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Silent myocardial ischemia, arrhythmias and sudden death: Are they related?
EDITORIALS
Silent MyocardialIschemia,Arrhythmias and SuddenDeath:Are TheyRelated? EZRA A. AMSTERDAM,
oronary artery disease(CAD) is the primary cause C of death in our society and its mechanism is usually a lethal arrhythmia? Epidemiologic studieshave further established that the initial clinical presentation of CAD is acute myocardial infarction in approximately 50% of patients and is sudden death in 10 to 209’0.~ Thus, the first overt evidence of CAD in most patients is a catastrophicevent causingloss of life or irreversible myocardial damage.These findings underscore the importance of both prevention and early detection in any effort to curb morbidity and mortality from the coronary epidemic. One growing areaof investigation with potential importance for early detection of CAD is silent myocardial ischemia. Silent myocardial ischemia is common in patients with CAD. Objective evidence of asymptomaticmyocardial ischemia has been found throughoutthe clinical spectrum of CAD, including stable3and unstable angina4 and myocardial infarction.5 Objective evidence of asymptomatic ischemia also is evident in CAD patients in the form of stress-inducedischemic ST-segmentalterations6 scintigraphic perfusion defects7and left ventricular wall motion abnormalities.8 These findings represent the descriptive stageof investigationof silent myocardial ischemia in which this entity has been defined and documentedand its high prevalencein patientswith CAD hasbeenestablished. The clinical significance of this phenomenonin terms of prognosisand managementhas not been clarified, but recent studies on this matter are of considerable interest. Silent myocardial ischemia has been shown to be associatedwith increasedprognosticrisk in several categoriesof CAD patients, including those with overt or occult CAD. In the latter category,mortality and coronary event rate have been elevated in subjectswith silent ischemia by exerciseelectrocardiography.g-ll In postinfarction patients who undergo exerFrom the Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis School of Medicine and Medical Center, Davis and Sacramento, California. Manuscript received and accepted January 12, 1987. Address for reprints: Ezra A. Amsterdam, MD, Cardiology, 4301 X Street, Sacramento, California 95851. 919
MD
cise testing, survival has been closely related to ischemic ST-segmentchanges,irrespective of the occurrence of angina.l2 Finally, silent &hernia in patients with unstableangina has predicted an unfavorable clinical outcome.13 A natural concern regarding silent myocardial ischemia is whether it plays a role in thegenesisof lethal arrhythmias and thereby of suddendeath.Limited information on this question is available from patients undergoingambulatory electrocardiographicmonitoring at the time of unexpected sudden death. These data show that most ventricular tachyarrhythmiasare not clearly related to silent ischemia.14While the technical limitations of such data are recognized, our group’s experience with ambulatory monitoring also doesnot indicate electrocardiographicevidence of ischemia in associationwith most ventricular tachyarrhythmias.However, severalcasereportsdo reflect an associationbetween silent myocardial ischemia and arrhythmic suddendeath.Thesestudiesreveal evolution of ischemic ST-segmentalterationsin the absence of symptoms before the onset of a lethal ventricular tachyarrhythmia,l5-l7suggestingthat there may be a causal relation between silent ischemia and sudden death in some cases.In this regard, the report by Sharmaet all8 in this issueof the Tournalis of interest. In their study of 15patientswith CAD who survived out-of-hospital ventricular fibrillation, Sharma et al found that 9 had no prior symptomsof anginaor myocardial infarction. While no patient had anginaduring exercisetesting,12of 15patientshad exercise-induced myocardial ischemia [ST-segment alteration or left ventricular regional dysfunction or both]. Therefore, silent myocardial ischemia is an important feature of thesesurvivors of arrhythmic sudden death. In addition, the dynamic left ventricular functional abnormalities in this groupmay be an important arrhythmogenie factor, potentially increasing the risk of sudden death. The foregoingconceptslinking silent ischemia and lethal arrhtyhmias are provocative, and this study therefore provides a basis for further investigation of these and other questionswhich it raises. Thus, although 80% of the patientsdescribedby Sharma et al
920
EDITORIALS
had findings interpreted as exercise-inducedsilent References myocardial &hernia, the electrocardiographiccriteria usedfor ischemia differ somewhatfrom conventional 1. Surawicz B. VentricuIar fibrillation. JACC 1985;5:43B-54B. Oberman A, Kouchoukos NT, Holt JH Jr, Russell RO Jr. Long-term results criteria. Further, mechanismsother than active ische- 2.of the medical treatment of coronary artery disease. Angiology 1977;28:160mia, such as mechanical factors, may contribute to 168. worseningof a left ventricular wall motion abnormali- 3. Tzivoni D, Gavish A, Benhorin J, Keren A. Stern S. Myocardial ischemia daily activities and stress. Am J Cordiol 1986:58:47&508. ty during exercisein a region alreadyabnormal at rest. 4.during Cecchi AC, Dorellini EV, Morchi F, Pucci P, Santoro GM. Fazzini PF. Silent A broader question relates to the significance of the myocordial ischemia during ambulatory electrocardiographic monitoring in high prevalenceof silent ischemia in thesepatients.It patients with effort angina. JACC 1983;1:934-939. WB, Abbott RD. incidence and prognosis of unrecognized myocaris known that silent ischemia is common in all CAD 5.dialKannel infarction. An update on the Framingham study. N Engl I Med 1984; syndromes.Therefore,its presencein survivorsof sud- 311:1144-1147. EA, Martschinske R, Laslett LJ. Rutledge JR, Vera Z. Symptomden deathmay merely be a reflection of its prevalence 6.aticAmsterdam and silent myocordial ischemio during exercise testing in coronary artery in the CAD population at large.However, the 9 asymp- disease. Am J Cordiol 1986x58:438-468. tomatic patientsdescribedby Sharmaand co-workers 7. Deanfield JE. Shea M. Ribiero P. deLandsheere C. Wilson R. Horlock P, AP. Transient ST-segment depression (IS o marker of’myocordial are particularly noteworthy in that if silent ischemia Selwyn ischemia during dailv life. Am 1 Cardiol 1984:54:1195-1200. were presentbefore cardiacarrestasit was thereafter, 8. Cohn PF, Brown ES, Wynne J.‘Hohman BL. Atkins HA. GIohoI and regional ejection fraction abnormalities during exercise in patients it would have been the only evidence of underlying left ventricular silent myocardiol &hernia. JACC 1983;1:931-933. CAD with lethal potential. In this regard,silent ische- 9.withErikssen J, Thaulow E. Follow-up of patients with asymptomatic myocardimia may be associatedwith a spectrum of risk, de- al ischemia. In: Rutishauser W. Roskomm H, eds. Silent Myocardial Ischemio. Berlin: Springer VerIag, 1984:156-164. pending on asyet undefined characteristicsof this en- 10. JR Jr. Uhl GS. Cook RL, Engel PJ. Hopkirk A. A Natural history tity and other factors. Another question relates to studyHickman of asymptomatic coronary disease (obstr]. Am J Cardiol 1980;45:422. whether patientssuchasthosedescribedby Sharmaet 11. Langou RA, Huang EK, Kelley MJ. Cohen LS. Predicted accuracy of artery classification and abnormal exercise test for coronary artery al have arrhythmias during exercise-inducedsilent coronary disease in asymptomatic men. CircuIation 1980;82:1196-i203. myocardial ischemiaand whether thereis any associa- 12. Theroux P, Waters DD. Haluhen C. Devaisieux IC. Miznala HF. Prognosvalue of exercise testing seen after myocardial Inforcti&. N Engl J Med tion, on ambulatory monitoring, between ventricular tic1979;301:341-345. arrhythmiasand ST-segmentevidenceof silent ische- 13. Nademanee K, Intarachot V, Plontek M, Vaghaiwalla Mody F. Reider D, mia, thereby strengtheningthe relation betweensilent Josephson M, Singh BN. Silent myocordial ischemia on Hoher: has it clinical or prognostic significance? [abstr]. Circulation 1984;7O:suppi IHI-451. ischemia and sudden death in this group. 14. Meissner MD, Morganroth J. Silent myocardiol ischemia (IS (I mechanism The study of Sharma and co-workersis an impor- of sudden cardiac death. In Pepine CJ, ed. Silent Myocardial &hernia. Philatant addition to our developing knowledge of silent delphia: WB Saunders, 1986:593-605. Gradman AH, Bell PA, DeBusk RF. Sudden death during ambulatory myacardial ischemia.Their data show the coexistence 15. monitoring: clinical and electrocardiographic correlations. Report of a case. _ of silent myocardial ischemia with other important Circulation 1977;55:210-211. manifestationsof CAD in patients surviving fatal ar- 16. Bleifer SB, Bleifer DJ. Hansmann DR, Sheppard JJ. Karpman HL. Diagnosis of occult arrhythmias by Halter electrocardiography. Prog Cordiovasc Dis rhythmias, the primary lethal mechanism in CAD. 1974;16:569-599. These findings and the further work they stimulate 17. Savage DD, Castelli WP. Anderson SJ, Kannel WB. Sudden unexpected death during ambulatory electrocardiographic monitoring: the Framinghom should help to clarify the role of silent myocardial study. Am J Med 1983;74:148-152. ischemiain suddendeathwith the goal of early detec- 18. Sharma B, Asinger R, Francis GS. Hodges M, Wyeth RP. Painless ischemia in out of hospital ventricular fibrillation. Am J Cardiol 1987;59:740-745. tion and prevention.
Silent MyocardialIschemia,Arrhythmias and SuddenDeath:Are TheyRelated? EZRA A. AMSTERDAM,
oronary artery disease(CAD) is the primary cause C of death in our society and its mechanism is usually a lethal arrhythmia? Epidemiologic studieshave further established that the initial clinical presentation of CAD is acute myocardial infarction in approximately 50% of patients and is sudden death in 10 to 209’0.~ Thus, the first overt evidence of CAD in most patients is a catastrophicevent causingloss of life or irreversible myocardial damage.These findings underscore the importance of both prevention and early detection in any effort to curb morbidity and mortality from the coronary epidemic. One growing areaof investigation with potential importance for early detection of CAD is silent myocardial ischemia. Silent myocardial ischemia is common in patients with CAD. Objective evidence of asymptomaticmyocardial ischemia has been found throughoutthe clinical spectrum of CAD, including stable3and unstable angina4 and myocardial infarction.5 Objective evidence of asymptomatic ischemia also is evident in CAD patients in the form of stress-inducedischemic ST-segmentalterations6 scintigraphic perfusion defects7and left ventricular wall motion abnormalities.8 These findings represent the descriptive stageof investigationof silent myocardial ischemia in which this entity has been defined and documentedand its high prevalencein patientswith CAD hasbeenestablished. The clinical significance of this phenomenonin terms of prognosisand managementhas not been clarified, but recent studies on this matter are of considerable interest. Silent myocardial ischemia has been shown to be associatedwith increasedprognosticrisk in several categoriesof CAD patients, including those with overt or occult CAD. In the latter category,mortality and coronary event rate have been elevated in subjectswith silent ischemia by exerciseelectrocardiography.g-ll In postinfarction patients who undergo exerFrom the Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis School of Medicine and Medical Center, Davis and Sacramento, California. Manuscript received and accepted January 12, 1987. Address for reprints: Ezra A. Amsterdam, MD, Cardiology, 4301 X Street, Sacramento, California 95851. 919
MD
cise testing, survival has been closely related to ischemic ST-segmentchanges,irrespective of the occurrence of angina.l2 Finally, silent &hernia in patients with unstableangina has predicted an unfavorable clinical outcome.13 A natural concern regarding silent myocardial ischemia is whether it plays a role in thegenesisof lethal arrhythmias and thereby of suddendeath.Limited information on this question is available from patients undergoingambulatory electrocardiographicmonitoring at the time of unexpected sudden death. These data show that most ventricular tachyarrhythmiasare not clearly related to silent ischemia.14While the technical limitations of such data are recognized, our group’s experience with ambulatory monitoring also doesnot indicate electrocardiographicevidence of ischemia in associationwith most ventricular tachyarrhythmias.However, severalcasereportsdo reflect an associationbetween silent myocardial ischemia and arrhythmic suddendeath.Thesestudiesreveal evolution of ischemic ST-segmentalterationsin the absence of symptoms before the onset of a lethal ventricular tachyarrhythmia,l5-l7suggestingthat there may be a causal relation between silent ischemia and sudden death in some cases.In this regard, the report by Sharmaet all8 in this issueof the Tournalis of interest. In their study of 15patientswith CAD who survived out-of-hospital ventricular fibrillation, Sharma et al found that 9 had no prior symptomsof anginaor myocardial infarction. While no patient had anginaduring exercisetesting,12of 15patientshad exercise-induced myocardial ischemia [ST-segment alteration or left ventricular regional dysfunction or both]. Therefore, silent myocardial ischemia is an important feature of thesesurvivors of arrhythmic sudden death. In addition, the dynamic left ventricular functional abnormalities in this groupmay be an important arrhythmogenie factor, potentially increasing the risk of sudden death. The foregoingconceptslinking silent ischemia and lethal arrhtyhmias are provocative, and this study therefore provides a basis for further investigation of these and other questionswhich it raises. Thus, although 80% of the patientsdescribedby Sharma et al
920
EDITORIALS
had findings interpreted as exercise-inducedsilent References myocardial &hernia, the electrocardiographiccriteria usedfor ischemia differ somewhatfrom conventional 1. Surawicz B. VentricuIar fibrillation. JACC 1985;5:43B-54B. Oberman A, Kouchoukos NT, Holt JH Jr, Russell RO Jr. Long-term results criteria. Further, mechanismsother than active ische- 2.of the medical treatment of coronary artery disease. Angiology 1977;28:160mia, such as mechanical factors, may contribute to 168. worseningof a left ventricular wall motion abnormali- 3. Tzivoni D, Gavish A, Benhorin J, Keren A. Stern S. Myocardial ischemia daily activities and stress. Am J Cordiol 1986:58:47&508. ty during exercisein a region alreadyabnormal at rest. 4.during Cecchi AC, Dorellini EV, Morchi F, Pucci P, Santoro GM. Fazzini PF. Silent A broader question relates to the significance of the myocordial ischemia during ambulatory electrocardiographic monitoring in high prevalenceof silent ischemia in thesepatients.It patients with effort angina. JACC 1983;1:934-939. WB, Abbott RD. incidence and prognosis of unrecognized myocaris known that silent ischemia is common in all CAD 5.dialKannel infarction. An update on the Framingham study. N Engl I Med 1984; syndromes.Therefore,its presencein survivorsof sud- 311:1144-1147. EA, Martschinske R, Laslett LJ. Rutledge JR, Vera Z. Symptomden deathmay merely be a reflection of its prevalence 6.aticAmsterdam and silent myocordial ischemio during exercise testing in coronary artery in the CAD population at large.However, the 9 asymp- disease. Am J Cordiol 1986x58:438-468. tomatic patientsdescribedby Sharmaand co-workers 7. Deanfield JE. Shea M. Ribiero P. deLandsheere C. Wilson R. Horlock P, AP. Transient ST-segment depression (IS o marker of’myocordial are particularly noteworthy in that if silent ischemia Selwyn ischemia during dailv life. Am 1 Cardiol 1984:54:1195-1200. were presentbefore cardiacarrestasit was thereafter, 8. Cohn PF, Brown ES, Wynne J.‘Hohman BL. Atkins HA. GIohoI and regional ejection fraction abnormalities during exercise in patients it would have been the only evidence of underlying left ventricular silent myocardiol &hernia. JACC 1983;1:931-933. CAD with lethal potential. In this regard,silent ische- 9.withErikssen J, Thaulow E. Follow-up of patients with asymptomatic myocardimia may be associatedwith a spectrum of risk, de- al ischemia. In: Rutishauser W. Roskomm H, eds. Silent Myocardial Ischemio. Berlin: Springer VerIag, 1984:156-164. pending on asyet undefined characteristicsof this en- 10. JR Jr. Uhl GS. Cook RL, Engel PJ. Hopkirk A. A Natural history tity and other factors. Another question relates to studyHickman of asymptomatic coronary disease (obstr]. Am J Cardiol 1980;45:422. whether patientssuchasthosedescribedby Sharmaet 11. Langou RA, Huang EK, Kelley MJ. Cohen LS. Predicted accuracy of artery classification and abnormal exercise test for coronary artery al have arrhythmias during exercise-inducedsilent coronary disease in asymptomatic men. CircuIation 1980;82:1196-i203. myocardial ischemiaand whether thereis any associa- 12. Theroux P, Waters DD. Haluhen C. Devaisieux IC. Miznala HF. Prognosvalue of exercise testing seen after myocardial Inforcti&. N Engl J Med tion, on ambulatory monitoring, between ventricular tic1979;301:341-345. arrhythmiasand ST-segmentevidenceof silent ische- 13. Nademanee K, Intarachot V, Plontek M, Vaghaiwalla Mody F. Reider D, mia, thereby strengtheningthe relation betweensilent Josephson M, Singh BN. Silent myocordial ischemia on Hoher: has it clinical or prognostic significance? [abstr]. Circulation 1984;7O:suppi IHI-451. ischemia and sudden death in this group. 14. Meissner MD, Morganroth J. Silent myocardiol ischemia (IS (I mechanism The study of Sharma and co-workersis an impor- of sudden cardiac death. In Pepine CJ, ed. Silent Myocardial &hernia. Philatant addition to our developing knowledge of silent delphia: WB Saunders, 1986:593-605. Gradman AH, Bell PA, DeBusk RF. Sudden death during ambulatory myacardial ischemia.Their data show the coexistence 15. monitoring: clinical and electrocardiographic correlations. Report of a case. _ of silent myocardial ischemia with other important Circulation 1977;55:210-211. manifestationsof CAD in patients surviving fatal ar- 16. Bleifer SB, Bleifer DJ. Hansmann DR, Sheppard JJ. Karpman HL. Diagnosis of occult arrhythmias by Halter electrocardiography. Prog Cordiovasc Dis rhythmias, the primary lethal mechanism in CAD. 1974;16:569-599. These findings and the further work they stimulate 17. Savage DD, Castelli WP. Anderson SJ, Kannel WB. Sudden unexpected death during ambulatory electrocardiographic monitoring: the Framinghom should help to clarify the role of silent myocardial study. Am J Med 1983;74:148-152. ischemiain suddendeathwith the goal of early detec- 18. Sharma B, Asinger R, Francis GS. Hodges M, Wyeth RP. Painless ischemia in out of hospital ventricular fibrillation. Am J Cardiol 1987;59:740-745. tion and prevention.