Complete Recovery From Tachycardiomyopathy and Atrial Fibrillation Through Targeted Mitochondrial Support: A Case Report

Complete Recovery From Tachycardiomyopathy and Atrial Fibrillation Through Targeted Mitochondrial Support: 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 Complete Recovery From Tachycardiomyopathy and Atrial Fibrillation Through Targeted Mitochondrial Support: A Case Report Elmar Schwarz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7022774/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: Tachycardiomyopathy is a reversible form of heart failure caused by persistent tachyarrhythmias such as atrial fibrillation. Conventional therapy includes rate or rhythm control and neurohormonal modulation. Emerging evidence suggests that mitochondrial dysfunction may contribute to disease progression. Case presentation: We report the case of a 52-year-old male patient initially diagnosed in March 2024 with severe heart failure due to tachycardiomyopathy (LVEF 20–25%, NT-proBNP 6260 pg/mL, NYHA IV) in the context of persistent atrial fibrillation. Laboratory tests at admission showed elevated serum potassium and low-normal sodium, consistent with suppressed RAAS activity despite marked volume overload. After diuretic-induced decongestion, potassium and sodium normalized (4.18 and 143 mmol/L, respectively) prior to the initiation of neurohormonal therapy. Guideline-based pharmacological therapy and electrical cardioversion failed to restore rhythm or improve function. A mitochondria-targeted therapeutic approach—including ubiquinone, thiamine, L-carnitine, and NAC—was then initiated, leading to complete clinical and echocardiographic remission by March 2025 (LVEF 60%, NT-proBNP 49 pg/mL, sinus rhythm, asymptomatic). Conclusions: This case supports the therapeutic plausibility of mitochondrial-targeted interventions in patients with refractory heart failure due to tachycardiomyopathy. Further studies are warranted to validate this approach in larger populations. Heart Failure Atrial Fibrillation Mitochondrial Dysfunction Case Report Figures Figure 1 Introduction Tachycardiomyopathy is considered a reversible form of cardiomyopathy, typically managed through rhythm control and neurohormonal modulation. However, complete recovery remains rare in patients with persistent atrial fibrillation and advanced left ventricular dysfunction despite guideline-directed therapy. We report a unique case of a patient with severe tachycardiomyopathy and persistent atrial fibrillation who achieved full clinical and echocardiographic remission through a mitochondria-targeted therapeutic regimen—without neurohormonal modulation or conventional interventions to restore sinus rhythm. This recovery challenges prevailing paradigms in heart failure management and the treatment of atrial fibrillation. Initial Presentation In March 2024, a 52-year-old male (weight 130 kg, HR 173 bpm, BP 174/139 mmHg) presented with persistent atrial fibrillation and symptoms consistent with NYHA Class IV heart failure. Echocardiography confirmed a severely reduced LVEF (20–25%) and NT-proBNP was 6260 pg/mL. Comorbidities included arterial hypertension and mild renal dysfunction (eGFR 81). Labs showed elevated CRP (14.7 mg/L), HbA1c of 5.7%, elevated serum potassium (5.49 mmol/L) and low-normal sodium (138 mmol/L). Therapeutic Course Diuretic-induced decongestion also normalized potassium (4.18 mmol/L) and sodium (143 mmol/L) levels, consistent with appropriately regulated RAAS activity.The patient was subsequently treated with guideline-directed medical therapy (GDMT) including Lisinopril, Bisoprolol, Dapagliflozin (Forxiga), and Torasemide. However, he experienced symptomatic hypotension, muscle atrophy, renal impairment (eGFR down to 50), and depressive symptoms. Electrical cardioversion in June 2024 was unsuccessful. A mitochondria-targeted adjunctive regimen was initiated between July and November 2024, including Bisoprolol (5mg), Ubiquinone (300 mg), Thiamine (1.1 mg), Omega-3 (EPA 500 mg, DHA 250 mg), Vitamin D (5000 IU). This regimen was altered to Ubiquinone (275 mg), Thiamine (3.3 mg), L-Carnitine (500 mg), N-Acetylcysteine (600 mg), Omega-3 (EPA 500 mg, DHA 250 mg), Vitamin D (5000 IU) and oral Magnesium in December 2024. Bisoprolol was tapered off in January 2025. No adverse effects except transient diarrhea were reported. Follow-up By November 2024, the patient had regained normal LVEF (60%), improved renal function (eGFR 88), reduced inflammatory markers (hsCRP 3.4 mg/L), and achieved near-normal glycemic control (HbA1c 5.1%). By March 2025, NT-proBNP decreased to 49 pg/mL and atrial fibrillation had fully remitted. The patient is now asymptomatic, normotensive (blood pressure 120/80 mmHg), with heart rate of 75 bpm and a weight of 101 kg. The NT-proBNP time course is summarized below: Date NT-proBNP (pg/mL) March 2024 6260 April 2024 1528 May 2024 1544 July 2024 713 October 2024 318 January 2025 139 March 2025 49 Discussion This case challenges conventional assumptions regarding pathogenesis, prognosis and reversibility of heart failure with persistent atrial fibrillation. The applied therapy aligns with biochemical rationale targeting mitochondrial dysfunction—a recognized contributor to heart failure and arrhythmogenesis (Brown 2017; Dorn 2015; Rosca 2010 ; Bugger 2020 ; Xie 2021 ). Clinical evidence for selected components includes: Ubiquinone (Mortensen 2014; Morrisco 1993): significant reductions in mortality, improvement in remodeling L-Carnitine (DiNicolantonio 2013; Rizos 2000 ): significant reductions in mortality and NT-proBNP, improvement in remodeling Magnesium (Song 2025): significant reductions in mortality Thiamine (Yang 2023): reductions in mortality Omega-3: (Tavazzi 2008): reductions in mortality N-Acetylcysteine (Yazdi 2021): improvement in remodeling Vitamin D (Witte 2016): improvement in remodeling Conclusion Despite decades of emphasis on RAAS inhibition in heart failure management, a growing body of evidence now challenges its presumed centrality. The presented case documents not only a complete remission of advanced heart failure with persistent atrial fibrillation, but also a therapeutic trajectory fundamentally inconsistent with the traditional aldosterone–fibrosis hypothesis. Decompensation occurred in the absence of measurable RAAS activation. RAAS inhibition caused clinical deterioration. Full recovery was achieved through targeted mitochondrial support and recovery—without neurohormonal modulation. These observations align with mounting mechanistic and clinical research identifying mitochondrial dysfunction and ATP deficiency as central drivers of cardiac failure. As this case may reflect a broader but underrecognized phenotype, the prevailing therapeutic paradigm may require revision. The persistence of the RAAS paradigm may reflect less a failure of data than a failure of epistemic openness. In tightly knit academic circuits, dominant models are rarely falsified—not due to their resilience, but due to the absence of contradiction. RAAS modulation has defined heart failure management for decades. Sufficient scientific proof is broadening this perspective to include mitochondrial function as a primary therapeutic target. Abbreviations BPM – Beats Per Minute DHA – Docosahexaenoic Acid EPA – Eicosapentaenoic Acid eGFR – estimated Glomerular Filtration Rate IU – International Unit hsCRP – high-sensitivity C-reactive Protein LVEF – Left Ventricular Ejection Fraction mmHg – millimeters of mercury NT-proBNP – N-terminal pro–B-type Natriuretic Peptide RAAS – Renin-Angiotensin-Aldosterone System Declarations Disclosure of Artificial Intelligence Tool Usage Portions of this manuscript were prepared with the assistance of artificial intelligence based tools, including ChatGPT (OpenAI) for writing support and Python-based scripts for automated generation of tables and laboratory plots. All clinical content, data interpretation, and conclusions were reviewed and verified by the authors. No generative systems were used to fabricate or simulate clinical data. Funding Statement This research received no external funding. Informed Consent Statement Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. All efforts have been made to protect the identity of the patient. No identifiable personal information is disclosed. The case was handled in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. Author Contribution The author carried out all work related to the case study, including its conception, analysis, writing, and final approval. References Brown DA, Perry JB, Allen ME, et al. Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Circ Res. 2017;122(11):1737–1756. Dorn GW, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Nat Rev Cardiol. 2015;12(11):634–649. Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88(1):40–50. Bugger H, Pfeil K. Mitochondrial mechanisms of diabetic cardiomyopathy. Antioxid Redox Signal. 2020;32(9):651–668. Xie W, Santulli G. Mitochondrial dysfunction in atrial fibrillation—mechanisms and pharmacological interventions. Pharmacol Ther. 2021;224:107823. Mortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO. JACC Heart Fail. 2014;2(6):641–649. Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71(8 Suppl):S134–S136. DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544–551. Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt 3):S120–S123. Song L, Liu Z, Zhang Y, Wang Y, Guo W. Propensity score matched cohort study on magnesium supplementation and mortality in critically ill patients with HFpEF. J Crit Care. 2023;74:154221. doi: 10.1016/j.jcrc.2023.154221 Yang Y, Zhang L, Hu M, et al. Thiamine supplementation for patients with heart failure: a systematic review and meta-analysis. Front Pharmacol. 2023;14:1130229. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (GISSI-HF): a randomized, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1223–1230. Yazdi M, Rahimi HR, Pishgahi A, et al. Oral N-acetylcysteine as adjunct to standard therapy improves cardiac function in patients with stable class II and III systolic heart failure. J Res Med Sci. 2021;26:67. Witte KK, Byrom R, Gierula J, et al. Effects of vitamin D on left ventricular function in patients with chronic HF (VINDICATE Study). Eur Heart J. 2016;37(35):2734–2743. 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-7022774","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":483749581,"identity":"d21c8528-b492-46b8-a275-bc9ec92ba9b0","order_by":0,"name":"Elmar Schwarz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAoElEQVRIiWNgGAWjYLCCDyTrYJwBpRuI1sLMQ5IWfon0x59tfm1LbJBuPv6AKC2SM3IMjHP7bhszyBxLJM4Wg9s5DMm5PbflGCRyDInTYn87/cFhy57bPAwS+R+JtEU6wbCZ4QfYFiK9L3H/jTFjb8NtYzaJNMMZRGnh7zn++MOPP7cT+yWSH5AQpYxtDAxsxCsHgz8kqh8Fo2AUjIKRBQCoIi/CYNd+gAAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Elmar","middleName":"","lastName":"Schwarz","suffix":""}],"badges":[],"createdAt":"2025-07-01 17:53:12","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7022774/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7022774/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87052289,"identity":"b525ad00-df9f-4e87-be1b-d9771323e997","added_by":"auto","created_at":"2025-07-18 15:07:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87271,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the Follow-up section.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7022774/v1/defd5c197e99b1fe99a388ef.png"},{"id":97137813,"identity":"af6b4343-0252-4089-ba64-857482199ae2","added_by":"auto","created_at":"2025-12-01 09:58:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":400044,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7022774/v1/0600f98d-4e12-4410-854d-26bf943ade61.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Complete Recovery From Tachycardiomyopathy and Atrial Fibrillation Through Targeted Mitochondrial Support: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTachycardiomyopathy is considered a reversible form of cardiomyopathy, typically managed through rhythm control and neurohormonal modulation. However, complete recovery remains rare in patients with persistent atrial fibrillation and advanced left ventricular dysfunction despite guideline-directed therapy. We report a unique case of a patient with severe tachycardiomyopathy and persistent atrial fibrillation who achieved full clinical and echocardiographic remission through a mitochondria-targeted therapeutic regimen—without neurohormonal modulation or conventional interventions to restore sinus rhythm. This recovery challenges prevailing paradigms in heart failure management and the treatment of atrial fibrillation.\u003c/p\u003e\n\n\n\n\n\n\n\n\n"},{"header":"Initial Presentation","content":"\u003cp\u003eIn March 2024, a 52-year-old male (weight 130 kg, HR 173 bpm, BP 174/139 mmHg) presented with persistent atrial fibrillation and symptoms consistent with NYHA Class IV heart failure. Echocardiography confirmed a severely reduced LVEF (20–25%) and NT-proBNP was 6260 pg/mL. Comorbidities included arterial hypertension and mild renal dysfunction (eGFR 81). Labs showed elevated CRP (14.7 mg/L), HbA1c of 5.7%, elevated serum potassium (5.49 mmol/L) and low-normal sodium (138 mmol/L).\u003c/p\u003e"},{"header":"Therapeutic Course","content":"\u003cp\u003eDiuretic-induced decongestion also normalized potassium (4.18 mmol/L) and sodium (143 mmol/L) levels, consistent with appropriately regulated RAAS activity.The patient was subsequently treated with guideline-directed medical therapy (GDMT) including Lisinopril, Bisoprolol, Dapagliflozin (Forxiga), and Torasemide. However, he experienced symptomatic hypotension, muscle atrophy, renal impairment (eGFR down to 50), and depressive symptoms. Electrical cardioversion in June 2024 was unsuccessful.\u003c/p\u003e\u003cp\u003eA mitochondria-targeted adjunctive regimen was initiated between July and November 2024, including Bisoprolol (5mg), Ubiquinone (300 mg), Thiamine (1.1 mg), Omega-3 (EPA 500 mg, DHA 250 mg), Vitamin D (5000 IU). This regimen was altered to Ubiquinone (275 mg), Thiamine (3.3 mg), L-Carnitine (500 mg), N-Acetylcysteine (600 mg), Omega-3 (EPA 500 mg, DHA 250 mg), Vitamin D (5000 IU) and oral Magnesium in December 2024. Bisoprolol was tapered off in January 2025. No adverse effects except transient diarrhea were reported.\u003c/p\u003e"},{"header":"Follow-up","content":"\u003cp\u003eBy November 2024, the patient had regained normal LVEF (60%), improved renal function (eGFR 88), reduced inflammatory markers (hsCRP 3.4 mg/L), and achieved near-normal glycemic control (HbA1c 5.1%). By March 2025, NT-proBNP decreased to 49 pg/mL and atrial fibrillation had fully remitted. The patient is now asymptomatic, normotensive (blood pressure 120/80 mmHg), with heart rate of 75 bpm and a weight of 101 kg.\u003c/p\u003e\u003cp\u003eThe NT-proBNP time course is summarized below:\u003c/p\u003e\u003ctable id=\"Taba\" border=\"1\"\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eDate\u003c/p\u003e\n \u003c/th\u003e\u003cth align=\"left\"\u003e\n \u003cp\u003eNT-proBNP (pg/mL)\u003c/p\u003e\n \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eMarch 2024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e6260\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eApril 2024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1528\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eMay 2024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e1544\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eJuly 2024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e713\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eOctober 2024\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eJanuary 2025\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e139\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\"\u003e\n \u003cp\u003eMarch 2025\u003c/p\u003e\n \u003c/td\u003e\u003ctd align=\"char\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case challenges conventional assumptions regarding pathogenesis, prognosis and reversibility of heart failure with persistent atrial fibrillation. The applied therapy aligns with biochemical rationale targeting mitochondrial dysfunction\u0026mdash;a recognized contributor to heart failure and arrhythmogenesis (Brown 2017; Dorn 2015; Rosca \u003cspan class=\"CitationRef\"\u003e2010\u003c/span\u003e; Bugger \u003cspan class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xie \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e). Clinical evidence for selected components includes:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\n \u003cp\u003eUbiquinone (Mortensen 2014; Morrisco 1993): significant reductions in mortality, improvement in remodeling\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eL-Carnitine (DiNicolantonio 2013; Rizos \u003cspan class=\"CitationRef\"\u003e2000\u003c/span\u003e): significant reductions in mortality and NT-proBNP, improvement in remodeling\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eMagnesium (Song 2025): significant reductions in mortality\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eThiamine (Yang 2023): reductions in mortality\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eOmega-3: (Tavazzi 2008): reductions in mortality\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eN-Acetylcysteine (Yazdi 2021): improvement in remodeling\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eVitamin D (Witte 2016): improvement in remodeling\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Conclusion","content":"\u003cp\u003eDespite decades of emphasis on RAAS inhibition in heart failure management, a growing body of evidence now challenges its presumed centrality. The presented case documents not only a complete remission of advanced heart failure with persistent atrial fibrillation, but also a therapeutic trajectory fundamentally inconsistent with the traditional aldosterone\u0026ndash;fibrosis hypothesis. Decompensation occurred in the absence of measurable RAAS activation. RAAS inhibition caused clinical deterioration. Full recovery was achieved through targeted mitochondrial support and recovery\u0026mdash;without neurohormonal modulation.\u003c/p\u003e\n\u003cp\u003eThese observations align with mounting mechanistic and clinical research identifying mitochondrial dysfunction and ATP deficiency as central drivers of cardiac failure. As this case may reflect a broader but underrecognized phenotype, the prevailing therapeutic paradigm may require revision.\u003c/p\u003e\n\u003cp\u003eThe persistence of the RAAS paradigm may reflect less a failure of data than a failure of epistemic openness. In tightly knit academic circuits, dominant models are rarely falsified\u0026mdash;not due to their resilience, but due to the absence of contradiction. RAAS modulation has defined heart failure management for decades. Sufficient scientific proof is broadening this perspective to include mitochondrial function as a primary therapeutic target.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBPM – Beats Per Minute\u003c/p\u003e\u003cp\u003eDHA – Docosahexaenoic Acid\u003c/p\u003e\u003cp\u003eEPA – Eicosapentaenoic Acid\u003c/p\u003e\u003cp\u003eeGFR – estimated Glomerular Filtration Rate\u003c/p\u003e\u003cp\u003eIU – International Unit\u003c/p\u003e\u003cp\u003ehsCRP – high-sensitivity C-reactive Protein\u003c/p\u003e\u003cp\u003eLVEF – Left Ventricular Ejection Fraction\u003c/p\u003e\u003cp\u003emmHg – millimeters of mercury\u003c/p\u003e\u003cp\u003eNT-proBNP – N-terminal pro–B-type Natriuretic Peptide\u003c/p\u003e\u003cp\u003eRAAS – Renin-Angiotensin-Aldosterone System\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDisclosure of Artificial Intelligence Tool Usage\u003c/h2\u003e\n\u003cp\u003ePortions of this manuscript were prepared with the assistance of artificial intelligence based tools, including ChatGPT (OpenAI) for writing support and Python-based scripts for automated generation of tables and laboratory plots. All clinical content, data interpretation, and conclusions were reviewed and verified by the authors. No generative systems were used to fabricate or simulate clinical data.\u003c/p\u003e\n\u003ch2\u003eFunding Statement\u003c/h2\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\n\u003ch2\u003eInformed Consent Statement\u003c/h2\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the publication of this case report and any accompanying images. All efforts have been made to protect the identity of the patient. No identifiable personal information is disclosed. The case was handled in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe author carried out all work related to the case study, including its conception, analysis, writing, and final approval.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBrown DA, Perry JB, Allen ME, et al. Expert consensus document: Mitochondrial function as a therapeutic target in heart failure. Circ Res. 2017;122(11):1737\u0026ndash;1756.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDorn GW, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Nat Rev Cardiol. 2015;12(11):634\u0026ndash;649.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88(1):40\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBugger H, Pfeil K. Mitochondrial mechanisms of diabetic cardiomyopathy. Antioxid Redox Signal. 2020;32(9):651\u0026ndash;668.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXie W, Santulli G. Mitochondrial dysfunction in atrial fibrillation\u0026mdash;mechanisms and pharmacological interventions. Pharmacol Ther. 2021;224:107823.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMortensen SA, Rosenfeldt F, Kumar A, et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO. JACC Heart Fail. 2014;2(6):641\u0026ndash;649.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71(8 Suppl):S134\u0026ndash;S136.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O\u0026rsquo;Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544\u0026ndash;551.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt 3):S120\u0026ndash;S123.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong L, Liu Z, Zhang Y, Wang Y, Guo W. Propensity score matched cohort study on magnesium supplementation and mortality in critically ill patients with HFpEF. J Crit Care. 2023;74:154221. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jcrc.2023.154221\u003c/span\u003e\u003cspan address=\"10.1016/j.jcrc.2023.154221\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang Y, Zhang L, Hu M, et al. Thiamine supplementation for patients with heart failure: a systematic review and meta-analysis. Front Pharmacol. 2023;14:1130229.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (GISSI-HF): a randomized, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1223\u0026ndash;1230.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYazdi M, Rahimi HR, Pishgahi A, et al. Oral N-acetylcysteine as adjunct to standard therapy improves cardiac function in patients with stable class II and III systolic heart failure. J Res Med Sci. 2021;26:67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWitte KK, Byrom R, Gierula J, et al. Effects of vitamin D on left ventricular function in patients with chronic HF (VINDICATE Study). Eur Heart J. 2016;37(35):2734\u0026ndash;2743.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"Heart Failure, Atrial Fibrillation, Mitochondrial Dysfunction, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-7022774/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7022774/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTachycardiomyopathy is a reversible form of heart failure caused by persistent tachyarrhythmias such as atrial fibrillation. Conventional therapy includes rate or rhythm control and neurohormonal modulation. Emerging evidence suggests that mitochondrial dysfunction may contribute to disease progression.\u003cbr\u003e\n\u003cstrong\u003eCase presentation: \u003c/strong\u003eWe report the case of a 52-year-old male patient initially diagnosed in March 2024 with severe heart failure due to tachycardiomyopathy (LVEF 20–25%, NT-proBNP 6260 pg/mL, NYHA IV) in the context of persistent atrial fibrillation. Laboratory tests at admission showed elevated serum potassium and low-normal sodium, consistent with suppressed RAAS activity despite marked volume overload. After diuretic-induced decongestion, potassium and sodium normalized (4.18 and 143 mmol/L, respectively) prior to the initiation of neurohormonal therapy. Guideline-based pharmacological therapy and electrical cardioversion failed to restore rhythm or improve function. A mitochondria-targeted therapeutic approach—including ubiquinone, thiamine, L-carnitine, and NAC—was then initiated, leading to complete clinical and echocardiographic remission by March 2025 (LVEF 60%, NT-proBNP 49 pg/mL, sinus rhythm, asymptomatic).\u003cbr\u003e\n\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case supports the therapeutic plausibility of mitochondrial-targeted interventions in patients with refractory heart failure due to tachycardiomyopathy. Further studies are warranted to validate this approach in larger populations.\u003c/p\u003e","manuscriptTitle":"Complete Recovery From Tachycardiomyopathy and Atrial Fibrillation Through Targeted Mitochondrial Support: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 15:07:46","doi":"10.21203/rs.3.rs-7022774/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":"73dd9b48-2ed0-45b2-81c4-fb8394974029","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-28T06:54:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-18 15:07:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7022774","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7022774","identity":"rs-7022774","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}