Skip to main content

Left ventricular ejection fraction as therapeutic target: is it the ideal marker?

Heart Failure Reviews volume 22, pages 641–655 (2017)Cite this article

Abstract

Heart failure (HF) consists the fastest growing clinical cardiac disease. HF patients are categorized on the basis of underlying left ventricular ejection fraction (LVEF) into HF with preserved EF (HFpEF), reduced LVEF (HFrEF), and mid-range LVEF (HFmrEF). While LVEF is the most commonly used surrogate marker of left ventricular (LV) systolic function, the implementation of two-dimensional echocardiography in estimating this parameter imposes certain caveats on current HF classification. Most importantly, LVEF could fluctuate in repeated measurements or even recover after treatment, thus blunting the borders between proposed categories of HF and enabling upward classification of patients. Under this prism, we sought to summarize possible procedures to improve systolic function in patients with HFrEF either naturally or by the means of pharmacologic and non-pharmacologic treatment and devices. Therefore, we reviewed established pharmacotherapy, including beta-blockers, inhibitors of renin–angiotensin–aldosterone axis, statins, and digoxin as well as novel treatments like sacubitril–valsartan, ranolazine, and ivabradine. In addition, we assessed evidence in favor of cardiac resynchronization therapy and exercise training programs. Finally, innovative therapeutic strategies, including stem cells, xanthine oxidase inhibitors, antibiotic regimens, and omega-3 polyunsaturated fatty acids, were also taken into consideration. We concluded that LVEF is subject to changes in HF after intervention and besides the aforementioned HFrEF, HFpEF, and HFmrEF categories, a new entity of HF patients with recovered LVEF should be acknowledged. An improved global and refined LV function assessment by sophisticated imaging modalities and circulating biomarkers is expected to render HF classification more accurate and indicate patients with viable—yet dysfunctional—myocardium and favorable characteristics as the ideal candidates for LVEF recovery by individualized HF therapy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Figure 1

References

  1. Vos T et al (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2163–2196

    PubMed  Article  Google Scholar 

  2. Bui AL, Horwich TB, Fonarow GC (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8(1):30–41

    PubMed  Article  Google Scholar 

  3. Ziaeian B, Fonarow GC (2016) Epidemiology and aetiology of heart failure. Nat Rev Cardiol 13(6):368–378

    PubMed  PubMed Central  Article  Google Scholar 

  4. Mozaffarian D et al (2016) Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133(4):e38–e60

    PubMed  Article  Google Scholar 

  5. Ponikowski P, et al. (2016) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016

  6. Bhatia RS et al (2006) Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355(3):260–269

    CAS  PubMed  Article  Google Scholar 

  7. Roger VL (2013) Epidemiology of heart failure. Circ Res 113(6):646–659

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Ponikowski P et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 37(27):2129–2200

    PubMed  Article  Google Scholar 

  9. Owan TE et al (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355(3):251–259

    CAS  PubMed  Article  Google Scholar 

  10. Bursi F et al (2006) Systolic and diastolic heart failure in the community. JAMA 296(18):2209–2216

    CAS  PubMed  Article  Google Scholar 

  11. Steinberg BA et al (2012) Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation 126(1):65–75

    PubMed  Article  Google Scholar 

  12. Lee J-W, Kim J-Y (2011) Stress-induced cardiomyopathy: the role of echocardiography. J Cardiovasc Ultrason 19(1):7–12

    Article  Google Scholar 

  13. Magnani JW, Dec GW (2006) Myocarditis. Curr Trends Diagn Treat 113(6):876–890

    Google Scholar 

  14. Bellenger NG et al (2000) Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 21(16):1387–1396

    CAS  PubMed  Article  Google Scholar 

  15. Gruszczynska K et al (2012) Statistical agreement of left ventricle measurements using cardiac magnetic resonance and 2D echocardiography in ischemic heart failure. Med Sci Monit 18(3):MT19–MT25

    PubMed  PubMed Central  Article  Google Scholar 

  16. Gardner BI et al (2009) Cardiac magnetic resonance versus transthoracic echocardiography for the assessment of cardiac volumes and regional function after myocardial infarction: an intrasubject comparison using simultaneous intrasubject recordings. Cardiovasc Ultrasound 7:38

    PubMed  PubMed Central  Article  Google Scholar 

  17. Greupner J et al (2012) Head-to-head comparison of left ventricular function assessment with 64-row computed tomography, biplane left cineventriculography, and both 2- and 3-dimensional transthoracic echocardiography: comparison with magnetic resonance imaging as the reference standard. J Am Coll Cardiol 59(21):1897–1907

    PubMed  Article  Google Scholar 

  18. Rayatzadeh H et al (2013) Volumetric left ventricular ejection fraction is superior to 2-dimensional echocardiography for risk stratification of patients for primary prevention implantable cardioverter-defibrillator implantation. Am J Cardiol 111(8):1175–1179

    PubMed  PubMed Central  Article  Google Scholar 

  19. Joshi SB et al (2012) Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation. J Cardiovasc Magn Reson 14:69

    PubMed  PubMed Central  Article  Google Scholar 

  20. Rijnierse MT et al (2015) Clinical impact of cardiac magnetic resonance imaging versus echocardiography-guided patient selection for primary prevention implantable cardioverter defibrillator therapy. Am J Cardiol 116(3):406–412

    PubMed  Article  Google Scholar 

  21. Monaghan MJ (2006) Role of real time 3D echocardiography in evaluating the left ventricle. Heart 92(1):131–136

    PubMed  PubMed Central  Article  Google Scholar 

  22. Gopal AS et al (1995) Assessment of cardiac function by three-dimensional echocardiography compared with conventional noninvasive methods. Circulation 92(4):842–853

    CAS  PubMed  Article  Google Scholar 

  23. Solomon SD et al (2005) Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 112(24):3738–3744

    PubMed  Article  Google Scholar 

  24. St John Sutton M et al (1997) Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial. Circulation 96(10):3294–3299

    CAS  PubMed  Article  Google Scholar 

  25. Gula LJ et al (2008) Ejection fraction assessment and survival: an analysis of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Am Heart J 156(6):1196–1200

    PubMed  PubMed Central  Article  Google Scholar 

  26. Rector TS, Cohn JN (1994) Prognosis in congestive heart failure. Annu Rev Med 45:341–350

    CAS  PubMed  Article  Google Scholar 

  27. Doughty RN et al (1997) Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group. J Am Coll Cardiol 29(5):1060–1066

    CAS  PubMed  Article  Google Scholar 

  28. Ramahi TM et al (2001) Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy. J Am Coll Cardiol 37(3):818–824

    CAS  PubMed  Article  Google Scholar 

  29. Waagstein F et al (2003) Increased exercise ejection fraction and reversed remodeling after long-term treatment with metoprolol in congestive heart failure: a randomized, stratified, double-blind, placebo-controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy. Eur J Heart Fail 5(5):679–691

    CAS  PubMed  Article  Google Scholar 

  30. Lombardo RM et al (2006) Effects of nebivolol versus carvedilol on left ventricular function in patients with chronic heart failure and reduced left ventricular systolic function. Am J Cardiovasc Drugs 6(4):259–263

    CAS  PubMed  Article  Google Scholar 

  31. Spoladore R et al (2013) Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure. Fundam Clin Pharmacol 27(4):455–464

    CAS  PubMed  Article  Google Scholar 

  32. Karabacak M et al (2015) Carvedilol and nebivolol improve left ventricular systolic functions in patients with non-ischemic heart failure. Anatol J Cardiol 15(4):271–276

    PubMed  Article  Google Scholar 

  33. Solomon SD et al (2005) Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction. Circulation 111(25):3411–3419

    CAS  PubMed  Article  Google Scholar 

  34. Hong YJ et al (2005) Prognostic significance of simvastatin therapy in patients with ischemic heart failure who underwent percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 95(5):619–622

    CAS  PubMed  Article  Google Scholar 

  35. Nakagomi A et al (2012) Effects of statin therapy on the production of monocyte pro-inflammatory cytokines, cardiac function, and long-term prognosis in chronic heart failure patients with dyslipidemia. Circ J 76(9):2130–2138

    CAS  PubMed  Article  Google Scholar 

  36. DiBianco R et al (1989) A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 320(11):677–683

    CAS  PubMed  Article  Google Scholar 

  37. Packer M et al (1993) Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors RADIANCE Study. N Engl J Med 329(1):1–7

    CAS  PubMed  Article  Google Scholar 

  38. Uretsky BF et al (1993) Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group. J Am Coll Cardiol 22(4):955–962

    CAS  PubMed  Article  Google Scholar 

  39. Xiao J et al (2016) Allopurinol ameliorates cardiac function in non-hyperuricaemic patients with chronic heart failure. Eur Rev Med Pharmacol Sci 20(4):756–761

    CAS  PubMed  Google Scholar 

  40. Abraham WT et al (2002) Cardiac resynchronization in chronic heart failure. N Engl J Med 346(24):1845–1853

    PubMed  Article  Google Scholar 

  41. Higgins SL et al (2003) Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol 42(8):1454–1459

    PubMed  Article  Google Scholar 

  42. Kutyifa V et al (2013) The influence of left ventricular ejection fraction on the effectiveness of cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). J Am Coll Cardiol 61(9):936–944

    PubMed  Article  Google Scholar 

  43. Linde C et al (2013) Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Eur Heart J 34(33):2592–2599

    PubMed  Article  Google Scholar 

  44. Haddadzadeh MH et al (2011) Effect of exercise-based cardiac rehabilitation on ejection fraction in coronary artery disease patients: a randomized controlled trial. Heart Views 12(2):51–57

    PubMed  PubMed Central  Article  Google Scholar 

  45. Hollriegel R et al (2016) Long-term exercise training in patients with advanced chronic heart failure: sustained benefits on left ventricular performance and exercise capacity. J Cardiopulm Rehabil Prev 36(2):117–124

    PubMed  Article  Google Scholar 

  46. (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353(9169):2001–7

  47. (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353(9146):9–13

  48. Flather MD et al (2005) Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 26(3):215–225

    CAS  PubMed  Article  Google Scholar 

  49. Chatterjee S et al (2013) Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis. BMJ 346:f55

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  50. Bristow MR et al (1996) Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investig Circ 94(11):2807–2816

    CAS  Google Scholar 

  51. Packer M et al (2001) Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis. Am Heart J 141(6):899–907

    CAS  PubMed  Article  Google Scholar 

  52. Eichhorn EJ et al (2003) Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with beta-blockade in patients with heart failure: the Beta-Blocker Evaluation of Survival Trial (BEST). Circulation 108(19):2336–2341

    CAS  PubMed  Article  Google Scholar 

  53. Maejima Y et al (2011) Synergistic effect of combined HMG-CoA reductase inhibitor and angiotensin-II receptor blocker therapy in patients with chronic heart failure: the HF-COSTAR trial. Circ J 75(3):589–95

  54. Abdulla J et al (2007) A systematic review: effect of angiotensin converting enzyme inhibition on left ventricular volumes and ejection fraction in patients with a myocardial infarction and in patients with left ventricular dysfunction. Eur J Heart Fail 9(2):129–135

    CAS  PubMed  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  56. (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344(8934):1383–9

  57. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998) Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 339(19):1349–1357

    Article  Google Scholar 

  58. Sacks FM et al (1996) The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 335(14):1001–1009

    CAS  PubMed  Article  Google Scholar 

  59. (2002) MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360(9326):7–22.

  60. McMurray JJ et al (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 33(14):1787–1847

    PubMed  Article  Google Scholar 

  61. Koh KK (2000) Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res 47(4):648–657

    CAS  PubMed  Article  Google Scholar 

  62. Lefer DJ (2002) Statins as potent antiinflammatory drugs. Circulation 106(16):2041–2042

    PubMed  Article  Google Scholar 

  63. Hayashidani S et al (2002) Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 105(7):868–873

    CAS  PubMed  Article  Google Scholar 

  64. Zhang L et al (2011) Effects of statin treatment on cardiac function in patients with chronic heart failure: a meta-analysis of randomized controlled trials. Clin Cardiol 34(2):117–123

    PubMed  Article  Google Scholar 

  65. Bleske BE et al (2006) Neutral effect on markers of heart failure, inflammation, endothelial activation and function, and vagal tone after high-dose HMG-CoA reductase inhibition in non-diabetic patients with non-ischemic cardiomyopathy and average low-density lipoprotein level. J Am Coll Cardiol 47(2):338–341

    CAS  PubMed  Article  Google Scholar 

  66. Krum H et al (2007) Double-blind, randomized, placebo-controlled study of high-dose HMG CoA reductase inhibitor therapy on ventricular remodeling, pro-inflammatory cytokines and neurohormonal parameters in patients with chronic systolic heart failure. J Card Fail 13(1):1–7

    CAS  PubMed  Article  Google Scholar 

  67. Laufs U et al (2004) Beneficial effects of statins in patients with non-ischemic heart failure. Z Kardiol 93(2):103–108

    CAS  PubMed  Article  Google Scholar 

  68. Node K et al (2003) Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation 108(7):839–843

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. Sola S et al (2006) Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 47(2):332–337

    CAS  PubMed  Article  Google Scholar 

  70. Strey CH et al (2006) Short-term statin treatment improves endothelial function and neurohormonal imbalance in normocholesterolaemic patients with non-ischaemic heart failure. Heart 92(11):1603–1609

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  71. Tousoulis D et al (2005) Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure. Eur J Heart Fail 7(7):1126–1132

    CAS  PubMed  Article  Google Scholar 

  72. Vrtovec B et al (2005) Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure. J Card Fail 11(9):684–690

    CAS  PubMed  Article  Google Scholar 

  73. Wojnicz R et al (2006) Usefulness of atorvastatin in patients with heart failure due to inflammatory dilated cardiomyopathy and elevated cholesterol levels. Am J Cardiol 97(6):899–904

    CAS  PubMed  Article  Google Scholar 

  74. Xie RQ et al (2010) Statin therapy shortens QTc, QTcd, and improves cardiac function in patients with chronic heart failure. Int J Cardiol 140(2):255–257

    PubMed  Article  Google Scholar 

  75. Yamada T et al (2007) Long-term effect of atorvastatin on neurohumoral activation and cardiac function in patients with chronic heart failure: a prospective randomized controlled study. Am Heart J 153(6):1055e1–1055e8

    Article  CAS  Google Scholar 

  76. Slatton ML et al (1997) Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? J Am Coll Cardiol 29(6):1206–1213

    CAS  PubMed  Article  Google Scholar 

  77. Gheorghiade M et al (1995) Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors. Circulation 92(7):1801–1807

    CAS  PubMed  Article  Google Scholar 

  78. Khand AU et al (2003) Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J Am Coll Cardiol 42(11):1944–1951

    CAS  PubMed  Article  Google Scholar 

  79. (1988) Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group. JAMA 259(4):539–44.

  80. Arnold SB et al (1980) Long-term digitalis therapy improves left ventricular function in heart failure. N Engl J Med 303(25):1443–1448

    CAS  PubMed  Article  Google Scholar 

  81. Dawson J, Walters M (2006) Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 62(6):633–644

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Doehner W, Landmesser U (2011) Xanthine oxidase and uric acid in cardiovascular disease: clinical impact and therapeutic options. Semin Nephrol 31(5):433–440

    CAS  PubMed  Article  Google Scholar 

  83. Doehner W, Anker SD (2005) Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure? Heart 91(6):707–709

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Givertz MM et al (2015) Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: the xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) study. Circulation 131(20):1763–1771

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. Nasr G, Maurice C (2010) Allopurinol and global left myocardial function in heart failure patients. J Cardiovasc Dis Res 1(4):191–195

    PubMed  PubMed Central  Article  Google Scholar 

  86. Cingolani HE et al (2006) The effect of xanthine oxidase inhibition upon ejection fraction in heart failure patients: La Plata study. J Card Fail 12(7):491–498

    CAS  PubMed  Article  Google Scholar 

  87. Baldus S et al (2006) Inhibition of xanthine oxidase improves myocardial contractility in patients with ischemic cardiomyopathy. Free Radic Biol Med 41(8):1282–1288

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. Qurat-ul-ain J, Stuart D (2010) Treatment of anemia in heart failure: potential risks and benefits of intravenous iron therapy in cardiovascular disease. Cardiol Rev 18(5):240–250

    Article  Google Scholar 

  89. Gonzalez-Costello J, Comin-Colet J (2010) Iron deficiency and anaemia in heart failure: understanding the FAIR-HF trial. Eur J Heart Fail 12(11):1159–1162

    PubMed  Article  Google Scholar 

  90. Avni T, Leibovici L, Gafter-Gvili A (2012) Iron supplementation for the treatment of chronic heart failure and iron deficiency: systematic review and meta-analysis. Eur J Heart Fail 14(4):423–429

    CAS  PubMed  Article  Google Scholar 

  91. Lewis, G.D., et al. (2016) Oral iron therapy for heart failure with reduced ejection fraction: design and rationale for oral iron repletion effects on oxygen uptake in heart failure. Circ Heart Fail 9(5)

  92. Cha Y-M et al (2004) Atrial fibrillation and ventricular dysfunction. A Vicious Electromechanical Cycle. Circulation 109(23):2839–2843

    PubMed  Article  Google Scholar 

  93. Khan MA et al (2013) Atrial fibrillation in heart failure: the sword of Damocles revisited. World J Cardiol 5(7):215–227

    PubMed  PubMed Central  Article  Google Scholar 

  94. Zimmermann AJ et al (2015) Effects of sinus rhythm maintenance on left heart function after electrical cardioversion of atrial fibrillation: implications for tachycardia-induced cardiomyopathy. Can J Cardiol 31(1):36–43

    PubMed  Article  Google Scholar 

  95. Emilsson K, Wandt B (2000) The relation between ejection fraction and mitral annulus motion before and after direct-current electrical cardioversion. Clin Physiol 20(3):218–224

    CAS  PubMed  Article  Google Scholar 

  96. Raymond RJ et al (1998) Cardiac performance early after cardioversion from atrial fibrillation. Am Heart J 136(3):435–442

    CAS  PubMed  Article  Google Scholar 

  97. Wozakowska-Kaplon B, Opolski G (2004) Effects of sinus rhythm restoration in patients with persistent atrial fibrillation: a clinical, echocardiographic and hormonal study. Int J Cardiol 96(2):171–176

    PubMed  Article  Google Scholar 

  98. Shamim W et al (1999) Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol 70(2):171–178

    CAS  PubMed  Article  Google Scholar 

  99. Baldasseroni S et al (2002) Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J 143(3):398–405

    PubMed  Article  Google Scholar 

  100. Bristow MR et al (2004) Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 350(21):2140–2150

    CAS  PubMed  Article  Google Scholar 

  101. Cleland JG et al (2001) The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points. Eur J Heart Fail 3(4):481–489

    CAS  PubMed  Article  Google Scholar 

  102. Cazeau S et al (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344(12):873–880

    CAS  PubMed  Article  Google Scholar 

  103. St John Sutton MG et al (2003) Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 107(15):1985–1990

    PubMed  Article  Google Scholar 

  104. Aslani A et al (2016) Effect of cardiac resynchronisation therapy on electrical remodelling. Heart Lung Circ 25(5):471–475

    PubMed  Article  Google Scholar 

  105. McMurray JJ et al (2014) Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371(11):993–1004

    PubMed  Article  CAS  Google Scholar 

  106. Swedberg K et al (2010) Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 376(9744):875–885

    CAS  PubMed  Article  Google Scholar 

  107. Fox K et al (2008) Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 372(9641):807–816

    CAS  PubMed  Article  Google Scholar 

  108. Murray GL, Colombo J (2014) Ranolazine preserves and improves left ventricular ejection fraction and autonomic measures when added to guideline-driven therapy in chronic heart failure. Heart Int 9(2):66–73

    PubMed  PubMed Central  Google Scholar 

  109. van der Spoel TI et al (2011) Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease. Cardiovasc Res 91(4):649–658

    PubMed  Article  CAS  Google Scholar 

  110. Strauer BE, Steinhoff G (2011) 10 years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. J Am Coll Cardiol 58(11):1095–1104

    PubMed  Article  Google Scholar 

  111. Zimmet H et al (2012) Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. Eur J Heart Fail 14(1):91–105

    PubMed  Article  Google Scholar 

  112. Poulin MF, et al. (2016) Clinical benefits of stem cells for chronic symptomatic systolic heart failure a systematic review of the existing data and ongoing trials. Cell Transplant

  113. Seth S et al (2010) The ABCD (autologous bone marrow cells in dilated cardiomyopathy) trial a long-term follow-up study. J Am Coll Cardiol 55(15):1643–1644

    PubMed  Article  Google Scholar 

  114. Vrtovec B et al (2011) Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Card Fail 17(4):272–281

    PubMed  Article  Google Scholar 

  115. Vrtovec B et al (2013) Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res 112(1):165–173

    CAS  PubMed  Article  Google Scholar 

  116. Hamshere S et al (2015) Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial. Eur Heart J 36(44):3061–3069

    PubMed  PubMed Central  Article  Google Scholar 

  117. Pokushalov E et al (2010) Efficiency of intramyocardial injections of autologous bone marrow mononuclear cells in patients with ischemic heart failure: a randomized study. J Cardiovasc Transl Res 3(2):160–168

    PubMed  Article  Google Scholar 

  118. Strauer BE, Yousef M, Schannwell CM (2010) The acute and long-term effects of intracoronary stem cell transplantation in 191 patients with chronic heARt failure: the STAR-heart study. Eur J Heart Fail 12(7):721–729

    PubMed  Article  Google Scholar 

  119. Bartunek J et al (2013) Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 61(23):2329–2338

    PubMed  Article  Google Scholar 

  120. Perin EC et al (2012) Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA 307(16):1717–1726

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  121. Mathiasen AB et al (2015) Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). Eur Heart J 36(27):1744–1753

    CAS  PubMed  Article  Google Scholar 

  122. Patel AN et al (2005) Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study. J Thorac Cardiovasc Surg 130(6):1631–1638

    PubMed  Article  Google Scholar 

  123. Stamm C et al (2007) Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg 133(3):717–725

    PubMed  Article  Google Scholar 

  124. Zhao Q et al (2008) Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. Ann Thorac Surg 86(6):1833–1840

    PubMed  Article  Google Scholar 

  125. Hu S et al (2011) Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: a single-center, randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 57(24):2409–2415

    PubMed  Article  Google Scholar 

  126. Lu M et al (2013) A pilot trial of autologous bone marrow mononuclear cell transplantation through grafting artery: a sub-study focused on segmental left ventricular function recovery and scar reduction. Int J Cardiol 168(3):2221–2227

    PubMed  Article  Google Scholar 

  127. Haykowsky MJ et al (2007) A meta-analysis of the effect of exercise training on left ventricular remodeling in heart failure patients: the benefit depends on the type of training performed. J Am Coll Cardiol 49(24):2329–2336

    PubMed  Article  Google Scholar 

  128. Haykowsky M et al (2011) A meta-analysis of the effects of exercise training on left ventricular remodeling following myocardial infarction: start early and go longer for greatest exercise benefits on remodeling. Trials 12:92

    PubMed  PubMed Central  Article  Google Scholar 

  129. Chen YM et al (2012) Effects of exercise training on left ventricular remodelling in heart failure patients: an updated meta-analysis of randomised controlled trials. Int J Clin Pract 66(8):782–791

    CAS  PubMed  Article  Google Scholar 

  130. Cornelis J et al (2016) Comparing exercise training modalities in heart failure: a systematic review and meta-analysis. Int J Cardiol 221:867–876

    PubMed  Article  Google Scholar 

  131. O’Connor CM et al (2009) Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 301(14):1439–1450

    PubMed  PubMed Central  Article  Google Scholar 

  132. Gkouziouta A et al (2016) Pathogen-driven treatment strategy in new onset dilated cardiomyopathy. Impact on ventricular function and clinical outcome. Int J Cardiol 209:15–16

    PubMed  Article  Google Scholar 

  133. Sokos GG et al (2006) Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 12(9):694–699

    CAS  PubMed  Article  Google Scholar 

  134. Wilcox JE et al (2012) Factors associated with improvement in ejection fraction in clinical practice among patients with heart failure: findings from IMPROVE HF. Am Heart J 163(1):49–56 e2

    PubMed  Article  Google Scholar 

  135. Kalogeropoulos AP et al (2016) Characteristics and outcomes of adult outpatients with heart failure and improved or recovered ejection fraction. JAMA Cardiol 1(5):510–518

    PubMed  Article  Google Scholar 

  136. Shah AM, Solomon SD (2012) Myocardial deformation imaging Current Status and Future Directions. Circulation 125(2):e244–e248

    PubMed  Article  Google Scholar 

  137. Dandel M et al (2009) Strain and strain rate imaging by echocardiography—basic concepts and clinical applicability. Curr Cardiol Rev 5(2):133–148

    PubMed  PubMed Central  Article  Google Scholar 

  138. Kawamura R et al (2014) Feasibility of left ventricular volume measurements by three-dimensional speckle tracking echocardiography depends on image quality and degree of left ventricular enlargement: validation study with cardiac magnetic resonance imaging. J Cardiol 63(3):230–238

    PubMed  Article  Google Scholar 

  139. Thomas JD, Popovic ZB (2006) Assessment of left ventricular function by cardiac ultrasound. J Am Coll Cardiol 48(10):2012–2025

    PubMed  Article  Google Scholar 

  140. Nishikimi T et al (2003) Cardioprotective effect of adrenomedullin in heart failure. Hypertens Res 26(Suppl):S121–S127

    CAS  PubMed  Article  Google Scholar 

  141. Nicholls MG et al (2003) Adrenomedullin in heart failure. Hypertens Res 26(Suppl):S135–S140

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Author notes

  1. V. Katsi and G. Georgiopoulos contributed equally to this work.

Affiliations

  1. 1st Cardiology Department, National and Kapodistrian University of Athens, University Medical School, Hippokration Hospital, Vasilissis Sofias 114, 11528, Athens, Greece

    V. Katsi, G. Georgiopoulos, A. Laina, E. Koutli, J. Parissis, C. Tsioufis, P. Nihoyannopoulos & D. Tousoulis

Authors
  1. V. Katsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Georgiopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Laina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Koutli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Parissis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Tsioufis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Nihoyannopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Tousoulis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Georgiopoulos.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Katsi, V., Georgiopoulos, G., Laina, A. et al. Left ventricular ejection fraction as therapeutic target: is it the ideal marker?. Heart Fail Rev 22, 641–655 (2017). https://doi.org/10.1007/s10741-017-9624-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-017-9624-5

Keywords

  • heart failure with reduced ejection fraction
  • heart failure with preserved ejection fraction
  • recovered ejection fraction
  • increase ejection fraction
  • cardiac resynchronization therapy
  • exercise tolerance
  • drugs
  • devices