Hiroshi Yamabe

Effect of l-arginine administration on myocardial thallium-201 perfusion during exercise in patients with angina pectoris and normal coronary angiograms

ObjectivesWe tested the hypothesis that an exogenous supplement of l-arginine could alleviate coronary perfusion abnormality during exercise in patients with angina pectoris and normal coronary arteries.Methods and ResultsTwelve patients underwent exercise thallium-201 scintigraphy without medication (control) and after intravenous administration of l-arginine. Exercise time was prolonged in the l-arginine study compared with the control (482 s vs 540 s, P<.05). Tl-201 extent score was improved in the l-arginine study (0.33 vs 0.26, P<.05), and the severity score was also improved (23.7 vs 16.9, P<.05). In 7 of the 12 patients whose Tl-201 redistribution disappeared in the l-arginine study, the percent increase in serum l-citrulline concentration during exercise was larger than that of the remaining 5 patients (18% vs 0.9%, P<.01). The percent reduction in epicardial coronary diameter in response to acetylcholine was also greater in the former group (28.3% vs 11.1%, P<.05).ConclusionExogenous l-arginine improved myocardial perfusion during exercise in a subset of patients with angina pectoris and normal coronary arteries, probably by increasing production of nitric oxide.

Deep negative T waves and abnormal cardiac sympathetic image (123I-MIBG) after the Great Hanshin Earthquake of 1995.

The authors report the increased incidence of patients with deep negative T waves without Q wave after the Great Hanshin Earthquake of 1995. Subjects underwent cardiac metaiodobenzyl guanidine (123I-MIBG) imaging, 201Tl scintigraphy, and coronary angiography. Among 2,756 inpatients of the preceding 5-year period, 33 (1.2%) showed the deep negative T waves, whereas 6 of 94 (6.4%; P < 0.001) showed it after the earthquake. Four of six patients had an episode of chest pain. Cardiac metaiodobenzyl guanidine imaging revealed the extent defects in all six patients despite a minimal change of 201Tl image. In addition, cardiac metaiodobenzyl guanidine imaging washout rate was hastened not only in the defect area but also in the nondefect area, which suggested augmented sympathetic activation. Natural disasters can affect the frequency of deep negative T waves, which relate abnormal cardiac sympathetic imaging.

Resting123I-BMIPP scintigraphy for detection of organic coronary stenosis and therapeutic outcome in patients with chest pain

PurposeResting123I-BMIPP scintigraphy can detect coronary artery disease based on persistent abnormality of myocardial fatty acid metabolism after trasient ischemia. The present study aimed to determine the value of resting123I-BMIPP scintigraphy in diagnosing coronary artery disease and predicting the therapeutic outcome in patients with chest pain symptom.MethodFive hospitals participated in this study, and scintigraphic and angiographic studies were performed in 104 patients without myocardial infarction. Twenty of them had non-coronary artery disease (chest pain syndrome), 26 had stable effort angina, 35 had unstable angina with organic coronary lesions, and 23 had vasospastic angina without significant organic stenosis.ResultsOverall sensitivity for diagnosing angina pectoris (stable, unstable and vasospastic) was 45%, and overall specificity for excluding non-coronary artery disease was 80%. The incidence of positive123I-BMIPP was 54% among patients with organic coronary stenosis (50% in stable angina and 61% in unstable angina with organic stenosis), but it was low (22%) in vasospastic angina without organic stenosis. Patients with advanced coronary stenosis and multi-vessel disease were found to have a higher incidence of positive123I-BMIPP. A positive123I-BMIPP result was correlated with a higher rate of subsequent intervention therapy (catheter intervention or CABG) than a negative result (48% versus 27%, p=0.03 at one month; and 63% versus 35%, p=0.008 at one year).ConclusionResting123I-BMIPP scintigraphy was valuable in detecting advanced coronary lesions in angina patients associated with a high incidence of subsequent intervention therapy.

Myocardial defect detected by123I-BMIPP scintigraphy and left ventricular dysfunction in patients with idiopathic dilated cardiomyopathy

The present study examined the role of myocardial fatty acid in patients with idiopathic cardiomyopathy (DCM) by means of123I-β-methyl-p-iodophenyl pentadecanoic acid (123I-BMIPP) scintigraphy. Thirteen patients underwent123I-BMIPP imaging,201Tl imaging and echocardiography. All patients showed defective myocardial uptake of123I-BMIPP and201Tl. The left ventricular end-diastolic dimension (64.1 ± 7.3 mm vs. 55.6 ± 1.5 mm, p < 0.05) and end-systolic dimension (52.4 ± 8.0 mm vs. 40.6 ± 2.1 mm, p < 0.01) were significantly larger in the large defect group (123I-BMIPP defect score (DS) > 8) than the small defect group (DS < 7). The % fractional shortening (%FS) was also significantly smaller (18.6 ± 3.8% vs. 27.0 ± 3.3%, p < 0.01) in the large defect group. The123I-BMIPP DS correlated statistically with %FS (r = 0.75, p < 0.01), while the201Tl DS did not (r = 0.41, ns). We conclude that the patients with DCM revealed a123I-BMIPP uptake defect and the defect reflected the degree of left ventricular dysfunction.

Effect of nicorandil on abnormal coronary flow reserve assessed by exercise201Tl scintigraphy in patients with angina pectoris and nearly normal coronary arteriograms

SummaryThe purpose of the present study is to assess the effect of nicorandil, a coronary vasodilator with a mechanism of potassium channel opening, on the abnormal myocardial201Tl perfusion evoked by exercise. Eleven patients who had a history of typical angina, positive exercise electrocardiograms, positive201Tl scintigraphy, nearly normal coronary arteriograms, and negative coronary vasospasm underwent exercise201Tl scintigraphies under no medication (baseline test) and administration of nicorandil (nicorandil test).201Tl was injected at a matched workload in both tests. Nicorandil did not alter heart rate, blood pressure, or the rate-pressure product at the end of the exercise, but it significantly improved the extent score from 0.37±0.22 to 0.20±0.15 (p<0.05) and the severity score from 33.9±32.2 to 13.5±16.4 (p<0.05), and also significantly hastened the201Tl mean washout rate from 30.5±14.8% to 37.4±13.1% (p<0.05). Anginal symptoms disappeared in 3 of 5 cases and ST depression improved in 5 of 7 cases after nicorandil. We conclude that nicorandil augments coronary flow reserve, possibly due to a reduction of vasotone in the small coronary arteries.

Resting123I-BMIPP scintigraphy in diagnosis of effort angina pectoris with reference to subsets of the disease

This study was undertaken to assess the diagnostic value of resting123I-BMIPP scintigraphy in patients with effort angina pectoris. One hundred and four patients underwent scintigraphic and angiographic examinations. The subsets of the patients were stable effort angina pectoris (stable type) in 27 cases, new onset of effort angina pectoris (new onset type) in 21 cases, and worsening effort angina pectoris (worsening type) in 35 cases. The remaining 21 cases were subjects without evidences of coronary artery disease (non-CAD).l23I-BMIPP was injected under resting and pain free condition, then data for single photon emission tomography (SPECT) were acquired. The positive regional123I-BMIPP defects in three coronary territories were visually judged on the tomographic images. The overall sensitivity to diagnose the patients was 62.6% (52/83) and the overall specificity to exclude non-CAD subjects was 95.2% (20/21). The detection rate in each subset of the disease was 48.1% (13/27) in stable type, 47.6% (10/21) in new onset type and 77.1% (27/35) in worsening type (p < 0.05 versus two other types). For detection of stenosed vessels, the overall sensitivity was 41.4% (56/148) and the overall specificity was 93.8% (152/164). The rate of detection of stenosed vessels was 31.7% (13/41) in stable type, 31.4% (11/35) in new onset type, and 55.6% (40/72) in worsening type (p < 0.05 versus two other types). Vessels with 75% stenosis were more sensitively detected in the worsening type (33.3%; 4/12) compared to the remaining two types (8.3%; 1/12) even though the difference was not significant. The resting123I-BMIPP scintigraphy was therefore valuable in diagnosing patients with effort angina pectoris and involved coronary arteries especially in the subset of patients with worsening type.

Dependence of peak oxygen uptake on oxygen transport capacity in chronic heart failure: comparison of graded protocol and fixed protocol

Oxygen transport capacity is the most important determinant of maximum oxygen uptake (V(O2) max) in healthy subjects, however, its role is controversial in patients with chronic heart failure (CHF). The aim of this study was to clarify whether the oxygen transport capacity is an actual determinant of exercise capacity in CHF patients. Thirteen CHF patients underwent two maximum exercise tests, i.e., a graded protocol test and a fixed protocol test, measuring expiratory gases, leg blood flow (LBF), and arterial and venous blood gases. The workload of the fixed protocol was set to exceed the peak workload obtained by the graded protocol. Exercise with the fixed protocol caused significantly larger peak V(O2) compared to the graded protocol (813+/-194 to 971+/-203 ml/min, P<0.001). Peak LBF increased by 17%, while the peak leg arterio-venous oxygen difference increased by 5% from the graded protocol to the fixed protocol. The linear correlation between leg venous partial oxygen pressure and peak V(O2) was more clearly manifested in the fixed protocol (r=0.60, P<0.05) than in the graded protocol (r=0.47, NS). In conclusion, the exercise with graded protocol did not always conduct the upper limit of oxygen demand/supply relationship in CHF patients, whereas, the fixed protocol with a larger workload produced larger peak V(O2) and manifested the mechanism to limit V(O2) by oxygen transport capacity.

Serum beta2-microglobulin concentration as a novel marker to distinguish levels of risk in acute heart failure patients

BACKGROUND Recently, serum beta2-microglobulin, an endogenous marker for renal function, has been shown to be an independent predictor of mortality in older adults. However, the prognostic role of beta2-microglobulin in heart failure has not been elucidated. METHODS We prospectively evaluated serum beta2-microglobulin and creatinine concentrations, creatinine-based renal parameters (estimated glomerular filtration rate and creatinine clearance), and echocardiographic data in 131 patients with acute heart failure and creatinine concentrations < or =3.0mg/dL admitted to our hospitals. RESULTS During 2.3+/-1.3 years, 42 patients died of cardiovascular causes and 12 died of noncardiac causes. Cardiovascular events were observed in 63 patients: 53 were readmitted due to worsening heart failure, 5 readmitted for cerebral embolism, and 5 died from sudden cardiac death. According to multivariate stepwise Cox proportional hazard analysis, higher baseline serum beta2-microglobulin concentrations (X(2)=16, p<0.0001), previous congestive heart failure (X(2)=11, p<0.001), presence of chronic obstructive pulmonary disease (X(2)=8, p<0.01), and lower diastolic blood pressure (X(2)=6, p<0.05) were independent predictors of increased cardiovascular events. Also, higher baseline serum beta2-microglobulin (X(2)=20, p<0.0001), lower systolic blood pressure (X(2)=11, p<0.001), higher relative left ventricular wall thickness (X(2)=6, p<0.05), and lower body mass index (X(2)=5, p<0.05) were independent predictors of increased cardiac mortality. The adjusted hazard ratio for cardiovascular events increased with baseline serum beta2-microglobulin above 2.1 mg/L: 2.9 with beta2-microglobulin of 2.2-2.6 mg/L (95%CI 1.2-6.9, p<0.05), 2.9 with beta2-microglobulin of 2.7-3.9 mg/L (95%CI 1.2-7.2, p<0.05), and 4.7 with beta2-microglobulin of > or =4.0 mg/L (95%CI 2.0-11, p<0.001). CONCLUSIONS Higher baseline serum beta2-microglobulin concentration could be a promising risk marker in acute heart failure patients with creatinine < or =3.0 mg/dL.

Washout rate of123I-metaiodobenzylguanidine increased by posture change or exercise in normal volunteers

Abstract123I-metaiodobenzylguanidine (MIBG) imaging detects sympathetic nerve function in the heart. The present study was conducted to clarify whether posture change or exercise affects123I-MIBG kinetics in normal volunteers. Seven subjects underwent three123I-MIBG studies, i.e., supine protocol, sitting protocol and exercise protocol. Planar123I-MIBG images were obtained at 15 minutes, 1 hour and 4 hours after injection of123I-MIBG. The washout rate (WR) from 15 minutes to 1 hour in the supine position in all subjects was similar for all three protocols, whereas the WR from 1 hour to 4 hours was significantly augmented in the sitting protocol and the exercise protocol as compared to the supine protocol (p < 0.05 and p < 0.01). The serum concentration of noradrenaline was significantly increased from the baseline to the 4 hour sampling in the sitting protocol and the exercise protocol (both p < 0.01), but was not altered in the supine protocol. The WR from 1 hour to 4 hours significantly correlated with the noradrenaline concentration in 4 hour sampling (r = 0.59, p < 0.01). It also significantly correlated with an increase in the noradrenaline concentration from the baseline to the 4 hour sampling (r = 0.53, p < 0.05). It is concluded that posture change or exercise affects the WR of123I-MIBG in normal healthy subjects.

Impaired coronary circulation in acute myocardial infarction: A dipyridamole-thallium-201 study

Coronary flow reserve is not fully restored immediately after revascularization of an occluded vessel. The present study examined the coronary flow impairment in patients with acute myocardial infarction (AMI) after successful balloon angioplasty or spontaneous recanalization (without residual epicardial coronary stenosis). Fourteen patients underwent thallium-201 dipyridamole scintigraphy in the acute phase (mean 5.9 days) and in the chronic phase (mean 24.6 days) after AMI. A201Tl reinjection study was carried out only in the acute phase of AMI. The fill-in phenomenon was assessed by the %201Tl uptake in the infarct region after201Tl reijection, and positive (n=8) and negative (n=6) fill-in groups were distinguished. The %201Tl uptake increased from the acute phase study to the chronic phase study in the positive fill-in group (56.1%±4.1% to 74.4%±13.6%,P<0.001), whereas it decreased in the negative fill-in group (54.0%±10.6% to 43.7%±9.9%,P<0.05). The change in %201Tl uptake following reinjection was significantly correlated with the improvement in regional ventricular wall motion in the chronic phase (r=0.85,P<0.001). We conclude that the impaired coronary flow reserve persisted after balloon angioplasty or spontaneous recanalization, which might indicate the presence of “microvascular stunning”. The increase in %201Tl uptake predicted the change in ventricular wall motion.