Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 10 , Pages 783-791 , October 2011

Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: The AREA-in-CHF study

  • G. de Simone

      Affiliations

    • Federico II University Hospital, Department of Clinical and Experimental Medicine, v. S. Pansini 5, bld 1, 80131 Napoli, Italy
    • Corresponding Author InformationCorresponding author.
  • ,
  • M. Chinali

      Affiliations

    • Federico II University Hospital, Department of Clinical and Experimental Medicine, v. S. Pansini 5, bld 1, 80131 Napoli, Italy
  • ,
  • G.F. Mureddu

      Affiliations

    • San Giovanni-Addolorata Hospital, Department of Cardiovascular Diseases, Roma, Italy
  • ,
  • G. Cacciatore

      Affiliations

    • San Giovanni-Addolorata Hospital, Department of Cardiovascular Diseases, Roma, Italy
  • ,
  • D. Lucci

      Affiliations

    • ANMCO Research Center, Florence, Italy
  • ,
  • R. Latini

      Affiliations

    • Istituto Mario Negri, Department of Cardiovascular Research, Milan, Italy
  • ,
  • S. Masson

      Affiliations

    • Istituto Mario Negri, Department of Cardiovascular Research, Milan, Italy
  • ,
  • M. Vanasia

      Affiliations

    • Therabel Pharmaceutical Industries, Italy
  • ,
  • A.P. Maggioni

      Affiliations

    • ANMCO Research Center, Florence, Italy
  • ,
  • A. Boccanelli

      Affiliations

    • San Giovanni-Addolorata Hospital, Department of Cardiovascular Diseases, Roma, Italy
  • ,
  • on behalf of the AREA-in-CHF Investigators

Received 13 October 2009 ,Revised 9 January 2010 ,Accepted 15 February 2010.

References 

  1. Chinali M, Devereux RB, Howard BV, Roman MJ, Bella JN, Liu JE, et al. Comparison of cardiac structure and function in American Indians with and without the metabolic syndrome (the Strong Heart Study). Am J Cardiol. 2004;93:40–44
  2. Chinali M, de Simone G, Roman MJ, Best LG, Lee ET, Russell M, et al. Cardiac markers of pre-clinical disease in adolescents with the metabolic syndrome: the strong heart study. J Am Coll Cardiol. 2008;52:932–938
  3. Suzuki T, Katz R, Jenny NS, Zakai NA, LeWinter MM, Barzilay JI, et al. Metabolic syndrome, inflammation, and the incident heart failure in the elderly: the cardiovascular health study. Circ Heart Fail. September 23, 2008;
  4. Arcucci O, de Simone G, Izzo R, Rozza F, Chinali M, Rao MA, et al. Association of suboptimal blood pressure control with body size and metabolic abnormalities. J Hypertens. 2007;25:2296–2300
  5. de Simone G, Olsen MH, Wachtell K, Hille DA, Dahlof B, Ibsen H, et al. Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study. J Hum Hypertens. 2007;21:625–632
  6. de Simone G, Devereux RB, Chinali M, Best LG, Lee ET, Galloway JM, et al. Prognostic impact of metabolic syndrome by different definitions in a population with high prevalence of obesity and diabetes: the Strong Heart Study. Diabetes Care. 2007;30:1851–1856
  7. Grassi G, Quarti-Trevano F, Seravalle G, Dell'Oro R. Cardiovascular risk and adrenergic overdrive in the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2007;17:473–481
  8. Caprio M, Feve B, Claes A, Viengchareun S, Lombes M, Zennaro MC. Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis. FASEB J. 2007;21:2185–2194
  9. Frey FJ, Odermatt A, Frey BM. Glucocorticoid-mediated mineralocorticoid receptor activation and hypertension. Curr Opin Nephrol Hypertens. 2004;13:451–458
  10. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709–717
  11. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321
  12. Boccanelli A, Mureddu GF, Cacciatore G, Clemenza F, Di Lenarda A, Gavazzi A, et al. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results. Eur J Heart Fail. 2009;11:68–76
  13. Boccanelli A, Cacciatore G, Mureddu GF, de Simone G, Clemenza F, De Maria R, et al. Baseline characteristics of patients recruited in the AREA IN-CHF study (Antiremodelling Effect of Aldosterone Receptors Blockade with Canrenone in Mild Chronic Heart Failure). J Cardiovasc Med (Hagerstown). 2007;8:683–691
  14. Cacciatore G, Boccanelli A, Mureddu GF, Maggioni AP, Latini R, et al. The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade with canrenone in mild chronic heart failure): rationale and design. Ital Heart J. 2005;6(Suppl. 1):66S–74S
  15. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection . Evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106:3143–3421
  16. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109:433–438
  17. Latini R, Masson S, Wong M, Barlera S, Carretta E, Staszewsky L, et al. Incremental prognostic value of changes in B-type natriuretic peptide in heart failure. Am J Med. 2006;119:70.e23–30
  18. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450–458
  19. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992;20:1251–1260
  20. de Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation. 1996;93:259–265
  21. de Simone G, Chinali M, Galderisi M, Benincasa M, Girfoglio D, Botta I, et al. Myocardial mechano-energetic efficiency in hypertensive adults. J Hypertens. 2009;27:650–655
  22. Vanoverschelde JL, Wijns W, Essamri B, Bol A, Robert A, Labar D, et al. Hemodynamic and mechanical determinants of myocardial O2 consumption in normal human heart: effects of dobutamine. Am J Physiol. 1993;265:H1884–H1892
  23. de Simone G, Greco R, Mureddu G, Romano C, Guida R, Celentano A, et al. Relation of left ventricular diastolic properties to systolic function in arterial hypertension. Circulation. 2000;101:152–157
  24. Mishra RK, Galloway JM, Lee ET, Best LG, Russell M, Roman MJ, et al. The ratio of mitral deceleration time to E-wave velocity and mitral deceleration slope outperform deceleration time alone in predicting cardiovascular outcomes: the Strong Heart Study. J Am Soc Echocardiogr. 2007;20:1300–1306
  25. Chinali M, Aurigemma G, de Simone G, Mishra RK, Gerdts E, Wachtell K, et al. Mitral E wave deceleration time to peak E velocity ratio and cardiovascular outcome in hypertensive patients during anti-hypertensive treatment (from the LIFE echo-substudy). Am J Cardiol. 2009;104:1098–1104
  26. Douglas PS. The left atrium: a biomarker of chronic diastolic dysfunction and cardiovascular disease risk. J Am Coll Cardiol. 2003;42:1206–1207
  27. Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006;296:2209–2216
  28. In:  Klabunde R editors. Cardiovascular physiology concepts. Hagerstown, MD: Lippincott Williams & Wilkins; 2004;
  29. Indolfi C, Ross J. The role of heart rate in myocardial ischemia and infarction: implications of myocardial perfusion–contraction matching. Prog Cardiovasc Dis. 1993;36:61–74
  30. van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome?. Cardiovasc Res. 2004;61:218–226
  31. Tuunanen H, Ukkonen H, Knuuti J. Myocardial fatty acid metabolism and cardiac performance in heart failure. Curr Cardiol Rep. 2008;10:142–148
  32. Tuunanen H, Engblom E, Naum A, Scheinin M, Nagren K, Airaksinen J, et al. Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction. J Card Fail. 2006;12:644–652
  33. Kantor PF, Robertson MA, Coe JY, Lopaschuk GD. Volume overload hypertrophy of the newborn heart slows the maturation of enzymes involved in the regulation of fatty acid metabolism. J Am Coll Cardiol. 1999;33:1724–1734
  34. Wong C, Marwick TH. Obesity cardiomyopathy: pathogenesis and pathophysiology. Nat Clin Pract Cardiovasc Med. 2007;4:436–443
  35. Ventura-Clapier R, Garnier A, Veksler V. Energy metabolism in heart failure. J Physiol. 2004;555:1–13
  36. Ohtani T, Ohta M, Yamamoto K, Mano T, Sakata Y, Nishio M, et al. Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker. Am J Physiol Regul Integr Comp Physiol. 2007;292:R946–R954
  37. Burlew BS, Weber KT. Connective tissue and the heart. Functional significance and regulatory mechanisms. Cardiol Clin. 2000;18:435–442
  38. Orea-Tejeda A, Colin-Ramirez E, Castillo-Martinez L, Asensio-Lafuente E, Corzo-Leon D, Gonzalez-Toledo R, et al. Aldosterone receptor antagonists induce favorable cardiac remodeling in diastolic heart failure patients. Rev Invest Clin. 2007;59:103–107
  39. Ingelsson E, Arnlov J, Lind L, Sundstrom J. Metabolic syndrome and risk for heart failure in middle-aged men. Heart. 2006;92:1409–1413
  40. Levantesi G, Macchia A, Marfisi R, Franzosi MG, Maggioni AP, Nicolosi GL, et al. Metabolic syndrome and risk of cardiovascular events after myocardial infarction. J Am Coll Cardiol. 2005;46:277–283
  41. Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008;51:1775–1783
  42. Kuwahara F, Kai H, Tokuda K, Takeya M, Takeshita A, Egashira K, et al. Hypertensive myocardial fibrosis and diastolic dysfunction: another model of inflammation?. Hypertension. 2004;43:739–745

 Supported by an unrestricted funding from Therabel GiENNE Pharma to Heart Care Foundation, ANMCO Research Center.ClinicalTrials.gov Identifier: NCT00403910.

PII: S0939-4753(10)00061-X

doi: 10.1016/j.numecd.2010.02.012

Nutrition, Metabolism & Cardiovascular Diseases
Volume 21, Issue 10 , Pages 783-791 , October 2011