A case report of transthyretin cardiac amyloidosis in a 19-year old patient: From cardiac arrest to sinus rhythm

A case report of transthyretin cardiac amyloidosis in a 19-year old patient: From cardiac arrest to sinus rhythm | 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 A case report of transthyretin cardiac amyloidosis in a 19-year old patient: From cardiac arrest to sinus rhythm Sherif Abdelkhalek, Basant Ahmed Mahmoud This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7237179/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 Introduction : Wild-type transthyretin cardiac amyloidosis (ATTRwt) is generally an age-associated disease observed in older age groups. This case is exceptional in that it reports the aggressive presentation and course of ATTRwt in a young patient, defying traditional demographic characterizations and calling for more widespread diagnostic suspicion. Case Presentation : A 19-year-old Libyan male presented with out-of-hospital ventricular fibrillation (VF) cardiac arrest, requiring one hour and around 30 defibrillation shocks to achieve successful resuscitation. His background diagnosis of ATTRwt cardiac amyloidosis had been established at the age of 17, confirmed by cardiac magnetic resonance imaging (CMRI) which revealed diffuse concentric myocardial hypertrophy with characteristic late gadolinium enhancement and nulling difficulties, and a Technetium-99m Pyrophosphate (Tc-PYP) scintigraphy at age 18 (Perugini score 2). Serological and genetic investigations have excluded AL amyloidosis and hereditary ATTR. Interventions and Outcomes : After resuscitation, a secondary prevention Implantable Cardioverter-Defibrillator (ICD) was implanted. Although efforts were made previously to obtain certain TTR stabilizers, the drug Tafamidis was not available in Egypt. The patient is now treated with standard heart failure medications, such as Angiotensin Receptor Blockers (Candesartan) and Beta-Blockers (Metoprolol), in addition to diuretics. At the 4-month follow-up, his condition remained stable with no more documented ICD shocks. Conclusion : This case highlights the importance of suspecting ATTRwt even in young patients with cardiac presentations such as VF arrest, although ATTRwt is classically linked with very old age. It also draws attention to the difficulty caused by restricted availability of specific disease-modifying therapies for controlling the course of this uncommon and aggressive disease, exploring the health disparities and their effect on possible cessation of disease progression, if resolved. Transthyretin Cardiac Amyloidosis Wild-type ATTR Cardiac Arrest Ventricular Fibrillation Adolescent Implantable Cardioverter-Defibrillator (ICD) Tafamidis Access Figures Figure 1 Figure 2 Figure 3 Introduction Amyloidosis is a term used to refer to a group of diseases characterized by protein misfolding and deposition in tissues[1] leading to organ dysfunction, in a process known as proteotoxicity[2] Cardiac amyloidosis is caused either by misfolded immunoglobulin light chains (ALs) or by misfolding of a liver-synthesized transthyretin (TTR), causing transthyretin amyloidosis (ATTR). ATTR can be caused by autosomal dominant variants in the transthyretin gene TTR (ATTRv) or by the deposition of ATTRwt (wild-type transthyretin protein). Transthyretin amyloid cardiomyopathy (ATTR-CM) is a restrictive cardiomyopathy caused by transthyretin amyloid deposition extracellularly. This case highlights the possibility of ATTR-CM of ATTRwt origin in atypical age groups as seen here. Observational studies have revealed that ATTR-CM may be underrecognized in many heart failure patients, especially those in nontypical age groups[3][4][5]. Case Presentation A 19-year old male patient from Libya, presented to the emergency department, after experiencing an out-of-hospital cardiac arrest. There was no family history of inflammatory disease, heart failure, coronary artery disease or premature cardiac death. Upon presentation, the patient was found to have ventricular fibrillation (VF) on initial rhythm analysis (Fig. 1). Immediate cardiopulmonary resuscitation (CPR) was initiated, and the patient underwent 1 hour of continuous resuscitation efforts, including approximately 30 defibrillation shocks, before successful return of spontaneous circulation (ROSC). Postresuscitation, the patient was admitted to the ICU, ECG was repeated (Fig. 2), and the patient was put on mechanical ventilation for further management and work-up of the cardiac arrest etiology. Patient diagnostic history The patient had a significant preexisting diagnostic history of cardiac amyloidosis. When the patient was 17 years old, a Cardiac Magnetic Resonance Imaging (CMRI) study had revealed diffuse concentric myocardial hypertrophy with a maximum wall thickness of 17 mm (basal anterior and antero-septal segments) and a significantly increased overall myocardial mass index of 140 g/m2. The CMRI also demonstrated diffuse subendocardial and patchy mid-myocardial/sub-epicardial delayed gadolinium enhancement (LGE) and marked difficulty in myocardial nulling even at high inversion times (TI 700 msec), hallmarks of cardiac amyloidosis. The CMRI conclusion explicitly stated a "Pattern suggestive of infiltrative myocardial diseases in the form of amyloidosis." An abdominal and pelvic ultrasonography performed around the same time revealed a bulky spleen (13 cm) and a malrotated pelvic ectopic left kidney, findings that can be associated with systemic amyloidosis. To establish the specific type of amyloidosis, extensive investigations were done. Serum immunofixation, showed a normal immunoglobulin pattern with a normal Kappa/Lambda ratio, effectively ruling out monoclonal gammopathy and AL amyloidosis. Subsequent Bence Jones protein testing in urine was also absent, and serum immunoglobulins profile was normal, further confirming the exclusion of AL amyloidosis. A Technetium-99m Pyrophosphate (Tc-PYP) scintigraphy, performed, (when the patient was 18 years old) showed mildly positive cardiac uptake, with a semiquantitative visual analysis of grade 1/3 and a quantitative heart-to-contralateral lung ratio of 1.4 (Perugini score 2), highly suggestive of ATTR cardiac amyloidosis. Genetic testing for TTR gene mutations was conducted and yielded negative results. Coupled with the absence of any reported family history of amyloidosis or unexplained cardiomyopathy, these comprehensive findings confirmed the diagnosis of wild-type transthyretin cardiac amyloidosis. Indeed, a formal referral for Tafamidis treatment for his non-AL amyloidosis had already been prescribed. Despite efforts to start the Tafamidis treatment, the medication was not accessible to the patient due to its unavailability in Egypt. Given the current unavailability of specific transthyretin stabilizers, the patient then was the patient was initiated on optimized conventional heart failure management, including Angiotensin Receptor Blockers (ARBs) (Candesartan) and Beta-Blockers (Metoprolol), along with diuretics as needed for symptom control. Current measures taken During his current hospitalization following cardiac arrest, a bedside echocardiogram was performed in the ICU, revealing concentric left ventricular hypertrophy (IVS/LVPW: 1.8 cm), dilated left ventricle (LVEDD 5.7 cm), and significant left ventricular diastolic dysfunction with a restrictive filling pattern. LVEF was preserved at an estimated 50%. Other notable findings included thickened mitral and tricuspid valve leaflets with reduced excursion, mild pericardial effusion, and moderate pulmonary hypertension. An ECG performed during the patient's hospitalization, post-cardiac arrest showed sinus rhythm with biventricular hypertrophy patterns, notably prominent R waves in V1-V2 and classic LVH criteria, with associated ST-T abnormalities consistent with hypertrophy. Due to the life-threatening presentation of sudden cardiac death secondary to ventricular fibrillation, an Implantable Cardioverter-Defibrillator (ICD), specifically a Medtronic® Evera MRI S VR SureScan (DVMC3D4), was implanted. On follow-up, 4 months post-ICD implantation and initiation of medical therapy (fig.3), the patient's condition remained stable and had no further documented ICD shocks. He also has demonstrated adherence to his prescribed medical regimen and has had no significant side effects or disease progression signs. He expressed approval of the treatment reporting on feeling better Discussion Rarity of Wild-Type Transthyretin Amyloidosis in Young Patients Transthyretin amyloidosis, particularly the wild-type form, is predominantly a disease of older adults, with onset typically observed in individuals over 60 years of age [6]. This makes the occurrence of transthyretin cardiac amyloidosis in a 19-year-old an exceptionally rare presentation, challenging the typical demographic profile of the condition. Such an early onset underscores the atypical disease progression in this case, deviating significantly from the usual age-related manifestation of wild-type transthyretin amyloid cardiomyopathy [7]. This case highlights the need for a broader differential diagnosis in younger patients presenting with unexplained cardiomyopathy, even for conditions typically associated with advanced age [8]. The typical age distribution for ATTRwt is in individuals over 60 years old, with a male predominance (9). Autopsy studies have revealed that nearly 25% of individuals aged 80 years or older can have wild-type transthyretin fibrils in their hearts, regardless of symptomatic presentation (10). The presence of ATTRwt in a teenager, therefore, necessitates a thorough investigation to rule out any underlying genetic predispositions or novel pathological mechanisms that might accelerate amyloid deposition at such an uncharacteristically young age. This case prompts a re-evaluation of diagnostic paradigms for cardiac amyloidosis, encouraging clinicians to consider ATTRwt even in the absence of traditional risk factors. Justification for Implantable Cardioverter-Defibrillator Implantation The implantation of an Implantable Cardioverter-Defibrillator (ICD) in this patient was an appropriate intervention for secondary prevention of sudden cardiac death in this patient. According to the ACC/AHA/ASE/HFSA/HRS/SCAI/SCCT/SCMR 2025 (11) Appropriate Use Criteria for Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy, and Pacing, an "Appropriate procedure is one in which the potential benefits, in terms of survival and/or other health benefits (symptoms, functional status, and/or quality of life [QOL]), exceed the potential adverse health consequences related to the acute procedural risk and the long-term consequences of living with an implanted device." Our patient's presentation with a documented out-of-hospital ventricular fibrillation (VF) cardiac arrest, requiring prolonged resuscitation, represents a life-threatening arrhythmic event in the context of an underlying structural heart disease (ATTRwt cardiac amyloidosis). While specific indications for ATTR cardiac amyloidosis with VF are not exhaustively detailed across all tables, the fundamental principle for secondary prevention of sudden cardiac death, as defined by the AUC, is directly met. For patients who have survived an episode of sustained ventricular fibrillation or hemodynamically unstable ventricular tachycardia not due to a reversible cause, the benefits of preventing recurrent fatal arrhythmias with an ICD overwhelmingly outweigh the associated risks. Therefore, the placement of the Medtronic Evera MRI S VR SureScan ICD was an unequivocally appropriate and life-saving measure in this young patient with ATTRwt cardiac amyloidosis. That’s why secondary prevention with an ICD is reasonable in patients with documented sustained ventricular arrhythmias and reasonable life expectancy as our patient here (12). Challenges of Tafamidis Access in Egypt Overview of Tafamidis and its Efficacy Tafamidis is a pharmacotherapeutic agent that selectively binds to transthyretin, kinetically stabilizing the tetramer and inhibiting its dissociation into amyloidogenic monomers, thereby preventing the misfolding and subsequent deposition of amyloid fibrils in myocardial tissue (13) (14). Access Barriers and Cost Implications This challenge is particularly pronounced in regions like Egypt, where the drug's high cost and limited availability create significant hurdles for patients needing this life-saving therapy. This situation highlights the urgent need for local healthcare systems to address drug accessibility and affordability for rare diseases. Despite the patient's diagnosis of ATTRwt cardiac amyloidosis being established as early as age 17, and a formal referral for Tafamidis treatment having been initiated, the medication was not accessible due to its unavailability and high cost in Egypt. This inability to initiate disease-modifying therapy likely contributed to the aggressive and rapid progression observed in this young patient, culminating in a life-threatening ventricular fibrillation cardiac arrest by age 19, especially given that early intervention with tafamidis has been shown to slow disease progression and improve patient outcomes in ATTR-CM (15). Effective stabilization of the transthyretin protein by tafamidis mitigates the amyloidogenic cascade, offering a crucial therapy for patients afflicted with transthyretin amyloidosis (6) Alternative Treatment Strategies In the absence of tafamidis, alternative strategies may include liver transplantation for hereditary forms of the disease, though this does not entirely halt cardiac amyloid deposition, and other investigational therapies aimed at reducing TTR production or clearing amyloid deposits (8)(16). However, these approaches often carry substantial risks and may not be universally applicable, emphasizing the critical role of pharmacological interventions like tafamidis in managing ATTR-CM (17). Conclusion/ Take-away from this case This case highlights the exceptionally aggressive presentation of wild-type transthyretin cardiac amyloidosis in a young individual, leading to a life-threatening ventricular fibrillation cardiac arrest despite an early diagnosis. It underscores the critical need for clinicians to maintain a high index of suspicion for infiltrative cardiomyopathies in atypical age groups presenting with unexplained cardiac events, emphasizing that ATTRwt is not exclusively a disease of the elderly. Furthermore, this patient's course demonstrates the huge impact of limited access to specific disease-modifying therapies, where despite early diagnosis, the disease can progress severely. Finally, this case illustrates the life-saving role of an implantable cardioverter-defibrillator in secondary prevention and calls attention to the global disparities in advanced treatment availability for rare diseases. Abbreviations AL: Amyloid Light Chain ARBs: Angiotensin Receptor Blockers ATTR: Transthyretin Amyloidosis ATTR-CM: Transthyretin Amyloid Cardiomyopathy ATTRv: Autosomal Dominant Variants in Transthyretin Gene ATTRwt: Wild-Type Transthyretin Protein AUC: Appropriate Use Criteria BB: Beta-Blockers CMRI: Cardiac Magnetic Resonance Imaging CPR: Cardiopulmonary Resuscitation ECG: Electrocardiogram ICD: Implantable Cardioverter-Defibrillator ICU: Intensive Care Unit IVS/LVPW: Interventricular Septum/Left Ventricular Posterior Wall LGE: Late Gadolinium Enhancement LVEDD: Left Ventricular End-Diastolic Dimension LVEF: Left Ventricular Ejection Fraction QOL: Quality of Life ROSC: Return of Spontaneous Circulation Tc-PYP: Technetium-99m Pyrophosphate TI: Inversion Time TTR: Transthyretin VF: Ventricular Fibrillation Declarations Consent : Written informed consent was obtained from the patient for the publication of this case report. Available upon request. We have no funding statement to declare and no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper. Author Contribution S. A. collected the data, communicated with the patient and reviewed the final manuscriptB. A. M. : wrote the main manuscript, prepared the figures, and did final formatting and amendments Acknowledgement Thanks to Prof. Ahmed Salah, MD, Misr International Hospital, Egypt; the consultant managing the case presented References Merlini G, Bellotti V. Molecular Mechanisms of Amyloidosis. N Engl J Med. 2003 Aug 7;349(6):583-96. https://doi.org/10.1056/nejmra023144 Pepys MB. Amyloidosis. Annu Rev Med. 2006 Feb 1;57(1):223-41. https://doi.org/10.1146/annurev.med.57.121304.131243 Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020 Jul 7;142(1) https://doi.org/10.1161/CIR.0000000000000792 Lane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A, et al. Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis. Circulation. 2019 Jul 2;140(1):16-26. https://doi.org/10.1161/CIRCULATIONAHA.118.038169 Mohammed SF, Mirzoyev SA, Edwards WD, Dogan A, Grogan DR, Dunlay SM, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014 Apr;2(2):113-22. https://doi.org/10.1016/j.jchf.2013.11.004 Galant NJ, Westermark P, Higaki JN, Chakrabartty A. Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy. Clinical Science. 2017 Mar 1;131(5):395-409. https://doi.org/10.1042/cs20160413 Hund E, Linke RP, Willig F, Grau A. Transthyretin-associated neuropathic amyloidosis. Neurology. 2001 Feb 27;56(4):431-5. https://doi.org/10.1212/wnl.56.4.431 Poli L, Labella B, Cotti Piccinelli S, Caria F, Risi B, Damioli S, et al. Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy. Front Neurol. 2023 Oct 5;14 https://doi.org/10.3389/fneur.2023.1242815 Shah RJ, Pan S, Lanier GM, Mellela L, Aronow WS, Jain D. Recent advances in the pharmacotherapy of TTR amyloidosis of the heart. VP. 2021 https://doi.org/10.20517/2574-1209.2021.76 Marques N, Azevedo O, Almeida AR, Bento D, Cruz I, Correia E, et al. Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence‐Based Recommendations. JAHA. 2020 Oct 6;9(19): https://doi.org/10.1161/jaha.120.016614 Russo AM, Desai MY, Do MM, Butler J, Chung MK, Epstein AE, et al. ACC/AHA/ASE/HFSA/HRS/SCAI/SCCT/SCMR 2025 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy, and Pacing. Journal of the American College of Cardiology. 2025 Mar;85(11):1213-85. https://doi.org/10.1016/j.jacc.2024.11.023 De Michieli L, Lupi A, Sinigiani G, Tietto A, Salvalaggio A, Branca A, et al. Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going. JCM. 2025 May 16;14(10):3481. https://doi.org/10.3390/jcm14103481 Sukaina M, Rehman S, Waheed M, Shehryar M, Rasool R, Ahmed N, et al. Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis. Annals of Medicine & Surgery. 2023 Nov 7;86(1):433-8. https://doi.org/10.1097/ms9.0000000000001482 Hellenbart EL, Ipema HJ, Rodriguez‐Ziccardi MC, Krishna H, DiDomenico RJ. Disease‐modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications. Pharmacotherapy. 2025 Feb;45(2):124-44. https://doi.org/10.1002/phar.4639 Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024 Jan 11;390(2):132-42. https://doi.org/10.1056/nejmoa2305434 Marotta C, Ciccone L, Orlandini E, Rossello A, Nencetti S. A Snapshot of the Most Recent Transthyretin Stabilizers. IJMS. 2024 Sep 16;25(18):9969. https://doi.org/10.3390/ijms25189969 Judge DP, Alexander KM, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs SD, et al. Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy. Journal of the American College of Cardiology. 2025 Mar;85(10):1003-14. https://doi.org/10.1016/j.jacc.2024.11.042 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. 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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-7237179","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":501472333,"identity":"fbed631a-df20-4e2e-90c3-22547b520fdd","order_by":0,"name":"Sherif Abdelkhalek","email":"","orcid":"","institution":"Misr University for Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Sherif","middleName":"","lastName":"Abdelkhalek","suffix":""},{"id":501472334,"identity":"a7c26154-1808-4331-8f63-9a436274d3ea","order_by":1,"name":"Basant Ahmed Mahmoud","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYBACAyQ2G4hg7AeRCQWEtCQgaZnZABIwwKEeq5YNB9BtRwPm7Mcffi78wSDPIHb42aMbFYdlN59fnfjhgQGDPL/YAaxaLHtyjKVnJDAYNkinmRvnnDlsvO3G280SQIcZzpydgN1hB3IYpHkSGBgbpBPMpHPbDiduu3F2A0hLgsFtHFrOP3/8G6jFvkE6/RtYy+YZZzf/wKvlBtBwoJbEBukciC0b+Hu34bXFcsYbM2ueNInkNumcMumcM+nGM27wbrNIMJDA6Rdz/vTHt3lsbGz7pdO3SedUWMv295/dfPNHhY08vzR2LVAgAYkUCDsBIkIC4D9AiupRMApGwSgYAQAABhldikxGIrgAAAAASUVORK5CYII=","orcid":"","institution":"October 6 University","correspondingAuthor":true,"prefix":"","firstName":"Basant","middleName":"Ahmed","lastName":"Mahmoud","suffix":""}],"badges":[],"createdAt":"2025-07-28 20:53:18","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-7237179/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7237179/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89271891,"identity":"454cec02-441b-4ec8-85b6-f6c79f9e3551","added_by":"auto","created_at":"2025-08-18 09:02:29","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":616031,"visible":true,"origin":"","legend":"\u003cp\u003eECG which of patient upon presentation of cardiac arrest showing tachycardia and polymorphic ventricular fibrillation\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7237179/v1/963f7000980bf4e1d6b10072.png"},{"id":89271893,"identity":"600d69f4-b46d-4611-bf78-80fc97e8fc0c","added_by":"auto","created_at":"2025-08-18 09:02:29","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":189401,"visible":true,"origin":"","legend":"\u003cp\u003eECG which of patient, after successful resuscitation during ICU stay\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7237179/v1/0be4e3b04fcd7592553c3d14.png"},{"id":89271896,"identity":"747946a1-0c3d-444b-a5c1-36a388b2d12c","added_by":"auto","created_at":"2025-08-18 09:02:29","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":315396,"visible":true,"origin":"","legend":"\u003cp\u003echest X-ray showing ICD in place\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7237179/v1/907039958bb3d232e7505f46.png"},{"id":90735085,"identity":"a127ae54-d613-457d-8f20-1c5bd7dc12b4","added_by":"auto","created_at":"2025-09-06 20:01:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1991184,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7237179/v1/7e5f8c4d-bd6b-4271-83ca-b1acc5436156.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case report of transthyretin cardiac amyloidosis in a 19-year old patient: From cardiac arrest to sinus rhythm","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAmyloidosis is a term used to refer to a group of diseases characterized by protein misfolding and deposition in tissues[1] leading to organ dysfunction, in a process known as proteotoxicity[2] Cardiac amyloidosis is caused either by misfolded immunoglobulin light chains (ALs) or by misfolding of a liver-synthesized transthyretin (TTR), causing transthyretin amyloidosis (ATTR). ATTR can be caused by autosomal dominant variants in the transthyretin gene TTR (ATTRv) or by the deposition of ATTRwt (wild-type transthyretin protein). Transthyretin amyloid cardiomyopathy (ATTR-CM) is a restrictive cardiomyopathy caused by transthyretin amyloid deposition extracellularly. This case highlights the possibility of ATTR-CM of ATTRwt origin in atypical age groups as seen here. Observational studies have revealed that ATTR-CM may be underrecognized in many heart failure patients, especially those in nontypical age groups[3][4][5].\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 19-year old male patient from Libya, presented to the emergency department, after experiencing an out-of-hospital cardiac arrest. There was no family history of inflammatory disease, heart failure, coronary artery disease or premature cardiac death.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUpon presentation, the patient was found to have ventricular fibrillation (VF) on initial rhythm analysis (Fig. 1). Immediate cardiopulmonary resuscitation (CPR) was initiated, and the patient underwent 1 hour of continuous resuscitation efforts, including approximately 30 defibrillation shocks, before successful return of spontaneous circulation (ROSC). Postresuscitation, the patient was admitted to the ICU, ECG was repeated (Fig. 2), and the patient was put on mechanical ventilation for further management and work-up of the cardiac arrest etiology.\u003c/p\u003e\n\u003ch3\u003ePatient diagnostic history\u003c/h3\u003e\n\u003cp\u003eThe patient had a significant preexisting diagnostic history of cardiac amyloidosis. When the patient was 17 years old, a Cardiac Magnetic Resonance Imaging (CMRI) study had revealed diffuse concentric myocardial hypertrophy with a maximum wall thickness of 17 mm (basal anterior and antero-septal segments) and a significantly increased overall myocardial mass index of 140 g/m2. The CMRI also demonstrated diffuse subendocardial and patchy mid-myocardial/sub-epicardial delayed gadolinium enhancement (LGE) and marked difficulty in myocardial nulling even at high inversion times (TI 700 msec), hallmarks of cardiac amyloidosis. The CMRI conclusion explicitly stated a \u0026quot;Pattern suggestive of infiltrative myocardial diseases in the form of amyloidosis.\u0026quot; An abdominal and pelvic ultrasonography performed around the same time revealed a bulky spleen (13 cm) and a malrotated pelvic ectopic left kidney, findings that can be associated with systemic amyloidosis.\u003c/p\u003e\n\u003cp\u003eTo establish the specific type of amyloidosis, extensive investigations were done. Serum immunofixation, showed a normal immunoglobulin pattern with a normal Kappa/Lambda ratio, effectively ruling out monoclonal gammopathy and AL amyloidosis. Subsequent Bence Jones protein testing in urine was also absent, and serum immunoglobulins profile was normal, further confirming the exclusion of AL amyloidosis. A Technetium-99m Pyrophosphate (Tc-PYP) scintigraphy, performed, (when the patient was 18 years old) showed mildly positive cardiac uptake, with a semiquantitative visual analysis of grade 1/3 and a quantitative heart-to-contralateral lung ratio of 1.4 (Perugini score 2), highly suggestive of ATTR cardiac amyloidosis. Genetic testing for TTR gene mutations was conducted and yielded negative results. Coupled with the absence of any reported family history of amyloidosis or unexplained cardiomyopathy, these comprehensive findings confirmed the diagnosis of wild-type transthyretin cardiac amyloidosis. Indeed, a formal referral for Tafamidis treatment for his non-AL amyloidosis had already been prescribed. Despite efforts to start the Tafamidis treatment, the medication was not accessible to the patient due to its unavailability in Egypt. Given the current unavailability of specific transthyretin stabilizers, the patient then was \u0026nbsp;the patient was initiated on optimized conventional heart failure management, including Angiotensin Receptor Blockers (ARBs) (Candesartan) and Beta-Blockers (Metoprolol), along with diuretics as needed for symptom control.\u003c/p\u003e\n\u003ch3\u003eCurrent measures taken\u003c/h3\u003e\n\u003cp\u003eDuring his current hospitalization following cardiac arrest, a bedside echocardiogram was performed in the ICU, revealing concentric left ventricular hypertrophy (IVS/LVPW: 1.8 cm), dilated left ventricle (LVEDD 5.7 cm), and significant left ventricular diastolic dysfunction with a restrictive filling pattern. LVEF was preserved at an estimated 50%. Other notable findings included thickened mitral and tricuspid valve leaflets with reduced excursion, mild pericardial effusion, and moderate pulmonary hypertension. An ECG performed during the patient\u0026apos;s hospitalization, post-cardiac arrest showed sinus rhythm with biventricular hypertrophy patterns, notably prominent R waves in V1-V2 and classic LVH criteria, with associated ST-T abnormalities consistent with hypertrophy.\u003c/p\u003e\n\u003cp\u003eDue to the life-threatening presentation of sudden cardiac death secondary to ventricular fibrillation, an Implantable Cardioverter-Defibrillator (ICD), specifically a Medtronic\u0026reg; Evera MRI S VR SureScan (DVMC3D4), was implanted.\u003c/p\u003e\n\u003cp\u003eOn follow-up, 4 months post-ICD implantation and initiation of medical therapy (fig.3), the patient\u0026apos;s condition remained stable and had no further documented ICD shocks. He also has demonstrated adherence to his prescribed medical regimen and has had no significant side effects or disease progression signs. He expressed approval of the treatment reporting on feeling better\u003c/p\u003e"},{"header":"Discussion","content":"\u003ch3\u003eRarity of Wild-Type Transthyretin Amyloidosis in Young Patients\u003c/h3\u003e\n\u003cp\u003eTransthyretin amyloidosis, particularly the wild-type form, is predominantly a disease of older adults, with onset typically observed in individuals over 60 years of age [6]. This makes the occurrence of transthyretin cardiac amyloidosis in a 19-year-old an exceptionally rare presentation, challenging the typical demographic profile of the condition. Such an early onset underscores the atypical disease progression in this case, deviating significantly from the usual age-related manifestation of wild-type transthyretin amyloid cardiomyopathy [7]. This case highlights the need for a broader differential diagnosis in younger patients presenting with unexplained cardiomyopathy, even for conditions typically associated with advanced age [8]. The typical age distribution for ATTRwt is in individuals over 60 years old, with a male predominance (9). Autopsy studies have revealed that nearly 25% of individuals aged 80 years or older can have wild-type transthyretin fibrils in their hearts, regardless of symptomatic presentation (10). The presence of ATTRwt in a teenager, therefore, necessitates a thorough investigation to rule out any underlying genetic predispositions or novel pathological mechanisms that might accelerate amyloid deposition at such an uncharacteristically young age. This case prompts a re-evaluation of diagnostic paradigms for cardiac amyloidosis, encouraging clinicians to consider ATTRwt even in the absence of traditional risk factors.\u003c/p\u003e\n\u003ch3\u003eJustification for Implantable Cardioverter-Defibrillator Implantation\u003c/h3\u003e\n\u003cp\u003eThe implantation of an Implantable Cardioverter-Defibrillator (ICD) in this patient was an appropriate intervention for secondary prevention of sudden cardiac death in this patient. According to the ACC/AHA/ASE/HFSA/HRS/SCAI/SCCT/SCMR 2025 (11) Appropriate Use Criteria for Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy, and Pacing, an \"Appropriate procedure is one in which the potential benefits, in terms of survival and/or other health benefits (symptoms, functional status, and/or quality of life [QOL]), exceed the potential adverse health consequences related to the acute procedural risk and the long-term consequences of living with an implanted device.\"\u003c/p\u003e\n\u003cp\u003eOur patient's presentation with a documented out-of-hospital ventricular fibrillation (VF) cardiac arrest, requiring prolonged resuscitation, represents a life-threatening arrhythmic event in the context of an underlying structural heart disease (ATTRwt cardiac amyloidosis). While specific indications for ATTR cardiac amyloidosis with VF are not exhaustively detailed across all tables, the fundamental principle for secondary prevention of sudden cardiac death, as defined by the AUC, is directly met. For patients who have survived an episode of sustained ventricular fibrillation or hemodynamically unstable ventricular tachycardia not due to a reversible cause, the benefits of preventing recurrent fatal arrhythmias with an ICD overwhelmingly outweigh the associated risks. Therefore, the placement of the Medtronic Evera MRI S VR SureScan ICD was an unequivocally appropriate and life-saving measure in this young patient with ATTRwt cardiac amyloidosis.\u003c/p\u003e\n\u003cp\u003eThat’s why secondary prevention with an ICD is reasonable in patients with documented sustained ventricular arrhythmias and reasonable life expectancy as our patient here (12).\u003c/p\u003e\n\u003ch3\u003eChallenges of Tafamidis Access in Egypt\u003c/h3\u003e\n\u003ch4\u003eOverview of Tafamidis and its Efficacy\u003c/h4\u003e\n\u003cp\u003eTafamidis is a pharmacotherapeutic agent that selectively binds to transthyretin, kinetically stabilizing the tetramer and inhibiting its dissociation into amyloidogenic monomers, thereby preventing the misfolding and subsequent deposition of amyloid fibrils in myocardial tissue (13) (14).\u003c/p\u003e\n\u003cp\u003eAccess Barriers and Cost Implications\u003c/p\u003e\n\u003cp\u003eThis challenge is particularly pronounced in regions like Egypt, where the drug's high cost and limited availability create significant hurdles for patients needing this life-saving therapy. This situation highlights the urgent need for local healthcare systems to address drug accessibility and affordability for rare diseases. Despite the patient's diagnosis of ATTRwt cardiac amyloidosis being established as early as age 17, and a formal referral for Tafamidis treatment having been initiated, the medication was not accessible due to its unavailability and high cost in Egypt. This inability to initiate disease-modifying therapy likely contributed to the aggressive and rapid progression observed in this young patient, culminating in a life-threatening ventricular fibrillation cardiac arrest by age 19, especially given that early intervention with tafamidis has been shown to slow disease progression and improve patient outcomes in ATTR-CM (15). Effective stabilization of the transthyretin protein by tafamidis mitigates the amyloidogenic cascade, offering a crucial therapy for patients afflicted with transthyretin amyloidosis (6)\u003c/p\u003e\n\u003ch4\u003eAlternative Treatment Strategies\u003c/h4\u003e\n\u003cp\u003eIn the absence of tafamidis, alternative strategies may include liver transplantation for hereditary forms of the disease, though this does not entirely halt cardiac amyloid deposition, and other investigational therapies aimed at reducing TTR production or clearing amyloid deposits (8)(16). However, these approaches often carry substantial risks and may not be universally applicable, emphasizing the critical role of pharmacological interventions like tafamidis in managing ATTR-CM (17).\u003c/p\u003e\n\n"},{"header":"Conclusion/ Take-away from this case","content":"\u003cp\u003eThis case highlights the exceptionally aggressive presentation of wild-type transthyretin cardiac amyloidosis in a young individual, leading to a life-threatening ventricular fibrillation cardiac arrest despite an early diagnosis. It underscores the critical need for clinicians to maintain a high index of suspicion for infiltrative cardiomyopathies in atypical age groups presenting with unexplained cardiac events, emphasizing that ATTRwt is not exclusively a disease of the elderly. Furthermore, this patient's course demonstrates the huge impact of limited access to specific disease-modifying therapies, where despite early diagnosis, the disease can progress severely. Finally, this case illustrates the life-saving role of an implantable cardioverter-defibrillator in secondary prevention and calls attention to the global disparities in advanced treatment availability for rare diseases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eAL:\u003c/strong\u003e Amyloid Light Chain\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eARBs:\u003c/strong\u003e Angiotensin Receptor Blockers\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eATTR:\u003c/strong\u003e Transthyretin Amyloidosis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eATTR-CM:\u003c/strong\u003e Transthyretin Amyloid Cardiomyopathy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eATTRv:\u003c/strong\u003e Autosomal Dominant Variants in Transthyretin Gene\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eATTRwt:\u003c/strong\u003e Wild-Type Transthyretin Protein\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUC:\u003c/strong\u003e Appropriate Use Criteria\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBB:\u003c/strong\u003e Beta-Blockers\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCMRI:\u003c/strong\u003e Cardiac Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCPR:\u003c/strong\u003e Cardiopulmonary Resuscitation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eECG:\u003c/strong\u003e Electrocardiogram\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICD:\u003c/strong\u003e Implantable Cardioverter-Defibrillator\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICU:\u003c/strong\u003e Intensive Care Unit\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIVS/LVPW:\u003c/strong\u003e Interventricular Septum/Left Ventricular Posterior Wall\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLGE:\u003c/strong\u003e Late Gadolinium Enhancement\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLVEDD:\u003c/strong\u003e Left Ventricular End-Diastolic Dimension\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLVEF:\u003c/strong\u003e Left Ventricular Ejection Fraction\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQOL:\u003c/strong\u003e Quality of Life\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROSC:\u003c/strong\u003e Return of Spontaneous Circulation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTc-PYP:\u003c/strong\u003e Technetium-99m Pyrophosphate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTI:\u003c/strong\u003e Inversion Time\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTTR:\u003c/strong\u003e Transthyretin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVF:\u003c/strong\u003e Ventricular Fibrillation\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e: Written informed consent was obtained from the patient for the publication of this case report. Available upon request.\u003c/p\u003e\n\u003cp\u003eWe have no funding statement to declare and no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper.\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS. A. collected the data, communicated with the patient and reviewed the final manuscriptB. A. M. : wrote the main manuscript, prepared the figures, and did final formatting and amendments\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThanks to Prof. Ahmed Salah, MD, Misr International Hospital, Egypt; the consultant managing the case presented\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eMerlini G, Bellotti V. Molecular Mechanisms of Amyloidosis. N Engl J Med. 2003 Aug 7;349(6):583-96. https://doi.org/10.1056/nejmra023144\u003c/li\u003e\n\u003cli\u003ePepys MB. Amyloidosis. Annu Rev Med. 2006 Feb 1;57(1):223-41. https://doi.org/10.1146/annurev.med.57.121304.131243\u003c/li\u003e\n\u003cli\u003eKittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation. 2020 Jul 7;142(1) https://doi.org/10.1161/CIR.0000000000000792\u003c/li\u003e\n\u003cli\u003eLane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A, et al. Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis. Circulation. 2019 Jul 2;140(1):16-26. https://doi.org/10.1161/CIRCULATIONAHA.118.038169\u003c/li\u003e\n\u003cli\u003eMohammed SF, Mirzoyev SA, Edwards WD, Dogan A, Grogan DR, Dunlay SM, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014 Apr;2(2):113-22. https://doi.org/10.1016/j.jchf.2013.11.004\u003c/li\u003e\n\u003cli\u003eGalant NJ, Westermark P, Higaki JN, Chakrabartty A. Transthyretin amyloidosis: an under-recognized neuropathy and cardiomyopathy. Clinical Science. 2017 Mar 1;131(5):395-409. https://doi.org/10.1042/cs20160413\u003c/li\u003e\n\u003cli\u003eHund E, Linke RP, Willig F, Grau A. Transthyretin-associated neuropathic amyloidosis. Neurology. 2001 Feb 27;56(4):431-5. https://doi.org/10.1212/wnl.56.4.431\u003c/li\u003e\n\u003cli\u003ePoli L, Labella B, Cotti Piccinelli S, Caria F, Risi B, Damioli S, et al. Hereditary transthyretin amyloidosis: a comprehensive review with a focus on peripheral neuropathy. Front Neurol. 2023 Oct 5;14 https://doi.org/10.3389/fneur.2023.1242815\u003c/li\u003e\n\u003cli\u003eShah RJ, Pan S, Lanier GM, Mellela L, Aronow WS, Jain D. Recent advances in the pharmacotherapy of TTR amyloidosis of the heart. VP. 2021 https://doi.org/10.20517/2574-1209.2021.76\u003c/li\u003e\n\u003cli\u003eMarques N, Azevedo O, Almeida AR, Bento D, Cruz I, Correia E, et al. Specific Therapy for Transthyretin Cardiac Amyloidosis: A Systematic Literature Review and Evidence‐Based Recommendations. JAHA. 2020 Oct 6;9(19): https://doi.org/10.1161/jaha.120.016614\u003c/li\u003e\n\u003cli\u003eRusso AM, Desai MY, Do MM, Butler J, Chung MK, Epstein AE, et al. ACC/AHA/ASE/HFSA/HRS/SCAI/SCCT/SCMR 2025 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy, and Pacing. Journal of the American College of Cardiology. 2025 Mar;85(11):1213-85. https://doi.org/10.1016/j.jacc.2024.11.023\u003c/li\u003e\n\u003cli\u003eDe Michieli L, Lupi A, Sinigiani G, Tietto A, Salvalaggio A, Branca A, et al. Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going. JCM. 2025 May 16;14(10):3481. https://doi.org/10.3390/jcm14103481\u003c/li\u003e\n\u003cli\u003eSukaina M, Rehman S, Waheed M, Shehryar M, Rasool R, Ahmed N, et al. Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis. Annals of Medicine \u0026amp; Surgery. 2023 Nov 7;86(1):433-8. https://doi.org/10.1097/ms9.0000000000001482\u003c/li\u003e\n\u003cli\u003eHellenbart EL, Ipema HJ, Rodriguez‐Ziccardi MC, Krishna H, DiDomenico RJ. Disease‐modifying therapies for amyloid transthyretin cardiomyopathy: Current and emerging medications. Pharmacotherapy. 2025 Feb;45(2):124-44. https://doi.org/10.1002/phar.4639 \u003c/li\u003e\n\u003cli\u003eGillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024 Jan 11;390(2):132-42. https://doi.org/10.1056/nejmoa2305434\u003c/li\u003e\n\u003cli\u003eMarotta C, Ciccone L, Orlandini E, Rossello A, Nencetti S. A Snapshot of the Most Recent Transthyretin Stabilizers. IJMS. 2024 Sep 16;25(18):9969. https://doi.org/10.3390/ijms25189969\u003c/li\u003e\n\u003cli\u003eJudge DP, Alexander KM, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs SD, et al. Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy. Journal of the American College of Cardiology. 2025 Mar;85(10):1003-14. https://doi.org/10.1016/j.jacc.2024.11.042\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":true,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Transthyretin Cardiac Amyloidosis, Wild-type ATTR, Cardiac Arrest, Ventricular Fibrillation, Adolescent, Implantable Cardioverter-Defibrillator (ICD), Tafamidis Access","lastPublishedDoi":"10.21203/rs.3.rs-7237179/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7237179/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is generally an age-associated disease observed in older age groups. This case is exceptional in that it reports the aggressive presentation and course of ATTRwt in a young patient, defying traditional demographic characterizations and calling for more widespread diagnostic suspicion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation\u003c/strong\u003e: A 19-year-old Libyan male presented with out-of-hospital ventricular fibrillation (VF) cardiac arrest, requiring one hour and around 30 defibrillation shocks to achieve successful resuscitation. His background diagnosis of ATTRwt cardiac amyloidosis had been established at the age of 17, confirmed by cardiac magnetic resonance imaging (CMRI) which revealed diffuse concentric myocardial hypertrophy with characteristic late gadolinium enhancement and nulling difficulties, and a Technetium-99m Pyrophosphate (Tc-PYP) scintigraphy at age 18 (Perugini score 2). Serological and genetic investigations have excluded AL amyloidosis and hereditary ATTR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions and Outcomes\u003c/strong\u003e: After resuscitation, a secondary prevention Implantable Cardioverter-Defibrillator (ICD) was implanted. Although efforts were made previously to obtain certain TTR stabilizers, the drug Tafamidis was not available in Egypt. The patient is now treated with standard heart failure medications, such as Angiotensin Receptor Blockers (Candesartan) and Beta-Blockers (Metoprolol), in addition to diuretics. At the 4-month follow-up, his condition remained stable with no more documented ICD shocks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: This case highlights the importance of suspecting ATTRwt even in young patients with cardiac presentations such as VF arrest, although ATTRwt is classically linked with very old age. It also draws attention to the difficulty caused by restricted availability of specific disease-modifying therapies for controlling the course of this uncommon and aggressive disease, exploring the health disparities and their effect on possible cessation of disease progression, if resolved.\u003c/p\u003e","manuscriptTitle":"A case report of transthyretin cardiac amyloidosis in a 19-year old patient: From cardiac arrest to sinus rhythm","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 09:02:24","doi":"10.21203/rs.3.rs-7237179/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":"d5b43102-c2aa-4d64-acde-3ae4ee4c9c9e","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-06T19:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-18 09:02:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7237179","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7237179","identity":"rs-7237179","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}