Prognostic Significance of Silent Myocardiai lschemia in Variant Angina Pectoris Raffaele Bugiardini, MD, Alberico Borghi, MD, Biagio Sassone, MD, Andrea Pozzati, MD, and Paolo Puddu, MD
The present study investigates the prognostic significance of silent myocardial ischemia in variant angina. Forty-eight-hour Holter monitoring and coronary angiography were performed in 54 patients with transient ST elevation and no history of myocardial infarction admitted to the coronary care unit for worsening of symptoms. Coronary artery spasm was documented in most of these patients. Over the subsequent month, 20 patients (group 1) had a major coronary event (2 died, 6 had nonfatal myocardial infarction and 12 had urgent coronary revascularization), and the remaining 34 patients (group 2) had a good clinical outcome. From 2,578 hours of recording, 547 ischemic episodes were identified of which only 9% were associated with angina. The mean daily number of ST elevation in group 1 was similar to that in group 2 (4.8 f 5.1 vs 4.1 f 4.6; p = not significant). Conversely, the mean daily duration of such ischemic episodes was consistently greater in group 1 than in 2 (79 f 36 vs 37 f 25 minutes; p SO% stenoses) was found at angiography in 18 of 20 patients in group 1, and in 18 of 34 in group 2. Furthermore, morphologic analysis of coronary angiograms revealed the presence of a complex coronary stenosis (overhanging edges, irregular borders or intracoronary thrombus) in 16 of 20 patients in group 1, but only in 4 of 34 in group 2 (p 2 times normal, with MB fraction >6%], or both). Criteria for exclusion from the study were: age >75 years; noninterpretable electrocardiogram;adverse outcome due to concomitant nonmyocardial disease; and severeheart failure. Patients with severeheart failure were excluded owing to the following considerations: (1) An unpaired ejection fraction is predictive of unfavorable outcome in patients with unstable angina.’ (2) In the setting of left ventricular dysfunction, the remaining viable contractile elementscould be vulnerable to the cardiodepressanteffects of calcium antagonists. This would have made it difficult to use a standard drug treatment in all patients. Furthermore, patients who developedan acute myocardial infarction in the first 24 hours were not enrolled in the study, because our modeling strategy was based on Holter recordings that at the present may give prognostic information only after 24-hour analysis.4All patients were initially treated with a standard medical regimen (intravenous nitroglycerin [ 10 to 60 pg/min], oral calcium antagonists [verapamil 240 to 360 mg/day], /3 blockers [propranolol 60 to 240 mg/day] and oral aspirin [325 mg/day]). Also, 0.5 mg of intravenous nitroglycerin or 5 mg of sublingual isosorbide dinitrate were administered as needed.None of the patients had bradycardia or ventricular dysfunction during medical therapy. ST-segment monitoring: Forty-eight-hour ST-segment monitoring was begun 8 f 7 hours after the qualifying episode of chest pain. We used a 2-channel Holter system (Applied Cardiac System 8300 frequency modulated recorders;frequency response0.05 to 100 Hz). The 2 leads showing the most pronounced reversible ischemic changes on the initial qualifying 1Zlead electrocardiogram were selected for analysis. Recordings were printed in a minielectrocardiogram format by a Telemed Saturn 3200 analyzer. Holter monitoring was interpreted by investigators unaware of the clinical data. Of the 54 patients, 34 had ST elevation and 20 had isoelectric ST segmenton admission.Only episodes lasting 260 secondsand with LO.15 mV of ST-segment shift were consideredfor analytical purposes.All recordings were obtained while patients were resting in bed. Patients and attending nurses kept a careful diary of symptoms. Coronary angiography: Selective coronary angiography was performed within 1 week of admission. Of the 54 patients, 12 underwent urgent cardiac catheterization 2.3 f 1.2 days after admission. The remaining patients underwent elective catheterization 6.6 f 1.5 days after admission. The severity and morphology of coronary artery stenosiswere observed in multiple views. Analysis of the end-diastolic cineframeswas performed by 2 teams of investigators,each comprisedof 2 observers experienced in angiographic interpretation 1582
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and unaware of the clinical data. Differences were mediated by consensus.A stenosis 250% was considered significant. Complex angiographic morphology was defined as any significant asymmetric stenosiswith irregular borders, overhanging edgesor intraluminal thrombus. Correlation between electrocardiographic changes during angina and coronary anatomy at angiography has been describedelsewhere.9When recognition of the ischemia-relatedstenosiswas uncertain, the most severe narrowing of the artery was chosen for analysis. This applied only to 2 cases.None of the patients had stenosis
The present study investigates the prognostic significance of silent myocardial ischemia in variant angina. Forty-eight-hour Holter monitoring and coronary angiography were performed in 54 patients with transient ST elevation and no history of myocardial infarction admitted to the coronary care unit for worsening of symptoms. Coronary artery spasm was documented in most of these patients. Over the subsequent month, 20 patients (group 1) had a major coronary event (2 died, 6 had nonfatal myocardial infarction and 12 had urgent coronary revascularization), and the remaining 34 patients (group 2) had a good clinical outcome. From 2,578 hours of recording, 547 ischemic episodes were identified of which only 9% were associated with angina. The mean daily number of ST elevation in group 1 was similar to that in group 2 (4.8 f 5.1 vs 4.1 f 4.6; p = not significant). Conversely, the mean daily duration of such ischemic episodes was consistently greater in group 1 than in 2 (79 f 36 vs 37 f 25 minutes; p SO% stenoses) was found at angiography in 18 of 20 patients in group 1, and in 18 of 34 in group 2. Furthermore, morphologic analysis of coronary angiograms revealed the presence of a complex coronary stenosis (overhanging edges, irregular borders or intracoronary thrombus) in 16 of 20 patients in group 1, but only in 4 of 34 in group 2 (p 2 times normal, with MB fraction >6%], or both). Criteria for exclusion from the study were: age >75 years; noninterpretable electrocardiogram;adverse outcome due to concomitant nonmyocardial disease; and severeheart failure. Patients with severeheart failure were excluded owing to the following considerations: (1) An unpaired ejection fraction is predictive of unfavorable outcome in patients with unstable angina.’ (2) In the setting of left ventricular dysfunction, the remaining viable contractile elementscould be vulnerable to the cardiodepressanteffects of calcium antagonists. This would have made it difficult to use a standard drug treatment in all patients. Furthermore, patients who developedan acute myocardial infarction in the first 24 hours were not enrolled in the study, because our modeling strategy was based on Holter recordings that at the present may give prognostic information only after 24-hour analysis.4All patients were initially treated with a standard medical regimen (intravenous nitroglycerin [ 10 to 60 pg/min], oral calcium antagonists [verapamil 240 to 360 mg/day], /3 blockers [propranolol 60 to 240 mg/day] and oral aspirin [325 mg/day]). Also, 0.5 mg of intravenous nitroglycerin or 5 mg of sublingual isosorbide dinitrate were administered as needed.None of the patients had bradycardia or ventricular dysfunction during medical therapy. ST-segment monitoring: Forty-eight-hour ST-segment monitoring was begun 8 f 7 hours after the qualifying episode of chest pain. We used a 2-channel Holter system (Applied Cardiac System 8300 frequency modulated recorders;frequency response0.05 to 100 Hz). The 2 leads showing the most pronounced reversible ischemic changes on the initial qualifying 1Zlead electrocardiogram were selected for analysis. Recordings were printed in a minielectrocardiogram format by a Telemed Saturn 3200 analyzer. Holter monitoring was interpreted by investigators unaware of the clinical data. Of the 54 patients, 34 had ST elevation and 20 had isoelectric ST segmenton admission.Only episodes lasting 260 secondsand with LO.15 mV of ST-segment shift were consideredfor analytical purposes.All recordings were obtained while patients were resting in bed. Patients and attending nurses kept a careful diary of symptoms. Coronary angiography: Selective coronary angiography was performed within 1 week of admission. Of the 54 patients, 12 underwent urgent cardiac catheterization 2.3 f 1.2 days after admission. The remaining patients underwent elective catheterization 6.6 f 1.5 days after admission. The severity and morphology of coronary artery stenosiswere observed in multiple views. Analysis of the end-diastolic cineframeswas performed by 2 teams of investigators,each comprisedof 2 observers experienced in angiographic interpretation 1582
THE AMERICAN JOirRNAL OF CARDIOLOGY VOLUME 68
and unaware of the clinical data. Differences were mediated by consensus.A stenosis 250% was considered significant. Complex angiographic morphology was defined as any significant asymmetric stenosiswith irregular borders, overhanging edgesor intraluminal thrombus. Correlation between electrocardiographic changes during angina and coronary anatomy at angiography has been describedelsewhere.9When recognition of the ischemia-relatedstenosiswas uncertain, the most severe narrowing of the artery was chosen for analysis. This applied only to 2 cases.None of the patients had stenosis
