Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation


Endothelial dysfunction plays as an important role on mismatch responses that occur during exercise in patients with congestive heart failure (CHF). However, cardiac rehabilitation, a core component of management of CHF patients, can improve endothelial function, contributing to reduce the morbidity and mortality of these patients. The primary aims of this review were to describe the importance of flow-mediated dilatation (FMD) as a non-invasive validation tool to assess endothelial dysfunction and to highlight the relevance of scientific studies that evaluated the effects of exercise interventions on peripheral vascular endothelial function as measured by FMD in patients with CHF with both preserved and reduced ejection fraction.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

Change history

  • 11 November 2019

    The scholarship support information in Acknowledgement was missing.


  1. 1.

    Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxford) 196(2):193–222

    CAS  Google Scholar 

  2. 2.

    Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Phys 250(6 Pt 2):H1145–H1149

    CAS  Google Scholar 

  3. 3.

    Dharmashankar K, Welsh A, Wang J, Kizhakekuttu TJ, Ying R, Gutterman DD, Widlansky ME (2012) Nitric oxide synthase-dependent vasodilation of human subcutaneous arterioles correlates with noninvasive measurements of endothelial function. Am J Hypertens 25(5):528–534

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Doshi SN, Naka KK, Payne N, Jones CJ, Ashton M, Lewis MJ, Goodfellow J (2001) Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 101(6):629–635

    CAS  Google Scholar 

  5. 5.

    Landmesser U, Hornig B, Drexler H (2004a) Endothelial function: a critical determinant in atherosclerosis? Circulation 109(21 Suppl 1):II27–II33

    PubMed  Google Scholar 

  6. 6.

    Landmesser U, Engberding N, Bahlmann FH, Schaefer A, Wiencke A, Heineke A, Spiekermann S, Hilfiker-Kleiner D, Templin C, Kotlarz D, Mueller M, Fuchs M, Hornig B, Haller H, Drexler H (2004b) Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation 110(14):1933–1939

    CAS  PubMed  Google Scholar 

  7. 7.

    Miura H, Wachtel RE, Liu Y, Loberiza FR Jr, Saito T, Miura M, Gutterman DD (2001) Flow-induced dilation of human coronary arterioles: important role of ca (2+)-activated K(+) channels. Circulation 103(15):1992–1998

    CAS  PubMed  Google Scholar 

  8. 8.

    Phillips SA, Hatoum OA, Gutterman DD (2007a) The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD. Am J Physiol Heart Circ Physiol 292(1):H93–H100

    CAS  PubMed  Google Scholar 

  9. 9.

    de Jongh S, Lilien MR, Bakker HD, Hutten BA, Kastelein JJ, Stroes ES (2002) Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis 163(1):193–197

    PubMed  Google Scholar 

  10. 10.

    Gokce N, Holbrook M, Hunter LM, Palmisano J, Vigalok E, Keaney JF Jr, Vita JA (2002a Aug 21) Acute effects of vasoactive drug treatment on brachial artery reactivity. J Am Coll Cardiol 40(4):761–765

    CAS  PubMed  Google Scholar 

  11. 11.

    Gokce N, Vita JA, Bader DS, Sherman DL, Hunter LM, Holbrook M, O'Malley C, Keaney JF Jr, Balady GJ (2002b) Effect of exercise on upper and lower extremity endothelial function in patients with coronary artery disease. Am J Cardiol 90(2):124–127

    PubMed  Google Scholar 

  12. 12.

    Liu Y, Gutterman DD (2009) Vascular control in humans: focus on the coronary microcirculation. Basic Res Cardiol 104(3):211–227

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Hashimoto M, Eto M, Akishita M, Kozaki K, Ako J, Iijima K, Kim S, Toba K, Yoshizumi M, Ouchi Y (1999) Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol 19(11):2795–800

  14. 14.

    Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G (2011) Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? Hypertension 57(3):363–369

    CAS  PubMed  Google Scholar 

  15. 15.

    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115

    CAS  PubMed  Google Scholar 

  16. 16.

    Anderson TJ, Phillips SA (2015) Assessment and prognosis of peripheral artery measures of vascular function. Prog Cardiovasc Dis 57(5):497–509

    PubMed  Google Scholar 

  17. 17.

    Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R (2002) International brachial artery reactivity task force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force. J Am Coll Cardiol 39(2):257–265

    PubMed  Google Scholar 

  18. 18.

    Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ (2011) Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 300(1):H2–H12

    CAS  PubMed  Google Scholar 

  19. 19.

    Green DJ, Dawson EA, Groenewoud HM, Jones H, Thijssen DH (2014) Is flow-mediated dilation nitric oxide mediated? A meta-analysis. Hypertension 63(2):376–382

    CAS  PubMed  Google Scholar 

  20. 20.

    Greyling A, Van Mil AC, Zock PL, Green DJ, Ghiadoni L, Thijssen DH (2016) TIFN international working group on flow mediated dilation. Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation. Atherosclerosis 248:196–202

    CAS  PubMed  Google Scholar 

  21. 21.

    Yeboah J, Burke GL, Crouse JR, Herrington DM (2008) Relationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the cardiovascular health study. Atherosclerosis 97(2):840–845

  22. 22.

    Yeboah J, Crouse JR, Bluemke DA, Lima JA, Polak JF, Burke GL, Herrington DM (2011) Endothelial dysfunction is associated with left ventricular mass (assessed using MRI) in an adult population (MESA). J Hum Hypertens 25(1):25–31

    CAS  PubMed  Google Scholar 

  23. 23.

    Palmer RIM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    CAS  PubMed  Google Scholar 

  24. 24.

    Busse R, Mulsch A, Fleming I, Hecker M (1993) Mechanisms of nitric oxide release from the endothelium. Circulation 5:S18–S25

    Google Scholar 

  25. 25.

    Moncada S (1994) Physiology effects of nitric oxide. J Hypertens 2:35–39

    Google Scholar 

  26. 26.

    Philips AS, Mahmoud AM, Brown MD, Haus JM (2015) Exercise interventions and peripheral arterial function: Implecations for cardio-metabolic disease. Prog Cardiovasc Dis 57:521–534

    Google Scholar 

  27. 27.

    Negrão CE, Rondon MU, Tinucci T, Alves MJ, Roveda F, Braga AM, Reis SF, Nastari L, Barretto AC, Krieger EM, Middlekauff HR (2001) Abnormal neurovascular control during exercise is linked to heart failure severity. Am J Physiol Heart Circ Physiol 280(3):1286–1292

    Google Scholar 

  28. 28.

    Mehta PK, Griendling KK (2007) Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Phys Cell Phys 292(1):C82–C97

    CAS  Google Scholar 

  29. 29.

    Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, Möbius-Mikler S, Schubert A, Schuler G (2005) Hambrecht R. A ntioxidative effects of exercise training in patients with chronic heart failure increase in radical scavenger enzyme activity in skeletal muscle. Circulation 111:1763–1770

    CAS  PubMed  Google Scholar 

  30. 30.

    Brandes RP, Kreuzer J (2005) Vascular NADPH oxidase: molecular mechanisms of activation. Cardiovasc Res 65:16–27

    CAS  PubMed  Google Scholar 

  31. 31.

    Lang CC, Rayos GH, Chomsky DB, Wood AJJ, Wilson JR (1997) Effects of sympathoinhibition on exercise performance in patients with HF. Circulation 96:238–245

    CAS  PubMed  Google Scholar 

  32. 32.

    Shoemaker JK, Naylor HL, Hogemen CD, Sinoway LI (1999) Blood flow dynamics in HF. Circulation 238:238–245

    Google Scholar 

  33. 33.

    Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GD, Simon AB, Rector T (1984) Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311:819–823

    CAS  PubMed  Google Scholar 

  34. 34.

    Esler M, Kaye D (2000) Measurement of sympathetic nervous system activity in heart failure: the role of noripinephrinekinects. Heart Fail Rev 5:17–25

    CAS  PubMed  Google Scholar 

  35. 35.

    Watson AM, Hood SG, May CN (2006) Mechanisms of sympa- thetic activation in heart failure. Clin Exp Pharmacol Physiol 33:1269–1274

    CAS  PubMed  Google Scholar 

  36. 36.

    Santos AC, Alves MJ, Rondon MU, Barreto AC, Middlekauff HR, Negrao CE (2005) Sympathetic activation retrains endothelium – mediated muscle vasodilatation in heart failure patients. Am J Physiol Heart Circ Physiol 289:H593–H599

    CAS  PubMed  Google Scholar 

  37. 37.

    Fischer D, Rossa S, Landmesser U, Spiekermann S, Engberding N, Hornig B, Drexler H (2005a) Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 26:65–69

    CAS  PubMed  Google Scholar 

  38. 38.

    Shechter M, Matetzky S, Arad M, Feinberg MS, Freimark D (2009) Vascular endotelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure†. Eur J Heart Fail 11(6):588–593

    PubMed  Google Scholar 

  39. 39.

    Meyer B, Mörtl D, Strecker K, Hülsmann M, Kulemann V, Neunteufl T, Pacher R, Berger R (2005) Flow-mediated vasodilation predicts outcome in patients with chronic heart failure: comparison with B-type natriuretic peptide. J Am Coll Cardiol 46:1011–1018

    PubMed  Google Scholar 

  40. 40.

    Takishima I, Nakamura T, Hirano M, Kitta Y, Kobayashi T, Fujioka D, Saito Y, Watanabe K, Watanabe Y, Mishina H, Obata JE, Kawabata K, Tamaru S, Kugiyama K (2012) Predictive value of serial assessment of endothelial function in chronic heart failure. Int J Cardiol 158(3):417–422

    PubMed  Google Scholar 

  41. 41.

    TarroGenta F, Eleuteri E, Temporelli PL, Comazzi F, Tidu M, Bouslenko Z, Bertolin F, Vigorito C, Giannuzzi P, Giallauria F (2013) Flow-mediated dilation normalization predicts outcome in chronic heart failure patients. J CardFail 19(4):260–267

    Google Scholar 

  42. 42.

    Klosinska M, Rudzinski T, Grzelak P, Stefanczyk L, Drozdz J, Krzeminska-Pakula M (2009) Endothelium-dependent and -independent vasodilation is more attenuated in ischaemic than in non-ischaemic heart failure. Eur J Heart Fail 11(8):765–770

    CAS  PubMed  Google Scholar 

  43. 43.

    Shah A, Gkaliagkousi E, Ritter JM, Ferro A (2010) Endothelial function and arterial compliance are not impaired in subjects with heart failure of non-ischemic origin. J Card Fail 16(2):114–120

    CAS  PubMed  Google Scholar 

  44. 44.

    Ciccone MM, Iacoviello M, Puzzovivo A, Scicchitano P, Monitillo F, De Crescenzo F, Caragnano V, Sassara M, Quistelli G, Guida P, Favale S (2011) Clinical correlates of endothelial function in chronic heart failure. Clin Res Cardiol 100(6):515–521

    CAS  PubMed  Google Scholar 

  45. 45.

    Paine NJ, Hinderliter AL, Blumenthal JA, Adams KF Jr, Sueta CA, Chang PP, O'Connor CM, Sherwood A (2016) Reactive hyperemia is associated with adverse clinical outcomes in heart failure. Am Heart J 178:108–114

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø, Skjaerpe T (2007) Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 115(24):3086–3094

    PubMed  Google Scholar 

  47. 47.

    Guazzi M, Casali M, Berti F, Rossoni G, Colonna VD, Guazzi MD (2008) Endothelium-mediated modulation of ergoreflex and improvement in exercise ventilation by acute sildenafil in heart failure patients. Clin Pharmacol Ther 83(2):336–341

    CAS  PubMed  Google Scholar 

  48. 48.

    Witman MA, Fjeldstad AS, McDaniel J, Ives SJ, Zhao J, Barrett-O'Keefe Z, Nativi JN, Stehlik J, Wray DW, Richardson RS (2012) Vascular function and the role of oxidative stress in heart failure, heart transplant, and beyond. Hypertension 60(3):659–668

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Zuo L, Chuang CC, Hemmelgarn BT, Best TM (2015) Heart failure with preserved ejection fraction: Defining the function of ROS and NO. J Appl Physiol (1985) 119(8:)944–951

  50. 50.

    Brutsaert DL (2003) Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev 83:59–115

    CAS  PubMed  Google Scholar 

  51. 51.

    Ferrari R, Bachetti T, Agnoletti L, Comini L, Curello S (1998) Endothelial function and dysfunction in heart failure. Eur Heart J 19 SupplG:G41–G47

    Google Scholar 

  52. 52.

    Lam CS, Roger VL, Rodeheffer RJ, Francesca Bursi F, Barry A, Borlaug BA, Ommen SR et al (2007) Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota. Circulation 115:1982–1990

    PubMed  PubMed Central  Google Scholar 

  53. 53.

    Zeiher AM, Fisslthaler B, Schray-Utz B, Busse R (1995) Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. Circ Res 76:980–986

    CAS  PubMed  Google Scholar 

  54. 54.

    Khan BV, Harrison DG, Olbrych MT, Alexander MW, Medford RM (1996) Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redoxsensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci U S A 93:9114–9119

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Niu XF, Smith CW, Kubes P (1994) Intracellular oxidative stress induced by nitric oxide synthesis inhibition increases endothelial cell adhesion to neutrophils. Circ Res 74:1133–1140

    CAS  PubMed  Google Scholar 

  56. 56.

    Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J et al (2005) Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the working group on Endothelins and endothelial factors of the European Society of Hypertension. J Hypertens 23:233–246

    CAS  PubMed  Google Scholar 

  57. 57.

    Carsten T, Van Linthout S (2014) New insights in (inter) cellular mechanisms by heart failure with preserved ejection fraction. Curr Heart Fail Rep 11:436–444

    Google Scholar 

  58. 58.

    Gao X, Xu X, Belmadani S, Park Y, Tang Z, Feldman AM et al (2007) TNF-alpha contributes to endothelial dysfunction by upregulating arginase in ischemia/ reperfusion injury. Arterioscler Thromb Vasc Biol 27:1269–1275

    CAS  PubMed  Google Scholar 

  59. 59.

    Spillmann F, Van Linthout S, Miteva K, Lorenz M, Stangl V, Schultheiss HP et al (2014) LXR agonism improves TNF-alpha-induced endothelial dysfunction in the absence of its cholesterol-modulating effects. Atherosclerosis 232:1–9

    CAS  PubMed  Google Scholar 

  60. 60.

    Akiyama E, Sugiyama S, Matsuzawa Y, Konishi M, Suzuki H, Nozaki T et al (2012) Incremental prognostic significance of peripheral endothelial dysfunction in patients with heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol 60:1778–1786

    PubMed  Google Scholar 

  61. 61.

    Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501

    CAS  PubMed  Google Scholar 

  62. 62.

    Westermann D, Lindner D, Kasner M, Zietsch C, Savvatis K, Escher F, von Schlippenbach J, Skurk C, Steendijk P, Riad A, Poller W, Schultheiss HP, Tschope C (2011) Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail 4(1):44–52

    PubMed  Google Scholar 

  63. 63.

    Poole DC, Hirai DM, Copp SW, Musch TI (2012) Muscle oxygen transport and utilization in heart failure: implications for exercise (in)tolerance. Am J Physiol Heart Circ Physiol 302(5):H1050–H1063

    CAS  PubMed  Google Scholar 

  64. 64.

    Downing J, Balady GJ (2011) The role of exercise training in heart failure. J Am Coll Cardiol 58(6):561–569

    PubMed  Google Scholar 

  65. 65.

    Ramos JS, Dalleck LC, Tjonna AE, Beetham KS, Coombes JS (2015) The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis. Sports Med 45(5):679–692

    PubMed  Google Scholar 

  66. 66.

    Hornig B, Maier V, Drexler H (1996) Physical training improves endothelial function in patients with chronic heart failure. Circulation 93:210–214

    CAS  PubMed  Google Scholar 

  67. 67.

    Kobayashi N, Tsuruya Y, Iwasawa T, Ikeda N, Hashimoto S, Yasu T, Ueba H, Kubo N, Fujii M, Kawakami M, Saito M (2003) Exercise training in patients with chronic heart failure improves endothelial function predominantly in the trained extremities. Circ J 67:505–510

    PubMed  Google Scholar 

  68. 68.

    Erbs S, Höllriegel R, Linke A, Beck EB, Adams V, Gielen S, Möbius-Winkler S, Sandri M, Kränkel N, Hambrecht R, Schuler G (2010) Exercise training in patients with advanced chronic heart failure (NYHA IIIb) promotes restoration of peripheral vasomotor function, induction of endogenous regeneration, and improvement of left ventricular function. Circ Heart Fail 3(4):486–494

    PubMed  Google Scholar 

  69. 69.

    Vuckovic KM, Piano MR, Phillips SA (2013 May) Effects of exercise interventions on peripheral vascular endothelial vasoreactivity in patients with heart failure with reduced ejection fraction. Heart Lung Circ 22(5):328–340

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Pearson MJ, Smart NA (2017) Aerobic training intensity for improved endothelial function in heart failure patients: a systematic review and meta-analysis. Cardiol Res Pract 2017:1–10

    Google Scholar 

  71. 71.

    Ashor AW, Lara J, Siervo M, Celis-Morales C, Oggioni C, Jakovljevic DG, Mathers JC (2015 Feb) Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials. Sports Med 45(2):279–296

    PubMed  Google Scholar 

  72. 72.

    Haykowsky MJ, Tomczak CR, Scott JM, Paterson DI, Kitzman DW (2015) Determinants of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction. J Appl Physiol (1985) 119(6):739–744

    CAS  Google Scholar 

  73. 73.

    Kitzman DW, Brubaker PH, Herrington DM, Morgan TM, Stewart KP, Hundley WG, Abdelhamed A, Haykowsky MJ (2013) Effect of endurance exercise training on endothelial function and arterial stiffness in olderpatients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. J Am Coll Cardiol 62(7):584–592

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Haykowsky MJ, Herrington DM, Brubaker PH, Morgan TM, Hundley WG, Kitzman DW (2013) Relationship of flow mediated arterial dilation and exercise capacity in older patients with heart failure and preserved ejection fraction. J Gerontol A Biol Sci Med Sci 68:161–167

    PubMed  Google Scholar 

  75. 75.

    Kitzman DW, Haykowsky MJ (2016) Vascular dysfunction in heart failure with preserved ejection fraction. J Card Fail 22(1):12–16

    PubMed  Google Scholar 

  76. 76.

    Lee JF, Barrett-O'Keefe Z, Garten RS, Nelson AD, Ryan JJ, Nativi JN, Richardson RS, Wray DW (2016) Evidence of microvascular dysfunction in heart failure with preserved ejection fraction. Heart 102(4):278–284

    CAS  PubMed  Google Scholar 

  77. 77.

    Angadi SS, Mookadam F, Lee CD, Tucker WJ, Haykowsky MJ, Gaesser GA (2015) High-intensity interval training vs. moderate intensity continuous exercise training in heart failurewith preserved ejection fraction: a pilot study. J Appl Physiol (1985) 119(6):753–758

    CAS  Google Scholar 

  78. 78.

    McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V 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 33:1787–1847

    PubMed  Google Scholar 

  79. 79.

    McAlister FA, Ezekowitz J, Hooton N et al (2007) Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA 297:2502–2514

    CAS  PubMed  Google Scholar 

  80. 80.

    Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators (2005) The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 352:1539–1549

    CAS  PubMed  Google Scholar 

  81. 81.

    Yu CM, Gorcsan J 3rd, Bleeker GB, Zhang Q, Schalij MJ, Suffoletto MS, Fung JW et al (2007) Usefulness of tissue Doppler velocity and strain dyssynchrony for predicting left ventricular reverse remodeling response after cardiac resynchronization therapy. Am J Cardiol 100:1263–1270

    PubMed  Google Scholar 

  82. 82.

    Akar JG, Al-Chekakie MO, Fugate T et al (2008) Endothelial dysfunction in heart failure identifies responders to cardiac resynchronization therapy. Heart Rhythm 5:1229–1235

    PubMed  Google Scholar 

  83. 83.

    AlZadjali MA, Godfrey V, Khan F, Choy A, Doney AS, Wong AK, Petrie JR et al (2009) Insulin resistance is highly prevalent and is associated with reduced exercise tolerance in nondiabetic patients with heart failure. J Am Coll Cardiol 53:747–753

    CAS  PubMed  Google Scholar 

  84. 84.

    Katz SD, Hryniewicz K, Hriljac I, Balidemaj K, Dimayuga C, Hudaihed A, Yasskiy A (2005) Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 111:310–314

    PubMed  Google Scholar 

  85. 85.

    Yufu K, Shinohara T, Ebata Y, Ayabe R, Fukui A, Okada N, Nakagawa M, Takahashi N (2015) Endothelial Function Predicts New Hospitalization due to Heart Failure Following Cardiac Resynchronization Therapy. Pacing Clin Electrophysiol 38:1260–1266

    PubMed  Google Scholar 

  86. 86.

    Santini L, Capria A, Molfetta A, Mahfouz K, Panattoni G, Minni V, Sergi D, Forleo GB, Romeo F (2013) Endothelial dysfunction is a marker of systemic response to the cardiac resynchronization therapy in heart failure. J Card Fail 19(6):419–425

    CAS  PubMed  Google Scholar 

  87. 87.

    Tesselaar E, Schiffer A, Widdershoven J, Broers H, Hendriks E, Luijten K, Creusen J (2012) Effect of Cardiac Resynchronization Therapy on Endothelium-Dependent Vasodilatation in the Cutaneous Microvasculature. Pacing Clin Electrophysiol 35:377–384

    PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to A. Borghi-Silva.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Areas, G.P.T., Mazzuco, A., Caruso, F.R. et al. Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation. Heart Fail Rev 24, 69–80 (2019). https://doi.org/10.1007/s10741-018-9719-7

Download citation


  • Endothelial function
  • Exercise
  • Physical training
  • Cardiac rehabilitation
  • Heart failure