Tsuyoshi Shimonagata

Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: a prospective study.

OBJECTIVES We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF). BACKGROUND Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients. METHODS At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction <40%. The cardiac MIBG heart to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. The time and frequency domain parameters of HRV were calculated from 24-h Holter recordings. RESULTS At a mean follow-up of 34 +/- 19 months, WR (p < 0.0001), H/M on the delayed image (p = 0.01), and normalized very-low-frequency power (n-VLFP) (p = 0.047) showed a significant association with the cardiac events (sudden death in 3 and hospitalization for worsening chronic HF in 10 patients) on univariate analysis. Multivariate analysis revealed that WR was the only independent predictor of cardiac events, although the predictive accuracy for the combination of abnormal WR and n-VLFP significantly increased, compared with that for abnormal WR (82% vs. 66%, p < 0.05). CONCLUSIONS Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.

Prognostic significance of cardiac 123I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure: a prospective study

OBJECTIVE To determine whether cardiac iodine-123 metaiodobenzylguanidine (123I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. DESIGN Cardiac 123I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. SETTING Tertiary referral centre. PATIENTS 79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. RESULTS There were 37 patients in group 1 (washout rate of ⩾ 27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan–Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2. CONCLUSIONS Cardiac 123I MIBG washout rate seems to be a good predictor of prognosis in patients with chronic heart failure.

Prediction of paroxysmal atrial fibrillation in patients with congestive heart failure : A prospective study

OBJECTIVES We sought to prospectively determine whether patients with congestive heart failure (CHF) at risk for paroxysmal atrial fibrillation (PAF) could be identified by clinical and study variables including the P-wave signal-averaged electrocardiogram (P-SAECG). BACKGROUND Although it is important to assess the risk of developing PAF in patients with CHF, it still remains difficult to predict the PAF appearance in patients with CHF clinically. METHODS The study group consisted of 75 patients in sinus rhythm without a history of PAF, whose left ventricular ejection fraction, as measured by radionuclide angiography, was <40%. These patients underwent P-SAECG, echocardiography and 24-h Holter monitoring; in addition, the plasma concentration of atrial natriuretic peptide (ANP) was measured at study entry. RESULTS An abnormal P-SAECG was found at study entry in 29 of 75 patients. In the follow-up period of 21 +/- 9 months, the PAF attacks documented on the ECG significantly more frequently occurred in patients with (32%) rather than without an abnormal P-SAECG (2%) (p = 0.0002). The plasma ANP level was significantly higher in patients with rather than without PAF attacks (75 +/- 41 vs. 54 +/- 60 pg/ml, p = 0.01), although there were no significant differences in age, left atrial dimension or high grade atrial premature beats between the groups. The multivariate Cox analysis identified that the variables significantly associated with PAF development were an abnormal P-SAECG (hazard ratio 19.1, p = 0.0069) and elevated ANP level > or =60 pg/ml (hazard ratio 8.6, p = 0.018). CONCLUSIONS An abnormal P-SAECG and elevated ANP level could be predictors of PAF development in patients with CHF.

Prediction of Transition to Chronic Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation by Signal- Averaged Electrocardiography A Prospective Study

BACKGROUND It is well known that paroxysmal atrial fibrillation (PAF) often precedes the establishment of chronic atrial fibrillation (CAF). However, there have been no definite methods to predict the transition from PAF to CAF. The purpose of this report was to determine prospectively whether P-wave-triggered signal-averaged ECG (P-SAE) is useful for the prediction of the transition to CAF in patients with PAF. METHODS AND RESULTS One hundred twenty-two consecutive patients with PAF were prospectively followed after P-SAE, echocardiography, and 24-hour Holter monitoring at study entry. The duration (Ad) and root-mean-square voltage for the last 30 ms (LP30) of the filtered P wave were measured in P-SAE. The abnormality of P-SAE for the prediction of transition to CAF was defined as Ad > or = 145 ms and LP30 < 3.0 microV. Twenty-three (19%; group 1) of the patients had the abnormality of P-SAE, whereas the others (group 2) did not. During the follow-up period (mean, 26+/-12 months), 10 patients (43%) in group 1 acquired CAF, whereas the transition to CAF was observed in only 4 patients (4%) in group 2. Kaplan-Meier analysis revealed that the transition to CAF was significantly observed more often in group 1 than in group 2 (log-rank test, P<.0001). The Cox proportional hazards regression model identified that the variables most significantly associated with the transition to CAF were Ad (chi2=8.6, P=.003) and LP30 (chi2=5.1, P=.02), although significant differences in the left atrial dimension (40.8+/-5.3 versus 37.3+/-5.5 mm, P<.01) and the number of atrial premature contractions (3641+/-4524 versus 1489+/-2895 beats/d, P<.05) were observed between groups 1 and 2. CONCLUSIONS These results indicate that P-SAE could be useful to identify patients at risk for the transition from PAF to CAF.

Fatty acid myocardial imaging using 123I-β-methyl-iodophenyl pentadecanoic acid (BMIPP): comparison of myocardial perfusion and fatty acid utilization in canine myocardial infarction (Occlusion and reperfusion model)

To evaluate the relationship between myocardial perfusion and fatty acid metabolism in canine myocardial infarction, 16 dogs were studied using thallium and 123I-β-methyl-iodophenyl pentadecanoic acid (BMIPP). Eight dogs (group A) had left anterior coronary arterial occlusion (6 h ligation), 6 dogs (group B) had reperfusion (3 h ligation and 1 h reperfusion) and 2 dogs served as the normal control. Myocardial imaging with BMIPP was excellent, owing to its higher uptake and longer retention in myocardium and rapid blood disappearance in addition to diminished liver and lung uptake. The mean half time value which was generated from the BMIPP myocardial washout curve, was significantly larger in the reperfused myocardium. The gamma camera imaging showed uncoupling of BMIPP and thallium (BMIPP uptake greater than thallium uptake) in five dogs in group B. On the other hand, all dogs in group A had a persistent defect in BMIPP and thallium uptake. Our findings indicate that the combination of BMIPP and thallium for myocardial imaging supply different information about the zone of infarction and ischemia, which may be useful for the assessment of myocardial viability.

Mechanism of Impaired Left Ventricular Wall Motion in the Diabetic Heart Without Coronary Artery Disease

OBJECTIVE To elucidate whether impairment of the myocardial free fatty acid (FFA)metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease RESEARCH DESIGN AND METHODS We performed myocardial imaging with 123I-labeled β-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201 thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum RESULTS Nine patients with reduced wall motion documented by left ventriculography (LVG) (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 ± 0.2, mean ± SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 ± 0.2, P <0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P <0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes

Clinical results with β-methyl-p-(123I)iodophenylpentadecanoic acid, single-photon emission computed tomography in cardiac disease

This study was undertaken to evaluate the relationships between myocardial perfusion and metabolism. Simultaneous β-methyl-p-(123I)iodophenylpentadecanoic acid (123I-BMIPP) and thallium 201 myocardial single-photon emission computed tomography (SPECT) were performed in 25 patients with myocardial infarction (group A) and 16 patients with hypertrophic cardiomyopathy (group B). The severity scores of123I-BMIPP and201Tl myocardial SPECT images were evaluated semiquantitatively by segmental analysis. In Group A, dissociations between thallium- and123I-BMIPP-imaged defects were frequently observed in patients with successful reperfusion compared with those with no reperfusion and those with reinfarction. In four patients with successful reperfusion, repeated123I-BMIPP and201Tl myocardial SPECT showed gradual improvement of the123I-BMIPP severity score compared with the thallium severity score. In group B, dissociations between thallium- and123I-BMIPP-imaged defects were also demonstrated in hypertrophic myocardium. In addition, nonhypertrophic myocardium also had decreased123I-BMIPP uptake. In groups A and B,123I-BMIPP severity scores correlated well with left ventricular function compared with thallium severity scores. These findings indicate that123I-BMIPP is a suitable agent for the assessment of functional integrity, because left ventricular wall motion is energy dependent and123I-BMIPP may reflect an aspect of myocardial energy production. This agent may be useful for the early detection and patient management of various heart diseases as an alternative to positron emission tomographic study.

Discrepancies between myocardial perfusion and free fatty acid metabolism in patients with hypertrophic cardiomyopathy

To test the hypothesis that there arc discrepancies between 201T1− and 123I-β-methylpentadecanoic acid (BMIPP) distribution in the left ventricular myocardium and to assess whether BMIPP is a useful tracer agent for the assessment of left ventricular function in hypertrophic cardiomyopathy (HCM), myocardial single photon emission computed tomography (SPRCT) was performed with 201T1 and BMIPP in five normal subjects and 12 patients with asymmetric septal hypertrophy. Tracer uptake in the left ventricular myocardium was scored using a four-point grading System. A homogenous distribution of the tracer with no discrepancy between 201T1 and BMIPP uptake in the left ventricular myocardium was observed in each normal subject. In contrast, BMIPP uptake was reduced compared to 201T1 in 58 segments (40%) of the 144 myocardial segments in patients with HCM. Such discordant BMIPP uptake was observed in 15 segments (42%) of the septal segments, in 19 segments (53%) of the anterior segments, in eight segments (22%) of the lateral segments, and in 16 segments (44%) of the inferior segments. There was no significant correlation between 201T1 perfusion score and left ventricular ejection fraction, whereas there was a significant correlation between BMIPP perfusion score and left ventricular ejection fraction (r = 0.748; P <0.01). The results indicated that there were discrepancies between 201T1 and BMIPP uptake in a significant proportion of myocardial segments, suggesting the impairment of fatty acid metabolism and that BMIPP is a useful tracer agent for the assessment of left ventricular function in hypertrophic cardiomyopathy.

The effect of losartan and amlodipine on left ventricular diastolic function and atherosclerosis in Japanese patients with mild-to-moderate hypertension (J-ELAN) study.

This study was a prospective, randomized, open, blinded endpoint study to assess the effects of angiotensin II type 1 receptor blocker, losartan, compared with calcium channel blocker, amlodipine, on left ventricular (LV) diastolic function and atherosclerosis of the carotid artery in Japanese patients with mild-to-moderate hypertension, LV hypertrophy, diastolic dysfunction and preserved systolic function. Fifty-seven patients were randomly assigned to losartan- or amlodipine-based treatment groups and were followed up for 18 months. Blood pressure was similarly reduced by both regimens. Losartan shortened the transmitral E-wave deceleration time, and amlodipine reduced LV mass index; however, there was no significant difference in the percent changes of these indices between the two groups. Mean carotid intima–media thickness (mean IMT) as well as plaque score significantly increased in the amlodipine-based regimen (pre: 1.05±0.26 mm, follow-up: 1.23±0.33 mm, P=0.0015), but not in the losartan-based regimen (pre: 1.08±0.35 mm, follow-up: 1.16±0.52 mm, P=non-significant). The percent increase in mean IMT in the amlodipine-based regimen tended to be large compared with the losartan-based regimen (amlodipine: 19.8±23.7%, losartan: 6.9±23.3%, P=0.06). Under similar reduction of blood pressure, losartan is likely effective in protecting the progression of atherosclerosis of the carotid artery compared with amlodipine. Losartan may improve LV diastolic function, and amlodipine may attenuate LV hypertrophy; however, this study cannot make consecutive remarks about the superiority of either treatment regimen in the effects on cardiac function and geometry. This study has been registered at http://www.umin.ac.jp/ctr/listj/ (identifier C000000319).

Metabolic changes in hibernating myocardium after percutaneous transluminal coronary angioplasty and the relation between recovery in left ventricular function and free fatty acid metabolism

To elucidate the changes in oxidative metabolism in hibernating myocardium after coronary revascularization, we performed myocardial single-photon emission computed tomography with a free fatty acid analog, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP), and thallium-201 before and 1 month after percutaneous transluminal coronary angioplasty (PTCA) in 11 patients with angina pectoris caused by single artery stenosis. All patients had improvement in wall motion after PTCA at the region with coronary stenosis; the wall motion abnormality score evaluated by left ventriculography decreased from 5.5+/-0.8 (mean +/- SE) to 2.1+/-0.9, p <0.01) after PTCA. The defect score of I-123 BMIPP images was significantly larger than that of thallium-201 images either before (14+/-1.3 vs 8.9+/-1.1, p <0.01) or 1 month after (7.4+/-1.5 vs 3.7+/-0.8, p <0.01) PTCA. The decrease in the defect score of both images was significant (p <0.01). Changes in the wall motion abnormality score showed a significant correlation with both the change in the defect score of thallium-201 images (r = 0.58, p < 0.01) and that of I-123 BMIPP images (r = 0.75, p <0.01). These results indicate that the metabolism of free fatty acid is impaired in hibernating myocardium, and that improvement in left ventricular function after successful PTCA is strongly associated with the recovery of oxidative metabolism.