Abstract
Background: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation.
Hypothesis: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK‐MM and CK‐MB), and separated the isoforms of CK‐MM and CK‐MB.
Methods: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 ± 14 years (range 19–60). Patients had been symptomatic for 29 ± 38 months (range 0.5–200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow‐up of 27 months from diagnosis (range 0.6–165), 50 patients remained clinically stable and 27 had deteriorated.
Results: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11,14% vs. 1, 1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 ± 0.62 vs. 0.85 ± 0.56;p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8,30% vs. 3,6%;p=0.004) and CK and CK‐MM activities (5, 19% vs. 2, 4%;p = 0.03) than those who remained stable. Patients with DCM with high CK‐MB activity had 3.13‐fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53–6.40, p = 0.008). Thus, CK measurements, in particular CK‐MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.
Keywords: dilated cardiomyopathy, cardiac enzymes, myocardial damage
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References
- 253. Fuster V, Gersh BJ, Giuliani ER, Tajik AJ, Brandenburg RO, Frye RL: The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol 1981; 47: 525–531 [DOI] [PubMed] [Google Scholar]
- 254. Hofmann T, Meinertz T, Kasper W, Geibel A, Zehender M, Hohnloser S, Stienen U, Treese N, Just H: Mode of death in idiopathic dilated cardiomyopathy: A multivariate analysis of prognostic determinants. Am Heart J 1988; 116: 1455–1463 [DOI] [PubMed] [Google Scholar]
- 255. Brandenberg RO, Chazov E, Cherian G, Falase AO, Grosgogeat Y, Kawai C, Loogen F, Judez M, Orinius E, Goodwin G, Olsen EGJ, Oakley CM, Pisa Z: Report of the WHO/ISFC task force on definition and classification of the cardiomyopathies. Circulation 1981; 64: 1397–1399 [Google Scholar]
- 256. Why HJ, Meany BT, Richardson PJ, Olsen EG, Bowles NE, Cunningham L, Freeke CA, Archard LC: Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 1994; 89 (6): 2582–2589 [DOI] [PubMed] [Google Scholar]
- 257. Neu N, Craig SW, Rose NR, Alvarez F, Beisel KW: Coxsackievirus induced myocarditis in mice: Cardiac myosin autoantibodies do not cross‐react with the virus. Clin Exper Immun 1987; 69: 566–574 [PMC free article] [PubMed] [Google Scholar]
- 258. Neu N, Rose NR, Beisel KW, Herskowitz A, Gurri GG, Craig SW: Cardiac myosin induces myocarditis in genetically predisposed mice. J Immunol 1987; 139: 3630–3636 [PubMed] [Google Scholar]
- 259. Neumann DA: Autoimmunity and idiopathic dilated cardiomyopathy. Mayo Clin Proc 1994; 69: 193–195 [DOI] [PubMed] [Google Scholar]
- 260. Caforio ALP: Role of autoimmunity in dilated cardiomyopathy. Br Heart J 1994; 72 (suppl): S30–S34 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 261. Goldrach S, Haissaguerre M, Broustet JP: Prognostic value of the hemodynamic study at rest and during the exercise test in 103 cases of primary dilated cardiomyopathies. Arch Mal Coeur 1987; 80: 1333–1340 [PubMed] [Google Scholar]
- 262. Hagege A, Desnos M, Fernandez F, Cristofini P, Guenot O, Bourmayan C, Marcantoni JP, Guerot C: Prognostic factors in dilated cardiomyopathies. Arch Mal Coeur 1988; 81: 1473–1479 [PubMed] [Google Scholar]
- 263. Saxon LA, Stevenson WG, Middlekauff HR, Fonarrow G, Woo M, Moser D, Stevenson LW: Predicting death from progressive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1993; 72: 62–65 [DOI] [PubMed] [Google Scholar]
- 264. Komajda M, Jais JP, Goldfarb B, Bouhour JB, Juillieres Y, Lanfranchi J, Peycelon P, Geslin P, Carrie D, Grosgogeat Y: Analysis of predictive factors of mortality in dilated cardiomyopathy. A cooperative study by the Cardiomyopathy Working Group. Arch Mal Coeur 1990; 83: 899–906 [PubMed] [Google Scholar]
- 265. Romeo F, Pelliccia F, Cianfrocca C, Gallo P, Barilla F, Cristofani R, Reale A: Determinants of end‐stage idiopathic dilated cardiomyopathy: A multivariate analysis of 104 patients. Clin Cardiol 1989; 12: 387–392 [DOI] [PubMed] [Google Scholar]
- 266. Zanchetta M, Pedon L, Carlon R, Franceschetto L, Maiolino P: Dilated cardiomyopathy: Multivariate discriminant analysis of main hemodynamic‐angiographic indices. Giorn Ital Cardiol 1990; 20: 15–19 (in Italian) [PubMed] [Google Scholar]
- 267. Fazio G, Veltri EP, Tomaselli G, Lewis R, Griffith LS, Guarnieri T: Long‐term follow‐up of patients with nonischemic dilated cardiomyopathy and ventricular tachyarrhythmias treated with implantable cardioverter defibrillators. Pacing Clin Electrophysiol 1991; 14: 1905–1910 [DOI] [PubMed] [Google Scholar]
- 268. Teragaki M, Ohmura T, Iida H, Tahara A, Itagane H, Toda I, Akioka K, Yasuda M, Nishimoto M, Takeuchi K, Takeda T, Morita S, Tsukada H: Change of the isoform of creatine phosphokinase MM in hypertrophic cardiomyopathy. Am Heart J 1993; 125 (1): 251–253 [DOI] [PubMed] [Google Scholar]
- 269. Wu AHB, Gornet TG, Wu VH, Brockie RE, Nishikawa A: Early diagnosis of acute myocardial infarction by rapid analysis of creatine kinase isoenzyme‐3 (CK‐MM) subtypes. Clin Chem 1987; 33 (3): 358–362 [PubMed] [Google Scholar]
- 270. Annesley TM, Strongwater SL, Schitzer TJ: MM subisoenzymes of creatine kinase as an index of disease activity in polymyositis. Clin Chem 1985; 31: 1162–1169 [PubMed] [Google Scholar]
- 271. Hossein‐Nia M, Kallis P, Brown PA, Chester MR, Kaski JC, Murday AJ, Treasure T, Holt DW: Creatine kinase MB isoforms: Sensitive markers of ischaemic myocardial damage. Clin Chem 1994; 40 (7): 1265–1271 [PubMed] [Google Scholar]
- 272. Puleo PR, Guadagno PA, Roberts R, Scheel MV, Marian AJ, Churchill D, Perryman MB: Early diagnosis of myocardial infarction based on assay for subforms of creatine kinase‐MB. Circulation 1990; 82: 759–764 [DOI] [PubMed] [Google Scholar]
- 273. Manolio TA, Baughman KL, Rodeheffer R, Pearson TA, Bristow D, Michels VV, Abelmann WH, Harlan WR: Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of National Heart, Lung, and Blood Institute workshop). Am J Cardiol 1992; 69: 1458–1466 [DOI] [PubMed] [Google Scholar]
- 274. Aretz HT, Billingham ME, Edwards WD, Factor FM, Fallon JT, Fenolio JJ, Olsen EG, Schoen FJ: Myocarditis, a histopathologic definition and classification. Am J Cardiovasc Pathol 1987; 1: 3–14 [PubMed] [Google Scholar]
- 275. Greene HL, Richardson DW, Baker AH, Roden DM, Capone RJ, Echt DS, Friedman LM, Gillespie MJ, Hallstrom AP, Verter J: Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (The Cardiac Arrhythmia Pilot Study). Am J Cardiol 1989; 63: 1–6 [DOI] [PubMed] [Google Scholar]
- 276. Henry WL, Gardin JM, Ware JH: Echocardiographic measurements in normal subjects from infancy to old age. Circulation 1980: 62 (5): 1054–1061 [DOI] [PubMed] [Google Scholar]
- 277. Blackie SP, Fairbarn MS, McElvaney GN, Morrison NJ, Wilcox PG, Pardy RL: Prediction of maximal oxygen uptake and power during cycle ergometry in subjects older than 55 years of age. Am Rev Respir Dis 1989; 139: 1424–1429 [DOI] [PubMed] [Google Scholar]
- 278. Davies J, Reynolds T, Penney MD: Creatine kinase isoforms: Investigation of inhibitors of in vitro degradation and establishment of a reference range. Ann Clin Biochem 1992; 29: 202–205 [DOI] [PubMed] [Google Scholar]
- 279. Wicks RW, Usategui‐Gomez M, Miller M, Warshaw M: Immunochemical determination of CK‐MB isoenzyme in human serum: II. An enzymatric approach. Clin Chem 1982; 28: 54–58 [PubMed] [Google Scholar]
- 280. Puleo PR, Perryman MB, Bresser MA, Rokey R, Pratt CM, Roberts R: Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man. Circulation 1987; 5: 1162–1169 [DOI] [PubMed] [Google Scholar]
- 281. Puleo PR, Guadagno PA, Roberts R, Perryman MB: Sensitive and rapid assay of plasma subforms of creatine kinase MB. Clin Chem 1989; 35: 1452–1455 [PubMed] [Google Scholar]
- 282. Kanemitsu F, Okigaki T: Creatine kinase MB isoforms for early diagnosis and monitoring of acute myocardial infarction. Clin Chim Acta 1992; 206: 191–199 [DOI] [PubMed] [Google Scholar]
- 283. Kawai C, Matsumori A, Fujiwara H: Myocarditis and dilated cardiomyopathy. Ann Rev Med 1987; 38 (221): 221–239 [DOI] [PubMed] [Google Scholar]
- 284. Caforio AL, Stewart JT, Bonifacio E, Burke M, Davies MJ, McKenna WJ, Bottazzo GF: Inappropriate major histocompatibility complex expression on cardiac tissue in dilated cardiomyopathy. Relevance for autoimmunity? J Autoimmun 1990; 3 (2): 187–200 [DOI] [PubMed] [Google Scholar]
- 285. Caforio AL, Bonifacio E, Stewart JT, Neglia D, Parodi O, Bottazzo GF, McKenna WJ: Novel organ‐specific circulating cardiac autoantibodies in dilated cardiomyopathy. J Am Coll Cardiol 1990; 15 (7): 1527–1534 [DOI] [PubMed] [Google Scholar]
- 286. Caforio AL, Grazzini M, Mann JM, Keeling PJ, Bottazzo GF, McKenna WJ, Schiaffino S: Identification of alpha‐ and beta‐cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation 1992; 85 (5): 1734–1742 [DOI] [PubMed] [Google Scholar]
- 287. Caforio A, Keeling P, Gordon D, Holt D, McKenna W: T‐cell involvement in dilated cardiomyopathy: Interleukin‐2 receptor levels are high and related to endomyocardial biopsy markers of immune activation (abstr). Circulation 1993; 88: 1833 [Google Scholar]
- 288. Kuhl U, Daun B, Seeberg B, Schultheiss HP, Strauer BE: Dilated cardiomyopathy: A chronic myocarditis? Immunological characterisation of lymphocytic infiltrates. Herz 1992; 17: 97–106 [PubMed] [Google Scholar]