Kenichi Mitsunami

Quantitative Measurements of Cardiac Phosphorus Metabolites in Coronary Artery Disease by 31P Magnetic Resonance Spectroscopy

BACKGROUND 31P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. METHODS AND RESULTS Forty-one subjects with stenosis of the left anterior descending coronary artery (> 50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+], n = 29) who demonstrated redistribution at late image and a fixed 201Tl defect group (RD[-], n = 12). While the subjects lay supine within the magnet, 31P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (+/- SD) PCr at rest (C, 12.14 +/- 4.25 > RD[+], 7.64 +/- 3.00 > RD[-], 3.94 +/- 2.21 mumol/g wet heart tissue, P < .05) as well as a significant decrease in ATP in the RD(-) group (C, 7.72 +/- 2.97; RD[+], 6.35 +/- 3.17 > RD[-], 4.35 +/- 1.52 mumol/g wet heart tissue, P < .05). CONCLUSIONS Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed 201Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by 31P MRS is a clinically important method for the evaluation of myocardial viability.

Detection of myocardial ischemia by 31P magnetic resonance spectroscopy during handgrip exercise.

BACKGROUND The metabolic changes of myocardial ischemia in patients with coronary artery disease assessed by 31P magnetic resonance spectroscopy (MRS) have been reported previously. A significant decrease in the ratio of phosphocreatine (PCr) to ATP during handgrip exercise in a group of patients with severe coronary artery disease has been demonstrated. However, there are no reports at present that directly compare cardiac 31P MRS data with exercise 201Tl myocardial scintigraphy, now established as one of the most important clinical methods to assess myocardial ischemia. The purpose of this study was to investigate whether 31P MRS with handgrip exercise testing is able to detect myocardial ischemia, demonstrated by exercise 201Tl scintigraphy. METHODS AND RESULTS Twenty-seven patients with severe stenosis of the left anterior descending coronary artery (> or = 75%) and 11 normal control subjects composed the present study. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+]) who demonstrated redistribution at the late image and a fixed 201Tl defect group (RD[-]). While lying supine within the magnet, subjects performed handgrip exercise at 30% of maximal force once in every two cardiac cycles. 31P MR spectra were collected before and during handgrip exercise. Data were corrected for the saturation factor. ANOVA revealed significant differences among the three groups with respect to the mean +/- SD PCr/ATP ratio at rest (control, 1.85 +/- 0.28 > RD(+), 1.60 +/- 0.19 > RD(-), 1.24 +/- 0.30; P < .05). The PCr/ATP ratio decreased significantly from 1.60 +/- 0.19 at rest to 0.96 +/- 0.28 during exercise (P < .001) in the RD(+) group (n = 15). However, in the RD(-) group (n = 12), the ratio did not change significantly during handgrip exercise (1.24 +/- 0.30 at rest versus 1.19 +/- 0.28 during exercise). Similarly, the ratio did not change in the control group (n = 11) (1.85 +/- 0.28 at rest versus 1.90 +/- 0.23 during exercise). CONCLUSIONS Contrary to normal subjects or patients with fixed thallium defects, the PCr/ATP ratio was significantly altered by exercise in patients with reversible thallium defects. These results suggest that 31P MRS with handgrip exercise testing is a sensitive method for detecting myocardial ischemia.

A “natural experiment” in cardiovascular epidemiology in the early 21st century

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies

Comparative efficacy of high-dose versus low-dose nicorandil therapy for chronic stable angina pectoris

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-Month Effects of Candesartan Cilexetil, an Angiotensin II Type 1 (AT1) Receptor Antagonist, on Left Ventricular Mass and Hemodynamics in Patients with Essential Hypertension

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2–8 mg/day orally for 8–12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 ± 17.2 mmHg (mean ± SD) to 150.2 ± 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 ± 6.5 mmHg to 87.8 ± 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 ± 31.3 g/m2 to 102.6 ± 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 ± 31.1 g/m2 to 115.8 ± 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 ± 636.3 dynes·s·cm−5 to 1540.4 ± 432.0 dynes·s·cm−5 (P = 0.0034) on MRI and from 1820.4 ± 318.8 dynes·s·cm−5 to 1659.0 ± 317.7 dynes·s·cm−5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2–8 mg/day orally for 8–12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.

Evaluation of left ventricular mass: Comparison of ultrafast computed tomography, magnetic resonance imaging, and contrast left ventriculography

We measured and compared left ventricular mass in 20 patients by ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI), and contrast left ventriculography (LVG). Left ventricular mass was calculated by UFCT and MRI in two ways: (1) excluding papillary muscles and trabeculae (LV mass), and (2) including papillary muscles and trabeculae (LV mass + PM&T) by Simpsons method. Left ventricular mass excluding papillary muscles and trabeculae (LV mass) in LVG was calculated by Rackleys method by biplane angiocardiography. LV mass was significantly larger in LVG than in MRI and UFCT (p < 0.01). Although LV mass was significantly larger in MRI than in UFCT (p < 0.01), there was no significant difference in LV mass + PM&T between UFCT and MRI. Interobserver and intraobserver variability showed good correlation of coefficient in both UFCT and MRI. We therefore conclude that left ventricular mass is best measured by including papillary muscles and trabeculae by Simpsons method in UFCT or MRI.

Clinical features of myocardial triglyceride in different types of cardiomyopathy assessed by proton magnetic resonance spectroscopy: comparison with myocardial creatine.

BACKGROUND Myocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction. METHODS AND RESULTS In patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 μmol/g), but higher in ICM (7.59 ± 4.36 μmol/g) than in NML hearts (4.05 ± 1.94 μmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 μmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 μmol/g), DCM (14.8 ± 4.8 μmol/g), and ICM (19.4 ± 6.3 μmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 μmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake. CONCLUSIONS Myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG.

Left ventricular systolic/diastolic function evaluated by quantitative ECG-gated SPECT: comparison with echocardiography and plasma BNP analysis

Objective: The aim of this study was to evaluate the left ventricular (LV) functional parameters calculated using quantitative electrocardiography (ECG)-gated myocardial perfusion single photon emission computed tomography (QGS). In addition to LV systolic parameters, diastolic parameters were compared with those by ultrasound echocardiography (UCG) and also with plasma B-type natriuretic peptide (BNP) concentrations.Methods: We examined 46 patients with various forms of heart disease. By the QGS data with 16 framing data acquisition using technetium (Tc)-99m methoxyisobutylisonitrile (MIBI) perfusion, we calculated the following parameters: LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), peak filling rate (PFR), filling rate during the first third of the filling time ( 1/3FR) and first third filling fraction ( 1/3FF). By UCG, we measured mitral early to atrial (E/A) wave velocity ratio and pulmonary venous inflow systolic/diastolic (S/D) ratio as diastolic functional parameters. Plasma BNP concentrations were also measured.Results: There was a significant correlation between LVEDV, ESV and EF measured by QGS and UCG (EDV, r = 0.71, p < 0.001; ESV, r = 0.82, p < 0.001; EF, r = 0.75, p < 0.001). The PFR, 1/3FR and 1/3FF obtained by QGS correlated positively with E/A ratio (PFR, r = 0.54, p < 0.001; 1/3FR, r = 0.61, p < 0.001; 1/3FF, r = 0.42, p < 0.01) and negatively with S/D ratio (PFR, r = -0.40, p < 0.01; 1/3FR, r = -0.38, p < 0.05; 1/3FF, r = -0.39, p < 0.01) obtained by UCG. Plasma BNP concentrations in EF < 50% patients were greater than those in EF ≥ 50% patients (335.2 ± 60.2 vs. 101.2 ± 41.3 pg/m/, p < 0.01, both n = 17). Plasma BNP levels were also compared between higher and lower 1/3FF patients matched for LVEF. Plasma BNP concentrations in 1/3FF < 35% patients were significantly greater than those in 1/3FF ≥ 35% patients (312.9 ± 62.5 vs. 120.5 ± 32.8 pg/m/, p < 0.05, both n = 14).Conclusions: The degree of LV systolic and diastolic dysfunctions evaluated by QGS correlated with that by UCG or BNP. The QGS functional parameters offer useful information regarding cardiac failure.

Augmentation Index and Pulse Wave Velocity as Indicators of Cardiovascular Stiffness

The authors examine the clinical significance of radial augmentation index (rAI) and brachial-ankle pulse wave velocity (baPWV). In 78 hypertensive patients, rAI correlates inversely with pulse rate (PR; r = −0.57, P < .001), but baPWV does not. A weak correlation between rAI and systolic blood pressure (SBP) is observed (r = 0.28, P < .05). rAI has no significant correlation with diastolic blood pressure (DBP). In contrast, baPWV correlates positively with both SBP (r = 0.54, P < .001) and DBP (r = 0.43, P < .001). In 56 of these patients, baPWV correlates with the diastolic parameters—the mitral E/A ratio (r = —0.35, P < .01), pulmonary vein S/D ratio (r = 0.41, P < .01), and deceleration time (r = 0.28, P < .05)—by echocardiography, but AI.P75 (rAI corrected for PR 75 bpm because of PR dependence) does not. Therefore, for detection of diastolic dysfunction, baPWV may be more sensitive than rAI.

Comparison of antianginal activity of nicorandil, propranolol and diltiazem with reference to the antianginal mechanism

Nicorandil was compared with placebo, propranolol and low and high doses of diltiazem therapy in 12 patients with chronic stable angina pectoris to elucidate its antianginal mechanism. A computer-assisted treadmill exercise test was performed after administration of either placebo, 30 mg of nicorandil, 40 mg of propranolol, or low-dose 60 and high-dose 120 mg of diltiazem. Exercise duration and time to the onset of ischemia were significantly increased after each drug administration and there was no significant difference in the percent increase in exercise duration between nicorandil (44 +/- 7%), propranolol (47 +/- 11%) and high-dose diltiazem (39 +/- 5%) compared with placebo. Nicorandil increased exercise duration in patients with 1-vessel disease more effectively (7.5 +/- 0.7 minutes, p less than 0.05) than either propranolol or low-dose diltiazem (6.7 +/- 0.7, 6.1 +/- 0.9 minutes, respectively). The decrease in blood pressure obtained with nicorandil was approximately the same as that with diltiazem. Nicorandil increased exercise duration associated with higher peak double product compared with low-dose diltiazem. In contrast, high-dose diltiazem increased exercise duration at the same double product as low-dose diltiazem. Propranolol increased exercise duration at a lower level of peak double product. Because our previous study demonstrated that low-dose diltiazem yielded a plasma concentration high enough to reduce coronary tone, it appears unlikely that nicorandil will reduce coronary tone further and subsequently increased coronary reserve. Therefore, left ventricular preload reduction may be the mechanism responsible for higher values of double product obtained with nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)