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Correlation of improved left ventricular ejection fraction recovering from supine exercise with resting function in anterior wall healed myocardial infarction
Correlation of Improved Left Ventricular Ejection Fraction Recoverin from Supine Exercise with Resting Function in Anterior vf all Healed Myocardial Infarction Massimo Romano, MD, Albert0 Cuocolo, MD, Elisabetta de Arcangelis, MD, Ida Monteforte, Giovanni Carella, MD, Pietro Muto, MD, and Mario Condorelli, MD
E
xercise radionuclide angiography provides information about transient abnormalities in wall motion and ejection fraction (EF) suggesting the presence of myocardial ischemia.‘y2 It has been demonstrated that EF increased during recovery after supine or upright exercise.3,4 In particular, Rozanski et al4 suggested that the evaluation of recovery after exercise radionuclide angiography may be clinically important. This study investigates if EF response during recovery after exercise is intluenced by resting EF in patients with previous myocardial infarction and left ventricular (LV) dysfunction. We studied 21 consecutive patients (all men, mean age 52 f 4 years) with previous anterior wall myocardial infarction (>2 months) and regional LV dysfunction. Electrocardiographic evidence of Q waves in at least 2 of leads V2, V3 and Vd had been required for admission. None had history of postinfarction angina or clinical congestive heart failure. Cardiac imaging was pe$ormed after withdrawal of all antianginal medications. All patients had irreversible perfusion defects on exercise thallium-201 imaging with reinjection at rest. Ten subjects (all men, mean age 49 + 5 years) with atypical chest pain and normal exercise thallium-201 scintigraphy served as control subjects. Red blood cells were labeled in vivo with 25 mCi technetium-99m.j Radionuclide angiography was performed as previously described6 in the supine position at rest, at peak exercise and immediately after exercise (recovery). Briefly, imaging was peformed with a small field-of-view gamma camera oriented in a modtfied 45” left anterior oblique view. Imaging rate was 20 mslframe and EF was calculated on the raw time-activity curve.6 All patients and control subjects underwent supine bicycle exercise (25 W load, increased stepwise 25 WI3 minutes), interrupted for exhaustion andlor dyspnea (no angina or ST depression). Data are expressed as mean f SD. One-way analysis of variance and the Duncan test were used to compare EF at rest, during exercise and during recovery. To assess the relations between resting EF and changes of its value at peak exercise and during recovery, we calculated ratios between peak exercise and resting EF, recovery and peak exercise EF, and recovery and resting EF. Linear regression analysis was used to assess relations among resting EF and ratios. Unpaired t test was used when appropriate. A p value ~0.05 was considered sign$cant. From the Cardiopulmonary Stress Laboratory, Internal Medicine and Nuclear Medicine, University Federico II, and the National Cancer Institute, Napoli, Italy. Manuscript received May 13, 1993; revised manuscript received July 6, 1993, and accepted July 7.
MD,
In patients, heart rate increasedfrom 66 f IO beats1 min at rest to 110 + 8 beatslmin at peak exercise, and then declined to 90 f 12 beatslmin during recovery. In control subjects, heart rate was 80 + 4, 140 + 6 ana’ 116 + 4 beatslmin, respectively. Work rate was 135 + 10 Wlmin in control subjects and 88 f 15 Wlmin in patients (p
ao*
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B
I3
R
B
Ex
R
0
C FlBUREl.bftvcmtria1lar~-(EF)in10corr trols(C)mIdin2lpatienb(P)wRhpwwiausanteriormy~ uudialinfwcthandleR-lardysfunctionatrert(B), at peak exerciss (Ex) ad dwh@ CatSS Q <~o.~ vwsus B.
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(R). A-
I
Ml-
BRIEF REPORTS 515
tion induced by vasodilatation and catecholamine release after exercise in such patients.4 Thus, this response should be expected during recovery after exercise radionuclide angiography in patients with previous anterior myocardial infarction and without exercise-induced myocardial ischemia. 1. Holman BL. Nuclear cardiology. In: Brauwald E, ed. Heart Disease. Philadelphia: W.B. Saunders, 1988:83-139. 2. Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Selder SF, Epstein SE, Johnston GS. Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with comnaty artery disease. Ciwula-
tion1979;60:572-580. a. Ptisterer ME, Slutsky RA, Schuler G, Ricci DR. Swanson SS, Gordon DG, Battler A, Froelicher VF Jr, Peterson KE, Ashbum WL. Profiles of radionuclide left ventricular ejection fraction changes induced by supine bicycle exercise in normals and patients with coronary heart disease. Cather Cardiovasc Dia,qn 1979;5:305-317. 4. Rozanski A, Elkayam U, Bennan DS, Diamond GA, Prause JA, Swan HJC. Improvement of resting myocardial asynergy with cessation of upright bicycle exercise. Circulation 1983:67:529-535. 5. Callahan RJ, Fmelich JW, McKusick KA, Leppa J, Strauss HW. A modified method for the in viva labelling of red blood cells with Tc-99m: concise communication. J Nucl Med 1982;23:315-318, 6. Cuocolo A, Santomauro M, Pace L, Celentano L, Nappi A. Nicolai E, Chiariello M, Salvatore M. Comparison between exercise and transoesophageal ahial pacing in patients with coronary artery disease: technetium-99m sestamibi simultaneous evaluation of ventricular function and myocardial perfusion. Ew J Nucl Med 1992; 19:119-124.
AngitwFree Time on the Treadmill as an Alternate Evaluating Antianginal Therapy
Method for
Pamela M. Hartigan, PhD, Alfred F. Parisi, MD, and Edward D. Folland, MD, for the Veterans Affairs ACME investigators*
N
ew treatments for angina or ischemia are often evaluated by exercise tolerance tests (ETTs). Traditionally 2 different measures are used: the proportion of patients who develop angina or ST depression during the test and the mean time to the onset of angina or ST depression among those who develop it. Use of these results, however, can be misleading because they do not fully take into account the information available from the successfully treated patients who do not experience these events. Survival (or time-to-failure) methodology would incorporate information from all the patients.’ This methodology is described, related specifically to the development of angina on the treadmill, and applied to data from a recent trial comparing percutaneous transluminal coronary angioplasty (FICA) and medical therapy in patients with l-vessel coronary artery disease.2
In a clinical trial that uses death as a primary end point, the observation period is the time from when a patient is randomized until either he or she dies (fails) or the study ends. If the patient does not die during the trial, then, for the purposes of analysis, the patient is “censored” at the end of the trial. The term “censored’ means that the patient was known to be alive when last observed. Use of the time such a patient is observed during the trial contributes importantly to the comparison of the treatment regimens. When the same survival methods are applied to trials that evaluate the development of angina during an EIT, the observation period would be the time from when the patient begins the test until the patient either develops angina (Jails) or stops exercising (censored). These data would then be used to construct Kaplan-Meier (or angina-free exercise time [survival]) curves, and the curves would be compared using a log rank {or similar) statistic.’ Other statistical techniques such as Cox regression could also be used.’ This latter technique allows the incorporation of other information such as the patient’s pretreatment ETT result into the treatment comparison. Table I lists the hypothetical ETT results for a small study comparing 2 treatments, A and B, in which each
From the Research Service, Veterans Affairs Medical Centers, 950 Campbell Avenue, West Haven, Connecticut 06516; and West Roxbury, Massachusetts. This report was supported by the Cooperative Studies Program, Research Service, Department of Veterans Affairs, Washington, D.C. Manuscript received January 26, 1993; revised manuscript received and accepted July 13, 1993. *Investigators who participated in the Angioplasty Compared to Medicine (ACME) study are listed in the Appendix.
TABLE
I
Hypothetical
Outcomes
Treatment Number of Patients
1 1 1
1 1 13
516
After
Treatment
A
Treatment
Total ETT Time (min)
Angina
3.0 5.0 7.0
+ f +
9.0
+
11.0 + 3.0 0 Traditional analyses of angina Percent with angina Mean time to angina (min)
Time to Angina (min) 2.0 4.0 6.0 8.0
10.0
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 73
Number of Patients
Total ETT Time (min)
1 1 1
3.0 5.0 7.0
1 1
9.0 11.0 11.0
13
Treatment A 5118 = 28% 6.0
MARCH 1, 1994
B
Angina
+ + + + +
0
Time to Angina (min) 2.0 4.0 6.0 8.0
10.0 -
Treatment B 5118 = 28% 6.0
E
xercise radionuclide angiography provides information about transient abnormalities in wall motion and ejection fraction (EF) suggesting the presence of myocardial ischemia.‘y2 It has been demonstrated that EF increased during recovery after supine or upright exercise.3,4 In particular, Rozanski et al4 suggested that the evaluation of recovery after exercise radionuclide angiography may be clinically important. This study investigates if EF response during recovery after exercise is intluenced by resting EF in patients with previous myocardial infarction and left ventricular (LV) dysfunction. We studied 21 consecutive patients (all men, mean age 52 f 4 years) with previous anterior wall myocardial infarction (>2 months) and regional LV dysfunction. Electrocardiographic evidence of Q waves in at least 2 of leads V2, V3 and Vd had been required for admission. None had history of postinfarction angina or clinical congestive heart failure. Cardiac imaging was pe$ormed after withdrawal of all antianginal medications. All patients had irreversible perfusion defects on exercise thallium-201 imaging with reinjection at rest. Ten subjects (all men, mean age 49 + 5 years) with atypical chest pain and normal exercise thallium-201 scintigraphy served as control subjects. Red blood cells were labeled in vivo with 25 mCi technetium-99m.j Radionuclide angiography was performed as previously described6 in the supine position at rest, at peak exercise and immediately after exercise (recovery). Briefly, imaging was peformed with a small field-of-view gamma camera oriented in a modtfied 45” left anterior oblique view. Imaging rate was 20 mslframe and EF was calculated on the raw time-activity curve.6 All patients and control subjects underwent supine bicycle exercise (25 W load, increased stepwise 25 WI3 minutes), interrupted for exhaustion andlor dyspnea (no angina or ST depression). Data are expressed as mean f SD. One-way analysis of variance and the Duncan test were used to compare EF at rest, during exercise and during recovery. To assess the relations between resting EF and changes of its value at peak exercise and during recovery, we calculated ratios between peak exercise and resting EF, recovery and peak exercise EF, and recovery and resting EF. Linear regression analysis was used to assess relations among resting EF and ratios. Unpaired t test was used when appropriate. A p value ~0.05 was considered sign$cant. From the Cardiopulmonary Stress Laboratory, Internal Medicine and Nuclear Medicine, University Federico II, and the National Cancer Institute, Napoli, Italy. Manuscript received May 13, 1993; revised manuscript received July 6, 1993, and accepted July 7.
MD,
In patients, heart rate increasedfrom 66 f IO beats1 min at rest to 110 + 8 beatslmin at peak exercise, and then declined to 90 f 12 beatslmin during recovery. In control subjects, heart rate was 80 + 4, 140 + 6 ana’ 116 + 4 beatslmin, respectively. Work rate was 135 + 10 Wlmin in control subjects and 88 f 15 Wlmin in patients (p
ao*
30/
B
I3
R
B
Ex
R
0
C FlBUREl.bftvcmtria1lar~-(EF)in10corr trols(C)mIdin2lpatienb(P)wRhpwwiausanteriormy~ uudialinfwcthandleR-lardysfunctionatrert(B), at peak exerciss (Ex) ad dwh@ CatSS Q <~o.~ vwsus B.
P
raovsry
(R). A-
I
Ml-
BRIEF REPORTS 515
tion induced by vasodilatation and catecholamine release after exercise in such patients.4 Thus, this response should be expected during recovery after exercise radionuclide angiography in patients with previous anterior myocardial infarction and without exercise-induced myocardial ischemia. 1. Holman BL. Nuclear cardiology. In: Brauwald E, ed. Heart Disease. Philadelphia: W.B. Saunders, 1988:83-139. 2. Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Selder SF, Epstein SE, Johnston GS. Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with comnaty artery disease. Ciwula-
tion1979;60:572-580. a. Ptisterer ME, Slutsky RA, Schuler G, Ricci DR. Swanson SS, Gordon DG, Battler A, Froelicher VF Jr, Peterson KE, Ashbum WL. Profiles of radionuclide left ventricular ejection fraction changes induced by supine bicycle exercise in normals and patients with coronary heart disease. Cather Cardiovasc Dia,qn 1979;5:305-317. 4. Rozanski A, Elkayam U, Bennan DS, Diamond GA, Prause JA, Swan HJC. Improvement of resting myocardial asynergy with cessation of upright bicycle exercise. Circulation 1983:67:529-535. 5. Callahan RJ, Fmelich JW, McKusick KA, Leppa J, Strauss HW. A modified method for the in viva labelling of red blood cells with Tc-99m: concise communication. J Nucl Med 1982;23:315-318, 6. Cuocolo A, Santomauro M, Pace L, Celentano L, Nappi A. Nicolai E, Chiariello M, Salvatore M. Comparison between exercise and transoesophageal ahial pacing in patients with coronary artery disease: technetium-99m sestamibi simultaneous evaluation of ventricular function and myocardial perfusion. Ew J Nucl Med 1992; 19:119-124.
AngitwFree Time on the Treadmill as an Alternate Evaluating Antianginal Therapy
Method for
Pamela M. Hartigan, PhD, Alfred F. Parisi, MD, and Edward D. Folland, MD, for the Veterans Affairs ACME investigators*
N
ew treatments for angina or ischemia are often evaluated by exercise tolerance tests (ETTs). Traditionally 2 different measures are used: the proportion of patients who develop angina or ST depression during the test and the mean time to the onset of angina or ST depression among those who develop it. Use of these results, however, can be misleading because they do not fully take into account the information available from the successfully treated patients who do not experience these events. Survival (or time-to-failure) methodology would incorporate information from all the patients.’ This methodology is described, related specifically to the development of angina on the treadmill, and applied to data from a recent trial comparing percutaneous transluminal coronary angioplasty (FICA) and medical therapy in patients with l-vessel coronary artery disease.2
In a clinical trial that uses death as a primary end point, the observation period is the time from when a patient is randomized until either he or she dies (fails) or the study ends. If the patient does not die during the trial, then, for the purposes of analysis, the patient is “censored” at the end of the trial. The term “censored’ means that the patient was known to be alive when last observed. Use of the time such a patient is observed during the trial contributes importantly to the comparison of the treatment regimens. When the same survival methods are applied to trials that evaluate the development of angina during an EIT, the observation period would be the time from when the patient begins the test until the patient either develops angina (Jails) or stops exercising (censored). These data would then be used to construct Kaplan-Meier (or angina-free exercise time [survival]) curves, and the curves would be compared using a log rank {or similar) statistic.’ Other statistical techniques such as Cox regression could also be used.’ This latter technique allows the incorporation of other information such as the patient’s pretreatment ETT result into the treatment comparison. Table I lists the hypothetical ETT results for a small study comparing 2 treatments, A and B, in which each
From the Research Service, Veterans Affairs Medical Centers, 950 Campbell Avenue, West Haven, Connecticut 06516; and West Roxbury, Massachusetts. This report was supported by the Cooperative Studies Program, Research Service, Department of Veterans Affairs, Washington, D.C. Manuscript received January 26, 1993; revised manuscript received and accepted July 13, 1993. *Investigators who participated in the Angioplasty Compared to Medicine (ACME) study are listed in the Appendix.
TABLE
I
Hypothetical
Outcomes
Treatment Number of Patients
1 1 1
1 1 13
516
After
Treatment
A
Treatment
Total ETT Time (min)
Angina
3.0 5.0 7.0
+ f +
9.0
+
11.0 + 3.0 0 Traditional analyses of angina Percent with angina Mean time to angina (min)
Time to Angina (min) 2.0 4.0 6.0 8.0
10.0
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 73
Number of Patients
Total ETT Time (min)
1 1 1
3.0 5.0 7.0
1 1
9.0 11.0 11.0
13
Treatment A 5118 = 28% 6.0
MARCH 1, 1994
B
Angina
+ + + + +
0
Time to Angina (min) 2.0 4.0 6.0 8.0
10.0 -
Treatment B 5118 = 28% 6.0