Summary
In recent years it has become clear that episodes of transient myocardial ischemia commonly occur in patients with coronary artery disease in the absence of chest pain or angina equivalent. These episodes of “silent myocardial ischemia” are particularly well documented during continuous ambulatory electrocardiographic monitoring in daily life. Evidence suggests that these episodes represent true ischemia, and appear to be a marker of unfavorable outcome. While the pathophysiology is not completely understood, it appears as though the mechanisms of angina and silent ischemia are the same. Both forms of ischemia respond to conventional antianginal medication. While long-acting nitrates are effective in reducing or preventing myocardial ischemia, because of their propensity to cause tolerance they should be used intermittently and in association with either beta-blockers or calcium antagonists. Nitrates are safe and comparatively inexpensive, and will continue to play an important role in the treatment and prevention of angina. However, in the light of current knowledge, there is no specific indication for the treatment of silent ischemia by nitrates.
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References
Wood P, McGregor M, Magidson O, Whittaker W. The effort test in angina pectoris.Br Heart J 1950;12:363.
Stern S, Tzivoni D. Early detection of silent ischaemic heart disease by 24-hour electrocardiographic monitoring of active subjects.Br Heart J 1974;36:481–486.
Deanfield JE, Selwyn AP, Chierchia S, et al. Myocardial ischaemia during daily life in patients with stable angina: Its relation to symptoms and heart rate changes.Lancet 1983; 1:753–758.
Levy RD, Shapiro LM, Wright C, Mockus L, Fox KM. Haemodynamic response to myocardial ischaemia during unrestricted activity, exercise testing, and atrial pacing assessed by ambulatory pulmonary artery pressure monitoring.Br Heart J 1986;56:12–18.
Collins P, Fox KM. Pathophysiology of angina.Lancet 1990;335:94–96.
Rozanski A, Bairey N, Krantz DS, et al. Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease.N Engl J Med 1988;318:1005–12.
Mulcahy D, Keegan J, Fox KM. Characteristics of silent and painful ischaemia during ambulatory monitoring in patients with coronary arterial disease.Int J Cardiol 1990;28:377–379.
Pepine CJ. Is silent ischemia a treatable risk factor in patients with angina pectoris?Circulation 1990;82(Suppl II135–II142).
Cohn PF.Silent Myocardial Ischemia and Infarction, 2nd ed. New York: Marcel Dekker, 1989.
Mulcahy D, Keegan J, Crean P, et al. Silent myocardial ischaemia in chronic stable angina: A study of its frequency and characteristics in 150 patients.Br Heart J 1988;60:417–423.
Mulcahy D, Keegan J, Lindsay D, et al. Silent myocardial ischaemia in patients referred for coronary artery bypass surgery because of angina: A comparison with patients whose symptoms were well controlled on medical treatment.Br Heart J 1989;61:496–501.
Knight AA, Hollenberg M, London MJ, et al. Myocardial ischemia in patients awaiting coronary artery bypass grafting.Am Heart J 1989;117:1189–1195.
Mulcahy D, Phadke K, Eastick S, Walesby R, Davies M, Fox K. Recurrent transient episodes of myocardial ischemia: Effects at a cellular and clinical level.Circulation 1992;86(Suppl 1):1–116.
Hess OM, Schneider J, Nonogi H, et al. Myocardial structure in patients with exercise-induced ischemia.Circulation 1988;77:967–977.
Løchen M-L. The Tromso study; the prevalence of exercise-induced silent myocardial ischemia and relation to risk factors for coronary heart disease in an apparently healthy population.Eur Heart J 1992;13:728–731.
Epstein SE, Quyyumi AA, Bonow RO. Myocardial ischemia—silent or symptomatic.N Engl J Med 1988;318:1038–1043.
Mulcahy D, Parameshwar J, Holdright D, et al. Value of ambulatory ST segment monitoring in patients with chronic stable angina: Does measurement of the ‘total ischaemic burden’ assist with management?Br Heart J 1992;67:47–52.
Detry JMR, Luwaert RJ, Melin JA. Prognostic significance of silent exertional myocardial ischaemia in symptomatic men without previous myocardial infarction.Eur Heart J 1992;13:183–187.
Tzivoni D, Gavish A, Zin D, et al. Prognostic significance of ischemic episodes in patients with previous myocardial infarction.Am J Cardiol 1988;62:661–664.
Mulcahy D, Keegan J, Cunningham D, et al. Circadian variation of total ischaemic burden and its alteration with antianginal agents.Lancet 1988;2:755–759.
Willich SN, Linderer T, Wegscheider K, Leizorovicz A, Alamercery I, Schroder R. Increased morning incidence of myocardial infarction in the ISAM study: Absence with prior beta-adrenergic blockade.Circulation 1989;80:853–858.
Muller JE, Ludmer PL, Willich SN, et al. Circadian variation in the frequency of sudden cardiac death.Circulation 1987;75:131–138.
Purcell H, Mulcahy D, Fox K. Circadian patterns of myocardial ischaemia and the effects of antianginal drugs.Chronobiol Int 1991;8:309–320.
Egstrup K. Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia.Am Heart J 1991;122:648–655.
Barsotti A. Silent myocardial ischaemia; to treat or not to treat?Eur Heart J 1991;12(Suppl G):8–15.
Mulcahy D, Fox K. Can we really justify the treatment of silent ischemia in 1992? No!Cardiovasc Drugs Ther 1992;6:125–129.
Deedwania PC, Carbajal EV. Prevalence and patterns of silent myocardial ischemia during daily life in stable angina patients receiving conventional antianginal drug therapy.Am J Cardiol 1990;65:1090–1096.
Kaul U, Dev V, Manchanda SC, Wasir HS. Silent myocardial ischemia after percutaneous transluminal coronary angioplasty and its prognostic significance.Clin Cardiol 1991;14:563–566.
Egstrup K. Asymptomatic myocardial ischemia as a predictor of cardiac events after coronary artery bypass grafting for stable angina pectoris.Am J Cardiol 1988;61:248–252.
Bertolet BD, Hill JA, Pepine CJ. Treatment strategies for daily life silent myocardial ischemia: A correlation with potential pathogenic mechanisms.Proc Cardiovasc Dis 1992;2:97–118.
Koehn DK, Glasser SP. The impact of antianginal drug therapy on asymptomatic myocardial ischemia.J Clin Pharmacol 1989;29:722–727.
Schang SJ, Pepine CJ. Transient asymptomatic ST segment depression during daily activity.Am J Cardiol 1977;39:396–402.
Thadani U. Role of nitrates in angina pectoris.Am J Cardiol 1992;780:43B-53B.
Reiniger G, Lehmann G, Beyerle A, Wolf H, Rudolf W. Treatment of symptomatic and asymptomatic myocardial ischemia during everyday activities with 120 mg isosorbide dinitrate in sustained release form [German].Herz 1990;15:259–265.
Dubiel JP, Krzysztof W, Moczurad W, Bryniarski L. Efficacy of a single dose of slow-release isosorbide dinitrate in the treatment of silent or painful myocardial ischemia in stable angina pectoris.Am J Cardiol 1992;69:1156–1160.
Von Arnim T, Erath A. Nitrates and calcium antagonists for silent myocardial ischemia.Am J. Cardiol 1988;61:15E-18E.
Distante A, Maseri A, Severi S, Biagini N, Chierchia S. Management of vasospastic angina at rest with continuous infusion of isosorbide dinitrate: A double crossover study in a coronary care unit.Am J Cardiol 1979;44:533–539.
Quyyumi AA, Crake T, Wright C, Mockus L, Fox KM. Medical treatment of patients with severe exertional and rest angina; double-blind comparison of beta-blocker, calcium antagonist and nitrate.Br Heart J 1987;57:505–511.
Feng J, Feng X-H, Schneeweiss A. Efficacy of isosorbide-5-mononitrate on painful and silent myocardial ischemia after myocardial infarction.Am J Cardiol 1990;65:32J-35J.
Pepine CJ, Daily life ischemia and nitrate therapy.Am J Cardiol 1992;70:54B-63B.
Shell WE. Mechanisms and therapy of silent myocardial ischemia and the effect of transdermal nitroglycerin.Am J Cardiol 1985;56:231–271.
Shell WE, Dobson D. Dissociative of exercise tolerance and total ischemic burden in chronic stable angina pectoris.Am J Cardiol 1990;66:42–48.
Schneeweiss A, Marmor A. Transdermal nitroglycerin patches for silent ischemia during antianginal treatment.Am J Cardiol 1988;61:36E-38E.
Levin RI. Quantitation of transient myocardial ischemia by digital, ambulatory electrocardiography.Am J Cardiol 1988;61:13B-17B.
Nabel EG, Barry J, Rocco MB, Mead K, Selwyn AP. Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin.Am J Cardiol 1989;63:663–669.
Knuuti MJ, Wahl M, Wiklund I, et al. Acute and long-term effects on myocardial ischemia of intermittent and continuous transdermal nitrate therapy in stable angina.Am J Cardiol 1992;69:1525–1532.
Fox KM, Dargie HJ, Deanfield J, Maseri A, on behalf of the Transdermal Nitrate Investigators. Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate.Br Heart J 1991;66:151–155.
Rossetti E, Luca C, Bonetti F, Chierchia SL. Transdermal nitroglycerin reduces the frequency of animal attacks but fails to prevent silent ischemia.J Am Coll Cardiol 1993;21:337–42.
Shell WE, Kivowitz CF, Rubins SB, See J. Mechanisms and therapy of silent myocardial ischemia: The effect of transdermal nitroglycerin.Am Heart J 1986;112:222–229.
Cowan C. Clinical tolerance. In: Nitric Oxide—the Rational Basis for Nitrate Therapy. Wiliam Harvey Research Conferences (UK), Postgraduate Medical Education Series, Vol. 1, 1992. 51–52.
Maxwell SRJ, Kendall MJ. An update on nitrate tolerance: Can it be avoided?Postgrad Med J 1992;68:857–866.
Olsson G, Allgen J. Is there an optimal prophylactic nitrate therapy?Eur Heart J 1991;12(Suppl A):21–23.
Chatterjee K. Role of nitrates in silent myocardial ischemia.Am J Cardiol 1987;60:18H-25H.
Rubboli A, Sangiorgio P, Camillo Pavesi P, et al. Efficacy of long-term administration of transdermal nitroglycerin in asymptomatic patients with effort-induced silent myocardial ischemia.Cardiology 1994;84:247–254.
Knatterud GL, Bourassa MG, Pepine CJ, et al. Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12 week results of the Asymptomatic Cardiac Ischaemia Pilot (ACIP) Study.J Am Coll Cardiol 1994;24:11–20.
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Purcell, H., Mulcahy, D. & Fox, K. Nitrates in silent ischemia. Cardiovasc Drug Ther 8, 727–734 (1994). https://doi.org/10.1007/BF00877119
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DOI: https://doi.org/10.1007/BF00877119