation R723G in cardiomyocytes","volume":"57","author":"Kraft","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s00395-011-0205-9","article-title":"Unequal allelic expression of wild-type and mutated beta-myosin in familial hypertrophic cardiomyopathy","volume":"106","author":"Tripathi","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s10974-017-9486-4","article-title":"Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy","volume":"38","author":"Montag","year":"2017","journal-title":"J. Muscle Res. Cell Motil."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"14829","DOI":"10.1038\/s41598-017-13675-8","article-title":"Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes","volume":"7","author":"Vikhorev","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1093\/eurheartj\/ehu050","article-title":"Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy","volume":"35","author":"Posafalvi","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1113\/JP274145","article-title":"Genotype-specific pathogenic effects in human dilated cardiomyopathy","volume":"595","author":"Bollen","year":"2017","journal-title":"J. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e001631","DOI":"10.1161\/CIRCGENETICS.116.001631","article-title":"Lamin A\/C-Related Cardiac Disease: Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A\/C p.(Arg331Gln) Founder Mutation","volume":"10","author":"Hoorntje","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/cvr\/cvw192","article-title":"A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism","volume":"112","author":"Beqqali","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1161\/CIRCHEARTFAILURE.108.818237","article-title":"Functional analysis of a unique troponin c mutation, GLY159ASP, that causes familial dilated cardiomyopathy, studied in explanted heart muscle","volume":"2","author":"Dyer","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0014-5793(90)81234-F","article-title":"Molecular cloning of human cardiac troponin I using polymerase chain reaction","volume":"270","author":"Vallins","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1161\/CIRCULATIONAHA.109.850677","article-title":"Passive stiffness of myocardium from congenital heart disease and implications for diastole","volume":"121","author":"Chaturvedi","year":"2010","journal-title":"Circulation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0008-6363(02)00606-5","article-title":"Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins","volume":"57","author":"Papp","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1016\/j.ajpath.2017.08.022","article-title":"Myofilament Remodeling and Function Is More Impaired in Peripartum Cardiomyopathy Compared with Dilated Cardiomyopathy and Ischemic Heart Disease","volume":"187","author":"Bollen","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.yjmcc.2010.01.002","article-title":"Effect of troponin I Ser23\/24 phosphorylation on Ca2+-sensitivity in human myocardium depends on the phosphorylation background","volume":"48","author":"Kooij","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/cvr\/cvt144","article-title":"Differential changes in titin domain phosphorylation increase myofilament stiffness in failing human hearts","volume":"99","author":"Kotter","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/ehf2.12020","article-title":"Altered myocardial force generation in end-stage human heart failure","volume":"1","author":"Papp","year":"2014","journal-title":"ESC Heart Fail."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e004257","DOI":"10.1161\/CIRCHEARTFAILURE.117.004257","article-title":"Dose-Dependent Effects of the Myosin Activator Omecamtiv Mecarbil on Cross-Bridge Behavior and Force Generation in Failing Human Myocardium","volume":"10","author":"Mamidi","year":"2017","journal-title":"Circ. Heart Fail."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Jeong, M.Y., Lin, Y.H., Wennersten, S.A., Demos-Davies, K.M., Cavasin, M.A., Mahaffey, J.H., Monzani, V., Saripalli, C., Mascagni, P., and Reece, T.B. (2018). Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aao0144"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1038\/s41598-017-02247-5","article-title":"Associations between Left Ventricular Cavity Size and Cardiac Function and Overload Determined by Natriuretic Peptide Levels and a Covariance Structure Analysis","volume":"7","author":"Yoshida","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1038\/ejhg.2016.110","article-title":"Congenital dilated cardiomyopathy caused by biallelic mutations in Filamin C","volume":"24","author":"Reinstein","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/prca.200900071","article-title":"The use of phosphate-affinity SDS-PAGE to measure the cardiac troponin I phosphorylation site distribution in human heart muscle","volume":"3","author":"Messer","year":"2009","journal-title":"Proteom. Clin. Appl."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1161\/01.CIR.96.5.1495","article-title":"Troponin I phosphorylation in the normal and failing adult human heart","volume":"96","author":"Bodor","year":"1997","journal-title":"Circulation"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"27582","DOI":"10.1074\/jbc.M111.252320","article-title":"Molecular mechanism of the E99K mutation in cardiac actin (ACTC Gene) that causes apical hypertrophy in man and mouse","volume":"286","author":"Song","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/cvr\/cvm079","article-title":"Sarcomeric dysfunction in heart failure","volume":"77","author":"Hamdani","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/j.yjmcc.2010.09.007","article-title":"Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle","volume":"49","author":"Copeland","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/cvr\/cvn094","article-title":"The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy","volume":"79","author":"Jacques","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/cvr\/cvv181","article-title":"Uncoupling of myofilament Ca2+ sensitivity from troponin I phosphorylation by mutations can be reversed by epigallocatechin-3-gallate","volume":"108","author":"Papadaki","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.abb.2016.03.027","article-title":"Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation","volume":"601","author":"Messer","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fphys.2017.00348","article-title":"Investigations into the Sarcomeric Protein and Ca(2+)-Regulation Abnormalities Underlying Hypertrophic Cardiomyopathy in Cats (Felix catus)","volume":"8","author":"Messer","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1093\/cvr\/cvs322","article-title":"Myofibrillar Ca(2+) sensitivity is uncoupled from troponin I phosphorylation in hypertrophic obstructive cardiomyopathy due to abnormal troponin T","volume":"97","author":"Bayliss","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1016\/j.bpj.2014.10.024","article-title":"The dilated cardiomyopathy-causing mutation ACTC E361G in cardiac muscle myofibrils specifically abolishes modulation of Ca(2+) regulation by phosphorylation of troponin I","volume":"107","author":"Vikhorev","year":"2014","journal-title":"Biophys. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1161\/01.RES.0000267744.92677.7f","article-title":"The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23\/24 phosphorylation","volume":"100","author":"Biesiadecki","year":"2007","journal-title":"Circ. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3389\/fphys.2014.00315","article-title":"Investigating the role of uncoupling of troponin I phosphorylation from changes in myofibrillar Ca(2+)-sensitivity in the pathogenesis of cardiomyopathy","volume":"5","author":"Messer","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"R20","DOI":"10.1152\/ajpregu.00537.2006","article-title":"Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes","volume":"293","author":"Edes","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"McNamara, J.W., Li, A., Lal, S., Bos, J.M., Harris, S.P., van der Velden, J., Ackerman, M.J., Cooke, R., and Dos Remedios, C.G. (2017). MYBPC3 mutations are associated with a reduced super-relaxed state in patients with hypertrophic cardiomyopathy. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180064"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1161\/CIRCULATIONAHA.108.838672","article-title":"Cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy: Haploinsufficiency, deranged phosphorylation, and cardiomyocyte dysfunction","volume":"119","author":"Dooijes","year":"2009","journal-title":"Circulation"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1172\/JCI119555","article-title":"Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein","volume":"100","author":"Rottbauer","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1113\/JP273607","article-title":"Proteasome dysfunction in cardiomyopathies","volume":"595","author":"Gilda","year":"2017","journal-title":"J. Physiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/01.RES.0000143901.37063.2f","article-title":"Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts","volume":"95","author":"Makarenko","year":"2004","journal-title":"Circ. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1161\/01.CIR.0000135591.37759.AF","article-title":"Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy","volume":"110","author":"Nagueh","year":"2004","journal-title":"Circulation"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"270ra6","DOI":"10.1126\/scitranslmed.3010134","article-title":"Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease","volume":"7","author":"Roberts","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_114","first-page":"H1734","article-title":"Comparison of putative cooperative mechanisms in cardiac muscle: Length dependence and dynamic responses","volume":"276","author":"Rice","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1161\/01.CIR.85.3.1046","article-title":"Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure","volume":"85","author":"Beuckelmann","year":"1992","journal-title":"Circulation"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1172\/JCI114611","article-title":"Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium","volume":"85","author":"Gwathmey","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.hrthm.2010.04.008","article-title":"Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling","volume":"7","author":"Bayer","year":"2010","journal-title":"Heart Rhythm"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.yjmcc.2010.07.016","article-title":"Static and dynamic properties of the HCM myocardium","volume":"49","author":"Dewey","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10974-014-9374-0","article-title":"Muscle dysfunction in hypertrophic cardiomyopathy: What is needed to move to translation?","volume":"35","author":"Poggesi","year":"2014","journal-title":"J. Muscle Res. Cell. Motil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/8\/2234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:15:29Z","timestamp":1760195729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/8\/2234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,31]]},"references-count":119,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["ijms19082234"],"URL":"https:\/\/doi.org\/10.3390\/ijms19082234","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,31]]}}}