Takashi Ohtani

Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis.

This study compared the effects of long-term administration of nicorandil and isosorbide dinitrate (ISDN) on vascular endothelial function and the progression of arteriosclerosis. Forty-two patients with ischemic heart disease were randomly allocated to receive nicorandil (N group; 15 mg/d) or ISDN (I group, 40 mg/d). Twelve normal subjects served as controls. Vascular endothelial function and the progression of arteriosclerosis (intima-media thickness, IMT), as determined by carotid vascular ultrasound, were assessed 1 week before and 3 months after drug administration. Reactive hyperemia was induced in the forearm for 5 minutes, and the percentage change in the diameter of the brachial artery (% change in flow-mediated dilation, %FMD) was calculated. FMD was significantly lower in CAD groups than in controls. The %FMD significantly decreased (7.2 ± 1.9 to 4.2 ± 2.8) in the I group, while rising from 6.8 ± 1.6 to 8.0 ± 2.0 in the N group. IMT increased by 0.036 ± 0.015 mm in the I group but showed no significant change in the N group (−0.01 ± 0.012 mm). Thus, ISDN deteriorates IMT and FMD, whereas a beneficial effect of nicorandil is seen on FMD with no effect on IMT. Long-term treatment with nicorandil may be desirable for prevention of cardiovascular events.

Clinical implications of circulating soluble Fas and Fas ligand in patients with acute myocardial infarction.

BACKGROUND Apoptotic cell death is the major form of myocardial damage produced by coronary ischemic events. OBJECTIVE To assess whether circulating levels of soluble Fas (sFas), an inhibitor of apoptosis, and sFas ligand, an inducer of apoptosis, in patients with coronary artery disease are greater than normal. METHODS Forty-seven patients [acute myocardial infarction (AMI) in 17, old myocardial infarction (OMI) in 15, stable angina in 15] and 10 normal control subjects participated in this study. Serum levels of sFas and sFas ligand in all patients were measured, and cardiac catheterizations were performed. RESULTS Serum levels of sFas were greater than normal only in patients with AMI (4.6 +/- 1.6 ng/ml); the levels were significantly higher than those in patients with OMI (2.1 +/- 0.6 ng/ml) and stable angina (2.2 +/- 0.5 ng/ml), and in normal subjects (2.0 +/- 0.6 ng/ml; P < 0.0001). However, there was no difference among serum levels of sFas ligand for all groups. For patients with AMI, there was no significant correlation between serum levels of sFas and peak levels both of plasma creatine phosphokinase and of plasma myosin light chain type I as clinical indexes of infarct size. However, there were significant correlations between serum levels of sFas and both pulmonary artery wedge pressure (r = 0.767, P = 0.0003) and left ventricular end-diastolic pressure (r = 0.629, P = 0.03). CONCLUSIONS Circulating sFas increases in concentration in relation to the severity of hemodynamic conditions in patients with AMI, but it is independent from size of infarct. Therefore, circulating sFas could play an important role as the marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI.

Measurement of cardiac chamber volumes by cine magnetic resonance imaging.

Cardiac chamber volumes (both atria and ventricles) in 19 healthy volun teers were measured noninvasively by cine magnetic resonance imaging (MRI). First, cardiac localization was determined from the coronal image by 0.5-T superconducting magnetic imager. Then, transaxial ECG gated multislice spin echo images were obtained from the bottom to the top of the heart. In the last step, cine MRI was performed at each level of all these transaxial spin echo MR images involving the heart. Each cardiac chamber volume at the same phase was calculated by adding chamber areas in each anatomic section multiplied by slice thickness. Left ventricular (LV) end-diastolic volume (EDV) (132.0±26.9 mL) and LV end-systolic volume (ESV) (47.8 ±13.9 mL) were smaller than right ventricular (RV) EDV (141.1 ±24.8 mL) and RVESV (57.0± 12.6 mL), respec tively (p < 0.01). LV stroke volume (84.3±17.9 mL) was equivalent to RV stroke volume (84.2±17.6 mL) (r=0.91, p < 0.01). Left atrial (LA) and right atrial (RA) maximal volumes were 75.8 ±15.4 mL and 84.4±18.7 mL, respectively. LA minimal volume (37.5 ± 10.7 mL) was smaller than RA minimal volume (47.8 ± 12.2 mL). These values measured by cine MRI are satisfactory and cine MRI will be a useful method of determining cardiac chamber volumes, espe cially atrial volumes.

Effect of disopyramide on left ventricular diastolic function in patients with hypertrophic cardiomyopathy: Comparison with diltiazem

SummaryLeft ventricular diatolic function before and after the administration of disopyramide (100 mg) or diltiazem (30 mg) was assessed in 10 patients with nonobstructive-type hypertrophic cardiomyopathy. Left ventricular diastolic function was assessed by Doppler echocardiography. The peak early (E) and late (A) diatolic flow velocities and E/A ratio (E/A) were measured. Three hours after the administration of disopyramide, blood pressure did not significantly change, but heart rate was decreased significantly (p<0.01). Disopyramide increased the E velocity and E/A ratio from 43.8±15.0 cm/sec to 51.3±16.1 cm/sec and from 0.71±0.20 to 1.00±0.24 (each p<0.01), respectively, and decreased the A velocity from 63.9±18.5 cm/sec to 52.1±14.9 cm/sec (p<0.01). Diltiazem increased the E velocity and E/A ratio from 42.8±12.5 cm/sec to 46.4±13.4 cm/sec (p<0.05) and from 0.74±0.21 to 0.96±0.28 (p<0.01), respectively, and decreased the A velocity from 60.6±16.4 cm/sec to 50.2±15.6 cm/sec (p<0.01). These results indicate that disopyramide improved left ventricular diastolic filling in hypertrophic cardiomyopathy, and its effect was similar to that of diltiazem.

Effect of disopyramide on systolic and early diastolic time intervals in patients with hypertrophic cardiomyopathy.

The present study clarified the effect of disopyramide on left‐ventricular function in patients with hypertrophic cardiomyopathy (5 obstructive type: HOCM, 21 non‐obstructive type: HNCM). The systolic and early diastolic time intervals were assessed 3 hours after a single oral administration of 100‐mg disopyramide. The following parameters were evaluated at rest and after administration of disopyramide: 1) left‐ventricular ejection time index (LVETI), 2) pre‐ejection period index (PEPI), 3) the interval from aortic component of the second heart sound to mitral valve opening (IIA‐MVO), and 4) the interval from MVO to O point of apexcardiogram (MVO‐O). LVETI in HNCM did not change after disopyramide but that in HOCM was significantly shortened (P < .05). PEPI in both HOCM and HNCM was significantly prolonged after administration of disopyramide. IIA‐MVO time in both HOCM and HNCM was not influenced by disopyramide. MVO‐O time in both HOCM and HNCM was significantly shortened after disopyramide. These results suggest that 1) shortening of LVETI in HOCM after disopyramide seemed to be due to the decrease in pressure gradient, 2) PEPI prolongation after disopyramide reflected the decrease in myocardial contractility, and 3) shortening of MVO‐O time after disopyramide indicated the improvement of left‐ventricular filling. The authors conclude that disopyramide may be an important new therapeutic agent in the treatment of patients with hypertrophic cardiomyopathy.

Clinical Significance of the Calcification of Coronary Arteries in Patients with Angiographically Normal Coronary Arteries

In order to clarify the clinical significance of coronary calcification in pa tients with angiographically normal coronary arteries, exercise electrocardiog raphy was used and left ventricular function was examined noninvasively and invasively. The patient groups were as follows: (1) patients with coronary artery calcification on only the left anterior descending artery but no narrowing lesion on any other arteries (calcified group), (2) patients with a significant stenosis on only the left anterior descending artery (stenotic group), and (3) the control group. The left ventricular function in the calcified group, as indicated by systolic time intervals and invasive parameters such as ejection fraction and mean sys tolic ejection rate, showed a depression similar to that in the stenotic group, compared with the control group. The incidence of electrocardiographically is chemic responses to exercise testing was significantly higher in the calcified group (75%, p < 0.01) and the stenotic group (68%, p < 0.01) than in the control group (25%). Exercise tolerance time and the maximum double product were markedly smaller in the calcified and the stenotic groups as compared with the control group. These results indicate that the left ventricular function and coronary reserve in the calcified group were reduced and almost identical with those in the stenotic group. The authors conclude that a calcified coronary artery, even if patent, cannot supply an adequate blood flow for the myocardium, resulting in impaired left ventricular function.

Elevated Cardiac Enzymes in Hypertrophic Cardiomyopathy Patients With Heart Failure - A 20-Year Prospective Follow-up Study.

BACKGROUND To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling. METHODS AND RESULTS Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB ≥2.5%, n=33) and group L (CK-MB <2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P<0.0001), fractional shortening decreased (P<0.0004), and left atrial dimension increased (P<0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P<0.02) and left atrial dimension increased (P<0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H. CONCLUSIONS Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF.

Atrial Natriuretic Peptide and Left Atrial Systolic Function in Normal Subjects

The purpose of this study is to elucidate factors determining the release of atrial natriuretic peptide (ANP) in normal volunteers at rest. Ten normal volun teers were included in this study. Ages ranged between twenty-seven and thirty- three years (mean twenty-seven). The authors measured plasma levels of ANP, and four cardiac chamber volumes, and their functions by cine magnetic reso nance imaging using the rephased gradient-echo method. Plasma levels of ANP in 10 normal subjects were 15.0-37.1 pg/mL (mean 23.6 pg/mL). No significant relationship was seen between ANP level and heart rate or blood pressure. The level of ANP was positively correlated with left atrial (LA) emptying fraction and negatively correlated with LA minimal volume (r=0.85, P < 0.01; r = 0.64, P < 0.05, respectively). No significant relationship was observed between plasma ANP level and left ventricular, right ventricular, or right atrial parame ters. These results suggest that LA systolic function is one of the major determi nants for ANP release in normal subjects at rest.

A large conus artery in patients with hypertrophic cardiomyopathy

SummaryWe retrospectively analyzed coronary arteriograms in 66 patients with hypertrophic cardiomyopathy (HCM) who underwent coronary arteriography. Four of these patients showed a large conus artery supplying the interventricular septum, and the characteristics of their echocardiograms revealed a marked interventricular septal hypertropy.It is suggested that in some patients with HCM, the conus artery may develop in compensation for the relatively reduced coronary blood flow which is due to the hypertrophied myocardium.

Does Hypertrophic Cardiomyopathy Change into Dilated Cardiomyopathy-Like Features?

Hypertrophic cardiomyopathy sometimes progresses to dilated cardiomyopathy-like features [1–5]. The etiology of the progression remains to be determined. Recently, we reported a patient with hypertrophic cardiomyopathy who showed a persistent elevation of serum creatine kinase (CK)-MB and lactate dehydrogenase 1 (LDH1) activities for several years and developed dilated cardiomyopathy-like features [6]. Thus, the persistent elevation of cardiac enzymes might be closely related to the progression from a typical hypertrophic cardiomyopathy to a dilated left ventricle in the patient. To elucidate the prognosis of hypertrophic cardiomyopathy it is very important to know whether the cardiac enzymes elevation occurs usually in patients with hypertrophic cardiomyopathy or only in the specific type. The total CK activity of myocardial origin is composed of three different components, CK-MM, CK-MB and a lesser amount of CK-BB. CK-MM itself is also composed of three main isoforms, MMa, MMb and MMc. CK activity in the myocardium is primarily MMa, and in acute myocardial infarction a rapid and transient rise in MMa activity in the serum is observed. The serum MMa/MMc activity ratio is useful to estimate the process of myocardial injury due to myocardial infarction [7,8]. We recently reported that the measurement of MMa/MMc ratio was also useful to estimate the myocardial condition in patients with hypertrophic cardiomyopathy [9].