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Loop diuretic resistance complicating acute heart failure

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Abstract

Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices.

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References

  1. Fonarow GC, Heywood JT, Heidenreich PA, Lopatin M, Yancy CW (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 153:1021–1028

    PubMed  Google Scholar 

  2. Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, Nodari S, Lam CS, Sato N, Shah AN, Gheorghiade M (2014) The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol 63:1123–1133

    PubMed  Google Scholar 

  3. Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ (2019) The use of diuretics in heart failure with congestion—a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 21:137–155

    PubMed  Google Scholar 

  4. Chakko S, Woska D, Martinez H, de Marchena E, Futterman L, Kessler KM, Myerberg RJ (1991) Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care. Am J Med 90:353–359

    PubMed  CAS  Google Scholar 

  5. Elder A, Japp A, Verghese A (2016) How valuable is physical examination of the cardiovascular system? BMJ. 354:i3309

    PubMed  Google Scholar 

  6. Drazner MH, Hellkamp AS, Leier CV, Shah MR, Miller LW, Russell SD, Young JB, Califf RM, Nohria A (2008) Value of clinician assessment of hemodynamics in advanced heart failure: the ESCAPE trial. Circ Heart Fail 1:170–177

    PubMed  PubMed Central  Google Scholar 

  7. Stevenson LW, Perloff JK (1989) The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA 261:884–888

    PubMed  CAS  Google Scholar 

  8. 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 53:589–596

    PubMed  PubMed Central  Google Scholar 

  9. 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 51:1268–1274

    PubMed  Google Scholar 

  10. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R (2008) Cardiorenal syndrome. J Am Coll Cardiol 52:1527–1539

    PubMed  Google Scholar 

  11. Damman K, Testani JM (2015) The kidney in heart failure: an update. Eur Heart J 36:1437–1444

    PubMed  PubMed Central  Google Scholar 

  12. Testani JM, Kimmel SE, Dries DL, Coca SG (2011) Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction. Circ Heart Fail 4:685–691

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Michel A, Martin-Perez M, Ruigomez A, Garcia Rodriguez LA (2016) Incidence and risk factors for severe renal impairment after first diagnosis of heart failure: a cohort and nested case-control study in UK general practice. Int J Cardiol 207:252–257

    PubMed  Google Scholar 

  14. Daniels LB, Maisel AS (2007) Natriuretic peptides. J Am Coll Cardiol 50:2357–2368

    PubMed  CAS  Google Scholar 

  15. Desai AS (2013) Are serial BNP measurements useful in heart failure management? Serial natriuretic peptide measurements are not useful in heart failure management: the art of medicine remains long. Circulation. 127:509–516 discussion 516

    PubMed  Google Scholar 

  16. Stienen S, Salah K, Moons AH, Bakx AL, van Pol P, Kortz RAM, Ferreira JP, Marques I, Schroeder-Tanka JM, Keijer JT, Bayes-Genis A, Tijssen JGP, Pinto YM, Kok WE (2018) NT-proBNP (N-terminal pro-B-type natriuretic peptide)-guided therapy in acute decompensated heart failure: PRIMA II randomized controlled trial (can NT-ProBNP-guided therapy during hospital admission for acute decompensated heart failure reduce mortality and readmissions?). Circulation. 137:1671–1683

    PubMed  CAS  Google Scholar 

  17. Kociol RD, McNulty SE, Hernandez AF, Lee KL, Redfield MM, Tracy RP, Braunwald E, O’Connor CM, Felker GM, NHLBI Heart Failure Network Steering Committee and Investigators (2013) Markers of decongestion, dyspnea relief, and clinical outcomes among patients hospitalized with acute heart failure. Circ Heart Fail 6:240–245

    PubMed  CAS  Google Scholar 

  18. Cooper LB, Mentz RJ, Gallup D, Lala A, DeVore AD, Vader JM, AbouEzzeddine OF, Bart BA, Anstrom KJ, Hernandez AF, Felker GM (2016) Serum bicarbonate in acute heart failure: relationship to treatment strategies and clinical outcomes. J Card Fail 22:738–742

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW (2015) Relief and recurrence of congestion during and after hospitalization for acute heart failure: insights from Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF). Circ Heart Fail 8:741–748

    PubMed  PubMed Central  Google Scholar 

  20. Miller WL (2016) Fluid volume overload and congestion in heart failure: time to reconsider pathophysiology and how volume is assessed. Circ Heart Fail 9:e002922

    PubMed  CAS  Google Scholar 

  21. Neuberg GW, Miller AB, O’Connor CM, Belkin RN, Carson PE, Cropp AB, Frid DJ, Nye RG, Pressler ML, Wertheimer JH, Packer M (2002) Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J 144:31–38

    PubMed  Google Scholar 

  22. Testani JM, Cappola TP, Brensinger CM, Shannon RP, Kimmel SE (2011) Interaction between loop diuretic-associated mortality and blood urea nitrogen concentration in chronic heart failure. J Am Coll Cardiol 58:375–382

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Yilmaz MB, Gayat E, Salem R, Lassus J, Nikolaou M, Laribi S, Parissis J, Follath F, Peacock WF, Mebazaa A (2011) Impact of diuretic dosing on mortality in acute heart failure using a propensity-matched analysis. Eur J Heart Fail 13:1244–1252

    PubMed  CAS  Google Scholar 

  24. Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, Tang WH (2014) Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 7:261–270

    PubMed  CAS  Google Scholar 

  25. Testani JM, Hanberg JS, Cheng S, Rao V, Onyebeke C, Laur O, Kula A, Chen M, Wilson FP, Darlington A, Bellumkonda L, Jacoby D, Tang WH, Parikh CR (2016) Rapid and highly accurate prediction of poor loop diuretic natriuretic response in patients with heart failure. Circ Heart Fail 9:e002370

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Brinkley DM Jr, Burpee LJ, Chaudhry SP, Smallwood JA, Lindenfeld J, Lakdawala NK, Desai AS, Stevenson LW (2018) Spot urine sodium as triage for effective diuretic infusion in an ambulatory heart failure unit. J Card Fail 24:349–354

    PubMed  CAS  Google Scholar 

  27. Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, Tang WH (2014) Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail 20:392–399

    PubMed  PubMed Central  CAS  Google Scholar 

  28. Verbrugge FH, Nijst P, Dupont M, Penders J, Tang WH, Mullens W (2014) Urinary composition during decongestive treatment in heart failure with reduced ejection fraction. Circ Heart Fail 7:766–772

    PubMed  CAS  Google Scholar 

  29. Ambrosy AP, Cerbin LP, Armstrong PW, Butler J, Coles A, DeVore AD, Dunlap ME, Ezekowitz JA, Felker GM, Fudim M, Greene SJ, Hernandez AF, O’Connor CM, Schulte P, Starling RC, Teerlink JR, Voors AA, Mentz RJ (2017) Body weight change during and after hospitalization for acute heart failure: patient characteristics, markers of congestion, and outcomes: findings from the ASCEND-HF trial. JACC Heart Fail 5:1–13

    PubMed  PubMed Central  Google Scholar 

  30. Testani JM, Brisco MA, Kociol RD, Jacoby D, Bellumkonda L, Parikh CR, Coca SG, Tang WH (2015) Substantial discrepancy between fluid and weight loss during acute decompensated heart failure treatment. Am J Med 128:776–783 e4

    PubMed  PubMed Central  Google Scholar 

  31. Zile MR, Bennett TD, St John Sutton M, Cho YK, Adamson PB, Aaron MF, Aranda JM Jr, Abraham WT, Smart FW, Stevenson LW, Kueffer FJ, Bourge RC (2008) Transition from chronic compensated to acute decompensated heart failure: pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation. 118:1433–1441

    PubMed  Google Scholar 

  32. Chaudhry SI, Wang Y, Concato J, Gill TM, Krumholz HM (2007) Patterns of weight change preceding hospitalization for heart failure. Circulation. 116:1549–1554

    PubMed  PubMed Central  Google Scholar 

  33. Patarroyo M, Wehbe E, Hanna M, Taylor DO, Starling RC, Demirjian S, Tang WH (2012) Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure. J Am Coll Cardiol 60:1906–1912

    PubMed  Google Scholar 

  34. Kiernan MS, Stevens SR, Tang WHW, Butler J, Anstrom KJ, Birati EY, Grodin JL, Gupta D, Margulies KB, LaRue S, Davila-Roman VG, Hernandez AF, de Las FL, Investigators NHFCTN (2018) Determinants of diuretic responsiveness and associated outcomes during acute heart failure hospitalization: an analysis from the NHLBI heart failure network clinical trials. J Card Fail 24:428–438

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Valente MA, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O’Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Fiuzat M, Dittrich HC, Hillege HL (2014) Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 35:1284–1293

    PubMed  CAS  Google Scholar 

  36. Rubio-Gracia J, Demissei BG, Ter Maaten JM, Cleland JG, O’Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison BA, Givertz MM, Bloomfield DM, Dittrich H, Damman K, Perez-Calvo JI, Voors AA (2018) Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure. Int J Cardiol 258:185–191

    PubMed  Google Scholar 

  37. Felker GM, Mentz RJ (2012) Diuretics and ultrafiltration in acute decompensated heart failure. J Am Coll Cardiol 59:2145–2153

    PubMed  CAS  Google Scholar 

  38. Mentz RJ, Stevens SR, DeVore AD, Lala A, Vader JM, AbouEzzeddine OF, Khazanie P, Redfield MM, Stevenson LW, O’Connor CM, Goldsmith SR, Bart BA, Anstrom KJ, Hernandez AF, Braunwald E, Felker GM (2015) Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure. JACC Heart Fail 3:97–107

    PubMed  Google Scholar 

  39. Hanberg JS, Tang WHW, Wilson FP, Coca SG, Ahmad T, Brisco MA, Testani JM (2017) An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial. Int J Cardiol 241:277–282

    PubMed  PubMed Central  Google Scholar 

  40. 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 364:797–805

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Honda S, Nagai T, Nishimura K, Nakai M, Honda Y, Nakano H, Iwakami N, Sugano Y, Asaumi Y, Aiba T, Noguchi T, Kusano K, Yokoyama H, Ogawa H, Yasuda S, Anzai T, NaDEF Investigators (2018) Long-term prognostic significance of urinary sodium concentration in patients with acute heart failure. Int J Cardiol 254:189–194

    PubMed  Google Scholar 

  42. Collins SP, Jenkins CA, Baughman A, Miller KF, Storrow AB, Han JH, Brown NJ, Liu D, Luther JM, McNaughton CD, Self WH, Peng D, Testani JM, Lindenfeld J (2019) Early urine electrolyte patterns in patients with acute heart failure. ESC Heart Fail 6:80–88

    PubMed  Google Scholar 

  43. Luk A, Groarke JD, Desai AS, Mahmood SS, Gopal DM, Joyce E, Shah SP, Lindenfeld J, Stevenson L, Lakdawala NK (2018) First spot urine sodium after initial diuretic identifies patients at high risk for adverse outcome after heart failure hospitalization. Am Heart J 203:95–100

    PubMed  CAS  Google Scholar 

  44. Biegus J, Zymlinski R, Sokolski M, Todd J, Cotter G, Metra M, Jankowska EA, Banasiak W, Ponikowski P (2019) Serial assessment of spot urine sodium predicts effectiveness of decongestion and outcome in patients with acute heart failure. Eur J Heart Fail 21:624–633

    PubMed  CAS  Google Scholar 

  45. Ellison DH, Felker GM (2017) Diuretic treatment in heart failure. N Engl J Med 377:1964–1975

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Cox ZL, Testani JM (2020) Loop diuretic resistance in a patient with acute heart failure. In: Tang W, Verbrugge F, Mullens W (eds) Cardiorenal syndrome in heart failure. Springer, Cham. https://doi.org/10.1007/978-3-030-21033-5_11

    Google Scholar 

  47. Brater DC (1998) Diuretic therapy. N Engl J Med 339:387–395

    PubMed  CAS  Google Scholar 

  48. Wilcox CS (2002) New insights into diuretic use in patients with chronic renal disease. J Am Soc Nephrol 13:798–805

    PubMed  Google Scholar 

  49. Beermann B, Midskov C (1986) Reduced bioavailability and effect of furosemide given with food. Eur J Clin Pharmacol 29:725–727

    PubMed  CAS  Google Scholar 

  50. Phakdeekitcharoen B, Boonyawat K (2012) The added-up albumin enhances the diuretic effect of furosemide in patients with hypoalbuminemic chronic kidney disease: a randomized controlled study. BMC Nephrol 13:92

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Loon NR, Wilcox CS, Unwin RJ (1989) Mechanism of impaired natriuretic response to furosemide during prolonged therapy. Kidney Int 36:682–689

    PubMed  CAS  Google Scholar 

  52. McCrindle JL, Li Kam Wa TC, Barron W, Prescott LF (1996) Effect of food on the absorption of furosemide and bumetanide in man. Br J Clin Pharmacol 42:743–746

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Nakahama H, Orita Y, Yamazaki M, Itoh S, Okuda T, Yamaji A, Miwa Y, Yanase M, Fukuhara Y, Kamada T (1988) Pharmacokinetic and pharmacodynamic interactions between furosemide and hydrochlorothiazide in nephrotic patients. Nephron. 49:223–227

    PubMed  CAS  Google Scholar 

  54. Bock JS, Gottlieb SS (2010) Cardiorenal syndrome: new perspectives. Circulation. 121:2592–2600

    PubMed  Google Scholar 

  55. Gottlieb SS, Stebbins A, Voors AA, Hasselblad V, Ezekowitz JA, Califf RM, O’Connor CM, Starling RC, Hernandez AF (2013) Effects of nesiritide and predictors of urine output in acute decompensated heart failure: results from ASCEND-HF. J Am Coll Cardiol 62:1177–1183

    PubMed  CAS  Google Scholar 

  56. Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS, Massie BM, O’Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M (2002) Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 287:1541–1547

    PubMed  CAS  Google Scholar 

  57. Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigram MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O’Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O’Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM (2013) Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA 310:2533–2543

    PubMed  PubMed Central  CAS  Google Scholar 

  58. Packer M, O’Connor C, McMurray JJV, Wittes J, Abraham WT, Anker SD, Dickstein K, Filippatos G, Holcomb R, Krum H, Maggioni AP, Mebazaa A, Peacock WF, Petrie MC, Ponikowski P, Ruschitzka F, van Veldhuisen DJ, Kowarski LS, Schactman M, Holzmeister J, True-AHF Investigators (2017) Effect of ularitide on cardiovascular mortality in acute heart failure. N Engl J Med 376:1956–1964

    PubMed  CAS  Google Scholar 

  59. Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, Ponikowski P, Unemori E, Voors AA, Adams KF Jr, Dorobantu MI, Grinfeld LR, Jondeau G, Marmor A, Masip J, Pang PS, Werdan K, Teichman SL, Trapani A, Bush CA, Saini R, Schumacher C, Severin TM, Metra M, RELAX-AHF Investigators (2013) Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. 381:29–39

    PubMed  CAS  Google Scholar 

  60. Sharma K, Vaishnav J, Kalathiya R, Hu JR, Miller J, Shah N, Hill T, Sharp M, Tsao A, Alexander KM, Gupta R, Montemayor K, Kovell L, Chasler JE, Lee YJ, Fine DM, Kass DA, Weiss RG, Thiemann DR, Ndumele CE, Schulman SP, Russell SD, Osler Medical Housestaff (2018) Randomized evaluation of heart failure with preserved ejection fraction patients with acute heart failure and dopamine: the ROPA-DOP trial. JACC Heart Fail 6:859–870

    PubMed  Google Scholar 

  61. Chen HH, Redfield MM, Nordstrom LJ, Cataliotti A, Burnett JC Jr (2003) Angiotensin II AT1 receptor antagonism prevents detrimental renal actions of acute diuretic therapy in human heart failure. Am J Physiol Renal Physiol 284:F1115–F1119

    PubMed  CAS  Google Scholar 

  62. Kula AJ, Hanberg JS, Wilson FP, Brisco MA, Bellumkonda L, Jacoby D, Coca SG, Parikh CR, Tang WHW, Testani JM (2016) Influence of titration of neurohormonal antagonists and blood pressure reduction on renal function and decongestion in decompensated heart failure. Circ Heart Fail 9:e002333

    PubMed  CAS  Google Scholar 

  63. Guazzi MD, Agostoni P, Perego B, Lauri G, Salvioni A, Giraldi F, Matturri M, Guazzi M, Marenzi G (1994) Apparent paradox of neurohumoral axis inhibition after body fluid volume depletion in patients with chronic congestive heart failure and water retention. Br Heart J 72:534–539

    PubMed  PubMed Central  CAS  Google Scholar 

  64. Wilson DR, Honrath U, Sonnenberg H (1983) Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition. Am J Phys 244:F666–F673

    CAS  Google Scholar 

  65. Nies AS, Gal J, Fadul S, Gerber JG (1983) Indomethacin-furosemide interaction: the importance of renal blood flow. J Pharmacol Exp Ther 226:27–32

    PubMed  CAS  Google Scholar 

  66. Torsemide [package insert]. Roche Pharmaceuticals IN, NJ.; April 2003

  67. Furosemide [package insert]. Sanofi-aventis L, Bridgewater, NJ; November 2012

  68. Bumetanide [package insert]. Bedford Pharmaceuticals I, Bedford, OH.; February 2010

  69. Arques S, Ambrosi P (2011) Human serum albumin in the clinical syndrome of heart failure. J Card Fail 17:451–458

    PubMed  CAS  Google Scholar 

  70. Chalasani N, Gorski JC, Horlander JC Sr, Craven R, Hoen H, Maya J, Brater DC (2001) Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients. J Am Soc Nephrol 12:1010–1016

    PubMed  CAS  Google Scholar 

  71. Elwell RJ, Spencer AP, Eisele G (2003) Combined furosemide and human albumin treatment for diuretic-resistant edema. Ann Pharmacother 37:695–700

    PubMed  CAS  Google Scholar 

  72. Charokopos A, Sury K, Rao V, Ahmad T, Griffin M, Turner JM, Mahoney D, Cox ZL, Wilson FP and Testani JM (2019) The Influence of Serum and Urine Albumin on Loop Diuretic Response in Heart Failure. Clin J Am Soc Nephrol 14 (5) 712–718. https://doi.org/10.2215/CJN.11600918

    PubMed  CAS  PubMed Central  Google Scholar 

  73. Grodin JL, Lala A, Stevens SR, DeVore AD, Cooper LB, AbouEzzeddine OF, Mentz RJ, Groarke JD, Joyce E, Rosenthal JL, Vader JM, Tang WH (2016) Clinical implications of serum albumin levels in acute heart failure: insights from DOSE-AHF and ROSE-AHF. J Card Fail 22:884–890

    PubMed  PubMed Central  CAS  Google Scholar 

  74. Gupta D, Georgiopoulou VV, Kalogeropoulos AP, Dunbar SB, Reilly CM, Sands JM, Fonarow GC, Jessup M, Gheorghiade M, Yancy C, Butler J (2012) Dietary sodium intake in heart failure. Circulation. 126:479–485

    PubMed  CAS  Google Scholar 

  75. Nijst P, Verbrugge FH, Grieten L, Dupont M, Steels P, Tang WHW, Mullens W (2015) The pathophysiological role of interstitial sodium in heart failure. J Am Coll Cardiol 65:378–388

    PubMed  CAS  Google Scholar 

  76. Ellison DH (2001) Diuretic therapy and resistance in congestive heart failure. Cardiology. 96:132–143

    PubMed  CAS  Google Scholar 

  77. Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G (2000) Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur J Heart Fail 2:305–313

    PubMed  CAS  Google Scholar 

  78. Paterna S, Di Pasquale P, Parrinello G, Fornaciari E, Di Gaudio F, Fasullo S, Giammanco M, Sarullo FM, Licata G (2005) Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure: a double-blind study. J Am Coll Cardiol 45:1997–2003

    PubMed  CAS  Google Scholar 

  79. Licata G, Di Pasquale P, Parrinello G, Cardinale A, Scandurra A, Follone G, Argano C, Tuttolomondo A, Paterna S (2003) Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J 145:459–466

    PubMed  CAS  Google Scholar 

  80. Gandhi S, Mosleh W, Myers RB (2014) Hypertonic saline with furosemide for the treatment of acute congestive heart failure: a systematic review and meta-analysis. Int J Cardiol 173:139–145

    PubMed  Google Scholar 

  81. Kirchner KA, Voelker JR, Brater DC (1990) Intratubular albumin blunts the response to furosemide—a mechanism for diuretic resistance in the nephrotic syndrome. J Pharmacol Exp Ther 252:1097–1101

    PubMed  CAS  Google Scholar 

  82. Kirchner KA, Voelker JR, Brater DC (1991) Binding inhibitors restore furosemide potency in tubule fluid containing albumin. Kidney Int 40:418–424

    PubMed  CAS  Google Scholar 

  83. Green TP, Mirkin BL (1980) Resistance of proteinuric rats to furosemide: urinary drug protein binding as a determinant of drug effect. Life Sci 26:623–630

    PubMed  CAS  Google Scholar 

  84. Sabatine MS, Massachusetts General Hospital (2017) Pocket medicine: The Massachusetts General Hospital Handbook of Internal medicine. Sixth edition. Wolters Kluwer

  85. Agarwal R, Gorski JC, Sundblad K, Brater DC (2000) Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome. J Am Soc Nephrol 11:1100–1105

    PubMed  CAS  Google Scholar 

  86. Shem S (1979) The house of god. Bodley Head, London

    Google Scholar 

  87. Ter Maaten JM, Rao VS, Hanberg JS, Perry Wilson F, Bellumkonda L, Assefa M, Sam Broughton J, D'Ambrosi J, Wilson Tang WH, Damman K, Voors AA, Ellison DH, Testani JM (2017) Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure. Eur J Heart Fail 19:1014–1022

    PubMed  Google Scholar 

  88. Mullens W, Verbrugge FH, Nijst P, Tang WHW (2017) Renal sodium avidity in heart failure: from pathophysiology to treatment strategies. Eur Heart J 38:1872–1882

    PubMed  CAS  Google Scholar 

  89. Cox ZL, Lenihan DJ (2014) Loop diuretic resistance in heart failure: resistance etiology-based strategies to restoring diuretic efficacy. J Card Fail 20:611–622

    PubMed  CAS  Google Scholar 

  90. Ellison DH (1991) The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med 114:886–894

    PubMed  CAS  Google Scholar 

  91. Stanton BA, Kaissling B (1988) Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport. Am J Phys 255:F1269–F1275

    CAS  Google Scholar 

  92. Stanton BA, Kaissling B (1989) Regulation of renal ion transport and cell growth by sodium. Am J Phys 257:F1–F10

    CAS  Google Scholar 

  93. Rao VS, Planavsky N, Hanberg JS, Ahmad T, Brisco-Bacik MA, Wilson FP, Jacoby D, Chen M, Tang WHW, Cherney DZI, Ellison DH, Testani JM (2017) Compensatory distal reabsorption drives diuretic resistance in human heart failure. J Am Soc Nephrol 28:3414–3424

    PubMed  PubMed Central  CAS  Google Scholar 

  94. Bart BA, Goldsmith SR, Lee KL, Redfield MM, Felker GM, O’Connor CM, Chen HH, Rouleau JL, Givertz MM, Semigran MJ, Mann D, Deswal A, Bull DA, Lewinter MM, Braunwald E (2012) Cardiorenal rescue study in acute decompensated heart failure: rationale and design of CARRESS-HF, for the Heart Failure Clinical Research Network. J Card Fail 18:176–182

    PubMed  PubMed Central  Google Scholar 

  95. Felker GM, O’Connor CM, Braunwald E (2009) Loop diuretics in acute decompensated heart failure: necessary? Evil? A necessary evil? Circ Heart Fail 2:56–62

    PubMed  PubMed Central  Google Scholar 

  96. Brisco-Bacik MA, Ter Maaten JM, Houser SR, Vedage NA, Rao V, Ahmad T, Wilson FP, Testani JM (2018) Outcomes associated with a strategy of adjuvant metolazone or high-dose loop diuretics in acute decompensated heart failure: a propensity analysis. J Am Heart Assoc 7:e009149

    PubMed  PubMed Central  Google Scholar 

  97. Trullas JC, Morales-Rull JL, Casado J, Freitas Ramirez A, Manzano L, Formiga F, CLOROTIC Investigators (2016) Rationale and design of the “Safety and efficacy of the combination of loop with thiazide-type diuretics in patients with decompensated heart failure (CLOROTIC) trial:” a double-blind, randomized, placebo-controlled study to determine the effect of combined diuretic therapy (loop diuretics with thiazide-type diuretics) among patients with decompensated heart failure. J Card Fail 22:529–536

    PubMed  CAS  Google Scholar 

  98. Bart BA, Goldsmith SR, Lee KL, Givertz MM, O’Connor CM, Bull DA, Redfield MM, Deswal A, Rouleau JL, LeWinter MM, Ofili EO, Stevenson LW, Semigran MJ, Felker GM, Chen HH, Hernandez AF, Anstrom KJ, McNulty SE, Velazquez EJ, Ibarra JC, Mascette AM, Braunwald E (2012) Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med 367:2296–2304

    PubMed  PubMed Central  CAS  Google Scholar 

  99. Jentzer JC, DeWald TA, Hernandez AF (2010) Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol 56:1527–1534

    PubMed  CAS  Google Scholar 

  100. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., 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 and 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. Circulation 128:e240–e327

  101. Goodman LS, Brunton LL, Chabner B, Knollmann BC (2011) Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New York

    Google Scholar 

  102. Channer KS, McLean KA, Lawson-Matthew P, Richardson M (1994) Combination diuretic treatment in severe heart failure: a randomised controlled trial. Br Heart J 71:146–150

    PubMed  PubMed Central  CAS  Google Scholar 

  103. Knauf H, Mutschler E (1995) Diuretic effectiveness of hydrochlorothiazide and furosemide alone and in combination in chronic renal failure. J Cardiovasc Pharmacol 26:394–400

    PubMed  CAS  Google Scholar 

  104. Fliser D, Schroter M, Neubeck M, Ritz E (1994) Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure. Kidney Int 46:482–488

    PubMed  CAS  Google Scholar 

  105. Sica DA (2003) Metolazone and its role in edema management. Congest Heart Fail 9:100–105

    PubMed  CAS  Google Scholar 

  106. Metolazone [package insert]; Mylan Pharmaceuticals Inc; Morgantown W. October 2004

  107. Kissling KT, Pickworth KK (2014) Comparison of the effects of combination diuretic therapy with oral hydrochlorothiazide or intravenous chlorothiazide in patients receiving intravenous furosemide therapy for the treatment of heart failure. Pharmacotherapy. 34:882–887

    PubMed  CAS  Google Scholar 

  108. Ter Maaten JM, Damman K (2018) Chloride, what else? Eur J Heart Fail 20:1444–1446

    PubMed  Google Scholar 

  109. Grodin JL, Testani JM, Pandey A, Sambandam K, Drazner MH, Fang JC, Tang WHW (2018) Perturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT. Eur J Heart Fail 20:1436–1443

    PubMed  CAS  Google Scholar 

  110. Cuthbert JJ, Pellicori P, Rigby A, Pan D, Kazmi S, Shah P, Clark AL (2018) Low serum chloride in patients with chronic heart failure: clinical associations and prognostic significance. Eur J Heart Fail 20:1426–1435

    PubMed  CAS  Google Scholar 

  111. Ter Maaten JM, Damman K, Hanberg JS, Givertz MM, Metra M, O’Connor CM, Teerlink JR, Ponikowski P, Cotter G, Davison B, Cleland JG, Bloomfield DM, Hillege HL, van Veldhuisen DJ, Voors AA and Testani JM(2016) Hypochloremia, diuretic resistance, and outcome in patients with acute heart failure. Circ Heart Fail 9(8):e003109. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003109

  112. Hanberg JS, Rao V, Ter Maaten JM, Laur O, Brisco MA, Perry Wilson F, Grodin JL, Assefa M, Samuel Broughton J, Planavsky NJ, Ahmad T, Bellumkonda L, Tang WH, Parikh CR and Testani JM (2016) Hypochloremia and diuretic resistance in heart failure: mechanistic insights. Circ Heart Fail 9(8):e003180. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180

  113. Ernst ME, Moser M (2009) Use of diuretics in patients with hypertension. N Engl J Med 361:2153–2164

    PubMed  CAS  Google Scholar 

  114. Gines P, Cardenas A, Arroyo V, Rodes J (2004) Management of cirrhosis and ascites. N Engl J Med 350:1646–1654

    PubMed  CAS  Google Scholar 

  115. European Association for the Study of the Liver (2010) EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 53:397–417

    Google Scholar 

  116. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341:709–717

    PubMed  CAS  Google Scholar 

  117. 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 2:370–376

    PubMed  CAS  Google Scholar 

  118. Butler J, Hernandez AF, Anstrom KJ, Kalogeropoulos A, Redfield MM, Konstam MA, Tang WH, Felker GM, Shah MR, Braunwald E (2016) Rationale and design of the ATHENA-HF trial: Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure. JACC Heart Fail 4:726–735

    PubMed  PubMed Central  Google Scholar 

  119. Butler J, Anstrom KJ, Felker GM, Givertz MM, Kalogeropoulos AP, Konstam MA, Mann DL, Margulies KB, McNulty SE, Mentz RJ, Redfield MM, Tang WHW, Whellan DJ, Shah M, Desvigne-Nickens P, Hernandez AF, Braunwald E, National Heart Lung and Blood Institute Heart Failure Clinical Research Network (2017) Efficacy and safety of spironolactone in acute heart failure: the ATHENA-HF randomized clinical trial. JAMA Cardiol 2:950–958

    PubMed  PubMed Central  Google Scholar 

  120. Yang J, Young MJ (2016) Mineralocorticoid receptor antagonists—pharmacodynamics and pharmacokinetic differences. Curr Opin Pharmacol 27:78–85

    PubMed  CAS  Google Scholar 

  121. Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C (2007) Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST clinical status trials. JAMA 297:1332–1343

    PubMed  CAS  Google Scholar 

  122. Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial. JAMA 297:1319–1331

    PubMed  CAS  Google Scholar 

  123. Gheorghiade M, Gattis WA, Barbagelata A, Adams KF Jr, Elkayam U, Orlandi C, O’Connor CM (2003) Rationale and study design for a multicenter, randomized, double-blind, placebo-controlled study of the effects of tolvaptan on the acute and chronic outcomes of patients hospitalized with worsening congestive heart failure. Am Heart J 145:S51–S54

    PubMed  CAS  Google Scholar 

  124. Matsue Y, Suzuki M, Torii S, Yamaguchi S, Fukamizu S, Ono Y, Fujii H, Kitai T, Nishioka T, Sugi K, Onishi Y, Noda M, Kagiyama N, Satoh Y, Yoshida K, Goldsmith SR (2016) Clinical effectiveness of tolvaptan in patients with acute heart failure and renal dysfunction. J Card Fail 22:423–432

    PubMed  CAS  Google Scholar 

  125. Felker GM, Mentz RJ, Cole RT, Adams KF, Egnaczyk GF, Fiuzat M, Patel CB, Echols M, Khouri MG, Tauras JM, Gupta D, Monds P, Roberts R, O’Connor CM (2017) Efficacy and safety of tolvaptan in patients hospitalized with acute heart failure. J Am Coll Cardiol 69:1399–1406

    PubMed  CAS  Google Scholar 

  126. Konstam MA, Kiernan M, Chandler A, Dhingra R, Mody FV, Eisen H, Haught WH, Wagoner L, Gupta D, Patten R, Gordon P, Korr K, Fileccia R, Pressler SJ, Gregory D, Wedge P, Dowling D, Romeling M, Konstam JM, Massaro JM, Udelson JE, SECRET of CHF Investigators, Coordinators, and Committee Members (2017) Short-term effects of tolvaptan in patients with acute heart failure and volume overload. J Am Coll Cardiol 69:1409–1419

    PubMed  CAS  Google Scholar 

  127. Mullens W, Verbrugge FH, Nijst P, Martens P, Tartaglia K, Theunissen E, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M (2018) Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. Eur J Heart Fail 20:1591–1600

    PubMed  CAS  Google Scholar 

  128. Knauf H, Mutschler E (1997) Sequential nephron blockade breaks resistance to diuretics in edematous states. J Cardiovasc Pharmacol 29:367–372

    PubMed  CAS  Google Scholar 

  129. Verbrugge FH, Dupont M, Bertrand PB, Nijst P, Penders J, Dens J, Verhaert D, Vandervoort P, Tang WH, Mullens W (2015) Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload. Acta Cardiol 70:265–273

    PubMed  Google Scholar 

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  1. Department of Pharmacy Practice, Burton Health Science Center, Lipscomb University College of Pharmacy, One University Park Drive, Nashville, TN, 37204, USA

    Zachary L. Cox

  2. Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA

    Zachary L. Cox

  3. Division of Internal Medicine, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA

    Jeffrey M. Testani

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Cox, Z.L., Testani, J.M. Loop diuretic resistance complicating acute heart failure. Heart Fail Rev 25, 133–145 (2020). https://doi.org/10.1007/s10741-019-09851-9

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