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Regional left-ventricular diastolic wall motion assessed by a new program for ECG-gated myocardial perfusion SPECT in early-stage heart failure
Regional left-ventricular diastolic wall motion assessed by a new program for ECG-gated myocardial perfusion SPECT in early-stage heart failure Akira Yamamoto, MD,a Naoto Takahashi, MD,b Kazuya Abe, MD,a Yuko Kobayashi, MD,a Jin Tamai, MD,a and Kazuo Munakata, MDb Background. We developed a new program for gated single-photon emission computed tomography to estimate regional left-ventricular (LV) wall motion. We classified and graded diastolic wall motion, and compared its grading with global LV functions. Methods and Results. Forty New York Heart Association functional class I (NYHA class I) patients and 15 control subjects were examined. The global time to peak filling and the regional diastolic wall motion synchrony, as estimated by the time lag between the earliest and latest regional peak filling, were evaluated. Using the control group’s mean ⴙ 2 SD, diastolic wall motions were classified into four subsets: globally normal and regionally synchronous, globally normal but regionally dyssynchronous, globally prolonged and regionally dyssynchronous, and globally prolonged but regionally synchronous. These subsets were graded 0 to 3, respectively. Grade 0 was defined as normal. Grading was compared with global LV functions. Although 67.5% of patients demonstrated abnormal motion, the global diastolic parameter less frequently detected an abnormality (22.5% to 32.5%). Grading correlated with the first-third filling fraction (Spearman’s rank correlation coefficient [rs] ⴝ ⴚ0.74, P ⴝ 3.8 ⴛ 10ⴚ6) and the first-third filling rate (rs ⴝ ⴚ0.49, P < .005). Conclusions. Regional diastolic wall motion abnormality was frequently detected even in early-stage heart failure. Grading reflected early diastolic dysfunction. (J Nucl Cardiol 2008;15: 375-82.) Key Words: Heart failure • left-ventricular diastolic function • gated myocardial perfusion SPECT • regional quantitative analysis Global left-ventricular (LV) function can be analyzed by electrocardiogram (ECG)-gated myocardial perfusion single-photon emission computed tomography (GMPS). To advance the analysis of LV function, we developed a new program called cardio-gated singlephoton emission computed tomography (SPECT) regional assessment for LV function (cardioGRAF). This program enables the estimation of regional systolic and diastolic wall motions in 17 divided LV segments, using various regional time-volume changes. The functional and temporal parameters were validated in preliminary stud-
From the Department of Radiology,a Nippon Medical School, Tamanagayama Hospital, Tama City, Tokyo, Japan, and Department of Internal Medicine,b Nippon Medical School, Musashikosugi Hospital, Kawasaki City, Kanagawa, Japan. Received for publication July 7, 2007; final revision accepted Dec 18, 2007. Reprint requests: Akira Yamamoto, MD, Department of Radiology, Nippon Medical School, Tamanagayama Hospital, 1-7-1 Nagayama, Tama City, Tokyo 206-8512, Japan; [email protected]. 1071-3581/$34.00 Copyright © 2008 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2008.02.012
ies.1,2 Relationships among regional diastolic impairment, prolongation of global time to peak filling rate, and diastolic function were also been described previously.3 Recently, the importance of diastolic function has been emphasized in heart failure (HF).4-9 Hypertension (HT), ischemic heart disease (IHD), and many other diseases induce HF. However, early-stage HF has not been thoroughly investigated. In nuclear cardiology, the peak filling rate was established as a representative parameter to estimate diastolic function since the advent of gated blood-pool scintigraphy. Recently, time to peak filling rate was stated to be a more stable parameter.8 So far, diastolic abnormality has been estimated by such global LV functional and temporal parameters. Using a new program, we reported on the evaluation of regional diastolic wall motion by value-based assessment in earlystage HF.3 This program was also designed to distinguish a diastolic wall motion pattern by reviewing global and segmental curves. Synchronous and dyssynchronous regional diastolic wall-motion patterns were then estimated using this program. Such diastolic wall-motion patterns might reflect a diastolic function. In this study, we confirmed the usefulness of the new program in early-stage HF 375
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Table 1. Patient characteristics
CG SG (n ⴝ 15) (n ⴝ 40) Age (mean ⫾ SD) Male Hypertension Typical angina History of myocardial infarction Arrhythmia Cardiomyopathy Valvular disease Diabetes mellitus Hyperlipidemia Resting HR (bpm)
59 ⫾ 13 3 0 0 0 0 0 0 0 3 67 ⫾ 11
64 ⫾ 12 29 22 7 3 4 2 2 9 25 69 ⫾ 11
CG, Control group; SG, study group; bpm, beats per minute; HR, heart rate.
by classifying the diastolic LV wall-motion pattern and comparing its grading with global LV functions. MATERIALS AND METHODS Patient Population Patient characteristics are summarized in Table 1. The study group (SG) comprised 40 nonsymptomatic heart-disease or HT patients with early-stage HF, categorized as New York Heart Association (NYHA) functional class I. They were examined with resting GMPS. Patients with severe arrhythmias such as atrial fibrillation and tachycardia of more than 100 beats/minute were excluded. The control group (CG) comprised 15 patients who were examined with resting GMPS because of chest pain (n ⫽ 12), minor abnormalities on resting ECG (n ⫽ 2), or consciousness disorder (n ⫽ 1) (Table 1). These patients had not received any medication for heart disease. The low probability regarding the presence of a form of heart disease requiring treatment was confirmed by normal exercise-stress ECG and normal Holter ECG. Two-dimensional echocardiography also revealed normal wall motion in all CG patients who had neither HT nor diabetes mellitus (DM). Two patients exhibited hypercholesteremia (total cholesterol, 231 and 246 mg/dL) and one patient exhibited hypertrigliceremia (trigliceride, 191 mg/dL). To confirm reproducibility, 20 additional consecutive patients were examined. These patients were examined for the following reasons: myocardial infarction (MI; n ⫽ 3), angina pectoris or suspicious angina pectoris (AP; n ⫽ 9), arrhythmia or ECG abnormality (n ⫽ 4), and others (n ⫽ 4).
Data Acquisition and Analysis An intravenous injection of 600 MBq 99mTc-sestamibi was administered to patients at rest, and GMPS imaging was initiated after 30 to 60 minutes. Data were acquired for 40 to
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50 beats/projection with a parallel dual-detector camera (RC2600-I, Hitachi, Tokyo, Japan) under the following conditions: 64 projections during 360° rotation, with 16-frame gating, low-energy/high-resolution collimation, a 64 ⫻ 64 matrix, and step-and-shoot mode. The ECG-gated projection sets were filtered using a Butterworth filter (order 8, cutoff ⫽ 0.25 cycles/pixel, and pixel size of 5.1 to 7.6 mm), and reconstructed in a workstation using a filtered back-projection algorithm (RW3000, Hitachi). Neither attenuation nor scatter correction was employed. Short axial data were fed into a personal computer for subsequent processes.
Preprocessing for cardioGRAF Analysis To determine the inner LV edge, before processing with cardioGRAF, we used a program called “pFAST” (perfusion and function assessment by means of gated SPECT), version 2.4.2., which was developed at Sapporo Medical University (Hokkaido, Japan).10-13 For optimal LV edge detection, we regulated the magnification of two LV images at the first processing in pFAST. In the next step, LV centers on basal and apical short axial images were manually adjusted by moving the points at end-systole and end-diastole during 16 divided phases. At the same time, processing areas were also manually regulated by moving the points on x and y axes around the left ventricle for its extraction. After confirming the proper extraction of the LV edge, the regional volume data thus obtained were saved as files for future processing with cardioGRAF. Interobserver and intraobserver reproducibilities were evaluated in this process.
cardioGRAF Analysis The files that were obtained by pFAST contained regional (640 areas that comprised 40 areas/slice ⫻ 16 slices) volume data in terms of the number of voxels in each phase. According to the American Heart Association Scientific Statements,14 the 640 areas were grouped to obtain 17 segments, as described previously.1 The global and segmental time-volume curves (TVCs) were generated by Fourier curve-fitting analysis using two harmonics. The time-filling curve (TFC), which was the first derivative of TVC, was also created simultaneously, as shown in Figure 1. The values of global time from end-systole to peak filling (g-TPF1), and of regional time from 0 to peak filling (r-TPF2), were obtained from the global and regional TVCs and TFCs. The selected temporal and functional parameters were as follows: (1) (2) (3) (4) (5) (6)
Time from end systole to peak filling: TPF1 (ms); Time from 0 to peak filling: TPF2 (ms); Ejection fraction: EF (%) ⫽ V2 (%); First-third filling fraction: 1/3FF (%) ⫽ 100 ⫻ V1/V2 (%); First-third filling rate: 1/3FR (EDV/s); and Peak filling: PFR (EDV/s),
where V1 indicates first-third filling volume (%), and EDV indicates end-diastolic volume. These parameters were output as a spreadsheet that was then used in a calculation program. Regarding the parameters,
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Figure 1. Original graphs and Fourier-fitted global time-volume curves of the left ventricle (above) and the time filling curves (below) obtained by gated single-photon emission computed tomography at rest in a 57-year-old woman in the control group (A) and an 80-year-old woman with arrhythmia (B). ES, End-systole; PF, peak filling; TES, time to end-systole (ms); TPF1, time from end-systole to peak filling (ms); TPF2, time from 0 to peak filling; V, ejection volume (%); PFR, peak filling (EDV/s); 1/3FR, the first-third filling rate (EDV/s); ED, early diastole; LD, late-diastole.
Figure 2. The 17 regional time-volume curves of the left ventricle (above), and the time filling curves (below) obtained by gated single-photon emission computed tomography at rest, in a 56-year-old man with angina pectoris (A), a 66-year-old man with old myocardial infarction (B), a 54-year-old man with angina pectoris (C), and 80-year-old woman with arrhythmia (D). g-TPF1, Global time from end-systole to peak filling; ED, early diastole; LD, late diastole.
the median calculated by processing with pFAST three times was used to reduce the influence of manual adjustment.
Definition of TPF Prolongation and Grading of Diastolic Wall-Motion Abnormality Regarding global diastole, the prolongation of g-TPF1 was defined as the mean value ⫹ 2 SDs of the CG as a cutoff value. The mean ⫾ SD of g-TPF1 was 159.5 ⫾ 27.8 ms in the CG. Initially, HF was assigned to two groups: normal g-TPF1 (ⱕ215 ms, Figures 2A, B), or prolonged g-TPF1 (⬎215 ms, Figures 2C, D). To estimate the synchrony of regional diastolic LV wall motion, the intraventricular delay was measured by noting the difference between septal and lateral diastolic velocity curves in the study, using tissue Doppler imaging (TDI).15,16 For GMPS, we modified that method and proposed a new index, ie, the maximal difference (MD), which represents
the time lag between the earliest and latest regional filling peaks among the 17 LV segments (Figure 3). The maximal mean ⫾ SD difference of r-TPF2 (MD-rTPF2) was 64.7 ⫾ 41.5 ms in the CG. When we applied the 2-SD threshold, the normal limit of MD-r-TPF2 was 148 ms. The MD-r-TPF2 of less than or equal to 148 ms demonstrated synchronous filling peaks on the TFCs, and it was defined as a synchronous diastole. On the other hand, the MD-r-TPF2 of more than 148 ms demonstrated dyssynchronous filling peaks on the TFCs, and was defined as a dyssynchronous diastole. Finally, LV diastolic wall motion was divided into four subsets as follows: a globally normal and regionally synchronous group (NSG, Figures 2A, 3A), a globally normal but regionally dyssynchronous group (NDG, Figures 2B, 3B), a globally prolonged and regionally dyssynchronous group (PDG, Figures 2C, 3C), and a globally prolonged but regionally synchronous group (PSG, Figures 2D, 3D). As shown in Figure 3, the
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Figure 3. The 17 regional time-volume curves of the left ventricle (above) and the time filling curves (below). A and D, Normal maximal difference between earliest and latest regional time from 0 to peak filling (MD-r-TPF2) in a 56-year-old man with angina pectoris and an 80-year-old woman with arrhythmia, respectively. B and C, The increased MD-r-TPF2 in a 66-year-old man with old myocardial infarction and a 54-year-old man with angina pectoris, respectively.
number of r-TPF2 prolonged segments increased in the order NSG, NDG, PDG, and PSG, which suggested that r-TPF2 prolongation was extended in this order. Therefore, we graded NSG, NDG, PDG, and PSG as 0, 1, 2, and 3, respectively, with grade 0 defined as normal, and the other grades as abnormal. The reproducibility of MD-r-TPF2 was evaluated in the same manner as previously described.2,3
intraobserver reproducibilities were 19.6% and 25.0%, respectively. New Classification in SG
Regarding global systolic function, an EF of less than 50% was defined as abnormal. Regarding global diastolic functions, a mean value ⫺2 SD of the CG was used as the cutoff. Diastolic dysfunctions were defined as less than 27.8% during 1/3FF; less than 1.16 EDV/s during 1/3FR; and less than 1.70 EDV/s during PFR.
Table 2 shows the numbers and percentages of diastolic wall-motion patterns and these characteristics in the SG. We identified NSG, NDG, PDG, and PSG in 32.5%, 37.5%, 20%, and 10% of the patients, respectively. The resting heart rate was significantly greater in the PSG than in the NSG and NDG. The prolongation of TPF1 was observed in 30% of patients, but an abnormal diastolic wall-motion pattern was present as NDG, PDG, and PSG in 67% of the patients in the SG.
Statistical Analysis
Global Function Parameters in SG
Definition of LV Dysfunction
Values are expressed as the mean ⫾ SD. Parameters were compared using the Scheffé F-test after significant observation by one-way analysis of variance. Linear regression analysis and Spearman’s correlation coefficient by rank test were performed to determine the correlation between grading of diastolic wall motion and the LV functional parameters. P ⬍ .05 was considered significant.
Table 3 shows the percentages of patients with abnormal LV functions in the SG and four classifications. Global diastolic dysfunctions were identified in less than one-third of the SG (1/3FF, 30%; 1/3FR, 32.5%; and PFR, 22.5%). The decrease in 1/3FF was significantly more frequent in the PDG and PSG than in the NSG and NDG.
RESULTS All processing was successfully performed, and a few minutes were needed for the manual positioning of the LV center in the process of pFAST. Reproducibility of MD-r-TPF The reproducibility of MD-r-TPF2 was assessed by the coefficient of variation (CV). The interobserver and
Global Function Parameters in the New Patterns Figure 4 shows the correlation between grading and EF. There was neither a significant correlation between grading and EF, nor a significant difference among the four subsets. Figure 5 shows the correlation between grading and 1/3FF. Grading demonstrated a strong negative correlation with 1/3FF (Spearman’s rank correlation coefficient
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Table 2. Classification and characteristics
Cases* Age (y, mean ⫾ SD) Male Hypertension Typical angina History of myocardial infarction Arrhythmia Cardiomyopathy Valvular disease Diabetes mellitus Hyperlipidemia Resting heart rate (bpm)
NSG
NDG
PDG
PSG
13 (32.5) 56 ⫾ 9 9 6 4 1 1 0 1 2 6 64 ⫾ 10†
15 (37.5) 66 ⫾ 12 11 11 1 2 1 0 0 3 13 65 ⫾ 11†
8 (20) 70 ⫾ 13 6 2 2 0 1 2 1 2 3 75 ⫾ 6
4 (10) 70 ⫾ 11 3 3 0 0 1 0 0 2 3 86 ⫾ 4
NSG, Globally normal regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group. *Values in parentheses are percentages. † Significantly less than PSG.
Table 3. LV functions
LVEF ⬍50%* 1/3FF ⬍27.8%* 1/3FR ⬍1.16 EDV/s* PFR ⬍1.70 EDV/s*
SG (n ⴝ 40)
NSG (n ⴝ 13)
NDG (n ⴝ 15)
PDG (n ⴝ 8)
PSG (n ⴝ 4)
4 (10) 12 (30) 13 (32.5) 9 (22.5)
0 (0) 0 (0) 1 (8) 1 (8)
2 (13) 1 (7) 5 (33) 6 (40)
1 (13) 6 (75)† 3 (38) 2 (25)
0 (0) 4 (100)† 3 (75) 0 (0)
SG, Study group; NSG, globally normal and regionally synchronous group; NDG, globally normal regionally but dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group; LV, left-ventricular; LVEF, left-ventricular ejection fraction; 1/3FF, first-third filling fraction; 1/3FR, first-third filling rate; PFR, peak filling rate; EDV, end-diastolic volume. *Values in parentheses are percentages. † Significantly greater than NSG and NDG.
[rs] ⫽ – 0.74, P ⫽ 3.8 ⫻ 10⫺6). The value of 1/3FF was significantly greater in the NSG than in the NDG, PDG, or PSG (P ⬍ .05, P ⫽ 3.5 ⫻ 10⫺7, and P ⫽ 2.0 ⫻ 10⫺8, respectively). The 1/3FF was significantly greater in the NDG than in the PDG and PSG (P ⬍ .0005 and P ⫽ 4.8 ⫻ 10⫺6, respectively). Figure 6 shows the correlation between grading and 1/3FR. Grading demonstrated a significant negative correlation with 1/3FR (rs ⫽ ⫺0.49, P ⬍ .005). The 1/3FR in the NSG was significantly greater than in the PSG (P ⬍ .005). Figure 7 shows the correlation between grading and PFR. There was no significant correlation between grading and PFR, but PFR in the PSG was greater than PFR in the NSG, PDG, or PSG (P ⬍ .001, P ⫽ 2.6 ⫻ 10⫺6, and P ⫽ 2.5 ⫻ 10⫺5, respectively). After excluding the PSG, a weak but statistically insignificant correlation was demonstrated between grades 0 to 2 and PFR (y ⫽ ⫺0.27x ⫹ 2.2, rs ⫽ ⫺0.32, P ⫽ .06). In addition, one
patient with HT demonstrated an extremely high PFR (5.3 EDV/s). The same patient also demonstrated a high heart rate (90 beats/minute), high EF (86.7%), extremely low 1/3FF (5.9%), and extremely low 1/3FR (0.26 EDV/s).
DISCUSSION The importance of diastolic function has been emphasized in HF. In particular, early diastolic filling is impaired in the early stages of HF.9 So far, diastolic function has been evaluated using global functional parameters. Nuclear cardiology has limited the use of global assessment for the evaluation of diastolic function in early-stage HF, such as in cases of preserved EF. However, Akincioglu et al reported on the importance of g-TPF1 for the assessment of diastolic dysfunction.8
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Figure 4. Relationship between grading of regional diastolic wall-motion pattern and EF. EF, Ejection fraction; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
Therefore, we investigated the applicability of our new program for the estimation of regional diastolic impairment, using temporal parameters in nonsymptomatic patients. The global and regional temporal parameters derived from our program were previously validated in an earlier report,2 by comparing them with the results of gated equilibrium radionuclide angiography and speckletracking echocardiography. In addition, the lower limit of PFR and the upper limit of g-TPF that were derived from the data of the CG were nearly identical to the values reported by Akincioglu et al.8 We previously described a value-based diastolic assessment using this program.3 Therefore, we sought to confirm the usefulness of pattern-based diastolic assessment in the present study. The intraventricular time delay was measured by examining the differences between onsets of filling peak velocity, which was the same as MD-r-TPF2, using TDI.15,16 Although this study was performed using a value-based evaluation, the direct detection of wall motion abnormalities using the graphs was found to be superior. Using the cutoff values for g-TPF1 and MD-r-TPF2, wall-motion abnormalities could be determined using global and regional graphs. Regarding reproducibility, the CVs of g-TPF1, r-TPF2, EF, 1/3FF, 1/3FR, and PFR were approximately
Figure 5. Relationship between grading of regional diastolic wall-motion pattern and 1/3FF. 1/3FF, First-third filling fraction; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged regionally and dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
less than or equal to 5%.2,3 However, the CV of MD-r-TPF2 was relatively high. The border case between regionally synchronous and dyssynchronous groups presented a very high CV among the data obtained by processing three times, because a few segmental r-TPF2 prolongations resulted in a large MDr-TPF2. Automatic positioning may solve this problem, but it cannot guarantee that the correct position over the LV center will be obtained. The use of median values was one practical solution to counter this problem in the present study. In normal subjects, filling peaks are observed during early diastole, and the MD-r-TPF2 is very short (Figure 3A). On the other hand, the MD-r-TPF2 is increased when the regional filling peaks are generated during both early and late diastoles (Figures 3B,C). Therefore, we thought that an increase in MD-r-TPF2 over the normal range represented a regional diastolic impairment, as demonstrated by the prolongation of r-TPF. Using an
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Figure 6. Relationship between grading of regional diastolic wall-motion pattern and 1/3FR. 1/3FR, First-third filling rate; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
assessment of regional diastolic wall-motion synchrony with MD-r-TPF2 alone, we could not distinguish between the NSG and PSG. However, the NSG and PSG differed: regional filling peaks were generated during early diastole in the NSG, but these peaks were generated during late diastole in the PSG. Both global and regional temporal parameters were needed to distinguish these diastolic wall-motion patterns. Four patterns of regional diastolic wall motion were confirmed in the SG. The findings proved that regional diastolic impairment had already commenced during an asymptomatic period. A diastolic abnormality was identified in 30% of the patients in the SG based on the prolongation of g-TPF1, and it was revealed in approximately 30% of patients in the SG based on 1/3FF, 1/3FR, and PFR, which were the global diastolic function parameters. Our program identified other minor regional diastolic wall-motion abnormalities as NDG in 37.5% patients in the SG. This observation suggested that global temporal and functional assessments could not identify a regional diastolic wall-motion abnormality as NDG, probably because global LV analysis could not
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Figure 7. Relationship between grading of regional diastolic wall-motion pattern and peak filling. PFR, Peak filling rate; NSG, globally normal regionally and synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
detect regional impairment because of the averaging of regional data. The EF did not correlate with the grading of regional diastolic wall-motion abnormalities. However, 1/3FF and 1/3FR significantly correlated with that grading. This suggests that grading reflected early diastolic function. Such regional early diastolic impairment was probably related to regional LV relaxation disturbance, and it appeared prior to global diastolic dysfunction. Our program might enable the detection of such minor early diastolic impairments in early-stage HF, using graphs as well as value-based assessment. The PFR did not correlate with grades 0 to 3. However, the PFR demonstrated a weak correlation with grades 0 to 2, with the exception of the PSG. The PFR was significantly greater in the PSG than in the cases with other grades. The numbers of r-TPF2 prolonged segments in the PSG were higher than those in the PDG.
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In addition, early diastolic functions were significantly decreased in the PSG. The PFR in the PSG reflected a late filling rate, which was generated by atrial contraction. The PSG demonstrated a relatively high EF and a significantly increased heart rate compared with the NSG and NDG. In particular, one patient with HT demonstrated an extremely high PFR, high HR, and high EF, despite an extremely low 1/3FF and 1/3FR. Akincioglu et al previously reported that PFR correlated with heart rate.8 We speculated that, in this case, an increased heart rate might induce a high PFR because of overcompensation by the reinforced left-atrial contraction. The PSG comprised 3 patients (75%) with HT, and 2 patients (50%) with DM. The PSG in early-stage HF should be assigned a special status, but the difference between PSG and PDG remains to be determined through further investigation involving a large population. We used pFAST for preprocessing to obtain timevolume data. However, there are several commercially available preprocessing programs. If another program supplies the same type of data, cardioGRAF can be modified accordingly.
3. Yamamoto A, Takahashi N, Munakata K, Abe K, Kobayashi Y, Tamai J, et al. Relationships among regional diastolic impairment, prolongation of global time to peak filling rate, and diastolic function using ECG-gated myocardial perfusion SPECT in heart failure. Ann Nucl Med 2007;21:419-27. 4. Grossman WG. Defining diastolic dysfunction. Circulation 2000; 101:2020-1. 5. Vasan RS, Levy D. Defining diastolic heart failure. A call for standardized diagnostic criteria. Circulation 2000;101:2118-21. 6. Kidawa M, Coignard L, Drobinski G, Pakula MK, Thomas D, Kotnajda M, et al. Comparative value of tissue Doppler imaging and M-mode color Doppler mitral flow propagation velocity for the evaluation of left ventricular filling pressure. Chest 2005;128: 2544-50. 7. Hadano Y, Murata K, Liu J, Oyama R, Harada N, Okuda S, et al. Can transthoracic Doppler echocardiography predict the discrepancy between left ventricular end-diastolic pressure and mean pulmonary capillary wedge pressure in patients with heart failure? Circ J 2005;69:432-8. 8. Akincioglu C, Berman DS, Nishina H, Kavanagh PB, Slomka P, Abidov A, et al. Assessment of diastolic function using 16-frame 99mTc-sestamibi gated myocardial perfusion SPECT: Normal values. J Nucl Med 2005;46:1102-8. 9. Ohno M, Cheng CP, Little WC. Congestive heart failure: Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation 1994;89: 2241-50. 10. Nakata T, Katagiri Y, Odawara Y, Eguchi M, Masatoshi K, Tsuchihashi K, et al. Two- and three-dimensional assessment of myocardial perfusion and function by using technetium-99m sestamibi gated SPECT with a combination of count and image-based techniques. J Nucl Cardiol 2000;7:623-32. 11. Hashimoto A, Nakata T, Wakabayashi T, Kyuma M, Takahashi T, Tsuchihashi K, et al. Validation of quantitative gated single photon emission computed tomography and an automated scoring system for the assessment of regional left ventricular systolic function. Nucl Med Commun 2002;23:887-98. 12. Kasai T, Depuey EG, Shah AA. Compared with 3-dimensional analysis, 2-dimensional gated SPECT analysis overestimates left ventricular ejection fraction in patients with regional dyssynchrony. J Nucl Cardiol 2004;11:159-64. 13. Kasai T, Depuey EG, Shah AA. Decreased septal wall thickening in patients with left bundle branch block. J Nucl Cardiol 2004;11: 32-7. 14. American Heart Association Working Group. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council Cardiology of the American Heart Association. Circulation 2002;105:539-42. 15. Schuster I, Habib G, Jego C, Thuny J-F, Avierinos G, Derumeaux L, et al. Diastolic asynchrony is more frequent than systolic asynchrony in dilated cardiomyopathy and is less improved by cardiac resynchronization therapy. J Am Coll Cardiol 2005;46: 2250-7. 16. Wang J, Kurrelmeyer KM, Torre-Amione G, Nagueh SF. Systolic and diastolic dyssynchrony in patients with diastolic heart failure and the effect of medical therapy. J Am Coll Cardiol 2007;49: 88-96.
CONCLUSIONS Using the new method we developed, regional LV diastolic wall-motion abnormalities were frequently detected in the pattern of global and regional curves, even in early-stage HF. The grading reflected the dysfunction present during early diastole. Acknowledgments We thank Teruo Takahashi, Hiroshi Akimoto, and Akira Yakuwa for their technical assistance in the GMPS study, and Fujifilm RI Pharma Co., Ltd., for extending its cooperation in the development of this program.
References 1. Yamamoto A, Hosoya T, Takahashi N, Iwahara S, Munakata K. Quantification of left ventricular regional functions using ECGgated myocardial perfusion SPECT—validation of left ventricular systolic functions. Ann Nucl Med 2006;20:449-56. 2. Yamamoto A, Takahashi N, Munakata K, Hosoya T, Shiiba M, Okuyama T, et al. Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT—validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography. Ann Nucl Med 2007;21:115-21.
From the Department of Radiology,a Nippon Medical School, Tamanagayama Hospital, Tama City, Tokyo, Japan, and Department of Internal Medicine,b Nippon Medical School, Musashikosugi Hospital, Kawasaki City, Kanagawa, Japan. Received for publication July 7, 2007; final revision accepted Dec 18, 2007. Reprint requests: Akira Yamamoto, MD, Department of Radiology, Nippon Medical School, Tamanagayama Hospital, 1-7-1 Nagayama, Tama City, Tokyo 206-8512, Japan; [email protected]. 1071-3581/$34.00 Copyright © 2008 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2008.02.012
ies.1,2 Relationships among regional diastolic impairment, prolongation of global time to peak filling rate, and diastolic function were also been described previously.3 Recently, the importance of diastolic function has been emphasized in heart failure (HF).4-9 Hypertension (HT), ischemic heart disease (IHD), and many other diseases induce HF. However, early-stage HF has not been thoroughly investigated. In nuclear cardiology, the peak filling rate was established as a representative parameter to estimate diastolic function since the advent of gated blood-pool scintigraphy. Recently, time to peak filling rate was stated to be a more stable parameter.8 So far, diastolic abnormality has been estimated by such global LV functional and temporal parameters. Using a new program, we reported on the evaluation of regional diastolic wall motion by value-based assessment in earlystage HF.3 This program was also designed to distinguish a diastolic wall motion pattern by reviewing global and segmental curves. Synchronous and dyssynchronous regional diastolic wall-motion patterns were then estimated using this program. Such diastolic wall-motion patterns might reflect a diastolic function. In this study, we confirmed the usefulness of the new program in early-stage HF 375
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Table 1. Patient characteristics
CG SG (n ⴝ 15) (n ⴝ 40) Age (mean ⫾ SD) Male Hypertension Typical angina History of myocardial infarction Arrhythmia Cardiomyopathy Valvular disease Diabetes mellitus Hyperlipidemia Resting HR (bpm)
59 ⫾ 13 3 0 0 0 0 0 0 0 3 67 ⫾ 11
64 ⫾ 12 29 22 7 3 4 2 2 9 25 69 ⫾ 11
CG, Control group; SG, study group; bpm, beats per minute; HR, heart rate.
by classifying the diastolic LV wall-motion pattern and comparing its grading with global LV functions. MATERIALS AND METHODS Patient Population Patient characteristics are summarized in Table 1. The study group (SG) comprised 40 nonsymptomatic heart-disease or HT patients with early-stage HF, categorized as New York Heart Association (NYHA) functional class I. They were examined with resting GMPS. Patients with severe arrhythmias such as atrial fibrillation and tachycardia of more than 100 beats/minute were excluded. The control group (CG) comprised 15 patients who were examined with resting GMPS because of chest pain (n ⫽ 12), minor abnormalities on resting ECG (n ⫽ 2), or consciousness disorder (n ⫽ 1) (Table 1). These patients had not received any medication for heart disease. The low probability regarding the presence of a form of heart disease requiring treatment was confirmed by normal exercise-stress ECG and normal Holter ECG. Two-dimensional echocardiography also revealed normal wall motion in all CG patients who had neither HT nor diabetes mellitus (DM). Two patients exhibited hypercholesteremia (total cholesterol, 231 and 246 mg/dL) and one patient exhibited hypertrigliceremia (trigliceride, 191 mg/dL). To confirm reproducibility, 20 additional consecutive patients were examined. These patients were examined for the following reasons: myocardial infarction (MI; n ⫽ 3), angina pectoris or suspicious angina pectoris (AP; n ⫽ 9), arrhythmia or ECG abnormality (n ⫽ 4), and others (n ⫽ 4).
Data Acquisition and Analysis An intravenous injection of 600 MBq 99mTc-sestamibi was administered to patients at rest, and GMPS imaging was initiated after 30 to 60 minutes. Data were acquired for 40 to
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50 beats/projection with a parallel dual-detector camera (RC2600-I, Hitachi, Tokyo, Japan) under the following conditions: 64 projections during 360° rotation, with 16-frame gating, low-energy/high-resolution collimation, a 64 ⫻ 64 matrix, and step-and-shoot mode. The ECG-gated projection sets were filtered using a Butterworth filter (order 8, cutoff ⫽ 0.25 cycles/pixel, and pixel size of 5.1 to 7.6 mm), and reconstructed in a workstation using a filtered back-projection algorithm (RW3000, Hitachi). Neither attenuation nor scatter correction was employed. Short axial data were fed into a personal computer for subsequent processes.
Preprocessing for cardioGRAF Analysis To determine the inner LV edge, before processing with cardioGRAF, we used a program called “pFAST” (perfusion and function assessment by means of gated SPECT), version 2.4.2., which was developed at Sapporo Medical University (Hokkaido, Japan).10-13 For optimal LV edge detection, we regulated the magnification of two LV images at the first processing in pFAST. In the next step, LV centers on basal and apical short axial images were manually adjusted by moving the points at end-systole and end-diastole during 16 divided phases. At the same time, processing areas were also manually regulated by moving the points on x and y axes around the left ventricle for its extraction. After confirming the proper extraction of the LV edge, the regional volume data thus obtained were saved as files for future processing with cardioGRAF. Interobserver and intraobserver reproducibilities were evaluated in this process.
cardioGRAF Analysis The files that were obtained by pFAST contained regional (640 areas that comprised 40 areas/slice ⫻ 16 slices) volume data in terms of the number of voxels in each phase. According to the American Heart Association Scientific Statements,14 the 640 areas were grouped to obtain 17 segments, as described previously.1 The global and segmental time-volume curves (TVCs) were generated by Fourier curve-fitting analysis using two harmonics. The time-filling curve (TFC), which was the first derivative of TVC, was also created simultaneously, as shown in Figure 1. The values of global time from end-systole to peak filling (g-TPF1), and of regional time from 0 to peak filling (r-TPF2), were obtained from the global and regional TVCs and TFCs. The selected temporal and functional parameters were as follows: (1) (2) (3) (4) (5) (6)
Time from end systole to peak filling: TPF1 (ms); Time from 0 to peak filling: TPF2 (ms); Ejection fraction: EF (%) ⫽ V2 (%); First-third filling fraction: 1/3FF (%) ⫽ 100 ⫻ V1/V2 (%); First-third filling rate: 1/3FR (EDV/s); and Peak filling: PFR (EDV/s),
where V1 indicates first-third filling volume (%), and EDV indicates end-diastolic volume. These parameters were output as a spreadsheet that was then used in a calculation program. Regarding the parameters,
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Figure 1. Original graphs and Fourier-fitted global time-volume curves of the left ventricle (above) and the time filling curves (below) obtained by gated single-photon emission computed tomography at rest in a 57-year-old woman in the control group (A) and an 80-year-old woman with arrhythmia (B). ES, End-systole; PF, peak filling; TES, time to end-systole (ms); TPF1, time from end-systole to peak filling (ms); TPF2, time from 0 to peak filling; V, ejection volume (%); PFR, peak filling (EDV/s); 1/3FR, the first-third filling rate (EDV/s); ED, early diastole; LD, late-diastole.
Figure 2. The 17 regional time-volume curves of the left ventricle (above), and the time filling curves (below) obtained by gated single-photon emission computed tomography at rest, in a 56-year-old man with angina pectoris (A), a 66-year-old man with old myocardial infarction (B), a 54-year-old man with angina pectoris (C), and 80-year-old woman with arrhythmia (D). g-TPF1, Global time from end-systole to peak filling; ED, early diastole; LD, late diastole.
the median calculated by processing with pFAST three times was used to reduce the influence of manual adjustment.
Definition of TPF Prolongation and Grading of Diastolic Wall-Motion Abnormality Regarding global diastole, the prolongation of g-TPF1 was defined as the mean value ⫹ 2 SDs of the CG as a cutoff value. The mean ⫾ SD of g-TPF1 was 159.5 ⫾ 27.8 ms in the CG. Initially, HF was assigned to two groups: normal g-TPF1 (ⱕ215 ms, Figures 2A, B), or prolonged g-TPF1 (⬎215 ms, Figures 2C, D). To estimate the synchrony of regional diastolic LV wall motion, the intraventricular delay was measured by noting the difference between septal and lateral diastolic velocity curves in the study, using tissue Doppler imaging (TDI).15,16 For GMPS, we modified that method and proposed a new index, ie, the maximal difference (MD), which represents
the time lag between the earliest and latest regional filling peaks among the 17 LV segments (Figure 3). The maximal mean ⫾ SD difference of r-TPF2 (MD-rTPF2) was 64.7 ⫾ 41.5 ms in the CG. When we applied the 2-SD threshold, the normal limit of MD-r-TPF2 was 148 ms. The MD-r-TPF2 of less than or equal to 148 ms demonstrated synchronous filling peaks on the TFCs, and it was defined as a synchronous diastole. On the other hand, the MD-r-TPF2 of more than 148 ms demonstrated dyssynchronous filling peaks on the TFCs, and was defined as a dyssynchronous diastole. Finally, LV diastolic wall motion was divided into four subsets as follows: a globally normal and regionally synchronous group (NSG, Figures 2A, 3A), a globally normal but regionally dyssynchronous group (NDG, Figures 2B, 3B), a globally prolonged and regionally dyssynchronous group (PDG, Figures 2C, 3C), and a globally prolonged but regionally synchronous group (PSG, Figures 2D, 3D). As shown in Figure 3, the
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Figure 3. The 17 regional time-volume curves of the left ventricle (above) and the time filling curves (below). A and D, Normal maximal difference between earliest and latest regional time from 0 to peak filling (MD-r-TPF2) in a 56-year-old man with angina pectoris and an 80-year-old woman with arrhythmia, respectively. B and C, The increased MD-r-TPF2 in a 66-year-old man with old myocardial infarction and a 54-year-old man with angina pectoris, respectively.
number of r-TPF2 prolonged segments increased in the order NSG, NDG, PDG, and PSG, which suggested that r-TPF2 prolongation was extended in this order. Therefore, we graded NSG, NDG, PDG, and PSG as 0, 1, 2, and 3, respectively, with grade 0 defined as normal, and the other grades as abnormal. The reproducibility of MD-r-TPF2 was evaluated in the same manner as previously described.2,3
intraobserver reproducibilities were 19.6% and 25.0%, respectively. New Classification in SG
Regarding global systolic function, an EF of less than 50% was defined as abnormal. Regarding global diastolic functions, a mean value ⫺2 SD of the CG was used as the cutoff. Diastolic dysfunctions were defined as less than 27.8% during 1/3FF; less than 1.16 EDV/s during 1/3FR; and less than 1.70 EDV/s during PFR.
Table 2 shows the numbers and percentages of diastolic wall-motion patterns and these characteristics in the SG. We identified NSG, NDG, PDG, and PSG in 32.5%, 37.5%, 20%, and 10% of the patients, respectively. The resting heart rate was significantly greater in the PSG than in the NSG and NDG. The prolongation of TPF1 was observed in 30% of patients, but an abnormal diastolic wall-motion pattern was present as NDG, PDG, and PSG in 67% of the patients in the SG.
Statistical Analysis
Global Function Parameters in SG
Definition of LV Dysfunction
Values are expressed as the mean ⫾ SD. Parameters were compared using the Scheffé F-test after significant observation by one-way analysis of variance. Linear regression analysis and Spearman’s correlation coefficient by rank test were performed to determine the correlation between grading of diastolic wall motion and the LV functional parameters. P ⬍ .05 was considered significant.
Table 3 shows the percentages of patients with abnormal LV functions in the SG and four classifications. Global diastolic dysfunctions were identified in less than one-third of the SG (1/3FF, 30%; 1/3FR, 32.5%; and PFR, 22.5%). The decrease in 1/3FF was significantly more frequent in the PDG and PSG than in the NSG and NDG.
RESULTS All processing was successfully performed, and a few minutes were needed for the manual positioning of the LV center in the process of pFAST. Reproducibility of MD-r-TPF The reproducibility of MD-r-TPF2 was assessed by the coefficient of variation (CV). The interobserver and
Global Function Parameters in the New Patterns Figure 4 shows the correlation between grading and EF. There was neither a significant correlation between grading and EF, nor a significant difference among the four subsets. Figure 5 shows the correlation between grading and 1/3FF. Grading demonstrated a strong negative correlation with 1/3FF (Spearman’s rank correlation coefficient
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Table 2. Classification and characteristics
Cases* Age (y, mean ⫾ SD) Male Hypertension Typical angina History of myocardial infarction Arrhythmia Cardiomyopathy Valvular disease Diabetes mellitus Hyperlipidemia Resting heart rate (bpm)
NSG
NDG
PDG
PSG
13 (32.5) 56 ⫾ 9 9 6 4 1 1 0 1 2 6 64 ⫾ 10†
15 (37.5) 66 ⫾ 12 11 11 1 2 1 0 0 3 13 65 ⫾ 11†
8 (20) 70 ⫾ 13 6 2 2 0 1 2 1 2 3 75 ⫾ 6
4 (10) 70 ⫾ 11 3 3 0 0 1 0 0 2 3 86 ⫾ 4
NSG, Globally normal regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group. *Values in parentheses are percentages. † Significantly less than PSG.
Table 3. LV functions
LVEF ⬍50%* 1/3FF ⬍27.8%* 1/3FR ⬍1.16 EDV/s* PFR ⬍1.70 EDV/s*
SG (n ⴝ 40)
NSG (n ⴝ 13)
NDG (n ⴝ 15)
PDG (n ⴝ 8)
PSG (n ⴝ 4)
4 (10) 12 (30) 13 (32.5) 9 (22.5)
0 (0) 0 (0) 1 (8) 1 (8)
2 (13) 1 (7) 5 (33) 6 (40)
1 (13) 6 (75)† 3 (38) 2 (25)
0 (0) 4 (100)† 3 (75) 0 (0)
SG, Study group; NSG, globally normal and regionally synchronous group; NDG, globally normal regionally but dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group; LV, left-ventricular; LVEF, left-ventricular ejection fraction; 1/3FF, first-third filling fraction; 1/3FR, first-third filling rate; PFR, peak filling rate; EDV, end-diastolic volume. *Values in parentheses are percentages. † Significantly greater than NSG and NDG.
[rs] ⫽ – 0.74, P ⫽ 3.8 ⫻ 10⫺6). The value of 1/3FF was significantly greater in the NSG than in the NDG, PDG, or PSG (P ⬍ .05, P ⫽ 3.5 ⫻ 10⫺7, and P ⫽ 2.0 ⫻ 10⫺8, respectively). The 1/3FF was significantly greater in the NDG than in the PDG and PSG (P ⬍ .0005 and P ⫽ 4.8 ⫻ 10⫺6, respectively). Figure 6 shows the correlation between grading and 1/3FR. Grading demonstrated a significant negative correlation with 1/3FR (rs ⫽ ⫺0.49, P ⬍ .005). The 1/3FR in the NSG was significantly greater than in the PSG (P ⬍ .005). Figure 7 shows the correlation between grading and PFR. There was no significant correlation between grading and PFR, but PFR in the PSG was greater than PFR in the NSG, PDG, or PSG (P ⬍ .001, P ⫽ 2.6 ⫻ 10⫺6, and P ⫽ 2.5 ⫻ 10⫺5, respectively). After excluding the PSG, a weak but statistically insignificant correlation was demonstrated between grades 0 to 2 and PFR (y ⫽ ⫺0.27x ⫹ 2.2, rs ⫽ ⫺0.32, P ⫽ .06). In addition, one
patient with HT demonstrated an extremely high PFR (5.3 EDV/s). The same patient also demonstrated a high heart rate (90 beats/minute), high EF (86.7%), extremely low 1/3FF (5.9%), and extremely low 1/3FR (0.26 EDV/s).
DISCUSSION The importance of diastolic function has been emphasized in HF. In particular, early diastolic filling is impaired in the early stages of HF.9 So far, diastolic function has been evaluated using global functional parameters. Nuclear cardiology has limited the use of global assessment for the evaluation of diastolic function in early-stage HF, such as in cases of preserved EF. However, Akincioglu et al reported on the importance of g-TPF1 for the assessment of diastolic dysfunction.8
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Figure 4. Relationship between grading of regional diastolic wall-motion pattern and EF. EF, Ejection fraction; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
Therefore, we investigated the applicability of our new program for the estimation of regional diastolic impairment, using temporal parameters in nonsymptomatic patients. The global and regional temporal parameters derived from our program were previously validated in an earlier report,2 by comparing them with the results of gated equilibrium radionuclide angiography and speckletracking echocardiography. In addition, the lower limit of PFR and the upper limit of g-TPF that were derived from the data of the CG were nearly identical to the values reported by Akincioglu et al.8 We previously described a value-based diastolic assessment using this program.3 Therefore, we sought to confirm the usefulness of pattern-based diastolic assessment in the present study. The intraventricular time delay was measured by examining the differences between onsets of filling peak velocity, which was the same as MD-r-TPF2, using TDI.15,16 Although this study was performed using a value-based evaluation, the direct detection of wall motion abnormalities using the graphs was found to be superior. Using the cutoff values for g-TPF1 and MD-r-TPF2, wall-motion abnormalities could be determined using global and regional graphs. Regarding reproducibility, the CVs of g-TPF1, r-TPF2, EF, 1/3FF, 1/3FR, and PFR were approximately
Figure 5. Relationship between grading of regional diastolic wall-motion pattern and 1/3FF. 1/3FF, First-third filling fraction; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged regionally and dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
less than or equal to 5%.2,3 However, the CV of MD-r-TPF2 was relatively high. The border case between regionally synchronous and dyssynchronous groups presented a very high CV among the data obtained by processing three times, because a few segmental r-TPF2 prolongations resulted in a large MDr-TPF2. Automatic positioning may solve this problem, but it cannot guarantee that the correct position over the LV center will be obtained. The use of median values was one practical solution to counter this problem in the present study. In normal subjects, filling peaks are observed during early diastole, and the MD-r-TPF2 is very short (Figure 3A). On the other hand, the MD-r-TPF2 is increased when the regional filling peaks are generated during both early and late diastoles (Figures 3B,C). Therefore, we thought that an increase in MD-r-TPF2 over the normal range represented a regional diastolic impairment, as demonstrated by the prolongation of r-TPF. Using an
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Figure 6. Relationship between grading of regional diastolic wall-motion pattern and 1/3FR. 1/3FR, First-third filling rate; NSG, globally normal and regionally synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
assessment of regional diastolic wall-motion synchrony with MD-r-TPF2 alone, we could not distinguish between the NSG and PSG. However, the NSG and PSG differed: regional filling peaks were generated during early diastole in the NSG, but these peaks were generated during late diastole in the PSG. Both global and regional temporal parameters were needed to distinguish these diastolic wall-motion patterns. Four patterns of regional diastolic wall motion were confirmed in the SG. The findings proved that regional diastolic impairment had already commenced during an asymptomatic period. A diastolic abnormality was identified in 30% of the patients in the SG based on the prolongation of g-TPF1, and it was revealed in approximately 30% of patients in the SG based on 1/3FF, 1/3FR, and PFR, which were the global diastolic function parameters. Our program identified other minor regional diastolic wall-motion abnormalities as NDG in 37.5% patients in the SG. This observation suggested that global temporal and functional assessments could not identify a regional diastolic wall-motion abnormality as NDG, probably because global LV analysis could not
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Figure 7. Relationship between grading of regional diastolic wall-motion pattern and peak filling. PFR, Peak filling rate; NSG, globally normal regionally and synchronous group; NDG, globally normal but regionally dyssynchronous group; PDG, globally prolonged and regionally dyssynchronous group; PSG, globally prolonged but regionally synchronous group.
detect regional impairment because of the averaging of regional data. The EF did not correlate with the grading of regional diastolic wall-motion abnormalities. However, 1/3FF and 1/3FR significantly correlated with that grading. This suggests that grading reflected early diastolic function. Such regional early diastolic impairment was probably related to regional LV relaxation disturbance, and it appeared prior to global diastolic dysfunction. Our program might enable the detection of such minor early diastolic impairments in early-stage HF, using graphs as well as value-based assessment. The PFR did not correlate with grades 0 to 3. However, the PFR demonstrated a weak correlation with grades 0 to 2, with the exception of the PSG. The PFR was significantly greater in the PSG than in the cases with other grades. The numbers of r-TPF2 prolonged segments in the PSG were higher than those in the PDG.
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In addition, early diastolic functions were significantly decreased in the PSG. The PFR in the PSG reflected a late filling rate, which was generated by atrial contraction. The PSG demonstrated a relatively high EF and a significantly increased heart rate compared with the NSG and NDG. In particular, one patient with HT demonstrated an extremely high PFR, high HR, and high EF, despite an extremely low 1/3FF and 1/3FR. Akincioglu et al previously reported that PFR correlated with heart rate.8 We speculated that, in this case, an increased heart rate might induce a high PFR because of overcompensation by the reinforced left-atrial contraction. The PSG comprised 3 patients (75%) with HT, and 2 patients (50%) with DM. The PSG in early-stage HF should be assigned a special status, but the difference between PSG and PDG remains to be determined through further investigation involving a large population. We used pFAST for preprocessing to obtain timevolume data. However, there are several commercially available preprocessing programs. If another program supplies the same type of data, cardioGRAF can be modified accordingly.
3. Yamamoto A, Takahashi N, Munakata K, Abe K, Kobayashi Y, Tamai J, et al. Relationships among regional diastolic impairment, prolongation of global time to peak filling rate, and diastolic function using ECG-gated myocardial perfusion SPECT in heart failure. Ann Nucl Med 2007;21:419-27. 4. Grossman WG. Defining diastolic dysfunction. Circulation 2000; 101:2020-1. 5. Vasan RS, Levy D. Defining diastolic heart failure. A call for standardized diagnostic criteria. Circulation 2000;101:2118-21. 6. Kidawa M, Coignard L, Drobinski G, Pakula MK, Thomas D, Kotnajda M, et al. Comparative value of tissue Doppler imaging and M-mode color Doppler mitral flow propagation velocity for the evaluation of left ventricular filling pressure. Chest 2005;128: 2544-50. 7. Hadano Y, Murata K, Liu J, Oyama R, Harada N, Okuda S, et al. Can transthoracic Doppler echocardiography predict the discrepancy between left ventricular end-diastolic pressure and mean pulmonary capillary wedge pressure in patients with heart failure? Circ J 2005;69:432-8. 8. Akincioglu C, Berman DS, Nishina H, Kavanagh PB, Slomka P, Abidov A, et al. Assessment of diastolic function using 16-frame 99mTc-sestamibi gated myocardial perfusion SPECT: Normal values. J Nucl Med 2005;46:1102-8. 9. Ohno M, Cheng CP, Little WC. Congestive heart failure: Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation 1994;89: 2241-50. 10. Nakata T, Katagiri Y, Odawara Y, Eguchi M, Masatoshi K, Tsuchihashi K, et al. Two- and three-dimensional assessment of myocardial perfusion and function by using technetium-99m sestamibi gated SPECT with a combination of count and image-based techniques. J Nucl Cardiol 2000;7:623-32. 11. Hashimoto A, Nakata T, Wakabayashi T, Kyuma M, Takahashi T, Tsuchihashi K, et al. Validation of quantitative gated single photon emission computed tomography and an automated scoring system for the assessment of regional left ventricular systolic function. Nucl Med Commun 2002;23:887-98. 12. Kasai T, Depuey EG, Shah AA. Compared with 3-dimensional analysis, 2-dimensional gated SPECT analysis overestimates left ventricular ejection fraction in patients with regional dyssynchrony. J Nucl Cardiol 2004;11:159-64. 13. Kasai T, Depuey EG, Shah AA. Decreased septal wall thickening in patients with left bundle branch block. J Nucl Cardiol 2004;11: 32-7. 14. American Heart Association Working Group. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council Cardiology of the American Heart Association. Circulation 2002;105:539-42. 15. Schuster I, Habib G, Jego C, Thuny J-F, Avierinos G, Derumeaux L, et al. Diastolic asynchrony is more frequent than systolic asynchrony in dilated cardiomyopathy and is less improved by cardiac resynchronization therapy. J Am Coll Cardiol 2005;46: 2250-7. 16. Wang J, Kurrelmeyer KM, Torre-Amione G, Nagueh SF. Systolic and diastolic dyssynchrony in patients with diastolic heart failure and the effect of medical therapy. J Am Coll Cardiol 2007;49: 88-96.
CONCLUSIONS Using the new method we developed, regional LV diastolic wall-motion abnormalities were frequently detected in the pattern of global and regional curves, even in early-stage HF. The grading reflected the dysfunction present during early diastole. Acknowledgments We thank Teruo Takahashi, Hiroshi Akimoto, and Akira Yakuwa for their technical assistance in the GMPS study, and Fujifilm RI Pharma Co., Ltd., for extending its cooperation in the development of this program.
References 1. Yamamoto A, Hosoya T, Takahashi N, Iwahara S, Munakata K. Quantification of left ventricular regional functions using ECGgated myocardial perfusion SPECT—validation of left ventricular systolic functions. Ann Nucl Med 2006;20:449-56. 2. Yamamoto A, Takahashi N, Munakata K, Hosoya T, Shiiba M, Okuyama T, et al. Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT—validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography. Ann Nucl Med 2007;21:115-21.