Silent myocardial ischemia: Prognosis and therapy
- Prakash C Deedwania, MD
Prakash C Deedwania, MD
- Professor of Medicine
- University of California San Francisco School of Medicine
- Section Editor
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
Angina pectoris, the term used for symptoms thought to be attributable to myocardial ischemia, typically manifests as chest discomfort, although other associated symptoms with ischemia may be present (eg, exertional shortness of breath, nausea, diaphoresis, fatigue). While angina has long been considered the cardinal symptom of myocardial ischemia and coronary heart disease, "silent" (asymptomatic) myocardial ischemia is the most common manifestation of coronary heart disease (CHD), accounting for more than 75 percent of ischemic episodes during daily life as assessed by electrocardiographic (ECG) monitoring . (See "Angina pectoris: Chest pain caused by myocardial ischemia".)
Issues related to treatment and prognosis of silent myocardial ischemia will be reviewed here. The epidemiology, pathophysiology, and diagnosis of silent myocardial ischemia are discussed separately. (See "Silent myocardial ischemia: Epidemiology, pathophysiology, and diagnosis".)
Silent myocardial ischemia is defined as the presence of objective evidence of myocardial ischemia in the absence of chest discomfort or another anginal equivalent symptom. Objective evidence of silent myocardial ischemia may be obtained through ambulatory electrocardiographic (ECG) monitoring or cardiac stress testing. (See "Silent myocardial ischemia: Epidemiology, pathophysiology, and diagnosis", section on 'Definition'.)
The prognosis of patients with silent myocardial ischemia may be viewed from the standpoint of two groups of patients: those without a history of coronary heart disease (CHD) or angina pectoris, and those with a history of CHD . Additionally, there appears to be a "dose dependence," with patients who have more frequent or more sustained episodes of silent ischemia at greater risk for adverse events [3,4].
The precise reason for the adverse prognosis associated with silent ischemia is not known. Hypotheses center around abnormalities such as necrosis or progressive fibrosis leading to left ventricular dysfunction and/or ventricular arrhythmias [5-7].
- Deedwania PC, Carbajal EV. Silent myocardial ischemia. A clinical perspective. Arch Intern Med 1991; 151:2373.
- Kaski JC, Cosín Sales J, Arroyo Espliguero R. Silent myocardial ischaemia: clinical relevance and treatment. Expert Opin Investig Drugs 2005; 14:423.
- Forslund L, Hjemdahl P, Held C, et al. Prognostic implications of ambulatory myocardial ischemia and arrhythmias and relations to ischemia on exercise in chronic stable angina pectoris (the Angina Prognosis Study in Stockholm [APSIS]). Am J Cardiol 1999; 84:1151.
- Pepine CJ, Sharaf B, Andrews TC, et al. Relation between clinical, angiographic and ischemic findings at baseline and ischemia-related adverse outcomes at 1 year in the Asymptomatic Cardiac Ischemia Pilot study. ACIP Study Group. J Am Coll Cardiol 1997; 29:1483.
- Geft IL, Fishbein MC, Ninomiya K, et al. Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. Circulation 1982; 66:1150.
- Schaper J. Effects of multiple ischaemic events on human myocardium--an ultrastructural study. Eur Heart J 1988; 9 Suppl A:141.
- Hess OM, Schneider J, Nonogi H, et al. Myocardial structure in patients with exercise-induced ischemia. Circulation 1988; 77:967.
- Deedwania PC, Carbajal EV. Silent ischemia during daily life is an independent predictor of mortality in stable angina. Circulation 1990; 81:748.
- Yeung AC, Barry J, Orav J, et al. Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease. Circulation 1991; 83:1598.
- Gottlieb SO, Gottlieb SH, Achuff SC, et al. Silent ischemia on Holter monitoring predicts mortality in high-risk postinfarction patients. JAMA 1988; 259:1030.
- 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.
- Deedwania PC. Asymptomatic ischemia during predischarge Holter monitoring predicts poor prognosis in the postinfarction period. Am J Cardiol 1993; 71:859.
- Gehi AK, Ali S, Na B, et al. Inducible ischemia and the risk of recurrent cardiovascular events in outpatients with stable coronary heart disease: the heart and soul study. Arch Intern Med 2008; 168:1423.
- 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.
- Moss AJ, Goldstein RE, Hall WJ, et al. Detection and significance of myocardial ischemia in stable patients after recovery from an acute coronary event. Multicenter Myocardial Ischemia Research Group. JAMA 1993; 269:2379.
- Cohn PF, Fox KM, Daly C. Silent myocardial ischemia. Circulation 2003; 108:1263.
- Gottlieb SO, Weisfeldt ML, Ouyang P, et al. Silent ischemia as a marker for early unfavorable outcomes in patients with unstable angina. N Engl J Med 1986; 314:1214.
- Nørgaard BL, Andersen K, Dellborg M, et al. Admission risk assessment by cardiac troponin T in unstable coronary artery disease: additional prognostic information from continuous ST segment monitoring. TRIM study group. Thrombin Inhibition in Myocardial Ischemia. J Am Coll Cardiol 1999; 33:1519.
- Akkerhuis KM, Klootwijk PA, Lindeboom W, et al. Recurrent ischaemia during continuous multilead ST-segment monitoring identifies patients with acute coronary syndromes at high risk of adverse cardiac events; meta-analysis of three studies involving 995 patients. Eur Heart J 2001; 22:1997.
- Narins CR, Zareba W, Moss AJ, et al. Clinical implications of silent versus symptomatic exercise-induced myocardial ischemia in patients with stable coronary disease. J Am Coll Cardiol 1997; 29:756.
- Deedwania PC. Silent ischemia predicts poor outcome in high-risk healthy men. J Am Coll Cardiol 2001; 38:80.
- Exercise electrocardiogram and coronary heart disease mortality in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Am J Cardiol 1985; 55:16.
- Ekelund LG, Suchindran CM, McMahon RP, et al. Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial. J Am Coll Cardiol 1989; 14:556.
- Laukkanen JA, Kurl S, Lakka TA, et al. Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men. J Am Coll Cardiol 2001; 38:72.
- Gibbons LW, Mitchell TL, Wei M, et al. Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men. Am J Cardiol 2000; 86:53.
- Sheps DS, McMahon RP, Becker L, et al. Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: Results from the Psychophysiological Investigations of Myocardial Ischemia study. Circulation 2002; 105:1780.
- Sajadieh A, Nielsen OW, Rasmussen V, et al. Prevalence and prognostic significance of daily-life silent myocardial ischaemia in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 2005; 26:1402.
- Patel DJ, Mulcahy D, Norrie J, et al. Natural variability of transient myocardial ischaemia during daily life: an obstacle when assessing efficacy of anti-ischaemic agents? Heart 1996; 76:477.
- Stone PH, Chaitman BR, Forman S, et al. Prognostic significance of myocardial ischemia detected by ambulatory electrocardiography, exercise treadmill testing, and electrocardiogram at rest to predict cardiac events by one year (the Asymptomatic Cardiac Ischemia Pilot [ACIP] study). Am J Cardiol 1997; 80:1395.
- 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 Ischemia Pilot (ACIP) study. J Am Coll Cardiol 1994; 24:11.
- Davies RF, Goldberg AD, Forman S, et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization. Circulation 1997; 95:2037.
- Stone PH, Gibson RS, Glasser SP, et al. Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group. Circulation 1990; 82:1962.
- Deedwania PC, Carbajal EV, Nelson JR, Hait H. Anti-ischemic effects of atenolol versus nifedipine in patients with coronary artery disease and ambulatory silent ischemia. J Am Coll Cardiol 1991; 17:963.
- Pepine CJ, Cohn PF, Deedwania PC, et al. Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST). Circulation 1994; 90:762.
- Von Arnim T. Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study (TIBBs) follow-up. J Am Coll Cardiol 1996; 28:20.
- Andrews TC, Fenton T, Toyosaki N, et al. Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS). Circulation 1993; 88:92.
- Théroux P, Baird M, Juneau M, et al. Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise. Circulation 1991; 84:15.
- Davies RF, Habibi H, Klinke WP, et al. Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators. J Am Coll Cardiol 1995; 25:619.
- Kawanishi DT, Reid CL, Morrison EC, Rahimtoola SH. Response of angina and ischemia to long-term treatment in patients with chronic stable angina: a double-blind randomized individualized dosing trial of nifedipine, propranolol and their combination. J Am Coll Cardiol 1992; 19:409.
- Deedwania PC, Pool PE, Thadani U, Eff J. Effect of morning versus evening dosing of diltiazem on myocardial ischemia detected by ambulatory electrocardiographic monitoring in chronic stable angina pectoris. Dilacor XR Ambulatory Ischemia Study Group. Am J Cardiol 1997; 80:421.
- Friedman M, Breall WS, Goodwin ML, et al. Effect of type A behavioral counseling on frequency of episodes of silent myocardial ischemia in coronary patients. Am Heart J 1996; 132:933.
- Blumenthal JA, Jiang W, Babyak MA, et al. Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med 1997; 157:2213.
- Blumenthal JA, Babyak M, Wei J, et al. Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol 2002; 89:164.
- Jiang W, Velazquez EJ, Kuchibhatla M, et al. Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial. JAMA 2013; 309:2139.
- Andrews TC, Raby K, Barry J, et al. Effect of cholesterol reduction on myocardial ischemia in patients with coronary disease. Circulation 1997; 95:324.
- Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation 2007; 115:700.
- Rogers WJ, Bourassa MG, Andrews TC, et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study: outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization. The ACIP Investigators. J Am Coll Cardiol 1995; 26:594.
- Bourassa MG, Pepine CJ, Forman SA, et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study: effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia. The ACIP investigators. J Am Coll Cardiol 1995; 26:606.
- Madsen JK, Grande P, Saunamäki K, et al. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). DANish trial in Acute Myocardial Infarction. Circulation 1997; 96:748.
- Erne P, Schoenenberger AW, Burckhardt D, et al. Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial. JAMA 2007; 297:1985.
- Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; 356:1503.
- Aldweib N, Negishi K, Hachamovitch R, et al. Impact of repeat myocardial revascularization on outcome in patients with silent ischemia after previous revascularization. J Am Coll Cardiol 2013; 61:1616.
- Patients with known CHD
- Patients without known CHD (asymptomatic patients)
- Secondary prevention of cardiovascular disease
- Medical therapy directed at silent myocardial ischemia
- - Beta blockers
- - Calcium channel blockers
- - Combination therapy
- - Stress reduction
- - Statin therapy
- - Silent myocardial ischemia following MI
- - Silent myocardial ischemia not following MI
- - Silent myocardial ischemia following previous revascularization
- SUMMARY AND RECOMMENDATIONS