Successful Use of Levosimendan in Managing Refractory Coronary Vasospasm Leading to Recurrent Cardiac Arrests: A Case Report

Successful Use of Levosimendan in Managing Refractory Coronary Vasospasm Leading to Recurrent Cardiac Arrests: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Successful Use of Levosimendan in Managing Refractory Coronary Vasospasm Leading to Recurrent Cardiac Arrests: A Case Report Kristoffer Ken Ralota, Wendy Wang, Jamie Layland This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4594151/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Coronary vasospasm can be life threatening and can be refractory. First line therapies include calcium channel blockers and nitrates; however, they have variable effectiveness. This case report presents a case of refractory coronary artery vasospasm presenting with ST elevation and recurrent cardiac arrest who was treated with levosimendan, a distinctive inodilator with calcium-sensitising and ATP-sensitive potassium channel opening properties, highlighting its potential therapeutic role in this clinical setting. Case Presentation: A 57-year-old male with an established diagnosis of coronary vasospasm presenting with ST elevation in the inferior leads and suffered multiple cardiac arrests, initially treated with electrical defibrillation and advanced life support measures. Angiography showed mild coronary artery disease unchanged from previous angiograms. The patient was managed in the Intensive Care Unit (ICU) with Glyceryl trinitrate (GTN) infusion but continued to have episodes of inferior ST elevations on electrocardiogram (ECG). Given the refractory vasospasm, levosimendan infusion was initiated at 0.2 mcg/kg/min for 24 hours, leading to stabilization with no further episodes and was eventually discharged from hospital. Conclusions Levosimendan, with its unique pharmacological profile as a calcium sensitizer and potassium channel opener, offers a promising therapeutic option for managing refractory coronary vasospasm. Its dual action improves cardiac contractility and induces significant vasodilation, addressing the underlying pathophysiology of vasospasm. The presented case highlights the potential of levosimendan in stabilizing patients with refractory coronary vasospasm when conventional therapies fail. Further research and clinical trials are warranted to establish its efficacy and safety profile in a broader patient population. Levosimendan coronary epicardial vasospasm arrhythmia cardiac arrest Figures Figure 1 Figure 2 BACKGROUND Coronary artery vasospasm can present with recurrent and refractory angina, posing a significant clinical challenge and can be life threatening. Traditional therapies include calcium channel blockers and nitrates, but their effectiveness can vary ( 1 ). Levosimendan, a calcium sensitizer and ATP-sensitive potassium channel opener, has shown promise in managing various cardiac conditions including acute decompensated heart failure and cardiogenic shock ( 2 ) due to its unique inotropic and vasodilatory properties. This report presents a case where levosimendan was used in a patient with refractory coronary artery vasospasm, leading to multiple ventricular fibrillation (VF) and pulseless electrical activity (PEA) arrests, highlighting its potential therapeutic role in this clinical setting. CASE PRESENTATION A 57-year-old male with an established diagnosis of coronary vasospasm had recurrent presentations to the emergency department (ED) for chest pain, usually presenting with ST elevation in the inferior leads. His pain usually would settle with medical therapy while treated as an in-patient. He has a background of hypercholesteremia, hypertension, and hypothyroidism but had variable compliance with prescribed medical therapy and continued to smoke between 5 and 10 cigarettes a day. His prescribed medications included isosorbide mononitrate 120mg daily, nicorandil 5mg daily, and diltiazem 180mg daily. Approximately 6 months after his diagnosis of vasospasm, he was again brought to ED for chest pain. He had refractory ST elevation (Fig. 1 ) despite intravenous glyceryl trinitrate (GTN) and calcium channel blockers. He then had a witnessed ventricular fibrillatory arrest treated successfully with electrical defibrillation. However, he subsequently had recurrence of inferior ST elevations associated with complete heart block (Fig. 2 ) and went into pulseless electrical activity (PEA) cardiac arrest. He was intubated and ventilated and received appropriate Advanced Life Support (ALS) treatment with chest compressions and adrenaline, leading to Return of Spontaneous Circulation (ROSC) within 4 minutes and he was brought to the angiography suite. Coronary angiography demonstrated only mild coronary artery disease – unchanged from his previous coronary angiograms. He was brought back to the Intensive Care Unit (ICU) on a glyceryl trinitrate (GTN) infusion but was challenging due to hypotension. Despite treatment he continued to have persistent ST elevation in the inferior leads associated with hypotension and transient complete heart block (CHB) leading to another PEA arrest, where he had ROSC after receiving further ALS treatment. Given refractory vasospasm, we decided to trial a levosimendan infusion at 0.2mcg/kg/min for 24 hours. Within 2 hours of infusion, the ST segment and CHB resolved. He was extubated less than 48 hours since the infusion was started and the remainder of his admission was uncomplicated with no further episodes, and he was subsequently discharged on medical therapy. DISCUSSION AND CONCLUSION Coronary epicardial vasospasm is a relatively common problem with an incidence of approximately 40% among patients with non-obstructive coronary artery disease ( 3 ). Presentations of vasospasm can vary in clinical spectrum, yet it is associated with morbidity and mortality as it can lead to acute myocardial infarction, fatal arrhythmias, and sudden death ( 4 ). The underlying mechanism primarily involves hyperreactivity of vascular smooth muscle cells (VSMCs) to vasoconstrictive stimuli, driven by increased calcium influx and sensitivity. Endothelial dysfunction, which impairs the release of vasodilators like nitric oxide, further contributes to the spasm. Genetic factors, inflammation, oxidative stress, and autonomic nervous system imbalances are also thought to play significant roles in the pathophysiology of coronary vasospasm ( 5 ). Angina attacks are usually short lived (2–5 minute duration) but tends to recur. Current guidelines recommend treatment with nitrates and calcium channel antagonists as well as targeted therapy (e.g. statins/smoking cessation) to improve endothelial function. However, some cases are refractory to optimal vasodilator therapy ( 1 ) Vasospasm can affect the epicardial arteries and/or the microvasculature. The duration, extent, and location of the spasm can lead to a variety of clinical consequences of varying severity. In our case, recurrent inferior ST elevations, complete heart block, bradycardia, and cardiac arrest developed during the episodes despite maximally tolerated vasodilator therapy. Levosimendan is a distinctive inodilator that combines calcium sensitisation and opening of adenosine triphosphate-dependent potassium channels. Initially approved in Sweden in 2000 for short-term treatment of acutely decompensated severe heart failure, its clinical applications have now expanded ( 2 ). As a calcium sensitizer, levosimendan enhances cardiac contractility by increasing the sensitivity of cardiac myofilaments to calcium. Additionally, by opening ATP-sensitive potassium channels in VSMCs resulting in improved oxygen delivery to the myocardium in the absence of increased oxygen demand and promoting vasodilation. Levosimendan has also been investigated for cerebral vasospasm particularly following subarachnoid haemorrhage, demonstrating its effect in reducing the incidence of delayed cerebral ischaemia in this setting and quantitatively improving cerebral perfusion ( 6 ). Levosimendan, with its unique pharmacological profile, offers a promising therapeutic option for managing refractory coronary vasospasm. Its dual action as a calcium sensitizer and potassium channel opener not only improves cardiac contractility but also induces significant vasodilation, addressing the underlying pathophysiology of vasospasm. In the presented case, levosimendan was successful in stabilizing the patient’s condition when all other conventional therapies failed. The resolution of ST elevation and the absence of further arrhythmic events following the administration of levosimendan underscore its potential efficacy in managing refractory coronary vasospasm​ requiring hospitalisation. The remainder of the patient’s hospitalisation period was uncomplicated and may be attributed to levosimendan’s unique pharmacokinetics including an active metabolite OR-1896 which has a half-life of roughly 80 hours which can have haemodynamic benefits for up to 10–14 days after infusion ( 7 ). This presented case highlights the potential of levosimendan in stabilizing patients with refractory coronary vasospasm, suggesting that it could be considered in similar clinical scenarios. Further research and clinical trials are warranted to establish its efficacy and safety profile in a broader patient population. Abbreviations ALS – Advanced Life Support CHB – Complete Heart Block ECG – Electrocardiogram ED – Emergency Department GTN – Glyceryl trinitrate ICU – Intensive Care Unit PEA – Pulseless Electrical Activity VF – Ventricular Fibrillation ROSC – Return of Spontaneous Circulation VSMCs – Vascular Smooth Muscle Cells Declarations Authors’ Affiliation: Department of Cardiology, Frankston Hospital 2 Hasting Road, Frankston, Victoria, Australia 3199 Authors’ Contributions: KR and WW wrote the manuscript. JL provided supervision and required revision of the manuscript Acknowledgements: Not applicable Ethics approval and consent to participate: Not applicable. Written consent was obtained from the patient. Consent for publication: Written consent was obtained from the patient. Competing interests: The authors declare they have no competing interests. Availability of data and materials: The original contributions presented in this case report can be inquired directly to the author/s. Funding: No public or private funding was received in support of this study. References Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). The Who, What, Why, When, How and Where of Vasospastic Angina. Circ J. 2016;80(2):289-98. doi: 10.1253/circj.CJ-15-1202 Conti N, Gatti M, Raschi E, Diemberger I, Potena L. Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap. Drug Des Devel Ther . 2021;15:3391-3409. https://doi.org/10.2147/DDDT.S295214 Mileva N, Nagumo S, Mizukami T, Sonck J, Berry C, Gallinoro E, Monizzi G, Candreva A, Munhoz D, Vassilev D, Penicka M, Barbato E, De Bruyne B, Collet C. Prevalence of Coronary Disease and Coronary Vasospasm in Patients with Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis. J Am Heart Assoc. 2022 Apr 5;11(7):e023207. doi: 10.1161/JAHA.121.023207 Kusama Y, Kodani E, Nakagomi A, Otsuka T, Atarashi H, Kishida H, Mizuno K. Variant angina and coronary artery spasm: the clinical spectrum, pathophysiology, and management. J Nippon Med Sch. 2011;78(1):4-12. doi: 10.1272/jnms.78.4 Jenkins K, Pompei G, Ganzorig N, Brown S, Beltrame J, Kunadian V. Vasospastic angina: a review on diagnostic approach and management. Ther Adv Cardiovasc Dis. 2024 Jan-Dec;18:17539447241230400. doi: 10.1177/17539447241230400 Cane G, de Courson H, Robert C, Fukutomi H, Marnat G, Tourdias T, Biais M. Cerebral Hemodynamics and Levosimendan Use in Patients with Cerebral Vasospasm and Subarachnoid Hemorrhage: An Observational Perfusion CT-Based Imaging Study. Neurocrit Care. 2024 Feb 7. doi: 10.1007/s12028-023-01928-6 Masarone, D.; Kittleson, M.M.; Pollesello, P.; Marini, M.; Iacoviello, M.; Oliva, F.; Caiazzo, A.; Petraio, A.; Pacileo, G. Use of Levosimendan in Patients with Advanced Heart Failure: An Update. J. Clin. Med. 2022, 11 , 6408. https://doi.org/10.3390/jcm11216408 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4594151","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":320221346,"identity":"d1448a01-7e12-467a-a104-486ff410de34","order_by":0,"name":"Kristoffer Ken Ralota","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBACCQhlAcTMB0B8GWK1SDDwMLAlgBg8pGjhMQCxCGuRbO89wFxRIyFnz37m86sbNRY8DOyHj27Ap0Wa51wC45ljEsY8PLnbrHOOAR3Gk5Z2A58WOYkcA8YGNonEHobcbcY5bEAtEjxm+LXIvwFq+QfUwv/mmXHOPyK0SEvwGDA2tgG1SOQwP85tI0KLZE+OwcHGPqBfbjwzY87tk+BhI+QXieNnDB82fLORY+9Pfvw551udHD/74WN4tYDAASjNBo4kNkLKkQHzB1JUj4JRMApGwcgBAH3pPlmJYlZ8AAAAAElFTkSuQmCC","orcid":"","institution":"Frankston Hospital","correspondingAuthor":true,"prefix":"","firstName":"Kristoffer","middleName":"Ken","lastName":"Ralota","suffix":""},{"id":320221347,"identity":"61f30102-5770-4613-b986-017190da84c0","order_by":1,"name":"Wendy Wang","email":"","orcid":"","institution":"Frankston Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wendy","middleName":"","lastName":"Wang","suffix":""},{"id":320221348,"identity":"a3cbb5a4-d1ba-4d6a-a517-020e64dccdab","order_by":2,"name":"Jamie Layland","email":"","orcid":"","institution":"Frankston Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jamie","middleName":"","lastName":"Layland","suffix":""}],"badges":[],"createdAt":"2024-06-17 12:33:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4594151/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4594151/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60625773,"identity":"55262b98-a99d-4ac6-a0af-fa6193b617f1","added_by":"auto","created_at":"2024-07-18 22:27:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2583862,"visible":true,"origin":"","legend":"\u003cp\u003eECG showing dramatic ST elevations\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4594151/v1/758087f9d470a2e9341d7f4f.png"},{"id":60625772,"identity":"71190f8c-17cf-4ec9-b0f9-a942c4f831e9","added_by":"auto","created_at":"2024-07-18 22:27:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3014655,"visible":true,"origin":"","legend":"\u003cp\u003eRecurrence of ST elevations with associated complete heart block\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4594151/v1/fbc5851260e913d050c7e20d.png"},{"id":62911844,"identity":"676d02cb-7205-4458-a839-2554304a1cff","added_by":"auto","created_at":"2024-08-21 03:12:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6744582,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4594151/v1/02ab43c0-ce54-4224-b47c-b7775caaabed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Successful Use of Levosimendan in Managing Refractory Coronary Vasospasm Leading to Recurrent Cardiac Arrests: A Case Report","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCoronary artery vasospasm can present with recurrent and refractory angina, posing a significant clinical challenge and can be life threatening. Traditional therapies include calcium channel blockers and nitrates, but their effectiveness can vary (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Levosimendan, a calcium sensitizer and ATP-sensitive potassium channel opener, has shown promise in managing various cardiac conditions including acute decompensated heart failure and cardiogenic shock (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) due to its unique inotropic and vasodilatory properties. This report presents a case where levosimendan was used in a patient with refractory coronary artery vasospasm, leading to multiple ventricular fibrillation (VF) and pulseless electrical activity (PEA) arrests, highlighting its potential therapeutic role in this clinical setting.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 57-year-old male with an established diagnosis of coronary vasospasm had recurrent presentations to the emergency department (ED) for chest pain, usually presenting with ST elevation in the inferior leads. His pain usually would settle with medical therapy while treated as an in-patient. He has a background of hypercholesteremia, hypertension, and hypothyroidism but had variable compliance with prescribed medical therapy and continued to smoke between 5 and 10 cigarettes a day. His prescribed medications included isosorbide mononitrate 120mg daily, nicorandil 5mg daily, and diltiazem 180mg daily.\u003c/p\u003e \u003cp\u003eApproximately 6 months after his diagnosis of vasospasm, he was again brought to ED for chest pain. He had refractory ST elevation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) despite intravenous glyceryl trinitrate (GTN) and calcium channel blockers. He then had a witnessed ventricular fibrillatory arrest treated successfully with electrical defibrillation. However, he subsequently had recurrence of inferior ST elevations associated with complete heart block (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and went into pulseless electrical activity (PEA) cardiac arrest. He was intubated and ventilated and received appropriate Advanced Life Support (ALS) treatment with chest compressions and adrenaline, leading to Return of Spontaneous Circulation (ROSC) within 4 minutes and he was brought to the angiography suite. Coronary angiography demonstrated only mild coronary artery disease \u0026ndash; unchanged from his previous coronary angiograms. He was brought back to the Intensive Care Unit (ICU) on a glyceryl trinitrate (GTN) infusion but was challenging due to hypotension. Despite treatment he continued to have persistent ST elevation in the inferior leads associated with hypotension and transient complete heart block (CHB) leading to another PEA arrest, where he had ROSC after receiving further ALS treatment. Given refractory vasospasm, we decided to trial a levosimendan infusion at 0.2mcg/kg/min for 24 hours. Within 2 hours of infusion, the ST segment and CHB resolved. He was extubated less than 48 hours since the infusion was started and the remainder of his admission was uncomplicated with no further episodes, and he was subsequently discharged on medical therapy.\u003c/p\u003e"},{"header":"DISCUSSION AND CONCLUSION","content":"\u003cp\u003eCoronary epicardial vasospasm is a relatively common problem with an incidence of approximately 40% among patients with non-obstructive coronary artery disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Presentations of vasospasm can vary in clinical spectrum, yet it is associated with morbidity and mortality as it can lead to acute myocardial infarction, fatal arrhythmias, and sudden death (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The underlying mechanism primarily involves hyperreactivity of vascular smooth muscle cells (VSMCs) to vasoconstrictive stimuli, driven by increased calcium influx and sensitivity. Endothelial dysfunction, which impairs the release of vasodilators like nitric oxide, further contributes to the spasm. Genetic factors, inflammation, oxidative stress, and autonomic nervous system imbalances are also thought to play significant roles in the pathophysiology of coronary vasospasm (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Angina attacks are usually short lived (2\u0026ndash;5 minute duration) but tends to recur. Current guidelines recommend treatment with nitrates and calcium channel antagonists as well as targeted therapy (e.g. statins/smoking cessation) to improve endothelial function. However, some cases are refractory to optimal vasodilator therapy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eVasospasm can affect the epicardial arteries and/or the microvasculature. The duration, extent, and location of the spasm can lead to a variety of clinical consequences of varying severity. In our case, recurrent inferior ST elevations, complete heart block, bradycardia, and cardiac arrest developed during the episodes despite maximally tolerated vasodilator therapy.\u003c/p\u003e \u003cp\u003eLevosimendan is a distinctive inodilator that combines calcium sensitisation and opening of adenosine triphosphate-dependent potassium channels. Initially approved in Sweden in 2000 for short-term treatment of acutely decompensated severe heart failure, its clinical applications have now expanded (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). As a calcium sensitizer, levosimendan enhances cardiac contractility by increasing the sensitivity of cardiac myofilaments to calcium. Additionally, by opening ATP-sensitive potassium channels in VSMCs resulting in improved oxygen delivery to the myocardium in the absence of increased oxygen demand and promoting vasodilation. Levosimendan has also been investigated for cerebral vasospasm particularly following subarachnoid haemorrhage, demonstrating its effect in reducing the incidence of delayed cerebral ischaemia in this setting and quantitatively improving cerebral perfusion (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLevosimendan, with its unique pharmacological profile, offers a promising therapeutic option for managing refractory coronary vasospasm. Its dual action as a calcium sensitizer and potassium channel opener not only improves cardiac contractility but also induces significant vasodilation, addressing the underlying pathophysiology of vasospasm. In the presented case, levosimendan was successful in stabilizing the patient\u0026rsquo;s condition when all other conventional therapies failed. The resolution of ST elevation and the absence of further arrhythmic events following the administration of levosimendan underscore its potential efficacy in managing refractory coronary vasospasm​ requiring hospitalisation. The remainder of the patient\u0026rsquo;s hospitalisation period was uncomplicated and may be attributed to levosimendan\u0026rsquo;s unique pharmacokinetics including an active metabolite OR-1896 which has a half-life of roughly 80 hours which can have haemodynamic benefits for up to 10\u0026ndash;14 days after infusion (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis presented case highlights the potential of levosimendan in stabilizing patients with refractory coronary vasospasm, suggesting that it could be considered in similar clinical scenarios. Further research and clinical trials are warranted to establish its efficacy and safety profile in a broader patient population.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALS \u0026ndash; Advanced Life Support\u003c/p\u003e\n\u003cp\u003eCHB \u0026ndash; Complete Heart Block\u003c/p\u003e\n\u003cp\u003eECG \u0026ndash; Electrocardiogram\u003c/p\u003e\n\u003cp\u003eED \u0026ndash; Emergency Department\u003c/p\u003e\n\u003cp\u003eGTN \u0026ndash; Glyceryl trinitrate\u003c/p\u003e\n\u003cp\u003eICU \u0026ndash; Intensive Care Unit\u003c/p\u003e\n\u003cp\u003ePEA \u0026ndash; Pulseless Electrical Activity\u003c/p\u003e\n\u003cp\u003eVF \u0026ndash; Ventricular Fibrillation\u003c/p\u003e\n\u003cp\u003eROSC \u0026ndash; Return of Spontaneous Circulation\u003c/p\u003e\n\u003cp\u003eVSMCs \u0026ndash; Vascular Smooth Muscle Cells\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eAuthors\u0026rsquo; Affiliation:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Cardiology, Frankston Hospital\u003c/p\u003e\n\u003cp\u003e2 Hasting Road, Frankston, Victoria, Australia 3199\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026rsquo; Contributions:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eKR and WW wrote the manuscript. JL provided supervision and required revision of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgements:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEthics approval and consent to participate:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. Written consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and materials:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in this case report can be inquired directly to the author/s.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNo public or private funding was received in support of this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBeltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). The Who, What, Why, When, How and Where of Vasospastic Angina. Circ J. 2016;80(2):289-98. doi: 10.1253/circj.CJ-15-1202\u003c/li\u003e\n\u003cli\u003eConti N, Gatti M, Raschi E, Diemberger I, Potena L. Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap. \u003cem\u003eDrug Des Devel Ther\u003c/em\u003e. 2021;15:3391-3409. https://doi.org/10.2147/DDDT.S295214\u003c/li\u003e\n\u003cli\u003eMileva N, Nagumo S, Mizukami T, Sonck J, Berry C, Gallinoro E, Monizzi G, Candreva A, Munhoz D, Vassilev D, Penicka M, Barbato E, De Bruyne B, Collet C. Prevalence of Coronary Disease and Coronary Vasospasm in Patients with Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis. J Am Heart Assoc. 2022 Apr 5;11(7):e023207. doi: 10.1161/JAHA.121.023207\u003c/li\u003e\n\u003cli\u003eKusama Y, Kodani E, Nakagomi A, Otsuka T, Atarashi H, Kishida H, Mizuno K. Variant angina and coronary artery spasm: the clinical spectrum, pathophysiology, and management. J Nippon Med Sch. 2011;78(1):4-12. doi: 10.1272/jnms.78.4\u003c/li\u003e\n\u003cli\u003eJenkins K, Pompei G, Ganzorig N, Brown S, Beltrame J, Kunadian V. Vasospastic angina: a review on diagnostic approach and management. Ther Adv Cardiovasc Dis. 2024 Jan-Dec;18:17539447241230400. doi: 10.1177/17539447241230400\u003c/li\u003e\n\u003cli\u003eCane G, de Courson H, Robert C, Fukutomi H, Marnat G, Tourdias T, Biais M. Cerebral Hemodynamics and Levosimendan Use in Patients with Cerebral Vasospasm and Subarachnoid Hemorrhage: An Observational Perfusion CT-Based Imaging Study. Neurocrit Care. 2024 Feb 7. doi: 10.1007/s12028-023-01928-6\u003c/li\u003e\n\u003cli\u003eMasarone, D.; Kittleson, M.M.; Pollesello, P.; Marini, M.; Iacoviello, M.; Oliva, F.; Caiazzo, A.; Petraio, A.; Pacileo, G. Use of Levosimendan in Patients with Advanced Heart Failure: An Update. \u003cem\u003eJ. Clin. Med.\u003c/em\u003e 2022, \u003cem\u003e11\u003c/em\u003e, 6408. https://doi.org/10.3390/jcm11216408\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Levosimendan, coronary epicardial vasospasm, arrhythmia, cardiac arrest","lastPublishedDoi":"10.21203/rs.3.rs-4594151/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4594151/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCoronary vasospasm can be life threatening and can be refractory. First line therapies include calcium channel blockers and nitrates; however, they have variable effectiveness. This case report presents a case of refractory coronary artery vasospasm presenting with ST elevation and recurrent cardiac arrest who was treated with levosimendan, a distinctive inodilator with calcium-sensitising and ATP-sensitive potassium channel opening properties, highlighting its potential therapeutic role in this clinical setting.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA 57-year-old male with an established diagnosis of coronary vasospasm presenting with ST elevation in the inferior leads and suffered multiple cardiac arrests, initially treated with electrical defibrillation and advanced life support measures. Angiography showed mild coronary artery disease unchanged from previous angiograms. The patient was managed in the Intensive Care Unit (ICU) with Glyceryl trinitrate (GTN) infusion but continued to have episodes of inferior ST elevations on electrocardiogram (ECG). Given the refractory vasospasm, levosimendan infusion was initiated at 0.2 mcg/kg/min for 24 hours, leading to stabilization with no further episodes and was eventually discharged from hospital.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLevosimendan, with its unique pharmacological profile as a calcium sensitizer and potassium channel opener, offers a promising therapeutic option for managing refractory coronary vasospasm. Its dual action improves cardiac contractility and induces significant vasodilation, addressing the underlying pathophysiology of vasospasm. The presented case highlights the potential of levosimendan in stabilizing patients with refractory coronary vasospasm when conventional therapies fail. Further research and clinical trials are warranted to establish its efficacy and safety profile in a broader patient population.\u003c/p\u003e","manuscriptTitle":"Successful Use of Levosimendan in Managing Refractory Coronary Vasospasm Leading to Recurrent Cardiac Arrests: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-18 22:27:09","doi":"10.21203/rs.3.rs-4594151/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"274db67b-5873-44f7-8715-9259d40a8e33","owner":[],"postedDate":"July 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-04T09:23:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-18 22:27:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4594151","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4594151","identity":"rs-4594151","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}