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Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?

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Abstract

Despite significant improvements in diagnosis, understanding the pathophysiology and management of the patients with acute decompensated heart failure (ADHF), diuretic resistance, yet to be clearly defined, is a major hurdle. Secondary hyperaldosteronism is a pivotal factor in pathogenesis of sodium retention, refractory congestion in heart failure (HF) as well as diuretic resistance. In patients with decompensated cirrhosis who suffer from ascites, similar pathophysiological complications have been recognized. Administration of natriuretic doses of mineralocorticoid receptor antagonists (MRAs) has been well established in management of cirrhotic patients. However, this strategy in patients with ADHF has not been well studied. This article will discuss the potential use of natriuretic doses of MRAs to overcome the secondary hyperaldosteronism as an alternative diuretic regimen in patients with HF.

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References

  1. Lloyd-Jones D et al (2009) Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119(3):480–486

    Article  PubMed  Google Scholar 

  2. Ambrosy AP et al (2014) The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol 63(12):1123–1133

    Article  PubMed  Google Scholar 

  3. Gheorghiade M et al (2005) Acute heart failure syndromes: current state and framework for future research. Circulation 112(25):3958–3968

    Article  PubMed  Google Scholar 

  4. Felker GM et al (2003) The problem of decompensated heart failure: nomenclature, classification, and risk stratification. Am Heart J 145(2 Suppl.):S18–S25

    Article  PubMed  Google Scholar 

  5. Fonarow GC et al (2007) Influence of a performance-improvement initiative on quality of care for patients hospitalized with heart failure: results of the organized program to initiate lifesaving treatment in hospitalized patients with heart failure (OPTIMIZE-HF). Arch Intern Med 167(14):1493–1502

    Article  PubMed  Google Scholar 

  6. Gheorghiade M et al (2006) Congestion in acute heart failure syndromes: an essential target of evaluation and treatment. Am J Med 119(12 Suppl. 1):S3–S10

    Article  PubMed  Google Scholar 

  7. Fonarow GC et al (2007) Temporal trends in clinical characteristics, treatments, and outcomes for heart failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 153(6):1021–1028

    Article  PubMed  Google Scholar 

  8. Allen LA et al (2008) Improvements in signs and symptoms during hospitalization for acute heart failure follow different patterns and depend on the measurement scales used: an international, prospective registry to evaluate the evolution of measures of disease severity in acute heart failure (MEASURE-AHF). J Card Fail 14(9):777–784

    Article  PubMed Central  PubMed  Google Scholar 

  9. Lucas C et al (2000) Freedom from congestion predicts good survival despite previous class IV symptoms of heart failure. Am Heart J 140(6):840–847

    Article  CAS  PubMed  Google Scholar 

  10. Gheorghiade M et al (2004) Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291(16):1963–1971

    Article  CAS  PubMed  Google Scholar 

  11. Nohria A et al (2008) Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol 51(13):1268–1274

    Article  PubMed  Google Scholar 

  12. Damman K et al (2009) Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J Am Coll Cardiol 53(7):582–588

    Article  PubMed  Google Scholar 

  13. Aronson D, Burger AJ (2003) Neurohormonal prediction of mortality following admission for decompensated heart failure. Am J Cardiol 91(2):245–248

    Article  CAS  PubMed  Google Scholar 

  14. Pitt B et al (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341(10):709–717

    Article  CAS  PubMed  Google Scholar 

  15. The RALES Investigators (1996) Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 78(8):902–907

  16. Schmidt BM et al (2006) Rapid nongenomic effects of aldosterone on the renal vasculature in humans. Hypertension 47(4):650–655

    Article  CAS  PubMed  Google Scholar 

  17. Farquharson CA, Struthers AD (2000) Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 101(6):594–597

    Article  CAS  PubMed  Google Scholar 

  18. Struthers A, Krum H, Williams GH (2008) A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol 31(4):153–158

    Article  PubMed  Google Scholar 

  19. Schrier RW (2010) Aldosterone ‘escape’ vs ‘breakthrough’. Nat Rev Nephrol 6(2):61

    Article  PubMed  Google Scholar 

  20. Sowers JR, Whaley-Connell A, Epstein M (2009) Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. Ann Intern Med 150(11):776–783

    Article  PubMed Central  PubMed  Google Scholar 

  21. Gross E et al (2005) Effect of spironolactone on blood pressure and the renin–angiotensin–aldosterone system in oligo-anuric hemodialysis patients. Am J Kidney Dis 46(1):94–101

    Article  CAS  PubMed  Google Scholar 

  22. Pitt B et al (2008) Serum potassium and clinical outcomes in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation 118(16):1643–1650

    Article  CAS  PubMed  Google Scholar 

  23. Chai W et al (2005) Nongenomic effects of aldosterone in the human heart: interaction with angiotensin II. Hypertension 46(4):701–706

    Article  CAS  PubMed  Google Scholar 

  24. Schrier RW et al (1988) Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 8(5):1151–1157

    Article  CAS  PubMed  Google Scholar 

  25. Vallance P, Moncada S (1991) Hyperdynamic circulation in cirrhosis: a role for nitric oxide? Lancet 337(8744):776–778

    Article  CAS  PubMed  Google Scholar 

  26. Iwakiri Y, Groszmann RJ (2006) The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology 43(2 Suppl. 1):S121–S131

    Article  CAS  PubMed  Google Scholar 

  27. Guarner C et al (1986) Renal prostaglandins in cirrhosis of the liver. Clin Sci (Lond) 70(5):477–484

    CAS  Google Scholar 

  28. La Villa G et al (1992) Mineralocorticoid escape in patients with compensated cirrhosis and portal hypertension. Gastroenterology 102(6):2114–2119

    PubMed  Google Scholar 

  29. Gines P et al (1997) Pathogenesis of ascites in cirrhosis. Semin Liver Dis 17(3):175–189

    Article  CAS  PubMed  Google Scholar 

  30. Gines P et al (2005) Ascites and renal dysfunction in liver disease: pathogenesis, diagnosis, and treatment. 2nd edn. Wiley, Malden

  31. Henriksen JH et al (1992) Estimated central blood volume in cirrhosis: relationship to sympathetic nervous activity, beta-adrenergic blockade and atrial natriuretic factor. Hepatology 16(5):1163–1170

    Article  CAS  PubMed  Google Scholar 

  32. Arroyo V et al (1981) Plasma renin activity and urinary sodium excretion as prognostic indicators in nonazotemic cirrhosis with ascites. Ann Intern Med 94(2):198–201

    Article  CAS  PubMed  Google Scholar 

  33. Trevisani F et al (1989) Circadian variation in renal sodium and potassium handling in cirrhosis. The role of aldosterone, cortisol, sympathoadrenergic tone, and intratubular factors. Gastroenterology 96(4):1187–1198

    CAS  PubMed  Google Scholar 

  34. Henriksen JH et al (1998) The sympathetic nervous system in liver disease. J Hepatol 29(2):328–341

    Article  CAS  PubMed  Google Scholar 

  35. Esler M, Kaye D (1998) Increased sympathetic nervous system activity and its therapeutic reduction in arterial hypertension, portal hypertension and heart failure. J Auton Nerv Syst 72(2–3):210–219

    Article  CAS  PubMed  Google Scholar 

  36. Schrier RW (2006) Role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? J Am Coll Cardiol 47(1):1–8

    Article  PubMed  Google Scholar 

  37. Henry JP, Gauer OH, Reeves JL (1956) Evidence of the atrial location of receptors influencing urine flow. Circ Res 4(1):85–90

    Article  CAS  PubMed  Google Scholar 

  38. Linden RJ, Kappagoda CT (1982) Atrial receptors. Monogr Physiol Soc 39:1–363

    CAS  PubMed  Google Scholar 

  39. Packer M (1988) Neurohormonal interactions and adaptations in congestive heart failure. Circulation 77(4):721–730

    Article  CAS  PubMed  Google Scholar 

  40. Schrier RW (1990) Body fluid volume regulation in health and disease: a unifying hypothesis. Ann Intern Med 113(2):155–159

    Article  CAS  PubMed  Google Scholar 

  41. Schrier RW (2006) Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med 119(7 Suppl. 1):S47–S53

    Article  CAS  PubMed  Google Scholar 

  42. Schrier RW (2007) Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol 18(7):2028–2031

    Article  PubMed  Google Scholar 

  43. Schrier RW, Abraham WT (1999) Hormones and hemodynamics in heart failure. N Engl J Med 341(8):577–585

    Article  CAS  PubMed  Google Scholar 

  44. Fogel MR et al (1981) Diuresis in the ascitic patient: a randomized controlled trial of three regimens. J Clin Gastroenterol 3(Suppl. 1):73–80

    Article  PubMed  Google Scholar 

  45. Perez-Ayuso RM et al (1983) Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin–aldosterone system. Gastroenterology 84(5 Pt 1):961–968

    CAS  PubMed  Google Scholar 

  46. Pinzani M et al (1987) Altered furosemide pharmacokinetics in chronic alcoholic liver disease with ascites contributes to diuretic resistance. Gastroenterology 92(2):294–298

    CAS  PubMed  Google Scholar 

  47. Fernandez-Llama P et al (2005) Sodium retention in cirrhotic rats is associated with increased renal abundance of sodium transporter proteins. Kidney Int 67(2):622–630

    Article  CAS  PubMed  Google Scholar 

  48. Runyon BA (2013) Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 57(4):1651–1653

    Article  PubMed  Google Scholar 

  49. Gines P, Schrier RW (2009) Renal failure in cirrhosis. N Engl J Med 361(13):1279–1290

    Article  CAS  PubMed  Google Scholar 

  50. Pitt B (2008) Aldosterone blockade in patients with chronic heart failure. Cardiol Clin 26(1):15–21

    Article  PubMed  Google Scholar 

  51. McKelvie RS et al (1999) Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 100(10):1056–1064

    Article  CAS  PubMed  Google Scholar 

  52. Vittorio TJ et al (2007) Comparison of high- versus low-tissue affinity ACE-inhibitor treatment on circulating aldosterone levels in patients with chronic heart failure. J Renin Angiotensin Aldosterone Syst 8(4):200–204

    Article  CAS  PubMed  Google Scholar 

  53. Pitt B et al (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348(14):1309–1321

    Article  CAS  PubMed  Google Scholar 

  54. Zannad F et al (2011) Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 364(1):11–21

    Article  CAS  PubMed  Google Scholar 

  55. Pitt B et al (2014) Spironolactone for heart failure with preserved ejection fraction. N Engl J Med 370(15):1383–1392

    Article  CAS  PubMed  Google Scholar 

  56. Braunwald E, Plauth WH Jr, Morrow AG (1965) A method for the detection and quantification of impaired sodium excretion. Results of an oral sodium tolerance test in normal subjects and in patients with heart disease. Circulation 32:223–231

    Article  CAS  PubMed  Google Scholar 

  57. Hensen J et al (1991) Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention. Am J Nephrol 11(6):441–446

    Article  CAS  PubMed  Google Scholar 

  58. van Vliet AA et al (1993) Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor. Am J Cardiol 71(3):21a–28a

    Article  PubMed  Google Scholar 

  59. Ferreira JP et al (2014) Mineralocorticoid receptor antagonism in acutely decompensated chronic heart failure. Eur J Intern Med 25(1):67–72

    Article  CAS  PubMed  Google Scholar 

  60. Chamsi-Pasha MA et al (2014) Utilization pattern of mineralocorticoid receptor antagonists in contemporary patients hospitalized with acute decompensated heart failure: a single-center experience. J Card Fail 20(4):229–235

    Article  CAS  PubMed  Google Scholar 

  61. Juurlink DN et al (2004) Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 351(6):543–551

    Article  CAS  PubMed  Google Scholar 

  62. Wei L et al (2010) Spironolactone use and renal toxicity: population based longitudinal analysis. BMJ 340:c1768

    Article  PubMed  Google Scholar 

  63. Rossignol P et al (2014) Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circ Heart Fail 7(1):51–58

    Article  CAS  PubMed  Google Scholar 

  64. Eschalier R et al (2013) Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure). J Am Coll Cardiol 62(17):1585–1593

    Article  CAS  PubMed  Google Scholar 

  65. Hernandez AF et al (2012) Associations between aldosterone antagonist therapy and risks of mortality and readmission among patients with heart failure and reduced ejection fraction. JAMA 308(20):2097–2107

    Article  CAS  PubMed  Google Scholar 

  66. Yancy CW et al (2013) 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. Circulation 128(16):e240–e327

    Article  PubMed  Google Scholar 

  67. Schrier RW, Gheorghiade M (2011) Challenge of rehospitalizations for heart failure: potential of natriuretic doses of mineralocorticoid receptor antagonists. Am Heart J 161(2):221–223

    Article  PubMed  Google Scholar 

  68. Ezekowitz JA, McAlister FA (2009) Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials. Eur Heart J 30(4):469–477

    Article  CAS  PubMed  Google Scholar 

  69. Jeunemaitre X et al (1987) Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol 60(10):820–825

    Article  CAS  PubMed  Google Scholar 

  70. Garthwaite SM, McMahon EG (2004) The evolution of aldosterone antagonists. Mol Cell Endocrinol 217(1–2):27–31

    Article  CAS  PubMed  Google Scholar 

  71. Dimitriadis G, Papadopoulos V, Mimidis K (2011) Eplerenone reverses spironolactone-induced painful gynaecomastia in cirrhotics. Hepatol Int 5(2):738–739

    Article  PubMed Central  PubMed  Google Scholar 

  72. Albaghdadi M, Gheorghiade M, Pitt B (2011) Mineralocorticoid receptor antagonism: therapeutic potential in acute heart failure syndromes. Eur Heart J 32(21):2626–2633

    Article  CAS  PubMed  Google Scholar 

  73. Bansal S, Lindenfeld J, Schrier RW (2009) Sodium retention in heart failure and cirrhosis: potential role of natriuretic doses of mineralocorticoid antagonist? Circ Heart Fail 2(4):370–376

  74. Schrier RW, Masoumi A, Elhassan E (2010) Aldosterone: role in edematous disorders, hypertension, chronic renal failure, and metabolic syndrome. Clin J Am Soc Nephrol 5(6):1132–1140

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Authors and Affiliations

  1. Division of Cardiology, New York-Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Amirali Masoumi & Paolo C. Colombo

  2. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Fernando Ortiz

  3. Division of Nephrology, New York-Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Jai Radhakrishnan

  4. Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA

    Robert W. Schrier

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  1. Amirali Masoumi
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  2. Fernando Ortiz
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  3. Jai Radhakrishnan
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  5. Paolo C. Colombo
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Correspondence to Amirali Masoumi.

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Masoumi, A., Ortiz, F., Radhakrishnan, J. et al. Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?. Heart Fail Rev 20, 283–290 (2015). https://doi.org/10.1007/s10741-014-9467-2

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