{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:14:36Z","timestamp":1784758476497,"version":"3.55.0"},"reference-count":98,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency and shifts substrate utilization toward greater oxidation of fatty acids and ketones, effects that correlate with long-term reverse remodeling on cardiac magnetic resonance imaging. Earlier metabolomic profiling demonstrated that CRT normalizes circulating energy metabolites, improving Krebs cycle intermediates and substrate balance between glucose and lipids, while baseline metabolite patterns may differentiate responders from non-responders. These metabolic adaptations accompany favorable changes in diastolic performance, right ventricular function, and ventriculo-arterial coupling. In parallel, improved splanchnic perfusion and reduced congestion may ameliorate gut dysbiosis and endotoxemia, mitigating systemic inflammation. Collectively, these findings position CRT as a therapy capable of both mechanical and metabolic restoration in advanced HF. In this review, we discuss the emerging data on how CRT reconditions myocardial energy metabolism, influences ventricular\u2013arterial interactions, and modulates peripheral and gut-derived metabolic pathways.<\/jats:p>","DOI":"10.3390\/medicina62030465","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pleiotropic Effects of Cardiac Resynchronization Therapy on Cardiometabolic Modulation in Heart Failure"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-6306","authenticated-orcid":false,"given":"Panagiotis","family":"Theofilis","sequence":"first","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5768-9125","authenticated-orcid":false,"given":"Panagiotis","family":"Iliakis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-5697","authenticated-orcid":false,"given":"Aikaterini-Eleftheria","family":"Karanikola","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michail","family":"Botis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Mavromoustakou","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-6875","authenticated-orcid":false,"given":"Panagiotis","family":"Xydis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-7015","authenticated-orcid":false,"given":"Nikolaos","family":"Ktenopoulos","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3561-5713","authenticated-orcid":false,"given":"Paschalis","family":"Karakasis","sequence":"additional","affiliation":[{"name":"Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6992-2906","authenticated-orcid":false,"given":"Ioannis","family":"Leontsinis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6340-3996","authenticated-orcid":false,"given":"Christina","family":"Chrysohoou","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-6725","authenticated-orcid":false,"given":"Konstantinos","family":"Tsioufis","sequence":"additional","affiliation":[{"name":"First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhao, C., Ma, T., He, L., Song, C., Cheng, X., and Bai, Y. (Hell. J. Cardiol., 2025). The additive association of cardiometabolic diseases with incident heart failure: A prospective cohort study, Hell. J. Cardiol., in press.","DOI":"10.1016\/j.hjc.2025.06.005"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vlachakis, P.K., Theofilis, P., Kachrimanidis, I., Giannakopoulos, K., Drakopoulou, M., Apostolos, A., Kordalis, A., Leontsinis, I., Tsioufis, K., and Tousoulis, D. (2024). The Role of Inflammasomes in Heart Failure. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105372"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102411","DOI":"10.1016\/j.cpcardiol.2024.102411","article-title":"Unraveling the complex pathophysiology of heart failure: Insights into the role of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS)","volume":"49","author":"Pharm","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/eurheartj\/ehaf645","article-title":"Do obesity and visceral adiposity promote heart failure with reduced ejection fraction?","volume":"47","author":"Packer","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/CIRCRESAHA.124.323800","article-title":"Mitochondrial Structure and Function in Human Heart Failure","volume":"135","author":"Hinton","year":"2024","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11897-023-00589-y","article-title":"Myocardial Metabolism in Heart Failure","volume":"20","author":"Ng","year":"2023","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/j.jacc.2025.08.054","article-title":"Pharmacologic Treatment of Heart Failure with Reduced Ejection Fraction: An Updated Systematic Review and Network Meta-Analysis","volume":"86","author":"Ceelen","year":"2025","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s10741-024-10469-9","article-title":"Conduction system pacing in heart failure: Time for a paradigm shift?","volume":"30","author":"Vlachakis","year":"2025","journal-title":"Heart Fail. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"euae143","DOI":"10.1093\/europace\/euae143","article-title":"Evolution and prognosis of tricuspid and mitral regurgitation following cardiac implantable electronic devices: A systematic review and meta-analysis","volume":"26","author":"Yuyun","year":"2024","journal-title":"Europace"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/joa3.12331","article-title":"The effect of cardiac resynchronization therapy on arterial stiffness and central hemodynamic parameters","volume":"36","author":"Coksevim","year":"2020","journal-title":"J. Arrhythmia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10741-018-9734-8","article-title":"Understanding non-response to cardiac resynchronisation therapy: Common problems and potential solutions","volume":"24","author":"Sieniewicz","year":"2019","journal-title":"Heart Fail. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1056\/NEJMoa013168","article-title":"Cardiac resynchronization in chronic heart failure","volume":"346","author":"Abraham","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1056\/NEJM200103223441202","article-title":"Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay","volume":"344","author":"Cazeau","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1056\/NEJMoa032423","article-title":"Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure","volume":"350","author":"Bristow","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1056\/NEJMoa050496","article-title":"The effect of cardiac resynchronization on morbidity and mortality in heart failure","volume":"352","author":"Cleland","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1056\/NEJMoa0906431","article-title":"Cardiac-resynchronization therapy for the prevention of heart-failure events","volume":"361","author":"Moss","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1009540","article-title":"Cardiac-resynchronization therapy for mild-to-moderate heart failure","volume":"363","author":"Tang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.jacc.2008.08.027","article-title":"Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms","volume":"52","author":"Linde","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(23)00912-1","article-title":"Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): A global, prospective, randomised controlled trial","volume":"402","author":"Wilkoff","year":"2023","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"euad289","DOI":"10.1093\/europace\/euad289","article-title":"Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: A systematic review and meta-analysis","volume":"25","author":"Veres","year":"2023","journal-title":"Europace"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/ejhf.3029","article-title":"Comorbidities and clinical response to cardiac resynchronization therapy: Patient-level meta-analysis from eight clinical trials","volume":"26","author":"Fudim","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/CIRCULATIONAHA.122.062124","article-title":"Cardiac Resynchronization Therapy Improves Outcomes in Patients with Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials","volume":"147","author":"Friedman","year":"2023","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S0140-6736(18)32216-5","article-title":"Beyond pharmacological treatment: An insight into therapies that target specific aspects of heart failure pathophysiology","volume":"393","author":"Normand","year":"2019","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e000937","DOI":"10.1136\/openhrt-2018-000937","article-title":"Outcomes of cardiac resynchronisation therapy in patients with heart failure with atrial fibrillation: A systematic review and meta-analysis of observational studies","volume":"6","author":"Mustafa","year":"2019","journal-title":"Open Heart"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1093\/eurheartj\/ehz109","article-title":"Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: Results from Phase I","volume":"40","author":"Leclercq","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.hrthm.2024.05.057","article-title":"Cardiac resynchronization therapy (CRT) nonresponders in the contemporary era: A state-of-the-art review","volume":"22","author":"Gerra","year":"2025","journal-title":"Heart Rhythm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s12471-014-0556-6","article-title":"Incidence of lead dislodgement, malfunction and perforation during the first year following device implantation","volume":"22","author":"Ghani","year":"2014","journal-title":"Neth. Heart J."},{"key":"ref_28","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_29","first-page":"8","article-title":"Multipoint left ventricular pacing effects on hemodynamic parameters and functional status: HUMVEE single-arm clinical trial (NCT03189368)","volume":"63","author":"Antoniou","year":"2022","journal-title":"Hell. J. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"euaf070","DOI":"10.1093\/europace\/euaf070","article-title":"Multipoint pacing is associated with reduction of heart failure hospitalizations or death in patients who do not respond to cardiac resynchronization therapy: Results of the MORE-CRT MPP randomized trial","volume":"27","author":"Leclercq","year":"2025","journal-title":"Europace"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1161\/01.CIR.0000088782.99568.CA","article-title":"Regional alterations in protein expression in the dyssynchronous failing heart","volume":"108","author":"Spragg","year":"2003","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1161\/CIRCULATIONAHA.107.706291","article-title":"Reversal of global apoptosis and regional stress kinase activation by cardiac resynchronization","volume":"117","author":"Chakir","year":"2008","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI200316326","article-title":"Linkage of beta1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+\/calmodulin kinase II","volume":"111","author":"Zhu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1073\/pnas.211086598","article-title":"The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy","volume":"98","author":"Liao","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1161\/CIRCULATIONAHA.108.794834","article-title":"Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy","volume":"119","author":"Aiba","year":"2009","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1161\/CIRCGENETICS.108.832345","article-title":"Cardiac resynchronization therapy corrects dyssynchrony-induced regional gene expression changes on a genomic level","volume":"2","author":"Barth","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/S0735-1097(03)00257-2","article-title":"Cardiac resynchronization therapy homogenizes myocardial glucose metabolism and perfusion in dilated cardiomyopathy and left bundle branch block","volume":"41","author":"Nowak","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/S0735-1097(99)00068-6","article-title":"Mapping of regional myocardial strain and work during ventricular pacing: Experimental study using magnetic resonance imaging tagging","volume":"33","author":"Prinzen","year":"1999","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1161\/CIRCGENETICS.109.871236","article-title":"Modulation of mitochondrial proteome and improved mitochondrial function by biventricular pacing of dyssynchronous failing hearts","volume":"3","author":"Agnetti","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1093\/eurheartj\/ehaf033","article-title":"Metabolic flexibility and reverse remodelling of the failing human heart","volume":"46","author":"Green","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.cardfail.2015.04.005","article-title":"Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure","volume":"21","author":"Nemutlu","year":"2015","journal-title":"J. Card. Fail."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11897-013-0181-5","article-title":"The relationship between cardiac resynchronization therapy and diastolic function","volume":"11","author":"Egnaczyk","year":"2014","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.jacc.2005.05.094","article-title":"Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance","volume":"46","author":"Waggoner","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s10554-014-0412-1","article-title":"Systolic heart failure and cardiac resynchronization therapy: A focus on diastole","volume":"30","author":"Facchini","year":"2014","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ahj.2007.02.033","article-title":"Improvement in diastolic function and left ventricular filling pressure induced by cardiac resynchronization therapy","volume":"153","author":"Jansen","year":"2007","journal-title":"Am. Heart J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.jacc.2010.01.077","article-title":"Effect of biventricular pacing on diastolic dyssynchrony","volume":"56","author":"Shanks","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.echo.2025.03.011","article-title":"Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography and for Heart Failure with Preserved Ejection Fraction Diagnosis: An Update from the American Society of Echocardiography","volume":"38","author":"Nagueh","year":"2025","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1093\/ehjci\/jeab163","article-title":"Left atrial strain is a predictor of left ventricular systolic and diastolic reverse remodelling in CRT candidates","volume":"23","author":"Galli","year":"2022","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1161\/CIRCHEARTFAILURE.112.000127","article-title":"Right ventricular function, pulmonary pressure estimation, and clinical outcomes in cardiac resynchronization therapy","volume":"6","author":"Campbell","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.cardfail.2010.09.002","article-title":"Tricuspid annular plane systolic excursion and response to cardiac resynchronization therapy: Results from the REVERSE trial","volume":"17","author":"Kjaergaard","year":"2011","journal-title":"J. Card. Fail."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/j.jacc.2013.02.049","article-title":"Interplay between right ventricular function and cardiac resynchronization therapy: An analysis of the CARE-HF trial (Cardiac Resynchronization-Heart Failure)","volume":"61","author":"Damy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/clc.22762","article-title":"Changes in parameters of right ventricular function with cardiac resynchronization therapy","volume":"40","author":"Sharma","year":"2017","journal-title":"Clin. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sidiropoulos, G., Karakasis, P., Antoniadis, A., Saplaouras, A., Karamitsos, T., and Fragakis, N. (2024). The Effect of Cardiac Resynchronization Therapy on Right Ventricular Function: A Systematic Review and Meta-Analysis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13144173"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/ejhf.1436","article-title":"The role of ventricular-arterial coupling in cardiac disease and heart failure: Assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association","volume":"21","author":"Ikonomidis","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/ejechocard\/jen184","article-title":"Ventricular-arterial coupling in patients with heart failure treated with cardiac resynchronization therapy: May we predict the long-term clinical response?","volume":"10","author":"Zanon","year":"2009","journal-title":"Eur. J. Echocardiogr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1161\/CIRCULATIONAHA.105.540435","article-title":"Hemodynamic effects of long-term cardiac resynchronization therapy: Analysis by pressure-volume loops","volume":"113","author":"Steendijk","year":"2006","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/pace.12585","article-title":"Cardiac resynchronization therapy acutely improves ventricular-arterial coupling by reducing the arterial load: Assessment by pressure-volume loops","volume":"38","author":"Pieragnoli","year":"2015","journal-title":"Pacing Clin. Electrophysiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yao, M., Wu, Z., Zhang, L., Ji, M., Qin, S., He, Q., Lin, Y., Xie, M., and Li, Y. (2025). Clinical Usefulness of Right Ventricular-Pulmonary Artery Coupling in Patients with Heart Failure. Diagnostics, 15.","DOI":"10.3390\/diagnostics15162083"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e007813","DOI":"10.1161\/CIRCIMAGING.118.007813","article-title":"Effect of Cardiac Resynchronization Therapy on Exercise-Induced Pulmonary Hypertension and Right Ventricular-Arterial Coupling","volume":"11","author":"Martens","year":"2018","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1007\/s10554-024-03233-5","article-title":"Right ventricular-pulmonary artery coupling in patients undergoing cardiac resynchronization therapy","volume":"40","author":"Roccabruna","year":"2024","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1002\/ehf2.13857","article-title":"Right ventricular-pulmonary artery coupling in cardiac resynchronization therapy: Evolution and prognosis","volume":"9","author":"Stassen","year":"2022","journal-title":"ESC Heart Fail"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mu, F., Tang, M., Guan, Y., Lin, R., Zhao, M., Zhao, J., Huang, S., Zhang, H., Wang, J., and Tang, H. (2022). Knowledge Mapping of the Links Between the Gut Microbiota and Heart Failure: A Scientometric Investigation (2006\u20132021). Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.882660"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.jacc.2007.07.016","article-title":"Altered intestinal function in patients with chronic heart failure","volume":"50","author":"Sandek","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000522284","article-title":"The Gut in Heart Failure: Current Knowledge and Novel Frontiers","volume":"31","author":"Gallo","year":"2022","journal-title":"Med. Princ. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/S0002-9149(97)00159-8","article-title":"Elevated soluble CD14 receptors and altered cytokines in chronic heart failure","volume":"79","author":"Anker","year":"1997","journal-title":"Am. J. Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/SHK.0b013e3181a2bcd6","article-title":"Systemic inflammation increases intestinal permeability during experimental human endotoxemia","volume":"32","author":"Hietbrink","year":"2009","journal-title":"Shock"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ijcard.2010.12.016","article-title":"Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure","volume":"157","author":"Sandek","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.cardfail.2015.09.017","article-title":"Intersections Between Microbiome and Heart Failure: Revisiting the Gut Hypothesis","volume":"21","author":"Nagatomo","year":"2015","journal-title":"J. Card. Fail."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1161\/01.CIR.102.25.3060","article-title":"Plasma cytokine parameters and mortality in patients with chronic heart failure","volume":"102","author":"Rauchhaus","year":"2000","journal-title":"Circulation"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1161\/01.CIR.0000077913.60364.D2","article-title":"Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-\u03b1, in patients with moderate-to-severe heart failure: Results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial","volume":"107","author":"Chung","year":"2003","journal-title":"Circulation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Verhaar, B.J.H., Prodan, A., Nieuwdorp, M., and Muller, M. (2020). Gut Microbiota in Hypertension and Atherosclerosis: A Review. Nutrients, 12.","DOI":"10.3390\/nu12102982"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1590\/1806-9282.20220197","article-title":"The role of gut dysbiosis-associated inflammation in heart failure","volume":"68","author":"Siqueira","year":"2022","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"F1211","DOI":"10.1152\/ajprenal.00298.2018","article-title":"Chronic kidney disease and the gut microbiome","volume":"316","author":"Hobby","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.3748\/wjg.v27.i25.3837","article-title":"Gut microbiota in obesity","volume":"27","author":"Liu","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2174\/1570161115666170428124756","article-title":"Non-pharmacological Modulation of the Autonomic Nervous System for Heart Failure Treatment: Where do We Stand?","volume":"16","author":"Tsioufis","year":"2017","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/FJC.0000000000001644","article-title":"Modulating Sympathetic Nervous System with the Use of SGLT2 Inhibitors: Where There Is Smoke, There Is Fire?","volume":"85","author":"Dimitriadis","year":"2025","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"304","DOI":"10.5603\/CJ.2013.0076","article-title":"Acute effects of cardiac resynchronization therapy on arterial distensibility and serum norepinephrine levels in advanced heart failure","volume":"20","author":"Yildiz","year":"2013","journal-title":"Cardiol. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2012.06.021","article-title":"Adipose tissue renin-angiotensin-aldosterone system (RAAS) and progression of insulin resistance","volume":"378","author":"Marcus","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.pcad.2025.06.003","article-title":"Heart rate variability in patients with cardiovascular diseases","volume":"91","author":"Khan","year":"2025","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/CM9.0000000000001165","article-title":"Electrical stimulation induces mitochondrial autophagy via activating oxidative stress and Sirt3 signaling pathway","volume":"134","author":"Dong","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1161\/CIRCRESAHA.111.253864","article-title":"Cardiac resynchronization therapy and reverse molecular remodeling: Importance of mitochondrial redox signaling","volume":"109","author":"Zweier","year":"2011","journal-title":"Circ. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.jtcvs.2006.01.027","article-title":"Restoration of myocardial beta-adrenergic receptor signaling after left ventricular assist device support","volume":"131","author":"Pandalai","year":"2006","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Manolis, A.A., Manolis, T.A., and Manolis, A.S. (2023). Neurohumoral Activation in Heart Failure. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015472"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Manta, E., Iliakis, P., Fragoulis, C., Leontsinis, I., Stamoulopoulos, I., Chrysohoou, C., and Tsioufis, K. (2025). Tracking Pathways Linking Obesity with Heart Failure. Nutrients, 17.","DOI":"10.3390\/nu17071250"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7292564","DOI":"10.1155\/2016\/7292564","article-title":"Cardiac Resynchronization Therapy Outcomes in Type 2 Diabetic Patients: Role of MicroRNA Changes","volume":"2016","author":"Sardu","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_88","first-page":"1","article-title":"The impact of cardiac resynchronization therapy on routine laboratory parameters","volume":"9","author":"Boros","year":"2017","journal-title":"Interv. Med. Appl. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jacasi.2023.06.001","article-title":"A Comprehensive Insight and Mechanistic Understanding of the Lipidomic Alterations Associated with DCM","volume":"3","author":"Saha","year":"2023","journal-title":"JACC Asia"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bednarski, T.K., Duda, M.K., and Dobrzyn, P. (2022). Alterations of Lipid Metabolism in the Heart in Spontaneously Hypertensive Rats Precedes Left Ventricular Hypertrophy and Cardiac Dysfunction. Cells, 11.","DOI":"10.3390\/cells11193032"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"114058","DOI":"10.1016\/j.biopha.2022.114058","article-title":"Diuretic resistance in patients with kidney disease: Challenges and opportunities","volume":"157","author":"Guo","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.hroo.2021.05.007","article-title":"The physiological effects of cardiac resynchronization therapy on aortic and pulmonary flow and dynamic and static components of systemic impedance","volume":"2","author":"Sidhu","year":"2021","journal-title":"Heart Rhythm O2"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.cardfail.2008.03.009","article-title":"Cardiac resynchronization therapy improves renal function in human heart failure with reduced glomerular filtration rate","volume":"14","author":"Boerrigter","year":"2008","journal-title":"J. Card. Fail."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ipej.2016.11.006","article-title":"Cardiac Resynchronization Therapy prevents progression of renal failure in heart failure patients","volume":"16","author":"Jeevanantham","year":"2016","journal-title":"Indian Pacing Electrophysiol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1253\/circj.CJ-08-0424","article-title":"Preservation of renal function in response to cardiac resynchronization therapy","volume":"72","author":"Kimura","year":"2008","journal-title":"Circ. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jjcc.2017.04.001","article-title":"Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy","volume":"70","author":"Hosoda","year":"2017","journal-title":"J. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1161\/CIRCEP.112.973776","article-title":"Reasons for loss of cardiac resynchronization therapy pacing: Insights from 32,844 patients","volume":"5","author":"Cheng","year":"2012","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Theuns, D., Radhoe, S.P., and Brugts, J.J. (2021). Remote Monitoring of Heart Failure in Patients with Implantable Cardioverter-Defibrillators: Current Status and Future Needs. 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