Heart Failure Reviews

, Volume 24, Issue 1, pp 69–80 | Cite as

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

  • G. P. T. Areas
  • A. Mazzuco
  • F. R. Caruso
  • R. B. Jaenisch
  • R. Cabiddu
  • S. A. Phillips
  • R. Arena
  • A. Borghi-SilvaEmail author


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.


Endothelial function Exercise Physical training Cardiac rehabilitation Heart failure 


  1. 1.
    Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxford) 196(2):193–222Google 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–H1149Google 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):528–534PubMedPubMedCentralGoogle 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):629–635Google Scholar
  5. 5.
    Landmesser U, Hornig B, Drexler H (2004a) Endothelial function: a critical determinant in atherosclerosis? Circulation 109(21 Suppl 1):II27–II33PubMedGoogle 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):1933–1939PubMedGoogle 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):1992–1998PubMedGoogle 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–H100PubMedGoogle 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):193–197PubMedGoogle 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):761–765PubMedGoogle 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):124–127PubMedGoogle Scholar
  12. 12.
    Liu Y, Gutterman DD (2009) Vascular control in humans: focus on the coronary microcirculation. Basic Res Cardiol 104(3):211–227PubMedPubMedCentralGoogle 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):2795–800Google Scholar
  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):363–369PubMedGoogle 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):1111–1115PubMedGoogle Scholar
  16. 16.
    Anderson TJ, Phillips SA (2015) Assessment and prognosis of peripheral artery measures of vascular function. Prog Cardiovasc Dis 57(5):497–509PubMedGoogle 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):257–265PubMedGoogle 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–H12PubMedGoogle 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):376–382PubMedGoogle 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 248:196–202PubMedGoogle 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):840–845Google Scholar
  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):25–31PubMedGoogle Scholar
  23. 23.
    Palmer RIM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526PubMedGoogle Scholar
  24. 24.
    Busse R, Mulsch A, Fleming I, Hecker M (1993) Mechanisms of nitric oxide release from the endothelium. Circulation 5:S18–S25Google Scholar
  25. 25.
    Moncada S (1994) Physiology effects of nitric oxide. J Hypertens 2:35–39Google 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 57:521–534Google 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):1286–1292Google 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–C97Google 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 111:1763–1770PubMedGoogle Scholar
  30. 30.
    Brandes RP, Kreuzer J (2005) Vascular NADPH oxidase: molecular mechanisms of activation. Cardiovasc Res 65:16–27PubMedGoogle 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 96:238–245PubMedGoogle Scholar
  32. 32.
    Shoemaker JK, Naylor HL, Hogemen CD, Sinoway LI (1999) Blood flow dynamics in HF. Circulation 238:238–245Google 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 311:819–823PubMedGoogle Scholar
  34. 34.
    Esler M, Kaye D (2000) Measurement of sympathetic nervous system activity in heart failure: the role of noripinephrinekinects. Heart Fail Rev 5:17–25PubMedGoogle Scholar
  35. 35.
    Watson AM, Hood SG, May CN (2006) Mechanisms of sympa- thetic activation in heart failure. Clin Exp Pharmacol Physiol 33:1269–1274PubMedGoogle 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–H599PubMedGoogle 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 26:65–69PubMedGoogle 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):588–593PubMedGoogle 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 46:1011–1018PubMedGoogle 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):417–422PubMedGoogle 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):260–267Google 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):765–770PubMedGoogle 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):114–120PubMedGoogle 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):515–521PubMedGoogle 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 178:108–114PubMedPubMedCentralGoogle 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):3086–3094PubMedGoogle 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):336–341PubMedGoogle 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):659–668PubMedPubMedCentralGoogle 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:)944–951Google Scholar
  50. 50.
    Brutsaert DL (2003) Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev 83:59–115PubMedGoogle 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–G47Google 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 115:1982–1990PubMedPubMedCentralGoogle 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 76:980–986PubMedGoogle 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 93:9114–9119PubMedPubMedCentralGoogle 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 74:1133–1140PubMedGoogle 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 23:233–246PubMedGoogle 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 11:436–444Google 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 27:1269–1275PubMedGoogle 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 232:1–9PubMedGoogle 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 60:1778–1786PubMedGoogle Scholar
  61. 61.
    Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501PubMedGoogle 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):44–52PubMedGoogle 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–H1063PubMedGoogle Scholar
  64. 64.
    Downing J, Balady GJ (2011) The role of exercise training in heart failure. J Am Coll Cardiol 58(6):561–569PubMedGoogle 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):679–692PubMedGoogle Scholar
  66. 66.
    Hornig B, Maier V, Drexler H (1996) Physical training improves endothelial function in patients with chronic heart failure. Circulation 93:210–214PubMedGoogle 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 67:505–510PubMedGoogle 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):486–494PubMedGoogle 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):328–340PubMedPubMedCentralGoogle 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 2017:1–10Google 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):279–296PubMedGoogle 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):739–744Google 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):584–592PubMedPubMedCentralGoogle 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 68:161–167PubMedGoogle Scholar
  75. 75.
    Kitzman DW, Haykowsky MJ (2016) Vascular dysfunction in heart failure with preserved ejection fraction. J Card Fail 22(1):12–16PubMedGoogle 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):278–284PubMedGoogle 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):753–758Google 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 33:1787–1847PubMedGoogle 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 297:2502–2514PubMedGoogle 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 352:1539–1549PubMedGoogle 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 100:1263–1270PubMedGoogle 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 5:1229–1235PubMedGoogle 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 53:747–753PubMedGoogle 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 111:310–314PubMedGoogle 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 38:1260–1266PubMedGoogle 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):419–425PubMedGoogle 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 35:377–384PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • G. P. T. Areas
    • 1
    • 2
  • A. Mazzuco
    • 2
  • F. R. Caruso
    • 2
  • R. B. Jaenisch
    • 3
  • R. Cabiddu
    • 4
  • S. A. Phillips
    • 5
  • R. Arena
    • 5
  • A. Borghi-Silva
    • 2
    Email author
  1. 1.Physiological Science DepartamentUniversidade Federal do AmazonasManausBrazil
  2. 2.Cardiopulmonary Physiotherapy LaboratoryUniversidade Federal de Sao CarlosSao CarlosBrazil
  3. 3.Universidade Federal de Santa MariaSanta MariaBrazil
  4. 4.Biomedical EngineeringPolitecnico di MilanoMilanItaly
  5. 5.University of Illinois at ChicagoChicagoUSA

Personalised recommendations