Biomedical papers, 2016 (vol. 160), issue 4

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(4):524-532 | 10.5507/bp.2016.033

Improvement of left ventricular systolic function in inflammatory cardiomyopathy: What plays a role?

Jan Krejcia, Petr Hudea, Eva Ozabalovaa, Dalibor Mlejneka, Vita Zampachovab, Iva Svobodovab, Radka Stepanovac, Lenka Spinarovaa
a Department of Cardiovascular Diseases, St. Anne's University Hospital Brno and Masaryk University, Brno, Czech Republic
b First Department of Pathological Anatomy, St. Anne's University Hospital in Brno and Masaryk University, Brno, Czech Republic
c Department of Internal Medicine and Cardiology, University Hospital Brno, Czech Republic

Aims: To compare the differences between patients with inflammatory cardiomyopathy (ICM) with and without improvement in left ventricular (LV) systolic function and to identify the relevant predictors of LV improvement.

Patients and Methods: The study included 63 patients with biopsy-proven ICM and heart failure symptoms of at least NYHA II, symptom duration ≤ 6 months, LV ejection fraction (LVEF) ≤ 40% assessed by echocardiography and presence of >14 mononuclear leukocytes (LCA+ cells)/mm2 in biopsy samples. Patients were evaluated at baseline and after 6 months.

Results: In the group with LVEF improvement of ≥ 10% (I+ group, n = 41), LVEF increased from 24 ± 7% to 47 ± 8% (P < 0.001). In 22 patients (group I-), there was no or minimal LVEF increase (< 10%). In the I+ group, there were more LCA+ cells/mm2 at baseline (25.1 ± 16.5 vs. 18.5 ± 4.4 cells/mm2; P = 0.032) and a more significant decrease in LCA+ cells in the follow-up (reduction of 13.6 ± 14.3 cells/mm2 vs. 5.0 ± 7.7 cells/mm2 in the I- group; P = 0.009). The univariate logistic regression showed a possible association of number of LCA+ cells, LV end-diastolic diameter and N-terminal fragment of pro-brain natriuretic peptide (NTproBNP) value with LVEF improvement. In the multivariate analysis, only NTproBNP at diagnosis was confirmed as an independent predictor of LVEF improvement (OR=1.2; 1.003 to 1.394; P = 0.046).

Conclusion: The LV systolic function improvement was observed in 65% of the patients. In these patients, the number of inflammatory cells at baseline was higher and decreased more but the higher baseline NTproBNP value was the only independent predictor of LVEF improvement.

Keywords: inflammatory cardiomyopathy, endomyocardial biopsy, echocardiography, NTproBNP, right heart catheterization.

Received: April 16, 2016; Accepted: June 6, 2016; Prepublished online: June 20, 2016; Published: December 12, 2016


References

  1. Stehlik J, Edwards LB, Kucheryavaya AY, Aurora P, Christie JD, Kirk R, Dobbels F, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult heart transplant report-2010. J Heart Lung Transplant 2010;29:1089-103. Go to original source... Go to PubMed...
  2. Kühl U. Antiviral treatment of myocarditis and acute dilated cardiomyopathy. Heart Failure Clin 2005;1:467-74. Go to original source... Go to PubMed...
  3. Hufnagel G, Pankuweit S, Richter A, Schonian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID): first epidemiological results. Herz 2000;25:279-85. Go to original source... Go to PubMed...
  4. Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM. 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. Go to original source... Go to PubMed...
  5. Cooper LT. Myocarditis. N Engl J Med 2009;360:1526-38. Go to original source... Go to PubMed...
  6. Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, Ramondo A, Carturan E, Iliceto S, Thiene G, Daliento L. A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 2007;28:1326-33. Go to original source... Go to PubMed...
  7. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, Klingel K, Kandolf R, Sechtem U, Cooper LT, Böhm M. Update on myocarditis. J Am Coll Cardiol 2012;59:779-92. Go to original source... Go to PubMed...
  8. Dennert R, Crijns HJ, Heymans S. Acute viral myocarditis. Eur Heart J 2008;29:2073-82. Go to original source... Go to PubMed...
  9. Schultheiss HP, Kühl U, Cooper LT. The management of myocarditis. Eur Heart J 2011;32:2616-25. Go to original source... Go to PubMed...
  10. Caforio ALP, Marcolongo R, Basso C, Iliceto S. Clinical presentation and diagnosis of myocarditis. Heart 2015;101:1332-44. Go to original source... Go to PubMed...
  11. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P. Report of the 1995 World Health Organisation/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 1996;93:841-42. Go to original source... Go to PubMed...
  12. Aretz HAT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ Jr, Olsen EG, Schoen FJ. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14. Go to PubMed...
  13. Kühl U, Noutsias M, Seeberg B, Schultheiss HP. Immunohistological evidence for chronic intramyocardial inflammatory proces in dilated cardiomyopathy. Heart 1996;75:295-300. Go to original source... Go to PubMed...
  14. Maisch B, Portig I, Ristic A, Hufnagel G, Pankuweit S. Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report. Herz 2000;25:200-9. Go to original source... Go to PubMed...
  15. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T, Zembala M, Polonski L, Rozek MM, Wodniecki J. et al. Randomized, placebo controled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy. Circulation 2001;104:39-45. Go to original source... Go to PubMed...
  16. Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J 2009;30:1995-2002. Go to original source... Go to PubMed...
  17. Thiene G, Bruneval P, Veinot J, Leone O. Diagnostic use of endomyocardial biopsy: a consensus statement. Virchows Arch 2013;463:1-5. Go to original source... Go to PubMed...
  18. Palecek T, Kuchynka P, Hulinska D, Schramlova J, Hrbackova H, Vitkova I, Simek S, Horak J, Louch WE, Linhart A. Presence of Borrelia burgdorferi in endomyocardial biopsies in patients with new-onset unexplained dilated cardiomyopathy. Med Microbiol Immunol 2010;199:139-43. Go to original source... Go to PubMed...
  19. Kubanek M, Sramko M, Berenova D, Hulínská D, Hrbáèková H, Malu¹ková J, Lodererová A, Málek I, Kautzner J. Detection of Borrelia burgdorferi sensu lato in endomyocardial biopsy specimens in individuals with recent-onset dilated cardiomyopathy. Eur J Heart Fail 2012;14:588-96. Go to original source... Go to PubMed...
  20. Kuchynka P, Palecek T, Grus T, Lindner J, Berenova D, Kurzova Z, Balatova P, Krsek D, Vitkova I, Nemecek E, Podzimkova J, Danek AB, Linhart A. Absence of Borrelia burgdorferi in the myocardium of subjects with normal left ventricular systolic function: a study using PCR and electron microscopy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016;160:136-9. Go to PubMed...
  21. Caforio ALP, Bottaro S, Iliceto S. Dilated cardiomyopathy and myocarditis: Classification, clinical and autoimmune features. Applied Cardiopulmonary Pathophysiology 2012;16:82-95.
  22. Wehlou C, Delanghe JR. Detection of antibodies in cardiac autoimmmunity. Clinica Chimica Acta 2009;408:114-22. Go to original source...
  23. Krejci J, Poloczkova H, Hude P, Freiberger T , Nemcova E, Zampachova V, Sirotkova A, Stepanova R, Spinarova L, Nemec P, Vitovec J. Impact of inflammatory infiltration and viral genome presence in myocardium on the changes of echocardiographic parameters. Cor et Vasa 2013;55:e333-e340. Go to original source...
  24. Kühl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, Schultheiss HP. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation 2005;111:887-93. Go to original source... Go to PubMed...
  25. Krejci J, Hude P, Poloczkova H, Zampachova V, Stepanova R, Freiberger T, Nemcova E, Spinarova L. Correlations of the changes in bioptic findings with echocardiographic, clinical and laboratory parameters in patients with inflammatory cardiomyopathy. Heart Vessels 2016;31:416-26. Go to original source... Go to PubMed...
  26. McCarthy RE, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM, Baughman KL. Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med 2000;342:690-95. Go to original source... Go to PubMed...
  27. Corsten MF, Schroen B, Heymans S. Inflammation in viral myocarditis: friend or foe? Trends Molecular Med 2012;18:426-37. Go to original source...
  28. D'Ambrosio A, Patti G, Manzoli A, Sinagra G, Di Lenarda A, Silvestri F, Di Sciascio G. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart 2001;85:499-504. Go to original source... Go to PubMed...
  29. Escher F, Kühl U, Lassner D, Stroux A, Westermann D, Skurk C, Tschöpe C, Poller W, Schultheiss HP. Presence of perforin in endomyocardial biopsies of patients with inflammatory cardiomyopathy predicts poor outcome. Eur J Heart Fail 2014;16:1066-72. Go to original source... Go to PubMed...
  30. Fairweather D, Cooper LT, Blauwet LA. Sex and gender differences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 2013;38:7-46. Go to original source... Go to PubMed...
  31. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bültmann B, Müller T, Lindinger A, Böhm M. Predictors of outcome in patients with suspected myocarditis. Circulation 2008;118:639-48. Go to original source... Go to PubMed...
  32. Cooper LT, Mather PJ, Alexis JD, Pauly DF, Torre-Amione G, Wittstein IS, Dec GW, Zucker M, Narula J, Kip K, McNamara DM. Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women. J Cardiac Fail 2012;18:28-33. Go to original source...
  33. Maisch B, Pankuweit S. Current treatment options in (peri)myocarditis and inflammatory. Herz 2012;37:644-56. Go to original source... Go to PubMed...
  34. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendation for cardiac chambre quantificantions by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiocascular Imaging. Eur Heart J Cardiovasc Imaging 2015;16:233-70. Go to original source... Go to PubMed...
  35. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, LipGY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33:1787-847.
  36. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-239. Go to original source... Go to PubMed...
  37. Kubanek M, Sramko M, Maluskova J, Kautznerova D, Weichet J, Lupinek P, Vrbska J, Malek I, Kautzner J. Novel predictors of left ventricular reverse remodelling in individuals with recent onset dilated cardiomyopathy. J Am Coll Cardiol 2013;61:54-63. Go to original source... Go to PubMed...
  38. Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 1989;14:915-20. Go to original source... Go to PubMed...
  39. Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL, Hare JM. Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol 2000;36:227-32. Go to original source... Go to PubMed...
  40. Magnani JW, Dec GW. Myocarditis Current Trends in Diagnosis and Treatment. Circulation. 2006 Feb 14;113:876-90. Go to original source...
  41. Ukena C, Kindermann M, Mahfoud F, Geisel J, Lepper PM, Kandolf R, Böhm M, Kindermann I. Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis. Clin Res Cardiol 2014;103:743-51. Go to original source... Go to PubMed...
  42. McNamara DM, Holubkov R, Starling RC, Dec GW, Loh E, Torre-Amione G, Gass A, Janosko K, Tokarczyk T, Kessler P, Mann DL, Feldman AM. Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 2001;103:2254-59. Go to original source... Go to PubMed...
  43. Saegusa S, Fei Y, Takashi T, Sumino H, Moriya J, Kawaura K, Yamakawa J, Itoh T, Morimoto S, Nakahashi T, Iwai K, Matsumoto M, Kanda T. Oral administration of candesartan improves the survival of mice with viral myocarditis through modification of cardiac adiponectin expression. Cardiovasc Drug Ther 2007;21:155-60. Go to original source...
  44. Bahk TJ, Daniels MD, Leon JS, Wang K, Engman DM. Comparison of angiotensin converting enzyme inhibition and angiotensin II receptor blocade for prevention of experimental autoimmune myocarditis. Int J Cardiol 2008;125:85-93. Go to original source... Go to PubMed...
  45. Xiao J, Shimada M, Liu W, Hu D, Matsumori A. Antiinflammatory effect of eplerenone on viral myocarditis. Eur J Heart Fail 2009;11:349-53. Go to original source... Go to PubMed...
  46. Pauschinger M, Rutschow S, Chandrasekharan K, Westermann D, Weitz A, Peter Schwimmbeck L, Zeichhardt H, Poller W, Noutsias M, Li J, Schultheiss HP,Tschope C. Carvedilol improves left ventricular function in murine coxsackievirus induced acute myocarditis association with reduced myocardial interleukin-1beta and MMP-8 expression and a modulated immune response. Eur J Heart Fail 2005;7:444-52. Go to original source... Go to PubMed...
  47. Stanton C, Mookadam F, Cha S, McNamara D, Aukrust P, Wojnicz R, Bailey KR, Cooper LT. Greater symptom duration predicts response to immunomodulatory therapy in dilated cardiomyopathy. Int J Cardiol 2008;128:38-41. Go to original source... Go to PubMed...
  48. Frustaci A, Chimenti C, Calabrese F, Pieroni M, Thiene G, Maseri A. Immunosuppressive therapy for active lymphocytic myocarditis. Virological and immunologic profile of responders versus nonresponders. Circulation 2003;107:857-86. Go to original source... Go to PubMed...