A novel prediction model for myocardial fibrosis in patients suspected of myocarditis

Year 2024, Volume: 49 Issue: 1, 192 - 203, 29.03.2024

Aslan Erdoğan Omer Genç İhsan Demirtaş Muhammed Mert Göksu Berk Erdinç Duygu Genç Yiğit Can Kartal

https://doi.org/10.17826/cumj.1439074

Abstract

Purpose: This study aimed at establishing a predictive method that consists of clinical, electrocardiographic (ECG), and laboratory parameters for myocardial fibrosis, especially as detected on cardiac magnetic resonance imaging (CMRI), in patients examined with suspicion of myocarditis.
Materials and Methods: This study is a retrospective, single-centre study that includes patients admitted to our centre with suspected myocarditis between March 2020 and November 2023. Participants were categorised into two groups (myocardial fibrosis positive and myocardial fibrosis negative), and a detailed comparison of comorbidities, ECG changes, and laboratory parameters was performed. Multivariate analysis was conducted to identify independent predictors of myocardial fibrosis. A nomogram was constructed using the coefficients from the multivariate analysis to estimate the probability of myocardial fibrosis presence based on key predictors.
Results: This study included 98 participants with a median age of 30 years, predominantly male (80.6%), with 14.3% having hypertension, 8.2% having diabetes mellitus, and 10.2% being smokers. The myocardial fibrosis-negative group exhibited higher levels of left ventricular ejection fraction and lymphocyte count. Conversely, the myocardial fibrosis-positive group showed higher levels of ECG changes at admission, peak C-reactive protein (CRP), CRP velocity, peak troponin, N-terminal pro-brain natriuretic peptide (NT-proBNP), monocytes, and platelets (PLT). In multivariate analysis, PLT, lymphocyte, monocyte, peak troponin, and ECG changes were identified as independent predictors of myocardial fibrosis. Receiving operating characteristic (ROC) curve analysis showed the model's diagnostic accuracy for predicting myocardial fibrosis (area under the ROC (AUC): 0.959, 95% confidence interval (CI), and p<0.001).
Conclusion: This comprehensive analysis highlights the relationships between clinical and laboratory parameters and myocardial fibrosis and presents a predictive model with high diagnostic accuracy.

Keywords

Endomyocardial fibrosis, magnetic resonance ımaging, myocarditis

Miyokardit şüphesi olan hastalarda miyokardiyal fibrozis için yeni bir tahmin modeli

Abstract

Amaç: Bu çalışmanın amacı, miyokardit şüphesi ile tetkik edilen hastalarda özellikle kardiyak manyetik rezonans görüntülemede saptanan miyokardiyal fibrozisi klinik, elektrokardiyografik (EKG) ve laboratuvar parametrelerinden oluşan bir öngörücü metod ile saptamaya çalışmaktır.
Gereç ve Yöntem: Bu çalışma, Mart 2020 ile Kasım 2023 tarihleri arasında merkezimize şüpheli miyokardit ile başvuran hastaları içeren retrospektif, tek merkezli bir çalışmadır. Katılımcılar, miyokardiyal fibrosiz pozitif ve negatif olmak üzere iki gruba ayrıldı. Komorbid durumlar, EKG değişiklikleri ve laboratuvar parametrelerinin detaylı bir karşılaştırması yapıldı. Miyokard fibrozunun bağımsız belirleyicilerini tanımlamak için çok değişkenli analiz yapıldı. Çok değişkenli analizden elde edilen katsayılar kullanılarak miyokardiyal fibrosizin varlığını tahmin etmek amacıyla bir nomogram oluşturuldu.
Bulgular: Bu çalışma, yaş ortalaması 30 olan, %80.6’sı erkek, 98 katılımcıyı içermektedir. Hastaların %14.3'ünde hipertansiyon, %8.2'sinde diyabet varken %10.2'si sigara içicisiydi. Miyokardiyal fibrozis negatif grupta, sol ventrikül ejeksiyon fraksiyonu ve lenfosit sayısı daha yüksek oranlarda izlendi. Aksine miyokardiyal fibrozis pozitif grupta başvuruda EKG değişiklikleri, pik CRP, CRP velositesi, pik troponin, NT-proBNP, monosit ve trombosit (PLT) düzeyleri daha yüksek seviyelere sahipti. Çok değişkenli analizde PLT sayısı, lenfosit sayısı, monosit sayısı, pik troponin ve başvuru esnasındaki EKG değişiklikleri miyokard fibrozunun bağımsız belirleyicileri olarak saptandı. ROC eğrisi analizi, miyokardial fibrozisi tahmin etme modelinin doğru tanı koyma gücüne sahip olduğunu gösterdi. (AUC: 0.959, p<0.001).
Sonuç: Bu kapsamlı analiz, klinik ve laboratuvar parametreleri ile miyokard fibrozu arasındaki ilişkilere öngörüler sunarak, doğru tanı koyma oranına sahip bir tahmin modeli sunmaktadır.

Keywords

Endomiyokardiyal fibrozis, manyetik rezonans görüntüleme, miyokardit

References

• 1. McDonagh TA, Macro M, Adamo M, Gardner SR, Baumbach A, Böhm M et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599–3726
• 2. Tschöpe C, Ammirati E, Bozkurt B, Caforoi ALP, Cooper LT, Felix SB et al. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol. 2021;18:169–93.
• 3. Gupta S, Markham DW, Drazner MH, Mammen PPA. Fulminant myocarditis. Nat Clin Pract Cardiovasc Med. 2008;5:693-706.
• 4. Caforio ALP, Marcolongo R, Basso C, Iliceto S. Clinical presentation and diagnosis of myocarditis. Heart. 2015;101:1332–44.
• 5. Tschope C, Cooper LT, Torre-Amione G, Van Linthout S. Management of myocarditis-related cardiomyopathy in adults. Circ Res. 2019;124:1568–83.
• 6. Biesbroek PS, Beek AM, Germans T, Niessen HWM, van Rossum AC. Diagnosis of myocarditis: current state and future perspectives. Int J Cardiol. 2015;191:211–9.
• 7. Yilmaz A, Ferreira V, Klingel K, Kandolf R, Neubauer S, Sechtem U. Role of cardiovascular magnetic resonance imaging (CMR) in the diagnosis of acute and chronic myocarditis. Heart Fail Rev. 2012;18:747-60.
• 8. Krishnamurthy R, Cheong B, Muthupillai R. Tools for cardiovascular magnetic resonance imaging. Cardiovasc Diagn Ther. 2014;4:104-25.
• 9. Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB et al. The current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the european society of cardiology working group on myocardial and pericardial diseases. Eur Heart J. 2013;34:2636–48.
• 10. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on the detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.
• 11. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. Treatment of high blood pressure. National high blood pressure education program coordinating c. seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206-52.
• 12. Mitchell C, Rahko PS, Blauwet LA. Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American Society of Echocardiography. Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography. 2019;321:1–64.
• 13. Kociol RD, Cooper LT, Fang JC, Moslehi JJ, Pang PS, Sabe MA et al. Recognition and Initial Management of Fulminant Myocarditis. Circulation. 2020;141:e69–92.
• 14. Maisch B, Ristić AD, Hufnagel G, Pankuweit S. Pathophysiology of viral myocarditis: the role of a humoral immune response. Cardiovasc Patho. 2022;11:112-22.
• 15. Watanabe K, Sukumaran V, T Veeraveedu P, Thandavarayan R, Gurusamy N, Ma M, et al. Regulation of inflammation and myocardial fibrosis in experimental autoimmune myocarditis. Inflamm Allergy-Drug Targets .2011;10:218-25.
• 16. Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M et al. Management of acute myocarditis and chronic inflammatory cardiomyopathy. Circ Heart Fail. 2020;13:e007405.
• 17. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation. 1991;83:1849-657
• 18. Ambale-Venkatesh B, Lima JA . Cardiac MRI: a central prognostic tool in myocardial fibrosis. Nat Rev Cardiol.2015;12:18-29.
• 19. Karamitsos TD, Francis JM, Myerson S, Selvanayagam JB, Neubauer S. The role of cardiovascular magnetic resonance imaging in heart failure. J Am Coll Cardiol. 2009;54:1407-24.
• 20. Frangogiannis NG. Cardiac fibrosis. Cardiovasc Res. 2021;117:1450–88.
• 21. Mandawat A, Chattranukulchai P, Mandawat A, Blood AJ, Ambati S, Hayes B, et al. Progression of myocardial fibrosis in nonischemic DCM and association with mortality and heart failure outcomes. JACC Cardiovasc Imaging. 2021;14:1338–50.
• 22. Ozierański K, Tymińska A, Kobylecka M, Caforio ALP, Šobić-Šaranović D, Ristić AD et al. Positron emission tomography in clinically suspected myocarditis – STREAM study design. Int J Cardiol. 2021;332:113–8.
• 23. Smith SC, Ladenson JH, Mason JW, Jaffe AS. Elevations of cardiac troponin associated with myocarditis. Circulation. 1997;95:163–8.
• 24. Olejniczak M, Schwartz M, Webber E, Shaffer A, Perry TE. Viral myocarditis-incidence, diagnosis and management. J Cardiothorac Vasc Anesth. 2020;34:1591–601.
• 25. Kawasaki T, Sakai C, Harimoto K, Yamano M, Miki S et al. The usefulness of high-sensitivity cardiac troponin t and brain natriuretic peptide as biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Am J Cardiol. 2013;112:867-72.
• 26. Ammirati E, Veronese G, Bottiroli M, Wang DW, Cipriani M, Garascia A et al. Update on acute myocarditis. Trends Cardiovasc Med. 2021;31:370–9.
• 27. Butto A, Rossano JW, Nandi D, Ravishankar C, Lin KY et al . Elevated troponin in the First 72 h of hospitalization for pediatric viral myocarditis is associated with ECMO: an analysis of the PHIS+ database. Pediatr Cardiol. 2018;39:1139–43.
• 28. Yu SR, Zhang CY, Xiong WJ, Chen JT, Song J, Chen H. A hypothesis: disproportion between cardiac troponin and b-type natriuretic peptide levels-a high-risk and poor prognostic biomarker in patients with fulminant myocarditis? Heart Lung Circ. 2021;30:837-42.
• 29. Kociol RD, Cooper LT, Fang JC, Moslehi JJ, Pang PS, Sabe MA et al. Recognition and initial management of fulminant myocarditis: a scientific statement from the American Heart Association Circulation. 2020;141:69-92.
• 30. Buttà C, Zappia L, Laterra G, Roberto M. Diagnostic and prognostic role of electrocardiogram in acute myocarditis: a comprehensive review. Ann Noninvasive Electrocardiol. 2020;25:e12726.
• 31. Morgera T, Di Lenarda A, Dreas L, Pinamonti B, Humar F, Bussani R et al. Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes. Am Heart J. 1992;124:455–67.