Chinori Kurata

Comparison of effects of enalapril and nitrendipine on cardiac sympathetic nervous system in essential hypertension.

OBJECTIVES The purpose of this study was to assess the effects of enalapril and nitrendipine on the cardiac sympathetic nervous system. BACKGROUND Angiotensin-converting enzyme inhibitors and long-acting calcium channel blockers have been widely used in the treatment of cardiovascular diseases, in some of which sympathetic overactivity plays a major role in the pathophysiology and prognosis. However, little information is available on the effects of these drugs on the cardiac sympathetic nervous system. METHODS 123I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed before and 3 months after drug administration in 46 patients with mild essential hypertension. Twenty-two patients were treated with 5 to 10 mg of enalapril once a day, and the other 24 with 5 to 10 mg of nitrendipine once a day. For comparison, 20 normotensive subjects were also studied. RESULTS There were no significant differences between the basal characteristics in the 2 hypertensive groups. In both hypertensive groups, both systolic and diastolic blood pressures were significantly reduced to similar levels after the 3-month drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower MIBG uptake than the normotensive subjects. The heart-to-mediastinum ratio significantly increased (p < 0.0001), with decreased (p < 0.002) washout rate after drug treatment in the enalapril group, but with no significant changes in the nitrendipine group. CONCLUSION Enalapril could suppress cardiac sympathetic activity and nitrendipine had no effect on it. The knowledge of antihypertensive drugs on the cardiac sympathetic nervous system appears to be helpful in selecting appropriate treatment in cardiovascular diseases.

Cardiac Autonomic Neuropathy in Patients with Chronic Renal Failure on Hemodialysis

To characterize uremic cardiac autonomic neuropathy, we measured plasma catecholamines, analyzed the 24-hour heart rate variability (HRV), and acquired serial images with 123I-metaiodobenzylguanidine (MIBG) in 44 patients with chronic renal failure on hemodialysis and in 14 controls. Time-domain measures were calculated using the Marquette HRV program. MIBG clearance rates from the heart and lung were evaluated on planar images, and the regional MIBG uptake in the left ventricular myocardium was evaluated with single-photon emission computed tomography. Compared with controls, plasma dopamine and norepinephrine levels were elevated (p < 0.001 and p = 0.03, respectively), and all the time-domain measures of HRV were reduced in the patients (p < 0.001). The MIBG clearance rate from the heart was higher (p < 0.001), that from the lung was lower (p < 0.001), and the myocardial MIBG distribution was more heterogeneous in patients than in controls (total uptake score p ≤ 0.03). These variables were similar between 26 patients without and 18 patients with hypertension. Uremic cardiac autonomic neuropathy may be characterized by high plasma levels of dopamine and norepinephrine, reduced HRV, and abnormal MIBG kinetics in the heart with heterogeneous myocardial MIBG distribution, suggesting cardiac sympathetic overactivity and parasympathetic deterioration. In addition, abnormal MIBG kinetics in the lung may imply pulmonary sympathetic nervous dysfunction and/or endothelial dysfunction in uremic patients.

Exercise testing and thallium-201 emission computed tomography in patients with intraventricular conduction disturbances

The specificity of exercise thallium-201 emission computed tomography for coronary artery disease was assessed in patients with intraventricular conduction disturbances. Eighty-seven patients were studied: 33 with right bundle branch block (RBBB), 11 with RBBB and left-axis deviation, 11 with left (L)BBB, 12 on right ventricular pacing, and 20 with Wolff-Parkinson-White (WPW) syndrome. A control group of 349 consecutive patients with normal intraventricular conduction was also examined. The specificity of diagnosis of coronary artery disease in patients with LBBB (30%), right ventricular pacing (44%) or RBBB plus left-axis deviation (50%) was significantly lower than in patients with normal intraventricular conduction (94%; p less than 0.01). In contrast, there was no significant difference between specificity in patients with RBBB (86%) or WPW syndrome (90%) and patients with normal intraventricular conduction. Perfusion defects were found in the anterior, septal and inferior segments in patients with LBBB, and in the septal and inferior segments in patients with RBBB plus left-axis deviation despite the absence of coronary stenosis. Furthermore, diffuse slow washout was seen more often in patients with WPW syndrome (35%) than in controls who had normal intraventricular conduction (11%; p less than 0.05), despite a good exercise performance in the former group. This study suggests that there is an increased incidence of abnormal perfusion and clearance during exercise thallium-201 emission computed tomography in patients with intraventricular conduction disturbances.

Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina

To elucidate the circadian variation of fibrinolytic components in vasospastic angina, plasma levels of tissue plasminogen activator antigen (t-PA), free plasminogen activator inhibitor antigen (free PAI-1), t-PA/PAI-1 complex, and total PAI-1 were measured in venous plasma samples. Samples were taken every 6 hours (6:00 AM, noon, 6:00 PM, and midnight) for 24 hours in 14 patients with vasospastic angina, in 9 patients with exertional angina, and in 19 normal subjects. Twenty-four-hour Holter monitoring (Holter monitor, Del Mar Avionics, Irvine, Calif.) was also carried out in all subjects. All of the fibrinolytic components showed circadian variation, with a peak level at 6:00 AM in every study group except for the t-PA/PAI-1 complex in the group of patients with exertional angina. The values for all or the fibrinolytic components at each sampling time were higher in patients with coronary artery disease than in normal subjects. In particular, the mean value of free PAI-1 at 6:00 AM in patients with vasospastic angina was significantly higher than that in normal subjects and that in patients with exertional angina. This value of free PAI-1 in patients with vasospastic angina was closely associated with the duration of ischemic attacks. These results suggested that the circadian fluctuation of fibrinolytic components may be an important factor that leads to coronary thrombosis at the time of coronary spasm, especially in the early morning.

Prognosis of hypertrophic cardiomyopathy: Assessment by123I-BMIPP (β-methyl-p-(123I)iodophenyI pentadecanoic acid) myocardial single photon emission computed tomography

Abstract123I-BMIPP (β-methyl-iodophenyl pentadecanoic acid) has shown unique properties for potential use in assessing myocardial metabolism. Previous basic and clinical studies demonstrated that the disturbances of myocardial metabolism precede the occurrence of myocardial perfusion abnormalities by using201Tl in hypertrophic myocardium. The present study was therefore undertaken to determine whether or not123I-BMIPP myocardial SPECT is useful in predicting the prognosis of hypertrophic cardiomyopathy (HCM) in 65 patients in 6 facilities. There were 33 patients with non-obstructive HCM, 12 with obstructive HCM, 12 with apical HCM and 8 with dilated-phase HCM. Fasted patients at rest received an intravenous injection of 111 MBq of123I-BMIPP. Twenty to thirty minutes later, myocardial SPECT was carried out. The BMIPP severity score (BMIPP SS) was evaluated semiquantitatively by using representative short axial SPECT images. We followed up the incidence of cardiac events for a mean period of 3.0 ± 0.6 years. Cardiac events occurred in 13 patients. Of these, 11 developed heart failure and 6 died (4 from heart failure and 2 from sudden death). The BMIPP SS in the dilated-phase HCM was significantly higher than that in the remaining HCM patients. The BMIPP SS for the survivors was significantly lower than that for the non-survivors. The BMIPP SS was particularly high in patients with fatal heart failure. Furthermore, there was a close negative correlation between the BMIPP SS and percent fractional shortening measured by echocardiography (r = −0.49). Finally, the mortality over the three years increased according to the extent of the BMIPP SS. In conclusion, these results indicate that the BMIPP SS is useful in evaluating the severity of HCM. We conclude that123I-BMIPP is a valuable metabolic tracer in predicting the outcome of HCM.

Iodine-123 Metaiodobenzylguanidine Cardiac Imaging to Identify and Localize Vasospastic Angina Without Significant Coronary Artery Narrowing

OBJECTIVES We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing. BACKGROUND Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina. METHODS Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bulls-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bulls-eye was defined as an area > 2 SD below normal. An abnormal regional washout rate was defined as < 0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bulls-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement. RESULTS Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bulls-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis. CONCLUSIONS Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.

Sympathetic nerve activity in the spasm-induced coronary artery region is associated with disease activity of vasospastic angina

OBJECTIVES We assessed the relation between sympathetic nerve activity and disease activity of vasospastic angina. BACKGROUND The autonomic nervous system has been proposed to play a key role in attacks of vasospastic angina. A unique feature of vasospastic angina attacks is periodic fluctuation, which complicates the assessment of disease activity. METHODS Twenty-five patients with left anterior descending coronary artery (LAD) spasm were studied: 12 with recent onset of chest pain (group 1) and 13 free of angina for more than 3 months after discontinuing medication (group 2). Group 1 underwent iodine-123 metaiodobenzylguanidine (MIBG) imaging (in the active phase) and atropine-stress MIBG imaging early after diagnostic angiography, and repeat MIBG imaging when they were free of angina for more than 3 months with medication (in the stable phase). Group 2 also underwent MIBG imaging (in remission). On a bulls-eye map, quantitative analysis of percent uptake and washout rate of MIBG was performed regionally. RESULTS In group 1 in the active phase, the washout rate of the LAD territory was significantly lower than the rates in the stable phase, in remission and during atropine-stress MIBG imaging. The regional washout rate of the territories of the right coronary artery and the circumflex artery in the active phase was also significantly lower than that during atropine-stress MIBG imaging. The washout rate of the LAD territory in the active phase was significantly lower than the rates of the other two regions. In contrast, there were no significant differences in the distribution of regional percent uptake in every image. A similar distribution of washout rate was observed among group 1 patients in the stable phase, in group 1 patients during atropine-stress MIBG imaging and in group 2 patients. CONCLUSIONS The MIBG washout rate of the spasm-induced coronary artery territory changed according to the degree of disease activity. Thus, sympathetic nerve activity could reflect disease activity of vasospastic angina.

Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography

Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent.

SPECT imaging with Tl-201 and Ga-67 in myocardial sarcoidosis.

Two patients with myocardial sarcoidosis are presented, both of whom underwent SPECT imaging with TI-201 and Ga-67. The first had Ga-67 myocardial uptake with a TI-201 defect, which disappeared with corticosteroid therapy. The second had multiple TI-201 defects without Ga-67 uptake, which persisted despite corticosteroid therapy. Therefore, the combination of TI-201 and Ga-67 imaging may be useful for recognizing myocardial sarcoidosis and for predicting the response to corticosteroid therapy.