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Measurement of Myocardium at Risk and Salvage in Myocardial Infarction With ST-Segment Depression

      A patient with symptoms of acute myocardial infarction but ST-segment depression rather than elevation constitutes a clinical dilemma for which few guidelines exist. Herein we describe such a patient, in whom serial tomographic imaging with a new radiopharmaceutical agent, technetium-99m sestamibi, was useful in demonstrating a large area of myocardium at risk and subsequent substantial benefit from acute reperfusion therapy. Because this perfusion agent washes out slowly from the myocardium, imaging can be delayed for several hours; thus, acute reperfusion therapy can be performed without delay. Subsequent imaging, however, will reflect myocardial perfusion at the time of administration of the radionuclide. Additional studies with this agent may be valuable in identifying those patients with ST-segment depression who will benefit from acute reperfusion therapy.
      The benefit of thrombolytic therapy in acute myocardial infarction has been clearly established.
      • Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)
      Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI Study.
      ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.
      In most randomized clinical trials, however, ST-segment elevation has been a criterion for inclusion.
      • Chesebro JH
      • Knatterud G
      • Roberts R
      • Borer J
      • Cohen LS
      • Dalen J
      • Dodge HT
      • Francis CK
      • Hillis D
      • Ludbrook P
      • Markis JE
      • Mueller H
      • Passamani ER
      • Powers ER
      • Rao AK
      • Robertson T
      • Ross A
      • Ryan TJ
      • Sobel BE
      • Willerson J
      • Williams DO
      • Zaret BL
      • Braunwald E
      Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase; clinical findings through hospital discharge.
      • Kennedy JW
      • Martin GV
      • Davis KB
      • Maynard C
      • Stadius M
      • Sheehan FH
      • Ritchie JL
      The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial.
      In only a few studies
      • Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)
      Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI Study.
      ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.
      have patients with ST-segment depression been eligible for thrombolytic therapy. In one of these studies,
      ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.
      thrombolytic therapy seemed beneficial in the subgroup of patients who had ST-segment depression. In another study,
      • Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI)
      Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI Study.
      however, thrombolytic therapy seemed to have a negative effect on survival of patients in this subgroup. Thus, the role of thrombolytic therapy in patients with ST-segment depression is uncertain. Furthermore, the amount of myocardium at risk in patients with ST-segment depression is unknown.
      Imaging with a new myocardial perfusion radiopharmaceutical agent, technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (99mTc-sestamibi), facilitates determination of the area of hypoperfused myocardium “at risk” in patients with acute myocardial infarction.
      • Gibbons RJ
      • Verani MS
      • Behrenbeck T
      • Pellikka PA
      • O'Connor MK
      • Mahmarian JJ
      • Chesebro JH
      • Wackers FJ
      Feasibility of tomographic 99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction.
      Like thallium, it accumulates in normal myocardial tissue in direct proportion to blood flow.
      • Okada RD
      • Glover D
      • Gaffney T
      • Williams S
      Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methypropyl-isonitrile.
      Its extremely slow washout, however, allows imaging to be delayed for up to 6 hours but still provides information about the extent of myocardial perfusion at the time of intravenous administration. Thus, reperfusion therapy may be initiated without delay.
      Herein we describe a patient with extensive anterior ST-segment depression, in whom 99mTc-sestamibi was used to demonstrate an extensive area of the lateral wall of the myocardium in jeopardy for infarction. The subsequent clinical course and management of this patient are discussed.

      REPORT OF CASE

      A 71-year-old man had a 3-hour history of nausea and severe substernal chest pain with extension to his left arm, which had awakened him from sleep. He had no prior history of chest pain. He was an exsmoker who had chronic atrial fibrillation and an 8-year history of hypertension. Daily medications included hydrochlorothiazide (25 mg) and aspirin (325 mg).
      On physical examination, the blood pressure was 142/72 mm Hg. The pulse, which was 68 beats/min, was irregularly irregular. Results of a cardiac examination were otherwise normal. Scattered rales were detected at the base of the right lung. Chest roentgenographic findings were normal. An electrocardiogram showed atrial fibrillation, biphasic T waves inferiorly, and ST-segment depression in leads V1 through V5 (Fig. 1). The patient was treated with standard intravenous doses of nitroglycerin, heparin, and lidocaine.
      Figure thumbnail gr1
      Fig. 1Admission electrocardiogram of 71-year-old man with 3-hour history of nausea and severe chest pain, showing ST-segment depression in precordial leads.
      Informed consent was obtained, and 30 mCi of 99mTc-sestamibi was injected intravenously. Cardiac catheterization revealed occlusion of a large first obtuse marginal vessel with an intraluminal thrombus. Also noted were a 60% stenosis of the middle portion of the left anterior descending coronary artery, a 70% stenosis of the first diagonal artery, a 60% stenosis of the right posterior descending artery, and a 60% stenosis of the distal circumflex artery. Percutaneous transluminal coronary angioplasty of the first obtuse marginal vessel was successfully performed; the stenosis was reduced from 100% to 50%. Tomographic 99mTc-sestamibi imaging (Fig. 2) revealed a perfusion defect (quantitated at 34% of the left ventricle) that involved the basal inferior wall and the mid and basal lateral wall. Four hours after angioplasty, creatine kinase peaked at 650 U/liter (normal, 23 to 99 U/ liter) with 18% MB isoenzymes. Subsequent electrocardiograms showed tall R waves in leads V1 through V3, consistent with a posterior myocardial infarction.
      Figure thumbnail gr2
      Fig. 2Same patient as depicted in , before treatment. Representative short-axis tomographic 99mTc-sestamibi images of basal (A), mid (B), and apical (C) left ventricle are shown. Anterior wall is at top of these images, inferior wall is at bottom, septum is on the left, and lateral wall is on the right. In addition, horizontal long-axis slice (D) of left ventricle is depicted. Septum is on the left, apex is at top, and lateral wall is on the right.
      Repeat injection of 99mTc-sestamibi and tomographic imaging 24 hours later showed considerable improvement in perfusion (Fig. 3). A small persistent lateral wall perfusion defect involved 4% of the left ventricle. Repeat 99mTc-sestamibi images at 6 days showed no further change. A resting radionuclide angiogram at 7 days showed moderate hypokinesis of the lateral wall and an ejection fraction of 50%. During exercise, no change in wall motion or ejection fraction was noted. The patient was dismissed from the hospital on a program of nitrates, calcium channel blockers, and β-adrenergic blockers.
      Figure thumbnail gr3
      Fig. 3Same tomographic slices as shown in , 24 hours after reperfusion therapy.

      COMMENT

      Few guidelines have been established for the management of patients with symptoms of acute myocardial infarction but ST-segment depression rather than elevation. In this report, we describe a patient with ST-segment depression who had occlusion of a coronary artery, a large area of myocardium at risk, and substantial benefit from acute reperfusion therapy as demonstrated by 99mTc-sestamibi imaging. In a previous study, a significant decrease in the extent of hypoperfused myocardium in patients who received thrombolytic therapy was demonstrated by using 99mTc-sestamibi imaging, in comparison with an insignificant increase in patients who did not receive acute reperfusion therapy.
      • Gibbons RJ
      • Verani MS
      • Behrenbeck T
      • Pellikka PA
      • O'Connor MK
      • Mahmarian JJ
      • Chesebro JH
      • Wackers FJ
      Feasibility of tomographic 99mTc-hexakis-2-methoxy-2-methylpropyl-isonitrile imaging for the assessment of myocardial area at risk and the effect of treatment in acute myocardial infarction.
      Correlations of pathologic and electrocardiographic findings have demonstrated that many infarctions of the lateral myocardial wall escape electrocardiographic detection, even in their acute phase.
      • Myers GB
      • Klein HA
      • Stofer BE
      Correlation of electrocardiographic and pathologic findings in lateral infarction.
      QRS changes are seldom characteristic for infarction, and ST-segment elevation may be missing. These factors probably account for the paucity of occlusions of the left circumflex coronary artery in randomized trials; the left circumflex artery was the infarct-related vessel in only 12% of patients in the Thrombolysis in Myocardial Infarction I trial.
      • Chesebro JH
      • Knatterud G
      • Roberts R
      • Borer J
      • Cohen LS
      • Dalen J
      • Dodge HT
      • Francis CK
      • Hillis D
      • Ludbrook P
      • Markis JE
      • Mueller H
      • Passamani ER
      • Powers ER
      • Rao AK
      • Robertson T
      • Ross A
      • Ryan TJ
      • Sobel BE
      • Willerson J
      • Williams DO
      • Zaret BL
      • Braunwald E
      Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase; clinical findings through hospital discharge.
      During balloon occlusion of the left circumflex coronary artery in patients undergoing angioplasty, ST-segment elevation was present in less than half the patients; ST-segment depression or no electrocardiographic changes were more commonly seen.
      • Berry C
      • Zalewski A
      • Kovach R
      • Savage M
      • Goldberg S
      Surface electrocardiogram in the detection of transmural myocardial ischemia during coronary artery occlusion.
      ST-segment depression in the precordial leads may be the only early electrocardiographic manifestation of acute posterolateral myocardial infarction.
      • Boden WE
      • Kleiger RE
      • Gibson RS
      • Schwartz DJ
      • Schechtman KB
      • Capone RJ
      • Roberts R
      • Diltiazem Reinfarction Study Group
      Electrocardiographic evolution of posterior acute myocardial infarction: importance of early precordial ST-segment depression.
      Similar benefit from acute reperfusion therapy may be expected to occur in other patients who have chest pain and precordial ST-segment depression. The left circumflex coronary artery will be occluded in several of these patients, some of whom may have a large region of myocardium in jeopardy. Further studies are needed to characterize those patients with ST-segment depression who will benefit from acute reperfusion therapy.

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        • Markis JE
        • Mueller H
        • Passamani ER
        • Powers ER
        • Rao AK
        • Robertson T
        • Ross A
        • Ryan TJ
        • Sobel BE
        • Willerson J
        • Williams DO
        • Zaret BL
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        Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase; clinical findings through hospital discharge.
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        • Savage M
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