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Drugs

, Volume 68, Issue 5, pp 579–550 | Cite as

β-Blockers and Coronary Flow Reserve

The Importance of a Vasodilatory Action
  • Maurizio Galderisi
  • Arcangelo D’Errico
Current Opinion

Abstract

Coronary flow reserve (CFR) is the maximal increase in coronary blood flow (CBF) above its resting level for a given perfusion pressure when coronary vasculature is maximally dilated. Normally, hyperaemic CBF reaches values at least 2- to 3-fold greater than resting CBF. Reduction of CFR is mainly due to epicardial coronary artery stenosis or to coronary microvascular dysfunction. CFR can be determined by several techniques that measure CBF itself (e.g. positron emission tomography) or CBF velocities (Doppler methods) from which coronary flow velocity reserve is calculated. Hyperaemic coronary vasodilation can be obtained by pharmacological agents (e.g. adenosine and dipyridamole), but also by the cold pressure test. Long-term antihypertensive treatment induces significant improvement of CFR, which is parallel to the regression of left ventricular (LV) hypertrophy.

First-and second-generation β-adrenergic receptor antagonists (β-blockers) have shown contradictory influences on CFR. This can be explained by the interaction of the effects on CBF at rest, generally reduced by these drugs, and after hyperaemia, when minimal coronary resistance appears to be either increased or reduced. Third-generation β-blockers (e.g. carvedilol and nebivolol), which have vasodilating capacity, improve hyperaemic CBF. This occurs as a result of a reduction in minimal resistance, which can be attributed to α-adrenergic blockade and/or to a nitric oxide-mediated effect. This improvement is clearly beneficial in patients with coronary artery disease and indicates an improved coronary microvascular function. Changes of CFR due to vasodilating β-blockers improve microvascular angina pectoris or silent ischaemia in patients without epicardial artery stenosis, and are also helpful in predicting the response or the further improvement of LV function to treatment.

Keywords

Left Anterior Descend Carvedilol Coronary Flow Reserve Coronary Blood Flow Nebivolol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors have declared that they have no conflicts of interest that are directly relevant to the content of this review and that no sources of funding were used to assist in the preparation of this review.

References

  1. 1.
    Anversa P, Ricci R, Olivetti G. Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy. J Am Coll Cardiol 1988; 7: 1140–9Google Scholar
  2. 2.
    Muller JM, Davis MJ, Chilian WM. Integrated regulation of pressure and flow in the coronary microcirculation. Cardiovasc Res 1996; 32: 668–78PubMedGoogle Scholar
  3. 3.
    Schrader J. Adenosine: a homeostatic metabolite in cardiac energy metabolism. Circulation 1990; 81: 389–91PubMedGoogle Scholar
  4. 4.
    Di Carli MF, Tobes MC, Mangner T, et al. Effects of cardiac sympathetic innervation on coronary blood flow. N Engl J Med 1997; 336: 1208–15PubMedGoogle Scholar
  5. 5.
    Bassenge E, Heusch G. Endothelial and neuro-hormonal control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 1990; 116: 79–165Google Scholar
  6. 6.
    Moncada S, Higgs EA. The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 2006; 147 Suppl. 1: S193–201PubMedGoogle Scholar
  7. 7.
    Luscher TF. The endothelium and cardiovascular disease: a complex relation. N Engl J Med 1994; 330: 1081–3PubMedGoogle Scholar
  8. 8.
    Quyyumi AA, Dakak N, Andews NP, et al. Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995; 92: 320–6PubMedGoogle Scholar
  9. 9.
    Lefroy DC, Crake T, Uren NG, et al. An effect of inhibition of nitric oxide synthesis on epicardial coronary artery calibre and coronary blood flow in humans. Circulation 1993; 88: 43–54PubMedGoogle Scholar
  10. 10.
    Kuga T, Mohri M, Egashira K, et al. Bradykinin-induced vasodilation of human coronary arteries in vivo: role of nitric oxide and angiotensin converting enzyme. J Am Coll Cardiol 1997; 30: 108–12PubMedGoogle Scholar
  11. 11.
    Feigl EO. Coronary physiology. Physiol Rev 1983; 63: 1–205PubMedGoogle Scholar
  12. 12.
    Coffman JD, Gregg DE. Reactive hyperemia characteristics of the myocardium. Am J Physiol 1960; 199: 1143–9PubMedGoogle Scholar
  13. 13.
    Hoffman JIE. Maximal coronary flow and the concept of coronary flow reserve. Circulation 1984; 70: 153–9PubMedGoogle Scholar
  14. 14.
    Hoffmann JIE. Transmural myocardial perfusion. Progr Cardiovasc Dis 1987; 24: 429–64Google Scholar
  15. 15.
    Gould LK, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol 1974; 33: 87–94PubMedGoogle Scholar
  16. 16.
    Gould LK, Lipscomb K. Effects of coronary stenosis on coronary flow reserve and resistance. Am J Cardiol 1974; 34: 48–55PubMedGoogle Scholar
  17. 17.
    Marcus ML, Chilian WM, Kanatsuka H, et al. Understanding the coronary circulation through studies at the microvascular level. Circulation 1990; 82: 1–7PubMedGoogle Scholar
  18. 18.
    Strauer BE. The significance of coronary reserve in clinical heart disease. J Am Coll Cardiol 1990; 15: 775–83PubMedGoogle Scholar
  19. 19.
    Kozàkovà M, Galetta F, Gregorini L, et al. Coronary vasodilator capacity and epicardial vessel remodeling in physiological and hypertensive hypertrophy. Hypertension 2000; 36: 343–9PubMedGoogle Scholar
  20. 20.
    Galderisi M, de Simone G, Cicala S, et al. Coronary flow reserve in hypertensive patients with appropriate or inappropriate left ventricular mass. J Hypertens 2003; 21: 2183–8PubMedGoogle Scholar
  21. 21.
    Wilson RF, Laxson DD. Caveat emptor: a clinician’s guide to assessing the physiologic significance of arterial stenosis. Cathet Cardiovasc Diagn 1993; 29: 93–8PubMedGoogle Scholar
  22. 22.
    Dimitrow PP, Galderisi M, Rigo F. The non-invasive documentation of coronary macrocirculation impairment: role of transthoracic echocardiography. Cardiovasc Ultrasound 2005; 3: 18PubMedGoogle Scholar
  23. 23.
    Rigo F, Gherardi S, Galderisi M, et al. Coronary flow reserve evaluation in stress-echocardiography laboratory. J Cardiovasc Med 2006; 7: 472–9Google Scholar
  24. 24.
    De Bruyne B, Hersbach F, Pijls NH, et al. Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but ‘normal’ coronary angiography. Circulation 2001; 104: 2401–6PubMedGoogle Scholar
  25. 25.
    Schwartzkopff B, Motz W, Frenzel H, et al. Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension. Circulation 1993; 88: 993–1003PubMedGoogle Scholar
  26. 26.
    Quinones MJ, Pampaloni MH, Scheibert H, et al. Coronary vasomotor abnormalities in insulin-resistant individuals. Ann Intern Med 2004; 140: 700–8PubMedGoogle Scholar
  27. 27.
    Srinivasan M, Herrero P, McGill JB, et al. The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus. J Am Coll Cardiol 2005; 46: 42–8PubMedGoogle Scholar
  28. 28.
    Nitenberg A, Foult JM, Antony I, et al. Coronary flow and resistance reserve in patients with chronic aortic regurgitation, angina pectoris and normal coronary arteries. J Am Coll Cardiol 1998; 11: 478–86Google Scholar
  29. 29.
    Krams R, Kofflard MJ, Duncker DJ, et al. Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation. Circulation 1998; 97: 230–3PubMedGoogle Scholar
  30. 30.
    Canetti M, Akhter MW, Lerman A, et al. Evaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to idiopathic dilated cardiomyopathy. Am J Cardiol 2003; 92: 1246–9PubMedGoogle Scholar
  31. 31.
    Vassalli G, Hess OM. Measurement of coronary flow reserve and its role in patient care. Basic Res Cardiol 1998; 93: 339–53PubMedGoogle Scholar
  32. 32.
    Marcus M, Wright C, Doty D, et al. Measurements of coronary velocity and reactive hyperemia in the coronary circulation in humans. Circ Res 1981; 49: 877–91PubMedGoogle Scholar
  33. 33.
    Pijls NH, De Bruyne B, Smith L, et al. Coronary thermodilution to assess flow reserve: validation in humans. Circulation 2002; 105: 2482–6PubMedGoogle Scholar
  34. 34.
    Storto G, Cirillo P, Vicario ML, et al. Estimation of coronary flow reserve by Tc-99m sestamibi imaging in patients with coronary artery disease: comparison with the results of intracoronary Doppler technique. J Nucl Cardiol 2004; 11: 682–8PubMedGoogle Scholar
  35. 35.
    Wisenberg C, Schelbert HR, Hoffman EJ, et al. In vivo quantification of regional myocardial blood flow by positron-emission computed tomography. Circulation 1981; 63: 1248–58PubMedGoogle Scholar
  36. 36.
    Schwaiger M, Hutchins G. Quantification of regional myocardial perfusion by PET: rationale and first clinical results. Eur Heart J 1995; 16 Suppl. J: 84–91PubMedGoogle Scholar
  37. 37.
    Ibrahim T, Nekolla SG, Schreiber K, et al. Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography. J Am Coll Cardiol 2002; 39: 864–70PubMedGoogle Scholar
  38. 38.
    Rimoldi O, Camici PG. PET measurement of the coronary flow reserve and microcirculatory function. Hertz 1999; 24: 522–30Google Scholar
  39. 39.
    Iliceto S, Marangelli V, Memmola C, et al. Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline condition and during dipyridamole-induced coronary vasodilation. Circulation 1991; 83: 61–9PubMedGoogle Scholar
  40. 40.
    Hozumi T, Yoshida K, Ogata Y, et al. Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography. Circulation 1998; 97: 1557–62PubMedGoogle Scholar
  41. 41.
    Caiati C, Montaldo C, Zedda N, et al. New noninvasive method for coronary flow reserve assessment: contrast enhanced transthoracic second harmonic echo-Doppler. Circulation 1999; 99: 771–8PubMedGoogle Scholar
  42. 42.
    Voci P, Testa G, Plaustro G. Imaging of the distal left anterior descending coronary artery by transthoracic color Doppler echocardiography. Am J Cardiol 1998; 81: 74–8GGoogle Scholar
  43. 43.
    Sudhir K, MacGregor JS, Barbant SD, et al. Assessment of coronary conductance and resistance vessel reactivity in response to nitroglycerin, ergonovine and adenosine: in vivo studies with simultaneous intravascular two-dimensional and Doppler ultrasound. J Am Coll Cardiol 1993; 21: 1261–8PubMedGoogle Scholar
  44. 44.
    Wilson RF, White CW. Intracoronary papaverine: an ideal coronary vasodilation for studies of the coronary circulation in conscious humans. Circulation 1986; 73: 444–51PubMedGoogle Scholar
  45. 45.
    Christensen CW, Rosen LB, Gal RA, et al. Coronary vasodilator reserve: comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism. Circulation 1991; 83: 294–303PubMedGoogle Scholar
  46. 46.
    Rossen JD, Quillen JE, Lopez AG, et al. Comparison of coronary vasodilation with intravenous dipyridamole and adenosine. J Am Coll Cardiol 1991; 18: 485–91PubMedGoogle Scholar
  47. 47.
    Felder L, Vassalli G, Vassalli F, et al. Clinical significance of coronary flow reserve: effects of papaverine and exercise. Coron Artery Dis 1994; 5: 347–58PubMedGoogle Scholar
  48. 48.
    Voudris V, Manginas A, Vassilikos V, et al. Coronary flow velocity changes after intravenous dipyridamole infusion: measurements using intravascular Doppler guide wire. A documentation of flow inhomogeneity. J Am Coll Cardiol 1996; 27: 1148–55Google Scholar
  49. 49.
    Galderisi M, de Simone G, Cicala S, et al. Coronary flow reserve in hypertensive patients with appropriate or inappropriate left ventricular mass. J Hypertens 2003; 21: 2183–8PubMedGoogle Scholar
  50. 50.
    Takeuchi M, Miyazaki C, Yoshitani H, et al. Assessment of coronary flow velocity with transthoracic Doppler echocardiography during dobutamine stress echocardiography. J Am Coll Cardiol 2001; 38: 117–23PubMedGoogle Scholar
  51. 51.
    Lim HE, Shim WJ, Rhee H, et al. Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison among adenosine, standard-dose dipyridamole, and high-dose dipyridamole. J Am Soc Echocardiogr 2000; 13: 264–70PubMedGoogle Scholar
  52. 52.
    Rigo F, Cortigiani L, Pasanisi E, et al. The additional prognostic value of coronary flow reserve on left anterior descending artery in patients with negative stress echo by wall motion criteria: a transthoracic vasodilator stress echocardiography study. Am Heart J 2006; 151: 124–30PubMedGoogle Scholar
  53. 53.
    Rigo F, Gherardi S, Galderisi M, et al. The independent prognostic value of contractile and coronary flow reserve determined by dipyridamole stress echocardiography in patients with idiopathic dilated cardiomyopathy. Am J Cardiol 2007; 99: 1154–8PubMedGoogle Scholar
  54. 54.
    Drexler H, Zeiber AM, Wollschlager H, et al. Flow dependent coronary artery dilation in humans. Circulation 1989; 80: 466–74PubMedGoogle Scholar
  55. 55.
    Nabel EG, Ganz P, Gordon JB, et al. Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressure test. Circulation 1988; 77: 43–52PubMedGoogle Scholar
  56. 56.
    Zeiher AM, Drexler H, Wollschlaeger H, et al. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 1989; 14: 1181–90PubMedGoogle Scholar
  57. 57.
    Schächinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101: 1899–906PubMedGoogle Scholar
  58. 58.
    Schwartzkopff B, Brehm M, Mundhenke M, et al. Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 2000; 36: 220–5PubMedGoogle Scholar
  59. 59.
    Motz W, Strauer BE. Improvement of coronary flow reserve after long-term therapy with enalapril. Hypertension 1996; 27: 1031–8PubMedGoogle Scholar
  60. 60.
    Vogt M, Strauer BE. Response of hypertensive left ventricular hypertrophy and coronary microvascular disease to calcium antagonists. Am J Cardiol 1995; 76: 24–30DGoogle Scholar
  61. 61.
    Parodi O, Neglia D, Sambuceti G, et al. Regional myocardial blood flow and coronary reserve in hypertensive patients: the effect of therapy. Drugs 1992; 44 Suppl. 1: 48–55PubMedGoogle Scholar
  62. 62.
    Kuschnir E. Impact of calcium antagonists on the cardiovascular system: experience with lacidipine. Drugs 1999; 57 Suppl. 1: 11–7PubMedGoogle Scholar
  63. 63.
    Tomás JP, Moya JL, Barrios V, et al. Effect of candesartan on coronary flow reserve in patients with systemic hypertension. J Hypertens 2006; 24: 2109–14PubMedGoogle Scholar
  64. 64.
    Akinboboye OO, Chou RL, Bergmann SR. Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan. J Am Coll Cardiol 2002; 40: 703–9PubMedGoogle Scholar
  65. 65.
    Strauer BE, Schwartzkopff B, Kelm M. Assessing the coronary circulation in hypertension. J Hypertens 1998; 16: 1221–33PubMedGoogle Scholar
  66. 66.
    Young MA, Vatner SE, Vatner SF. Alpa- and beta-adrenergic control of large coronary arteries in conscious dogs. Circ Res 1974; 34: 812–23Google Scholar
  67. 67.
    Marshall RJ, Parratt JR. Comparative effects of propranolol and practolol in the early stages of experimental canine myocardial infarction. Br J Pharmacol 1976; 57: 295–303PubMedGoogle Scholar
  68. 68.
    Lichtlen PR, Rafflenbeul W, Jost S, et al. Coronary vasomotion tone in large epicardial coronary arteries with special emphasis on beta-adrenergic vasomotion, effect of beta-blockade. Basic Res Cardiol 1990; 85 Suppl. 1: 335–46PubMedGoogle Scholar
  69. 69.
    Billinger M, Seller C, Fleisch M, et al. Effect of beta-adrenergic blocking agents increase coronary flow reserve? J Am Coll Cardiol 2001; 38: 1866–71PubMedGoogle Scholar
  70. 70.
    Boettcher M, Czernin J, Sun K, et al. Effects of β1 adrenergic blockade on myocardial blood flow and vasodilatory capacity. J Nucl Med 1997; 38: 442–6Google Scholar
  71. 71.
    Gullu H, Erdogan D, Caliskan M, et al. Different effects of atenolol and nebivolol on coronary flow reserve. Heart 2006; 92: 1690–1PubMedGoogle Scholar
  72. 72.
    Strauer BE. The hypertensive heart: effect of atenolol on the function, coronary hemodynamics and oxygen uptake of the left ventricle. Dtsch Med Wochenschr 1978; 103: 1785–9PubMedGoogle Scholar
  73. 73.
    Kern MJ, Ganz P, Horowitz DJ, et al. Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease. Circulation 1983; 67: 1178–85PubMedGoogle Scholar
  74. 74.
    Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001; 357: 1385–90PubMedGoogle Scholar
  75. 75.
    Packer M, Coats AJ, Fowler MB, et al., on behalf of the Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344: 1651–8PubMedGoogle Scholar
  76. 76.
    Poole-Wilson PA, Swedberg K, Cleland JG, et al., on behalf of the Carvedilol or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet 2003; 362: 7–13PubMedGoogle Scholar
  77. 77.
    Fiather MD, Shibata MC, Coats AJ, et al., on behalf of the SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26: 215–25Google Scholar
  78. 78.
    Koepfli P, Wyss CA, Namdar M, et al. β-Adrenergic blockade and myocardial perfusion in coronary artery disease: differential effects in stenotic versus remote myocardial segments. J Nucl Med 2004; 45: 1628–31Google Scholar
  79. 79.
    Sugioka K, Hozumi T, Takemoto Y, et al. Early recovery of impaired coronary flow reserve by carvedilol therapy in patients with idiopathic dilated cardiomyopathy: a serial transthoracic Doppler echocardiographic study. J Am Coll Cardiol 2005; 45: 318–9PubMedGoogle Scholar
  80. 80.
    Neglia D, De Maria R, Masi S, et al. Effects of long-term treatment with carvedilol on myocardial blood flow in idiopathic dilated cardiomyopathy. Heart 2007; 93: 803–13Google Scholar
  81. 81.
    Sugioka K, Hozumi T, Takemoto Y, et al. Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy. Am Heart J 2007; 153: 1080e1-6PubMedGoogle Scholar
  82. 82.
    Galderisi M, Cicala S, D’Errico A, et al. Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease. J Hypertens 2004; 22: 2201–8PubMedGoogle Scholar
  83. 83.
    Erdogan D, Gullu H, Caliskan M, et al. Nebivolol improves coronary flow reserve in patients with idiopathic dilated cardiomyopathy. Heart 2007; 93: 319–24PubMedGoogle Scholar
  84. 84.
    Togni M, Vigorito F, Windecker S, et al. Does the beta-blocker nebivolol increase coronary flow reserve? Cardiovasc Drug Ther 2007; 21(2): 99–108Google Scholar
  85. 85.
    Lorenzoni R, Rosen SD, Camici PG. Effect of alphal-adrenoceptor blockade on resting and hyperemic myocardial blood flow in normal humans. Am J Physiol 1996; 271: H1302–6PubMedGoogle Scholar
  86. 86.
    Yue TL, Ruffolo Jr RR, Feuerstein G. Antioxidant action of carvedilol: a potential role in treatment of heart failure. Heart Fail Rev 1999; 4: 39–51Google Scholar
  87. 87.
    Kuo L, Davis MJ, Chilian WH. Endothelium-dependent, flow induced dilation of isolated coronary arterioles. Am J Physiol 1990; 259: H1063–70PubMedGoogle Scholar
  88. 88.
    Ignarro LJ, Byrns RE, Trinh K, et al. Nebivolol: a selective beta(1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide- and cyclic GMP-dependent mechanisms. Nitric Oxide 2002; 7: 75–82PubMedGoogle Scholar
  89. 89.
    Brehm BR, Bertsch D, von Fallois J, et al. Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells. J Cardiovasc Pharmacol 2000; 36: S401–3PubMedGoogle Scholar
  90. 90.
    Mundhenke M, Schwartzkopff B, Köstering M, et al. Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy. Heart 1999; 81: 278–84PubMedGoogle Scholar
  91. 91.
    Lekakis JP, Protogerou A, Papamichael C, et al. Effect of nebivolol and atenolol on brachial artery flow-mediated vasodilation in patients with coronary artery disease. Cardiovasc Drugs Ther 2005; 19: 277–81PubMedGoogle Scholar
  92. 92.
    Corretti MC, Anderson TJ, Benjamin EJ, et al. 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 2002; 39: 257–65Google Scholar
  93. 93.
    Zeiher AM, Krause T, Schächinger V, et al. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 1995; 91: 2345–52PubMedGoogle Scholar
  94. 94.
    Olsen SL, Gilbert EM, Renlund DG, et al. Carvedilol improves left ventricular function and symptoms in chronic heart failure: a double-blind randomized study. J Am Coll Cardiol 1995; 25: 1225–31PubMedGoogle Scholar
  95. 95.
    Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997; 349: 375–80Google Scholar
  96. 96.
    Di Lenarda A, Sabbadini G, Salvatore L, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol: the Heart-Muscle Disease Study Group. J Am Coll Cardiol 1999; 33: 1926–34PubMedGoogle Scholar
  97. 97.
    Palazzuoli A, Quatrini I, Vecchiato L, et al. Left ventricular diastolic function improvement by carvedilol therapy in advanced heart failure. J Cardiovasc Pharmacol 2005; 45: 563–8PubMedGoogle Scholar
  98. 98.
    Wisenbaugh T, Katz I, Davis J, et al. Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. J Am Coll Cardiol 1993; 21: 1094–100PubMedGoogle Scholar
  99. 99.
    Nodari S, Metra M, Dei Cas L. Beta-blocker treatment of patients with diastolic heart failure and arterial hypertension: a prospective, randomized, comparison of the long-term effects of atenolol vs nebivolol. Eur J Heart Fail 2003; 5: 621–7PubMedGoogle Scholar
  100. 100.
    Edes I, Gasior Z, Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. Eur J Heart Fail 2005; 7: 631–9PubMedGoogle Scholar
  101. 101.
    Ghio S, Magrini G, Serio A, et al. Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy. Eur Heart J 2006; 27: 506–7Google Scholar
  102. 102.
    Galderisi M, de Simone G, D’Errico A, et al. Three-month nebivolol therapy induces improvement of both left ventricular filling pressure and coronary flow reserve in hypertensive patients without coronary artery disease [abstract]. Eur J Echocardiogr 2006; 7 Suppl. 1: S185Google Scholar
  103. 103.
    Cortigiani L, Rigo F, Gherardi S, et al. Additional prognostic value of coronary flow reserve in diabetic and non diabetic patients with negative dipyridamole stress echocardiography by wall motion criteria. J Am Coll Cardiol 2007; 50: 1354–61PubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Laboratory of Echocardiography, Cardioangiology Unit with CCU, Department of Clinical and Experimental MedicineFederico II University HospitalNaplesItaly

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