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Pathophysiologic Insights into Heart Rate Reduction in Heart Failure: Implications in the Use of Beta-Blockers and Ivabradine

  • Heart Failure (W Tang, Section Editor)
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Opinion statement

In patients with heart failure, an elevated heart rate is associated with worse cardiovascular outcomes and is increasingly recognized as a modifiable risk factor. Beta-blockers are the mainstay of therapy for heart failure. However, up-titration of beta-blockers in response to persistently elevated heart rate can be associated with increased risk of adverse reactions besides negative chronotropism. Recently, the specific heart rate-lowering agent, ivabradine, which acts by directly and selectively inhibiting the I f current in the sinoatrial node, generated renewed interest in potential benefits of pharmacologic modification of heart rate in heart failure. Several placebo-controlled, multicenter clinical trials showed the benefits of ivabradine in patients with angina and heart failure, which is largely confined to those with left ventricular systolic dysfunction. In addition, the other potential effects of ivabradine have been proposed.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352:1539–49.

    Article  CAS  PubMed  Google Scholar 

  2. Packer M. Pathophysiology of chronic heart failure. Lancet. 1992;340:88–92.

    Article  CAS  PubMed  Google Scholar 

  3. Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and outcomes in chronic heart failure (shift): a randomised placebo-controlled study. Lancet. 2010;376:875–85. This landmark randomized trial of ivabradine in patients with heart failure confirmed the substudy findings of BEAUTIFUL in that it only included those with a heart rate above 70 bpm and found reduced cardiac events. The reduction in events was largely due to reduced heart failure hospitalizations and heart failure death.

    Article  CAS  PubMed  Google Scholar 

  4. Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (beautiful): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16. This randomized trial found that ivabradine did not reduce mortality and cardiac events in patients with stable coronary artery disease and left ventricular systolic dysfunction, but appeared to be effective in the subgroup with a heart rate above 70 bpm.

    Article  CAS  PubMed  Google Scholar 

  5. Bohm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, et al. Heart rate as a risk factor in chronic heart failure (shift): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376:886–94. This substudy of the SHIFT trial found that patients with highest heart rates (≥87 bpm) were at more than twofold higher risk for cardiac events than were patients with the lowest heart rates (<72 bpm). The risks of cardiac events increased by 3 % with every beat increase from baseline heart rate and 16 % for every 5-bpm increase.

    Article  PubMed  Google Scholar 

  6. Levine HJ. Rest heart rate and life expectancy. J Am Coll Cardiol. 1997;30:1104–6.

    Article  CAS  PubMed  Google Scholar 

  7. Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50:823–30.

    Article  PubMed  Google Scholar 

  8. Fosbol EL, Seibaek M, Brendorp B, Moller DV, Thune JJ, Gislason GH, et al. Long-term prognostic importance of resting heart rate in patients with left ventricular dysfunction in connection with either heart failure or myocardial infarction: the diamond study. Int J Cardiol. 2010;140:279–86.

    Article  PubMed  Google Scholar 

  9. Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II trial. Circulation. 2001;103:1428–33.

    Article  CAS  PubMed  Google Scholar 

  10. Ahmadi-Kashani M, Kessler DJ, Day J, Bunch TJ, Stolen KQ, Brown S, et al. Heart rate predicts outcomes in an implantable cardioverter-defibrillator population. Circulation. 2009;120:2040–5.

    Article  PubMed  Google Scholar 

  11. Butler J, Arbogast PG, BeLue R, Daugherty J, Jain MK, Ray WA, et al. Outpatient adherence to beta-blocker therapy after acute myocardial infarction. J Am Coll Cardiol. 2002;40:1589–95.

    Article  PubMed  Google Scholar 

  12. de Groote P, Isnard R, Assyag P, Clerson P, Ducardonnet A, Galinier M, et al. Is the gap between guidelines and clinical practice in heart failure treatment being filled? Insights from the IMPACT RECO survey. Eur J Heart Fail. 2007;9:1205–11.

    Article  PubMed  Google Scholar 

  13. Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-Solal A, et al. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J. 2003;24:464–74.

    Article  CAS  PubMed  Google Scholar 

  14. Mulieri LA, Hasenfuss G, Leavitt B, Allen PD, Alpert NR. Altered myocardial force-frequency relation in human heart failure. Circulation. 1992;85:1743–50.

    Article  CAS  PubMed  Google Scholar 

  15. Tanaka N, Nozawa T, Yasumura Y, Futaki S, Hiramori K, Suga H. Heart-rate-proportional oxygen consumption for constant cardiac work in dog heart. Jpn J Physiol. 1990;40:503–21.

    Article  CAS  PubMed  Google Scholar 

  16. van den Wijngaard JP, Kolyva C, Siebes M, Dankelman J, van Gemert MJ, Piek JJ, et al. Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis. Med Biol Eng Comput. 2008;46:421–32.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Hoppe UC, Jansen E, Sudkamp M, Beuckelmann DJ. Hyperpolarization-activated inward current in ventricular myocytes from normal and failing human hearts. Circulation. 1998;97:55–65.

    Article  CAS  PubMed  Google Scholar 

  18. Soliman EZ, Elsalam MA, Li Y. The relationship between high resting heart rate and ventricular arrhythmogenesis in patients referred to ambulatory 24 h electrocardiographic recording. Europace. 2010;12:261–5.

    Article  PubMed  Google Scholar 

  19. Hasenfuss G, Holubarsch C, Hermann HP, Astheimer K, Pieske B, Just H. Influence of the force-frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy. Eur Heart J. 1994;15:164–70.

    Article  CAS  PubMed  Google Scholar 

  20. Kurita T, Onishi K, Dohi K, Tanabe M, Fujimoto N, Tanigawa T, et al. Impact of heart rate on mechanical dyssynchrony and left ventricular contractility in patients with heart failure and normal QRS duration. Eur J Heart Fail. 2007;9:637–43.

    Article  PubMed  Google Scholar 

  21. Mulder P, Barbier S, Chagraoui A, Richard V, Henry JP, Lallemand F, et al. Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation. 2004;109:1674–9.

    Article  CAS  PubMed  Google Scholar 

  22. Adabag AS, Grandits GA, Prineas RJ, Crow RS, Bloomfield HE, Neaton JD. Relation of heart rate parameters during exercise test to sudden death and all-cause mortality in asymptomatic men. Am J Cardiol. 2008;101:1437–43.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349–55.

    Article  CAS  PubMed  Google Scholar 

  24. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13

  25. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–2007

  26. Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106:2194–9.

    Article  PubMed  Google Scholar 

  27. Gullestad L, Wikstrand J, Deedwania P, Hjalmarson A, Egstrup K, Elkayam U, et al. What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker? Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). J Am Coll Cardiol. 2005;45:252–9.

    Article  PubMed  Google Scholar 

  28. Metra M, Torp-Pedersen C, Swedberg K, Cleland JG, Di Lenarda A, Komajda M, et al. Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial. Eur Heart J. 2005;26:2259–68.

    Article  CAS  PubMed  Google Scholar 

  29. Gelbrich G, Edelmann F, Inkrot S, Lainscak M, Apostolovic S, Neskovic AN, et al. Is target dose the treatment target? Uptitrating beta-blockers for heart failure in the elderly. Int J Cardiol. 2012;155:160–6.

    Article  PubMed  Google Scholar 

  30. McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009;150:784–94.

    Article  PubMed  Google Scholar 

  31. Flannery G, Gehrig-Mills R, Billah B, Krum H. Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol. 2008;101:865–9.

    Article  CAS  PubMed  Google Scholar 

  32. Tandon P, McAlister FA, Tsuyuki RT, Hervas-Malo M, Dupuit R, Ezekowitz J, et al. The use of beta-blockers in a tertiary care heart failure clinic: dosing, tolerance, and outcomes. Arch Intern Med. 2004;164:769–74.

    Article  CAS  PubMed  Google Scholar 

  33. Brown HF, DiFrancesco D, Noble SJ. How does adrenaline accelerate the heart? Nature. 1979;280:235–6.

    Article  CAS  PubMed  Google Scholar 

  34. Bucchi A, Baruscotti M, DiFrancesco D. Current-dependent block of rabbit sino-atrial node I(f) channels by ivabradine. J Gen Physiol. 2002;120:1–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. DiFrancesco D. The role of the funny current in pacemaker activity. Circ Res. 2010;106:434–46.

    Article  CAS  PubMed  Google Scholar 

  36. DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64:1757–65. Comprehensive review of the mechanisms of action of ivabradine.

    Article  CAS  PubMed  Google Scholar 

  37. Manz M, Reuter M, Lauck G, Omran H, Jung W. A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. Cardiology. 2003;100:149–55.

    Article  CAS  PubMed  Google Scholar 

  38. Musialek P, Casadei B. Nitrovasodilators and heart rate: more than the arterial baroreflex. Cardiovasc Res. 2000;47:404–5.

    Article  CAS  PubMed  Google Scholar 

  39. Musialek P, Lei M, Brown HF, Paterson DJ, Casadei B. Nitric oxide can increase heart rate by stimulating the hyperpolarization-activated inward current, I(f). Circ Res. 1997;81:60–8.

    Article  CAS  PubMed  Google Scholar 

  40. Musialek P, Rigg L, Terrar DA, Paterson DJ, Casadei B. Role of cGMP-inhibited phosphodiesterase and sarcoplasmic calcium in mediating the increase in basal heart rate with nitric oxide donors. J Mol Cell Cardiol. 2000;32:1831–40.

    Article  CAS  PubMed  Google Scholar 

  41. Umar S, van der Laarse A. Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010;333:191–201.

    Article  CAS  PubMed  Google Scholar 

  42. Borer JS, Fox K, Jaillon P, Lerebours G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107:817–23.

    Article  PubMed  Google Scholar 

  43. Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP. Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49. Br J Pharmacol. 1994;112:37–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Bois P, Bescond J, Renaudon B, Lenfant J. Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol. 1996;118:1051–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Simon L, Ghaleh B, Puybasset L, Giudicelli JF, Berdeaux A. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995;275:659–66.

    CAS  PubMed  Google Scholar 

  46. Bel A, Perrault LP, Faris B, Mouas C, Vilaine JP, Menasche P. Inhibition of the pacemaker current: a bradycardic therapy for off-pump coronary operations. Ann Thorac Surg. 1998;66:148–52.

    Article  CAS  PubMed  Google Scholar 

  47. Lechat P, Escolano S, Golmard JL, Lardoux H, Witchitz S, Henneman JA, et al. Prognostic value of bisoprolol-induced hemodynamic effects in heart failure during the Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation. 1997;96:2197–205.

    Article  CAS  PubMed  Google Scholar 

  48. Stillitano F, Lonardo G, Zicha S, Varro A, Cerbai E, Mugelli A, et al. Molecular basis of funny current (if) in normal and failing human heart. J Mol Cell Cardiol. 2008;45:289–99.

    Article  CAS  PubMed  Google Scholar 

  49. Cerbai E, Sartiani L, DePaoli P, Pino R, Maccherini M, Bizzarri F, et al. The properties of the pacemaker current I(f) in human ventricular myocytes are modulated by cardiac disease. J Mol Cell Cardiol. 2001;33:441–8.

    Article  CAS  PubMed  Google Scholar 

  50. Colin P, Ghaleh B, Monnet X, Su J, Hittinger L, Giudicelli JF, et al. Contributions of heart rate and contractility to myocardial oxygen balance during exercise. Am J Physiol Heart Circ Physiol. 2003;284:H676–82.

    Article  CAS  PubMed  Google Scholar 

  51. Miyamoto Y, Higuchi J, Abe Y, Hiura T, Nakazono Y, Mikami T. Dynamics of cardiac output and systolic time intervals in supine and upright exercise. J Appl Physiol Respir Environ Exerc Physiol. 1983;55:1674–81.

    CAS  PubMed  Google Scholar 

  52. Dedkov EI, Zheng W, Christensen LP, Weiss RM, Mahlberg-Gaudin F, Tomanek RJ. Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen. Am J Physiol Heart Circ Physiol. 2007;293:H590–8.

    Article  CAS  PubMed  Google Scholar 

  53. Heusch G, Baumgart D, Camici P, Chilian W, Gregorini L, Hess O, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101:689–94.

    Article  CAS  PubMed  Google Scholar 

  54. Seitelberger R, Guth BD, Heusch G, Lee JD, Katayama K, Ross Jr J. Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise. Circ Res. 1988;62:436–42.

    Article  CAS  PubMed  Google Scholar 

  55. Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371:1091–9. In this trial, ivabradine failed to affect the primary end point of death from cardiovascular causes of nonfatal myocardial infarction in patients with stable coronary artery disease without clinical HF and a HR of ≥70 bpm.

    Article  PubMed  Google Scholar 

  56. Bucchi A, Tognati A, Milanesi R, Baruscotti M, DiFrancesco D. Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels. J Physiol. 2006;572:335–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Borer JS, Bohm M, Ford I, Komajda M, Tavazzi L, Sendon JL, et al. Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study. Eur Heart J. 2012;33:2813–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Ekman I, Chassany O, Komajda M, Bohm M, Borer JS, Ford I, et al. Heart rate reduction with ivabradine and health related quality of life in patients with chronic heart failure: results from the SHIFT study. Eur Heart J. 2011;32:2395–404.

    Article  PubMed  Google Scholar 

  59. Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ. Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail. 2009;11:130–9.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Tavazzi L, Swedberg K, Komajda M, Bohm M, Borer JS, Lainscak M, et al. Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. Int J Cardiol. 2013;170:182–8.

    Article  CAS  PubMed  Google Scholar 

  61. Olenchock BA, Fonarow GG, Pan W, Hernandez A, Cannon CP. Current use of beta blockers in patients with reactive airway disease who are hospitalized with acute coronary syndromes. Am J Cardiol. 2009;103:295–300.

    Article  CAS  PubMed  Google Scholar 

  62. Chen J, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. J Am Coll Cardiol. 2001;37:1950–6.

    Article  CAS  PubMed  Google Scholar 

  63. Liao L, Allen LA, Whellan DJ. Economic burden of heart failure in the elderly. Pharmacoeconomics. 2008;26:447–62.

    Article  PubMed  Google Scholar 

  64. Griffiths A, Paracha N, Davies A, Branscombe N, Cowie MR, Sculpher M. The cost effectiveness of ivabradine in the treatment of chronic heart failure from the U.K. National Health Service perspective. Heart. 2014;100:1031–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Kourlaba G, Parissis J, Karavidas A, Beletsi A, Milonas C, Branscombe N, et al. Economic evaluation of ivabradine in the treatment of chronic heart failure in Greece. BMC Health Serv Res. 2014;14:631.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Sarullo FM, Fazio G, Puccio D, Fasullo S, Paterna S, Novo S, et al. Impact of “off-label” use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther. 2010;15:349–55.

    Article  CAS  PubMed  Google Scholar 

  67. Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834–40.

    Article  PubMed  Google Scholar 

  68. Greener ID, Monfredi O, Inada S, Chandler NJ, Tellez JO, Atkinson A, et al. Molecular architecture of the human specialised atrioventricular conduction axis. J Mol Cell Cardiol. 2011;50:642–51.

    Article  CAS  PubMed  Google Scholar 

  69. Fox K, Komajda M, Ford I, Robertson M, Bohm M, Borer JS, et al. Effect of ivabradine in patients with left-ventricular systolic dysfunction: a pooled analysis of individual patient data from the BEAUTIFUL and SHIFT trials. Eur Heart J. 2013;34:2263–70.

    Article  CAS  PubMed  Google Scholar 

  70. Lefroy DC, Fang JC, Stevenson LW, Hartley LH, Friedman PL, Stevenson WG. Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence. Am J Cardiol. 1998;82:444–50.

    Article  CAS  PubMed  Google Scholar 

  71. Lage-Galle E, Romero-Rodriguez N, Nevado-Portero J, Guisado-Rasco A, Sobrino-Marquez M, Machuca MG, et al. Safety and effectiveness of ivabradine after cardiac transplantation. Transplant Proc. 2010;42:3191–2.

    Article  CAS  PubMed  Google Scholar 

  72. Doesch AO, Celik S, Ehlermann P, Frankenstein L, Zehelein J, Koch A, et al. Heart rate reduction after heart transplantation with beta-blocker versus the selective if channel antagonist ivabradine. Transplantation. 2007;84:988–96.

    Article  CAS  PubMed  Google Scholar 

  73. Doesch AO, Ammon K, Konstandin M, Celik S, Kristen A, Frankenstein L, et al. Heart rate reduction for 12 months with ivabradine reduces left ventricular mass in cardiac allograft recipients. Transplantation. 2009;88:835–41.

    Article  PubMed  Google Scholar 

  74. Zhang R, Haverich A, Struber M, Simon A, Pichlmaier M, Bara C. Effects of ivabradine on allograft function and exercise performance in heart transplant recipients with permanent sinus tachycardia. Clin Res Cardiol. 2008;97:811–9.

    Article  CAS  PubMed  Google Scholar 

  75. Link A, Reil JC, Selejan S, Bohm M. Effect of ivabradine in dobutamine induced sinus tachycardia in a case of acute heart failure. Clin Res Cardiol. 2009;98:513–5.

    Article  PubMed  Google Scholar 

  76. Vitale D, De Santis V, Guarracino F, Fontana A, Pellegrini F, Tritapepe L. Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac surgery. Clin Res Cardiol. 2010;99:853–5.

    Article  PubMed  Google Scholar 

  77. Sargento L, Satendra M, Longo S, Lousada N, dos Reis RP. Heart rate reduction with ivabradine in patients with acute decompensated systolic heart failure. Am J Cardiovasc Drugs. 2014;14:229–35.

    CAS  PubMed  Google Scholar 

  78. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation. 2008;117:686–97.

    Article  PubMed  Google Scholar 

  79. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683–91.

    Article  PubMed  Google Scholar 

  80. Gallet R, Ternacle J, Damy T, Guendouz S, Bremont C, Seemann A, et al. Hemodynamic effects of ivabradine in addition to dobutamine in patients with severe systolic dysfunction. Int J Cardiol. 2014;176:450–5.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the National Institutes of Health (R01HL103931).

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Takeshi Kitai declares no potential conflicts of interest.

Wilson Tang is a section editor for Current Treatment Options in Cardiovascular Medicine.

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Kitai, T., Tang, W.H.W. Pathophysiologic Insights into Heart Rate Reduction in Heart Failure: Implications in the Use of Beta-Blockers and Ivabradine. Curr Treat Options Cardio Med 18, 13 (2016). https://doi.org/10.1007/s11936-015-0435-5

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