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Analysis of apical remodeling in gated myocardial perfusion SPECT imaging in ischemic cardiomyopathy
Analysis of apical remodeling in gated myocardial perfusion SPECT imaging in ischemic cardiomyopathy Guillermo Romero-Farina, MD, PhD, FESC,a Jaume Candell-Riera, MD, PhD, FESC,a Santiago Aguadé-Bruix, MD,b Joan Castell-Conesa, MD, PhD,b and Gustavo de León, MDa Background. A divergent pattern (DP) of the left ventricle (LV) is an expression of apical remodeling in myocardial perfusion gated single-photon emission computed tomography (SPECT) of patients with ischemic cardiomyopathy (ICM). Methods and Results. We consecutively studied 156 patients (mean age, 63 years; 24 women) with ICM (LV ejection fraction, <40%) using gated SPECT and technetium-labeled agents. Apical remodeling was considered to exist when a DP was observed. Apical remodeling was noted in 30% of patients, all of whom had a history of anterior myocardial infarction. A divergent pattern was observed more frequently in younger patients and in those with ST-segment elevation on their electrocardiograms. The longer the interval between the infarction and the performance of gated SPECT, the more prevalent were the LV dilatation and DP. A divergent pattern was associated with cardiac death and heart failure only in patients with scintigraphic criteria for myocardial viability. Conclusions. A divergent pattern in gated SPECT, as an expression of apical remodeling, can be observed in up to a third of patients with ICM, all with a history of anterior infarction. The longer the time between the infarction and the gated SPECT, the more prevalent the LV dilatation becomes. Apical remodeling is a variable predicts mortality in patients with scintigraphic criteria for viability. (J Nucl Cardiol 2008;15:225-31.) Key Words: Ischemic heart disease • systolic dysfunction • scintigram • divergent pattern • prognostic • ventricular remodeling Left-ventricular remodeling has been studied using different techniques, but has rarely been assessed using gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with ischemic cardiomyopathy. In gated myocardial perfusion SPECT studies, one of the signs of apical remodeling is the presence of a divergent pattern (DP) of the left ventricle. This pattern is characterized by a larger transverse From the Servei de Cardiologia,a and Servei de Medicina Nuclear,b Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. This study was partially funded by grants from Fundación Carolina (Madrid, Spain) and the Redes Temáticas de Investigación Cooperativa, Instituto Carlos III (Red C03/01, red temática de entermedades cardiovasculares [RECAVA] (Madrid, Spain). Received for publication Sept 14, 2007; final revision accepted Nov 9, 2007. Reprint requests: Jaume Candell-Riera, Servei de Cardiologia, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Paseo Vall d’Hebron 119-129, 08035 Barcelona, Spain; jcandell@ vhebron.net. 1071-3581/$34.00 Copyright © 2008 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2007.11.017
diameter at the apex than at the base. A divergent pattern has been associated with the presence of ventricular aneurysm and a higher rate of cardiac death (CD).1-5 The objective of this study was to analyze DPs in gated myocardial perfusion SPECT imaging with technetium-labeled agents, in a patient population with ischemic heart disease and systolic dysfunction. METHODS Patients All consecutive patients who underwent gated myocardial perfusion SPECT in our Nuclear Cardiology Unit for risk stratification of their ischemic heart disease between May 1997 and July 2002 were investigated. A left-ventricular ejection fraction (EF) of ⱕ40% was observed in 365 patients. From that group, 209 were excluded because of the presence of any other type of heart disease (n ⫽ 70), implanted pacemakers (n ⫽ 3), previous revascularization (n ⫽ 86), or an inability to perform exercise (n ⫽ 50). In 7 patients, clinical follow-up could not be completed. One hundred and fifty-six patients with an EF ⱕ40% and 225
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without previous revascularization procedures who were able to undergo stress testing as a provocation maneuver were included.
Resting Electrocardiogram An electrocardiogram (ECG) was performed in all patients on the same day as gated SPECT. Heart rate, the presence of Q-waves and their topography, ST segment changes, and bundle branch blocks were recorded.
Stress Test The 156 patients underwent a symptom-limited exercise test on an ergometer-cycle. One hundred and forty-two patients underwent only the ergometer-cycle test, and in 14, intravenous dipyridamole was administered during exercise when they did not reach 80% of their maximum heart rate.6 The initial load was 50 W, with 25-W increments every 3 minutes until exhaustion, the appearance of symptoms, ST segment depression ⬎2 mm, the appearance of ventricular or supraventricular arrhythmias, or the failure of systemic blood pressure to increase. At the time the stress test was performed, all patients were receiving medical treatment. An assessment was made, including symptoms, test duration, maximum oxygen consumption estimated in metabolic equivalents (METs), maximum heart rate, maximum heart rate as a percentage of theoretical value for the patient’s age (220 – age), maximum systolic blood pressure, the product of both, and a downsloping or upsloping ST segment ⱖ1 mm at 0.08 seconds beyond the J point, angina, and dyspnea.
Gated Myocardial Perfusion SPECT Stress/rest gated SPECT was performed in all patients using a 1-day protocol (first stress, then rest) with technetiumbased components (30% methoxy isobutyl isonitrile [MIBI], 70% tetrofosmin) A first dose of 8 mCi was given 30 to 60 seconds before the completion of exercise, followed by a second dose of 24 mCi (at rest), with an interval of ⬎45 minutes between them. The equipment used was a Siemens E.CAM dual-head 90° gamma camera with a high-resolution collimator and a 180° semicircular orbit in “step-and-shoot” mode, initiated at 45° right anterior oblique (Siemens, Berlin, Germany). Images were obtained every 3° (25 seconds). Acquisition was synchronized with the ECG R-wave, with 8 frames/cardiac cycle. Frames were reconstructed using filtered back-projection (Butterworth filter, order of 5, cutoff frequency of 0.4). No corrections were made for attenuation and scatter. To quantify perfusion and wall-thickening, the left ventricle was divided into 17 segments,7 and each was given a score from 0 to 4 for perfusion (0, normal perfusion; 1, mild hypoperfusion; 2, moderate hypoperfusion; 3, severe hypoperfusion; and 4, no uptake) and wall-thickening (0, normal; 1, mildly impaired; 2, moderately impaired; 3, severely impaired; and 4, no wall thickening). A summed rest score (SRS), summed stress score (SSS), and summed difference score (SDS) for perfusion, and the SRS for wall-thickening, were
Figure 1. Example of a divergent pattern in myocardial perfusion single-photon emission computed tomography in a patient with ischemic cardiomyopathy. The transverse diameters of the left ventricle at the apex (A ( ) are greater than the transverse diameters at the base (B) in the horizontal (right) and vertical (left) long-axis slices. calculated. Rest gated SPECT was used to analyze myocardial viability. Significant myocardial viability was defined as the presence of relatively preserved perfusion (perfusion score of 0-3) in ⱖ3 severely hypokinetic, akinetic, or dyskinetic segments.8,9 The percentage of myocardial viability was calculated from the following equation: ([number of viable segments]/[total segments]) ⫻ 100, and the percentage of myocardial necrosis was calculated from the following equation: ([number of necrosis segments]/[total segments]) ⫻ 100. Myocardial ischemia was defined as having an SDS ⱖ2, and the ischemia percentage was calculated from the following equation: ([number of ischemic segments]/[total segments]) ⫻ 100. End-diastolic volume (EDV), end-systolic volume (ESV), and left-ventricular EF were assessed, as was the presence of a DP. A divergent pattern was considered to exist when the transverse diameter was greater at the apex than at the base (Figure 1). Calculation of the EF and ventricular volumes was performed automatically during rest gated SPECT, using the QGS program (Cedars-Sinai Medical Center, Los Angeles, Calif).10
Follow-up In the follow-up until the performance of gated SPECT (mean, 2.3 years; standard deviation [SD], 1,1; range, between 1 month and 6 years), overall CD, CD because of heart failure (HF), sudden CD, and coronary revascularization (CR) by surgery or angioplasty were assessed.
Statistical Analysis Clinical and electrocardiographic characteristics, the results of the ergometer test and stress/rest gated SPECT testing, and the follow-up of patients with and without DP were compared. Ventricular volumes, EF, the presence of viability, and myocardial ischemia were anayzed in groups of patients studied at different periods after myocardial infarction. Continuous variables were compared using Student’s t test for independent samples, and were expressed as mean values and SDs. The differences between two proportions were
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Table 1. Clinical characteristics of patients
Characteristics Clinical Age (y) Women Functional class (NYHA) I-II III-IV Angina grade (CCS) I-II III-IV Diabetes Dyslipemia Arterial hypertension Smoking Stroke Myocardial infarction Anterior infarction Inferior infarction Coronary angiography Electrocardiographic Q-wave Sinus rhythm 1 ST segment ⬎1 mm 2 ST segment ⬎1 mm RBBB LBBB AHB PHB Follow-up Years Overall cardiac death Death because of HF Sudden death Coronary revascularization Surgical revascularization Coronary angioplasty
Global values (n ⴝ 156)
No divergent pattern (n ⴝ 109)
Divergent pattern (n ⴝ 47)
62.9 (SD, 11.6) 25 (16%)
64.2 (SD, 11) 18 (16.5%)
59.8 (SD, 12) 7 (14.9%)
P
.031 .800
19 (12.2%) 20 (12.8%)
16 (14.7%) 17 (15.6%)
3 (6.4%) 3 (6.4%)
.146 .114
28 (17.9%) 21 (13.5) 54 (34%) 93 (59.6%) 83 (53.2%) 97 (62.2%) 6 (3.8%) 131 (84%) 86 (55.1%) 37 (23.7%) 107 (68.6%)
21 (19.3%) 15 (13.8%) 35 (32.1%) 64 (58.7%) 58 (53.2%) 69 (63.3%) 5 (4.6%) 84 (77.1%) 44 (40.4%) 31 (28.4%) 74 (67.9%)
7 (14.9%) 6 (12.8%) 19 (40.4%) 29 (61.7%) 25 (53.2%) 28 (59.6%) 1 (2.1%) 47 (100%) 41 (87.2%) 6 (12.8%) 33 (70.2%)
.54 .867 .317 .727 .998 .660 .669 .003 ⬍.001 .035 .774
107 (68.6%) 150 (96.2%) 93 (59.6%) 26 (16.7%) 21 (13.5%) 12 (7.7%) 29 (18.6%) 12 (9.2%)
64 (58.7%) 105 (96.3%) 57 (52.3%) 22 (20.2%) 15 (13.8%) 8 (7.3%) 17 (15.6%) 7 (7.8%)
43 (91.5%) 45 (95.7%) 36 (76.6%) 4 (8.5%) 6 (12.8%) 4 (8.5%) 12 (25.5%) 5 (12.5%)
⬍.001 .860 .005 .073 .867 .754 .143 .512
2.3 (SD, 1.1) 23 (14.7%) 17 (10.9%) 6 (3.8%) 46 (29.5%) 35 (22.4%) 11 (7.1%)
2.3 (SD, 1.2) 17 (15,6%) 12 (11%) 5 (4.6%) 37 (33.9%) 30 (27.5%) 7 (6.4%)
2.2 (SD, 2) 6 (12.8%) 5 (10.6%) 1 (2.1%) 9 (19.1%) 5 (10.6%) 4 (8.5%)
.659 .647 .946 .669 .069 .020 .735
RBBB, Right-bundle branch block; LBBB, left-bundle branch block; CCS, Canadian Cardiovascular Society; HF, heart failure; AHB, anterior hemiblock; PHB, posterior hemiblock; NYHA, New York Heart Association; SD, standard deviation; 1, ST evaluation; 2, ST depression.
compared using the 2 test or Fisher’s exact test, and were expressed as a percentage. In patients with previous infarction (n ⫽ 131), a multiple linear regression model was used to determine the adjusted increase in EDV and ESV for each year of postinfarction follow-up. The relationship between trends of mean EDV, ESV, and EF, and time elapsed since myocardial infarction (classified into categories by years: ⬍5 years, between 5 and 10 years, and ⱖ10 years), was studied using the nonparametric Jonckheere-Terpstra test. In addition, a multiple linear regression model was used to analyze the quadratic and linear trends
(with code for orthogonal polynomials) between time postinfarction, volumes, and EF. The Kaplan-Meier method was used for survival analysis, and survival curves of the different groups were compared using log-rank and Breslow tests, adjusted for CR. The prognostic value of a DP was determined with the Cox regression method (forward stepwise [FSTEP], inclusion criteria P ⱕ .05, and exclusion criteria P ⬎ .10), adjusted for age, gender, and CR. P ⬍ .05 was considered a statistically significant difference. The program used was SPSS for Windows, version 13.0 (SPSS, Inc., Chicago, Ill).
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Table 2. Characteristics of gated SPECT in patients with and without a divergent pattern
SPECT SRS for perfusion SSS for perfusion SDS for perfusion Percent ischemia Percent viability Percent necrosis Ischemic patients Viable patients Viable ⫹ ischemia Gated EF (%) ESV (mL) EDV (mL) SRS, wall-thickening
No divergent pattern (n ⴝ 109)
Divergent pattern (n ⴝ 47)
P
19.4 (SD, 8.5) 23.4 (SD, 8) 4.2 (SD, 3) 21.6 (SD, 19) 49.7 (SD, 20) 4.7 (SD, 3) 74 (67.9%) 93 (85.3%) 67 (61.5%)
30.4 (SD, 7) 33.7 (SD, 6) 3.4 (SD, 3) 17.8 (SD, 20) 51.4 (SD, 14) 17.4 (SD, 8) 26 (55.3%) 17 (36.2%) 13 (27.7%)
⬍.001 ⬍.001 .204 .28 .44 ⬍.001 .133 ⬍.001 ⬍.001
32.5 (SD, 6) 117.3 (SD, 50) 171.3 (SD, 64) 18.1 (SD, 8.1)
28.7 (SD, 6.8) 150.6 (SD, 62) 207.4 (SD, 72) 29.2 (SD, 8)
.001 .001 .002 ⬍.001
SPECT, Single-photon emission computed tomography; EF, ejection fraction; DP, divergent pattern; SDS, summed difference score; SSS, summed stress score; SRS, summed rest score; EDV, end-diastolic volume; ESV, end-systolic volume; SD, standard deviation.
RESULTS The prevalence of a DP of the left ventricle was 30.1% (47/156). Patients with a DP were significantly younger, had more often experienced a previous anterior and inferior myocardial infarction, and had a higher percentage of Q-waves and ST segment elevations on their ECGs (Table 1). A divergent pattern was not observed in patients with only an inferior infarction; the six inferior infarctions with a DP were all associated with anterior infarctions. No significant differences were found in the frequency of symptoms, functional class, angina grade, or ergometric variables. All patients were receiving medical treatment (55.5%, angiotensin enzymeconverting inhibitors; 47.3%, beta blockers; 50.9%, nitrates; 20.9%, diuretics; 25%, anticoagulants; 7.3%, digoxin; 7.3%, calcium channel blockers; and 3.6%, amiodarone). There were no significant differences between patients with and without a DP. In patients who underwent coronary angiography (n ⫽ 107), occlusion of the anterior descending coronary artery was significantly more prevalent when there was a DP (2, 4.079; P ⫽ .043). In the gated SPECT analysis (Table 2), rest and stress perfusions (n ⫽ 47) were significantly more impaired in patients with a DP, and the necrotic area was larger. The percentage of myocardial viability and viability plus myocardial ischemia was significantly lower in patients with a DP. Wall-thickening and EF were significantly reduced, whereas EDV and ESV were significantly higher when patients had a DP.
In patients with a previous infarction (n ⫽ 131), it was observed that the longer the time interval between acute myocardial infarction and the performance of gated SPECT, the greater the probability of finding a DP. Figure 2 shows the increase in mean probability of having a DP for different time categories (Figure 2A, ⬍ 5; Figure 2B, ⱖ5 to 10; and Figure 2C, ⱖ10 years). The same finding was observed for left-ventricular volumes (EDV and ESV). When multiple linear regression was used to evaluate the effect of time interval between infarction and gated SPECT on ventricular volumes (adjusted for ischemia, viability, and number of infarctions), it was seen that for each additional year elapsed since the infarction, EDV increased by 2.3 mL (95% confidence interval [CI], 0.42-4.2; analysis of variance [ANOVA] F, 4.565; P ⫽ .002]), and ESV increased by 2 mL (95% CI, 0.1-3.1; ANOVA F, 4.692; P ⫽ .001). When the time interval was classified by years (⬍5, ⱖ5 to ⬍10, and ⱖ10 years), the degree of significance pointed to an upward trend in mean EDV and mean ESV as the interval increased (ESV, 2Jonckheere-Terpstra ⫽ 2.994; P ⫽ .003; EDV, 2Jonckheere-Terpstra ⫽ 2.903; P ⫽ .004; Figure 3). In the linear trend analysis, a level of significance was reached for EDV ( ⫽ 22.966; 95% CI, 2.9-42.9; P ⫽ .025) and for ESV ( ⫽ 19.226; 95% CI, 3.22-35.2; P ⫽ .019), but not for EF. Follow-up and Prognosis Overall CD over a mean follow-up of 2.26 years after gated SPECT amounted to 6.3/100 patients/year;
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Figure 2. Analysis of the probability of a divergent pattern (DP) in patients with ischemic cardiomyopathy, based on the time elapsed between the myocardial infarction and gated single-photon emission computed tomography (SPECT) T (A, ⬍5 years; B, 5 to ⬍10 years; C, ⱖ10 years). As this interval increases, the probability of developing a DP becomes significantly higher. MI, Myocardial infarction; Sq r, square.
CD because of heart failure amounted to 4.6/100 patients/year; and sudden death amounted to 1.6/100 patients/year. In total, 29.5% patients were revascularized (Table 1), and 70.5% were not; 32% were nonviable patients; 35% did not have suitable coronaries; and 33% exhibited renal failure, high risk, or advanced age. Annual coronary revascularization amounted to 15.9/100 patients/year (surgery, 12.1/100 patients/year; and angioplasty, 3.8/ patients/year). In patients with DP, CR by surgery was significantly lower than in the other patients, although the difference with respect to CR by percutaneous transluminal coronary angioplasty (PTCA) was not significant (Table 1). The presence of a DP did not in itself constitute a prognostic variable for overall CD (HR, 0.8; 95% CI, 0.34-2.2; P ⫽ .795), CD because of HF (HR, 1.04; 95% CI, 0.36-2.9; P ⫽ .935), and sudden death (HR, 0.49; 95% CI, 0.58-4.29; P ⫽ .527). Nevertheless, when only patients with scintigraphic criteria for viability were considered (n ⫽ 110), a DP showed prognostic value (variables in the regression model included DP, previous myocardial infarction, myocardial ischemia, ejection fraction, and end-systolic volume) for overall CD (adjusted for age, gender, and CR: HR, 3.1; 95% CI, 1.1-8.7; P ⫽ .028; ⫺2log likelihood: 169,266; degrees of freedom [df], 4; P ⫽ .03) and CD because of heart failure
Figure 3. Relationship between end-diastolic volume (EDV), V end-systolic volume (ESV), V and different time intervals between a myocardial infarction and gated single-photon emission computed tomography (SPECT) T (A, ⬍5 years; B, 5 to ⬍10 years; C, ⱖ10 years). EDV: linear trend test, P ⫽ .025; quadratic trend test, P ⫽ .93. ESV: linear trend test, P ⫽ .019; quadratic trend test, P ⫽ .77. MI, Myocardial infarction.
(adjusted for age, gender, and CR: HR, 3.9; 95% CI, 1.2-12.8; P ⫽ .02; ⫺2log likelihood: 122,167; df, 4; P ⫽ .01; Figure 4), but not for sudden death (adjusted for age, gender, and CR: HR, 1.6; 95% CI, 0.16-15; P ⫽ .706; ⫺2log likelihood: 29,013; df, 4; P ⫽ .354). DISCUSSION A divergent pattern of the left ventricle is one of the scintigraphic signs of extensive left-ventricular remodeling. In our population of patients with ischemic heart disease and EF ⱕ40%, the prevalence of a DP of the left ventricle in gated myocardial perfusion SPECT with technetium (Tc)-labeled agents was 30%, a result comparable to the findings of earlier studies with 201thallium (Tl) (31%)1 and 99Tc-MIBI (41%).2 The sensitivity and specificity of this pattern for the diagnosis of ventricular aneurysm are ⬎94% when contrast ventriculography is used as the gold standard.2 More than 80% of ventricular
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Figure 4. Survival analysis using a Kaplan-Meier curve in viable patients with and without a divergent pattern (DP) for overall cardiac death (CD) (left) and for CD because of heart failure (right).
aneurysms are located in the antero-apical wall, and only 5% to 10% are located in the lateral wall. In our series, all patients with a DP had a previous anterior infarction. These results are comparable to those of Hirai et al,11 who found that aneurysms and coronary lesions were correlated; they observed that aneurysms of the anterior wall were associated with total occlusion of the anterior descending artery in the presence of poor collateral circulation. In our series, no patient with isolated inferior infarction showed a DP. One of the electrocardiographic criteria for the diagnosis of left-ventricular aneurysm is a persistent ST segment elevation in the postinfarction ECG.12 This sign appeared in 75% of the patients in our series who had a DP. Generally speaking, left-ventricular remodeling develops secondary to extensive transmural myocardial infarction,13-18 and is arbitrarily divided into an early phase (within the first 72 hours) and a late phase (⬎72 hours).19 The early phase includes expansion of the infarcted area, occasionally causing myocardial rupture or ventricular aneurysm. It was shown that the late phase compromises the left ventricle as a whole, and is characterized by time-dependent dilatation, a distorsion of ventricular shape, and compensating wall hypertrophy. As necrotic tissue is replaced by myocardial scar tissue, myocytes become enlarged, and interstitial fibrosis appears in remote areas, resulting in dilatation and the alteration of ventricular morphology.18,20-25 All of our patients were assessed during the late phase, and our results corroborate these findings. In our series, we observed a significant increase in ventricular volumes and a smaller percentage of patients with viability criteria as the time interval between the infarction and gated SPECT increased. Goto et al,26 in SPECT studies with 201Tl, observed that myocardial ischemia detected during exercise in regions remote from the myocardial
infarction might be one of the causes of ventricular remodeling. Furthermore, the remodeling itself increases myocardial oxygen consumption and thus wall stress, facilitating the development of myocardial ischemia during exercise.27 These results are comparable to magnetic resonance studies in which a close linear relationship between size of infarction, ventricular volumes, and EF was found.28 In our population of patients with ischemic cardiomyopathy, a DP of the left ventricle appearing in gated SPECT was not independently correlated with CD. This result approximates the findings of Pace et al,29 in which aneurysms identified in SPECT imaging with MIBI did not constitute a prognostic variable. Nonetheless, in our study, we observed that in patients with scintigraphic criteria for myocardial viability, a DP correlated significantly with both overall CD and CD because of heart failure. These results are comparable to those obtained in earlier studies, in which patients with viability on positron emission tomography imaging who had substantial ventricular remodeling had a worse prognosis than when there was less remodeling.30 CONCLUSION A divergent pattern in gated myocardial perfusion SPECT can be found in 30% of patients with ischemic cardiomyopathy, all of whom had a previous anterior infarction. The longer the interval between the infarction and gated SPECT, the more prevalent that the apical remodeling and left-ventricular dilatation become. A divergent pattern does not in and of itself constitute a prognostic variable for CD, but in patients with scintigraphic criteria for viability, it correlates significantly both with overall CD and with CD because of heart failure.
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References 1. Morton KA, Alazraki NP, Taylor AT, Datz FL. SPECT thallium201 scintigraphy for the detection of left-ventricular aneurysm. J Nucl Med 1987;28:168-72. 2. Krawczynska EG, Alazraki NP, Karatela R, Jones ME, Cooke CD, Garcia EV, et al. Prognosis in patients with left ventricular apical aneurysm diagnosed by thallium-201 or Tc-99m sestamibi SPECT images. Am J Cardiol 1997;79:406-11. 3. Weizenberg A, Goodenday LS, Leighton RF. Scintigraphic detection of ventricular aneurysm with thallium-201. J Nucl Med 1983; 24:34-5. 4. Winzelberg GG, Strauss HW, Bingham JB, McKusick KA. Scintigraphic evaluation of left ventricular aneurysm. Am J Cardiol 1980;46:1138-43. 5. Gerson MC, Varma DG, Nishiyama H, Gelfand MJ. Evidence of left ventricular aneurysm by thallium-201 myocardial scintigraphy. Clin Nucl Med 1983;8:133-8. 6. Candell-Riera J, Santana-Boado C, Castell-Conesa J, AguadéBruix S, Bermejo-Fraile B, Soler-Soler J. Dipyridamole administration at the end of an insufficient exercise 99mTc-MIBI SPECT improves detection of multivessel coronary artery disease in patients with previous myocardial infarction. Am J Cardiol 2000; 85:532-5. 7. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42. 8. González JM, Castell-Conesa J, Candell-Riera J, Rossello-Urgell J, Spanish Working Group of Nuclear Cardiology. Relevance of 99m Tc-MIBI rest uptake, ejection fraction and contractile abnormality location in predicting myocardial recovery after revascularization. Nucl Med Commun 2001;22:795-805. 9. Romero-Farina G, Candell-Riera J, Aguadé-Bruix S, CastellConesa J, de León G, Igual A. Predictors of left ventricular systolic function improvement in surgical revascularized patients with ischemic cardiomyopathy. Rev Esp Cardiol 2007;60:943-51. 10. Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, et al. Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995;36:2138-47. 11. Hirai T, Fujita M, Nakajima H, Asanoi H, Yamanishi K, Ohno A, et al. Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. Circulation 1989;79:791-6. 12. Candell-Riera J, Santana-Boado C, Armadans-Gil L, Blanch P, Aguade S, Castell J, et al. Comparison of patients with anterior wall healed myocardial infarction with and without exerciseinduced ST-segment elevation. Am J Cardiol 1998;81:12-6. 13. Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction: potential mechanisms and early predictors. Circulation 1993;87:755-63. 14. Golia G, Marino P, Rametta F, Nidasio GP, Prioli MA, Anselmi M, et al. Reperfusion reduces left ventricular dilation by preventing infarct expansion in the acute and chronic phases of myocardial infarction. Am Heart J 1994;127:499-509. 15. Chareonthaitawee P, Christian TF, Hirose K, Gibbons RJ, Rumberger JA. Relation of initial infarct size to extent of left ventric-
16.
17.
18.
19.
20.
21.
22.
23. 24.
25.
26.
27.
28.
29.
30.
231
ular remodeling in the year after acute myocardial infarction. J Am Coll Cardiol 1995;25:567-73. Peels KH, Visser CA, Dombrink JHE, Jaarsma W, Wielenga RP, Kamp O, et al. Left ventricular wall motion score as an early predictor of left ventricular dilation and mortality after first anterior infarction treated with thrombolysis. Am J Cardiol 1996;77:1149-54. Udelson JE, Patten RD, Konstam MA. New concepts in postinfarction ventricular remodeling. Rev Cardiovasc Med 2003; 4(Suppl):S3-12. Carluccio E, Biagioli P, Alunni G, Murrone A, Giombolini C, Ragni T, et al. Patients with hibernating myocardium show altered left ventricular volumes and shape, which revert after revascularization. Evidence that dyssynergy might directly induce cardiac remodeling. J Am Coll Cardiol 2006;47:969-77. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000; 101:2981-8. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation 1990;81:1161-72. Rouleau JL, de Champlain J, Klein M, Bichet D, Moye L, Packer M, et al. Activation of neurohumoral systems in postinfarction left ventricular dysfunction. J Am Coll Cardiol 1993;22:390-8. Warren SE, Royal HD, Markis JE, Grossman W, McKay RG. Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis. J Am Coll Cardiol 1988;11:12-9. Weber KT. Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation 1997;96:4065-82. Erlebacher JA, Weiss JL, Weisfeldt ML, Bulkley BH. Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement. J Am Coll Cardiol 1984;4:201-8. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76:44-51. Goto T, Ohte N, Miyabe H, Mukai S, Sakata S, Hayano J, et al. Tl-201 washout rate in remote normal regions in patients with prior myocardial infarction and left ventricular remodeling. J Nucl Cardiol 2005;12:179-85. Porenta G, Cherry S, Czernin J, Brunken R, Kuhle W, Hashimoto T, et al. Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency in normal humans by carbon-11 acetate positron emission tomography imaging. Eur J Nucl Med 1999;26:1465-74. Orn S, Manhenke C, Anand IS, Squire I, Nagel E, Edvardsen T, et al. Effect of left ventricular scar size, location, and transmurality on left ventricular remodeling with healed myocardial infarction. Am J Cardiol 2007;99:1109-14. Pace L, Cuocolo A, Salvatore M. A comparison of TI-201 and Tc-99m MIBI in a patient with an apical aneurysm. Clin Nucl Med 1992;17:325-7. Santana CA, Shaw LJ, Garcia EV, Soler-Peter M, Candell-Riera J, Grossman GB, et al. Incremental prognostic value of left ventricular function by myocardial ECG-gated FDG PET imaging in patients with ischemic cardiomyopathy. J Nucl Cardiol 2004;11: 542-50.
diameter at the apex than at the base. A divergent pattern has been associated with the presence of ventricular aneurysm and a higher rate of cardiac death (CD).1-5 The objective of this study was to analyze DPs in gated myocardial perfusion SPECT imaging with technetium-labeled agents, in a patient population with ischemic heart disease and systolic dysfunction. METHODS Patients All consecutive patients who underwent gated myocardial perfusion SPECT in our Nuclear Cardiology Unit for risk stratification of their ischemic heart disease between May 1997 and July 2002 were investigated. A left-ventricular ejection fraction (EF) of ⱕ40% was observed in 365 patients. From that group, 209 were excluded because of the presence of any other type of heart disease (n ⫽ 70), implanted pacemakers (n ⫽ 3), previous revascularization (n ⫽ 86), or an inability to perform exercise (n ⫽ 50). In 7 patients, clinical follow-up could not be completed. One hundred and fifty-six patients with an EF ⱕ40% and 225
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without previous revascularization procedures who were able to undergo stress testing as a provocation maneuver were included.
Resting Electrocardiogram An electrocardiogram (ECG) was performed in all patients on the same day as gated SPECT. Heart rate, the presence of Q-waves and their topography, ST segment changes, and bundle branch blocks were recorded.
Stress Test The 156 patients underwent a symptom-limited exercise test on an ergometer-cycle. One hundred and forty-two patients underwent only the ergometer-cycle test, and in 14, intravenous dipyridamole was administered during exercise when they did not reach 80% of their maximum heart rate.6 The initial load was 50 W, with 25-W increments every 3 minutes until exhaustion, the appearance of symptoms, ST segment depression ⬎2 mm, the appearance of ventricular or supraventricular arrhythmias, or the failure of systemic blood pressure to increase. At the time the stress test was performed, all patients were receiving medical treatment. An assessment was made, including symptoms, test duration, maximum oxygen consumption estimated in metabolic equivalents (METs), maximum heart rate, maximum heart rate as a percentage of theoretical value for the patient’s age (220 – age), maximum systolic blood pressure, the product of both, and a downsloping or upsloping ST segment ⱖ1 mm at 0.08 seconds beyond the J point, angina, and dyspnea.
Gated Myocardial Perfusion SPECT Stress/rest gated SPECT was performed in all patients using a 1-day protocol (first stress, then rest) with technetiumbased components (30% methoxy isobutyl isonitrile [MIBI], 70% tetrofosmin) A first dose of 8 mCi was given 30 to 60 seconds before the completion of exercise, followed by a second dose of 24 mCi (at rest), with an interval of ⬎45 minutes between them. The equipment used was a Siemens E.CAM dual-head 90° gamma camera with a high-resolution collimator and a 180° semicircular orbit in “step-and-shoot” mode, initiated at 45° right anterior oblique (Siemens, Berlin, Germany). Images were obtained every 3° (25 seconds). Acquisition was synchronized with the ECG R-wave, with 8 frames/cardiac cycle. Frames were reconstructed using filtered back-projection (Butterworth filter, order of 5, cutoff frequency of 0.4). No corrections were made for attenuation and scatter. To quantify perfusion and wall-thickening, the left ventricle was divided into 17 segments,7 and each was given a score from 0 to 4 for perfusion (0, normal perfusion; 1, mild hypoperfusion; 2, moderate hypoperfusion; 3, severe hypoperfusion; and 4, no uptake) and wall-thickening (0, normal; 1, mildly impaired; 2, moderately impaired; 3, severely impaired; and 4, no wall thickening). A summed rest score (SRS), summed stress score (SSS), and summed difference score (SDS) for perfusion, and the SRS for wall-thickening, were
Figure 1. Example of a divergent pattern in myocardial perfusion single-photon emission computed tomography in a patient with ischemic cardiomyopathy. The transverse diameters of the left ventricle at the apex (A ( ) are greater than the transverse diameters at the base (B) in the horizontal (right) and vertical (left) long-axis slices. calculated. Rest gated SPECT was used to analyze myocardial viability. Significant myocardial viability was defined as the presence of relatively preserved perfusion (perfusion score of 0-3) in ⱖ3 severely hypokinetic, akinetic, or dyskinetic segments.8,9 The percentage of myocardial viability was calculated from the following equation: ([number of viable segments]/[total segments]) ⫻ 100, and the percentage of myocardial necrosis was calculated from the following equation: ([number of necrosis segments]/[total segments]) ⫻ 100. Myocardial ischemia was defined as having an SDS ⱖ2, and the ischemia percentage was calculated from the following equation: ([number of ischemic segments]/[total segments]) ⫻ 100. End-diastolic volume (EDV), end-systolic volume (ESV), and left-ventricular EF were assessed, as was the presence of a DP. A divergent pattern was considered to exist when the transverse diameter was greater at the apex than at the base (Figure 1). Calculation of the EF and ventricular volumes was performed automatically during rest gated SPECT, using the QGS program (Cedars-Sinai Medical Center, Los Angeles, Calif).10
Follow-up In the follow-up until the performance of gated SPECT (mean, 2.3 years; standard deviation [SD], 1,1; range, between 1 month and 6 years), overall CD, CD because of heart failure (HF), sudden CD, and coronary revascularization (CR) by surgery or angioplasty were assessed.
Statistical Analysis Clinical and electrocardiographic characteristics, the results of the ergometer test and stress/rest gated SPECT testing, and the follow-up of patients with and without DP were compared. Ventricular volumes, EF, the presence of viability, and myocardial ischemia were anayzed in groups of patients studied at different periods after myocardial infarction. Continuous variables were compared using Student’s t test for independent samples, and were expressed as mean values and SDs. The differences between two proportions were
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Table 1. Clinical characteristics of patients
Characteristics Clinical Age (y) Women Functional class (NYHA) I-II III-IV Angina grade (CCS) I-II III-IV Diabetes Dyslipemia Arterial hypertension Smoking Stroke Myocardial infarction Anterior infarction Inferior infarction Coronary angiography Electrocardiographic Q-wave Sinus rhythm 1 ST segment ⬎1 mm 2 ST segment ⬎1 mm RBBB LBBB AHB PHB Follow-up Years Overall cardiac death Death because of HF Sudden death Coronary revascularization Surgical revascularization Coronary angioplasty
Global values (n ⴝ 156)
No divergent pattern (n ⴝ 109)
Divergent pattern (n ⴝ 47)
62.9 (SD, 11.6) 25 (16%)
64.2 (SD, 11) 18 (16.5%)
59.8 (SD, 12) 7 (14.9%)
P
.031 .800
19 (12.2%) 20 (12.8%)
16 (14.7%) 17 (15.6%)
3 (6.4%) 3 (6.4%)
.146 .114
28 (17.9%) 21 (13.5) 54 (34%) 93 (59.6%) 83 (53.2%) 97 (62.2%) 6 (3.8%) 131 (84%) 86 (55.1%) 37 (23.7%) 107 (68.6%)
21 (19.3%) 15 (13.8%) 35 (32.1%) 64 (58.7%) 58 (53.2%) 69 (63.3%) 5 (4.6%) 84 (77.1%) 44 (40.4%) 31 (28.4%) 74 (67.9%)
7 (14.9%) 6 (12.8%) 19 (40.4%) 29 (61.7%) 25 (53.2%) 28 (59.6%) 1 (2.1%) 47 (100%) 41 (87.2%) 6 (12.8%) 33 (70.2%)
.54 .867 .317 .727 .998 .660 .669 .003 ⬍.001 .035 .774
107 (68.6%) 150 (96.2%) 93 (59.6%) 26 (16.7%) 21 (13.5%) 12 (7.7%) 29 (18.6%) 12 (9.2%)
64 (58.7%) 105 (96.3%) 57 (52.3%) 22 (20.2%) 15 (13.8%) 8 (7.3%) 17 (15.6%) 7 (7.8%)
43 (91.5%) 45 (95.7%) 36 (76.6%) 4 (8.5%) 6 (12.8%) 4 (8.5%) 12 (25.5%) 5 (12.5%)
⬍.001 .860 .005 .073 .867 .754 .143 .512
2.3 (SD, 1.1) 23 (14.7%) 17 (10.9%) 6 (3.8%) 46 (29.5%) 35 (22.4%) 11 (7.1%)
2.3 (SD, 1.2) 17 (15,6%) 12 (11%) 5 (4.6%) 37 (33.9%) 30 (27.5%) 7 (6.4%)
2.2 (SD, 2) 6 (12.8%) 5 (10.6%) 1 (2.1%) 9 (19.1%) 5 (10.6%) 4 (8.5%)
.659 .647 .946 .669 .069 .020 .735
RBBB, Right-bundle branch block; LBBB, left-bundle branch block; CCS, Canadian Cardiovascular Society; HF, heart failure; AHB, anterior hemiblock; PHB, posterior hemiblock; NYHA, New York Heart Association; SD, standard deviation; 1, ST evaluation; 2, ST depression.
compared using the 2 test or Fisher’s exact test, and were expressed as a percentage. In patients with previous infarction (n ⫽ 131), a multiple linear regression model was used to determine the adjusted increase in EDV and ESV for each year of postinfarction follow-up. The relationship between trends of mean EDV, ESV, and EF, and time elapsed since myocardial infarction (classified into categories by years: ⬍5 years, between 5 and 10 years, and ⱖ10 years), was studied using the nonparametric Jonckheere-Terpstra test. In addition, a multiple linear regression model was used to analyze the quadratic and linear trends
(with code for orthogonal polynomials) between time postinfarction, volumes, and EF. The Kaplan-Meier method was used for survival analysis, and survival curves of the different groups were compared using log-rank and Breslow tests, adjusted for CR. The prognostic value of a DP was determined with the Cox regression method (forward stepwise [FSTEP], inclusion criteria P ⱕ .05, and exclusion criteria P ⬎ .10), adjusted for age, gender, and CR. P ⬍ .05 was considered a statistically significant difference. The program used was SPSS for Windows, version 13.0 (SPSS, Inc., Chicago, Ill).
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Table 2. Characteristics of gated SPECT in patients with and without a divergent pattern
SPECT SRS for perfusion SSS for perfusion SDS for perfusion Percent ischemia Percent viability Percent necrosis Ischemic patients Viable patients Viable ⫹ ischemia Gated EF (%) ESV (mL) EDV (mL) SRS, wall-thickening
No divergent pattern (n ⴝ 109)
Divergent pattern (n ⴝ 47)
P
19.4 (SD, 8.5) 23.4 (SD, 8) 4.2 (SD, 3) 21.6 (SD, 19) 49.7 (SD, 20) 4.7 (SD, 3) 74 (67.9%) 93 (85.3%) 67 (61.5%)
30.4 (SD, 7) 33.7 (SD, 6) 3.4 (SD, 3) 17.8 (SD, 20) 51.4 (SD, 14) 17.4 (SD, 8) 26 (55.3%) 17 (36.2%) 13 (27.7%)
⬍.001 ⬍.001 .204 .28 .44 ⬍.001 .133 ⬍.001 ⬍.001
32.5 (SD, 6) 117.3 (SD, 50) 171.3 (SD, 64) 18.1 (SD, 8.1)
28.7 (SD, 6.8) 150.6 (SD, 62) 207.4 (SD, 72) 29.2 (SD, 8)
.001 .001 .002 ⬍.001
SPECT, Single-photon emission computed tomography; EF, ejection fraction; DP, divergent pattern; SDS, summed difference score; SSS, summed stress score; SRS, summed rest score; EDV, end-diastolic volume; ESV, end-systolic volume; SD, standard deviation.
RESULTS The prevalence of a DP of the left ventricle was 30.1% (47/156). Patients with a DP were significantly younger, had more often experienced a previous anterior and inferior myocardial infarction, and had a higher percentage of Q-waves and ST segment elevations on their ECGs (Table 1). A divergent pattern was not observed in patients with only an inferior infarction; the six inferior infarctions with a DP were all associated with anterior infarctions. No significant differences were found in the frequency of symptoms, functional class, angina grade, or ergometric variables. All patients were receiving medical treatment (55.5%, angiotensin enzymeconverting inhibitors; 47.3%, beta blockers; 50.9%, nitrates; 20.9%, diuretics; 25%, anticoagulants; 7.3%, digoxin; 7.3%, calcium channel blockers; and 3.6%, amiodarone). There were no significant differences between patients with and without a DP. In patients who underwent coronary angiography (n ⫽ 107), occlusion of the anterior descending coronary artery was significantly more prevalent when there was a DP (2, 4.079; P ⫽ .043). In the gated SPECT analysis (Table 2), rest and stress perfusions (n ⫽ 47) were significantly more impaired in patients with a DP, and the necrotic area was larger. The percentage of myocardial viability and viability plus myocardial ischemia was significantly lower in patients with a DP. Wall-thickening and EF were significantly reduced, whereas EDV and ESV were significantly higher when patients had a DP.
In patients with a previous infarction (n ⫽ 131), it was observed that the longer the time interval between acute myocardial infarction and the performance of gated SPECT, the greater the probability of finding a DP. Figure 2 shows the increase in mean probability of having a DP for different time categories (Figure 2A, ⬍ 5; Figure 2B, ⱖ5 to 10; and Figure 2C, ⱖ10 years). The same finding was observed for left-ventricular volumes (EDV and ESV). When multiple linear regression was used to evaluate the effect of time interval between infarction and gated SPECT on ventricular volumes (adjusted for ischemia, viability, and number of infarctions), it was seen that for each additional year elapsed since the infarction, EDV increased by 2.3 mL (95% confidence interval [CI], 0.42-4.2; analysis of variance [ANOVA] F, 4.565; P ⫽ .002]), and ESV increased by 2 mL (95% CI, 0.1-3.1; ANOVA F, 4.692; P ⫽ .001). When the time interval was classified by years (⬍5, ⱖ5 to ⬍10, and ⱖ10 years), the degree of significance pointed to an upward trend in mean EDV and mean ESV as the interval increased (ESV, 2Jonckheere-Terpstra ⫽ 2.994; P ⫽ .003; EDV, 2Jonckheere-Terpstra ⫽ 2.903; P ⫽ .004; Figure 3). In the linear trend analysis, a level of significance was reached for EDV ( ⫽ 22.966; 95% CI, 2.9-42.9; P ⫽ .025) and for ESV ( ⫽ 19.226; 95% CI, 3.22-35.2; P ⫽ .019), but not for EF. Follow-up and Prognosis Overall CD over a mean follow-up of 2.26 years after gated SPECT amounted to 6.3/100 patients/year;
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Figure 2. Analysis of the probability of a divergent pattern (DP) in patients with ischemic cardiomyopathy, based on the time elapsed between the myocardial infarction and gated single-photon emission computed tomography (SPECT) T (A, ⬍5 years; B, 5 to ⬍10 years; C, ⱖ10 years). As this interval increases, the probability of developing a DP becomes significantly higher. MI, Myocardial infarction; Sq r, square.
CD because of heart failure amounted to 4.6/100 patients/year; and sudden death amounted to 1.6/100 patients/year. In total, 29.5% patients were revascularized (Table 1), and 70.5% were not; 32% were nonviable patients; 35% did not have suitable coronaries; and 33% exhibited renal failure, high risk, or advanced age. Annual coronary revascularization amounted to 15.9/100 patients/year (surgery, 12.1/100 patients/year; and angioplasty, 3.8/ patients/year). In patients with DP, CR by surgery was significantly lower than in the other patients, although the difference with respect to CR by percutaneous transluminal coronary angioplasty (PTCA) was not significant (Table 1). The presence of a DP did not in itself constitute a prognostic variable for overall CD (HR, 0.8; 95% CI, 0.34-2.2; P ⫽ .795), CD because of HF (HR, 1.04; 95% CI, 0.36-2.9; P ⫽ .935), and sudden death (HR, 0.49; 95% CI, 0.58-4.29; P ⫽ .527). Nevertheless, when only patients with scintigraphic criteria for viability were considered (n ⫽ 110), a DP showed prognostic value (variables in the regression model included DP, previous myocardial infarction, myocardial ischemia, ejection fraction, and end-systolic volume) for overall CD (adjusted for age, gender, and CR: HR, 3.1; 95% CI, 1.1-8.7; P ⫽ .028; ⫺2log likelihood: 169,266; degrees of freedom [df], 4; P ⫽ .03) and CD because of heart failure
Figure 3. Relationship between end-diastolic volume (EDV), V end-systolic volume (ESV), V and different time intervals between a myocardial infarction and gated single-photon emission computed tomography (SPECT) T (A, ⬍5 years; B, 5 to ⬍10 years; C, ⱖ10 years). EDV: linear trend test, P ⫽ .025; quadratic trend test, P ⫽ .93. ESV: linear trend test, P ⫽ .019; quadratic trend test, P ⫽ .77. MI, Myocardial infarction.
(adjusted for age, gender, and CR: HR, 3.9; 95% CI, 1.2-12.8; P ⫽ .02; ⫺2log likelihood: 122,167; df, 4; P ⫽ .01; Figure 4), but not for sudden death (adjusted for age, gender, and CR: HR, 1.6; 95% CI, 0.16-15; P ⫽ .706; ⫺2log likelihood: 29,013; df, 4; P ⫽ .354). DISCUSSION A divergent pattern of the left ventricle is one of the scintigraphic signs of extensive left-ventricular remodeling. In our population of patients with ischemic heart disease and EF ⱕ40%, the prevalence of a DP of the left ventricle in gated myocardial perfusion SPECT with technetium (Tc)-labeled agents was 30%, a result comparable to the findings of earlier studies with 201thallium (Tl) (31%)1 and 99Tc-MIBI (41%).2 The sensitivity and specificity of this pattern for the diagnosis of ventricular aneurysm are ⬎94% when contrast ventriculography is used as the gold standard.2 More than 80% of ventricular
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Figure 4. Survival analysis using a Kaplan-Meier curve in viable patients with and without a divergent pattern (DP) for overall cardiac death (CD) (left) and for CD because of heart failure (right).
aneurysms are located in the antero-apical wall, and only 5% to 10% are located in the lateral wall. In our series, all patients with a DP had a previous anterior infarction. These results are comparable to those of Hirai et al,11 who found that aneurysms and coronary lesions were correlated; they observed that aneurysms of the anterior wall were associated with total occlusion of the anterior descending artery in the presence of poor collateral circulation. In our series, no patient with isolated inferior infarction showed a DP. One of the electrocardiographic criteria for the diagnosis of left-ventricular aneurysm is a persistent ST segment elevation in the postinfarction ECG.12 This sign appeared in 75% of the patients in our series who had a DP. Generally speaking, left-ventricular remodeling develops secondary to extensive transmural myocardial infarction,13-18 and is arbitrarily divided into an early phase (within the first 72 hours) and a late phase (⬎72 hours).19 The early phase includes expansion of the infarcted area, occasionally causing myocardial rupture or ventricular aneurysm. It was shown that the late phase compromises the left ventricle as a whole, and is characterized by time-dependent dilatation, a distorsion of ventricular shape, and compensating wall hypertrophy. As necrotic tissue is replaced by myocardial scar tissue, myocytes become enlarged, and interstitial fibrosis appears in remote areas, resulting in dilatation and the alteration of ventricular morphology.18,20-25 All of our patients were assessed during the late phase, and our results corroborate these findings. In our series, we observed a significant increase in ventricular volumes and a smaller percentage of patients with viability criteria as the time interval between the infarction and gated SPECT increased. Goto et al,26 in SPECT studies with 201Tl, observed that myocardial ischemia detected during exercise in regions remote from the myocardial
infarction might be one of the causes of ventricular remodeling. Furthermore, the remodeling itself increases myocardial oxygen consumption and thus wall stress, facilitating the development of myocardial ischemia during exercise.27 These results are comparable to magnetic resonance studies in which a close linear relationship between size of infarction, ventricular volumes, and EF was found.28 In our population of patients with ischemic cardiomyopathy, a DP of the left ventricle appearing in gated SPECT was not independently correlated with CD. This result approximates the findings of Pace et al,29 in which aneurysms identified in SPECT imaging with MIBI did not constitute a prognostic variable. Nonetheless, in our study, we observed that in patients with scintigraphic criteria for myocardial viability, a DP correlated significantly with both overall CD and CD because of heart failure. These results are comparable to those obtained in earlier studies, in which patients with viability on positron emission tomography imaging who had substantial ventricular remodeling had a worse prognosis than when there was less remodeling.30 CONCLUSION A divergent pattern in gated myocardial perfusion SPECT can be found in 30% of patients with ischemic cardiomyopathy, all of whom had a previous anterior infarction. The longer the interval between the infarction and gated SPECT, the more prevalent that the apical remodeling and left-ventricular dilatation become. A divergent pattern does not in and of itself constitute a prognostic variable for CD, but in patients with scintigraphic criteria for viability, it correlates significantly both with overall CD and with CD because of heart failure.
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References 1. Morton KA, Alazraki NP, Taylor AT, Datz FL. SPECT thallium201 scintigraphy for the detection of left-ventricular aneurysm. J Nucl Med 1987;28:168-72. 2. Krawczynska EG, Alazraki NP, Karatela R, Jones ME, Cooke CD, Garcia EV, et al. Prognosis in patients with left ventricular apical aneurysm diagnosed by thallium-201 or Tc-99m sestamibi SPECT images. Am J Cardiol 1997;79:406-11. 3. Weizenberg A, Goodenday LS, Leighton RF. Scintigraphic detection of ventricular aneurysm with thallium-201. J Nucl Med 1983; 24:34-5. 4. Winzelberg GG, Strauss HW, Bingham JB, McKusick KA. Scintigraphic evaluation of left ventricular aneurysm. Am J Cardiol 1980;46:1138-43. 5. Gerson MC, Varma DG, Nishiyama H, Gelfand MJ. Evidence of left ventricular aneurysm by thallium-201 myocardial scintigraphy. Clin Nucl Med 1983;8:133-8. 6. Candell-Riera J, Santana-Boado C, Castell-Conesa J, AguadéBruix S, Bermejo-Fraile B, Soler-Soler J. Dipyridamole administration at the end of an insufficient exercise 99mTc-MIBI SPECT improves detection of multivessel coronary artery disease in patients with previous myocardial infarction. Am J Cardiol 2000; 85:532-5. 7. Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42. 8. González JM, Castell-Conesa J, Candell-Riera J, Rossello-Urgell J, Spanish Working Group of Nuclear Cardiology. Relevance of 99m Tc-MIBI rest uptake, ejection fraction and contractile abnormality location in predicting myocardial recovery after revascularization. Nucl Med Commun 2001;22:795-805. 9. Romero-Farina G, Candell-Riera J, Aguadé-Bruix S, CastellConesa J, de León G, Igual A. Predictors of left ventricular systolic function improvement in surgical revascularized patients with ischemic cardiomyopathy. Rev Esp Cardiol 2007;60:943-51. 10. Germano G, Kiat H, Kavanagh PB, Moriel M, Mazzanti M, Su HT, et al. Automatic quantification of ejection fraction from gated myocardial perfusion SPECT. J Nucl Med 1995;36:2138-47. 11. Hirai T, Fujita M, Nakajima H, Asanoi H, Yamanishi K, Ohno A, et al. Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction. Circulation 1989;79:791-6. 12. Candell-Riera J, Santana-Boado C, Armadans-Gil L, Blanch P, Aguade S, Castell J, et al. Comparison of patients with anterior wall healed myocardial infarction with and without exerciseinduced ST-segment elevation. Am J Cardiol 1998;81:12-6. 13. Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction: potential mechanisms and early predictors. Circulation 1993;87:755-63. 14. Golia G, Marino P, Rametta F, Nidasio GP, Prioli MA, Anselmi M, et al. Reperfusion reduces left ventricular dilation by preventing infarct expansion in the acute and chronic phases of myocardial infarction. Am Heart J 1994;127:499-509. 15. Chareonthaitawee P, Christian TF, Hirose K, Gibbons RJ, Rumberger JA. Relation of initial infarct size to extent of left ventric-
16.
17.
18.
19.
20.
21.
22.
23. 24.
25.
26.
27.
28.
29.
30.
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ular remodeling in the year after acute myocardial infarction. J Am Coll Cardiol 1995;25:567-73. Peels KH, Visser CA, Dombrink JHE, Jaarsma W, Wielenga RP, Kamp O, et al. Left ventricular wall motion score as an early predictor of left ventricular dilation and mortality after first anterior infarction treated with thrombolysis. Am J Cardiol 1996;77:1149-54. Udelson JE, Patten RD, Konstam MA. New concepts in postinfarction ventricular remodeling. Rev Cardiovasc Med 2003; 4(Suppl):S3-12. Carluccio E, Biagioli P, Alunni G, Murrone A, Giombolini C, Ragni T, et al. Patients with hibernating myocardium show altered left ventricular volumes and shape, which revert after revascularization. Evidence that dyssynergy might directly induce cardiac remodeling. J Am Coll Cardiol 2006;47:969-77. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 2000; 101:2981-8. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation 1990;81:1161-72. Rouleau JL, de Champlain J, Klein M, Bichet D, Moye L, Packer M, et al. Activation of neurohumoral systems in postinfarction left ventricular dysfunction. J Am Coll Cardiol 1993;22:390-8. Warren SE, Royal HD, Markis JE, Grossman W, McKay RG. Time course of left ventricular dilation after myocardial infarction: influence of infarct-related artery and success of coronary thrombolysis. J Am Coll Cardiol 1988;11:12-9. Weber KT. Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation 1997;96:4065-82. Erlebacher JA, Weiss JL, Weisfeldt ML, Bulkley BH. Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement. J Am Coll Cardiol 1984;4:201-8. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76:44-51. Goto T, Ohte N, Miyabe H, Mukai S, Sakata S, Hayano J, et al. Tl-201 washout rate in remote normal regions in patients with prior myocardial infarction and left ventricular remodeling. J Nucl Cardiol 2005;12:179-85. Porenta G, Cherry S, Czernin J, Brunken R, Kuhle W, Hashimoto T, et al. Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency in normal humans by carbon-11 acetate positron emission tomography imaging. Eur J Nucl Med 1999;26:1465-74. Orn S, Manhenke C, Anand IS, Squire I, Nagel E, Edvardsen T, et al. Effect of left ventricular scar size, location, and transmurality on left ventricular remodeling with healed myocardial infarction. Am J Cardiol 2007;99:1109-14. Pace L, Cuocolo A, Salvatore M. A comparison of TI-201 and Tc-99m MIBI in a patient with an apical aneurysm. Clin Nucl Med 1992;17:325-7. Santana CA, Shaw LJ, Garcia EV, Soler-Peter M, Candell-Riera J, Grossman GB, et al. Incremental prognostic value of left ventricular function by myocardial ECG-gated FDG PET imaging in patients with ischemic cardiomyopathy. J Nucl Cardiol 2004;11: 542-50.