Skip to main content
SpringerLink
Log in

CMD in the Absence of Myocardial Diseases and Obstructive CAD

  • Chapter
  • First Online:
Coronary Microvascular Dysfunction

  • 1127 Accesses

Abstract

Cardiovascular risk factors (e.g., hypercholesterolemia, smoking, hypertension, diabetes, etc.) have all been shown to cause CMD, as indicated by reduced CFR, before any obstructive stenosis can be detected in epicardial coronary arteries. The occurrence of chest pain in the absence of any other cardiac or systemic disease results in the clinical picture of primary microvascular angina (MVA), which usually presents with a stable, exercise-related angina syndrome, but can also occur as an acute syndrome suggesting a non-ST elevation ACS. Takotsubo cardiomyopathy is likely also caused by a sudden acute vasoconstriction of resistive coronary arteries resulting in severe impairment of med-distal LV segments.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Camici PG, Crea F (2007) Coronary microvascular dysfunction. N Engl J Med 356:830–840

    Article  PubMed  CAS  Google Scholar 

  2. Sackett DL, Gibson RW, Bross IDJ, Pickren JW (1968) Relation between aortic atherosclerosis and the use of cigarettes and alcohol: an autopsy study. N Engl J Med 279:1413–1420

    Article  PubMed  CAS  Google Scholar 

  3. Jonas MA, Oates JA, Ockene JK, Hennekens CH (1992) Statement on smoking and cardiovascular disease for health care professionals. Circulation 86:1664–1669

    Article  PubMed  CAS  Google Scholar 

  4. Celermajer DS, Sorensen KE, Georgakopoulos D et al (1993) Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium- dependent dilation in healthy young adults. Circulation 88:2149–2155

    Article  PubMed  CAS  Google Scholar 

  5. Zeiher AM, Schachinger V, Minners J (1995) Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 92:1094–1100

    Article  PubMed  CAS  Google Scholar 

  6. Celermajer DS, Adams MR, Clarkson P et al (1996) Passive smoking and impaired endothelium-dependent arterial dilation in healthy young adults. N Engl J Med 334:150–154

    Article  PubMed  CAS  Google Scholar 

  7. Sumida H, Watanabe H, Kugiyama K, Ohgushi M, Matsumura T, Yasue H (1998) Does passive smoking impair endothelium-dependent coronary artery dilation in women? J Am Coll Cardiol 31:811–815

    Article  PubMed  CAS  Google Scholar 

  8. Kaufmann PA, Gnecchi-Ruscone T, Di Terlizzi M, Schäfers KP, Lüscher TF, Camici PG (2000) Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation 102:1233–1238

    Article  PubMed  CAS  Google Scholar 

  9. Booyse FM, Osikowicz G, Quaarfoot AJ (1981) Effect of chronic oral consumption of nicotine on the rabbit aortic endothelium. Am J Pathol 102:229–238

    PubMed  CAS  Google Scholar 

  10. Asmussen G, Kjeldsen K (1975) Intimal ultrastructure of human umbilical arteries: observation on arteries from newborn children of smoking and non-smoking mothers. Circ Res 36:579–589

    Article  PubMed  CAS  Google Scholar 

  11. Church DF, Pryor WA (1985) Free radical chemistry of cigarettes smoke and its toxicological implications. Environ Health Perspect 64:111–126

    Article  PubMed  CAS  Google Scholar 

  12. Hein WH, Kuo L (1998) LDLs impair vasomotor function of the coronary microcirculation: role of superoxide anions. Circ Res 83:404–414

    Article  PubMed  CAS  Google Scholar 

  13. Campisi R, Czernin J, Schröder H, Sayre JW, Schelbert HR (1999) l-Arginine normalizes coronary vasomotion in long-term smoker. Circulation 99:491–497

    Article  PubMed  CAS  Google Scholar 

  14. Kugiyama K, Ohgushi M, Motoyama T et al (1998) Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation 97:2299–2301

    Article  PubMed  CAS  Google Scholar 

  15. Kugiyama K, Motoyama T, Hirashima O et al (1998) Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina. J Am Coll Cardiol 32:103–109

    Article  PubMed  CAS  Google Scholar 

  16. Seiler C, Hess OM, Buechi M, Suter TM, Krayenbuehl HP (1993) Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries. Circulation 88:2139–2148

    Article  PubMed  CAS  Google Scholar 

  17. Zeiher AM, Drexler H, Wollschlager H, Just H (1991) Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83:391–401

    Article  PubMed  CAS  Google Scholar 

  18. Drexler H, Zeiher AM, Meinzer K, Just J (1991) Correction of endothelial dysfunction in coronary microcirculation of hyperholesterolaemic patients by l-arginine. Lancet 338:1546–1550

    Article  PubMed  CAS  Google Scholar 

  19. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP (1992) l-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 90:1248–1253

    Article  PubMed  CAS  Google Scholar 

  20. Leung WH, Lau CP, Wong CK (1993) Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent coronary vasomotion in hypercholesterolemic patients. Lancet 341:1496–1500

    Article  PubMed  CAS  Google Scholar 

  21. Egashira K, Hirooka Y, Kai H et al (1994) Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 89:2519–2524

    Article  PubMed  CAS  Google Scholar 

  22. Treasure CB, Klein JL, Weintraub WS et al (1995) Beneficial effects of cholesterol lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 332:481–487

    Article  PubMed  CAS  Google Scholar 

  23. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P (1995) The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 332:488–493

    Article  PubMed  CAS  Google Scholar 

  24. Kaufmann PA, Frielingsdorf J, Mandinov L, Seiler C, Hug R, Hess OM (1998) Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia. Circulation 97:1348–1354

    Article  PubMed  CAS  Google Scholar 

  25. Gould KL, Martucci JP, Goldberg DI et al (1994) Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. Circulation 89:1530–1538

    Article  PubMed  CAS  Google Scholar 

  26. Czernin J, Barnard RJ, Sun KT et al (1995) Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve. Circulation 92:197–204

    Article  PubMed  CAS  Google Scholar 

  27. Guethlin M, Kasel AM, Coppenrath K, Ziegler S, Delius W, Schwaiger M (1999) Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin. Circulation 99:475–481

    Article  PubMed  CAS  Google Scholar 

  28. Dayanikli F, Grambow D, Muzik O, Mosca L, Rubenfire M, Schwaiger M (1994) Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation 90:808–817

    Article  PubMed  CAS  Google Scholar 

  29. Yokoyama I, Ohtake T, Momomura S, Nishikawara J, Sasaki Y, Omata M (1996) Reduced coronary flow reserve in hypercholesterolemic patients without overt coronary stenosis. Circulation 94:3232–3238

    Article  PubMed  CAS  Google Scholar 

  30. Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imamizumi T (1997) Single LDL apheresis improves endothelium-dependent vasodilation in hypercholesterolemic humans. Circulation 95:76–82

    Article  PubMed  CAS  Google Scholar 

  31. Kaufmann PA, Gnecchi-Ruscone T, Schafers KP, Luscher TF, Camici PG (2000) Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol 36:103–109

    Article  PubMed  CAS  Google Scholar 

  32. Yokoyama I, Murakami T, Ohtake T et al (1996) Reduced coronary flow reserve in familial hypercholesterolemia. J Nucl Med 37:1937–1942

    PubMed  CAS  Google Scholar 

  33. Pitkänen OP, Nuutila P, Raitakari OT et al (1999) Coronary flow reserve in young men with familial combined hyperlipidemia. Circulation 99:1678–1684

    Article  PubMed  Google Scholar 

  34. Pajukanta P, Nuotio I, Terwilliger JD et al (1998) Linkage of familial combined hyperlipidemia to chromosome 1q21–q23. Nat Genet 18:369–373

    Article  PubMed  CAS  Google Scholar 

  35. Shepherd J (1998) A call to action. Eur Heart J 19:M2–M7

    Article  PubMed  Google Scholar 

  36. Durrington PN, Prais H, Bhatnagar D et al (1999) Indications for cholesterol-lowering medication: comparison of risk-assessment methods. Lancet 353:278–281

    Article  PubMed  CAS  Google Scholar 

  37. Grover S (1999) Gambling with cardiovascular risk: picking the winners and the loser. Lancet 353:254–255

    Article  PubMed  CAS  Google Scholar 

  38. Casale PN, Devereux RB, Milner M et al (1986) Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 105:173–178

    Article  PubMed  CAS  Google Scholar 

  39. Devereux RB, Wachtell K, Gerdts E et al (2004) Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA 292:2350–2356

    Article  PubMed  CAS  Google Scholar 

  40. Turnbull F, Neal B, Ninomiya T et al (2008) Blood pressure lowering treatment trialists’ collaboration. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ 336:1121–1123

    Article  PubMed  CAS  Google Scholar 

  41. Turnbull F, Neal B, Pfeffer M et al (2007) Blood pressure lowering treatment trialists’ collaboration. Blood pressure-dependent and independent effects of agents that inhibit the renin–angiotensin system. J Hypertens 25:951–958

    Article  PubMed  CAS  Google Scholar 

  42. Brush JE, Cannon RO 3rd, Schenke WH et al (1988) Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy. N Engl J Med 319:1302–1307

    Article  PubMed  Google Scholar 

  43. Treasure CB, Klein JL, Vita JA et al (1993) Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation 87:86–93

    Article  PubMed  CAS  Google Scholar 

  44. Strauer BE (1979) Ventricular function and coronary hemodynamics in hypertensive heart disease. Am J Cardiol 44:999–1006

    Article  PubMed  CAS  Google Scholar 

  45. Opherk D, Mall G, Zebe H et al (1984) Reduction of coronary reserve: a mechanism for angina pectoris in patients with arterial hypertension and normal coronary arteries. Circulation 69:1–7

    Article  PubMed  CAS  Google Scholar 

  46. Erdogan D, Yildirim I, Ciftci O et al (2007) Effects of normal blood pressure, prehypertension, and hypertension on coronary microvascular function. Circulation 115:593–599

    Article  PubMed  Google Scholar 

  47. Vogt M, Motz W, Strauer BE (1992) Coronary haemodynamics in hypertensive heart disease. Eur Heart J 13(suppl D):44–49

    Google Scholar 

  48. Schwartzkopff B, Motz W, Frenzel H, Vogt M, Knauer S, Strauer BE (1993) Structural and functional alterations of the intramyocardial coronary arterioles in patients with arterial hypertension. Circulation 88:993–1003

    Article  PubMed  CAS  Google Scholar 

  49. Weber KT (2000) Fibrosis and hypertensive heart disease. Curr Opin Cardiol 15:264–272

    Article  PubMed  CAS  Google Scholar 

  50. Levy BI, Duriez M, Samuel JL (2001) Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. Am J Hypertens 14:7–13

    Article  PubMed  CAS  Google Scholar 

  51. Rakusan K, Cicutti N, Maurin A, Guez D, Schiavi P (2000) The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats. Microvasc Res 59:243–254

    Article  PubMed  CAS  Google Scholar 

  52. Wangler RD, Peters KG, Marcus ML, Tomanek RJ (1982) Effects of duration and severity of arterial hypertension and cardiac hypertrophy on coronary vasodilator reserve. Circ Res 51:10–18

    Article  PubMed  CAS  Google Scholar 

  53. Gimelli A, Schneider-Eicke J, Neglia D et al (1998) Homogeneously reduced versus regionally impaired myocardial blood flow in hypertensive patients: two different patterns of myocardial perfusion associated with degree of hypertrophy. J Am Coll Cardiol 31:366–373

    Article  PubMed  CAS  Google Scholar 

  54. Buus NH, Bottcher M, Jorgensen CG et al (2004) Myocardial perfusion during long-term angiotensin-converting enzyme inhibition or beta-blockade in patients with essential hypertension. Hypertension 44:465–470

    Article  PubMed  CAS  Google Scholar 

  55. Schiffrin EL, Deng LY, Larochelle P (1994) Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension. Hypertension 23:83–91

    Article  PubMed  CAS  Google Scholar 

  56. Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ (1995) Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 25:474–481

    Article  PubMed  CAS  Google Scholar 

  57. Agabiti-Rosei E, Heagerty AM, Rizzoni D (2009) Effects of antihypertensive treatment on small artery remodelling. J Hypertens 27:1107–1114

    Article  PubMed  CAS  Google Scholar 

  58. Rizzoni D, Palombo C, Porteri E et al (2003) Relationships between coronary flow vasodilator capacity and small artery remodelling in hypertensive patients. J Hypertens 21:625–631

    Article  PubMed  CAS  Google Scholar 

  59. Schwartzkopff B, Brehm M, Mundhenke M, Strauer BE (2000) Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. Hypertension 36:220–225

    Article  PubMed  CAS  Google Scholar 

  60. Chilian WM (1997) Coronary microcirculation in health and disease. Summary of an NHLBI workshop. Circulation 95:522–528

    Article  PubMed  CAS  Google Scholar 

  61. Mourad JJ, Hanon O, Deverre JR et al (2003) Improvement of impaired coronary vasodilator reserve in hypertensive patients by low-dose ACE inhibitor/diuretic therapy: a pilot PET study. J Renin Angiotensin Aldosterone Syst 4:94–95

    Article  PubMed  CAS  Google Scholar 

  62. Neglia D, Fommei E, Varela-Carver A et al (2011) Perindopril and indapamide reverse coronary microvascular remodelling and improve flow in arterial hypertension. J Hypertens 29:364–372

    Article  PubMed  CAS  Google Scholar 

  63. Ghiadoni L, Magagna A, Kardasz I, Taddei S, Salvetti A (2009) Fixed dose combination of perindopril and indapamide improves peripheral vascular function in essential hypertensive patients. Am J Hypertens 22:506–512

    Article  PubMed  CAS  Google Scholar 

  64. Garcia MJ, McNamara PM, Gordon T, Kannel WB (1974) Morbidity and mortality in diabetics in the Framingham population: sixteen year follow-up study. Diabetes 23:105–111

    PubMed  CAS  Google Scholar 

  65. Wiernsperger N, Rapin JR (2012) Microvascular diseases: is a new era coming? Cardiovasc Hematol Agents Med Chem 10:167–183

    Article  PubMed  CAS  Google Scholar 

  66. Shankar A, Sabanayagam C, Klein BE, Klein R (2011) Retinal microvascular changes and the risk of developing obesity: population-based cohort study. Microcirculation 18:655–662

    Article  PubMed  Google Scholar 

  67. Harris MI, Klein R, Welborn TA, Knuiman MW (1992) Onset of NIDDM occurs at least 4–7 yr before clinical diagnosis. Diab Care 15:815–819

    Article  CAS  Google Scholar 

  68. Ramasamy R, Yan SF, Schmidt AM (2011) Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann N Y Acad Sci 1243:88–102

    Article  PubMed  CAS  Google Scholar 

  69. Thomas MC (2011) Advanced glycation end products. Contrib Nephrol 170:66–74

    Article  PubMed  CAS  Google Scholar 

  70. Moore TC, Moore JE, Kaji Y et al (2003) The role of advanced glycation end products in retinal microvascular leukostasis. Invest Ophthalmol Vis Sci 44:4457–4464

    Article  PubMed  Google Scholar 

  71. Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease: the Framingham study. JAMA 241:2035–2038

    Article  PubMed  CAS  Google Scholar 

  72. Nitenberg A, Valensi P, Sachs R, Dali M, Aptecar E, Attali JR (1993) Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angiographically normal coronary arteries and normal left ventricular systolic function. Diabetes 42:1017–1025

    Article  PubMed  CAS  Google Scholar 

  73. Yokoyama I, Momomura S, Ohtake T et al (1997) Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 30:1472–1477

    Article  PubMed  CAS  Google Scholar 

  74. Pitkänen OP, Nuutila P, Raitakari OT et al (1998) Coronary flow reserve is reduced in young men with IDDM. Diabetes 47:248–254

    Article  PubMed  Google Scholar 

  75. Di Carli MF, Bianco-Batlles D, Landa ME et al (1999) Effects of autonomic neuropathy on coronary blood flow in patients with diabetes mellitus. Circulation 100:813–819

    Article  PubMed  Google Scholar 

  76. Caballero AE, Arora S, Saouaf R et al (1999) Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 48:1856–1862

    Article  PubMed  CAS  Google Scholar 

  77. Di Carli MF, Janisse J, Grunberger G, Ager J (2003) Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 41:1387–1393

    Article  PubMed  CAS  Google Scholar 

  78. Grundy SM (2012) Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol 59:635–643

    Google Scholar 

  79. Murthy VL, Naya M, Foster CR et al (2012) Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation 126:1858–1868

    Article  PubMed  CAS  Google Scholar 

  80. Iozzo P, Chareonthaitawee P, Rimoldi O, Betteridge DJ, Camici PG, Ferrannini E (2002) Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type II diabetes. Diabetologia 45:1404–1409

    Article  PubMed  CAS  Google Scholar 

  81. Mather K, Laakso M, Edelman S, Hook G, Baron A (2000) Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow. Am J Physiol Endocrinol Metab 279:E1264–E1270

    PubMed  CAS  Google Scholar 

  82. Barrett EJ, Eggleston EM, Inyard AC et al (2009) The vascular actions of insulin control its delivery to muscle and regulate the rate-limiting step in skeletal muscle insulin action. Diabetologia 52:752–764

    Article  PubMed  CAS  Google Scholar 

  83. De Boer MP, Meijer RI, Wijnstok NJ et al (2011) Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Microcirculation 19:5–18

    Article  CAS  Google Scholar 

  84. Czernichow S, Greenfield JR, Galan P et al (2010) Microvascular dysfunction in healthy insulin-sensitive overweight individuals. J Hypertens 28:325–333

    Article  PubMed  CAS  Google Scholar 

  85. Kraemer-Aguiar LG, Laflor CM, Bouskela E (2008) Skin microcirculatory dysfunction is already present in normoglycemic subjects with metabolic syndrome. Metabolism 57:1740–1746

    Article  PubMed  CAS  Google Scholar 

  86. Lakhani K, Leonard A, Seifalian AM, Hardiman P (2005) Microvascular dysfunction in women with polycystic ovary syndrome. Hum Reprod 20:3219–3224

    Article  PubMed  CAS  Google Scholar 

  87. Sprague RS, Ellsworth ML (2010) Vascular disease in pre-diabetes: new insights derived from systems biology. Mo Med 107:265–269

    PubMed  Google Scholar 

  88. Naoumova RP, Kindler H, Leccisotti L et al (2007) Pioglitazone improves myocardial blood flow and glucose utilization in nondiabetic patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 50:2051–2058

    Article  PubMed  CAS  Google Scholar 

  89. Hanefeld M (2009) The role of pioglitazone in modifying the atherogenic lipoprotein profile. Diabetes Obes Metab 11:742–756

    Google Scholar 

  90. Recio-Mayoral A, Mason JC, Kaski JC, Rubens MB, Harari OA, Camici PG (2009) Chronic inflammation and coronary microvascular dysfunction in patients without risk factors for coronary artery disease. Eur Heart J 30:1837–1843

    Article  PubMed  CAS  Google Scholar 

  91. Cosin-Sales J, Pizzi C, Brown S, Kaski JC (2003) C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms. J Am Coll Cardiol 41:1468–1474

    Article  PubMed  CAS  Google Scholar 

  92. Teragawa H, Fukuda Y, Matsuda K et al (2004) Relation between C reactive protein concentrations and coronary microvascular endothelial function. Heart 90:750–754

    Article  PubMed  CAS  Google Scholar 

  93. Lanza GA, Sestito A, Cammarota G et al (2004) Assessment of systemic inflammation and infective pathogen burden in patients with cardiac syndrome X. Am J Cardiol 94:40–44

    Article  PubMed  Google Scholar 

  94. Kovacs I, Toth J, Tarjan J, Koller A (2006) Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE. Eur J Heart Fail 8:451–459

    Article  PubMed  CAS  Google Scholar 

  95. Lanza GA, Crea F (2010) Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation 121:2317–2325

    Article  PubMed  Google Scholar 

  96. Gulati M, Cooper-DeHoff RM, McClure C et al (2009) Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women’s ischemia syndrome evaluation study and the St James women take heart project. Arch Intern Med 169:843–850

    Article  PubMed  Google Scholar 

  97. Jespersen L, Hvelplund A, Abildstrøm SZ et al (2012) Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 33:734–744

    Article  PubMed  Google Scholar 

  98. Kaul S, Newell JB, Chesler DA, Pohost GM, Okada RD, Boucher CA (1986) Quantitative thallium imaging findings in patients with normal coronary angiographic findings and in clinically normal subjects. Am J Cardiol 57:509–512

    Article  PubMed  CAS  Google Scholar 

  99. Cavusoglu Y, Entok E, Timuralp B et al (2005) Regional distribution and extent of perfusion abnormalities, and the lung to heart uptake ratios during exercise thallium-201 SPECT imaging in patients with cardiac syndrome X. Can J Cardiol 21:57–62

    PubMed  Google Scholar 

  100. Ritchie JL, Bateman TM, Bonow RO et al (1995) Guidelines for clinical use of cardiac radionuclide imaging. Report of the American College of Cardiology/American Heart Association task force on assessment of diagnostic and therapeutic cardiovascular procedures (Committee on Radionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology. J Am Coll Cardiol 25:521–547

    Article  PubMed  CAS  Google Scholar 

  101. Arbogast R, Bourassa MG (1973) Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms. Comparison with patients having significant coronary artery disease. Am J Cardiol 32:257–263

    Article  PubMed  CAS  Google Scholar 

  102. Kemp HG Jr (1973) Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol 32:375–376

    Article  PubMed  Google Scholar 

  103. Kemp HG Jr, Vokonas PS, Cohn PF, Gorlin R (1973) The anginal syndrome associated with normal coronary arteriograms. Report of a six year experience. Am J Med 54:735–742

    Article  PubMed  Google Scholar 

  104. Bøtker HE, Sonne HS, Bagger JP, Nielsen TT (1997) Impact of impaired coronary flow reserve and insulin resistance on myocardial energy metabolism in patients with syndrome X. Am J Cardiol 79:1615–1622

    Article  PubMed  Google Scholar 

  105. Bemiller CR, Pepine CJ, Rogers AK (1973) Long-term observations in patients with angina and normal coronary arteriograms. Circulation 47:36–43

    Article  PubMed  CAS  Google Scholar 

  106. Richardson PJ, Livesley B, Oram S, Olsen EGJ, Armstrong P (1974) Angina pectoris with normal coronary arteries. Transvenous myocardial biopsy in diagnosis. Lancet 2:677–680

    Article  PubMed  CAS  Google Scholar 

  107. Mammohansingh P, Parker JO (1975) Angina pectoris with normal coronary arteriograms: hemodynamic and metabolic response to atrial pacing. Am Heart J 90:555–561

    Article  PubMed  CAS  Google Scholar 

  108. Boudoulas H, Cobb TC, Leighton RF, Wilt SM (1974) Myocardial lactate production in patients with angina-like chest pain and angiographically normal coronary arteries and left ventricle. Am J Cardiol 34:501–505

    Article  PubMed  CAS  Google Scholar 

  109. Jackson G, Richardson PJ, Atkinson L, Armstrong P, Oram S (1978) Angina with normal coronary arteriograms. Value of coronary sinus lactate estimation in diagnosis and treatment. Br Heart J 40:976–978

    Article  PubMed  CAS  Google Scholar 

  110. Greenberg MA, Grose RM, Neuburger N, Silverman R, Strain JE, Cohen MV (1987) Impaired coronary vasodilator responsiveness as a cause of lactate production during pacing-induced ischemia in patients with angina pectoris and normal coronary arteries. J Am Coll Cardiol 9:743–751

    Article  PubMed  CAS  Google Scholar 

  111. Lagerqvist B, Bylund H, Götell P, Mannting F, Sandhagen B, Waldenström A (1991) Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. J Intern Med 230:55–65

    Article  PubMed  CAS  Google Scholar 

  112. Camici PG, Marraccini P, Lorenzoni R et al (1991) Coronary hemodynamics and myocardial metabolism in patients with syndrome X: response to pacing stress. J Am Coll Cardiol 17:1461–1470

    Article  PubMed  CAS  Google Scholar 

  113. Waldenström A, Ronquist G, Lagerqvist B (1992) Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge. J Intern Med 231:327–331

    Article  PubMed  Google Scholar 

  114. Nagayama M, Fujita Y, Kanai T et al (1996) Changes in myocardial lactate metabolism during ramp exercise in patients with effort angina and microvascular angina. Jpn Circ J 60:876–888

    Article  PubMed  CAS  Google Scholar 

  115. Crake T, Canepa-Anson R, Shapiro L, Poole-Wilson PA (1988) Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X. Br Heart J 59:31–38

    Article  PubMed  CAS  Google Scholar 

  116. Rosano GM, Kaski JC, Arie S et al (1996) Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism. Eur Heart J 17:1175–1180

    Article  PubMed  CAS  Google Scholar 

  117. Buchthal SD, den Hollander JA, Merz CN et al (2000) Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med 342:829–835

    Article  PubMed  CAS  Google Scholar 

  118. Buffon A, Rigattieri S, Santini SA et al (2000) Myocardial ischemia-reperfusion damage after pacing-induced tachycardia in patients with cardiac syndrome X. Am J Physiol Heart Circ Physiol 279:H2627–H2633

    PubMed  CAS  Google Scholar 

  119. Nihoyannopoulos P, Kaski JC, Crake T, Maseri A (1991) Absence of myocardial dysfunction during stress in patients with syndrome X. J Am Coll Cardiol 18:1463–1470

    Article  PubMed  CAS  Google Scholar 

  120. Panza JA, Laurienzo JM, Curiel RV et al (1997) Investigation of the mechanism of chest pain in patients with angiographically normal coronary arteries using transesophageal dobutamine stress echocardiography. J Am Coll Cardiol 29:293–301

    Article  PubMed  CAS  Google Scholar 

  121. Cannon RO 3rd, Camici PG, Epstein SE (1992) Pathophysiological dilemma of syndrome X. Circulation 85:883–892

    Article  PubMed  Google Scholar 

  122. Cannon RO 3rd, Schenke WH, Quyyumi A, Bonow RO, Epstein SE (1991) Comparison of exercise testing with studies of coronary flow reserve in patients with microvascular angina. Circulation 83:III77–III81

    Google Scholar 

  123. Demir H, Kahraman G, Isgoren S, Tan YZ, Kilic T, Berk F (2008) Evaluation of post-stress left ventricular dysfunction and its relationship with perfusion abnormalities using gated SPECT in patients with cardiac syndrome X. Nucl Med Commun 29:208–214

    Article  PubMed  Google Scholar 

  124. Nadazdin A, Shahi M, Foale RA (1991) Impaired left ventricular filling during ST-segment depression provoked by dipyridamole infusion in patients with syndrome X. Clin Cardiol 14:821–826

    Article  PubMed  CAS  Google Scholar 

  125. Picano E (1999) The alternative “ischemic” cascade in coronary microvascular disease. Cardiologia 44:791–795

    PubMed  CAS  Google Scholar 

  126. Maseri A, Crea F, Kaski JC, Crake T (1991) Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol 17:499–506

    Article  PubMed  CAS  Google Scholar 

  127. Mosseri M, Yarom R, Gotsman MS, Hasin Y (1986) Histologic evidence for small-vessel coronary artery disease in patients with angina pectoris and patent large coronary arteries. Circulation 74:964–972

    Article  PubMed  CAS  Google Scholar 

  128. Satake O, Kajiami K, Ishikawa Y et al (2004) Myocardial glucose metabolism assessed by positron emission tomography and the histopathologic findings of microvessels in syndrome X. Circ J 68:220–226

    Article  Google Scholar 

  129. Zorc-Pleskovic R, Vraspir-Porenta O, Zorc M, Milutinović A, Petrovic D (2008) Inflammatory changes in small blood vessels in the endomyocardium of cardiac syndrome X in female patients with increased C-reactive protein. Folia Biol (Praha) 54:30–32

    CAS  Google Scholar 

  130. Chimenti C, Sale P, Verardo R et al (2010) High prevalence of intramural coronary infection in patients with drug-resistant cardiac syndrome X: comparison with chronic stable angina and normal controls. Heart 96:1926–1931

    Article  PubMed  CAS  Google Scholar 

  131. Antonios TF, Kaski JC, Hasan KM, Brown SJ, Singer DR (2001) Rarefaction of skin capillaries in patients with anginal chest pain and normal coronary arteriograms. Eur Heart J 22:1144–1148

    Article  PubMed  CAS  Google Scholar 

  132. Opherk D, Zebe H, Weihe E et al (1981) Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. Circulation 63:817–825

    Article  PubMed  CAS  Google Scholar 

  133. Chauhan A, Mullins PA, Taylor G, Petch MC, Schofield PM (1997) Both endothelium-dependent and endothelium-independent function is impaired in patients with angina pectoris and normal coronary angiograms. Eur Heart J 18:60–68

    Article  PubMed  CAS  Google Scholar 

  134. Bøttcher M, Bøtker HE, Sonne H, Nielsen TT, Czernin J (1999) Endothelium-dependent and -independent perfusion reserve and the effect of l-arginine on myocardial perfusion in patients with syndrome X. Circulation 99:1795–1801

    Article  PubMed  Google Scholar 

  135. Panting JR, Gatehouse PD, Yang GZ et al (2002) Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 346:1948–1953

    Article  PubMed  Google Scholar 

  136. Lanza GA, Buffon A, Sestito A et al (2008) Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X. J Am Coll Cardiol 51:466–472

    Article  PubMed  Google Scholar 

  137. Galiuto L, Sestito A, Barchetta S et al (2007) Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X. Am J Cardiol 99:1378–1383

    Article  PubMed  Google Scholar 

  138. Galassi AR, Crea F, Araujo LI et al (1993) Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease. Am J Cardiol 72:134–139

    Article  PubMed  CAS  Google Scholar 

  139. Meeder JG, Blanksma PK, Crijns HJ et al (1995) Mechanisms of angina pectoris in syndrome X assessed by myocardial perfusion dynamics and heart rate variability. Eur Heart J 16:1571–1577

    PubMed  CAS  Google Scholar 

  140. Motz W, Vogt M, Rabenau O, Scheler S, Lückhoff A, Strauer BE (1991) Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Cardiol 68:996–1003

    Article  PubMed  CAS  Google Scholar 

  141. Egashira K, Inou T, Hirooka Y, Yamada A, Urabe Y, Takeshita A (1993) Evidence of impaired endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary angiograms. N Engl J Med 328:1659–1664

    Article  PubMed  CAS  Google Scholar 

  142. Quyyumi AA, Dakak N, Diodati JG, Gilligan DM, Panza JA, Cannon RO 3rd (1997) Effect of l-arginine on human coronary endothelium-dependent and physiologic vasodilation. J Am Coll Cardiol 30:1220–1227

    Article  PubMed  CAS  Google Scholar 

  143. Cannon RO 3rd, Watson RM, Rosing DR, Epstein SE (1983) Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol 1:1359–1373

    Article  PubMed  Google Scholar 

  144. Sestito A, Lanza GA, Di Monaco A et al (2011) Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X. J Cardiovasc Med (Hagerstown) 12:322–327

    Article  Google Scholar 

  145. Holdright DR, Clarke D, Poole-Wilson PA, Fox K, Collins P (1993) Endothelium dependent and independent responses in coronary artery disease measured at angioplasty. Br Heart J 70:35–42

    Article  PubMed  CAS  Google Scholar 

  146. Piatti P, Fragasso G, Monti LD et al (2003) Acute intravenous l-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: correlation with asymmetric dimethylarginine levels. Circulation 107:429–436

    Article  PubMed  CAS  Google Scholar 

  147. Setoguchi S, Mohri M, Shimokawa H, Takeshita A (2001) Tetrahydrobiopterin improves endothelial dysfunction in coronary microcirculation in patients without epicardial coronary artery disease. J Am Coll Cardiol 38:493–498

    Article  PubMed  CAS  Google Scholar 

  148. Shmilovich H, Deutsch V, Roth A, Miller H, Keren G, George J (2007) Circulating endothelial progenitor cells in patients with cardiac syndrome X. Heart 93:1071–1076

    Article  PubMed  Google Scholar 

  149. Scalone G, De Caterina A, Leone AM et al. Effect of exercise on circulating endothelial progenitor cells in patients with microvascular angina. Circ J 77:1777–1782

    Google Scholar 

  150. Chauhan A, Mullins PA, Taylor G, Petch MC, Schofield PM (1993) Effect of hyperventilation and mental stress on coronary blood flow in syndrome X. Br Heart J 69:516–524

    Article  PubMed  CAS  Google Scholar 

  151. Chauhan A, Petch MC, Schofield PM (1993) Effect of oesophageal acid instillation on coronary blood flow. Lancet 341:1309–1310

    Article  PubMed  CAS  Google Scholar 

  152. Kaski JC, Elliott PM, Salomone O et al (1995) Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J 74:620–624

    Article  PubMed  CAS  Google Scholar 

  153. Cox ID, Bøtker HE, Bagger JP, Sonne HS, Kristensen BO, Kaski JC (1999) Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms. J Am Coll Cardiol 34:455–460

    Article  PubMed  CAS  Google Scholar 

  154. Lanza GA, Lüscher TF, Pasceri V et al (1999) Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X. Am J Cardiol 84:1187–1191

    Article  PubMed  CAS  Google Scholar 

  155. Gaspardone A, Ferri C, Crea F et al (1998) Enhanced activity of sodium-lithium countertransport in patients with cardiac syndrome X: a potential link between cardiac and metabolic syndrome X. J Am Coll Cardiol 32:2031–2034

    Article  PubMed  CAS  Google Scholar 

  156. De Candia E, Lanza GA, Romagnoli E et al (2005) Abnormal pH-sensing of platelet Na+/H+ exchanger in patients with cardiac syndrome X. Int J Cardiol 100:371–376

    Article  PubMed  Google Scholar 

  157. Mohri M, Shimokawa H, Hirakawa Y, Masumoto A, Takeshita A (2003) Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J Am Coll Cardiol 41:15–19

    Article  PubMed  CAS  Google Scholar 

  158. Czernin J, Sun K, Brunken R, Böttcher M, Phelps M, Schelbert H (1995) Effect of acute and long-term smoking on myocardial blood flow and flow reserve. Circulation 91:2891–2897

    Article  PubMed  CAS  Google Scholar 

  159. Antony I, Lerebours G, Nitenberg A (1995) Loss of flow-dependent coronary artery dilatation in patients with hypertension. Circulation 91:1624–1628

    Article  PubMed  CAS  Google Scholar 

  160. Rosano GM, Collins P, Kaski JC, Lindsay DC, Sarrel PM, Poole-Wilson PA (1995) Syndrome X in women is associated with oestrogen deficiency. Eur Heart J 16:610–614

    PubMed  CAS  Google Scholar 

  161. Bøtker HE, Moller N, Schmitz O, Bagger JP, Nielsen TT (1997) Myocardial insulin resistance in patients with syndrome X. J Clin Invest 100:1919–1927

    Article  PubMed  Google Scholar 

  162. Dean JD, Jones CJ, Hutchison SJ, Peters JR, Henderson AH (1991) Hyperinsulinaemia and microvascular angina (“syndrome X”). Lancet 337:456–457

    Article  PubMed  CAS  Google Scholar 

  163. Conti E, Andreotti F, Sestito A et al (2002) Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol 89:973–975

    Article  PubMed  CAS  Google Scholar 

  164. Recio-Mayoral A, Rimoldi OE, Camici PG, Kaski JC. Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease. JACC Cardiovasc Imaging. In press

    Google Scholar 

  165. Galassi AR, Kaski JC, Crea F et al (1991) Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X. Am Heart J 122:458–463

    Article  PubMed  CAS  Google Scholar 

  166. Cemin R, Erlicher A, Fattor B, Pitscheider W, Cevese A (2008) Reduced coronary flow reserve and parasympathetic dysfunction in patients with cardiovascular syndrome X. Coron Artery Dis 19:1–7

    Article  PubMed  Google Scholar 

  167. Lanza GA, Giordano AG, Pristipino C et al (1997) Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidin myocardial scintigraphy. Circulation 96:821–826

    Article  PubMed  CAS  Google Scholar 

  168. Di Monaco A, Bruno I, Sestito A et al (2009) Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac syndrome X. Heart 95:550–554

    Article  PubMed  Google Scholar 

  169. Di Monaco A, Lanza GA, Bruno I et al (2010) Usefulness of impairment of cardiac adrenergic nerve function to predict outcome in patients with cardiac syndrome X. Am J Cardiol 106:1813–1818

    Article  PubMed  Google Scholar 

  170. Cannon RO 3rd, Quyyumi AA, Schenke WH et al (1990) Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. J Am Coll Cardiol 16:1359–1366

    Article  PubMed  Google Scholar 

  171. Pasceri V, Lanza GA, Buffon A, Montenero AS, Crea F, Maseri A (1998) Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol 31:62–66

    Article  PubMed  CAS  Google Scholar 

  172. Shapiro LM, Crake T, Poole-Wilson PA (1988) Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries? Clinical observations during cardiac catheterization. Br Med J 296:170–171

    Article  CAS  Google Scholar 

  173. Lagerqvist B, Silven C, Waldenstrom A (1992) Low threshold for adenosine induced chest pain in patients with angina pectoris and normal coronary angiogram. Br Heart J 68:282–283

    Article  PubMed  CAS  Google Scholar 

  174. Lanza GA, Crea F (2002) The complex link between brain and heart in cardiac syndrome X. Heart 88:328–330

    Article  PubMed  CAS  Google Scholar 

  175. Rosen SD, Paulesu E, Wise RJ, Camici PG (2002) Central neural contribution to the perception of chest pain in cardiac syndrome X. Heart 87:513–519

    Article  PubMed  CAS  Google Scholar 

  176. Valeriani M, Sestito A, Le Pera D et al (2005) Abnormal cortical pain processing in patients with cardiac syndrome X. Eur Heart J 26:975–982

    Article  PubMed  Google Scholar 

  177. Rosen SD, Paulesu E, Nihoyannopoulos P et al (1996) Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia. Ann Intern Med 124:939–949

    Article  PubMed  CAS  Google Scholar 

  178. Cohn PF, Fox KM, Daly C (2003) Silent myocardial ischemia. Circulation 108:1263–1277

    Article  PubMed  Google Scholar 

  179. Lanza GA, Manzoli A, Bia E, Crea F, Maseri A (1994) Acute effects of nitrates on exercise testing in patients with syndrome x. clinical and pathophysiological implications. Circulation 90:2695–2700

    Article  PubMed  CAS  Google Scholar 

  180. Picano E, Lattanzi F, Masini M, Distante A, L’Abbate A (1987) Usefulness of a high-dose dipyridamole-echocardiography test for diagnosis of syndrome X. Am J Cardiol 60:508–512

    Article  PubMed  CAS  Google Scholar 

  181. Russo G, Di Franco A, Lamendola P et al (2013) Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther [Epub ahead of print]

    Google Scholar 

  182. Lamendola P, Lanza GA, Spinelli A et al (2010) Long-term prognosis of patients with cardiac syndrome X. Int J Cardiol 140:197–199

    Article  PubMed  Google Scholar 

  183. Kaski JC, Rosano GMC, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA (1995) Cardiac syndrome X: clinical characteristics and left ventricular function: long-term follow-up study. J Am Coll Cardiol 25:807–814

    Article  PubMed  CAS  Google Scholar 

  184. Romeo F, Rosano GM, Martuscelli E, Lombardo L, Valente A (1993) Long-term follow-up of patients initially diagnosed with syndrome X. Am J Cardiol 71:669–673

    Article  PubMed  CAS  Google Scholar 

  185. Radice M, Giudici V, Marinelli G (1995) Long-term follow-up in patients with positive exercise test and angiographically normal coronary arteries (syndrome X). Am J Cardiol 75:620–621

    Article  PubMed  CAS  Google Scholar 

  186. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G (2004) Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation 109:2518–2523

    Article  PubMed  Google Scholar 

  187. Bugiardini R, Manfrini O, De Ferrari GM (2006) Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography. Arch Intern Med 166:1391–1395

    Article  PubMed  Google Scholar 

  188. Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U (2008) Coronary artery spasm as a frequent cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study. J Am Coll Cardiol 52:523–527

    Article  PubMed  Google Scholar 

  189. Lanza GA (2007) Cardiac syndrome X: a critical overview and future perspectives. Heart 93:159–166

    Article  PubMed  CAS  Google Scholar 

  190. Lanza GA, Sestito A, Iacovella S et al (2003) Relation between platelet response to exercise and coronary angiographic findings in patients with effort angina. Circulation 107:1378–1382

    Article  PubMed  Google Scholar 

  191. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators (1997) A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 336:1621–1628

    Google Scholar 

  192. Chauhan A, Mullins PA, Thuraisingham SI, Petch MC, Schofield PM (1993) Clinical presentation and functional prognosis in syndrome X. Br Heart J 70:346–351

    Article  PubMed  CAS  Google Scholar 

  193. Beltrame JF, Limaye SB, Horowitz JD (2002) The coronary slow flow phenomenon: a new coronary microvascular disorder. Cardiology 97:197–202

    Article  PubMed  Google Scholar 

  194. Beltrame JF, Limaye SB, Wuttke RD, Horowitz JD (2003) Coronary hemodynamic and metabolic studies of the coronary slow flow phenomenon. Am Heart J 146:84–90

    Article  PubMed  Google Scholar 

  195. Mangieri E, Macchiarelli G, Ciavolella M et al (1996) Slow coronary flow: clinical and histopathological features in patients with otherwise normal epicardial coronary arteries. Cathet Cardiovasc Diagn 37:375–381

    Article  PubMed  CAS  Google Scholar 

  196. Reynolds HR, Srichai MB, Iqbal SN et al (2011) Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease. Circulation 124:1414–1425

    Article  PubMed  Google Scholar 

  197. Yilmaz A, Mahrholdt H, Athanasiadis A et al (2008) Coronary vasospasm as the underlying cause for chest pain in patients with PVB19 myocarditis. Heart 94:1456–1463

    Article  PubMed  CAS  Google Scholar 

  198. Mohri M, Koyanagi M, Egashira K et al (1998) Angina pectoris caused by coronary microvascular spasm. Lancet 351:1165–1169

    Article  PubMed  CAS  Google Scholar 

  199. Bybee KA, Prasad A (2008) Stress-related cardiomyopathy syndromes. Circulation 118:397–409

    Article  PubMed  Google Scholar 

  200. Parodi G, Bellandi B, Del Pace S et al (2011) Tuscany registry of Tako-Tsubo cardiomyopathy. Natural history of Tako-Tsubo cardiomyopathy. Chest 139:887–892

    Article  PubMed  Google Scholar 

  201. Wittstein IS, Thiemann DR, Lima JAC et al (2005) Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352:539–548

    Article  PubMed  CAS  Google Scholar 

  202. Baumgart D, Heusch G (1995) Neuronal control of coronary blood flow. Basic Res Cardiol 90:142–159

    Article  PubMed  CAS  Google Scholar 

  203. Galiuto L, De Caterina AR, Porfidia A et al (2010) Reversible coronary microvascular dysfunction: a common pathogenetic mechanism in apical ballooning or Tako-Tsubo syndrome. Eur Heart J 31:1319–1327

    Article  PubMed  Google Scholar 

  204. Kume T, Akasaka T, Kawamoto T et al (2004) Relationship between coronary flow reserve and recovery of regional left ventricular dysfunction in patients with tako-tsubo-like transient left ventricular dysfunction. J Cardiol 43:123–129

    PubMed  Google Scholar 

  205. Meimoun P, Malaquin D, Sayah S et al (2008) The coronary flow reserve is transiently impaired in tako-tsubo cardiomyopathy: a prospective study using serial doppler transthoracic echocardiography. J Am Soc Echocardiogr 21:72–77

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiovascular Sciences, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli, 8, 00168, Rome, Italy

    Filippo Crea & Gaetano A. Lanza

  2. Division of Cardiovascular Medicine, “Vita e Salute” University and Istituto Scientifico San Raffaele, Via Olgettina, 60, 20132, Milan, Italy

    Paolo G. Camici

Authors
  1. Filippo Crea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaetano A. Lanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo G. Camici
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Filippo Crea .

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Italia

About this chapter

Cite this chapter

Crea, F., Lanza, G.A., Camici, P.G. (2014). CMD in the Absence of Myocardial Diseases and Obstructive CAD. In: Coronary Microvascular Dysfunction. Springer, Milano. https://doi.org/10.1007/978-88-470-5367-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-5367-0_4

  • Published:

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-5366-3

  • Online ISBN: 978-88-470-5367-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation