{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:08:36Z","timestamp":1788962916233,"version":"build-2803163510"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome in which coronary microvascular dysfunction (CMD) emerges as a central, prevalent pathobiologic substrate across multiple phenotypic clusters. CMD in HFpEF arises from intertwined mechanisms including systemic inflammation, impaired NO-cGMP-PKG signaling, microvascular rarefaction and fibrosis, mitochondrial dysfunction, and ventriculoarterial decoupling that together promote subendocardial ischemia, diastolic stiffness, reduced reserve, and adverse outcomes. Advances in diagnostics, both invasive and non-invasive, as well as individualized medical and surgical intervention, create avenues of opportunity to prevent CMD-mediated HFpEF at a precise level. Sepsis and septic shock can superimpose an acute second hit on this chronically injured microvasculature, precipitating acute decompensation and potentially accelerating long-term CMD-driven remodeling in vulnerable HFpEF patients. While mechanistically plausible, this association remains hypothesis-generating. Advanced hemodynamics and diagnostics with tailored vasopressor and inotropic management need to be better studied in complex states of septic shock in HFpEF patients to understand the influence of CMD in such states.<\/jats:p>","DOI":"10.3389\/fmed.2026.1812235","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:14:42Z","timestamp":1788959682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Coronary microvascular dysfunction in HFpEF: pathophysiologic mechanisms, diagnosis, treatments, and the amplifying potential of sepsis"],"prefix":"10.3389","volume":"13","author":[{"given":"Sharnvir","family":"Chattha","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Sunrise Health GME Consortium, HCA Healthcare","place":["Las Vegas, NV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kush","family":"Kapadia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Sunrise Health GME Consortium, HCA Healthcare","place":["Las Vegas, NV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lynch","sequence":"additional","affiliation":[{"name":"ATSU-Kirksville College of Osteopathic Medicine","place":["Kirksville, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"McWhorter","sequence":"additional","affiliation":[{"name":"Department of Intensive Critical Care, Sunrise Health GME Consortium, HCA Healthcare","place":["Las Vegas, NV, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.hfc.2014.04.008","article-title":"Phenotypic Spectrum of heart failure with preserved ejection fraction","volume":"10","author":"Shah","year":"2014","journal-title":"Heart Fail Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1161\/CIRCULATIONAHA.114.010637","article-title":"Phenomapping for novel classification of heart failure with preserved ejection fraction","volume":"131","author":"Shah","year":"2015","journal-title":"Circulation"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.3389\/fphys.2019.01347","article-title":"Microvascular dysfunction in heart failure with preserved ejection fraction","volume":"10","author":"D'Amario","year":"2019","journal-title":"Front Physiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"4431","DOI":"10.1093\/eurheartj\/ehab653","article-title":"Untangling the pathophysiologic link between coronary microvascular dysfunction and heart failure with preserved ejection fraction","volume":"42","author":"Sinha","year":"2021","journal-title":"Eur Heart J"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1097\/HCO.0000000000001082","article-title":"Coronary microvascular dysfunction and heart failure with preserved ejection fraction: what are the mechanistic links?","volume":"38","author":"Sinha","year":"2023","journal-title":"Curr Opin Cardiol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"102714","DOI":"10.1016\/j.jchf.2025.102714","article-title":"Rationale and design of the HeartShare\/AMP-HF deep phenotyping study to improve understanding of heart failure with preserved ejection fraction","volume":"13","author":"Borlaug","year":"2025","journal-title":"JACC: Heart Failure"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/ejhf.3105","article-title":"Clinical phenogroup diversity and multiplicity: impact on mechanisms of exercise intolerance in heart failure with preserved ejection fraction","volume":"26","author":"Larson","year":"2024","journal-title":"Eur J Heart Fail"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1161\/CIRCULATIONAHA.106.678359","article-title":"Sepsis and the heart","volume":"116","author":"Merx","year":"2007","journal-title":"Circulation"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.4266\/acc.2020.00248","article-title":"Sepsis-induced cardiac dysfunction: a review of pathophysiology","volume":"35","author":"Habimana","year":"2020","journal-title":"Acute Crit Care"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1164\/rccm.200109-016OC","article-title":"Microvascular blood flow is altered in patients with sepsis","volume":"166","author":"De Backer","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"100983","DOI":"10.1016\/j.ajpc.2025.100983","article-title":"Coronary microvascular dysfunction and its role in heart failure with preserved ejection fraction for future prevention and treatment","volume":"22","author":"Bond","year":"2025","journal-title":"Am J Prev Cardiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1016\/j.jcin.2020.04.040","article-title":"The impact of coronary physiology on contemporary clinical decision making","volume":"13","author":"Kogame","year":"2020","journal-title":"J Am Coll Cardiol Intv"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"100302","DOI":"10.1016\/j.ahjo.2023.100302","article-title":"INOCA\/ANOCA: mechanisms and novel treatments","volume":"30","author":"Ashokprabhu","year":"2023","journal-title":"Am Heart J Plus"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12928-025-01197-4","article-title":"Interventional diagnostic procedures in INOCA: an essential approach in ischemic heart disease","volume":"41","author":"Matsuzawa","year":"2025","journal-title":"Cardiovasc Interv Ther"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"102345","DOI":"10.1016\/j.jacadv.2025.102345","article-title":"The role of coronary microvascular dysfunction in heart failure with preserved ejection fraction","volume":"4","author":"Tzoumas","year":"2025","journal-title":"JACC Adv"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1093\/eurheartj\/ehab775","article-title":"Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis","volume":"43","author":"Kelshiker","year":"2022","journal-title":"Eur Heart J"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.ijcard.2017.08.068","article-title":"International standardization of diagnostic criteria for microvascular angina","volume":"250","author":"Ong","year":"2018","journal-title":"Int J Cardiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1600947","DOI":"10.3389\/fcvm.2025.1600947","article-title":"Exploring coronary microvascular dysfunction from functional impairment and structural damage","volume":"12","author":"Wen","year":"2026","journal-title":"Front Cardiovasc Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.amjcard.2012.05.014","article-title":"Prevalence, clinical phenotype, and outcomes associated with Normal B-type natriuretic peptide levels in heart failure with preserved ejection fraction","volume":"110","author":"Anjan","year":"2012","journal-title":"Am J Cardiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1093\/eurheartj\/ehy531","article-title":"Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF","volume":"39","author":"Shah","year":"2018","journal-title":"Eur Heart J"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1161\/CIRCULATIONAHA.118.034271","article-title":"Sex differences in cardiovascular pathophysiology: why women are overrepresented in heart failure with preserved ejection fraction","volume":"138","author":"Beale","year":"2018","journal-title":"Circulation"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.jacc.2019.12.049","article-title":"Menopause-related estrogen decrease and the pathogenesis of HFpEF: JACC review topic of the week","volume":"75","author":"Sabbatini","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1056\/NEJMoa1908655","article-title":"Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction (PARAGON-HF)","volume":"381","author":"Solomon","year":"2019","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"103611","DOI":"10.1016\/j.jaccas.2025.103611","article-title":"Transient coronary microvascular dysfunction in septic shock","volume":"30","author":"Lorstad","year":"2025","journal-title":"JACC Case Rep"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e70605","DOI":"10.14814\/phy2.70605","article-title":"Myocardial blood flow in patients with sepsis","volume":"13","author":"Christiansen","year":"2025","journal-title":"Physiol Rep"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"46","DOI":"10.14336\/ad.2022.0523","article-title":"The NO-cGMP-PKG axis in HFpEF: from pathological mechanisms to potential therapies","volume":"14","author":"Cai","year":"2022","journal-title":"Aging Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"517999","DOI":"10.3389\/fmed.2020.517999","article-title":"Clinical outcome of septic patients with heart failure with preserved ejection fraction presenting to the emergency department of a tertiary hospital: a retrospective cohort study","volume":"7","author":"Bou Chebl","year":"2020","journal-title":"Front Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e2235331","DOI":"10.1001\/jamanetworkopen.2022.35331","article-title":"Association between preexisting heart failure with reduced ejection fraction and fluid administration among patients with Sepsis","volume":"5","author":"Powell","year":"2022","journal-title":"JAMA Netw Open"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"102696","DOI":"10.1016\/j.cpcardiol.2024.102696","article-title":"Sepsis and septic shock outcomes and 90-day readmissions in heart failure with reduced ejection fraction: a national readmission database study","volume":"49","author":"Mohamoud","year":"2024","journal-title":"Curr Probl Cardiol"},{"key":"ref30","article-title":"In-hospital outcomes and sex differences in septic heart failure patients","author":"Antia","year":"2024","journal-title":"J Hosp Med"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"20","DOI":"10.2478\/jccm-2026-0005","article-title":"Evidence-based fluid resuscitation of the septic HFpEF patient: a narrative review of the literature","volume":"12","author":"Ward","year":"2025","journal-title":"J Crit Care Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e12718","DOI":"10.1111\/micc.12718","article-title":"Coronary microvascular dysfunction pathophysiology in COVID-19","volume":"28","author":"Yin","year":"2021","journal-title":"Microcirculation"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1001\/jama.288.23.2981","article-title":"Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic (ALLHAT)","volume":"288","year":"2002","journal-title":"JAMA"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction","volume":"62","author":"Paulus","year":"2013","journal-title":"J Am Coll Cardiol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e70521","DOI":"10.14814\/phy2.70521","article-title":"Coronary microvascular disease in heart failure with preserved ejection fraction","volume":"13","author":"Sen","year":"2025","journal-title":"Physiol Rep"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1161\/CIRCULATIONAHA.120.045810","article-title":"Proteomic evaluation of the comorbidity-inflammation paradigm in heart failure with preserved ejection fraction","volume":"142","author":"Sanders-van Wijk","year":"2020","journal-title":"Circulation"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.15420\/ecr.2020.47","article-title":"Role of inflammation in coronary Epicardial and microvascular dysfunction","volume":"16","author":"Godo","year":"2021","journal-title":"Eur Cardiol Rev"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.jcmg.2021.11.022","article-title":"Prevalence and prognostic significance of microvascular dysfunction in heart failure with preserved ejection fraction","volume":"15","author":"Arnold","year":"2022","journal-title":"JACC Cardiovasc Imaging"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1159\/000501100","article-title":"Endothelin 1 is associated with heart failure hospitalization and long-term mortality in patients with heart failure with preserved ejection fraction and pulmonary hypertension","volume":"143","author":"Chowdhury","year":"2019","journal-title":"Cardiology"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e003381","DOI":"10.1161\/CIRCHEARTFAILURE.116.003381","article-title":"Dual endothelin-a\/endothelin-B receptor blockade and cardiac remodeling in heart failure with preserved ejection fraction","volume":"9","author":"Valero-Munoz","year":"2016","journal-title":"Circ Heart Fail"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12968-018-0511-6","article-title":"The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study","volume":"20","author":"Mahmod","year":"2018","journal-title":"J Cardiovasc Magn Reson"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1161\/circresaha.123.324103","article-title":"Blunted cardiac mitophagy in response to metabolic stress contributes to HFpEF","volume":"135","author":"Yoshii","year":"2024","journal-title":"Circ Res"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1159\/000548233","article-title":"The mechanisms associated with inflammation and coronary microvascular dysfunction in heart failure with preserved ejection fraction","volume":"35","author":"Yan","year":"2025","journal-title":"Med Princ Pract"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"795","DOI":"10.21037\/atm.2020.04.10","article-title":"Understanding ventriculo-arterial coupling","volume":"8","author":"Monge Garcia","year":"2020","journal-title":"Ann Transl Med"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1097\/MCC.0000000000000721","article-title":"How to assess ventriculoarterial coupling in sepsis","volume":"26","author":"Pinsky","year":"2020","journal-title":"Curr Opin Crit Care"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1002\/ejhf.1542","article-title":"Application of the H2FPEF score to a global clinical trial of patients with heart failure with preserved ejection fraction: the TOPCAT trial","volume":"21","author":"Myhre","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1161\/circheartfailure.121.008935","article-title":"The value of passive leg raise during right heart catheterization in diagnosing heart failure with preserved ejection fraction","volume":"15","author":"van de Bovenkamp","year":"2022","journal-title":"Circ Heart Fail"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1002\/ehf2.13979","article-title":"Exercise haemodynamics in heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"9","author":"Baratto","year":"2022","journal-title":"ESC Heart Fail"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1161\/CIRCRESAHA.117.312180","article-title":"Teasing apart heart failure with preserved ejection fraction phenotypes with echocardiographic imaging","volume":"122","author":"Argulian","year":"2018","journal-title":"Circ Res"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","article-title":"Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"29","author":"Nagueh","year":"2016","journal-title":"J Am Soc Echocardiogr"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.jjcc.2019.06.004","article-title":"Use of speckle tracking to assess heart failure with preserved ejection fraction","volume":"74","author":"Hiebert","year":"2019","journal-title":"J Cardiol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"4438","DOI":"10.3390\/jcm12134438","article-title":"Prognostic role of metabolic exercise testing in heart failure","volume":"12","author":"Agdamag","year":"2023","journal-title":"J Clin Med"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s11883-023-01116-z","article-title":"Coronary microvascular dysfunction: what clinicians and investigators should know","volume":"25","author":"Marano","year":"2023","journal-title":"Curr Atheroscler Rep"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ijcard.2022.09.047","article-title":"Ischemia with no obstructive coronary artery disease (INOCA): a patient self-report quality of life survey from INOCA international","volume":"371","author":"Gulati","year":"2023","journal-title":"Int J Cardiol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/j.jcmg.2019.09.006","article-title":"Cardiovascular imaging techniques to assess microvascular dysfunction","volume":"13","author":"Mathew","year":"2020","journal-title":"JACC Cardiovasc Imaging"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e012568","DOI":"10.1161\/CIRCINTERVENTIONS.122.012568","article-title":"Coronary microvascular disease in contemporary clinical practice","volume":"16","author":"Smilowitz","year":"2023","journal-title":"Circ Cardiovasc Interv"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1016\/j.jacc.2018.09.006","article-title":"Stratified medical therapy using invasive coronary function testing in angina (CORMICA)","volume":"72","author":"Ford","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.jacc.2021.07.042","article-title":"Coronary microvascular dysfunction across the spectrum of cardiovascular diseases","volume":"78","author":"Del Buono","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.jcmg.2024.07.023","article-title":"Myocardial blood flow quantification using stress cardiac magnetic resonance improves detection of coronary artery disease","volume":"17","author":"Wang","year":"2024","journal-title":"JACC Cardiovasc Imaging"},{"key":"ref60","doi-asserted-by":"crossref","DOI":"10.1016\/j.jcmg.2022.12.015","article-title":"PET for detection and reporting coronary microvascular dysfunction","author":"Schindler","year":"2023","journal-title":"JACC Cardiovasc Imaging"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.autrev.2018.09.002","article-title":"Nailfold avascular score and coronary microvascular dysfunction in systemic sclerosis: a newsworthy association","volume":"18","author":"Zanatta","year":"2018","journal-title":"Autoimmun Rev"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/s0735-1097(22)01983-0","article-title":"Neutrophils and NETosis in women with coronary microvascular dysfunction: a hypothesis generating study","volume":"79","author":"Levit","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1097\/SHK.0000000000002290","article-title":"Invasive hemodynamic monitoring with pulmonary artery catheter in Sepsis-associated cardiogenic shock","volume":"61","author":"Sato","year":"2023","journal-title":"Shock"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"105786","DOI":"10.1016\/j.jaccas.2025.105786","article-title":"Using dP\/dt contour analysis to wean IABP\/inotropic support in a cardiogenic shock patient","volume":"30","author":"Kapadia","year":"2025","journal-title":"JACC Case Rep"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1186\/s13054-019-2654-8","article-title":"Continual measurement of arterial dP\/dtmax enables minimally invasive monitoring of left ventricular contractility in patients with acute heart failure","volume":"23","author":"Ostadal","year":"2019","journal-title":"Crit Care"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N Engl J Med"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1056\/nejmoa2206286","article-title":"Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction","volume":"387","author":"Solomon","year":"2022","journal-title":"N Engl J Med"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1186\/s12872-025-05127-3","article-title":"The role of SGLT2 inhibitors in heart failure with preserved ejection fraction: a systematic review and meta-analysis of randomized controlled trials","volume":"25","author":"Minisy","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"key":"ref69","doi-asserted-by":"crossref","DOI":"10.15420\/cfr.2022.11","article-title":"Clinical evidence and proposed mechanisms of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction","author":"Deschaine","year":"2022","journal-title":"Card Fail Rev"},{"key":"ref70","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa2306963","article-title":"Semaglutide in patients with heart failure with preserved ejection fraction and obesity","volume":"389","author":"Kosiborod","year":"2023","journal-title":"N Engl J Med"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for heart failure with preserved ejection fraction and obesity","volume":"392","author":"Packer","year":"2024","journal-title":"N Engl J Med"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.cardfail.2025.01.022","article-title":"Efficacy of GLP-1 receptor agonists in patients with heart failure and mildly reduced or preserved ejection fraction: a systematic review and meta-analysis","volume":"31","author":"Waqas","year":"2025","journal-title":"J Card Fail"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/S0140-6736(24)01498-3","article-title":"Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial","volume":"404","author":"Deanfield","year":"2024","journal-title":"Lancet"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"e28145","DOI":"10.7759\/cureus.28145","article-title":"The efficacy of various pharmacological agents on long-term outcomes in patients with heart failure with preserved ejection fraction: a Meta-analysis of randomized control trials","volume":"14","author":"Faisal","year":"2022","journal-title":"Cureus"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1056\/NEJMoa1313731","article-title":"Spironolactone for heart failure with preserved ejection fraction (TOPCAT)","volume":"370","author":"Pitt","year":"2014","journal-title":"N Engl J Med"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJMoa2407107","article-title":"Finerenone in heart failure with mildly reduced or preserved ejection fraction (FINEARTS-HF)","volume":"391","author":"Solomon","year":"2024","journal-title":"N Engl J Med"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1093\/ejhf\/xuag083","article-title":"Finerenone, eplerenone, and spironolactone in heart failure with preserved ejection fraction: a Bayesian network meta-analysis of efficacy and safety","author":"Bagattoli","year":"2026","journal-title":"Eur J Heart Fail"},{"key":"ref78","volume-title":"Nebivolol ANOCA Treatment Randomized Trial (MOTORS)","year":""},{"key":"ref79","doi-asserted-by":"crossref","DOI":"10.1001\/jamacardio.2025.0103","article-title":"Novel controlled metabolic accelerator for obesity-related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial","author":"Pandey","year":"2025","journal-title":"JAMA Cardiol"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1161\/CIRCRESAHA.120.317046","article-title":"NAD+ repletion reverses heart failure with preserved ejection fraction","volume":"128","author":"Tong","year":"2021","journal-title":"Circ Res"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.cardfail.2023.04.003","article-title":"Myeloperoxidase inhibition in heart failure with preserved or mildly reduced ejection fraction: SATELLITE trial results","volume":"30","author":"Lam","year":"2023","journal-title":"J Card Fail"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1371\/journal.pone.0042623","article-title":"Stimulators of soluble guanylyl cyclase: future clinical indications","volume":"13","author":"Nossaman","year":"2013","journal-title":"Ochsner J"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/clc.20935","article-title":"Effect of phosphodiesterase type 5 inhibition on microvascular coronary dysfunction in women: a women's ischemia syndrome evaluation (WISE) ancillary study","volume":"34","author":"Denardo","year":"2011","journal-title":"Clin Cardiol"},{"key":"ref84","author":"Jiang","year":"2021"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1001\/jama.2013.2024","article-title":"Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction (RELAX)","volume":"309","author":"Redfield","year":"2013","journal-title":"JAMA"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1001\/jama.2020.15922","article-title":"Effect of vericiguat vs placebo on quality of life in patients with heart failure and preserved ejection fraction (VITALITY-HFpEF)","volume":"324","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1001\/jama.2020.16641","article-title":"Effect of praliciguat on peak rate of oxygen consumption in patients with heart failure with preserved ejection fraction (CAPACITY HFpEF)","volume":"324","author":"Udelson","year":"2020","journal-title":"JAMA"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"e010802","DOI":"10.1161\/CIRCINTERVENTIONS.121.010802","article-title":"Autologous CD34+ stem cell therapy increases coronary flow reserve and reduces angina in patients with coronary microvascular dysfunction","volume":"15","author":"Henry","year":"2022","journal-title":"Circ Cardiovasc Interv"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"e002360","DOI":"10.1136\/openhrt-2023-002360","article-title":"Colchicine in patients with heart failure and preserved left ventricular ejection fraction: rationale and design of a prospective, randomised, open-label, crossover clinical trial","volume":"10","author":"Shchendrygina","year":"2023","journal-title":"Open Heart"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1001\/jamacardio.2024.2435","article-title":"Verinurad plus allopurinol for heart failure with preserved ejection fraction","volume":"9","author":"Kitzman","year":"2024","journal-title":"JAMA Cardiol"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1001\/jamacardio.2024.3810","article-title":"Cardiac myosin inhibition in heart failure with normal and supranormal ejection fraction","volume":"10","author":"Shah","year":"2024","journal-title":"JAMA Cardiol"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"e011381","DOI":"10.1161\/CIRCHEARTFAILURE.123.011381","article-title":"Macitentan for heart failure with preserved or mildly reduced ejection fraction and pulmonary vascular disease: results of the SERENADE randomized clinical trial and open-label extension study","volume":"18","author":"Shah","year":"2025","journal-title":"Circ Heart Fail"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1056\/NEJMoa1402556","article-title":"Efficacy of a device to narrow the coronary sinus in refractory angina (COSIRA)","volume":"372","author":"Verheye","year":"2015","journal-title":"N Engl J Med"},{"key":"ref94","volume-title":"Efficacy of the Coronary Sinus Reducer in Patients With Refractory Angina II (COSIRA-II)","year":""},{"key":"ref95","doi-asserted-by":"publisher","first-page":"2275","DOI":"10.1002\/ejhf.2619","article-title":"Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF)","volume":"24","author":"Linde","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"ref96","volume-title":"Assessment of CCM in HF With Higher Ejection Fraction (AIM HIGHer)","year":""},{"key":"ref97","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1016\/j.jacc.2019.08.1062","article-title":"Effects of interatrial shunt on pulmonary vascular function in heart failure with preserved ejection fraction","volume":"74","author":"Obokata","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1161\/CIRCULATIONAHA.124.070870","article-title":"Interatrial shunt treatment for heart failure: the randomized RELIEVE-HF trial","volume":"150","author":"Stone","year":"2024","journal-title":"Circulation"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1001\/jamacardio.2024.0520","article-title":"Atrial shunt device effects on cardiac structure and function in heart failure with preserved ejection fraction: The REDUCE LAP-HF II Randomized Clinical Trial.","volume":"9","author":"Patel","year":"2024","journal-title":"JAMA Cardiol"},{"key":"ref100","volume-title":"Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure (RESPONDER-HF)","year":""},{"key":"ref101","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jacbts.2024.02.010","article-title":"Heart failure solutions","volume":"9","author":"Borlaug","year":"2024","journal-title":"JACC Basic Transl Sci"},{"key":"ref102","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.230142","article-title":"A numerical study of a left ventricular expander for heart failure with preserved ejection fraction","volume":"10","author":"Weissmann","year":"2023","journal-title":"R Soc Open Sci"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1097\/CCM.0000000000007016","article-title":"Vasoactive medications and the microcirculation in septic shock: a scoping review","volume":"54","author":"Sathianathan","year":"2026","journal-title":"Crit Care Med"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1186\/s13054-025-05540-2","article-title":"Vasopressin and its analogues in patients with septic shock: holy grail or unfulfilled promise?","volume":"29","author":"Lajoye","year":"2025","journal-title":"Crit Care"},{"key":"ref105","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1016\/j.jcmg.2021.03.031","article-title":"Cardiac sympathetic activity by 123I-Meta-Iodobenzylguanidine imaging in women with coronary microvascular dysfunction","volume":"14","author":"Mehta","year":"2021","journal-title":"JACC Cardiovasc Imaging"},{"key":"ref106","first-page":"438","article-title":"Vasopressor and inotropic management of patients with septic shock","volume":"40","author":"Pollard","year":"2015","journal-title":"Pharm Therap"},{"key":"ref107","doi-asserted-by":"publisher","first-page":"e015026","DOI":"10.1161\/JAHA.119.015026","article-title":"Extended-release Oral Milrinone for the treatment of heart failure with preserved ejection fraction","volume":"9","author":"Nanayakkara","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1016\/j.jacc.2016.03.539","article-title":"Effects of Milrinone on rest and exercise hemodynamics in heart failure with preserved ejection fraction","volume":"67","author":"Kaye","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3389\/fcvm.2024.1520596","article-title":"Levosimendan for sepsis-induced myocardial dysfunction: friend or foe?","volume":"11","author":"Du","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"ref110","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1358735","article-title":"Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis","volume":"15","author":"Tan","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref111","first-page":"360","article-title":"Levosimendan improves hemodynamics and exercise tolerance in PH-HFpEF","volume":"9","author":"Burkhoff","year":"2021","journal-title":"JACC: Heart Fail"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"18968","DOI":"10.1038\/s41598-025-02400-5","article-title":"Tailored treatment of specific diagnosis improves symptoms and quality of life in patients with myocardial ischemia and non-obstructive coronary arteries","volume":"15","author":"Szolc","year":"2025","journal-title":"Sci Rep"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"1111721","DOI":"10.3389\/fcvm.2023.1111721","article-title":"Coronary microvascular dysfunction: a review of recent progress and clinical implications","volume":"10","author":"Rehan","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"ref114","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1177\/0885066620928299","article-title":"Sepsis with preexisting heart failure: management of confounding clinical features","volume":"36","author":"Jones","year":"2020","journal-title":"J Intensive Care Med"},{"key":"ref115","volume-title":"Coronary Microvascular Dysfunction in HFpEF: The hidden Endotype behind Diastolic Heart Failure","author":"Rahaman","year":"2025"},{"key":"ref116","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1093\/eurheartj\/ehx721","article-title":"Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction","volume":"39","author":"Taqueti","year":"2018","journal-title":"Eur Heart J"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.11.003","article-title":"Optical coherence tomography angiography","volume":"64","author":"Spaide","year":"2018","journal-title":"Prog Retin Eye Res"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.cardfail.2023.10.024","article-title":"HERMES: effects of ziltivekimab versus placebo on morbidity and mortality in patients with heart failure with mildly reduced or preserved ejection fraction and systemic inflammation","volume":"30","author":"Petrie","year":"2024","journal-title":"J Card Fail"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1812235\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:14:46Z","timestamp":1788959686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1812235\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":118,"alternative-id":["10.3389\/fmed.2026.1812235"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1812235","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"article-number":"1812235"}}