Heart Failure Reviews

, Volume 17, Issue 3, pp 355–366

The cardiorenal syndrome in heart failure: cardiac? renal? syndrome?

  • Filippos Triposkiadis
  • Randall C. Starling
  • Harisios Boudoulas
  • Gregory Giamouzis
  • Javed Butler


There has been increasing interest on the so-called cardiorenal syndrome (CRS), defined as a complex pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. In this review, we contend that there is lack of evidence warranting the adoption of a specific clinical construct such as the CRS within the heart failure (HF) syndrome by demonstrating that: (a) the approaches and tools regarding the definition of kidney involvement in HF are suboptimal; (b) development of renal failure in HF is often confounded by age, hypertension, and diabetes; (c) worsening of renal function (WRF) in HF may be largely independent of alterations in cardiac function; (d) the bidirectional association between HF and renal failure is not unique and represents one of the several such associations encountered in HF; and (e) inflammation is a common denominator for HF and associated noncardiac morbidities. Based on these arguments, we believe that dissecting one of the multiple bidirectional associations in HF and constructing the so-called cardiorenal syndrome is not justified pathophysiologically. Fully understanding of all morbid associations and not only the cardiorenal is of great significance for the clinician who is caring for the patient with HF.


Heart failure Cardiorenal syndrome Worsening renal function Noncardiac morbidities 


  1. 1.
    National Heart L, Blood Institute: NHLBI Working Group. -cardio-renal connections in heart failure and cardiovascular disease-august 20, 2004. Available at http://www.Nhlbi.Nih.Gov/meeting/workshops/cardiorenalhf-hd.Htm
  2. 2.
    Liang KV, Williams AW, Greene EL, Redfield MM (2008) Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med 36:S75–S88PubMedCrossRefGoogle Scholar
  3. 3.
    Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B (2005) The severe cardiorenal syndrome: ‘Guyton revisited’. Eur Heart J 26:11–17PubMedCrossRefGoogle Scholar
  4. 4.
    Heywood JT (2004) The cardiorenal syndrome: lessons from the adhere database and treatment options. Heart Fail Rev 9:195–201PubMedCrossRefGoogle Scholar
  5. 5.
    Boerrigter G, Burnett JC Jr (2004) Cardiorenal syndrome in decompensated heart failure: prognostic and therapeutic implications. Curr Heart Fail Rep 1:113–120PubMedCrossRefGoogle Scholar
  6. 6.
    Ronco C, McCullough PA, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R, Berl T, Bobek I, Cruz DN, Daliento L, Davenport A, Haapio M, Hillege H, House A, Katz NM, Maisel A, Mankad S, Zanco P, Mebazaa A, Palazzuoli A, Ronco F, Shaw A, Sheinfeld G, Soni S, Vescovo G, Zamperetti N, Ponikowski P (2010) Cardiorenal syndromes: an executive summary from the consensus conference of the acute dialysis quality initiative (adqi). Contrib Nephrol 165:54–67PubMedCrossRefGoogle Scholar
  7. 7.
    Carubelli V, Metra M, Lombardi C, Bettari L, Bugatti S, Lazzarini V, Dei Cas L (2011) Renal dysfunction in acute heart failure: epidemiology, mechanisms and assessment. Heart Fail Rev. doi:10.1007/s10741-011-9265-z
  8. 8.
    El Nahas M (2010) Cardio-kidney-damage: a unifying concept. Kidney Int 78:14–18PubMedCrossRefGoogle Scholar
  9. 9.
    Schroten NF, Gaillard CA, van Veldhuisen DJ, Szymanski MK, Hillege HL, de Boer RA (2011) New roles for renin and prorenin in heart failure and cardiorenal crosstalk. Heart Fail Rev. doi:10.1007/s10741-011-9262-2
  10. 10.
    Hauptman PJ, Mann DL (2011) The vagus nerve and autonomic imbalance in heart failure: past, present, and future. Heart Fail Rev 16:97–99PubMedCrossRefGoogle Scholar
  11. 11.
    Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J (2009) The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J Am Coll Cardiol 54:1747–1762PubMedCrossRefGoogle Scholar
  12. 12.
    Schwartz PJ, De Ferrari GM (2011) Sympathetic-parasympathetic interaction in health and disease: abnormalities and relevance in heart failure. Heart Fail Rev 16:101–107PubMedCrossRefGoogle Scholar
  13. 13.
    Damman K, Navis G, Smilde TD, Voors AA, van der Bij W, van Veldhuisen DJ, Hillege HL (2007) Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction. Eur J Heart Fail 9:872–878PubMedCrossRefGoogle Scholar
  14. 14.
    Braam B, Cupples WA, Joles JA, Gaillard C (2011) Systemic arterial and venous determinants of renal hemodynamics in congestive heart failure. Heart Fail Rev. doi:10.1007/s10741-011-9246-2
  15. 15.
    Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, Yancy CW, Califf RM, Stevenson LW, Hill JA (2008) Cardiorenal interactions: insights from the escape trial. J Am Coll Cardiol 51:1268–1274PubMedCrossRefGoogle Scholar
  16. 16.
    Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB, Tang WH (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53:589–596PubMedCrossRefGoogle Scholar
  17. 17.
    Sinkeler SJ, Damman K, van Veldhuisen DJ, Hillege H, Navis G (2011) A re-appraisal of volume status and renal function impairment in chronic heart failure: Combined effects of pre-renal failure and venous congestion on renal function. Heart Fail Rev. doi:10.1007/s10741-011-9233-7
  18. 18.
    Costanzo MR, Jessup M (2011) Treatment of congestion in heart failure with diuretics and extracorporeal therapies: Effects on symptoms, renal function, and prognosis. Heart Fail Rev. doi:10.1007/s10741-011-9248-0
  19. 19.
    Uthoff H, Breidthardt T, Klima T, Aschwanden M, Arenja N, Socrates T, Heinisch C, Noveanu M, Frischknecht B, Baumann U, Jaeger KA, Mueller C (2011) Central venous pressure and impaired renal function in patients with acute heart failure. Eur J Heart Fail 13:432–439PubMedCrossRefGoogle Scholar
  20. 20.
    Mullens W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, Paganini E, Tang WH (2008) Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J Am Coll Cardiol 51:300–306PubMedCrossRefGoogle Scholar
  21. 21.
    Funaya H, Kitakaze M, Node K, Minamino T, Komamura K, Hori M (1997) Plasma adenosine levels increase in patients with chronic heart failure. Circulation 95:1363–1365PubMedGoogle Scholar
  22. 22.
    Massie BM, O’Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Weatherley BD, Cleland JG, Givertz MM, Voors A, DeLucca P, Mansoor GA, Salerno CM, Bloomfield DM, Dittrich HC (2010) Rolofylline, an adenosine a1-receptor antagonist, in acute heart failure. N Engl J Med 363:1419–1428PubMedCrossRefGoogle Scholar
  23. 23.
    Metra M, O’Connor CM, Davison BA, Cleland JG, Ponikowski P, Teerlink JR, Voors AA, Givertz MM, Mansoor GA, Bloomfield DM, Jia G, DeLucca P, Massie B, Dittrich H, Cotter G (2011) Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the protect study. Eur Heart J 32:1519–1534PubMedCrossRefGoogle Scholar
  24. 24.
    Voors AA, Dittrich HC, Massie BM, DeLucca P, Mansoor GA, Metra M, Cotter G, Weatherley BD, Ponikowski P, Teerlink JR, Cleland JG, O’Connor CM, Givertz MM (2011) Effects of the adenosine a1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: Results from protect (placebo-controlled randomized study of the selective adenosine a1 receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function). J Am Coll Cardiol 57:1899–1907PubMedCrossRefGoogle Scholar
  25. 25.
    Fildes JE, Shaw SM, Yonan N, Williams SG (2009) The immune system and chronic heart failure: is the heart in control? J Am Coll Cardiol 53:1013–1020PubMedCrossRefGoogle Scholar
  26. 26.
    Colombo PC, Ganda A, Lin J, Onat D, Harxhi A, Iyasere JE, Uriel N, Cotter G (2011) Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome. Heart Fail Rev. doi:10.1007/s10741-011-9261-3
  27. 27.
    Li W, Olshansky B (2011) Inflammatory cytokines and nitric oxide in heart failure and potential modulation by vagus nerve stimulation. Heart Fail Rev 16:137–145PubMedCrossRefGoogle Scholar
  28. 28.
    Szymanski MK, de Boer RA, Navis GJ, van Gilst WH, Hillege HL (2011) Animal models of cardiorenal syndrome: a review. Heart Fail Rev. doi:10.1007/s10741-011-9279-6
  29. 29.
    Karayannis G, Giamouzis G, Alexandridis E, Kamvrogiannis P, Butler J, Skoularigis J, Triposkiadis F (2011) Prevalence of impaired coronary flow reserve and its association with left ventricular diastolic function in asymptomatic individuals with major cardiovascular risk factors. Eur J Cardiovasc Prev Rehabil 18:326–333PubMedCrossRefGoogle Scholar
  30. 30.
    Willemsen S, Hartog JW, Heiner-Fokkema MR, van Veldhuisen DJ, Voors AA (2011) Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome. Heart Fail Rev. doi:10.1007/s10741-010-9225-z
  31. 31.
    Groenveld HF, Januzzi JL, Damman K, van Wijngaarden J, Hillege HL, van Veldhuisen DJ, van der Meer P (2008) Anemia and mortality in heart failure patients a systematic review and meta-analysis. J Am Coll Cardiol 52:818–827PubMedCrossRefGoogle Scholar
  32. 32.
    Palazzuoli A, Antonelli G, Nuti R (2011) Anemia in cardio-renal syndrome: clinical impact and pathophysiologic mechanisms. Heart Fail Rev 16:603–607PubMedCrossRefGoogle Scholar
  33. 33.
    Silverberg DS (2011) The role of erythropoiesis stimulating agents and intravenous (iv) iron in the cardio renal anemia syndrome. Heart Fail Rev 16:609–614PubMedCrossRefGoogle Scholar
  34. 34.
    Young JB, Abraham WT, Albert NM, Gattis Stough W, Gheorghiade M, Greenberg BH, O’Connor CM, She L, Sun JL, Yancy CW, Fonarow GC (2008) Relation of low hemoglobin and anemia to morbidity and mortality in patients hospitalized with heart failure (insight from the optimize-hf registry). Am J Cardiol 101:223–230PubMedCrossRefGoogle Scholar
  35. 35.
    Felker GM (2011) Loop diuretics in heart failure. Heart Fail Rev. doi:10.1007/s10741-011-9245-3
  36. 36.
    Felker GM, O’Connor CM, Braunwald E (2009) Loop diuretics in acute decompensated heart failure: necessary? evil? a necessary evil? Circ Heart Fail 2:56–62PubMedCrossRefGoogle Scholar
  37. 37.
    Schrier RW (2006) Role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? J Am Coll Cardiol 47:1–8PubMedCrossRefGoogle Scholar
  38. 38.
    Chittineni H, Miyawaki N, Gulipelli S, Fishbane S (2007) Risk for acute renal failure in patients hospitalized for decompensated congestive heart failure. Am J Nephrol 27:55–62PubMedCrossRefGoogle Scholar
  39. 39.
    Giamouzis G, Butler J, Triposkiadis F (2011) Renal function in advanced heart failure. Congest Heart Fail 17:180–188PubMedCrossRefGoogle Scholar
  40. 40.
    Giamouzis G, Kalogeropoulos A, Georgiopoulou V, Laskar S, Smith AL, Dunbar S, Triposkiadis F, Butler J (2011) Hospitalization epidemic in patients with heart failure: risk factors, risk prediction, knowledge gaps, and future directions. J Card Fail 17:54–75PubMedCrossRefGoogle Scholar
  41. 41.
    Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B (2006) Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (posh). Eur Heart J 27:1216–1222PubMedCrossRefGoogle Scholar
  42. 42.
    Cruz DN, Gheorghiade M, Palazuolli A, Ronco C, Bagshaw SM (2011) Epidemiology and outcome of the cardio-renal syndrome. Heart Fail Rev 16:531–542PubMedCrossRefGoogle Scholar
  43. 43.
    Klein L, Massie BM, Leimberger JD, O’Connor CM, Pina IL, Adams KF Jr, Califf RM, Gheorghiade M (2008) Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the outcomes of a prospective trial of intravenous milrinone for exacerbations of chronic heart failure (optime-chf). Circ Heart Fail 1:25–33PubMedCrossRefGoogle Scholar
  44. 44.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute dialysis quality initiative (adqi) group. Crit Care 8:R204–R212PubMedCrossRefGoogle Scholar
  45. 45.
    Winearls CG, Glassock RJ (2009) Dissecting and refining the staging of chronic kidney disease. Kidney Int 75:1009–1014PubMedCrossRefGoogle Scholar
  46. 46.
    Bakris GL, Weir MR (2000) Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 160:685–693PubMedCrossRefGoogle Scholar
  47. 47.
    Toto RD (1994) Renal insufficiency due to angiotensin-converting enzyme inhibitors. Miner Electrolyte Metab 20:193–200PubMedGoogle Scholar
  48. 48.
    Giamouzis G, Butler J, Starling RC, Karayannis G, Nastas J, Parisis C, Rovithis D, Economou D, Savvatis K, Kirlidis T, Tsaknakis T, Skoularigis J, Westermann D, Tschope C, Triposkiadis F (2010) Impact of dopamine infusion on renal function in hospitalized heart failure patients: results of the dopamine in acute decompensated heart failure (dad-hf) trial. J Card Fail 16:922–930PubMedCrossRefGoogle Scholar
  49. 49.
    Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O’Connor CM (2011) Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 364:797–805PubMedCrossRefGoogle Scholar
  50. 50.
    Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ (2005) Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 293:572–580PubMedCrossRefGoogle Scholar
  51. 51.
    Filippatos G, Rossi J, Lloyd-Jones DM, Stough WG, Ouyang J, Shin DD, O’Connor C, Adams KF, Orlandi C, Gheorghiade M (2007) Prognostic value of blood urea nitrogen in patients hospitalized with worsening heart failure: insights from the acute and chronic therapeutic impact of a vasopressin antagonist in chronic heart failure (activ in chf) study. J Card Fail 13:360–364PubMedCrossRefGoogle Scholar
  52. 52.
    Giamouzis G, Kalogeropoulos AP, Georgiopoulou VV, Agha SA, Rashad MA, Laskar SR, Smith AL, Butler J (2009) Incremental value of renal function in risk prediction with the Seattle heart failure model. Am Heart J 157:299–305PubMedCrossRefGoogle Scholar
  53. 53.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedCrossRefGoogle Scholar
  54. 54.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470PubMedGoogle Scholar
  55. 55.
    Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A (2005) Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis 46:233–241PubMedCrossRefGoogle Scholar
  56. 56.
    Rule AD, Bailey KR, Schwartz GL, Khosla S, Lieske JC, Melton LJ 3rd (2009) For estimating creatinine clearance measuring muscle mass gives better results than those based on demographics. Kidney Int 75:1071–1078PubMedCrossRefGoogle Scholar
  57. 57.
    Poggio ED, Rule AD, Tanchanco R, Arrigain S, Butler RS, Srinivas T, Stephany BR, Meyer KH, Nurko S, Fatica RA, Shoskes DA, Krishnamurthi V, Goldfarb DA, Gill I, Schreiber MJ Jr (2009) Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors. Kidney Int 75:1079–1087PubMedCrossRefGoogle Scholar
  58. 58.
    Lee DS, Gona P, Vasan RS, Larson MG, Benjamin EJ, Wang TJ, Tu JV, Levy D (2009) Relation of disease pathogenesis and risk factors to heart failure with preserved or reduced ejection fraction: insights from the Framingham heart study of the national heart, lung, and blood institute. Circulation 119:3070–3077PubMedCrossRefGoogle Scholar
  59. 59.
    Parikh NI, Hwang SJ, Larson MG, Meigs JB, Levy D, Fox CS (2006) Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control. Arch Intern Med 166:1884–1891PubMedCrossRefGoogle Scholar
  60. 60.
    Fehrman-Ekholm I, Skeppholm L (2004) Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance. Scand J Urol Nephrol 38:73–77PubMedCrossRefGoogle Scholar
  61. 61.
    Roderick PJ, Atkins RJ, Smeeth L, Mylne A, Nitsch DD, Hubbard RB, Bulpitt CJ, Fletcher AE (2009) Ckd and mortality risk in older people: a community-based population study in the united kingdom. Am J Kidney Dis 53:950–960PubMedCrossRefGoogle Scholar
  62. 62.
    Hermans MM, Henry R, Dekker JM, Kooman JP, Kostense PJ, Nijpels G, Heine RJ, Stehouwer CD (2007) Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the hoorn study. J Am Soc Nephrol 18:1942–1952PubMedCrossRefGoogle Scholar
  63. 63.
    Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, O’Connor CM, Rich MW, Stevenson LW, Wang Y, Young JB, Krumholz HM (2004) Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 147:331–338PubMedCrossRefGoogle Scholar
  64. 64.
    Cioffi G, Tarantini L, Pulignano G, Del Sindaco D, De Feo S, Opasich C, Dilenarda A, Stefenelli C, Furlanello F (2007) Prevalence, predictors and prognostic value of acute impairment in renal function during intensive unloading therapy in a community population hospitalized for decompensated heart failure. J Cardiovasc Med (Hagerstown) 8:419–427CrossRefGoogle Scholar
  65. 65.
    Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, Horwitz RI (2000) Correlates and impact on outcomes of worsening renal function in patients > or = 65 years of age with heart failure. Am J Cardiol 85:1110–1113PubMedCrossRefGoogle Scholar
  66. 66.
    Weinfeld MS, Chertow GM, Stevenson LW (1999) Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J 138:285–290PubMedCrossRefGoogle Scholar
  67. 67.
    Forman DE, Butler J, Wang Y, Abraham WT, O’Connor CM, Gottlieb SS, Loh E, Massie BM, Rich MW, Stevenson LW, Young JB, Krumholz HM (2004) Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 43:61–67PubMedCrossRefGoogle Scholar
  68. 68.
    Testani JM, Chen J, McCauley BD, Kimmel SE, Shannon RP (2010) Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 122:265–272PubMedCrossRefGoogle Scholar
  69. 69.
    Testani JM, McCauley BD, Kimmel SE, Shannon RP (2010) Characteristics of patients with improvement or worsening in renal function during treatment of acute decompensated heart failure. Am J Cardiol 106:1763–1769PubMedCrossRefGoogle Scholar
  70. 70.
    Stevenson LW (2006) Are hemodynamic goals viable in tailoring heart failure therapy? hemodynamic goals are relevant. Circulation. 113:1020–1027 (discussion 1033)Google Scholar
  71. 71.
    Damman K, Voors AA (2007) Levosimendan improves renal function in acute decompensated heart failure: cause and clinical application: editorial to: “Levosimendan improves renal function in patients with acute decompensated heart failure: Comparison with dobutamine by yilmaz et al.”. Cardiovasc Drugs Ther 21:403–404Google Scholar
  72. 72.
    Binanay C, Califf RM, Hasselblad V, O’Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW (2005) Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the escape trial. JAMA 294:1625–1633PubMedCrossRefGoogle Scholar
  73. 73.
    Ungar A, Fumagalli S, Marini M, Di Serio C, Tarantini F, Boncinelli L, Baldereschi G, Valoti P, La Cava G, Olianti C, Masotti G, Marchionni N (2004) Renal, but not systemic, hemodynamic effects of dopamine are influenced by the severity of congestive heart failure. Crit Care Med 32:1125–1129PubMedCrossRefGoogle Scholar
  74. 74.
    Elkayam U, Ng TM, Hatamizadeh P, Janmohamed M, Mehra A (2008) Renal vasodilatory action of dopamine in patients with heart failure: magnitude of effect and site of action. Circulation 117:200–205PubMedCrossRefGoogle Scholar
  75. 75.
    Shippy CR, Appel PL, Shoemaker WC (1984) Reliability of clinical monitoring to assess blood volume in critically ill patients. Crit Care Med 12:107–112PubMedCrossRefGoogle Scholar
  76. 76.
    Waxman AB (2001) Pulmonary function test abnormalities in pulmonary vascular disease and chronic heart failure. Clin Chest Med 22:751–758PubMedCrossRefGoogle Scholar
  77. 77.
    Iversen KK, Kjaergaard J, Akkan D, Kober L, Torp-Pedersen C, Hassager C, Vestbo J, Kjoller E (2010) The prognostic importance of lung function in patients admitted with heart failure. Eur J Heart Fail 12:685–691PubMedCrossRefGoogle Scholar
  78. 78.
    Sullivan MJ, Higginbotham MB, Cobb FR (1988) Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities. Circulation 77:552–559PubMedCrossRefGoogle Scholar
  79. 79.
    Agostoni PG, Bussotti M, Palermo P, Guazzi M (2002) Does lung diffusion impairment affect exercise capacity in patients with heart failure? Heart 88:453–459PubMedCrossRefGoogle Scholar
  80. 80.
    Agostoni P, Cattadori G, Bussotti M, Apostolo A (2007) Cardiopulmonary interaction in heart failure. Pulm Pharmacol Ther 20:130–134PubMedCrossRefGoogle Scholar
  81. 81.
    Butler J, Chomsky DB, Wilson JR (1999) Pulmonary hypertension and exercise intolerance in patients with heart failure. J Am Coll Cardiol 34:1802–1806PubMedCrossRefGoogle Scholar
  82. 82.
    Guglin M, Khan H (2010) Pulmonary hypertension in heart failure. J Card Fail 16:461–474PubMedCrossRefGoogle Scholar
  83. 83.
    Ahmed MS, Oie E, Vinge LE, von Lueder TG, Attramadal T, Attramadal H (2007) Induction of pulmonary connective tissue growth factor in heart failure is associated with pulmonary parenchymal and vascular remodeling. Cardiovasc Res 74:323–333PubMedCrossRefGoogle Scholar
  84. 84.
    Jiang BH, Tardif JC, Sauvageau S, Ducharme A, Shi Y, Martin JG, Dupuis J (2010) Beneficial effects of atorvastatin on lung structural remodeling and function in ischemic heart failure. J Card Fail 16:679–688PubMedCrossRefGoogle Scholar
  85. 85.
    Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ (2009) Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail 11:130–139PubMedCrossRefGoogle Scholar
  86. 86.
    Lainscak M, Hodoscek LM, Dungen HD, Rauchhaus M, Doehner W, Anker SD, von Haehling S (2009) The burden of chronic obstructive pulmonary disease in patients hospitalized with heart failure. Wien Klin Wochenschr 121:309–313PubMedCrossRefGoogle Scholar
  87. 87.
    Kwon BJ, Kim DB, Jang SW, Yoo KD, Moon KW, Shim BJ, Ahn SH, Cho EJ, Rho TH, Kim JH (2010) Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease. Eur J Heart Fail 12:1339–1344PubMedCrossRefGoogle Scholar
  88. 88.
    Rutten FH, Cramer MJ, Lammers JW, Grobbee DE, Hoes AW (2006) Heart failure and chronic obstructive pulmonary disease: an ignored combination? Eur J Heart Fail 8:706–711PubMedCrossRefGoogle Scholar
  89. 89.
    Curkendall SM, DeLuise C, Jones JK, Lanes S, Stang MR, Goehring E Jr, She D (2006) Cardiovascular disease in patients with chronic obstructive pulmonary disease, saskatchewan canada cardiovascular disease in copd patients. Ann Epidemiol 16:63–70PubMedCrossRefGoogle Scholar
  90. 90.
    Zvezdin B, Milutinov S, Kojicic M, Hadnadjev M, Hromis S, Markovic M, Gajic O (2009) A postmortem analysis of major causes of early death in patients hospitalized with copd exacerbation. Chest 136:376–380PubMedCrossRefGoogle Scholar
  91. 91.
    Sin DD (2009) Is copd really a cardiovascular disease? Chest 136:329–330PubMedCrossRefGoogle Scholar
  92. 92.
    Macnee W, Maclay J, McAllister D (2008) Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5:824–833PubMedCrossRefGoogle Scholar
  93. 93.
    Jilek C, Krenn M, Sebah D, Obermeier R, Braune A, Kehl V, Schroll S, Montalvan S, Riegger GA, Pfeifer M, Arzt M (2011) Prognostic impact of sleep disordered breathing and its treatment in heart failure: an observational study. Eur J Heart Fail 13:68–75PubMedCrossRefGoogle Scholar
  94. 94.
    Bitter T, Westerheide N, Prinz C, Hossain MS, Vogt J, Langer C, Horstkotte D, Oldenburg O (2011) Cheyne-stokes respiration and obstructive sleep apnoea are independent risk factors for malignant ventricular arrhythmias requiring appropriate cardioverter-defibrillator therapies in patients with congestive heart failure. Eur Heart J 32:61–74PubMedCrossRefGoogle Scholar
  95. 95.
    Kasai T, Bradley TD (2011) Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications. J Am Coll Cardiol 57:119–127PubMedCrossRefGoogle Scholar
  96. 96.
    Bradley TD, Floras JS (2003) Sleep apnea and heart failure: part i: obstructive sleep apnea. Circulation 107:1671–1678PubMedCrossRefGoogle Scholar
  97. 97.
    Chan JY, Li AM, Au CT, Lo AF, Ng SK, Abdullah VJ, Ho C, Yu CM, Fok TF, Wing YK (2009) Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study. Thorax 64:233–239PubMedCrossRefGoogle Scholar
  98. 98.
    Chami HA, Devereux RB, Gottdiener JS, Mehra R, Roman MJ, Benjamin EJ, Gottlieb DJ (2008) Left ventricular morphology and systolic function in sleep-disordered breathing: the sleep heart health study. Circulation 117:2599–2607PubMedCrossRefGoogle Scholar
  99. 99.
    Koshino Y, Villarraga HR, Orban M, Bruce CJ, Pressman GS, Leinveber P, Saleh HK, Konecny T, Kara T, Somers VK, Lopez-Jimenez F (2010) Changes in left and right ventricular mechanics during the Mueller maneuver in healthy adults: a possible mechanism for abnormal cardiac function in patients with obstructive sleep apnea. Circ Cardiovasc Imaging 3:282–289PubMedCrossRefGoogle Scholar
  100. 100.
    Chan KH, Wilcox I (2010) Obstructive sleep apnea: novel trigger and potential therapeutic target for cardiac arrhythmias. Expert Rev Cardiovasc Ther 8:981–994PubMedCrossRefGoogle Scholar
  101. 101.
    Coumel P (1993) Cardiac arrhythmias and the autonomic nervous system. J Cardiovasc Electrophysiol 4:338–355PubMedCrossRefGoogle Scholar
  102. 102.
    Allen LA, Felker GM, Pocock S, McMurray JJ, Pfeffer MA, Swedberg K, Wang D, Yusuf S, Michelson EL, Granger CB (2009) Liver function abnormalities and outcome in patients with chronic heart failure: data from the candesartan in heart failure: assessment of reduction in mortality and morbidity (charm) program. Eur J Heart Fail 11:170–177PubMedCrossRefGoogle Scholar
  103. 103.
    Gelow JM, Desai AS, Hochberg CP, Glickman JN, Givertz MM, Fang JC (2010) Clinical predictors of hepatic fibrosis in chronic advanced heart failure. Circ Heart Fail 3:59–64PubMedCrossRefGoogle Scholar
  104. 104.
    Giallourakis CC, Rosenberg PM, Friedman LS (2002) The liver in heart failure. Clin Liver Dis.6:947–967, viii-ixGoogle Scholar
  105. 105.
    Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, Van Tassell BW, Afeltra A, Sanyal AJ (2010) Cirrhotic cardiomyopathy. J Am Coll Cardiol 56:539–549PubMedCrossRefGoogle Scholar
  106. 106.
    Moller S, Henriksen JH (2010) Cirrhotic cardiomyopathy. J Hepatol 53:179–190PubMedCrossRefGoogle Scholar
  107. 107.
    Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR (1994) Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 331:574–578PubMedCrossRefGoogle Scholar
  108. 108.
    Metivier F, Marchais SJ, Guerin AP, Pannier B, London GM (2000) Pathophysiology of anaemia: focus on the heart and blood vessels. Nephrol Dial Transplant 15(Suppl 3):14–18PubMedGoogle Scholar
  109. 109.
    Anand IS (2008) Anemia and chronic heart failure implications and treatment options. J Am Coll Cardiol 52:501–511PubMedCrossRefGoogle Scholar
  110. 110.
    From AM, Leibson CL, Bursi F, Redfield MM, Weston SA, Jacobsen SJ, Rodeheffer RJ, Roger VL (2006) Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med 119:591–599PubMedCrossRefGoogle Scholar
  111. 111.
    Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC (2006) Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the acute decompensated heart failure national registry (adhere) database. J Am Coll Cardiol 47:76–84PubMedCrossRefGoogle Scholar
  112. 112.
    MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the candesartan in heart failure: Assessment of reduction in mortality and morbidity (charm) programme. Eur Heart J 29:1377–1385PubMedCrossRefGoogle Scholar
  113. 113.
    Kamalesh M, Cleophas TJ (2009) Heart failure due to systolic dysfunction and mortality in diabetes: pooled analysis of 39, 505 subjects. J Card Fail 15:305–309PubMedCrossRefGoogle Scholar
  114. 114.
    AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR, Struthers AD, Lang CC (2009) Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol 53:747–753PubMedCrossRefGoogle Scholar
  115. 115.
    Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116:434–448PubMedCrossRefGoogle Scholar
  116. 116.
    Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000) Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 101:2271–2276PubMedGoogle Scholar
  117. 117.
    Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L (2005) Insulin resistance and risk of congestive heart failure. JAMA 294:334–341PubMedCrossRefGoogle Scholar
  118. 118.
    Matsushita K, Blecker S, Pazin-Filho A, Bertoni A, Chang PP, Coresh J, Selvin E (2010) The association of hemoglobin a1c with incident heart failure among people without diabetes: the atherosclerosis risk in communities study. Diabetes 59:2020–2026PubMedCrossRefGoogle Scholar
  119. 119.
    Thrainsdottir IS, Aspelund T, Gudnason V, Malmberg K, Sigurdsson G, Thorgeirsson G, Hardarson T, Ryden L (2007) Increasing glucose levels and BMI predict future heart failure experience from the reykjavik study. Eur J Heart Fail 9:1051–1057PubMedCrossRefGoogle Scholar
  120. 120.
    Triposkiadis F, Giamouzis G, Butler J (2011) The importance of managing diabetes correctly to prevent heart failure. Expert Rev Cardiovasc Ther 9:257–259PubMedCrossRefGoogle Scholar
  121. 121.
    MacDonald MR, Petrie MC, Hawkins NM, Petrie JR, Fisher M, McKelvie R, Aguilar D, Krum H, McMurray JJ (2008) Diabetes, left ventricular systolic dysfunction, and chronic heart failure. Eur Heart J 29:1224–1240PubMedCrossRefGoogle Scholar
  122. 122.
    Giamouzis G, Triposkiadis F, Butler J (2010) Metformin use in patients with diabetes mellitus and heart failure: friend or foe? J Card Fail 16:207–210PubMedCrossRefGoogle Scholar
  123. 123.
    Mancini DM, Walter G, Reichek N, Lenkinski R, McCully KK, Mullen JL, Wilson JR (1992) Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation 85:1364–1373PubMedGoogle Scholar
  124. 124.
    Minotti JR, Pillay P, Oka R, Wells L, Christoph I, Massie BM (1993) Skeletal muscle size: relationship to muscle function in heart failure. J Appl Physiol 75:373–381PubMedGoogle Scholar
  125. 125.
    Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA (1996) Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol 27:140–145PubMedCrossRefGoogle Scholar
  126. 126.
    Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zamboni M, Tosoni P, Zardini P (2001) Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure. J Am Coll Cardiol 37:2080–2085PubMedCrossRefGoogle Scholar
  127. 127.
    Coats AJ (1996) The “muscle hypothesis” of chronic heart failure. J Mol Cell Cardiol 28:2255–2262PubMedCrossRefGoogle Scholar
  128. 128.
    Duscha BD, Schulze PC, Robbins JL, Forman DE (2008) Implications of chronic heart failure on peripheral vasculature and skeletal muscle before and after exercise training. Heart Fail Rev 13:21–37PubMedCrossRefGoogle Scholar
  129. 129.
    Finsterer J, Stollberger C (2008) Primary myopathies and the heart. Scand Cardiovasc J 42:9–24PubMedCrossRefGoogle Scholar
  130. 130.
    Fatkin D, Otway R, Richmond Z (2010) Genetics of dilated cardiomyopathy. Heart Fail Clin 6:129–140PubMedCrossRefGoogle Scholar
  131. 131.
    Picano E, Morales MA, del Ry S, Sicari R (2010) Innate inflammation in myocardial perfusion and its implication for heart failure. Ann N Y Acad Sci 1207:107–115PubMedCrossRefGoogle Scholar
  132. 132.
    Turpeinen AK, Vanninen E, Magga J, Tuomainen P, Kuusisto J, Sipola P, Punnonen K, Vuolteenaho O, Peuhkurinen K (2009) Cardiac sympathetic activity is associated with inflammation and neurohumoral activation in patients with idiopathic dilated cardiomyopathy. Clin Physiol Funct Imaging 29:414–419PubMedCrossRefGoogle Scholar
  133. 133.
    Cottone S, Lorito MC, Riccobene R, Nardi E, Mule G, Buscemi S, Geraci C, Guarneri M, Arsena R, Cerasola G (2008) Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J Nephrol 21:175–179PubMedGoogle Scholar
  134. 134.
    Kelly KJ, Dominguez JH (2010) Rapid progression of diabetic nephropathy is linked to inflammation and episodes of acute renal failure. Am J Nephrol 32:469–475PubMedCrossRefGoogle Scholar
  135. 135.
    McNicholas WT (2009) Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med 180:692–700PubMedCrossRefGoogle Scholar
  136. 136.
    Ryan S, Taylor CT, McNicholas WT (2005) Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation 112:2660–2667PubMedCrossRefGoogle Scholar
  137. 137.
    Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev 7:35–51PubMedCrossRefGoogle Scholar
  138. 138.
    Iredale JP (2007) Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 117:539–548PubMedCrossRefGoogle Scholar
  139. 139.
    Maher JJ, McGuire RF (1990) Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. J Clin Invest 86:1641–1648PubMedCrossRefGoogle Scholar
  140. 140.
    Anand IS (2010) Pathophysiology of anemia in heart failure. Heart Fail Clin 6:279–288PubMedCrossRefGoogle Scholar
  141. 141.
    Opasich C, Cazzola M, Scelsi L, De Feo S, Bosimini E, Lagioia R, Febo O, Ferrari R, Fucili A, Moratti R, Tramarin R, Tavazzi L (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26:2232–2237PubMedCrossRefGoogle Scholar
  142. 142.
    Means RT Jr (2003) Recent developments in the anemia of chronic disease. Curr Hematol Rep 2:116–121PubMedGoogle Scholar
  143. 143.
    Cianetti L, Gabbianelli M, Sposi NM (2010) Ferroportin and erythroid cells: an update. Adv Hematol 2010, Art ID 404173. doi:10.1155/2010/404173
  144. 144.
    Garcia C, Feve B, Ferre P, Halimi S, Baizri H, Bordier L, Guiu G, Dupuy O, Bauduceau B, Mayaudon H (2010) Diabetes and inflammation: fundamental aspects and clinical implications. Diabetes Metab 36:327–338PubMedCrossRefGoogle Scholar
  145. 145.
    Kolb H, Mandrup-Poulsen T (2010) The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia 53:10–20PubMedCrossRefGoogle Scholar
  146. 146.
    Ehses JA, Ellingsgaard H, Boni-Schnetzler M, Donath MY (2009) Pancreatic islet inflammation in type 2 diabetes: from alpha and beta cell compensation to dysfunction. Arch Physiol Biochem 115:240–247PubMedCrossRefGoogle Scholar
  147. 147.
    Reid MB, Li YP (2001) Cytokines and oxidative signalling in skeletal muscle. Acta Physiol Scand 171:225–232PubMedCrossRefGoogle Scholar
  148. 148.
    Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, Kempf W, Schubert A, Schuler G, Hambrecht R (2003) Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol 42:861–868PubMedCrossRefGoogle Scholar
  149. 149.
    Adams V, Jiang H, Yu J, Mobius-Winkler S, Fiehn E, Linke A, Weigl C, Schuler G, Hambrecht R (1999) Apoptosis in skeletal myocytes of patients with chronic heart failure is associated with exercise intolerance. J Am Coll Cardiol 33:959–965PubMedCrossRefGoogle Scholar
  150. 150.
    Tsutsui H, Ide T, Hayashidani S, Suematsu N, Shiomi T, Wen J, Nakamura K, Ichikawa K, Utsumi H, Takeshita A (2001) Enhanced generation of reactive oxygen species in the limb skeletal muscles from a murine infarct model of heart failure. Circulation 104:134–136PubMedCrossRefGoogle Scholar
  151. 151.
    Middlekauff HR (2010) Making the case for skeletal myopathy as the major limitation of exercise capacity in heart failure. Circ Heart Fail 3:537–546PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Filippos Triposkiadis
    • 1
  • Randall C. Starling
    • 2
  • Harisios Boudoulas
    • 3
  • Gregory Giamouzis
    • 1
  • Javed Butler
    • 4
  1. 1.Department of CardiologyLarissa University HospitalLarissaGreece
  2. 2.Cardiology DivisionCleveland ClinicClevelandUSA
  3. 3.Foundation of Biomedical ResearchAcademy of AthensAthensGreece
  4. 4.Cardiology DivisionEmory UniversityAtlantaUSA

Personalised recommendations