Serious and potentially life threatening complications of cardiac stress testing: Physiological mechanisms and management strategies

Journal of Nuclear Cardiology

Volumn 22, Issue 6, 2015, Pages 1198-1213

  Dilsizian, Vasken ^a   Gewirtz, Henry ^b   Paivanas, Nicholas ^c   Kitsiou, Anastasia N ^d   Hage, Fadi G ^e   Crone, Nathan E ^f   Schwartz, Ronald G ^c  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^d SISMANOGLIO HOSPITAL   (Greece)

^e University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center   (United States)

^f JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; CORONARY VASODILATING AGENT; DIPYRIDAMOLE; DOBUTAMINE; REGADENOSON; VASODILATOR AGENT;

ACUTE HEART INFARCTION; AORTA STENOSIS; AORTA VALVE DISEASE; ARTICLE; ATRIAL FIBRILLATION; ATRIOVENTRICULAR BLOCK; BRONCHOCONSTRICTION; CARDIOMYOPATHY; CARDIOPULMONARY EXERCISE TEST; CEREBROVASCULAR ACCIDENT; CLINICAL EVALUATION; COMORBIDITY; DIZZINESS; DYSPNEA; GASTROINTESTINAL SYMPTOM; HEADACHE; HEART ARREST; HEART ATRIUM FLUTTER; HEART FAILURE; HEART LEFT VENTRICLE HYPERTROPHY; HEART LEFT VENTRICLE OUTFLOW TRACT OBSTRUCTION; HEART MUSCLE ISCHEMIA; HEART SINOATRIAL BLOCK; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE TACHYCARDIA; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; HYPOTENSION; ISCHEMIC HEART DISEASE; JAW PAIN; NECK PAIN; PATHOPHYSIOLOGY; PHARMACOLOGIC STRESS TESTING; PRIORITY JOURNAL; RISK FACTOR; SEIZURE; THORAX PAIN; TRANSIENT ISCHEMIC ATTACK; TREADMILL EXERCISE; ADVERSE EFFECTS; CHEMICALLY INDUCED; EVIDENCE BASED MEDICINE; EXERCISE TEST; HEART FUNCTION TEST; HYPERTENSION; MYOCARDIAL ISCHEMIA; RISK ASSESSMENT;

EVIDENCE-BASED MEDICINE; EXERCISE TEST; HEART FUNCTION TESTS; HUMANS; HYPERTENSION; HYPOTENSION; MYOCARDIAL ISCHEMIA; RISK ASSESSMENT; VASODILATOR AGENTS;

EID: 84947614608     PISSN: 10713581     EISSN: 15326551     Source Type: Journal    
DOI: 10.1007/s12350-015-0141-4     Document Type: Article

References (125)

1. Henzlova MJ, Cerqueira MD, Hansen CL, Taillefer R, Yao S-S. ASNC imaging guidelines for nuclear cardiology procedures. J Nucl Cardiol 2009;16:331.
2. Douglas PS, Khandheria B, Stainback RF, Weissman NJ. ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress echocardiography. J Am Coll Cardiol 2008;51:1127-47.
3. Marwick TH, Case C, Vasey C, Allen S, Short L, Thomas JD. Prediction of mortality by exercise echocardiography: A strategy for combination with the Duke treadmill score. Circulation 2001;103:2566-71.
4. Schwartz RG, Pearson TA, Kalaria VG, Mackin ML, Williford DJ, Awasthi A, et al. Prospective serial evaluation of myocardial perfusion and lipids during the first six months of pravastatin therapy: Coronary artery disease regression single photon emission computed tomography monitoring trial. J Am Coll Cardiol 2003;42:600-10.
5. AlJaroudi WA, Alraies MC, Cerquiera MD, Jaber WA. Safety and tolerability of regadenoson in 514 SPECT MPI patients with and without coronary artery disease and submaximal exercise heart rate response. Eur J Nucl Med Mol Imaging 2013;40:341-8.
6. Cavalcante JL, Barboza J, Ananthasubramaniam K. Regadenoson is a safe and well-tolerated pharmacological stress agent for myocardial perfusion imaging in post-heart transplant patients. J Nucl Cardiol 2011;18:628-33.
7. Cerqueira MD, Nguyen P, Staehr P, Underwood SR, Iskandrian AE. Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results. J Am Coll Cardiol Img 2008;1:307-16.
8. Doukky R, Morales Demori R, Jain S, Kiriakos R, Mwansa V, Calvin JE. Attenuation of the side effect profile of regadenoson: A randomized double-blinded placebo-controlled study with aminophylline in patients undergoing myocardial perfusion imaging. “The ASSUAGE trial”. J Nucl Cardiol 2012;19:448-57.
9. Ghimire G, Hage FG, Hoe J, Iskandrian AE. Regadenoson: A focused update. J Nucl Cardiol 2013;20:284-8.
10. Hage FG. Regadenoson for myocardial perfusion imaging: Is it safe? J Nucl Cardiol 2014;21:871-6.
11. Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA, et al. Exercise standards for testing and training: A scientific statement from the American Heart Association. Circulation 2013;128:873-934.
12. Mark DB, Shaw L, Harrell FE, Hlatky MA, Lee KL. Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease. N Engl J Med 1991;325:849-53.
13. Hachamovitch R, Berman DS, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA. Exercise myocardial perfusion SPECT in patients without known coronary artery disease: Incremental prognostic value and use in risk stratification. Circulation 1996;93(5):905-14.
14. Navarre SM, Mather JF, Shaw LJ, Fowler MS, Heller GV. Comparison of risk stratification with pharmacologic and exercise stress myocardial perfusion imaging: A meta-analysis. J Nucl Cardiol 2004;11:551-61.
15. Mahmarian JJ, Shaw LJ, Olszewski GH, Pounds BK, Frias ME, Pratt CM. INSPIRE Investigators. Adenosine sestamibi SPECT post-infarction evaluation (INSPIRE) trial: A randomized, prospective multicenter trial evaluating the role of adenosine Tc-99m sestamibi SPECT for assessing risk and therapeutic outcomes in survivors of acute myocardial infarction. J Nucl Cardiol 2004;11:458-69.
16. Geleijnse ML, Elhendy A, van Domburg RT, Cornel JH, Reijs AE, Roelandt JR, Krenning EP, Fioretti PM. Prognostic value of dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain. J Am Coll Cardiol 1996;28:447-54.
17. Dorbala S, Di Carli MF, Beanlands RS, Merhige ME, Williams BA, Veledar E, Chow BJ, Min JK, Pencina MJ, Berman DS, Shaw LJ. Prognostic value of stress myocardial perfusion positron emission tomography: Results from a multicenter observational registry. J Am Coll Cardiol 2013;61:176-84.
18. Taqueti VR, Hachamovitch R, Murthy VL, Naya M, Foster CR, Hainer J, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation 2015;131:19-27.
19. Poliner LR, Dehmer GJ, Lewis SE, Parkey RW, Blomqvist CG, Willerson JT. Left ventricular performance in normal subjects: A comparison of the responses to exercise in the upright and supine positions. Circulation 1980;62:528-34.
20. Tune JD, Richmond KN, Gorman MW, Olsson RA, Feigl EO. Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise. Am J Physiol Heart Circ Physiol 2000;278:H74-84.
21. Bache RJ, Dai XZ, Schwartz JS, Homans DC. Role of adenosine in coronary vasodilation during exercise. Circ Res 1988;62:846-53.
22. De Feo P, Di Loreto C, Lucidi P, Murdolo G, Parlanti N, De Cicco A, Piccioni F, Santeusanio F. Metabolic response to exercise. J Endocrinol Invest 2003;26:851-4.
23. Biagini E, Shaw LJ, Poldermans D, Schinkel AF, Rizzello V, Elhendy A, et al. Accuracy of non-invasive techniques for diagnosis of coronary artery disease and prediction of cardiac events in patients with left bundle branch block: A meta-analysis. Eur J Nucl Med Mol Imaging 2006;33:1442-51.
24. Kumar V, Venkataraman R, Aljaroudi W, Osorio J, Heo J, Iskandrian AE, et al. Implications of left bundle branch block in patient treatment. Am J Cardiol 2013;111:291-300.
25. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, et al. 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2013;61:e6-75.
26. Pediatric and Congenital Electrophysiology Society. (PACES)1; Heart Rhythm Society (HRS); American College of Cardiology Foundation (ACCF); American Heart Association (AHA); American Academy of Pediatrics (AAP); Canadian Heart Rhythm Society (CHRS). PACES/HRS expert consensus statement on the management of the asymptomatic young patient with a Wolff-Parkinson-White (WPW, ventricular preexcitation) electrocardiographic pattern. Heart Rhythm 2012;9:1006-24.
27. Myers J, Forman DE, Balady GJ, Franklin BA, Nelson-Worel J, Martin B-J, et al. Supervision of exercise testing by nonphysicians: A scientific statement from the American Heart Association. Circulation 2014;130:1014-27.
28. Myers J, Arena R, Franklin B, Pina I, Kraus WE, McInnis K, et al. Recommendations for clinical exercise laboratories: A scientific statement from the American Heart Association. Circulation 2009;119:3144-61.
29. Varga A, Garcia MA, Picano E. Safety of stress echocardiography (from the International Stress Echo Complication Registry). Am J Cardiol 2006;98:541-3.
30. Myers J, Voodi L, Umann T, Froelicher VF. A survey of exercise testing: Methods, utilization, interpretation, and safety in the VAHCS. J Cardiopulm Rehabil 2000;20:251-8.
31. Iskandrian AS, Heo J, Kong B, Lyons E. Effect of exercise level on the ability of thallium-201 tomographic imaging in detecting coronary artery disease: Analysis of 461 patients. J Am Coll Cardiol 1989;14:1477-86.
32. Overgaard CB, Dzavik V. Inotropes and vasopressors: Review of physiology and clinical use in cardiovascular disease. Circulation 2008;118:1047-56.
33. Lattanzi F, Picano E, Adamo E, Varga A. Dobutamine stress echocardiography safety in diagnosing coronary artery disease. Drug Saf 2000;22:251-62.
34. Elhendy A, van Domburg RT, Bax JJ, Valkema R, Reijs AE, Krenning EP, Roelandt JR. Safety, hemodynamic profile, and feasibility of dobutamine stress technetium myocardial perfusion single-photon emission CT imaging for evaluation of coronary artery disease in the elderly. Chest 2000;117:649-56.
35. Mathias W Jr, Arruda A, Santos FC, Arruda AL, Mattos E, Osório A, et al. Safety of dobutamine-atropine stress echocardiography: A prospective experience of 4033 consecutive studies. J Am Soc Echocardiogr 1999;12:785-91.
36. Sheldon SH, Askew JW 3rd, Klarich KW, Scott CG, Pellikka PA, McCully RB. Occurrence of atrial fibrillation during dobutamine stress echocardiography: Incidence, risk factors, and outcomes. J Am Soc Echocardiogr 2011;24:86-90.
37. Geleijnse ML, Elhendy A, Fioretti PM, Roelandt JR. Dobutamine stress myocardial perfusion imaging. J Am Coll Cardiol 2000;36:2017-27.
38. Elhendy A, Valkema R, van Domburg RT, Bax JJ, Nierop PR, Cornel JH, et al. Safety of dobutamine-atropine stress myocardial perfusion scintigraphy. J Nucl Med 1998;39:1662-6.
39. Geleijnse ML, Krenning BJ, Nemes A, van Dalen BM, Soliman OI, Ten Cate FJ, et al. Incidence, pathophysiology, and treatment of complications during dobutamine-atropine stress echocardiography. Circulation 2010;121:1756-67.
40. Lexi-Drugs: Dobutamine [online] (Wolters Kluwer Health, 2015). Accessed January 15, 2015.
41. Tanimoto M, Pai RG, Jintapakorn W, Shah PM. Mechanisms of hypotension during dobutamine stress echocardiography in patients with coronary artery disease. Am J Cardiol 1995;76:26-30.
42. Lewandowski TJ, Armstrong WF, Bach DS. Reduced test time by early identification of patients requiring atropine during dobutamine stress echocardiography. J Am Soc Echocardiogr 1998;11:236-42.
43. Tsutsui JM, Osório AF, Lario FA, Fernandes DR, Sodre G, Andrade JL, et al. Comparison of safety and efficacy of the early injection of atropine during dobutamine stress echocardiography with the conventional protocol. Am J Cardiol 2004;94:1367-72.
44. Auchampach JA, Bolli R. Adenosine receptor subtypes in the heart: Therapeutic opportunities and challenges. Am J Physiol 1999;276(3 Pt 2):H1113-6.
45. Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Muller CE. International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors—an update. Pharmacol Rev 2011;63:1-34.
46. Lerman BB, Belardinelli L. Cardiac electrophysiology of adenosine. Basic and clinical concepts. Circulation 1991;83:1499-509.
47. Chan SY, Brunken RC, Czernin J, Porenta G, Kuhle W, Krivokapich J, et al. Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men. J Am Coll Cardiol 1992;20:979-85.
48. Kubo S, Tadamura E, Toyoda H, Mamede M, Yamamuro M, Magata Y, et al. Effect of caffeine intake on myocardial hyperemic flow induced by adenosine triphosphate and dipyridamole. J Nucl Med 2004;45:730-8.
49. Al Jaroudi W, Iskandrian AE. Regadenoson: A new myocardial stress agent. J Am Coll Cardiol 2009;54:1123-30.
50. Gewirtz H, Brown P, Most AS. Measurement of plasma adenosine concentration: Methodologial and physiological considerations. Proc Soc Exp Biol Med 1987;185:93-100.
51. Mahmarian JJ, Cerqueira MD, Iskandrian AE, Bateman TM, Thomas GS, Hendel RC, Moye LA, Olmsted AW. Regadenoson induces comparable left ventricular perfusion defects as adenosine: A quantitative analysis from the ADVANCE MPI 2 trial. J Am Coll Cardiol Img 2009;2:959-68.
52. Johnson NP, Gould KL. Regadenoson versus dipyridamole hyperemia for cardiac positron emission tomography imaging. J Am Coll Cardiol Img 2015;8(4):438–47.
53. Sinusas AJ. Does a shortened hyperemia with regadenoson stress pose a concern for quantitative rubidium-82 PET imaging? Optimization of regadenoson PET imaging. J Am Coll Cardiol Img 2015;8(4):448–50.
54. Dilsizian V, Narula J. Capturing maximal coronary vasodilation for myocardial perfusion imaging: Is Timing Everything? J Am Coll Cardiol Img 2015;8(4):499–500.
55. Dilsizian V. Connectivity of radiotracers to vasodilators: Is thallium the missing link ? J Am Coll Cardiol Img 2009;2:1209-12.
56. Dilsizian V, Narula J. Qualitative and quantitative scrutiny by regulatory process: Is the truth subjective or objective ? J Am Coll Cardiol Img 2009;2:1037-8.
57. Iskandrian AE, Bateman TM, Belardinelli L, Blackburn B, Cerqueira MD, Hendel RC, et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: Results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol 2007;14:645-58.
58. Gui L, Duan W, Tian H, Li C, Zhu J, Chen JF, Adenosine A, et al. 2A receptor deficiency reduces striatal glutamate outflow and attenuates brain injury induced by transient focal cerebral ischemia in mice. Brain Res 2008;1297(185-193):59.
59. Thomas GS, Tammelin BR, Schiffman GL, Marquez R, Rice DL, Milikien D, et al. Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial). J Nucl Cardiol 2008;15:319-28.
60. Doran JA, Sajjad W, Gupta R, Mackin ML, Schwartz RG. Caffeine reversal of adverse effects associated with regadenoson radionuclide tomographic myocardial perfusion imaging. Accepted Poster Presentation, ASNC Boston, MA. J Nucl Cardiol 2014;21:769.
61. Lette J, Tatum JL, Fraser S, Miller DD, Waters DD, Heller G, et al. Safety of dipyridamole testing in 73,806 patients: The multicenter dipyridamole safety study. J Nucl Cardiol 1995;2:3-17.
62. Sadeghi M, Schwartz RG, Beanlands RS, Al-Mallah MH, Bengel MF, Borges-Neto S, et al. Balancing proven clinical value and potential radiation risk. J Nucl Med 2011;52:1162-4.
63. Gerber TC, Gibbons RJ. Weighing the risks and benefits of cardiac imaging with ionizing radiation. J Am Coll Cardiol Img 2010;3:528-35.
64. Beanlands R. Re: Radiation exposure from medical imaging. Letter to the editor; CMA 2011 Published May 12, 2011.
65. Thomas GS, Thompson RC, Miyamoto MI, et al. The RegEx trial: A randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A(2A) adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging. J Nucl Cardiol 2008;16:63-72.
66. Prenner BM, Bukofzer S, Behm S, et al. A randomized, double-blind, placebo-controlled study assessing the safety and tolerability of regadenoson in subjects with asthma or chronic obstructive pulmonary disease. J Nucl Cardiol 2012;19:681-92.
67. Ananthasubramaniam K, Weiss R, McNutt B, et al. A randomized, double-blind, placebo-controlled study of the safety and tolerance of regadenoson in subjects with stage 3 or 4 chronic kidney disease. J Nucl Cardiol 2012;19:319-29.
68. Parker MW, Morales DC, Slim HB, et al. A strategy of symptom-limited exercise with regadenoson-as-needed for stress myocardial perfusion imaging: A randomized controlled trial. J Nucl Cardiol 2013;20:185-96.
69. Ross MI, Wu E, Wilkins JT, et al. Safety and feasibility of adjunctive regadenoson injection at peak exercise during exercise myocardial perfusion imaging: The both exercise and regadenoson stress test (BERST) trial. J Nucl Cardiol 2013;20:197-204.
70. McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol 2008;51:1419-28.
71. http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm142889.htm.
72. Wang Y, Alkasab TK, Narin O, Nazarian RM, Kaewlai R, Kay J, Abujudeh HH. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011;260(1):105-11.
73. Zou Z, Zhang HL, Roditi GH, Leiner T, Kucharczyk W, Prince MR. Nephrogenic systemic fibrosis: Review of 370 biopsy-confirmed cases. J Am Coll Cardiol Img 2011;4(11):1206-16.
74. Cerqueira MD, Verani MS, Schwaiger M, Hoe J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: Results from the Adenoscan Multicenter Trial Registry. J Am Coll Cardiol 1994;23:384-9.
75. FDA. FDA warns of rare but serious risk of heart attack and death with cardiac nuclear stress test drugs Lexiscan (regadenoson) and Adenoscan (adenosine). 2013:1-4. at http://www.fda.gov/Drugs/DrugSafety/ucm375654.htm.
76. AMR Data at www.amr-data.com. Accessed June 9, 2014.
77. Doukky R, Rangel MO, Wassouf M, Dick R, Alqaid A, Morales Demori R. The safety and tolerability of regadenoson in patients with end-stage renal disease: The first prospective evaluation. J Nucl Cardiol 2013;20:205-13.
78. AlJaroudi W, Iqbal F, Koneru J, Bhambhvani P, Heo J, Iskandrian AE. Safety of regadenoson in patients with end-stage liver disease. J Nucl Cardiol 2011;18:90-5.
79. Gao Z, Li Z, Baker SP, Lasley RD, Meyer S, Elzein E, et al. Novel short-acting A 2A adenosine receptor agonists for coronary vasodilation: Inverse relationship between affinity and duration of action of A 2A agonists. J Pharmacol Exp Ther 2001;298:209-18.
80. Rosenblatt J, Mooney D, Dunn T, Cohen M. Asystole following regadenoson infusion in stable outpatients. J Nucl Cardiol 2014;21:862-8.
81. Pandit A, Unzek Freiman S. Complete heart block associated with regadenoson: A real side effect. J Nucl Cardiol 2012;19:1236-9.
82. Underwood SR, Latus KA, Reyes E, Standbridge K, Walker S, Wechalekar K. Regadenoson-induced bradycardia and hypotension: Possible mechanism and antidote. J Nucl Cardiol 2014;21:1040-83.
83. Grady EC, Barron JT, Wagner RH. Development of asystole requiring cardiac resuscitation after the administration of regadenoson in a patient with pulmonary fibrosis receiving n-acetylcysteine. J Nucl Cardiol 2011;18:521-5.
84. Dhalla AK, Wong M, Wang W, Biaggioni I, Belardinelli L. Tachycardia caused by A 2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats. J Pharmacol Exp Ther 2006;316:695-702.
85. Zhao G, Serpllion S, Shryock J, Messina E, Xu X, Ochoa M, et al. Regadenoson, a novel pharmacologic stress agent for use in myocardial perfusion imaging, does not have a direct effect on the QT interval in conscious dogs. J Cardiovasc Pharmacol 2008;52:467-73.
86. Zoghbi GJ, Iskandrian AE. Selective adenosine agonists and myocardial perfusion imaging. J Nucl Cardiol 2012;19:126-41.
87. Golzar Y, Doukky R. Regadenoson use in patients with chronic obstructive pulmonary disease: The state of current knowledge. Int J Chron Obstruct Pulmon Dis 2014;9:129-37.
88. Doukky R, Hayes K, Frogge N, Balakrishnan G, Dontaraju VS, Rangel MO, et al. Impact of appropriate use on the prognostic value of single-photon emission computed tomography myocardial perfusion imaging. Circulation 2013;128:1634-43.
89. Page RL, Spurck P, Bainbridge JL, Michalek J, Quaife RA. Seizures associated with regadenoson: A case series. J Nucl Cardiol 2012;19:389-91.
90. Lexiscan and Convulsion. DrugCite (2014) Retrieved from http://www.drugcite.com/indi/?q=LEXISCAN&s=&a=&i=CONVULSION.
91. Masino SA, Kawamura M Jr, Ruskin DN. Chapter eleven—adenosine receptors and epilepsy: Current evidence and future potential. Int Rev Neurobiol 2014;119:233-55.
92. Fukuda M, Suzuki Y, Hino H, Morimoto T, Ishii E. Activation of central adenosine A(2A) receptors lowers the seizure threshold of hyperthermia-induced seizure in childhood rats. Seizure 2011;20:156-9.
93. Chen J, Pedata F. Modulation of ischemic brain injury and neuroinflammation by adenosine A2A receptors. Curr Pharm Des 2008;14:1-2.
94. Melani A, Pugliese AM, Pedata F. Chapter thirteen—adenosine receptors in cerebral ischemia. Int Rev Neurobiol 2014;11:309-48.
95. Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947.
96. http://www.fda.gov/Drugs/DrugSafety/ucm375654.htm.
97. Hsi DH, Marreddy R, Moshiyakhov M, Luft U. Regadenoson induced acute ST-segment elevation myocardial infarction and multivessel coronary thrombosis. J Nucl Cardiol 2013;20:481-4.
98. Shah S, Parra D, Rosenstein RS. Acute myocardial infarction during regadenoson myocardial perfusion imaging. Pharmacotherapy 2013;33:e90-5.
99. Johnson NP, Gould KL. Physiological basis for angina and ST-segment change PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve. J Am Coll Cardiol Img 2011;4:990-8.
100. Seiler C. The human coronary collateral circulation. Heart 2003;89:1352-7.
101. Gewirtz H, Gross SL, Williams DO, Most AS. Contrasting effects of nifedipine and adenosine on regional myocardial flow distribution and metabolism distal to a severe coronary arterial stenosis: Observations in sedated, closed-chest, domestic swine. Circulation 1984;69:1048-57.
102. Kern MJ. Walking with Sir William. Reflections on collateral steal, recruitment, and ischemic protection. J Am Coll Cardiol 2006;48:66-9.
103. Akinboboye OO, Idris O, Chou RL, Sciacca RR, Cannon PJ, Bergmann SR. Absolute quantitation of coronary steal induced by intravenous dipyridamole. J Am Coll Cardiol 2001;37:109-16.
104. Werner GS, Figulla HR. Direct assessment of coronary steal and associated changes of collateral hemodynamics in chronic total coronary occlusions. Circulation 2002;106:435-40.
105. Dilsizian V, Taillefer R. Journey in evolution of nuclear cardiology: Will there be another quantum leap with the F-18 labeled myocardial perfusion tracers? J Am Coll Cardiol Img 2012;5:1269-84.
106. He ZX, Shi RF, Wu YJ, et al. Direct imaging of exercise-induced myocardial ischemia with fluorine-18-labeled deoxyglucose and Tc-99m sestamibi in coronary artery disease. Circulation 2003;108:1208-13.
107. Dilsizian V. FDG uptake as a surrogate marker for antecedent ischemia. J Nucl Med 2008;49:1909-11.
108. Dilsizian V, Bateman TM, Bergmann SR, Des Prez R, Magram M, Goodbody AE, et al. Metabolic imaging with β-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) identifies ischemic memory following demand ischemia. Circulation 2005;112:2169-74.
109. Marwick TH, Dilsizian V, Narula J. Ischemic episode and hanging on to a painful memory…. J Am Coll Cardiol Img 2012;5:126-8.
110. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78-140.
111. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;64:e139-228.
112. Gimelli A, Schneider-Eicke J, Neglia D, Sambuceti G, Giorgetti A, Bigalli G, et al. 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 1998;31:366-73.
113. Strauer BE, Schwartzkopff B, Kelm M. Assessing the coronary circulation in hypertension. J Hypertens 1998;16:1221-33.
114. Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res 2012;110:1109-24.
115. Davies MJ, McKenna WJ. Hypertrophic cardiomyopathy-pathology and pathogenesis. Histopathology 1995;26:493-500.
116. Dilsizian V, Bonow RO, Epstein SE, Fananapazir L. Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1993;22:796-804.
117. Dilsizian V, Panza JA, Bonow RO. Myocardial perfusion imaging in hypertrophic cardiomyopathy. J Am Coll Cardiol Img 2010;3:1078-80.
118. Rajappan K, Rimoldi OE, Dutka DP, Ariff B, Pennell DJ, Sheridan DJ, et al. Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries. Circulation 2002;105:470-6.
119. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:e57-185.
120. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96.
121. Samuels B, Kiat H, Friedman JD, Berman DS. Adenosine pharmacologic stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis. Diagnostic efficacy and comparison of clinical, hemodynamic and electrocardiographic variables with 100 age-matched control subjects. J Am Coll Cardiol 1995;25:99-106.
122. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356:830-40.
123. Udelson JE. Heart failure with preserved ejection fraction. Circulation 2011;124:e540-3.
124. Shannon RP, Komamura K, Shen YT, Bishop SP, Vatner SF. Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure. Am J Physiol 1993;265(3 Pt 2):H801-9.
125. Neglia D, Parodi O, Gallopin M, Sambuceti G, Giorgetti A, Pratali L, et al. Myocardial blood flow response to pacing tachycardia and to dipyridamole infusion in patients with dilated cardiomyopathy without overt heart failure. A quantitative assessment by positron emission tomography. Circulation 1995;92:796-804.